Global Perspectives on Pediatric Antimicrobial Resistance: A Systematic Literature Review
Published : May 28, 2024

Abstract

Antimicrobial resistance (AMR) is currently one of the biggest global threats to public health and should be given top priority by all healthcare providers and organizations. It is raising the menace of a post-antibiotic era where children will once again die because of simple, previously treatable infections. Specific pediatric issues, such as reckless antibiotic prescriptions for wrong diagnoses, the limited options, the lack of trials on children, and the evolving nature of this diverse population, are the culprits in this complex perspective. This review focused on antibiotic resistance in pediatric populations in the world. PubMed, Google Scholar, ClinicalTrials.gov were searched using different keywords and period of January 2021 to March 2024.  Publications were selected according to pre-defined inclusion and exclusion criteria. Out of 941 unique retrievals, 84 studies were included. Most of the studies were conducted in China. Multi drug resistance was extensively observed in infectious diseases (both gram-positive and gram-negative bacteria). Multidrug resistance is linked to biofilms, which can make infection control difficult. Staphylococcus aureus, Clostridium difficile, and virulence enterococci resistant to vancomycin infection. There is need to the various diagnostic techniques for antibiotic susceptibility test and to expand antibiotic resistance surveillance studies.

Keywords

Antimicrobial resistance, Antibiotics, Children, Multi-drug resistance, Infections

Introduction

The 21st century has seen the rise of bacterial AMR, which is the phenomenon whereby alterations in bacteria render antibiotics less effective in treating infections. AMR could kill 10 million people annually by 2050, according to the UK Government-commissioned Review on Antimicrobial Resistance [1]. Hence, it is a serious threat to public health, particularly for children. According to World Health Organization (WHO) data, infections with bacteria that are resistant to drugs cause 700,000 deaths annually in all age groups, with about 200,000 of those deaths occurring in neonates [2].

 

AMR-related deaths in 2019 were estimated to be 4·95 million (3·62–6·57), of which 1·27 million (95% UI 0·911–1·71) were directly related to bacterial AMR. Calculated the regional all-age death rate attributable to resistance to be 27·3 deaths per 100 000 (20·9–35·3) in western sub-Saharan Africa and 6·5 deaths (4·3–9·4) per 100,000 in Australasia. The most common infectious syndrome in 2019, lower respiratory infections were linked to over 1.5 million resistance-related deaths. Ninety-nine thousand (660,000–1,270,000) deaths attributable to antimicrobial resistance (AMR) and thirty-seven million (262–478) deaths associated with resistance were caused by the six leading pathogens for deaths associated with resistance: Escherichia coli, Staphylococcus aureus, Streptococcus pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa [3,4].

 

High prevalence of multi drug resistance organism (MDRO) carriers in children poses a great public health concern, especially in developing countries where the health care system is already overburdened. The WHO estimates that if this trend continues, drug-resistant diseases could result in 10 million annual deaths and $300 billion in losses to the gross domestic product and healthcare systems by 2050 [5]. Hence, by encouraging antimicrobial stewardship and discouraging the misuse of antibiotics in all fields, we can lessen its burden on our society. This systematic literature review highlighted antibiotic resistance in pediatrics in different countries.

Methodology

This study is conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PRISMA).

Data Sources and Search Strategy

For this study total three databases such as PubMed, Google Scholar, ClinicalTrials.gov were used for searching studies systematically by using the keywords like Antibiotic resistance, Antimicrobial Resistance, Antibacterial resistance, drug resistance, pediatric, children. Strings and terms were prepared using Boolean operators such as “AND” and “OR”. Finally search was limited from January 2021 to March 2024. Titles were selected using the following strigs and terms: ((“antibiotic*”[All Fields] OR “Antimicrobial”[All Fields] OR “Antibacterial”[All Fields]) AND (“Drug Resistant”[All Fields] OR “Drug Resistance”[All Fields]) AND (“Children”[All Fields] OR “Pediatric”[All Fields])) AND ((humans[Filter]) AND (2021/1/31:2024/3/31[pdat]) AND (english[Filter]).

Inclusion and Exclusion Criteria

The PICOs (P-Population; I-Intervention; C-Comparison; O-Outcome; S-Study design) inclusion/exclusion criteria were applied to screen title/abstracts and subsequently full-texts. The inclusion criteria were as follow: publications related to 1) humans; 2) all sexes; 3) children with antimicrobial or antibiotic resistance or multi drug resistance; 4) year (January 2021 to March 2024); 5) all clinical studies, systematic literature review and meta-analysis. The exclusion criteria were as follow: 1) Animal studies; 2) general reviews, conference abstracts, Editorial commentaries, Letters, case reports, case series, clinical studies without results; 3) publications containing duplicate data; 4) publication not in the search period range.

Data Synthesis and Extraction

Screened all the articles in different databases using keywords and reported in Microsoft Excel spreadsheet. Initially eliminating articles that were duplicate or irrelevant by screening each title and abstract independently. The remaining articles were then evaluated for inclusion criteria (Primary level screening). To find any more studies that might have escaped the search, double-check the references listed in the included articles (Secondar level screening). Finally summarized the articles in Microsoft Excel spreadsheet.

Results

By searching the electronic database, a total of 941 articles were identified, including 826 from the PubMed, 100 from Google Scholar, and 15 from ClinicalTrials.gov. Initially 18,000 search results were identified during Google Scholar screening, but the first 100 were screened systematically and contained high-quality publications. After 5 duplicates were removed, 936 articles remained to be screened. According to the inclusion and exclusion criteria, 251 eligible full-text articles were retrieved. At secondary screening total 131 were excluded and finally 84 articles were included. PRISMA for this review was represented in Figure 1 and included study details were summarized in Table 1.

 

Figure 1: PRISMA process for screening process

 

Table 1: Summary of Included articles

 

S.No Title of study Study location Summary
1 Bacterial distribution and drug resistance in blood samples of children in Jiangxi Region, 2017-2021 [6]  China Between 2017 and 2021, a total of 7,977 bacterial strains were isolated from blood samples of children. Among these, 2,334 strains (29.3%) were Gram-negative bacteria, while 5,643 strains (70.7%) were Gram-positive bacteria. Notably, Gram-positive cocci emerged as the predominant clinical pathogens in blood samples from children in Jiangxi province. Over the years, there was a slight variation in the composition of pathogen species. Escherichia coli and Klebsiella pneumoniae strains exhibited resistance to third-generation cephalosporins (cefotaxime/ceftriaxone) at rates of 45.9% and 56.0%, respectively. Additionally, resistance to carbapenems was noted in 4.6% and 20.3% of these strains, respectively. Salmonella strains demonstrated resistance to third-generation cephalosporins (cefotaxime/ceftriaxone) at a rate of 15.5%, while no resistance to imipenem was observed. Carbapenem resistance was detected in 17.1% (20/117) of Acinetobacter baumannii strains and in 13% (14/108) of Pseudomonas aeruginosa strains. Methicillin-resistant Staphylococcus aureus (MRSA) was present in 32.7% of the strains, and methicillin-resistant coagulase-negative Staphylococcus was identified in 64.3% of coagulase-negative Staphylococcus strains. No vancomycin-resistant Staphylococcus bacteria were found. The study concluded that although the isolation rate of common carbapenem-resistant Enterobacter bacteria has decreased, it remains elevated.
2 A pattern of antibiotic drug resistance of Salmonella Typhi and Salmonella Paratyphi among children with enteric fever in a tertiary care hospital in Lahore, Pakistan [7] Pakistan Out of the 105 children studied, with a mean age of 8.48 ± 4.18 years, the highest antibiotic resistance was observed against ampicillin, with 91 cases (86.7%). Interestingly, all isolates were found to be sensitive to both imipenem and meropenem. Among the cultured organisms, 23 (21.9%) were classified as multidrug-resistant (MDR), while 54 (56.8%) were categorized as extensively drug-resistant (XDR).
3 Antibiotic resistance of Streptococcus pneumoniae in Vietnamese children with severe pneumonia: a cross-sectional study [8] Vietnam Among 239 children with severe community-acquired pneumonia (CAP), 89 strains of Streptococcus pneumoniae were isolated. The majority of these isolates exhibited significant resistance patterns: 1.1% were intermediate and 98.9% were resistant to penicillin, while 96.6% showed high resistance to erythromycin and 88.8% to clarithromycin. Additionally, resistance to ceftriaxone was observed in 16.9% of strains, with 46.0% showing intermediate resistance. However, all strains were susceptible to vancomycin and linezolid. The study highlights a concerning prevalence of S. pneumoniae strains resistant to multiple antibiotics, including those with high minimum inhibitory concentrations (MICs), among children with severe CAP. Consequently, the study suggests that penicillin should not be the primary antibiotic choice, advocating instead for the use of ceftriaxone at an enhanced dosage.
4 Pathogenic Role and Antibiotic Resistance of Methicillin-Resistant Staphylococcus aureus (MRSA) Strains Causing Severe Community-Acquired Pneumonia in Vietnamese Children [9] Vietnam Study concluded that in Vietnamese children with severe community-acquired pneumonia (CAP), S. aureus, particularly Methicillin-resistant Staphylococcus aureus (MRSA), was identified as the second most common causative agent. These MRSA strains displayed resistance to numerous antibiotics, yet they were entirely susceptible to vancomycin and linezolid, with their minimum inhibitory concentrations (MICs) well below the Clinical and Laboratory Standards Institute (CLSI) threshold as of 2021. As a result, vancomycin and linezolid could be considered suitable treatment options for severe CAP caused by MRSA.
5 Tracheostomized children tracheal colonization and antibiotic resistance profile – A STROBE analysis [10] Brazil Out of forty-four patients who underwent tracheostomy aspirate culture, all but one exhibited growth of Potentially Pathogenic Bacteria (PPB), accounting for a prevalence rate of 97.7%. The median age of these patients was 3 years old. Pseudomonas aeruginosa was the most frequently isolated bacteria, present in 56.9% of cases. Among the culture tests, this bacterium showed resistance rates of 36% to gentamicin, 28% to amikacin, and 12% to cefepime. The resistance of P. aeruginosa to gentamicin and cefepime appeared to correlate with the number of antibiotic classes used in the preceding 12 months (both p = 0.04) and with two or more hospital admissions during the same period (p = 0.03 and p = 0.02, respectively). Staphylococcus aureus was found in 9.1% of cases, with no presence of methicillin-resistant Staphylococcus aureus (MRSA) detected.
6 Antibiotic resistance and genomic features of Clostridioides difficile in southwest China [11] China All 49 strains exhibited sensitivity to metronidazole, meropenem, amoxicillin/clavulanic acid, and vancomycin. Additionally, all isolates displayed intermediate resistance to cefotaxime. However, a substantial proportion of the Clostridioides difficile strains demonstrated resistance to other antibiotics: 87.80% (43/49) were resistant to erythromycin, 81.60% (40/49) to gentamicin, 61.20% (30/49) to clindamycin, 36.70% (18/49) to ceftazidime, and 28.60% (14/49) to levofloxacin. In Concluded that, the majority of the strains exhibited resistance to erythromycin, gentamicin, and clindamycin.
7 Uropathogenic Escherichia coli virulence characteristics and antimicrobial resistance amongst pediatric urinary tract infections [12] Iraq In summary, virulent and resistant Uropathogenic Escherichia coli (UPEC) strains emerge as a primary cause of urinary tract infections (UTIs) in Iraqi pediatric cases. The coexistence of antimicrobial resistance and virulence factors potentially escalates the pathogenicity of these strains. The effectiveness of gentamicin, ampicillin, and ciprofloxacin in controlling and treating UPEC-induced UTIs in Iraq appears limited based on the findings. Nonetheless, additional investigations are warranted to evaluate other epidemiological aspects of UPEC-related UTIs.
8 Clinical Characteristics and Drug Resistance Analysis of 90 Cases of Children with Salmonella Enteritis [13] China Found that the susceptibility rates of 15 antibiotics, ranked from high to low, were as follows: imipenem and meropenem, piperacillin, cefoperazone, compound trimethoprim, chloramphenicol, and ceftazidime. Salmonella strains exhibited resistance to both imipenem and meropenem. However, Salmonella showed sensitivity with a low rate of resistance to quinolones (ciprofloxacin) and a high rate of resistance to cephalosporins (ceftriaxone, cefotaxime, ceftazime, and cefpiramide), with rates exceeding 28%. Additionally, Salmonella demonstrated the highest resistance rates to penicillin and erythromycin, both surpassing 85.00%.
9 Antibiotic resistance patterns and therapeutic outcomes of pediatric Helicobacter pylori infection in a high-migrant Singaporean cohort [14] Singapore The analysis included a total of 70 children, with a median age of 14 years (range 2-17 years). Within the cohort, 42.9% (30/70) exhibited some form of antibiotic resistance, with clarithromycin resistance being the most prevalent (30.0%), followed by metronidazole (27.5%) and amoxicillin (7.1%). When comparing natives to non-native Singaporeans, non-natives presented at a significantly younger age (mean 11.7 vs. 13.7 years, p = 0.043). Additionally, a significantly higher proportion of non-natives carried clarithromycin-resistant (51.4% vs. 8.6%, p < 0.001) and metronidazole-resistant (47.1% vs. 8.6%, p < 0.001) strains, as well as multidrug-resistant strains (resistant to ≥2 drugs) (40.0% vs. 2.9%, p < 0.001). Non-natives also exhibited a significantly higher failure rate of first-line eradication therapy (48.5% vs. 23.3%, p = 0.038). Furthermore, the proportion of pan-sensitive H. pylori was significantly lower in first-generation immigrants (25.0%, p = 0.001) and second-generation immigrants (42.9%, p = 0.018) compared to natives (82.86%).
10 Antimicrobial resistance profile of methicillin-resistant Staphylococcus aureus isolates in children reported from the ISPED surveillance of bacterial resistance, 2016-2021 [15] China The most common age group affected by Methicillin-resistant Staphylococcus aureus (MRSA) infection is children under 3 years old, with newborns being particularly susceptible. MRSA isolates showed high resistance rates to erythromycin and clindamycin, but low resistance rates to levofloxacin, TMP-SMX, gentamicin, and rifampin. Notably, no isolates were resistant to vancomycin or linezolid.Changes in antibiotic resistance rates among MRSA isolates from 2016 to 2021 were observed, including an increase in levofloxacin and TMP-SMX resistance rates, and a decrease in erythromycin, clindamycin, tetracycline, gentamicin, and rifampin resistance rates. Bone and joint-derived MRSA isolates exhibited a higher clindamycin resistance rate compared to isolates from other clinical sources. In regions where clindamycin-resistant MRSA strains are prevalent, empirical vancomycin therapy is recommended for treating pediatric osteomyelitis, while clindamycin is not advised for osteomyelitis treatment.
11 Antimicrobial Resistance and the Successful Eradication of Helicobacter pylori-Induced Gastroduodenal Ulcers in Vietnamese Children [16] South Asia A total of 76 participants, comprising 52.6% males and 47.4% females, were included in the study, with an average age of 9.3 ± 2.8 years (range: 4–15 years). The antibiotic resistance rates observed were as follows: clarithromycin, 92.1%; amoxicillin, 50%; levofloxacin, 31.6%; metronidazole, 14.5%; and tetracycline, 0%. The overall successful eradication rate was 44.7%. The addition of bismuth resulted in a 3.69-fold increase in the eradication rate compared to regimens without bismuth (p = 0.030). Levofloxacin exhibited a high eradication rate (100%, p = 0.038) compared to other antibiotics. However, the effectiveness of high-dose amoxicillin in cases with >50% H. pylori amoxicillin resistance was only 32.6% (p = 0.015). In Concluded that, the study found a decreased eradication efficacy of H. pylori at 44.7% due to increased antibiotic resistance. However, combinations of drugs, such as levofloxacin and bismuth, were shown to enhance H. pylori eradication efficacy in children.
12 Clinical profiles and antimicrobial resistance patterns of invasive Salmonella infections in children in China [17] China Among Salmonella 170 Typhi isolates, 50% exhibited resistance to ampicillin or piperacillin, followed by ampicillin/sulbactam (20%), chloramphenicol (20%), sulfamethoxazole/trimethoprim (9.1%), and cefepime (9.1%). In contrast, non-Typhi Salmonella (NTS) serovars displayed high rates of resistance to ampicillin (57.3%), ampicillin/sulbactam (54.7%), piperacillin (45.3%), and tetracycline (32%).
13 Antimicrobial resistance in shigellosis: A surveillance study among urban and rural children over 20 years in Bangladesh [18] Bangladesh In Concluded that, our study findings identified changing pattern of Shigella species, and emerging resistance in Shigella isolates to WHO recommended 1st and 2nd line antimicrobial agents such as ciprofloxacin, azithromycin, mecillinam, and ceftriaxone in the last 20 years in Bangladesh. Multidrug-resistant shigellosis is also gradually increasing both in urban and rural settings. physicians should be aware of the high rates of antimicrobial resistance to Shigella spp. in Bangladesh. Undoubtedly, the treatment of shigellosis among under-5 children demands careful and judicial use of antimicrobials to avoid rapid emergence and spread of resistance.
14 Antimicrobial Resistance Profile of Bacteria Causing Pediatric Infections at the University Teaching Hospital in Rwanda [19] Rwanda The study conducted from June 1, 2018, to May 30, 2019, involved the collection of microbiological samples from 712 children with suspected bacterial infections. Antimicrobial sensitivity testing was performed on 177 positive cultures (24%) considered for data analysis. The major bacterial isolates identified were Klebsiella pneumoniae (n = 50, 28.2%), Escherichia coli (n = 47, 26.5%), and Staphylococcus aureus (n = 38, 21.4%). Overall, the highest antibiotic resistance rates were observed with ampicillin (n = 125, 86.2%), amoxicillin–clavulanic acid (n = 84, 82.4%), amoxicillin (n = 64, 79%), cefadroxil (n = 83, 69.2%), tetracycline (n = 72, 59.7%), ceftazidime (n = 42, 55.3%), and cefuroxime (n = 14, 53.8%). Specifically, Klebsiella pneumoniae exhibited 100% resistance to amoxicillin-clavulanic acid, cefuroxime, trimethoprim–sulfamethoxazole, ceftazidime, erythromycin, and clindamycin. Staphylococcus aureus showed 86.7% resistance to ampicillin, while Escherichia coli demonstrated 91.7% resistance to tetracycline, 90.6% resistance to ampicillin, 83.3% resistance to amoxicillin–clavulanic acid, 79.3% resistance to cefadroxil, and 78.6% resistance to ceftazidime. Furthermore, Klebsiella pneumoniae isolated from blood and urine showed 96.8% and 100% sensitivity, respectively, to meropenem. Staphylococcus aureus isolated from blood exhibited 100% sensitivity to vancomycin, whereas Escherichia coli isolated from urine was sensitive to clindamycin (100%), nitrofurantoin (80.6%), and ciprofloxacin (72.7%). In Concluded that, the study findings indicate a high resistance rate to commonly used antibiotics, highlighting the need for caution in empirical therapy and continued surveillance of antimicrobial resistance.
15 The increasing antimicrobial resistance of Shigella species among Iranian pediatrics: a systematic review and meta-analysis [20] Iran In a comprehensive analysis of 28 eligible studies published between 2008 and 2021, the pooled prevalence rate of multidrug-resistant (MDR) Shigella species was found to be 63% (95% CI 50–76). Regarding suggested antimicrobial agents for Shigella species, the prevalence of resistance to ciprofloxacin, azithromycin, and ceftriaxone as first- and second-line treatments for shigellosis was 3%, 30%, and 28%, respectively. In contrast, resistance rates to cefotaxime, cefixime, and ceftazidime were 39%, 35%, and 20%, respectively. Of particular note, subgroup analyses revealed an increase in resistance rates over the studied periods (2008–2014, 2015–2021) for ciprofloxacin (from 0% to 6%) and ceftriaxone (from 6% to 42%). These findings underscore the importance of continuous surveillance and strategic antimicrobial stewardship to address the rising challenge of antimicrobial resistance in Shigella infections.
16 Primary Antibiotic Resistance And Effectiveness Of Clarithromycin Vs Metronidazole Based Therapy For Helicobacter Pylori Infection In Children [21] Pakistan Out of 54 children diagnosed with H. pylori infection, 40 (74.074%) had strains susceptible to antimicrobials, while 14 (25.92%) exhibited resistance to antimicrobials. Based on the pattern of antimicrobial sensitivity, they were categorized into three groups: (a) Clarithromycin and Metronidazole sensitive group (18/40, 45%), (b) Clarithromycin sensitive and Metronidazole resistant group (12/40, 30%), and (c) Metronidazole sensitive group (10/40, 25%). It was concluded that Clarithromycin and Metronidazole should not be used as first-line treatment for H. pylori eradication in children. Instead, they should only be used when antimicrobial susceptibility is known to avoid treatment failure due to resistance.
17 Antibiotic Susceptibility, Carrier State and Predictors of Outcome of Staphylococcus aureus Infections in Hospitalized Children [22] India Skin and soft tissue infections emerged as the most prevalent (47%), followed closely by respiratory infections (37%). Among these cases, Methicillin-resistant Staphylococcus aureus (MRSA) was detected in 62% of instances, with 63% (39/62) of these MRSA strains exhibiting multi-drug resistance. Additionally, a carrier state was present in 49% of patients, with MRSA being present in 93% of carriers, predominantly as axillary carriers (80%). A noteworthy finding was the high minimum inhibitory concentration (MIC) (>1 µg/mL) for vancomycin observed in 65% of patients. Importantly, this elevated MIC for vancomycin was identified as the sole factor associated with poor recovery [adjusted odds ratio (aOR) 5.3; 95% confidence interval (CI) 1.6, 18.5; p = 0.008] on multivariable logistic regression analysis.
18 Resistance genomics and molecular epidemiology of high-risk clones of ESBL-producing Pseudomonas aeruginosa in young children [23] China Based on the findings of this study, it is evident that multidrug-resistant Pseudomonas aeruginosa presents a substantial threat to young children in clinical settings in China. The elevated resistance rates observed for commonly prescribed antibiotics, including piperacillin–tazobactam, cefepime, ceftazidime, and carbapenems, underscore the pressing need to explore novel or alternative therapeutic approaches for effective disease management.
19 Etiology, antibiotic susceptibility and prognostic factors of pediatric community-acquired sepsis in Addis Ababa, Ethiopia [24] Ethiopia he prevalence of culture-positive community-acquired sepsis (CAS) was found to be 18.81% (19 out of 101 cases). Streptococcus pneumoniae (21.1%), including serotypes 19A (n = 2), 33C, and 12F, as well as Klebsiella pneumoniae (21.1%), were identified as the most common causative agents of CAS. Notably, half of the Klebsiella pneumoniae isolates exhibited resistance to gentamicin and ceftriaxone.
20 Paediatric Osteomyelitis and Septic Arthritis Pathogen Distribution and Antimicrobial Resistance in a Single Centre: A 15-Year Retrospective Analysis [25] China In Concluded that, Staphylococcus aureus remains the predominant causative pathogen of acute hematogenous osteomyelitis and septic arthritis in local children. There has been a gradual increase in the proportion of S. aureus cases over time, reaching 96.15% in the past 5 years. The distribution of S. aureus cases did not show significant variations across different age groups or infection types. However, the proportion of methicillin-resistant S. aureus (MRSA) within S. aureus infections has also risen over time, reaching 76% in the past 5 years. Notably, while the proportion of MRSA is lowest in children younger than 3 months old, it does not vary significantly based on infection type. Furthermore, the resistance of S. aureus to multiple drugs is progressively increasing in this region.
21 Antibiotic resistance in paediatric UTIs in Norway [26] Norway Among the 13,211 urinary isolates recorded in the NORM register, 589 (4.5%) were from children. Escherichia coli, weighted by the number of data collection days, accounted for 85.2% of these isolates from children. Comparing resistance rates between children and adults, we found a higher proportion of trimethoprim resistance in urine samples from children (27.0%) compared to adults (22.9%) with E. coli, p = 0.02. Conversely, for ciprofloxacin, we observed a lower resistance rate in E. coli from urine samples of children (5.7%) compared to adults (8.7%), p = 0.03. For other selected antibiotics, the resistance rates in E. coli isolated from children were as follows: nitrofurantoin (0.5%), mecillinam (4.0%), cephalexin (4.3%), amoxicillin-clavulanic acid (7.2%), and trimethoprim-sulfamethoxazole (24.1%).
22 Characterization and drug susceptibility pattern of Salmonella and Shigella in children below five years: a cross-sectional study conducted in Lodwar, Turkana County, in Northern Kenya [27] Northern Kenya Out of the total samples collected (196), cases of Shigella dysenteriae were 4 (5%), Shigella flexneri were 7 (9%), Shigella sonnei were 3 (4%), Shigella boydii were 4 (5%), and Salmonella typhimurium were 2 (2.4%). Among these, approximately 70% of the isolated Salmonella and Shigella strains exhibited high antibiotic resistance to Amoxiclav and Ampicillin, with both showing high minimum inhibitory concentrations (MICs) values of about 8 µg/ml. Conversely, over 80% drug susceptibility was observed in Amikacin (1 µg/ml), Ciprofloxacin (2 µg/ml), Ceftriaxone (4 µg/ml), and Ceftazidime (4 µg/ml). Salmonella and Shigella are prominent causes of diarrhea in children under five years of age. The emergence of drug resistance among commonly used antibiotics is a concerning trend, signaling potential misuse of antibiotics, particularly beta-lactam penicillins. This underscores the need for judicious antibiotic prescribing practices and comprehensive strategies to combat antimicrobial resistance in pediatric populations.
23 Characterization of genotypes and antimicrobial resistance profiles of clinical isolates of Shigella from patients in the southern region of Iran [28] Iran Out of 448 stool samples analyzed, Shigella was detected in 62 cases, resulting in a prevalence rate of 13.84%. Among the identified isolates, the majority were attributed to S. flexneri, accounting for 53.23% of the cases, followed by S. sonnei at 24.19% and S. boydii at 22.58%. Notably, no instances of S. dysenteriae were found. The highest prevalence of Shigella isolates was observed in infants and children under the age of five. A significant proportion of the identified isolates demonstrated resistance to various antibiotics. Specifically, high resistance rates were noted for ampicillin (90.78%), piperacillin-tazobactam (87.1%), cefixime (83.87%), trimethoprim-sulfamethoxazole (83.87%), cefotaxime (82.26%), and ceftriaxone (80.65%). Additionally, a substantial number (87.1%) of the isolates exhibited a multidrug-resistant (MDR) phenotype. Using the ERIC-PCR method, a total of 11 clusters and 6 distinct single types were identified among all the Shigella isolates, highlighting the genetic diversity within the sampled population.
24 High frequency of antimicrobial resistance and virulence gene in Shigella species isolated from pediatric patients in an Iranian Referral Hospital [29] Iran Among the total of 183 Shigella strains isolated, 128 (70%) were Shigella sonnei and 55 (30%) were S. flexneri. Interestingly, the resistance rate to antibiotics was higher in S. sonnei strains compared to S. flexneri. For S. flexneri, the most sensitive antibiotics were gentamicin (98%), amikacin (85%), and ciprofloxacin (82%). However, a high resistance rate was observed for trimethoprim-sulfamethoxazole (96%), ampicillin (96%), nalidixic acid (64%), and cefotaxime (60%). In terms of genetic markers, the frequency of invE, virF, and sigA genes in S. flexneri strains was 89%, 93%, and 56%, respectively. In comparison, these genes were found in 93%, 96%, and 100% of S. sonnei strains, respectively. Notably, the sigA gene was identified significantly more often in S. sonnei strains (100%). However, there was no significant difference between the presence of virF and invE genes among Shigella strains.
25 Bacterial pathogens and antimicrobial resistance in acute otitis media [30] Spain During the research period, there were 14,684 documented instances of care for children diagnosed with AOM. Among these, 768 care episodes included an ear drainage culture. The median age of the patients was 2 years, with 57% being male, and 70% having a history of AOM. The most commonly found pathogens were: Haemophilus influenzae (188 cases, 24.5%; 15.5% of them showed resistance to ampicillin), Streptococcus pyogenes (86 cases, 11.2%), Staphylococcus aureus (82 cases, 10.7%), Streptococcus pneumoniae (54 cases, 6.9%; with 9.4% showing intermediate resistance to penicillin), Pseudomonas aeruginosa (42 cases, 5.5%), and Moraxella catarrhalis (11 cases, 1.4%).
26 Antimicrobial Resistance in Pneumococcal Carriage Isolates from Children under 2 Years of Age in Rural Pakistan [31] Pakistan Among the 3,140 enrolled children, pneumococcal isolates were found in 2,370, which accounts for 75% of the total. Vaccine coverage rose from 41% to 68.4%. Out of these isolates, 88.4%, 37.6%, and 25% exhibited resistance to cotrimoxazole, tetracycline, and erythromycin, respectively. No resistance was observed against penicillin, ceftriaxone, or vancomycin. Resistance to erythromycin increased from 20% in 2014/15 to 30.8% in 2017/18, and to tetracycline from 34.9% to 41.8%, both attributed to the increased prevalence of serotype 19A. Pneumococcal isolates remained susceptible to penicillin, ceftriaxone, and vancomycin, but largely resistant to cotrimoxazole and tetracycline. The rise in erythromycin and tetracycline resistance was linked to the growing prevalence of serotype 19A.
27 Persistent high macrolide resistance rate and increase of macrolide-resistant ST14 strains among Mycoplasma pneumoniae in South Korea, 2019-2020 [32] South Korea In contrast to the previous outbreak spanning from 2014 to 2016, the general level of macrolide resistance persisted at a high rate; nonetheless, there was a notable rise in the proportion of macrolide resistance specifically within ST14 strains during the period of 2019 to 2020.
28 Three-year evaluation of the nosocomial infections in pediatrics: bacterial and fungal profile and antimicrobial resistance pattern [33] Iran In this investigation, a total of 718 patients diagnosed with NIs were identified, with 61.3% being male (N = 440). The median age of the patients was 2.5 years (IQR: 1 month to 3 years). The most prevalent microorganisms were Klebsiella pneumonia and Candida spp. isolates (N = 125, 17.4%, N = 121, 16.9%, respectively), followed by Pseudomonas aeruginosa (N = 72, 10%) and Coagulase-negative Staphylococci (CoNS) (N = 69, 9.6%). Pseudomonas aeruginosa strains exhibited high sensitivity to the antibiotics under study. Acinetobacter baumannii strains showed more than 90% resistance to almost all antibiotics. All tested isolates of S. maltophilia were susceptible to Trimethoprim−sulfamethoxazole (100%) and displayed a high susceptibility rate to ciprofloxacin (96.4%). Vancomycin resistance was not observed in S. aureus isolates, while 64% of Enterococcus spp. were resistant to vancomycin. The rates of methicillin resistance for S. aureus and CoNS isolates were 45.5% and 85.7%, respectively.
29 Prevalence and risk factors associated with drug resistant bacteria in neonatal and pediatric intensive care units: A retrospective study in Saudi Arabia [34] Saudi Arabia The primary sites of infection among these patients were predominantly the urinary tract (35%), followed by the bloodstream (20.0%), wounds/skin (12.9%), and the respiratory system (11.4%). Methicillin-resistant Staphylococcus aureus (MRSA) was identified as the most prevalent microorganism across these infection sites (30.7%), followed by Escherichia coli (25.0%), Klebsiella pneumoniae (22.9%), and Serratia (10.0%). A notably high mortality rate was significantly linked with patients on mechanical ventilators (28.9%, OR 5.5; 95% CI), those undergoing invasive procedures (27.5%, OR, 8.04; 95% CI), and those requiring total parental nutrition (TPN), with nearly half of these cases (46.2%) resulting in death. Moreover, mortality rates were relatively higher among patients infected with Serratia (28.6%) and Enterobacter (20.0%). These findings underscore the prominence of MRSA as the predominant multidrug-resistant (MDR) bacterium isolated from patients in the Pediatric Intensive Care Unit (PICU) and Neonatal Intensive Care Unit (NICU), followed by gram-negative bacteria, which are associated with elevated mortality rates. Thus, implementing infection control measures and continuously monitoring emerging MDR bacteria are imperative to mitigate bacterial infections in NICU and PICU patients.
30 Evaluation of Pediatric Screening for Resistant Pathogens in an Israeli Tertiary Center [35] Israel Information was gathered from all patients under the age of 18 who adhered to our internal criteria between 2015 and 2016. Screening was conducted for carbapenem-resistant Enterobacteriaceae (CRE), extended-spectrum beta-lactamase (ESBL), methicillin-resistant Staphylococcus aureus (MRSA), and vancomycin-resistant enterococci (VRE). Screening was indicated for non-resident, non-Israeli patients (from the Palestinian Authority, Syria, and foreign patients), internal transfers from intensive care units, admission to high-risk departments, recent carriage of multidrug-resistant (MDR) bacteria, transfers from other hospitals, and recent hospitalizations. Analysis of MDR bacteria included screening from at least one site (rectal, nasal, axillary, groin, throat). All data were examined on a per-patient and per-sample basis.
In summary, individuals who are non-Israeli residents and those with prior positive screening for multidrug-resistant (MDR) bacteria are at a heightened risk of encountering MDR pathogens. The indications utilized to identify high-risk patients for drug-resistant pathogens proved effective. However, there is a necessity for increased efforts to minimize excessive sampling.
31 Antibiotic Susceptibility and Biofilm Formation of Bacterial Isolates Derived from Pediatric Patients with Cystic Fibrosis from Tehran, Iran [36] Iran The cross-sectional study involved a study population of 8,908 children suspected of having cystic fibrosis (CF) due to clinical symptoms, spanning from March 2015 to August 2017, and referred to Tehran Pediatric Central Hospital in Iran. Each participant underwent various tests including a sweat test screening, sputum culture, antibiotic susceptibility test using the Kirby-Bauer disk diffusion method, and assessment of biofilm formation using microtiter plates. Among these children, 183 (2.05%) tested positive for CF based on clinical examination and sweat test screening. The average age of the children was approximately 2.93 years, with a majority being male (n=103, 56.2%). No significant gender-based difference in CF prevalence was observed in the study (P>0.05). Sputum culture results indicated that 153 (83.6%) CF patients yielded microorganisms (bacteria and fungi). Normal flora was found in 30 (16.4%) patients, while multiple bacterial species were isolated in 7.2% of patients. Pseudomonas aeruginosa emerged as the most prevalent bacteria, followed by Staphylococcus aureus and Klebsiella pneumoniae. Regarding antibiotic susceptibility, P. aeruginosa displayed the highest resistance rate (11.7%) against gentamicin, whereas the lowest resistance rate (2.3%) was seen with piperacillin/tazobactam. All K. pneumoniae isolates were resistant to Cefotaxime. Among S. aureus isolates, 83.4% were methicillin-susceptible Staphylococcus aureus, while 16.6% were Methicillin-resistant Staphylococcus aureus. Concerning biofilm formation, 76%, 67%, and 72.5% of P. aeruginosa, S. aureus, and K. pneumoniae isolates, respectively, demonstrated biofilm production. The study findings highlighted P. aeruginosa as the predominant pathogen in pediatric CF patients from Tehran, Iran, with a significant proportion exhibiting biofilm formation. While no severe antibiotic resistance was observed in the isolates, regular monitoring of antimicrobial resistance profiles is recommended for CF patients.
32 Klebsiella spp. cause severe and fatal disease in Mozambican children: antimicrobial resistance profile and molecular characterization [37] Republic of Mozambique (southeast Africa) Klebsiella isolates obtained from postmortem blood samples were more likely to exhibit resistance to ceftriaxone (69.6%, 16/23 vs. 48.9%, 43/88, p = 0.045) or be producers of extended-spectrum β-lactamase (ESBL) (60.9%, 14/23 vs. 25%, 22/88, p = 0.001) compared to isolates from patients upon admission.
33 The intestinal carrier status of Enterococcus spp. in children: clonal diversity and alterations in resistance phenotypes before and after admission to a pediatric intensive care unit [38] Iran The findings indicated that Enterococci colonization was present in 31% of cases at admission, 28.7% at discharge, and in 40.1% at both time points. At admission and discharge, there were notably high rates of fecal Enterococcus isolates exhibiting vancomycin-resistance (32.6% and 41.9%, respectively), high-level gentamicin-resistance (25.6% and 27.9%, respectively), and multi-drug resistance (48.8% and 65.1%, respectively). Resistance to vancomycin, ampicillin, and rifampicin was more prevalent among E. faecium, whereas resistance to ciprofloxacin was higher in E. faecalis isolates. Prolonged hospital stays were associated with the carriage of resistant strains to vancomycin, ampicillin, and ciprofloxacin. While there was low homology among isolates from different patients during hospitalization, identical (9%) and similar (21%) RAPD-PCR patterns were identified between pairs of isolates from individual patients.
34 Risk of community- and hospital-acquired bacteremia and profile of antibiotic resistance in children hospitalized with severe acute malnutrition in Niger [39] Niger (West Africa) Upon admission, the prevalence of community-acquired bacteremia was determined to be at least 9.1% (95% confidence interval [CI]: 8.1, 10.4%), with non-typhoid Salmonella being identified in more than half (57.8%) of these cases. The cumulative incidence of hospital-acquired bacteremia was estimated to be 1.2% (95% CI: 0.8, 1.7%), with Klebsiella pneumoniae (19.4%), Acinetobacter baumannii (16.1%), Enterococcus faecalis (12.9%), and Escherichia coli (12.9%) being the most common organisms isolated. Among community-acquired bacteremia cases, 58% displayed resistance to amoxicillin-clavulanate, while all hospital-acquired bacteremia cases were resistant to both amoxicillin and amoxicillin-clavulanate. Children with hospital-acquired bacteremia exhibited a significantly elevated mortality risk (risk ratio [RR] = 9.32), as did those with community-acquired bacteremia (RR = 2.67).
35 Population genetic structure, serotype distribution and antibiotic resistance of Streptococcus pneumoniae causing invasive disease in children in Argentina [40] Argentina A total of 1713 pneumococcal isolates, characterized by serotype (Quellung) and antimicrobial resistance (agar dilution) to ten antibiotics, were included in the study, spanning three periods: pre-PCV7 era 1998–1999 (pre-PCV), before the introduction of PCV13 2010–2011 (PCV7), and after the introduction of PCV13 2012–2013 (PCV13). The collection comprised fifty-four serotypes, with serotypes 14, 5, and 1 collectively representing 50% of the isolates. Resistance rates were observed as follows: penicillin 34.9%, cefotaxime 10.6%, meropenem 4.9%, cotrimoxazole 45%, erythromycin 21.5%, tetracycline 15.4%, and chloramphenicol 0.4%. However, all isolates demonstrated susceptibility to levofloxacin, rifampin, and vancomycin. Among the 1713 isolates, 61.9% (1061) exhibited non-susceptibility to at least one antibiotic, with 13.7% (235) classified as multidrug resistant.
36 Clinical characteristics, antimicrobial resistance, and risk factors for mortality in paediatric invasive pneumococcal disease in Beijing, 2012-2017 [41] Beijing Antibiotic sensitivity test results were obtained for 181 (97.3%) patients (Table 2). Among them, 147 (81.2%) exhibited multidrug-resistant strains, defined as resistance to three or more antibiotics simultaneously. Within this group, 128 (87.1%) were resistant to erythromycin, clindamycin, and tetracycline concurrently. The rates of nonsusceptibility to penicillin, cefotaxime, and cefepime among nonmeningitis patients showed an increase from 31.3%, 14.3%, and 38.5% in 2012 to 68.2%, 57.1%, and 66.7% in 2017, respectively (Fig. 3). Meanwhile, the nonsusceptibility rates of meningitis isolates fluctuated over the years.
37 The dynamic change of serotype distribution and antimicrobial resistance of pneumococcal isolates since PCV13 administration and COVID-19 control in Urumqi, China [42] China In this study, a total of 317 isolates were analyzed. The most prevalent serotypes were type 19F (34.4%), followed by 19A (15.8%), 23F (11.7%), 6B (11.4%), and 6A (5.0%). The combined coverage rate of both PCV13 and PCV15 was 83.0%, slightly increased to 85.2% with PCV20. Penicillin resistance was observed in 28.6% of isolates based on oral penicillin breakpoints, but would escalate to 91.8% using parenteral penicillin breakpoints for meningitis. Resistance rates to erythromycin, clindamycin, tetracycline, and sulfamethoxazole-trimethoprim were notably high at 95.9%, 90.2%, 88.9%, and 78.8%, respectively. PCV13 isolates demonstrated higher penicillin resistance compared to non-PCV13 strains. There were no significant changes observed in serotype distribution following the introduction of PCV13 and during COVID-19 control measures. However, the resistance rate against oral penicillin slightly increased to 34.5% in 2018–2019 from 30.7% in 2014–2015, subsequently decreasing significantly to 18.1% in 2020–2021 (χ2 = 7.716, P < 0.05). Meanwhile, the resistance rate to ceftriaxone (non-meningitis) steadily declined from 16.0% in 2014–2015 to 1.4% in 2018–2019 and 0% in 2020–2021 (Fisher = 24.463, P < 0.01).
38 Alarming antibiotics resistance of Helicobacter pylori from children in Southeast China over 6 years [43] China This study aimed to assess the temporal changes in antibiotic resistance among children in southeast China by culturing gastric biopsies for H. pylori from 2015 to 2020. Susceptibility testing was conducted for clarithromycin (CLA), amoxicillin (AML), metronidazole (MTZ), furazolidone (FZD), tetracycline (TET), and levofloxacin (LEV). Data from 2012 to 2014, previously reported, were utilized for comparison of temporal trends in antibiotic resistance. Out of 3111 children recruited, 1638 (52.7%) H. pylori strains were isolated. The resistance rates to CLA, MTZ, and LEV were found to be 32.8%, 81.7%, and 22.8%, respectively. Notably, 52.9% of strains exhibited single resistance, 28.7% displayed double resistance, and 9.0% showed triple resistance. The total resistance rate and resistance rates to CLA, MTZ, LEV, CLA+LEV, and CLA+MTZ+LEV exhibited linear annual increases. From 2015 to 2017 and 2018 to 2020, all resistant patterns, except single resistance, notably increased compared to the period from 2012 to 2014. Double resistance to CLA+MTZ demonstrated a significant increase with age. Additionally, the resistance rate to CLA and triple resistance to CLA, MTZ, and LEV were higher in children with prior H. pylori treatment compared to those without prior treatment. The findings underscore the high antibiotic resistance rates of H. pylori in a significant pediatric population in southeast China from 2015 to 2020. Individual treatment based on susceptibility testing is deemed imperative, and optimal regimens should be selected for H. pylori eradication therapy.
39 Prevalence, Antimicrobial Susceptibility Patterns, and Risk Factors Associated with Enterococci among Pediatric Patients at Dessie Referral Hospital, Northeastern Ethiopia [44] Ethiopia The overall prevalence of enterococci was found to be 2.7% (11 out of 403 cases). Among these cases, the highest number of enterococci infections were identified in urine samples (54.5%), followed by blood samples (27.3%), wound swabs (9.1%), and other body fluids (9%). The overall multidrug resistance rate was 54.5%, with notably higher resistance observed against tetracycline, chloramphenicol, and amoxicillin/clavulanate. Several statistically significant associated risk factors for pediatric enterococci infection were identified, including a history of invasive procedures (P < 0.001), chronic illness (P < 0.001), and previous admissions of the children to healthcare facilities (P < 0.001). In summary, the prevalence of enterococci among pediatric patients in our study was relatively low compared to findings from other studies. However, we identified significant rates of multidrug-resistant (MDR) and vancomycin-resistant enterococci (VRE). The risk of infection escalated notably in children with a history of various chronic illnesses, prior admissions, and undergoing invasive treatment procedures. Consequently, proactive measures should be implemented to prevent enterococci infections and curb the spread of multidrug-resistant strains.
40 Antimicrobial resistance including Extended Spectrum Beta Lactamases (ESBL) among E. coli isolated from kenyan children at hospital discharge [45] Kenya Fecal samples were gathered from 406 children aged 1–59 months in western Kenya upon hospital discharge and cultured for E. coli. Susceptibility to various antibiotics, including ampicillin, ceftriaxone, cefotaxime, ceftazidime, cefoxitin, imipenem, ciprofloxacin, gentamicin, combined amoxicillin/clavulanic acid, trimethoprim-sulfamethoxazole, azithromycin, and chloramphenicol, was assessed using disc diffusion in accordance with Clinical and Laboratory Standards Institute (CLSI) guidelines. The study found high rates of non-susceptibility to ampicillin (95%), gentamicin (44%), ceftriaxone (46%), and the presence of extended-spectrum beta-lactamases (ESBL) (44%). Antibiotic use during hospitalization was linked to the presence of ESBL (adjusted prevalence ratio [aPR] = 2.23; 95% CI: 1.29–3.83), as was a history of hospitalization within the prior year (aPR = 1.32 [1.07–1.69]). Other factors associated with ESBL E. coli carriage included open defecation (aPR = 2.02; 95% CI: 1.39–2.94), sharing a toilet with other households (aPR = 1.49; 95% CI: 1.17–1.89), and being female (aPR = 1.42; 95% CI: 1.15–1.76).
41 Antimicrobial resistance of Streptococcus pneumoniae from invasive pneumococcal diseases in Latin American countries: a systematic review and meta-analysis [46] Latin American countries From a pool of 8,600 records, 103 studies were included, comprising 49,660 positive samples of S. pneumoniae for antimicrobial resistance (AMR) analysis. The majority of studies originated from Brazil (29.1%) and Argentina (18.4%), with cross-sectional studies being the most common (57.3%). Data on AMR were predominantly derived from invasive pneumococcal disease (IPD) cases (52.4%), and about half of the studies were classified as having a moderate risk of bias (50.5%). The resistance rate to penicillin was determined to be 21.7% (95% confidence interval [CI] 18.7–25.0, I2: 95.9), while for ceftriaxone/cefotaxime, it stood at 4.7% (95% CI 3.2–6.9, I2: 96.1). Notably, the highest resistance rates for both penicillin and ceftriaxone/cefotaxime were observed in the age group of 0 to 5 years, with rates of 32.1% (95% CI 28.2–36.4, I2: 87.7) and 9.7% (95% CI 5.9–15.6, I2: 96.9), respectively. Serotype 14 was most frequently associated with resistance to penicillin, while serotype 19A was the predominant serotype linked to resistance to ceftriaxone/cefotaxime. In Concluded that, our findings reveal that approximately one-quarter of invasive pneumococcal disease isolates in Latin America and the Caribbean exhibit penicillin resistance, with higher rates observed in young children. Given these concerning trends, ongoing surveillance becomes crucial to monitor serotype evolution and antimicrobial resistance patterns, especially following the introduction of pneumococcal conjugate vaccines. Such surveillance efforts will be invaluable in guiding public health strategies aimed at combating the spread of resistant strains and optimizing treatment approaches for pneumococcal infections in the region.
42 Virulence genes, antimicrobial resistance profile, phylotyping and pathotyping of diarrheagenic Escherichia coli isolated from children in Southwest Mexico [47] Mexico The antimicrobial resistance profile of DEC (Diarrheagenic Escherichia coli) strains, comprising 182 isolates from children with diarrhea (n = 147), is presented in Table 5. Overall, more than 50% of the strains exhibited resistance to cefazolin (89.5%), ampicillin (71.4%), streptomycin (64.2%), and trimethoprim (55.4%). When stratified by pathotype, EAEC (Enteroaggregative E. coli) displayed statistically significant (p ≤ 0.05) higher resistance to cefotaxime (60.7%), ceftriaxone (28.5%), and streptomycin (82.1%). DAEC (Diffusely Adherent E. coli) showed resistance to amoxicillin-clavulanic acid, ampicillin-sulbactam (57.1% each), and tetracycline (75.8%). ETEC (Enterotoxigenic E. coli) exhibited complete resistance to cefazolin (100%) and 25% resistance to imipenem. EIEC (Enteroinvasive E. coli) displayed 100% resistance to cefazolin and 25% resistance to chloramphenicol. Finally, EHEC (Enterohemorrhagic E. coli) showed complete resistance to cefazolin (100%). In terms of the number of antibiotics, 73.9% of DEC strains were resistant to 1–7 antibiotics, while the remaining strains were resistant to 8–14 antibiotics. Categorized by resistance, 79.7% were resistant to at least one antibiotic, while only 3.8% were sensitive to all antibiotics. Multidrug resistance (MDR) was observed in 43.9% of strains, while extensively drug-resistant (XDR) strains accounted for 41.2%. When analyzed by pathotype, typical Enteropathogenic E. coli (tEPEC) strains exhibited a higher prevalence of antibiotic-sensitive bacteria (23%, p = 0.008), while Enterotoxigenic E. coli (ETEC) showed a higher proportion of MDR strains (75%, p = 0.026), and Diffusely Adherent E. coli (DAEC) displayed a higher prevalence of XDR strains (64.2%, p = 0.047) compared to other pathotypes.
43 High prevalence of multidrug-resistant Gram-negative bacteria carriage in children screened prospectively for multidrug resistant organisms at admission to a paediatric hospital, Hamburg, Germany, September 2018 to May 2019 [48] Germany The prevalence of multi-drug resistant gram-negative (MRGN) carriage surpassed that of methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE). Given this observation, implementing an extended risk-factor-based admission screening system appears justified.
44 High frequency of antimicrobial resistance in Salmonella and Escherichia coli causing diarrheal diseases at the Yirimadio community health facility, Mali [49] Mali (west africa) In total, 554 patients were enrolled in the study, with children under 3 years of age comprising the majority at 88.8% (492 out of 554). Two bacterial species were identified: Escherichia coli accounted for 31.8% (176 out of 554), while Salmonella constituted 2.9% (16 out of 554) of the isolates. Among the 176 E. coli strains, resistance to amoxicillin and cotrimoxazole was observed in 93.8% (165 out of 176) and 92.6% (163 out of 176) of cases, respectively. The extended-spectrum beta-lactamase (ESBL) resistance phenotype was detected in 39.8% (70 out of 176) of E. coli strains. Of the 16 Salmonella strains identified, one strain (6.3%) exhibited resistance to amoxicillin and amoxicillin + clavulanic acid. Another strain (6.3%) was resistant to chloramphenicol. Additionally, two Salmonella strains (12.5%) showed resistance to cotrimoxazole, while two others (12.5%) were resistant to cefoxitin. In Concluded that, the findings indicate that Escherichia coli is commonly associated with diarrhea in children under 3 years old in the peri-urban area of Bamako, Mali. Furthermore, there is a notable prevalence of resistance to amoxicillin and cotrimoxazole, which are commonly prescribed antibiotics for the management of diarrhea in this region. This highlights the importance of judicious antibiotic use and the necessity for alternative treatment strategies to combat antimicrobial resistance in pediatric diarrheal illnesses in this setting.
45 Antibiotic susceptibility of Escherichia coli isolated from neonates admitted to neonatal intensive care units across China from 2015 to 2020 [50] China This study collected 370 strains of Escherichia coli from neonates. The E. coli isolated from these specimens underwent antimicrobial susceptibility testing using the broth microdilution method, as well as Multilocus Sequence Typing (MLST) analysis. The study found an overall resistance rate of 82.68% among the collected strains of E. coli. The highest resistance rate was observed for methicillin/sulfamethoxazole (55.68%), followed by cefotaxime (46.22%). Additionally, a multiple resistance rate of 36.74% was recorded, with 35.68% of strains exhibiting the extended-spectrum β-lactamase (ESBL) phenotype, and 1.35% showing insensitivity to the tested carbapenem antibiotics. Variations in resistance were noted among E. coli strains isolated from different pathogenicity and infection sites, with strains derived from sputum demonstrating significantly higher resistance to β-lactams and tetracyclines. In NICUs across China, the prevalence spectrum was dominated by specific sequence types (STs), including ST1193, ST95, ST73, ST69, and ST131. Among these, ST410 exhibited the most severe multidrug resistance, with the highest resistance rate observed for cefotaxime (86.67%). The most common multidrug resistance pattern associated with ST410 included resistance to β-lactams, aminoglycosides, quinolones, tetracyclines, and sulfonamides.
46 Temporal Trends in Phenotypic Macrolide and Nonmacrolide Resistance for Streptococcus pneumoniae Nasopharyngeal Samples Up to 36 Months after Mass Azithromycin Administration in a Cluster-Randomized Trial in Niger [51] Niger (West Africa) In a cluster-randomized trial, children aged 1–59 months received either azithromycin or placebo biannually. Antimicrobial resistance testing was conducted in fifteen villages from each arm, with 10–15 randomly selected swabs from enrolled children at each village processed for Streptococcus pneumoniae isolation and resistance testing. The primary prespecified outcome was the macrolide resistance fraction for azithromycin versus placebo villages at 36 months. Secondary non-prespecified outcomes included comparisons of azithromycin and placebo for: 1) macrolide resistance at 12, 24, and 36 months; 2) nonmacrolide resistance at 36 months; and 3) suspected-erm mutation. At 36 months, a total of 423 swabs were obtained, with 322 showing S. pneumoniae growth (azithromycin: 146/202, placebo: 176/221). The mean resistance prevalence was non-significantly higher in the treatment group compared to placebo (mixed-effects model: 14.6% vs. 8.9%; odds ratio [OR] = 2.0, 95% confidence interval [CI]: 0.99–3.97). However, when evaluating all time points, macrolide resistance prevalence was significantly higher in the azithromycin group (β = 0.102, 95% CI: 0.04–0.167). Resistance prevalence for all nonmacrolides at 36 months did not differ between the two groups. Azithromycin and placebo did not differ in suspected-erm mutation prevalence. Macrolide resistance was higher in the azithromycin group over all time points, but not specifically at 36 months. This suggests that resistance may not continue to increase after biannual Mass Drug Administration (MDA), but further studies are required to determine when MDA can safely decrease mortality and morbidity in lower- and middle-income countries.
47 Co-Amoxiclav as empiric treatment of UTI in children: importance of surveillance in ensuring optimal empiric treatment choice [52] Ireland In Concluded that, a significant proportion of children in this cohort were found to have urinary tract infections caused by uropathogens resistant to co-amoxiclav. Co-amoxiclav resistance was associated with recurrent infections and prolonged hospital stays. However, a combination therapy involving co-amoxiclav and gentamicin exhibited a high susceptibility rate of over 96%. This suggests that such combination therapy could be a promising option for the treatment of urinary tract infections in children, particularly in cases where co-amoxiclav resistance is prevalent.
48 Epidemiology of community origin of major multidrug-resistant ESKAPE uropathogens in a paediatric population in South-East Gabon [53] Gabon (central africa)  The prevalence of urinary tract infections (UTIs) in this study was 59%, with Escherichia coli (35%) and Klebsiella pneumoniae (34%) being the primary ESKAPE pathogens involved, followed by Enterococcus spp. (8%) and Staphylococcus aureus (6%). Among the major ESKAPE pathogens, drug-resistant E. coli strains such as DTR-E. coli (p = 0.01), CRE-E. coli (p = 0.02), and XDR-E. coli (p = 0.03), as well as Trimethoprim-sulfamethoxazole-resistant bacteria (p = 0.03), were associated with abdomino-pelvic pain. Male children exhibited a higher frequency of multidrug-resistant E. coli (p < 0.001), extensively drug-resistant E. coli (p = 0.02), extended-spectrum cephalosporin-resistant E. coli (p < 0.001), multidrug-resistant Enterococcus (p = 0.04), and other drug-resistant bacteria including Ampicillin (p < 0.01), Cefotaxime (p = 0.04), Ciprofloxacin (p < 0.001), Benzylpenicillin (p = 0.03), and Amikacin (p = 0.04). MDR-Enterococcus (p < 0.01), bacteria resistant to Amoxicillin-clavulanic acid (p = 0.03), Cefalotin (p = 0.01), Ampicillin (p = 0.02), and Gentamicin (p = 0.03) were associated with treatment failure. Additionally, Trimethoprim-sulfamethoxazole-resistant bacteria (p = 0.03) were associated with recurrent UTIs, while resistance to Ciprofloxacin was associated with symptoms such as pollakiuria (p = 0.01) and urinary burning (p = 0.04). Moreover, extensively drug-resistant K. pneumoniae (p = 0.02) was more frequent in neonates and infants.
49 Drug resistance and susceptibility of amikacin in children with extended-spectrum beta-lactamase-producing Enterobacterales: a systematic review with meta-analysis [54] USA, Nigeria, Canada, Switzerland, Colombia, Kuwait, Israel, Iran, China, Bangladesh, Mexico, Ireland, France This systematic review with meta-analysis indicates that among children with ESBL-producing Enterobacteriaceae (ESBL-PE) infections, amikacin demonstrated low drug resistance and high drug susceptibility.
50 Multi-drug resistance in Streptococcus pneumoniae among children in rural Vietnam more than doubled from 1999 to 2014 [55] Vietnam In our study, we identified Streptococcus pneumoniae in 221 out of 546 cultures, representing a prevalence of 40%. Susceptibility rates to various antibiotics were observed as follows: trimethoprim-sulphamethoxazole (5%), erythromycin (8%), ciprofloxacin (12%), benzyl-penicillin (35%), tetracycline (49%), cefotaxime (55%), moxifloxacin (99%), and vancomycin (99%). Interestingly, all susceptibility rates were lower in 2014 compared to 1999 and 2007, except for tetracycline. Multi-drug resistance was particularly alarming, reaching 80% in 2014, compared to 60% in 2007 and 31% in 1999. Antibiotic usage was reported by 191 individuals (35%) within one month, with cephalosporins being the most commonly used (45%), followed by amoxicillin/ampicillin (36%) and macrolides (16%). In Concluded that, our findings reveal a concerning trend of Streptococcus pneumoniae displaying high resistance to commonly prescribed antibiotics, including cephalosporins. Moreover, multi-drug resistance has significantly escalated over the 15-year study period, highlighting the urgent need for effective antimicrobial stewardship and surveillance programs.
51 Prevalence and risk factors for antimicrobial resistance among newborns with gram-negative sepsis [56] Ethiopia Among the 119 newborns diagnosed with gram-negative bacteremia, a substantial majority, 80 (67%), were born prematurely, and 82 (70%) experienced early-onset sepsis. Klebsiella pneumoniae was the most prevalent gram-negative species, detected in 94 cases (79%), followed by Escherichia coli in 10 cases (8%). Resistance to ampicillin was observed in 113 cases (95%), cefotaxime in 104 cases (87%), gentamicin in 101 cases (85%), ampicillin-gentamicin combination (AmpGen) in 101 cases (85%), piperacillin-tazobactam in 47 cases (39%), amikacin in 10 cases (8.4%), and imipenem in 1 case (0.8%). The prevalence of multidrug resistance (MDR) was notably high, accounting for 88% (105 cases). Factors such as low birth weight and late-onset sepsis (LOS) were identified as associated with increased risks of acquiring AmpGen-resistant infections. Moreover, newborns treated with ineffective antibiotics experienced higher all-cause mortality rates. In Concluded that, our findings reveal significant resistance to current first-line antibiotics and cephalosporins among gram-negative bacteremia cases in newborns. This underscores the urgent need for additional data from primary care and community settings to better understand the scope of antimicrobial resistance. While amikacin and piperacillin-tazobactam exhibited lower rates of resistance, their suitability as potential first-line alternatives requires context-specific assessments, considering factors such as adverse effects, local availability, and cost-effectiveness. Such evaluations would be crucial for informing clinical decision-making and optimizing treatment strategies in neonatal care settings.
52 Antibiotic-Resistant Strains of Helicobacter pylori in 50 Antibiotic Treatment-Naive Children in Northeast Poland Diagnosed by Gastric or Duodenal Biopsy Between February 2019 and May 2022 [57] Poland Based on biopsy culture, Helicobacter pylori infection was confirmed in 50 out of 82 children, accounting for 61%. Among the infected children, Helicobacter pylori exhibited the highest resistance to clarithromycin, observed in 19 cases (38%), followed by metronidazole in 15 cases (30%), and least frequently to amoxicillin in 13 cases (26%). Monoresistance, defined as resistance to a single antibiotic, was identified in 14 children (28%). Additionally, double-drug resistance was noted in 3 children (6%), while triple-drug resistance was observed in 9 children (18%). In the entire cohort, 24 children (48%) exhibited susceptibility to all three antibiotics tested.
53 Analysis of Factors Related to Neonatal Infection and Monitoring of Bacterial Drug Resistance [58] China Among the 209 bacterial strains isolated from infected neonates, 90 were gram-positive, with the four most common isolates being coagulase-negative Staphylococcus, Staphylococcus aureus, Enterococcus, and Streptococcus agalactiae. The remaining 119 strains were gram-negative, including Klebsiella pneumoniae, Acinetobacter baumannii, and Enterobacter aerogenes. Drug sensitivity testing revealed that methicillin-resistant Staphylococcus aureus isolates were sensitive to linezolid, vancomycin, rifampicin, levofloxacin, and gentamicin. All Klebsiella pneumoniae isolates were sensitive to amikacin, ertapenem, imipenem, and gentamicin. However, both strains exhibited varying degrees of resistance to other antibiotics.
54 Antibiotic resistance in neonates in China 2012-2019: A multicenter study [59] China Among 3770 full-term neonates who underwent lumbar puncture and blood culture, invasive bacterial infections (IBIs) were diagnosed in 460 neonates (12.2%). Escherichia coli and Group B Streptococcus (GBS) were the predominant pathogens, followed by Enterococcus spp. and Staphylococcus aureus. E. coli exhibited high resistance rates to ampicillin (72.0%) and third-generation cephalosporins (cefotaxime: 34.8%; ceftriaxone: 38.1%). The prevalence of extended-spectrum beta-lactamase (ESBL)-producing E. coli was 34.1%. Enterococcus spp. showed resistance rates of 60% and 54.1% to penicillin and ampicillin, respectively. All S. aureus isolates were resistant to ampicillin and penicillin, with a 50% resistance rate to methicillin. While all GBS were susceptible to penicillin and ampicillin, a high proportion showed resistance to erythromycin (75.9%) and clindamycin (77.3%). There appeared to be an improvement in antibiotic susceptibility in 2019, with E. coli showing increased susceptibility to ampicillin, cefotaxime, and ceftriaxone (42.9%, 76.9%, and 71.4% respectively in 2019, compared to 12.5%, 37.5%, and 50% in 2012). The prevalence of ESBL-producing E. coli declined to 20% in 2019 from 100% in 2012. Susceptibility of GBS to erythromycin and clindamycin also improved from 0% in 2012 to 28.6% and 25% respectively in 2019. The Concluded thats drawn from the study indicate a high prevalence of antibiotic resistance among neonates in China, though there is a positive trend of decline in recent years.
55 The drug resistance of multidrug-resistant bacterial organisms in pediatric pneumonia patients [60] China There were 219 children in all, with 3 cases (1.37%) of mixed infections with sensitive and MDRO bacteria, 110 cases (50.23%) of MDRO infections, and 106 cases (48.40%) of sensitive bacterial infections. Vancomycin was sensitive to MRSA, while imipramine was sensitive to MDR-PA, MDRAB, ESBL KP, and ESBL E. coli. ICU care, mechanical ventilation, arterial and venous intubation, fiberoptic bronchoscopy, concurrent chronic lung disease, and chronic cardiovascular disease were the independent risk factors for MDRO (P < 0.05), according to a logistic regression model and a multifactorial analysis. The children in the MDRO group experienced a significantly higher 30-day mortality rate, longer hospital stays, and higher treatment costs compared to the children infected with sensitive bacteria (P < 0.05). In summary: Ipenem or vancomycin
56 Prevalence, Clinical Characteristics and Changes of Antibiotic Resistance in Children with Nontyphoidal Salmonella Infections from 2009–2018 in Chongqing, China [61] China A total of 501 isolates were identified, with most NTS infections occurring in children under three years old, primarily between July and October. Among the patients, 472 (94.2%) had diarrhea, 422 (84.2%) had fever, and 146 (29.1%) experienced vomiting. Serogroup B was the most prevalent, comprising 67.5% of the isolates, and Salmonella Typhimurium was the most common serotype at 79.2%. The study compared NTS drug resistance from 2009-2013 to 2014-2018, revealing an increase in resistance to cefazolin, cefotaxime, ciprofloxacin, levofloxacin, and imipenem. Although resistance to chloramphenicol, ampicillin, ceftriaxone, cefepime, and compound sulfamethoxazole decreased slightly, these rates remained high. Notably, resistance to piperacillin/tazobactam and ceftazidime significantly declined over the last decade. Multi-drug resistant (MDR) isolates were found in 69 (13.7%) of the 501 children with NTS infections.
The overall antibiotic resistance rates in Chongqing remained high. Continuous monitoring of antibiotic resistance in NTS, along with measures to avoid unnecessary antibiotic use for general NTS gastroenteritis, are crucial. For severe or invasive NTS infections in Southwest China, ceftazidime is recommended until antibiotic sensitivity test results are available. The selection of antibiotics should be guided by their effectiveness and the results of sensitivity tests.
57 Multi-drug resistance in Streptococcus pneumoniae among children in rural Vietnam more than doubled from 1999 to 2014 [62] Vietnam We found that 221 out of 546 (40%) cultures tested positive for Streptococcus pneumoniae. The susceptibility rates were as follows: trimethoprim-sulfamethoxazole (5%), erythromycin (8%), ciprofloxacin (12%), benzyl-penicillin (35%), tetracycline (49%), cefotaxime (55%), moxifloxacin (99%), and vancomycin (99%). Except for tetracycline, all susceptibility rates were lower in 2014 compared to 1999 and 2007. Multi-drug resistance was 80% in 2014, up from 60% in 2007 and 31% in 1999. Within one month, 191 patients (35%) had used antibiotics, mainly cephalosporins (86, 45%), amoxicillin/ampicillin (69, 36%), and macrolides (30, 16%). Concluded that Streptococcus pneumoniae exhibited significantly high resistance to commonly used antibiotics, including cephalosporins. Multi-drug resistance increased from 31% to 80% over the 15-year study period.
58 Drug-Resistant Tuberculosis Among Children: A Systematic Review and Meta-Analysis [63] USA, Nigeria, Canada, Switzerland, Colombia, Kuwait, Israel, Iran, China, Bangladesh, Mexico, Ireland, France Out of 4,063 studies identified, 37 were included. Among 23,652 pediatric TB patients, the proportions of DR-TB, MDR-TB, mono-resistant TB, polydrug-resistant TB, and extensively drug-resistant TB were 13.59% (1,964/14,453), 3.72% (881/23,652), 6.07% (529/8,719), 1.61% (119/7,361), and 0.44% (30/6,763), respectively. The pooled proportion of MDR-TB among the 23,652 children across 37 studies was 3.7% (95% CI, 3.5–4.0%). The rate of MDR-TB was significantly lower in high-income countries (1.8%) compared to lower-middle-income (6.3%) and upper-middle-income countries (7.3%). Specifically, the rates of MDR-TB were 1.7% in the USA, 1.7% in the UK, 2.9% in India, 6.0% in South Africa, and 9.8% in China.
59 Antibiotic Resistant Bloodstream Infections in Pediatric Patients Receiving Chemotherapy or Hematopoietic Stem Cell Transplant: Factors Associated with Development of Resistance, Intensive Care Admission and Mortality [64] Australia, Brazil, Canada, Chile, Germany, Italy, Russia,  Switzerland A multinational, multicenter retrospective study was conducted on patients aged ≤ 18 years, who underwent chemotherapy or hematopoietic stem cell transplantation (HSCT) from 2015 to 2017. The study aimed to analyze antimicrobial resistance (AR) among non-common skin commensals causing bloodstream infections (BSI). Risk factors associated with AR, intensive care unit (ICU) admission, and mortality were analyzed using multilevel mixed effects or standard logistic regressions. A total of 1,291 BSIs involving 1,379 strains were reported in 1,031 patients. Among Gram-negative bacteria, over 20% showed resistance to ceftazidime, cefepime, piperacillin-tazobactam, and ciprofloxacin, while 9% were resistant to meropenem. Methicillin resistance was observed in 17% of Staphylococcus aureus, and vancomycin resistance was found in 40% of Enterococcus faecium. Previous exposure to antibiotics, especially carbapenems, was significantly associated with resistant Gram-negative BSI, while previous colonization with methicillin-resistant S. aureus was associated with BSI caused by this pathogen. Hematological malignancies, neutropenia, and Gram-negatives resistant to >3 antibiotics were significantly associated with a higher risk of ICU admission. Underlying disease in relapse/progression, previous exposure to antibiotics, and the need for ICU admission were significantly associated with mortality. Center-level variation had a greater impact on AR, while patient-level variation had a greater effect on ICU admission and mortality. The findings suggest that previous antibiotic exposure or colonization by resistant pathogens may contribute to AR BSI. Resistant Gram-negative bacteria are significantly associated with ICU admission and mortality, with the treating center also playing a significant role. The significant evidence of center-level variations underscores the importance of local antibiotic stewardship and infection control programs.
60 Antibiotic resistance in neonates in China 2012–2019: A multicenter study [65] China Out of 3,770 full-term neonates who underwent lumbar puncture and blood culture, invasive bacterial infections (IBIs) were diagnosed in 460 neonates (12.2%). Escherichia coli and Group B Streptococcus (GBS) were the most common pathogens, followed by Enterococcus spp. and Staphylococcus aureus. E. coli exhibited high resistance rates to ampicillin (72.0%) and third-generation cephalosporins (cefotaxime: 34.8%; ceftriaxone: 38.1%). The prevalence of extended-spectrum beta-lactamase (ESBL)-producing E. coli was 34.1%. Enterococcus spp. showed resistance rates of 60% and 54.1% to penicillin and ampicillin, respectively. All S. aureus isolates were resistant to ampicillin and penicillin, and 50% were resistant to methicillin. Although all GBS were susceptible to penicillin and ampicillin, a significant proportion showed resistance to erythromycin (75.9%) and clindamycin (77.3%). There was evidence of improved antibiotic susceptibility in 2019. The susceptibility of E. coli to ampicillin, cefotaxime, and ceftriaxone increased to 42.9%, 76.9%, and 71.4% in 2019, compared to 12.5%, 37.5%, and 50% in 2012. The prevalence of ESBL-producing E. coli declined to 20% in 2019, down from 100% in 2012. Susceptibility of GBS to erythromycin and clindamycin improved from 0% in 2012 to 28.6% and 25% in 2019, respectively.
61 Multi-drug resistance and high mortality associated with community-acquired bloodstream infections in children in conflict-affected northwest Nigeria [66] Nigeria Pediatric community-acquired bloodstream infections (CA-BSIs) in sub-Saharan African humanitarian contexts are infrequently documented. Effective treatment is further challenged by rising antimicrobial resistance. This study presents findings from epidemiological and microbiological surveillance conducted in pediatric patients with suspected CA-BSIs at a secondary hospital in the conflict-affected area of Zamfara state, Nigeria. From November 2018 to August 2020, any child over 2 months old presenting to Anka General Hospital with clinical severe sepsis at admission had clinical and epidemiological data collected along with a blood culture. Bacterial isolates were tested for antibiotic susceptibility, and frequencies of epidemiological, microbiological, and clinical parameters were calculated. Risk factors for death among severe sepsis cases were examined using univariable and multivariable Poisson regression, adjusting for the time between admission and hospital exit. The study included 234 severe sepsis patients, with 195 blood culture results, of which 39 were positive. Among the bacterial isolates, 14 were Gram-positive and 18 were Gram-negative. Five isolates were resistant to empiric antibiotics: methicillin-resistant Staphylococcus aureus (MRSA; n = 2) and Extended Spectrum Beta-Lactamase (ESBL)-producing enterobacterales (n = 3). No significant association was found between sex, age group, ward, CA-BSI, appropriate intravenous antibiotic use, malaria positivity at admission, suspected focus of sepsis, clinical severity, and death in the multivariable regression. The findings underscore the urgent need for access to effective clinical microbiological services, including point-of-care methods, and for improved awareness and practice of rational antibiotic use among healthcare staff in humanitarian settings to reduce morbidity and mortality from sepsis in children.
62 Increased Antibiotic Resistance in Children with Helicobacter pylori Infection: A Retrospective Study [67] Germany The data from 124 subjects with frequent gastrointestinal symptoms who underwent an EGD were retrospectively collected and analyzed. The mean age of the patients was 13 ± 3.6 years. The most common complaints were epigastric pain (84%; n = 100/119) and dyspepsia (79%; n = 94/119). Helicobacter pylori (HP) gastritis was diagnosed in 54% (n = 67) of the patients. Among the isolates, 40% (n = 49) were resistant to at least one antibiotic: amoxicillin (20%; n = 10/49), clarithromycin (45%; n = 22/49), or metronidazole (59%; n = 29/49). Furthermore, 16% (n = 20) of the isolates were resistant to two or more antibiotics. In Concluded that, the study revealed notably high resistance rates to amoxicillin, metronidazole, and clarithromycin in this cohort. The presence of resistance to multiple antibiotics was significantly increased among HP-infected patients, which may adversely affect eradication treatment.
63 Retrospective 8-Year Study on the Antibiotic Resistance of Uropathogens in Children Hospitalised for Urinary Tract Infection in the Emilia-Romagna Region, Italy [68] Italy This observational, retrospective, multicenter study analyzed the medical records of 1,801 pediatric patients hospitalized for urinary tract infections (UTIs) between January 1, 2012, and June 30, 2020, in Emilia-Romagna, Italy. Escherichia coli was the most frequently detected pathogen (75.6%), followed by Klebsiella pneumoniae (6.9%) and Pseudomonas aeruginosa (2.5%). Overall, 46.7% of cases (840) involved antimicrobial-resistant uropathogens: 83 cases (4.7%) were due to extended spectrum beta-lactamase (ESBL)-producing bacteria, 119 cases (6.7%) were multidrug-resistant (MDR), and 4 cases (0.2%) were extensively drug-resistant (XDR). Empirical antibiotic therapy failed in 9.6% (172) of cases. Factors significantly associated with treatment failure included having ESBL or MDR/XDR uropathogens, a history of recurrent UTIs, antibiotic therapy in the preceding 30 days, and empirical treatment with amoxicillin or amoxicillin/clavulanate. In contrast, first-line therapy with third-generation cephalosporins was associated with protection against negative outcomes. In Concluded that, the study indicates a rising resistance of uropathogens to commonly used antibiotics, necessitating continuous monitoring and updated recommendations for antibiotic choice. In this epidemiological context, amoxicillin/clavulanate is no longer suitable as first-line therapy for children hospitalized with UTIs, whereas third-generation cephalosporins remain effective. Efforts to reduce and rationalize antibiotic consumption are essential to limit the emergence of resistance.
64 Prevalence and risk factors associated with multi-drug resistant organisms (MDRO) carriage among pediatric patients at the time of admission in a tertiary care hospital of a developing country. A cross-sectional study [69] Pakistan Among 347 participants, 237 (68.3%) were identified as carriers of multidrug-resistant organisms (MDROs). Specifically, 49 nasal swabs from 346 children (14.2%) showed growth of methicillin-resistant Staphylococcus aureus (MRSA). A majority of the stool/rectal swabs (222 out of 322; 69%) were positive for MDROs. The most frequently isolated species were extended spectrum beta-lactamase (ESBL) Escherichia coli (174/222; 78.3%), followed by ESBL Enterobacter species (37/222; 16.7%) and ESBL Klebsiella pneumoniae (35/222; 15.8%). Univariate analysis revealed that none of the assessed risk factors were statistically significant in association with MDRO carriage. In Concluded that, there was a high prevalence of MDRO carriage among admitted pediatric patients. Systematic screening could help in identifying the true burden of MDRO carriage in healthcare settings.
65 Alarming antibiotics resistance of Helicobacter pylori from children in Southeast China over 6 years [70] China The increasing antibiotic resistance in Helicobacter pylori (H. pylori) is a significant concern due to the declining eradication rates. There is a scarcity of large-scale, long-term studies on the antimicrobial susceptibility of H. pylori in children. This study aimed to describe the changes in antibiotic resistance over time among children in southeast China. Gastric biopsies from children, obtained between 2015 and 2020, were cultured for H. pylori. The susceptibility of these strains to clarithromycin (CLA), amoxicillin (AML), metronidazole (MTZ), furazolidone (FZD), tetracycline (TET), and levofloxacin (LEV) was tested. Data from 2012 to 2014 were used for comparison to identify temporal trends in antibiotic resistance. A total of 1,638 (52.7%) H. pylori strains were isolated from 3,111 children. The resistance rates to CLA, MTZ, and LEV were 32.8%, 81.7%, and 22.8%, respectively. Among these strains, 52.9% showed resistance to one antibiotic, 28.7% to two, and 9.0% to three antibiotics. The overall resistance rate and the specific resistance rates to CLA, MTZ, LEV, CLA + LEV, and CLA + MTZ + LEV increased annually in a linear fashion. All resistance patterns, except for single antibiotic resistance, showed a marked increase from 2015 to 2017 and from 2018 to 2020 compared to 2012 to 2014. Notably, double resistance to CLA + MTZ increased significantly with age. Children with a history of H. pylori treatment exhibited higher resistance rates to CLA and triple resistance to CLA, MTZ, and LEV than those without prior treatment. In Concluded that, the antibiotic resistance rates of H. pylori were notably high among a large pediatric population in southeast China from 2015 to 2020. Individualized treatment based on susceptibility testing is crucial, and optimal regimens should be selected for H. pylori eradication therapy.
66 Resistance Patterns from Urine Cultures in Children Aged 0 to 6 Years: Implications for Empirical Antibiotic Choice [71] China A retrospective study analyzing positive urine cultures from 13 public laboratories in Tuscany, Italy, was conducted by reviewing records from the “Microbiological and Antibiotic-Resistance Surveillance System” (SMART). The study collected a total of 2,944 positive urine cultures from 2,445 children. The majority of isolates were Escherichia coli (54.2%), followed by Enterococcus faecalis (12.3%), Proteus mirabilis (10.3%), and Klebsiella pneumoniae (6.6%). Resistance Rates: Uropathogens exhibited high resistance rates to amoxicillin-clavulanate (>25%), especially in children under one year of age or those hospitalized within the 12 months prior to sample collection. Susceptibility Rates: High susceptibility rates were noted for aminoglycosides, cephalosporins, and quinolones (>90%).
Impact of Previous Antibiotic Prescriptions: Previous antibiotic prescriptions by general pediatricians did not correlate with increased resistance rates.
The study highlights a significant resistance rate of 25% to amoxicillin-clavulanate, particularly in young children under one year of age and those with recent hospitalizations. Therefore, cautious use of amoxicillin-clavulanate is recommended in these populations, especially for those presenting severe symptoms.
67 Changing Antimicrobial Resistance and Epidemiology of Non-Typhoidal Salmonella Infection in Taiwanese Children [72] This study focused on the epidemiology and antimicrobial resistance patterns in children with non-typhoidal Salmonella (NTS) infections in a tertiary medical center in Taiwan from 2012 to 2019. It involved a retrospective analysis of pediatric patients with culture-confirmed NTS infections, comparing clinical features, serogroup categories, and resistance rates over time. Key Findings
Total Isolates and Bacteremia: A total of 797 NTS isolates were collected, with 55 cases resulting in NTS bacteremia. Increasing Resistance Rates:
Third-Generation Cephalosporins: Resistance increased from 4.1% in 2012 to 14.3% in 2019 (P < 0.001). Ciprofloxacin: Resistance rose significantly from 1.9% in 2012 to 28.6% in 2019 (P < 0.001).
Specific Serogroups: Higher resistance rates were noted especially in serogroups B, D, and E.
Infant Group: Approximately half of the NTS isolates in infants were multidrug-resistant, which was a higher rate compared to other age groups.
Invasive NTS Infections: Invasive NTS cases were associated with a longer fever duration, lower hemoglobin levels, and absence of elevated C-reactive protein (P < 0.05).
Non-Invasive NTS Isolates in 2019: These showed significantly higher resistance to ceftriaxone (P < 0.001) and ciprofloxacin (P < 0.001) than those in 2012.
Overall Trends: There was a notable increase in antimicrobial resistance over the years, with different resistance patterns observed among various serogroups.
The study highlights a progressive increase in antimicrobial resistance among pediatric NTS infections over the past decade in Taiwan. Infants were particularly at a higher risk of acquiring third-generation cephalosporin-resistant NTS infections. This trend underscores the need for continual surveillance and careful selection of antibiotics to manage NTS infections effectively. Regular monitoring and updated treatment guidelines are essential to combat the rising resistance and ensure effective management of NTS infections in children.
68 Antimicrobial Resistance Analysis of Clinical Escherichia coli Isolates in Neonatal Ward [73] Beijing A study conducted at Beijing Children’s Hospital analyzed 100 Escherichia coli strains isolated from various samples of hospitalized neonates, including sputum, blood, cerebrospinal fluid, and umbilical discharge. The findings revealed significant resistance rates among these strains to several antibiotics commonly used in clinical treatment.
Key Findings:
Sample Sources: The majority of E. coli strains were isolated from sputum (78%), with smaller numbers from blood (10%), cerebrospinal fluid (5%), and umbilical discharge (7%) samples.
Antibiotic Resistance Rates: The highest resistance rates were observed against amoxicillin (85%), cefuroxime (65%), and ceftriaxone (60%). A smaller percentage of isolates exhibited resistance solely to amoxicillin/clavulanic acid (6%) or cefoperazone-sulbactam (5%).
Resistance to Other Antibiotics: Resistance rates to ceftazidime, gentamicin, ciprofloxacin, and sulfonamides were noted at 31%, 20%, 33%, and 47%, respectively. However, all isolates remained susceptible to meropenem.
Multidrug Resistance: Approximately 26% of the E. coli isolates were identified as multidrug-resistant, indicating resistance to multiple antibiotic classes.
ESBL-Producing E. coli: The detection rate of Extended Spectrum Beta-Lactamase (ESBL)-Producing E. coli was high, reported at 55%.
The study underscores the emergence of multi-drug-resistant E. coli as a significant challenge in neonatal clinical treatment. Continuous monitoring of E. coli resistance patterns in neonates is crucial to inform treatment strategies and mitigate the risks associated with antibiotic resistance in this vulnerable population.
69 Antibiotic resistance of Streptococcus pneumoniae in Vietnamese children with severe pneumonia: a cross-sectional study [74] Vietnam Eighty-nine strains of S. pneumoniae were identified from 239 children diagnosed with severe CAP. The vast majority of these strains exhibited complete resistance to penicillin (1.1% showed intermediate susceptibility, while 98.9% were resistant) and demonstrated high levels of resistance to erythromycin (96.6%) and clarithromycin (88.8%). Ceftriaxone resistance was observed in 16.9% of cases, with 46.0% showing intermediate resistance. However, all strains remained susceptible to vancomycin and linezolid. The MIC50 and MIC90 values for most antibiotics matched the resistance threshold outlined by the Clinical and Laboratory Standards Institute in 2021. Notably, penicillin displayed an eight-fold increase in MIC90 (64 mg/L), while ceftriaxone showed a 1.5-fold increase in MIC90 (6 mg/L).
70 Evidence of Community-Wide Spread of Multi-Drug Resistant Escherichia coli in Young Children in Lusaka and Ndola Districts, Zambia [75] Zambia This research aimed to investigate the prevalence, trends, and potential factors influencing antimicrobial resistance (AMR) in E. coli obtained from children under five years old in Zambia. A hospital-based cross-sectional study was carried out in the Lusaka and Ndola districts. Rectal swabs were obtained from 565 diarrheic and 455 healthy children, resulting in a total of 1020 E. coli isolates, which were then analyzed for antibiotic susceptibility. The E. coli isolates exhibited the highest resistance rates to ampicillin (78.0%), trimethoprim-sulfamethoxazole (70.4%), and tetracycline (62.8%), while demonstrating greater susceptibility to chloramphenicol (83.8%) and gentamicin (80.1%) (refer to Figure 2a). This pattern persisted across both healthy and diarrheic children, albeit with varying percentages. Notably, a notable contrast in susceptibility and resistance profiles to imipenem was evident between healthy and diarrheic children. Approximately 62% and 24% of isolates from healthy and diarrheic children, respectively, were found to be resistant to imipenem.
71 Prevalence, Pathogenic Bacterial Profile and Antimicrobial Susceptibility Pattern of Urinary Tract Infection Among Children  with Congenital Anomalies of the Kidney and Urinary Tract [76] China A total of 568 children were included in the study, with a culture-positive UTI rate of 59.15% (336/568). Over nine types of bacteria were isolated, predominantly Gram-negative species. The most common Gram-negative bacteria were Escherichia coli (30.95%, 104/336) and Klebsiella pneumoniae (9.23%). Escherichia coli isolates showed high sensitivity to amikacin (95.19%), ertapenem (94.23%), nitrofurantoin (93.27%), imipenem (91.35%), and piperacillin-tazobactam (90.38%), but high resistance rates to ampicillin (92.31%), cephazolin (73.08%), ceftriaxone (70.19%), trimethoprim-sulfamethoxazole (61.54%), and ampicillin-sulbactam (57.69%). Klebsiella pneumoniae isolates were highly sensitive to ertapenem (96.77%), amikacin (96.77%), imipenem (93.55%), piperacillin-tazobactam (90.32%), and gentamicin (83.87%), but showed high resistance to ampicillin (96.77%), cephazolin (74.19%), ceftazidime (61.29%), ceftriaxone (61.29%), and aztreonam (61.29%). The isolated Gram-positive bacteria mainly included Enterococcus faecalis and Enterococcus faecium (each 15.77%). Enterococcus faecalis was sensitive to vancomycin, penicillin-G, tigecycline, nitrofurantoin, and linezolid (100%, 94.34%, 88.68%, 88.68%, and 86.79%, respectively) and resistant to tetracycline (86.79%), quinupristin (83.02%), and erythromycin (73.58%). Enterococcus faecium exhibited similar sensitivity and resistance patterns. Multidrug resistance (MDR) was observed in 264 (80.00%) of the 336 bacterial isolates. Age was the only factor significantly associated with a culture-positive UTI. In Concluded that, a high prevalence of culture-positive UTI was found, with Escherichia coli being the most prevalent uropathogen, followed by Enterococcus faecalis and Enterococcus faecium. These uropathogens showed significant resistance to commonly used antibiotics, and MDR was prevalent. Therefore, empiric therapy may be inadequate as antibiotic resistance patterns change over time.
72 Bacterial profile, their antibiotic susceptibility pattern, and associated factors of urinary tract infections in children at Hiwot Fana Specialized University Hospital, Eastern Ethiopia [77] Ethiopia We conducted a hospital-based quantitative study on 332 consecutively selected children under five years old from March 20 to June 10, 2021. The overall prevalence of bacterial urinary tract infections was 80 cases (24.1%, 95% CI: 19.40–29.00%). Most bacterial isolates, 55 (68.75%), were Gram-negative, predominantly E. coli (23, 28.75%) and K. pneumoniae (10, 12.50%). Factors associated with higher odds of a culture-positive result included being a rural resident (AOR: 4.10, 95% CI: 1.45–11.54), being an uncircumcised male (AOR: 3.52, 95% CI: 1.33–9.39), having a previous history of antibiotic usage (AOR: 7.32, 95% CI: 2.11–25.37), undergoing indwelling catheterization (AOR: 10.35, 95% CI: 3.74–28.63), having a previous history of urinary tract infections (AOR: 5.64, 95% CI: 1.36–23.38), and experiencing urinary frequency (AOR: 5.56, 95% CI: 2.03–15.25). The majority of the isolates exhibited high levels of antibiotic resistance. Meropenem, ciprofloxacin, and amoxicillin-clavulanic acid were effective against Gram-negative uropathogens, whereas rifampin and ciprofloxacin were the most sensitive drugs for Gram-positive isolates. Among the tested bacterial isolates, 53 out of 86 (61.6%) were found to have multidrug resistance (MDR), 11 out of 86 (11.6%) exhibited extreme drug resistance (XDR), and 2 out of 86 (2.3%) showed pan drug resistance (PDR).
73 Prevalence, serotype, and antimicrobial resistance profiles of children infected with Salmonella in Guangzhou, southern China, 2016–2021 [78] The study identified 1,338 cases of Salmonella, primarily isolated from feces and blood samples, with infants under three years old being the most affected age group. The incidence was highest in the summer and autumn seasons. A total of 48 serotypes were detected, with S. typhimurium being the predominant serogroup, accounting for 78.7% of the cases. Antimicrobial susceptibility testing revealed the highest resistance to ampicillin (84.5%), while lower resistance rates were observed for piperacillin/tazobactam, cefoperazone/sulbactam, and ciprofloxacin. Fecal isolates exhibited higher resistance rates compared to blood isolates. Over the past five years, the average detection rate of multi-drug resistant (MDR) Salmonella was 8.5% (114/1,338), with the MDR rate for S. typhimurium being the lowest at 6.9% (73/1,053). Our Concluded that emphasizes the importance of carefully selecting antibacterial treatment based on serotype and antimicrobial sensitivity results, especially in pediatric cases. Additionally, we stress the ongoing necessity for antimicrobial resistance monitoring, particularly for multi-drug resistant Salmonella strains. This proactive approach is vital for effective management and control of Salmonella infections in children.
74 Antimicrobial resistance in shigellosis: A surveillance study among urban and rural children over 20 years in Bangladesh [79] Bangladesh Antimicrobial resistance in shigellosis is becoming increasingly concerning, yet there are significant knowledge gaps due to the limited longitudinal data on antimicrobial resistance trends. Our study aimed to fill this gap by evaluating antimicrobial resistance patterns against shigellosis over the past 20 years among children under five in both urban and rural areas of Bangladesh. These findings highlight the importance of implementing therapeutic interventions for shigellosis using appropriate drugs based on current antibiogram data for children under five. Such observations can assist policymakers in developing more effective case management strategies for shigellosis.
75 Social and Environmental Determinants of Community-Acquired Antimicrobial-Resistant Escherichia coli in Children Living in Semirural Communities of Quito, Ecuador [80] Ecuador The 3GC-R (third-generation cephalosporin-resistant) isolates from both cycles exhibited high resistance rates to several antibiotics, notably cefazoline (99.8%), ampicillin (99.4%), and cefotaxime (93.6%). It’s worth noting that if an E. coli isolate is resistant to ceftriaxone, it’s generally considered resistant to cefotaxime as well, although exceptions exist. According to CLSI guidelines, the ability to predict resistance to ceftriaxone and cefotaxime was observed in 95% of the tested isolates. However, it’s acknowledged in the guidelines that this prediction accuracy can vary between 3% to 10% across a large population of tested bacteria.
76 Active Surveillance, Drug Resistance, and Genotypic Profiling of Staphylococcus aureus Among School-Age Children in China [81] China Nasal colonization by both methicillin-susceptible (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA) poses a significant risk for endogenous infections, particularly in children. Recently, a new variant, oxacillin/cefoxitin-susceptible mecA-positive S. aureus (OS-MRSA), has emerged globally. In this prospective, cross-sectional study conducted across five schools representing three educational stages in Guangzhou, China, nasal swabs from 2,375 students were cultured for S. aureus. All isolates underwent phenotypic antibiotic susceptibility testing and were confirmed by femB and mecA genetic detection, categorized as MSSA, MRSA, or OS-MRSA, and subjected to multi-locus sequence typing. Among the 2,375 swabs, S. aureus was detected in 744 children (31.3%, 95% CI: 25.9–36.7%), with 72 identified as MRSA (3.0%, 95% CI: 0.6–5.4%) and 4 as OS-MRSA (0.2%, 95% CI: 0.1–0.3%). The prevalence of S. aureus and MRSA was higher among younger children. The most common drug resistances among the S. aureus isolates (n = 744) were to penicillin (85.5%), followed by erythromycin (43.3%) and clindamycin (41.0%). Multi-locus sequence typing revealed ST30, ST45, and ST188 as the most prevalent sequence types (STs) in MSSA, while ST45, ST59, and ST338 predominated among MRSA isolates. Additionally, ST338 was the primary sequence type among OS-MRSA isolates. MRSA and OS-MRSA isolates (n = 76) clustered into three clades and one singleton, with clonal complex (CC) 45 being the most prevalent linkage. The top nine multi-locus sequence typing-based clonal complexes (CCs) represented 86.7% of all S. aureus isolates. Notably, all CC30 isolates were resistant to erythromycin and clindamycin, with almost all also resistant to penicillin (99.2%). CC45 and CC59 isolates exhibited high resistance rates to oxacillin, at 31.5% and 59.0%, respectively. This study provides updated data crucial for designing effective control strategies to reduce disease burden and enhance the adequacy of empirical antimicrobial treatments for potentially harmful infections.
77 Prevalence, Antimicrobial Susceptibility Patterns, and Risk Factors Associated with Enterococci among Pediatric Patients at Dessie Referral Hospital, Northeastern Ethiopia [82] The overall prevalence of enterococci among pediatric patients in our study was 2.7% (11/403). Urine samples accounted for the highest number of enterococci infections (54.5%), followed by blood (27.3%), wound swab (9.1%), and other body fluids (9%). Multidrug resistance was observed in 54.5% of cases, with higher resistance patterns noted against tetracycline, chloramphenicol, and amoxicillin/clavulanate. Significant risk factors associated with pediatric enterococci infection included a history of invasive procedures (P < 0.001), chronic illness (P < 0.001), and previous admissions (P < 0.001). In Concluded that, although the prevalence of enterococci among pediatric patients in our study was relatively low compared to other studies, we identified significant rates of multidrug-resistant (MDR) and vancomycin-resistant enterococci (VRE). The risk of infection was particularly elevated in children with a history of chronic illnesses, previous admissions, and invasive treatment procedures. Therefore, it is imperative to implement measures to prevent enterococci infections and curb the spread of multidrug-resistant strains.
78 Prevalence, Antibiotic Susceptibility Profile and Associated Factors of Group A Streptococcal pharyngitis Among Pediatric Patients with Acute Pharyngitis in Gondar, Northwest Ethiopia [83] Ethiopia A total of 215 children with acute pharyngitis were enrolled in the study, with 23 (10.7%) testing positive for S. pyogenes through culture. Factors such as inflamed tonsils, tonsillar exudate, scalariform rash, and dysphagia were associated with streptococcal pharyngitis. Children aged 5 to 15 exhibited higher susceptibility to streptococcal throat infection compared to younger children. Penicillin, vancomycin, chloramphenicol, clindamycin, and ceftriaxone demonstrated effectiveness against 100%, 95.7%, 95.7%, 91%, and 87% of isolates, respectively. In contrast, reduced susceptibility to tetracycline, erythromycin, and azithromycin was observed in 56.5%, 39.1%, and 30.4% of isolates, respectively. In Concluded that, Streptococcus pyogenes accounted for 10.7% of acute pharyngitis cases in pediatric patients in the study area. While all isolates remained sensitive to penicillin, many exhibited reduced susceptibility to tetracycline and macrolides. Therefore, it is recommended to screen children with acute pharyngitis for S. pyogenes and test the antibiotic susceptibility of isolates before prescribing antibiotics.
79 Antimicrobial resistance and clonality of Staphylococcus aureus causing bacteraemia in children admitted to the Manhiça District Hospital, Mozambique, over two decades [84] Republic of Mozambique (southeast Africa) The majority of S. aureus isolates (94%, 317/336) exhibited resistance to at least one class of antibiotics, with a quarter (25%) displaying a multidrug-resistant (MDR) phenotype. Particularly high rates of resistance were observed against penicillin (90%) and tetracycline (48%), followed by erythromycin/clindamycin (25%/23%), and co-trimoxazole (11%), while resistance to methicillin (MRSA strains) or gentamicin was less frequent (≤5%). This underscores the importance of promptly recognizing S. aureus bacteremia caused by drug-resistant clones to facilitate more targeted clinical management of patients.
80 Burden of antibiotic resistance among children with typhoid in Gadap Town, Karachi, Pakistan [85] Pakistan A total of 275 peripheral blood samples were collected from children up to 14 years old who exhibited clinical features of typhoid and were admitted to Fatima Hospital, Baqai Medical University, over a span of two years. These samples underwent aerobic and facultative anaerobic bacterial culture, with identification based on biochemical reactions. Antimicrobial susceptibility testing was conducted using Kirby-Bauer disc diffusion with eight different antibiotics. Results revealed that among all samples, 30 (10.9%) tested positive for S. Typhi by blood culture. The positivity rate was highest among children aged 5–14 years, with 23 cases (76.7%), followed by three cases (10.0%) in each of the age groups 2.0–2.9 and 4.0–4.9 years, and one case (3.3%) in the 3.0–3.9 years age group. The majority of S. Typhi isolates exhibited resistance to co-trimoxazole (66.7%), ampicillin (63.3%), nalidixic acid (60.0%), chloramphenicol (50.0%), and aztreonam (50.0%). However, most isolates remained susceptible to ceftriaxone (76.7%) and ciprofloxacin (66.7%). Fifteen isolates demonstrated multidrug resistance, but no typhoid-related deaths were reported. In Concluded that, our findings highlight evidence of antimicrobial resistance among S. Typhi isolated from children in Karachi, residing in impoverished areas with suboptimal water quality and sanitation. Karachi, as Pakistan’s most populous city, is recognized as a focal point for typhoid cases. Therefore, this initial report of confirmed cases of multidrug-resistant S. Typhi from the sole public hospital in its largest neighborhood underscores a significant public health concern.
81 Antibiotic resistance in paediatric UTIs in Norway [86] Norway We conducted an observational study utilizing data from the Norwegian Surveillance System for Antimicrobial Drug Resistance (NORM), focusing on culture responses with resistance determination in urine samples. We included all urinary isolates from children (0-17 years) during the period 2013-17 and compared them with urinary isolates from adults. Data on cephalexin resistance were obtained from two Norwegian hospitals, covering the period 2015-19. Results: Out of 13,211 urinary isolates recorded in the NORM register, 589 (4.5%) were from children. Escherichia coli constituted the majority (85.2%) of isolates from children, weighted by the number of data collection days. Among E. coli isolates, urine samples from children showed a higher proportion of trimethoprim resistance (27.0%) compared to adults (22.9%), with a p-value of 0.02. Conversely, resistance to ciprofloxacin was lower in E. coli isolated from children (5.7%) compared to adults (8.7%), with a p-value of 0.03. For other selected antibiotics, resistance rates in E. coli from children were as follows: nitrofurantoin (0.5%), mecillinam (4.0%), cephalexin (4.3%), amoxicillin-clavulanic acid (7.2%), and trimethoprim-sulfamethoxazole (24.1%). Interpretation: Pivmecillinam, cephalexin, and amoxicillin-clavulanic acid are recommended choices for empirical treatment of upper urinary tract infections, while nitrofurantoin and pivmecillinam are suitable for lower urinary tract infections. Trimethoprim and trimethoprim-sulfamethoxazole should be reserved for use only after resistance determination.
82 Retrospective Analysis of Antimicrobial Susceptibility of Uropathogens Isolated from Pediatric Patients in Tertiary Hospital at Al-Baha Region, Saudi Arabia [87] Saudi Arabia Prompt diagnosis and initiation of treatment play a crucial role in preventing long-term renal scarring, yet increasing antibiotic resistance poses a challenge in promptly starting appropriate therapy. Methodology: We conducted a retrospective chart review of patients admitted to the pediatric department with urinary tract infection (UTI) diagnosis at a large tertiary care hospital in Al Baha, Saudi Arabia, from May 2017 to April 2018. Children of both sexes under the age of 14 years were included in the study.
Results: Out of 118 urinary bacterial samples analyzed, Escherichia coli was identified as the main etiologic agent in both community- and hospital-acquired infections. The infection rate was higher in girls (68.64%) compared to boys (31.36%). The most common isolates were Escherichia coli (44.07%), extended-spectrum beta-lactamase-producing Escherichia coli (11.86%), Klebsiella pneumoniae (9.32%), Enterococcus faecalis (7.63%), methicillin-resistant Staphylococcus epidermidis (4.24%), and coagulase-negative Staphylococci (3.39%). The study found that nitrofurantoin (19%) was the most commonly prescribed medication in both inpatient and outpatient settings, followed by trimethoprim/sulfamethoxazole (16%), amoxicillin/clavulanic acid (15%), cefuroxime (10%), azithromycin (8%), ceftriaxone (7%), and ciprofloxacin (4%). Less commonly prescribed antibiotics included amikacin, amoxicillin, ampicillin, cefepime, imipenem, and phenoxymethylpenicillin due to high resistance rates. Routine microbial culture and sensitivity testing of isolates from urine samples are crucial before initiating antimicrobial therapy. Understanding the antibiotic susceptibility patterns of uropathogens in specific geographical locations is essential for selecting appropriate empirical antimicrobial treatment, emphasizing the need to supplement standard guidelines with regional data.
83 Antibiotic susceptibility profile of bacterial isolates from febrile children under 5 years of age in Nanoro, Burkina Faso [88] Burkina Faso (west africa) Blood, stool, and urine samples were collected from 1099 febrile children attending peripheral health facilities and the referral hospital in Nanoro Health district. Bacterial isolates from these samples were evaluated for susceptibility against commonly used antibiotics using the Kirby–Bauer method.  A total of 141 bacterial isolates were recovered from 127 febrile children, with 65 from blood, 65 from stool, and 11 from urine. Salmonella isolates were the most frequently encountered, demonstrating high resistance to ampicillin (70%; 56/80) and trimethoprim–sulphamethoxazole (65%; 52/80). Escherichia coli isolates exhibited a notable resistance rate to trimethoprim–sulphamethoxazole (100%), ampicillin (100%), ciprofloxacin (71.4%; 10/14), amoxicillin–clavulanate (64.3%; 9/14), ceftriaxone (64.3%; 9/14), and gentamicin (50%; 7/14). Additionally, half of the E. coli isolates produced ß‐lactamase, indicating multi‐drug resistance against β‐lactam as well as non‐β‐lactam antibiotics. Multi‐drug resistance was observed in 54.6% (59/108) of the isolates, primarily among Gram‐negative bacteria. The study revealed high resistance rates to common antibiotics used for treating bacterial infections in Nanoro. These findings underscore the urgency to expand antibiotic resistance surveillance studies in Burkina Faso.
84 MORDOR II Burkina Faso: Longitudinal Trial (GAMIN) [89]

 

USA A single oral dose of azithromycin selected for macrolide and β-lactam resistance in S. pneumoniae isolated from the nasopharynx of children in the short term, but not 6 months after treatment in children receiving azithromycin compared with placebo. Although surveillance of antimicrobial resistance following antibiotic treatment remains a high priority, the reduction of prevalence of resistance once selection pressure is removed is reassuring.

Key Findings from Included Studies

  • Children under the age of three are the most common age group to contract MRSA infections, with newborns being especially vulnerable. MRSA isolates had low resistance to levofloxacin, Trimethoprim-sulfamethoxazole(TMP-SMX), gentamicin, and rifampin, but high resistance to erythromycin and clindamycin.
  • When using parenteral penicillin breakpoints for meningitis, penicillin resistance increased to 91.8% of isolates, compared to 28.6% when using oral penicillin breakpoints.
  • The most prevalent bacteria in neonates were Staphylococcus aureus, Enterococcus species, and Escherichia coli. Group B streptococcus (GBS) was the next most common pathogen. E. Coli showed high percentages of resistance to third-generation cephalosporins (ceftriaxone, cefotaxime) and ampicillin. Enterococcus species were shown to be 60% resistant to ampicillin and penicillin.
  • Decreased eradication efficacy of H. pylori at 44.7% due to increased antibiotic resistance. However, combinations of drugs, such as levofloxacin and bismuth, were shown to enhance H. pylori eradication efficacy in children.
  • As a result of increasing antibiotic resistance (mainly clarithromycin and amoxicillin), the eradication efficacy of H. pylori was reduced in children. Hence, the effectiveness of H. pylori eradication in children has been demonstrated to be increased by medication combinations, such as levofloxacin and bismuth.
  • Multidrug-resistant Pseudomonas aeruginosa is a serious risk for children due to high resistance to commonly prescribed antibiotics, such as including piperacillin–tazobactam, cefepime, ceftazidime, and carbapenems,
  • Infants and young children under five years old had the highest prevalence of Shigella isolates which showing high resistance rates antibiotics like cefixime, trimethoprim-sulfamethoxazole, ampicillin, cefotaxime, and ceftriaxone.
  • Amikacin demonstrated both high drug susceptibility and low drug resistance in children with extended-spectrum ESBL-PE infection.

Discussion

Since the advent of antibiotics in medicine, a relatively new issue requires fresh approaches. These could include the establishment of new clinical teams to prescribe antibiotics in wards, the use of software that can analyze numerous factors and return a specific medication and dosage, the use of rapid antimicrobial susceptibility tests to guide empirical therapy, the promotion of the use of novel antibiotics, and the preference for including children in clinical trials for both old and new medications. High prevalence of multi drug resistance organism (MDRO) carriers in children poses a great public health concern, especially in developing countries where the health care system is already overburdened. Our findings call for the systematic screening of patients at the time of admission as well as in communities to identify asymptomatic carriers who act as disseminators, to find out true burden of MDROs. There should be more targeted epidemiologic and genotypic studies to provide insights on MDRO acquisition and carriage in children [90].

 

Antibiotic overuse and misuse are primarily caused by empirical treatments: 50% of antibiotic therapies are initiated incorrectly and without a proper identification of the etiologic agent [91].

 

Antimicrobial susceptibility testing (AST) must be completed promptly and accurately in order to prevent the spread of AMR and to select the appropriate antimicrobial agent at the appropriate time. A prompt diagnosis is crucial for the proper management of infectious diseases. As of right now, technological advancements are encouraging the use of fresh diagnostic instruments for quick AST. Validation is being done on apparatus and procedures utilizing nucleic acid amplification that combine mass spectrometry and biosensor-based AST. Furthermore, third-generation whole genome sequencing (WGS) technologies are available in most sophisticated diagnostic centers and can be used to swiftly identify pathogens and check for genes linked to drug susceptibility [92].

 

Chronic diseases like cystic fibrosis (CF) are linked to significant morbidity and early mortality because of recurrent acute and chronic infections. These infections can arise from the specific pathophysiology of the disease, or they can result from frequent and extended hospital stays because the long-term use of multiple antibiotics raises the risk of multidrug resistance (MDR). Because different bacteria use type VI secretion systems to mediate interbacterial competition, pediatric CF patients appear to harbor distinct opportunistic infections than adult CF patients [93].

 

For the first time, a multicenter retrospective cohort study provided the Worldwide Antibiotic Resistance and Prescribing in European Children (ARPEC) group with comprehensive data on antibiotic use in hospitalized neonates and children in 2012. A total of 226 hospitals from 41 countries around the world with over 17,000 pediatric hospital admissions were examined; 6499 of these inpatients received at least one antibiotic. They revealed a high prevalence of broad-spectrum antibiotic use in some areas, which could be attributed to a high prevalence of Gram-negative bacteria that are resistant to carbapenem or that produce ESBLs. The high rate of empirical broad-spectrum antibiotic use, however, might suggest that some of this prescribing isn’t necessary [94].

 

According to WHO 2022 report, By the end of the 2021 data call, 109 countries plus two territories and areas were enrolled in Global Antimicrobial Resistance and Use Surveillance System (GLASS)-AMR, 99 countries, territories, and areas (CTAs) provided information on the status of AMR surveillance implementation, and 87 CTAs on AMR rates during 2020. Acinetobacter spp. have high rates of carbapenem and aminoglycoside resistance (≥56% regardless of testing coverage), which is concerning, as is the global spread of Enterobacterales that produce carbapenemase. Isolates that are resistant to carbapenems are typically multidrug resistant and frequently result in treatment failure. With respect to the AMR indicators tracked by the Sustainable Development Goals (SDG)1 framework, 76 CTAs reported median rates of bloodstream infections caused by methicillin-resistant S. aureus (MRSA) and third-generation cephalosporin-resistant E. Col. (42% and 35%, respectively). In 19 CTAs with greater testing coverage, these rates are significantly lower (11% for third-generation cephalosporin-resistant E. Coli and 7% for MRSA). When compared to CTAs with higher incomes, the majority of low- and middle-income countries (LMICs) showed lower testing coverage for both SDG indicators [95].

Conclusion

From this systematic review it was concluded that the remarkable health benefits of antibiotics in children are at risk due to the emergence of resistant bacteria that spread quickly. Need for Pharmacodynamics/pharmacokinetic-guided dosing, rapid diagnosis for AMR and regular auditing and reviewing of local antimicrobial prescriptions. Pharmaceutical companies should be focused on the development of novel antibiotics directed against MDR pathogens.

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Sheikh Raziya Begum MPharmacy, Author, medtigo

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DOI

10.5281/zenodo.11366564

Cite this Article

Raziya Begum, S. (2024). Global Perspectives on Pediatric Antimicrobial Resistance: A Systematic Literature Review. medtigo Journal, 2(2). https://doi.org/10.5281/zenodo.11366564.

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