Spectrum of World Health Organization global priority pathogens in hospitalized children - A single center experience

INTRODUCTION

The World Health Organization (WHO) was requested by Member States to develop a global priority pathogens list (PPL) of antibiotic-resistant bacteria to help in prioritizing the research and development of new and effective antibiotic treatments. Antibiotic-resistant bacteria were defined as bacterial isolates that became resistant to the administered drug with a change from “susceptible” to “intermediate” or “resistant,” or from “intermediate” to “resistant” in the susceptibility pattern.^[1-3] The main drivers of antibiotic resistance (AR) are misuse and overuse of antibiotics due to presumptive treatment and inappropriate use of broad-spectrum antibiotics with erratic dosing.^[4,5]

Other factors include transmission of resistant bacteria between patients, from healthcare workers to patients and vice versa, prophylactic use in animal husbandry, and lack of guidelines and policies for the use of antibiotics. A report from the World Bank forewarned that antimicrobial resistance (AMR) that includes AR could cause as much damage to the global economy as the 2008 financial crisis.^[1] AMR is one of the most complex global health challenges today. The world has long ignored warnings that antibiotics and other medicines are losing their effectiveness after decades of overuse and misuse in human medicine, animal health, and agriculture.

Common illnesses such as pneumonia, post-operative infections, urinary tract infection (UTI), diarrheal, and sexually transmitted diseases, as well as the world’s largest infectious disease killers-tuberculosis, human immunodeficiency virus, and malaria-are increasingly becoming untreatable because of the emergence and spread of drug resistance worsening AMR could have serious public health, economic, and social implications. The threat of AMR is also becoming a key consideration for programs addressing maternal and child health, sexual and reproductive health, foodborne diseases, water and sanitation, and infection prevention and control. Moreover, although the 21^st century is being shaped by technology and innovation, humans could soon find themselves in an era where simple infections would once again kill millions every year.

Antibiotics have greatly reduced morbidity and mortality from classical and opportunistic infections in the last few decades.^[1] Contrasting the gains made, the accelerated global consumption of antibiotics and lapses in the infection prevention and control practices, have hastened the frequency and severity of AR.

MATERIAL AND METHODS

In this cross sectional study, all children admitted in the Paediatric and Adolescent Medicine Department i.e., Ward, Pediatric Intensive Care Unit (PICU) and neonatal intensive care unit (NICU), and Pediatric Surgical Intensive Care Unit (PSICU) of Sri Aurobindo Institute of Medical Sciences between April 2021 and September 2022 and had culture (blood, urine, cerebrospinal fluid, other body fluids/tissue) reports showing the presence of one of the WHO priority pathogens, were evaluated. The clinical syndromes associated with these pathogens were also noted.

RESULTS

In this study, there were 100 children who had various cultures growing an organism. Urine specimens had the maximum bacterial isolations [35 (35%)], followed by blood [24 (24%)] [Table 1]. Escherichia coli was the most frequent isolated organism 24 (24%), followed by S. aureus 20 (20%). About 80% of E. coli and 70.6% of Klebsiella spp. were resistant to third-generation cephalosporins due to extended-spectrum beta-lactamase (ESBL), while 50% of S. aureus were methicillin-resistant. In all, over half of the Enterobacteriaceae were resistant to carbapenem (49.21%) or third-generation cephalosporins (55.56%) due to ESBL. P. aeruginosa carbapenem resistance was determined to be modest (11.11%). Over the past 4 years, a time trend study of selected WHO “Critical priority” pathogens revealed a significant proportion of carbapenem resistance in E coli, Klebsiella pneumoniae, and Enterobacter cloacae. E. coli, and K. pneumoniae also continued to have a high prevalence of ESBL. S. aureus continues to have a high percentage of methicillin resistance among the WHO’s “High priority” pathogens.

Three of the WHO’s “High priority” infections were not discovered in our cohort - namely H. pylori (clarithromycin-resistant), Campylobacter spp. (fluoroquinolone-resistant), and N. gonorrhoeae (third-generation cephalosporin-resistant and fluoroquinolone-resistant). Similarly, one of the WHO’s “Medium priority” pathogens, H. influenzae (ampicillin-resistant), was not found in this cohort, and antibiotic sensitivity data were unavailable.

DISCUSSION

The WHO advice paper from 2017 found that A. baumannii (91%) and P. aeruginosa (82%), both of which are classified as Critical Priority^[6] infections, had the greatest levels of carbapenem resistance globally. Carbapenem resistance was found to be more than 50% in A. baumannii and between 31 and 50% in P. aeruginosa in the general population of the Indian subcontinent, according to the same research. Early findings from the monitoring data collected from up to 22 The Indian Council of Medical Research-Antimicrobial Resistance Surveillance and Research Network (ICMR-AMRSN) locations in India indicated that over 80% of A. baumannii strains were resistant to carbapenem, whereas approximately 30% of P. aeruginosa strains were resistant. On the other hand, a different research that was conducted on children in Mumbai, India, found that only 15% of P. aeruginosa strains are resistant to carbapenem.^[7,8] This finding is similar to the present study. In the present investigation, the prevalence of carbapenem-resistant strains of P. aeruginosa among pediatric patients was found to be 11.1%.

In the general population, the WHO report found significant levels of carbapenem resistance in E. coli (55%), Klebsiella (70%), and Enterobacter spp. (59%), which is not too dissimilar to the results in our investigation in the pediatric population. In the general population, the results from ICMR-AMRSN indicated a prevalence of carbapenem resistance that was comparable in K. pneumoniae (40–50%) but much lower in E. coli (15–25%).^[7]

In this study, the prevalence of methicillin-resistant S. aureus was high and comparable to that found in the WHO report. About 80% of E. coli and seventy-five and a half percent of Klebsiella spp. were resistant to third-generation cephalosporins as a result of ESBL, and 50% of S. aureus were resistant to methicillin. However, because of the small sample size of Salmonella spp., Shigella spp., and S. pneumoniae, it is possible that the findings of this research cannot be compared to those of other studies.

Over the last several years,^[8-10] India has seen the publication of a number of papers on AMR. A retrospective investigation with a 5-year follow-up that was conducted in a tertiary care hospital in North India revealed rising rates of AMR in urinary tract infection-causing isolates.^[9] However, the reported carbapenem resistance prevalence in Klebsiella spp. (39%) and E. coli (12%) were lower than what was found in the current study.^[10] Increasing trends of AMR were observed among gram-negative isolates from samples collected across seven hospitals in India over the course of 4 years. About 24% of the Enterobacteriaceae that were isolated from a pediatric tertiary care hospital in Mumbai produced ESBL, and 27% of the Enterobacteriaceae that were isolated showed a lesser degree of resistance to carbapenem than the isolates in the present study.^[8]

CONCLUSION

Of the WHO PPL pathogens, Enterobacteriaceae, methicillin-resistant S. aureus, Klebsiella species, and E. coli all show significant AMR in the research site. On the other hand, AMR trends for A. baumanni, P. aeruginosa, and S. aureus (vancomycin resistant) are lower than the estimations provided by the WHO globally. These results have the potential to influence the priorities, policies, and practices of the local community. We strongly suggest that big health institutions monitor and assess developing patterns and trends in AMR on a periodic basis to prioritize, plan, and execute health facility level policies and recommendations for the most effective use of antimicrobials.