Various pathogens increasingly becoming resistant to critically important antimicrobials: ICMR report

The Antimicrobial Resistance Research and Surveillance Network of the Indian Council of Medical Research (ICMR) released its annual report for 2022. This is the sixth report which sheds light on the evolving landscape of antimicrobial resistance (AMR) in the country. 

The analysis showed a trend of declining susceptibility towards critically important antimicrobials (CIA). CIAs and Highest Priority Critically Important Antimicrobials (HPCIA) are the categories of antimicrobial agents identified by the World Health Organization (WHO) based on their importance in human medicine and the urgency to preserve their effectiveness. 

The report is based on the analysis of 107,053 culture-positive isolates, which were sourced from 21 tertiary care hospitals as participating centres and obtained from different specimen types such as blood, urine, superficial infections, deep infections, sterile sites, cerebrospinal fluid (CSF) and faeces. 

Escherichia coli was identified as the most commonly occurring pathogen, followed by Klebsiella pneumoniae, Pseudomonas aeruginosa, Acinetobacter baumannii and Staphylococcus aureus. All these isolates were analysed across different clinical settings, including out-patient departments (OPD), wards and intensive care units (ICU). 

ICMR reported E coli as the most frequently encountered isolate in OPD and wards, while A baumannii was identified as the most common isolate in ICU.

The isolates were also assessed for their susceptibility to a panel of antibiotics, which included CIAs such as amikacin (a member of aminoglycosides class); cefotaxime and ceftazidime (third generation cephalosporins); ciprofloxacin and levofloxacin (fluoroquinolones); piperacillin-tazobactam (a type of penicillin); imipenem, meropenem, and ertapenem (carbapenems) and colistin (a polymyxin). 

E coli, a bacterium known to cause a wide range of infections in both clinical and commercial settings, exhibited low susceptibility percentages to many of the CIAs. Notably, the lowest susceptibilities were observed to levofloxacin (16 per cent), ciprofloxacin (12 per cent), cefotaxime (18 per cent), ceftazidime (19 per cent) and piperacillin-tazobactam (35 per cent). 

These low susceptibilities indicate that E coli has become highly resistant to these antibiotics, thus posing significant health concerns.

A five-year trend analysis from all samples (except faeces and urine) showed a decline in susceptibility of E coli to fluoroquinolones, cephalosporins, penicillins and carbapenems from 2017 to 2022, according to the report. The notable drops were reported for ceftazidime (from 23.5 to 18.8 per cent), imipenem (from 81.4 to 66.1 per cent), meropenem (from 73.2 to 69.7 per cent), ciprofloxacin (from 19.2 to 12.3 per cent) and piperacillin-tazobactam (from 56.8 to 35.1 per cent), indicating an increasing resistance to these CIAs over time. 

K pneumoniae, a common cause of hospital-acquired pneumonia, also exhibited low susceptibility percentages to cefotaxime (21 per cent), ceftazidime (19 per cent), ciprofloxacin (20 per cent) and levofloxacin (25 per cent), the authors of the report found. Additionally, it showed lower susceptibilities to amikacin, imipenem, meropenem and ertapenem, ranging from 40-46 per cent, they added.

The yearly trend for K pneumonia isolated from all samples (except faeces and urine) showed a decrease in the susceptibility to imipenem, ciprofloxacin, ceftazidime and piperacillin-tazobactam by 16.3, 11.7, 8.2 and 20.6, respectively, from 2017 to 2022, the researchers wrote.

Overall, E coli and K pneumoniae isolates from out-patients showed higher susceptibility compared to those from in-patients for all the tested drugs, they observed. Furthermore, among the in-patients, the isolates from the general wards demonstrated higher susceptibility compared to those from ICU.

Notably, P aeruginosa isolates identified from ward and ICU were found to be multidrug-resistant, underlining the growing challenge of drug-resistant strains in hospital settings. Among all the antibiotics tested, susceptibility of P aeruginosa to fluoroquinolones was the lowest, especially in the samples collected from deep infection, CSF and urine. Additionally, 36 per cent of P aeruginosa isolates were found to be resistant to carbapenems, and this number was even higher in ICU (49 per cent) and wards (63 per cent). 

Nearly 88 per cent of A baumannii isolates tested in this study showed resistance to carbapenems. The pathogen is known to cause a range of diseases, including pneumonia, bloodstream infections and urinary tract infections. 

It exhibited low susceptibilities to CIAs like cefepime (10.8 per cent), ceftazidime (9.1 per cent), amikacin (17.4 per cent), levofloxacin (17.5 per cent), imipenem (12.2 per cent), meropenem (14.2 per cent) and piperacillin-tazobactam (13 per cent), according to the report.

In addition, A baumannii was found to be more prevalent in wards and ICUs, as compared to the OPDs. Over a five-year trend analysis, a decrease in susceptibility to most of the tested antibiotics was reported, with levofloxacin dropping the most from 29.1 to 17.5 per cent, the authors noted.

S aureus, a bacterium responsible for a wide range of clinical diseases, is becoming increasingly challenging due to the emergence of multi-drug resistant strains including Methicillin-Resistant S aureus (MRSA). 

The susceptibility percentages of S aureus and MRSA to tested antibiotics showed varying levels, with particularly low susceptibilities to erythromycin (38.6 per cent for S aureus and 23.9 per cent for MRSA) and ciprofloxacin (21.5 per cent for S aureus and 12.8  per cent for MRSA). Erythromycin, an antibiotic from the class of macrolides and ketolides, is also classified as an HPCIA. 

Yearly trends for S aureus further indicated a decline in susceptibility to antibiotics such as cefoxitin (67.1 per cent to 55.5 per cent), erythromycin (49.5 per cent to 38.6 per cent) and ciprofloxacin (23.3 per cent to 21.5 per cent) from 2017 to 2022. 

The ICMR also analysed E faecalis and E faecium, two commonly encountered pathogens. E faecium isolates showed high resistance to antibiotics ampicillin, gentamicin and ciprofloxacin, while E faecalis primarily showed resistance to ciprofloxacin.

The researchers also found that Salmonella typhi, the primary strain responsible for typhoid fever in India, exhibited a resistance rate of more than 95 per cent against the fluoroquinolones, severely limiting its use. 

Furthermore, yearly susceptibility trends of S typhi from blood showed a concerning decline in susceptibility to ciprofloxacin, dropping from 11.6 per cent in 2017 to a mere 3 per cent in 2022. 

The report pointed out that there is increasing resistance among common infection-causing pathogens against antibiotics especially belonging to cephalosporins, fluoroquinolones and carbapenems classes of CIAs. If this trend continues, it will severely limit treatment options for many diseases, the authors said. 

An earlier 2021 report by Delhi-based think tank, Centre for Science and Environment, also highlighted  the misuse of several antibiotics from these classes in food-producing animals in India. It identified 27 different types of CIAs from seven classes, including macrolides and ketolides, third generation cephalosporins and fluoroquinolones, which were found to be used in dairy, poultry and aquaculture for both therapeutic and non-therapeutic purposes.

The weak and fragile global pipeline for new antibiotics adds to the concerns. It is imperative that efforts are directed towards ensuring responsible use and conservation of these CIAs in human and animal health settings. 

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