Emerging and re-emerging antimicrobial agents in typhoid and para-typhoid: A big data insight on AMR

A large proportion of population in low and middle income countries such as India is predisposed to be affected by enteric fever (Typhoid and para-typhoid). Typhoid and para-typhoid fevers are common in India. According to a systematic review by Jacob john, pooled incidence of typhoid and para-typhoid in India was 377 and 105 per 100,000 person years respectively.

High antimicrobial resistance in salmonella against commonly used antibiotics such as fluoroquinolones rendered treatment of typhoid and para-typhoid very difficult. According to a report by ICMR (Indian council of medical research) antimicrobial resistance surveillance network, sensitivity of salmonella typhi to ciprofloxacin and nalidixic acid was only 20% and 24% respectively, while in case of salmonella paratyphi A it was 15% and 1% respectively.

We conducted an analysis on results of positive blood culture and sensitivity tests of 561 samples for salmonella typhi and 141 samples for salmonella paratyphi A. Analysis assessed sensitivity of salmonella typhi and salmonella paratyphi A against commonly used antibiotics. Following antimicrobial agents were included in the analysis.

1. Cephalosporins: Cefepime, Cefixime, Cefotaxime, Ceftazidime and Ceftriaxone 2. Fluoroquinolones: Levofloxacin, Ciprofloxacin and Nalidixic acid (synthetic quinolone) 3. Penicillins: Amoxicillin, Ampicillin 4. Macrolide: Azithromycin 5. Cotrimoxazole 6. Chloramphenicol

Results showed a very low sensitivity (<5%) of salmonella typhi to ciprofloxacin, levofloxacin and nalidixic acid, while of salmonella paratyphi A sensitivity was even less than 2% to any of these antibiotics. Salmonella typhi and paratyphi A both showed very high sensitivity to chloramphenicol (>95%)and cotrimoxazole (>95%).

Cefepime, Cefixime and Ceftazidime have high coverage (> 99%) for salmonella paratyphi A and more than 95% coverage for salmonella typhi. Azithromycin, ampicillin and amoxicillin have little less coverage in comparison to cephalosporins but it was more than 90% for salmonella typhi. Sensitivity of salmonella paratyphi A for Amoxicillin, Ampicillin and Azithromycin was less (~80%) in comparison to salmonella typhi. Cotrimoxazole showed 100% coverage to salmonella paratyphi A.

To conclude our analysis showed irrelevance of commonly used antibiotics (Fluoroquinolones) and re-emergence of antimicrobial agents (Cotrimoxazole, Chloramphenicol), which were obsolete once, in management of typhoid and paratyphoid. Lab based antimicrobial surveillance is a key to understand changing trends of antimicrobial resistance.