Renaissance of Conventional First-Line Antibiotics inSalmonella entericaClinical Isolates: Assessment of MICs for Therapeutic Antimicrobials in Enteric Fever Cases from Nepal

Abstract

Enteric fever caused by Salmonella enterica is a life-threatening systemic illness of gastrointestinal tract especially in tropical countries. Antimicrobial therapy is generally indicated but resistance towards commonly used antibiotics has limited their therapeutic usefulness. Therefore, we aimed to determine the antimicrobial susceptibility pattern by minimum inhibitory concentration method of common therapeutic regimens against Salmonella enterica from enteric fever clinical cases. Salmonella enterica clinical isolates recovered from the patients with suspected enteric fever whose blood samples were submitted to microbiology laboratory of Manmohan Memorial Community Hospital, Kathmandu, from March 2016 to August 2016, were studied. These isolates were subjected to antimicrobial susceptibility testing against common therapeutic antimicrobials by Kirby-Bauer disk diffusion method. The minimum inhibitory concentration of ciprofloxacin, azithromycin, chloramphenicol, and cefixime was determined by Agar dilution method based on the latest CLSI protocol. A total of 88 isolates of Salmonella enterica were recovered from blood samples of enteric fever cases. Out of them, 74 (84.09%) were Salmonella Typhi and 14 (15.91%) were Salmonella Paratyphi A. On Kirby-Bauer disk diffusion antimicrobial susceptibility testing, entire isolates were susceptible to cotrimoxazole, cefixime, ceftriaxone, azithromycin, and chloramphenicol. Sixty-four (72.7%) Salmonella enterica isolates were nalidixic acid resistant and nonsusceptible to ciprofloxacin and levofloxacin. On MIC determination, four Salmonella isolates were ciprofloxacin resistant with MIC 1 µg/ml and two isolates were ciprofloxacin intermediate with MIC 0.5 µg/ml. The MIC range of azithromycin was from 0.125 µg/ml to 2.0 µg/ml, whereas that for chloramphenicol was 2.0 µg/ml–8.0 µg/ml and for cefixime was 0.0075–0.5 µg/ml, respectively. Despite global surge of antimicrobial resistance among Salmonella enterica clinical isolates, the level of drug resistance in our study was not so high. However, higher level of NARST strains limits therapeutic use of fluoroquinolones and necessitates the routine monitoring of such resistance determinants in order to effectively and rationally manage enteric fever cases.

Antimicrobial susceptibility pattern of Salmonella enterica, blood-stream isolates, among febrile children: a prospective study from Nepal

“…However, we observed a very high level of FQs and nalidixic-acid resistance, but relatively low rates to conventional drugs. The findings are in line with recent epidemiological studies conducted in the Nepalese population(11)(13)(14) (16).The low rate of resistance to conventional drugs was observed, probably due to discontinuation in the therapeutic regimen for a longer time, high molecular weight self-transmissible plasmid inducing resistance could have lost or de novo susceptible strain might have emerged in these days (11) (22). Due to mutation in the genes coding for DNA gyrase (gyrA and gyrB) and topoisomerase IV (parC and parE), the high level of nalidixic-acid resistance occurs, in general (23).…”

“…In our study, among tested antibiotics, low rate of azithromycin resistant strain was observed on MIC which is similar as Khanal et al reported such efficacy-lower MIC and resistance trend against the isolates, in his study (22). In the Nepalese population, treatment failure on azithromycin treatment is yet not reported; nevertheless, an increase in MIC was reported in the patients from other countries.…”

Antimicrobial Sensitivity Trend in Blood Culture Positive Enteric Fever at Kathmandu Model Hospital

“…2 In our study, cotrimoxazole and chloramphenicol are 100% sensitive to all salmonella species, which is similar to the study done in 2002. 10 Similarly, in another study done by Khanal et al, 11 the conventional first line antibiotics, namely, co-trimoxazole and chloramphenicol showed 100% sensitivity to salmonella species. The quinolones group of drugs emerged as useful drugs in the 90s for the treatment of multiple drug resistant cases.…”

Revisiting the Revised CLSI Breakpoint for Detecting Fluoroquinolones Resistance in Salmonella

“…In Nepal, antibiotic resistance among Gram negative bacteria is increasing (Thapa et al, 2006) and screening of such resistance is routinely done using the disc diffusion (DD) method following CLSI standard guidelines. But this DD method has been claimed inadequate to determine to reduce susceptibility of fluoroquinolones by many studies (Gupta et al, 2020;Bhetwal et al, 2017;Khanal et al,2017) so NAR was used as a surrogate marker in those cases. Unfortunately, the fluoroquinolones resistance among Salmonella continued to increase in Nepal (Gupta et al, 2020;Pokharel et al, 2016;Karki et al, 2013) and to implement an appropriate treatment for enteric fever patients, an efficient screening method along with a standard CLSI guideline is utmost necessary (Bhetwal et al, 2017;Khanal et al,2017).…”