Azithromycin resistance mechanisms in typhoidal salmonellae in India: A 25 years analysis.

Background & objectives: : Azithromycin has been in use as an alternate treatment option for enteric fever even when the guidelines on the susceptibility testing were not available. There is lack of data on susceptibility and mechanisms of resistance of azithromycin in Salmonella Typhi and S. Paratyphi A. The aim of the present study was to determine the azithromycin susceptibility and resistance mechanisms in typhoidal salmonellae isolates archived in a tertiary care centre in north India for a period of 25 years. Methods: : Azithromycin susceptibility was determined in 602 isolates of S. Typhi (469) and S. Paratyphi A (133) available as archived collection isolated during 1993 to 2016, by disc diffusion and E-test method.PCR was done for ereA, ermA, ermB, ermC, mefA, mphA and msrA genes from plasmid and genomic DNA and sequencing was done to detect mutations in acrR, rplD and rplV genes. Results: : Azithromycin susceptibility was seen in 437/469 [93.2%; 95% confidence interval (CI), 90.5 to 95.1%] isolates of S. Typhi. Amongst 133 isolates of S. Paratyphi A studied, minimum inhibitory concentration (MIC) of ≤16 mg/l was found in 102 (76.7%; 95% CI, 68.8 to 83.0). MIC value ranged between 1.5 and 32 mg/l with an increasing trend in MIC50and MIC90with time. Mutations were found in acrR in one and rplV in two isolates of S. Typhi. No acquired mechanism for macrolide resistance was found. Interpretation & conclusions: : Azithromycin could be considered as a promising agent against typhoid fever on the basis of MIC distribution in India. However, due to emergence of resistance in some parts, there is a need for continuous surveillance of antimicrobial susceptibility and resistance mechanisms. There is also a need to determine the breakpoints for S. Paratyphi A.

Changing trends of culture-positive typhoid fever and antimicrobial susceptibility in a tertiary care North Indian Hospital over the last decade.

PURPOSE: The present study was undertaken to analyse the trend in prevalence of culture-positive typhoid fever during the last decade and to determine antimicrobial susceptibility profile of Salmonella Typhi and Salmonella Paratyphi A isolated from patients of enteric fever presenting to our hospital. METHODS: All the culture-positive enteric fever cases during 2005-2016 presenting to our Hospital were included in the study. Antimicrobial susceptibility was done against chloramphenicol, amoxicillin, co-trimoxazole, ciprofloxacin, ofloxacin, levofloxacin, pefloxacin, ceftriaxone and azithromycin as per corresponding CLSI guidelines for each year. We also analysed the proportion of culture positivity during 1993-2016 in light of the antibiotic consumption data from published literature. RESULTS: A total of 1066 strains-S. Typhi (772) and S. Paratyphi A (294) were isolated from the blood cultures during the study. A maximum number of cases were found in July-September. Antimicrobial susceptibility for chloramphenicol, amoxicillin and co-trimoxazole was found to be 87.9%, 75.5%, 87.3% for S. Typhi and 94.2%, 90.1% and 94.2% for S. Paratyphi A, respectively. Ciprofloxacin, ofloxacin and levofloxacin susceptibility were 71.3%, 70.8% and 70.9% for S. Typhi and 58.1%, 57.4% and 57.1% for S. Paratyphi A, respectively. Azithromycin susceptibility was 98.9% in S. Typhi. Although susceptibility to ceftriaxone and cefixime was 100% in our isolates, there is a continuous increase in ceftriaxone minimum inhibitory concentration (MIC)50and MIC90values over the time. The proportion of blood culture-positive cases during 1993-2016 ranged from a minimum of 0.0006 in 2014 to a maximum of 0.0087 in 1999. CONCLUSION: We found that the most common etiological agent of enteric fever is S. Typhi causing the majority of cases from July to October in our region. MIC to ceftriaxone in typhoidal salmonellae is creeping towards resistance and more data are needed to understand the azithromycin susceptibility.

Characterisation of antimicrobial resistance in Salmonellae during 2014-2015 from four centres across India: An ICMR antimicrobial resistance surveillance network report.

PURPOSE: The main purpose of this study was to establish 'Antimicrobial Resistance Surveillance Network' in India and to monitor the antimicrobial susceptibility profile of clinical isolates to establish a national network across the country for monitoring antimicrobial resistance in Salmonella. MATERIALS AND METHODS: This study was conducted at All India Institute of Medical Sciences, nodal centre with clinical isolates of Salmonellae collected from four centres across India, which included Christian Medical College, Vellore; Postgraduate Institute of Medical Education and Research, Chandigarh and Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry. Total 20% of the selected strains from each centre were characterised for molecular studies which included molecular mechanism of fluoroquinolones resistance and multiple locus sequence type. RESULTS: A total of 622 Salmonellae were received from all centres during January 2014 to December 2015. Out of these 622 isolates, 380 were Salmonella Typhi, 162 were Salmonella Paratyphi A and 7 were S. Paratyphi B isolated from blood and 73 were other Salmonella serotypes. Multiple drug resistance (resistant to ampicillin, chloramphenicol and co-trimoxazole) was less than 3% in S. Typhi. In S. Paratyphi A, chloramphenicol and co-trimoxazole susceptibility was 100% and 99%, respectively, whereas ampicillin susceptibility was 86% (139/161). Ciprofloxacin and nalidixic acid susceptibility was 15% (24/162) and 1% (2/162) from all centres. S. Paratyphi B was isolated from 7 patients. All isolates were third-generation cephalosporin sensitive. The most common mutations found were at codon 83 and at codon 87. We did not find any mutation in acrR gene. Efflux pump and qnr genes were not found in any isolate tested. All 86 S. Typhi isolates clustered into two sequence types - ST1 and ST2. Out of these 86 isolates, 70 S. Typhi were ST1 and 16 were ST2. All S. Paratyphi A was clustered in ST85 and ST129 on the basis of mutation in sucA gene. Out of 27 S. Paratyphi A, 13 were grouped into ST85 and 14 were grouped into ST129. CONCLUSIONS: Enteric fever is one such infection which poses challenges in antimicrobial resistance. Hence, continuous surveillance is important to track bacterial resistance and to treat infections in a cost-effective manner.