Emergence of Azithromycin Resistance Mediated by Phosphotransferase-Encoding mph(A) in Diarrheagenic Vibrio fluvialis

The azithromycin resistance conferred by phosphotransferase is encoded in the gene mph(A). This gene has been discovered in and reported for many bacterial species. We examined the prevalence of azithromycin resistance in Vibrio fluvialis (AR-VF) isolated during 2014 to 2015 from the hospitalized acute diarrheal patients in Kolkata, India. Most of the V. fluvialis isolates are identified as the sole pathogen (54%). The prevalence of AR-VF was higher in 2015 (19 [68%]) than in 2014 (9 [32%]). Among AR-VF isolates, the azithromycin MICs ranged from 4 to >256 mg/liter. Twenty-eight of the 48 (58%) V. fluvialis isolates harbored the gene mph(A) and phenotypically resistant to azithromycin. All the AR-VF isolates remained susceptible to doxycycline. In addition to azithromycin, other antimicrobial resistance-encoding genes of AR-VF were also characterized. All the AR-VF isolates were positive for class 1 integron, and most of them (17/28) carried the dfrA1 gene cassettes. Only one isolate was positive for the ereA gene, which encodes resistance to erythomycin. The majority of the isolates were resistant to β-lactam antibiotics (bla_OXA-1 [96%], bla_OXA-7 [93%], and bla_TEM-9 [68%]) and aminoglycoside actetyltransferase, conferring resistance to ciprofloxacin-modifying enzyme [aac(6')Ib-cr] (96%). Analyses by pulsed-field gel electrophoresis (PFGE) showed that the AR-VF isolates belonged to different genetic lineages. This is the first study to report azithromycin resistance and the presence of the mph(A) gene in V. fluvialis isolates. Circulation of AR-VF isolates with high azithromycin MICs is worrisome, since it may limit the treatment options for diarrheal infections.IMPORTANCE The progressive rise in antibiotic resistance among enteric pathogens in developing countries is becoming a big concern. India is one of the largest consumers of antibiotics, and their use is not well regulated. V. fluvialis is increasingly recognized as an emerging diarrheal pathogen of public health importance. Here we report the emergence of azithromycin resistance in V. fluvialis isolates from diarrheal patients in Kolkata, India. Azithromycin has been widely used in the treatment of various infections, both in children and in adults. Resistance to azithromycin is encoded in the gene mph(A). Emerging azithromycin resistance in V. fluvialis is a major public health challenge, and future studies should be focused on identifying ways to prevent the dissemination of this antibiotic resistance gene.