In Vitro Assessment of Antimicrobial Activity of Novel Fluoroquinolone, Levonadifloxacin (WCK 771) Against Multi-Drug-Resistant Clinical Isolates from Cancer Patients in India.

Introduction: Rapid increase in antimicrobial-resistance is leading to urgent need for newer broad-spectrum antimicrobials. Therefore, we have evaluated the antimicrobial résistance spectrum of India-discovered novel antibiotics (levonadifloxacin) against clinical isolates recovered from cancer patients. Materials and Methods: The study was conducted in the microbiology department, over a period of 1 year between May 2021 and June 2022 and 374 consecutive and nonduplicate Gram-positive (GPC) and MDR Gram Negative Bacteria (GNB) isolate were analyzed from 3,880 cancer patients in study. The identification and antimicrobial sensitivities of bacterial isolates were performed according to standard laboratory protocols by using automated identification system (VITEK-2-8.01; BioMérieux, Germany). The activity of levonadifloxacin and comparator antibiotics was evaluated using disk diffusion methods as per Clinical and Laboratory Standards Institute 2022 guidelines. Results: The mean age of the patients were 51.6 ± 14.59 years with male: female ratio of 1.2:1. The prevalence of GPC was 167 (44.65%) and MDR-GNB was 207 (55.34%). The most common GPC was Staphylococcus aureus; 97 (58.08%) followed by Enterococcus species 66 (39.52%). In GNB, Escherichia coli; 93 (44.92%) was the most common followed by Klebsiella pneumoniae; 45 (21.73%). Levonadifloxacin susceptibility was present in 98.7% methicillin-resistant S. aureus and 96% methicillin-susceptible S. aureus and 77.1% Enterococcus-species. Additionally, all the fluoroquinolones-resistant S. aureus isolates were susceptible to levonadifloxacin (WCK-771) except one isolate. Also, levonadifloxacin-(WCK-771) exhibits 100% susceptibility fluoroquinolone susceptible GNB, such as E. coli, K. pneumoniae, Pseudomonas species, and Acinetobacter species. Interestingly, all fluoroquinolones-resistant Salmonella species and Stenotrophomonas maltophilla exhibited 100% susceptibility to levonadifloxacin (WCK-771). Conclusion: Levonadifloxacin (WCK-771) possesses potent activity against all the MDR Gram-positive pathogens including the coverage of susceptible Enterobacterales and MDR S. maltophilla and Burkholderia cepacia suggesting its potential utility in the management of polymicrobial infections.

Drug Resistance Pattern in the Recent Isolates of Salmonella Typhi with Special Reference to Cephalosporins and Azithromycin in the Gangetic Plain.

INTRODUCTION: Typhoid fever is an endemic disease in India against which many antibiotics are available. In the recent times, emerging resistance to traditional antibiotics, such as Ampicillin, Chloramphenicol and Trimethoprim/sulfamethoxazole, Azithro-mycin and third generation Cephalosporins are being reported and increasingly being used in the treatment of invasive Salmonella infections. However, the latter two drugs have been reported with occasional clinical failures. Currently, we do not have data regarding their drug resistance levels in the recent isolates of Salmonella enterica subspecies enterica serotype Typhi. AIM: To determine the current levels of drug resistance of the two drugs (i.e., cephalosporins and azithromycin) against S. Typhi isolates. MATERIALS AND METHODS: It is a prospective case study. A total of 47 recent strains of S. Typhi were isolated from blood and stool specimens. These isolates were subjected to identification and confirmation by biochemical, serological tests followed by genotypic methods. The antimicrobial testing was done by disc diffusion and Minimum Inhibitory Concentration (MIC) methods for various in use antibiotics including ceftriaxone and azithromycin from February 2011 to March 2013 in the Department of Microbiology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India. RESULTS: It was intriguing to see the return of conventional drugs such as chloramphenicol, amoxicillin and co-trimoxazole. The drugs like quinolones, ceftriaxone and azithromycin were found to be ineffective against >20% of the isolates. However, nalidixic acid was found to have maximum resistance (36/47,76.6%) while highest sensitivity was observed for chloramphenicol (1/47,2.1%). Moreover, co-trimoxazole (9/47,19.1%) has displayed with significant come back. CONCLUSION: It could be concluded that combination of amoxicillin and co-trimoxazole would prove as good as azithromycin or ceftriaxone alone for empirical therapy of S. Typhi infection. However, detection of an isolate (1/47, 2.1%), sensitive only to chloramphenicol, a drug known for causing bone marrow suppression, is an alarming sign.