In Vitro Activity of Two Cefepime-Based Novel Combinations, Cefepime/Taniborbactam and Cefepime/Zidebactam, against Carbapenemase-Expressing Enterobacterales Collected in India.

In recent times, discovery efforts for novel antibiotics have mostly targeted carbapenemase-producing Gram-negative organisms. Two different combination approaches are pertinent: ß-lactam-ß-lactamase inhibitor (BL/BLI) or ß-lactam-ß-lactam enhancer (BL/BLE). Cefepime combined with a BLI, taniborbactam, or with a BLE, zidebactam, has been shown to be promising. In this study, we determined the in vitro activity of both these agents along with comparators against multicentric carbapenemase-producing Enterobacterales (CPE). Nonduplicate CPE isolates of Escherichia coli (n = 270) and Klebsiella pneumoniae (n = 300), collected from nine different tertiary-care hospitals across India during 2019 to 2021, were included in the study. Carbapenemases in these isolates were detected by PCR. E. coli isolates were also screened for the presence of the 4-amino-acid insert in penicillin binding protein 3 (PBP3). MICs were determined by reference broth microdilution. Higher MICs of cefepime/taniborbactam (>8 mg/L) were linked to NDM, both in K. pneumoniae and in E. coli. In particular, such higher MICs were observed in 88 to 90% of E. coli isolates producing NDM and OXA-48-like or NDM alone. On the other hand, OXA-48-like-producing E. coli or K. pneumoniae isolates were nearly 100% susceptible to cefepime/taniborbactam. Regardless of the carbapenemase types and the pathogens, cefepime/zidebactam showed potent activity (>99% inhibited at ≤8 mg/L). It seems that the 4-amino-acid insert in PBP3 (present universally in the study E. coli isolates) along with NDM adversely impact the activity of cefepime/taniborbactam. Thus, the limitations of the BL/BLI approach in tackling the complex interplay of enzymatic and nonenzymatic resistance mechanisms were better revealed in whole-cell studies where the activity observed was a net effect of ß-lactamase inhibition, cellular uptake, and target affinity of the combination. IMPORTANCE The study revealed the differential ability of cefepime/taniborbactam and cefepime/zidebactam in tackling carbapenemase-producing Indian clinical isolates that also harbored additional mechanisms of resistance. NDM-expressing E. coli with 4-amino-acid insert in PBP3 are predominately resistant to cefepime/taniborbactam, while the ß-lactam enhancer mechanism-based cefepime/zidebactam showed consistent activity against single- or dual-carbapenemase-producing isolates including E. coli with PBP3 inserts.

Association of Urinary Tract Infection in Married Women Presenting with Urinary Incontinence in a Hospital based Population.

INTRODUCTION: Urinary incontinence (UI) is increasingly recognized as a significant health problem, which remains a hygienic as well as social problem. Women have higher risk of developing incontinence in their lifetime compared with men. Urinary tract infection can increase the incidence of incontinence. Present study was undertaken to assess the association of UTI in married women who presented with UI. AIM: The present study was aimed to identify the patients (married women) with complaints of UI and determining its association with UTI; and to identify the causative organism for the UTI along with its antimicrobial susceptibility pattern. MATERIALS AND METHODS: This is a cross-sectional, non-randomized study of 107 married women with UI, who attended outpatient department in our hospital. Mid-stream urine (MSU) samples were collected from these patients with positive history of incontinence. Screening of urine for significant bacteriuria and culture to identify the etiological agents were performed followed by evaluation of their antimicrobial susceptibility profiles using Kirby Bauer disc diffusion method. RESULTS: Overall 25.2% of patients with incontinence had a positive urine culture. History of UTI was elicited in around 38.3% of patients, among which 15% had positive urine culture and 10.3% of the patients who did not have a history had positive culture. Escherichia coli was the commonest causative organism (66.6) causing UTI, followed by Enterococcus spp. (22.3%), Klebsiella pneumoniae (7.4%) and Proteus mirabilis (3.7%). The antimicrobial susceptibility pattern for Escherichia coli showed high sensitivity to Nitrofurantoin (94.4%) and high resistance to Ampicillin (94.4%). CONCLUSION: Our study revealed one in every four incontinent patients had UTI and almost half of them suffered from previous episodes of UTI. Thus appropriate correction of the existing UTI can help in the treatment of UI.