<i>In Vitro</i> Activity of Two Cefepime-Based Novel Combinations, Cefepime/Taniborbactam and Cefepime/Zidebactam, against Carbapenemase-Expressing <i>Enterobacterales </i>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: b-lactam-b-lactamase inhibitor (BL/BLI) or b-lactam-b-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#8mg/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 b-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 b-lactam enhancer mechanism-based cefepime/zidebactam showed consistent activity against single-or dual-carbapenemase-producing isolates including E. coli with PBP3 inserts.</p

Clinical characteristics of and antibody response to spotted fever group rickettsial infections in South India: Case series and serological cohort study.

OBJECTIVE: The clinical and serological characteristics of spotted fever group rickettsial (SFGR) infections in South Asia are poorly understood. We studied the clinical presentation and the IgM/IgG response in cases enrolled at two health care centres in South India. METHOD: We enrolled 77 patients. Fifty-seven of these patients were recruited at a tertiary care centre, the remaining 20 at a community hospital (secondary care level). Diagnostic tests included IgM and IgG enzyme-linked immunosorbent assay and polymerase chain reaction. Over a period of 1 year, 41 cases were followed up for repeated sero-analysis. RESULTS: Median age was 9 years (range 1-79). A rash was present in 74% of cases (57/77). In cases aged <15 years, rash was present in 94% (44/47) vs. 43% (13/30) in cases aged ≥15 years. An eschar was found in two cases (3%). Severe infection or complications occurred in 10 cases (13%). These included central nervous system infection (6/77, 8%), kidney injury (3/77, 4%), shock (3/77, 4%), lung involvement (2/77, 3%) and peripheral gangrene (2/77, 3%). IgM antibody levels increased faster after fever onset than IgG antibodies, peaking at 50 and 60 days, respectively. After the peak, IgM and IgG levels showed a slow decline over one year with less than 50% of cases showing persistent IgG antibody levels. CONCLUSION: Spotted fever group rickettsial infections in South India may be under-diagnosed, as many cases may not develop a rash. The proportion of cases developing severe infection seems lower than for scrub typhus in this region. IgG seroprevalence may substantially underestimate the proportion in a population with past SFGR infection

Impact of COVID-19 Vaccination on Seroprevalence of SARS-CoV-2 among the Health Care Workers in a Tertiary Care Centre, South India

Global vaccine development efforts have been accelerated in response to the devastating COVID-19 pandemic. The study aims to determine the seroprevalence of SARS-CoV-2 IgG antibodies among vaccine-na&iuml;ve healthcare workers and to describe the impact of vaccination roll-out on COVID-19 antibody prevalence among the health care centers in tertiary care centers in South India. Serum samples collected from vaccinated and unvaccinated health care workers between January 2021 and April 2021were subjected to COVID-19 IgG ELISA, and adverse effects after the first and second dose of receiving the Covishield vaccine were recorded. The vaccinated group was followed for a COVID-19 breakthrough infection for a period of 6 months. Among the recruited HCW, 156 and 157 participants were from the vaccinated and unvaccinated group, respectively. The seroprevalence (COVID-19 IgG ELISA) among the vaccinated and unvaccinated Health Care Workers (HCW) was 91.7% and 38.2%, respectively, which is statistically significant. Systemic and local side-effects after Covishield vaccination occur at lower frequencies than reported in phase 3 trials. Since the COVID-19 vaccine rollout has commenced in our tertiary care hospital, seropositivity for COVID-19 IgG has risen dramatically and clearly shows trends in vaccine-induced antibodies among the health care workers