Pallab Ray

Necrotizing soft tissue infections (NSTIs) carry 10 to 30% mortality. Current empirical antimicrobial guidance derives almost entirely from Western cohorts dominated by Streptococcus pyogenes and aerobic-anaerobic consortia, yet whether this microbial paradigm applies to tropical, high-antimicrobial-pressure settings has not been tested with culture-independent methods. We did a prospective cohort study of 169 patients with intraoperatively confirmed NSTI at a North Indian tertiary center (2021 to 2024). Wound tissue underwent aerobic and anaerobic culture, QIIME2-based 16S rRNA gene amplicon sequencing (V3-V4), and targeted SYBR Green quantitative PCR (qPCR) for Acinetobacter baumannii and S. pyogenes . The wound microbiota was overwhelmingly Gram-negative and polymicrobial, anchored by A. baumannii (culture, 33.7%; metagenomics, 49.1%; qPCR, 37.9%), Escherichia coli (32.0%), and Klebsiella pneumoniae (20.7%); S. pyogenes contributed only 4.7% of culture-positive cases. Polymicrobial wounds had higher Shannon diversity (2.59 versus 2.33; P = 0.048) and discrete community composition (PERMANOVA R ² = 0.511; P = 0.010). Culture-metagenomics agreement ranged from almost perfect for Escherichia (κ = 0.849) to slight for Streptococcus (κ = 0.131). North Indian NSTIs present a microbial picture distinct from the Western paradigm, with implications for empirical therapy.

Objective: Definitive guidance regarding the duration of antibiotics for neonatal sepsis is lacking. We hypothesised that a 7-day antibiotic course is non-inferior to a 14-day course for treating culture-proven sepsis. Design: Randomised, controlled, non-inferiority trial with masked outcome assessment in eight centres in a low and middle-income country. Patients: Neonates with a birth weight (BW) ≥1000 g and blood culture-proven sepsis were randomised on day 7 of sensitive antibiotic therapy provided sepsis had clinically remitted. Exclusions: Staphylococcus aureus or fungal sepsis, and infections requiring prolonged antibiotics. We planned to enrol 350 per group, assuming 10% rate of primary outcome, +7% non-inferiority margin, one-sided 5% alpha, 90% power, 10% loss to follow-up. Intervention: 7 days (no further treatment); comparison: 14 days (7 days postrandomisation). Outcomes: Primary: relapse (definite or probable) within day 21 postantibiotic completion. Secondary outcomes: composite of mortality or definite/probable/secondary sepsis and duration of hospitalisation. One interim analysis (per protocol (PP)) was planned. Results: 126 and 135 subjects were recruited in 7-day and 14-day groups, respectively, with mean (SD) birth weight (BW) 2250.9 (741.1) and 2187.8 (718.8) g. The trial was terminated early, based on interim PP analysis. 2/125 and 6/130 subjects had the primary outcome in 7-day and 14-day groups, respectively (risk difference (RD)=−3.0% (99.5% CI −9.2%, +3.1%), below non-inferiority margin). The composite secondary outcome also favoured the 7-day regimen (RD: −3.7% (99.5% CI −12.4% to +5.1%)). Duration of hospitalisation was shorter in 7-day group (median difference: −4 days (95% CI −5 to –3)). Conclusions: A 7-day course of antibiotics may be non-inferior to a 14-day course for uncomplicated bacterial neonatal sepsis. Trial registration number: NCT03280147.

Background: Accurate estimates of incremental cost (IC) attributable to antimicrobial resistance (AMR) provide information of immense public health importance to the policy makers. Here, we present the IC from patient perspective for treating antimicrobial-resistant pathogens in India. Methods: This cohort study was conducted in eight hospitals including government (GH), private (PH) and trust hospitals (TH), considering their ownership, geographical location and categories of cities. This study had a retrospective component, which calculated the direct cost of treating resistant and susceptible blood stream infections caused by selected WHO priority pathogens. The prospective component estimated indirect cost and financial coping strategies for the treatment of AMR. In the retrospective component, 1723 records were included and 170 patients were recruited in the prospective component. Results: The median total cost for management of antimicrobial-resistant infections was US$199 (IQR 89, 377) as opposed to US$109 (IQR 55, 229) for susceptible infection in GH. Our study has revealed that the ICs for Enterobacteriaceae (53.9%), Acinetobacter (43.8%) and Staphylococcus (49.7%) at GHs were higher for resistant pathogens. Pharmaceutical cost was the major contributor to IC at GHs (61.5%) and PHs (27.1%). In the prospective component, 46.5% of patients resorted to borrowing money for hospitalisation expenses and the per day median total cost for resistant and sensitive infection was estimated to be US$65 and US$35, respectively. Conclusions: The current study concluded that the presence of any critical or high priority pathogens led to an increase in the direct and indirect medical costs. The IC varied with hospital type, length of stay, pathogen, comorbidities and diagnosis. Prospective studies are needed for precise understanding of variations in the costs of treating AMR infections.