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We conducted a multicenter surveillance study to identify changes in antimicrobial susceptibility patterns of Salmonella Typhi and S. Paratyphi in India since the COVID-19 pandemic began. We collected S. Typhi and S. Paratyphi isolates from blood or bone marrow culture-confirmed enteric fever cases at eight sites in seven cities across India between 2021 and 2024. We tested the antibiotic susceptibility of 1150 S. Typhi isolates and 265 S. Paratyphi isolates via disc diffusion and determined their minimum inhibitory concentrations (MICs) of ceftriaxone and azithromycin via broth dilution. We identified 18 S. Typhi isolates from Ahmedabad that were resistant to ceftriaxone, indicating a larger emergence of third-generation cephalosporin-resistant S. Typhi in Western India with a novel plasmid profile. Furthermore, we observed yearly increases in the mean, median and 90th percentile of azithromycin MICs for S. Typhi and S. Paratyphi isolates throughout India between 2021 and 2023. Finally, we found that only 0.70% of S. Typhi isolates and 1.13% of S. Paratyphi isolates exhibited susceptibility to ciprofloxacin. Our results indicate the necessity for a shift from ciprofloxacin in the treatment of enteric fever, and the importance of implementing long-term monitoring of resistance to alternative antibiotics such as azithromycin and ceftriaxone.

ObjectiveDefinitive 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.DesignRandomised, controlled, non-inferiority trial with masked outcome assessment in eight centres in a low and middle-income country.PatientsNeonates 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.Intervention7 days (no further treatment); comparison: 14 days (7 days postrandomisation).OutcomesPrimary: 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.Results126 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)).ConclusionsA 7-day course of antibiotics may be non-inferior to a 14-day course for uncomplicated bacterial neonatal sepsis.Trial registration number NCT03280147.

Paratyphoid fever caused by S . Paratyphi A is endemic in parts of South Asia and Southeast Asia. The proportion of enteric fever cases caused by S . Paratyphi A has substantially increased, yet only limited data is available on the population structure and genetic diversity of this serovar. We examined the phylogenetic distribution and evolutionary trajectory of S . Paratyphi A isolates collected as part of the Indian enteric fever surveillance study “Surveillance of Enteric Fever in India (SEFI).” In the study period (2017–2020), S . Paratyphi A comprised 17.6% (441/2503) of total enteric fever cases in India, with the isolates highly susceptible to all the major antibiotics used for treatment except fluoroquinolones. Phylogenetic analysis clustered the global S . Paratyphi A collection into seven lineages (A-G), and the present study isolates were distributed in lineages A, C and F. Our analysis highlights that the genome degradation events and gene acquisitions or losses are key molecular events in the evolution of new S . Paratyphi A lineages/sub-lineages. A total of 10 hypothetically disrupted coding sequences (HDCS) or pseudogenes-forming mutations possibly associated with the emergence of lineages were identified. The pan-genome analysis identified the insertion of P2/PSP3 phage and acquisition of IncX1 plasmid during the selection in 2.3.2/2.3.3 and 1.2.2 genotypes, respectively. We have identified six characteristic missense mutations associated with lipopolysaccharide (LPS) biosynthesis genes of S . Paratyphi A, however, these mutations confer only a low structural impact and possibly have minimal impact on vaccine effectiveness. Since S . Paratyphi A is human-restricted, high levels of genetic drift are not expected unless these bacteria transmit to naive hosts. However, public-health investigation and monitoring by means of genomic surveillance would be constantly needed to avoid S . Paratyphi A serovar becoming a public health threat similar to the S . Typhi of today.

Streptococcus pneumoniae is the major cause of childhood pneumonia and related deaths in India. Widespread use of erythromycin for the treatment of pneumonia has led to the emergence of erythromycin resistance. Despite this increase in erythromycin resistance, there are very little data on resistance determinants from India. Hence, we aimed to perform the molecular characterization of erythromycin-resistant invasive pneumococcal isolates in India. In this study, 250 erythromycin-resistant invasive isolates obtained from four Indian hospitals between 2014 and 2019 were included. The isolates were reconfirmed by standard CDC protocols, followed by detection of erm(B), mef(A/E) genes, and screening for mutations in 23S rRNA, ribosomal proteins L4 and L22. Among the 250 erythromycin-resistant isolates, 46% (n = 114) and 35% (n = 87) carried the mef(A/E) gene and erm(B) gene, respectively; both genes were present in 8% (n = 20) of the isolates and 12% (n = 29) of the studied strains did not bear any of them. The major mutations associated with erythromycin resistance in 23S rRNA, such as A2060C, A2061G, and C2613G, were absent. The predominant serotypes were 19F, 14, 23F, 6A, 6B, 19A, and 9V. The major clonal complexes were CC320, followed by CC230 and CC63. The predominant gene was mef(A/E), and most of the serotypes were PCV13 (54%). This study contributes to the baseline understanding of the erythromycin resistance determinants associated with the serotypes and sequence types (ST) of Indian invasive S. pneumoniae.

Background Neonatal sepsis is a global public health problem. There is no consensus regarding the optimum duration of antibiotics for culture-proven neonatal sepsis. Published randomized controlled trials (RCTs) comparing shorter versus longer courses of antibiotics provide low-quality evidence with serious risk of bias. We hypothesized that among neonates with uncomplicated culture-proven sepsis, antibiotic duration of 7 days is not inferior to 14 days. Methods This is a multi-centric, parallel-group, stratified, block-randomized, active-controlled, non-inferiority trial with outcome assessment blinded. Stratification is by center and birth weight. Neonates weighing ≥1000 g at birth, with blood-culture-proven sepsis (barring Staphylococcus aureus and fungi), without conditions warranting > 14 days antibiotics, and who clinically remit, are enrolled in the RCT on day 7 of administration of sensitive antibiotics. They are randomly allocated to no further antibiotics (intervention arm: total 7 days) or 7 more days of the same antibiotics (control arm: total 14 days). Allocation is concealed by opaque, sealed envelopes. The primary outcome is “definite or probable relapse” within 21 days after antibiotic completion. Secondary outcomes include definite and probable relapses at various timepoints until day 35 post-randomization, secondary infections, and adverse events. The neonatologist adjudicating probable relapses and lab personnel are blinded. Three hundred fifty subjects will be recruited in each arm, assuming a non-inferiority margin of 7%, one-sided alpha error 5%, and power of 90%. Analysis will be per protocol and by intention-to-treat. An independent Data Safety Monitoring Board monitors adverse events and will perform one interim analysis when 50% of expected primary outcomes have occurred or 50% of subjects have completed follow-up, whichever is earlier. O’Brien-Fleming criteria will be used to stop for mid-term benefit and Pocock’s to stop for mid-term harm. A priori subgroup analyses are planned by birth weight categories, gram-stain status of pathogens, and radiological pneumonia. Discussion This trial will provide evidence to guide practice regarding optimum duration of antibiotics for culture-proven neonatal bacterial sepsis. If a 7-day regime is proved to be non-inferior to a 14-day regime, it is likely to reduce hospital stay, costs, adverse effects of drugs, and nosocomial infections. Trial registration Clinical Trials Registry India CTRI/2017/09/009743 . Registered on 13 September 2017.

Objectives To assess the proportion of children, symptomatic for urinary tract infection (UTI), with urine culture showing single bacterial species >10 4 CFU/mL, and to compare patient and disease characteristics between children having low counts (from >10 4 -10 5 CFU/mL) and those with counts >10 5 CFU/mL. Methods Prospective observational study, enrolling symptomatic children aged 1 month to 12 years. Mid-stream clean-void or catheter collected urine were cultured. Children with single species >10 4 CFU/mL were scheduled for imaging studies, following age criteria of Indian Society of Pediatric Nephrology guidelines. The main outcome was proportion with single bacterial species >10 4 CFU/mL in urine culture. Results Of 216 children (132 males) with median (IQR) age of 24 (12, 48) months, 38 (17.6%) showed single species growth >10 4 CFU/mL. Of these, 29 (13.4%) were diagnosed as UTI at cutoff >10 5 CFU/mL, and an additional 9 (4.2%) were found to have ‘probable low-count UTI’ (from >10 4 to 10 5 CFU/mL). One child in the latter group had bilateral hydroureteronephrosis, vesico-ureteral reflux and renal scarring. There was largely no difference in parameters between children with low counts and those with counts >10 5 CFU/mL. Conclusion An additional proportion of symptomatic children with probable urinary tract infection and possible underlying urological abnormalities may be identified by lowering bacterial colony count cutoff to >10 4 CFU/mL, in clean-voided and catheter-based urine samples.

We report a case of Chlamydia trachomatis serovar G urogenital tract infection in a 33-year-old human immunodeficiency virus-1 (HIV-1) seropositive Indian bisexual male. This case highlights the emergence of a new serovar in India. The patient was tested positive for C. trachomatis by both cryptic plasmid and omp A gene polymerase chain reaction (PCR). On further characterization using polymerase chain reaction - restriction fragment length polymorphism (PCR-RFLP) and omp A gene sequencing, the strain was found to be C. trachomatis serovar G. His spouse was also found to be infected with C. trachomatis serovar G. Phylogenetic analysis was performed on the clinical isolates obtained from both partners and were found to be identical to the isolates available in GenBank. The sexual network could not be traced further. Detection of a new genotype suggests importation of a new strain into the population probably by sexual contact with a person from a geographical area where the strain is common. Identifying circulating genotypes in the community can assist in developing strategies for improved sexually transmitted disease control.

Background Acinetobacter baumannii has emerged as an important opportunistic pathogen. Its ability to develop resistance to multiple antibiotics leaves few treatment options. AdeRS, a two-component regulatory system, which controls expression of the adeABC efflux pump is involved in multidrug resistance. There is lack of data regarding presence of virulence factors leading to antimicrobial resistance and their correlation with the outcome of the patients. The study was done to evaluate the prevalence of virulence factors AdeRS gene responsible for the accentuation of drug resistance, and correlation with the clinical outcome of the patient. Methods Clinical details of 80 patients with labeled A. baumannii infection were collected and analyzed with the resistance patterns of the isolates and molecular detection of the AdeRS virulence gene. Results 80 patients with labeled A. baumannii infection were included in the study. Most common presentation among patients with A. baumannii was pneumonia (46.25%) followed by sepsis. 63.75% of patients were admitted in the ICU. Neonates were mostly affected. Of the total 37 neonates with A. baumannii infections, 26 were hospital acquired. Mean weight of neonates with infection was 2.1 kg. 45.9% neonates with A. baumannii infections had undergone surgery for congenital anomalies. Sepsis was the most common presentation among neonates. Overall, mortality was 41.25%. The maximum mortality was among neonates (57.6%). Children presenting with sepsis had a higher mortality. Mortality in ICU patients was 78.8% compared with 21% in the wards. Average length of stay in the hospital after acquisition of A. baumannii infection was 20.2 days. Of the total 80 isolates, 2.5% were MDR and 86.25% were XDR strains. AdeRS was present in 90% of the isolates. All the isolates with XDR pattern of drug resistance had AdeRS gene. 27.5% of the isolates were tigecycline resistant and AdeRS gene was present in all them. Thirty-three patients who died all possessed AdesRS gene and were XDR strains. Conclusion A. baumannii is responsible for a substantial percentage of nosocomial infections. Presence of AdeRS gene reduces the susceptibility to large number of drugs and thus selects out XDR A. baumannii with high mortality rates in the hospital settings, leaving efflux pump inhibitors as the therapy of choice. Disclosures All authors: No reported disclosures.