Information about antimicrobial use is scarce and poorly understood among neonatal intensive care units (NICUs) in India. In this study, we describe antimicrobial use in eight NICUs using four point prevalence surveys (PPSs).

The prevalence of antimicrobial resistance in India is among the highest in the world. Antimicrobial use in inpatient settings is an important driver of resistance, but is poorly characterized, particularly in hospitalized children. In this study, conducted as part of the Global Antimicrobial Resistance, Prescribing, and Efficacy in Neonates and Children (GARPEC) project, we examined the prevalence of and indications of antimicrobial use, as well as antimicrobial agents used among hospitalized children by conducting four point prevalence surveys in six hospitals between February 2016 and February 2017. A total of 681 children were hospitalized in six hospitals across all survey days, and 419 (61.5%) were prescribed one or more antimicrobials (antibacterials, antivirals, antifungals). Antibacterial agents accounted for 90.8% (547/602) of the total antimicrobial prescriptions, of which third-generation cephalosporins (3GCs) accounted for 38.9% (213/547) and penicillin plus enzyme inhibitor combinations accounted for 14.4% (79/547). Lower respiratory tract infection (LRTI) was the most common indication for prescribing antimicrobials (149 prescriptions; 24.8%). Although national guidelines recommend the use of penicillin and combinations as first-line agents for LRTI, 3GCs were the most commonly prescribed antibacterial agents (55/149 LRTI prescriptions; 36.9%). In conclusion, 61.5% of hospitalized children were on at least one antimicrobial agent, with excessive use of 3GCs. Hence there is an opportunity to limit their inappropriate use.

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.