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. 2023 Jul 5;77(Suppl 1):S38-S45.
doi: 10.1093/cid/ciad282.

Maternal Colonization Versus Nosocomial Transmission as the Source of Drug-Resistant Bloodstream Infection in an Indian Neonatal Intensive Care Unit: A Prospective Cohort Study

Matthew L Robinson  1 , Julia Johnson  2   3 , Shilpa Naik  4 , Sunil Patil  4 , Rajesh Kulkarni  5 , Aarti Kinikar  5 , Vaishali Dohe  6 , Swati Mudshingkar  6 , Anju Kagal  6 , Rachel M Smith  7 , Matthew Westercamp  7 , Bharat Randive  8 , Abhay Kadam  8 , Ahmed Babiker  9 , Vandana Kulkarni  8 , Rajesh Karyakarte  6 , Vidya Mave  1   8 , Amita Gupta  1 , Aaron M Milstone  10 , Yukari C Manabe  1
Affiliations

Maternal Colonization Versus Nosocomial Transmission as the Source of Drug-Resistant Bloodstream Infection in an Indian Neonatal Intensive Care Unit: A Prospective Cohort Study

Matthew L Robinson et al. Clin Infect Dis. .

Abstract

Background: Drug-resistant gram-negative (GN) pathogens are a common cause of neonatal sepsis in low- and middle-income countries. Identifying GN transmission patterns is vital to inform preventive efforts.

Methods: We conducted a prospective cohort study, 12 October 2018 to 31 October 2019 to describe the association of maternal and environmental GN colonization with bloodstream infection (BSI) among neonates admitted to a neonatal intensive care unit (NICU) in Western India. We assessed rectal and vaginal colonization in pregnant women presenting for delivery and colonization in neonates and the environment using culture-based methods. We also collected data on BSI for all NICU patients, including neonates born to unenrolled mothers. Organism identification, antibiotic susceptibility testing, and next-generation sequencing (NGS) were performed to compare BSI and related colonization isolates.

Results: Among 952 enrolled women who delivered, 257 neonates required NICU admission, and 24 (9.3%) developed BSI. Among mothers of neonates with GN BSI (n = 21), 10 (47.7%) had rectal, 5 (23.8%) had vaginal, and 10 (47.7%) had no colonization with resistant GN organisms. No maternal isolates matched the species and resistance pattern of associated neonatal BSI isolates. Thirty GN BSI were observed among neonates born to unenrolled mothers. Among 37 of 51 BSI with available NGS data, 21 (57%) showed a single nucleotide polymorphism distance of ≤5 to another BSI isolate.

Conclusions: Prospective assessment of maternal GN colonization did not demonstrate linkage to neonatal BSI. Organism-relatedness among neonates with BSI suggests nosocomial spread, highlighting the importance of NICU infection prevention and control practices to reduce GN BSI.

Keywords: antimicrobial resistance; newborn; sepsis.

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Conflict of interest statement

Potential conflicts of interest. Y. C. M. reports payments to their institution from the CDC, consulting fees from Abbott STI Ad Board, honoraria payments from DKB Med on COVID, patents with TB polymer diagnostic, and holds a leadership role on the board with the Infectious Diseases Institution. They also report receipt of equipment from Hologic, Cepheid, Roche, ChemBio, Becton Dickinson, and miDiagnostics. A. G. reports funding from NIH, UNITAID, and CDC. They report participation in an advisory council with NIH/NIAID and the governing board with Indo US Science Technology and leadership roles with the IMPAACT Network TB Scientific Committee and the WHO MDR TB Guidelines Committee. J. J. reports funding from the CDC (grant number NU3HCK000001) and (grant number U54CK000617). They also report holding a position on the AAP Section on Neonatal-Pinatal Medicine Global Health Subcommittee and the Society for Healthcare Epidemiology of America Pediatric Leadership Council Steering Committee. M. R. Reports research and travel support from the CDC. V. M. reports funding support from NIH, NIAID, and CDC. A. M. reports research funding from CDC, NIH, AHRQ, and Merck. \ All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

Figures

Figure 1.
Figure 1.
Organism recovery from swabs and match to 21 neonatal BSI isolates from Cohort A by sample source and time of collection from birth, Pune, India, October 2018 to October 2019. Each tile represents a single time point and swab sample source for an individual neonate. There were no exact matches between neonatal BSI isolate species and drug susceptibility profile to maternal colonization swabs. Drug-resistant GN defined as those resistant to 3rd/4th generation cephalosporins or piperacillin/tazobactam. Abbreviations: BSI, bloodstream infection; GN, gram-negative.
Figure 2.
Figure 2.
Strain relatedness, dates of hospitalization, bacteremia onset, and select AMR genes for 19 neonates (Cohort A, n = 6; Cohort B, n = 13) with Klebsiella pneumoniae bloodstream infection during the study period, Pune, India, October 2018 to October 2019. Strain relatedness is expressed on the left as a rooted maximum likelihood phylogenetic tree followed by the ST assigned by MLST. Next to the right, pairwise SNPs between each pair of isolates is presented as a rotated distance matrix with the diagonal aligned with the corresponding isolate from the phylogenetic tree. Corresponding period of hospitalization and bacteremia onset are displayed on the right followed by presence of select AMR genes. Abbreviations: AMR, antimicrobial resistance; MLST, multilocus sequence typing; SNP, single nucleotide polymorphism; ST, sequence type.
Figure 3.
Figure 3.
Network graph of pairwise SNPs between Klebsiella pneumoniae, Burkholderia cenocepacia, and Acinetobacter baumannii isolates from Cohort A and B neonatal bloodstream infections and sink samples with available sequencing data, Pune, India, October 2018 to October 2019. Relative position of unconnected isolates is arbitrary. An additional 10 BSI isolates of other species without linkage to other isolates are not plotted. Abbreviations: BSI, bloodstream infection; SNP, single nucleotide polymorphism.
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