Evaluating the Source of Neonatal Bloodstream Infections due to Classically Hospital Acquired Pathogens in the Neonatal Intensive Care Unit in Pune, India

This study is part of CDC's Safe Healthcare, Epidemiology, and Prevention Research Development (SHEPheRD) Program under Domain 7: International HAI and Other Adverse Healthcare Event Prevention. The PIs for this study are Dr. Julia Johnson of Johns Hopkins and Dr. Shilpa Naik of BJGMC. CoPIs are Dr. Aarti Kinikar and Renu Bharadwaj of BJGMC.

While childhood mortality has declined significantly throughout the world, progress has been much slower in reducing neonatal mortality. In regions with the highest mortality for neonates, infection accounts for 30-50% of deaths. These trends hold true in India, the country with the highest absolute burden of neonatal infection and mortality. Substantial gains have been made in improving survival of children, but the neonatal mortality rate continues to be high at 28 per 1,000 live births as of 2015. Facility-based births are on the rise, and low and middle income countries (LMIC) increasingly are caring for neonates in the hospital setting, including in the Neonatal Intensive Care Unit (NICU). In a recent Indian study, the incidence of sepsis in inborn neonates admitted to the NICU was 14.3%. Strikingly, this study revealed that the pathogen mix in early onset (<72 hours of life) and late onset (>72 hours of life) neonatal sepsis was similar; Acinetobacter spp. (22%), Klebsiella spp. (17%), and E. coli (14%) were the three most common pathogens isolated. Drug resistance was ubiquitous, with 82% of Acinetobacter isolates, 54% of Klebsiella isolates, and 14% of E. coli isolates meeting criteria for multidrug resistance. In the United States and other high income countries, these pathogens are more typically associated with late-onset hospital acquired infection (HAI). In designing interventions to reduce early onset sepsis (EOS) in neonates, one must consider potential reservoirs of transmission for these pathogens. 

Preliminary data from the Sassoon General Hospital in Pune, India, corroborates the surprisingly high prevalence of Gram-negative pathogens isolated from blood cultures from infants in the NICU. In the last 6 months, the NICU has averaged 290 infant admissions per month, >85% of whom were inborn and 70% of whom were low birth weight (<2500 grams). Of 468 blood cultures in the last 8 months, 20% were positive. The most common bacterial isolate was Klebsiella pneumoniae. 

The neonatal microbiome gradually evolves after delivery, through acquisition of flora during the delivery process and contact with caregivers and the environment. Colonization with pathogenic bacteria, especially antimicrobial-resistant (AMR) Gram-negative bacteria, during hospitalization places neonates at risk of developing infection. Colonization pressure increases transmission in hospitalized patients, increasing risk of outbreaks in the most vulnerable patients. Infants with sepsis due to multidrug-resistant (MDR) pathogens are more likely to develop septic shock and have higher mortality, and those who survive have prolonged hospital stays. Data on prevalence of AMR colonization and reservoirs of transmission in LMIC, including India, are sparse and are often limited to investigations during outbreaks. In an Indian cohort study assessing infection in neonates with extended-spectrum beta-lactamase-producing organisms (ESBL), gestational age and duration of hospital stay were found to be risk factors, whereas previous antibiotic exposure and low birth weight were not found to be statistically significant.

Sources of colonization with AMR Gram-negative bacteria in neonates may be endogenous after exposure to empiric antibiotics, due to acquisition from mothers during delivery or after birth, due to environmental sources including the hospital’s water supply, or due to contact with colonized healthcare workers. The relative importance of these sources of colonization and infection in Indian NICUs is not well understood. One study of neonates conducted at an Indian tertiary care center did assess the role of gut colonization with Gram-negative bacteria by evaluating the relatedness of isolates recovered in the bloodstream with those cultured from the gut prior to infection. However, this study did not evaluate colonization of other body sites, nor did it assess potential sources of colonization, highlighting a significant gap in the understanding of acquisition of colonization and infection in neonates.

Primary Objective

To describe the correlation between maternal vaginal and gastrointestinal colonization with Gram-negative bacteria, including with AMR strains, and Gram-negative bloodstream infections among neonates admitted to the NICU

Secondary Objectives

1. 
   To describe the correlation of maternal vaginal and gastrointestinal colonization with non-GN organisms and bloodstream infections due to non-GN organisms among neonates admitted to the NICU; 
2. 
   To identify environmental reservoirs of Gram-negative bacteria in the NICU; and
3. 
   To establish a repository of environmental swabs, maternal vaginal and rectal swabs, maternal stool samples, neonatal skin and perirectal swabs, and neonatal blood bacterial isolates that can be used to further assess microbial and host factors associated with neonatal blood infections