High Burden of Bloodstream Infections Associated With Antimicrobial Resistance and Mortality in the Neonatal Intensive Care Unit in Pune, India

Abstract

Background: Antimicrobial resistance (AMR) is a growing threat to newborns in low- and middle-income countries (LMIC).

Methods: We performed a prospective cohort study in 3 tertiary neonatal intensive care units (NICUs) in Pune, India, to describe the epidemiology of neonatal bloodstream infections (BSIs). All neonates admitted to the NICU were enrolled. The primary outcome was BSI, defined as positive blood culture. Early-onset BSI was defined as BSI on day of life (DOL) 0-2 and late-onset BSI on DOL 3 or later.

Results: From 1 May 2017 until 30 April 2018, 4073 neonates were enrolled. Among at-risk neonates, 55 (1.6%) developed early-onset BSI and 176 (5.5%) developed late-onset BSI. The majority of BSIs were caused by gram-negative bacteria (GNB; 58%); among GNB, 61 (45%) were resistant to carbapenems. Klebsiella spp. (n = 53, 23%) were the most common cause of BSI. Compared with neonates without BSI, all-cause mortality was higher among neonates with early-onset BSI (31% vs 10%, P < .001) and late-onset BSI (24% vs 7%, P < .001). Non-low-birth-weight neonates with late-onset BSI had the greatest excess in mortality (22% vs 3%, P < .001).

Conclusions: In our cohort, neonatal BSIs were most commonly caused by GNB, with a high prevalence of AMR, and were associated with high mortality, even in term neonates. Effective interventions are urgently needed to reduce the burden of BSI and death due to AMR GNB in hospitalized neonates in LMIC.

Keywords: antimicrobial resistance; low- and middle-income countries; neonatal intensive care unit; neonatal sepsis.

Figure 1.

Study flow diagram. Neonates included in the early cohort were considered at risk for experiencing the outcome of early-onset BSI by their presence in the NICU during the risk period, DOL 0 through DOL 2. Neonates not at risk for early-onset BSI, those admitted on or after DOL 3, were excluded from the early cohort. Neonates included in the late cohort were considered at risk for experiencing the outcome of late-onset BSI by their presence in the NICU during the risk period, DOL 3 or later. Neonates not at risk for late-onset BSI, those who exited the NICU before DOL 3, were excluded from the late cohort. *Early exit, discharge (n = 26), or transfer to ward (n = 426) on same calendar day as admission. **Insufficient data, no birth weight or admission weight. Abbreviations: BSI, bloodstream infection; DOL, day of life; NICU, neonatal intensive care unit.

Figure 2.

Distribution of BSIs by day of life (DOL). BSI cases by DOL on which blood culture was obtained. Day of birth is DOL 0. Early-onset BSI cases (n = 55) occurred on DOL 0–2, whereas late-onset BSI cases (n = 176) occurred on DOL 3 or later. Figure is censored at DOL 20; 92% (n = 212) of BSIs occurred during the first 3 weeks of life. Abbreviations: BSI, bloodstream infection; CRO, carbapenem-resistant organism; GN, gram-negative; GP, gram-positive.

Figure 3.

A, All-cause mortality by birth weight strata and early-onset BSI, early cohort. All-cause mortality among early cohort neonates, expressed as proportion of neonates deceased by birth weight strata with 95% confidence intervals (CIs); CI for neonates with birth weight ≥2500 g and BSI is a 1-sided 97.5% CI. B, All-cause mortality by birth weight strata and late-onset BSI, late cohort. All-cause mortality among late cohort neonates, expressed as proportion of neonates deceased by birth weight strata with 95% CIs. Abbreviations: BSI, bloodstream infection; ELBW, extremely low birth weight; LBW, low birth weight; NS, not significant; VLBW, very low birth weight.