Research Article: Multiple antibiotic resistance as a risk factor for mortality and prolonged hospital stay: A cohort study among neonatal intensive care patients with hospital-acquired infections caused by gram-negative bacteria in Vietnam

Date Published: May 8, 2019

Publisher: Public Library of Science

Author(s): Lynn Peters, Linus Olson, Dung T. K. Khu, Sofia Linnros, Ngai K. Le, Håkan Hanberger, Ngoc T. B. Hoang, Dien M. Tran, Mattias Larsson, Laura Folgori.


Antibiotic resistance (ABR) is an increasing burden for global health. The prevalence of ABR in Southeast Asia is among the highest worldwide, especially in relation to hospital-acquired infections (HAI) in intensive care units (ICU). However, little is known about morbidity and mortality attributable to ABR in neonates.

This study aimed to assess mortality and the length of hospitalization attributable to ABR in gram-negative bacteria (GNB) causing HAI in a Vietnamese neonatal ICU (NICU).

We conducted a prospective cohort study (n = 296) in a NICU in Hanoi, Vietnam, from March 2016 to October 2017. Patients isolated with HAI caused by GNB were included. The exposure was resistance to multiple antibiotic classes, the two outcomes were mortality and length of hospital stay (LOS). Data were analysed using two regression models, controlling for confounders and effect modifiers such as co-morbidities, time at risk, severity of illness, sex, age, and birthweight.

The overall case fatality rate was 44.3% and the 30 days mortality rate after infection was 31.8%. For every additional resistance to an antibiotic class, the odds of a fatal outcome increased by 27% and LOS increased by 2.1 days. These results were statistically significant (p < 0.05). ABR was identified as a significant risk factor for adverse outcomes in neonates with HAI. These findings are generally in line with previous research in children and adults. However, heterogeneous study designs, the neglect of important confounders and varying definitions of ABR impair the validity, reliability, and comparability of results.

Partial Text

Antimicrobial resistance (AMR), in general, is the ability of a pathogen to withstand the effects of antimicrobials. Consequently, simple infections can become lethal again without effective tools to fight them. Antibiotic resistance (ABR) in bacteria is a consequence of selective antibiotic pressure in the environment, in human and veterinary medicine and food production or cross-transmission between individuals [1–4]. With a high number of antibiotics used in a limited area, healthcare settings and intensive care units (ICU) in particular are one of the main routes of emergence and transmission for resistant bacteria [3,5–10].

In a prospective cohort study, we assessed the effect of multiple antibiotic resistance (MAR) in gram-negative bacteria (GNB) causing hospital-acquired infections (HAI) in Vietnamese neonates and young infants on mortality and the length of hospital stay (LOS). The isolates showed a high level of resistance against multiple antibiotic classes. Higher rates of antibiotic resistance were significantly associated with higher mortality and a longer hospital stay when confounding factors were held constant.

Antibiotic resistance in gram-negative bacteria, here measured as resistance to multiple antibiotic classes, is a significant risk factor for mortality and prolonged hospital stay in patients admitted to a neonatal intensive care unit with hospital-acquired infections in the Vietnamese context. The adjustment for confounders such as co-morbidities, severity of illness and time at risk is essential to prevent biased results, yet not common practice in the field.