Nosocomial Outbreak of New Delhi Metallo-β-Lactamase-1-Producing Gram-Negative Bacteria in South Africa: A Case-Control Study

PLoS One. 2015 Apr 24;10(4):e0123337. doi: 10.1371/journal.pone.0123337. eCollection 2015.

Abstract

Objective: New Delhi metallo-β-lactamase (NDM)-producing Gram-negative bacteria have spread globally and pose a significant public health threat. There is a need to better define risk factors and outcomes of NDM-1 clinical infection. We assessed risk factors for nosocomial infection with NDM-1-producers and associated in-hospital mortality.

Methods: A matched case-control study was conducted during a nosocomial outbreak of NDM-1-producers in an adult intensive care unit (ICU) in South Africa. All patients from whom NDM-1-producers were identified were considered (n=105). Cases included patients admitted during the study period in whom NDM-1 producing Gram-negative bacteria were isolated from clinical specimens collected ≥48 hours after admission, and where surveillance definitions for healthcare-associated infections were met. Controls were matched for age, sex, date of hospital admission and intensive-care admission. Conditional logistic regression was used to identify risk factors for NDM-1 clinical infection and associated in-hospital mortality.

Findings: 38 cases and 68 controls were included. Klebsiella pneumoniae was the most common NDM-1-producer (28/38, 74%). Cases had longer mean hospital stays (44.0 vs. 13.3 days; P < 0.001) and ICU stays (32.5 vs. 8.3 days; P < 0.001). Adjusting for co-morbid disease, the in-hospital mortality of cases was significantly higher than controls (55.3% vs. 14.7%; AOR, 11.29; P < 0.001). Higher Charlson co-morbidity index score (5.2 vs. 4.1; AOR, 1.59; P = 0.005), mechanical ventilation days (7.47 vs. 0.94 days; AOR, 1.32; P = 0.003) and piperacillin/tazobactam exposure (11.03 vs. 1.05 doses; AOR, 1.08; P = 0.013) were identified as risk factors on multivariate analysis. Cases had a significantly higher likelihood of in-hospital mortality when the NDM-1-producer was Klebsiella pneumoniae (AOR, 16.57; P = 0.007), or when they had a bloodstream infection (AOR, 8.84; P = 0.041).

Conclusion: NDM-1 infection is associated with significant in-hospital mortality. Risk factors for hospital-associated infection include the presence of co-morbid disease, mechanical ventilation and piperacillin/tazobactam exposure.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Anti-Bacterial Agents / pharmacology
  • Case-Control Studies
  • Cross Infection*
  • Disease Outbreaks*
  • Gram-Negative Bacteria / metabolism*
  • Gram-Negative Bacterial Infections / epidemiology*
  • Gram-Negative Bacterial Infections / microbiology*
  • Hospital Mortality
  • Humans
  • Intensive Care Units
  • Microbial Sensitivity Tests
  • Middle Aged
  • Odds Ratio
  • Risk Factors
  • South Africa / epidemiology
  • Young Adult
  • beta-Lactamases / biosynthesis*

Substances

  • Anti-Bacterial Agents
  • beta-Lactamases
  • beta-lactamase NDM-1

Grants and funding

This work was supported by the School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.