title: Nosocomial Outbreak of New Delhi Metallo-β-Lactamase-1-Producing Gram-Negative Bacteria in South Africa: A Case-Control Study.
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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Epidemiology and Surveillance Unit, National Institute for Occupational Health, National Health Laboratory Service, Johannesburg, South Africa; Department of Community Health, School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Pieter
authors.initials: P
authors.lastname: de Jager
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Tobias
authors.initials: T
authors.lastname: Chirwa
authors.affiliation: Department of Community Health, School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Shan
authors.initials: S
authors.lastname: Naidoo
authors.affiliation: Centre for Opportunistic, Tropical and Hospital Infections, National Institute for Communicable Diseases, National Health Laboratory Service, Johannesburg, South Africa; Department of Clinical Microbiology and Infectious Diseases, School of Pathology, Faculty of Health Science, University of Witwatersrand, Johannesburg, South Africa.
authors.forename: Olga
authors.initials: O
authors.lastname: Perovic
authors.affiliation: Outbreak Response Unit, National Institute for Communicable Diseases, National Health Laboratory Service, Johannesburg, South Africa.
authors.forename: Juno
authors.initials: J
authors.lastname: Thomas
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D016022:Case-Control Studies; D003428:Cross Infection; D004196:Disease Outbreaks; D006090:Gram-Negative Bacteria / Q000378:metabolism*; D016905:Gram-Negative Bacterial Infections / Q000453:epidemiology* / Q000382:microbiology*; D017052:Hospital Mortality; D006801:Humans; D007362:Intensive Care Units; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D016017:Odds Ratio; D012307:Risk Factors; D013019:South Africa / Q000453:epidemiology; D055815:Young Adult; D001618:beta-Lactamases / Q000096:biosynthesis*
chemical_list: D000900:Anti-Bacterial Agents; D001618:beta-Lactamases; C552864:beta-lactamase NDM-1