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Background: Multi-drug resistant organisms are an increasingly important cause of neonatal sepsis. Aim: This study aimed to review neonatal sepsis caused by multi-drug resistant Enterobacteriaceae (MDRE) in neonates in Johannesburg, South Africa. Methods: This was a cross sectional retrospective review of MDRE in neonates admitted to a tertiary neonatal unit between 1 January 2013 and 31 December 2015. Results: There were 465 infections in 291 neonates. 68.6% were very low birth weight (< 1500 g). The median age of infection was 14.0 days. Risk factors for MDRE included prematurity (p = 0.01), lower birth weight (p = 0.04), maternal HIV infection (p = 0.02) and oxygen on day 28 (p < 0.001). The most common isolate was Klebsiella pneumoniae (66.2%). Total MDRE isolates increased from 0.39 per 1000 neonatal admissions in 2013 to 1.4 per 1000 neonatal admissions in 2015 (p < 0.001). There was an increase in carbapenem-resistant Enterobacteriaceae (CRE) from 2.6% in 2013 to 8.9% in 2015 (p = 0.06). Most of the CRE were New Delhi metallo – β lactamase- (NDM) producers. The all-cause mortality rate was 33.3%. Birth weight (p = 0.003), necrotising enterocolitis (p < 0.001) and mechanical ventilation (p = 0.007) were significantly associated with mortality. Serratia marcescens was isolated in 55.2% of neonates that died. Conclusions: There was a significant increase in MDRE in neonatal sepsis during the study period, with the emergence of CRE. This confirms the urgent need to intensify antimicrobial stewardship efforts and address infection control and prevention in neonatal units in LMICs. Overuse of broad- spectrum antibiotics should be prevented.
This is a retrospective descriptive cross-sectional study. All newborn neonates admitted to the neonatal unit between 01 January 2013 and 31 December 2015 were eligible for inclusion. The study group included all neonates with culture proven blood stream infection (BSI) caused by MDRE. A control group of 30% of all neonates without infection admitted to the neonatal unit during the study period was randomly generated from the neonatal database using SPSS IBM 24. Subjects were identified through the laboratory information system of the National Health Laboratory Service (NHLS). Patient characteristics were obtained from the neonatal computer database. Information was obtained from hospital records on discharge of each neonatal patient and was entered into a computerised database for the purpose of quality control. Data was managed using Research Electronic Data Capture (REDCAP), hosted by the University of the Witwatersrand [9]. Maternal information, demographic and clinical characteristics, as well as survival to hospital discharge, were described for each patient. Causative organisms and their antimicrobial sensitivity patterns were described. Organism identification and antimicrobial susceptibility testing was done on the Vitek 2® (bioMerieux, Marcy-I’Etoile, France). Vitek 2 breakpoint interpretation was based on the Clinical and Laboratory Standards Institute (CLSI) guidelines. Isolates were characterised as CRE based on carbapenem Etest® (bioMerieux, Marcy-I’Etoile, France) minimum inhibitory concentration (MIC) testing. Colistin broth micro-dilution testing was not performed and hence colistin susceptibility rates cannot be reported for all isolates. Multiplex PCR for the carbapenemase genes (for blaNDM, blaKPC, blaOXA-48 and its variants, blaGES, blaIMP and blaVIM; LightMix Modular kits, Roche Diagnostics, Basel, Switzerland) was performed on a subset of the CRE isolates. Typing of isolates was not performed. IBM SPSS 24 was used to analyse the data.. Maternal and neonatal characteristics were described for each patient (not bacterial isolate). Microbiological information (resistance patterns, isolates over time) was analysed for each bacterial isolate. Mean and standard deviation or median and range, were used to describe central tendency in continuous variables, depending on the distribution of the data. Categorical variables were described using frequency and percentages. Only valid cases were analysed for each variable (i.e. missing cases were excluded). Two comparisons were performed. Firstly, survivors and non- survivors within the MDRE group were compared to determine risk factors for mortality. Secondly, the MDRE group and control group were compared to establish associations with MDRE infection. Frequencies were compared using Chi Square analysis, while unpaired t tests were used to compare continuous variables, as the data was normally distributed. A p value of 0.05 was considered to be statistically significant. Adjusted odds ratios were determined through binary logistic regression for significant associations with mortality and MDRE infection respectively. Ethics clearance was obtained from the Human Research Ethics Committee of the University of the Witwatersrand (Certificate M 151108). Permission was obtained to access the Laboratory information system from the NHLS. Early-onset sepsis (EOS) was defined as culture proven sepsis within the first 72 h of life, while late onset sepsis (LOS) was referred to as culture proven sepsis after 72 h of life [1]. Multidrug resistance was defined as the isolate being non-susceptible to ≥1 agent in ≥3 antimicrobial categories [10]. The presence of resistance to third generation cephalosporins was used as a marker for ESBL production. The presence of cefoxitin resistance was used as a marker for Amp C beta-lactamase production. Necrotising enterocolitis (NEC) was defined as modified Bell’s stages 2 or 3 [11]. Resuscitation at birth was defined as the need for bag mask ventilation. “Outborn” referred to all neonates born outside the study hospital. Very low birth weight indicated neonates with a birth weight below 1500 g. Mortality was defined as all-cause mortality during hospitalization.
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