A retrospective analysis of pathogen profile, antimicrobial resistance and mortality in neonatal hospital-acquired bloodstream infections from 2009-2018 at Tygerberg Hospital, South Africa

Abstract

Background: Analysis of hospital-acquired bloodstream infection (HA-BSI) trends is important to monitor emerging antimicrobial resistance (AMR) threats and guide empiric antibiotic choices.

Methods: A retrospective 10-year review of neonatal HA-BSI was performed at Tygerberg Hospital's neonatal unit in Cape Town, South Africa. Neonatal clinical and laboratory data from 2014 to 2018 (Period 2) was compared with published data from 2009 to 2013 (Period 1).

Results: The neonatal unit's HA-BSI rate declined between periods from 3.9/1000 inpatient-days in Period 1 to 3.3/1000 inpatient-days in Period 2 (p = 0.002). Pathogen yield and blood culture contamination rate were unchanged (11.0% to 10.4%, p = 0.233; 5.1% to 5.3%, p = 0.636 respectively). Gram-negative pathogens predominated (1047/1636; 64.0%); Klebsiella species, Staphylococcus aureus, Serratia marcescens, Enterococcus species and Acinetobacter baumannii were the most frequent pathogens. Extended spectrum beta-lactamase production was observed in 319/432 (73.8%) of Klebsiella species, methicillin resistance in 171/246 (69.5%) of Staphylococcus aureus and extensive drug resistance in 115/137 (83.9%) of Acinetobacter species (2009-2018). The crude mortality rate of neonatal HA-BSI episodes increased from Period 1 to Period 2 from 139/717 (19.4%) to 179/718 (24.9%) (p = 0.014), but HA-BSI attributable mortality remained unchanged (97/139 [69.8%] vs 118/179 [65.9%], p = 0.542). The in-vitro activity of piperacillin-tazobactam and amikacin declined during Period 2 (74.6% to 61.4%; p<0.001).

Conclusion: Although HA-BSI rates declined in the neonatal unit, antimicrobial resistance rates in BSI pathogens remained high. Continuous BSI surveillance is a valuable tool to detect changes in pathogen and AMR profiles and inform empiric antibiotic recommendations for neonatal units in resource-limited settings.

Fig 1. Trends in neonatal hospital-acquired bloodstream infection (HA-BSI) rate, pathogen yield and blood culture contamination rate (2009–2018).

*HA-BSI rate calculated using number of HA-BSI episodes over total inpatient-days multiplied by 1000, from 2009–2018. HA-BSI comparisons made using Poisson regression. Pathogen yield and blood culture contamination rate calculated as number of pathogen-containing and contaminant-containing blood cultures respectively, as a proportion of all blood cultures submitted from 2009–2018; compared using a χ² test for linear trend. Two-sided p-values were used.

Fig 2. Phenotypic susceptibility patterns for the most commonly isolated pathogens in neonatal hospital-acquired bloodstream infections, Period 1 (2009–2013) vs Period 2 (2014–2018).

*Phenotypic susceptibility patterns established using the relevant year’s Clinical and Laboratory Standards Institute (CLSI) breakpoints. Isolates classified according to standard definitions for wild-type and acquired resistance, and reported as a proportion of the total number of isolates per species. Two-sided p-values were used. ESBL: extended-spectrum β-lactamase, detected by third-generation cephalosporin resistance; MRSA: methicillin-resistant S. aureus, detected by cefoxitin resistance;3GCR: 3^rd-generation cephalosporin resistance in chromosomal ampC beta-lactamase producers; CRE: carbapenem-resistant Enterobacterales, detected by reduced susceptibility to any carbapenem (usually ertapenem), in isolates not known to have chromosomally-mediated mechanisms for reduced susceptibility, XDR: extensively drug resistant, classified using a standard definition [14]. *Including Candida spp. with established fluconazole resistance, C. krusei and C. glabrata, which were the only isolates in which fluconazole resistance was found. No C. auris isolates were detected in this setting during the period of study.