Epidemiology and complications of late-onset sepsis: an Italian area-based study

Abstract

Background: Most studies regarding late-onset sepsis (LOS) address selected populations (i.e., neonates with low birth weight or extremely preterm neonates). Studying all age groups is more suitable to assess the burden of single pathogens and their clinical relevance.

Methods: This is a retrospective regional study involving paediatric departments and NICUs in Emilia-Romagna (Italy). Regional laboratory databases were searched from 2009 to 2012. Records of infants (aged 4 to 90 days) with a positive blood or cerebrospinal fluid (CSF) culture were retrospectively reviewed and analysed according to acquisition mode (whether hospital- or community-acquired).

Results: During the study period, there were 146,682 live births (LBs), with 296 patients experiencing 331 episodes of LOS (incidence rate: 2.3/1000 LBs). Brain lesions upon discharge from the hospital were found in 12.3% (40/296) of cases, with death occurring in 7.1% (23/296; 0.14/1000 LBs). With respect to full-term neonates, extremely preterm or extremely low birth weight neonates had very high risk of LOS and related mortality (> 100- and > 800-fold higher respectively). Hospital-acquired LOS (n = 209) was significantly associated with very low birth weight, extremely preterm birth, pneumonia, mechanical ventilation, and death (p< 0.01). At multivariate logistic regression analysis, catecholamine support (OR = 3.2), central venous line before LOS (OR = 14.9), and meningitis (OR = 44.7) were associated with brain lesions or death in hospital-acquired LOS (area under the ROC curve 0.81, H-L p = 0.41). Commonly identified pathogens included coagulase-negative staphylococci (CoNS n = 71, 21.4%), Escherichia coli (n = 50, 15.1%), Staphylococcus aureus (n = 41, 12.4%) and Enterobacteriaceae (n = 41, 12.4%). Group B streptococcus was the predominant cause of meningitis (16 of 38 cases, 42%). Most pathogens were sensitive to first line antibiotics.

Conclusions: This study provides the first Italian data regarding late-onset sepsis (LOS) in all gestational age groups. Compared to full-term neonates, very high rates of LOS and mortality occurred in neonates with a lower birth weight and gestational age. Group B streptococcus was the leading cause of meningitis. Excluding CoNS, the predominant pathogens were Escherichia coli and Staphylococcus aureus. Neonates with hospital-acquired LOS had a worse outcome. Antibiotic associations, recommended for empirical treatment of hospital- or community-acquired LOS, were adequate.

Fig 1. Prominent pathogens in hospital- or community-acquired late-onset sepsis cases.

CoNS, coagulase-negative staphylococci; GBS, group B streptococcus. One neonate had both community and hospital acquired LOS. Full bars, hospital-acquired LOS. Empty bars, community-acquired LOS. Pathogens causing LOS include: CoNS: Staphylococcus epidermidis (n = 52), S. warneri (n = 7), S. haemolyticus (n = 2), S. capitis (n = 5), S. hominis (n = 1), S. caprae (n = 1), polymicrobial CoNS (n = 3). Enterococci: E. faecalis (n = 25), E. faecium (n = 11), E. avium (n = 1), Enterobacteriaceae: Klebsiella pneumoniae (n = 18), Klebsiella oxytoca (n = 5), Enterobacter aerogenes (n = 3), Enterobacter cloacae (n = 10), Serratia marcescens (n = 3), Pantoea spp (n = 1), Proteus mirabilis (n = 1) Pseudomonas spp: Pseudomonas aeruginosa (n = 7), Putida (n = 1), Oryzihabitans (n = 1), Candida spp: Candida albicans (n = 8), C. tropicalis (n = 1), C. lusitaniae (n = 1), C. famata (n = 1), C. Glabrata (n = 1), C. parapsilosis (n = 2).

Fig 2. Pathogens according to age at presentation in hospital- and community-acquired LOS.

CoNS, coagulase-negative staphylococci; GBS, group B streptococcus. Continuous line, hospital-acquired LOS. Dashed line, community-acquired LOS.

Fig 3

Sensitivity and resistance of gram positive (panel A) and gram negative (panel B) pathogens as a whole. Amp, ampicillin; Gent, gentamicin; Cep, third generation cephalosporins; LOS, late-onset sepsis; Oxac, oxacillin; Vanc, vancomycin. White columns, sensitive. Black columns, resistant or intermediate.

Fig 4

Number of total cases, meningitis, brain lesions and case fatalities according to each pathogen in hospital- (panel A) and community-acquired LOS (panel B). CoNS, coagulase-negative staphylococci; GBS, group B streptococcus. Empty bars, total cases of late-onset sepsis. Oblique striped bars, cases of meningitis. Grey bars, cases with brain lesions. Black bars, case fatalities.