Group B streptococcal disease in infants aged younger than 3 months: systematic review and meta-analysis.

BACKGROUND: Despite widespread use of intrapartum antibiotic prophylaxis, group B streptococcus remains a leading cause of morbidity and mortality in infants in Europe, the Americas, and Australia. However, estimates of disease burden in many countries outside of these regions is not available. We aimed to examine the current global burden of invasive disease and the serotype distribution of group B streptococcus isolates. METHODS: We searched Medline, Embase, and Wholis databases for studies on invasive early-onset (day 0-6) and late-onset (day 7-89) group B streptococcal disease. Eligible studies were those that described incidence, deaths, or serotypes. We also reviewed reference lists and contacted experts to seek unpublished data and data missed by our search. Random effects meta-analysis was used to pool data. FINDINGS: 74 studies met the inclusion criteria; 56 studies reported incidence, 29 case fatality, and 19 serotype distribution. An additional search for studies that reported serotype distribution from Jan 1, 1980, yielded a total of 38 articles. Only five low-income countries were represented in the review and contributed 5% weight to the meta-analysis. 47 (69%) studies reported use of any intrapartum antibiotic prophylaxis. Substantial heterogeneity existed between studies. Mean incidence of group B streptococcus in infants aged 0-89 days was 0·53 per 1000 livebirths (95% CI 0·44-0·62) and the mean case fatality ratio was 9·6% (95% CI 7·5-11·8). Incidence of early-onset group B streptococcus (0·43 per 1000 livebirths [95% CI 0·37-0·49]) and case fatality (12·1%, [6·2-18·3]) were two-times higher than late-onset disease. Serotype III (48·9%) was the most frequently identified serotype in all regions with available data followed by serotypes Ia (22·9%), Ib (7·0%), II (6·2%), and V (9·1%). Studies that reported use of any intrapartum antibiotic prophylaxis were associated with lower incidence of early-onset group B streptococcus (0·23 per 1000 livebirths [95% CI 0·13-0·59]) than studies in which patients did not use prophylaxis (0·75 per 1000 livebirths [0·58-0·89]). INTERPRETATION: More high-quality studies are needed to accurately estimate the global burden of group B streptococcus, especially in low-income countries. A conjugate vaccine incorporating five serotypes (Ia, Ib, II, III, V) could prevent most global group B streptococcal disease. FUNDING: Child Epidemiology Reference Group (CHERG), WHO.

Standardising the elusive diagnosis of NEC in the premature infant - A practical score.

OBJECTIVE: The perceived risk of necrotising enterocolitis (NEC) can result in overtreatment of the otherwise adapting preterm neonate. We aim to develop an assessment tool to aid the decision making in the management of preterm neonates at risk of NEC. METHOD: An evidence-based assessment tool was designed bringing together clinical, laboratory and radiological signs commonly associated with NEC. A numerical score was awarded for each sign, with those more specific to NEC being graded higher. A multi-centre validation was conducted of the proposed assessment tool over three tertiary neonatal units. RESULTS: A total of 125 patients were included, 53 (42.4 %) with a final diagnosis of NEC and 72 (57.6 %) with an alternative diagnosis. The NEC group had a significantly higher total score compared to the non-NEC group; 15(2-28) vs. 4(1-9) (p ≤ 0.0001). In ROC analysis, using a cut-off of eight, the assessment tool gave a sensitivity of 92.3 % and a specificity of 90.4 % for identifying NEC compared to an alternative diagnosis. CONCLUSION: This comprehensive scoring system encourages a full assessment of the infant before deciding on withholding feeds, starting antibiotics, and transferring to a surgical centre. It is a safe objective measure to support a diagnosis of NEC in the presence of certain clinical signs.

Epidemiology and healthcare factors associated with neonatal enterococcal infections.

OBJECTIVE: To investigate the epidemiology and healthcare factors associated with late-onset neonatal enterococcal infections. DESIGN: Multicentre, multinational retrospective cohort study using prospectively collected infection data from a neonatal infection surveillance network between 2004 and 2016; this was supplemented with healthcare data from a questionnaire distributed to participating neonatal units. SETTING: Sixty neonatal units across Europe (UK, Greece, Estonia) and Australia. PATIENTS: Infants admitted to participating neonatal units who had a positive culture of blood, cerebrospinal fluid or urine after 48 hours of life. RESULTS: In total, 414 episodes of invasive Enterococcus spp infection were reported in 388 infants (10.1% of a total 4083 episodes in 3602 infants). Enterococcus spp were the second most common cause of late-onset infection after coagulase-negative Staphylococcus spp and were strongly associated with necrotising enterocolitis (NEC) (adjusted OR 1.44, 95% CI 1.02 to 2.03, p=0.038), total parenteral nutrition (TPN) (adjusted OR 1.34, 95% CI 1.06 to 1.70, p=0.016), increasing postnatal age (per 1-week increase: adjusted OR 1.04, 95% CI 1.02 to 1.06, p<0.001) and decreasing birth weight (per 1 kg increase: adjusted OR 0.85, 95% CI 0.74 to 0.97, p=0.017). There was no evidence that inadequate nurse to patient staffing ratios in high-dependency units were associated with a higher risk of enterococcal infections. CONCLUSIONS: Enterococcus spp were the second most frequent cause of late-onset infections. The association between enterococcal infections, NEC and TPN may inform empiric antimicrobial regimens in these contexts and provide insights into reducing these infections.

Epidemiology of infections and antimicrobial use in Greek Neonatal Units.

OBJECTIVE: To describe the epidemiology of neonatal infections and of antimicrobial use in Greek Neonatal Units (NNUs) in order to develop national, evidence-based guidelines on empiric antimicrobial use for neonatal sepsis in Greece. DESIGN: Retrospective analysis of prospectively collected infection surveillance data from 2012 to 2015, together with a Point Prevalence Survey (PPS) on antimicrobial use and the collection of data on local empiric antimicrobial policies. SETTING: 16 NNUs in Greece participating in the neonIN infection surveillance network PATIENTS: Newborns in participating NNUs who had a positive blood, cerebrospinal fluid or urine culture and were treated with at least 5 days of antibiotics. RESULTS: 459 episodes were recorded in 418 infants. The overall incidence of infection was 50/1000 NNU-admissions. The majority of episodes were late-onset sepsis (LOS) (413, 90%). Coagulase-negative Staphylococci (80%) were the most common Gram-positive organisms causing LOS and Klebsiella spp (39%) the most common Gram-negative. Nearly half (45%) of the Klebsiella spp were resistant to at least one aminoglycoside. The PPS revealed that 196 of 484 (40%) neonates were on antimicrobials. The survey revealed wide variation in empiric antimicrobial policies for LOS. CONCLUSIONS: This is the largest collection of data on the epidemiology of neonatal infections in Greece and on neonatal antimicrobial use. It provides the background for the development of national evidence-based guidelines. Continuous surveillance, the introduction of antimicrobial stewardship interventions and evidence-based guidelines are urgently required.

Epidemiology of UK neonatal infections: the neonIN infection surveillance network.

OBJECTIVE: To describe the epidemiology of neonatal infection over the past decade in UK neonatal units. DESIGN: Retrospective analysis of prospectively collected infection surveillance network data from 2005 to 2014. SETTING: 30 neonatal units in the UK. PATIENTS: Newborns on participating neonatal units who had a positive blood, cerebrospinal fluid or urine culture and were treated with at least 5 days of appropriate antibiotics. RESULTS: 2171 episodes of neonatal infection in 1922 infants were recorded. The incidence of infection was 6.1/1000 live births and 48.8/1000 neonatal admissions (2.9 and 23.5 respectively if coagulase-negative staphylococci (CoNS) cultures excluded). The incidence of infection showed a statistically significant reduction over time with reductions in the rates of both early-onset sepsis (EOS) and late-onset sepsis (LOS).The majority of episodes (76%) represented LOS (diagnosed > 48 hours after birth), and infection was more common in premature (<37 weeks gestation) and low birth weight (<2500 g) neonates (84% and 81%, respectively). Commonly identified pathogens included group B streptococci (43%) and Escherichia coli (18%) for EOS, while E. coli (15%), Staphylococcus aureus (14%) and CoNS were prominent causes of LOS. CONCLUSIONS: This paper describes the epidemiology of neonatal infection in the UK over the past decade. These data enable benchmarking of practice and inform areas of future research and guideline development. The results support the hypothesis that the introduction of infection prevention care bundles and antibiotic stewardship programmes in the UK has reduced the burden of LOS.

Antimicrobial resistance in UK neonatal units: neonIN infection surveillance network.

OBJECTIVE: To define the susceptibilities of the common causative pathogens of neonatal sepsis in the UK. DESIGN: Retrospective analysis of the prospectively collected neonIN infection surveillance network data between 2005 and 2014. SETTING: 30 neonatal units in the UK. PATIENTS: Newborns admitted to participating neonatal units who return a positive blood, cerebrospinal fluid or urine culture and are treated with at least 5 days of appropriate antibiotics. RESULTS: 1568 isolates with recorded antimicrobial data were collected including 328 early-onset sepsis (EOS) isolates and 1240 late-onset sepsis (LOS) isolates. The majority of EOS pathogens (>92%) were susceptible to the four empirical commonly used antimicrobial combinations (eg, 93% for benzylpenicillin/gentamicin), while LOS pathogens demonstrated higher levels of resistance (eg, 89% for flucloxacillin/gentamicin). Among infants<1500 g and <32 weeks gestation, an amoxicillin/gentamicin combination demonstrated a trend towards improved coverage of EOS isolates than benzylpenicillin/gentamicin (93% vs 86%, p=0.211). CONCLUSIONS: This analysis provides insights into the patterns of antimicrobial resistance among UK neonatal pathogens. These data will inform areas of future research and can be used to update national evidence-based guidelines on antimicrobial usage.

Neonatal listeriosis in the UK 2004-2014.

OBJECTIVE: To define the clinical features and outcomes of neonatal listeriosis, and identify the maternal risk factors to seek scope for improvement. METHODS: Neonatal listeriosis was identified prospectively from a United Kingdom neonatal infection surveillance network (neonIN) between 2004 and 2014. The participating neonatal units completed a study-specific proforma. RESULTS: The incidence of neonatal listeriosis was 3.4 per 100,000 live births. Of the 21 cases identified, 19 were confirmed with a median gestational age of 33 weeks and a median birth weight of 1960 g. The majority had clinical features (95%, 18/19), presented within the first 24 h (95%, 18/19), and received penicillin empirically (94%, 18/19). The neonatal case-fatality rate was 21% (24% if probable cases were included). A proportion of mothers were investigated (60%, 12/18) and diagnosed with listeriosis (58%, 7/12); 32% (6/19) were treated with antibiotics but only 33% (6/12) included penicillin. DISCUSSION: Despite its rarity and the prompt and appropriate use of antibiotics neonatal listeriosis has a high case-fatality rate. There is room for improvement in the adherence to the empiric antibiotic choice for puerperal sepsis, according to the national guidelines as this, would target listeriosis. Strategies should be in place to prevent pregnancy-associated listeriosis in higher risk population.

Neonatal gram-negative infections, antibiotic susceptibility and clinical outcome: an observational study.

BACKGROUND: Neonatal gram-negative (GN) infections are associated with high mortality and morbidity. Early appropriate antibiotic treatment is vital and gentamicin is the most frequently used antibiotic on neonatal units (NNUs). Antimicrobial breakpoints are predominantly based on adult data and the relationship between minimum inhibitory concentrations (MICs) and outcome in neonates is unclear. We aimed to determine the MIC of GN pathogens causing neonatal infections and relate this to clinical outcomes. METHODS: MICs for eight antibiotics plus extended spectrum ß-lactamase (ESBL) production were determined for invasive GN bacterial isolates from eight UK NNUs. European Committee on Antimicrobial Susceptibility Testing breakpoints were applied. MIC was correlated with clinical outcome using multivariable regression analysis. RESULTS: 118 isolates from 116 patients were analysed. The median birth gestation and postnatal age was 27 weeks (IQR 24.6-32.3) and 20 days (IQR 5-44), respectively. Pathogens included Escherichia coli (51%), Klebsiella spp (23%) and Enterobacter spp (22%). 10-day attributable mortality was 18.1% (21 patients) with the highest mortality from Pseudomonas aeruginosa infections. ESBL producers accounted for 13.8% of the isolates. In regression analysis, increasing gentamicin MIC was associated with increased mortality in gentamicin treated patients across the full MIC range (OR per loge increase in MIC: 2.29; 95% CI 1.23 to 4.26, p=0.009), including susceptible isolates only (MIC ≤4) (OR 3.05; 95% CI 1.10 to 8.46, p=0.032). CONCLUSIONS: Neonatal mortality from GN infections remains high and is associated with increasing gentamicin MIC, even for isolates deemed susceptible. A better understanding of population-specific MICs and aminoglycoside dosing is required to guide empiric antibiotic treatment.

The current and future roles of neonatal infection surveillance programmes in combating antimicrobial resistance.

Neonatal sepsis is an important cause of morbidity and mortality, particularly in premature or low birth weight babies. Hospital-acquired blood stream infections represent a significant and largely preventable cause of disease in this population. Neonatal units have been identified as a common site for the development and transmission of antimicrobial-resistant pathogens, a significant issue in modern medicine. Neonatal surveillance programmes collect prospective data on infection rates and may be used to optimise therapy, benchmark practice and develop quality improvement programmes. Despite this, the number of networks is relatively few and these are largely concentrated in resource-rich nations. Furthermore, surveillance definitions may vary between programmes impairing our ability to draw comparisons between them. Better harmonisation is required between networks to ensure that they achieve their potential as a valuable tool for benchmarking of hospital-acquired infection rates between units.