Central-line-associated bloodstream infection burden among Dutch neonatal intensive care units.

BACKGROUND: The establishment of an epidemiological overview provides valuable insights needed for the (future) dissemination of infection-prevention initiatives. AIM: To describe the nationwide epidemiology of central-line-associated bloodstream infections (CLABSI) among Dutch Neonatal Intensive Care Units (NICUs). METHODS: Data from 2935 neonates born at <32 weeks' gestation and/or with a birth weight <1500 g admitted to all nine Dutch NICUs over a two-year surveillance period (2019-2020) were analysed. Variations in baseline characteristics, CLABSI incidence per 1000 central-line days, pathogen distribution and CLABSI care bundles were evaluated. Multi-variable logistic mixed-modelling was used to identify significant predictors for CLABSI. RESULTS: A total of 1699 (58%) neonates received a central line, in which 160 CLABSI episodes were recorded. Coagulase-negative staphylococci were the most common infecting organisms of all CLABSI episodes (N=100, 63%). An almost six-fold difference in the CLABSI incidence between participating units was found (2.91-16.14 per 1000 line-days). Logistic mixed-modelling revealed longer central line dwell-time (adjusted odds ratio (aOR):1.08, P<0.001), umbilical lines (aOR:1.85, P=0.03) and single rooms (aOR:3.63, P=0.02) to be significant predictors of CLABSI. Variations in bundle elements included intravenous tubing care and antibiotic prophylaxis. CONCLUSIONS: CLABSI remains a common problem in preterm infants in The Netherlands, with substantial variation in incidence between centres. Being the largest collection of data on the burden of neonatal CLABSI in The Netherlands, this epidemiological overview provides a solid foundation for the development of a collaborative platform for continuous surveillance, ideally leading to refinement of national evidence-based guidelines. Future efforts should focus on ensuring availability and extraction of routine patient data in aggregated formats.

The influence of prenatal and intrapartum antibiotics on intestinal microbiota colonisation in infants: A systematic review.

OBJECTIVES: The intestinal microbiota develops in early infancy and is essential for health status early and later in life. In this review we focus on the effect of prenatal and intrapartum maternally administered antibiotics on the infant intestinal microbiota. METHODS: A systematic literature search was conducted in PubMed and EMBASE. All studies reporting effect on diversity or microbiota profiles were included. RESULTS: A total of 4.030 records were encountered. A total of 24 articles were included in the final analysis. Infants from mothers exposed to antibiotics during delivery showed a decreased microbial diversity compared to non-exposed infants. The microbiota of infants exposed to antibiotics was characterised by a decreased abundance of Bacteriodetes and Bifidobacteria, with a concurrent increase of Proteobacteria. These effects were most pronounced in term vaginally born infants. CONCLUSION: Maternal administration of antibiotics seems to have profound effects on the infant gut microbiota colonisation. Interpretation of microbiota aberrations in specific populations, such as preterm and caesarean born infants, is complicated by multiple confounding factors and by lack of high quality studies and high heterogeneity in study design. Further research is needed to investigate the potential short- and long-term clinical consequences of these microbial alterations.

Diagnostic accuracy of a uniform research case definition for TBM in children: a prospective study.

BACKGROUND: Bacteriological confirmation of tuberculous meningitis (TBM) is problematic, and rarely guides initial clinical management. A uniform TBM case definition has been proposed for research purposes. METHODS: We prospectively enrolled patients aged 3 months to 13 years with meningitis confirmed using cerebrospinal fluid analysis at Tygerberg Hospital, Cape Town, South Africa. Criteria that differentiated TBM from other causes were explored and the accuracy of a probable TBM score assessed by comparing bacteriologically confirmed cases to 'non-TBM' controls. RESULTS: Of 139 meningitis patients, 79 were diagnosed with TBM (35 bacteriologically confirmed), 10 with bacterial meningitis and 50 with viral meningitis. Among those with bacteriologically confirmed TBM, 15 were Mycobacterium tuberculosis culture-positive and 20 were culture-negative but positive on GenoType(®) MTBDRplus or Xpert(®) MTB/RIF; 18 were positive on only a single commercial nucleic acid amplification test. A probable TBM score provided a sensitivity of 74% (95%CI 57-88) and a specificity of 97% (95%CI 86-99) compared to bacteriologically confirmed TBM. CONCLUSION: A probable TBM score demonstrated excellent specificity compared to bacteriological confirmation. However, 26% of children with TBM would be missed due to the limited accuracy of the case definition. Further prospective testing of an algorithm-based approach to TBM is advisable before recommendation for general clinical practice.

The diagnostic value of cerebrospinal fluid chemistry results in childhood tuberculous meningitis.

PURPOSE: Cerebrospinal fluid (CSF) hypoglycorrhachia and elevated protein is well-described in bacterial meningitis, but evidence for its differential diagnostic value in tuberculous meningitis (TBM) is lacking. We aimed to assess the diagnostic utility of CSF glucose, CSF to serum glucose ratio and CSF protein in children with suspected TBM. METHODS: We describe CSF glucose and protein values as well as CSF to serum glucose ratios in a prospective evaluation of TBM suspects seen at Tygerberg Children's Hospital, Cape Town, South Africa, from January 1985 to January 2014. RESULTS: Of 615 TBM suspects, 88 (14%) had microbiologically confirmed TBM, 381 (62%) 'probable' TBM and 146 (24%) 'non-TBM'. Mean absolute CSF glucose concentration was significantly lower in the microbiologically confirmed (1.87 ± 1.15 mmol/L) and 'probable' TBM (1.82 ± 1.19 mmol/L) groups compared to non-TBM (3.66 ± 0.88 mmol/L). A CSF glucose concentration of <2.2 mmol/L diagnosed TBM with sensitivity 0.68 and specificity 0.96. Sensitivity using a CSF to serum glucose ratio of <0.5 was 0.90. Mean CSF protein was significantly elevated in the microbiologically confirmed TBM (1.91 ± 1.44 g/L) and 'probable' TBM (2.01 ± 1.49 g/L) groups compared to the non-TBM (0.31 ± 0.31 g/L). A CSF protein >1 g/L diagnosed TBM with sensitivity 0.78 and specificity 0.94. CONCLUSION: Absolute CSF glucose values of <2.2 mmol/L and protein values of >1 g/L differentiated between TBM and non-bacterial meningitis with good specificity, although sensitivity was poor. A CSF to serum glucose ratio is more informative than the absolute value.

Chest radiograph findings in children with tuberculous meningitis.

BACKGROUND: Tuberculous meningitis (TBM) is diagnosed based on a combination of clinical, laboratory and radiological findings, including signs suggestive of tuberculosis (TB) on a standard chest X-ray (CXR). METHODS: We describe the radiological features suggestive of intrathoracic TB in children diagnosed with TBM during a prospective evaluation of TBM suspects seen at Tygerberg Children's Hospital, Cape Town, South Africa. RESULTS: Of 84 children treated for TBM, 31 (37%) had 'definite' TBM, 45 (55%) 'probable' TBM and 8 (9%) 'possible' TBM. In total, 37 (44%) TBM patients had CXR findings suggestive of TB, 9 (11%) with disseminated (miliary) TB. Only 1 in 4.39 children aged ≤3 years with TBM had suggestive CXR findings. The presence of complicated intrathoracic lymph node disease was significantly higher in children aged ≤3 years (OR 21.69, 95%CI 2.73-172.67, P < 0.01). Among 6 human immunodeficiency virus infected children, 3 (50%) had intrathoracic lymphadenopathy. CONCLUSION: The majority of the children with TBM, including the very young, did not have signs suggestive of TB on CXR.

Improved diagnosis of childhood tuberculous meningitis using more than one nucleic acid amplification test.

BACKGROUND: Early treatment is critical to reducing tuberculous meningitis (TBM) related morbidity and mortality. Diagnosis based on cerebrospinal fluid (CSF) culture is impractical due to slow turnaround times, while microscopy has poor sensitivity. Enhanced detection methods are essential to guide early treatment initiation, especially in vulnerable young children. METHODS: We assessed the diagnostic accuracy of the GenoType(®) MTBDRplus and Xpert(®) MTB/RIF assays on CSF collected from paediatric meningitis suspects prospectively enrolled at Tygerberg Hospital, Cape Town, South Africa. Fluorescent auramine-O microscopy, liquid culture for Mycobacterium tuberculosis, GenoType and Xpert assays were performed on all CSF samples. RESULTS: Of 101 meningitis suspects, 55 were diagnosed with TBM and 46 served as non-TBM controls. Using a pre-defined TBM case definition as reference standard, sensitivities and specificities were 4% and 100% for fluorescent microscopy, 22% and 100% for culture, 33% and 98% for GenoType, 26% and 100% for Xpert, 22% and 100% for microscopy and culture combined and 49% and 98% for GenoType and Xpert combined. Culture, GenoType and Xpert combined performed best, with 56% sensitivity and 98% specificity. CONCLUSION: Although commercial nucleic-acid amplification tests performed on CSF revealed incrementally improved diagnostic accuracy, providing rapid microbiological confirmation, they cannot serve as a rule-out test.

Apparent Life-Threatening Event following Maternal Use of Temazepam during Labour.

Benzodiazepines are one of the most frequently prescribed psychotropic drugs during pregnancy. Despite the fact that these drugs have been in use for a long time, there is still debate about the safety for the developing fetus and neonate. We present a case of a newborn with an apparent life-threatening event shortly after birth following maternal temazepam use during labour and advise to be reserved in prescribing any dose of any kind of benzodiazepine during labour.

Lipoarabinomannan enzyme-linked immunosorbent assay for early diagnosis of childhood tuberculous meningitis.

SETTING: Tuberculous meningitis (TBM) is a severe complication of tuberculosis (TB) predominantly affecting young children. Early initiation of treatment is important to prevent morbidity and mortality associated with TBM, emphasising the importance of early diagnosis. Among the most promising new methods for diagnosing TB are antigen-detection assays based on the detection of lipoarabinomannan (LAM). OBJECTIVE: To evaluate the diagnostic value of a commercial, antigen-capture enzyme-linked immunosorbent assay (ELISA) test based on the detection of LAM in urine for the early diagnosis of TBM in children. METHOD: A cross-sectional study in which urine samples from paediatric patients with suspected TBM attending the Tygerberg Children's Hospital, Cape Town, South Africa, were tested for LAM. RESULTS: Complete data were available for 50 of 56 patients with suspected TBM. TBM was diagnosed in 21 (42%) patients and excluded in 29 (58%). The LAM ELISA had a sensitivity of 4.8% and a specificity of 93.1%. Serial measurements in the first 2 weeks after treatment initiation did not improve test performance. CONCLUSION: We have shown that urinary LAM detection was of little value for the diagnosis of TBM in a cohort of paediatric patients with suspected TBM.

Seasonal variation in the incidence rate of tuberculous meningitis is associated with sunshine hours.

Tuberculous meningitis (TBM) is a severe complication of tuberculosis and occurs mainly during early childhood. The incidence rate of TBM varies with season, and serum vitamin D levels, which are dependent on sunlight, might play a role. We studied the association between TBM incidence rate and hours of sunshine in Cape Town, South Africa and found a significant association between the incidence rate of TBM and hours of sunshine 3 months earlier (incidence rate ratio per 100 sunshine hours 0·69, 95% confidence interval 0·54-0·88, P = 0·002). The association supports the hypothesis that vitamin D might play a role in the pathophysiology of TBM. Further prospective studies in which vitamin D status is measured are necessary to determine causality.