Predictive value of repeated cerebrospinal fluid parameters in the outcomes of bacterial meningitis in infants <90 days of age.

BACKGROUND: There are variations in recommendations from different guidelines regarding the indications for repeat lumbar puncture (LP) in young infants with the diagnosis of bacterial meningitis. OBJECTIVE: To evaluate the frequency of repeat LPs and the characteristics of cerebrospinal fluid (CSF) parameters in repeated sampling and their predictive values for adverse outcomes in a national cohort. METHODS: This cohort study included infants born January 1, 2013 through December 31, 2014, who had proven or suspected bacterial meningitis within the first 90 days of life at seven paediatric tertiary care hospitals across Canada, and who underwent a repeat LP at the discretion of the treating physicians. RESULTS: Forty-nine of 111 infants (44%) underwent repeat LP at a median of 5 (IQR: 3, 13) days after the LP that led to the diagnosis of bacterial meningitis. Those who had meningitis caused by gram negative bacilli were more likely to have repeat LP than those with gram positive bacteria (77% versus 57%; p = 0.012). White blood cell (WBC) count on the second spinal tap yielded an area under the curve of 0.88 for predicting sequelae of meningitis at discharge from the hospital, with a cut-off value of 366 × 106/L, providing a sensitivity of 91% and specificity of 88%. CONCLUSION: In this multi-centre retrospective cohort study, infants with gram negative meningitis were more likely to have repeated LP. A high WBC on the second CSF sample was predictive of adverse outcome at the time of discharge from the hospital.

Enteroviral and herpes simplex virus central nervous system infections in infants < 90 days old: a Paediatric Investigators' Collaborative Network on Infections in Canada (PICNIC) study.

BACKGROUND: The relative contribution of viruses to central nervous system (CNS) infections in young infants is not clear. For viral CNS infections, there are limited data on features that suggest HSV etiology or on predictors of unfavorable outcome. METHODS: In this cross-sectional retrospective study, seven centers from the Pediatric Investigators Collaborative Network on Infections in Canada identified infants < 90 days of age with CNS infection proven to be due to enterovirus (EV) or herpes simplex virus (HSV) January 1, 2013 through December 31, 2014. RESULTS: Of 174 CNS infections with a proven etiology, EV accounted for 103 (59%) and HSV for 7 (4%). All HSV cases and 41 (40%) EV cases presented before 21 days of age. Four HSV cases (57%) and 5 EV cases (5%) had seizures. Three (43%) HSV and 23 (23%) EV cases lacked cerebrospinal fluid (CSF) pleocytosis. HSV cases were more likely to require ICU admission (p = 0.010), present with seizures (p = 0.031) and have extra-CNS disease (p < 0.001). Unfavorable outcome occurred in 12 cases (11% of all EV and HSV infections) but was more likely following HSV than EV infection (4 (57%) versus 8 (8%); p = 0.002). CONCLUSIONS: Viruses accounted for approximately two-thirds of proven CNS infections in the first 90 days of life. Empiric therapy for HSV should be considered in suspected CNS infections in the first 21 days even in the absence of CSF pleocytosis unless CSF parameters are suggestive of bacterial meningitis. Neurodevelopmental follow-up should be considered in infants whose course of illness is complicated by seizures.

The Epidemiology, Management, and Outcomes of Bacterial Meningitis in Infants.

OBJECTIVES: The pathogens that cause bacterial meningitis in infants and their antimicrobial susceptibilities may have changed in this era of increasing antimicrobial resistance, use of conjugated vaccines, and maternal antibiotic prophylaxis for group B Streptococcus (GBS). The objective was to determine the optimal empirical antibiotics for bacterial meningitis in early infancy. METHODS: This was a cohort study of infants <90 days of age with bacterial meningitis at 7 pediatric tertiary care hospitals across Canada in 2013 and 2014. RESULTS: There were 113 patients diagnosed with proven meningitis (n = 63) or suspected meningitis (n = 50) presented at median 19 days of age, with 63 patients (56%) presenting a diagnosis from home. Predominant pathogens were Escherichia coli (n = 37; 33%) and GBS (n = 35; 31%). Two of 15 patients presenting meningitis on day 0 to 6 had isolates resistant to both ampicillin and gentamicin (E coli and Haemophilus influenzae type B). Six of 60 infants presenting a diagnosis of meningitis from home from day 7 to 90 had isolates, for which cefotaxime would be a poor choice (Listeria monocytogenes [n = 3], Enterobacter cloacae, Cronobacter sakazakii, and Pseudomonas stutzeri). Sequelae were documented in 84 infants (74%), including 8 deaths (7%). CONCLUSIONS: E coli and GBS remain the most common causes of bacterial meningitis in the first 90 days of life. For empirical therapy of suspected bacterial meningitis, one should consider a third-generation cephalosporin (plus ampicillin for at least the first month), potentially substituting a carbapenem for the cephalosporin if there is evidence for Gram-negative meningitis.

Characteristics of invasive Haemophilus influenzae serotype a (Hia) from Nunavik, Canada and comparison with Hia strains in other North American Arctic regions.

OBJECTIVE: This study examines the microbiological characteristics of invasive Haemophilus influenae serotype a (Hia) isolates from Nunavik (northern Quebec), Canada. The relationship between invasive Hia isolates from Nunavik, Nunavut, Canada, and Alaska, USA will be discussed. METHODS: Twenty invasive Hia isolates were recovered from patients in Nunavik from 2010 to 2013 and characterized by biotype, multi-locus sequence typing, IS1016-bexA deletion, antibiotic susceptibility and pulsed field gel electrophoresis (PFGE). RESULTS: All 20 Hia isolates were biotype II, sequence type -23, did not have IS1016-bexA deletions and were susceptible to all antibiotics tested. PFGE showed only two patterns, with 19 isolates giving identical molecular fingerprints, and the remaining isolate gave a PFGE pattern >95% similar. CONCLUSION: One major clone of Hia appears to be causing invasive disease in Nunavik, Canada. Based on previous studies, Hia from Nunavut were also typed as ST-23, while invasive Hia isolates from Alaska belonged to either ST-23 or closely related STs. Thus invasive Hia in the North America Arctic belonged to the ST-23 clonal complex and lacked the IS1016-bexA partial deletion.

Microbial Biofilms in Pulmonary and Critical Care Diseases.

Microbial biofilms can colonize medical devices and human tissues, and their role in microbial pathogenesis is now well established. Not only are biofilms ubiquitous in natural and human-made environments, but they are also estimated to be associated with approximately two-thirds of nosocomial infections. This multicellular aggregated form of microbial growth confers a remarkable resistance to killing by antimicrobials and host defenses, leading biofilms to cause a wide range of subacute or chronic infections that are difficult to eradicate. We have gained tremendous knowledge on the molecular, genetic, microbiological, and biophysical processes involved in biofilm formation. These insights now shape our understanding, diagnosis, and management of many infectious diseases and direct the development of novel antimicrobial therapies that target biofilms. Bacterial and fungal biofilms play an important role in a range of diseases in pulmonary and critical care medicine, most importantly catheter-associated infections, ventilator-associated pneumonia, chronic Pseudomonas aeruginosa infections in cystic fibrosis lung disease, and Aspergillus fumigatus pulmonary infections.