The Epidemiology, Management, Lynda Ouchenir, MD, a Christian Renaud, MD, MSc, a Sarah Khan, MD,b Ari Bitnun, MD, MSc, b Andree-Anne Boisvert, MD,c andJane McDonald, Outcomes MD, c Jennifer Bowes, MSc, d Jasonof Brophy, Bacterial MD, MSc, d Michelle Barton, MD, MSc, e f f g g MeningitisJoseph Ting, MBBS, MPH, Ashley Roberts,in MD,Infants MEd, Michael Hawkes, MD, PhD, Joan L. Robinson, MD OBJECTIVES: abstract The pathogens that cause bacterial meningitis in infants andStreptococcus their antimicrobial susceptibilities may have changed in this era of increasing antimicrobial resistance, use of conjugated vaccines, and maternal antibiotic prophylaxis for group B (GBS). The objective was to determine the optimal empirical antibiotics for bacterial meningitis in METHODS: early infancy. This was a cohort study of infants <90 days of age with bacterial meningitis at 7 RESULTS: n pediatric tertiary care hospitals across Canada in 2013 and 2014. n There were 113 patients diagnosed with provenEscherichia meningitis coli ( =n 63) or suspected meningitisn ( = 50) presented at median 19 days of age, with 63 patients (56%) presenting a diagnosis from home. Predominant pathogensE coli were Haemophilus influenzae ( = 37; 33%) and GBS ( = 35; 31%). Two of 15 patients presenting meningitis on day 0 to 6 had isolates resistant to both ampicillin and gentamicin ( Listeria and monocytogenes n Enterobacter type B). Six cloacaeof 60 infantsCronobacter presenting sakazakii a diagnosisPseudomonas of meningitis stutzeri from home from day 7 to 90 had isolates, for which cefotaxime would be a poor choice ( [ = 3], , , and ). Sequelae were documented in 84 CONCLUSIONS: E coli infants (74%), including 8 deaths (7%). 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. WHA T’S KNOWN ON THIS SUBJECT: Before the use of aCentre hospitalier universitaire Sainte-Justine, University of Montreal, Montreal, Quebec, Canada; bDepartment of Pediatrics, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada; cMontreal Children’s intrapartum antibiotics for group B Streptococcus Hospital, McGill University, Montreal, Quebec, Canada; dChildren’s Hospital of Eastern Ontario, University of (GBS), common pathogens in bacterial meningitis Ottawa, Ottawa, Ontario, Canada; eLondon Health Sciences Centre, Western University, London, Ontario, Canada; in the first 90 days of life were GBS and Escherichia fBritish Columbia Children’s Hospital, University of British Columbia, Vancouver, British Columbia, Canada; and coli. Ampicillin and cefotaxime were effective for gDepartment of Pediatrics, Stollery Children s Hospital, University of Alberta, Edmonton, Alberta, Canada ’ almost all community-acquired cases. Dr Ouchenir collected data from her site, performed the initial data analysis, and wrote the first WHAT THIS StUDY ADDS: GBS and E coli are still the draft of the manuscript; Drs Khan and Boisvert and Ms Bowes collected data from their sites and main pathogens. Three of 60 cases of community- critically reviewed the manuscript; Drs Barton, Ting, and Roberts provided input for the protocol and case report form, collected data from their sites, and critically reviewed the manuscript; acquired late-onset bacterial meningitis were Drs Renaud, Bitnun, McDonald, and Brophy provided input for the protocol and case report form, with Gram-negative pathogens for which a third- supervised data collection from their sites, and critically reviewed the manuscript; Dr Hawkes generation cephalosporin would be suboptimal provided input for the protocol and case report form, performed the data analysis, and critically therapy. reviewed the manuscript; Dr Robinson wrote the first draft of the protocol, designed the case report form, and finalized the manuscript for submission; and all authors approved the final To cite: Ouchenir L, Renaud C, Khan S, et al. The Epide- manuscript as submitted. miology, Management, and Outcomes of Bacterial Men- ingitis in Infants. Pediatrics. 2017;140(1):e20170476 Downloaded from www.aappublications.org/news by guest on September 29, 2021 PEDIATRICS Volume 140, number 1, July 2017:e20170476 ARTICLE ρ There is a paucity of information (including urine) and either sterile rank correlation coefficient ( ). on the characteristics of neonatal CSF pleocytosis or head imaging The Statistical Package for the Haemophilus influenzae × meningitis in the era of infant consistent with bacterial meningitis. Social Sciences version 19 (IBM type B (Hib) CSF pleocytosis was defined as >30 Corporation, Armonk, NY) and Streptococcus 6 × and pneumococcal immunization, 10 /L white blood6 cells (WBCs) and GraphPad Prism version 5 (GraphPad maternal group B (1) <100 10 /L red blood cells Software, La Jolla, CA) were used (GBS) prophylaxis, and emerging1 (RBCs), or (2) WBC:RBC ratio >1:100. for statistical analysis and graphical antimicrobial resistance. The Early-onset was defined as diagnosis display of data, respectively. primary objective of this study was on day 0 to 6, late-onset as day 7 to In analyzing antimicrobial to describe pathogens in bacterial 29, and extremely late-onset as day 2 susceptibility data, it is an accepted meningitis in the first 90 days of E30xclusion to 90. Criteria principle that empirical treatment of life in Canada. Secondary objectives bacterial meningitis should almost were to make inferences about always include an antibiotic to which optimal empirical antimicrobial Exclusion criteria were (1) growth the pathogen is susceptible. agents, outline the typical duration of a common skin contaminant RESULTS of treatment, and describe outcomes. (including coagulase negative The hypothesis was that third- staphylococci) from a single CSF ≤ generation cephalosporins may culture, (2) full recovery despite no longer be optimal for empirical 4 days intravenous antimicrobial There were 424 charts with 1 or therapy of late-onset, community- more target discharge diagnoses, Dagents,ata Collection or (3) fungal isolate. n acquired meningitis. yielding 113 cases of provenn bacterial METHODS meningitis ( = 63) or suspected bacterial meningitis ( = 50) in Data collected via the Research 61 boys and 52 girls (68 term; 45 – Electronic Data Capture included preterm) with a median age of Study results were reported by demographics, microbiologic diagnosis of 19 days (IQR 10 33) using The Strengthening the results (including susceptibilities, (Table 1). Sixty-three patients (56%) Reporting of Observational Studies ≥ CSF sampling results, and head were presented from home, of which in Epidemiology guidelines (https:// ’ / imaging results from symptom 54 (86%) were term infants ( 37 www. equator- network. org/ onset until antibiotic completion), weeks gestation). The other 50 reporting-guidelines/ strobe ). duration of antimicrobial agents patients (44%) presented during Ethics approval was obtained at 7 for meningitis, complications of their birth hospitalization, of pediatric hospitals for a retrospective meningitis (including seizures, which 14 (28%) were term infants chart review of infants born January hydrocephalus, brain abscesses, (Table 2). International1, 2013 through Statistical December Classification 31, suspected ventriculitis, or infarcts), E coli of2014. Diseases Cases and were Related identified Health by the and sequelae at last encounter Pathogens are shown in Table 1 Problems, Tenth Revision, Canada (seizure disorder, hearing or vision with (37/113; 33%) and GBS loss, motor deficits, developmental (35/113; 31%) dominating. Blood Ddelay,ata A ornalysis death). cultures performed in 61 of 63 diagnostic codes for target discharge proven cases were positive for the (SupplementalInclusion Criteria Information). meningitis pathogen in 40 of those cases (66%). Descriptive and comparative statistics were calculated as Forty (80%) of the 50 patients with Infants with onset of bacterial appropriate, expressing continuous suspected meningitis had bacteremia meningitis in the first 90 days of variables by using median and with CSF sampled only post- life were included in this study. interquartile range (IQR) because antibiotics. Nine of the remaining 10 Proven meningitis was defined data were generally not normally patients had sterile CSF pleocytosis as the detection of bacteria from distributed. Comparisons of pre-antibiotics (data missing for 1 – E coli cerebrospinal fluid (CSF) by culture continuous variables were performed patient) with a median CSF leukocyte – U or molecular techniques during life by using nonparametric methods count of 132 (rangen 5 545). or at autopsy. Suspected meningitis (Mann Whitney test). Comparisons was isolated from 7 patients from χ ’ n was defined as the detection of a of proportions2 were performed by blood and urine ( = 2), blood and bacteria recognized to cause central using test or Fisher s exact test, endotracheal secretions ( = 1), ’ n n E nervous system infection from blood as appropriate. Correlations were urine and endotracheal secretions or another normally sterile site quantified by using Spearman s ( = 1), and urine alone ( = 3). Downloaded from www.aappublications.org/news by guest on September 29, 2021 2 OUCHENIR et al TABLE 1 Characteristics of 113 Neonates With Proven or Suspected Bacterial