Sergio Fanella

Effectiveness of neuraminidase inhibitors in reducing mortality in patients admitted to hospital with influenza A H1N1pdm09 virus infection: a meta-analysis of individual participant data

BACKGROUND Neuraminidase inhibitors were widely used during the 2009-10 influenza A H1N1 pandemic, but evidence for their effectiveness in reducing mortality is uncertain. We did a meta-analysis of individual participant data to investigate the association between use of neuraminidase inhibitors and mortality in patients admitted to hospital with pandemic influenza A H1N1pdm09 virus infection. METHODS We assembled data for patients (all ages) admitted to hospital worldwide with laboratory confirmed or clinically diagnosed pandemic influenza A H1N1pdm09 virus infection. We identified potential data contributors from an earlier systematic review of reported studies addressing the same research question. In our systematic review, eligible studies were done between March 1, 2009 (Mexico), or April 1, 2009 (rest of the world), until the WHO declaration of the end of the pandemic (Aug 10, 2010); however, we continued to receive data up to March 14, 2011, from ongoing studies. We did a meta-analysis of individual participant data to assess the association between neuraminidase inhibitor treatment and mortality (primary outcome), adjusting for both treatment propensity and potential confounders, using generalised linear mixed modelling. We assessed the association with time to treatment using time-dependent Cox regression shared frailty modelling. FINDINGS We included data for 29,234 patients from 78 studies of patients admitted to hospital between Jan 2, 2009, and March 14, 2011. Compared with no treatment, neuraminidase inhibitor treatment (irrespective of timing) was associated with a reduction in mortality risk (adjusted odds ratio [OR] 0·81; 95% CI 0·70-0·93; p=0·0024). Compared with later treatment, early treatment (within 2 days of symptom onset) was associated with a reduction in mortality risk (adjusted OR 0·48; 95% CI 0·41-0·56; p<0·0001). Early treatment versus no treatment was also associated with a reduction in mortality (adjusted OR 0·50; 95% CI 0·37-0·67; p<0·0001). These associations with reduced mortality risk were less pronounced and not significant in children. There was an increase in the mortality hazard rate with each days delay in initiation of treatment up to day 5 as compared with treatment initiated within 2 days of symptom onset (adjusted hazard ratio [HR 1·23] [95% CI 1·18-1·28]; p<0·0001 for the increasing HR with each days delay). INTERPRETATION We advocate early instigation of neuraminidase inhibitor treatment in adults admitted to hospital with suspected or proven influenza infection. FUNDING F Hoffmann-La Roche.

Invasive Meningococcal Disease in the 21st Century—An Update for the Clinician

Neisseria meningitidis is a gram-negative diplococcus, for which humans are the only reservoir. While colonization is common, invasive meningococcal disease in the form of meningitis or bacteremia can be devastating and potentially fatal. Certain populations are at higher risk for disease including infants, adolescents, those with asplenia or complement deficiencies, and potentially those with human immunodeficiency virus (HIV) infection. Use of conjugate meningococcal vaccines has impacted disease epidemiology in both high- and low-income countries. Outbreaks of serogroup B disease at university campuses have drawn further attention to the recent development of a novel serogroup B vaccine now approved in many countries. This review covers key aspects of the pathogenesis and management of meningococcal disease, as well as the very recent developments in disease epidemiology, outbreaks, and the evolution of meningococcal immunizations.

Blastomycosis in children and adolescents: a 30-year experience from Manitoba

Blastomyces dermatitidis, a thermally dimorphic fungus endemic to areas of North America, causes a granulomatous infection which may affect any organ system. Since limited clinical data exist about pediatric blastomycosis, we conducted a retrospective review of medical records of pediatric patients with a laboratory-confirmed diagnosis of blastomycosis treated during a 30-year period at a tertiary care center. Thirty-four pediatric patients with blastomycosis were identified (20 [59%] male), with a mean age at diagnosis of 10 ± 5 years. Two patients were immunocompromised. Pulmonary disease was noted in 27 (79%) patients, and extrapulmonary disease was found in 13 (38%) patients (concurrent pulmonary and extrapulmonary disease, six patients), including five cases of central nervous system (CNS) disease. Delay in diagnosis was greater with extrapulmonary or central nervous system infections as compared with pulmonary blastomycosis. All patients received antifungal chemotherapy, with 19 (56%) patients receiving amphotericin B as initial therapy for 27.5 ± 17 days. Five patients required treatment in the intensive care unit. One patient died of non-Hodgkins lymphoma. Blastomycosis may occur in healthy children, including very young infants. Due to the frequency of extra-pulmonary disease, diagnosis may be difficult and frequently delayed, especially in cases of CNS infection.

Pandemic (H1N1) 2009 Influenza in Hospitalized Children in Manitoba: Nosocomial Transmission and Lessons Learned from the First Wave

OBJECTIVE To review the experiences at Winnipeg Childrens Hospital (WCH) during the 2009 influenza season, with an emphasis on nosocomial transmission and infection prevention and control responses. DESIGN A case series of patients admitted to WCH who had laboratory-confirmed cases of influenza between January 1 and July 31, 2009, with a comparison of patients with seasonal influenza and those with pandemic (H1N1) 2009 influenza; a review of the impact of infection prevention and control modifications on nosocomial transmission. PATIENTS AND SETTING A total of 104 inpatients with influenza, 81 of whom had pandemic (H1N1) 2009 influenza, were reviewed at a large Canadian pediatric tertiary care center. RESULTS There were no differences in risk factors, presentation, or outcome between patients with seasonal influenza and those with pandemic (H1N1) 2009 influenza. There were 8 nosocomial cases of pandemic (H1N1) 2009 influenza. Excluding patients with nosocomial cases, mean length of hospital stay was significantly shortened to 3.7 days for individuals who had pandemic (H1N1) 2009 influenza and who received empiric oseltamivir on admission to the hospital, compared with 12.0 days for patients for whom treatment was delayed (P = .02). Treatment with oseltamivir of all patients with suspected cases of influenza and prompt modifications to infection control practices, including playroom closures and enhanced education of visitors and staff, terminated nosocomial transmission. CONCLUSIONS Infection with pandemic (H1N1) 2009 influenza virus resulted in a substantial number of hospitalizations of pediatric patients in Manitoba, including those with nosocomial cases, thereby stressing the capacity of WCH. Immediate therapy with oseltamivir on admission to the hospital resulted in a significantly reduced length of hospitalization. This, coupled with intensified infection prevention and control practices, halted nosocomial transmission. These strategies should be considered in future pandemic influenza or other respiratory viral outbreaks.

Comparison of pathogens and their antimicrobial resistance patterns in paediatric, adult and elderly patients in Canadian hospitals

OBJECTIVES The purpose of this study was to describe the association between age groups and antimicrobial resistance in the most commonly identified pathogens in Canadian hospitals. METHODS Between 2007 and 2011, 27,123 clinically significant isolates, comprising 3580 isolates from children ≤ 18 years old, 12,119 isolates from adults 19-64 years old and 11,424 isolates from elderly patients aged ≥ 65 years old, were collected as part of the CANWARD surveillance study from tertiary-care centres across Canada. Antimicrobial susceptibility testing was performed according to CLSI guidelines. A multifactorial logistic regression model was used to determine the impact of demographic factors, including age groups, on antimicrobial resistance. RESULTS Staphylococcus aureus, Escherichia coli, Streptococcus pneumoniae and Pseudomonas aeruginosa were in the top five organisms for all of the age groups. The proportions of S. aureus that were methicillin resistant, enterococci that were vancomycin resistant and E. coli that produced extended-spectrum β-lactamases were 11.2%, 0.7% and 1.0% for children, 22.8%, 4.6% and 4.3% for adults, and 28.0%, 3.8% and 4.9% for the elderly, respectively. Notable age-related differences in antimicrobial resistance patterns included the following: significantly less methicillin, clindamycin, clarithromycin and trimethoprim/sulfamethoxazole resistance in S. aureus from children; for E. coli, higher cefazolin and ciprofloxacin resistance in the elderly and less ceftriaxone, ciprofloxacin and gentamicin resistance in isolates from children; more S. pneumoniae isolates with penicillin MICs >1 mg/L in children; and for P. aeruginosa, higher resistance rates for meropenem, ciprofloxacin and levofloxacin in adults. CONCLUSIONS The assessment of antimicrobial susceptibility patterns by age group revealed that resistance rates are often higher in the older age groups; however, considerable variability in age-specific resistance trends for different pathogen-antimicrobial combinations was noted.

Presentation and management of pediatric orbital cellulitis

BACKGROUND Orbital cellulitis is a serious, vision-threatening infection. OBJECTIVE To review the epidemiology and clinical data of pediatric orbital cellulitis in Manitoba. METHODS A 12-year retrospective review was conducted of all children (younger than 18 years of age) with orbital cellulitis admitted to Manitobas only tertiary pediatric centre. Admission rates for orbital cellulitis were compared over three distinct time periods, based on licensure and funding levels of the heptavalent pneumococcal conjugate vaccine (PCV7) in Manitoba. RESULTS Thirty-eight patients with orbital cellulitis were identified. Of these, 11% were of Aboriginal ethnicity in contrast with 30% to 40% of children who were admitted for other respiratory illnesses. Subperiosteal abscesses occurred in 31.5%. Only eight patients (21%) required surgery. Follow-up imaging after presentation usually did not indicate a need for subsequent surgical drainage. The mean number of orbital cellulitis cases per 1000 admissions for the following periods - before PCV7 licensure, after licensure and before full provincial funding, and after licensure and full funding - were 0.39, 0.53 and 0.90, respectively. No significant difference was noted among any of the periods as PCV7 coverage increased. CONCLUSIONS The rate of subperiosteal abscesses was lower than other reports. This may be due to the median age at presentation. In contrast to admissions for most other respiratory infections at the Winnipeg Childrens Hospital (Winnipeg, Manitoba), Aboriginal ethnicity was uncommon. Surprisingly, rates of admissions for orbital cellulitis appeared to show an increasing trend with increasing access to PCV7 in Manitoba, although overall the number of cases was very small. Studies into the changing microbiology of orbital cellulitis and sinusitis are warranted.

Septic arthritis due to Roseomonas gilardii in an immunocompetent adolescent.

The genus Roseomonas comprises groups of slow-growing, Gram-negative coccobacilli, which only infrequently cause infection in humans. When identified, they are associated with immunocompromised adults, often causing bacteraemia. Due to their rarity, members of this genus can be overlooked or misidentified using automated laboratory identification systems. We report on an immunocompetent adolescent patient who developed septic arthritis due to Roseomonas gilardii following surgery for a sports injury. The isolate was initially misidentified as Bordetella bronchiseptica using the Vitek 2 system, but confirmed as R. gilardii based on 16S rRNA gene sequencing. To the best of our knowledge, this is the first case of a healthy paediatric patient with septic arthritis due to R. gilardii.

Impact of neuraminidase inhibitors on influenza A(H1N1)pdm09‐related pneumonia: an individual participant data meta‐analysis

The impact of neuraminidase inhibitors (NAIs) on influenza‐related pneumonia (IRP) is not established. Our objective was to investigate the association between NAI treatment and IRP incidence and outcomes in patients hospitalised with A(H1N1)pdm09 virus infection.

A Study of the Infant Nasal Microbiome Development over the First Year of Life and in Relation to Their Primary Adult Caregivers Using cpn60 Universal Target (UT) as a Phylogenetic Marker.

Whereas the infant gut microbiome is the subject of intense study, relatively little is known regarding the nares microbiome in newborns and during early life. This study aimed to survey the typical composition and diversity of human anterior nare microflora for developing infants over time, and to explore how these correlate to their primary caregivers. Single nare swabs were collected at five time points over a one-year period for each subject from infant-caregiver pairs. Our study comprised of 50 infants (recruited at 2 weeks, post delivery) and their 50 primary caregivers. Applying the chaperonin-60 (cpn60) universal target (UT) amplicon as our molecular barcoding marker to census survey the microbial communities, we longitudinally surveyed infant nares microbiota at 5 time points over the course of the first year of life. The inter- and intra-subject diversity was catalogued and compared, both longitudinally and relative to their adult primary caregivers. Although within-subject variability over time and inter-subject variability were both observed, the assessment detected only one or two predominant genera for individual infant samples, belonging mainly to phyla Actinobacteria, Firmicutes, and Proteobacteria. Consistent with previously observed microbial population dynamics in other body sites, the diversity of nares microflora increased over the first year of life and infants showed differential operational taxonomic units (OTUs) relative to their matched primary caregiver. The collected evidence also support that both temporal and seasonal changes occur with respect to carriage of potentially pathogenic bacteria (PPBs), which may influence host predisposition to infection. This pilot study surveying paired infant/caregiver nare microbiomes provides novel longitudinal diversity information that is pertinent to better understanding nare microbiome development in infants.

Osteomyelitis Due to Multiple Carbapenemase-Producing Gram-Negative Bacteria: The First Case Report of a GES-13-Producing Pseudomonas aeruginosa Isolate in Canada

A case of osteomyelitis in an infant following a burn injury sustained in Pakistan caused by a GES-13-producing Pseudomonas aeruginosa (the first reported in Canada) and an OXA-48 producing Klebsiella pneumoniae is described. The present case serves to highlight the importance of international travel as a risk factor for infection with carbapenemase-producing bacteria and the challenges in the laboratory detection of these organisms.