Biologic response modifiers are a novel class of drugs used by sub-specialists to treat immune-mediated conditions such as juvenile idiopathic arthritis and inflammatory bowel disease. Also known as ‘cytokine inhibitors’, they are proteins whose purpose is to block the action of cytokines involved in inflammation. The desired therapeutic effect is to reduce or control inflammation. Tumour necrosis factor-α (TNF-α) inhibitors are the prototypes, but newer agents in this class target other cytokines such as interleukin(IL)-6, IL-12, and IL-23, or the proteins that target cytokine receptors on lymphocytes. They typically act by inhibiting the normal inflammatory processes involved in the immune response, particularly for macrophages. These agents are often used in combination with other immunosuppressive drugs such as methotrexate or steroids. The immune-modulating effects can persist days to weeks after discontinuation. Evidence indicates that patients treated with biologic response modifiers are at higher risk of tuberculosis infection and may be at higher risk of fungal or other infections with intracellular pathogens. This practice point offers guidelines on the preventive strategies that should be used in patients who will be or who are taking these immune-modifying agents.

Background

We report the first multi-site rotavirus genotype analysis in Canada. Prior to this study, there was a dearth of rotavirus G and P genotyping data in Canada. Publically funded universal rotavirus vaccination in Canada started in 2011 and has been introduced by four provinces to date. Uptake of rotavirus vaccines in Canada prior to 2012 has been very limited. The aim of this study was to describe the genotypes of rotavirus strains circulating in Canada prior to widespread implementation of rotavirus vaccine by genotyping samples collected from selected paediatric hospitals. Secondly we identified rotavirus strains that differed genetically from those included in the vaccines and which could affect vaccine effectiveness.

Methods

Stool specimens were collected by opportunity sampling of children with gastroenteritis who presented to emergency departments. Samples were genotyped for G (VP7) genotypes and P (VP4) genotypes by hemi-nested multiplex PCR methods. Phylogenetic analysis was carried out on Canadian G9 strains to investigate their relationship to G9 strains that have circulated in other regions of the world.

Results

348 samples were collected, of which 259 samples were rotavirus positive and genotyped. There were 34 rotavirus antigen immunoassay negative samples genotyped using PCR-based methods. Over the four rotavirus seasons, 174 samples were G1P[8], 45 were G3P[8], 22 were G2P[4], 13 were G9P[8], 3 were G4P[8] and 2 were G9P[4]. Sequence analysis showed that all Canadian G9 isolates are within lineage III.

Conclusions

Although a limited number of samples were obtained from a median of 4 centres during the 4 years of the study, it appears that currently approved rotavirus vaccines are well matched to the rotavirus genotypes identified at these hospitals. Further surveillance to monitor the emergence of rotavirus genotypes in Canada is warranted.

Background

Community-acquired pneumonia (CAP) is a common cause of pediatric admission to hospital. The objectives of this study were twofold: 1) to describe the clinical characteristics of CAP in children admitted to a tertiary care pediatric hospital in the pneumococcal vaccination era and, 2) to examine the antimicrobial selection in hospital and on discharge.

Methods

A retrospective review of healthy immunocompetent children admitted to a tertiary pediatric hospital from January 2007 to December 2008 with clinical features consistent with pneumonia and a radiographically-confirmed consolidation was performed. Clinical, microbiological and antimicrobial data were collected.

Results

One hundred and thirty-five hospitalized children with pneumonia were evaluated. Mean age at admission was 4.8 years (range 0–17 years). Two thirds of patients had been seen by a physician in the 24 hours prior to presentation; 56 (41.5%) were on antimicrobials at admission. 52 (38.5%) of patients developed an effusion, and 22/52 (42.3%) had pleural fluid sampled. Of 117 children who had specimens (blood/pleural fluid) cultured, 9 (7.7%) had pathogens identified (7 Streptococcus pneumoniae, 1 Group A Streptococcus, and 1 Rhodococcus). 55% of patients received 2 or more antimicrobials in hospital. Cephalosporins were given to 130 patients (96.1%) in hospital. Only 21/126 patients (16.7%) were discharged on amoxicillin. The median length of stay was 3 days (IQR 2–4) for those without effusion and 9 (IQR 5–13) for those with effusion. No deaths were related to pneumonia.

Conclusions

This study provides comprehensive data on the clinical characteristics of hospitalized children with CAP in the pneumococcal 7-valent vaccine era. Empiric antimicrobial choice at our institution is variable, highlighting a need for heightened antimicrobial stewardship.

BACKGROUND:

The Canadian Immunization Monitoring Program, ACTive (IMPACT) surveillance for rotavirus relies on monitoring hospital admissions. Because a diagnosis of rotavirus is not necessary for treatment purposes, and rotavirus is not a reportable disease, wide variation may exist in the admitting and testing practices for this disease. From 2005 to 2007, the number of rotavirus admissions differed significantly among IMPACT centres, and this variation could not be explained by population differences alone. Understanding this variation is important when interpreting surveillance data and estimating the cost-effectiveness of rotavirus vaccination programs.

METHODS:

Key informant interviews were conducted with pediatric infectious disease physicians and IMPACT nurse monitors involved with rotavirus surveillance to obtain in-depth information about rotavirus testing and admitting practices at each of the 12 IMPACT centres.

RESULTS:

A total of 18 of 24 interviews were completed, with at least one interview conducted with physicians and/or nurses at each centre. Four major differences were identified among the centres: case-identification methods, admission definitions, admission criteria and testing criteria. The criteria for admitting and testing patients as well as which patients were defined as admissions had the greatest influence on case totals.

DISCUSSION:

The present study found that differences in admitting and testing practices may contribute to significant differences in rotavirus admission totals. Given these differences, caution should be used when using local case estimates for cost-effectiveness analyses and immunization program decisions. The present study illustrates that understanding the factors that influence the identification of a disease is important when interpreting and applying surveillance data.

In Canada, antimicrobial treatment is the most common approach for acute otitis media. The aim of the present study was to compare the cost effectiveness of treatment with amoxicillin versus a watch-and-wait approach (WAIT) within a Canadian pediatric setting. Four hundred eighty-eight children, six months to five years of age, who participated in a randomized controlled trial were included in the study. The average medication costs per patient were higher for the amoxicillin group ($17.26) than for the WAIT group ($4.33). However, both health care ($148.44 versus $162.48) and patient costs ($23.50 versus $31.87) were greater for the WAIT group. The mean cost of treatment for the amoxicillin group was $189.20, compared with $198.68 for the WAIT group. Amoxicillin may be cost effective in treating children with acute otitis media. The potential development of antimicrobial resistance was not addressed in the present study.

BACKGROUND:

Nontuberculous mycobacteria (NTM) infections appear to be increasing in number and severity in developed countries worldwide. Surgical excision has been considered the standard treatment for NTM lymphadenitis, but the use of medical therapy seems to be increasing.

OBJECTIVE:

To determine the disease characteristics as well as the current therapeutic management of NTM infections in Canadian children.

METHODS:

Cases of definite or probable NTM infections were identified prospectively in children up to 18 years of age seen in 10 Canadian paediatric tertiary care centres from September 2005 to August 2006. Clinical, microbiological and pathological data were collected.

RESULTS:

A total of 60 cases were identified. Data were complete for 45 patients, including 34 cases of lymphadenitis, four cases of skin and soft tissue infection, and seven cases of pulmonary NTM infection. Seventy-nine per cent of children (27 of 34) with lymphadenitis had an unsuccessful course of antibiotics before diagnosis. Sixty-eight per cent of purified protein derivative tests (15 of 22) were positive. NTM was detected in 76% of samples (29 of 38), of which 62% were Mycobacterium avium complex. All patients with lymphadenitis underwent surgical therapy and most patients (74%) also received antimicrobials.

CONCLUSIONS:

Current trends indicate that the majority of the study centres are using medical therapy with variable regimen and duration as an adjunct to surgical excision in the treatment of NTM lymphadenitis. Larger numbers and longer follow-up times are needed to better evaluate the efficacy of medical therapy and outcome of disease. A randomized controlled study comparing surgical therapy alone and chemotherapy for NTM lymphadenitis is required.

Canada is a leader in establishing routine infant immunization programs against meningococcal C disease. Currently, all provinces have routine programs to provide meningococcal C conjugate vaccines to infants and children. The result of the existing programs has been a decrease in serogroup C incidence. The second most common vaccine-preventable serogroup in Canada is serogroup Y, the incidence of which has been stable. The availability of a quadrivalent conjugate vaccine against serogroups A, C, Y and W135 focuses attention on serogroup Y disease as it becomes relatively more prominent as a cause of vaccine-preventable invasive meningococcal disease. This vaccine was licensed in November 2006 but is not routinely used except in Nunavut, New Brunswick and Prince Edward Island. To allow a better understanding of the ‘value added’ by a serogroup Y-containing vaccine, it is necessary to have a contemporary profile of Y disease in Canada. In the present paper, recent surveillance data on invasive meningococcal disease across Canada are summarized.

Background

Although the incidence of serious morbidity with childhood pneumonia has decreased over time, empyema as a complication of community-acquired pneumonia continues to be an important clinical problem. We reviewed the epidemiology and clinical management of empyema at 8 pediatric hospitals in a period before the widespread implementation of universal infant heptavalent pneumococcal vaccine programs in Canada.

Methods

Health records for children < 18 years admitted from 1/1/00–31/12/03 were searched for ICD-9 code 510 or ICD-10 code J869 (Empyema). Empyema was defined as at least one of: thoracentesis with microbial growth from pleural fluid, or no pleural fluid growth but compatible chemistry or cell count, or radiologist diagnosis, or diagnosis at surgery. Patients with empyemas secondary to chest trauma, thoracic surgery or esophageal rupture were excluded. Data was retrieved using a standard form with a data dictionary.

Results

251 children met inclusion criteria; 51.4% were male. Most children were previously healthy and those ≤ 5 years of age comprised 57% of the cases. The median length of hospitalization was 9 days. Admissions occurred in all months but peaked in winter. Oxygen supplementation was required in 77% of children, 75% had chest tube placement and 33% were admitted to an intensive care unit. While similarity in use of pain medication, antipyretics and antimicrobial use was observed, a wide variation in number of chest radiographs and invasive procedures (thoracentesis, placement of chest tubes) was observed between centers. The most common organism found in normally sterile samples (blood, pleural fluid, lung biopsy) was Streptococcus pneumoniae.

Conclusion

Empyema occurs most commonly in children under five years and is associated with considerable morbidity. Variation in management by center was observed. Enhanced surveillance using molecular methods could improve diagnosis and public health planning, particularly with regard to the relationship between immunization programs and the epidemiology of empyema associated with community-acquired pneumonia in children.

Background

We studied the effects of access to point-of-care medical evidence in a computerised physician order entry system (CPOE) on management and clinical outcome of children with bronchiolitis.

Methods

This was a before-after study that took place in a Canadian tertiary care paediatric teaching hospital. The intervention was a clinical evidence module (CEM) for bronchiolitis management, adapted from Clinical Evidence (BMJ Publishing Group) and integrated into the hospital CPOE. CPOE users were medical trainees under the supervision of staff physicians working in the infant ward. Use of antibiotics, bronchodilators and corticosteroids; disease severity; length of hospital admission; and trainee use and perception of the CEM were measured before and after CEM introduction.

Results

334 paediatric inpatients age 2 weeks to 2 years, with a clinical diagnosis of bronchiolitis; 147 children the year preceding and 187 children the year following introduction of a Clinical Evidence Module (CEM). The percentage of patients receiving antibiotics fell from 35% to 22% (relative decrease 37%) following the introduction of the CEM (p = 0.016). Bronchodilator use was high but following the CEM patients no longer received more than one variety. Steroid usage and length of hospitalisation were low and unaffected. Trainees found the CEM to be educational.

Conclusion

Readily accessible clinical evidence at the point of care was associated with a significant decrease in antibiotic use and an end to multiple bronchodilator use. The majority of physician trainees found the CEM to be a useful educational tool.

Objectives

Debate continues with respect to a “watch and wait” approach versus immediate antibiotic treatment for the initial treatment of acute otitis media. In this double-blind noninferiority trial, we compared clinical improvement rates at 14 days for children (6 months to 5 years of age) with acute otitis media who were randomly assigned to receive amoxicillin or placebo.

Methods

We enrolled healthy children who presented to clinics or the emergency department with a new episode of acute otitis media during the fall and winter months in Ottawa (from December 1999 to the end of March 2002). The children were randomly assigned to receive amoxicillin (60 mg/kg daily) or placebo for 10 days. Telephone follow-up was performed on each of days 1, 2 and 3 and once between day 10 and day 14. The primary outcome was clinical resolution of symptoms, defined as absence of receipt of an antimicrobial (other than the amoxicillin in the treatment group) at any time during the 14-day period. Secondary outcomes were the presence of pain and fever and the activity level in the first 3 days, recurrence rates, and the presence of middle ear effusion at 1 and 3 months.

Results

According to clinical scoring, 415 of the 512 children who could be evaluated had moderate disease. At 14 days 84.2% of the children receiving placebo and 92.8% of those receiving amoxicillin had clinical resolution of symptoms (absolute difference –8.6%, 95% confidence interval –14.4% to –3.0%). Children who received placebo had more pain and fever in the first 2 days. There were no statistical differences in adverse events between the 2 groups, nor were there any significant differences in recurrence rates or middle ear effusion at 1 and 3 months.

Interpretation

Our results did not support the hypothesis that placebo was noninferior to amoxicillin (i.e., that the 14-day cure rates among children with clinically diagnosed acute otitis media would not be substantially worse in the placebo group than the treatment group). Nevertheless, delaying treatment was associated with resolution of clinical signs and symptoms in most of the children.

Background

Absenteeism due to communicable illness is a major problem encountered by North American elementary school children. Although handwashing is a proven infection control measure, barriers exist in the school environment, which hinder compliance to this routine. Currently, alternative hand hygiene techniques are being considered, and one such technique is the use of antimicrobial rinse-free hand sanitizers.

Methods

A systematic review was conducted to examine the effectiveness of antimicrobial rinse-free hand sanitizer interventions in the elementary school setting. MEDLINE, EMBASE, Biological Abstract, CINAHL, HealthSTAR and Cochrane Controlled Trials Register were searched for both randomized and non-randomized controlled trials. Absenteeism due to communicable illness was the primary outcome variable.

Results

Six eligible studies, two of which were randomized, were identified (5 published studies, 1 published abstract). The quality of reporting was low. Due to a large amount of heterogeneity and low quality of reporting, no pooled estimates were calculated. There was a significant difference reported in favor of the intervention in all 5 published studies.

Conclusions

The available evidence for the effectiveness of antimicrobial rinse-free hand sanitizer in the school environment is of low quality. The results suggest that the strength of the benefit should be interpreted with caution. Given the potential to reduce student absenteeism, teacher absenteeism, school operating costs, healthcare costs and parental absenteeism, a well-designed and analyzed trial is needed to optimize this hand hygiene technique.

FOLLOWING THE LAUNCH OF A PUBLICLY FUNDED influenza immunization program for all residents of Ontario over the age of 6 months, we evaluated 203 parents of children who presented to our emergency department between January and March of the following year (2001). Overall, 54 (27%) of the children had been vaccinated. Parents of non-immunized children were more likely to believe that immunization resulted in a flu-like illness (42% v. 17%; p = 0.001), caused side effects that were more severe than having influenza (36% v. 17%; p = 0.010) and weakened the immune system (52% v. 24%; p < 0.001). Parents of both immunized and non-immunized children incorrectly identified gastrointestinal symptoms as symptoms of influenza. The primary reason for deciding against immunization was the belief that their child was not at risk. After adjustment, children with a chronic disease were more likely than those without a chronic disease to be immunized (adjusted odds ratio [OR] 4.7, 95% confidence interval [CI] 1.8–12.6). Children of parents who discussed immunization with a physician were more likely to be immunized than those who had not discussed immunization with a physician (OR 6.8, 95% CI 2.4–19.2).

Background

Acute hematogenous osteomyelitis (AHO) occurs primarily in children and is believed to evolve from bacteremia followed by localization of infection to the metaphysis of bones. Currently, there is no consensus on the route and duration of antimicrobial therapy to treat AHO.

Methods

We conducted a systematic review of a short versus long course of treatment for AHO due primarily to Staphylococcus aureus in children aged 3 months to 16 years. We searched Medline, Embase and the Cochrane trials registry for controlled trials. Clinical cure rate at 6 months was the primary outcome variable, and groups receiving less than 7 days of intravenous therapy were compared with groups receiving one week or longer of intravenous antimicrobials.

Results

12 eligible prospective studies, one of which was randomized, were identified. The overall cure rate at 6 months for the short course of intravenous therapy was 95.2% (95% CI = 90.4, 97.7) compared to 98.8% (95% CI = 93.6, 99.8) for the longer course of therapy. There was no significant difference in the duration of oral therapy between the two groups.

Conclusions

Given the potential increased morbidity and cost associated with longer courses of intravenous therapy, this finding should be confirmed through a randomized controlled equivalence trial.

A single clone, Neisseria meningitidis serogroup C (C:2a:P1.2), was isolated from seven patients during a cluster of cases of meningococcal disease in Ontario in 1989. To determine whether the clone was present in asymptomatic individuals in the same population, pharyngeal swabs were taken from 7% (644 of 9125) of residents who were vaccinated during the outbreak. Rates of isolation of Neisseria species were also compared to those in two other geographical areas which did not have an elevated incidence of meningococcal disease. The rate of carriage of N meningitidis in the asymptomatic individuals sampled was between 1.9% and 5.4%. The clone isolated from patients was not present among the carrier strains as determined by sero- and subtyping and electrophoretic analysis of metabolic enzymes. Age greater than six years was the only factor associated with colonization with N meningitidis.

Background

There is limited information in the literature on the presentation and prognosis of candidal urinary tract infection (UTI) in infants in the neonatal intensive care unit (NICU).

Methods

This was a prospective cohort study performed in 13 Canadian NICUs. Infants with candidal UTI without extra-renal candidal infection at presentation were enrolled.

Results

Thirty infants fit the study criteria. Median birth weight and gestational age were 2595 grams (range 575-4255) and 35 weeks (range 24-41) with 10 infants being < 30 weeks gestation. The most common primary underlying diagnosis was congenital heart disease (n = 10). The median age at initial diagnosis was 16 days (range 6-84 days). Renal ultrasonography findings were compatible with possible fungal disease in 15 of the 26 infants (58%) in whom it was performed. Treatment was variable, but fluconazole and either amphotericin B deoxycholate or lipid-based amphotericin B in combination or sequentially were used most frequently. Extra-renal candidiasis subsequently developed in 4 infants. In 2 of these 4 infants, dissemination happened during prolonged courses of anti-fungal therapy. Three of 9 deaths were considered to be related to candidal infection. No recurrences of candiduria or episodes of invasive candidiasis following treatment were documented.

Conclusion

Candidal UTI in the NICU population occurs both in term infants with congenital abnormalities and in preterm infants, and is associated with renal parenchymal disease and extra-renal dissemination. A wide variation in clinical approach was documented in this multicenter study. The overall mortality rate in these infants was significant (30%). In one third of the deaths, Candida infection was deemed to be a contributing factor, suggesting the need for antifungal therapy with repeat evaluation for dissemination in infants who are slow to respond to therapy.