Clinical Presentations and Outcomes of Children in Canada With Recurrent Invasive Pneumococcal Disease From the IMPACT Surveillance Network.

BACKGROUND: Invasive pneumococcal disease due to Streptococcus pneumoniae can cause mortality and severe morbidity due to sepsis, meningitis and pneumonia, particularly in young children and the elderly. Recurrent invasive pneumococcal disease is rare yet serious sequelae of invasive pneumococcal disease that is associated with the immunocompromised and leads to a high mortality rate. METHOD: This retrospective study reviewed recurrent invasive pneumococcal disease cases from the Canadian Immunization Monitoring Program, ACTive (IMPACT) between 1991 and 2019, an active network for surveillance of vaccine-preventable diseases and adverse events following immunization for children ages 0-16 years. Data were collected from 12 pediatric tertiary care hospitals across all 3 eras of public pneumococcal conjugate vaccine implementation in Canada. RESULTS: The survival rate within our cohort of 180 recurrent invasive pneumococcal disease cases was 98.3%. A decrease of 26.4% in recurrent invasive pneumococcal disease due to vaccine serotypes was observed with pneumococcal vaccine introduction. There was also a 69.0% increase in the rate of vaccination in children with preexisting medical conditions compared with their healthy peers. CONCLUSION: The decrease in recurrent invasive pneumococcal disease due to vaccine-covered serotypes has been offset by an increase of non-vaccine serotypes in this sample of Canadian children.

Rationale and development of a business case for antimicrobial stewardship programs in acute care hospital settings.

Background: Antimicrobial stewardship programs (ASPs) have been shown to reduce inappropriate antimicrobial use and its consequences. However, these programs lack legislative requirements in many places and it can be difficult to determine what human resources are required for these programs and how to create a business case to present to hospital administrators for program funding. The objectives of the current paper were to review legislative requirements and outline human resource requirements for ASPs, and to create a base business case for ASPs. Methods: A working group of antimicrobial stewardship experts from across Canada met to discuss the necessary components for creation of a business case for antimicrobial stewardship. A narrative review of the literature of the regulatory requirements and human resource recommendations for ASPs was conducted. Informed by the review and using a consensus decision-making process, the expert working group developed human resource recommendations based on a 1000 bed acute care health care facility in Canada. A spreadsheet based business case model for ASPs was also created. Results: Legislative and /or regulatory requirements for ASPs were found in 2 countries and one state jurisdiction. The literature review and consensus development process recommended the following minimum human resources complement: 1 physician, 3 pharmacists, 0.5 program administrative and coordination support, and 0.4 data analyst support as full time equivalents (FTEs) per 1000 acute care beds. Necessary components for the business case model, including the human resource requirements, were determined to create a spreadsheet based model. Conclusions: There is evidence to support the negative outcomes of inappropriate antimicrobial use as well as the benefits of ASPs. Legislative and /or regulatory requirements for ASPs are not common. The available evidence for human resource recommendations for ASPs using a narrative review process was examined and a base business case modelling scenario was created. As regulatory requirements for ASPs increase, it will be necessary to create accurate business cases for ASPs in order to obtain the necessary funding to render these programs successful.

Pneumonia in healthy Canadian children and youth: Practice points for management.

Although immunization has decreased the incidence of bacterial pneumonia in vaccinated children, pneumonia remains common in healthy children. Unless it is totally impractical, a chest radiograph should be performed to confirm the diagnosis of pneumonia. Factors such as age, vital signs and other measures of illness severity are critical in the decision regarding whether to admit a patient to hospital. Because Streptococcus pneumoniae continues to be the most common cause of bacterial pneumonia in children, prescribing amoxicillin or ampicillin for seven to 10 days remains the mainstay of empirical therapy for non-severe pneumonia. If improvement does not occur, consideration should be given to searching for complications (empyema or lung abscess). Routine chest radiographs at the end of therapy are not recommended unless clinically indicated.

Pediatric antifungal therapy. Part II: neonatal infections.

The management of neonatal fungal infections poses several challenges, including the fact that the choices of available agents are limited, given the paucity of data relating to the use of newer antifungal agents in the group of infants. The information summarized herein represents in part the consensus of a group of clinicians involved in the care of neonates at risk of and with fungal infections. The document addresses the prophylaxis and treatment of fungal infections in neonates. It highlights the role of current and emerging antifungal agents, including the lipid amphotericin B products, echinocandins and triazoles.

Pediatric antifungal therapy. Part I: focus on febrile neutropenia, invasive aspergillosis, combination antifungal therapy and invasive candidiasis in immunocompromised pediatric patients.

The number of available antifungal agents has significantly increased in recent years. These agents are starting to take over niches that were previously occupied by conventional amphotericin B. For many of these agents, pediatric data from randomized trials are generally lacking and clinicians are faced with extrapolating from data generated in adult patients. This notwithstanding, this report summarizes recommendations that define the roles of newer antifungal agents in the treatment of selected scenarios among immunocompromised pediatric patients. The report includes the outcome of a Canadian conference on the use of antifungal agents in children, supplemented by literature reviews and incorporating information from existing national or international guidelines, where appropriate. The focus of the report is on febrile neutropenia, invasive aspergillosis, combination antifungal therapy and selected aspects of the management of invasive candidiasis.

Recommendations for the use of rotavirus vaccines in infants.

Rotavirus infection occurs in the majority of healthy children before five years of age, and is the most common diarrheal illness associated with hospitalization. The majority of children present with symptoms of vomiting, diarrhea and fever. As a result, rotavirus gastroenteritis is responsible for greater morbidity than other common childhood diarrheal illnesses. The highest risk of severe disease is in children younger than two years of age. It is estimated that one in 20 children will require an emergency department visit. In addition to community-acquired infections, hospital-acquired infections are also significant. There are currently two licensed rotavirus vaccines in Canada. Both vaccines are administered orally and are highly effective against severe disease and hospitalization. Large pre- and postmarketing studies have shown no increased risk of intussusception with the current rotavirus vaccines. The present statement provides information concerning the clinical disease and rotavirus vaccines in Canada.

Granulocyte inflammatory markers and airway infection during acute exacerbation of chronic obstructive pulmonary disease.

There is increasing evidence that chronic obstructive pulmonary disease (COPD) is associated with chronic inflammation in the airways and lung parenchyma; however, little is known about the inflammatory response during acute COPD exacerbation. The objectives of this study were (1) to determine if inflammatory markers associated with neutrophilic inflammation and activation increase at times of acute COPD exacerbation relative to the clinically stable state, and (2) to determine whether the presence of acute bacterial or viral infection at the time of COPD exacerbation could be correlated with increases in sputum markers of inflammation. Induced sputum was collected from patients with COPD when they were clinically stable, during the time of an acute exacerbation, and 1 mo later. Sputum was analyzed at each time point for soluble markers associated with neutrophilic inflammation; myeloperoxidase (MPO), tumor necrosis factor-alpha (TNF-alpha), and interleukin-8 (IL-8). Serologic assays on acute and convalescent sera were performed for respiratory viruses, and induced sputum was also subject to quantitative bacterial cultures, viral cultures, and polymerase chain reaction (PCR) for detection of respiratory viruses. Fourteen of the 50 patients enrolled in the study met predetermined criteria for an acute COPD exacerbation over the 15-mo study period. TNF-alpha and IL-8 were significantly elevated in the sputum of patients during acute COPD exacerbation compared with when they were clinically stable (p = 0.01 and p = 0.05, respectively). Concentrations of these cytokines declined significantly 1 mo after the exacerbation. Three of 14 patients (21%) had confirmed bacterial or viral respiratory tract infections. Patients with documented infection did not demonstrate greater increases in sputum levels of inflammatory cytokines during exacerbations compared with patients without demonstrable infection. We conclude that markers of airway neutrophilic inflammation increase at the time of acute COPD exacerbation and then decline 1 mo later, and that this acute inflammatory response appears to occur independently of a demonstrable viral or bacterial airway infection.

Evaluating the benefits of antimicrobial prophylaxis to prevent urinary tract infections in children: a systematic review.

BACKGROUND: The recurrence rate for urinary tract infections in children is estimated at between 30% and 40%. The use of low doses of antibiotics as prophylaxis for recurrent urinary tract infections is common clinical practice. However, prolonged antimicrobial therapy has the potential to contribute to problems of bacterial resistance and antimicrobial side effects. The aim of this review was to systematically examine the available evidence for the effectiveness of this intervention. METHODS: We conducted a literature search of 3 electronic databases for the period 1966 to 1999. We also searched bibliographies from conference proceedings and contacted content experts to ensure completeness of our database. Each trial was evaluated on the basis of the following inclusion criteria: target population (children), intervention (antibiotic v. no antibiotic), outcome (number of urinary tract infections) and study design (randomized controlled trial). Quality was assessed for the studies that met these criteria. RESULTS: Most of the studies identified were case series and cohort studies. Only 6 randomized trials fulfilled the inclusion criteria. All were of low quality (median 2, range 0 to 2 [maximum quality score 5]). Three trials dealt with children who had anatomically normal urinary tracts, and three included children with neurogenic bladder. The rate of infections for patients with normal urinary tracts ranged from 0 to 4.0 per 10 patient-years for the treatment groups and from 4.0 to 16.7 for the control groups. The recurrence rates for patients with neurogenic bladders in 2 trials were 2.9 and 17.1 per 10 patient-years for the treatment groups and 1.5 and 33.0 for the control groups. INTERPRETATION: The available evidence for using antimicrobial prophylaxis to prevent urinary tract infection in children with normal urinary tracts or neurogenic bladder is of low quality. This suggests that the magnitude of any benefit should at best be questioned. The surprising lack of data for children with reflux is of concern. Well-designed trials are needed to optimize the use of antimicrobials in children with recurrent urinary tract infection.

Antimicrobial use in febrile children diagnosed with respiratory tract illness in an emergency department.

BACKGROUND: In an era of increasing antibiotic resistance, the prevalence of antibiotic usage and associated factors should be ascertained to optimize their use. We set out to determine the prevalence of antibiotic use in febrile children diagnosed with respiratory tract illnesses at a children's hospital emergency department; to determine how often viral studies were conducted; and to identify patient characteristics associated with antibiotic use. METHODS: We conducted a retrospective study of antibiotic use in febrile children 3 months to 10 years old presenting with respiratory illnesses during two 1-month periods. Patient charts and laboratory tests were reviewed. Antibiotic use was related to diagnosis by logistic regression. RESULTS: A total of 836 patient visits were selected. Antibiotics were prescribed for otitis media in 96% of patients, for pneumonia in 100%, for pharyngitis in 66%, for bronchiolitis in 38%, for reactive airway disease in 24% and for viral or "upper respiratory tract illness" in 14%. For viral illness or upper respiratory tract infection, antibiotic use was associated with a fever duration of >48 h [odds ratio (OR), 3.2; 95% confidence interval (CI) 1.7, 5.9] and having a chest radiograph performed (OR 2.1; 95% CI 1.02, 4.37). Patients with pharyngitis who had a throat swab were less likely to receive an antibiotic (OR 0.08; 95% CI 0.02, 0.4) than those who did not have a swab. In this emergency department antibiotic use for these indications decreased by 11% during the 1997 to 1998 study interval (P < 0.001). CONCLUSION: Antibiotics were commonly prescribed for pharyngitis, bronchiolitis and reactive airway disease, which are conditions principally caused by viruses. Addressing reasons why there is a difference between guidelines and antibiotic use in these conditions may be important.

Carriage of Neisseria species in communities with different rates of meningococcal disease.

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.

Epidemic of nosocomial Legionnaires' disease in renal transplant recipients: a case-control and environmental study.

An outbreak of Legionella pneumophila pneumonia occurred in 6 of 49 new renal transplant recipients over the course of 13 months. We compared infected patients (cases) and uninfected patients (controls) with respect to potential risk factors. Corticosteroid use, need for hemodialysis and number of days of hemodialysis were significantly greater among the cases. Logistic regression analysis identified corticosteroid dosage and number of days of hemodialysis as independent risk factors. Lymphopenia and monocytopenia were correlated with the amount of corticosteroid administered and occurred to a greater degree in the cases. All clinical isolates were of L. pneumophila serogroup 1, subtype Philadelphia 1, which was also cultured from a recovery room sink outside the operating room where the transplants were done. Other areas of the hospital were colonized with other, heterogeneous strains of L. pneumophila. The organism was not eliminated from the hospital water supply despite shock chlorination and superheating of water tanks. The epidemic ended when new transplant recipients routinely received prophylactic trimethoprim-sulfamethoxazole (160-800 mg given orally once daily) while in hospital after transplantation. Corticosteroid-induced monocytopenia and lymphopenia and the complement activation and monocyte depletion effects of hemodialysis may combine to increase susceptibility to Legionnaires' disease.

Role of ceftriaxone in sexually transmitted diseases.

Ceftriaxone is a third-generation cephalosporin with antibacterial and pharmacokinetic characteristics that make it an excellent choice for the treatment of gonococcal infection and chancroid. Adverse effects are unusual. Clinical efficacy in all reported studies has been excellent. Additional studies are required for further elucidation of the role of ceftriaxone in the treatment of pelvic inflammatory disease and syphilis. Chlamydial infections are not altered by ceftriaxone, and additional treatment is necessary if Chlamydia is present concurrently with Neisseria gonorrhoeae.

In vitro activity of ceftriaxone, cefetamet (Ro 15-8074), ceftetrame (Ro 19-5247; T-2588), and fleroxacin (Ro 23-6240; AM-833) versus Neisseria gonorrhoeae and Haemophilus ducreyi.

We examined 300 strains of Neisseria gonorrhoeae and 100 strains of Haemophilus ducreyi to determine their in vitro susceptibility to two new cephalosporins, cefetamet (Ro 15-8074) and ceftetrame (Ro 19-5247; T-2588), and a new fluroquinolone, fleroxacin (Ro 23-6240; AM-833). Their activity was compared with that of ceftriaxone, penicillin, spectinomycin, tetracycline, and erythromycin. Cefetamet, ceftetrame, and fleroxacin had excellent in vitro activity against both groups of microorganisms. beta-Lactamase production did not significantly affect the MICs of these agents. The Mtr phenotype of N. gonorrhoeae raised the MICs two- to fourfold, but the MICs remained within the range of achievable levels in serum. These newer compounds have a distinct advantage over existing therapeutic agents in that they can be administered orally. Clinical trials are warranted to assess their usefulness in the therapy of gonorrhea and chancroid.

Bacillus cereus endophthalmitis.

The authors present a case of a young man with post-traumatic endophthalmitis caused by Bacillus cereus. The clinical course was typical of the panophthalmitis caused by this toxin-producing organism: rapid onset of signs of systemic infection, a corneal ring abscess and eventual loss of the globe requiring enucleation. Studies of experimental rabbit models of the infection have indicated that the most efficacious regimen consists of systemic and topical clindamycin and gentamicin. Successful therapy depends upon immediate systemic administration of these agents when the clinical setting suggests Bacillus cereus infection.