Clinical and epidemiologic features of group a streptococcal pneumonia in Ontario,Canada

BACKGROUND: Since the 1960s, group A streptococcus (GAS) has accounted for less than 1% of cases of community-acquired pneumonia. During the past 2 decades there has been a resurgence of invasive GAS infection, but no large study of GAS pneumonia has been performed. METHODS: To determine the clinical and epidemiologic features of GAS pneumonia, we conducted prospective, population-based surveillance of all invasive GAS infection in residents of Ontario from January 1, 1992, through December 31, 1999. RESULTS: Of 2079 cases of invasive GAS infection, 222 (11%) represented GAS pneumonia. The incidence of GAS pneumonia ranged from 0.16 per 100 000 in 1992 to 0.35 per 100 000 in 1999. Most cases were community acquired (81%). Forty-four percent of nursing home-acquired cases occurred during outbreaks. The case fatality rate was 38% for GAS pneumonia, compared with 12% for the entire cohort with invasive GAS infection and 26% for patients with necrotizing fasciitis. The presence of streptococcal toxic shock syndrome (odds ratio, 19; 95% confidence interval, 8.4-42; P =.001) and increasing age (odds ratio per decade, 1.45; 95% confidence interval, 1.2-1.7; P<.001) were associated with fatal outcome. Time to death was rapid, with a median of 2 days despite antimicrobial therapy and supportive measures. CONCLUSIONS: Group A streptococcal pneumonia is a common form of invasive GAS disease but remains an uncommon cause of community-acquired pneumonia. Progression is rapid despite appropriate therapy. The incidence is similar to, and the case fatality rate higher than, that of necrotizing fasciitis.     

Antibodies to capsular polysaccharides of group B Streptococcus in pregnant Canadian women: relationship to colonization status and infection in the neonate.

In a cohort study of 1207 pregnant women in Alberta, Canada, the serotype distributions of vaginal-rectal group B Streptococcus (GBS) isolates were compared with all isolates from neonates with invasive GBS disease identified by population-based surveillance. Serum concentrations of Ia, Ib, II, III, and V capsular polysaccharide (CPS)-specific IgG also were determined, according to serotype of the vaginal-rectal colonizing GBS strain. GBS colonization was detected in 19.5% (235 of 1207) of women. Serotype III accounted for 20.6% (48 of 233) of colonizing strains available for typing but for 37% (27 of 73) of invasive isolates from neonates (P<.01). Maternal colonization with type III was least likely to be associated with moderate concentrations of III CPS-specific IgG. Serotype III GBS is more invasive than other serotypes in this population; this may be due, at least in part, to poor maternal type III CPS-specific antibody response.     

Optimizing antibiotics in residents of nursing homes: protocol of a randomized trial

BACKGROUND: Antibiotics are frequently prescribed for older adults who reside in long-term care facilities. A substantial proportion of antibiotic use in this setting is inappropriate. Antibiotics are often prescribed for asymptomatic bacteriuria, a condition for which randomized trials of antibiotic therapy indicate no benefit and in fact harm. This proposal describes a randomized trial of diagnostic and therapeutic algorithms to reduce the use of antibiotics in residents of long-term care facilities. METHODS: In this on-going study, 22 nursing homes have been randomized to either use of algorithms (11 nursing homes) or to usual practise (11 nursing homes). The algorithms describe signs and symptoms for which it would be appropriate to send urine cultures or to prescribe antibiotics. The algorithms are introduced by inservicing nursing staff and by conducting one-on-one sessions for physicians using case-scenarios. The primary outcome of the study is courses of antibiotics per 1000 resident days. Secondary outcomes include urine cultures sent and antibiotic courses for urinary indications. Focus groups and semi-structured interviews with key informants will be used to assess the process of implementation and to identify key factors for sustainability.     

Neonatal group B streptococcal disease: incidence, presentation, and mortality.

OBJECTIVES: To ascertain the incidence, and compare the clinical characteristics, laboratory parameters, and immediate mortality of neonates with early-onset (symptomatic and asymptomatic) and late-onset group B streptococcal (GBS) disease. METHODS: A chart review of 81 neonates with GBS disease (either blood and/or cerebrospinal fluid culture-proven) born between 1995 and 2002 admitted to two tertiary care perinatal centers in Toronto was conducted. Clinical characteristics were compared for (1) asymptomatic early-onset, symptomatic early-onset, and late-onset GBS disease and (2) survivors and non-survivors. RESULTS: The incidence of GBS disease was 1.13/1000 live births. One or more antepartum or intrapartum predisposing factors were recognized in 62% of cases. Early-onset was noted in 65 (80%) neonates (23 asymptomatic and 42 symptomatic). All full-term infants survived. The mortality was 6% and was confined to preterm neonates with early symptomatic disease who presented with shock and had thrombocytopenia. CONCLUSION: Antepartum or intrapartum known predisposing risk factors of GBS disease were lacking in one third of patients. Patients who died were preterm infants in the early symptomatic group.     

Incorporating variations in the quality of individual randomized trials into meta-analysis.

Meta-analysis is a method of synthesizing evidence from multiple sources. It has been increasingly applied to combine results from randomized trials of therapeutic strategies. Unfortunately there is often variation in the quality of the trials that are included in meta-analyses, limiting the value of combining the results in an overview. This variation in quality can lead to both bias and reduction in precision of the estimate of the therapy's effectiveness. There are a number of methods for quantifying the quality of trials including the detailed Chalmers system and simple scales. The nature of the relationship between these quality scores and the true estimate of effectiveness is unknown at this time. We discuss four methods of incorporating quality into meta-analysis: threshold score as inclusion/exclusion criterion, use of quality score as a weight in statistical pooling, visual plot of effect size against quality score and sequential combination of trial results based on quality score. The last method permits an examination of the relation between quality and both bias and precision on the pooled estimates. We conclude that while it is possible to incorporate the effect of variation of quality of individual trials into overviews, this issue requires more study.     

Expression of the complement membrane attack complex and its inhibitors in Pick disease brain

The immunohistochemical localization of the complement membrane attack complex (MAC) was examined in Pick disease brain and compared with the distribution of three of its inhibitors, vitronectin, protectin and clusterin. Pick bodies were stained intensely for both the MAC and protectin, weakly for vitronectin, but negatively for clusterin. However, the clusterin antibody intensely stained some pyramidal neurons in affected cortical areas, including ballooned neurons. The present study indicates that a complement-mediated attack is associated with the formation of Pick bodies, and provides further suggestive evidence that clusterin may be a marker for active neuronal degeneration.     

Lewy bodies in Parkinson's disease are recognized by antibodies to complement proteins

Summary The substantia nigra (SN) in 11 Parkinson's disease (PD) patients and 5 neurologically normal controls was examined immunohistochemically using antibodies to various proteins of the complement system. In PD, but not in control SN, intra-and extraneuronal Lewy bodies and dendritic spheroid bodies were stained with anti-human C3d, C4d, C7 and C9 antibodies, but not with antibodies to C1q, fraction Bb of factor B or properdin. Axonal spheroid bodies in the nigrostriatal tract were not stained by any of the complement antibodies. However, complement-activated oligodendroglia were revealed by anti-C3d and anti-C4d antibodies in the PD substantia nigral area. These data indicate that some pathological structures in PD activate the classical complement pathway.Supported by grants from the Medical Research Council of Canada and the Parkinson's Disease Foundation of Canada, as well as donations from individual British Columbians.     

Oropharyngeal candidiasis in patients with human immunodeficiency virus: correlation of clinical outcome with in vitro resistance, serum azole levels, and immunosuppression.

Azole-resistant thrush has emerged as a problem in people who are infected with human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS), especially those who have low CD4 cell counts who have had a previous relapse of oral candidiasis, and in those who require long-term suppressive antifungal therapy. Because of the development of a standardized methodology for antifungal susceptibility testing and interpretive criteria for resistance testing, studies of the clinical predictive value of in vitro results are possible. In this study, 61% of organisms isolated from patients who were receiving azole therapy and who had clinically resistant thrush had minimal inhibitory concentration values that would classify the isolate as "resistant" or "susceptible dose dependent." In contrast, 86% of isolates from patients with thrush that was clinically responsive to an azole were classified in vitro as "susceptible" or "susceptible dose dependent." No resistant isolates were detected in samples obtained from asymptomatic control patients who were not exposed to azole drugs. Serum levels of azole and CD4 cell counts were also important parameters with regard to prediction of response. We conclude that in vivo and in vitro correlations compare favorably to studies of susceptibility testing in bacteria.