Antibiotic Selection Pressure and Macrolide Resistance in Nasopharyngeal Streptococcus pneumoniae: A Cluster-Randomized Clinical Trial

Jeremy Keenan and colleagues report that during a cluster-randomized clinical trial in Ethiopia, nasopharyngeal pneumococcal resistance to macrolides was significantly higher in communities randomized to receive azithromycin compared with untreated control communities

Population-Based Epidemiology and Microbiology of Community-Onset Bloodstream Infections

SUMMARY: Bloodstream infection (BSI) is a major cause of infectious disease morbidity and mortality worldwide. While a positive blood culture is mandatory for establishment of the presence of a BSI, there are a number of determinants that must be considered for establishment of this entity. Community-onset BSIs are those that occur in outpatients or are first identified <48 h after admission to hospital, and they may be subclassified further as health care associated, when they occur in patients with significant prior health care exposure, or community associated, in other cases. The most common causes of community-onset BSI include Escherichia coli, Staphylococcus aureus, and Streptococcus pneumoniae. Antimicrobial-resistant organisms, including methicillin-resistant Staphylococcus aureus and extended-spectrum β-lactamase/metallo-β-lactamase/carbapenemase-producing Enterobacteriaceae, have emerged as important etiologies of community-onset BSI

Factors Influencing Early and Late Mortality in Adults with Invasive Pneumococcal Disease in Calgary, Canada: A Prospective Surveillance Study

BACKGROUND: Invasive pneumococcal disease continues to be an important cause of mortality. In Calgary, 60% of deaths occur within 5 days of presenting to hospital. This proportion has not changed since before the era of penicillin. The purpose of this study was to investigate what factors may influence death within 5 days of presentation with pneumococcal disease. METHODS AND FINDINGS: Demographic and clinical data from the CASPER (Calgary Area Streptococcus pneumoniae Epidemiology Research) study on 1065 episodes of invasive pneumococcal disease in adults (≥18 years) from 2000 to 2010 were analyzed. Adjusted multinomial regression was performed to analyze 3 outcomes: early mortality (<5 days post-presentation), late mortality (5-30 days post-presentation), and survival, generating relative risk ratios (RRR). Patients with severe disease had increased risk of early and late death. In multinomial regression with survivors as baseline, the risk of early death increased in those with a Charlson index ≥2 (RRR: 6.3, 95% CI: 1.8-21.9); the risk of late death increased in those with less severe disease and a Charlson ≥2 (RRR: 6.1, 95% CI: 1.4-27.7). Patients who never received appropriate antibiotics had 5.6X (95% CI: 2.4-13.1) the risk of early death. Risk of both early and late death increased by a RRR of 1.3 (95% CI: 1.2-1.4) per 5-year increase in age. In multinomial regression, there were no significant differences in the effects of the factors tested between early and late mortality. CONCLUSIONS: Presenting with severe invasive pneumococcal disease, multiple comorbidities, and older age increases the risk of both early and late death. Patients who died early often presented too late for effective antibiotic therapy, highlighting the need for an effective vaccine

Evaluation of coseasonality of influenza and invasive pneumococcal disease: results from prospective surveillance

BACKGROUND: The wintertime co-occurrence of peaks in influenza and invasive pneumococcal disease (IPD) is well documented, but how and whether wintertime peaks caused by these two pathogens are causally related is still uncertain. We aimed to investigate the relationship between influenza infection and IPD in Ontario, Canada, using several complementary methodological tools. METHODS AND FINDINGS: We evaluated a total number of 38,501 positive influenza tests in Central Ontario and 6,191 episodes of IPD in the Toronto/Peel area, Ontario, Canada, between 1 January 1995 and 3 October 2009, reported through population-based surveillance. We assessed the relationship between the seasonal wave forms for influenza and IPD using fast Fourier transforms in order to examine the relationship between these two pathogens over yearly timescales. We also used three complementary statistical methods (time-series methods, negative binomial regression, and case-crossover methods) to evaluate the short-term effect of influenza dynamics on pneumococcal risk. Annual periodicity with wintertime peaks could be demonstrated for IPD, whereas periodicity for influenza was less regular. As for long-term effects, phase and amplitude terms of pneumococcal and influenza seasonal sine waves were not correlated and meta-analysis confirmed significant heterogeneity of influenza, but not pneumococcal phase terms. In contrast, influenza was shown to Granger-cause pneumococcal disease. A short-term association between IPD and influenza could be demonstrated for 1-week lags in both case-crossover (odds ratio [95% confidence interval] for one case of IPD per 100 influenza cases  = 1.10 [1.02-1.18]) and negative binomial regression analysis (incidence rate ratio [95% confidence interval] for one case of IPD per 100 influenza cases  = 1.09 [1.05-1.14]). CONCLUSIONS: Our data support the hypothesis that influenza influences bacterial disease incidence by enhancing short-term risk of invasion in colonized individuals. The absence of correlation between seasonal waveforms, on the other hand, suggests that bacterial disease transmission is affected to a lesser extent. Please see later in the article for the Editors' Summary