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Author(s): Birgitta Henriques Normark [1]; Staffan Normark [1]; Anna Norrby-Teglund [1] Staphylococcus aureus colonizes the noses of about 30% of healthy humans, normally without causing disease [1]. But it can [...]

Rationale Host and bacterial factors as well as different treatment regimens are likely to influence the outcome in patients with bacteraemic pneumococcal pneumonia. Objectives To estimate the relative contribution of host factors as well as bacterial factors and antibiotic treatment to mortality in bacteraemic pneumococcal pneumonia. Methods A cohort study of 1580 adult patients with community-acquired bacteraemic pneumococcal pneumonia was conducted between 2007 and 2009 in Sweden. Data on host factors and initial antibiotic treatment were collected from patient records. Antibiotic resistance and serotype were determined for bacterial isolates. Logistic regression analyses were performed to assess risk factors for 30-day mortality. Results Smoking, alcohol abuse, solid tumour, liver disease and renal disease attributed to 14.9%, 13.1%, 13.1%, 8.0% and 7.4% of the mortality, respectively. Age was the strongest predictor, and mortality increased exponentially from 1.3% in patients <45 years of age to 26.1% in patients aged =85 years. There was considerable confounding by host factors on the association between serotype and mortality. Increasing age, liver disease and serotype were associated with mortality in patients admitted to the ICU. Combined treatment with ß-lactam antibiotics and macrolide/quinolone was associated with reduced mortality in patients in the ICU, although confounding could not be ruled out. Conclusions Host factors appear to be more important than the specific serotype as determinants of mortality in patients with bacteraemic pneumococcal pneumonia. Several host factors were identified that contribute to mortality, which is important for prognosis and to guide targeted prevention strategies. [ABSTRACT FROM AUTHOR]

Background: Infection caused by Streptococcus pneumoniae is the leading cause of mortality in children worldwide. The aim of this study was to determine if a noted increase in non-susceptibility to penicillin among pneumococcal clinical isolates from young children reflected a similar increase in healthy children. Methods: During 2004-2005, before the conjugate pneumococcal vaccine was introduced in Sweden, 663 healthy children (13-24 months of age) attending 17 child health centres in Gothenburg, Sweden, were cultured for bacteria in the nasopharynx. Social factors were identified through a parental questionnaire. Pneumococcal serotypes and antibiotic resistance rates were determined. Antibiotic resistance was also monitored in 162 simultaneously obtained nasopharyngeal pneumococci isolated from clinical samples. Results: The healthy children frequently carried pneumococci (45%), Moraxella catarrhalis (54%), and Haemophilus influenzae (22%). The carriage rates for all these pathogens were higher in children attending day care centres compared to children staying at home ( p < 0.001). The dominating pneumococcal serotypes were 6B, 19F, 23F, and 6A. Non-susceptibility to penicillin was low (4.0%) and only exceeded by that to trimethoprim-sulfamethoxazole (9.8%). Both rates were higher in the clinical isolates (9.3% and 16.7%, respectively; p < 0.05). No relationships to geographic area, day care attendance, recent antibiotic use, or travel abroad were shown for any specific serotype or for the presence of penicillin-non-susceptible pneumococci in the healthy children. Conclusions: Pneumococcal resistance rates in the healthy child population were low and did not reflect the higher rates noted at the laboratory in clinical samples obtained before and during the study. [ABSTRACT FROM AUTHOR]

Background: Streptococcus pneumoniae is a major cause of morbidity and mortality worldwide, but Salso a common colonizer of the upper respiratory tract. The emergence and spread of antibiotic resistant pneumococcal strains has threatened effective therapy. The long-term effects of measures aiming to limit pneumococcal spread are poorly understood. Computational modeling makes it possible to conduct virtual experiments that are impractical to perform in real life and thereby allows a more full understanding of pneumococcal epidemiology and control efforts. Methods: We have developed a contact network model to evaluate the efficacy of interventions aiming to control pneumococcal transmission. Demographic data from Sweden during the mid- 2000s were employed. Analyses of the model's parameters were conducted to elucidate key determinants of pneumococcal spread. Also, scenario simulations were performed to assess candidate control measures. Results: The model made good predictions of previous findings where a correlation has been found between age and pneumococcal carriage. Of the parameters tested, group size in day-care centers was shown to be one of the most important factors for pneumococcal transmission. Consistent results were generated from the scenario simulations. Conclusion: We recommend, based on the model predictions, that strategies to control pneumococcal disease and organism transmission should include reducing the group size in daycare centers. [ABSTRACT FROM AUTHOR]

Background: Streptococcus pneumoniae is a genetically diverse major human pathogen, yet a common colonizer of the nasopharynx. Here we analyzed the influence of defects affecting in vitro growth rate, on the ability of S. pneumoniae to colonize and to cause invasive disease in vivo. Results: Of eleven different clinical isolates one serotype 14 carrier isolate showed a significantly longer generation time as compared to other isolates, and was severely attenuated in mice. To directly investigate the impact of growth rate on virulence, a panel of mutants in five non-essential housekeeping genes was constructed in the virulent TIGR4 background by insertion-deletion mutagenesis. Three of these mutants (ychF, hemK and yebC) were, to different degrees, growth defective, and showed a reduced invasiveness in an intranasal murine challenge model that correlated to their in vitro growth rate, but remained capable of colonizing the upper airways. The growth defect, as well as virulence defect of the hemK insertion-deletion mutant, was mediated by polarity effects on the downstream yrdC gene, encoding a probable chaperone in ribosome assembly. Conclusion: We conclude that large fitness defects are needed to completely prevent pneumococci from causing invasive disease after intranasal challenge. However, even severe growth defects still allow pneumococci to persistently colonize the upper airways. [ABSTRACT FROM AUTHOR]

The Toll-like receptors (TLRs) and the myeloid differentiation factor 88 (MyD88) are key players in the activation of the innate immune defence during microbial infections. Using different murine infection models, we show that MyD88-dependent signalling is crucial for the activation of the innate immune defence against Streptococcus pneumoniae. Our data demonstrate that both local and systemic inflammatory response to S. pneumoniae depends on the presence of MyD88 to clear bacterial colonization of the upper respiratory tract and to prevent pulmonary and systemic infection in mice. Finally, we described a strong correlation between enhanced bacterial growth in the bloodstream of MyD88-deficient mice and the inability to lower the serum iron concentration in response to infection. [ABSTRACT FROM AUTHOR]

Surveillance of group A streptococcus (GAS) infections in Sweden during 1996–1997 indicated that T28 isolates were dominant, whereas T1M1 infections were uncommon. Circulating T28 isolate were nearly all emm28, MLST52, and these clones had also been prevalent 10 years earlier. Isolates from invasive and noninvasive infections were of similar types and prevalences. The average national incidence of invasive episodes was 2.9⁄100,000 population but varied between 0 and 8.3⁄100,000 population in different counties. It increased markedly with age, reaching 22.9 episodes/100,000 among people aged ≥90 years. The incidence of puerperal sepsis was higher than expected (22.4⁄100,000 of those at risk), with 1 death. Overall mortality was 16% and was associated with preexisting chronic disease (P = .002.) Streptococcal toxic shock syndrome (STSS) developed in ∼15% of patients with invasive episodes, with a mortality rate of 45%. The use of nonsteroidal anti-inflammatory drugs was not found to be associated with the development of STSS. [ABSTRACT FROM AUTHOR]

Describes the role of neutrophil production of cyclic ADP-ribose catalyzed by the ADP-ribosyl cyclase enzyme CD38 in eliciting a sustained calcium signal that allows chemotactic movement of neutrophils to the infected lung tissue in the U.S. Cause of community-acquired pneumonia; Invasion of the epithelial linings of bronchioli and alveoli; Prevention of the spread of bacterial infection.

Abstract: Competence for genetic transformation seems to play a fundamental role in the biology of Streptococcus pneumoniae and is believed to account for serotype switching, evolution of virulence factors, and rapid emergence of antibiotic resistance. The initiation of competence is regulated by the quorum sensing system referred as the ComABCDE pathway. Experimental studies reveal that competence is down-regulated a short time after its induction and several hypotheses about the mechanism(s) responsible for this shut-down have been presented. Possibly, a ComX-dependent gene product, such as a repressor or a phosphatase, is involved. To better understand the down-regulation of the competence-evoking system in S. pneumoniae, a mathematical model was set up. By analyzing the model, we suggest that shut-down of competence possibly occurs at the transcriptional level on the comCDE operon. As a result of introducing a putative comX-dependent repressor, which inhibits expression of comCDE and comX, in the mathematical model, competence is demonstrated to appear in waves. This is supported by experimental studies showing the appearance of successive competence cycles in pneumococcal batch cultures. [Copyright &y& Elsevier]