Pneumonia Bacterial Publications (38833)


Pneumonia Bacterial Publications

BMJ Case Rep
BMJ Case Rep 2017 Jan 17;2017. Epub 2017 Jan 17.
Department of Infectious Diseases, Ohio State University College of Medicine, Columbus, Ohio, USA.
Ann. Clin. Microbiol. Antimicrob.
Ann Clin Microbiol Antimicrob 2017 Jan 17;16(1). Epub 2017 Jan 17.
Center for Anti-Infective Research and Development, Hartford Hospital, 80 Seymour Street, Hartford, CT, 06102, USA.

Amikacin inhale (BAY41-6551), a unique drug-device combination of a specially formulated drug solution and a pulmonary drug delivery system device (AMK-I) is currently under phase III study as an adjunctive therapy to IV antibiotics for the treatment of Gram-negative pneumonia in mechanically ventilated patients. While the epidemiology of nosocomial pneumonia is predominated by Gram-negative pathogens such as Pseudomonas aeruginosa and the Enterobacteriaceae, Staphylococcus aureus is increasingly recognized as a pathogen of concern for these pulmonary based infections. Since the aminoglycosides are historically quite active against S. Read More

aureus the use of adjunctive AMK-I may enhance bacterial eradication. Herein, we aimed to characterize the in vitro pharmacodynamic (PD) profile of human-simulated ELF exposures of AMK-I against both methicillin-sensitive (MSSA) and -resistant (MRSA) S. aureus.
An in vitro model was used to simulate the resultant ELF pharmacokinetic profile of amikacin after the administration of AMK-I 400 mg q12h. The antibacterial activity of this regimen was tested against 7 S. aureus isolates that display MIC profiles encountered clinically (4 MRSA; MIC range 4-64, 3 MSSA; MIC range 8-16 mg/L). Experiments were conducted over 24 h and samples were taken throughout this period to assess the bacterial density in both control and treatments.
The mean ± SD inoculum 0 h bacterial density was 6.4 ± 0.09 which increased to 8.6 ± 0.19 log10 CFU/mL in the control models by the end of 24 h experiments. Simulated ELF concentrations of AMK-I resulted in a rapid, 5 log10 declined in CFU over the initial 12 h for all MRSA and MSSA isolates. After 12 h, all bacterial counts remained below the limit of detection (LOD, 1.7 log10 CFU/mL) and no regrowth was evident at the end of the study.
AMK-I produced an ELF exposure profile that was rapidly bactericidal against S. aureus displaying typical MICs to amikacin irrespective of their phenotypic profile to methicillin. While the Gram-negative organisms are the target pathogens for AMK-I in the ongoing clinical trials, these data suggest that this adjunctive regimen may also have the potential to eradicate both MSSA and MRSA from lower airway which needs to be further evaluated in randomized-controlled clinical trials.

J. Thromb. Haemost.
J Thromb Haemost 2017 Jan 16. Epub 2017 Jan 16.
Center for Experimental and Molecular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.

Innate immunity and coagulation are closely linked during sepsis. Their interaction can be detrimental for outcome due to microvascular failure but can also enhance host defense. The role of thrombin herein has not been fully elucidated. Read More

We aimed to investigate the contribution of thrombin to the host response during pneumonia derived sepsis.
Mice treated with the specific thrombin inhibitor Dabigatran or control chow were infected with the common human sepsis pathogen Klebsiella (K.) pneumoniae via the airways. In subsequent infection experiments, mice were additionally treated with Ancrod to deplete fibrinogen. Ex vivo Klebsiella growth was assessed by incubating human whole blood or specific blood components in various conditions with Klebsiella.
Thrombin inhibition by Dabigatran enhanced bacterial outgrowth and spreading, and accelerated mortality. Thrombin inhibition did not influence neutrophil recruitment to the lung or activation or neutrophil extracellular trap formation. Dabigatran reduced D-dimer formation and fibrin deposition in the lung. Fibrin depletion also enhanced bacterial outgrowth and spreading, and thrombin inhibition had no additional effect herein. Both thrombin and fibrin polymerization inhibited ex vivo Klebsiella outgrowth in human whole blood, which was neutrophil dependent and the effect of thrombin required the presence of platelets and platelet protease activated receptor-1. In vivo thrombin inhibition reduced platelet-neutrophil complex formation and endothelial cell activation, but did not prevent sepsis-induced thrombocytopenia or organ damage.
These results suggest that thrombin plays an important role in protective immunity during pneumonia derived sepsis by fibrin polymerization and enhancement of platelet-neutrophil interactions. This article is protected by copyright. All rights reserved.

Pseudomonas aeruginosa is a common cause of ventilator-associated pneumonia (VAP). Guidelines recommend dual coverage of P. aeruginosa, but the beneficial effect of combination therapy is controversial. Read More

We described antibiotic prescriptions and evaluated the clinical impact of initial combination antibiotic therapy and de-escalation strategy in patients with VAP caused by P. aeruginosa.
Between 1994 and 2014, all 100 patients with VAP caused by P. aeruginosa in our intensive care unit (ICU) were included in a retrospective cohort study to evaluate the prognostic impact of initial combination antibiotic therapy.
Eighty-five patients received initial combination antibiotic therapy and 15 monotherapy. Nine patients received inadequate initial antibiotic therapy. De-escalation was performed in 42 patients. Thirty-nine patients died in the ICU. Factors independently associated with death were SAPS II score [SAPS II ≥40 versus <40: hazard ratio (HR) 2.49, 95% confidence interval (CI) 1.08-5.70, p = 0.03] and septic shock (HR = 4.80, 95% CI = 1.90-12.16, p < 0.01) at onset of VAP. Initial combination antibiotic therapy (HR = 1.97, 95% CI = 0.56-6.93, p = 0.29) and early de-escalation (HR = 0.59, 95% CI = 0.27-1.31, p = 0.19) had no impact on mortality. In multivariate analysis, the risk for inappropriate initial antibiotic therapy was higher in cases with multi-drug resistant P. aeruginosa [odd ratio (OR) = 7.11, 95% CI = 1.42-35.51, p = 0.02], but lower in cases with initial combination antibiotic therapy (OR = 0.12, 95% CI = 0.02-0.63, p = 0.01).
In our cohort, combination therapy increased the likelihood of appropriate therapy but did not seem to impact on mortality.

J Athl Train
J Athl Train 2017 Jan 16. Epub 2017 Jan 16.
Department of Human Performance and Sports Sciences, Ohio Northern University, Ada.

 At the request of the National Wrestling Coaches Association and the head wrestling coach at our university, we conducted a study of infection transmission in collegiate wrestlers.
 To examine disinfectant effectiveness and develop best-practice guidelines for minimizing the spread of skin infections via wrestling mats.
 Controlled laboratory study and crossover study. Read More

 Laboratory and two 15-college wrestling invitational meets.
 A total of 231 collegiate wrestlers and 8 officials.
 In the laboratory-based part of the study, we measured the bacterial load of mats disinfected with 10% bleach, OxiTitan, Benefect, eWater, and KenClean and inoculated with Staphylococcus epidermidis (strain ATCC 12228) at a concentration of 6.5 × 10(4) bacteria/cm(2). In the empirical part of the study, we used these disinfectants during 2 invitational meets and measured mat and participant bacterial load during competition. Participants were swabbed at weigh-in and after their last bout. Mat bacterial load was monitored hourly.
 We determined total colony counts and species.
 With controlled testing, we observed that products claiming to have residual activity reduced bacterial load by 63% over the course of competition compared with nonresidual agents. Only 4 of 182 participating wrestlers tested positive for methicillin-resistant Staphylococcus aureus , which is the normal population occurrence. The predominant species on mats were skin bacteria ( Staphylococcus epidermidis ) and substantial levels of respiratory bacteria ( Streptococcus pneumonia ), as well as several soil species and a surprisingly low incidence of fecal bacteria ( Escherichia coli ). Disinfectant effectiveness during the meets was consistent with controlled study findings. Cleaning mats with residual disinfectants reduced the average bacterial load by 76% compared with nonresidual cleaners. Using a footbath did not reduce the bacterial load compared with a bleach-cleaned mat, but using alcohol-based hand gel reduced it by 78%.
 Best practices based on these data include backward mopping of the mats with a residual disinfectant pulled behind the cleaner, allowing mats to dry before walking on them, having wrestlers use hand gel before each bout, and strongly recommending that all wrestlers receive annual influenza vaccinations.

J. Vet. Pharmacol. Ther.
J Vet Pharmacol Ther 2017 Jan 16. Epub 2017 Jan 16.
Department of Comparative Biological Sciences, The Royal Veterinary College, Hatfield, UK.
Microbes Infect.
Microbes Infect 2017 Jan 10. Epub 2017 Jan 10.
Laboratoire Ecologie et Biologie des Interactions, Equipe Microbiologie de l'Eau, Université de Poitiers, UMR CNRS 7267, F-86073 Poitiers, France; Laboratoire de parasitologie et mycologie médicale, Faculté de médecine et de pharmacie, 6, Rue de la Milétrie, 86034 Poitiers Cedex, France.
Am. J. Respir. Crit. Care Med.
Am J Respir Crit Care Med 2017 Jan 13. Epub 2017 Jan 13.
Royal Brompton Hospital, Interstitial Lung Disease Unit , Sydney Street , London, United Kingdom of Great Britain and Northern Ireland , SW3 6NP ;

Changes in the respiratory microbiome are associated with disease progression in Idiopathic pulmonary fibrosis (IPF). The role of the host response to the respiratory microbiome however remains unknown.
To explore the host-microbial interaction in IPF. Read More

Sixty patients diagnosed with IPF were prospectively enrolled, together with 20 matched controls. Subjects underwent bronchoalveolar lavage (BAL) and peripheral whole blood was collected into PAXgene tubes for all subjects at baseline. For IPF subjects additional samples were taken at 1, 3, and 6 months and (if alive) a year. Gene expression profiles were generated using Affymetrix Human Gene1.1ST Arrays.
Network analysis of gene expression data identified two gene modules that strongly associate with a diagnosis of IPF, BAL bacterial burden (determined by 16S quantitative PCR) and specific microbial OTUs, as well as lavage and peripheral blood neutrophilia. Genes within these modules that are involved in the host defence response include NLRC4, PGLYRP1, MMP9, DEFA4. The modules also contain two genes encoding specific antimicrobial peptides (SLPI and CAMP). Many of these particular transcripts were associated with survival and showed longitudinal over expression in subjects experiencing disease progression, further strengthening their relationship with disease.
Integrated analysis of the host transcriptome and microbial signatures demonstrates an apparent host response to the presence of an altered or more abundant microbiome. These responses remain elevated on longitudinal follow up, suggesting that the bacterial communities of the lower airways may be acting as persistent stimuli for repetitive alveolar injury in IPF.

Immunol. Lett.
Immunol Lett 2017 Jan 9. Epub 2017 Jan 9.
Emergency Medicine Department, University of Sao Paulo, Sao Paulo, Brazil.

Antimicrobial peptides are key components of the innate immune system. They act as broad-spectrum antimicrobial agents against Gram-positive and -negative bacteria, viruses, and fungi. More recently, antimicrobial peptides have been ascribed immunomodulatory functions, including roles in wound healing, induction of cytokines, and altering host gene expression. Read More

Cathelicidins are a class of antimicrobial peptide found in humans, mice, and rats, among others. Known as LL-37 in humans and cathelin-related antimicrobial peptide (CRAMP) in rodents, cathelicidins are produced by many different cells, including macrophages, neutrophils, and epithelial cells. The role of cathelicidins is somewhat confounding, as they exhibit both pro-and anti-inflammatory activity. A major obstacle in the study of cathelicidins is the inability of exogenous LL-37 or CRAMP to mimic the activity of their endogenous counterparts. Nevertheless, studies have shown that LL-37 is recognized by multiple receptors, and may stabilize or modulate Toll-like receptor signaling. In addition, cathelicidins play a role in apoptosis, inflammasome activation, and phagocytosis. However, many studies are revealing the dual effects of cathelicidins. For example, CRAMP appears to be protective in models of group A Streptococcus skin infection, pneumonia, and meningitis, but detrimental in cases of severe bacterial infection, such as septic shock. It is becoming increasingly clear that the activity of cathelicidins is modulated by complex interactions with the microenvironment, as well as the disease background. This article reviews what is currently known about the activity of cathelicidins in an attempt to understand their complex roles in systemic diseases.