How deadly is seasonal influenza-associated pneumonia? The German Competence Network for Community-Acquired Pneumonia.

The emergence of new influenza virus subtypes has rekindled the interest in the clinical course and outcome of patients with influenza-associated pneumonia. Based on prospective data from 5,032 patients with community-acquired pneumonia (CAP) included in the German Competence Network for Community-Acquired Pneumonia (CAPNETZ), we studied the incidence, clinical characteristics and outcome of patients with influenza-associated CAP and compared these findings with patients without influenza. Diagnosis relied on a positive PCR for influenza in throat washings. 160 patients with influenza-associated CAP were identified (3.2% of total population, 12% of those with defined aetiology). 34 (21%) patients with seasonal influenza had a concomitant pathogen (mostly Streptococcus pneumoniae). Patients with influenza-associated CAP were significantly older, had been vaccinated less often and had preceding antibacterial treatment less often. 30-day mortality was low (4.4%) and not different to that of patients with pneumonia caused by bacterial (6.2%) or viral (other than influenza) pathogens (4%). Patients with influenza plus a bacterial pathogen (mixed influenza-associated pneumonia) had a higher mortality than those with pure influenza-associated pneumonia (9% versus 3.2%). Mortality was higher in patients with mixed compared with pure influenza-associated pneumonia. However, we could not observe any excess mortality in patients with influenza-associated pneumonia.

Community-acquired pneumonia through Enterobacteriaceae and Pseudomonas aeruginosa: Diagnosis, incidence and predictors.

The aim of the present study was to determine the relevance of the presence of Enterobacteriaceae (EB) and Pseudomonas aeruginosa (PA) in patients with community-acquired pneumonia (CAP) and how the true incidence of these pathogens can be assessed. Based on prospective data from 5,130 patients with CAP included in the German Competence Network for Community-Acquired Pneumonia (CAPNETZ), the incidence, clinical characteristics, outcome and predictors of patients with CAP due to EB and PA were studied applying strict case definitions. The incidence of EB was 67 (1.3%) out of 5,130, including 27 patients with bacteraemia. PA was found in 22 (0.4%) out of 5,130 patients. These microorganisms were judged to be indeterminate pathogens in an additional 172 and 27 isolates, respectively. Patients with indeterminate pathogens differed considerably from those with definite isolates in terms of clinical presentation, comorbidity, pneumonia severity and outcome. Independent risk factors for EB included cardiac and cerebrovascular disease, and for PA chronic respiratory disease and enteral tube feeding. The 30-day mortality was significantly higher in patients with definite pathogens. In the present large population, the incidence of CAP due to EB/ PA was low. The risk of the presence of these pathogens can be assessed using several predictors, which may identify those patients in need of an extended diagnostic work-up and initial antimicrobial treatment.

Impact of intravenous {beta}-lactam/macrolide versus {beta}-lactam monotherapy on mortality in hospitalized patients with community-acquired pneumonia.

OBJECTIVES: Guidelines recommend dual-therapy consisting of a beta-lactam/macrolide (BLM) for hospitalized patients with community-acquired pneumonia. Nevertheless, the superiority over beta-lactam-monotherapy (BL) remains unproven. METHODS: Analyses from an observational study initiated by the German competence network CAPNETZ were performed. RESULTS: One thousand eight hundred and fifty-four patients were treated with either BL (49.0%) or BLM (51.0%). BLM therapy was associated with lower adjusted 14 day mortality [odds ratio (OR) 0.53; 95% confidence interval (CI): 0.30-0.94]. CRB65, neoplastic disease, age and nursing home residency were confirmed as independent predictors of death. Adjusted 14 day mortality risk was clearly reduced in patients with CRB65 = 2 (n = 411; OR 0.35; CI: 0.12-0.99) and CRB65 > or = 2 (n = 519; OR 0.42; CI: 0.18-0.997). However, this could not be shown for adjusted 30 day mortality. Patients with CRB65 < or = 1 showed low mortality (2.1%) without the influence of BLM. BLM therapy was associated with lower adjusted risk of treatment failure at 14 days (n = 1854; OR 0.65; CI: 0.47-0.89) and 30 days (OR 0.69; CI: 0.51-0.94) as well as in the subgroup of patients with CRB65 = 2 and CRB65 > or = 2. CONCLUSIONS: This study suggests the superiority of BLM therapy in patients with CRB65 risk classes of 2 or higher on 14 day mortality. BLM therapy was also associated with lower risk of treatment failure.

Outcome of community-acquired pneumonia: influence of age, residence status and antimicrobial treatment.

Community-acquired pneumonia remains a major cause of mortality in developed countries. There is much discrepancy in the literature regarding factors influencing the outcome in the elderly population. Data were derived from a multicentre prospective study initiated by the German Competence Network for Community-Acquired Pneumonia. Patients with community-acquired pneumonia (n = 2,647; 1,298 aged < 65 yrs and 1,349 aged > or = 65 yrs) were evaluated, of whom 72.3% were hospitalised and 27.7% treated in the community. Clinical history, residence status, course of disease and antimicrobial treatment were prospectively documented. Microbiological investigations included cultures and PCR of respiratory samples and blood cultures. Factors related to mortality were included in multivariate analyses. The overall 30-day mortality was 6.3%. Elderly patients exhibited a significantly higher mortality rate that was independently associated with the following: age; residence status; confusion, urea, respiratory frequency and blood pressure (CURB) score; comorbid conditions; and failure of initial therapy. Increasing age remained predictive of death in the elderly. Nursing home residents showed a four-fold increased mortality rate and an increased rate of gram-negative bacillary infections compared with patients dwelling in the community. The CURB score and cerebrovascular disease were confirmed as independent predictors of death in this subgroup. Age and residence status are independent risk factors for mortality after controlling for comorbid conditions and disease severity. Failure of initial therapy was the only modifiable prognostic factor.

Procalcitonin predicts patients at low risk of death from community-acquired pneumonia across all CRB-65 classes.

The aim of the present study was to investigate the prognostic value, in patients with community-acquired pneumonia (CAP), of procalcitonin (PCT) compared with the established inflammatory markers C-reactive protein (CRP) and leukocyte (WBC) count alone or in combination with the CRB-65 (confusion, respiratory rate >or=30 breaths x min(-1), low blood pressure (systolic value <90 mmHg or diastolic value or=65 yrs) score. In total, 1,671 patients with proven CAP were enrolled in the study. PCT, CRP, WBC and CRB-65 score were all determined on admission and patients were followed-up for 28 days for survival. In contrast to CRP and WBC, PCT levels markedly increased with the severity of CAP, as measured by the CRB-65 score. In 70 patients who died during follow-up, PCT levels on admission were significantly higher compared with levels in survivors. In receiver operating characteristic analysis for survival, the area under the curve (95% confidence interval) for PCT and CRB-65 was comparable (0.80 (0.75-0.84) versus 0.79 (0.74-0.84)), but each significantly higher compared with CRP (0.62 (0.54-0.68)) and WBC (0.61 (0.54-0.68)). PCT identified low-risk patients across CRB classes 0-4. In conclusion, procalcitonin levels on admission predict the severity and outcome of community-acquired pneumonia with a similar prognostic accuracy as the CRB-65 score and a higher prognostic accuracy compared with C-reactive protein and leukocyte count. Procalcitonin levels can provide independent identification of patients at low risk of death within CRB-65 (confusion, respiratory rate >or=30 breaths x min(-1), low blood pressure (systolic value <90 mmHg or diastolic value or=65 yrs) risk classes.

Changes in Escherichia coli resistance patterns during and after antibiotic therapy: a longitudinal study among outpatients in Germany.

There is worldwide concern about the appearance and rise of bacterial resistance to commonly used antibiotics. Although the gut is an important reservoir for resistant Escherichia coli, data from large-scale epidemiological studies concerning the colonisation dynamics of the normal gut flora with resistant E. coli during and after antibiotic therapy are sparse. Accordingly, a large community-based study was conducted to ascertain changes in the prevalence of resistant E. coli during and after antibiotic treatment. Stool samples before, during and after antibiotic therapy were obtained from 541 patients (aged >/=40 years) with a febrile infection who attended a general practitioner in southern Germany. The MICs of commonly prescribed antibiotics for E. coli isolates from the stools were determined. The prevalence of resistance to the corresponding antibiotics rose from 18% to 38%, from 29% to 58% and from 33% to 67% during treatment with beta-lactam antibiotics, doxycycline and co-trimoxazole, respectively. Prevalences of resistance in the E. coli isolates also rose for other antibiotic classes. With the exception of co-trimoxazole resistance, prevalences of resistance returned to baseline levels in <2 weeks after the cessation of antibiotic therapy. Thus, there was a substantial, but rapidly reversible, increase in the prevalence of resistant E. coli isolates during antibiotic treatment.

[Scope and limitations of risk-adjusted evaluation of lethality in community-acquired pneumonia using data collected according to section 21 of the German Hospital Reimbursement Law (Krankenhaus-Entgeltgesetz, KHEntG)]. / Möglichkeiten und Grenzen der risikoadjustierten Bewertung der Letalität bei der ambulant erworbenen Pneumonie mithilfe der section 21-Daten des Krankenhaus-Entgeltgesetzes (KHEntG).

INTRODUCTION: Several institutions are currently evaluating whether it is possible to gather valid, risk-adjusted quality indicators from routine billing data according to section 21 of the German Hospital Reimbursement Law (Krankenhaus-Entgeltgesetz, KHEntG). It is hoped that this method will enable hospitals to obtain quality assurance data in an easy and timely fashion. MATERIALS AND METHODS: For analysis, section 21 data according to KHEntG, quality assurance forms, and patients' medical records of the University Medical Center Ulm were evaluated in comparison to state and federal benchmark data from 2006. RESULTS: With regard to the quality indicator "Lethality in community-acquired pneumonia", it is possible to identify those cases that need to be included in quality assurance analysis by using predefined diagnosis lists. Risk adjustment can likewise be done according to the requirements set forth by the Federal Quality Assurance Office (Bundesgeschäftsstelle Qualitätssicherung, BQS), using only those data routinely collected for billing purposes. The results obtained are comparable to state and federal benchmark data. In addition, the analysis shows that the S3 recommendation to measure breathing rate as part of pneumonia risk assessment is not sufficiently being practiced at the moment. CONCLUSIONS: Risk-adjusted quality indicators can be generated from routine billing data according to section 21 KHEntG. Taking the patients' medical records as a reference, these indicators can even be shown to be more valid than those generated from BQS quality assurance data at the University Medical Center Ulm.

[Interobserver agreement in the assessment of pulmonary infiltrates on chest radiography in community-acquired pneumonia]. / Detektion pneumonischer Infiltrate bei ambulant erworbener Pneumonie: Ubereinstimmung in der Befundung der Röntgen-Thoraxaufnahme.

PURPOSE: To assess interobserver agreement (IOA) in the diagnosis of pulmonary infiltrates on chest x-rays for patients with community-acquired pneumonia (CAP). MATERIALS AND METHODS: From 7/2002 to 12/2005, 806 adults with CAP were included in the multicenter study "CAPNETZ" (7 hospitals). Inclusion criteria were clinical signs of pneumonia and pulmonary opacification on chest x-rays. Each x-ray was reevaluated by two radiologists from the university hospital in consensus reading against the interpreter at the referring hospital in regard to: presence of infiltrate (yes/no/equivocal), transparency (50%), localization, and pattern of infiltrates (alveolar/interstitial). The following parameters were documented: digital or film radiography, hospitalization, fever, findings of auscultation, microbiological findings. RESULTS: The overall IOA concerning the detection of infiltrates was 77.7% (n=626; CI 0.75-0.81), the infiltrates were not verified in 16.4% (n=132) by the referring radiologist with equivocal findings in 5.9% (n=48). The IOA of the different clinical centers varied between 63.2% (n=38, CI 0.48-0.78) and 92.3% (n=65, CI 0.86-0.99). The IOA for the diagnosis of infiltrates was significantly higher for inpatients with 82.6% (n=546; CI 0.80-0.85) than for outpatients with 55.2 % (n=80; CI 0.47-0.63), p<0.0001. The IOA of infiltrates with a transparency >50% was 95.1% (n=215; CI 0.92-0.98) versus 80.4% (n=403; CI 0.77-0.84) for infiltrates with a transparency >50% (p<0.0001). In patients with positive auscultation, the IOA was higher (p=0,034). Chest x-rays of patients with antibiotic therapy or an alveolar infiltrate showed more equivocal findings compared to patients without these features. CONCLUSION: There is considerable interobserver variability in the diagnosis of pulmonary infiltrates on chest radiographs. The IOA is higher in more opaque infiltrates, positive auscultation and inpatients.

Cleavage of tumor necrosis factor-alpha by Legionella exoprotease.

The role of the major secretory protein of Legionella pneumophila, a zinc protease, in Legionella infection is not known. Since an important step of the host reaction in Legionnaires' disease is the production of tumor necrosis factor-alpha (TNF-alpha) by alveolar macrophages, we studied the interaction of Legionella protease and U-937 cells with respect to TNF-alpha. The Legionella protease was purified by fractionated precipitation, gel filtration and hydrophobic interaction chromatography. The purified enzyme was added to U-937 cells, a promyelocytic cell line. In the supernatants of PMA-treated U-937 cells we found low concentrations of TNF-alpha after incubation with protease. Therefore we pursued the hypothesis of direct enzymatic degradation of TNF-alpha by Legionella protease. Enzymatic cleavage of TNF-alpha was proven by SDS-PAGE, ELISA and TNF-alpha bioassay with L-929 cells. The degradation of TNF-alpha by the Legionella protease was shown in all three systems. Enzymatic degradation of TNF-alpha might be important for the pathogenesis of Legionnaires' disease.

Genome analysis of Legionella ssp. by orthogonal field alternation gel electrophoresis (OFAGE).

Various Legionella isolates from different sources and origins were analysed by orthogonal field alternation gel electrophoresis of NotI cleaved genomic DNA. The genome of L. pneumophila Philadelphia I, the original isolate of the epidemics in 1976, exhibits only five NotI fragments. Two virulent derivatives, derived from L. pneumophila Philadelphia I, which were obtained by prolonged passage on artificial culture media, did not differ from their isogenic virulent strain according the NotI fragment pattern. By summing the lengths of the NotI fragments, the genome size of L. pneumophila Philadelphia I was calculated as approximately 3.9 Mb. Environmental L. pneumophila strains exhibited different NotI patterns, as did Legionella strains not belonging to the species pneumophila. The usefulness of DNA long range mapping of Legionella ssp. with NotI for epidemiology and evaluation of their evolutionary relationships is discussed.

Identification of 27-oxo-octacosanoic acid and heptacosane-1,27-dioic acid in Legionella pneumophila.

Two long-chain fatty acids, 27-oxo-octacosanoic acid (28:0(27-oxo)) and heptacosane-1,27-dioic acid (27:0-dioic) were identified for the first time in phenol-chloroform-petroleum ether extracts of Legionella pneumophila, indicating that they are constituents of lipopolysaccharide. The fatty acids were characterised by combined gas-liquid chromatography/mass spectrometry and proton nuclear magnetic resonance spectroscopy. Moreover, minor amounts of 29-oxo-triacontanoic (30:0(29-oxo)) acid and nonacosane-1,29-dioic acid (29:0-dioic) as well as 27-hydroxy-octacosanoic acid (28:0(27-OH)) were present in the phenol-chloroform-petroleum ether extract.

Purification and characterisation of elastase from Staphylococcus epidermidis.

An elastase of Staphylococcus epidermidis was purified by ion exchange chromatography on CM-Sepharose and characterised. Its M(r) is c. 21 kDa, its optimal temperature for activity is 42 degrees C and the pH optimum is 6.8. The enzyme is activated by cysteine and other SH-donators and inhibited by L-trans-epoxy-succinylleucylamido-(4-guanidino)butane (E64), an inhibitor of cysteine proteases, but not by 3,4-dichloroisocoumarin (3,4-DCI), an inhibitor of serine proteases. This finding suggests that the elastase of S. epidermidis is a cysteine protease. Because S. epidermidis elastase degrades human sIgA, IgM, serum albumin, fibrinogen, and fibronectin, this enzyme may be regarded as a virulence factor.

Evaluation of a competitive ELISA method for the determination of Klebsiella O antigens.

Strains of Klebsiella spp. are often inagglutinable by O-specific antisera because of the copious capsule produced by most isolates. A competitive ELISA method based on the observation that bacterial supernates containing homologous O antigen specifically inhibited the reaction of type-specific antisera with purified LPS coated on ELISA plates was used to examine the O antigen of 82 isolates of different Klebsiella species and subspecies. The O antigens O1/2ab (19 isolates), O2ab (13 isolates), O2ac (11 isolates) and O3 (16 isolates) were found to account for > 70% of the O antigenic types. Overall, 65 (79%) of the strains could be assigned to a specific O serogroup. The method is suitable for examining the role of individual O antigens in systemic klebsiella infections such as nosocomial septicaemia and pneumonia.

Bacterial colonization and endotoxin contamination of intravenous infusion fluids.

Bacterial colonization and endotoxin contamination of intravenous infusion fluids and catheter systems were examined in a surgical intensive care unit. Nineteen consecutive patients were randomly assigned to 48 h (N = 8) or 96 h (N = 11) change of infusion systems. Fluid from infusion bottles (51), infusion bottles plus burettes (102) and catheter systems (104) was cultured quantitatively for aerobic and anaerobic bacteria. Swabs (362) were taken from three-way stopcocks before and after the in-line infusion filters. Total and free endotoxin levels in infusion fluids were measured by quantitative chromogenic Limulus assay. The overall rate of bacterial colonization of bottles/burettes was 7.8% at 48 h and 15.7% at 96 h, while colonization rates of catheter fluid were 34.0% and 24.1%, respectively (n.s.). These high rates of colonization, despite regularly reinforced hand disinfection practices, may be explained by the high frequency of manipulations of the catheter systems, during acute interventions in emergency situations. Cell-bound endotoxin was found in 8.8% of the samples, but only 2.5% of the samples contained free endotoxin. The data support the use of in-line infusion filters, with bacterial-retaining property; however, these filters need not have endotoxin-retaining properties.

[Community-acquired respiratory tract infections. Current data on the efficacy of various classes of antibiotics and antibiotic resistance of the main prevalent bacteria species]. / Ambulant erworbene Atemwegsinfektionen. Aktuelle Daten zur Wirksamkeit und Resistenzsituation verschiedener Antibiotikagruppen gegenüber den wichtigsten bakteriellen Spezies.

BACKGROUND: The American Thoracic Society regards fluoroquinolones together with macrolides and doxycycline as first choice antibiotics in the empirical treatment of community acquired pneumoniae in non-hospitalized patients, while the Deutsche Gesellschaft für Pneumology only recommends macrolides and doxycycline for these patients. MATERIAL AND METHODS: In order to find out if the German recommendations still adequately reflect the local resistance situation, we analyzed antibiotic resistance of clinically relevant isolates of Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis in a multicenter study with special reference to sparfloxacine and ciprofloxacin according to DIN recommendations. RESULTS: In contrast to other European countries and the USA the prevalence of antibiotic resistance in Germany is low. Betalactam antibiotics were effective against more than 95% of strains of Haemophilus influenzae and Streptococcus pneumoniae. However, 10% of the strains of Streptococcus pneumoniae were resistant to tetracycline and 7% resistant to erythromycin. Resistances against ciprofloxacin and sparfloxacine were not detectable. Of both quinolone antibiotics, sparfloxacine was always more active than ciprofloxacin. CONCLUSIONS: These susceptibility data and the known prevalence of other respiratory tract pathogens such as Chlamydia pneumoniae and Mycoplasma pneumoniae which are sensitive to erythromycin and tetracycline therefore support the recommendations of the Deutsche Gesellschaft für Pneumology. However, newer fluoroquinolones with increased activity against pneumococci may be a helpful alternative for patients with persistent and recurrent exacerbations of respiratory infections and patients with relevant underlying diseases or relevant risk factors.

Nocardial infection in a renal transplant recipient--a case report.

Report is given about a 50 year old renal transplant recipient who developed signs of a severe pneumonia 37 days post transplantation. The diagnosis following chest X-ray and physical examination was multifocal nodular pneumonia of unknown origin in an immunosuppressed patient. Although a varying antibiotic chemotherapy was administered at high doses he died 4 weeks later without identification of the infective agent. Post-mortem and microbiological examinations revealed a systemic suppurative infection caused by Nocardia asteroides. Percutaneous or open lung biopsy within the first 10 days after onset of clinical symptoms has to be recommended to secure the diagnosis and treatment with sulphonamides.

Moxifloxacin monotherapy versus ß-lactam mono- or combination therapy in hospitalized patients with community-acquired pneumonia.

OBJECTIVE: In this observational study, we compared the outcomes of moxifloxacin monotherapy as compared to ß-lactam monotherapy as well as ß-lactam combination therapy in patients with community-acquired pneumonia (CAP). METHODS: Patients recruited within the German Competence Network for CAP (CAPNETZ) were evaluated for treatment regimen. Primary outcome variables were six months overall mortality, pneumonia-related mortality according to clinical judgment and treatment failures (necessity for treatment change and death). RESULTS: Overall, 4091 patients (mean age 64.4±17.8 (range 18-101) years, 2433 male (59.5%)) were included. 2068 patients received moxifloxacin (n=365) or ß-lactam monotherapy (n=1703). 330 patients died within six months. After controlling for confounders in multivariate analysis, moxifloxacin monotherapy had higher survival as compared to ß-lactam monotherapy (hazard ratio for moxifloxacin 0.57, 95% CI 0.35-0.92). Multivariate analysis including interaction terms showed that the protective effect of moxifloxacin was not present for CRB-65 class 0 but increased with higher CRB-65 scores (HR 0.69, 95% CI 0.50-0.96). Regarding pneumonia-related death, moxifloxacin monotherapy was also protective in multivariate analysis (HR 0.36, 95% CI 0.13-0.99). Moxifloxacin was also significantly associated with less treatment failures (p<0.001). In addition, it was not inferior to combination ß-lactam treatment (p=0.062). CONCLUSIONS: In CRB-65 class 0 moxifloxacin was equivalent to ß-lactams. Our observations are in support of a use of moxifloxacin monotherapy in hospitalized patients with moderate CAP (CRB-65 classes 1 and 2).