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).

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.

[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.

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.

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.

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.

[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.

Prevalence of antibiotic resistance in Escherichia coli: overview of geographical, temporal, and methodological variations.

The increase in bacterial antibiotic resistance is of major concern worldwide, but pertinent epidemiologic studies have used strongly divergent approaches and are widely scattered in the literature. The aim of this study was to conduct a systematic review of studies reporting on the prevalence of antibiotic resistance in Escherichia coli in different parts of the world. Studies published from 1970 to 2006 on the prevalence of E. coli resistance were identified by a systematic Medline research and reviewed with respect to characteristics of the study design and study population, the method of resistance detection, and the prevalence of resistance. The prevalence of resistance to specific antibiotics was highly variable in different populations and in different countries and ranged from 0 to 100%. The prevalence of resistance reported in studies from Middle and South America, Spain, and Turkey was higher than that reported in the USA and Central Europe. Moreover, a tendency towards higher prevalence rates of resistance in recent years was observed. The findings indicate a need for regular monitoring of antimicrobial susceptibility rates in different human and animal populations by standardized sampling and measurement procedures. Such monitoring would help identify relevant factors that contribute to the spread of resistant pathogens and would support the prudent use of antibiotics.

Moxifloxacin prophylaxis in neutropenic patients.

OBJECTIVES: Recent studies have shown a beneficial impact of fluoroquinolones on infection-related morbidity and mortality for patients with haematological malignancies during neutropenia. Among the fluoroquinolones moxifloxacin currently provides one of the broadest spectra of antibacterial activity and may be suitable for prophylaxis during neutropenia. PATIENTS AND METHODS: In this controlled before and after observational study, moxifloxacin chemoprophylaxis was used during prolonged neutropenia in haemato-oncological patients (period 2; 282 episodes). Data were compared with two periods with levofloxacin prophylaxis, one preceding period (period 1; 399 episodes) and a post-observational period (period 3; 53 episodes). Endpoints for evaluation were the rates of Gram-negative and Gram-positive bacteraemia and infection-related mortality. RESULTS: We found similar survival rates as compared with levofloxacin. The rate of Gram-negative bacteraemia was higher during prophylaxis with moxifloxacin (11%) when compared with levofloxacin (6% for period 1 and 6% for period 3). In addition we observed a marked increase in diarrhoea associated with Clostridium difficile toxin A (CDAD) after a formula change from levofloxacin to moxifloxacin (attack rate 6% versus 33%). A decrease was attained after changing back to levofloxacin and reinforcing hygienic measures (13%). CONCLUSIONS: During moxifloxacin prophylaxis, we observed a significantly increased incidence of Gram-negative bacteraemia and CDAD. Careful attention must be paid not to trade the particularly beneficial effects of fluoroquinolones in the neutropenic setting for such disadvantageous effects. Until further data are obtained, caution is warranted when applying fluoroquinolones with high anaerobic activity in the neutropenic setting.

CRB-65 predicts death from community-acquired pneumonia.

OBJECTIVE: The study was performed to validate the CURB, CRB and CRB-65 scores for the prediction of death from community-acquired pneumonia (CAP) in both the hospital and out-patient setting. DESIGN: Data were derived from a large multi-centre prospective study initiated by the German competence network for community-acquired pneumonia (CAPNETZ) which started in March 2003 and were censored for this analysis in October 2004. SETTING: Out- and in-hospital patients in 670 private practices and 10 clinical centres. SUBJECTS: Analysis was done for n = 1343 patients (n = 208 out-patients and n = 1135 hospitalized) with all data sets completed for the calculation of CURB and repeated for n = 1967 patients (n = 482 out-patients and n = 1485 hospitalized) with complete data sets for CRB and CRB-65. INTERVENTION: None. 30-day mortality from CAP was determined by personal contacts or a structured interview. RESULTS: Overall 30-day mortality was 4.3% (0.6% in out-patients and 5.5% in hospitalized patients, P < 0.0001). Overall, the CURB, CRB and CRB-65 scores provided comparable predictions for death from CAP as determined by receiver-operator-characteristics (ROC) curves. However, in hospitalized patients, CRB misclassified 26% of deaths as low risk patients. Availability of the CRB-65 score (90%) was far superior to that of CURB (65%), due to missing blood urea nitrogen values (P < 0.001). CONCLUSIONS: Both the CURB and CRB-65 scores can be used in the hospital and out-patients setting to assess pneumonia severity and the risk of death. Given that the CRB-65 is easier to handle, we favour the use of CRB-65 where blood urea nitrogen is unavailable.

Antibiotic resistant fecal isolates of Enterococci among unselected patients outside the clinical sector: an epidemiological study from Southern Germany.

PURPOSE: The aim of the study was to assess the prevalence and determinants of antibiotic-resistant Enterococci in a large group of outpatients in Southern Germany. METHODS: Stool samples were collected from 497 unselected patients aged 40-75 years attending general practitioners. Enterococcus faecium (E. faecium) and Enterococcus faecalis (E. faecalis) were cultured and minimal inhibitory concentrations of antibiotics used inside and outside the clinical sector were tested. RESULTS: E. faecium and E. faecalis could be identified and cultured in 60 (12.4%) and 205 (41.2%) of the stool samples, respectively. Under non-selective culture conditions no vancomycin-resistant Enterococcus (VRE) isolate was found. Only E. faecium isolates showed resistance to fluoroquinolones, 40% were resistant to ciprofloxacin. The prevalences of E. faecium resistance to ampicillin and doxycycline were 3.3% and 13.3%, respectively, whereas 0.5% and 29.6% of the E. faecalis isolates were resistant to ampicillin and doxycycline, respectively. Antibiotic use during the last 3 months was significantly associated with antibiotic resistance (to either ampicillin, imipenem, or doxycycline) of E. faecalis isolates (OR: 2.9; CI: 1.2-6.8). CONCLUSIONS: Prevalences of resistance were generally lower than and patterns of resistance were quite different from previous investigations in the clinical setting. Recent antibiotic use was associated with increased colonization with resistant strains.

[New therapeutic strategies for community acquired pneumonia]. / Was gibt es Neues in der Behandlung der ambulant erworbenen Pneumonie?

Community Acquired Pneumonia (CAP) is the most important infectious disease in Germany. In the acute phase, lethality is almost 10%, and in the six months follow up period following the acute infection, lethality is more than 15%. Problems with resistances had not been found in Germany, except for a decreasing susceptibility of S. pneumoniae against macrolides. The CRB-65 score allows a reliable discrimination between patients with a high and low risk of dying. The new S3 guideline for diagnosis and treatment of community acquired pneumonia recommends a risk adapted treatment. Low risk patients shall receive a monotherapy with e. g. amoxicillin, high risk patients should be treated with a broad spectrum combination therapy (beta-lactam and macrolide).

Fluoroquinolone resistance of Escherichia coli at a cancer center: epidemiologic evolution and effects of discontinuing prophylactic fluoroquinolone use in neutropenic patients with leukemia.

The aim of the present study was to investigate the epidemiologic evolution of fluoroquinolone resistance of E. coli clinical isolates from patients admitted to a hematology-oncology service where fluoroquinolone prophylaxis during neutropenia was recommended as the standard of care for many years but was then discontinued in a trial conducted in patients with acute leukemia. Fluoroquinolones had been shown to decrease the incidence of gram-negative bacteremia in cancer patients with neutropenia, yet it was thought that the emergence of resistance in Escherichia coli and other gram-negative bacteria may have caused a progressive lack of efficacy of fluoroquinolone prophylaxis. Epidemiologic surveillance of fluoroquinolone resistance of E. coli clinical isolates at our cancer center since 1992 showed a continuing influx of new clones not previously observed in the population of cancer patients, an increase in the number of cancer patients per year colonized and/or infected by fluoroquinolone-resistant E. coli (1992-1994, 10-16 patients; 1995-1997, 24-27 patients), and a resistance rate of >50% among E. coli bloodstream isolates of hematology-oncology patients. A 6-month fluoroquinolone prophylaxis discontinuation intervention trial in 1998 suggested that despite increasing resistance among E. coli isolates, fluoroquinolone prophylaxis in acute leukemia patients was still effective in the prevention of gram-negative bacteremia (incidence rates, 8% during the pre-intervention period vs. 20% after discontinuation; p<0.01). The resumption of fluoroquinolone prophylaxis in acute leukemia patients thereafter decreased the incidence of gram-negative bacteremia to the pre-intervention level (9%; p=0.03), while the proportion of in vitro fluoroquinolone resistance in E. coli bacteremia isolates again increased (from 15% during the intervention period to >50% in the post-intervention period). Relative rates of resistance thus were a poor indicator of the potential clinical benefits associated with fluoroquinolone prophylaxis in cancer patients.

Prevalence and determinants of nasal colonization with antibiotic-resistant Staphylococcus aureus among unselected patients attending general practitioners in Germany.

Although the great majority of antibiotics are prescribed outside hospitals, little is known about the prevalence and determinants of antibiotic resistance in the group of outpatients. Nasal swabs were taken from 627 consecutive patients aged 40 years or above attending general practitioners in Southern Germany. Staphylococcus aureus was cultured and minimal inhibitory concentrations to various antibiotics were tested. Nasal swabs of 152 patients were positive for S. aureus. Prevalence of resistance was 68.3, 8.3 and 0.7% for penicillin G, erythromycin, and oxacillin respectively. Antibiotic use within the last month was associated with erythromycin resistance [adjusted odds ratio (OR) 7.4; 95 % confidence interval (CI) 1.0-53]. Besides a high prevalence of resistance to penicillinase-instable antibiotics we found only one (0.7%) methicillin-resistant S. aureus. Recent antibiotic use was associated with increased resistance to erythromycin.