Reinhard Marre

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 ≥30 breaths·min−1, low blood pressure (systolic value <90 mmHg or diastolic value ≤60 mmHg) and age ≥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 ≥30 breaths·min−1, low blood pressure (systolic value <90 mmHg or diastolic value ≤60 mmHg) and age ≥65 yrs) risk classes.

Detection of Legionellae in Hospital Water Samples by Quantitative Real-Time LightCycler PCR

ABSTRACT Contamination of hospital water systems with legionellae is a well-known cause of nosocomial legionellosis. We describe a new real-time LightCycler PCR assay for quantitative determination of legionellae in potable water samples. Primers that amplify both a 386-bp fragment of the 16S rRNA gene from Legionellaspp. and a specifically cloned fragment of the phage lambda, added to each sample as an internal inhibitor control, were used. The amplified products were detected by use of a dual-color hybridization probe assay design and quantified with external standards composed ofLegionella pneumophila genomic DNA. The PCR assay had a sensitivity of 1 fg of Legionella DNA (i.e., less than one Legionella organism) per assay and detected 44Legionella species and serogroups. Seventy-seven water samples from three hospitals were investigated by PCR and culture. The rates of detection of legionellae were 98.7% (76 of 77) by the PCR assay and 70.1% (54 of 77) by culture; PCR inhibitors were detected in one sample. The amounts of legionellae calculated from the PCR results were associated with the CFU detected by culture (r= 0.57; P < 0.001), but PCR results were mostly higher than the culture results. Since L. pneumophila is the main cause of legionellosis, we further developed a quantitativeL. pneumophila-specific PCR assay targeting the macrophage infectivity potentiator (mip) gene, which codes for an immunophilin of the FK506 binding protein family. All but one of the 16S rRNA gene PCR-positive water samples were also positive in the mip gene PCR, and the results of the two PCR assays were correlated. In conclusion, the newly developedLegionella genus-specific and L. pneumophila species-specific PCR assays proved to be valuable tools for investigation of Legionella contamination in potable water systems.

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.

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 ≥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.

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 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.

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.

The Hfq Homolog in Legionella pneumophila Demonstrates Regulation by LetA and RpoS and Interacts with the Global Regulator CsrA

A gene in Legionella pneumophila that has significant homology to published hfq genes demonstrated regulation by RpoS and the transcriptional regulator LetA. Additionally, Hfq has a positive effect on the presence of transcripts of the genes for CsrA and the ferric uptake regulator Fur. Mutants lacking hfq demonstrate defects in growth and pigmentation and slight defects in virulence in both amoeba and macrophage infection models. Hfq appears to play a major role in exponential-phase regulatory cascades of L. pneumophila.

The response regulator LetA regulates the stationary-phase stress response in Legionella pneumophila and is required for efficient infection of Acanthamoeba castellanii

In order to identify a potential regulator of virulence gene expression in Legionella pneumophila, the L. pneumophila homologue of the response regulator GacA, LetA, was identified and cloned, facilitating the generation of a L. pneumophila letA insertion mutant. The L. pneumophila letA insertion mutant was more sensitive to oxidative and acid stress than the wild-type. The letA mutant exhibited reduced infectivity and was defective for intracellular growth within Acanthamoeba castellanii. Transcription of the rpoS and dotA genes was reduced in the letA mutant. Our data indicate that the response regulator LetA functions as a regulator of the stationary-phase stress response in L. pneumophila and is required for efficient replication within A. castellanii.

CAPNETZ: Community-acquired pneumonia competence network

Introduction In 1999, the German Ministry of Education and Research published a call for research proposals on competence centers in infectious diseases.The competence centers were defined as centers which combine clinical and basic research in different German health care and research institutions and which deal with diseases of high incidence or/and prevalence and with a high impact on health economy. Out of 17 short proposals, six were selected by an international committee to submit a full-length proposal and to present the proposal at an internal meeting.Two proposals were finally accepted for funding. One of these competence centers focuses on hepatitis, the other one on community-acquired pneumonia (CAP). The funding will cover 5 years, depending on a successful evaluation after 3 years. Within these 5 years the competence centers are expected to create structures and funding, which allow a sustained existence.The objective of this paper is to inform the scientific community on the scientific background, the structure, and the main research topics of CAPNETZ, the competence center on community-acquired pneumoniae. This manuscript is based on a German article which appeared in Pneumologie [1].