[CAPNETZ. The competence network for community-acquired pneumonia (CAP)]. / CAPNETZ. Das Kompetenzzentrum für ambulant erworbene Pneumonie.

CAPNETZ is a medical competence network for community-acquired pneumonia (CAP), which was funded by the German Ministry for Education and Research. It has accomplished seminal work on pneumonia over the last 15 years. A unique infrastructure was established which has so far allowed us to recruit and analyze more than 11,000 patients. The CAPNETZ cohort is the largest cohort worldwide and the results obtained relate to all relevant aspects of CAP management (epidemiology, risk stratification via biomarkers or clinical scores, pathogen spectrum, pathogen resistance, antibiotic management, prevention and health care research). Results were published in more than 150 journals and informed the preparation and update of the national S3-guideline. CAPNETZ was also the foundation for further networks like the Pneumonia Research Network on Genetic Resistance and Susceptibility for the Evolution of Severe Sepsis) (PROGRESS), the Systems Medicine of Community Acquired Pneumonia Network (CAPSyS) and SFB-TR84 (Sonderforschungsbereich - Transregio 84). The main recipients (Charité Berlin, University Clinic Ulm and the Hannover Medical School) founded the CAPNETZ foundation and transferred all data and materials rights to this foundation. Moreover, the ministry granted the CAPNETZ foundation the status of being eligible to apply for research proposals and receive research funds. Since 2013 the CAPNETZ foundation has been an associated member of the German Center for Lung Research (DZL). Thus, a solid foundation has been set up for CAPNETZ to continue its success story.

Assessment of inflammatory markers in patients with community-acquired pneumonia--influence of antimicrobial pre-treatment: results from the German competence network CAPNETZ.

BACKGROUND: There is almost no data about the influence of antimicrobial pre-treatment (APT) on levels of inflammatory markers in community acquired pneumonia (CAP). The aim of this study was to investigate the influence of APT on inflammatory markers in CAP. METHODS: 991 hospitalized patients (64.3±17.6 years, 61% male) with CAP were enrolled. In all patients procalcitonin (PCT), C-reactive protein (CRP), and leukocyte count (WBC) were determined. Patients were followed-up for 28 days for survival. RESULTS: 232 patients (23.4%) had APT, 759 had no APT. Patients without APT had significantly higher levels of PCT and WBC but not of CRP compared to those with APT. In patients without APT, survivors compared to non-survivors had lower values of PCT (0.20 ng/mL; 0.02-169.10 vs. 0.83 ng/mL; 0.04-516.30, p<0.0001), WBC (12.4×10(9)/L; 1.3-49.9 vs. 14.9×10(9)/L; 3.7-34.5, p=0.047) and CRP (107.0mg/mL; 0.3-567.0 vs. 143.5mg/mL; 5.0-589.0, p=0.006). However, in patients with APT, the values of PCT, WBC and CRP were not significantly different in survivors and non-survivors. Cox regression analysis confirmed that PCT, CRP and WBC were predictive for 28 day mortality in patients without APT but not in those with APT. CONCLUSIONS: PCT and WBC but not CRP levels are higher in patients without APT compared to those with APT. PCT, CRP and WBC are predictive for 28 days mortality exclusively in patients without APT. Interpretation of inflammatory parameters has to take into account possible APT.

[Why it is necessary to improve data quality and data validity by implementing a timely and integrated controlling system for BQS-compliant quality assurance]. / Notwendigkeit der Verbesserung von Datenqualität und -validität durch Einführung eines zeitnahen und ganzheitlichen Controllings im Bereich der Qualitätssicherung nach BQS.

Since 2007, all German hospitals are obliged to publish 27 quality indicators in their biannual "structured quality reports" as defined by the BQS (= Federal Office for Quality Assurance). Thus, hospitals are required to establish a timely controlling system for process and outcome quality that goes beyond the mere control of documentation rates. The University Medical Center Ulm has implemented an IT solution that allows for the continuous and timely evaluation of the quality assurance reports of the different modules. By developing an internal dialogue with colleagues of all specialties it was possible to optimise adherence to documentation and process standards, and to react promptly to deviations in outcome quality. This improved the quality of documentation and therefore the validity of quality assurance data. It even led to the identification of a programme error in the export file of one of the external modules. By cross-checking quality assurance data and accounting data according to Sect. 21 KHEntG (= regulation for DRG case invoicing), it was possible to detect down-coding in several cases and therefore increase revenue by correcting the accounting record. In current times it should be mandatory for hospitals to establish an internal IT supported medical/quantitative control system of BQS data records for external quality assurance. Quality and quantity of documentation forms the basis for the so-called internal dialogue (standardised review process of substandard quality assurance results), and they allow to identify the potentials for improvement in the quality of care for our patients.

Inflammatory parameters predict etiologic patterns but do not allow for individual prediction of etiology in patients with CAP: results from the German competence network CAPNETZ.

BACKGROUND: Aim of this study was to evaluate the correlation of inflammatory markers procalcitonin (PCT), C-reactive protein (CRP) and leukocyte count (WBC) with microbiological etiology of CAP. METHODS: We enrolled 1337 patients (62 +/- 18 y, 45% f) with proven CAP. Extensive microbiological workup was performed. In all patients PCT, CRP, WBC and CRB-65 score were determined. Patients were classified according to microbial diagnosis and CRB-65 score. RESULTS: In patients with typical bacterial CAP, levels of PCT, CRP and WBC were significantly higher compared to CAP of atypical or viral etiology. There were no significant differences in PCT, CRP and WBC in patients with atypical or viral etiology of CAP. In contrast to CRP and WBC, PCT markedly increased with severity of CAP as measured by CRB-65 score (p < 0.0001). In ROC analysis for discrimination of patients with CRB-65 scores > 1, AUC for PCT was 0.69 (95% CI 0.66 to 0.71), which was higher compared to CRP and WBC (p < 0.0001). CRB-65, PCT, CRP and WBC were higher (p < 0.0001) in hospitalised patients in comparison to outpatients. CONCLUSION: PCT, CRP and WBC are highest in typical bacterial etiology in CAP but do not allow individual prediction of etiology. In contrast to CRP and WBC, PCT is useful in severity assessment of CAP.

C-terminal provasopressin (copeptin) in patients with community-acquired pneumonia--influence of antibiotic pre-treatment: results from the German competence network CAPNETZ.

BACKGROUND: Recently, C-terminal provasopressin (copeptin) turned out to be predictive for mortality in community-acquired pneumonia (CAP). The aim of this study was to evaluate the influence of antibiotic pre-treatment on copeptin levels in CAP. METHODS: We enrolled 370 hospitalized patients (66 +/- 17 years; 42% females) with proven CAP. Venous blood samples were collected at the time of inclusion into the study and as soon as possible after the diagnosis of CAP. Copeptin (B.R.A.H.M.S. AG, Henningsdorf, Germany) levels were determined in venous blood on admission. RESULTS: Eighty-five patients had antibiotic pre-treatment and 285 patients did not. Copeptin levels increased with increasing severity of CAP in patients without antibiotic pre-treatment but not in patients with antibiotic pre-treatment. Patients with prior antibiotic treatment showed significantly lower levels of copeptin [median (interquartile range): 12.8 (5.3-22.6) versus 20.8 (11.1-37.8) pmol/L, P < 0.0001] and procalcitonin [0.15 (0.07-0.38) versus 0.27 (0.10-1.52) ng/mL, P = 0.0003], but not C-reactive protein [113 (46-229) versus 122 (49-231) mg/mL, not significant] and leucocytes [12.2 x 10(3) (8.1 x 10(3)-15.4 x 10(3)) versus 12.5 x 10(3) (9.4 x 10(3)-16.3 x 10(3)) cells/mm(3), not significant] compared with those without antibiotic pre-treatment. CONCLUSIONS: Copeptin serum levels are higher in patients without antibiotic pre-treatment compared with those with antibiotic pre-treatment. Copeptin serum levels increase with an increasing severity of CAP in patients without, but not in patients with, antibiotic pre-treatment. Thus, antibiotic pre-treatment has to be taken into account for the correct interpretation of copeptin levels in CAP.

Mycoplasma pneumoniae pneumonia revisited within the German Competence Network for Community-acquired pneumonia (CAPNETZ).

BACKGROUND: Currently, broad empiric antimicrobial treatment including atypical coverage is recommended for patients with mild to moderate community-acquired pneumonia (CAP). Therefore, the relative impact of each atypical pathogen, particularly Mycoplasma pneumoniae deserves renewed attention. METHODS: Based on prospective data from 4532 patients with CAP included in the German CAP-Competence Network (CAPNETZ), we studied the incidence, clinical characteristics, and outcome of patients with Mycoplasma pneumoniae pneumonia (MPP). The diagnosis of MPP was based on a positive PCR from respiratory samples and/or a positive IgM-titer from an acute phase serum sample. RESULTS: 307 patients (6.8%) had definite MPP (148 with positive PCR, 204 with positive IgM, 46 with positive PCR and IgM). Compared to patients with other definite and unknown etiologies, patients with MPP were significantly younger (41 +/- 16 versus 62 +/- 17 and 61 +/- 18 years), had fewer co-morbidities, presented with a less severe disease, showed a lower inflammatory response in terms of leukocyte counts (median 8850 versus 13200 and 11000 microL) and CRP values (60 versus 173 and 73 mg/L), and had better outcomes, including a shorter length of hospitalization (9 +/- 5 versus 14 +/- 11 and 12 +/- 9 days), fewer patients requiring mechanical ventilation (0.3 versus 4.5 and 2.1%), and a minimal mortality (0.7 versus 8.7 and 6.5%). CONCLUSION: In this large series of patients with definite MPP according to very strict criteria, MPP appears as a condition with a high incidence, quite specific clinical presentation, and a largely benign course. In view of a widely favorable clinical outcome, recent recommendations including regular coverage of atypical pathogens in patients with mild to moderate CAP might be reconsidered for patients in Germany as well as in other countries with comparable epidemiological settings.

Community-acquired Legionella pneumonia: new insights from the German competence network for community acquired pneumonia.

BACKGROUND: The Competence Network for Community Acquired Pneumonia (CAPNETZ) offers a unique opportunity to study the epidemiology of legionellosis throughout Germany, applying sophisticated diagnostic tools. METHODS: The incidence, clinical characteristics, and outcome of Legionella pneumonia in 2503 adult patients with community-acquired pneumonia, participating in the German Multicenter Study of the CAPNETZ, were studied. RESULTS: Legionella pneumonia was diagnosed in 94 patients (3.8%), thus identifying Legionella species as one of the most common pathogens to cause community-acquired pneumonia. It was equally common among ambulatory and hospitalized patients (3.7% and 3.8%, respectively). The predominant species causing community-acquired pneumonia was Legionella pneumophila; however, 10% of cases were caused by other species not detectable by the urinary antigen test. Patients whose disease was diagnosed by urinary antigen testing experienced a more severe clinical course. Compared with hospitalized patients, ambulatory patients with Legionella pneumonia showed an equal sex distribution, were younger, had fewer comorbidities, fewer cases of discordant initial antimicrobial treatment, and a milder clinical course without fatalities. Thirty percent of patients with Legionella pneumonia received discordant initial antimicrobial treatment without increased mortality. CONCLUSIONS: Legionella is a leading cause of community-acquired pneumonia in Germany. It needs to be considered equally in hospitalized and ambulatory patients. A positive result of a urine antigen test is associated with a more severe clinical course and leads to a potentially relevant underrecognition of species other than L. pneumophila. Legionella pneumonia in outpatients differs significantly from that in hospitalized patients in terms of clinical presentation and outcome. There was an unacceptably high rate of discordant initial antimicrobial treatment.

Pro-atrial natriuretic peptide and pro-vasopressin to predict severity and prognosis in community-acquired pneumonia: results from the German competence network CAPNETZ.

OBJECTIVE: Community acquired pneumonia (CAP) is the most important clinical infection. Therefore, the CAP competence network CAPNETZ was instituted in Germany. The aim of this substudy was to evaluate the value of pro-atrial natriuretic peptide (MR-proANP) and pro-vasopressin (CT-proAVP) for severity assessment and outcome prediction in CAP. DESIGN: Prospective observational study. SETTING: German CAP competence network CAPNETZ. METHODS: We enrolled 589 patients (age 61+/-18 years, 46% female) with proven CAP. MR-proANP, CT-proAVP, C-reactive protein (CRP), procalcitonin (PCT) and CRB-65 score were determined on admission. RESULTS: MR-proANP, CT-proAVP and PCT levels, but not CRP, increased with increasing severity of CAP, classified according to the CRB-65 score. In patients who died during 28-day follow-up, median MR-proANP and CT-proAVP levels (respectively 237.0 vs. 93.5 pmol/l and 44.2 vs. 12.4 pmol/l, each p<0.0001) were significantly higher than in survivors. In receiver operating characteristic (ROC) analysis for survival, the area under the curve (AUC) values for CT-proAVP (0.86, 95% CI 0.83-0.89) and MR-proANP (0.76, 95% CI 0.72-0.80) were similar to the AUC of CRB-65 (0.73, 95% CI 0.70-0.77). In multivariable Cox proportional-hazards regression analyses including MR-proANP/CT-proAVP, coexisting illnesses and CRB-65, increased MR-proANP and CT-proAVP concentrations were the strongest predictors of mortality. CONCLUSIONS: MR-proANP and CT-proAVP are useful new biomarkers for the risk stratification of CAP patients. They are significantly lower in CAP survivors and correlate with the severity of the disease measured by CRB-65 score.

Household contacts were key factor for children's colonization with resistant Escherichia coli in community setting.

OBJECTIVE: In young children infections with resistant Escherichia coli (E. coli) can lead to life-threatening situations. Epidemiological data on the prevalence and major determinants of carriage of antibiotic resistant E. coli among children in the community setting are sparse. STUDY DESIGN AND SETTING: In a population-based study from Germany, stool samples were obtained from children aged 6 months to 4 years attending a pediatrician for a regular health screening (N=568) or an acute infection (N=316), as well as from their parents (N=1,594) and siblings (N=624). E. coli was cultured, and minimal inhibitory concentrations to various antibiotics were tested. We determined prevalences of E. coli resistance to commonly prescribed antibiotics and their association with potential risk factors. RESULTS: Prevalence of E. coli resistance was 16.6%, 8.7%, and 11.6% for ampicillin, cotrimoxazole, and doxycycline, respectively. Strong associations were found with antibiotic resistance among siblings (odds ratios [95% confidence intervals] for ampicillin, doxycycline, and cotrimoxazole resistance: 4.4 [1.8-10.8], 8.0 [3.0-21.2], and 10.8 [3.5-32.7], respectively). CONCLUSION: Resistance prevalences in this community-based study were much lower than those reported from the clinical sector. Household contacts seem to be the key factor for children;s colonization with resistant E. coli in the community setting.

Antibiotic treatment of community acquired pneumonia varies widely across Germany.

UNLABELLED: Community Acquired Pneumonia (CAP) is a frequent and potentially fatal infectious disease which, in the majority of cases, needs an antibiotic intervention. OBJECTIVES: Aim was to evaluate antibiotic treatment patterns regarding all types of mono- and combination-therapy throughout the local clinical centres (LCCs) represented in the German competence network CAPNETZ (=Community Acquired Pneumonia Network) and to identify clinical indicators for regional differences. METHODS: We analysed outpatients and inpatients recruited between March 2003 and April 2005. Patient and treatment details were registered online using standardised data entry forms. A logistic regression model was issued for the 4 most frequently applied antibiotics, adjusting for potentially relevant confounders. RESULTS: The study sample consisted of 3221 patients at the age of 18 to 102 years. Overall, aminopenicillins plus betalactamase inhibitor (20.4%), fluoroquinolone (17.0%), macrolides combined with cephalosporins third generation (10.6%) and cephalosporins third generation (8.9%) were most frequently prescribed. After control for potential confounders, significant treatment differences remained between study sites. Regional variability of antibiotic CAP-treatment could not be attributed to a number of clinical or sociodemographic factors. CONCLUSIONS: The presented treatment variability ranges within given guidelines, but indicates the need for an ongoing implementation of evidence-based guidelines in order to avoid potential negative clinical or economic consequences.

Low prevalence of Chlamydia pneumoniae in adults with community-acquired pneumonia.

The incidence of community-acquired pneumonia (CAP) due to Chlamydia pneumoniae was determined in a prospective study of 546 adult patients with CAP included in the German CAP Competence Network (CAPNETZ) project. Three different PCR protocols for detection of C. pneumoniae in respiratory specimens were compared by a multicenter, inter-laboratory comparison involving three laboratories. A case was defined as a patient with a respiratory sample positive by PCR in at least two laboratories. CAP was caused by C. pneumoniae in 5/546 cases (0.9%). Antibody testing by microimmunofluorescence was done in 376 of 546 patients. All patients were negative for IgM antibodies. In the five PCR-positive patients, neither specific IgG nor IgA antibodies were found. Patients with CAP caused by C. pneumoniae had a lower median age (36 years) than the general study population (62 years). C. pneumoniae is currently a rare cause of CAP in adult patients in Germany. Analysis of a single serum sample is not useful for diagnosis of acute C. pneumoniae infection in CAP.

Clustering of antibiotic resistance of E. coli in couples: suggestion for a major role of conjugal transmission.

BACKGROUND: Spread of antibiotic resistance in hospitals is a well-known problem, but studies investigating the importance of factors potentially related to the spread of resistant bacteria in outpatients are sparse. METHODS: Stool samples were obtained from 206 healthy couples in a community setting in Southern Germany in 2002-2003. E. coli was cultured and minimal inhibition concentrations were tested. Prevalences of E. coli resistance to commonly prescribed antibiotics according to potential risk factors were ascertained. RESULTS: Prevalences of ampicillin resistance were 15.7% and 19.4% for women and men, respectively. About ten percent and 15% of all isolates were resistant to cotrimoxazole and doxycycline, respectively. A partner carrying resistance was the main risk factor for being colonized with resistant E. coli. Odds ratios (95% CI) for ampicillin and cotrimoxazole resistance given carriage of resistant isolates by the partner were 6.9 (3.1-15.5) and 3.3 (1.5-18.0), respectively. CONCLUSION: Our data suggest that conjugal transmission may be more important for the spread of antibiotic resistance in the community setting than commonly suspected risk factors such as previous antibiotic intake or hospital contacts.

Culture-independent molecular subtyping of Mycoplasma pneumoniae in clinical samples.

A new molecular subtyping approach was developed which is based on the amplification and sequencing of a repetitive region of the P1 gene of Mycoplasma pneumoniae. It allows the differentiation of all known subtypes and variants of M. pneumoniae as well as the identification of new subtypes directly in clinical samples to characterize endemic and epidemic M. pneumoniae infections.

[What is new in the treatment of 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. After 3 years of data recording, the country-wide competence network CAPNETZ presents reliable data on etiology and course of the disease, based on more than 3,500 prospectively observed patients. In the acute phase, lethality is as high as nearly 10%, and in the 6-month follow-up period after the acute infection, lethality is > 15%. A reliable detection of the underlying pathogen is possible in less than half of all patients studied. The most frequent pathogens are Streptococcus pneumoniae (40%), Haemophilus influenzae, and Mycoplasma pneumoniae (8% each). Legionella (3%) and Chlamydia pneumoniae (< 1%) are rarely found, and gram-negative enterobacteriaceae (< 5%) are restricted to high-risk patient groups (nursing home, multimorbidity). CAPs due to pneumococci, legionella or enterobacteriaceae were associated with increased lethality. Problems with resistances had not been found in Germany, except for a decreasing susceptibility of S. pneumoniae to macrolides. Viruses could be detected in nearly 15% of all pneumonia patients. 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 CAP 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).

The global regulatory proteins LetA and RpoS control phospholipase A, lysophospholipase A, acyltransferase, and other hydrolytic activities of Legionella pneumophila JR32.

Legionella pneumophila possesses a variety of secreted and cell-associated hydrolytic activities that could be involved in pathogenesis. The activities include phospholipase A, lysophospholipase A, glycerophospholipid:cholesterol acyltransferase, lipase, protease, phosphatase, RNase, and p-nitrophenylphosphorylcholine (p-NPPC) hydrolase. Up to now, there have been no data available on the regulation of the enzymes in L. pneumophila and no data at all concerning the regulation of bacterial phospholipases A. Therefore, we used L. pneumophila mutants in the genes coding for the global regulatory proteins RpoS and LetA to investigate the dependency of hydrolytic activities on a global regulatory network proposed to control important virulence traits in L. pneumophila. Our results show that both L. pneumophila rpoS and letA mutants exhibit on the one hand a dramatic reduction of secreted phospholipase A and glycerophospholipid:cholesterol acyltransferase activities, while on the other hand secreted lysophospholipase A and lipase activities were significantly increased during late logarithmic growth phase. The cell-associated phospholipase A, lysophospholipase A, and p-NPPC hydrolase activities, as well as the secreted protease, phosphatase, and p-NPPC hydrolase activities were significantly decreased in both of the mutant strains. Only cell-associated phosphatase activity was slightly increased. In contrast, RNase activity was not affected. The expression of plaC, coding for a secreted acyltransferase, phospholipase A, and lysophospholipase A, was found to be regulated by LetA and RpoS. In conclusion, our results show that RpoS and LetA affect phospholipase A, lysophospholipase A, acyltransferase, and other hydrolytic activities of L. pneumophila in a similar way, thereby corroborating the existence of the LetA/RpoS regulation cascade.

The Legionella pneumophila global regulatory protein LetA affects DotA and Mip.

Several genes have been identified in Legionella pneumophila which are necessary for its virulence properties. These genes include the dot/icm type IV secretion system (T4SS), mip and letA. Genes of the dot/icm system, in particular dotA, have been found to be essential for intracellular growth. The macrophage infectivity protein (Mip) is also necessary for full virulence of the bacteria. Although these genes are well characterized, the regulation of such virulence factors is not. The LetA transcriptional activator interacts with the global regulator CsrA in controlling the switch from the replicative, non-infectious to the transmissive, highly infectious form of L. pneumophila. Regulation by LetA of the dot/icm genes has also been previously postulated. Here we show that the letA mutation exerts effects not only on DotA but on a substrate of the secretion system, RalF as well. LetA was found to be necessary for full transcriptional expression of the dotA and ralF genes. Although at the transcriptional level dotA was reduced, this did not result in a decrease of DotA protein in whole cell lysates. The letA mutation, however, does result in decreased amounts of the DotA protein found in the membrane and increased amounts in the culture supernatant. Additionally, the letA mutation dramatically decreased the secretion of Mip. This work demonstrates the participation of the global regulatory protein LetA in the regulation of an essential part of the dot/icm T4SS. Also shown is the presence of secreted Mip and a decrease in this secretion in the letA(-) strain. Exactly how LetA is regulating these virulence factors remains to be elucidated but it obviously occurs at both transcriptional and post-transcriptional levels.

Chlamydia pneumoniae in an ex vivo human artery culture model.

The role of the obligate intracellular pathogen Chlamydia pneumoniae in the development of atherosclerosis could not be completely clarified. Reasons are the highly discrepant results obtained in the hitherto existing studies and the lack of an experimental system allowing the direct examination of chlamydial effects in the human vasculature. We established a human ex vivo organ culture model for the characterization of vascular chlamydial infection. Ninety sections of renal arteries, obtained from nephrectomies, were inoculated with Chlamydia pneumoniae. Using a monoclonal FITC-conjugated antibody, chlamydial LPS was broadly detected in inoculated arteries during the entire observation period of 35 days. However, recultivation of viable organisms from the artery vessel wall was impossible, indicating that productive infection in human arteries did not occur even under optimized conditions. This was substantiated by low recovery rates of Chlamydia pneumoniae, low amounts of detectable chlamydial 16S rRNA and ultramorphological presence of polymorph multilamellar bodies in experimentally infected smooth muscle cells originating from aortas, coronary and renal arteries. We could demonstrate that the complex environment of a human artery did not support the growth of Chlamydia pneumoniae although the presence of chlamydial LPS in the artery vessel wall following experimental infection was a common event. The presence of chlamydial LPS in the absence of viable organisms within the artery vessel wall may explain the failure of antibiotic treatment strategies for atherosclerosis.

Antimicrobial resistance of Escherichia coli and therapeutic implications.

Widespread antibiotic resistance has been recognized in Escherichia coli isolates from human, animal and environmental sources. Although prevalence rates for resistant E. coli strains are significantly distinct for various populations and environments, the impact of resistance to antimicrobial drugs is ubiquitous. This article provides information about the epidemiology, mechanisms and molecular principles of resistance, shows consequences for the antiinfective treatment of selected infections and describes measures to control the spread of antibiotic-resistant E. coli.

Impact of fluoroquinolone prophylaxis on reduced infection-related mortality among patients with neutropenia and hematologic malignancies.

BACKGROUND: Fluoroquinolone prophylaxis during neutropenia in patients with cancer has been associated with decreased incidence of gram-negative bacteremia. Bacterial antimicrobial resistance is likely to cause a progressive lack of efficacy of fluoroquinolones, but no convincing evidence from clinicoepidemiologic observations has proved this hypothesis. METHODS: This prospective observational study assessed the impact of discontinuing fluoroquinolone prophylaxis on the incidences of fever and bacteremia and on mortality among patients with neutropenia, after chemotherapy for hematologic malignancies. RESULTS: After a 12-month baseline period of levofloxacin prophylaxis, a period of discontinuation of fluoroquinolone prophylaxis was planned but was stopped prematurely after 9 neutropenic episodes over 3 weeks, because the mortality rate (33.3%) was higher than that with routine fluoroquinolone prophylaxis (2.9%) (odds ratio [OR], 16.6; 95% confidence interval [CI], 3.6-77.2). Fewer patients had gram-negative bacteremia during the baseline period (4.8%; n=15) than during the discontinuation period (44.4%; n=4) (OR, 16.9; 95% CI, 4.1-70.0). After levofloxacin therapy was reintroduced, the incidence of gram-negative bacteremia and the mortality rate were comparable to those during the first period. Escherichia coli isolated during the discontinuation period was susceptible to levofloxacin in vitro, whereas all E. coli isolates isolated during both prophylaxis periods were resistant. Bloodstream infections were caused by a single agent when the patient had received levofloxacin prophylaxis, whereas most cases of gram-negative bacteremia were polymicrobial after discontinuation. CONCLUSIONS: These findings suggest that, despite increasing rates of antimicrobial resistance, levofloxacin prophylaxis during neutropenia may have a beneficial impact on morbidity and infection-related mortality. Continued monitoring of the rate of gram-negative bacteremia is warranted for timely detection of the loss of efficacy of fluoroquinolone prophylaxis.

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.