Delay in the administration of appropriate antimicrobial therapy in Staphylococcus aureus bloodstream infection: a prospective multicenter hospital-based cohort study.

OBJECTIVES: Early broad-spectrum antimicrobial treatment reduces mortality in patients with septic shock. In a multicenter, prospective observational study, we explored whether delayed appropriate antimicrobial therapy (AAT) influences outcome in Staphylococcus aureus bloodstream infection (SAB). METHODS: Two hundred and fifty-six patients with SAB from ten German study centers were enrolled and followed for 3 months. Predisposing factors, clinical features, diagnostic procedures, antimicrobial therapy, and outcome were recorded. The appropriateness of antimicrobial therapy was judged by a trained physician based on in vitro activity, dosage, and duration of therapy. Therapy was considered to be delayed when more than 24 h elapsed between the first positive blood culture and the start of appropriate therapy. The association of delayed therapy with overall mortality and SAB-related events (i.e., attributable mortality or late SAB-related complications) was assessed by crosstabulation and propensity score-based logistic regression. RESULTS: One hundred and sixty-eight patients received AAT during their hospital stay, of whom 42 (25%) received delayed AAT. The overall mortality and the occurrence of severe sepsis or septic shock were lower in patients with delayed AAT, pointing towards confounding by indication. Adjusted 90-day mortality (adjusted odds ratio [OR] 0.91, 95% confidence interval [CI] [0.39-2.13], p 0.82) and SAB-related events (adjusted OR 1.46, 95% CI [0.47-4.51], p 0.52) also failed to show a significant impact of delayed AAT on outcome. CONCLUSION: In patients with SAB, early AAT may not improve survival. However, confounding by indication is a major challenge when analyzing and interpreting observational studies on the impact of delayed AAT.

[Does technical progress mean clinical advantage? Analysis of clinical and histopathological parameters of renal cell carcinomas in long-term course]. / Bedeutet technischer Fortschritt auch klinischen Vorteil? Eine Analyse des Nierenzellkarzinoms im Langzeitverlauf.

PURPOSE: Renal cell carcinoma is the third most frequent urogenital malignancy. The increased incidence in the past few years can be attributed in particular to increased incidental findings since the introduction of routine ultrasound and radiological imaging. In the current contribution we analyse in a long-term approach the actual impact of these advances on indications for surgical management. MATERIAL AND METHODS: From January 1992 until December 2007, 1,113 renal cell carcinoma patients underwent a total of 1,129 surgical interventions in our department. Retrospectively, we collected the clinical and histopathological data of these patients, comparing them in terms of the entire study period and the four 4-year time spans 1992-1995, 1996-1999, 2000-2003 and 2004-2007. RESULTS: 59 % of the patients were male, the median age being 64 years [range: 26-91 years]. In the study period, the number of patients 75 years increased statistically significantly (p = 0.012). The number of incidental findings -remained constant at approximately 72 %, while that of patients who had received preoperative cross-sectional imaging diagnostics rose statistically significantly from 88 % to 98 % (p < 0.001). Tumours of stage pT1a increased statististically significantly to 42 %, the number of partial renal resections in the same period to 25 % (p < 0.001). There was no difference in residual tumour rate between nephron-sparing surgery and tumour nephrectomy. CONCLUSIONS: We were able to confirm that the major developments in the diagnostic and surgical approaches to renal cell carcinoma over the past few years do translate into clinical benefits for patients who are increasingly being subjected to partial renal resection.

[Experiences with the detection of E. coli and coliform bacteria with reference to the drinking water regulation of 1986]. / Erfahrungen mit dem Nachweis von E. coli und coliformen Bakterien unter Berücksichtigung der Trinkwasserverordnung von 1986.

After the introduction of a limiting value for coliform bacteria in the German Drinking Water Regulation from May 22, 1986 the detection of coliform bacteria has become as important as that of E. coli to indicate pathogenic Enterobacteriaceae and fecal contamination. 130 water samples from different steps of drinking water treatment and distribution have been investigated for Enterobacteriaceae, even when typical indicating marks for such as acid- and gas-formation in the enrichment media were absent. We found the total of 46 isolates of Enterobacteriaceae, among which E. coli was the most frequent one. Whereas in 7 samples with acid- and gas-formation in the enrichment media Enterobacteriaceae could not be isolated, coliform bacteria and other enterobacteriaceae were found in 6 samples without these characteristics. As our experiences have show, those 'false positive' results can be avoided by a careful identification procedure of isolated microorganisms. The hygienically much more important 'false negative' results would not be recognized in routine control of drinking water following the prescribed methods.

Genus-specific epitope on the 60-kilodalton Legionella heat shock protein recognized by a monoclonal antibody.

A monoclonal antibody (MAb) immunoglobulin G2a (2125) was produced against a 60-kDa Legionella heat shock protein (HSP), recognizing a unique epitope common to all species of the genus Legionella. The antibody reacted in the immunoblot with 59 Legionella species and serogroups that were tested and showed no cross-reactivity with other bacteria, including Acinetobacter spp., Bordetella spp., Pseudomonas spp., Mycobacterium spp., and Escherichia coli. Two other MAbs (2122 and 2130) reacted with the 60-kDa Legionella protein as well but showed different cross-reactivities with other gram-negative bacteria in the same molecular mass range. The genus-specific MAb 2125 as well as the cross-reacting MAbs 2122 and 2130 were shown to be reactive with the expressed protein of the cloned gene of the 60-kDa HSP of Legionella micdadei and Legionella pneumophila. These antibodies demonstrate that Legionella-specific and nonspecific epitopes are present on this protein. A sandwich enzyme-linked immunosorbent assay (ELISA) in which the genus-specific MAb is used both as a capture antibody and as a biotinylated second antibody has been established. With this test it is possible to detect Legionella whole cells, sonicated cells, and cell fractions containing the 60-kDa HSP. The main part of the 60-kDa HSP is found in the cytoplasmic fraction. The sandwich ELISA can be used to demonstrate the increased expression of the 60-kDa protein in Legionella cells following heat shock as well as marked differences in the detection of the 60-kDa HSP on whole cells of different Legionella strains. The high specificity and sensitivity of the sandwich ELISA for sonicated cells might be very useful to screen on a genus level for Legionella cells or the 60-kDa antigen in environmental isolates or body fluids of patients.

Rapid determination of members of the family Enterobacteriaceae in drinking water by an immunological assay using a monoclonal antibody against enterobacterial common antigen.

An immunological method for the detection of members of the family Enterobacteriaceae in drinking water was developed. The method was based on a sandwich enzyme-linked immunosorbent assay (ELISA) with monoclonal antibody immunoglobulin G2a 898 against enterobacterial common antigen. The enterobacterial common antigen sandwich ELISA combined with selective preenrichment culture could be performed in only 24 h. Six hundred sixty-eight water samples from a variety of German public water supplies were screened to verify the effectiveness of the new method. Ninety-eight percent of the results obtained by the immunological method could be confirmed by conventional microbiological methods. The immunological method proved to be considerably faster and more specific and sensitive than the standard method specified by the German drinking water regulations.

Effects of cardiac output on disposition kinetics of sorbitol: recirculatory modelling.

1. The purpose of this study was to determine the effects of cardiac output on distribution and elimination kinetics of the marker compound sorbitol. 2. The disposition kinetics of sorbitol were investigated after rapid intravenous injection and arterial sampling in nine patients who had undergone cardiac catheterization whereby the cardiac output was measured. 3. A minimal circulatory model consisting of pulmonary and systemic subsystems, both of which were characterized by an inverse Gaussian transit time density function, fitted the data very well. The method involves numerical inverse Laplace transform of the model equations. 4. The mixing clearance introduced as a novel non-compartmental parameter of distribution dynamics was significantly correlated with cardiac output. The steady-state volume of 14 l matched the extracellular volume. The systemic extraction ratio of 23% may reflect the fractional liver blood flow. 5. This pharmacokinetic model can be applied when an independent observation of cardiac output is available. In contrast to the conventional compartmental (or sum of exponential) approach it contains fewer adjustable parameters which can be more readily interpreted in physiological terms.