Biomedical subjects

Wolfgang A Krueger

Publications and source records attributed to Wolfgang A Krueger.

12 recordsLinked to original sources

PubMed2006

Effects of long-term routine use of selective digestive decontamination on antimicrobial resistance.

OBJECTIVE: To assess the distribution of bacterial species and antimicrobial resistance in an ICU during long-term use of selective digestive decontamination (SDD) in the context of national reference data. DESIGN AND SETTING: Five-year prospective observational study in a 24-bed interdisciplinary surgical ICU of a university hospital (study ICU) participating in the project "Surveillance of Antimicrobial Use and Antimicrobial Resistance in German Intensive Care Units" (SARI; reference ICUs). PATIENTS: Resistance data were obtained from all patients; patients intubated for at least 2 days received SDD (colistin, tobramycin, amphotericin B). INTERVENTIONS AND MEASUREMENTS: SDD was performed in 1,913 of 7,270 patients. Antimicrobial resistance was examined in 4,597 (study ICU) and 46,346 (reference ICUs) isolates. RESULTS: Methicillin-resistant Staphylococcus aureus (MRSA) remained stable (2.76 and 2.58 isolates/1000 patient days) in the study ICU; this was below the German average (4.26 isolates/1000 patient days). Aminoglycoside- and betalactam-resistant Gram-negative rods did not increase during SDD use. Aminoglycoside resistance of Pseudomonas aeruginosa was 50% below the mean value of SARI (0.24 vs. 0.52 isolates/1,000 patient days). The relative frequency of enterococci and coagulase-negative staphylococci (CNS) was higher than in the SARI ICUs (23.2% vs. 17.3%, and 25.0% vs. 20.6%, respectively). CONCLUSION: Routine 5-year-use of SDD was not associated with increased antimicrobial resistance in our ICU with low baseline resistance rates. Vigorous surveillance and control measures to search and destroy MRSA were considered a mandatory component of the SDD program. The relative increase in enterococci and CNS is of concern requiring further investigation.

Amphotericin B↗

PubMed2006

Selective decontamination of the digestive tract: cumulating evidence, at last?

Selective decontamination of the digestive tract (SDD), an infection-control strategy designed to prevent nosocomial pneumonia in mechanically ventilated patients, has been implemented in numerous studies for more than 2 decades, but its role remains controversial. Sentinel studies in the 1960s and 1970s identified a link between colonization of the upper respiratory tract and subsequent increased risk of developing nosocomial pneumonia in critically ill patients. Studies in the 1980s found that prophylaxis with topical and systemic antibiotics to decontamination of the upper respiratory tract and gastrointestinal tract (particularly depleting gram-negative aerobic bacteria) was associated with lower rates of infections. However, impact on survival was not substantiated. However, several recent studies (including randomized trials and meta-analyses) suggest that SDD may improve survival in selected cohorts of critically ill patients in intensive care units (ICUs). Because liberal use of SDD (or any antimicrobial prophylactic strategy) may lead to escalating antimicrobial resistance, the risk of resistance varies according to local pathogens and resistance patterns. This review describes the development of the SDD concept, discusses recently published trials, and develops points for discussion and research. Additional studies are required to further define appropriate indications and limitations of this preventative strategy.

Anti-Bacterial Agents↗

PubMed2006

Dose-dependent influence of barbiturates but not of propofol on human leukocyte phagocytosis of viable Staphylococcus aureus.

OBJECTIVE: Deep sedation with barbiturates or propofol is a standard therapy for patients with critically elevated intracranial pressure. Such patients are prone to infectious complications, especially to pneumonias, which are most commonly caused by Staphylococcus aureus. Although various immunomodulatory effects of barbiturates have been described in vitro, their influence on the phagocytosis of viable S. aureus has yet to be investigated. Therefore, we examined the effects of thiopentone, methohexitone, and propofol on the phagocytosis of viable S. aureus. DESIGN: Laboratory study. SETTING: University laboratory. PATIENTS: Ten healthy volunteers aged 32.5 +/- 7 yrs. INTERVENTIONS: Blood sampling. MEASUREMENTS AND MAIN RESULTS: Whole blood samples were preincubated with different concentrations of thiopentone, methohexitone, and propofol, which is an isopropylphenol derivate. After viable S. aureus was added, phagocytosis was stopped at different time points. Leukocytes were then stained with monoclonal antibodies for flow cytometric analysis of granulocyte recruitment (ratio of ingesting granulocytes) and phagocytosis activity (fluorescence intensity of ingested bacteria). Both barbiturates inhibited granulocyte recruitment and phagocytosis activity in a dose-dependent manner, whereas propofol did not affect any of the investigated variables. At concentrations higher than 7.6 x 10(-3) M (for thiopentone, p < .008) and 1.1 x 10(-3) M (for methohexitone, p < .04), granulocyte recruitment and phagocytosis activity were significantly inhibited. The calculated inhibitory concentrations (IC50) of thiopentone for granulocyte recruitment and for phagocytosis activity were 1.3 x 10(-2) M and 1.1 x 10(-2) M, respectively. The corresponding values for methohexitone were 3.6 x 10(-3) M and 1.1 x 10(-3) M. CONCLUSIONS: Our in vitro model points at substantially different effects of barbiturates and propofol on phagocytosis of S. aureus, which is one of the most important pathogens in patients who need neuroprotective therapy. The inhibitory effects of both barbiturates demonstrate a strong dose-dependency, with more pronounced effects for methohexitone. Impairment of phagocytosis activity was more pronounced than granulocyte recruitment.

Adult↗

PubMed2005

Evaluation by monte carlo simulation of the pharmacokinetics of two doses of meropenem administered intermittently or as a continuous infusion in healthy volunteers.

Meropenem is a broad-spectrum carbapenem antibacterial agent. In order to optimize levels in plasma relative to the MICs, the ideal dose level and dosage regimen need to be determined. The pharmacokinetics of meropenem were studied in two groups, each comprising eight healthy volunteers who received the following doses: 500 mg as an intravenous infusion over 30 min three times a day (t.i.d.) versus a 250-mg loading dose followed by a 1,500 mg continuous infusion over 24 h for group A and 1,000 mg as an intravenous infusion over 30 min t.i.d. versus a 500-mg loading dose followed by a 3,000-mg continuous infusion over 24 h for group B. Meropenem concentrations in plasma and urine were determined by liquid chromatography-mass spectrometry/mass spectrometry and high-performance liquid chromatography with UV detection, respectively. Pharmacokinetic calculations were done by use of a two-compartment open model, and the data were extrapolated by Monte Carlo simulations for 10,000 simulated subjects for pharmacodynamic evaluation. There were no significant differences in total clearance and renal clearance between group A and group B or between the intermittent treatment and the continuous infusion. The analyses of the probability of target attainment by MIC for the high- and low-dose continuous infusions were robust up to MICs of 4 mg/liter and 2 mg/liter, respectively. The corresponding values for intermittent infusions were only 0.5 mg/liter and 0.25 mg/liter. When these observations were correlated with MICs obtained from the MYSTIC database, intermittent infusion results in adequate activity against two of the most common nosocomially acquired pathogens, Klebsiella pneumoniae and Enterobacter cloacae. However, against Pseudomonas aeruginosa, the evaluation shows a clear advantage of high-dose therapy administered as a continuous infusion. We believe that in the empirical therapy situation, the continuous-infusion mode of administration is most worth the extra efforts. We conclude that clinical trials for evaluation of the continuous infusions of meropenem in critically ill patients are warranted.

Adolescent↗

PubMed2004

Rationale for the development of immunotherapy regimens against enterococcal infections.

Enterococci are the third most common pathogen isolated in bloodstream infections. Increasing resistance against multiple antimicrobial agents has left few treatment options for enterococcal infections, and alternative therapeutic approaches are needed. Although a variety of virulence factors have been described for Enterococcus faecalis, only aggregation substance (AS) and a teichoic acid-like capsular polysaccharide have been evaluated for their potential for vaccine development. Antibodies raised against purified capsular polysaccharide are highly opsonic and protect mice against bacteremia after active and passive immunization. Since E. faecalis expresses only a limited number of capsular serotypes, this antigen may be an attractive candidate for development of a conjugate vaccine.

Antigens, Bacterial↗

PubMed2004

Assessment of the role of antibiotics and enterococcal virulence factors in a mouse model of extraintestinal translocation.

OBJECTIVE: To study the relative contribution of antibiotics and bacterial virulence factors in the process of translocation of Enterococcus faecalis from the gut to extraintestinal organs. DESIGN: Prospective controlled animal study. SETTING: Animal experimental laboratory at a university medical center. SUBJECTS: Fifty-two female Balb/c mice. INTERVENTIONS: We developed a mouse model to study the translocation of Enterococcus faecalis from the intestinal tract. Balb/c mice received sterile drinking water or antibiotic combinations to deplete their indigenous intestinal microflora. The animals subsequently were fed genetically engineered enterococci expressing different combinations of the putative enterococcal virulence factors aggregation substance and binding substance. Animals were killed, and their livers, spleens, and mesenteric lymph nodes were aseptically removed and cultured along with fecal samples for enumeration of bacteria. MEASUREMENTS AND MAIN RESULTS: All animals were colonized with the test strains at 2-6 x 109 colony forming units/g of feces; in the antibiotic-treated animals, feces were free from anaerobes and Enterobacteriaceae. In animals fed the identical bacterial mutant, the colony counts in mesenteric lymph nodes were significantly lower in mice not treated with antibiotics than in those treated with antibiotics (p =.016). Multigroup analysis of variance revealed no significant differences of the translocation frequencies for the different mutant strains; however, the differences were statistically significant for all groups receiving antibiotics vs. the group not receiving antibiotics (p <.05-.01). There was a trend (although not statistically significant) for a higher proportion of positive cultures from either spleen or liver in mice that had enterococci recovered from their mesenteric lymph nodes (28%) relative to those that did not have enterococci isolated from the lymph nodes (12%; rate ratio 2.39, p =.30 by logistic regression analysis). CONCLUSIONS: Oral antibiotics can select for extraintestinal translocation of Enterococcus faecalis, and neither aggregation substance nor binding substance seems to be required for this process. The experiments encourage further exploration of host and microbial factors contributing to translocation and may provide a better understanding of the pathogenesis of enterococcal infections in patients in intensive care units.

Animals↗

PubMed2004

Treatment of meningitis due to methicillin-resistant Staphylococcus epidermidis with linezolid.

Methicillin-resistant Staphylococcus epidermidis (MRSE) can cause nosocomial meningitis in the presence of prosthetic devices. Vancomycin is the treatment of choice, but its penetration into the cerebrospinal fluid is poor, especially in cases without severe meningeal inflammation. We successfully used linezolid to treat a case of posttraumatic MRSE meningitis with a low-level inflammatory response. Therapeutic effectiveness was documented microbiologically and by the simultaneous measurement of linezolid levels in serum and cerebrospinal fluid.

Accidents, Traffic↗

PubMed2003

Local anesthetics impair human granulocyte phagocytosis activity, oxidative burst, and CD11b expression in response to Staphylococcus aureus.

BACKGROUND: With invasion of bacteria, the host defense system is activated by a complex cascade of various mechanisms. Local anesthetics previously were shown to interact with diverse components of the immune response, such as leukocyte adherence on endothelial monolayers, oxidative burst, or crosstalk within lymphocyte subset populations. However, effects of newer local anesthetics like bupivacaine and ropivacaine on antibacterial host defense-primarily phagocytosis activity, oxidative burst, or CD11b expression-still remain unclear. METHODS: Whole blood samples were preincubated with local anesthetics (lidocaine, 9.2, 92.2, and 1,846 microm bupivacaine, 6.1, 61, and 770 microm; ropivacaine, 6.4, 64, and 801 microm). For the oxidative burst and CD11b assay, dihydroethidium was added to the probes. After viable Staphylococcus aureus was added in a 5 to 1 ratio following leukocyte count, phagocytosis was stopped at different times, and staining with monoclonal antibodies was performed for subsequent flow cytometric analysis of phagocytosis activity, oxidative burst, and CD11b expression. RESULTS: Granulocyte phagocytosis activity, CD11b expression, and generation of reactive oxygen species were significantly reduced by lidocaine (P < 0.0002) and bupivacaine (P < 0.005) in the highest concentration (1,846 microm and 770 microm, respectively). The capability of granulocytes to ingest bacteria was significantly depressed only by lidocaine (P < 0.003). Ropivacaine had no significant effect on any parameter investigated. CONCLUSIONS: Local anesthetic dose and structure dependently inhibit inflammatory and immunologic parameters of granulocyte functions. Ropivacaine shows low interference with granulocyte immunologic and inflammatory functions.

Adult↗

PubMed2003

Correlation of meropenem plasma levels with pharmacodynamic requirements in critically ill patients receiving continuous veno-venous hemofiltration.

BACKGROUND: In patients with acute renal failure, the pharmacokinetics of meropenem depend on the operational characteristics of the renal replacement therapy. Dosage recommendations are based on the correlation of plasma levels with pharmacodynamic requirements. METHODS: Eight critically ill patients with acute renal failure were treated by continuous veno-venous hemofiltration with a filtrate flow of 1,600 ml/h and received 500 mg of meropenem every 12 h. Plasma and hemofiltrate concentrations of meropenem at steady state were determined by HPLC. RESULTS: Peak levels in plasma amounted to 39.5 +/- 10.5 mg/l (mean +/- SD) and trough levels were 2.4 +/- 1.5 mg/l. The minimal inhibitory concentration (MIC) for susceptible bacteria (4 mg/l) was covered for 40% of the dosing interval or longer in all patients. The MIC for intermediately susceptible organisms (8 mg/l) was covered for 33% in 6 of the 8 patients. The elimination half-life was prolonged to 3.63 +/- 0.77 h. The sieving coefficient of meropenem was 0.91 +/- 0.10 and the recovery in hemofiltrate amounted to 30.9 +/- 11.5% of the dose. CONCLUSIONS: A dosage of 500 mg twice daily provides appropriate serum levels for the treatment of infections caused by susceptible bacteria. A higher dosage is adequate for infections by intermediately susceptible bacteria or for renal replacement therapies with markedly higher filtrate flow rates.

Acute Kidney Injury↗

PubMed2002

Influence of combined intravenous and topical antibiotic prophylaxis on the incidence of infections, organ dysfunctions, and mortality in critically ill surgical patients: a prospective, stratified, randomized, double-blind, placebo-controlled clinical trial.

We prospectively studied the impact of an antibiotic prophylaxis regimen on the incidence of infections, organ dysfunctions, and mortality in a predominantly surgical and trauma intensive care unit (ICU) population. A total of 546 patients were enrolled and stratified according to Acute Physiology and Chronic Health Evaluation (APACHE)-II scores. They were then randomized to receive either 2 x 400 mg of intravenous ciprofloxacin for 4 days, together with a mixture of topical gentamicin and polymyxin applied to the nostrils, mouth, and stomach throughout their ICU stay or to receive intravenous and topical placebo. When receiving prophylaxis, significantly fewer patients acquired infections (p = 0.001, risk ratio [RR], 0.477; 95% confidence interval [CI], 0.367-0.620), especially pneumonias (6 versus 29, p = 0.007), other lower respiratory tract infections (39 versus 70, p = 0.007), bloodstream infections (14 versus 36, p = 0.007), or urinary tract infections (36 versus 60, p = 0.042). Also, significantly fewer patients acquired severe organ dysfunctions (63 versus 96 patients, p = 0.0051; RR, 0.636; 95% CI, 0.463-0.874), especially renal dysfunctions (17 versus 38; p = 0.018). Within 5 days after admission, 24 patients died in each group, whereas 28 patients receiving prophylaxis and 51 receiving placebo died in the ICU thereafter (p = 0.0589; RR, 0.640; 95% CI, 0.402-1.017). The overall ICU mortality was not statistically different (52 versus 75 fatalities), but the mortality was significantly reduced for 237 patients of the midrange stratum with APACHE-II scores of 20-29 on admission (20 versus 38 fatalities, p = 0.0147; RR, 0.508; 95% CI, 0.295-0.875); there was still a favorable trend after 1 year (51 versus 60 fatalities; p = 0.0844; RR, 0.720; 95% CI, 0.496-1.046). Surveillance cultures from tracheobronchial, oropharyngeal, and gastric secretions and from rectal swabs did not show any evidence for the selection of resistant microorganisms in the patients receiving prophylaxis.

APACHE↗

PubMed2002

Ventilator-associated pneumonia.

Ventilator-associated pneumonia is the most serious infectious complication in critically ill patients, associated with increased length of intensive care unit treatment and high mortality rates. Investigations focused on outcome variables have improved the database to estimate diagnostic and therapeutic management strategies. This knowledge has diminished the importance of the discussion on how to diagnose the pneumonia. This review summarizes recent data on epidemiology and mortality, risk factors and prevention, diagnosis, microbiology and antimicrobial treatment of ventilator-associated pneumonia.

Journal Article↗

PubMed2002

Selective decontamination of the digestive tract.

Ventilator-associated pneumonia usually originates from the patient's oropharyngeal microflora. In selective digestive decontamination, topical antibiotics are applied to the oropharynx and stomach for prevention of pneumonia and other infections, possibly reducing infection-related mortality. Selective digestive decontamination is also used for the prevention of gut-derived infections in acute necrotizing pancreatitis and liver transplantation. Despite numerous clinical trials, selective digestive decontamination remains controversial. Reduction of the incidence of pneumonia is accepted, but the extent of reduction is debated. Mortality was not reduced in most individual trials, but this finding was calculated in meta-analyses, especially for combined use of topical and systemic antibiotics in surgical ICU patients. Some investigators reported increased resistance and a shift to Gram-positive pathogens. Today, it appears that selective means not only selective suppression of pathogenic bacteria but also selection of appropriate groups of patients for underlying diseases and severity of illness, and selection of ICUs, where the endemic resistance patterns might allow the use of selective digestive decontamination at a relatively low risk for increased selection pressure.

Antibiotic Prophylaxis↗