Pharmacokinetics of intraperitoneal and intravenous fosfomycin in automated peritoneal dialysis patients without peritonitis.

Blood and dialysate concentrations of fosfomycin were determined after intravenous and intraperitoneal application of 4 mg/liter in patients undergoing automated peritoneal dialysis. Maximum serum concentrations after intravenous (287.75 ± 86.34 mg/liter) and intraperitoneal (205.78 ± 66.78 mg/liter) administration were comparable. Ratios of intraperitoneal to systemic exposure were 1.12 (intraperitoneal administration) and 0.22 (intravenous administration), indicating good systemic exposure after intraperitoneal application but limited penetration of fosfomycin into the peritoneal fluid after the intravenous dose.

Clinical and molecular characterization of a near fatal case of human babesiosis in Austria.

A previously healthy febrile patient with travel history to Nicaragua showed rapid clinical deterioration with hemodynamic shock and anuria. Diagnosis of severe malaria was established based on intra-erythrocytic parasites and antimalarial treatment was initiated. However, upon reevaluation Babesia microti infection was suspected and molecular characterization by polymerase chain reaction and sequence analysis was performed.

Likelihood of inadequate treatment: a novel approach to evaluating drug-resistance patterns.

OBJECTIVE: To provide a novel way to predict the likelihood that antibiotic therapy will result in prompt, adequate therapy on the basis of local microbiological data. DESIGN AND SETTING: Prospective study conducted at 3 medical intensive care units at the Viennese General Hospital, a tertiary care medical university teaching hospital in Vienna, Austria. PATIENTS: One hundred one patients who received mechanical ventilation and who met the criteria for having ventilator-associated pneumonia. DESIGN: Fiberoptic bronchoscopic examination was performed, and bronchoalveolar samples were collected. Samples were analyzed immediately by a single technician. Minimum inhibitory concentrations were determined for imipenem, cephalosporins (cefepime and cefpirome), ciprofloxacin, and piperacillin-tazobactam, and drug resistance rates were calculated. These drug resistance rates were translated into the likelihood of inadequate therapy (LIT; the frequency of inadequately treated patients per antibiotic and drug-resistant strain), cumulative LIT (the cumulative frequency of inadequately treated patients), and syndrome-specific LIT. RESULTS: Among the 101 bronchoalveolar samples, culture yielded significant (at least 1 x 10(4) colony-forming units per mL) polymicrobial findings for 34 and significant monomicrobial findings for 31; 36 culture results were negative. Of the isolates from patients with ventilator-associated pneumonia who had monomicrobial culture findings, 33% were gram-positive bacteria and 20% were gram-negative bacteria. LIT suggested that 1 of 2 patients was treated inadequately for Pseudomonas aeruginosa infection. The LIT for patients with ventilator-associated pneumonia revealed that the rank order of antibiotics for appropriate therapy was (1) imipenem, (2) cephalosporins, (3) ciprofloxacin, and (4) piperacillin-tazobactam. These calculations were based solely on microbiological data. CONCLUSIONS: The novel ratio LIT may help clinicians use microbiological data on drug resistance to predict which antimicrobial agents will provide adequate therapy. In daily practice, this new approach may be helpful for choosing adequate antimicrobial therapy.

Comparison of copeptin, B-type natriuretic peptide, and amino-terminal pro-B-type natriuretic peptide in patients with chronic heart failure: prediction of death at different stages of the disease.

OBJECTIVES: This study sought to evaluate the predictive value of copeptin over the entire spectrum of heart failure (HF) and compare it to the current benchmark markers, B-type natriuretic peptide (BNP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP). BACKGROUND: Vasopressin has been shown to increase with the severity of chronic HF. Copeptin is a fragment of pre-pro-vasopressin that is synthesized and secreted in equimolar amounts to vasopressin. Both hormones have a short lifetime in vivo, similar to BNPs, but in contrast to vasopressin, copeptin is very stable in vitro. The predictive value of copeptin has been shown in advanced HF, where it was superior to BNP for predicting 24-month mortality. METHODS: This was a long-term observational study in 786 HF patients from the whole spectrum of heart failure (New York Heart Association [NYHA] functional class I to IV, BNP 688 +/- 948 pg/ml [range 3 to 8,536 pg/ml], left ventricular ejection fraction 25 +/- 10% [range 5% to 65%]). RESULTS: The NYHA functional class was the most potent single predictor of 24-month outcome in a stepwise Cox regression model. The BNP, copeptin, and glomerular filtration rate were related to NYHA functional class (p < 0.0001 for trend). Copeptin was the most potent single predictor of mortality in patients with NYHA functional class II (p < 0.0001) and class III (p < 0.0001). In NYHA functional class IV, the outcome of patients was best predicted by serum sodium, but again, copeptin added additional independent information. CONCLUSIONS: Increased levels of copeptin are linked to excess mortality, and this link is maintained irrespective of the clinical signs of severity of the disease. Copeptin was superior to BNP or NT-proBNP in this study, but the markers seem to be closely related.

Bone marrow infection with bacillus Calmette-Guérin (BCG) after intravesical immunotherapy.

Instillation of bacillus Calmette-Guérin (BCG) into the urine bladder is an effective treatment of superficial bladder cancer. BCG-mediated anti-tumor activity appears to be a local phenomenon in which cell-mediated immunity, involving cytotoxic T cells, lymphokine-activated killer cells and natural killer cells, is important for the elimination of malignant cells. Serious side-effects of BCG therapy are rare; nevertheless, BCG is a live, attenuated strain of Mycobacterium (M.) bovis and may exhibit invasive properties. Both local and distant or generalized infections have been reported after treatment with BCG. We describe the case of a 68-year-old man who developed bone marrow infection with BCG two years after intravesical instillation of BCG for treatment of superficial bladder cancer. He presented with intermittent fever, weight loss and pronounced pancytopenia. A bone marrow biopsy specimen showed granulomatous inflammation and BCG was cultured from the urine. Anti-mycobacterial treatment with isoniazid, rifampicin and ethambutol (pyrazinamide is inactive against M. bovis) led to full clinical recovery of the patient.

Community-acquired bacteria frequently detected by means of quantitative polymerase chain reaction in nosocomial early-onset ventilator-associated pneumonia.

OBJECTIVE: To test whether real-time polymerase chain reaction allows for rapid quantitative detection of Streptococcus pneumoniae, Chlamydia pneumoniae, Mycoplasma pneumoniae, and Legionella pneumophila in bronchoalveolar lavage fluids and to determine the prevalence of these pathogens in nosocomial ventilator-associated pneumonia. DESIGN: Prospective epidemiologic study applying a new molecular biology-based diagnostic tool during a 27-month period. SETTING: Three medical intensive care units of a tertiary care university hospital. PATIENTS: One hundred patients suffering from nosocomial ventilator-associated pneumonia, hospitalized for > or =14 days, intubated for reasons other than pneumonia, and mechanically ventilated for >48 hrs. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: S. pneumoniae, M. pneumoniae, and C. pneumoniae were detected in bronchoalveolar lavage fluids of 100 patients in 20 (20%), three (3%), and two (2%) cases, respectively. There of 17 (71%) revealed no growth or no significant growth by conventional culture. In one patient, S. pneumoniae and M. pneumoniae were detected simultaneously. Corresponding colony-forming units/mL were partly up to 10 CFU/mL with Gram stainings showing signs of acute inflammation in 80%. A significant temporary correlation between the number of days on ventilator, development of nosocomial pneumonia, and the frequency of detection of these pathogens was found for day 4. CONCLUSIONS: S. pneumoniae, M. pneumoniae, and C. pneumoniae should be considered as causative agents in critically ill patients who develop early-onset nosocomial ventilator-associated pneumonia. Thus, empirical antimicrobial regimens should cover S. pneumoniae, Chlamydia, and Mycoplasma alike. Quantitative polymerase chain reaction is a fast diagnostic tool allowing for detection of these bacteria within 3 hrs in pretreated patients.

Ventilator-associated pneumonia: Increased bacterial counts in bronchoalveolar lavage by using urea as an endogenous marker of dilution.

OBJECTIVE: Invasive diagnostic procedures such as bronchoalveolar lavage (BAL) with quantitative microbiological cultures are currently recommended for the diagnosis of nosocomial pneumonia. Commonly, in clinical practice, a threshold of > or =10 colony forming units/mL is used for therapeutic decisions. The use of these measurements in daily practice assumes that their repeatability is acceptable. However, many variations among the positive results have been noted. One of the most important is dilution of BAL, which may influence the quantitative results by minimizing bacterial counts. Knowledge of the extent of dilution may increase dramatically the value of quantitative cultures. The aim of this study was to determine to what extent specimens are diluted in BAL by measuring urea in BAL and blood. Furthermore, the impact of a potential dilution effect on the diagnosis of ventilator-associated pneumonia was studied. PATIENTS AND SETTING: A total of 47 patients with ventilator-associated pneumonia in two medical intensive care units at the Vienna General Hospital, a university-affiliated facility. DESIGN: Prospective study performed between January 2001 and July 2002. METHODS: BAL fluid was divided immediately into two samples: one for direct microscopic examination of cytocentrifuge preparations for Gram staining to determine percentages of cells containing intracellular bacteria and one for quantitative cultures according to the Cumitech 7A guidelines. Epithelial lining fluid volume was calculated using urea as a marker of dilution and correlated with colony forming units per milliliter. RESULTS: Nineteen out of 47 patients (40%) revealed significant bacterial growth (> or =10 colony forming units/mL). Eight additional patients (17%) would have reached the cutoff level after correction of the dilution effect, which varied between 1.8- and 130-fold. CONCLUSIONS: Data suggest a great variation of dilution during BAL procedures, which influences quantitative results. Using urea to determine the dilution quotient could increase the value of bacterial thresholds in the diagnosis and therapeutic decision of ventilator-associated pneumonia.

Efficacy and tolerability of non-invasive ventilation delivered via a newly developed helmet in immunosuppressed patients with acute respiratory failure.

OBJECTIVES: To assess efficacy and tolerability of a newly developed helmet for the delivery of non-invasive ventilation in patients with acute respiratory failure. PATIENTS AND METHODS: Ten consecutive immunocompromised patients with acute respiratory failure admitted to our intensive care unit were included in the study. The patients were equipped with the helmet and non-invasive ventilation (NIV) was performed. Oxygenation and tolerability were assessed during the first 24 hours of NIV. RESULTS: All patients tolerated the helmet well and their oxygenation improved. Two patients developed septic shock and had to be endotracheally intubated during the study period, eight patients survived to be weaned from NIV. CONCLUSIONS: NIV delivered via the helmet is effective and may serve as a better tolerated alternative to endotracheal intubation and to NIV via a standard face mask.

Circulating tuberculostearic acid in tuberculosis patients.

Tuberculostearic acid (TBSA), a mycobacterial cell wall constituent, was measured in plasma samples using a highly sensitive high-performance liquid chromatography method. Plasma TBSA concentrations in patients with active tuberculosis (20 [0.5-347] nmol/l; n = 125) were higher than in patients with a variety of non-tuberculous pulmonary and extrapulmonary inflammatory conditions (0.1 [0-29] nmol/l; n = 116) and in healthy controls (0 [0-2] nmol/l; n = 102) (p = < 0.001). The calculated sensitivity, specificity, positive and negative predictive values for tuberculosis were 95.2%, 87.9%, 89.5% and 94.4%, respectively, indicating that assay of plasma TBSA might be a valuable complementary diagnostic tool.

Local warming and insertion of peripheral venous cannulas: single blinded prospective randomised controlled trial and single blinded randomised crossover trial.

OBJECTIVE: To determine whether local warming of the lower arm and hand facilitates peripheral venous cannulation. DESIGN: Single blinded prospective randomised controlled trial and single blinded randomised crossover trial. SETTING: Neurosurgical unit and haematology ward of university hospital. PARTICIPANTS: 100 neurosurgical patients and 40 patients with leukaemia who required chemotherapy. INTERVENTIONS: Neurosurgical patients' hands and forearms were covered for 15 minutes with a carbon fibre heating mitt. Patients were assigned randomly to active warming at 52 degrees C or passive insulation (heater not activated). The same warming system was used for 10 minutes in patients with leukaemia. They were assigned randomly to active warming or passive insulation on day 1 and given alternative treatment during the subsequent visit. MAIN OUTCOME MEASURES: PRIMARY: success rate for insertion of 18 gauge cannula into vein on back of hand. SECONDARY: time required for successful cannulation. RESULTS: In neurosurgical patients, it took 36 seconds (95% confidence interval 31 to 40 seconds) to insert a cannula in the active warming group and 62 (50 to 74) seconds in the passive insulation group (P=0.002). Three (6%) first attempts failed in the active warming group compared with 14 (28%) in the passive insulation group (P=0.008). The crossover study in patients with leukaemia showed that insertion time was reduced by 20 seconds (8 to 32, P=0.013) with active warming and that failure rates at first attempt were 6% with warming and 30% with passive insulation (P<0.001). CONCLUSIONS: Local warming facilitates the insertion of peripheral venous cannulas, reducing both time and number of attempts required. This may decrease the time staff spend inserting cannulas, reduce supply costs, and improve patient satisfaction.

Frequent development of lupus anticoagulants in critically ill patients treated under intensive care conditions.

OBJECTIVE: To investigate how often a prolongation of the activated partial thromboplastin time in critically ill patients is caused by lupus anticoagulants and to identify possible triggering events. DESIGN: Prospective study. SETTING: Internal medicine intensive care unit (University Hospital of Vienna, Vienna, Austria). PATIENTS: Fifty-one critically ill patients without severe coagulopathy, hepatopathy, or anticoagulant treatment (35 male, 16 female, median age 60 yrs, range: 22-85 yrs). INTERVENTIONS: All patients were screened daily for lupus anticoagulants with the activated partial thromboplastin time STA assay. MEASUREMENTS AND MAIN RESULTS: Diluted Russell's viper venom time, plasma mixing studies, and confirmation assays were used to identify lupus anticoagulants at the time of an unexplained prolongation of the activated partial thromboplastin time. The influence of heparin was excluded by determination of thrombin clotting time and anti-Xa activity. In 27 of 51 patients (52.9 %) lupus anticoagulants were found after a median stay of 13 days. None of the patients had concomitant immune thrombocytopenia, hypoprothrombinemia, bleeding, or thromboembolic complications. Sepsis (p =.006) and/or catecholamine treatment (p =.002) were significantly associated with the development of lupus anticoagulants. Extracorporeal circulation, transfusion of blood products, or surgery did not increase this risk. Lupus anticoagulants resolved spontaneously in 63% of the patients after a median stay of 17 days. CONCLUSIONS: Lupus anticoagulants are frequent in critically ill patients and associated with sepsis syndrome and/or catecholamine treatment. The prolonged activated partial thromboplastin time does not warrant the administration of coagulation factors or the cessation of anticoagulant therapy or prophylaxis, inasmuch as this phenomenon is not associated with bleeding or thromboembolic complications.