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W Zimmerli

Publications and source records attributed to W Zimmerli.

At least 19 recordsLinked to original sources
PubMed2001

[Para-infectious vasculitis].

Vasculitis is histologically characterized by inflammatory infiltrates of the vessels. In case of secondary vasculitis, the etiology is known. It may be an infection, a neoplasia, drugs or an autoimmune disease. In contrast, in primary vasculitis, no triggering event can be detected. In case of vasculitis associated to infection, the skin lesion may be the clue for the underlying infection. In case of endocarditis (Osler node, Janeway lesion) or sepsis due to Pseudomonas aeruginosa (ecthyma gangrenosum), the skin lesions are quite specific for the underlying disease. Other skin lesions are just an unspecific reaction to a microbial stimulus. Five clinical examples of vasculitis associated to infection, and an important non-infectious differential diagnosis are presented. The cases underline that a broad general work-up with multiple serological tests is neither cost-effective nor diagnostically rewardable. In contrast, if vasculitis is suspected to be caused by infection, the individual work-up should be based on the case-history, the epidemiology and the clinical presentation.

Adult↗
PubMed2001

Impact of the regulatory loci agr, sarA and sae of Staphylococcus aureus on the induction of alpha-toxin during device-related infection resolved by direct quantitative transcript analysis.

The cytotoxic alpha-toxin (encoded by hla) of Staphylococcus aureus is regulated by three loci, agr, sarA and sae, in vitro. Here, we assess the regulation of hla in a guinea pig model of device-related infection by quantifying RNAIII (the effector molecule of agr) and hla directly in exudates accumulating in infected devices without subculturing of the bacteria. LightCycler reverse transcription-polymerase chain reaction (RT-PCR) was used to quantify the transcripts. Strains RN6390 and Newman expressed considerably smaller amounts of RNAIII in the guinea pig than during in vitro growth. The residual RNAIII expression decreased during the course of infection and was negatively correlated with bacterial densities. As with RNAIII, the highest hla expression was detected in both strains early in infection. Even in strain Newman, a weak hla producer in vitro, a pronounced expression of hla was observed during infection. Likewise, four S. aureus isolates from cystic fibrosis (CF) patients expressed Q1hla despite an inactive agr during device-related infection as in the CF lung. Mutation of agr and sarA in strain Newman and RN6390 had no consequence for hla expression in vivo. In contrast, the mutation in sae resulted in severe downregulation of hla in vitro as well as in vivo. In conclusion, S. aureus seems to be provided with regulatory circuits different from those characterized in vitro to ensure alpha-toxin synthesis during infections.

Animals↗
PubMed2001

Lenercept (p55 tumor necrosis factor receptor fusion protein) in severe sepsis and early septic shock: a randomized, double-blind, placebo-controlled, multicenter phase III trial with 1,342 patients.

OBJECTIVE: Phase III study to confirm a trend observed in a previous phase II study showing that a single dose of lenercept, human recombinant p55 tumor necrosis factor receptor-immunoglobulin G1 (TNFR55-IgG1) fusion protein, decreased mortality in patients with severe sepsis or early septic shock. DESIGN: Multicenter, double-blind, phase III, placebo-controlled, randomized study. SETTING: A total of 108 community and university-affiliated hospitals in the United States (60), Canada (6) and Europe (42). PATIENTS: A total of 1,342 patients were recruited who fulfilled the entry criteria within the 12-hr period preceding the study drug administration. INTERVENTION: After randomization, an intravenous dose of 0.125 mg/kg lenercept or placebo was given. The patient was monitored for up to 28 days, during which standard diagnostic, supportive, and therapeutic care was provided. MEASUREMENTS AND MAIN RESULTS: The primary outcome measure was 28-day all-cause mortality. Baseline characteristics were as follows: a total of 1,342 patients were randomized; 662 received lenercept and 680 received placebo. The mean age was 60.5 yrs (range, 17-96 yrs); 39% were female; 65% had medical admissions, 8% had scheduled surgical admissions, and 27% had unscheduled surgical admissions; 73% had severe sepsis without shock, and 27% had severe sepsis with early septic shock. Lenercept and placebo groups were similar at baseline with respect to demographic characteristics, simplified acute physiology score II-predicted mortality, profiles of clinical site of infection and microbiological documentation, number of dysfunctioning organs, and interleukin-6 (IL-6) plasma concentration. Lenercept pharmacokinetics were similar in severe sepsis and early septic shock patients. Tumor necrosis factor was bound in a stable manner to lenercept as reflected by the accumulation of total serum tumor necrosis factor alpha concentrations. There were 369 deaths, 177 on lenercept (27% mortality) and 192 on placebo (28% mortality). A one-sided Cochran-Armitage test, stratified by geographic region and baseline, predicted 28-day all-cause mortality (simplified acute physiology score II), gave a p value of .141 (one-sided). Lenercept treatment had no effect on incidence or resolution of organ dysfunctions. There was no evidence that lenercept was detrimental in the overall population. CONCLUSION: Lenercept had no significant effect on mortality in the study population.

APACHE↗
PubMed2000

[Diagnosis and antibiotic therapy of infections in outpatients].

BACKGROUND: The study aim was to analyse the diagnostic and therapeutic approach to selected infectious diseases, in particular with regard to the use of antibiotics, in the light of current guidelines and the problem of developing resistance. METHODS: A questionnaire was sent to all physicians with a general or internal medicine practice in the Cantons Basel-Stadt and Basel-Landschaft, Switzerland. RESULTS: Of 440 physicians, 286 (65%) took part in the study. The most frequent diagnoses of infection were cystitis (16.6%), flu-like syndrome (16.4%), acute bronchitis (12.3%), and tonsillopharyngitis (10.1%). The most frequent indications for antimicrobial therapy were cystitis (19.9%), acute sinusitis (14.1%), acute bronchitis (11.5%), and tonsillopharyngitis (9.2%). Macrolides (24.0%), aminopenicillins (22.6%), and fluoroquinolones (16.8%) were the most frequently prescribed antibiotics. CONCLUSIONS: The majority of physicians diagnosed and treated according to rational principles. However, a few exceptions were found, e.g. omission of x-ray in the diagnosis of pneumonia (24%), the use of antibiotics in the treatment of viral diseases and antibiotic therapy for tonsillopharyngitis despite a negative rapid antigen detection test against group A streptococci (75%).

Adult↗
PubMed2000

Effect of antiretroviral therapy on viral load, CD4 cell count, and progression to acquired immunodeficiency syndrome in a community human immunodeficiency virus-infected cohort. Swiss HIV Cohort Study.

OBJECTIVE: To examine the effect of different antiretroviral treatment regimens on viral load, CD4 lymphocyte counts, and rates of progression to clinical acquired immunodeficiency syndrome events among treatment-naive human immunodeficiency virus (HIV)-infected patients enrolled in a large community cohort study. METHODS: Based in 7 outpatient clinics, the Swiss HIV Cohort Study is a cohort with national coverage. Virological, immunologic, and clinical results of 755 treatment-naive patients (median age, 36 years; 28.2% female) who initiated antiretroviral therapy between July 1, 1995, and June 30, 1997, were analyzed. Patients started undergoing monotherapy with 1 reverse transcriptase inhibitor (RTI), combination therapy with at least 2 RTIs, or highly active antiretroviral therapy (HAART) with RTIs and protease inhibitors. RESULTS: Antiretroviral treatment led to a mean reduction of viremia of 1.8 log10 copies per milliliter with HAART, 1.2 log10 copies per milliliter with RTI combination therapy, and 0.4 log10 copies per milliliter with monotherapy. Virological failure, defined as less than 1 log10 reduction per milliliter in viremia, was present in 45 (20%) patients undergoing HAART, 180 (38%) undergoing RTI combination therapy, and 47 (82%) undergoing monotherapy. The proportion of patients reaching undetectable viremia was 12% (n = 7) for monotherapy, 41% (n = 197) for RTI combination therapy, and 63% (n = 137) for HAART. Similar gains of CD4 cells were achieved with RTI combination therapy and HAART. Kaplan-Meier estimates of progression rates to a new acquired immunodeficiency syndrome event at 18 months were 13.6% (monotherapy), 4.7% (RTI combination therapy), and 3.9% (HAART). CONCLUSIONS: The rate of virological failure of antiretroviral treatments was high in this population of treatment-naive patients, even among patients receiving combination regimens. Clinical progression rates were, however, low in patients treated with RTI combination therapy and HAART.

Acquired Immunodeficiency Syndrome↗
PubMed2000

Clinical impact of an infectious disease service on the management of bloodstream infection.

The impact of an infectious disease (ID) service on the optimal antibiotic management of 103 patients with bloodstream infections, defined as bacteremia and systemic inflammatory response syndrome, was evaluated. The optimal antibiotic management was defined according to the Sanford Guide to Antimicrobial Therapy (1996) or written internal guidelines. The judgment on optimal antibiotic management was made at the time of reporting the positive blood culture results. Switching from a broad-spectrum to a narrow-spectrum agent was carried out significantly more often by the ID service than by the attending physicians (25 of 25 vs. 20 of 40; P<0.001). In patients without empirical therapy, the ID service initiated optimal antimicrobial therapy significantly more often than physicians without training in infectious diseases (12 of 12 vs. 4 of 10, P=0.0028). Three of 12 patients in whom the attending physician misinterpreted the positive blood culture result needed 8 days to 4 months of additional hospitalization. In summary, patients for whom an ID service was provided received appropriate treatment more often and experienced significantly fewer complications.

Adult↗
PubMed2000

Spondylodiscitis associated with bacteraemia due to coagulase-negative staphylococci.

Three cases are reported of spondylodiscitis caused by coagulase-negative staphylococci in patients without osteosynthetic material. All three patients had bacteraemia associated with an infected intravascular device left in place. On the basis of this observation, it is concluded that such devices should be removed promptly in cases of prolonged or relapsing bacteraemia. Furthermore, spondylodiscitis should be suspected in patients with back pain after bacteraemia caused by coagulase-negative staphylococci.

Aged↗
PubMed2000

Thrombocytopenia after kidney transplantation.

We report a case of posttransplant malaria in which the patient developed progressive thrombocytopenia after receiving living related donor kidney transplantation. The donor, who flew in from Sri Lanka for the procedure, had suffered from malaria 18 months earlier. Malaria should be suspected in transplant patients receiving organs from donors originating from countries with a high prevalence of malaria.

Adult↗
PubMed2000

CD14, new aspects of ligand and signal diversity.

The glycosyl-phosphatidylinositol-linked glycoprotein CD14 is expressed in myeloid cells and serum. It binds Gram-negative and -positive bacterial cell wall components and endogenous phospholipids. Toll-like receptors, NF-kappaB and MAP kinases participate in CD14 signaling of inflammation. Alterations of CD14 in inflammatory diseases support a pathogenic role for this microbial receptor.

Animals↗
PubMed2000

Disordered calcium homeostasis of sepsis: association with calcitonin precursors.

BACKGROUND: Hypocalcemia and increased serum levels of calcitonin precursors are common in critically ill patients, especially in those with sepsis. We investigated calcium homeostasis in such patients. PATIENTS AND METHODS: Serum concentrations of total and ionized calcium and known factors influencing or reflecting calcium homeostasis were measured in 101 consecutive patients of a medical intensive care unit. Calcitonin precursor levels were determined using a highly sensitive radioimmunoassay. RESULTS: Critical illness per se was associated with decreased serum total and ionized calcium levels, which correlated with the severity of the underlying disease as measured by the APACHE II score. In addition, total and ionized hypocalcemia was more pronounced with increasing severity of infection (P < 0.02), and occurred in parallel with a marked increase of calcitonin precursors (P < 0.001). Mature calcitonin levels, however, remained normal. Changes of serum ionized calcium concentrations from admission to discharge correlated significantly with changes in the serum calcitonin precursor concentration (r2 = - 0.14, P < 0.001). Circulating vitamin D levels, parathyroid hormone levels and other markers reflecting calcium homeostasis did not correlate with the severity of infection. CONCLUSIONS: In critically ill patients with sepsis, markedly elevated circulating calcitonin precursors might play a role in the development of the pronounced hypocalcemia. The specific calcitonin precursor(s) responsible for this effect and the pathophysiological mechanism remain to be elucidated.

Adult↗
PubMed2000

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Journal Article↗
PubMed2000

Calcitonin precursors are reliable markers of sepsis in a medical intensive care unit.

OBJECTIVE: The diagnosis of infection in critically ill patients is challenging because traditional markers of infection are often misleading. For example, serum concentrations of calcitonin precursors are increased in patients with infections. However, their predictive accuracy for the diagnosis of sepsis in unselected patients in a medical intensive care unit (ICU) is unknown. Therefore, we compared the usefulness of serum concentrations of calcitonin precursors, C-reactive protein, interleukin-6, and lactate for the diagnosis of sepsis in consecutive patients suffering from a broad range of diseases with an anticipated stay of > or =24 hrs in a medical ICU. DESIGN: Prospective cohort study. SETTING: Medical intensive care unit in a university medical center. PATIENTS: 101 consecutive critically ill patients. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Blood samples were collected at various time points during the course of the disease. Systemic inflammatory response syndrome, sepsis, severe sepsis, and septic shock were diagnosed according to standardized criteria, and patients were reclassified daily without prior knowledge of the serum concentrations of calcitonin precursors or interleukin-6. At admission, 99% of the patients had systemic inflammatory response syndrome, 53% had sepsis, and 5% developed sepsis during their stay in the ICU. Calcitonin precursors, C-reactive protein, interleukin-6, and lactate levels increased with the severity of infection (p < .01, one-way analysis of variance). In a receiver operating characteristic curve analysis, calcitonin precursors were found to be the most reliable laboratory variable for the diagnosis of sepsis as compared with C-reactive protein, interleukin-6, and lactate (p < .01, for each comparison). Calcitonin precursor concentrations of >1 ng/mL had sensitivity of 89% and specificity of 94% for the diagnosis of sepsis. High serum concentrations of calcitonin precursors were associated with poor prognosis (p = .01). CONCLUSIONS: In a medical ICU, serum calcitonin precursor concentrations are more sensitive and are specific markers of sepsis as compared with serum C-reactive protein, interleukin-6, and lactate levels.

Adult↗
PubMed2000

Pharmacokinetics and pharmacodynamics of levofloxacin against Streptococcus pneumoniae and Staphylococcus aureus in human skin blister fluid.

The pharmacokinetics of levofloxacin in serum and in skin blister fluid (SBF) was determined for 20 volunteers after a single 500-mg oral dose of levofloxacin. In addition, ex vivo bactericidal activity of SBF against Streptococcus pneumoniae and Staphylococcus aureus was studied. SBF containing levofloxacin and granulocytes killed 5.2 log of Streptococcus pneumoniae bacteria and 2.0 log of Staphylococcus aureus bacteria during a 6-h incubation.

Anti-Infective Agents↗
PubMed1999

[The infected artificial hip joint: possibilities, follow-up and results of treatment].

Infections after total hip replacement are still a severe problem. With current therapies they can be managed successfully. In the present study we investigated 38 patients who were treated in our clinic because of infected total hip arthroplasties. All patients had a minimal follow-up of two years. The three main therapeutical forms are explained: the revision without removal of the prosthesis, the one-stage exchange and the two-stage exchange. 35 of the 38 patients could be healed within the observation period (from 1984-1996). Two patients died in the postoperative period from cardiopulmonary diseases. One patient could not be healed and has still an ongoing infection. The success rate was 92%, with good clinical results regarding pain, and walking ability. For the patient, the treatment of an infection can be very perturbing. With the new therapeutical forms the strain for the patient can be decreased. The type and duration of the therapy before definitive treatment has no influence on the success rate. In cases with a previous long-term therapy, a more complex treatment may be necessary. The treatment should be performed in an experienced clinic. The general practitioner plays an important part in the diagnosis and after care. An adequate treatment can be offered to nearly every patient with an infected total hip arthroplasty. This also applies to patients with long-term infection and chronic fistulation.

Anti-Bacterial Agents↗
PubMed1999

The origin and function of soluble CD14 in experimental bacterial meningitis.

Murine experimental meningitis models induced by either Escherichia coli LPS, live Streptococcus pneumoniae, or Listeria monocytogenes were used to study the origin and potential function of soluble CD14 (sCD14) in the brain during bacterial meningitis. Whereas intracerebral infection caused only a minor and/or transient increase of sCD14 levels in the serum, dramatically elevated concentrations of sCD14 were detected in the cerebrospinal fluid. Reverse-transcriptase PCR and FACS analysis of the leukocytes invading the subarachnoid compartment revealed an active amplification of CD14 transcription and concomitant surface expression. These findings were confirmed by in situ hybridization and immunohistochemical analysis. In contrast, parenchymal astrocytes and microglial cells were shown not to significantly contribute to the elevated levels of sCD14. Simultaneous intracerebral inoculation of rsCD14 and S. pneumoniae resulted in a markedly increased local cytokine response. Taken together, these data provide the first evidence that sCD14 can act as an inflammatory co-ligand in vivo. Thus, during bacterial meningitis, sCD14 is massively released by intrathecal leukocytes, and the sCD14 found in the cerebrospinal fluid can play an important role in the pathogenesis of this disease.

Animals↗