Soluble CD14 in septic shock.
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Biomedical subjects
Publications and source records attributed to W Zimmerli.
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Outpatients with pneumonia are usually treated empirically. Therefore, the knowledge of the most important causative agents is a prerequisite for the 'educated guess'. With a broad microbiological evaluation, the etiology of a pneumonia can be detected in only half of the cases. In outpatients, 30% of the causative agents are viruses, 45% 'atypical bacteria' such as Mycoplasma sp. and Chlamydia pneumoniae, and 25% pneumococci and Hemophilus. In hospitalized patients, pneumococci and Hemophilus cause 60%, and 'atypical bacteria' only 25% of the community acquired pneumonias. The most relevant microbiological examination in outpatients is the Gram stain of the sputum. The sputum culture is seldom useful and sometimes even misleading, especially if the result is not interpreted in connection with the Gram stain. The most appropriate treatment of outpatients without underlying disease is a macrolide. In patients with chronic bronchitis, alcoholism or preceding influenza infection, amoxicillin/clavulanic acid or a new oral cephalosporin is the best choice. The detection of risk factors for fatal outcome is important for the decision to admit the patient to a hospital.
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The response of infective endocarditis to antimicrobial therapy is slow because host defence mechanisms in heart valves are absent, high bacterial densities occur in vegetations and the infecting agents have a low metabolic activity. In this situation, only an optimal antibiotic treatment can be effective; therefore early identification of the microorganism by means of blood cultures and the use of bactericidal antibiotics with proven efficacy in clinical trials are essential. The antibiotics should be administered intravenously, because constant and high serum levels are important. The choice of the empirical therapy is based on the patient's history, on clinical signs and symptoms as well as on some additional examinations in order to define the most probable organisms involved. As soon as the infecting agent is identified, the treatment should be optimized. A daily clinical examination of the patient and frequent laboratory controls are needed. In case of poor clinical response to the antimicrobial therapy, the search for complications is frequently more appropriate than changing the antibiotics. The duration of therapy depends on the infecting agent, the evolution and the antibiotic regimen that has been chosen. After treatment, blood cultures should be taken at four and eight weeks, since most relapses appear within this period.
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Treatment outcome of experimental device-related infections cannot be predicted by the results of standard susceptibility tests such as MIC. Microorganisms involved in such infections have a slow growth rate and adhere to surfaces. Therefore, laboratory tests were developed taking into account these properties and compared with the treatment outcome in an animal model. Vancomycin, teicoplanin, ciprofloxacin and fleroxacin were tested alone, or in combination with rifampicin for their ability to cure experimental device-related infections in guinea pigs due to Staphylococcus aureus ATCC 29213. Rifampicin alone or in combination was significantly more effective than the other four drugs (P < 0.001). Combined treatment with rifampicin had a higher cure rate than rifampicin alone. Treatment success was not predicted by an antibiotic trough level exceeding the MIC at site of infection. In contrast, drug efficacy was predicted if the stationary-phase MBC was in the sensitive range, and if glass-adherent S. aureus was killed by low drug concentrations.
Nosocomial pneumonia and sepsis, as well as severe diffuse peritonitis, must be treated early in order to prevent complications such as septic shock and organ dysfunctions. With the availability of new broad-spectrum and highly bactericidal antibiotics, the need of combining beta-lactams with aminoglycosides for the treatment of severe infections should be reassessed. A prospective randomized controlled study was performed to compare imipenem monotherapy with a combination of imipenem plus netilmicin in the empiric treatment of nosocomial pneumonia, nosocomial sepsis, and severe diffuse peritonitis. A total of 313 patients were enrolled, and 280 were assessable. The antibiotic treatment was successful in 113 of 142 patients (80%) given the monotherapy and in 119 of 138 patients (86%) given the combination (P = 0.19). The failure rates for the most important type of infection, i.e., pneumonia, were similar in the two groups, as well as the number of superinfections. While creatinine increase was associated with factors not related to antibiotic therapy for all eight patients of the monotherapy group, no factor other than the antibiotics could be found for 6 of the 14 cases of nephrotoxicity observed in the combination group (P = 0.014). Finally, the emergence of Pseudomonas aeruginosa resistant to imipenem occurred in 8 monotherapy patients and in 13 combination therapy patients. In conclusion, imipenem monotherapy appeared as effective as the combination of imipenem plus netilmicin for the treatment of severe infection. The addition of netilmicin increased nephrotoxicity, and it did not prevent the emergence of P. aeruginosa resistant to imipenem.
Mycoplasma hominis (M. hominis) frequently colonizes the genital tract, but is rarely isolated from the respiratory tract. Dissemination of M. hominis has been documented in women with a febrile illness after delivery. Spontaneous recovery is the rule. A 32-year-old woman in the 29th week of pregnancy was hospitalized for pneumonia. She had to be ventilated for respiratory insufficiency and thoracic empyema. The child was delivered by section due to signs of stress in cardiotocography. In the ensuing days the mother's condition worsened, with fever, weight loss and persistent pleural effusion. Even after decortication and treatment with ceftriaxone fever and pleural effusion persisted. M. hominis was found in pleural fluid cultures. Treatment with doxycycline led to rapid defervescence and an improvement of the patient's condition.
Cervical lymphadenitis and lymphadenopathy are common in children and may be caused by local or systemic infection. There are a large number of possible etiologies. We report the case of a five-year-old boy with unilateral cervical lymphadenitis who was in good health and showed neither clinical nor laboratory signs of systemic infection. Despite repetitive empirical antimicrobial treatment, the lymph nodes increased in size. After surgical excision Mycobacterium malmoense grew from the lymph node culture. Based on a literature search (Embase and Medline 1980-1992), the most frequent infectious etiologies of pediatric cervical lymphadenitis and lymphadenopathies are summarized. Nontuberculous mycobacterial lymphadenitis is most frequent in children between one and five years of age, and is more common in girls than boys. The treatment of choice is surgical excision. In immunocompetent children treatment with antimycobacterial drugs is not needed even if relapse occurs.
In neurosurgery, the antibiotic prophylaxis of choice has not yet been determined. The ideal drug should have an appropriate antimicrobial spectrum and favourable pharmacokinetic properties. In addition it should be nontoxic and easy to apply. We therefore conducted in 90 patients a prospective, randomized, placebo-controlled, double-blind trial in clean neurosurgery at increased risk of wound infection using a single pre-operative dose of 500 mg fusidic acid. Fusidic acid is a steroid-like antibiotic with a serum half-life of about 10 hours and excellent activity against gram-positive bacteria, including methicillin-resistant staphylococci. The neurosurgical infection rates for craniotomies, posterior fossa surgery and implantation of foreign bodies were 2.4% in the treatment group and 9.1% in the placebo group, respectively. This difference is statistically significant at a 95% confidence level.
Penetration of fusidic acid into brain tissue in six patients and cerebrospinal fluid in seven patients was determined. Tissue samples, taken during surgery revealed drug levels at about 7% of simultaneous serum concentrations. In contrast, cerebrospinal fluid concentrations were below 1% of serum levels. Since serum- and tissue levels of fusidic acid were far above the minimal inhibitory concentration (MICs) of staphylococci and streptococci, and since it has a long serum half-life of about 10 hours, it is a promising candidate for prophylaxis in neurosurgery.
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In a retrospective survey of patients hospitalized in the University Hospital of Basel, Switzerland, the course and outcome of 281 cases of true bacteremia due to Staphylococcus aureus over a 7-year period were analyzed. The main purpose was to evaluate different case definitions. In 78% of cases the source of bacteremia was obvious; vascular access sites (27%) and wounds (10%) were the most common sources. Metastasizing foci were more common in cases of primary vs. secondary bacteremia (P < .001). The incidence of endocarditis was higher in cases in which no portal of entry was defined (P < .03). The overall mortality rate was high at 34% partly because of inappropriate initial antibiotic therapy. With the introduction of an infectious disease service at the hospital, the fraction of misjudged results of blood culture diminished 2.5-fold. Among the differently defined cases, the mortality rate was significantly higher for cases of complicated vs. uncomplicated bacteremia (P < .01), for cases of primary vs. secondary bacteremia (P = .05), and for patients with endocarditis or other secondary foci (P < .001). Since only one methicillin-resistant strain was isolated, multiresistant staphylococci were not a problem in the hospital. Different case definitions allowed the detection of patients at increased risk for complications and death. In the treatment of sepsis with no evident focus, initial antimicrobial therapy should include the use of agents with antistaphylococcal activity.
Rifampicin is used to treat neurosurgical shunt infections because of its excellent in-vitro activity against staphylococci and its adequate penetration into the CSF. However, nothing is known about rifampicin concentrations in the cerebral extra-cellular space (CES). We measured the penetration of rifampicin into the CES of anaesthetized rats by microdialysis using low-flow and equilibrium methods. Depending on the method, rifampicin concentrations in the CES were 0.3-1% of the serum concentration or 3-8% of brain tissue concentration, respectively. These experimental data in animals suggest that the recommended dose of rifampicin in man might be inadequate for treatment of some brain infections.
There has been an increasing concern with the problem of device-related infections, ever since foreign materials such as metal or plastic began to be used in implant surgery. The prophylaxis and treatment of such infections is difficult to evaluate in clinical studies, because placebo-controlled prophylaxis trials are thought to be unethical, and no single centre has enough patients for comparative treatment studies. For this reason different experimental models have been developed to study aspects of device-related infections. In this review, these infection models are presented. Different applications of the tissue-cage guinea pig model are summarized. This model allows the study of pathogenesis, natural course, prophylaxis, and treatment of device-related infection. In addition, by using this infection model, novel microbiological in-vitro tests could be developed, and questions of biocompatibility analysed.
OBJECTIVE: To determine the value of serum concentrations of interleukin-6 (IL-6), C-reactive protein, and glycosylation of alpha 1-acid glycoprotein as tools for diagnosing nosocomial infection in surgical intensive care unit (ICU) patients. DESIGN: Prospective, consecutive entry study of patients with an anticipated stay of at least 24 hrs in a surgical ICU. SETTING: University hospital, a major provider of acute surgical care. PATIENTS: One hundred four consecutive patients admitted to the surgical ICU between March and June 1990. MEASUREMENTS: Concentrations of IL-6, C-reactive protein, and glycosylation of alpha 1-acid glycoprotein were measured on days 1 and 6 after ICU admission. Clinical evaluation for infection was performed daily in a blinded fashion, i.e., without knowing the results of the acute-phase parameters. MAIN RESULTS: On day 6 after surgery or trauma, nosocomial infection could be ascertained in 13 cases. The clinical parameter of fever > 38 degrees C had a sensitivity of 54% and a specificity of 90% to demonstrate nosocomial infection. Infected patients showed increased concentrations of IL-6 (p < .001), C-reactive protein (p < .001), and increased reactivity of alpha 1-acid glycoprotein to concanavalin A (p < .001) compared with patients without infections. By choosing appropriate cutoff values, IL-6 determinations had the highest specificity (97%), and C-reactive protein values had the highest sensitivity (85%) for diagnosing nosocomial infections. In uninfected patients, 81% of the IL-6 values, but only 29% of the C-reactive protein values, were back to the normal range on day 6 after injury. CONCLUSION: Due to the rapid normalization after trauma, a single measurement of the serum IL-6 concentration may be useful to support or refute the clinical suspicion of nosocomial infection.
The pharmacokinetics of an antimicrobial drug in human plasma and in vitro susceptibility testing of an antimicrobial drug do not necessarily predict its efficacy in vivo. Therefore, the combined activity of an antimicrobial drug and blood-derived polymorphonuclear leukocytes (PMN) against Staphylococcus aureus were investigated in vitro. In addition, a pharmacological model allowing analysis of the bactericidal activity of a drug-containing exudate against S. aureus ex vivo was developed. For this purpose, a phagocytic-bactericidal assay was miniaturized to a volume of 100 microliters in order to test the bactericidal activities of an antimicrobial drug with blood PMN in vitro and with skin blister fluid (CBF) ex vivo. Ro 40-6890, the active metabolite of the ester prodrug Ro 41-3399, was used as the test drug. Killing of S. aureus was clearly enhanced when Ro 41-6890 was combined in vitro with a suboptimal number of blood-derived PMN. In eight healthy volunteers, skin blisters were provoked by plasters containing cantharidin. Following a single oral dose of Ro 41-3399, CBF containing PMN was sampled at regular intervals and incubated ex vivo with S. aureus (5 x 10(5) CFU/ml) for 2, 4, 6, and 24 h at 37 degrees C. Concentrations of Ro 40-6890 were measured in CBF (CCBF) and plasma. Ro 40-6890 distributed well from plasma into CBF. When CCBF was below the MIC, an enhanced effect of Ro 40-6890 and host defense factors present in CBF against S. aureus was observed. In conclusion, the present model can provide additional information on human plasma drug concentrations and MICs established in vitro.