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Biomedical subjects

W Zimmerli

Publications and source records attributed to W Zimmerli.

At least 19 recordsLinked to original sources
PubMed1995

[Therapeutic problems in pneumonia].

In Switzerland 10 out of 1000 adults suffer from pneumonia each year. It is of note that mycoplasma, influenza virus and pneumococci are the most common causative agents of community-acquired pneumonia. For the latter macrolides are presently the antibiotics of choice. Pneumonias occurring in patients with immune disorders should be treated primarily with amoxicillin + clavulanic acid or with cephalosporins of the second generation, because infestation with germs like haemophilus influenzae and klebsiella pneumoniae have to be considered. If the empirically chosen therapy should fail, the therapeutic strategy should not be changed blindly. Differential diagnosis and appropriate investigations are necessary (other germ, other disease, complications?). Problems in treating patients with pneumonia are illustrated by three case examples.

Adult↗
PubMed1995

LPS directly induces oxygen radical production in human monocytes via LPS binding protein and CD14.

In human monocytes, superoxide (O2-) generation accompanies phagocytosis and is important for bactericidal activity. It also contributes to tissue damage in inflammation. In the present study we investigated, whether lipopolysaccharide (LPS) directly stimulates monocyte O2- production with kinetics known for other LPS effects and, if so, by which mechanism. LPS caused a time- and dose-dependent O2- release in nonadherent purified monocytes. The effect appeared after 5 min, peaked at 30 min, and disappeared after 2 h. It was maximal with 10 ng/ml lipid A (+148 +/- 22%, P < .001), 1 ng/ml LPS Escherichia coli Re (+226 +/- 68%, P < .001), and 100 ng/ml LPS Salmonella abortus equi sm (+272 +/- 52%, P < .001), respectively. The effect was not observed in buffer, even when using 10 micrograms/ml LPS. It was dependent on the presence of heat-inactivated AB serum, with a maximal effect at > or = 0.5%. Serum could be replaced by LPS-binding protein (LBP). Polymyxin B and anti-LBP antiserum, respectively, blocked the LPS effect. LPS-induced O2- generation was also completely blocked by anti-CD14 antibodies (3C10 and 63D3) and by their corresponding F(ab')2 fragments. Monocytes treated with phosphoinositol-specific phospholipase C and monocytes from patients with paroxysmal nocturnal hemoglobinuria, lacking the phosphatidylinositol-anchored CD14, did not respond to LPS stimulation with O2- production. Similarly to LPS, E. coli caused stronger O2- production with heat-inactivated serum than without, and this effect was blocked by anti-CD14 antibodies. In conclusion, these data indicate that LPS directly stimulates O2- production in human monocytes via CD14 depending on LBP.

Acute-Phase Proteins↗
PubMed1995

Increased circulating soluble CD14 is associated with high mortality in gram-negative septic shock.

The soluble glycoprotein sCD14 binds lipopolysaccharide, a complex that activates endothelial cells and that may be crucial in gram-negative sepsis. Therefore, serum sCD14 was analyzed in 54 patients with gram-negative septic shock and in 26 healthy controls. sCD14 was tested by ELISA and Western blotting. Patients had higher sCD14 concentrations than controls (median, 3.23 vs. 2.48 micrograms/mL, P = .002). Increased levels were associated with high mortality (median, 4.2 micrograms/mL in nonsurvivors vs. 2.8 micrograms/mL in survivors, P = .001). sCD14 was found in two isoforms (49 and 55 kDa) in monocyte cultures. In sera only one of either form was detectable. Controls had the 49-kDa form, and patients had either the 49- or 55-kDa form, but patients with high levels of sCD14 had only the 55-kDa form. Twenty-one (53%) of 39 with the 55-kDa form and 8 (57%) of 14 with the 49-kDa form died. Thus, the level of sCD14 but not its biochemical form had a prognostic value in patients with gram-negative septic shock.

Adolescent↗
PubMed1995

In vivo verification of in vitro model of antibiotic treatment of device-related infection.

Device-related infections are difficult to treat with antibiotics alone. Standard susceptibility tests do not correlate with treatment success. Therefore, the utility of a pharmacokinetic in vitro model has been evaluated in comparison with the tissue-cage infection model in guinea pigs. The bactericidal activity of 28 treatment regimens has been studied by using three different test strains. In vitro efficacy was defined as reduction in the number of suspended or adherent bacteria, and in vivo efficacy was defined as reduction in the number of bacteria in tissue-cage fluid. Test results between the two models (in vivo and in vitro) correlated well, with correlation coefficients of 0.85 for in vivo efficacy versus in vitro efficacy against suspended bacteria and 0.72 for in vivo efficacy versus in vitro efficacy against adherent bacteria (P < 0.05) for Staphylococcus aureus, 0.96 and 0.82 (P < 0.05) for Staphylococcus epidermidis, and 0.89 and 0.97 for Escherichia coli, respectively. In contrast, standard susceptibility tests, ratios of MICs to trough or peak levels, ratios of the area under the curve to the MIC, or time above the MIC were not predictive for therapeutic outcome in either the in vitro or in vivo model. In both models, the bactericidal activity levels with combination regimens were significantly higher than those with single-drug regimens (P < 0.001). Furthermore, rifampin combinations with either vancomycin, teicoplanin, fleroxacin, or ciprofloxacin were significantly more bactericidal against adherent bacteria than netilmicin combinations with vancomycin or daptomycin (P < 0.01). Thus, in vivo verification of the pharmacokinetic in vitro model correlated well with the animal model. The in vitro model offers an alternative to ther animal model in experiments that screen and assess antibiotic regimens against device-related infections.

Animals↗
PubMed1995

[Role of antibiotics in the treatment of infected joint prosthesis].

Infection is a rare, but extremely severe, complication of prosthetic joint surgery. Until recently, antimicrobial agents were not generally used in the management of such infections. Antibiotics now have an important role, either combined with replacement surgery or even as the only treatment in selected cases. In earlier studies, high failure rates were reported with conservative therapy. These unsatisfactory results were probably due to a lack of collaboration between surgeons, infectious disease specialists and microbiologists. All patients with a long history of infection or with loosened implants should undergo joint replacement. Early or rapidly diagnosed hematogenous infection in patients with stable prostheses can be treated conservatively. In most cases, such a treatment is preceded by revision surgery, which is needed for microbiological diagnosis and for debridement. The choice of antibiotics depends on the microorganism involved and the results of susceptibility testing. The most important etiologic agents are Staphylococcus aureus and coagulase-negative staphylococci. Antimicrobial drugs used in device-related infections should act on surface-adherent and stationary-phase bacteria. In an animal model, rifampin combined with a quinolone has proved to have the highest cure rate against staphylococcal foreign-body infection. Rifampin is indeed highly efficacious on surface-adherent and stationary-phase bacteria. These experimental data were confirmed in clinical studies; cure rates of 60-80% were observed with rifampin combinations without joint replacement. Antimicrobial therapy should be continued over at least 3 months in hip implant infection and at least 6 months in knee implant infection. Before treatment is stopped, signs and symptoms of infection must have been absent with C-reactive protein normal for at least 1 month.

4-Quinolones↗
PubMed1994

[Pneumonia in clinical practice: diagnosis and therapy].

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.

Anti-Bacterial Agents↗
PubMed1992

[Role of antibiotics in surgically treated active endocarditis].

In a retrospective study of 30 patients in whom a valve was replaced during active endocarditis, the role of the concomitant antimicrobial therapy was analyzed. In 75% of the patients with less than 1 week of adequate treatment before surgery, but only in 13% (p less than 0.001) with at least 1 week of therapy, could the microorganism be cultivated from the excised valve. Patients with bacteria on the valve had a 4-fold increased risk for prosthetic valve endocarditis and 2.7-fold more frequent paravalvular leakage. Therefore, in the absence of severe cardiac failure, the valve replacement should not be performed before the second week of therapy. Patients in whom microorganisms can be cultivated from the valve need a complete postoperative course of antimicrobial therapy.

Adult↗
PubMed1992

Failure to control AIDS-related CMV-retinitis with intravenous ganciclovir.

Between January 1988 and May 1991 intravenous ganciclovir (GCV) treatment was administered to eight male AIDS-patients with unilateral cytomegalovirus (CMV)-retinitis. Despite of continuous therapy with at least the recommended dose of GCV, three patients developed slowly progressive CMV-retinitis in the fellow eye after 4 to 13 months. The progression could not be stopped by GCV and thus bilateral blindness resulted after 12 to 22 months. The number of CD4-lymphocytes in the blood was reduced in all patients, but particularly in patients with progressive disease. Treatment failure was partly related to the duration of CMV-retinitis and partly to the degree of immunodeficiency. Intravenous treatment with GCV alone can not stop the progression of CMV-retinitis in long-term survivors and in those with advanced immunodeficiency.

AIDS-Related Opportunistic Infections↗
PubMed1992

[Morphologic aspects of therapy-resistant cytomegalovirus retinitis].

Intravenous ganciclovir treatment was performed in eight male AIDS patients with primary unilateral CMV-retinitis. Three patients developed slowly progressive CMV-retinitis in the fellow eye despite adequate dose of ganciclovir. These different CMV-manifestations are shown in a sequence of fundus pictures. Three types of CMV-lesions were observed in connection with this study. Untreated central lesions showed the aspect of crumbled cheese and ketchup. Untreated lesions in the peripherie were yellowish-white, granular, "dry" and showed in most cases no haemorrhages. Lesions appearing during treatment showed initially "dry" white opaque subretinal areas, turning later on to the typical aspect of untreated lesions. The progression could not be stopped by highdose ganciclovir i.v. and thus bilateral blindness resulted after 12 to 22 months. The level of CD4-lymphocytes in the blood was diminished in all patients, but much more in patients with progressive disease.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Successful treatment of disseminated nocardiosis complicated by cerebral abscess with ceftriaxone and amikacin: case report.

We report the case of an 85-year-old female patient who suffered from disseminated Nocardia asteroides infection complicated by a cerebral abscess. Treatment with amikacin for 2 weeks and ceftriaxone for 6 weeks led to complete recovery, and there was no recurrence of disease over a follow-up period of 12 months after therapy. The use of ceftriaxone in combination with amikacin might significantly shorten the duration of treatment for patients with disseminated nocardiosis. This combination of antibiotics merits further investigation with use of a larger sample of patients.

Aged↗
PubMed1992

Antimicrobial treatment of orthopedic implant-related infections with rifampin combinations.

The purpose of this prospective clinical study is to evaluate the role of combination chemotherapy with rifampin in the treatment of orthopedic device-related infections in which the implant could not be removed. Eleven patients with orthopedic implant-related infections due to staphylococci or streptococci were treated with the implant in situ. Each antimicrobial regimen included rifampin in combination with a beta-lactam antibiotic or ciprofloxacin. The median duration of treatment with rifampin was 86 days (range, 15-336 days) with a median follow-up of greater than 24 months after cessation of therapy. Treatment was successful for 82% of patients. Failures were associated with documented inappropriate treatment. These preliminary clinical data are supported by data from in vitro studies and animal experiments. Combination therapy with rifampin, in particular rifampin and a quinolone, should be considered for patients with orthopedic implant-related infections if the implant cannot be removed.

Adult↗
PubMed1992

[Double incision for operation of carpal tunnel syndrome--14 years experience].

15 years ago I started to do the surgical release of carpal tunnel syndrome by the "double incision technique", avoiding the postoperative tenderness in the so called carpal barrier. The postoperative results of 293 operations prove the small morbidity, the short inability for work, the small loss of strength and the few postoperative complications. The danger of this very well tolerated method is that the extend of the ulnar artery, the motor branch and the palmar cutaneous branch of the median nerve may be abnormal and the mentioned structures may be harmed by the operation. A well trained surgeon will practice this technique with success, but it should not be applicated by beginners.

Adult↗
PubMed1992

[Localized bacterial skin infections and dermatologic manifestations of systemic infections].

Localized bacterial skin infections are frequent. In furunculosis, a local treatment is usually sufficient. In case of frequent recurrence a possible staphylococcus aureus colonization should be looked for and eliminated. Erysipela is treated by systemic antibiotics in order to avoid complications such as streptococcal gangrena or parainfectious glomerulonephritis. Anaerobic cellulitis and gas gangrena are postoperative or posttraumatic infections of the soft tissues which require a combined surgical and antibiotic treatment. Systemic infections may be recognized by characteristic skin lesions. These skin lesions are the consequence of bacterial emboli, vasculitis, intravascular coagulation or toxins, respectively. Examples for such manifestations are lesions in endocarditis, purpura fulminans, ekthyma gangrenosum, disseminated candidemia and toxic shock syndrome.

Anti-Bacterial Agents↗
PubMed1991

Glycosylation of alpha 1-acid glycoprotein in relation to duration of disease in acute and chronic infection and inflammation.

Microheterogeneity of acute phase proteins frequently differs in acute and chronic types of inflammation. However, it is unknown whether these changes depend on the duration of the inflammation in a given disease. We therefore investigated the microheterogeneity of alpha 1-acid glycoprotein (AGP) in sera from patients with acute and chronic bacterial infection in comparison to rheumatoid arthritis and ankylosing spondylitis. In acute bacterial infection Con A-reactivity of AGP was significantly elevated. By contrast, AGP in chronic bacterial infection showed the same glycosylation pattern as rheumatoid arthritis and ankylosing spondylitis being characterized by a decreased reactivity to Con A. Serial measurements in individual patients with bacterial infections showed a transition from the initially elevated to decreased reactivity to Con A as the disease became chronic.

Acute Disease↗
PubMed1991

[Nosocomial pneumonia in ventilated patientsø].

Nosocomial pneumonia is a complication in 20-65% of patients on mechanical ventilation. The tracheal tubes cannot avoid aspiration from the upper respiratory tract or the stomach. According to several (but not all) authors, gastric colonization with a high density of microorganisms is a major risk factor for the genesis of nosocomial pneumonia in ventilated patients. In most but not all intensive care units, gram negative microorganisms are the predominant etiologic agents of nosocomial pneumonia. In neurosurgical patients other microorganisms such as Staphylococcus aureus and Hemophilus influenzae play an important role. For rapid and correct diagnosis, new techniques such as bronchoalveolar lavage or the protected specimen brush have been developed. In prophylaxis, endotracheally administered antibiotics have not proved to be efficacious. In contrast, selective decontamination of the gut has a beneficial effect. However, long-term studies with this technique have still to prove that emergence of resistant microorganisms is not a major problem. Empirical treatment of pneumonia in ventilated patients should be guided by the results of surveillance cultures.

Bronchoalveolar Lavage Fluid↗
PubMed1991

Influence of the anti-inflammatory compound flosulide on granulocyte function.

Polymorphonuclear leukocytes (PMN) are involved in inflammatory reactions. It is thought that oxygen-derived free radicals released from activated PMN may participate in tissue damage during inflammation. We have shown that flosulide (6-(2,4-difluorophenoxy)-5-methylsulfonylamino-1-indanone ), a novel highly potent anti-inflammatory compound, inhibits superoxide production induced by N-formyl-Met-Leu-Phe (FMLP), C5a and PMA without impairing bacterial killing or chemotaxis. Flosulide (10(-5)-10(-7) M) was more potent in inhibiting the FMLP-induced respiratory burst of PMN than the structurally related compound nimesulide. FMLP-induced superoxide generation was also inhibited by two human flosulide metabolites. A good correlation between this in vitro effect and in vivo anti-inflammatory potency in rat adjuvant arthritis was found for flosulide and its metabolites. Indomethacin, piroxicam and ibuprofen did not inhibit the respiratory burst at 10(-5) M. FMLP receptor number was decreased by 36% in the presence of 10(-5) M flosulide. However, a 250-fold molar excess of flosulide could not displace labeled FMLP from the receptor. Inhibition of degranulation of primary and secondary granules was a common effect of all anti-inflammatory compounds tested. At a concentration of 10(-5) M, all drugs inhibited degranulation to about the same degree, independent of their in vivo anti-inflammatory activity.

Anti-Inflammatory Agents, Non-Steroidal↗