[Antibiotic prophylaxis in the ENT specialty].
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Antibiotic Prophylaxis↗
Biomedical subjects
W Zimmerli
Publications and source records attributed to W Zimmerli.
[Routine bacteriological screening of intensive care patients: contra].
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Bacterial Infections↗
[Clinical aspects and prognosis of candidemia, a 6-year retrospective study].
In recent decades an increase in the incidence of fungal infection has been reported. We retrospectively analyzed 41 patients with candidemia seen at Basel University Hospital over a six-year period. 1.2-6.7 candidemias per 10000 admissions were observed. In contrast to other studies, there was no increase during the study period. Out of 41 patients, 19 were hospitalized in ICUs. All patients had risk factors such as intravascular catheters (92.7%), antibiotic therapy (88%), immunosuppressive therapy (31%), indwelling Foley catheters (54%) and previous surgery (63%). The most frequent symptoms were fever with rigor, tachycardia and hypotension. The isolates were Candida albicans (n = 28), Torulopsis glabrata (n = 5), C. krusei (n = 3), C. parapsilosis (n = 2), C. guilliermondii, C. kefyr and C. lusitaniae (n = 1 each). In 22 patients, candida colonization had been documented and 5 patients had superficial mucocutaneous candidiasis before candidemia. The initial foci were the gastrointestinal tract (n = 13), an intravascular catheter (n = 8), the urinary tract (n = 5), the respiratory tract, or intravenous drug use (n = 3 each). Out of 32 patients who were treated either with amphotericin B or fluconazole, 13 died. 5 of the untreated patients died, in 3 instances before microbiological diagnosis. The mortality was similar for treatment with amphotericin B and with fluconazole (50% vs. 33%) (p = 0.3).
Adult↗
[Current antibiotics for clinical practice].
During the last decade a large number of novel antimicrobial agents has been developed and marketed. For the practitioner, three groups of oral substances are important, namely cephalosporins, fluoroquinolones and macrolides. The new oral cephalosporins have an improved beta-lactamase stability. Their serum half-life of 2 to 4 h is more than twice as long as that of older substances; however, their oral bioavailability is lower than that of older cephalosporins. They have an excellent activity against gram-negative bacteria, but no or only little activity against staphylococci. They are especially indicated in ENT and UT infections. The fluoroquinolones have an excellent bioavailability and are therefore ideal as oral drugs. Their microbiological spectrum is best against gram negative microorganisms. Pneumococci are not very susceptible to quinolones, with the exception of sparfloxacin. There is an increasing emergency of resistance due to a broad use of these substances. Main indications are UT infections, febrile enterocolitis, and bone and joint infections. New macrolides give less side effects and improved pharmacokinetics. Clarithromycin and azithromycin have high tissue concentrations. The main indications are upper respiratory tract infections and the community-acquired pneumonia. Newer indications for clarithromycin and azithromycin are non-tuberculous mycobacteriosis and in special cases toxoplasmosis in AIDS patients. Despite the different advantages of the new oral antibiotics, older substances such as aminopenicillins and cotrimoxazole are still important agents in the outpatient treatment.
Administration, Oral↗
Function of soluble CD14 in serum from patients with septic shock.
Soluble CD14 (sCD14) mediates lipopolysaccharide (LPS) activation of epithelial cells in vitro and may thereby be harmful in sepsis. sCD14 function was analyzed in sera from 62 patients with septic shock and compared with data from appropriate controls. sCD14 function was measured as sCD14-dependent LPS-induced interleukin (IL)-8 release in the SW620 epithelial cell line. In these cells, IL-8 production correlated with LPS concentration and the amount of sCD14. The effect of natural recombinant sCD14 was maximal at 100 ng/mL and blocked by anti-CD14 antibodies. Patient and control sera (0.5% final concentration) promoted induction of IL-8 by 100 ng/mL LPS in SW620 cells. In sepsis patients (highest serum sCD14), values were significantly higher than in the other groups. The LPS-induced IL-8 response was blocked by anti-CD14 and correlated with the serum CD14 level in sepsis patients. Thus, sCD14 could play a pathogenic role in sepsis.
Adult↗
Incidence and spectrum of severe medical complications among hospitalized HIV-seronegative and HIV-seropositive narcotic drug users.
OBJECTIVE: To examine differences in the incidence and spectrum of diseases, as well as duration of inpatient stay, between HIV-seronegative and HIV-seropositive narcotic drug, users (NDU). DESIGN: Retrospective analysis of 9 years of experience. Data collection by chart review using preset criteria for diagnoses. Estimation of hospital admission densities by assuming a dynamic but stable population of 2000 NDU (with a mean HIV-seroprevalence of 25%) throughout the study period. PATIENTS: Comprising 314 HIV-seronegative NDU. 217 HIV-seropositive NDU, and 10 NDU with admissions registered in either group (from a total of 1011 admissions). RESULTS: The overall admission incidence density was 35 and 120 per 1000 person-years among HIV-seronegative NDU and HIV-seropositive NDU, respectively [risk ratio (RR) 3.5, 95% confidence interval (CI) 3.2-3.7]. Compared with seronegative NDU, HIV-seropositive NDU were more frequently admitted for various non-opportunistic infections (RR 7.2, 95% CI 6.1-8.4), including pneumonia (RR 10.9, 95% CI 7.6-16.6), tuberculosis (RR 30.0, 95% CI 3.6-233.8), soft-tissue infections (RR 3.5, 95% CI 1.7-7.2), osteoarticular infections (RR 6.0, 95% CI 1.5-23.9), endocarditis (RR 5.3, 95% CI 1.5-17.9), and various other infections (RR 5.8, 95% CI 3.2-10.5). HIV-seropositive NDU were also more frequently admitted for non-infectious medical complications (RR 2.3, 95% CI 1.8-3.0). Seronegative NDU had a shorter median inpatient stay (2 versus 9 days, P < 0.00001). HIV infection accounted for an estimated excess burden of at least 2700 inpatient care days in 9 years among the 500 local HIV-seropositive NDU. CONCLUSIONS: Among NDU, HIV infection adds considerable excess burden in terms of severe complications needing inpatient care.
AIDS-Related Opportunistic Infections↗
Pharmacokinetics of cefetamet in plasma and skin blister fluid.
Cefetamet pivoxil is an oral cephalosporin with enhanced affinity for the target penicillin-binding proteins 1 and 3 and an increased stability to beta-lactamases compared with older cephalosporins, such as cefalexin or cefaclor. The pharmacokinetics of cefetamet pivoxil was determined after the seventh and final dose of 500 mg of cefetamet pivoxil in eight healthy volunteers. Concentrations in plasma and cantharidin-induced skin blister fluid were determined by a high-performance liquid chromatography method. In addition, protein binding was assessed. Cmax was 4.8 +/- 1.7 micrograms/ml in skin blister fluid and 5.1 +/- 2.1 micrograms/ml in plasma. Tmax was delayed in skin blister fluid compared with plasma (3.9 +/- 1 versus 2.8 +/- 0.8 h; P < 0.001), and t1/2 was longer in skin blister fluid than in plasma (3.1 +/- 0.5 versus 2.3 +/- 0.3; P < 0.005). The mean percent penetration into cantharide blister fluid was 129% +/- 24% when measured as total drug and 149% +/- 28% when measured as free drug (P < 0.001). These data suggest that cefetamet has an excellent penetration into inflammatory interstitial fluid.
Adult↗
Human monocyte CD14 is upregulated by lipopolysaccharide.
Membrane CD14 is involved in lipopolysaccharide (LPS)-induced monocyte activation; it binds LPS, and antibodies against CD14 block the effects of low-dose LPS. It is unknown how LPS regulates its own receptor CD14 in vitro. Therefore, we investigated the effects of LPS on CD14 mRNA and membrane and soluble CD14 (mCD14 and sCD14, respectively) in human monocytes and macrophages. No changes were observed during the first 3 h of LPS stimulation. After 6 to 15 h, LPS weakly reduced CD14 mRNA and mCD14 and transiently enhanced sCD14 release. A 2-day incubation with LPS caused increases in the levels of CD14 mRNA (2-fold), mCD14 (2-fold), sCD14 (1.5-fold), and LPS-fluorescein isothiocyanate binding (1.5-fold); a 5-h incubation with LPS was sufficient to induce the late effects on mCD14 and sCD14. The maximal effect on mCD14 and sCD14 was reached with > or = 1 ng of LPS per ml; the proportional distribution of the two sCD14 isoforms was not modified by LPS. Besides rough and smooth LPS, lipid A, heat-killed Escherichia coli, lipoteichoic acid, and Staphylococcus aureus cell wall extract (10 micrograms/ml) caused similar increases of mCD14. The LPS effect was blocked by polymyxin B but not by anti-tumor necrosis factor alpha, anti-interleukin-6, anti-gamma interferon, and anti-LPS-binding protein. LPS-induced tumor necrosis factor alpha production was abolished after a second 4-h challenge. In contrast, the LPS-induced increases CD14 mRNA, mCD14, and sCD14 were stronger and appeared earlier after a second LPS challenge. In conclusion, CD14 is transcriptionally upregulated by LPS and other bacterial cell wall constituents.
Adaptation, Physiological↗
Oral manifestation of disseminated Mycobacterium kansasii infection in a patient with AIDS.
We report the case of a 46-year-old male patient with advanced HIV infection who developed an oral ulcer caused by Mycobacterium kansasii. It is the first description of an aphthous-like ulcer caused by this nontuberculous mycobacterium. As the AIDS epidemy is still growing, more cases might be observed and the current spectrum of differential diagnosis should be expanded.
AIDS-Related Opportunistic Infections↗
Comparison of chemotaxis and superoxide generation of indium-111-oxine- and technetium-99m-HMPAO-labelled granulocytes.
The diagnostic value of imaging infection with labelled granulocytes depends on the functional integrity of the reinfused cells. The aim of this study was to compare the functional integrity of granulocytes labelled with indium-111-oxine and technetium-99m-hexamethylpropyleneamineoxime (HMPAO), respectively, in comparison to unlabelled control granulocytes. Granulocytes were purified from healthy subjects and labelled with either 111In-oxine or 99mTc-HMPAO. Chemotaxis and superoxide production induced by formyl-peptide and phorbol-myristate-acetate were measured. Granulocytes labelled with 111In-oxine had significantly (p < 0.001) decreased chemotaxis. Superoxide production of granulocytes stimulated with phorbol-myristate-acetate showed no significant difference between control cells and those labelled using either technique. In contrast, formyl-peptide-stimulated superoxide production was increased in granulocytes labelled with 111In-oxine (p < 0.01) and in cells labelled with 99mTc-HMPAO (p < 0.03), indicating a priming compared to unlabelled cells. In conclusion, 99mTc-HMPAO-labelled granulocytes show biological properties superior to 111In-oxine-labelled cells, and should therefore be favoured for use in leucocyte labelling and infectious disease imaging.
Chemotaxis, Leukocyte↗
Invasive candidiasis complicating spontaneous esophageal perforation (Boerhaave syndrome).
Spontaneous esophageal perforation is a rare condition that frequently results in infectious complications. Empirical broad-spectrum antibacterial therapy is therefore part of the standard management. We describe two patients suffering from spontaneous esophageal perforation who developed invasive candidiasis with hematogenous dissemination. One patient died of multiple organ failure due to Candida sepsis. Preexistent Candida colonization, incomplete mediastinal drainage, broad-spectrum antibacterial therapy, and prolonged intensive care therapy place patients with esophageal perforation at high risk for secondary fungal infection. Intense microbiological searching is mandatory, but the distinction between colonization and infection may be impossible. Empirical antifungal treatment with imidazole derivatives, particularly in patients with potential risk factors, should be considered.
Candidiasis↗
[Diagnosis of infective spondylitis. Value of bone marrow scintigraphy with 99mTC monoclonal granulocyte antibodies in combination with 99mTc-DPD bone scintigraphy].
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Adult↗
[Advantages of the laser in laparoscopic cholecystectomy].
Use of the holmium and Nd:YAG laser is clearly advantageous in laparoscopic cholecystectomy, i.e., less perforation of the gallbladder when compared to the use of the hook electrode, shorter intervention time and less postoperative pain. Laser-operated patients can therefore be discharged 1.5 days earlier than those patients in whom cholecystectomy had been performed using electrocautery.
Cholecystectomy, Laparoscopic↗
[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↗
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↗
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↗
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↗
[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↗