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Biomedical subjects

A U Gerber

Publications and source records attributed to A U Gerber.

At least 19 recordsLinked to original sources
PubMed2006

[Clinical thermometry--theory and critical approach].

The assessment of fever is complex. It must not only focus on the patient in question. Rather, as a first factor to be considered, clinical thermometry has its technical and methodological problems. Every method has its own pitfalls. Second, any assessed body temperature reflects a "local" body temperature which, again, is affected by many factors. In addition, physiological set points of normal body temperature vary among individuals, and, even in a given individual, body temperature has its physiological variations. In all, intra- and interindividual variabilities in measured "normal" body temperature are large (< 2 degrees C) which makes it difficult to define normality. No question, all the factors mentioned are equally involved when body temperature is assessed in the febrile patient. Results (particularly those of tympanic measurements) may be deceptive and must be interpreted with scrutiny in the broad context of the patient assessment. In adults, fever should be measured by the sublingual method, in the non-cooperating patient, in the newborn and in toddlers rectally.

Adult↗
PubMed2002

[Microbial resistance to antibiotics from the clinical viewpoint. Paradoxical therapy failures and the significance of pharmacokinetic-pharmacodynamic interactions in vivo].

Antimicrobial efficacy in vivo is not exclusively defined by the activity of an antibiotic as determined in the in vitro susceptibility test where constant inocula of log-phase bacteria are exposed to a steady concentration of drug for short periods of time in a well defined biochemical environment tailored to optimize antimicrobial activity. In vivo, many additional factors come into play which may be decisive for the clinical result of antimicrobial therapy. Clinically, high numbers of bacteria in various states of growth and metabolic activity are to be eliminated in an environment which may be unfavorable for antimicrobial activity. Low pH, low pO2, the presence of proteins, cell debris and biofilms, are all known to interfere with antimicrobial activity in vivo. Moreover, drug concentrations in vivo are fluctuating and vary greatly depending on a variety of pharmacokinetic factors. Finally, clinical treatment usually lasts for days. The impact of the pharmacokinetic profile of an antibiotic on its in vivo activity may be decisive. It is dependent on both, the type of drug in question and its target organisms. The time of supra-MIC concentrations appears to be the main parameter for the activity of macrolides, clindamycin, linezolide and betalactam antibiotics, particularly against gram-negative organisms. In contrast, peak concentrations and the AUC/MIC relationship are key parameters for the activity of aminoglycosides and fluoroquinolones. Regarding upcoming resistant bacterial strains, an as yet ill-defined mutation-prevention concentration has recently been discussed. Thus, in addition to the aim of eliminating target bacteria at the site of infection, in vivo concentrations of antibiotics may be important for both, the suppression of antimicrobial resistance and its epidemic spread. We are looking forward to prospective clinical trials to better understand the clinical relevance of the discussed phenomena.

Anti-Bacterial Agents↗
PubMed1997

[A young man with sore throat and infection].

Postanginal septicemia (Lemierre's syndrome) is an infection with anaerobes that ensues from certain oropharyngeal infections: septic thrombophlebitis of the internal jugular vein leads to abscess formation in the lungs and possibly in other organs. Based upon a recently observed typical case the syndrome is presented and its possible importance for empirical therapy of tonsillopharyngitis and septicemias involving unknown organisms is briefly discussed.

Adolescent↗
PubMed1995

[Sources of error in the pre-analytical phase of blood gas analysis].

Analysis of blood gases and blood pH yield important information in many situations of clinical emergencies. We report on a patient in whom pre-analytic errors in blood gas and blood pH measurements resulted in unnecessary further investigations. We therefore studied various pre-analytic sources of error in blood pH and blood gas analysis. Delay in sample processing for more than one hour resulted in an increase of pO2 and pCO2 and a decrease of pH. Excess sodium heparin solution as an anticoagulant (> or = 10% of total volume) led to a significant decrease of pH and pCO2 and to an increase of pO2. Air bubbles (10% of total volume) left in the syringe for 10 min significantly increased pO2. For accurate estimations of pO2, pCO2 and pH, it is necessary to keep the heparin solution below 10% of total volume, to expel all air bubbles from the syringe and to process the blood sample within one hour. Instructions to medical staff on handling blood samples for blood gas analysis should include these possible sources of errors.

Aged↗
PubMed1993

The impact of the pre-treatment interval on antimicrobial efficacy in a biological model.

The impact of pre-treatment intervals on the antipseudomonal efficacy of gentamicin, ticarcillin and ceftazidime was studied in an experimental thigh infection model in normal and granulocytopenic mice. Human-equivalent doses were used for simulating human pharmacokinetic profiles of the two study beta-lactam drugs. A lethal inoculum of a virulent strain of Pseudomonas aeruginosa was injected into the thigh muscle. Treatment was started at various post-infection intervals. Antimicrobial efficacy was assessed by determinations of surviving organisms at the site of infection, and plasma drug concentrations were determined in the same mice. The age of infection had a substantial impact on antipseudomonal efficacy of the three study drugs even though high, brief supra-MIC concentrations of gentamicin and persistent supra-MIC concentrations of the beta-lactam drugs were obtained. A pre-treatment interval of six or more hours abolished the bactericidal effect of all three study drugs despite accumulation of the drugs to multiple-MBC plasma concentrations. We believe that the impact of pre-treatment intervals on antimicrobial efficacy is of paramount importance for the interpretation of antimicrobial activity studies in experimental models of infection, although the mechanisms remain to be elucidated.

Agranulocytosis↗
PubMed1992

[Chronic bronchitis: when are antibiotics indicated?].

The role of bacterial infections in chronic obstructive pulmonary diseases is still poorly understood, and so is the importance of antimicrobial chemotherapy. Based on the present knowledge from clinical studies, it is suggested that antibiotic treatment should be initiated for seven to ten days in patients suffering from an 'Anthonisen type-1 exacerbation', i.e. clinical deterioration with a significant increase in sputum production and sputum purulence, but not in others. The best tolerated, least toxic and least expensive oral antibiotic with adequate activity against pneumococci and H. influenzae is probably most appropriate. These prerequisites are still best fit by aminopenicillins and cotrimoxazol.

Anti-Bacterial Agents↗
PubMed1991

[Therapy with aminoglycoside antibiotics: once daily (q.d.)?].

Theoretical and experimental arguments favor administration of aminoglycosides once daily (q.d.). Results of clinical studies with a limited number of patients support these arguments. However, some practical and clinical questions remain unanswered. Therefore, q.d. infusion of aminoglycosides must still be considered experimental and must remain in the hands of infectious disease specialists until the results of ongoing clinical studies yield the ultimate proof that this novel dosing schedule is as efficacious and no more toxic than the conventional dosing regimens.

Aminoglycosides↗
PubMed1991

[Continuous quinidine infusion and blood exchange transfusion in severe tropical malaria: a case report].

We report on a serious case of malaria due to Plasmodium falciparum. Although the 46-year-old Swiss female had strictly followed the recommended prophylaxis with proguanil and chloroquine she was infected during a stay in Namibia which had lasted several month. The patient had poor prognostic signs such as encephalopathy (cerebral malaria), a parasitemia of 34% but only moderate renal impairment. Instead of the classical treatment with quinine, the patient was treated with a constant infusion of quinidine over 3 days which was combined with an exchange transfusion of approximately 2 liters on the first day of treatment. All clinical signs of the infection improved within less than 2 days as did the parasitemia. The patient was discharged after a hospital stay of 11 days. Quinidine as opposed to quinine may be more readily available, less toxic and more efficacious. Treatment with quinidine must carefully be monitored. Exchange blood transfusions may be an important additional therapeutic modality in severe plasmodium falciparum malaria.

Animals↗
PubMed1991

Integration of pharmacokinetics and pharmacodynamics of imipenem in a human-adapted mouse model.

The relationship between the pharmacokinetics and bactericidal activity of imipenem against Pseudomonas aeruginosa and Escherichia coli was investigated in a neutropenic mouse thigh infection model. To circumvent the problem of short elimination time in small animals, imipenem was administered in fractionized, decreasing doses such that the pharmacokinetic profiles as observed in humans after intravenous and intramuscular injections were approximated in mice. The human-simulated kinetic profile corresponding to an intramuscular injection of 500 mg at 12-h intervals proved to be as effective as the human-simulated profile of the same dose injected intravenously every 6 h. In contrast, the human-simulated profile corresponding to only one intravenous injection every 12 h resulted in bacterial breakthrough growth between 8 and 12 h after the onset of treatment. The results of our investigations confirm the hypothesis that the bactericidal effect of imipenem against P. aeruginosa and E. coli in vivo depends mainly on the time during which drug levels remain above the MIC rather than on the plasma peak/MIC ratio.

Animals↗
PubMed1990

Impact of the antibiotic dosage schedule on efficacy in experimental soft tissue infections.

Soft tissue infection models have been used to study both the postantibiotic effect (PAE) and the effect of dosage intervals on antimicrobial efficacy. In vitro findings were mostly confirmed. For drug-organism combinations which showed a predominantly time-dependent killing pattern and absence of a PAE (beta-lactams vs Gram-negative organisms), frequent drug dosing was most efficacious. In contrast, a fast, predominantly concentration-dependent bactericidal effect followed by a PAE in vitro (e.g. aminoglycosides vs Gram-negative bacteria) correlated (though inconsistently) with superiority of bolus dosing over more continuous drug administration in vivo. Thus, the ratio of peak serum concentrations to MICs of target pathogens is possibly a valid predictor of efficacy for the aminoglycosides but not so for the activity of beta-lactam antibiotics where the duration of coverage at supra-MIC levels was clearly more important than the magnitude by which initial peaks exceeded the MIC of the target organism. It is not clear to what extent the results obtained in experimental soft tissue infections may hold true in man. Thus far, only a limited number of drug-organism combinations have been studied in well defined experimental settings using mostly small, granulocytopenic animals which differ pharmacokinetically from man. In addition, results are probably affected by the density of bacteria, their growth rate and metabolic activity, but also by the extent of inflammation at the site of infection.

Animals↗
PubMed1990

Simulation of human pharmacokinetic profiles in mice, and impact on antimicrobial efficacy of netilmicin, ticarcillin and ceftazidime in the peritonitis-septicemia model.

Pharmacokinetic profiles in small animals substantially differ from those observed in man. We hence devised a man adapted animal model to critically assess the impact of such differences on antimicrobial efficacy. We approximated in mice the human pharmacokinetic profiles of netilmicin, ticarcillin and ceftazidime. The CD50 (curative dose for 50% of lethally intra-peritoneally infected animals) against Pseudomonas aeruginosa was comparatively determined for murine versus man-adapted pharmacokinetic profiles. With netilmicin the man-adapted profile was significantly less efficacious than the murine profile. In contrast, a significant superiority of the man-adapted profile was found with the beta-lactam drugs. We conclude that determinations of antimicrobial activity in small animals may yield misleading results in respect to man. Depending on the drug in question, murine pharmacokinetics may lead to overestimation or underestimation of antimicrobial activity. Our findings are of particular importance for the interpretation of studies in small animals comparing different antimicrobial compounds or different dosage regimens.

Animals↗
PubMed1989

Once-daily versus thrice-daily administration of netilmicin in combination therapy of Pseudomonas aeruginosa infection in a man-adapted neutropenic animal model.

A granulocytopenic mouse model was used to elucidate the impact of dose spacing on the activity of netilmicin against Pseudomonas aeruginosa. A thigh infection was produced and then treated with netilmicin combined with azlocillin. Netilmicin was injected subcutaneously at decreasing doses every 20 min to result in plasma-concentration-time curves similar to those observed in patients on intravenous netilmicin treatment. A once-daily regimen was simulated and compared to a simulated conventional schedule of every 8 h. Identical total amounts of drug were used in both groups of comparatively treated mice. Therapeutic efficacy was quantitated by repeated determinations of surviving organisms in thigh homogenates. Combination therapy was significantly more effective than azlocillin treatment alone. In combination regimens the simulated once-daily netilmicin schedule killed the target organisms faster than the simulated thrice-daily regimen and was significantly more efficacious by 24 and 32 h in two out of three strains of Pseudomonas aeruginosa tested. It is concluded that the results of combination therapy of severe Pseudomonas aeruginosa infections in the immunocompromised host might be improved by choosing an aminoglycoside dosage interval of 24 h instead of the conventional 8 h.

Animals↗
PubMed1988

[Pericarditis following meningococcal septicemia without meningitis].

We report on a 68-year-old female patient with subacute septicemia caused by Neisseria meningitidis type C. While under adequate antibiotic therapy on the 10th day after onset of the initial symptoms, she developed pericarditis with impending cardiac tamponade. The administration of high-dose steroid therapy brought about an immediate improvement in the clinical picture.

Aged↗
PubMed1987

Postantibiotic effect of roxithromycin, erythromycin, and clindamycin against selected gram-positive bacteria and Haemophilus influenzae.

Recent experimental work has shown that a so-called PAE (postantibiotic effect, i.e. persistent suppression of regrowth after short exposure of bacteria to the study drug in vitro) is a feature of most current antibiotics. However, marked quantitative differences were found between different types of antibiotics and also between Gram-positive and Gram-negative organisms studied. A PAE has not yet been demonstrated for roxithromycin, a new macrolide antibiotic. Therefore, we compared the PAE of roxithromycin, erythromycin, and clindamycin against laboratory strains and clinical isolates of Staphylococcus aureus, Streptococcus pyogenes, Str. pneumoniae, and Haemophilus influenzae in vitro. Identical multiples of the MIC and identical exposure times resulted in similar PAEs for the three study drugs tested. Good correlations could be found between the area under the in-vitro concentration-vs-time curve (AUC) and PAEs. The longest PAE of 9.6 h was observed after exposure of Str. pneumoniae to 1.9 mg/l of roxithromycin for 6 h.

Clindamycin↗
PubMed1986

Antibiotic therapy of infections due to Pseudomonas aeruginosa in normal and granulocytopenic mice: comparison of murine and human pharmacokinetics.

An effort was made to elucidate the limits of drug-activity tests in small animals. Human plasma kinetics of gentamicin, netilmicin, ticarcillin, ceftazidime, and ceftriaxone were approximated in normal and in granulocytopenic mice infected with various strains of Pseudomonas aeruginosa in the thigh muscle or intraperitoneally. The effect of such dosing on bacterial time-kill curves and on survival was compared with the effect of identical amounts of drug given as a single-bolus injection. With beta-lactams, a highly significant superiority of fractionated dosing (simulated human kinetics) over bolus injections (murine plasma kinetics) was demonstrated, whereas with aminoglycosides it was a single-bolus injection that tended to be more active. Thus, when tested in conventional small-animal models, aminoglycoside activity may be overestimated, whereas beta-lactam activity may be underestimated in respect to humans. These differences found in vivo most probably reflect the different pharmacodynamics between aminoglycosides and beta-lactam drugs (time-kill curves, dose-response curves, and postantibiotic effect) similar to those previously observed in vitro.

Agranulocytosis↗