Andreas Gerber - Academia.edu (original) (raw)

Papers by Andreas Gerber

Journal of Antimicrobial Chemotherapy, 1993

The impact of pre-treatment intervals on the antipseudomonal efficacy of gentamicin, ticarcillin ... more 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 0-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 /Mactam 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.

The Journal of Infectious Diseases, Apr 1, 1982

Comparative studies were performed in vitro to test the advocated superiority of infusion over in... more Comparative studies were performed in vitro to test the advocated superiority of infusion over intermittent injection of aminoglycosides. Pseudomonas aeruginosa was exposed to constant and to continuously decreasing (simulating in vivo kinetics) concentrations of gentamicin. In comparing the effect with similar area-under-the-concentrationvs.-time curves, a substantial difference in killing and regrowth could not be demonstrated. Regrowth occurred only when the gentamicin concentration had continuously decreased below one fourth of the minimal inhibitory concentration for >2 hr. Exposure of P. aeruginosa to gentamicin for 30 min was followed by persistent suppression

Forum Médical Suisse ‒ Swiss Medical Forum, 2003

Journal of Infectious Diseases, 1983

The influence of dosing intervals on the activity of gentamicin and ticarcillin against Pseudomon... more The influence of dosing intervals on the activity of gentamicin and ticarcillin against Pseudomonas aeruginosa was studied in vivo. Granulocytopenic mice infected with P. aeruginosa in the thigh muscle were treated with l-hr or 3-hr injections of gentamicin, ticarcillin, or gentamicin-ticarcillin. Plasma pharmacokinetics of the drugs were correlated with antibacterial activity. Gentamicin injected every 1 hr tended to be less active than gentamicin injected at longer intervals. In contrast, ticarcillin given every 1 hr was significantly more efficacious than equivalent total doses injected every 3 hr. The dosing schedule of gentamicin-ticarcillin was again important for ticarcillin but did not appreciably affect the antibacterial activity of gentamicin. Thus, antimicrobial chemotherapy of P. aeruginosa infections in the granulocytopenic host might be improved by administering ticarcillin rather than gentamicin as a constant infusion.

Journal of Antimicrobial Chemotherapy, 1985

Time-kill curves of Pseudomonas aeruginosa exposed to gentamicin or ticarcilhn in vitro were corr... more Time-kill curves of Pseudomonas aeruginosa exposed to gentamicin or ticarcilhn in vitro were correlated with time-kill curves obtained with various dosage schedules of the same study drugs in granulocytopenic mice. An instantaneous, fast and drugdependent killing pattern was found in vitro with gentamicin. This pattern corresponded to bacterial killing m vivo which was clearly dependent on peak drug levels. In contrast, slow bacterial killing with little relationship to concentration was found in vitro with ticarcilhn and proved to correlate with an antibacterial effect in vivo seen at trough levels. We conclude that in-vitro time-kill curves of antimicrobial agents may be predictive for optimizing dosage regimens in vivo.

Journal of Antimicrobial Chemotherapy, 1987

Recent experimental work has shown that a so-called PAE (postantibiotic effect, i.e. persistent s... more 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 aweus. Streptococcus pyogenes, Sir. 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/1 of roxithromycin for 6 h.

Antimicrobial Agents and Chemotherapy, 1991

The relationship between the pharmacokinetics and bactericidal activity of imipenem against Pseud... more 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 inijection 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.

The Journal of Infectious Diseases, 1986

An effort was made to elucidate the limits of drug-activity tests in small animals. Human plasma ... more 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 fl-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 singlebolus injection that tended to be more active. Thus, when tested in conventional smallanimal models, aminoglycoside activity may be overestimated, whereas fl-lactam activity may be underestimated in respect to humans. These differences found in vivo most probably reflect the different pharmacodynamics between aminoglycosides and f3-lactam drugs (time-kill curves, dose-response curves, and postantibiotic effect) similar to those previously observed in vitro.

Antimicrobial Agents and Chemotherapy, 1983

The pharmacokinetics of piperacillin were examined after single intravenous doses to three groups... more The pharmacokinetics of piperacillin were examined after single intravenous doses to three groups of male patients with creatinine clearances of greater than or equal to 60 (group I), greater than or equal to 20 but less than 60 (group II), and less than 20 (group III) ml/min per 1.73 m2. Each of 32 patients received either 1 or 4 g of piperacillin as a bolus injection. Three patients received both doses. After a rapid 0.5- to 1-h distribution phase, antibiotic levels in serum declined monoexponentially. After the 1-g dose, mean peak piperacillin levels in serum were 60, 103, and 67 micrograms/ml and the beta phase elimination half-lives were 1.0, 1.6, and 3.9 h in groups I, II, and III, respectively. After the 4-g dose, the respective mean peak piperacillin levels in serum were 329, 232, and 262 micrograms/ml and beta phase half-lives were 1.4, 2.3, and 2.6 h in the three groups. There was no clear evidence of significant dose-dependent effects on any pharmacokinetic parameters in ...

The journal of nutrition, health & aging, 2004

Protecting the interests of a chronic severely brain-damaged patient is difficult, and the decisi... more Protecting the interests of a chronic severely brain-damaged patient is difficult, and the decision processes involved are complex. Ideally, the patient will have made his full wishes known in advance. If this is not the case, the presumed wishes of the patient must be established and taken into consideration. A further difficulty is the uncertainty of the prognosis. Patients with brain damage due to trauma are often expected to recover, even after a long period of unconsciousness; however, in those with severe brain damage due to illness the prognosis is significantly poorer, although even here it is not possible to be definitive.

Forum Médical Suisse ‒ Swiss Medical Forum

Swiss Medical Forum ‒ Schweizerisches Medizin-Forum

Hinter dem Begriff «Harnwegsinfektion» (HWI) versteckt sich ein grosses Spektrum von Infektionen ... more Hinter dem Begriff «Harnwegsinfektion» (HWI) versteckt sich ein grosses Spektrum von Infektionen unterschiedlicher Atiologie, Pathogenese, Diagnostik und Therapie. Das Spektrum reicht von der asymptomatischen, nicht therapiebedurftigen Bakteriurie einer adulten, nicht schwangeren Frau bis zur komplizierten, lebensbedrohlichen Urosepis beim immundeprimierten Mann mit Prostatitis und liegendem Blasenkatheter. Wegen dieser Heterogenitat der Harnwegsinfektionen spricht man am besten von HWI-Syndromen. Die Ubergange zwischen den verschiedenen HWI-Syndromen sind z.T. fliessend. Trotzdem sollen diese einzeln besprochen werden. Der vorliegende Artikel konzentriert sich auf die Labordiagnostik der HWI ganz allgemein sowie auf die Atiologie, Pathogenese und die Therapie der unkomplizierten HWI und der Pyelonephritis der Frau. Ein an dieser Stelle nachfolgender Artikel fokussiert auf die Harnwegsinfektionen des Mannes und auf die komplizierten, schwierig behandelbaren HWI-Syndrome. Nicht behandelt werden an dieser Stelle Harnwegsinfektionen bei Kindern. Diese haben ihre eigene Pathogenese und Klinik und damit ihre eigene Problematik betreffend Diagnostik, Therapie und Prophylaxe. Die hier zu besprechenden einfachen HWI definieren wir als HWI, welche unter begunstigenden Ko-Faktoren, jedoch ohne Vorliegen von Fremdkorpern meist spontan auftreten und auf die untersten Harnwegsabschnitte (Urethra, Blase) beschrankt bleiben [1] (Tab. 1). Den einfachen HWI ist gemeinsam, dass sie unter einer einfachen antibiotischen Kurztherapie (oder auch spontan) abheilen. Grundsatzlich ist jeder HWI, der unter/nach einer Kurztherapie nicht abheilt, suspekt, ein komplizierter HWI zu sein.

Therapeutische Umschau

The assessment of fever is complex. It must not only focus on the patient in question. Rather, as... more 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°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 ...