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Biomedical subjects

A U Gerber

Publications and source records attributed to A U Gerber.

At least 37 records · Page 2Linked to original sources

Effects of an acute bacterial infection on serum thyroid hormones and nuclear triiodothyronine receptors in mice.

Serum T3, T4, and rT3 levels as well as liver nuclear T3 receptors (NT3R) were measured in mice with a bacterial infection. Pseudomonas aeruginosa were injected into one thigh of ICR mice, resulting in a severe infection at sacrifice 15 h later. Since food intake, which influences serum thyroid hormone levels and NT3R, was 75% lower in infected than in control mice, infected mice were either fed and compared with pair-fed controls or fasted and compared with fasted and fed controls. Fasting induced a fall in serum T3 and T4 levels, which was even more pronounced in infected fasted animals. However, while fasting caused an approximately 80% increase in serum rT3 concentrations, serum rT3 levels in infected fasted animals were not different from those in fed controls. The combination of infection and fasting thus prevented the rise in serum rT3 otherwise invariably associated with fasting. NT3R measurements on isolated nuclei revealed the presence of NT3R in mouse liver similar to those reported in rat liver. The NT3R Kd (approximately 2 X 10(-10) M) was not affected by decreased food intake, infection, or a combination thereof. The NT3R maximum binding capacity (MBC) was decreased in fasted animals (460 vs. 306 pg/mg DNA). However, the MBC of infected fasted mice was not different from that of fasted mice. Similarly, no difference in MBC was found between infected fed and pair-fed control mice. In mice injected with heat-killed P. aeruginosa to evaluate potential effects of endotoxins, neither serum thyroid hormone levels nor hepatic NT3R were different from those of controls. These data show that in mice, a severe bacterial infection with P. aeruginosa has effects on serum hormone levels not explained by the disease-associated diminished food intake, whereas it has no effects on liver NT3R beyond those due to the disease-related decreased food intake.

Animals↗

In-vivo assessment of in-vitro killing patterns of Pseudomonas aeruginosa.

Time-kill curves of Pseudomonas aeruginosa exposed to gentamicin or ticarcillin 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 drug-dependent killing pattern was found in vitro with gentamicin. This pattern corresponded to bacterial killing in vivo which was clearly dependent on peak drug levels. In contrast, slow bacterial killing with little relationship to concentration was found in vitro with ticarcillin 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.

Animals↗

[Dosage interval and in vivo action of penicillin against pneumococci].

The relationship between dosage intervals of penicillin and bactericidal efficacy was investigated in an experimental model using normal and granulocytopenic mice and Streptococcus pneumoniae. Pulsdosing at 4-hour intervals proved to be significantly less efficient than fractional doses of the same total amount of penicillin injected at 1-hour intervals.

Agranulocytosis↗

[Microbiologic principles of antibiotic therapy].

Antibiotic therapy, in contrast to other drug treatments, is aimed at the etiology of a given disease state. The main basis of antimicrobial chemotherapy is thus identification of the causative pathogen and documentation of its susceptibility to the least toxic antibiotic. However, these requirements are frequently impossible to meet in everyday management of infections. In many situations, therefore, decision-making in antimicrobial chemotherapy must be based on a "best-guess" diagnosis regarding the causative pathogen and its susceptibility to the antibiotic. The process of decision-making in antimicrobial chemotherapy for the single most frequent infections encountered in outpatients is discussed, and the pertinent antimicrobial treatment for these infections (pharyngo-tonsillitis, otitis media, sinusitis, bronchitis and urinary tract infections) is outlined.

Adult↗

Impact of dosing intervals on activity of gentamicin and ticarcillin against Pseudomonas aeruginosa in granulocytopenic mice.

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 1-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.

Agranulocytosis↗

Pharmacokinetics of piperacillin in subjects with various degrees of renal function.

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 any of the groups. Piperacillin levels in urine were far higher than those in serum, generally exceeding the minimal inhibitory concentrations for susceptible organisms during the 24 h after both the 1- and the 4-g dose. Piperacillin dosage modification is required only in patients with severe renal impairment.

Aged↗

[Experimental study of optimal dose interval in antibiotic therapy].

A postantibiotic effect (PAE) was demonstrated for various antibiotics which suppressed bacterial regrowth for at least two hours beyond the termination of a short drug exposure in vitro. Rifampin, tetracycline and erythromycin already exhibit a PAE at low concentrations. In contrast, in the case of beta-lactams high concentrations - higher than those obtained in serum during oral treatment - were needed to demonstrate a PAE of these antibiotics in vitro. The PAE phenomenon may be of clinical importance with regard to dosage regimens in antimicrobial chemotherapy.

Anti-Bacterial Agents↗

Constant infusions vs. intermittent doses of gentamicin against Pseudomonas aeruginosa in vitro.

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-concentration-vs.-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 greater than 2 hr. Exposure of P. aeruginosa to gentamicin for 30 min was followed by persistent suppression of bacterial regrowth for 1.4-1.9 hr. Thus, intermittent exposure of P. aeruginosa to gentamicin is as effective as constant exposure in vitro. The demonstrated persistent postantibiotic effect might cover in part the periods between intermittent doses of gentamicin in vivo as well as in vitro.

Dose-Response Relationship, Drug↗