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  • Author or Editor: Eberhard Rosin x
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Summary

The susceptibility of 50 clinical Escherichia coli isolates to various antibacterials, including cefoxitin and cefotetan was ascertained, and the minimal inhibitory concentration (mic) of cefoxitin and cefotetan for each of these isolates was determined. The pharmacokinetics of cefoxitin and cefotetan after a single iv or sc injection (30 mg/kg of body weight) were determined in 4 dogs. Of the 50 E coliisolates, 98% were susceptible in vitro to cefotetan, 90% were susceptible to cefoxitin, and 88% were susceptible to gentamicin. The mic that would inhibit the growth of 90% of the E coliisolates (mic 90) was 0.25 µg/ml for cefotetan and 4 µg/ml for cefoxitin. Plasma cefotetan concentrations remained above mic 90 for (mean ± SD) 8.2 ± 1.72 8.2 ± 1.72 hours and 13.52 ± 0.28 hours after iv and sc administration, respectively. Plasma cefoxitin concentrations remained above mic 90 for (mean ± SD) 5.37 ± 1.18 hours and 7.95 ± 0.71 hours after iv and sc administration, respectively. We concluded that cefotetan was superior to cefoxitin·was superior to cefoxitin in activity against E coli in vitro. We recommend that cefotetan be given at a dosage of 30 mg/kg, iv, every 8 hours, Or sc, every 12 hours.

Free access
in American Journal of Veterinary Research

Abstract

Objective

To derive pharmacokinetic data for 3 amikacin dosing regimens in guinea pigs and to determine whether the antibacterial activity of 15 mg/kg of body weight given twice daily is equivalent to administering the drug more frequently.

Animals

10 guinea pigs in pharmacokinetic trials, and 10 guinea pigs in pretreatment, control, and amikacin treatment groups.

Procedure

Amikacin pharmacokinetic data were determined in guinea pigs after single IM administration of 3.75, 7.5, and 15 mg/kg. Guinea pigs had been made neutropenic by treatment with cyclophosphamide. All guinea pigs were inoculated with 2.8 × 108 colony-forming units (CFU) of Escherichia coli in the thigh muscle, then were allotted to 5 groups: pretreatment (euthanatized 4 hours after inoculation), control, and 3 amikacin treatment groups (3.75 mg/kg, q 3 h; 7.5 mg/kg, q 6 h; and 15 mg/kg, q 12 h). Amikacin administration was begun 4 hours after E coli inoculation and was continued for 72 hours. Numbers of E coli CFU in infected thigh muscle were determined for each guinea pig.

Results

Difference in survival between control and the amikacin-treated groups was significant. The E coli infection concentration (log10 CFU) increased significantly in the control, compared with the pretreatment, group. Infection concentration decreased significantly in all treatment groups, compared with the pretreatment group. There was no significant difference in bacterial killing among the 3 treatment groups.

Conclusion

Amikacin had a significant effect on survival of neutropenic guinea pigs with E coli infection. Antibacterial activity did not differ among 3 doses of amikacin administered at different intervals.

Clinical Relevance

Aminoglycoside dosing regimen with high peak concentration and long drug-free interval is as efficacious as divided dose regimens. (Am J Vet Res 1998;59:750-755)

Free access
in American Journal of Veterinary Research

Abstract

Objective

To determine whether the antibacterial activity of 6 mg of gentamicin/kg of body weight given SC once daily, is equivalent to the standard gentamicin dose of 2 mg/kg given SC every 8 hours.

Animals

Guinea pigs with infected thigh wound: 5 in an untreated control group and 12 in 6 and 2 mg/kg gentamicin treatment groups.

Procedure

Guinea pigs were inoculated with 109 Escherichia coli in the thigh muscle. Gentamicin treatment (2 mg/kg, SC, q 8 h or 6 mg/kg, SC, q 24 h) was begun 4 hours after E coli inoculation and continued for 72 hours. Four hours after the last gentamicin treatment, all guinea pigs were euthanatized and the cranial thigh muscle containing the entire inoculum was removed. Colony forming units were counted to determine the E coli concentration in each thigh.

Results

Mean ± SD log10 colony-forming units was 9.293 ± 0.074 in the control group, 8.161 ± 0.478 in the 2 mg/kg treatment group, and 7.796 ± 0.182 in the 6 mg/kg treatment group. One-way ANOVA revealed a significant (P < 0.05) difference between the control group and both treatment groups, and between both treatment groups.

Conclusion

Bacterial killing did not differ between gentamicin given at a dosage of 6 mg/kg once daily, compared with 2 mg/kg every 8 hours in guinea pigs infected with E coli.

Clinical Relevance

Gentamicin dosage regimens with high peak concentration and long dosing interval are as efficacious as divided dosage regimens. These data support the concept that once daily administration of gentamicin for treatment of E coli infection should be investigated clinically. (Am J Vet Res 1996;57:1627–1630)

Free access
in American Journal of Veterinary Research

SUMMARY

Pharmacodynamic variables of enrofloxacin were investigated in a neutropenic mouse Escherichia coli and staphylococcal thigh infection model. Enrofloxacin pharmacokinetics in clinically normal mice and dogs were compared to confirm that doses evaluated in the mouse model would include enrofloxacin doses appropriate for use in dogs. Mice were made neutropenic by treatment with cyclophosphamide and injected in the thigh muscle with approximately 106 colony-forming units of E coli (n = 2) or a staphylococcal (n = 2) clinical isolate. Enrofloxacin dosages tested ranged from 0.78 to 50 mg/kg of body weight and 6.25 to 200 mg/kg in the E coli and staphylococcal infection trials, respectively. In each 24-hour dosage trial, enrofloxacin was administered SC as a single dose or in divided doses given every 3, 6, or 12 hours. Comparison of log10 colonyforming units per thigh muscle in untreated control mice and mice treated with enrofloxacin was used as a measure of efficacy. Two-way anova was used to determine that the enrofloxacin total dose, but not the dose frequency, was significant in determining drug efficacy. Pharmacokinetic values analyzed by use of multivariant stepwise linear regression analysis indicated that the area under the concentration-time curve, but not time above minimum inhibitory concentration, was significant in predicting efficacy of enrofloxacin treatment. We conclude that enrofloxacin killing of E coli and staphylococci is concentration dependent and not time dependent.

Free access
in American Journal of Veterinary Research

Summary

An antibiotic selected for surgical antimicrobial prophylaxis must be present in the surgical site throughout the operation in concentration sufficient to prevent growth of contaminating pathogens. The antimicrobial spectrum, minimal toxicity, and low cost of cefazolin make this first-generation cephalosporin a logical choice for antimicrobial prophylaxis in small animal surgical procedures in which the normal microbiologic flora of skin and gastrointestinal tract are the most likely pathogens. Pharmacokinetic variables of cefazolin were determined in serum and surgical wounds in dogs. Drug concentration in interstitial fluid of muscle biopsy specimens taken at random from wound surfaces and in postoperative wound fluid samples were determined. Effective surgical wound concentration of cefazolin was defined as 4 μg/ml, a concentration that inhibited the growth in vitro of 100% of staphylococcal and 80% of Escherichia coli clinical isolates. After iv and sc administrations, cefazolin equilibrated rapidly between serum and the surgical wound, and concentrations in the 2 sites decreased in parallel. With a bolus dose of 20 mg/kg of body weight given iv at the beginning of surgery and repeated by sc administration at 6 hours, cefazolin concentration in the surgical wound remained > 4 μg/ml for longer than 12 hours.

Free access
in American Journal of Veterinary Research

Abstract

Objective—To determine the pharmacokinetics of ceftazidime following subcutaneous administration and continuous IV infusion to healthy dogs and to determine the minimum inhibitory concentration (MIC) of ceftazidime for clinical isolates of Pseudomonas aeruginosa.

Animals—10 healthy adult dogs.

Procedure—MIC of ceftazidime for 101 clinical isolates of P aeruginosa was determined in vitro. Serum concentrations of ceftazidime were determined following subcutaneous administration of ceftazidime (30 mg/kg of body weight) to 5 dogs and continuous IV infusion of ceftazidime (loading dose, 4.4 mg/kg; infusion rate, 4.1 mg/kg/h) for 36 hours to 5 dogs.

Results—The MIC of ceftazidime for P aeruginosa was ≤ 8 µg/ml; all isolates were considered susceptible. Following SC administration of ceftazidime, mean β disappearance half-life was 0.8 hours, and mean serum ceftazidime concentration exceeded the MIC for P aeruginosa for only 4.3 hours. Two dogs had gastrointestinal tract effects. Mean serum ceftazidime concentration exceeded 16 µg/ml during continuous IV infusion. None of the dogs developed adverse effects.

Conclusions and Clinical Relevance—Administration of ceftazidime subcutaneously (30 mg/kg, q 4 h) or as a constant IV infusion (loading dose, 4.4 mg/kg; rate, 4.1 mg/kg/h) would maintain serum ceftazidime concentrations above the MIC determined for 101 clinical isolates of P aeruginosa. Use of these dosages may be appropriate for treatment of dogs with infections caused by P aeruginosa. (Am J Vet Res 2000;61:1204–1208)

Full access
in American Journal of Veterinary Research