Teichomycin: <i>in-vitro</i> and <i>in-vivo</i> evaluation in comparison with other antibiotics

One hundred clinical isolates of methicillin-resistant (Metr) Staphylococcus aureus from five different geographical origins were tested for their susceptibility to 12 non-li-lactam antibiotics by the broth microdilution technique recommended by the National Committee for Clinical Laboratory Standards.Coumermycin and rifampin showed the highest activity with of MIC90s of 0.032 jig/ml for each compound. No resistance was found to coumermycin, whereas a single Metr S. aureus strain was found to be resistant to rifampin. Ciprofloxacin, vancomycin, and teicoplanin were the next most active compounds with MIC90s of 0.25, 0.5, and 0.5 ,ug/ml, respectively. Norfloxacin was less active, with an MIC90 of 1.0 ,ug/ml. Amikacin was the most active aminoglycoside tested, whereas high levels of resistance were found to tobramycin and gentamicin. Doxycycline and chloramphenicol showed variable results. Geographical variations in results were seen with doxycycline, chloramphenicol, and aminoglycosides. Kill-curve studies showed that coumermycin, ciprofloxacin, teicoplanin, vancomycin, and rifampin were highly bactericidal; more than 90% of the inoculum was killed within 8 h.

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“…Coumermycin, ciprofloxacin, and norfloxacin inhibit DNA gyrase activity within bacterial cells (10,19 (16,17,20).…”

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confidence: 99%

Comparison of the activities of coumermycin, ciprofloxacin, teicoplanin, and other non-beta-lactam antibiotics against clinical isolates of methicillin-resistant Staphylococcus aureus from various geographical locations

Aldridge¹,

Janney²,

Sanders³

1985

Antimicrob Agents Chemother

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“…The effect of glycopeptide antibiotics has been studied in animal models (2,3,11,19,(21)(22)(23)(24)(25), including the relationship to dosing regimens (3,22,25), but more often one glycopeptide regimen has been compared to regimens with other drugs (2,11,19,21,23,24). Until now, it has not been possible to clearly identify which one or more of the PK/PD parameters are the most important in treatment with glycopeptides in animal studies.…”

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confidence: 99%

Pharmacodynamics of Glycopeptides in the Mouse Peritonitis Model ofStreptococcus pneumoniaeorStaphylococcus aureusInfection

Knudsen

Fuursted

Raber

et al. 2000

Antimicrob Agents Chemother

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The emergence of resistance to various antibiotics in pneumococci leaves the glycopeptides as the only antibiotics against which pneumococci have no resistance mechanism. This situation has led to a renewed interest in the use of glycopeptides. It has not yet been possible to conclude which one or more of the pharmacokinetic or pharmacodynamic (PK/PD) parameters are the most important and best predictors for the effects of treatment with glycopeptides in animal models or in humans. We used the mouse peritonitis model with immunocompetent mice and with Staphylococcus aureus and Streptococcus pneumoniae as infective organisms. A wide spectrum of different treatment regimens with vancomycin and teicoplanin was tested to study the pharmacodynamics of these drugs. In studies in which the single dose that protected 50% of lethally infected mice (ED 50 ) was given as one dose or was divided into two doses, survival was significantly decreased when the dose was divided. The only statistically significant correlations between the percentage of survival of the mice after 6 days and each of the PK/PD parameters were for peak concentration (C max )/MIC and S. aureus and for the free fraction of C max (C max-free )/MIC and S. pneumoniae. For S. pneumoniae, the ED 50 for different dosing regimens increased with the number of doses given; e.g., the single-dose ED 50 s for vancomycin and teicoplanin were 0.65 and 0.45 mg/kg, respectively, but the ED 50 s for dosing regimens with 2-h doses given for 48 h were 6.79 and 5.67 mg/kg, respectively. In experiments with 39 different vancomycin dosing regimens and 40 different teicoplanin dosing regimens against S. pneumoniae, the different PK/PD parameters were analyzed using logistic regression. The C max-free /MIC was one of two parameters that best explained the effect for both drugs; for vancomycin, the other important parameter was the AUC/MIC, and for teicoplanin, the other parameter was the time the free fraction of the drug is above the MIC. The effect analyzed as a function of C max-free /MIC disclosed thresholds with shifts from almost no effect to full effect at ratios of five to six for vancomycin and two to three for teicoplanin.

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“…In vitro studies show that it is active against most gram-positive cocci at concentrations <1 mg/liter [4]. In vivo, it protects mice against experimental staphylococcal septicemia [4,5] and compares favorably with nafcillin and vancomycin in experimentally induced endocarditis [6].…”

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Early Termination of a Prospective, Randomized Trial Comparing Teicoplanin and Flucloxacillin for Treating Severe Staphylococcal Infections

Calain

Krause

Vaudaux

et al. 1987

Journal of Infectious Diseases

120

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In a prospective, randomized trial, teicoplanin (at a 400-mg intravenous loading dose followed by 200 mg/day intravenously or intramuscularly) was compared with flucloxacillin (8 g/day) in patients with severe staphylococcal infections. Teicoplanin proved unsatisfactory for the following reasons: (1) failures or relapses were more frequent in the teicoplanin group, and (2) blood levels were difficult to predict and tended to be low 24 hr after the loading dose. Future trials with this agent should use much-higher doses.Treating severe staphylococcal infections remains difficult. The most-widely used drugs, such as the antistaphylococcal penicillins and vancomycin, are administered intravenously several times daily and expose patients to the dangers of prolonged intravenous treatment and to the expense and discomfort of hospitalization. Both types of drugs have side effects, such as allergic reactions for the penicillins [1] and ototoxicity, nephrotoxicity, and neutropenia for vancomycin [2].Teicoplanin is a new antibiotic chemically related to vancomycin [3]. In vitro studies show that it is active against most gram-positive cocci at concentrations <1 mg/liter [4]. In vivo, it protects mice against experimental staphylococcal septicemia [4, 5] and compares favorably with nafcillin and vancomycin in experimentally induced endocarditis [6].Toxicological studies of teicoplanin in animals show a potential for nephrotoxicity at high doses but no ototoxicity, in contrast to vancomycin (unpublished data).Studies in humans have demonstrated good tolerance after intravenous [7] and intramuscular [8] injection and slow elimination, with a terminal halflife of 70-100 hr [9,10], factors suggesting that a once-daily intramuscular injection might be an appropriate and highly practical treatment schedule for staphylococcal infections. In previous clinical trials [11][12][13][14], teicoplanin was given at a dose of 400 mg Received for publication 23 April 1986, and in revised form 4 August 1986.We thank all of the physicians who collaborated in this study and thank E. Huggler for technical assistance.Please address requests for reprints to Dr. B. Hirschel, Hopital Cantonal Universitaire, rue Micheli du Crest, 1211 Geneve 4, Switzerland. 187(first day), followed by 200 mg/day. Reported success rates were as high as 940/0 [11], but these studies included soft-tissue infections. Cure rates were never compared with those for standard treatments. On the basis of these data we decided to compare teicoplanin with parenteral flucloxacillin in patients with severe staphylococcal infections.As suggested by the Ethics Committee of our hospital (Dr. Jean Fabre), a preliminary analysis of the results was performed after treating the first 18 patients. This analysis revealed a high failure rate in patients treated with teicoplanin and led to the premature termination of our study. Patients and MethodsPatients. Patients were considered for the study if they met at least one of the following criteria: (1) two or more separate cultures of blood...

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Teichomycin: in-vitro and in-vivo evaluation in comparison with other antibiotics

Cited by 94 publications

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Comparison of the activities of coumermycin, ciprofloxacin, teicoplanin, and other non-beta-lactam antibiotics against clinical isolates of methicillin-resistant Staphylococcus aureus from various geographical locations

Comparison of the activities of coumermycin, ciprofloxacin, teicoplanin, and other non-beta-lactam antibiotics against clinical isolates of methicillin-resistant Staphylococcus aureus from various geographical locations

Pharmacodynamics of Glycopeptides in the Mouse Peritonitis Model ofStreptococcus pneumoniaeorStaphylococcus aureusInfection

Early Termination of a Prospective, Randomized Trial Comparing Teicoplanin and Flucloxacillin for Treating Severe Staphylococcal Infections

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