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Query: UMLS:C0014118 (endocarditis)
 15,629 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The proper dosage schedule of antibiotics has generally been determined empirically, due to the difficulty of clinical trials. Initially, the dosage was chosen to allow high sustained levels greater than MIC in the blood. Antibiotics (beta lactams, tetracyclins, macrolides) were given at high doses three to six times daily, whatever their kinetic properties. The data obtained by Eagle3 with beta lactams in animal models of streptococcal and treponemal infections outlined the importance of interval between doses on the in vivo efficacy. They also showed that increasing the dose of penicillin had a positive effect on the bactericidal activity only through the persistence of effective levels (greater than MIC) at the site of infection. Further illustrations were given through experimental and clinical studies with beta lactams or other compounds on different types of infections: LRTIs, UTIs, meningitis, and endocarditis. The importance of both dynamic (i.e., pattern of bactericidal effect) and kinetic (elimination half-life) parameters was thus further identified. Information on toxicity with some compounds with a narrow therapeutic index, such as aminoglycosides, indicated that increasing the dose to enhance efficacy had some limitations. This led to numerous studies on the relations between concentration and toxicity, stating that nephro- or ototoxicity were not directly related to peak level in serum. Experimental studies showed that OD administration of aminoglycosides was both more efficient and less toxic than the multiple-dose regimen of the same daily amount. Economic considerations progressively justified attempts to both reduce the dose and the work load related to multiple administrations.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Single-dose antibiotic therapy: what has the past taught us? 148 56

The combination of penicillin and aminoglycoside is the recommended therapy for endocarditis caused by nutritionally variant streptococci (NVS). However, the optimal aminoglycoside dosing regimen remains controversial. We compared the efficacies of four regimens of tobramycin alone or combined with procaine penicillin in the therapy of rabbits with endocarditis caused by Streptococcus adjacens, a new species of NVS. Animals were injected intramuscularly for 4 days with procaine penicillin (150,000 U/kg of body weight twice daily) or tobramycin at a low dose (3 mg/kg every 24 h) or a high dose (12 mg/kg every 24 h) either once or three times daily (t.i.d.) alone or in combination with procaine penicillin. Additional groups of animals were treated with the combination regimens for a shorter period of time (2 days) in order to demonstrate a possible difference in the rapidity of efficacy between the regimens. The MICs and MBCs were 0.015 and 1 micrograms/ml and 8 and 16 micrograms/ml for penicillin and tobramycin, respectively. The mean peak tobramycin levels in plasma were 2.4 +/- 1.3 (1 mg/kg t.i.d.), 5.4 +/- 3.7 (4 mg/kg t.i.d.), and 25 +/- 9.3 (12 mg/kg once daily). The mean penicillin levels in serum were always above the MIC. In vitro kill curves plotted at the time that peak concentrations were reached in plasma showed a concentration-dependent killing effect of tobramycin alone but not in combination with penicillin. In vivo, low-dose tobramycin was significantly less effective than the high dose. Results for the combinations of the different dosing regimens of tobramycin with procaine penicillin were not significantly different. Our results suggest that (i) against susceptible strains of streptococci, aminoglycoside alone exhibits a concentration-dependent killing effect both in vitro and in vivo; (ii) against NVS strains, combinations of penicillin and high- or low-dose tobramycin are equally effective; and (iii) aminoglycoside given once daily or at a low dose t.i.d. with penicillin could be a cost-effective alternative with reduced toxic risk for patients with NVS endocarditis when the bacteria are susceptible to the killing activities of both compounds.
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PMID:Optimal aminoglycoside dosing regimen for penicillin-tobramycin synergism in experimental Streptococcus adjacens endocarditis. 148 84

Endocarditis due to Lactobacillus is rare. Its main features were a subacute course and greater difficulties for achieving a complete recovery even using appropriate antimicrobial therapy with serum levels above MIC. We present one case of Lactobacillus endocarditis in a patient with allergy to penicillin, due to a vancomycin-resistant strain. She was successfully treated with clindamycin and gentamicin. We emphasize the need and importance of sensitivity tests and antibiotic tolerance when choosing an optimal treatment for this infection.
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PMID:[Endocarditis caused by Lactobacillus]. 149 71

MDL 62,873 is an amide derivative of teicoplanin A2-2. Like those of natural glycopeptides, its antibacterial activity is mediated by inhibition of cell wall peptidoglycan synthesis. Against streptococci and enterococci, the in vitro activity of MDL 62,873 was similar to that of teicoplanin and greater than that of vancomycin. Against staphylococci, it has activity similar to that of vancomycin, and it was significantly more active than teicoplanin against coagulase-negative isolates. Like teicoplanin and vancomycin, MDL 62,873 had slow but significant bactericidal activity (99 to 99.9% killing in 24 h) against staphylococci at concentrations near the MIC. In murine septicemia studies with Staphylococcus aureus, Streptococcus pyogenes, and Streptococcus pneumoniae, the 50% effective doses were lower than those of vancomycin. In staphylococcal endocarditis in rats, MDL 62,873 at 20 mg/kg of body weight and vancomycin at 40 mg/kg, both doses given intravenously twice daily, had similar efficacies in reducing the heart bacterial load. These results probably reflect the longer half-life of MDL 62,873, which has a pharmacokinetic profile in rats similar to that of teicoplanin.
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PMID:Antimicrobial activity of MDL 62,873, a semisynthetic derivative of teicoplanin, in vitro and in experimental infections. 153 78

The relative importance of pharmacokinetic and pharmacodynamic parameters for the feasibility of a single daily dose (SDD) of antibiotics remains to be established. Therefore, we studied the relationship between in vitro bacteriological parameters (MIC, MBC, and killing rate [KR], defined as the reduction in the inoculum within 3 h), pharmacokinetic parameters (t1/2 and protein binding [PB], and in vivo antibacterial effect of a single antibiotic dose in an experimental rabbit model of Escherichia coli endocarditis. Nine antibiotics were investigated: two aminoglycosides, two quinolones, and five beta-lactams. For each drug, the minimal effective dose (MED) (in milligrams per kilogram) was defined as the lowest dose able to achieve a significant difference (P less than 0.05) of CFU in the vegetations in comparison with controls 24 h after a single intravenous injection. Aminoglycosides and quinolones had the lowest MEDs, followed by beta-lactams. Univariate regression analysis showed that KR was the major determinant of MED. A stepwise regression analysis showed that t1/2 significantly improved the predictive value of KR, while PB, MIC, and MBC did not. The final equation was MED = 1,586-238 KR-297 t1/2 (r = 0.90, P = 0.01). We concluded that the pharmacodynamic parameters (especially the high KR) of aminoglycosides and quinolones explained their low MEDs and might allow SDD. In contrast, the low KR of beta-lactams emphasized the critical importance of a long t1/2, as for ceftriaxone, allowing the use of this beta-lactam alone in SDD.
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PMID:Single daily dosing of antibiotics: importance of in vitro killing rate, serum half-life, and protein binding. 175 31

Emergence of vancomycin-resistant strains among enterococci raises a new clinical challenge. Rabbits with aortic endocarditis were infected with Enterococcus faecium BM4172, a clinical strain resistant to low levels of vancomycin (MIC, 16 micrograms/ml) and susceptible to teicoplanin (MIC, 1 micrograms/ml), and against its susceptible variant E. faecium BM4172S obtained in vitro by insertional mutagenesis (MICs, 2 and 0.5 micrograms/ml, respectively). Control animals retained 8 to 10.5 log10 CFU/g of vegetation. We evaluated in this model the efficacy of vancomycin (30 mg/kg of body weight; mean peak and trough serum levels, 27 and 5 micrograms/ml, respectively), teicoplanin (standard dose, 10 mg/kg; mean peak and trough levels, 23 and 9 micrograms/ml, respectively; and high dose, 20 mg/kg; mean peak and trough levels, 63 and 25 micrograms/ml, respectively), gentamicin (6 mg/kg; mean peak and trough levels, 8.6 and less than 0.1 micrograms/ml, respectively), alone or in combination, given every 12 h intramuscularly for 5 days. Teicoplanin standard dose was as active as vancomycin against both strains. Vancomycin was not effective against E. faecium BM4172 but was highly effective against E. faecium BM4172S (7.5 +/- 1.1 log10 CFU/g of vegetation versus 4.9 +/- 1.0 log10 CFU/g of vegetation for vancomycin against E. faecium BM4172 and E. faecium BM4172S, respectively; P = 0.0012). A high dose of teicoplanin was more effective than vancomycin against E. faecium BM4172 (4.4 +/- 1.8 log10 CFU/g of vegetation versus 7.5 +/- 1.1 log10 CFU/g of vegetation for teicoplanin high dose and vancomycin, respectively; P less than 0.05). Against E. faecium BM4172 glycopeptide-gentamicin combinations were the most effective regimens in vitro and in vivo (2.8 +/- 0.7 and 3.5 +/- 1.3 log10 CFU/g of vegetation for vancomycin plus gentamicin and teicoplanin standard dose plus gentamicin, respectively; P < 0.05 versus single-drug regimens). We concluded that high-dose teicoplanin or the combination of a glycopeptide antibiotic plus gentamicin was effective against experimental infection due to E. faecium with low-level resistance to vancomycin.
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PMID:Influence of low-level resistance to vancomycin on efficacy of teicoplanin and vancomycin for treatment of experimental endocarditis due to Enterococcus faecium. 183 13

We studied the activity of the combination of sulbactam and ceftriaxone against a Klebsiella pneumoniae strain producing TEM-3, a new extended-broad-spectrum beta-lactamase, in an endocarditis model. In vitro, ceftriaxone was strongly inactivated in the presence of TEM-3 (MBC, 128 micrograms/ml with an inoculum of 5 x 10(5) CFU/ml). A marked inoculum effect was demonstrated with sulbactam: effective concentrations of inhibitor needed to reduce the MIC and MBC of ceftriaxone to similar levels increased from 1 microgram/ml in the presence of an inoculum of 5 x 10(5) CFU/ml to 20 micrograms/ml in the presence of an inoculum of 1 x 10(7) CFU/ml. In vivo, sulbactam given at 200 mg/kg of body weight every 12 h, a dosage higher than that previously reported to be effective against rabbit endocarditis caused by other microorganisms, was not sufficient to restore the complete activity of ceftriaxone given at 30 mg/kg once daily for 4 days. This insufficient activity may be correlated with the presence of a high level of beta-lactamase inside the vegetations, as indicated by a quantitative in vitro assay of beta-lactamase activity in the cardiac vegetation, suggesting an insufficient inactivation of the extended-broad-spectrum beta-lactamase in vivo.
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PMID:Ceftriaxone-sulbactam combination in rabbit endocarditis caused by a strain of Klebsiella pneumoniae producing extended-broad-spectrum TEM-3 beta-lactamase. 207 99

The animal model of endocarditis provides a reliable and reproducible model of acute infection and appears appropriate for studying the parameters involved in the in vivo efficacy of antibiotic therapy. The following points are discussed: (i) beta-lactam antibiotics exhibit a time-dependent bactericidal effect which explains the importance of t1/2 beta in the determination of dosing intervals and the need for large unitary doses for increasing efficacy through extending the period of serum levels greater than MIC (ii). The impact of unitary doses and dosing intervals of aminoglycosides on their in vivo synergism with beta-lactams has been investigated in Escherichia coli and streptococcal infections. Once- daily dosing of netilmicin appears very synergistic with ceftriaxone on E. coli, and the aminoglycoside has a significant dose effect. Conversely, divided doses are necessary to exhibit full synergistic effect with penicillin G on E. faecalis. Different patterns of in vivo synergism can therefore be individualized (iii). The rapid bactericidal effect of quinolones and their in vivo post-antibiotic effect allowing large intervals between doses have been investigated with ciprofloxacin (iv). The importance of t1/2 beta on the in vivo effect of glycopeptides is illustrated by data comparing teicoplanin and vancomycin. It is concluded that in vitro killing rate within 3 h is the major factor interfering with the dose interval, followed by t1/2 beta which is of major importance for those drugs whose bactericidal effect is time-dependent. These parameters appear to have a similar importance in experimental endocarditis to that in other experimental models. However, infected vegetations represent a particular focus of infection incorporating heterogeneity of antibiotic distribution, high density of bacteria and reduced metabolic activity of microorganisms. These factors may explain the lack of in vivo postantibiotic effect observed with some antibiotics, correspondingly shorter dosage intervals in endocarditis than in other types of infections and a need for high unitary doses.
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PMID:Impact of the antibiotic dosage schedule on efficacy in experimental endocarditis. 209 5

To assess the potential efficacy of trimethoprim-sulfamethoxazole (TMP-SMX) against serious enterococcal infections, we used a rat enterococcal endocarditis model comparing TMP-SMX therapy (500 mg of TMP plus 2,500 mg of SMX per kg of body weight per day given every 8 h by intragastric gavage) with intravenous ampicillin therapy (1,000 mg/kg per day). Despite concentrations of active drug in serum well in excess of the MIC and MBC, the mean residual vegetation bacterial titer in TMP-SMX-treated rats was similar to that in untreated controls (8.4 +/- 1.1 versus 8.6 +/- 1.3 log10 CFU/g) and significantly higher than that in the ampicillin-treated group (3.6 +/- 1.5 log10 CFU/g; P less than or equal to 0.001). This demonstrates discordance between in vitro activity and in vivo efficacy of TMP-SMX in serious enterococcal infection.
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PMID:Failure of trimethoprim-sulfamethoxazole therapy in experimental enterococcal endocarditis. 212 91

The effect of dosage and the relative importance of peak and trough concentrations in serum for efficacy of teicoplanin were examined in a rabbit model of aortic valve endocarditis. Concentrations of teicoplanin in serum exceeded the MIC by several hundredfold, yet teicoplanin was less rapidly bactericidal than penicillin both in vitro and for endocarditis caused by a strain of Streptococcus sanguis. Because teicoplanin was 90% protein bound in rabbit serum, low free-drug concentrations probably resulted in less activity in vivo than in vitro. Because teicoplanin has a relatively low bactericidal rate and a high degree of protein binding, a sustained concentration in serum several times greater than the MIC may be important for efficacy in vivo. An intravenous regimen with relatively high peak concentrations in serum was less effective than an intramuscular regimen for endocarditis caused by a strain of Staphylococcus aureus, indicating that high peaks are unlikely to be an important determinant of efficacy. The therapeutically more relevant concentration in serum may be the trough.
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PMID:Effects of dosage, peak and trough concentrations in serum, protein binding, and bactericidal rate on efficacy of teicoplanin in a rabbit model of endocarditis. 214 Apr 96


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