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

The pharmacokinetics of ampicillin and sulbactam, a new beta-lactamase inhibitor, were investigated in 16 patients undergoing prosthetic cardiac valve insertion. The combination of 2 g of ampicillin and 1 g of sulbactam was administered as perioperative prophylaxis intravenously over 3 to 6 days. Several serum pharmacokinetic parameters were similar for the two drugs after three intravenous doses were given to patients following surgery. The half-lives of elimination of ampicillin and sulbactam were 79 +/- 4.9 and 88 +/- 5.9 min, the volumes of distribution were 15.6 +/- 1.4 and 17.7 +/- 1.2 liters/70 kg, and the total plasma clearances were 144.4 +/- 14.5 and 147.2 +/- 14.5 ml/min, respectively. The peak concentrations of ampicillin and sulbactam in serum were calculated to be 134.3 +/- 1.3 and 58.3 +/- 1.2 micrograms/ml, respectively. Ampicillin and sulbactam rapidly penetrated from the blood into various tissues collected during heart surgery, such as sternum, pericardium, myocardium, and endocardium. The concentrations of ampicillin in tissue ranged from 17.8 +/- 9.9 to 50 +/- 29.5 micrograms/g, and those of sulbactam in tissue ranged from 8.8 +/- 6.2 to 19.6 +/- 10.1 micrograms/g. The concentrations of ampicillin and sulbactam in serum and tissue also apparently exceeded the MICs against most beta-lactamase-producing bacteria usually involved in postoperative wound infections and prosthetic valve endocarditis. The ratio of the two compounds was approximately 2:1 in serum and in the various tissues affected by the operation. The pharmacokinetics of ampicillin and sulbactam in serum and investigated tissues suggest that the combination of the two beta-lactams will be effective in the perioperative prophylaxis of patients undergoing heart surgery.
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PMID:Pharmacokinetics of ampicillin and sulbactam in patients undergoing heart surgery. 195 46

In vitro and in vivo activity of amoxicillin and penicillin G alone or combined with a penicillinase inhibitor (clavulanate) were tested against five isogenic pairs of methicillin-resistant Staphylococcus aureus (MRSA) producing or not producing penicillinase. Loss of the penicillinase plasmid caused an eight times or greater reduction in the MICs of amoxicillin and penicillin G (from greater than or equal to 64 to 8 micrograms/ml), but not of the penicillinase-resistant drugs methicillin and cloxacillin (greater than or equal to 64 micrograms/ml). This difference in antibacterial effectiveness correlated with a more than 10 times greater penicillin-binding protein 2a affinity of amoxicillin and penicillin G than of methicillin and a greater than or equal to 90% successful amoxicillin treatment of experimental endocarditis due to penicillinase-negative MRSA compared with cloxacillin, which was totally ineffective (P less than .001). Amoxicillin was also effective against penicillinase-producing parent MRSA, provided it was combined with clavulanate. Penicillinase-sensitive beta-lactam antibiotics plus penicillinase inhibitors might offer a rational alternative treatment for MRSA infections.
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PMID:Beta-lactam resistance mechanisms of methicillin-resistant Staphylococcus aureus. 199 24

The efficacy of amoxycillin/clavulanic acid was compared with that of flucloxacillin, vancomycin and amoxycillin in an experimental model of Staphylococcus aureus endocarditis. Doses of the antibiotics were selected to produce peak concentrations in rat serum similar to those achievable in man after administration of parenteral therapeutic doses. Amoxycillin clavulanic acid was more effective than amoxycillin alone against endocarditis caused by beta-lactamase producing strains of Staph. aureus, illustrating the beta-lactamase inhibitory activity of clavulanic acid in vivo. Amoxycillin/clavulanic acid was as effective as flucloxacillin in these infections whereas vancomycin was generally less active. These results illustrate the clinical potential of amoxycillin/clavulanic acid in the prophylaxis, or in the therapy of severe staphylococcal infections.
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PMID:Efficacy of amoxycillin/clavulanic acid in experimental Staphylococcus aureus endocarditis in the rat. 205 May 88

Optimal therapeutic strategies for serious infections caused by borderline and heterotypic oxacillin-resistant Staphylococcus aureus (BORSA and ORSA) strains have not been fully characterized. Recent evidence suggests that the dominant penicillin-binding protein of ORSA strains (PBP 2a) shows good affinity for ampicillin and that these strains commonly produce beta-lactamase. Therefore, we compared the in vivo efficacy of the combination of ampicillin plus sulbactam with that of vancomycin against ORSA strains. Also, the moderate resistance of BORSA strains appears to be attributable mainly to the hyperproduction of beta-lactamase. Therefore, we also studied the in vivo efficacy of ampicillin plus sulbactam against such organisms. Experimental aortic endocarditis was induced in rabbits by the following three strains: beta-lactamase-producing BORSA strain VP-986, beta-lactamase-producing ORSA strain 67-0, and its beta-lactamase-negative clone. In animals with BORSA endocarditis, ampicillin plus sulbactam and oxacillin were highly effective in reducing mean intravegetation bacterial densities, with each being significantly better than either ampicillin alone or no therapy. In animals with endocarditis caused by the beta-lactamase-producing ORSA strain, ampicillin plus sulbactam was significantly better at reducing mean vegetation bacterial densities than the other regimens. For endocarditis caused by the beta-lactamase-negative ORSA clone, ampicillin was better than vancomycin in reducing mean intravegetation bacterial densities. These data show that infections caused by beta-lactamase-producing BORSA strains respond therapeutically in a manner similar to that of infections caused by oxacillin-susceptible strains, with both oxacillin and ampicillin plus sulbactam being highly efficacious. Moreover, high-dose ampicillin treatment strategies were effective in the therapy of ORSA endocarditis; this efficacy is presumably related to the relatively high affinity profile of this compound (compare with that of oxacillin) for the functionally dominant ORSA PBP 2a.
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PMID:Beta-Lactam-beta-lactamase-inhibitor combinations are active in experimental endocarditis caused by beta-lactamase-producing oxacillin-resistant staphylococci. 206 74

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

We studied the prevention of experimental aortic endocarditis caused by a beta-lactamase-producing, aminoglycoside-resistant strain of Enterococcus faecalis (HH22) in 146 catheterized rabbits. Both vancomycin and ampicillin-sulbactam readily killed this resistant enterococcus strain in vitro. At a challenge inoculum of approximately 10(9) CFU, vancomycin (40 mg/kg intravenously [i.v.]), ampicillin (40 mg/kg i.v.), or a combination of ampicillin plus a beta-lactamase inhibitor, sulbactam (20 mg/kg, i.v.), did not prevent the development of endocarditis in any of the animals, although mean intravegetation bacterial densities were significantly lower in animals that received vancomycin than they were in animals that received other therapies (P less than 0.001). At a challenge inoculum of 10(6) CFU, vancomycin was 100% effective in preventing enterococcal endocarditis compared with ampicillin (29%; P less than 0.00001) and ampicillin-sulbactam (65%; P less than 0.01). Factors associated with the superior prophylactic efficacy of vancomycin in this model included prolonged serum inhibitory activity and time above MICs. Factors not associated with the antienterococcal prophylactic efficacy of vancomycin included the duration of the in vitro postantibiotic effect of the drug and the magnitude of the ability of this drug to enhance enterococcal in vitro opsonophagocytic killing by polymorphonuclear leukocytes. The superior prophylactic efficacy of vancomycin in this endocarditis model related to the superior pharmacokinetic profile of the drug when it was given intermittently at dose intervals of every 6 h.
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PMID:Chemoprophylactic efficacy against experimental endocarditis caused by beta-lactamase-producing, aminoglycoside-resistant enterococci is associated with prolonged serum inhibitory activity. 211 23

Optimal therapy for the treatment of infections caused by strains of enterococci demonstrating high-level resistance to gentamicin and other aminoglycosides has not been established. The present study examined the efficacy of teicoplanin, a glycopeptide antibiotic active against gram-positive bacterial infections in various animal models, in the treatment of experimental endocarditis due to a beta-lactamase-producing strain of Enterococcus faecalis with high-level resistance to gentamicin. Vancomycin was used as a comparative antibiotic. In the first set of experiments, both antimicrobial agents were administered by continuous intravenous infusion for 5 days at dosages which yielded comparable mean levels in serum (plus or minus the standard deviation) of 14.6 +/- 4.3 micrograms/ml for teicoplanin and 14.3 +/- 2.2 micrograms/ml for vancomycin. These regimens proved similarly effective in sterilizing cardiac vegetations (38 versus 50% of treated animals, respectively; P greater than 0.05). Mean (plus or minus the standard deviation) residual bacterial titers within vegetations were reduced to 3.2 +/- 1.2 log10 CFU/g and 3.4 +/- 1.7 log10 CFU/g, respectively. In separate experiments, the potential of teicoplanin to cure endocarditis was assessed, using two dosage regimens: (i) 30 mg/kg per day (mean level in serum, 13 micrograms/ml) for 10 days or (ii) 150 mg/kg per day (mean level in serum, 84 micrograms/ml) for 5 days. Surviving animals were sacrificed 10 days after the discontinuation of therapy. Both teicoplanin regimens were more effective than the comparative vancomycin (150 mg/kg per day) regimen: 92 versus 43% cured (P =0.025) in the standard-dose group, and 82 versus 37% cured (P = 0.015) in the high-dose group. Results in this rat model of enterococcal endocarditis show that teicoplanin may prove useful in the treatment of serious infections due to high level-gentamicin-resistant enterococci in humans.
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PMID:Efficacy of teicoplanin in two dosage regimens for experimental endocarditis caused by a beta-lactamase-producing strain of Enterococcus faecalis with high-level resistance to gentamicin. 214 78

We studied the efficacy of sulbactam, a beta-lactamase inhibitor, in combination with ceftriaxone in vitro and in experimental endocarditis due to an Escherichia coli strain producing an extended-spectrum beta-lactamase most similar to SHV-2, a new mechanism of resistance to broad-spectrum cephalosporins among members of the family Enterobacteriaceae. In vitro, ceftriaxone demonstrated an important inoculum effect (MICs were 2 and 256 micrograms/ml with 5 X 10(5) and 5 X 10(7) CFU of inoculum per ml, respectively). Sulbactam inhibited the beta-lactamase degradation of ceftriaxone and enhanced the killing by ceftriaxone with both inocula tested. In vivo, sulbactam (100 mg/kg every 8 h) or ceftriaxone (15 or 30 mg/kg every 24 h) alone were ineffective after a 4-day therapy. The addition of sulbactam to ceftriaxone (15 mg/kg) or to the ceftriaxone (15 mg/kg)-netilmicin (6 mg/kg every 24 h) combination produced a reduction of 2 log10 CFU/g of vegetation greater than that produced by therapy without sulbactam. The sulbactam-ceftriaxone (30 mg/kg) combination produced a reduction of almost 5 log10 CFU/g of vegetation greater than that produced by single-drug therapy (P less than 0.01), sterilized five of eight vegetations (versus none of seven for ceftriaxone [30 mg/kg] alone; P less than 0.05), and was as effective as the ceftriaxone (15 mg/kg)-sulbactam-netilmicin combination. We concluded that (i) SHV-2 production was responsible for ceftriaxone failure in vivo, probably because of the high inoculum present in vegetations; (ii) sulbactam used in a regimen which provided levels in serum constantly above 4 micrograms/ml and a vegetation/serum peak ratio of approximately 1:3 enhanced the activity of a broad-spectrum cephalosporin in a severe experimental infection; and (iii) the highest dose of ceftriaxone in combination with sulbactam was as effective as the lowest dose of ceftriaxone plus sulbactam plus an aminoglycoside.
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PMID:Activity of sulbactam in combination with ceftriaxone in vitro and in experimental endocarditis caused by Escherichia coli producing SHV-2-like beta-lactamase. 218 86

Optimal therapy of infections caused by borderline oxacillin-susceptible, beta-lactamase-hyperproducing Staphylococcus aureus has not been established. We used a rat model of aortic valve endocarditis to examine efficacies of antibiotic regimens against a borderline oxacillin-susceptible strain as compared with a fully susceptible S. aureus strain. Animals were treated with oxacillin alone or in combination with sulbactam or with ampicillin-sulbactam combinations at two dose levels. Infections caused by the borderline susceptible and fully susceptible strains responded equally well to oxacillin alone, with residual bacterial titers in vegetations falling to 4.8 +/- 1.6 and 4.4 +/- 1.7 (mean +/- standard deviation) log10 CFU/g, respectively. Addition of sulbactam to oxacillin (1:2) did not enhance the efficacy of oxacillin against either strain in the animal model. A high-dose regimen of ampicillin-sulbactam (2:1) yielding mean (+/- standard deviation) levels in serum of 16.8 +/- 7.4 and 9.5 +/- 1.1 micrograms/ml, respectively, proved equally effective against both strains (bacterial titers, 6.6 log10 CFU/g). However, at lower doses (8.3 +/- 2.6 and 5.9 +/- 2.4 micrograms/ml, the combination showed greater efficacy against the fully susceptible strain, with residual titers of 7.1 +/- 2.0 versus 9.0 +/- 1.6 log10 CFU/g (P less than 0.05). In vitro studies revealed that the beta-lactamase inhibitor sulbactam was also a potent inducer of staphylococcal beta-lactamase at clinically relevant concentrations. Based on this short-term in vivo therapy study, oxacillin would be predicted to be clinically effective in the therapy of infections caused by borderline oxacillin-susceptible strains of S. aureus, while the combination of ampicillin with sulbactam appears to be inferior to oxacillin alone against such infections.
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PMID:Efficacy of oxacillin and ampicillin-sulbactam combination in experimental endocarditis caused by beta-lactamase-hyperproducing Staphylococcus aureus. 236 Aug 13

The beta-lactam antibiotics ticarcillin, nafcillin, imipenem, and ampicillin, which differ in antibacterial activity against methicillin-resistant strains of Staphylococcus aureus, were examined for affinity to penicillin-binding protein (PBP) 2a, which mediates methicillin resistance. The relative efficacy of each antibiotic was compared to vancomycin in a rabbit model of aortic valve endocarditis caused by either a methicillin-susceptible or methicillin-resistant strain of beta-lactamase-producing S. aureus. beta-lactamase inhibitors clavulanate and sulbactam were used in combination with ticarcillin and ampicillin, respectively. All beta-lactam antibiotics were effective against the susceptible strain. beta-lactam antibiotic activity in vitro and in vivo against the resistant strain correlated with its affinity for binding to PBP 2a. Lack of efficacy of beta-lactam antibiotics for the resistant strain was due to an inability to eradicate the resistant subpopulation of cells. Vancomycin was the most effective agent.
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PMID:Binding affinity for penicillin-binding protein 2a correlates with in vivo activity of beta-lactam antibiotics against methicillin-resistant Staphylococcus aureus. 238 96


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