Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0014118 (endocarditis)
 15,629 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The efficacy of nafcillin and gentamicin used alone and in combination at doses giving serum concentrations comparable to those achieved in patients was studied in rabbits with experimental Staphylococcus aureus endocarditis. The organism used was a penicillinase-producing, methicillin-susceptible, clinical isolate. The addition of gentamicin to nafcillin significantly increased the rate of killing of organisms in valvular vegetations, compared to the effect of nafcillin alone. Gentamicin alone delayed mortality but was not effective in reducing the bacterial populations of the vegetations. Bacteremia persisted in the animals treated with gentamicin alone, in contrast to the groups treated with nafcillin or the combination. Selection of a subpopulation of aminoglycoside-resistant small-colony variants occurred in animals treated with gentamicin alone. This variant was subsequently employed in the rabbit model and produced endocarditis, metastatic infection, and bacteremia comparable to those caused by the parent strain. Animals with infection produced by the variant died later than animals infected by the parent strain. Nafcillin was equally effective in reducing the population of both parent and variant strains in vitro and in therapy of the infected animals. Population studies showed the variant to be a mutant emerging at a rate of 1.9 x 10(-7). It was shown to differ from the parent strain in coagulase and hemolysin production, colonial morphology, and aminoglycoside susceptibility, but was similar by light and electron microscopy and in phage type, pigmentation of colonies, deoxyribonuclease production, mannitol fermentation, and growth rate.
 ...
PMID:Single and combination antibiotic therapy of Staphylococcus aureus experimental endocarditis: emergence of gentamicin-resistant mutants. 25 Oct 69

Staphylococcus epidermidis is a major pathogen in early prosthetic valve endocarditis and cerebrospinal fluid shunt infections. Approximately 10 to 15% of hospital isolates are methicillin resistant. Ten clinically significant isolates of the latter were collected for antibiotic studies in vitro and in an experimental infection in animals. Time-kill studies of five strains showed gentamicin to be the single most effective antibiotic; however, dwarf colony variants emerged as survivors with two of these strains when challenged with gentamicin alone. The addition of a second antibiotic to gentamicin did not significantly improve the bactericidal rate but prevented the emergence of variant strains. A blood culture isolate of methicillin-resistant S. epidermidis combined with 5% hog gastric mucin was used to establish an experimental intraperitoneal infection in mice. Neither methicillin nor nafcillin treatment reduced mortality below that of untreated animals. Cephalothin treatment delayed early mortality but did not diminish overall mortality. Gentamicin was the most effective single antibiotic, and gentamicin in combination with vancomycin was the most effective regimen overall. The combination of rifampin plus vancomycin was as effective as gentamicin alone. The combinations of cephalothin or nafcillin with gentamicin and cephalothin with vancomycin demonstrated antagonism. The antagonism was not due to multiple injections or drug-drug inactivation.
 ...
PMID:Antibiotic activity in vitro against methicillin-resistant Staphylococcus epidermidis and therapy of an experimental infection. 25 21

An outbreak of prosthetic valve endocarditis due to methicillin-resistant Staphylococcus epidermidis prompted a change in antimicrobial prophylaxis for open heart surgery in a general hospital from a regimen of aqueous penicillin G, methicillin, and kanamycin to a 5-day regimen of cefazolin and gentamicin. As a result, total gentamicin use in the hospital more than doubled. Increased resistance of pseudomonas and serratia isolates paralleled the increased total use of gentamicin. For pseudomonas species, the incidence of gentamicin resistance increased from 3 to 15%; for serratia species, from 8 to 88%; and for the total of both organisms, from 4 to 28%. Resistance decreased rapidly after removal of gentamicin from the prophylaxis regimen. Review of serratia isolates from the urinary tract showed that gentamicin resistance was associated with prior antibiotic therapy, especially with gentamicin, care on the surgical services, especially the surgical intensive care unit, and presence of indwelling bladder catheters. Gentamicin use in a 5-day antimicrobial prophylaxis regimen for open heart surgery can represent a large proportion of the total hospital use of that antibiotic, with potential adverse effects on hospital flora.
 ...
PMID:Gentamicin use and Pseudomonas and Serratia resistance: effect of a surgical prophylaxis regimen. 34 94

Stable nonhemolytic small colony variants were isolated in pure culture from nine of 30 Staphylococcus aureus clinical strains after incubation of log10 7.0 cfu for 48 hr in MH broth containing 1.0 microgram/ml gentamicin. The variants resembled Staphylococcus epidermidis on blood agar, but they were positive for tube coagulase and thermostable nuclease at 24 hr and fermented mannitol slowly. The infectivity and virulence of four variants were compared to four parent S. aureus and three S. epidermidis strains in a rabbit model of endocarditis. Log10 5.0 cfu of the variant S. aureus, parent S. aureus, or S. epidermidis strains were injected intravenously into rabbits with intracardiac catheters. Quantitative culture of vegetations demonstrated endocardial infection in 47 of 49 (96%) animals injected with S. aureus variants, 44 of 44 injected with S. aureus parent strains, and four of 21 (19%) S. epidermidis-injected animals. The mortality rate in untreated animals within 4 days was five of 49 (10%) for variant S. aureus, 33 of 44 (75%) for parent S. aureus, and 0 of 21 for S. epidermidis. Small colony variants of S. aureus may be mistaken for S. epidermidis, but the variants are significantly more infective than S. epidermidis and are more likely to cause endocarditis. Gentamicin-induced S. aureus small colony variants are as infective but less virulent than their parent S. aureus strains.
 ...
PMID:Virulent gentamicin-induced small colony variants of Staphylococcus aureus. 45 50

The amikacin sensitivity of bacteria cultured from 3282 clinical cases of mixed type was determined. Gentamicin and amikacin were equally effective against E. coli strains. Amikacin inhibited the growth of more Pseudomonas aeruginosa strains than did gentamicin. Against Gram-positive bacteria gentamicin proved to be more effective. Many of the gentamicin-resistant strains were sensitive to amikacin. Amikacin levels were measured during 21 pulmonary and 14 heart operations, subsequent to a intramuscular administration of 500 mg amikacin. The serum contained 17-20 microgram/ml amikacin, in the intact, inflamed and tumourous parts of removed lung tissue 9, 6 and 6 microgram/g concentrations were detected, respectively, whereas the cardiac auricle and the pericardial fluid contained 3-4 and 2-4 microgram/ml, respectively. These amikacin levels reach or in most cases even exceed the minimal inhibiting concentrations against the bacteria. Therefore, amikacin is excellent for the treatment of respiratory infections, pericarditis and endocarditis caused by Gram-negative, gentamicin-resistant bacteria. Amikacin treatment of 8 patients with grave diseases as well as the successful local administration of amikacin based on the therapy of 55 cases of surgical suppurations is reported.
 ...
PMID:Amikacin: in vitro bacteriological studies, levels in human serum, lung and heart tissue, and clinical results. 51 16

The bactericidal rate of nafcillin and the combination of nafcillin and gentamicin against Staphylococcus aureus were compared in vitro and in experimental endocarditis. The combination proved synergistic against 8 strains of S. aureus in broth. In rabbits with S. aureus endocarditis, the organism was eradicated more rapidly from cardiac vegetations when animals were treated with the combination than with nafcillin alone. Gentamicin alone was ineffective. This combination is under study in the therapy of acute endocarditis caused by penicillinase-producing S. aureus.
 ...
PMID:Nafcillin-gentamicin synergism in experimental staphylococcal endocarditis. 104 88

From 1969 to 1974, 19 cases of Serratia marcescens endocarditis were observed in the San Francisco Bay Area. Seventeen patients were intravenous drug users, and Serratia caused 14% of all addict-associated endocarditis in San Francisco. Serratia strains were nonpigmented and had typical antibiotic sensitivities, except that 9 of the isolates exhibited colonial variation, with each variant having different antibiotic sensitivities. Aortic or mitral valves were involved in 13 patients, and heart failure developed in 9 of these. Twelve patients had embolic episodes to brain, iliofemoral arteries, or lung. Five of 6 patients with tricuspid valvulitis were cured by antibiotics either with (1) or without excision of the valve. All 12 patients with aortic or mitral valvulitis treated medically died; 11 had unremitting sepsis. Aortic valve replacement and antibiotics were effective in 1. Gentamicin combined with either carbenicillin or chloramphenicol was the most effective treatment regimen.
 ...
PMID:Serratia marcescens endocarditis: a regional illness associated with intravenous drug abuse. 110 90

The rate at which various antimicrobial agents eradicated Staphylococcus aureus from cardiac vegetations in a rabbit model of endocarditis was studied. The rate at which various drugs and combinations killed high titers of bacteria in broth correlated with the relative effectiveness of the agents in vivo. Gentamicin plus penicillin proved to be synergistic in vitro and more effective in eradicating bacteria from cardiac vegetations in vivo than was penicillin alone. Vancomycin killed bacteria at a rate similar to that for the combination of penicillin and gentamicin, and the rate for cefazolin was similar to that for penicillin alone. Clindamycin was less effective in vivo and in vitro than penicillin. Therapy with rifampin led to the emergence of resistant organisms, and, when penicillin, this drug was less effective in vitro and in vivo than was penicillin alone. This model appears to offer an effective method for evaluation of antimicrobial treatment of staphylococcal endocarditis.
 ...
PMID:Antimicrobial therapy of experimental endocarditis caused by Staphylococcus aureus. 111 94

The addition of gentamicin therapy in a case of S aureua endocarditis, in which the response to methicillin therapy alone was unsatisfactory, resulted in clinical improvement, enhanced serum bactericidal activity, and a bacteriologic cure. Gentamicin and methicillin were synergistic in vitro. Since the mortality in staphlococcal endocarditis remains exceedingly high, we suggest that the combination of a cell wall active antibiotic, such as methicillin, and an aminoglycoside may prove to be effective alternate theraphy for this disease.
 ...
PMID:Combination antibiotic therapy in staphylococcal endocarditis. The use of methicillin sodium-gentamicin sulfate therapy. 126 57

The efficacy of tazobactam, a beta-lactamase inhibitor, in combination with piperacillin, was studied in vitro and in rabbit experimental endocarditis due to a Klebsiella pneumoniae strain (KpR) producing an extended-spectrum beta-lactamase, TEM-3, or its nonproducing variant (KpS). In vitro, piperacillin was active against KpS (MIC = 4 micrograms/ml, MBC = 8 micrograms/ml with 10(7)-CFU/ml inoculum) but not against KpR (MIC = MBC = 256 micrograms/ml). Tazobactam (1 microgram/ml) restored the activity of piperacillin against KpR (MIC = 2 micrograms/ml, MBC = 4 micrograms/ml). Gentamicin was active against both strains (MIC = 0.25 and 0.5 micrograms/ml for KpS and KpR, respectively). The piperacillin-tazobactam-gentamicin combination was synergistic in vitro. The piperacillin/tazobactam ratio in plasma and in vegetations was always lower than the 4/1 injected dose ratio. In vivo, piperacillin (300 mg/kg of body weight four times a day [QID]) was active against KpS but not against KpR. Tazobactam (75 mg/kg QID) was able to restore the in vivo effect of piperacillin (300 mg/kg QID) against KpR (-3.0 log10 CFU/g of vegetation versus that of controls). Gentamicin (4 mg/kg twice a day [BID]) was active against both strains. Compared with controls, the combination of gentamicin plus piperacillin against KpS (-5.6 log10 CFU/g of vegetation), and the gentamicin-piperacillin-tazobactam combination against KpR (-4.4 log10 CFU/g of vegetation) achieved the greatest decrease in bacterial counts in vegetations and were the only regimens that significantly increased the proportion of sterile vegetations. It is concluded that (i) tazobactam was able to restore the effect of piperacillin against a TEM-3 extended-spectrum Beta-lactamase-producing strain of K. pneumoniae, both in vitro and in a severe experimental infection with high inoculum, when used in a 4/1 piperacillin/tazobactam dose ratio; (ii) gentamicin alone was effective because of the high peak/MBC ratio in plasma; (iii) piperacillin-tazobactam-gentamicin, probably because of the effect of gentamicin in reducing bacterial inoculum in vivo, as stressed by the results obtained by piperacillin-gentamicin against KpS, may be the most effective regimen against KpR.
 ...
PMID:Piperacillin, tazobactam, and gentamicin alone or combined in an endocarditis model of infection by a TEM-3-producing strain of Klebsiella pneumoniae or its susceptible variant. 132 34


1 2 3 4 5 Next >>