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

Penicillin--"tolerant" Staphylococcus aureus strains are resistant to the lethal action of penicillins, but are inhibited by normal (low) concentrations. They are deficient in autolytic enzyme activity which appears to be necessary for bacteriolysis and the lethal action of penicillins. This "deficiency" is caused by a large excess of an inhibitor of autolysin. Seven such tolerant strains have been isolated from blood, bone, or sputum of patients who responded poorly to penicillin treatment of endocarditis, osteomyelitis, or staphylococcal pneumonia. These isolates were of different phage-types, and most showed cross-tolerance to the killing action of cephalosporins or vancomycin, antibiotics to which they were sensitive (inhibited). They were killed at normal rates by gentamicin, cycloserine, and rifampicin. Population analysis indicated that the proportion of tolerant organisms within a resistant strain is 7% or less; their ability to inhibit autolytic activity within their own and neighbouring cells appears to account for the net decreased autolytic activity of the entire strain; 44% of the bacteraemic strains studied showed penicillin tolerance. Tolerance is thus a common, clinically important form of penicillin resistance, that differs from previously described forms of pencillin resistance, that due to beta-lactamase, and that due to "intrinsic" (e.g., methicillin resistance) mechanisms.
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PMID:A new type of penicillin resistance of Staphylococcus aureus. 6 61

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.
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PMID:Single and combination antibiotic therapy of Staphylococcus aureus experimental endocarditis: emergence of gentamicin-resistant mutants. 25 Oct 69

Haemophilus influenzae is an aerobic pleomorphic gram-negative coccobacillus that requires both X and V factors for growth. It grows poorly, if at all, on ordinary blood agar unless streaked with Staph. aureus. It grows well on chocolate agar. Because this medium is often not used in culturing specimens from adults and because the organism may be overgrown by other bacteria, the frequency of H. influenzae infections has undoubtedly been seriously underestimated. This is aggravated by the failure of many physicians to obtain blood cultures in suspected bacterial infections and the failure of many laboratories to subculture them routinely onto chocolate agar. H. influenzae, along with Streptococcus pneumoniae, is a major factor in acute sinusitis. It is probably the most frequent etiologic agent of acute epiglottitis. It is probably a common, but commonly unrecognized, cause of bacterial pneumonia, where it has a distinctive appearance on Gram stain. It is unusual in adult meningitis, but should particularly be considered in alcoholics; in those with recent or remote head trauma, especially with cerebrospinal fluid rhinorrhea; in patients with splenectomies and those with primary or secondary hypogammaglobulinemia. It may rarely cause a wide variety of other infections in adults, including purulent pericarditis, endocarditis, septic arthritis, obstetrical and gynecologic infections, urinary and biliary tract infections, and cellulitis. Antimicrobial susceptibility testing is somewhat capricious in part from the marked effect of inoculum size in some circumstances. In vitro and in vivo results support the use of ampicillin, unless the organism produces beta-lactamase. Alternatives in minor infections include tetracycline, erythromycin, and sulfamethoxazole-trimethoprim. For serious infections chloramphenicol is the best choice if the organism is ampicillin-resistant or the patient is penicillin-allergic.
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PMID:Haemophilus influenzae infections in adults: report of nine cases and a review of the literature. 31 Sep 43

To assess the effect of protein binding by human serum on the synergistic interaction of penicillins with gentamicin, time-kill curves were determined for four penicillins alone and in combination with gentamicin against 10 blood isolates of enterococci. Killing curves demonstrated synergism with penicillin G plus gentamicin against all 10 strains in either broth or 50% human serum. In broth the combinations of nafcillin plus gentamicin and oxacillin plus gentamicin were synergistic against 10 of 10 strains and 4 of 10 strains, respectively. However, in serum, nafcillin plus gentamicin was synergistically bactericidal against only two strains and oxacillin plus gentamicin against none. Methicillin plus gentamicin was synergistic against none of the enterococci in either medium. Thus, the semisynthetic, penicillinase-resistant penicillins are unlikely to be effective in the therapy of patients with enterococcal endocarditis.
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PMID:Effect of protein binding on the activity of penicillins in combination with gentamicin against enterococci. 42 8

The effectiveness of cefazolin in Staphylococcus aureus endocarditis has been questioned because of in vitro inactivation by staphylococcal beta-lactamase. Cefazolin, although inactivated in vitro by S. aureus beta-lactamase, was as effective as cephalothin in the treatment of left-sided S. aureus endocarditis in rabbits. Cefazolin (20 mg/kg every 6 or 8 h), cephalothin (40 mg/kg every 6 h), and methicillin (40 mg/kg every 6 h), administered intramuscularly, were compared in the treatment of left-sided endocarditis caused in rabbits by a highly penicillin-resistant strain of S. aureus. The three antibiotics were all effective in reducing titers in vegetations. However, at the dose used, methicillin reduced the titers more rapidly than cephalothin or cefazolin. Cefazolin concentrations in serum were about double those achieved with cephalothin or methicillin. However, cefazolin was only half as active as methicillin and one-eighth as active as cephalothin in vitro in a serum assay. The half life in serum of cefazolin, cephalothin, and methicillin were each about 30 min. Serum bactericidal activities of the three antibiotics were very similar.
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PMID:Treatment of experimental Staphylococcus aureus endocarditis: comparison of cephalothin, cefazolin, and methicillin. 62 93

Semisynthetic penicillinase-resistant penicillins are recommended for therapy of Staphylococcus aureus endocarditis, but evaluation of the efficacy and safety of individual agents has received little attention. At The New York Hospital, 11 heroin addicts and 5 nonaddicts were treated with nafcillin. The 11 addicts did well clinically, but four of the five nonaddicts had severe complications, and three of them died. Important adverse reactions to nafcillin occurred in two patients: one developed leukopenia, and one developed an extensive rash. Methicillin was employed to treat two heroin addicts and four nonaddicts. Five of the six patients were cured bacteriologically, but three patients developed nephritis and one patient developed an extensive rash. Nafcillin appears to be highly efficacious for the treatment of S. aureus endocarditis, yielding results at least equal to those obtained with other drugs. Because adverse reactions appear to occur more frequently with methicillin than with nafcillin, we regard nafcillin as the preferable penicillinase-resistant penicillin for the treatment of S. aureus endocarditis.
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PMID:Nafcillin therapy for Staphylococcus aureus endocarditis. 70 23

The in vitro activity of sisomicin, netilmicin, nafcillin, and oxacillin against 35 strains of Staphylococcus aureus isolated from blood cultures of patients with endocarditis or septicemia was studied. The effects of combinations of either of the two newer aminoglycosides and either of the two penicillinase-resistant penicillins on the killing of S. aureus were investigated. All S. aureus strains were susceptible to the four antibiotics. Enhancement of antistaphylococcal activity was demonstrated by the antibiotic combinations.
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PMID:Enhancement of antistaphylococcal activity of nafcillin and oxacillin by sisomicin and netilmicin. 90 28

Previous in vitro studies demonstrating that the penicillinase-resistant penicillins act synergistically in combination with gentamicin against some enterococci have suggested that these combinations might be effective therapy for enterococcal infections in vivo. To determine the in vivo effectiveness of such combinations, we treated rabbits with enterococcal endocarditis with gentamicin and either nafcillin, oxacillin, or methicillin. Despite doses of the penicillins equivalent to 12 or 24 g/day in a 70-kg patient, the percentage of animals in each treatment group with sterile valves at autopsy after spontaneous death or sacrifice after 21 days of therapy was low. High-dose therapy with the penicillins did not significantly increase survival over the low-dose treatment groups. Thus, it seems prudent to include penicillin with a penicillinase-resistant penicillin and gentamicin as the initial therapy of patients with endocarditis possibly caused by enterococci.
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PMID:Penicillinase-resistant penicillins plus gentamicin in experimental enterococcal endocarditis. 92 Dec 43

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.
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PMID:Nafcillin-gentamicin synergism in experimental staphylococcal endocarditis. 104 88

The in vivo activity of the combination of daptomycin and fosfomycin against a beta-lactamase-producing, highly gentamicin-resistant strain of Enterococcus faecalis in a relapse model of rat endocarditis was studied. Minimum inhibitory concentrations (MICs) (micrograms per milliliter) for these agents against this strain were 4 (daptomycin) and 16 (fosfomycin). Time-kill studies demonstrated synergistic bactericidal activity when daptomycin (0.5 micrograms/ml) and fosfomycin (32 micrograms/ml) were combined. There was no significant difference between the number of valves sterilized by daptomycin alone [six (35%) of 17 valves sterilized] and daptomycin+fosfomycin [ten (59%) of 17 valves sterilized] p = 0.3. These results suggest that the in vitro bactericidal synergism demonstrable between these two agents against strains of enterococci will not necessarily translate into greater therapeutic efficacy in clinical infections.
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PMID:In vivo activity of the combination of daptomycin and fosfomycin compared with daptomycin alone against a strain of Enterococcus faecalis with high-level gentamicin resistance in the rat endocarditis model. 131 34


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