Combination Antibiotic Therapy in Staphylococcal Endocarditis

Murray, Henry W.

doi:10.1001/archinte.1976.03630040082017

Cited by 36 publications

(7 citation statements)

References 25 publications

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“…With limited clinical experiences (9), synergistic combinations of penicillinase-resistant penicillins with aminoglycoside (3, [11][12][13][14] offer some promise. Rifampin, which has high activity against S. aureus in vitro (5,7), is another possibility for either a single or combination drug regimen (2,4,10).…”

mentioning

confidence: 99%

In Vitro Activity of Rifampin Alone and in Combination with Nafcillin and Vancomycin Against Pathogenic Strains of Staphylococcus aureus

Tuazon

Lin

Sheagren

1978

Antimicrob Agents Chemother

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Twenty strains of Staphylococcus aureus isolated from patients with endocarditis were examined in vitro for susceptibility to rifampin, nafcillin, and vancomycin and to combinations of rifampin with nafcillin or vancomycin. Minimum bactericidal concentrations of rifampin ranged from 0.0031 to 0.0125 yg/ml, of nafcillin ranged from 0.078 to 0.312 ,ug/ml, and of vancomycin ranged from 0.312 to 1.25 pg/ml. The combination of rifampin with nafcillin was synergistic for 12 strains; the combination of rifampin plus vancomycin was synergistic for 5 of the isolates.Although penicillins resistant to penicillinase are currently the drugs of choice for treatment of Staphylococcus aureus infections, there is a need for more effective agents and/or therapeutic regimens. With limited clinical experiences (9), synergistic combinations of penicillinase-resistant penicillins with aminoglycoside (3,(11)(12)(13)(14) offer some promise. Rifampin, which has high activity against S. aureus in vitro (5, 7), is another possibility for either a single or combination drug regimen (2, 4, 10). The current study deals with the activity of rifampin, nafcillin, and vancomycin, singly and in combination, against strains of S. aureus known to be pathogenic for man. MATERIALS AND METHODSTwenty strains of coagulase-positive S. aureus recently isolated from patients with endocarditis were studied. Nafcillin sodium, vancomycin hydrochloride, and rifampin were supplied by Wyeth Laboratories Inc., Eli Lilly and Co., and Ciba Pharmaceutical Co., respectively. Standard stock solutions of each antibiotic, prepared by dissolving the lyophilized powders in sterile solutions per the manufacturer's instructions, were stored at -70°C and thawed immediately before use. At the time of each study, drug dilutions were done in brain heart infusion (BHI) broth.Minimal inhibitory concentrations and minimal bactericidal concentrations (MBCs) of nafcillin, vancomycin, and rifampin alone and in combination were determined in vitro using a microtiter checkerboard dilution method (8,15). Nafcillin concentrations ranged from 2.5 to 0.02 ,g/ml, vancomycin concentrations ranged from 5.0 to 0.039 ug/ml, and rifampin concentrations ranged from 0.01 to 0.0004 gsg/ml. An The MBC was read as the lowest concentration of drug in which there was no growth of the test organism after plating 10 A1 of solution from each well and reincubating at 37°C for 18 to 24 h. Since the MBC was always within one dilution of the minimal inhibitory concentration, all data are based on MBCs.Drug combinations were considered "fully synergistic" if inhibition occurred at one-fourth or less of the MBC for both drugs. If inhibition had occurred with concentrations exceeding the MBC of either drug, "antagonism" between the two antibiotics would have been demonstrated. "Partial synergism" was judged to have occurred when the MBC of one of the antibiotics in the combination was at least one-fourth of the MBC of that antibiotic alone, whereas the MBC of the second antibiotic was only one-half of the concen...

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In Vitro Activity of Rifampin Alone and in Combination with Nafcillin and Vancomycin Against Pathogenic Strains of Staphylococcus aureus

Tuazon

Lin

Sheagren

1978

Antimicrob Agents Chemother

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“…Penicillin therapy alone has usually proved unsuccessful [1], Several suggestions have been made recommending combined antimicrobial therapy, even in cases of Streptococcus viridans [2,3] or Staphylococcus aureus endocarditis [4], tra-' ■ This work was a cooperative effort and was not supported by any granting agency.…”

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confidence: 99%

Is Penicillin Alone Effective in Enterococcal Endocarditis?

Thadepalli¹,

Mandal²,

Rambhatla³

et al. 1981

Chemotherapy

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Enterococcal endocarditis in man is traditionally treated with penicillin and an aminoglycoside. Whether penicillin alone is adequate has not been fully evaluated. Experimental enterococcal endocarditis (EEE) in male New Zealand rabbits, when untreated, was fatal in all animals within 2 weeks. When crystalline penicillin G was given at 30,000 U/day in three equally divided doses, the fatality rate was 63.3%; when the dosage was increased to 600,000 U/day, the mortality was 37.5%, demonstrating the ineffectiveness of crystalline penicillin alone in EEE. Procaine penicillin at 300,000 U/day given as a single dose provided increased protection, but was still associated with unacceptably high mortality (17.5%). A higher dose level, 600,000 U/day, of procaine penicillin protected all animals with EEE. High and sustained levels of penicillin in the serum and the myocardium cured enterococcal endocarditis in rabbits.

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“…In vitro synergy between penicillin and gentamicin against GBS has been reported (2, 4, 7). However, this combination may prove to be clinically impractical in cases of meningitis since the aminoglycosides do not achieve high levels in the cerebrospinal fluid (5).Recently, rifampin has become important in the combination therapy of clinical and experimental staphylococcal endocarditis (12,13 …”

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“…Recently, rifampin has become important in the combination therapy of clinical and experimental staphylococcal endocarditis (12,13 …”

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Effect of rifampin on ampicillin killing of group B streptococci

Smith¹,

Eng²,

Landesman³

1982

Antimicrob Agents Chemother

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The activity of rifampin against group B streptococci as a single agent and in combination with ampicillin was examined. The minimum concentration of rifampin required to inhibit 90% of the isolates of group B streptococci (18 of 20 isolates) was 0.6 ,ug/ml. The checkerboard double-dilution studies of these two antibiotics and the time-killing studies both indicate that rifampin inhibits the bactericidal activity of ampicillin for group B streptococci.Group B streptococci (GBS) are the leading causes of meningitis, septicemia, and other severe infections within the first few weeks of life (14). Other serious infections, such as septic arthritis, pyelonephritis, and endometritis, can also be caused by GBS in adults (3, 10). In general, GBS are susceptible to penicillin and ampicillin, and these have been the antibiotics of choice in treating the wide range of diseases caused by these organisms. Recently, clinical failures and relapses due to GBS have been reported after appropriate therapy with penicillin or ampicillin (4,16). Some failures may result from the persistence of tolerant organisms (8,15) or from infection involving a high density of organisms (1).Clinically, the combination of ampicillin or penicillin and an aminoglycoside has resulted in the improvement of several cases of endocarditis, septic arthritis, and pyelonephritis (15, 16). In vitro synergy between penicillin and gentamicin against GBS has been reported (2, 4, 7). However, this combination may prove to be clinically impractical in cases of meningitis since the aminoglycosides do not achieve high levels in the cerebrospinal fluid (5).Recently, rifampin has become important in the combination therapy of clinical and experimental staphylococcal endocarditis (12,13

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Combination Antibiotic Therapy in Staphylococcal Endocarditis

Cited by 36 publications

References 25 publications

In Vitro Activity of Rifampin Alone and in Combination with Nafcillin and Vancomycin Against Pathogenic Strains of Staphylococcus aureus

In Vitro Activity of Rifampin Alone and in Combination with Nafcillin and Vancomycin Against Pathogenic Strains of Staphylococcus aureus

Is Penicillin Alone Effective in Enterococcal Endocarditis?

Effect of rifampin on ampicillin killing of group B streptococci

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