F. Meunier-Carpentier

Significance of antimicrobial synergism for the outcome of gram negative sepsis.

Amikacin plus penicillin (A+P) was compared to amikacin plus carbenicillin (A+C) in a double-blind study. Therapy with one of these combinations was given, as soon as servere infection was suspected, to 117 patients with proved gram negative infection, none of whom was granulocytopenic. Gram negative bacteremia was documented retrospectively in 52 patients; 25 had received A+P and 27 had been treated with A+C. All the isolated gram negative pathogens were sensitive to amikacin (MIC less than 12 microng/ml). In the A+P group, 55 per cent of the patients responded favorably while in the A+C group 63 per cent did respond; the difference was more striking for bacteremic patients: 52 per cent responded in the A+P group and 70 per cent in the A+C group. This difference, however, was not statistically significant. The outcome of patients whose infection was treated by synergistic combinations against the offending pathogen was better (66 per cent) than that observed in patients who received nonsynergistic combinations (48 per cent) (p less than 0.05). Once again the results were more striking in the bacteremic patients (p less than 0.01). A favorable outcome was associated also with a high (larger than or equal to 1/8) bactericidal activity of the diluted serum of the treated patient against the offending pathogen (p less than 0.05). This study suggests that the optimal therapy in gram negative septicemia might be the administration of synergistic combinations of antibiotics.

Clinical evaluation of teicoplanin for therapy of severe infections caused by gram-positive bacteria.

Teicoplanin was evaluated in 47 patients with severe infections, including 14 patients with bone infections, 11 patients with soft-tissue infections, 7 patients with endocarditis, 5 patients with pneumonia, 3 patients with septic thrombophlebitis, 3 patients with septicemia of unknown origin, and 4 patients with miscellaneous infections. Overall, bacteremia was documented in 24 patients. The pathogens isolated were 35 strains of Staphylococcus aureus (including 8 methicillin-resistant strains), 4 strains of Staphylococcus epidermidis, 4 strains of Streptococcus faecalis, 2 strains of Streptococcus pneumoniae, 5 strains of other streptococci, and 1 Micrococcus luteus strain. A total of 22 patients (46.8%) were clinically cured, 8 patients (17.0%) improved, 2 patients (4.3%) had relapses after initial improvement, and 15 patients (31.9%) failed to respond. The results were better in nonbacteremic patients (19 of 23 patients [82.6%] were cured or improved) than in patients with bacteremia (12 of 24 patients [50%] were cured or improved). Bacteriological cure occurred in 25 patients (53.2%), and superinfections were documented in 6 patients (12.8%). No major adverse effects were observed. We conclude that teicoplanin is a potentially effective and well-tolerated antimicrobial agent for therapy of nonbacteremic infections caused by gram-positive bacteria.

Double-blind, placebo-controlled study of oxacillin combined with rifampin in the treatment of staphylococcal infections.

A total of 101 patients with proven Staphylococcus aureus infection were included in a double-blind, placebo-controlled study; this study compared oxacillin (12 g/day, intravenously) or vancomycin (2 g/day, intravenously) plus rifampin (1,200 mg/day, orally) with oxacillin or vancomycin plus placebo. We evaluated 65 patients. Of the patients tested, 33 received oxacillin plus rifampin (13 bacteremias), and 32 received oxacillin plus placebo (16 bacteremias). Clinical cure was achieved in 61% of the patients treated with oxacillin plus rifampin and in 56% of the patients treated with oxacillin plus placebo. Improvement was noted in 27 and 25%, respectively, and failure occurred in 9 and 18%, respectively. These differences were not statistically significant. Bacteriological failure occurred in 3 and 28%, respectively (P less than 0.05). None of the failures within the rifampin-treated group was associated with the emergence of a rifampin-resistant mutant. The rates of superinfection were similar in both groups. The geometric means of the serum bactericidal activity after 1, 6, and 11 h were, respectively, 22, 17, and 9 after treatment with oxacillin plus rifampin and 25, 3.4, and 2.3 after treatment with oxacillin plus placebo. It was suggested that the addition of rifampin to oxacillin or vancomycin might only be beneficial to severely ill patients.

Comparative Trial of Single‐Dose Versus Twice‐Daily Sisomicin in Bacteriuric Patients

Sisomicin was administered as a single daily intramuscular injection (160 mg) or as two daily injections (80 mg) to 50 patients with bacteriuria superimposed on chronic urologic diseases in a randomized controlled fashion. The administration of two daily doses was significantly more effective (P less than 0.01) in achieving cure than the injection of a single daily dose. The renal function, as expressed by creatinine clearance, became impaired significantly more often (P less than 0.05) in the patients receiving the single daily dose of sisomicin.

Comparative study of three routes of administration of sisomicin.

A comparative study was performed using three routes of administration of sisomicin (1 mg/kg as single dose): intramuscular injection, intravenous rapid injection, and 1-hour infusion. Intravenous administration resulted in higher blood levels immediately after the injections than by the intramuscular route; however, later, the intramuscular injection resulted in optimal blood levels. High levels of sisomicin which were bactericidal for most Gram-negative bacilli were found in the urine of the treated patients. The antimicrobial activity of the serum obtained 1 hour after administration of sisomicin, as determined against 20 strains of Gram-negative microorganisms isolated from blood cultures, was identical with all three routes of administration of sisomicin.