Persistent Salmonella infection in a female carrier for chronic granulomatous disease.
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Biomedical subjects
Publications and source records attributed to R C Moellering.
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Commercially available sealed blood-agar plates have been demonstrated to retain their usefulness for as long as 3 months under jungle conditions without refrigeration.
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The activities of cefotaxime and other aminothiazoyl oxime cephalosporins against Enterococcus faecalis were enhanced by addition of 5% sheep blood to Mueller-Hinton agar. This effect was not seen with aztreonam (aminothiazoyl oxime monobactam), cefotiam (aminothiazoyl, nonoxime), or other cephalosporins, and it was specific to the syn-configuration of the oxime moiety. Enhancement of cefotaxime activity was demonstrable against approximately 50% of 86 clinical isolates and could only be shown at low bacterial inocula. Human serum, serum alpha 1-, beta- and gamma-globulin fractions and albumin often antagonized or did not affect significantly the antimicrobial activity of cefotaxime, while the alpha 2-globulin fraction usually enhanced drug activity. The in vivo activity of cefotaxime against E. faecalis was examined in a rat peritoneal abscess model. The test organism was resistant to cefotaxime by standard methods (MIC greater than 128 micrograms/ml) but was inhibited by 1.0 microgram/ml when rat serum was presented in the medium. Cefotaxime reduced titers of bacteria within abscesses after 5 days of therapy (5.77 +/- 0.68 log10 CFU/g) in comparison with those in control animals (7.38 +/- 0.28 log10 CFU/g, p less than 0.05). Moxalactam, the in vitro activity of which was not augmented by serum, proved ineffective in the animal model. While these observations do not have direct therapeutic relevance, they offer a possible explanation for the relatively infrequent occurrence of enterococcal superinfection in patients treated with cefotaxime.
Combination with tazobactam substantially enhanced the activity of piperacillin against routine isolates of staphylococci, various Enterobacteriaceae, Acinetobacter anitratus, and Bacteroides fragilis. Tazobactam enhanced the activity of piperacillin more than fourfold against Pseudomonas aeruginosa spp. harboring eight of 12 plasmid-mediated beta-lactamases.
The clinical benefits of antimicrobial combinations in certain situations have been appreciated for over 30 years. Combinations of cell wall-active agents with aminoglycosides, of beta-lactams with inhibitors of beta-lactamase, and of drugs that inhibit separate steps along a critical metabolic pathway may produce an enhanced bactericidal effect. The concept that combination therapy may be advantageous when resistance to a single agent develops rapidly has been applied in the treatment of tuberculosis and in the design of regimens employing rifampin, a drug with excellent antimicrobial activity but against which resistance frequently develops. By permitting successful treatment of fungal infections with a smaller total dose of amphotericin B, combination therapy may reduce the risk of nephrotoxicity. Despite the drawbacks inherent in the use of multiple drugs, antimicrobial combinations continue to play an important role in clinical therapeutics.
Moxalactam and the third-generation cephalosporins are ineffective against enterococci in vitro. Therefore, the case reports of 2,107 patients treated with moxalactam for a variety of infections were reviewed for determination of the incidence of superinfection with enterococci. This complication occurred in 2.1% of the cases, most frequently in patients with urinary tract infections and urinary catheters. Seven patients developed enterococcal bacteremia during moxalactam therapy. It was not demonstrated that the presence of enterococci in initial cultures was associated with adverse therapeutic results in patients with skin, soft tissue, intraabdominal, and gynecologic infections.
Rifampin is active against enterococci in vitro; virtually all clinical isolates are inhibited by concentrations of less than or equal to 16 micrograms/ml. However, rifampin is bacteriostatic, not bactericidal, and resistance emerges rapidly when the drug is employed alone against enterococci in vitro. The combination of rifampin with beta-lactam drugs, aminoglycosides, or vancomycin generally gives indifferent results. Limited data from studies done in vivo are contradictory and do not document unequivocally that rifampin is strikingly active, even in combination with other agents, against enterococcal infections. Whether rifampin will ever play a role in therapy for enterococcal infections in humans remains to be determined.
Treatment with antimicrobial combinations is generally used to provide broad-spectrum coverage and/or to enhance antimicrobial activity (synergism). Extensive in vitro documentation of synergism exists for many such combinations, but an obvious benefit has been difficult to demonstrate clinically. Several types of therapeutically useful combinations often result in synergism; these combinations include a cell wall-active agent with an aminoglycosidic aminocyclitol, a beta-lactamase inhibitor with a beta-lactam antibiotic, and agents that inhibit sequential steps in a metabolic pathway. Combinations of beta-lactam antibiotics may be synergistic by means of several mechanisms, but such combinations have significant potential for antagonism when used against gram-negative bacilli and, thus, must be evaluated closely before clinical use.