Showing papers by "Robert C. Moellering published in 1979"

Species-Specific Resistance to Antimicrobial Synergism in Streptococcus faecium and Streptococcus faecalis

Abstract: Combinations of penicillin with various aminoglycosidic aminocyclitols were tested against a collection of clinical isolates of Streptococcus faecium in vitro and were used to treat endocarditis caused by S. faecium in the rabbit model. S. faecium proved more resistant to penicillin than Streptococcus faecalis. Even more striking, however, was the resistance to in vitro synergism by combinations of penicillin and various aminoglycosides. At clinically achievable concentrations, penicillin-gentamicin was the only combination that was synergistic against all strains that were tested. Combinations of penicillin and streptomycin and penicillin and amikacin were synergistic only against those strains that were not highly resistant to streptomycin and kanamycin, respectively. Combinations of penicillin with kanamycin, tobramycin, sisomicin, or netilmicin failed to produce synergism against any of these strains. The possible clinical significance of these findings was verified by use of the rabbit model of endocarditis. Combinations of penicillin with gentamicin or streptomycin were synergistic in the therapy of endocarditis that was produced by a strain of S. faecium that did not have a high level of resistance to aminoglycosides. However, the combination of penicillin and netilmicin was no more effective than penicillin alone.

Endocarditis Due to Resistant Viridans Streptococci during Oral Penicillin Chemoprophylaxis

Abstract: OPTIMAL management of patients with rheumatic heart disease or a previous bout of acute rheumatic fever includes the administration of prophylactic antibiotics to prevent pharyngeal infection with Group A streptococci.1 , 2 Several studies have shown that oral penicillin prophylaxis is associated with a high prevalence of penicillin-resistant bacteria in the gingival flora.3 4 5 6 7 8 9 An original concern was that continuous low-dose prophylaxis would result in a high incidence of endocarditis due to resistant organisms that would be difficult to cure. Follow-up studies of large numbers of patients taking prophylactic penicillin have found no increase in the incidence of endocarditis,10 and few cases of . . .

Single-antibiotic therapy for streptococcal endocarditis.

Abstract: Ninety-nine patients treated with penicillin G potassium, cephalothin sodium, or vancomycin hydrochloride were studied to evaluate single-drug therapy for nonenterococcal streptococcal endocarditis. Eighty-six patients survived; of these, 66 received penicillin alone. The maximum serum bactericidal titer obtained at the expected nadir of serum antibiotic concentration was 1:8 or greater in 70 (95%) of the 74 patients studied. No relapse occurred among the 66 patients treated with penicillin. Only one patient experienced a relapse that occurred following therapy with suboptimal doses of vancomycin. Distinct second episodes of endocarditis occurred in five patients. While 13 patients died, none died of intractable infection. The treatment of endocarditis due to penicillin-susceptible streptococci with high-dose parenteral penicillin or a bactericidal penicillin substitute for four weeks or longer results in bacteriologic cure rates comparable with those achieved with combined penicillin-streptomycin regimens. ( JAMA 241:1801-1806, 1979)

Aminoglycoside-modifying enzymes among clinical isolates of Acinetobacter calcoaceticus subsp. anitratus (Herellea vaginicola): explanation for high-level aminoglycoside resistance.

Abstract: Acinetobacter calcoaceticus subsp. anitratus (Herellea vaginicola) is an important cause of nosocomial infection in our hospital where A. calcoaceticus subsp. anitratus is the most frequently isolated gram-negative species resistant to one or more of the aminoglycoside antibiotics. Of 167 strains tested for susceptibility to aminoglycosides, only 6 strains were found that were resistant to ≥128 μg of kanamycin per ml; all others were susceptible to ≤32 μg/ml. Five of these six strains were found to produce aminoglycoside-modifying enzymes. Two strains produced a phosphotransferase which mediates resistance to kanamycin and neomycin; three strains produced an acetyltransferase which mediates resistance to kanamycin, tobramycin, and amikacin (minimal inhibitory concentration ≥ 128 μg/ml for each drug). No strain with lower level resistance to kanamycin, tobramycin, or amikacin had enzyme activity. Fourteen strains resistant to gentamicin failed to show significant enzymatic modification of that antibiotic. Although agarose gel electrophoresis of deoxyribonucleic acid preparations from the enzyme-producing strains showed plasmid bands in all, no transfer of aminoglycoside resistance could be achieved, nor was it cured by exposure to novobiocin, ethidium bromide, acridine orange, heat, or prolonged storage. Resistance to mercuric chloride, present in 2 of 60 strains, was lost by 1 strain after exposure to novobiocin, and the loss of resistance was associated with an apparent deletion of plasmid deoxyribonucleic acid.

Effect of Protein Binding on the Activity of Penicillins in Combination with Gentamicin Against Enterococci

Abstract: 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.

In vitro activity of three tetracycline antibiotics against Acinetobacter calcoaceticus subsp. anitratus.

Abstract: The in vitro activity of three tetracycline antibiotics against 127 strains of Acinetobacter calcoaceticus (Herella vaginicola) were compared. Almost all strains were susceptible to minocycline and doxycycline, whereas most strains were resistant to tetracycline.

The effect of hypotensive anesthesia on cephalothin concentrations in bone and muscle of patients undergoing total hip replacement.

Abstract: Serial blood, muscle, and bone concentrations of cephalothin following intravenous infusion were determined in forty-eight patients during total hip replacement. Thirty patients received hypotensive anesthesia and the remaining eighteen received anesthesia without induced hypotension. The concentrations of cephalothin were determined during the first (early) and second (late) hours of the operation. Late serum levels were lower in the patients who had induced hypotension. In all patients at least one bone specimen contained measurable amounts of cephalothin. When pentolinium (Ansolysen) was used to induce hypotension, the late serum and early bone cephalothin concentrations were lower, while use of trimethaphan (Arfonad) did not appear to result in lower cephalothin concentrations in serum, muscle, or bone compared with patients with normotensive anesthesia.