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Biomedical subjects

R C Moellering

Publications and source records attributed to R C Moellering.

At least 19 recordsLinked to original sources

Single-antibiotic therapy for streptococcal endocarditis.

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 wih 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.

Administration, Oral

Species-specific resistance to antimocrobial synergism in Streptococcus faecium and Streptococcus faecalis.

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.

Aminoglycosides

Effect of protein binding on the activity of penicillins in combination with gentamicin against enterococci.

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.

Blood Bactericidal Activity

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

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 mug of kanamycin per ml; all others were susceptible to </=32 mug/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 mug/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.

Acinetobacter

Isolation of Mycoplasma bovis from a patient with systemic illness.

Mycoplasma bovis was cultured from the sputum of a patient with lobar pneumonia, psychosis, and probable myocarditis, nephritis, and hemolytic anemia. Although we cannot be certain that this species of mycoplasma was the etiological agent of the patient's acute illness, this case report is of interest because, to the best of our knowledge, it represents the first isolation of M. bovis from a human source.

Adult

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

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.

Arthroplasty

Penicillin-netilmicin synergism against Streptococcus faecalis.

The combination of penicillin plus netilmicin was synergistic in vitro against 28 strains of Streptococcus faecalis and compared favorably with penicillin in combination with gentamicin. Similarly, penicillin plus netilmicin was as effective as penicillin plus gentamicin in the therapy of 67 rabbits with enterococcal endocarditis produced with a streptomycin-susceptible (S) or a streptomycin-resistant (R) strain of S. faecalis. After 5 days of infection, control rabbits had bacterial titers of 10(10) colony-forming units (CFU)/g of vegetation. Those treated with penicillin plus netilmicin had mean titers of 10(5.2) and 10(5.1) CFU/g for S and R strains, respectively, and those treated with penicillin plus gentamicin had mean valve titers of 10(5.8) CFU/g for both strains. After 10 days of therapy, mean valve titers with penicillin plus netilmicin were 10(3.8) and 10(4.7) CFU/g, and with penicillin plus gentamicin they were 10(4.5) and 10(5.4) CFU/g for S and R strains, respectively. Thus, if netilmicin proves to be less toxic than other aminoglycoside antibiotics, it may have potential usefulness in the therapy of enterococcal endocarditis.

Animals

Antimicrobial susceptibility of flavobacteria.

Antimicrobial susceptibility patterns of 28 clinical isolates of Flavobacterium sp. were determined by standard disk diffusion technique and by antimicrobial dilution in agar. Rifampin, clindamycin, trimethoprim-sulfamethoxazole, cefoxitin, and vancomycin are among the antimicrobial agents which may be clinically useful to treat infections caused by flavobacteria. All 28 isolates were resistant to erythromycin with minimal inhibitory concentrations of 32 mug/ml or more. Currently recommended interpretive zones of inhibition by disk diffusion did not reliably predict antimicrobial susceptibility of the 28 flavobacteria isolates when compared with the agar dilution technique, and, therefore, a more direct measurement of minimal inhibitory or bactericidal concentration is recommended.

Anti-Bacterial Agents

Plasmid-mediated resistance to antibiotic synergism in enterococci.

Mating experiments have shown that high-level resistance (minimal inhibitory concentration greater than 2,000 microgram/ml) to streptomycin and kanamycin, and resistance to penicillin-streptomycin and penicillin-kanamycin synergism are transferable by conjugation from resistant clinical isolates of enterococci to a sensitive recipient strain. Cesium chloride-ethidium bromide ultracentrifugation revealed a satellite (plasmid) band in resistant clinical isolates and the transconjugant strains but not in the sensitive recipient. Examination of these satellite bands by agarose gel electrophoresis and electron microscopy demonstrated a common plasmid with a weight of 45 megadaltons. Novobiocin treatment of a resistant clinical isolate produced simultaneous loss of high-level resistance to streptomycin and kanamycin, and of resistance to penicillin-aminoglycoside synergism. These results suggest that (a) high-level resistance to streptomycin and kanamycin among some clinical isolates of enterococci is associated with a 45 megadalton plasmid, and (b) the same plasmid is also responsible for the resistance to penicillin-aminoglycoside synergism observed in these strains.

Aminoglycosides