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Biomedical subjects

R C Moellering

Publications and source records attributed to R C Moellering.

At least 163 records · Page 9Linked to original sources

Common adverse effects of antibacterial agents on major organ systems.

Antibiotics contribute significantly to the management of the surgical patient. However, their potential for adverse effects, both toxic and allergic, must always be kept in mind. We have reviewed the major adverse reactions to antibiotics, so that side effects may be promptly recognized and treated. Armed with this information, the surgeon can more effectively utilize this valuable class of drugs for the benefit of the patient.

Adult↗

A novel mechanism of resistance to penicillin-gentamicin synergism in Streptococcus faecalis.

A patient with enterococcal endocarditis, who relapsed after repeated courses of apparently adequate treatment with ampicillin plus gentamicin, was subsequently cured with ampicillin-tobramycin therapy. The organisms isolated from this patient were strains of Streptococcus faecalis that were resistant to penicillin (or ampicillin)-gentamicin synergism but not to penicillin (or ampicillin)-tobramycin synergism. The mechanism of resistance in these strains appears to be related to a specific defect in the intracellular uptake of gentamicin (but not tobramycin) in the presence of penicillin.

Dose-Response Relationship, Drug↗

Evidence of plasmid-mediated production of aminoglycoside-modifying enzymes not previously described in Acinetobacter.

Two blood culture isolates of Acinetobacter calcoaceticus subsp. anitratus (Herellea vaginicola) were recently observed to be unusually resistant to aminoglycosides. Each strain was found to contain aminoglycoside-modifying enzymes which have not been described previously in this species, including 2"-adenylyltransferase, 3"-adenylyltransferase, 3'-phosphotransferase-III, and 3-acetyltransferase. Treatment of one strain (H-S) with novobiocin led to a loss of resistance to multiple antimicrobial agents and a loss of two aminoglycoside-modifying enzymes; agarose gel electrophoresis of lysates of this strain revealed that the loss of resistance markers was associated with the loss of a large-molecular-weight plasmid. Treatment of the second strain (H-D) with novobiocin produced derivative strains with three different resistance patterns. Agarose gel electrophoresis of deoxyribonucleic acid from crude lysates and from cesium chloride-ethidium bromide gradients of this strain showed only a small plasmid (molecular weight, 5 X 10(6)) common to all variants and failed to explain the loss of resistance markers.

Acinetobacter↗

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↗