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Biomedical subjects

F D Lowy

Publications and source records attributed to F D Lowy.

43 records · Page 3Linked to original sources

Synergy of combinations of vancomycin, gentamicin, and rifampin against methicillin-resistant, coagulase-negative staphylococci.

The activity of combinations of vancomycin (2 or 10 micrograms/ml), gentamicin (0.3 micrograms/ml), and rifampin (0.03 micrograms/ml) against methicillin-resistant, coagulase-negative staphylococcal isolates was determined by the time-kill method. Combinations of rifampin with gentamicin or with vancomycin 2 micrograms/ml demonstrated enhanced killing against 13 of 17 and 13 of 25 strains, respectively. However, rifampin-resistant strains were selected with the latter combination in the remaining 12 of 25 studies.

Coagulase↗

Reliability of in vitro susceptibility tests for detecting coagulase-negative staphylococcal resistance to penicillinase-resistant semisynthetic penicillins.

The reliabilities of five in vitro susceptibility tests (agar dilution, broth microdilution, automated MS-2, Kirby-Bauer disk diffusion, and ability to grow on methicillin-containing agar) to predict the susceptibility of 204 coagulase-negative staphylococcal isolates to penicillinase-resistant semisynthetic penicillins were compared. There was wide variation in susceptibility, with results ranging from 86.3% susceptible by MS-2 to 38.2% by growth on methicillin-containing agar. The results of the broth dilution techniques, including the MS-2, were significantly different (P less than 0.02) from the remaining tests. Nafcillin disks were less effective (P less than 0.02) than oxacillin disks in predicting resistance. Kirby-Bauer oxacillin disks and the ability to grow on methicillin-containing agar were the most reliable predictors of resistance. The MS-2 did not reliably predict resistance.

Coagulase↗

Effect of penicillin on the adherence of Streptococcus sanguis in vitro and in the rabbit model of endocarditis.

The effect of penicillin treatment of Streptococcus sanguis in vitro, on subsequent bacterial density in the bloodstream and on cardiac valves in the rabbit model of endocarditis was studied. As experimental tools for this study, isogenic pairs of S. sanguis differing in resistance to streptomycin or rifampin were prepared by genetic transformation. Rabbits with traumatized heart valves received an intravenous inoculation of penicillin treated (1 mug/ml) and untreated S. sanguis, each marked by resistance to either streptomycin or rifampin. The number of penicillin-treated and untreated bacteria attached to the valvular surfaces was determined by differential counting on streptomycin or rifampin containing media. Penicillin pretreatment reduced cardiac valve colonization 5 min after inoculation ("adherence ratio" x 10(8) was 4.11 for the control and 3.66 for the penicillin-treated bacteria, P < 0.001). The results were not due to differences in serum killing or bacterial densities in the bloodstream. There was no difference in valvular bacterial densities 24 h after bacterial inoculation (adherence ratio x 10(8), 7.26 untreated vs. 6.34 penicillin-pretreated, P > 0.10). In vitro experiments were performed using platelet-fibrin surfaces to test the possibility that penicillin-induced loss of lipoteichoic acid was responsible for decreased streptococcal adherence. Pretreatment of S. sanguis cultures with inhibitory concentrations of penicillin or with antiserum against lipoteichoic acid and precoating of the platelet-fibrin surfaces with lipoteichoic acid, all caused reduction in bacterial adherence. The findings are interpreted as support for the role of lipoteichoic acid as an adhesin in S. sanguis interactions with particular host tissue surfaces.

Adhesiveness↗

Staphylococcus epidermidis infections.

Staphylococcus epidermidis, an organism routinely found on the skin and in the hospital environment, has become a primary pathogen in infections associated with prosthetic devices. Because these infections are indolent and often clinically silent, diagnosis and therapy are often difficult. Pathogens are often misidentified as contaminants. Their variable, often resistant antibiotic susceptibility pattern and the uncertain correlation of in-vitro beta-lactam sensitivity testing with therapeutic efficacy make selection of an effective antibiotic regimen difficult. Vancomycin combined with rifampin, gentamicin, or both, is recommended for empiric therapy of these infections. Usually, removal of the prosthetic device is also necessary and may contribute equally to a successful therapeutic outcome.

Anti-Bacterial Agents↗

Therapy of methicillin-resistant Staphylococcus epidermidis experimental endocarditis.

Antibiotic therapy of methicillin-resistant Staphylococcus epidermidis endocarditis was investigated with the rabbit endocarditis model. Time-kill studies in vitro demonstrated that gentamicin and rifampin had the most rapid early bactericidal rates. With rifampin alone, rifampin-resistant subpopulations emerged. Combinations of antibiotics with gentamicin or rifampin in vitro did not significantly alter the killing rate but prevented emergence of subpopulations resistant to the latter. In the rabbit endocarditis model, gentamicin and vancomycin were the most effective single antibiotic regimens in terms of ability to reduce the bacterial densities on cardiac valve vegetations. Five treatment regimens were equally effective, including vancomycin, gentamicin, vancomycin plus rifampin or gentamicin, and rifampin plus gentamicin. The three-drug combination of vancomycin, rifampin, and gentamicin did not significantly improve the results. Cephalothin therapy was significantly less effective than any of the regimens noted above. It was no more effective than no treatment at 2 days and was only slightly more effective at 4 days. This result with cephalothin treatment was not predicted by routine types of in vitro antibiotic susceptibility testing. Treatment of rabbits with methicillin or cephalothin was associated with an increase in the subpopulation of bacteria resistant to the respective drugs. A number of regimens show potential for therapy of these infections, including vancomycin plus rifampin or gentamicin, rifampin plus gentamicin, and vancomycin alone.

Animals↗

Antibiotic activity in vitro against methicillin-resistant Staphylococcus epidermidis and therapy of an experimental infection.

Staphylococcus epidermidis is a major pathogen in early prosthetic valve endocarditis and cerebrospinal fluid shunt infections. Approximately 10 to 15% of hospital isolates are methicillin resistant. Ten clinically significant isolates of the latter were collected for antibiotic studies in vitro and in an experimental infection in animals. Time-kill studies of five strains showed gentamicin to be the single most effective antibiotic; however, dwarf colony variants emerged as survivors with two of these strains when challenged with gentamicin alone. The addition of a second antibiotic to gentamicin did not significantly improve the bactericidal rate but prevented the emergence of variant strains. A blood culture isolate of methicillin-resistant S. epidermidis combined with 5% hog gastric mucin was used to establish an experimental intraperitoneal infection in mice. Neither methicillin nor nafcillin treatment reduced mortality below that of untreated animals. Cephalothin treatment delayed early mortality but did not diminish overall mortality. Gentamicin was the most effective single antibiotic, and gentamicin in combination with vancomycin was the most effective regimen overall. The combination of rifampin plus vancomycin was as effective as gentamicin alone. The combinations of cephalothin or nafcillin with gentamicin and cephalothin with vancomycin demonstrated antagonism. The antagonism was not due to multiple injections or drug-drug inactivation.

Animals↗