Myles E. Gombert

Disseminated Mycobacterium marinum Infection After Renal Transplantation

Excerpt Despite its widespread occurrence in nature,Mycobacterium marinuminfrequently causes disease in humans (1). Although first isolated from saltwater fish (2) and later seen as a cause of tube...

Synergism of imipenem and amikacin in combination with other antibiotics against Nocardia asteroides.

The in vitro activities of imipenem (formerly imipemide, N-formimidoyl thienamycin, or MK0787) and amikacin in combination with cefotaxime, trimethoprim-sulfamethoxazole, and each other were tested against 26 Nocardia asteroides strains. The agar dilution method was used for all tests. Synergy was present in 80% of tests with imipenem-trimethoprim-sulfamethoxazole, in 92% of tests with imipenem-cefotaxime, and in 83% of tests with amikacin-trimethoprim-sulfamethoxazole. Indifference was found on rare occasions, and no antagonism was seen.

Diffusion of a new beta-lactam (LY 127935) into cerebrospinal fluid: Implications for therapy of gram-negative bacillary meningitis

LY 127935, a new oxa beta-lactam with an expanded gram-negative spectrum, was administered intravenously to seven patients, including two patients with documented gram-negative bacillary meningitis. In the patients receiving continuous therapy (2 g intravenously every 8 hours) cerebrospinal fluid trough levels of LY were never less than 6 micrograms/ml. Peak cerebrospinal fluid levels of LY ranged from 25 to 39 micrograms/ml and occurred approximately 2.5 hours after the intravenous administration of the drug. Cerebrospinal fluid levels of LY were 19 per cent to greater than 100 per cent of simultaneous serum levels. Cerebrospinal fluid bactericidal activity was 1:4 to 1:256. Intravenous LY, because of its expanded gram-negative spectrum and excellent cerebrospinal fluid penetration, is a potentially useful antibiotic in the treatment of gram-negative bacillary meningitis.

Therapy of experimental cerebral nocardiosis with imipenem, amikacin, trimethoprim-sulfamethoxazole, and minocycline.

A mouse model of cerebral nocardiosis was used to determine relative antibiotic efficacy by reducing bacterial colony counts per gram of brain tissue. The antimicrobial agents employed were demonstrated in vitro to be inhibitory to most strains of Nocardia asteroides at very low concentrations. The agents used in this study were imipenem-cilastatin, amikacin, trimethoprim-sulfamethoxazole, and minocycline. Antibiotics were administered every 4 h for 72 h before animal sacrifice. Bacterial colony counts were assayed at various time points before the completion of therapy. Imipenem-cilastatin and amikacin were the most effective agents tested. Trimethoprim-sulfamethoxazole was less effective than imipenem and amikacin but more effective than minocycline. Minocycline did not eradicate intracerebral organisms and was similar to saline (control) in its effects.

Therapy of pulmonary nocardiosis in immunocompromised mice.

We compared the bactericidal efficacies of various antimicrobial agents and combinations thereof in experimentally induced Nocardia asteroides pneumonia in immunocompromised mice. Cortisone acetate treatment, which produced impaired cell-mediated immune function, was followed by nasal inoculation of 5 x 10(4) CFU of N. asteroides into each mouse. Therapy was begun 24 h after inoculation and continued for the next 96 h. Dosages of antimicrobial agents resulted in concentrations approximating levels in human serum. Animals from each of nine treatment groups were sacrificed every 24 h. The pulmonary tissue obtained was homogenized and quantitatively cultured. Results were calculated to indicate the number of CFU per gram of lung tissue. Amikacin and imipenem were the two most effective single agents studied. Sulfadiazine and ciprofloxacin were ineffective, and ceftriaxone reduced bacterial counts modestly. Combination therapy did not enhance the bactericidal activities of the agents tested. We conclude that amikacin and imipenem, as well as select broad-spectrum cephalosporins, represent therapy superior to the sulfonamides in this experimental model and may represent alternative treatment for patients who cannot tolerate sulfa agents (e.g., human immunodeficiency virus-infected patients) or who fail primary treatment.

Susceptibility of Nocardia asteroides to new quinolones and beta-lactams.

The susceptibility of 31 strains of Nocardia asteroides to various quinolones and beta-lactams, as well as coumermycin, amikacin, and minocycline, was determined by the agar dilution technique. Ciprofloxacin was the most active fluoroquinolone tested on a weight basis, as it inhibited approximately 50% of the isolates at achievable drug levels in serum. Ceftriaxone and cefpirome were the most active cephalosporins in this system with MICs of 8 micrograms/ml for 80% of strains tested. Imipenem, amikacin, and minocycline were the most effective agents tested.

Susceptibility of Gram-Positive Cocci to Various Antibiotics, Including Cefotaxime, Moxalactam, and N-Formimidoyl Thienamycin

The activities of cefotaxime, moxalactam, MK 0787 (N-formimidoyl thienamycin), ampicillin, oxacillin, vancomycin, and clindamycin were compared against gram-positive cocci. MK 0787 was the most active and moxalactam was the least active of these drugs, except against methicillin-resistant Staphylococcus aureus, where vancomycin was most active, and penicillin-resistant pneumococci, where cefotaxime was more active.

Strategies for the management of varicella-susceptible healthcare workers after a known exposure.

Three different sequentially applied post-varicella zoster virus (VZV) exposure management strategies were employed over a 43-month period. We began by using a standard post-exposure protocol in which 50 susceptible healthcare workers (HCW) involved in hospital exposures were furloughed from work at a loss to the hospital of 424 workdays and

Synergistic Effect of N-Formimidoyl Thienamycin with Gentamicin and Amikacin Against Streptococcus faecalis

46,000. Of the eight nosocomial cases of VZV infection in HCWs, four (50%) caused future HCW and patient exposure. In trial I, we substituted a post-exposure screening procedure for the standard work furlough procedure. We screened 77 exposed staff resulting in one nosocomial VZV infection that was the source of another exposure incident. No secondary cases of varicella resulted from this exposure and only 20 days of furlough time were used during trial I. As VZV resulting from a home exposure source was responsible for most hospital exposures in which HCWs were the source, our trial II protocol added the Centers for Disease Controls (CDC) off-duty procedure, but limited its use to susceptibles exposed at home. The 43-month overall attack rate of nosocomial varicella was 4.7%, while the true home exposure attack rate was 79% (p less than .00001). There was an average of 42.4 lost workdays charged to the hospital per incident under the standard protocol and three days per incident in the combined experience of trials I and II (p less than .0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Cefoperazone Therapy of Complicated Urinary Tract Infections: Pharmacokinetics in Renal Transplant Recipients

The in vitro activities of N-formimidoyl thienamycin alone and in combination with amikacin and gentamicin were tested against 10 strains of Streptococcus faecalis. Synergy was demonstrated in 35% of the combinations tested by the microtiter checkerboard technique; 50% were found to be synergistic with time killing curves.