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M D Iseman

Publications and source records attributed to M D Iseman.

At least 109 records · Page 6Linked to original sources
PubMed1986

Pyrazinamide is not active in vitro against Mycobacterium avium complex.

Strains of M. tuberculosis that elaborate pyrazinamidase are typically susceptible in vitro and in vivo to pyrazinamide (PZA). However, we found that 33 strains of M. avium complex (MAC), all of which were pyrazinamidase-positive, were resistant in vitro to a high concentration (100 micrograms/ml) of PZA when tested at low pH in 7H12 broth by radiometric (BACTEC) method. The drug was equally ineffective against these bacteria within cultured normal human macrophages. We conclude that the pyrazinamidase test is not suitable for susceptibility studies against M. avium complex. On the basis of our in vitro studies, which support earlier data, we believe that PZA is not appropriate for therapy of MAC disease.

Amidohydrolases↗
PubMed1986

Short-course chemotherapy of tuberculosis: the harsh realities.

Recent studies have indicated that it is possible to successfully treat even far-advanced tuberculosis with a variety of chemotherapy regimens ranging in duration from 4.5 to 9 months. Furthermore, much or all of some regimens can be given twice-weekly. However, three major barriers remain to widespread success: (1) Noncompliance with prescribed treatment; (2) increasing prevalence of drug resistance; and, (3) sorely limited resources in impoverished segments of the third world. While noncompliance is responsible for a greater number of treatment failures, increasing levels of drug resistance pose a greater long-term threat due to a protracted carrier-vector state, soaring costs for adequate drug regimens, and--ultimately--the conversion of an imminently treatable infection into an unmanageable scourge--the resurrection of the "White Plague."

Antitubercular Agents↗
PubMed1985

Disseminated infection with Mycobacterium avium-intracellulare. A report of 13 cases and a review of the literature.

Thirteen cases of disseminated infection with Mycobacterium avium-intracellulare (MAI) seen at the National Jewish Hospital and Research Center and 24 cases from the literature were analyzed to define clinical and therapeutic features of the disease. Disseminated MAI infection was a disease of immunocompromised and apparently normal hosts. It was acquired from the environment by unknown mechanisms, usually entering the body through the lungs and spreading to include the reticuloendothelial system, bones, and less commonly, the skin. Diagnosis was often delayed and required culture of tissue or secretions. Medical personnel must maintain a high index of suspicion for MAI disease, especially in immunocompromised hosts. These patients should be monitored carefully for evidence of MAI with frequent cultures of blood and bone marrow. Blood culture systems able to recover MAI promptly and reliably should be employed (52, 64). New diagnostic aids, such as the standardized preparation of PPD-B currently being prepared or tests for antibody to MAI, will help in differentiating MAI from other processes. If MAI is recovered, broad-spectrum therapy should be instituted. Response to combination antimicrobial chemotherapy in the patients surveyed in this report was gratifying. Over two-thirds of treated patients responded to therapy. New antimycobacterial agents such as ansamycin and thienamycin have been shown to have activity against MAI in vitro (40, 81, 92) and may further improve therapeutic efficacy. Studies of in vitro synergy, currently in progress in our laboratory, will also help define the optimal therapeutic regimen for each individual patient. While the patients presented in this report had a reassuring response to therapy, those who had many bacilli in the tissues had a poorer outcome. Patients with AIDS often have this lepromatous histology (37) and thus may respond more poorly than the patients in this report even when optimal therapy is employed. Careful monitoring of AIDS patients for MAI infection may permit earlier institution of therapy and improve the chances for control of the infection. Studies to assess the relationship of in vitro sensitivity to therapeutic response in these patients are currently underway in our laboratory. It is hoped that early institution of therapy and optimization of regimens according to in vitro sensitivity data will lead to decreased morbidity and mortality in all patients with MAI infection.

Acquired Immunodeficiency Syndrome↗
PubMed1985

Determination of in vitro susceptibility of Mycobacterium tuberculosis to cephalosporins by radiometric and conventional methods.

Among eight cephalosporins and cephamycins tested in preliminary in vitro screening against Mycobacterium tuberculosis, the most promising for further study was found to be ceforanide, followed by ceftizoxime, cephapirin, and cefotaxime. Moxalactam, cefoxitin, cefamandole, and cephalothin were found to be not active enough against M. tuberculosis to be considered for further in vitro studies. The antibacterial activity of various ceforanide concentrations was investigated by three methods: (i) the dynamics of radiometric readings (growth index) in 7H12 broth; (ii) the number of CFU in the same medium; and (iii) the proportion method on 7H11 agar plates. There was a good correlation among the results obtained with these methods. The MIC for most strains ranged from 6.0 to 25.0 micrograms/ml. The BACTEC radiometric method is a reliable, rapid, and convenient method for preliminary screening and determination of the level of antibacterial activity of drugs not commonly used against M. tuberculosis.

Biotransformation↗
PubMed1985

Determination of ansamycin MICs for Mycobacterium avium complex in liquid medium by radiometric and conventional methods.

A radiometric method to determine the MIC of ansamycin (LM427) for Mycobacterium avium complex clinical isolates has been developed. It is based on a comparison of the conventional growth curve determination and the radiometric detection of growth (growth index) in the same liquid medium (7H12 broth). This new method requires less time and labor than does a conventional determination of MIC in liquid medium (CFU). Other advantages of this method include relatively short periods of exposure of the drug to 37 degrees C and the composition of 7H12 broth, which has practically no substrates which could absorb or bind the drug. Thus, a more accurate estimation of the MIC in this medium can be expected than by the conventional agar dilution (proportion) method. The MICs of ansamycin appeared to be higher in agar plates than in 7H12 broth. More than 70% of the isolates had a broth-determined MIC one to three times lower than the average peak concentration of ansamycin achieved in sera of patients. The wide range of MICs suggests the importance of testing susceptibility in broth with many concentrations in addition to, or rather than in, agar plates with concentrations of 2.0 or 1.0 micrograms/ml only. Taking into account relatively low levels of ansamycin in sera of patients, it would be appropriate to compare the MICs with the levels in serum to make the outcome of chemotherapy more predictable.

Anti-Bacterial Agents↗
PubMed1985

Radiometric method for testing susceptibility of mycobacteria to pyrazinamide in 7H12 broth.

The test of susceptibility to pyrazinamide requires an acid environment (pH less than or equal to 5.5). This, however, is not favorable to the growth of Mycobacterium tuberculosis, especially in solid agar media. To obviate this difficulty, we developed a testing method with 7H12 broth medium and based on radiometric readings of the growth. The radiometric method employed in this study (BACTEC system) provides an opportunity to detect the dynamics of growth by daily recording of the growth index, which reflects the metabolic activity of the multiplying bacteria. In our technique, M. tuberculosis isolates were initially cultivated at pH 6.8. After logarithmic growth had begun, phosphoric acid solution was added to obtain pH 5.5. When pyrazinamide was added simultaneously with the acid, the growth index of susceptible cultures decreased, whereas it continued to increase in pH 5.5 control vials and in tests with pyrazinamide-resistant strains.

Amidohydrolases↗
PubMed1985

Determination of in vitro susceptibility of mycobacteria to ansamycin.

The in vitro susceptibility of different mycobacterial species to ansamycin (LM427) in concentrations of 2.0, 1.0, 0.5, and 0.2 micrograms/ml was determined by the agar dilution method. For those strains of M. tuberculosis and M. avium complex tested, susceptibility to ansamycin was compared with susceptibility to rifampin. All M. tuberculosis strains susceptible to rifampin were susceptible to ansamycin; the strains that were highly resistant to rifampin also were resistant to ansamycin. The majority of M. avium complex strains were "naturally" resistant to rifampin (1.0 micrograms/ml and higher), but only approximately 13% of them were resistant to ansamycin in a concentration of 1.0 microgram/ml. The cross-resistance in M. avium strains was made apparent only by comparing patterns of resistance to low concentrations of ansamycin (0.5 microgram/ml) with patterns of resistance to higher concentrations of rifampin (5.0 and 10.0 micrograms/ml).

Anti-Bacterial Agents↗
PubMed1985

Dynamic aspects of the in vitro chemotherapeutic activity of ansamycin (rifabutine) on mycobacterium intracellulare.

The in vitro action of ansamycin against Mycobacterium intracellulare was studied using continuous, dynamic (a rapidly falling off concentration simulating that existing in vivo in humans), and pulsed exposures. Ansamycin at a concentration of 5 micrograms/ml showed bactericidal activity starting from as early as 3 days after constant exposure. In the dynamic model with the drug present in bactericidal concentration for only 2 h a day, bactericidal activity was demonstrated. With pulsed exposure, a minimal period of 72 to 96 h is necessary for effective inhibitory action.

Anti-Bacterial Agents↗
PubMed1981

Tuberculosis in association with pregnancy.

A review was made of the records of 27 patients admitted to National Jewish Hospital who developed or experienced a reactivation of pulmonary tuberculosis during pregnancy or the first 12 month post partum. Sixteen patients had drug-resistant disease, and 11 had drug-susceptible disease. The drug-resistant group had more extensive radiographic abnormalities(p less than 0.01), longer sputum conversion times (p less than 0.05), and a higher incidence of pulmonary complications and death (p = 0.05). Patients with tuberculosis associated with pregnancy have the same clinical presentation as nonpregnant patients. Tuberculosis during pregnancy should be treated, and the drugs that appear to be safest for the fetus include isoniazid, para-aminosalicylic acid, ethambutol, and rifampin.

Adolescent↗