Aminoglycoside use is limited by ototoxicity and nephrotoxicity. This study compared the incidences of toxicities associated with 2 recommended dosing regimens. Eighty-seven patients with tuberculosis or nontuberculous mycobacterial infections were prospectively randomized by drug to receive 15 mg/kg per day or 25 mg/kg 3 times per week of intravenous streptomycin, kanamycin, or amikacin. Doses were adjusted to achieve target serum concentrations. The size of the dosage and the frequency of administration were not associated with the incidences of ototoxicity (hearing loss determined by audiogram), vestibular toxicity (determined by the findings of a physical examination), or nephrotoxicity (determined by elevated serum creatinine levels). Risk of ototoxicity (found in 32 [37%] of the patients) was associated with older age and with a larger cumulative dose received. Vestibular toxicity (found in 8 [9%] of the patients) usually resolved, and nephrotoxicity (found in 13 [15%] of the patients) was mild and reversible in all cases. Subjective changes in hearing or balance did not correlate with objective findings. Streptomycin, kanamycin, and amikacin can be administered either daily or 3 times weekly without affecting the likelihood of toxicity.

Low antituberculosis drug serum concentrations occur frequently during the treatment of tuberculosis in patients with AIDS. Additional research is required for patients with drug-resistant tuberculosis, and to clarify the nature of the potential drug-drug interactions.

XDR TB and pre-XDR TB cases comprise a substantial fraction of MDR TB cases in California, indicating the need for interventions that improve surveillance, directly observed therapy, and rapid drug susceptibility testing and reporting.

From 1997 to 2000, Mycobacterium tuberculosis was diagnosed in two Asian elephants ( Elephas maximus ), three Rocky Mountain goats ( Oreamnos americanus ), and one black rhinoceros ( Diceros bicornis ) in the Los Angeles Zoo. DNA fingerprint patterns suggested recent transmission. An investigation found no active cases of tuberculosis in humans; however, tuberculin skin-test conversions in humans were associated with training elephants and attending an elephant necropsy.

Use of rifampin is required for short-course treatment regimens for tuberculosis. Tuberculosis caused by isolates of M. tuberculosis with resistance to rifampin and susceptibility to isoniazid is unusual, but it has been recognized through surveillance. Patients with tuberculosis (cases) with rifampin mono-resistance were compared with HIV-matched controls with tuberculosis caused by a drug-susceptible isolate. A total of 77 cases of rifampin mono-resistant tuberculosis were identified in this multicenter study. Three were determined to be laboratory contaminants, and 10 cases had an epidemiologic link to a case with rifampin mono-resistant tuberculosis, suggesting primary acquisition of rifampin-resistant isolates. Of the remaining 64 cases and 126 controls, there was no difference between cases and controls with regard to age, sex, race, foreign birth, homelessness, or history of incarceration. Cases were more likely to have a history of prior tuberculosis than were controls. Of the 38 cases and 74 controls with HIV infection, there was no difference between cases and controls with regard to age, sex, race, foreign birth, homelessness, history of incarceration, or prior tuberculosis. Cases were more likely to have histories of diarrhea, rifabutin use, or antifungal therapy. Laboratory analysis of available isolates showed that there was no evidence of spread of a single clone of M. tuberculosis. Further studies are needed to identify the causes of the development of rifampin resistance in HIV-infected persons with tuberculosis and to develop strategies to prevent its emergence.

Para-aminosalicylic acid granules produce adequate serum concentrations and appear to be safe.

Preventing transmission of multidrug-resistant tuberculosis is critical because of treatment toxicity, cost, and the lack of effective therapy for latent infection. We attempted to determine the extent of transmission in Los Angeles County by comparing relatedness of multidrug-resistant tuberculosis cases using restriction fragment length polymorphism and by cross-matching contact information to the Tuberculosis Registry. Strain typing was done on isolates of 102 pulmonary multidrug-resistant cases identified between August 1993 and 1998. Seventy-one (70%) of the cases had cavitary lesions on chest radiograph, and 94 (92%) had sputa smear-positive for acid fast bacilli. Fifteen (15%) of the cases were known to be infected with human immunodeficiency virus. Four molecular clusters of two cases each and one closely related pair were identified among the 102 cases; contact investigation successfully identified all clusters but one. Among 946 contacts identified and cross-matched with the county's Tuberculosis Registry, one secondary case due to drug-resistant Mycobacterium bovis was found. To summarize, a very high proportion of pulmonary multidrug-resistant tuberculosis cases in Los Angeles County were infectious. Molecular strain typing indicated limited spread of disease, although it underestimated transmission compared with contact investigation. We believe aggressive surveillance and case management were critical to limiting the spread of multidrug- resistant tuberculosis.

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