Resection of the right middle lobe and lingula for mycobacterial infection.

BACKGROUND: In a series of 229 patients infected with mycobacterial organisms, we noted a specific female phenotype that involves isolated infections of the middle lobe and lingula. METHODS: Thirteen patients were found to have infections of the middle lobe, lingula, or both. All of them were infected with Mycobacterium other then Mycobacterium tuberculosis, all were women, 12 of the 13 were slender, and most had variable combinations of skeletal abnormalities. All underwent resection of the middle lobe, lingula, or both. RESULTS: There were no operative deaths. Only 2 patients have had reactivation requiring additional antibiotic therapy. All patients have had a decreased number of pulmonary infections in the postoperative period. Anatomic findings at operation included a complete major fissure and at least a partially complete minor fissure with middle lobe resections or an elongated lingula. CONCLUSIONS: Mycobacterial infection of the middle lobe and lingula is primarily a disease of asthenic women and is often associated with skeletal abnormalities and complete fissures or an elongated lingula. We recommend that surgical intervention be performed early once the condition is identified.

Potential interaction between itraconazole and clarithromycin.

Three patients negative for human immunodeficiency virus infection were admitted for pulmonary Mycobacterium avium complex (MAC) and aspergillosis infections. They were treated with different drug combinations, but all regimens included clarithromycin for MAC and itraconazole for aspergillosis. All patients experienced an increase in clarithromycin concentrations and clarithromycin: 14-OH-clarithromycin ratio compared with expected range values. They had no clinical side effects. The time course suggested a possible interaction between clarithromycin and itraconazole, presumably through itraconazole's effects on cytochrome P450 3A4 activity. A bidirectional interaction cannot be ruled out. The data suggest that, when necessary, these two drugs can be administered together safely. Further investigation is necessary to determine the extent and clinical consequences of coadministration in humans.

Pharmacokinetic evaluation of para-aminosalicylic acid granules.

STUDY OBJECTIVE: To determine the bioavailability and renal elimination of para-aminosalicylic acid (PAS) and its inactive metabolite acetyl-para-aminosalicylic acid (AcPAS) from a new PAS formulation. DESIGN: (a) Single-dose pharmacokinetic study in healthy volunteers; (b) Day-1 and day-8 pharmacokinetic comparison in patients with multidrug-resistant tuberculosis (MDR-TB). SETTING: Referral hospital that specializes in the treatment of mycobacterial infections. PATIENTS: (a) Twelve healthy male and female volunteers recruited by the investigators. Eleven subjects (92%) completed the study; one subject could not maintain venous access and was removed from the study. (b) Six sequential male and female patients receiving multidrug treatment for advanced MDR-TB. All patients completed the study. INTERVENTIONS: (a) Volunteers received a single 4-g dose of enteric-coated PAS granules administered with food. Blood and urine samples were collected over 24 hours after the dose. (b) Patients received 4-g doses of enteric-coated PAS granules every 8 hours for 7 days as part of their treatment regimen. Blood samples were obtained at approximately 2, 4, and 8 hours after the first dose on day 1 and the twenty-second dose on day 8. MEASUREMENTS AND MAIN RESULTS: Concentrations of PAS and AcPAS were determined using high-performance liquid chromatography. The serum concentration-time curves from volunteers and patients showed sustained PAS concentrations, in contrast to immediate-release sodium PAS tablets. In the six patients with tuberculosis, day 8 concentrations were considerably higher than those on day 1, and all were sustained well above the PAS minimal inhibitory concentration for Mycobacterium tuberculosis. CONCLUSIONS: Para-aminosalicylic acid granules produce adequate serum concentrations and appear to be safe.

CT findings in 14 patients with Mycobacterium chelonae pulmonary infection.

OBJECTIVE: The purpose of this report is to describe helical and high-resolution CT findings in 14 patients with pulmonary infection caused by Mycobacterium chelonae, a nontuberculous mycobacterial species that has become increasingly recognized as a rare but significant cause of chronic lung infection in immunocompetent patients. CONCLUSION: Bronchiectasis, nodules, and consolidation are the most common CT features of M. chelonae pulmonary infection. Cavities are less common. These CT findings resemble those reported for Mycobacterium avium complex. In this study, M. chelonae pulmonary infection occurred exclusively in middle-aged and older women.

Mycobacterium terrae: case reports, literature review, and in vitro antibiotic susceptibility testing.

Mycobacterium terrae infection can cause debilitating disease that is relatively resistant to antibiotic therapy. Two cases are presented, and data from an additional 52 reports from the literature are reviewed. Tenosynovitis of the upper extremity, often following trauma, was the most commonly reported presentation (59% of cases), with pulmonary disease occurring in an additional 26% of cases. Underlying medical problems were absent (44%) or not reported (28%) in 72% of the cases. One-half of the patients with upper extremity tenosynovitis were treated with local or systemic corticosteroids, before microbiological identification. Only one-half of the patients with tenosynovitis who were followed up for 6 months had clinical improvement or were cured. The other one-half of the patients required repeated debridement, tendon extirpation, or amputation. The best antimicrobial therapy for M. terrae infection is unknown but might include a macrolide antibiotic plus ethambutol and one other effective drug for at least 12 months after clinical response. Parenteral treatment with an aminoglycoside and surgery may be useful in selected cases.

Once-daily and twice-daily dosing of p-aminosalicylic acid granules.

The study objective was to determine the minimum frequency of dosing for standard 4-g doses of p-aminosalicylic acid (PAS) granules. Two sequential six-patient pharmacokinetic studies are described, followed by clinical data from 40 subsequent patients. All patients had multidrug-resistant tuberculosis (MDR-TB). Serum was collected at two to three time points after dosing, and assayed by a validated high performance liquid chromatography (HPLC) assay. Data were analyzed using noncompartmental methods. In six patients, twice-daily dosing produced median serum concentrations at 4, 8, and 12 h post-dose of 25.8, 23.2, and 16.4 microgram/ml. In six patients, once-daily dosing produced median serum concentrations at 6, 12, and 24 h post-dose of 23.4, 3.7, and 0 microgram/ml. In 40 patients, twice-daily dosing produced median serum concentrations at 4 to 8 and 9 to 12 h post-dose of 24.8 and 20.6 microgram/ml. Unlike once-daily dosing, twice-daily PAS maintained serum concentrations in excess of 1 microgram/ml, the typical minimal inhibitory concentration against Mycobacterium tuberculosis, for the entire dosing interval. We now use twice-daily PAS granules for our patients with MDR-TB.

Nontuberculous mycobacterial disease following hot tub exposure.

Nontuberculous mycobacteria (NTM) have been recognized as an important cause of disease in immunocompromised hosts. Pulmonary disease caused by NTM is increasingly recognized in previously healthy persons. Investigation of pulmonary disease affecting a family of five identified an indoor hot tub as the source of NTM-related disease.

Dual skin testing with Mycobacterium avium sensitin and purified protein derivative: an open study of patients with M. avium complex infection or tuberculosis.

The sensitivity and specificity of dual mycobacterial skin testing were assessed in an unblinded study of 22 patients with culture-confirmed Mycobacterium avium complex (MAC) infection and 20 patients with culture-confirmed Mycobacterium tuberculosis infection. Intradermal skin tests were performed with 0.1 mL of M. avium sensitin, 0.1 mL of PPD (purified protein derivative), and two control antigens (mumps and Candida). All patients with M. tuberculosis infection reacted to the skin tests; the mean reaction size was 19.7 +/- 1.4 mm when PPD was administered and 10.3 +/- 1.5 mm when M. avium sensitin was administered. Four patients with MAC were anergic; for the remaining 18, mean reactions of 15.2 +/- 1.4 mm to M. avium sensitin and 4.3 +/- 1.3 to PPD were noted. A skin test was defined as M. avium-dominant or PPD (M. tuberculosis)-dominant if there was a minimum reaction size of > or = 5 mm to the given species, and the reaction to the given species was > or = 3 mm greater than the reaction to the heterologous species. Dominant skin test reactions were present in 18 (90%) of 20 patients with M. tuberculosis and 15 (83%) of 18 nonanergic patients with MAC. The specificity of dominant skin tests was 100% for infection with M. tuberculosis and 100% for infection with MAC. M. avium-dominant skin tests identify subjects with prior MAC infection and distinguish them from patients with M. tuberculosis infection.

Abscesses due to mycobacterium abscessus linked to injection of unapproved alternative medication.

An unlicensed injectable medicine sold as adrenal cortex extract (ACE*) and distributed in the alternative medicine community led to the largest outbreak of Mycobacterium abscessus infections reported in the United States. Records from the implicated distributor from January 1, 1995, to August 18, 1996, were used to identify purchasers; purchasers and public health alerts were used to identify patients. Purchasers and patients were interviewed, and available medical records were reviewed. Vials of ACE* were tested for mycobacterial contamination, and the product was recalled by the U.S. Food and Drug Administration. ACE* had been distributed to 148 purchasers in 30 states; 87 persons with postinjection abscesses attributable to the product were identified. Patient and vial cultures contained M. abscessus identical by enzymatic and molecular typing methods. Unusual infectious agents and alternative health practices should be considered in the diagnosis of infections that do not respond to routine treatment.