Mycobacterial Infections

Mycobacterium tuberculosis

Overview

Tuberculosis is considered a serious complication of organ transplantation, with associated mortality approaching 30%. The worldwide incidence of M. tuberculosis infections in recipients of organ transplantation is 0.35% to 15%. Transplant recipients are at risk for both primary and reactivation infection, and disseminated infection occurs more frequently than in immunocompetent hosts. The diagnosis and treatment of tuberculosis in this population is often delayed because of atypical and extra-pulmonary presentations of this disease. This infection is rarely transmitted by the allograft.

Clinical Presentation

Transplant recipients may present with cavitary pulmonary, genitourinary, intestinal, cutaneous, central nervous system, bone, or disseminated disease. Because these many different presentations, symptoms and signs depend on the site(s) of involvement. Usually, patients have fever accompanied by malaise, night sweats, and weight loss.

The diagnosis of tuberculosis requires a high index of suspicion. The tuberculin skin test is positive in approximately 25% to 33% of infected transplant recipients. Tuberculosis needs to be excluded as a diagnosis in any transplant recipient with pulmonary infiltrates. In cases of suspected tuberculosis, acid fast smears and special cultures are performed on the appropriate clinical specimens. In the event that the initial expectorated sputum and gastric washings are unrevealing, bronchoalveolar lavage or lung biopsy are required to make the diagnosis. Histo-pathology of biopsy specimens can demonstrate granulomas. All M. tuberculosis isolates require susceptibility testing to exclude resistance to anti-tuberculosis agents.

Treatment

Transplant patients with active tuberculosis require nine to twelve months of therapy with at least two bactericidal agents to which the isolate is susceptible, preferably with combinations of isoniazid, rifampin, and pyrazinamide. Several regimens are available and have been extensively reviewed in the literature. The treatment of multi-drug resistant tuberculosis poses a particular challenge, and second-line agents must be used. However, outcomes in other immunosuppressed populations have not been very satisfactory, and surgical approaches to eliminate disease are undertaken frequently.

Anti-tuberculous agents have potential toxicities and interactions with immu-nosuppressive agents: isoniazid is hepatotoxic, rifampin is hepatotoxic, streptomycin is ototoxic and nephrotoxic, and ethambutol may cause optic neuritis.

Rifampin is a potent inducer of hepatic metabolic enzymes. During rifampin therapy, careful monitoring of immunosuppressant drug levels (such as cyclosporine and tacrolimus) is recommended because rifampin therapy is associated with subtherapeutic immunosuppressive drug levels and allograft rejection. Rifabutin may be an alternative agent to rifampin as it has a lesser effect on drug levels.

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