Which drugs are most effective to prevent tuberculosis in organ transplant recipients?

Organ transplantation is often the best treatment option for patients with end-stage kidney, pancreas, heart, liver and lung disease. A major risk for transplant recipients is organ rejection. Although anti-rejection drugs improve survival, they weaken the immune system and increase the risk of infection, cancer, and cardiovascular disease.

Preventing and managing infection is a major challenge in organ transplant recipients. Tuberculosis (TB) is a particular concern because organ transplant recipients are up to 300 times more likely to contract this infection than people in the general population. TB can be difficult to diagnose because it can develop in different organs and body tissues aside from lungs.

We investigated whether drugs to prevent TB after transplant could reduce the disease in the post-transplant period. We found three studies that looked at 558 kidney transplant recipients in India and Pakistan where TB rates are high.

We found that taking the drug isoniazid (a tablet) during the first year after kidney transplant provided protection against developing TB. However, this drug also significantly increased the risk of liver damage. Most drug-related liver damage occurred in people who already had liver problems caused by hepatitis B or C. We also found that there was no difference in numbers of deaths from any cause between those who received the anti-TB drug and those who did not.

Although we found that isoniazid should be given to kidney transplant recipients in areas where TB is known to be a risk, further studies are needed in people who have received other organ transplants such as liver, lungs and heart, and where TB rates are low, to determine the wider benefits and harms of anti-TB drugs.

Authors' conclusions: 

Isoniazid prophylaxis for kidney transplant recipients reduced the risk of developing TB post-transplant. Kidney transplant recipients in settings that have high prevalence of TB should receive isoniazid during the first year following transplant. There is however, significant risk of liver damage, particularly among those who are hepatitis B or C positive. Further studies are needed among recipients of other solid organ transplants and in settings with low prevalence of TB to determine the benefits and harms of anti-TB prophylaxis in those populations.

Read the full abstract...
Background: 

Organ transplant recipients are at increased risk of infection as a result of immunosuppression caused inadvertently by medical treatment. Tuberculosis (TB) is a challenging infection to manage among organ transplant recipients that can be transmitted from infected people or triggered from latent infection. Organ transplant recipients have been reported to be up to 300 times more likely to develop TB than the general population. Consensus about the use of antibiotic prophylaxis to prevent post solid organ transplant TB has not been achieved.

Objectives: 

This review assessed the benefits and harms of antibiotic prophylaxis to prevent post solid organ transplant TB.

Search strategy: 

We searched the Cochrane Renal Group's Specialised Register up to 30 April 2013 through contact with the Trials' Search Co-ordinator using search terms relevant to this review. Studies contained in the Specialised Register are identified through search strategies specifically designed for CENTRAL, MEDLINE and EMBASE and handsearching conference proceedings.

Selection criteria: 

All randomised controlled trials (RCTs) and quasi-RCTs that compared antibiotic prophylaxis with a placebo or no intervention for recipients of solid organ transplants were included.

Data collection and analysis: 

Two authors independently assessed studies for inclusion and extracted data. We derived risk ratios (RR) for dichotomous data and mean differences (MD) for continuous data with 95% confidence intervals (CI). Methodological risk of bias was assessed using the Cochrane risk of bias tool.

Main results: 

We identified three studies (10 reports) that involved 558 kidney transplant recipients which met our inclusion criteria. All studies were conducted in countries that have high prevalence of TB (India and Pakistan), and investigated isoniazid, an oral antibacterial drug. Control in all studies was no antibiotic prophylaxis. Prophylactic administration of isoniazid reduced the risk of developing TB post-transplant (3 studies, RR 0.35 95% CI 0.14 to 0.89), and there was no significant effect on all-cause mortality (2 studies, RR 1.39, 95% CI 0.70 to 2.78). There was however substantial risk of liver damage (3 studies, RR 2.74, 95% CI 1.22 to 6.17).

Reporting of methodological quality parameters was incomplete in all three studies. Overall, risk of bias was assessed as suboptimal.

Share/Save