Use of rifabutin for the treatment of a latent tuberculosis infection in a patient after solid organ transplantation.

Latent tuberculosis infection is an important problem for solid organ transplant recipients because of the frequency of its occurrence and its potential for reactivation. Because of the high mortality rate associated with active tuberculosis infections in transplant recipients, guidelines from the American Thoracic Society recommend treatment for latent tuberculosis in this population. However, the choice of treatments is often difficult because liver transplant recipients may be more sensitive to isoniazid hepatotoxicity, and rifampin has significant drug interactions with the calcineurin inhibitors used for immunosuppression. Two prior case reports described success with the use of rifabutin, a rifampin alternative, as part of a multidrug treatment regimen for active tuberculosis in posttransplant patients; however, there is no prior literature describing any experience with rifabutin for the treatment of latent tuberculosis in the posttransplant setting. We present a summary of tacrolimus drug levels and corresponding dose requirements for a single posttransplant patient during the administration of 3 different latent tuberculosis drug regimens: rifampin alone, rifampin plus ketoconazole, and rifabutin. In this patient's case, rifabutin allowed the maintenance of adequate tacrolimus levels, although an approximate 2.5-fold increase in the dose was required. Rifampin alone was associated with inadequate immunosuppressant levels, and rifampin plus ketoconazole was associated with a problematically prolonged QT interval and concerns about inadequate tuberculosis treatment.

Appropriately assessing renal function for drug dosing.

Chronic kidney disease affects millions of Americans. Many drugs are eliminated from the body by the kidneys. As renal function declines due to the disease, drugs that are normally eliminated by the kidneys can accumulate, potentially leading to toxicity. Assessing kidney function in patients is essential in determining the appropriate dose of medications to achieve the desired clinical outcome while minimizing the potential for toxicity.

A brief history in nephrology pharmacotherapy.

Advances in drug therapy for patients with kidney disease have contributed to increased exercise capacity, reduced cardiovascular disease, decreased renal bone disease, improved quality of life, and most importantly, reduced morbidity and mortality. New insights into the pathophysiology of chronic kidney disease (CKD) have helped lead to the development of many novel drugs and treatments. The purpose of this article is to highlight some of the developments in nephrology pharmacotherapy that occurred during the first 40 years of the American Nephrology Nurses' Association.

Pharmacotherapy of hepatitis C virus infection: a brief review.

Infection with the hepatitis C virus is a major public health problem and is the leading cause of liver disease in the United States. Chronic infection with hepatitis C virus can lead to liver disease, cirrhosis, and hepatocellular carcinoma. Treatment options include interferon or peginterferon, and ribavirin. The objective of treatment is to eradicate the infection in an effort to prevent complications of hepatitis C virus infection.

A primer on pharmacokinetics.

Pharmacokinetics describes the time course of the drug concentration following administration of a specific dosage regimen. An understanding of pharmacokinetic principles will assist the clinician in designing an individualized dosage regimen that achieves the desired drug concentration.

Pharmacotherapy of hepatitis B infection: a brief review.

Chronic infection with hepatitis B virus can lead to liver disease, cirrhosis, and hepatocellular carcinoma. Treatment options include interferons and antiviral drugs. The interferons have immunomodulatory, antiproliferative, and antiviral effects. Nucleoside analogs, such as entecavir, lamivudine and telbivudine, and neucleotide analogs, such as adefovir and tenofovir, exhibit antiviral effects by inhibiting viral replication. Treatment is directed at suppressing viral replication and halting the progression of disease.

Short Course of Postoperative Hepatitis B Immunoglobulin Plus Antivirals Prevents Reinfection of Liver Transplant Recipients.

BACKGROUND: Hepatitis B immune globulin (HBIG) has been an integral component of prophylaxis against hepatitis B virus (HBV) recurrence in liver transplantation (LT) recipients, but HBIG is costly and inconvenient to administer, prompting consideration of alternative regimens. METHODS: In this retrospective cohort, we report on the success of antiviral therapy combined with a short course (in hospital only) HBIG in liver transplant recipients with HBV DNA less than 100 IU/mL pre-LT. RESULTS: A total of 42 hepatitis B surface antigen (HBsAg) positive, human immunodeficiency virus and hepatitis D virus-negative patients with pretransplant HBV DNA undetectable to 100 IU/mL who received HBIG 5000 IU in anhepatic phase and daily for 5 days together with nucleos(t)ide analogues indefinitely yielded 1- and 3-year cumulative incidences of recurrence, defined by positive serum HBsAg, of 2.9% (upper 95% confidence interval, 19%). One patient had HBV viremia 16 months post-LT without detectable HBsAg. Both patients with either HBsAg positivity or viremia had recurrent hepatocellular carcinoma diagnosed within a month of detection. Post-LT survival was 98% and 94% at 1 and 5 years, respectively. CONCLUSIONS: We conclude that a very short course of HBIG combined with long-term antiviral therapy is highly effective in preventing HBV recurrence and should be the preferred strategy for LT recipients with undetectable or low-level viremia at time of LT.

Antiviral therapy: nucleotide and nucleoside analogs.

For the management of HBV infection, an increasing number of nucleotide and nucleoside analogs are active against wild-type HBV and some against HBV with YMDD and other compensatory mutations. Table 2 depicts the IC50 and susceptibilities of HBV to various antiviral agents. The dichotomy between in vitro and in vivo susceptibilities to YMDD mutants is due to a change in IC50 between wild-type and mutant virus. Thus a drug may have less activity in vitro but at doses used in vivo show activity against YMDD and other compensatory mutations. Some HBV drugs share activity against HIV, which may be useful in the co-infected patient. Other nucleoside analogs are in various stages of development, including MCC-478 and DAPD. In the future, clinicians will have a plethora of reagents to chose from, and combination therapies may be invoked.