Sulfonamide desensitization in solid organ transplant recipients: A protocol-driven approach during the index transplant hospitalization.

Trimethoprim-sulfamethoxazole (TMP-SMX) is the first-line agent for Pneumocystis jiroveci pneumonia (PJP) prophylaxis for solid organ transplant (SOT) recipients because of its efficacy for this indication, extended antimicrobial coverage, and favorable cost. Reported sulfonamide allergy is not uncommon and often results in TMP-SMX avoidance. Desensitization offers an efficacious and cost-effective alternative to TMP-SMX avoidance. Herein, we reviewed our experience with desensitization during the index transplant hospitalization among 52 SOT recipients with history of a non-anaphylactic sulfonamide allergy. Of those enrolled in the desensitization protocol, 92% (48/52) completed the protocol, with nearly 80% (41/52) still on TMP-SMX at 3 months without adverse reaction. Eleven patients discontinued TMP-SMX (7 for allergic reactions and 4 for non-allergic reasons) and switched to pentamidine. A cost savings of $575 per desensitization was calculated based on annual wholesale drug prices, for a total savings of $23 575. Additionally, the protocol did not delay discharge in any patient nor was it associated with any severe allergic reactions. These findings suggest TMP-SMX desensitization is safe and effective in SOT recipients with a history of non-anaphylactic, non-life-threatening sulfonamide hypersensitivity.

The role of the pharmacist in the management of kidney transplant recipients.

Pharmacists may play a key role on the multidisciplinary transplant team. This article describes the development and current status of pharmacists in the management of transplant recipients in the United States. Traditionally, pharmacists played an important support role in transplant medicine. This role has been expanded to include direct patient care for the avoidance, detection, and/or treatment of side effects from the polypharmacy necessary in the management of these complex patients. Pharmacists provide pre- and post-transplant education to transplant recipients to enhance adherence to complicated medical regimens and thereby reduce readmission to hospital and unscheduled, costly visits to urgent care centers and/or hospital emergency departments.

Drug dosing in elderly patients with chronic kidney disease.

As the elderly population in the United States increases, health care professionals need to be aware of potential age-related changes that affect medication prescribing. Increased emphasis on careful patient assessment and safety can reduce the incidence of adverse events related to medications.

The old and new methods of assessing kidney function.

Chronic kidney disease is a worldwide problem. Accurate assessment of kidney function is important for defining stages of kidney disease and assisting with drug dosing. Glomerular filtration rate (GFR) is a good index of the health of the kidney. Although measured GFR using an exogenous substance is the most accurate, it is difficult to obtain due to cost and resources. Equations calculating creatinine clearance and estimated GFR as a measure of kidney function have been developed using serum creatinine as a marker of kidney function. The Cockcroft-Gault, Modification of Diet in Renal Disease, and Chronic Kidney Disease Epidemiology Collaboration equations have been shown to have statistically significant differences in estimating GFR in various populations. Drug-dosing adjustments based on the various equations may differ. However, without clinical outcome data, it is yet to be determined whether these differences are clinically significant.

A quantitative approach to drug dosing in chronic kidney disease.

Chronic kidney disease (CKD) is increasing at an alarming rate. Medication prescribing in this growing population is especially difficult. Many pharmacological agents or their metabolites are eliminated unchanged through the kidney. Drug dosing in CKD is challenging as most patients have a number of comorbid conditions. Patients with CKD take pharmacological agents with potential for drug interactions. Most patients also have alterations to the normal functioning of a number of different organs or systems (e.g. heart, liver, gastrointestinal system) which affect pharmacokinetics of commonly used drugs in CKD. Pharmacokinetic behaviors of most drugs are highly variable in patients with CKD. In addition, pharmacological management of patients with CKD is imprecise and requires estimating renal function, applying clinical judgment and, if available, therapeutic drug monitoring to provide adequate pharmacotherapeutic concentrations to optimize pharmacodynamic response while minimizing toxicities. For drugs that are removed through the renal system unchanged, a dosing modification should be considered according to patient- and drug-specific factors. Renal replacement therapy and dialysis remove pharmacologic agents extensively, and thus a replacement dose is needed to avoid therapeutic failure. By applying a quantitative approach, health care providers can improve pharmacotherapeutic outcomes while reducing adverse drug reactions.

Drug dosing in the elderly patients with chronic kidney disease.

Chronic kidney disease is a common disorder that affects many patients with a prevalence approaching 19 million people in the United States. Kidney failure and renal impairment is a common occurrence in the geriatric population. Most types of kidney diseases are chronic conditions and frequently manifest at the late stages of life. Epidemiologic studies suggest that older patients are at a greater risk for renal failure if the kidney experiences insults from ischemia or exposure to pharmacologic and diagnostic nephrotoxins. Pharmacologic management of most common diseases in elderly individuals is a difficult task, particularly in older individuals with chronic kidney disease. Thus, primary care providers must proceed with caution when prescribing drugs for elderly patients with kidney disease.

Epidemiology and outcomes of candidemia in 2019 patients: data from the prospective antifungal therapy alliance registry.

BACKGROUND: Candidemia remains a major cause of morbidity and mortality in the health care setting, and the epidemiology of Candida infection is changing. METHODS: Clinical data from patients with candidemia were extracted from the Prospective Antifungal Therapy (PATH) Alliance database, a comprehensive registry that collects information regarding invasive fungal infections. A total of 2019 patients, enrolled from 1 July 2004 through 5 March 2008, were identified. Data regarding the candidemia episode were analyzed, including the specific fungal species and patient survival at 12 weeks after diagnosis. RESULTS: The incidence of candidemia caused by non-Candida albicans Candida species (54.4%) was higher than the incidence of candidemia caused by C. albicans (45.6%). The overall, crude 12-week mortality rate was 35.2%. Patients with Candida parapsilosis candidemia had the lowest mortality rate (23.7%; P<.001) and were less likely to be neutropenic (5.1%; P<.001) and to receive corticosteroids (33.5%; P<.001) or other immunosuppressive drugs (7.9%; P=.002), compared with patients infected with other Candida species. Candida krusei candidemia was most commonly associated with prior use of antifungal agents (70.6%; P<.001), hematologic malignancy (52.9%; P<.001) or stem cell transplantation (17.7%; P<.001), neutropenia (45.1%; P<.001), and corticosteroid treatment (60.8%; P<.001). Patients with C. krusei candidemia had the highest crude 12-week mortality in this series (52.9%; P<.001). Fluconazole was the most commonly administered antimicrobial, followed by the echinocandins, and amphotericin B products were infrequently administered. CONCLUSIONS: The epidemiology and choice of therapy for candidemia are rapidly changing. Additional study is warranted to differentiate host factors and differences in virulence among Candida species and to determine the best therapeutic regimen.

Presentation of the PATH Alliance registry for prospective data collection and analysis of the epidemiology, therapy, and outcomes of invasive fungal infections.

Randomized clinical trials for patients with invasive fungal infections (IFIs) are often limited or precluded, necessitating alternate sources of information. The Prospective Antifungal Therapy Alliance (PATH Alliance) is a registry that collects data on patients with IFIs at medical centers in North America. Patients with a diagnosis of proven or probable IFI are enrolled and followed prospectively for 12 weeks. Using a Web-based electronic data capture and reporting system, the registry collects anonymous data to address end points in epidemiology, diagnosis, treatment, and outcome of IFIs. As of October 2006, 1892 IFIs were observed in 1710 patients enrolled at 22 sites. The most commonly encountered IFIs were caused by Candida spp. (73.0%), presenting predominantly as candidemia, followed by Aspergillus spp. (14.8%). A small number of IFIs with uncommon and emerging moulds were observed. Culture remains the main diagnostic tool for most IFIs (91.8%). Antifungal agent choice depended on the fungal species isolated, with fluconazole being the most frequently administered agent (58.2%). The overall crude 12-week mortality, excluding the patients lost to follow-up, was 43.9%. PATH Alliance is a network of medical institutions gathering significant information about IFIs in North America. Significant trends and treatment practices concerning yeasts and moulds were observed. As enrollment continues, additional data will be analyzed and published, which will provide valuable information concerning the epidemiology, therapy, and outcomes of IFIs.

Hepatitis C infection increases the risk of new-onset diabetes after transplantation in liver allograft recipients.

BACKGROUND: Recent evidence suggests that new-onset diabetes after transplant (NODAT) adversely affects orthotopic liver transplant (OLTX) patient and graft survival. The objective of this study is to evaluate the effect of hepatitis C infection on the natural history of NODAT. METHODS: A retrospective review of 492 OLTX recipients at a single center was conducted from January 1993 to January 2003. Patients were followed for a minimum of 12 months (range 12 months-10 years). The study population consisted of 444 OLTX recipients who were either HCV positive (n = 206) or HCV negative (n = 238). NODAT was defined by the need for antidiabetic medication for at least 7 days starting anytime after OLTX. Statistical analysis was performed by using the Student t test, Kaplan-Meier survival, and chi-square tests. RESULTS: The overall incidence of NODAT was 33% (146/444). There was a significant difference in the development of NODAT between the HCV-positive group (82/206, 40%) and the HCV-negative group (64/238, 27%) (P < .001). Other independent risk factors for development of NODAT were male gender and age >50 years. CONCLUSION: Hepatitis C infection contributes to the development of diabetes mellitus in OLTX recipients. The mechanisms behind HCV infection and associated NODAT in HCV-positive OLTX recipients warrant further investigation.

Cardiovascular complications of immunosuppressive agents in renal transplant recipients.

Fatal and nonfatal cardiovascular events are the most important cause of graft loss in patients with a functioning graft following transplantation. The available data indicate that transplant patients have a high prevalence of hypertension, hyperlipidaemia and new onset diabetes mellitus after transplantation. The aetiology and pathogenesis of post-transplant hypertension, hyperlipidaemia and diabetes are multifactorial. In addition, disease of the native kidney and recurrence of renal disease can contribute to the development of cardiovascular disease in transplant recipients. Most transplant patients are at risk of clinically important drug-drug interactions involving immunosuppressive agents. Adverse reactions and drug-drug interactions should not be neglected when selecting an agent for treatment of cardiovascular risk factors in transplant recipients.

Autosomal-dominant polycystic kidney disease as a risk factor for diabetes mellitus following renal transplantation.

BACKGROUND: Posttransplant diabetes mellitus is an important complication of renal transplantation that is associated with a significant impact on quality of life and an increase in long-term morbidity and mortality. Autosomal-dominant polycystic kidney disease (ADPKD) is a hereditary disease that commonly leads to end-stage renal disease (ESRD) in adulthood. The association between ADPKD and posttransplant diabetes mellitus has not been previously studied in a large cohort of patients. METHODS: To address this question, we studied a cohort of 135 patients with ADPKD who received a first renal-only transplant between January 1985 and December 1999. An age, race, and date of transplant-matched cohort of 135 non-ADPKD subjects were used as the control population. RESULTS: The cohorts were similar at baseline for gender distribution, body mass index (BMI), proportion of obese subjects (BMI greater than 30 kg/m(2)), family history of diabetes mellitus, and type of donor (deceased or living). At 12 months, the incidence of posttransplant diabetes mellitus was significantly higher in patients with ADPKD when compared to the controls (17% vs. 7.4%) (P= 0.016), despite no significant differences in the BMI, percent increase in BMI, number of acute rejections, prednisone dose at 3 and 6 months, use of diuretics or beta blockers, delayed graft function, or serum creatinine levels. The proportion of subjects requiring insulin was significantly higher in the ADPKD group (11.1% vs. 3%) (P= 0.009). Variables significantly associated with posttransplant diabetes mellitus at 1 year by bivariate analyses were the diagnosis of ADPKD (P= 0.02), BMI at transplant (P= 0.04), obesity at 12 months (P= 0.01), and delayed graft function (P= 0.02). Gender of recipient (P= 0.9), family history of diabetes (P= 0.3), prednisone dose at 3 months (P= 0.9) and 6 months (P= 0.7), acute rejection (P= 0.9), use of beta blockers or tacrolimus (P= 0.8), deceased donor transplant (P= 0.2), and serum creatinine at 1 year (P= 0.5) were not associated with posttransplant diabetes mellitus. A trend toward increased incidence of posttransplant diabetes mellitus was found with the use of diuretics post transplant (P= 0.054). By multivariable analyses, in patients with ADPKD, the adjusted (by all the variables listed above) relative risk for development of posttransplant diabetes mellitus was 2.87 (95% CI = 1.24-6.65) (P= 0.014). Only the diagnosis of ADPKD (RR = 2.9) (P= 0.01), obesity at 1 year (RR 2.5) (P= 0.017), and delayed graft function (RR 2.4) (P= 0.03) contributed significantly to the fit of a stepwise logistic regression model. Patient survival was significantly worse in the cohort of patients who developed posttransplant diabetes mellitus (median survival 109.3 vs. 121 months) (P= 0.008). CONCLUSION: In our study patients with ADPKD were at a threefold increased risk for development of posttransplant diabetes mellitus within the first year following renal transplantation. Development of posttransplant diabetes mellitus was associated with a significant detrimental impact on patient survival. Further studies are needed to provide insight into the mechanisms of the association between ADPKD and posttransplant diabetes mellitus.

Management of invasive aspergillosis in high-risk patients.

Invasive aspergillosis can be difficult to diagnose and control, and conventional drug treatment is often highly toxic, producing medical complications that further compromise patients' health status and escalate health care costs. This article describes the clinical manifestations of Aspergillus infection and discusses approaches to its therapy, including newer pharmaceutical agents with fewer adverse effects, which offer the potential to improve outcomes and substantially lower the cost of treating aspergillosis.

Graft failure from severe recurrent primary sclerosing cholangitis following orthotopic liver transplantation.

UNLABELLED: Speculation that primary sclerosing cholangitis (PSC) may recur in the transplanted liver is based on the relative increase in frequency of biliary abnormalities and histologic evidence of periportal fibrosis without other causes. A recent study demonstrated almost 9% of patients undergoing liver transplantation (OLT) for primary sclerosing cholangitis (PSC) develop recurrent sclerosing cholangitis although the patient and graft survival is not different from those in whom recurrence does not develop. Most reports of PSC recurrence post-OLT estimate rates of 1% to 14%, but to date, no center has reported rapidly progressive fibro-obliterative cholangitis leading to graft failure. CASE REPORT: DV was a 39-year-old white man with ulcerative colitis, since age 21, who developed jaundice and pruritus in 1992. ERCP and liver biopsy were consistent with PSC, and he developed thrombocytopenia and bleeding esophageal varices. He underwent an uneventful OLT in May 1994 with an ABO-compatible organ and normal ischemic times. There was no evidence of postoperative cytomegalovirus infection, hepatic artery thrombosis, or rejection. In October 1994, mild abnormalities of liver function tests (LFTs) led to liver biopsy that revealed inflammatory infiltrate in triad with spillover into lobules and mild periportal fibrosis. LFTs normalized without any treatment, but in February 1995 repeat liver biopsy for increased LFTs revealed moderate periportal fibrosis with inflammatory cells in triads and lobules. Viral shell and CMV titers were negative. No evidence of infectious etiology or rejection was noted. The patient was started on ursodeoxycholic acid at that time and percutaneous transhepatic cholangiogram (PTC) revealed marked narrowing of the intrahepatic ducts. Esophagogastroduodenoscopy (EGD) revealed esophageal varices. Hepatic arteriogram and Doppler ultrasound were negative. He developed progressive graft failure, and died at home while awaiting re-transplant. CONCLUSIONS: Although most series report mild recurrence of PSC following OLT, this case illustrates that early, severe recurrence of PSC may occur, leading to graft failure and need for re-transplantation.

Renal transplantation at Oregon Health and Science University: recent results and protocols.

Renal transplants have been performed at the University Hospital, Portland, OR since 1959. In the 5-year period between January 1997 and December 2001, 736 kidney-only transplants were performed at our institution. Living donor transplants comprise an increasing proportion of the transplants performed. Our patient and graft survival rates, both short- and long-term reflect the close collaboration between the transplantation medicine and transplantation surgery faculties, and the excellent support from nurse-coordinators, histocompatibility laboratory specialists and the organ procurement organization. Since September 2001, we have used a risk-based immunosuppression algorithm. The incidence of acute rejection within the first 3 months following transplantation ranged from 7-18% in the different risk groups. We have incorporated surveillance renal allograft biopsies into our standard of care and biopsies are performed at 3 months and one year after transplantation. The incidence of subclinical rejection was 15% on the 3-month surveillance biopsies and 4% on the one-year biopsies. The majority of these rejection episodes were CCTT type I acute rejection, which responded to treatment with pulse steroids. Since 1991, we have been transplanting kidneys from blood group A2 donors into blood group B or O recipients. Graft survival is similar to that in patients receiving an ABO compatible transplant. We have recently adopted the use of intravenous immune globulin to abrogate a positive crossmatch and allow transplantation of a kidney from a living donor. Six patients have been successfully transplanted using this protocol. In an effort to speed up the work-up of recipients waiting for a deceased donor kidney transplant, we have implemented a computer-driven algorithm. By generating a list of patients who should be crossmatched, and by automating generation of work sheets and reports, this computer-driven program has expedited deceased donor workups.

Immunosuppression impact on long-term cardiovascular complications after liver transplantation.

BACKGROUND: With current early transplant patient and allograft survivals nearly optimized, long-term medical complications have become a significant focus for potential improvement in patient outcomes. Cardiovascular disease and associated risk factors have been shown in renal transplant patients to be related to the pharmacologic immunosuppression employed. OBJECTIVE: The objective of this study is to investigate at 3 years postliver transplant (OLTx) the incidence of hypertension (HTN), hyperlipidemia (HLIP), diabetes mellitus (DM), nephrotoxicity (NTX), and cardiovascular disease (MI, angioplasty, CHF, CVA, and seborth) as well as rejection in two cohorts of liver transplant recipients who received either tacrolimus (FK-506) or cyclosporine (CSA) and to analyze the consequences of these complications on mortality following transplantation. METHODS: Eighty-seven sequential patients (CSA: n = 50, mean age 48 years, M/F 32/18; and FK-506: n = 37, mean age 45 years, M/F 22/15) who underwent OLTx between 1994 and 1998, were >/=18 years, and had a minimum of 3 years of complete follow-up were included in the analysis. All OLTx candidates over age 50, who had a history of alcoholic cirrhosis, or had a history of cardiac conditions/events underwent complete cardiac consultation including an echocardiogram with additional cardiac investigation as indicated prior to OLTx. RESULTS: At 3 years following OLTx, the incidence of acute rejection (40% versus 19%, P < 0.05), HTN (62% versus 38%, P < 0.05), HLIP (14% versus 5%, P = 0.08), and cardiovascular disease (18% versus 0%, P < 0.001), were significantly greater for the CSA patients compared with the FK-506 patients. Eight (20%) of the CSA patients who died before 3 years had their death attributed to cardiovascular events versus none in the FK-506 group. CONCLUSION: Compared with CSA, FK-506 was associated with significantly less rejection and a reduced incidence of HTN and cardiovascular disease.