Resistant cytomegalovirus in intestinal and multivisceral transplant recipients.

BACKGROUND: Intestinal and multivisceral transplantation can be complicated by cytomegalovirus (CMV)-related viremia and disease. Intravenous ganciclovir (GCV) and oral valganciclovir remain the treatment of choice in this setting. Limited data are available on GCV-resistant (GCV-R) CMV infection in small intestine and multivisceral transplant recipients. METHOD: A retrospective review was performed on all patients who underwent small intestine or multivisceral transplantation from November 8, 2003 through November 30, 2008. Those with CMV viremia and invasive disease were identified. GCV resistance was suspected in patients who continued to have viremic episodes or invasive disease despite appropriate GCV treatment. Genotypic analyses were performed to detect the presence of GCV resistance genes UL97 and UL54. RESULTS: During the study period, 88 small intestine or multivisceral transplants were performed on 85 patients. Of the 88 transplantations, 16 patients developed CMV viremia with or without end-organ disease (18.2%) and 5.7% developed GCV-R CMV infection. In patients diagnosed with CMV infection, 31.3% (5/16) had GCV-R CMV infection. Of patients with GCV-R CMV infection, 80% (4/5) developed CMV allograft enteritis, resulting in allograft explantation in 3 patients. All patients with GCV-R CMV infection were CMV donor positive/recipient negative. Patients with tissue-invasive CMV disease were 18 times more likely to be infected with GCV-R CMV (95% confidence interval 1.24-260.93; P-value 0.0341). CONCLUSION: Small intestinal and multivisceral transplant recipients have a higher rate of GCV-R CMV infection compared with other solid organ transplant recipients, which is often associated with tissue-invasive disease and allograft loss.

Infection among adult small bowel and multivisceral transplant recipients in the 30-day postoperative period.

BACKGROUND: Intestinal transplantation is a potential option for patients with short gut syndrome (SGS), and infection is common in the postoperative period. The aim of our study was to identify the incidence and characteristics of bacterial and fungal infections of adult small bowel or multivisceral (SB/MV) transplantation recipients in the 30-day postoperative period. METHODS: This retrospective chart review assessed the incidence and characteristics of bacterial and fungal infections in patients who underwent SB/MV transplant at our center between April 2004 and November 2008. Patient data were retrieved from computerized databases, flow-charts, and medical records. RESULTS: A total of 40 adult patients with a mean age of 38.7 ± 13.4 years received transplants during this period: 27 patients received isolated SB, 12 received MV, and 1 received SB and kidney. Our immunosuppressive regimen included basiliximab for induction, and tacrolimus, sirolimus, and methylprednisolone for maintenance therapy. The most common indications for transplant were SGS, intestinal ischemia, Crohn's disease, trauma, motility disorders, and Gardner's syndrome. We report a 30-day postoperative infection rate of 57.5% and mean time to first infection of 10.78 ± 8.99 days. A total of 36 infections were documented in 23 patients. Of patients who developed infections, 56.5% developed 1 infection, 30.4% developed 2 infections, and 13% developed 3 infections. The most common site of infection was the abdomen, followed by blood, urine, lung, and wound infection. The isolates were gram-negative bacteria in 49.3%, gram-positive bacteria in 39.4%, and 11.3% were fungi. The most common organisms were Pseudomonas (19%), Enterococcus (15%), and Escherichia coli (13%). Overall, 47% of infections were due to drug-resistant pathogens; 31% of E. coli and Klebsiella species were extended-spectrum beta-lactamase-producing organisms, 36% of Pseudomonas was multidrug resistant (MDR), 75% of Enterococcus was vancomycin resistant, and 100% of Staphylococcus aureus was methicillin resistant. CONCLUSION: These findings demonstrate that bacterial and fungal infections remain an important complication in SB/MV transplant recipients within the early postoperative period. Infections due to MDR organisms have emerged as an important clinical problem in this patient population.

The safety and pharmacokinetics of single-agent and combination therapy with megestrol acetate and dronabinol for the treatment of HIV wasting syndrome. The DATRI 004 Study Group. Division of AIDS Treatment Research Initiative.

This randomized, open-labeled, multicenter study was designed to assess safety and pharmacokinetics of dronabinol (Marinol) tablets and megestrol acetate (Megace) micronized tablets, alone and in combination, for treatment of HIV wasting syndrome. Weight and quality of life data were also collected. Fifty-two patients (mean CD4+ count, 59 cells/microliter) were randomized to one of four treatment arms: dronabinol 2.5 mg twice/day (D); megestrol acetate 750 mg/day (M750); megestrol acetate 750 mg/day+dronabinol 2.5 mg twice/day (M750+D); or megestrol acetate 250 mg/day+dronabinol 2.5 mg twice/day (M250+D). After therapy initiation, 47 patients returned for at least one visit, and 39 completed the planned 12 weeks of study visits. Occurrence of adverse events, drug discontinuation, new AIDS-defining conditions, or CD4+ T lymphocyte changes were not statistically significantly different among arms. Serious adverse events assessed as related to dronabinol included CNS events (e.g., confusion, anxiety, emotional lability, euphoria, hallucinations) and those assessed as related to megestrol acetate included dyspnea, liver enzyme changes, and hyperglycemia. The mean weight change +/- SE over 12 weeks was as follows: D, -2.0 +/- 1.3 kg; M750, +6.5 +/- 1.1 kg; M750+D, +6.0 +/- 1.0 kg; and M250+D, -0.3 +/- 1.0 kg (difference among treatment arms, p = 0.0001). Pharmacokinetic parameters measured after 2 weeks of therapy for M750 were Cmax = 985 ng/ml and AUC = 22,487 ng x hr/ml, and for dronabinol and its active metabolite (HO-THC), respectively, were Cmax = 2.01; 4.61 ng/ml and AUC = 5.3; 23.7 ng x hr/ml. For megestrol acetate, but not dronabinol, there was a positive correlation at week 2 between both Cmax and AUC with each of the following: (1) weight change, (2) breakfast visual analog scale for hunger (VASH) score, and (3) dinner VASH score.

Immune-based therapeutics: scientific rationale and the promising approaches to the treatment of the human immunodeficiency virus-infected individual.

The primary approach to therapy for infection with human immunodeficiency virus (HIV) continues to be centered around antiretroviral agents that have conferred significant clinical benefits. The considerable degree of immunologic dysfunction in HIV infection, however, has led to intense interest in methods of immune stimulation and reconstitution. Immunomodulatory intervention in HIV infection is highly controversial. Over the years a number of immunomodulatory agents--many with only a poor rationale for their clinical use--have been evaluated. In this review we concentrate on immunomodulatory approaches that are currently being investigated. We group these interventions, reviewing the rationale and clinical data for each category: passive immunity (administration of immunoglobulins and use of apheresis), thymic hormone treatment, cytokine treatment (administration of interleukins, tumor necrosis factor, and interferons), adoptive cellular immunity, and therapeutic vaccination. At present, the only interventions supported by data from well-controlled studies are the parenteral administration of interferon alpha to patients with HIV-associated Kaposi's sarcoma and the administration of pooled immunoglobulin (to decrease the rate of bacterial infections) to children who cannot take trimethoprim-sulfamethoxazole. However, several other approaches under development show promise in reversing some of the immune deficits of HIV infection. Clinical evaluation of these approaches should yield valuable insights into the immunopathogenesis of HIV infection, and these insights should facilitate the formulation of new modalities of treatment.

Emergence of unusual opportunistic pathogens in AIDS: a review.

Opportunistic infections are a major cause of morbidity and death among patients infected with the human immunodeficiency virus (HIV), particularly late in the disease, when immunosuppression is severe. Some pathogens, such as Pneumocystis carinii and Toxoplasma gondii, are extremely common in this population and are readily recognized by clinicians caring for these patients. However, many other organisms occasionally cause conditions that clinically mimic the more commonly encountered pathogens. Clinicians must be alert to the threat posed by these less frequently occurring organisms and of the broader differential diagnosis that must be considered for infections in patients with HIV infection.