valganciclovir and Diarrhea

Reactivated cytomegalovirus (CMV) infection has been known to cause significant morbidity and mortality in immunocompromised patients. However, CMV disease rarely develops in immunocompetent patients, and reported cases often present with a mild, self-limiting course, without severe life-threatening sequelae. While the colon is the most common gastrointestinal site affected by CMV disease in immunocompetent patients, rectal involvement is rarely reported. CMV proctitis can present in two distinct forms, primary and reactivated. However, reactivated CMV proctitis is rarely reported as a causative etiology of nosocomial diarrhea, except in transplant patients. Herein we present a case of reactivated CMV proctitis in an immunocompetent patient, presenting as nosocomial diarrhea. Previously reported cases of reactivated CMV proctitis in immunocompetent patients are also reviewed.. A 79-year-old female was admitted because of metabolic encephalopathy caused by dehydration and hypernatremia. The patient's consciousness level returned rapidly after fluid supplementation. However, she subsequently presented with abdominal pain and diarrhea on day 8 of admission. Abdominal contrast-enhanced computed tomography on day 10 of admission demonstrated inflammation around the rectum, suggesting proctitis. Colonoscopy on day 16 of admission showed a giant ulcer at the rectum. Pathology of rectal biopsy confirmed CMV infection. The patient recovered without sequelae after 38 days of valganciclovir treatment. Follow-up colonoscopy revealed a healed ulcer over the rectum. Ten cases in the literature, plus our case, with reactivated CMV proctitis in immunocompetent patients were reviewed. We found that most patients were elderly (mean, 72 years) with a high prevalence of diabetes mellitus (54.5%). Cardinal manifestations are often non-specific (diarrhea, hematochezia, tenesmus), and eight (72.7%) developed CMV proctitis following a preceding acute, life-threatening disease, rather than as an initial presentation on admission. These manifestations frequently develop during hospitalization, and are thus often regarded as nosocomial diarrhea.. Clinicians should be aware of the possibility of nosocomial onset of reactivated CMV proctitis in patients hospitalized due to a preceding critical illness, although the benefits of antiviral therapy remain unclear.

Topics: Abdominal Pain; Aged; Biopsy; Colonoscopy; Cross Infection; Cytomegalovirus; Cytomegalovirus Infections; Diarrhea; Female; Ganciclovir; Humans; Immunocompetence; Middle Aged; Proctitis; Rectum; Tomography, X-Ray Computed; Valganciclovir; Virus Activation

As a result of the low oral bioavailability of ganciclovir, a prodrug was developed to improve the bioavailability of ganciclovir. This study was designed to investigate the fasting, single-dose pharmacokinetics as well as the absolute and relative bioavailability of a valine ester prodrug of ganciclovir, valganciclovir, as compared to oral and intravenous ganciclovir in asymptomatic HIV+ and CMV+ subjects. In this open-label, randomized, three-period crossover study, 18 subjects received, in random order, single oral doses of valganciclovir 360 mg and ganciclovir 1000 mg and an intravenous infusion of ganciclovir 5 mg/kg over 1 hour. Valganciclovir was rapidly and extensively hydrolyzed to ganciclovir, resulting in significantly greater bioavailability compared to 1000 mg oral ganciclovir (60.9% vs. 5.6%, respectively). Higher peak serum concentrations were reached earlier following valganciclovir (ganciclovir [2.98 +/- 0.77 micrograms/mL at 1.0 +/- 0.3 h]) than following oral ganciclovir (0.47 +/- 0.17 microgram/mL and 2.2 +/- 1.0 h). Mean total ganciclovir AUCs following oral ganciclovir (1000 mg) and 360 mg valganciclovir (3.8 +/- 1.2 and 10.8 +/- 1.9 micrograms-h/mL) were less than that following a standard 5 mg/kg intravenous infusion of ganciclovir (25.1 +/- 3.8 micrograms-h/mL). In summary, valganciclovir is a prodrug with a favorable safety profile with enhanced bioavailability and significantly higher serum concentrations of ganciclovir than following oral administration of ganciclovir itself.

Topics: Adult; Anti-HIV Agents; Antiviral Agents; Area Under Curve; Biological Availability; Cross-Over Studies; Cytomegalovirus Infections; Diarrhea; Dizziness; Dyspnea; Exanthema; Female; Fever; Ganciclovir; Headache; HIV Seropositivity; Humans; Hypertension; Male; Metabolic Clearance Rate; Middle Aged; Pain; Prodrugs; Syncope; Valganciclovir

We present the case of a 28-year-old man with recently-diagnosed human immunodeficiency virus and hepatitis C virus infection. He developed obstructive cholangiopathy secondary to cytomegalovirus and Kaposi sarcoma, both diagnosed by endoscopic retrograde cholangiopancreatography and biopsies. He received antiretroviral therapy, chemotherapy and valganciclovir with full recovery.

Topics: Abdominal Pain; Adult; AIDS-Related Opportunistic Infections; Antiretroviral Therapy, Highly Active; Bile Duct Diseases; Biopsy; Cholangiopancreatography, Endoscopic Retrograde; Cytomegalovirus; Diarrhea; Fever; Hepatitis C; HIV Infections; Humans; Male; Sarcoma, Kaposi; Valganciclovir; Weight Loss

A 54-year-old man presented with a 6-week history of chronic diarrhea and weight loss of 11 kg after returning from a holiday in Thailand. The patient had a 9-year history of an untreated HIV infection. Despite treatment of a culture-proven Shigella enteritis and strongyloidiasis the symptoms persisted. Finally, cytomegalovirus (CMV) colitis was diagnosed by colonoscopy. The patient recovered completely after starting antiretroviral and valganciclovir treatment. An additional opportunistic infection with multiresistant pulmonary tuberculosis was diagnosed.

Topics: Anti-Retroviral Agents; Chronic Disease; Colitis; Cytomegalovirus Infections; Diarrhea; Ganciclovir; HIV Infections; Humans; Male; Middle Aged; Thinness; Treatment Outcome; Valganciclovir; Weight Loss

Colectomy with ileoanal pouch formation is usually contraindicated in patients with Crohn's disease (CD) due to the risk of recurrent disease and pouch failure. We report the case of a patient, initially thought to have ulcerative colitis (UC), who underwent such surgery but subsequently developed perianal CD. She presented with diarrhoea and weight loss. Inflammatory markers were raised. Pouchoscopy revealed deep ulcers within the pouch. The main differential diagnoses were idiopathic pouchitis and recurrent CD. However, immunohistochemical staining demonstrated positivity for cytomegalovirus (CMV). Stool frequency, C reactive protein and albumin normalised within 48 h of starting oral valgancyclovir. At 15 weeks, pouch appearances were improved, no histological evidence of CMV was found and baseline pouch function had returned. This case highlights that CD can present many years after surgery for apparent UC. Also, CMV pouchitis should be considered as a differential cause of pouchitis especially as it is treatable with antiviral therapy.

Topics: Adult; Anal Canal; Anastomosis, Surgical; Antiviral Agents; Chronic Disease; Colectomy; Colitis, Ulcerative; Colonic Pouches; Crohn Disease; Cytomegalovirus; Cytomegalovirus Infections; Diarrhea; Endoscopy; Female; Ganciclovir; Humans; Inflammation; Postoperative Complications; Pouchitis; Proctocolectomy, Restorative; Ulcer; Valganciclovir; Weight Loss

Topics: Antiviral Agents; Cytomegalovirus; Cytomegalovirus Infections; Dehydration; Diarrhea; Duodenum; Ganciclovir; Humans; Inclusion Bodies; Infant; Malabsorption Syndromes; Male; Microvilli; Mucolipidoses; Valganciclovir

To report the improvement of diarrhea in a patient with cytomegalovirus (CMV) colitis who was treated with octreotide after failure of loperamide.. An 84-year-old male presented with chronic diarrhea and CMV colitis; he had been experiencing protracted diarrhea since 2006. In October 2009 he failed a 21-day course of valgancyclovir 900 mg orally twice daily. Several months later, due to continuing diarrhea and progressive malnutrition, a colonoscopy and subsequent biopsy again showed CMV. In March 2010 he was started on a 28-day course of intravenous ganciclovir 130 mg daily. Three weeks into treatment he continued with copious amounts of diarrhea, with no relief from loperamide, which was titrated from 2 mg/day to 2 mg every 6 hours. On day 20 of ganciclovir treatment he was started on octreotide 50 μg subcutaneously every 8 hours; within a few days, the patient began to experience decreased stool frequency and consistency. He completed the full 28-day course of ganciclovir, with octreotide continuing unchanged, with much improvement in his diarrheal symptoms and improvement in appetite, nutritional status, and quality of life.. Studies regarding the treatment of CMV colitis-associated diarrhea are scarce, and are typically limited to treating the underlying cause with antiviral medications and with the addition of antimotility agents. Three cases have been reported in the literature in which octreotide was used for the symptomatic treatment of diarrhea, none of which was refractory to loperamide.. This is the first known case of a patient with chronic diarrhea due to CMV colitis that was unresponsive to loperamide, required protracted antiviral treatment (valgancyclovir and gancyclovir), and subsequently experienced relief by the use of octreotide 50 μg subcutaneously every 8 hours.

Topics: Aged, 80 and over; Antidiarrheals; Antiviral Agents; Colitis; Cytomegalovirus; Cytomegalovirus Infections; Diarrhea; Drug Resistance, Viral; Drug Therapy, Combination; Ganciclovir; Humans; Male; Octreotide; Valganciclovir