Mycobacterium genavense and Chronic Intermittent Diarrhea in a Kidney and Pancreas Transplant Recipient

A 48-year-old man received a kidney transplant in 2004 and a pancreas transplant in 2007. His medical historywas also significant for bicuspid aortic stenosis. Maintenance immunosuppression consisted of mycophenolate mofetil (MMF), tacrolimus, and prednisone. He presented in May 2011 with recurrentdiarrhea after an empirical short-course antimicrobial treatment. Three weeks before admission, nonbloody diarrhea associated with abdominal discomfort and night sweats occurred. Fever was not reported. Physical examination revealed anasarca, systolic heart murmur, and a soft and distended abdomen that was mildly tender to palpation in the right upper quadrant. Results of blood tests and microbiological stool examination are shown in Figure 1. Abdominal computed tomography (CT) scan showed ascites and mesenteric lymphadenopathy. Colonoscopy was normal. Esogastroduodenoscopy showed candidal esophagitis and abnormal duodenal mucosa (Fig. 1). Duodenal biopsy showed infiltration with histiocytes containing abundant Ziehl-Neelsen–positive bacilli (Fig. 1). Upper endoscopy was repeated to obtain tissue specimens for culture. Thoracic CT scan showed multiple mediastinal lymph nodes.FIGURE 1: A, laboratory tests on admission and 2 months before admission: laboratory results mainly revealed deterioration of renal function, leucopenia, and thrombopenia. B, upper endoscopy showed mild thickening of the duodenal folds, and the duodenal mucosa had fine nodules and superficial ulcers. C, duodenal biopsy showed infiltration with foamy histiocytes (hematein-eosin-safran). D, duodenal biopsy demonstrated numerous acid-fast bacilli in the foamy histiocytes (Ziehl).A provisional diagnosis of Mycobacterium avium complex (MAC) infection was made, and treatment was started with clarithromycin, ethambutol, and rifabutin; estimated glomerular filtration rate was then at 14 mL/min/1.73 m2. MMF had been stopped on admission. Tacrolimus was reduced because of high trough levels. After 12 weeks, the mycobacterial culture of the duodenal tissue specimen grew Mycobacterium genavense, as stools (which were positive for auramine staining), blood, and ascites fluid cultures for mycobacteria were negative. Ethambutol was stopped and moxifloxacin was started. After 1 month of antibiotherapy, diarrhea and abdominal pains improved. Because of progression of heart disease, the patient resumed hemodialysis and underwent aortic valve replacement. After 6 months, findings of a new CT scan and repeat endoscopy with biopsy specimen were unremarkable. After 13 months of antibiotherapy, the patient died from recurrent aortic valve stenosis. M. genavense is a fastidious nontuberculous mycobacterium (NTM) identified in 1991 (1). It is presumed to be ubiquitous in environmental reservoirs, including tap water, and the gastrointestinal tract of birds and mammals (2). Our patient’s household included four cats potentially contaminated with M. genavense. Disease is uncommon and has been described in immunocompromised patients (3, 4), but rarely in transplant recipients, with just 10 reported cases after heart (2 cases), liver (2 cases), and kidney (6 cases) transplantations (2–8). In our patient, chronic renal failure and the prolonged immunosuppressive therapy for multivisceral transplantation may have contributed to severe immune dysfunction. Including the present report, the age range of M. genavense infections in kidney transplant recipients was 41 to 73 years and infection was diagnosed at 7 months to 18 years after transplantation. The dominant presentation of M. genavense infection is gastrointestinal with diarrhea, abdominal pain (often associated with weight loss, fever, and/or night sweats), hepatosplenomegaly, abdominal lymphadenitis, and pancytopenia (2–12). Extra-abdominal presentations with pulmonary (2, 7) or subcutaneous (13) lesions are less frequent. Diagnosis in transplant recipients can be challenging because of the low index of suspicion, misdiagnosis as MMF toxicity, and the unique growth requirements of the pathogen (1). However, M. genavense infection should be rapidly identified and treated due to potentially lethal dissemination (4). A diagnosis of gastrointestinal involvement relies on endoscopic biopsies with histopathologic and specific microbiological analyses. The main endoscopic findings include thickening of the gastric and duodenal folds, villous flattening, nodular lesions with a velvety appearance, and superficial ulcers (8–12). The endoscopic aspect can be misdiagnosed as Whipple disease (14) or neoplasms. The main histopathologic feature of duodenal involvement is massive foamy histiocytic reaction in the submucosal connective tissue, which contains acid-fast bacilli (8–12). These clinical and histopathologic features are similar to those reported for infection with other NTM including MAC. However, with M. genavense, stools specimens are more often acid-fast bacillus smear positive although culture negative (1, 4). Moreover, in contrast with MAC, M. genavense grows poorly on the solid culture media routinely used for mycobacteria (1). It is essential to use broth media for primary culture and a prolonged incubation time (minimum of 8–12 weeks). Amplification by polymerase chain reaction or similar techniques represents the only possibility of detecting and identifying M. genavense from tissue specimens. It is important to identify the specific species of NTM because of differences in susceptibility profiles between species. M. genavense shows a high level of resistance to standard antituberculosis drugs. Although optimal therapy for M. genavense infection has not been established, treatment usually includes clarithromycin (4) with rifabutin and either fluoroquinolone, ethambutol, or amikacin according to recommended dosages (15). When possible, immunosuppressive drugs are tapered, with close monitoring of anticalcineurin: rifabutin (less than rifampin) may accelerate, as clarithromycin may decelerate the metabolism of this immunosuppressant. Duration of treatment is not well defined and depends on the therapeutic response and degree of immunosuppression. Disseminated disease should be treated for a minimum of 12 months. In conclusion, a kidney transplant recipient with chronic diarrhea should prompt further evaluation that includes careful histologic and microbiological assessment of endoscopic tissue samples to detect potential NTMs such as M. genavense. Edith Renoult 1 Claude Fortin2 Judy Dorais3 Rachid Hadjeres4 Michel Pâquet1 Marie-Chantal Fortin1 Catherine Girardin1 Gilles St-Louis1 Héloïse Cardinal1 Renée Lévesque1 Marie-Josée Hébert1 1 Département de Médecine Service de néphrologie Centre Hospitalier de l’Université de Montréal Montreal, Quebec, Canada 2 Département de Microbiologie et Infectiologie Centre Hospitalier de l’Université de Montréal Montreal, Quebec, Canada 3 Département de Médecine Service de gastro-entérologie Centre Hospitalier de l’Université de Montréal Montreal, Quebec, Canada 4 Département de Pathologie Centre Hospitalier de l’Université de Montréal Montreal, Quebec, Canada

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