SURGICAL INFECTIONS Volume 15, Number 5, 2014 ª Mary Ann Liebert, Inc. DOI: 10.1089/sur.2014.088
Coexistence of Diffuse Malignant Peritoneal Mesothelioma and Candida norvegensis Peritonitis Edoardo Virgilio,1 Paolo Mercantini,1 Mario Ferri,1 Marco Cavallini,1 Antonella Teggi,2 and Vincenzo Ziparo1
To the Editor:
C
andida norvegensis is a fluconazole-resistant yeast that was first isolated in Norway in 1954 from the sputum cultures of asthmatic patients [1]. Since then, it has remained a rare clinical isolate, and its pathogenicity is still debated, as witnessed by the few cases of infection published in the world literature [1–8]. We would like to pique interest by offering our experience with a case of proved peritonitis caused by C. norvegensis—an event rare in itself—associated with diffuse malignant peritoneal mesothelioma (DMPM), an uncommon cancer of the abdomen having a poor prognosis [9,10]. We investigated the possible relations between these two infrequent diseases by reviewing the literature [11–14]. In 2007, a 54-year-old male was admitted to the Division of Infectious Diseases of our hospital because of a high fever (up to 38.2C) of three weeks’ duration that proved refractory to common oral antibiotics. His medical history was unrewarding. His face appeared pallid and emaciated. The rest of the physical examination was remarkable for tachypnea, tachycardia, and diffuse abdominal tenderness with hypoactive bowel sounds. Laboratory investigations revealed a leukocyte count of 18,400/mm3 with 85.5% neutrophils, hemoglobin of 7.2 g/dL, platelet count of 728,000/mm3, C-reactive protein of 403.5 mg/dL, and an erythrocyte sedimentation rate of 140 mm/h. The results of antibody assays for human immunodeficiency virus (HIV), hepatitis B and C, EpsteinBarr virus, Mycoplasma, Chlamydia, typhoid fever, and leishmaniasis were negative, as were the purified protein derivative test for tuberculosis and the Legionella urinary antigen test. Contrast-enhanced thoraco-abdominal computed tomography documented modest perihepatic ascites and diffuse thickening of the right anterolateral parietal peritoneum (Fig. 1). Candida norvegensis was isolated from blood and ascites; additionally, paracentesis, retrieved some neoplastic cellular elements. Following first- and second-line antifungal treatment failure (with fluconazole and itraconazole, respectively), switching to the third-line oral voriconazole (200 mg bid) finally normalized the body temperature in one week. Thereafter, the patient was scheduled for exploratory laparoscopy in order to find the origin of the neoplastic cells: At
surgery, all serous membranes, both visceral and parietal, appeared thickened, hyperemic, and gelatinous. Omentectomy appeared the only possible resection to perform, and histologic review revealed diffuse malignant peritoneal mesothelioma (DMPM). Systemic chemotherapy was started shortly afterward; however, patient’s condition deteriorated gradually until he succumbed to cancer two months after the intervention. From the published studies, we can outline the leading pathobiologic features of Candida norvegensis infection as follows. The species is uncommon and involved rarely in invasive infections [1–8]. A certain degree of fluconazole resistance is inherent [2–6]. The presence of a vascular catheter, history of broad-spectrum antibiotic therapy, and immunocompromise (mostly as a result of acquired immunodeficiency syndrome [AIDS], acute leukemia, or post-transplant drug treatment) are the main risk factors associated with invasive infections [2,7,8]. The respiratory and digestive tracts are the
FIG. 1. Contrast-enhanced computed tomography scan of abdomen documenting diffuse thickening of right-sided parietal peritoneum (within rectangle) along with mild perihepatic ascites.
Departments of 1Medical and Surgical Sciences and Translational Medicine and 2Infectious Diseases, Faculty of Medicine and Psychology ‘‘Sapienza,’’ Rome, Italy.
660
C. NORVEGENSIS AND MESOTHELIOMA
sites involved most frequently; a combination of the two is reported not infrequently, as suggested by some authors positing upstream colonization from the digestive system to the lower airways during mechanical ventilation or by aspiration of gastrointestinal contents [2,3]. Apart from the aforementioned characteristics, the pathogenic significance of C. norvegensis is not unequivocal, and knowledge needs to be improved. In fact, fewer than 30 reports have described a severe infection produced by this yeast. Most of the time, infection occurred in immunocompromised patients affected by AIDS, acute myelogenous leukemia, or immunosuppressive therapy following renal transplant and involved the respiratory, digestive, or urinary tracts [3,4]. The association between this yeast and peritoneal infection has been documented in only three patients having abdominal drainage for peritoneal dialysis or postoperative surveillance and in one patient who suffered from intra-abdominal abscess complicating expanded polytetra fluoroethylene mesh insertion [3,5,6]. Although the overall mortality rate for invasive infection caused by C. norvegensis is around 50%, it is not possible to determine with certainty the related adverse prognostic factors, given the small number of cases [2]. However, the presence of a vascular catheter, history of prior broad-spectrum antibiotic therapy, and immunocompromise appear to be the most common predisposing conditions [2,7,8]. Additionally, we believe that solid-organ malignant tumors could represent a further event favoring this kind of fungal infection. Diffuse malignant peritoneal mesothelioma is a rare and, in most cases, fatal cancer that affects the serosal membranes of the abdomen; 400 new cases are diagnosed annually in the United States (ca. 1:750,000); in Europe, the yearly incidence is about one or two new cases per million [9]. Abdominal distention and pain are the usual presenting features; fever (20%) is an uncommon initial complaint and usually signals far-advanced disease and reduced overall survival [10]. Persistent high-grade fever as the clinical presentation of DMPM has been described in only six instances. No fungal infection was detected in those patients but, characteristically, all of them received broad-spectrum antibiotic therapy or fluconazole without defervescence [11–14]. Given the strong analogies with our patient, who received similar medication, it is tenable to posit that those patients also suffered from an undiagnosed peritoneal or invasive infection attributable to C. norvegensis. Intravenous liposomal amphotericin B has been advocated as the antimycotic agent to eradicate peritoneal or invasive infections caused by this yeast [2–6]. Of interest, our case represents the first successful attempt to use oral voriconazole to treat C. norvegensis peritonitis, as it succeeded in normalizing the temperature of our patient. This is the first case of DMPM heralded by persistent high-grade fever associated with proved C. norvegensis peritonitis. We invite infectious disease specialists, oncologists, and oncologic surgeons to consider this type of fungal peritonitis in febrile patients affected with DMPM.
661 References
1. Dietrichson E. [Study of a Norwegian collection of yeasts] (Fre). Ann Parasitol Hum Comp 1954;29:460–498. 2. Guitard J, Angoulvant A, Letscher-Bru V, et al. Invasive infections due to Candida norvegensis and Candida inconspicua: Report of 12 cases and review of the literature. Med Mycol 2013;51:795–799. 3. Nielsen H, Stenderup J, Bruun B, Ladefoged J. Candida norvegensis peritonitis and invasive disease in a patient on continuous ambulatory peritoneal dialysis. J Clin Microbiol 1990;28:1664–1665. 4. Nielsen H, Stenderup J. Invasive Candida norvegensis infection in immunocompromised patients. Scand J Infect Dis 1996;28:311–312. 5. Sandven P, Nilsen K, Digranes A, et al. Candida norvegensis: A fluconazole-resistant species. Antimicrob Agents Chemother 1997;41:1375–1376. 6. Nolla-Salas J, Torres-Rodrı`guez JM, Grau S, et al. Successful treatment with liposomial amphotericin B of an intraabdominal abscess due to Candida norvegensis associated with a Gore-Tex mesh infection. Scand J Infect Dis 2000;32:560–562. 7. Kiraz N, Akay OM, Sen Y, et al. Candida norvegensis fungaemia in a neutropenic patient with acute nonlymphoblastic leukaemia. Mycoses 2010;53:460–462. 8. Hood SV, Moore CB, Denning DW. Isolation of Candida norvegensis from clinical specimens: Four case reports. Clin Infect Dis 1996;23:1185–1187. 9. Deraco M, Baratti D, Hutanu I, et al. The role of perioperative systemic chemotherapy in diffuse malignant peritoneal mesothelioma patients treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. Ann Surg Oncol 2013;20:1093–1100. 10. Munkholm-Larsen S, Cao CQ, Yan TD. Malignant peritoneal mesothelioma. World J Gastrointest Surg 2009;1:38–48. 11. Hermann J, Bajko G, Stajgis M, et al. Fever of unknown origin: A clinical mask of malignant peritoneal mesothelioma. Contemp Oncol (Pozn) 2012;16:596–599. 12. Chen LY, Huang LX, Wang J, et al. Malignant peritoneal mesothelioma presenting with persistent high fever. J Zhejiang Univ Sci B 2011;12:381–384. 13. Tejido Garcı`a R, Anta Ferna`ndez M, Herna`ndez Herna`ndez JL, et al. [Fever of unknown origin as the clinical presentation of malignant peritoneal mesothelioma] (Spa). Ann Med Interna 1997;14:573–575. 14. Melero M, Lloveras J, Waisman H, et al. Malignant peritoneal mesothelioma: An infrequent cause of prolonged fever syndrome and leukocytosis in a young adult. Medicina (B Aires) 1995;55:48–50.
Address correspondence to: Dr. Edoardo Virgilio Department of Medical and Surgical Sciences and Translational Medicine Faculty of Medicine and Psychology ‘‘Sapienza’’ St. Andrea Hospital via di Grottarossa 1035-39 Rome, 00189, Italy E-mail: [email protected]
Coexistence of Diffuse Malignant Peritoneal Mesothelioma and Candida norvegensis Peritonitis Edoardo Virgilio,1 Paolo Mercantini,1 Mario Ferri,1 Marco Cavallini,1 Antonella Teggi,2 and Vincenzo Ziparo1
To the Editor:
C
andida norvegensis is a fluconazole-resistant yeast that was first isolated in Norway in 1954 from the sputum cultures of asthmatic patients [1]. Since then, it has remained a rare clinical isolate, and its pathogenicity is still debated, as witnessed by the few cases of infection published in the world literature [1–8]. We would like to pique interest by offering our experience with a case of proved peritonitis caused by C. norvegensis—an event rare in itself—associated with diffuse malignant peritoneal mesothelioma (DMPM), an uncommon cancer of the abdomen having a poor prognosis [9,10]. We investigated the possible relations between these two infrequent diseases by reviewing the literature [11–14]. In 2007, a 54-year-old male was admitted to the Division of Infectious Diseases of our hospital because of a high fever (up to 38.2C) of three weeks’ duration that proved refractory to common oral antibiotics. His medical history was unrewarding. His face appeared pallid and emaciated. The rest of the physical examination was remarkable for tachypnea, tachycardia, and diffuse abdominal tenderness with hypoactive bowel sounds. Laboratory investigations revealed a leukocyte count of 18,400/mm3 with 85.5% neutrophils, hemoglobin of 7.2 g/dL, platelet count of 728,000/mm3, C-reactive protein of 403.5 mg/dL, and an erythrocyte sedimentation rate of 140 mm/h. The results of antibody assays for human immunodeficiency virus (HIV), hepatitis B and C, EpsteinBarr virus, Mycoplasma, Chlamydia, typhoid fever, and leishmaniasis were negative, as were the purified protein derivative test for tuberculosis and the Legionella urinary antigen test. Contrast-enhanced thoraco-abdominal computed tomography documented modest perihepatic ascites and diffuse thickening of the right anterolateral parietal peritoneum (Fig. 1). Candida norvegensis was isolated from blood and ascites; additionally, paracentesis, retrieved some neoplastic cellular elements. Following first- and second-line antifungal treatment failure (with fluconazole and itraconazole, respectively), switching to the third-line oral voriconazole (200 mg bid) finally normalized the body temperature in one week. Thereafter, the patient was scheduled for exploratory laparoscopy in order to find the origin of the neoplastic cells: At
surgery, all serous membranes, both visceral and parietal, appeared thickened, hyperemic, and gelatinous. Omentectomy appeared the only possible resection to perform, and histologic review revealed diffuse malignant peritoneal mesothelioma (DMPM). Systemic chemotherapy was started shortly afterward; however, patient’s condition deteriorated gradually until he succumbed to cancer two months after the intervention. From the published studies, we can outline the leading pathobiologic features of Candida norvegensis infection as follows. The species is uncommon and involved rarely in invasive infections [1–8]. A certain degree of fluconazole resistance is inherent [2–6]. The presence of a vascular catheter, history of broad-spectrum antibiotic therapy, and immunocompromise (mostly as a result of acquired immunodeficiency syndrome [AIDS], acute leukemia, or post-transplant drug treatment) are the main risk factors associated with invasive infections [2,7,8]. The respiratory and digestive tracts are the
FIG. 1. Contrast-enhanced computed tomography scan of abdomen documenting diffuse thickening of right-sided parietal peritoneum (within rectangle) along with mild perihepatic ascites.
Departments of 1Medical and Surgical Sciences and Translational Medicine and 2Infectious Diseases, Faculty of Medicine and Psychology ‘‘Sapienza,’’ Rome, Italy.
660
C. NORVEGENSIS AND MESOTHELIOMA
sites involved most frequently; a combination of the two is reported not infrequently, as suggested by some authors positing upstream colonization from the digestive system to the lower airways during mechanical ventilation or by aspiration of gastrointestinal contents [2,3]. Apart from the aforementioned characteristics, the pathogenic significance of C. norvegensis is not unequivocal, and knowledge needs to be improved. In fact, fewer than 30 reports have described a severe infection produced by this yeast. Most of the time, infection occurred in immunocompromised patients affected by AIDS, acute myelogenous leukemia, or immunosuppressive therapy following renal transplant and involved the respiratory, digestive, or urinary tracts [3,4]. The association between this yeast and peritoneal infection has been documented in only three patients having abdominal drainage for peritoneal dialysis or postoperative surveillance and in one patient who suffered from intra-abdominal abscess complicating expanded polytetra fluoroethylene mesh insertion [3,5,6]. Although the overall mortality rate for invasive infection caused by C. norvegensis is around 50%, it is not possible to determine with certainty the related adverse prognostic factors, given the small number of cases [2]. However, the presence of a vascular catheter, history of prior broad-spectrum antibiotic therapy, and immunocompromise appear to be the most common predisposing conditions [2,7,8]. Additionally, we believe that solid-organ malignant tumors could represent a further event favoring this kind of fungal infection. Diffuse malignant peritoneal mesothelioma is a rare and, in most cases, fatal cancer that affects the serosal membranes of the abdomen; 400 new cases are diagnosed annually in the United States (ca. 1:750,000); in Europe, the yearly incidence is about one or two new cases per million [9]. Abdominal distention and pain are the usual presenting features; fever (20%) is an uncommon initial complaint and usually signals far-advanced disease and reduced overall survival [10]. Persistent high-grade fever as the clinical presentation of DMPM has been described in only six instances. No fungal infection was detected in those patients but, characteristically, all of them received broad-spectrum antibiotic therapy or fluconazole without defervescence [11–14]. Given the strong analogies with our patient, who received similar medication, it is tenable to posit that those patients also suffered from an undiagnosed peritoneal or invasive infection attributable to C. norvegensis. Intravenous liposomal amphotericin B has been advocated as the antimycotic agent to eradicate peritoneal or invasive infections caused by this yeast [2–6]. Of interest, our case represents the first successful attempt to use oral voriconazole to treat C. norvegensis peritonitis, as it succeeded in normalizing the temperature of our patient. This is the first case of DMPM heralded by persistent high-grade fever associated with proved C. norvegensis peritonitis. We invite infectious disease specialists, oncologists, and oncologic surgeons to consider this type of fungal peritonitis in febrile patients affected with DMPM.
661 References
1. Dietrichson E. [Study of a Norwegian collection of yeasts] (Fre). Ann Parasitol Hum Comp 1954;29:460–498. 2. Guitard J, Angoulvant A, Letscher-Bru V, et al. Invasive infections due to Candida norvegensis and Candida inconspicua: Report of 12 cases and review of the literature. Med Mycol 2013;51:795–799. 3. Nielsen H, Stenderup J, Bruun B, Ladefoged J. Candida norvegensis peritonitis and invasive disease in a patient on continuous ambulatory peritoneal dialysis. J Clin Microbiol 1990;28:1664–1665. 4. Nielsen H, Stenderup J. Invasive Candida norvegensis infection in immunocompromised patients. Scand J Infect Dis 1996;28:311–312. 5. Sandven P, Nilsen K, Digranes A, et al. Candida norvegensis: A fluconazole-resistant species. Antimicrob Agents Chemother 1997;41:1375–1376. 6. Nolla-Salas J, Torres-Rodrı`guez JM, Grau S, et al. Successful treatment with liposomial amphotericin B of an intraabdominal abscess due to Candida norvegensis associated with a Gore-Tex mesh infection. Scand J Infect Dis 2000;32:560–562. 7. Kiraz N, Akay OM, Sen Y, et al. Candida norvegensis fungaemia in a neutropenic patient with acute nonlymphoblastic leukaemia. Mycoses 2010;53:460–462. 8. Hood SV, Moore CB, Denning DW. Isolation of Candida norvegensis from clinical specimens: Four case reports. Clin Infect Dis 1996;23:1185–1187. 9. Deraco M, Baratti D, Hutanu I, et al. The role of perioperative systemic chemotherapy in diffuse malignant peritoneal mesothelioma patients treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. Ann Surg Oncol 2013;20:1093–1100. 10. Munkholm-Larsen S, Cao CQ, Yan TD. Malignant peritoneal mesothelioma. World J Gastrointest Surg 2009;1:38–48. 11. Hermann J, Bajko G, Stajgis M, et al. Fever of unknown origin: A clinical mask of malignant peritoneal mesothelioma. Contemp Oncol (Pozn) 2012;16:596–599. 12. Chen LY, Huang LX, Wang J, et al. Malignant peritoneal mesothelioma presenting with persistent high fever. J Zhejiang Univ Sci B 2011;12:381–384. 13. Tejido Garcı`a R, Anta Ferna`ndez M, Herna`ndez Herna`ndez JL, et al. [Fever of unknown origin as the clinical presentation of malignant peritoneal mesothelioma] (Spa). Ann Med Interna 1997;14:573–575. 14. Melero M, Lloveras J, Waisman H, et al. Malignant peritoneal mesothelioma: An infrequent cause of prolonged fever syndrome and leukocytosis in a young adult. Medicina (B Aires) 1995;55:48–50.
Address correspondence to: Dr. Edoardo Virgilio Department of Medical and Surgical Sciences and Translational Medicine Faculty of Medicine and Psychology ‘‘Sapienza’’ St. Andrea Hospital via di Grottarossa 1035-39 Rome, 00189, Italy E-mail: [email protected]
