Overview of Fungal Infections - The Italian Experience

Abstract

The incidence of severe fungal infections has increased worldwide and represents a serious threat, especially among immunocompromised and critically ill patients. Most common pulmonary fungal infections include aspergillosis, cryptococcosis, and Pneumocystis jiroveci pneumonia. Among nosocomial bloodstream infections, Candida spp. is the most common isolated fungus. Mortality rates up to 60% in critically ill patients with Candida infections and 90% in hematological patients with invasive aspergillosis are reported. Furthermore, fungal infections contribute to high morbidity and prolonged hospitalizations. Since standard cultural methods can show low sensitivity or provide delayed responses, new non–culture-dependent methods such as galactomannan β-D-glucan are now available. Novel antifungal compounds (e.g., amphotericin B lipid formulations, last-generation azoles, and echinocandins) have been introduced in the recent years. Nevertheless, despite new advances the appropriate use of diagnostic assays along with a thorough therapeutic management remain the key to ensure an early appropriate targeted treatment that represents the crucial factor to attain a successful approach to severe fungal infections.

Keywords

fungal infections - aspergillosis - Candida - Pneumocystis jiroveci pneumonia - cryptococcosis - antifungal treatment

• References

• 1 McNeil MM, Nash SL, Hajjeh RA , et al. Trends in mortality due to invasive mycotic diseases in the United States, 1980-1997. Clin Infect Dis 2001; 33 (5) 641-647
• 2 Blot SI, Vandewoude KH. Estimating attributable mortality of candidemia: clinical judgement vs matched cohort studies. Eur J Clin Microbiol Infect Dis 2003; 22 (2) 132-133 , author reply 134
• 3 Martin GS, Mannino DM, Eaton S, Moss M. The epidemiology of sepsis in the United States from 1979 through 2000. N Engl J Med 2003; 348 (16) 1546-1554
• 4 Fishman JA. Infection in solid-organ transplant recipients. N Engl J Med 2007; 357 (25) 2601-2614
• 5 Kontoyiannis DP, Marr KA, Park BJ , et al. Prospective surveillance for invasive fungal infections in hematopoietic stem cell transplant recipients, 2001-2006: overview of the Transplant-Associated Infection Surveillance Network (TRANSNET) Database. Clin Infect Dis 2010; 50 (8) 1091-1100
• 6 Jarvis WR. Epidemiology of nosocomial fungal infections, with emphasis on Candida species. Clin Infect Dis 1995; 20 (6) 1526-1530
• 7 Richards MJ, Edwards JR, Culver DH, Gaynes RP. Nosocomial infections in combined medical-surgical intensive care units in the United States. Infect Control Hosp Epidemiol 2000; 21 (8) 510-515
• 8 Wey SB, Mori M, Pfaller MA, Woolson RF, Wenzel RP. Hospital-acquired candidemia. The attributable mortality and excess length of stay. Arch Intern Med 1988; 148 (12) 2642-2645
• 9 Trick WE, Fridkin SK, Edwards JR, Hajjeh RA, Gaynes RP ; National Nosocomial Infections Surveillance System Hospitals. Secular trend of hospital-acquired candidemia among intensive care unit patients in the United States during 1989-1999. Clin Infect Dis 2002; 35 (5) 627-630
• 10 Marchetti O, Bille J, Fluckiger U , et al; Fungal Infection Network of Switzerland. Epidemiology of candidemia in Swiss tertiary care hospitals: secular trends, 1991-2000. Clin Infect Dis 2004; 38 (3) 311-320
• 11 Voss A, le Noble JL, Verduyn Lunel FM, Foudraine NA, Meis JF. Candidemia in intensive care unit patients: risk factors for mortality. Infection 1997; 25 (1) 8-11
• 12 Cornet M, Fleury L, Maslo C, Bernard JF, Brücker G ; Invasive Aspergillosis Surveillance Network of the Assistance Publique-Hôpitaux de Paris. Epidemiology of invasive aspergillosis in France: a six-year multicentric survey in the Greater Paris area. J Hosp Infect 2002; 51 (4) 288-296
• 13 Mattner F, Chaberny IF, Weissbrodt H , et al. Surveillance of invasive mold infections in lung transplant recipients: effect of antimycotic prophylaxis with itraconazole and voriconazole [in German]. Mycoses 2005; 48 (Suppl. 01) 51-55
• 14 Patterson TF. Invasive mycoses: management and unmet medical needs. Curr Opin Infect Dis 2001; 14 (6) 669-671
• 15 Berenguer J, Buck M, Witebsky F, Stock F, Pizzo PA, Walsh TJ. Lysis-centrifugation blood cultures in the detection of tissue-proven invasive candidiasis. Disseminated versus single-organ infection. Diagn Microbiol Infect Dis 1993; 17 (2) 103-109
• 16 Zilberberg MD, Kollef MH, Arnold H , et al. Inappropriate empiric antifungal therapy for candidemia in the ICU and hospital resource utilization: a retrospective cohort study. BMC Infect Dis 2010; 10: 150
• 17 von Eiff M, Roos N, Schulten R, Hesse M, Zühlsdorf M, van de Loo J. Pulmonary aspergillosis: early diagnosis improves survival. Respiration 1995; 62 (6) 341-347
• 18 Morrell M, Fraser VJ, Kollef MH. Delaying the empiric treatment of candida bloodstream infection until positive blood culture results are obtained: a potential risk factor for hospital mortality. Antimicrob Agents Chemother 2005; 49 (9) 3640-3645
• 19 Tissot F, Lamoth F, Hauser PM , et al; Fungal Infection Network of Switzerland (FUNGINOS). β-glucan antigenemia anticipates diagnosis of blood culture-negative intraabdominal candidiasis. Am J Respir Crit Care Med 2013; 188 (9) 1100-1109
• 20 Pfeiffer CD, Fine JP, Safdar N. Diagnosis of invasive aspergillosis using a galactomannan assay: a meta-analysis. Clin Infect Dis 2006; 42 (10) 1417-1427
• 21 Shorr AF, Susla GM, O'Grady NP. Pulmonary infiltrates in the non-HIV-infected immunocompromised patient: etiologies, diagnostic strategies, and outcomes. Chest 2004; 125 (1) 260-271
• 22 Bitar D, Lortholary O, Le Strat Y , et al. Population-based analysis of invasive fungal infections, France, 2001-2010. Emerg Infect Dis 2014; 20 (7) 1149-1155
• 23 Yeghen T, Kibbler CC, Prentice HG , et al. Management of invasive pulmonary aspergillosis in hematology patients: a review of 87 consecutive cases at a single institution. Clin Infect Dis 2000; 31 (4) 859-868
• 24 Kosmidis C, Denning DW. The clinical spectrum of pulmonary aspergillosis. Thorax 2015; 70 (3) 270-277
• 25 Perfect JR, Cox GM, Lee JY , et al; Mycoses Study Group. The impact of culture isolation of Aspergillus species: a hospital-based survey of aspergillosis. Clin Infect Dis 2001; 33 (11) 1824-1833
• 26 Cenci E, Mencacci A, Fè d'Ostiani C , et al. Cytokine- and T helper-dependent lung mucosal immunity in mice with invasive pulmonary aspergillosis. J Infect Dis 1998; 178 (6) 1750-1760
• 27 Pahls S, Schaffner A. Aspergillus fumigatus pneumonia in neutropenic patients receiving fluconazole for infection due to Candida species: is amphotericin B combined with fluconazole the appropriate answer?. Clin Infect Dis 1994; 18 (3) 484-486
• 28 Schaffner A. Macrophage-Aspergillus interactions. Immunol Ser 1994; 60: 545-552
• 29 Saugier-Veber P, Devergie A, Sulahian A , et al. Epidemiology and diagnosis of invasive pulmonary aspergillosis in bone marrow transplant patients: results of a 5 year retrospective study. Bone Marrow Transplant 1993; 12 (2) 121-124
• 30 Won HJ, Lee KS, Cheon JE , et al. Invasive pulmonary aspergillosis: prediction at thin-section CT in patients with neutropenia—a prospective study. Radiology 1998; 208 (3) 777-782
• 31 Denning DW. Chronic forms of pulmonary aspergillosis. Clin Microbiol Infect 2001; 7 (Suppl. 02) 25-31
• 32 Denning DW, Riniotis K, Dobrashian R, Sambatakou H. Chronic cavitary and fibrosing pulmonary and pleural aspergillosis: case series, proposed nomenclature change, and review. Clin Infect Dis 2003; 37 (Suppl. 03) S265-S280
• 33 Barberan J, Sanz F, Hernandez JL , et al. Clinical features of invasive pulmonary aspergillosis vs. colonization in COPD patients distributed by gold stage. J Infect 2012; 65 (5) 447-452
• 34 Sganga G, Bianco G, Frongillo F, Lirosi MC, Nure E, Agnes S. Fungal infections after liver transplantation: incidence and outcome. Transplant Proc 2014; 46 (7) 2314-2318
• 35 Baddley JW. Clinical risk factors for invasive aspergillosis. Med Mycol 2011; 49 (Suppl. 01) S7-S12
• 36 Martin SI, Marty FM, Fiumara K, Treon SP, Gribben JG, Baden LR. Infectious complications associated with alemtuzumab use for lymphoproliferative disorders. Clin Infect Dis 2006; 43 (1) 16-24
• 37 Bassetti M, Pecori D, Della Siega P, Corcione S, De Rosa FG. Current and future therapies for invasive aspergillosis. Pulm Pharmacol Ther 2015; 32: 155-165
• 38 Blot SI, Taccone FS, Van den Abeele AM , et al; AspICU Study Investigators. A clinical algorithm to diagnose invasive pulmonary aspergillosis in critically ill patients. Am J Respir Crit Care Med 2012; 186 (1) 56-64
• 39 Walsh TJ, Anaissie EJ, Denning DW , et al; Infectious Diseases Society of America. Treatment of aspergillosis: clinical practice guidelines of the Infectious Diseases Society of America. Clin Infect Dis 2008; 46 (3) 327-360
• 40 Ascioglu S, Rex JH, de Pauw B , et al; Invasive Fungal Infections Cooperative Group of the European Organization for Research and Treatment of Cancer; Mycoses Study Group of the National Institute of Allergy and Infectious Diseases. Defining opportunistic invasive fungal infections in immunocompromised patients with cancer and hematopoietic stem cell transplants: an international consensus. Clin Infect Dis 2002; 34 (1) 7-14
• 41 Levy H, Horak DA, Tegtmeier BR, Yokota SB, Forman SJ. The value of bronchoalveolar lavage and bronchial washings in the diagnosis of invasive pulmonary aspergillosis. Respir Med 1992; 86 (3) 243-248
• 42 Tanriover MD, Ascioglu S, Altun B, Uzun O. Galactomannan on the stage: prospective evaluation of the applicability in routine practice and surveillance. Mycoses 2010; 53 (1) 16-25
• 43 Latgé JP, Kobayashi H, Debeaupuis JP , et al. Chemical and immunological characterization of the extracellular galactomannan of Aspergillus fumigatus . Infect Immun 1994; 62 (12) 5424-5433
• 44 Meersseman W, Lagrou K, Maertens J , et al. Galactomannan in bronchoalveolar lavage fluid: a tool for diagnosing aspergillosis in intensive care unit patients. Am J Respir Crit Care Med 2008; 177 (1) 27-34
• 45 Denning DW, Evans EG, Kibbler CC , et al; British Society for Medical Mycology. Guidelines for the investigation of invasive fungal infections in haematological malignancy and solid organ transplantation. Eur J Clin Microbiol Infect Dis 1997; 16 (6) 424-436
• 46 Sulahian A, Boutboul F, Ribaud P, Leblanc T, Lacroix C, Derouin F. Value of antigen detection using an enzyme immunoassay in the diagnosis and prediction of invasive aspergillosis in two adult and pediatric hematology units during a 4-year prospective study. Cancer 2001; 91 (2) 311-318
• 47 Posteraro B, De Pascale G, Tumbarello M , et al. Early diagnosis of candidemia in intensive care unit patients with sepsis: a prospective comparison of (1→3)-β-D-glucan assay, Candida score, and colonization index. Crit Care 2011; 15 (5) R249
• 48 Ostrosky-Zeichner L. Invasive mycoses: diagnostic challenges. Am J Med 2012; 125 (1, Suppl): S14-S24
• 49 Rhame FS, Streifel AJ, Kersey Jr JH, McGlave PB. Extrinsic risk factors for pneumonia in the patient at high risk of infection. Am J Med 1984; 76 (5A): 42-52
• 50 Park SY, Lim C, Lee SO , et al. Computed tomography findings in invasive pulmonary aspergillosis in non-neutropenic transplant recipients and neutropenic patients, and their prognostic value. J Infect 2011; 63 (6) 447-456
• 51 Limper AH, Knox KS, Sarosi GA , et al; American Thoracic Society Fungal Working Group. An official American Thoracic Society statement: treatment of fungal infections in adult pulmonary and critical care patients. Am J Respir Crit Care Med 2011; 183 (1) 96-128
• 52 Herbrecht R, Denning DW, Patterson TF , et al; Invasive Fungal Infections Group of the European Organisation for Research and Treatment of Cancer and the Global Aspergillus Study Group. Voriconazole versus amphotericin B for primary therapy of invasive aspergillosis. N Engl J Med 2002; 347 (6) 408-415
• 53 Lat A, Thompson III GR. Update on the optimal use of voriconazole for invasive fungal infections. Infect Drug Resist 2011; 4: 43-53
• 54 ESCMID Guidelines for Diagnosis and Treatment of Aspergillus Diseases, Organized Jointly with the ESCMID Study Group for Infections in Compromised Hosts (ESGICH). Available at: https://www.escmid.org/research_projects/study_groups/efisg/
• 55 Cushion MT. Are members of the fungal genus pneumocystis (a) commensals; (b) opportunists; (c) pathogens; or (d) all of the above?. PLoS Pathog 2010; 6 (9) e1001009
• 56 Edman JC, Kovacs JA, Masur H, Santi DV, Elwood HJ, Sogin ML. Ribosomal RNA sequence shows Pneumocystis carinii to be a member of the fungi. Nature 1988; 334 (6182) 519-522
• 57 Pifer LL, Hughes WT, Stagno S, Woods D. Pneumocystis carinii infection: evidence for high prevalence in normal and immunosuppressed children. Pediatrics 1978; 61 (1) 35-41
• 58 Kovacs JA, Gill VJ, Meshnick S, Masur H. New insights into transmission, diagnosis, and drug treatment of Pneumocystis carinii pneumonia. JAMA 2001; 286 (19) 2450-2460
• 59 Thomas Jr CF, Limper AH. Pneumocystis pneumonia. N Engl J Med 2004; 350 (24) 2487-2498
• 60 Shah RM, Kaji AV, Ostrum BJ, Friedman AC. Interpretation of chest radiographs in AIDS patients: usefulness of CD4 lymphocyte counts. Radiographics 1997; 17 (1) 47-58 , discussion 59–61
• 61 Tasaka S, Hasegawa N, Kobayashi S , et al. Serum indicators for the diagnosis of pneumocystis pneumonia. Chest 2007; 131 (4) 1173-1180
• 62 Fei MW, Kim EJ, Sant CA , et al. Predicting mortality from HIV-associated Pneumocystis pneumonia at illness presentation: an observational cohort study. Thorax 2009; 64 (12) 1070-1076
• 63 Bozzette SA, Sattler FR, Chiu J , et al; California Collaborative Treatment Group. A controlled trial of early adjunctive treatment with corticosteroids for Pneumocystis carinii pneumonia in the acquired immunodeficiency syndrome. N Engl J Med 1990; 323 (21) 1451-1457
• 64 Colby C, McAfee S, Sackstein R, Finkelstein D, Fishman J, Spitzer T. A prospective randomized trial comparing the toxicity and safety of atovaquone with trimethoprim/sulfamethoxazole as Pneumocystis carinii pneumonia prophylaxis following autologous peripheral blood stem cell transplantation. Bone Marrow Transplant 1999; 24 (8) 897-902
• 65 Yale SH, Limper AH. Pneumocystis carinii pneumonia in patients without acquired immunodeficiency syndrome: associated illness and prior corticosteroid therapy. Mayo Clin Proc 1996; 71 (1) 5-13
• 66 Hughes WT, Rivera GK, Schell MJ, Thornton D, Lott L. Successful intermittent chemoprophylaxis for Pneumocystis carinii pneumonitis. N Engl J Med 1987; 316 (26) 1627-1632
• 67 Wheat LJ, Goldman M, Sarosi G. State-of-the-art review of pulmonary fungal infections. Semin Respir Infect 2002; 17 (2) 158-181
• 68 Lortholary O, Nunez H, Brauner MW, Dromer F. Pulmonary cryptococcosis. Semin Respir Crit Care Med 2004; 25 (2) 145-157
• 69 Mirza SA, Phelan M, Rimland D , et al. The changing epidemiology of cryptococcosis: an update from population-based active surveillance in 2 large metropolitan areas, 1992-2000. Clin Infect Dis 2003; 36 (6) 789-794
• 70 Chen SC ; Australasian Society for Infectious Diseases (ASID) Mycoses Interest Group. Cryptococcosis in Australasia and the treatment of cryptococcal and other fungal infections with liposomal amphotericin B. J Antimicrob Chemother 2002; 49 (Suppl. 01) 57-61
• 71 Amornkul PN, Hu DJ, Tansuphasawadikul S , et al. Human immunodeficiency virus type 1 subtype and other factors associated with extrapulmonary Cryptococcosis among patients in Thailand with AIDS. AIDS Res Hum Retroviruses 2003; 19 (2) 85-90
• 72 Corbett EL, Churchyard GJ, Charalambos S , et al. Morbidity and mortality in South African gold miners: impact of untreated disease due to human immunodeficiency virus. Clin Infect Dis 2002; 34 (9) 1251-1258
• 73 Saag MS, Graybill RJ, Larsen RA , et al; Infectious Diseases Society of America. Practice guidelines for the management of cryptococcal disease. Clin Infect Dis 2000; 30 (4) 710-718
• 74 Cebular S, Lee S, Tolaney P, Lutwick L. Community-acquired pneumonia in immunocompromised patients. Opportunistic infections to consider in differential diagnosis. Postgrad Med 2003; 113 (1) 65-66 , 69–70, 73–74 passim
• 75 Pappas PG, Perfect JR, Cloud GA , et al. Cryptococcosis in human immunodeficiency virus-negative patients in the era of effective azole therapy. Clin Infect Dis 2001; 33 (5) 690-699
• 76 Lacomis JM, Costello P, Vilchez R, Kusne S. The radiology of pulmonary cryptococcosis in a tertiary medical center. J Thorac Imaging 2001; 16 (3) 139-148
• 77 Aberg JA, Mundy LM, Powderly WG. Pulmonary cryptococcosis in patients without HIV infection. Chest 1999; 115 (3) 734-740
• 78 Singh N, Alexander BD, Lortholary O , et al. Pulmonary cryptococcosis in solid organ transplant recipients: clinical relevance of serum cryptococcal antigen. Clin Infect Dis 2008; 46 (2) e12-e18
• 79 Vilchez RA, Linden P, Lacomis J, Costello P, Fung J, Kusne S. Acute respiratory failure associated with pulmonary cryptococcosis in non-aids patients. Chest 2001; 119 (6) 1865-1869
• 80 Lortholary O, Poizat G, Zeller V , et al. Long-term outcome of AIDS-associated cryptococcosis in the era of combination antiretroviral therapy. AIDS 2006; 20 (17) 2183-2191
• 81 Perfect JR, Dismukes WE, Dromer F , et al. Clinical practice guidelines for the management of cryptococcal disease: 2010 update by the Infectious Diseases Society of America. Clin Infect Dis 2010; 50 (3) 291-322
• 82 Dromer F, Mathoulin-Pélissier S, Launay O, Lortholary O ; French Cryptococcosis Study Group. Determinants of disease presentation and outcome during cryptococcosis: the CryptoA/D study. PLoS Med 2007; 4 (2) e21
• 83 Spellberg B, Edwards JE. The Pathophysiology and Treatment of Candida Sepsis. Curr Infect Dis Rep 2002; 4 (5) 387-399
• 84 Wisplinghoff H, Bischoff T, Tallent SM, Seifert H, Wenzel RP, Edmond MB. Nosocomial bloodstream infections in US hospitals: analysis of 24,179 cases from a prospective nationwide surveillance study. Clin Infect Dis 2004; 39 (3) 309-317
• 85 Bassetti M, Marchetti M, Chakrabarti A , et al. A research agenda on the management of intra-abdominal candidiasis: results from a consensus of multinational experts. Intensive Care Med 2013; 39 (12) 2092-2106
• 86 Eggimann P, Garbino J, Pittet D. Epidemiology of Candida species infections in critically ill non-immunosuppressed patients. Lancet Infect Dis 2003; 3 (11) 685-702
• 87 Kontoyiannis DP, Luna MA, Samuels BI, Bodey GP. Hepatosplenic candidiasis. A manifestation of chronic disseminated candidiasis. Infect Dis Clin North Am 2000; 14 (3) 721-739
• 88 Gudlaugsson O, Gillespie S, Lee K , et al. Attributable mortality of nosocomial candidemia, revisited. Clin Infect Dis 2003; 37 (9) 1172-1177
• 89 Bassetti M, Merelli M, Righi E , et al. Epidemiology, species distribution, antifungal susceptibility, and outcome of candidemia across five sites in Italy and Spain. J Clin Microbiol 2013; 51 (12) 4167-4172
• 90 Bassetti M, Righi E, Costa A , et al. Epidemiological trends in nosocomial candidemia in intensive care. BMC Infect Dis 2006; 6: 21
• 91 Leroy O, Gangneux JP, Montravers P , et al; AmarCand Study Group. Epidemiology, management, and risk factors for death of invasive Candida infections in critical care: a multicenter, prospective, observational study in France (2005-2006). Crit Care Med 2009; 37 (5) 1612-1618
• 92 Garey KW, Rege M, Pai MP , et al. Time to initiation of fluconazole therapy impacts mortality in patients with candidemia: a multi-institutional study. Clin Infect Dis 2006; 43 (1) 25-31
• 93 Kollef M, Micek S, Hampton N, Doherty JA, Kumar A. Septic shock attributed to Candida infection: importance of empiric therapy and source control. Clin Infect Dis 2012; 54 (12) 1739-1746
• 94 Delaloye J, Calandra T. Invasive candidiasis as a cause of sepsis in the critically ill patient. Virulence 2014; 5 (1) 161-169
• 95 Guery BP, Arendrup MC, Auzinger G , et al. Management of invasive candidiasis and candidemia in adult non-neutropenic intensive care unit patients: Part II. Treatment. Intensive Care Med 2009; 35 (2) 206-214
• 96 Cornely OA, Bassetti M, Calandra T , et al; ESCMID Fungal Infection Study Group. ESCMID* guideline for the diagnosis and management of Candida diseases 2012: non-neutropenic adult patients. Clin Microbiol Infect 2012; 18 (Suppl. 07) 19-37
• 97 Reboli AC, Rotstein C, Pappas PG , et al; Anidulafungin Study Group. Anidulafungin versus fluconazole for invasive candidiasis. N Engl J Med 2007; 356 (24) 2472-2482
• 98 Nivoix Y, Ubeaud-Sequier G, Engel P, Levêque D, Herbrecht R. Drug-drug interactions of triazole antifungal agents in multimorbid patients and implications for patient care. Curr Drug Metab 2009; 10 (4) 395-409
• 99 Smith J, Safdar N, Knasinski V , et al. Voriconazole therapeutic drug monitoring. Antimicrob Agents Chemother 2006; 50 (4) 1570-1572
• 100 Krishna G, Moton A, Ma L, Medlock MM, McLeod J. Pharmacokinetics and absorption of posaconazole oral suspension under various gastric conditions in healthy volunteers. Antimicrob Agents Chemother 2009; 53 (3) 958-966
• 101 Bowyer P, Moore CB, Rautemaa R, Denning DW, Richardson MD. Azole antifungal resistance today: focus on Aspergillus. Curr Infect Dis Rep 2011; 13 (6) 485-491
• 102 Maertens J, Patterson T, Rahav G , et al. A phase 3 randomised, double-blind trial evaluating isavuconazole vs. voriconazole for the primary treatment of invasive fungal disease caused by Aspergillus spp. or other filamentous fungi (secure). Presented at 24th ECCMID, Barcelona, Spain,2014
• 103 Falci DR, Pasqualotto AC. Profile of isavuconazole and its potential in the treatment of severe invasive fungal infections. Infect Drug Resist 2013; 6: 163-174
• 104 Cornely OA, Maertens J, Bresnik M , et al; AmBiLoad Trial Study Group. Liposomal amphotericin B as initial therapy for invasive mold infection: a randomized trial comparing a high-loading dose regimen with standard dosing (AmBiLoad trial). Clin Infect Dis 2007; 44 (10) 1289-1297
• 105 Philip A, Odabasi Z, Rodriguez J , et al. In vitro synergy testing of anidulafungin with itraconazole, voriconazole, and amphotericin B against Aspergillus spp. and Fusarium spp. Antimicrob Agents Chemother 2005; 49 (8) 3572-3574
• 106 Caillot D, Thiébaut A, Herbrecht R , et al. Liposomal amphotericin B in combination with caspofungin for invasive aspergillosis in patients with hematologic malignancies: a randomized pilot study (Combistrat trial). Cancer 2007; 110 (12) 2740-2746
• 107 Singh N, Limaye AP, Forrest G , et al. Combination of voriconazole and caspofungin as primary therapy for invasive aspergillosis in solid organ transplant recipients: a prospective, multicenter, observational study. Transplantation 2006; 81 (3) 320-326
• 108 Marr KA, Boeckh M, Carter RA, Kim HW, Corey L. Combination antifungal therapy for invasive aspergillosis. Clin Infect Dis 2004; 39 (6) 797-802
• 109 Panackal AA, Parisini E, Proschan M. Salvage combination antifungal therapy for acute invasive aspergillosis may improve outcomes: a systematic review and meta-analysis. Int J Infect Dis 2014; 28: 80-94
• 110 Kousha M, Tadi R, Soubani AO. Pulmonary aspergillosis: a clinical review. Eur Respir Rev 2011; 20 (121) 156-174
• 111 Radisic M, Lattes R, Chapman JF , et al. Risk factors for Pneumocystis carinii pneumonia in kidney transplant recipients: a case-control study. Transpl Infect Dis 2003; 5 (2) 84-93
• 112 Mori S, Cho I, Sugimoto M. A followup study of asymptomatic carriers of Pneumocystis jiroveci during immunosuppressive therapy for rheumatoid arthritis. J Rheumatol 2009; 36 (8) 1600-1605
• 113 Ritter ML, Pirofski L. Mycophenolate mofetil: effects on cellular immune subsets, infectious complications, and antimicrobial activity. Transpl Infect Dis 2009; 11 (4) 290-297
• 114 Husain S, Wagener MM, Singh N. Cryptococcus neoformans infection in organ transplant recipients: variables influencing clinical characteristics and outcome. Emerg Infect Dis 2001; 7 (3) 375-381
• 115 Eggimann P, Que YA, Revelly JP, Pagani JL. Preventing invasive candida infections. Where could we do better?. J Hosp Infect 2015; 89 (4) 302-308