Article Figures & Data
Figures
- FIG. 1.
Kaplan-Meier survival curves for underlying disease, zygomycosis infection, and actuarial disease (all 24 subjects). Crosses indicate deaths or end of treatment with posaconazole. The solid line represents percent survival from underlying disease; it does not consider any specific antifungal therapy or surgery. Those deaths were due to complications from patients underlying condition and not due to zygomycosis. The dotted line represents percent survival from zygomycosis. Those deaths were due only to zygomycosis. The hatched line represents survival considering all causes. The inset expands the view of percent survival during the first 40 days of posaconazole treatment. All deaths from zygomycosis occurred early in treatment, suggesting posaconazole treatment for more than 30 days is associated with long-term survival. Deaths not due to zygomycosis but from underlying disease were more likely after 40 days of posaconazole treatment.
Tables
- TABLE 1.
Summary of 24 subjects treated with posaconazole (POS) for zygomycosis
Subject no. Age (yr)/sexa Risk factor(s)b Antifungal agents before POS (days) Infection site Organism Surgery prior to POS Reason for enrollment Duration of POS therapy (days) Outcomef (days after starting POS) 1 57/M CLL treated with alloBMT, ongoing GVHD ITC (53), then AMB 1 mg/kg of body weight/day (3) Rhinocerebral Mucor sp. Radical debridement of right face Refractory: progressive sinusitis 128 CR (167) 2 23/M AML treated with alloBMT, ongoing GVHD ITC (46), then LAM 12-15 mg/kg/day (13) Skin (2.5-cm lesion) —e Radical skin excision that had normal margins Refractory: continued fever 86 CR (121) 3 58/M Refractory anemia treated with alloBMT (×2) FLC (95), then ABLC 5 mg/kg/day (12) with VRC (6), then CAS (4) Rhinocerebral and peritonsillar abscess Mucor sp. Tonsillar debridement Refractory: extension of sinus and tonsillar disease 751 Partial ethmoidectomy day 23; CR (791) 4 46/F CLL treated with alloBMT ×2, ongoing GVHD ITC (48) with CAS (48) and with LAM 7.5 mg/kg/day (27) Rhinocerebral and jaw Mucor sp. Sinus and ethmoid debridement ×2 Refractory: progression of maxillary sinus disease 256 CR (286) 5 54/F CML treated with alloBMT, ongoing GVHD ABLC 5 mg/kg/day (8), then LAM 7.5 mg/kg/day (18) Disseminated (brain abscess, rhinocerebral, lung, and gastrocnemius muscle) Cunninghamella sp. None Refractory: progression of brain lesion 148 PR; died day 148 due to failure to thrive 6 17/M AML treated with T-cell-depleted alloPBSCT, ongoing GVHD ITC (279), then LAM 5 mg/kg/day (27) Lung Rhizopus stolonifer Partial lobectomy Refractory: progression of lung lesions 1004 PR 7 29/M CML treated with alloBMT, subsequent AML treated with alloBMT with donor lymphocyte infusion ×2, maintenance chemotherapy for relapsing AML LAM 5 mg/kg/day, (10) Rhinocerebral pharyngeal — None Refractory: progression of sinus pharyngeal disease 37 PR; died day 37 from UD and bacterial pneumonia 8 55/M MDS treated with alloPBSCT, subsequent AML treated with alloPBSCT, ongoing GVHD ITC (1,483), then VRC (36) Rhinocerebral and jaw Rhizopus sp. Partial debridement of jaw and palate Refractory: progression of palate, sinus, and brain lesions 631 ABLC 5 mg/kg/day and hyperbaric oxygen treatments days 92 to 268; CR (814) 9 22/M CML, subsequent ALL treated with alloBMT, ongoing GVHD AMB 0.5 to 1.3 mg/kg/day (20) Disseminated (lung, skin, and brain) Cunninghamella sp. None Refractory: progression of lung lesions 13 Failure; died day 14 from clinical progression of skin and brain infection 10 55/M Metastatic renal cell carcinoma after nephrectomy treated with alloBMT, ongoing GVHD VRC (136), then ITC (25) GId (duodenal biopsy) Rhizopus microsporus None Intolerant: elevated serum creatinine 12 Failure; POS discontinued day 12 after duodenal biopsy showed zygomycosis (no additional information) 11 62/M AML treated with alloBMT FLC (18), then LAM 5 mg/kg/day, (6) with topical AMB 0.65 mg/kg/day (5) Rhinocerebral Mucor sp. Enucleation, sphenoid and orbital debridement ×2 Refractory: progression of sinus and orbital disease 30 Failure; died day 31 from zygomycosis 12 57/M SOT (kidney, heart) AMB 1.3 mg/kg/day (34) Chest, pericardium, and peritoneum Rhizopus sp. Chest, pericardial, and peritoneal debridement ×2 Refractory: progression of chest and peritoneal lesions 166 CR (197) 13 56/M SOT (liver) LAMc(111) Rhinocerebral — Rhinotomy, maxillary debridement ×2 Refractory: continued bony invasion 66 CR (100) 14 42/M SOT (kidney, pancreas) ABLC 5 to 10 mg/kg/day (33) Intestines and liver Rhizopus sp. Excision of necrotic jejunum Refractory: enlarging liver abscess 672 CR (820) 15 54/M SOT (kidney) FLC (2), then VRC (7), then ABLC 5 mg/kg/day (14) Skin and bone Mucor sp. Debridement of skin and bone ×2 Refractory: progression of bony invasion 279 Debridement of skin and bone days 73 and 85; PR 16 61/M Type 1 DM LAMc(16) Rhinocerebral — Caldwell Luc procedure Intolerant: elevated serum creatinine 294 CR (1,212) 17 67/M Type 2 DM AMBc(60) Rhinocerebral — Debridement of antrum, sinuses, and palate ×2 Refractory: progression of orbital, sinus, and palatal disease 157 POS stopped on day 157 due to a purpuric rash over face and upper shoulders; CR (331) 18 7/F Type 1 DM, chronic use of inhaled steroids for asthma LAM 10 to 15 mg/kg/day (10) and intraorbital AMB Rhinocerebral Mucor sp. Debridement of paranasal sinuses and orbit ×5 Refractory: progression of orbital and sinus disease 547 POS, 200 mg TID, and LAM continued; hyperbaric oxygen and intraorbital AMB (day 1 to 14); PR 19 74/F Type 2 DM with renal disease LAM 7 mg/kg/day, (5) Trachea and neck — None Intolerant: elevated serum creatinine 352 PR; died day 352 from noninfectious causes 20 18/M Type 1 DM, ALL, undergoing chemotherapy AMB 1 to 1.5 mg/kg/day (21) Skin Rhizomucor sp. Debridement Intolerant: elevated serum creatinine 901 CR (1,084) 21 50/M AML AMB (6), then LAM 7 mg/kg/day (69) Rhinocerebral Rhizopus sp. Debridement of sinuses ×2 and partial extirpation of right eye Refractory: progression of sinus and orbital disease 197 PR; died day 198 from UD 22 65/M Stage 4 NK-cell leukemia LAM 6 mg/kg/day (59) Lung — Wedge resection Intolerant: renal disease 245 PR; died day 245 from UD 23 62/F Non-Hodgkin lymphoma CAS (17) with ABLC 6 mg/kg/day (17) Disseminated (rhinocerebral and lung) Rhizomucor pusillus None Refractory: orbital extension of infection 28 Failure; died from zygomycosis day 29 24 32/M RBC aplasia treated with antithymocyte globulin, cyclosporine, prednisone FLC (>30), then CAS (2) with LAM 3 to 10 mg/kg/day (14 days prior to POS and continued for 8 days with POS) Disseminated (endocarditis with septic emboli) Cunninghamella sp. Aortic valve replacement Refractory: progression of brain and heart lesions 8 Failure; died day 8 from zygomycosis ↵ a M, male; F, female.
↵ b ALL, acute lymphocytic leukemia; alloBMT, allogenic bone marrow transplant; alloPBSCT, allogenic peripheral-blood stem cell transplant; CLL, chronic lymphocytic leukemia; CML, chronic myelogenous leukemia; DM, diabetes mellitus; GVHD, graft-versus-host disease; MDS, myelodysplastic syndrome; NK, natural killer; RBC, red blood cell; SOT, solid-organ transplant.
↵ c Doses for LAM or AMB were not available for patients 13, 16, and 17.
↵ d GI, gastrointestinal tract.
↵ e —, patient had a negative culture but had histopathology for zygomycosis.
↵ f CR, complete response; PR, partial response; TID, three times a day; UD, underlying disease.
