Institutional experience with voriconazole compared with liposomal amphotericin B as empiric therapy for febrile neutropenia

STUDY OBJECTIVE: To assess the effectiveness, safety, and cost of empiric treatment of febrile neutropenia before and after implementing an algorithm in which voriconazole was substituted for liposomal amphotericin B (L-AmB). DESIGN: Retrospective cohort analysis. SETTING: An 850-bed tertiary care hospital, which is also a referral site for patients with acute leukemia. PATIENTS: Fifty-five adult patients who started empiric antifungal therapy for febrile neutropenia between January 1, 2002, and December 31, 2003, encompassing 58 treatment episodes (defined as a hospitalization during which empiric antifungal therapy was administered). MEASUREMENTS AND MAIN RESULTS: Medical charts, including patients' pharmacy and laboratory data, were reviewed. Twenty-six and 32 episodes of L-AmB and voriconazole use, respectively, were identified. No significant differences between the L-AmB and voriconazole groups were noted at baseline. Rates of fever resolution (54% vs 59%, p=0.791) and breakthrough invasive fungal infections (11% vs 12%, p>0.999) were similar for the L-AmB and voriconazole episodes. Premature drug discontinuation due to the prescriber's perceived lack of efficacy occurred most frequently in the voriconazole group (25% vs 8%, p=0.160). Survival was significantly higher in the voriconazole than in the L-AmB group (100% vs 77%, p=0.006). Adverse effects that were significantly more common in the L-AmB group than in the voriconazole group were elevated serum creatinine levels (27% vs 3%, p=0.017) and electrolyte disturbances (19% vs 0%, p=0.014). Adverse effects reported more frequently in the voriconazole group than in the L-AmB group were visual disturbances (9% vs 0%, p=0.245) and elevated hepatic enzyme levels (9% vs 8%, p>0.999). Mean drug expenditures/episode for initial empiric antifungal therapy were lower for voriconazole than for L-AmB ($1593 vs $4144, or $153 vs $380/day). CONCLUSION: Our institution's algorithm incorporating voriconazole into the empiric management of febrile neutropenia was associated with effectiveness outcomes comparable to those observed with L-AmB as well as a lower frequency of adverse effects and overall expenditures for antifungal drugs.     

Safe and effective outpatient treatment of adults with chemotherapy-induced neutropenic fever.

PURPOSE: The safe and effective outpatient treatment of adults with chemotherapy- induced neutropenic fever is reviewed. SUMMARY: Chemotherapy-induced neutropenic fever is a potentially life-threatening circumstance in high-risk patients. The standard of care for neutropenic fever is inpatient treatment with i.v. broad-spectrum antibiotics. Within the past 5-10 years, there has been growing interest in oral therapy and outpatient treatment for carefully selected low-risk patients. Outpatient treatment has the potential to avoid patient exposure to multidrug-resistant organisms found in the hospital, provide a more comfortable environment for the patient and his or her family, and achieve significant cost savings. Two risk-assessment tools have been developed to identify patients with a low risk of developing complications from neutropenic fever. A limited number of clinical trials have been conducted to evaluate outpatient treatment of low-risk patients. The evidence from well-designed randomized controlled trials comparing the safety and efficacy of outpatient therapy with standard therapy is not extensive. However, some centers have reported successful outpatient therapy in low-risk patients with febrile neutropenia. The greatest amount of evidence for outpatient treatment of neutropenic fever is available for the combination regimen of ciprofloxacin plus amoxicillin-clavulanate. Clinical practice guidelines are available to guide patient evaluation, antibiotic selection, monitoring, and follow-up. CONCLUSION: The accepted standard for treatment of neutropenic fever remains inpatient therapy with i.v. broad-spectrum antibiotics. However, some centers have had success treating selected low-risk patients with neutropenic fever as outpatients.     

Empiric antimicrobial therapy of febrile neutropenic patients undergoing haematopoietic stem cell transplantation

This study was conducted to assess the efficacy and toxicity of intravenous (i.v.) ceftazidime and ciprofloxacin in neutropenic febrile patients undergoing high dose myeloablative therapy and hematopoietic stem cell transplantation (HSCT). All patients undergoing HSCT for leukaemia, lymphoma, multiple myeloma and solid tumours received open-label ceftazidime 2 g i.v. every 8 h and ciprofloxacin 400 mg i.v. every 12 h if they developed fever while they were neutropenic. Success with or without modification of this regimen was defined as survival through the neutropenic period; failure was defined as death secondary to infection. Of 106 patients treated with this regimen, the success rate was 99%. Sixty-one of the patients (57.5%) defervesced within 48-72 h and remained afebrile without regimen modification. In 41.5% of the cases (44/106), the regimen was modified because of persistent fever. One patient died secondary to sepsis. The combination of ceftazidime and ciprofloxacin as initial empiric antibacterial therapy in febrile neutropenic patients undergoing myeloablative therapy and HSCT is highly effective and is associated with minimal toxicity.     

Current research in empirical therapy for febrile neutropenia in cancer patients: what should be necessary and what is going on

Introduction: Fever is an important complication in neutropenic patients and standard of care calls for empirical broad-spectrum antibiotics, followed by ‘empirical' antifungal therapy in persisting fever. Emergence of infections due to resistant bacteria, especially Gram-negatives, and usefulness of empirical antifungal therapy represent the major concerns in this field.

Areas covered: Clinical trials registered in 5 international databases were referred for randomized clinical trials (RCTs) of empirical antibacterial therapy or empirical antifungal therapy in neutropenic cancer patients. The majority of RCTs compared antibiotics without major differences in the spectrum of activity, especially in the wake of the present epidemiology with an increase of infections and mortality due to resistant Gram-negatives; oral therapy and home care were analyzed in 3 RCTs. As regards empirical antifungal therapy, 1 ongoing study is comparing ‘standard' empirical treatment vs diagnostic-driven approach.

Expert opinion: In an era of increasing antibiotic resistance the comparison of different strategies more than that of different drugs will probably represent the future in studies in this field. The next future will tell us if a diagnostic-driven approach is safe for fungal infections, or if we should continue to treat them only on the basis of the persistence of febrile neutropenia.     

Modifications of therapy

Rates of response to empirical therapy in the neutropenic patient with fever, range between 40 and 90%. Modifications of therapy are needed in patients who do not respond but may also be considered in patients who respond. In patients with unexplained fever and rapid defervescence, switch to oral therapy is an acceptable option and there is no need to continue the regimen until neutrophil recovery. Neutropenic patients with persistent undefined fever and those with progressive pneumonia benefit from the addition of antifungals while the empiric addition of a glycopeptide is unlikely to be effective. In patients with gram-negative bacterial infection initially treated with monotherapy, response may be increased after the addition of an aminoglycoside. In cases of a defined etiology, the institution of narrow-spectrum antimicrobials in a persistent neutropenic patient carries a substantial risk for superinfection and is not generally recommended. Improved diagnostic tools and sensitive clinical risk-assessment methods will allow selecting and targeting therapy modifications better.     

Safety and efficacy of low-dose amphotericin B lipid complex for empirical antifungal therapy of neutropenic fever in patients with hematologic malignancies

Amphotericin B lipid complex (ABLC) has been investigated as an empirical antifungal treatment for neutropenic patients with persistent fever of unknown origin (FUO). We studied the safety and efficacy of low dose ABLC (1 mg/kg/day) for empirical treatment of neutropenic FUO. Sixty-one patients with hematologic malignancies developing 69 episodes of neutropenic FUO after chemotherapy or hematopoietic stem cell transplantation were included in the study. The median patient age was 47 years (18-68). The median duration of neutropenia (< 0.5 x 10(9)/l) was 17 days (7-45) and the median duration of ABLC therapy was 8 days (2-19). Thirteen patients (19%) suffered from mild to moderate infusion-related adverse events. Creatinine levels were stable in 42 cases (61%), improved in 9 (13%) and deteriorated in 18 (26%), with no other significant toxicities. Among 67 evaluable episodes, the response rate (resolution of fever during the period of neutropenia without developing a fungal infection) was 67%, while 33% were treatment failures. Low-dose ABLC is safe, well tolerated and seems to be at least as effective as c-AmB for empirical antifungal therapy of FUO. Randomized trials at this dose level comparing ABLC with c-AmB or other lipid formulations are warranted.     

Antifungal agents

At this year's ICAAC Meeting, new data on approximately 20 different antifungal agents were presented, while no new agents were disclosed. Drugs in late development include the triazoles, voriconazole (Pfizer Ltd) and Sch-56592 (Schering-Plough Corp), and the echinocandins, caspofungin (Merck & Co Inc) and FK-463 (Fujisawa Pharmaceutical Co Ltd). In contrast to previous years, presentations on these and earlier developmental compounds were relatively modest in scope, with few significant new data. Little new information appeared on the most recent novel class of agents, the sordarins (Glaxo Wellcome plc). Early clinical results were presented for FK-463, showing acceptable tolerability and dose-dependent efficacy in AIDS-associated esophageal candidiasis. A new liposomal formulation of nystatin (Nyotran; Aronex Pharmaceuticals Inc) was shown to be equivalent to conventional amphotericin B in empiric therapy of presumed fungal infection in neutropenic patients, but with reduced toxicity. Intravenous itraconazole (Janssen Pharmaceutica NV) was an effective prophylactic therapy in invasive pulmonary aspergillosis, while oral itraconazole was discussed as a treatment for fungal infection in heart and liver transplant patients. The allylamine compound, terbinafine (Novartis AG), showed good clinical efficacy against fungal mycetoma, a serious tropical infection. A major highlight was the first presentation of inhibitors of fungal efflux pumps as a strategy for overcoming resistance. MC-510027 (milbemycin alpha-9; Microcide Pharmaceuticals Inc) and its derivatives, potentiated the antifungal activity of triazoles and terbinafine in a number of Candida spp. Another pump inhibitor, MC-005172 (Microcide Pharmaceuticals Inc) showed in vivo potentiation of fluconazole in a mouse kidney infection model. Microcide Pharmaceuticals Inc also presented inhibitors of bacterial efflux pumps.     

Voriconazole : a review of its use in the management of invasive fungal infections

Voriconazole (VFEND), a synthetic second-generation, broad-spectrum triazole derivative of fluconazole, inhibits the cytochrome P450 (CYP)-dependent enzyme 14-alpha-sterol demethylase, thereby disrupting the cell membrane and halting fungal growth. In the US, intravenous and/or oral voriconazole is recommended in adults for the treatment of invasive aspergillosis, candidaemia in non-neutropenic patients, disseminated infections caused by Candida spp., oesophageal candidiasis, and in patients with scedosporiosis and fusariosis who are refractory to or intolerant of other antifungal therapy. In Europe, intravenous and/or oral voriconazole is recommended in adults and paediatric patients of at least 2 years of age for the treatment of invasive aspergillosis, candidaemia in non-neutropenic patients, fluconazole-resistant serious invasive Candida spp. infections, scedosporiosis and fusariosis.In large randomised trials, voriconazole was an effective and generally well tolerated primary treatment for candidiasis and invasive aspergillosis in adults and adolescents. More limited data also support the use of voriconazole for the treatment of invasive fungal infections in children, in those with rare fungal infections, such as Fusarium spp. or Scedosporium spp., and in those refractory to or intolerant of other standard antifungal therapies. The availability of both parenteral and oral formulations and the almost complete absorption of the drug after oral administration provide for ease of use and potential cost savings, and ensure that therapeutic plasma concentrations are maintained when switching from intravenous to oral therapy. On the other hand, the numerous drug interactions associated with voriconazole may limit its usefulness in some patients. Further clinical experience will help to more fully determine the position of voriconazole in relation to other licensed antifungal agents. In the meantime, voriconazole is a valuable emerging option for the treatment of invasive aspergillosis and rare fungal infections, including Fusarium spp. and Scedosporium spp. infections, and provides an alternative option for the treatment of candidiasis, particularly where the causative organism is inherently resistant to other licensed antifungal agents.     

Empirical antifungal therapy

The number of fungal infections is increasing, particularly in patients with cancer, and represent a major problem given the relatively poor response rates, especially for aspergillosis, and the high cost. Empirical therapy has become an accepted practice as delay in instituting therapy is clearly associated with increased morbidity and mortality. In terms of efficacy for the management of persistent febrile neutropenic patients, there is no convincing evidence that conventional amphotericin B (ampho B) is inferior to any other agent; the lipid formulations of ampho B provide similar efficacy with lower toxicity but at a much higher cost. Fluconazole is equivalent to ampho B, provided patients at high risk of aspergillus infections are excluded. Itraconazole and voriconazole, as empirical therapies, are equivalent to conventional ampho B and liposomal ampho B, respectively; toxicity is definitely lower and voriconazole is more effective at preventing breakthrough fungal infections.     

89例儿童侵袭性肺部真菌感染临床特征分析

目的:探讨儿童侵袭性肺部真菌感染(IPFI)的临床特点,以提高临床医师对IPFI的认识,为有效防治IPFI提供参考。方法:回顾性分析我院2015年1月至2020年6月确诊、临床诊断、拟诊的89例IPFI患儿临床特征、治疗及预后等情况。结果:89例IPFI患儿中,男57例,女32例,中位年龄6.5岁。其中,79例患儿有基础疾病,以血液系统恶性肿瘤为主;10例无基础疾病患儿的宿主因素主要为重症腺病毒感染病史、诊断前抗菌药物使用时间>10 d、住院期间接受侵入性操作。临床表现以高热、咳嗽、咳痰为主。常见胸部CT表现：肺炎样表现75例(84.3%)、结节影34例(38.2%)、空气支气管征29例(32.6%)。所有患儿均接受抗真菌药物治疗,86.5%治疗有效,抗真菌药物以伏立康唑为主。73例有反复发热,加用抗真菌药物后64例(87.7%)体温稳定。患儿抗真菌治疗前中性粒细胞缺乏时间与住院抗真菌治疗时间呈正相关(r=0.519,P<0.01)。结论:有基础疾病的患儿是IPFI好发人群,对于无基础疾病患儿抗菌药物的长期使用、重症感染及接受侵入性操作是主要危险因素。儿童IPFI确诊率较低...     

Lipid-based amphotericin B: a review of the last 10 years of use

The last decade has been remarkable for the dramatic increase in the prevalence of serious fungal infections in patients with haematological disorders and neutropenic cancer patients. The mortality rate of deep-seated infection has been in excess of 90% and there is no doubt that this is one of the greatest challenges currently facing haematologists and oncologists. The development of the lipid-based drugs - liposomal amphotericin (AmBisome(R)), amphotericin B lipid complex, ABLC (Abelcet(R)), amphotericin B colloidal dispersion, Amphocil (ABCD(R)), has meant that doses of amphotericin B can be safely escalated for the first time whilst the problems of nephrotoxicity, infusion related reactions (including chills, rigors, fevers and hypoxia) can be reduced. These toxicities are variably reduced with AmBisome more than Abelcet and more than Amphocil and there is little information from randomised trials other than for AmBisome. AmBisome used in the setting of persistent fever and neutropenia not responding after 3-4 days of intravenous antibiotics, is associated with less breakthrough systemic fungal infections. There is also much less need for premedication, including steroids, compared with amphotericin B and Abelcet. The use of intermittent doses of Ambisome given prophylactically is now being explored. A new and exciting era of antifungal therapy is opening up with new compounds, such as itraconazole voriconazole, posaconazole and echinocandins, being investigated and for the first time, we also have options for combination therapy and prophylaxis.     

An evaluation of combination antibiotic therapy in infections with hematological disorders. Hyogo Cooperative Study Group of Infectious Diseases Complicating Hematological Disorders

A clinical study was undertaken to determine the effects of combination antibiotic therapy in 104 patients with infections associated with hematological disorders. All patients were treated with sulbactam/cefoperazone (SBT/CPZ) plus an aminoglycoside as an empiric therapy for fever. The overall efficacy rate of the therapy was 63.5%. Efficacy rates were 61.2% and 71.9% when initial neutrophil counts were less than 500/mm3 and over 500/mm3, respectively. No significant difference was found between the cases in which initially used antibiotics were continued (efficacy rate 62.5%) and those in which antibiotics were switched during the course of therapy (65.6%). Antibiotic therapy with SBT/CPZ plus an aminoglycoside provides adequate antibiotic coverage against infections associated with hematological disorders. This combination was highly effective even in the neutropenic periods of febrile patients.     

伏立康唑治疗92例肺部侵袭性真菌感染的疗效与评价

目的 评价伏立康唑对呼吸科肺部侵袭性真菌感染患者的疗效与副作用.方法 选取我院呼吸科92例侵袭性真菌感染患者,均给予伏立康唑,观察症状体征、实验室及细菌学指标,并对该药疗效与副作用进行描述与评价.结果 可评价疗效的患者中,临床痊愈率为58.33%,总有效率为80.56%.真菌学疗效清除率为76.67%.不良反应主要为精神神经症状,包括幻觉49例（53.26%）,视觉异常26例（28.26%）,失眠22例（23.91%）,其中2例患者停用伏立康唑或换用其他抗真菌药,其余均在足疗程停药后,自动恢复.因原发病病情加重死亡18例.结论 伏立康唑是一种新型的抗真菌药物,作为治疗侵袭性肺部真菌感染治疗的一线药物,具有高效安全的特点.     

Voriconazole: in the treatment of invasive aspergillosis

Voriconazole, a broad-spectrum triazole antifungal agent, inhibits the cytochrome P450-dependent enzyme 14-alpha-sterol demethylase, thereby disrupting the fungal membrane and stopping fungal growth. The drug shows excellent in vitro activity against Aspergillus spp., including itraconazole- and amphotericin B-resistant A. fumigatus isolates. At 12 weeks, 52.8% of voriconazole recipients achieved a successful outcome (complete or partial response) versus 31.6% of amphotericin B recipients in a randomised, nonblind trial in 392 patients (aged > or =12 years) with invasive aspergillosis. Patients received intravenous voriconazole (6 mg/kg once every 12 hours on day 1, then 4 mg/kg once every 12 hours for > or =7 days; patients could then be switched to oral voriconazole 200mg once every 12 hours) or intravenous amphotericin B (1 to 1.5 mg/kg/day for > or=14 days). At the investigators' discretion, those who failed to respond to or experienced toxicity with the initial randomised drug could be switched to other licensed antifungal therapy. Voriconazole was generally well tolerated. The most common treatment-related adverse events were transient visual disturbances (approximately 30% of patients) and skin rashes (6%). Voriconazole was generally better tolerated than amphotericin B; voriconazole recipients experienced significantly (p < 0.02 both comparisons) fewer treatment-related adverse events or serious adverse events. The incidence of visual disturbances was significantly (p < 0.001) higher with voriconazole than amphotericin B treatment.     

Evaluation of empiric vancomycin therapy in children with fever and neutropenia.

A retrospective evaluation was conducted to determine which children admitted for fever and neutropenia required empiric vancomycin therapy, and to develop a clinical pathway for appropriate treatment. Chart review identified 109 admissions of 36 pediatric oncology patients for fever and neutropenia, of which 88 were eligible for analysis. Blood cultures isolated 17 gram-positive organisms; coagulase-negative staphylococci and viridans group streptococci were cultured most frequently (82%). We concluded that previous high-dose cytarabine therapy, inflamed central access site, and hypotension or septic shock are possible indicators of febrile, neutropenic patients at high risk for gram-positive pathogen isolation. These predictors then were used to determine which children would receive empiric vancomycin therapy.     

Caspofungin: a review of its use in the treatment of fungal infections

Caspofungin (Cancidas) is the first of a new class of antifungal agents, the echinocandins, that inhibit the synthesis of the fungal cell wall component beta-(1,3)-D-glucan. Caspofungin is administered once daily by slow intravenous infusion and is used to treat infections caused by Candida spp. and Aspergillus spp.Caspofungin is a valuable new antifungal agent with a novel mechanism of action. In comparative clinical trials, caspofungin was no less effective than liposomal amphotericin B in the empirical treatment of neutropenic patients with persistent fever, amphotericin B deoxycholate in the treatment of invasive candidiasis or fluconazole in the treatment of oesophageal candidiasis. Caspofungin also displayed broadly similar efficacy to amphotericin B deoxycholate in oesophageal or oropharyngeal candidiasis and was effective as salvage therapy in patients with invasive aspergillosis who were refractory to or intolerant of standard therapy. The tolerability profile of caspofungin was similar to that of fluconazole and superior to that of amphotericin B deoxycholate and liposomal amphotericin B. Therefore, in the appropriate indications, caspofungin is a viable alternative to amphotericin B deoxycholate, liposomal amphotericin B or fluconazole.     

Role of therapeutic drug monitoring of voriconazole in the treatment of invasive fungal infections

Background:

Voriconazole is a broad-spectrum, second-generation triazole antifungal agent with demonstrated efficacy in the treatment of invasive fungal infections caused by Aspergillus spp. and Candida spp. Given the characteristically poor prognosis of patients with invasive fungal infections and the protracted duration of treatment required, therapeutic monitoring of voriconazole is, in theory, an attractive method to optimize antifungal therapy.

Objective:

To determine the utility of therapeutic drug monitoring for voriconazole.

Methods:

A previously published decision-making algorithm was used to assess the currently available literature on therapeutic drug monitoring of voriconazole.

Results:

Several analytical methods can be used to quantify plasma or serum concentrations of voriconazole. Reasons for therapeutic monitoring of this drug include wide variability both within and between individuals secondary to drug properties, drug–drug interactions, and disease states. Furthermore, voriconazole follows nonlinear pharmacokinetics with saturable hepatic clearance. Another potential factor in favour of therapeutic drug monitoring for voriconazole is genetic polymorphism of CYP2C19, whereby patients who are homozygous for poor metabolism (about 19% of non-Indian Asians) can have 4-fold greater exposure to voriconazole. The concentrations of this drug are also greater in patients with hepatic impairment. Drug–drug interactions with other substrates of CYP2C9, CYP2C19, and CYP3A4 can also alter voriconazole concentrations. However, the correlations between plasma concentrations of voriconazole and its efficacy and toxicity are not well defined. Although lower and upper target thresholds of 0.25–2 mg/L and 4–6 mg/L, respectively, have been suggested, studies to date have not been appropriately designed or powered to reveal any definitive association.

Conclusions:

Routine therapeutic drug monitoring of voriconazole is not recommended except in certain circumstances, such as lack of response to therapy or evidence of toxicity, in which case selective monitoring of voriconazole concentrations may be of clinical utility.     

Voriconazole treatment of invasive aspergillosis: real-world versus health-economic model results

OBJECTIVE: The objective of this study was to assess, in a real-world setting, the predictive validity (in terms of clinical outcome and treatment cost) of the voriconazole arm of a health-economic model applied in the Belgian reimbursement submission for use of voriconazole in the treatment of invasive aspergillosis. METHODS: A non-interventional study was designed to prospectively collect clinical response and direct costs data related to the treatment of invasive aspergillosis with voriconazole (oral, intravenous) in real-world practice. The outcomes of this study were compared with the inputs and outputs of the health-economic model. For the analysis, unit costs of 2002 from the public payer's perspective, as used in the model, were applied. RESULTS: Data from 116 patients with invasive aspergillosis starting treatment with voriconazole were collected. At 12 weeks, there were similar rates of satisfactory clinical response for the observational study and the model, the latter based on the results of a clinical study (50% vs 53%, respectively). Overall mortality rates at 84 days were 42% in the observational study and 29% in the model. Average total healthcare cost associated with voriconazole treatment was lower in the observational study compared with the model for all patients. When the cost for all hospitalization days from the start until the end of the fungal infection was included in the analysis, the average total cost was euro19,674. When the cost for only those hospitalization days solely related to the fungal infection was included in the analysis, the average total cost was euro12,376. These costs are below the cost predicted by the model of euro21,298. CONCLUSIONS: This analysis demonstrates that the results provided in the voriconazole arm of the health-economic model were valid estimates with regard to real-world outcomes but with a slightly better survival rate and higher costs than in real life.     

Posaconazole as salvage therapy in a patient with disseminated zygomycosis: case report and review of the literature

Zygomycosis refers to any fungal infection originating from the class Zygomycetes and the order Mucorales. In immunocompromised patients, these fungi produce a relatively rapid, violently destructive, and highly fatal infection. Treatment approaches include both aggressive antifungal pharmacotherapy and surgical intervention. Unfortunately, even with optimal therapy, morbidity and mortality rates remain relatively high. As failure rates are elevated with commercial antifungals, new treatment options are needed. Posaconazole is an orally available, extended-spectrum triazole antifungal being investigated in phase III clinical trials for the treatment and prevention of invasive fungal infections, including zygomycosis. We report the case of a 26-year-old Vietnamese man with a medical history of acute lymphocytic leukemia who had undergone consolidation chemotherapy and had neutropenic fever when he came to the emergency department. The patient was admitted to the hospital and treated with broad-spectrum antibiotics and caspofungin. Two weeks into his admission, however, abscesses in the pelvis, prostate, and musculature surrounding the hip were detected radiographically; these abscesses eventually cultured for Mucor sp. Disseminated zygomycosis was diagnosed. Caspofungin was immediately discontinued, and high-dose liposomal amphotericin B 10 mg/kg/day was begun. Over the next month, infection spread to the right lung, left kidney, middle thoracic spine, and epidural space. As a result, oral posaconazole 200 mg 4 times/day was added to the liposomal amphotericin B. Significant clinical, hematologic, mycologic, and radiologic improvements were demonstrated as early as 10 days after start of posaconazole therapy and continued through 41 days of inpatient treatment. Liposomal amphotericin B was discontinued after 3 weeks of posaconazole, and the patient was discharged on hospital day 92 receiving oral posaconazole, with no major adverse events reported. Five months after discharge, the patient had no evidence of fungal disease recurrence or progression. Posaconazole appears to be a well-tolerated and effective salvage treatment for zygomycosis, including disseminated disease.