Enhanced Biofilm Eradication and Reduced Cytotoxicity of a Novel Polygalacturonic and Caprylic Acid Wound Ointment Compared with Common Antiseptic Ointments.

Antiseptic wound ointments are widely used to treat dermal wounds that are microbially contaminated. Polygalacturonic acid (PG)+caprylic acid (CAP) is a novel combination that has been shown to eradicate biofilms. We developed a novel PG+CAP ointment and compared the biofilm eradication capability and cytotoxicity of PG+CAP with that of commercially available antiseptic wound ointments. We used a well-established biofilm model to quantitatively assess the eradication of organisms following exposure to the wound ointments for 2 hours. PG+CAP ointment completely eradicated Candida albicans, multidrug-resistant Pseudomonas aeruginosa, and methicillin-resistant Staphylococcus aureus biofilms, whereas MediHoney, polyhexamethylene biguanide (PHMB), and benzalkonium chloride (BZK) ointments failed to eradicate all biofilms within 2 hours. We assessed cytotoxicity by exposing L-929 fibroblasts to extracts of each ointment; Trypan blue exclusion was used to assess cell viability, and Alamar blue conversion was used to assess metabolic function. After exposure to PG+CAP and MediHoney, fibroblast viability was 96.23% and 95.23%, respectively (Trypan blue), and was comparable to untreated cells (98.77%). PHMB and BZK showed reduced viability (83.25% and 77.83%, respectively, p < 0.05). Metabolic activity results followed a similar pattern. Cytotoxicity of PG+CAP ointment towards erythrocytes was comparable to saline. PG+CAP ointment seems to be safe and can rapidly eradicate microbial biofilm; thus, PG+CAP ointment merits further in vivo testing as a potential antimicrobial wound ointment.

Surveillance and identification of clusters of healthcare workers with coronavirus disease 2019 (COVID-19): Multidimensional interventions at a comprehensive cancer center.

BACKGROUND: Cases of novel coronavirus disease 2019 (COVID-19) were first reported in Wuhan, China, in December 2019. In this report, we describe 3 clusters of COVID-19 infections among healthcare workers (HCWs), not associated with patient exposure, and the interventions undertaken to halt ongoing exposure and transmission at our cancer center. METHODS: A cluster of cases was defined as 2 or more cases of severe acute respiratory coronavirus virus 2 (SARS-CoV-2)-positive COVID-19 among HCWs who work in the same unit area at the same time. Cases were identified by real-time reverse transcription polymerase chain reaction testing. Contact tracing, facility observations, and infection prevention assessments were performed to investigate the 3 clusters between March 1 and April 30, 2020, with subsequent implementation of containment strategies. RESULTS: The initial cluster involved HCWs from an ancillary services unit, with contacts traced back to a gathering in a break room in which 1 employee was symptomatic, although not yet diagnosed with COVID-19, with subsequent transmission to 7 employees. The second cluster involved 4 employees and was community related. The third cluster involved only 2 employees with possible transmission while working in the same office at the same time. A step-up approach was implemented to control the spread of infection among employees, including universal masking, enhanced cleaning, increase awareness, and surveillance testing. No nosocomial transmission to patients transpired. CONCLUSIONS: To our knowledge, this is the first report of a hospital-based cluster of COVID-19 infections among HCWs in a cancer hospital describing our steps to mitigate further transmission.

Minocycline-EDTA-Ethanol Antimicrobial Catheter Lock Solution Is Highly Effective In Vitro for Eradication of Candida auris Biofilms.

Candida auris is an emerging pathogen that can cause virulent central-line-associated bloodstream infections. Catheter salvage through the eradication of biofilms is a desirable therapeutic option. We compared taurolidine and minocycline-EDTA-ethanol (MEE) catheter lock solutions in vitro for the eradication of biofilms of 10 C. auris strains. MEE fully eradicated all C. auris biofilms, while taurolidine lock partially eradicated all of the C. auris biofilms. The superiority was significant for all C. auris strains tested (P = 0.002).

International experience with minocycline, EDTA and ethanol lock for salvaging of central line associated bloodstream infections.

BACKGROUND: The use of long-term central venous catheters (CVCs) could lead to serious bloodstream infections. Removal of the infected CVC and reinsertion of a new CVC are not always feasible and alternative lock therapy may be considered. We conducted a multicenter trial to assess the efficacy and safety of the lock therapy. METHODS: Between October 2013 and August 2014, we prospectively enrolled 20 patients with catheter-related bloodstream infections (CRBSIs) or central line-associated bloodstream infections (CLABSIs) in our sister institutions in three countries including Brazil, Lebanon, and Japan. The 20 patients who received M-EDTA-EtOH lock therapy were compared to 24 control patients who had their CVCs removed and a new CVC inserted. RESULTS: Both groups had comparable clinical characteristics. In the lock therapy group, 95% of the patients had microbiological eradication within 96 h after starting lock therapy versus 83% of the patients in the control group (p = .36). In the lock group, the CVC was salvaged and retained for a median of 21 days (range 7-51) from the onset of bacteremia. CONCLUSION: Our study suggests that M-EDTA-EtOH lock therapy may be an effective intervention to salvage long-term CVCs in the setting of CLABSI/CRBSI and hemodialysis cancer patients with limited vascular access.

Glyceryl trinitrate complements citrate and ethanol in a novel antimicrobial catheter lock solution to eradicate biofilm organisms.

Antimicrobial catheter lock therapy is practiced to prevent lumenal-sourced infections of central venous catheters. Citrate has been used clinically as an anticoagulant in heparin-free catheter locks. Ethanol has also been widely studied as an antimicrobial lock solution component. This study reports on the synergy of glyceryl trinitrate (GTN) with citrate and ethanol in rapidly eradicating methicillin-resistant Staphylococcus aureus, methicillin-resistant Staphylococcus epidermidis, Pseudomonas aeruginosa, and Candida albicans biofilms in an in vitro model for catheter biofilm colonization. GTN has a long history of intravenous use as a hypotensive agent. It is potentially attractive as a component of a catheter lock solution because its physiologic half-life is quite short and its metabolic pathways are known. A lock containing 7% citrate and 20% ethanol required 0.01% GTN to fully eradicate biofilms of all test organisms within 2 h in the model. This GTN concentration is below the levels where clinically significant hypotensive effects are expected.

Characteristics and outcomes of methicillin-resistant staphylococcus aureus bloodstream infections in patients with cancer treated with vancomycin: 9-year experience at a comprehensive cancer center.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infections (BSIs) can cause significant morbidity and mortality in patients with cancer. However, data on outcomes of patients treated with vancomycin are lacking. METHODS: We identified 223 patients with cancer who developed MRSA BSIs between January 2001 and June 2009 and were treated with vancomycin. Treatment failure was defined as death within 60 days of infection, persistent bacteremia ≥5 days, fever ≥4 days, recurrence or relapse, and secondary MRSA infection. RESULTS: The treatment failure rate was 52% (116 of 223 patients). These patients were more likely to have been hospitalized, been treated with steroids within the previous 3 months, developed acute respiratory distress syndrome, required mechanical ventilation, required intensive care unit care, and community-onset infections (all p < .05). Risk factors for MRSA-associated mortality (27 of 223 patients; 12%) included hematologic malignancy and hematopoietic stem cell transplantation, community-onset infection, secondary BSI, MRSA with minimum inhibitory concentration (MIC) ≥2.0 µg/mL, mechanical ventilation, and a late switch to an alternative therapy (≥4 days after treatment failure; all p < .05). On multivariate analysis, mechanical ventilation and recent hospitalization were identified as independent predictors of vancomycin failure, and community-onset infection, secondary BSIs, and MIC ≥2 µg/mL were identified as significant predictors of MRSA-associated mortality. CONCLUSIONS: We found a high treatment failure rate for vancomycin in patients with cancer and MRSA BSIs, as well as a higher mortality. A vancomycin MIC ≥2 µg/mL was an independent predictor of MRSA-associated mortality. An early switch to an alternative therapy at the earliest sign of failure may improve outcome.

Characteristics and outcomes of pandemic 2009/H1N1 versus seasonal influenza in children with cancer.

BACKGROUND: Novel 2009/H1N1 influenza has significant impact on immunocompromised children with cancer; however, it is uncertain how it compares with seasonal influenza (SFlu) in this vulnerable population. We compared clinical characteristics and outcomes for these 2 infections in children with cancer and identified risk factors for progression to lower respiratory infection (LRI) and/or death. METHODS: Influenza infections confirmed by positive viral culture and/or fluorescence antigen test between January 1998 and February 2010 were identified from microbiology databases at a comprehensive cancer center. Characteristics and outcomes were compared for the 2 groups. Kaplan-Meier survival curves and Cox proportional hazards model were generated to identify risk factors for LRI and/or death. RESULTS: When compared with SFlu, 2009/H1N1 cases had significantly lower acute physiology and chronic health evaluation II score (median: 9 versus 14), fewer comorbidities (15% versus 46%), fewer hematopoietic stem-cell transplantation (5% versus 16%), more solid tumors (45% versus 16%), higher LRI at presentation (20% versus 4%), higher rates of antiviral therapy (90% versus 48%) and higher mortality (10% versus 0%). Male gender (hazard ratio [HR]: 8.4, 95% confidence interval [CI]: 1.08-65.2, P = 0.042), acute physiology and chronic health evaluation II score > 15 (HR: 3.29, 95% CI: 1.04-10.39, P = 0.027) and a 24-hour delay in initiation of antiviral treatment (HR: 1.12, 95% CI: 1.02-1.23, P = 0.015) were the most significant predictors of progression to LRI and mortality, regardless of virus strain. CONCLUSIONS: Significant differences between 2009/H1N1 and SFlu with respect to clinical presentation, management and associated outcomes were identified. Early diagnosis and prompt initiation of antiviral therapy may prevent serious complications of influenza in children with cancer.

Monotherapy with caspofungin for candidaemia in adult patients with cancer: a retrospective, single institution study.

This study was performed to evaluate retrospectively the efficacy and safety of caspofungin monotherapy for candidaemia in patients with cancer. The medical records were reviewed of 63 consecutive adult patients with cancer who had candidaemia treated with caspofungin alone for at least 3 consecutive days at The University of Texas M.D. Anderson Cancer Center (March 2001-February 2007). Twenty patients (32%) had haematological malignancies. Most of the candidaemia cases (54%) were caused by non-albicans Candida spp. The most frequent isolates were C. albicans (38%) followed by Candidaparapsilosis (21%), Candidatropicalis (16%) and Candidaglabrata (10%). In vitro susceptibility studies showed that of 30 Candida isolates tested, only one C. parapsilosis isolate had a caspofungin minimum inhibitory concentration > 1 microg/mL. The clinical and mycological response rates after 7 days of treatment with caspofungin were 78% and 77%, respectively. The overall mortality rate was 5% on Day 7, 12% on Day 14 and 21% on Day 30. The 30-day Candida-attributable mortality rate was 11% and was significantly higher in patients with fluconazole-resistant or susceptible-dose-dependent Candida isolates. Caspofungin was well tolerated in all patients. Although selection of candidaemic patients with cancer who received caspofungin monotherapy may have accounted for the favourable outcomes, it was observed that caspofungin had efficacy and safety comparable with those in candidaemic patients without malignancy.

Infections in 100 cord blood transplantations: spectrum of early and late posttransplant infections in adult and pediatric patients 1996-2005.

Cord blood-derived stem cells are successfully used in the treatment of cancer and congenital disorders in children. This alternative source of stem cells is also explored for adult cancer patients with limited donor options. However, delayed engraftment, prolonged neutropenia, secondary graft loss, and graft-versus-host disease (GVHD) in recipients of cord blood transplantation (CBT) make opportunistic infections a serious concern. We evaluated the spectrum of infections in adults and children undergoing CBT at our National Cancer Institute-designated comprehensive cancer center. The infection incidence rate ratio (total infection episodes/days at risk [survival after CBT] x 100) was 2.4 times higher in 35 adult patients than in 62 children, especially in adults with neutropenia (3 x higher) and GVHD (1.9 x higher). Ninety-two percent of fungal infection episodes occurred within 100 days after transplantation; half of these infections occurred in the first 30 days after CBT. Most bacterial infections (80%) were also diagnosed in the first 100 days, whereas late (>100 d) post-CBT cytomegalovirus and varicella zoster virus infections occurred only in children with chronic GVHD. Multivariate analysis showed that resolution of lymphocytopenia (> or =1000 cells/microL) (hazard ratio [HR] 0.71; p < 0.0001) and successful engraftment (HR 0.20; p < 0.0001) were associated with a low risk of serious infection. Children (HR 0.36; p < 0.0002) with sustained engraftment (HR 0.39; p < 0.004) and those with cancer in remission (HR 0.47; p < 0.007) were less likely to die from infection. More effective measures for surveillance and prevention of late cytomegalovirus and varicella zoster virus infections in children with CBT and chronic GVHD are needed.

Colistin is effective in treatment of infections caused by multidrug-resistant Pseudomonas aeruginosa in cancer patients.

The increasing incidence of infections caused by multidrug-resistant Pseudomonas aeruginosa is a worldwide health problem. Because no new antipseudomonal agents are expected to be available in the near future, we evaluated the safety and efficacy of colistin, an old drug with bactericidal activity against this organism. We collected clinical and demographic data on 95 cancer patients diagnosed with infections caused by multidrug-resistant P. aeruginosa between January 2001 and January 2004 and treated with either colistin (colistin group) or at least one active antipseudomonal agent (a beta-lactam antibiotic or a quinolone) (control group). We compared the results obtained for both groups. Thirty-one patients had been treated with colistin and 64 had been treated with an antipseudomonal non-colistin-containing regimen. Compared with the control group, patients in the colistin group had a lower median age (52 and 62 years, respectively; P = 0.012) but were more likely to have had nosocomial infections (87% and 64%, respectively; P = 0.02). Twenty-five patients (81%) in the colistin group and 40 patients (63%) in the control group had an APACHE II score of >15 (P = 0.074). The overall clinical response rates were 52% in the colistin group and 31% in the control group (P = 0.055). Multiple logistic regression analysis showed that those patients treated with colistin were 2.9 times (95% confidence interval, 1.1 to 7.6 times) more likely than those in the control group to experience a clinical response to therapy (P = 0.026). Colistin therapy was at least as effective and as safe a beta-lactam antibiotic or a quinolone in the treatment of infections caused by multidrug-resistant P. aeruginosa and, hence, may be a useful or preferred alternative therapy for this infection in cancer patients.

Culture-positive and culture-negative endocarditis in patients with cancer: a retrospective observational study, 1994-2004.

Endocarditis is uncommon in patients with cancer. The characteristics of culture-positive (CPE) and culture-negative endocarditis (CNE) in high-risk cancer patients are not known; therefore we sought to evaluate the disease characteristics in patients with endocarditis at a comprehensive cancer center. We retrospectively reviewed the transthoracic (TTE) and transesophageal (TEE) echocardiograms obtained from 654 consecutive cancer patients in whom endocarditis was suspected between 1994 and 2004. Endocarditis was confirmed in 45 (7%) of 654 patients using modified Duke University criteria based on information obtained from hospital records and computerized data systems. In 21 (95%) of 22 cases, TEE examinations were diagnostic, and 16 (42%) of 38 patients with initially nondiagnostic TTE studies had the diagnosis confirmed by TEE study; this difference between diagnostic TEE and initial nondiagnostic TTE was significant (p < 0.0001). Among the 26 (58%) patients with CPE, Staphylococcus aureus (35%) was the most common organism isolated, followed by coagulase-negative Staphylococcus species (23%). Eighteen (78%) of 23 patients with a central venous catheter had CPE, whereas only 8 (36%) of 22 patients without a central venous catheter had CPE (odds ratio [OR], 6.3; 95% confidence interval [CI], 1.69-23.53; p < 0.006). Vegetations were larger in patients with CPE than in patients with CNE (median +/- standard deviation, 10 +/- 8.8 vs. 8.7 +/- 3.9 mm). Fifteen patients (58%) with CPE and 10 (53%) with CNE had embolic complications. We note that cutaneous and septic pulmonary emboli were more common in patients with CPE than in patients with CNE (31% vs. 11% and 15% vs. 0%, respectively), whereas embolic cerebrovascular and fatal embolic coronary events were more common in patients with CNE than in those with CPE (37% vs. 12% and 21% vs. 0%, respectively; p = 0.026). The 4-week endocarditis-attributable death rate did not differ significantly between the groups (CPE, 15% vs. CNE, 32%; p = 0.28). On stepwise multivariate regression analysis, patients with neutropenia (OR, 22.52; 95% CI, 2.25-225.48; p < 0.008) and those with embolic cerebrovascular events (OR, 17.07; 95% CI, 1.63-178.45; p < 0.01) had an increased probability of death due to endocarditis. The clinical spectrums of CPE and CNE differed in these patients with cancer. In patients with CNE, embolic cerebrovascular and fatal myocardial infarction were relatively common.

Pentamidine is active in a neutropenic murine model of acute invasive pulmonary fusariosis.

We studied the efficacy of pentamidine (PNT) as prophylaxis or early treatment in acute pulmonary fusariosis in neutropenic mice. PNT-preexposed mice had significantly improved survival and reduced fungal burden compared to amphotericin B-preexposed and untreated mice. PNT-treated mice had increased survival but no difference in fungal burden versus untreated mice.

Posaconazole: a broad-spectrum triazole antifungal.

Posaconazale is a new triazole drug being investigated in phase III clinical trials for the treatment and prevention of invasive fungal infections. In-vitro and in-vivo studies showed that posaconazole has broad-spectrum activity against most Candida species, Cryptococcus neoformans, Aspergillus species, Fusarium species, zygomycetes, and endemic fungi. Posaconazole is given orally two to four times daily. This triazole is widely distributed in the body, metabolised mainly by the liver, and is well tolerated, even in long-term courses. Adverse events are generally mild and include headache and gastrointestinal complaints. Posaconazole has shown promising clinical efficacy against life-threatening fungal infections that are often refractory to the currently available antifungal therapies-eg, invasive aspergillosis, fusariosis, and the emerging zygomycosis.

Streptococcus pneumoniae bacteremia in patients with cancer: disease characteristics and outcomes in the era of escalating drug resistance (1998-2002).

In the current era of multidrug-resistant organisms, the clinical spectrum of Streptococcus pneumoniae infection remains unclear, especially in immunosuppressed patients with cancer. We sought to define the characteristics of pneumococcal bacteremia in patients who were receiving care at a comprehensive cancer center. All consecutive episodes of S. pneumoniae bacteremia between January 1998 and December 2002 were evaluated retrospectively. One hundred thirty-five episodes of pneumococcal bacteremia occurred in 122 patients. Sixty-three (52%) of 122 patients had hematologic malignancies; the others had solid tumors. The median Acute Physiology and Chronic Health Evaluation II score was 14 +/- 5. Twenty-four episodes (18%) occurred during neutropenia (<500 cells/microL). Sixty-five patients (53%) were receiving antineoplastic therapy, and 36 (30%) were receiving systemic corticosteroids. Twelve (41%) of 29 hematopoietic stem cell transplant (HSCT) recipients had received transplantation within 12 months of the infection diagnosis; 11 patients had graft-versus-host disease (chronic in 10). In 27 episodes (22%), S. pneumoniae bacteremia was considered as a breakthrough infection. Nine (56%) of 16 hospital-acquired episodes of S. pneumoniae bloodstream infection occurred in patients with profound neutropenia, whereas 15 (13%) of 119 episodes of community-acquired infection occurred during neutropenia (p < 0.0002). In 91 episodes (67%), patients had radiographic evidence of pneumonia. Infected catheters were associated with 21 episodes (16%). Forty-eight (36%) of 135 isolates were not susceptible to penicillin (minimum inhibitory concentration [MIC] > or = 2 microg/mL); 9 (7%) showed intermediate susceptibility to ceftriaxone (MIC >0.5 and <2.0 microg/mL). Nineteen patients (16%) died within 2 weeks of diagnosis; 18 deaths were attributed to systemic pneumococcal infection. Univariate analysis showed no significant increase in the risk of short-term death in patients with infection due to penicillin non-susceptible organisms (OR [odds ratio], 1.47; 95% confidence intervals [CI], 0.53-4.05; p < 0.46), initially discordant treatment (OR, 1.0; 95% CI, 0.62-665.4; p < 0.16), presence of pneumonia (OR, 1.19; 95% CI, 0.39-3.62; p < 0.76), neutropenia (OR, 1.0; 95% CI, 0.28-4.09; p < 0.92), systemic corticosteroid use (OR, 1.96; 95% CI, 0.69-5.60; p < 0.21), or antineoplastic therapy (OR, 1.45; 95% CI, 1.52-4.05; p < 0.47). Similarly, patients with hematologic cancers compared to those with solid cancers (OR, 1.0; 95% CI, 0.49-3.70; p < 0.56) and recipients of HSCT compared to those with no history of transplantation (OR, 1.0; 95% CI 0.59-12.71; p < 0.20) did not have a less favorable outcome. In conclusion, most pneumococcal bloodstream infections were community acquired, although hospital-acquired infections were common in neutropenic patients. It is noteworthy that initially discordant therapy, penicillin non-susceptible S. pneumoniae, and other conventional predictors of unfavorable outcome were not associated with increased mortality rates in these high-risk patients with cancer.

Increased frequency of non-fumigatus Aspergillus species in amphotericin B- or triazole-pre-exposed cancer patients with positive cultures for aspergilli.

Invasive aspergillosis (IA) can occur despite prior prophylactic or empiric use of triazoles or amphotericin B (AMB). Although profound immunosuppression may account for breakthrough IA, resistance of Aspergillus to antifungals may also play a role. To examine this question, we measured the minimal inhibitory concentration of 105 Aspergillus isolates recovered from 105 cancer patients (64 with IA, 41 with Aspergillus colonization) to AMB, itraconazole (ITC), and voriconazole (VRC) using the National Committee for Clinical Laboratory Standards (NCCLS) M38-A microdilution and E-test methods. We also determined the minimal fungicidal concentration (MFC) of these agents and the minimal effective concentration (MEC) of caspofungin (CAS) using standardized methods. We then collected information regarding pre-exposure to AMB or triazoles (fluconazole, ITC, VRC) within 3 months before Aspergillus isolation. Pre-exposure of cancer patients to AMB or triazoles was associated with increased frequency of non-fumigatus Aspergillus species. Aspergillus isolates recovered from patients who previously received AMB exhibited higher E-test AMB MICs compared with isolates from patients without prior AMB exposure (P = 0.01). In addition, the AMB MICs by E-test were higher in triazole-pre-exposed patients compared with those not exposed to triazoles (P = 0.001). The ITC and VRC MICs by E-test were not affected by prior AMB or triazole exposure. Finally, neither the AMB, ITC, and VRC MICs and MFCs by NCCLS method nor CAS MECs showed such changes. In conclusion, cancer patients with positive Aspergillus cultures who are pre-exposed to AMB or triazoles have high frequency of non-fumigatus Aspergillus species. These Aspergillus isolates were found to be AMB-resistant by the more sensitive E-test method.

Candidemia in a tertiary care cancer center: in vitro susceptibility and its association with outcome of initial antifungal therapy.

Since the 1990s, changing trends have been documented in species distribution and susceptibility to bloodstream infections caused by Candida species in cancer patients. However, few data are available regarding the association between in vitro antifungal susceptibility and outcome of candidemia in this patient population. We therefore evaluated the association of in vitro antifungal susceptibility and other risk factors with failure of initial antifungal therapy in cancer patients with candidemia. Candidemia cases in cancer patients from 1998 to 2001 (n = 144) were analyzed retrospectively along with their in vitro susceptibility to amphotericin B, fluconazole, and itraconazole (National Committee for Clinical and Laboratory Standards M27-A method). Patients were evaluable for outcome analysis if they received continuous unchanged therapy with either fluconazole or amphotericin B for >/=5 days. We excluded cases of mixed candidemia. In vitro susceptibility testing data of the first Candida bloodstream isolate were analyzed. Appropriate therapy was defined as that using an active in vitro antifungal for >/=5 days. For fluconazole susceptible-dose dependent Candida species, we defined appropriate therapy as a fluconazole dose of >/=600 mg/day. The Candida species distribution was 30% Candida albicans, 24% Candida glabrata, 23% Candida parapsilosis, 10% Candida krusei, 9% Candida tropicalis, and 3% other. Overall, amphotericin B was the most active agent in vitro, with only 3% of the isolates exhibiting resistance to it (>1 mg/L). Dose-dependent susceptibility to fluconazole and itraconazole was seen in 13% and 21% of the isolates, respectively, while resistance to fluconazole and itraconazole was seen in 13% and 26%, respectively.Eighty patients were evaluable for outcome analysis. In multivariate analysis, the following factors emerged as independent predictors of failure of initial antifungal therapy: leukemia (p = 0.01), bone marrow transplantation (p = 0.006), and intensive care unit stay at onset of infection (p = 0.02). Inappropriate antifungal therapy, as defined by daily dose and in vitro susceptibility, was not shown consistently to be a significant factor (it was significant in multivariate analysis, p = 0.04, but not in univariate analysis), indicating the complexity of the variables that influence the response to antifungal treatment in cancer patients with candidemia.