A comparison of strategies for identifying patients at risk for carbapenem-resistant or extended ß-lactam-resistant Pseudomonas aeruginosa.

OBJECTIVES: To assess risk factors for carbapenem-resistant Pseudomonas aeruginosa (CR) and extended-ß-lactam-resistant P. aeruginosa (EBR) infection/colonization, and to develop and compare tools for predicting isolation of CR and EBR from clinical cultures. METHODS: This retrospective study analysed hospitalized patients with positive P. aeruginosa cultures between 2015 and 2021. Two case-control analyses were performed to identify risk factors and develop scoring tools for distinguishing patients with CR versus carbapenem-susceptible (CS) P. aeruginosa and EBR versus CS P. aeruginosa. The performance of institutionally derived scores, externally derived scores and the presence/absence of key risk factors to predict CR and EBR were then compared. RESULTS: A total of 2379 patients were included. Of these, 8.3% had a positive culture for CR, 5.0% for EBR and 86.7% for CS P. aeruginosa. There was substantial overlap in risk factors for CR and EBR. Institutional risk scores demonstrated modestly higher area under the ROC curve values than external scores for predicting CR (0.67 versus 0.58) and EBR (0.76 versus 0.70). Assessing the presence/absence of ≥1 of the two strongest predictors (prior carbapenem use or CR isolation within 90 days) was slightly inferior to scoring tools for predicting CR, and comparable for predicting EBR. CONCLUSIONS: Clinicians concerned about CR in P. aeruginosa should consider the likelihood of EBR when making treatment decisions. A simple approach of assessing recent history of CR isolation or carbapenem usage performed similarly to more complex scoring tools and offers a more pragmatic way of identifying patients who require coverage for resistant P. aeruginosa.

Population pharmacokinetic/pharmacodynamic target attainment analysis of IV fosfomycin for the treatment of MDR Gram-negative bacterial infections.

BACKGROUND: IV fosfomycin is used against MDR Gram-negative bacilli (GNB) but has dose-limiting side effects, especially in patients with impaired kidney function. OBJECTIVES: To determine the optimal dosage of IV fosfomycin for patients with varying degrees of kidney function. METHODS: Adult patients receiving IV fosfomycin for treatment of GNB were eligible. Five serial blood samples were collected after at least three doses of fosfomycin; plasma was assayed by LC-MS/MS and modelled by population pharmacokinetic analysis. The PTA for AUC24/MIC of 98.9 for Escherichia coli and Klebsiella pneumoniae, and 40.8 for Pseudomonas aeruginosa were computed by Monte Carlo simulations. Cumulative fractions of response (CFR) were analysed for each pathogen using EUCAST MIC distributions. RESULTS: A total of 24 patients were included. Creatinine clearance (CLCR) and gender significantly influenced fosfomycin clearance. The kidney function-adjusted dosing regimens are proposed by using the lowest dose that can achieve ≥90% PTA for AUC24/MIC of 98.9 at an MIC of ≤32 mg/L (EUCAST v.13 susceptibility breakpoint for Enterobacterales). For patients with normal kidney function (CLCR 91-120 mL/min), a dosage of 15 g/day is suggested. This regimen achieved 97.1% CFR against E. coli, whereas CFR was 72.9% for K. pneumoniae and 76.7% for P. aeruginosa. CONCLUSIONS: A fosfomycin dosage of 15 g/day with adjustment according to kidney function provided high PTA and CFR when treating E. coli. This dosage is lower than that used in current practice and may improve tolerability. Higher dosages may be needed for P. aeruginosa; however, safety data are limited.

Case Commentary: When Voldemort Meets Sauron: Treatment Considerations for Emerging Dual-Carbapenemase-Producing Extensively Drug-Resistant Pseudomonas aeruginosa.

Infections caused by extensively drug-resistant Pseudomonas aeruginosa are difficult to treat due to limited effective treatment options. In this issue, a patient with a corneal infection caused by a Verona integron-encoded metallo-ß-lactamase (VIM)- and Guiana extended-spectrum ß-lactamase (GES)-coproducing P. aeruginosa strain associated with the recent artificial tears-related outbreak in the United States is described. This resistance genotype/phenotype further compromises therapeutic options, and this report provides insights into diagnostic and treatment approaches for clinicians dealing with infections due to this highly resistant P. aeruginosa.

Development and Implementation of a Mobile Application for Choosing Empirical Antimicrobial Therapy for Bacteremia, Pneumonia, Urinary Tract Infection, and Skin and Soft Tissue Infection among Hospitalized Patients.

Clinical practice guidelines (CPGs) and computerized clinical decision support programs are effective antimicrobial stewardship strategies. The DigitalAMS™, a mobile-based application for choosing empirical antimicrobial therapy under the hospital's CPGs, was implemented at Siriraj Hospital and evaluated. From January to June 2018, a cross-sectional study was conducted among 401 hospitalized adults who received ≥1 dose of antimicrobials and had ≥1 documented site-specific infection. The antimicrobial regimen prescribed by the ward physician (WARD regimen), recommended by the DigitalAMS™ (APP regimen), and recommended by two independent infectious disease (ID) physicians before (Emp-ID regimen) and after (Def-ID regimen) the final microbiological results became available were compared in a pairwise fashion. The percent agreement of antimicrobial prescribing between the APP and Emp-ID regimens was 85.7% in the bacteremia group, 59.1% in the pneumonia group, 78.6% in the UTI group, and 85.2% in the SSTI group. The percent agreement between the APP and Emp-ID regimens was significantly higher than that between the WARD and Emp-ID regimens in three site-specific infection groups: the bacteremia group (85.7% vs. 47.9%, p < 0.001), the UTI group (78.6% vs. 37.8%, p < 0.001), and the SSTI group (85.2% vs. 40.2%, p < 0.001). Furthermore, the percent agreement between the APP and Def-ID regimens was similar to that between the Emp-ID and Def-ID regimens in all sites of infection. In conclusions, the implementation of DigitalAMS™ seems useful but needs some revisions. The dissemination of this ready-to-use application with customized clinical practice guidelines to other hospital settings may be beneficial.

Epidemiology of Carbapenem-Resistant Enterobacterales Infection and Colonization in Hospitalized Patients at a University Hospital in Thailand.

Purpose: To investigate the epidemiology of carbapenem-resistant Enterobacterales (CRE) colonization or CRE infection relative to the natural history and clinical course of CRE colonization or CRE infection in hospitalized patients during admission and after discharge. Material and Methods: Two adult cohorts were enrolled. Cohort I comprised hospitalized patients who had CRE isolated from their clinical specimens during 2018-2020. CRE colonization or CRE infection was based on the absence/presence of clinical features of infection. Information regarding the natural history and clinical course of these patients was collected during hospitalization. Stool samples were evaluated for CRE once a week during hospitalization, and then once every few months after discharge until negative for CRE. Cohort II comprised patients who had CRE isolated from clinical specimens during hospitalization and who were discharged during 2015-2018. CRE in stool samples collected from these patients every few months was assessed to determine duration of CRE in stool. Results: CRE in stool was detected in 69.7% of 353 patients in cohort I. K. pneumoniae was the predominant CRE isolated from clinical samples (76.8%) and stool samples (65.7%). Among the 225 CRE-colonized patients, 20.4% developed subsequent CRE infections with a median duration from CRE colonization to CRE infection of 14 days. Among 174 CRE-infected patients, the most common infection was pneumonia with mortality at discharge of 47.7%. Duration of CRE colonization in stool was <1 year in 50.0% of cohort I patients, and <2 years in 91.4% of patients in cohort II. Conclusion: CRE isolated from clinical specimens in hospitalized patients are more likely to cause colonization than infection. Patients with CRE colonization are at risk of subsequent CRE infection with high mortality. Stool culture for CRE is needed to verify if contact precautions can be discontinued because the duration of CRE colonization in stool varied from days to years.

Active Surveillance for Carbapenem-Resistant Enterobacterales (CRE) Colonization and Clinical Course of CRE Colonization among Hospitalized Patients at a University Hospital in Thailand.

Optimal measures for preventing and controlling carbapenem-resistant Enterobacterales (CRE) depend on their burden. This prospective observational study investigated the prevalence and clinical course of CRE colonization in hospitalized patients at Siriraj Hospital, the largest university hospital in Thailand. Stool/rectal swab samples were collected from the patients upon admission, once weekly during hospitalization and every 1-3 months after discharge, to determine the presence of CRE in the stool. Between 2018 and 2021, a total of 528 patients were included. The prevalence of CRE colonization upon admission was 15.5%, while 28.3% of patients who tested negative for CRE on admission acquired CRE during their hospitalization. CRE colonization upon admission was usually associated with prior healthcare exposure. Among CRE-colonized patients, 4.7% developed a CRE clinical infection, with 60% mortality. No cutoff period that ensured that patients were free of CRE colonization in stool was identified, and isolation precautions should only be ceased if stool tests are negative for CRE. In conclusion, the prevalence of CRE colonization among hospitalized patients at Siriraj Hospital is high. CRE-colonized patients are at risk of developing subsequent CRE infection. To prevent CRE transmission within the hospital, patients at high risk of colonization should undergo CRE screening upon admission.

JMM Profile: Fosfomycin: a potential antibiotic for multi- and extensively resistant bacteria.

Fosfomycin (FOF) is the first antimicrobial of the epoxide class. It is commercially available in oral and parenteral formulations. Oral FOF is widely used to treat uncomplicated cystitis in women, while parenteral FOF is extensively utilized for upper urinary tract infections. FOF has a broad-spectrum bactericidal activity with a low risk of cross-resistance to other antimicrobial classes. Therefore, parenteral FOF is increasingly prescribed adjunctive therapy to treat extra-urinary tract infections caused by multidrug-resistant, Gram-negative bacteria.

Implementation of Clinical Practice Guidelines for Empirical Antibiotic Therapy of Bacteremia, Urinary Tract Infection, and Pneumonia: A Multi-Center Quasi-Experimental Study.

A quasi-experimental study was conducted on the implementation of locally developed clinical practice guidelines (CPGs) for empirical antibiotic (ATB) therapy of common infections (bacteremia, urinary tract infection (UTI), pneumonia) in the hospitals from January 2019 to December 2020. The CPGs were developed using data from patients with these infections at individual hospitals. Relevant CPG data pre- and post-implementation were collected and compared. Of the 1644 patients enrolled in the study, 808 and 836 were in the pre- and post-implementation periods, respectively, and patient outcomes were compared. Significant reductions in the mean durations of intensive care unit stay (3.44 ± 9.08 vs. 2.55 ± 7.89 days; p = 0.035), ventilator use (5.73 ± 12.14 vs. 4.22 ± 10.23 days; p = 0.007), piperacillin/tazobactam administration (0.954 ± 3.159 vs. 0.660 ± 2.217 days, p = 0.029), and cefoperazone/sulbactam administration (0.058 ± 0.737 vs. 0.331 ± 1.803 days, p = 0.0001) occurred. Multivariate analysis demonstrated that CPG-implementation was associated with favorable clinical outcomes (adjusted odds ratio 1.286, 95% confidence interval: 1.004-1.647, p = 0.046). Among patients who provided follow-up cultures (n = 284), favorable microbiological responses were significantly less frequent during the pre-implementation period than the post-implementation period (80.35% vs. 91.89%; p = 0.01). In conclusion, the locally developed CPG implementation is feasible and effective in improving patient outcomes and reducing ATB consumption. Hospital antimicrobial stewardship teams should be able to facilitate CPG development and implementation for antimicrobial therapy for common infections.

Safety and Efficacy of Ivermectin for the Prevention and Treatment of COVID-19: A Double-Blinded Randomized Placebo-Controlled Study.

The safety and efficacy of ivermectin for the prevention and treatment of COVID-19 are still controversial topics. From August to November 2021, we conducted a double-blinded, randomized controlled trial at Siriraj Hospital, Thailand. Eligible participants were adults ≥ 18 years with suspected COVID-19 who underwent a SARS-CoV-2 RT-PCR test. After enrollment, the participants were randomized to receive either ivermectin (400−600 µg/kg/d) or placebo once daily for 3 days. Among 983 participants, 536 (54.5%) with a negative RT-PCR result were enrolled in the prevention study, and 447 (45.5%) with a positive RT-PCR result were enrolled in the treatment study. In the prevention study, the incidence of COVID-19 on Day 14 was similar between the ivermectin and the placebo group (4.7% vs. 5.2%; p = 0.844; Δ = −0.4%; 95% CI; −4.3−3.5%). In the treatment study, there was no significant difference between the ivermectin and placebo group for any Day 14 treatment outcome: proportion with oxygen desaturation (2.7% vs. 1.9%; p = 0.75), change in WHO score from baseline (1 [−5, 1] vs. 1 [−5, 1]; p = 0.50), and symptom resolution (76% vs. 82.2%; p = 0.13). The ivermectin group had a significantly higher proportion of transient blurred vision (5.6% vs. 0.6%; p < 0.001). Our study failed to demonstrate the efficacy of a 3-day once daily of ivermectin for the prevention and treatment of COVID-19. The given regimen of ivermectin should not be used for either prevention or treatment of COVID-19 in populations with a high rate of COVID-19 vaccination.

Feasibility, Challenges, and Benefits of Global Antimicrobial Resistance Surveillance System Implementation: Results from a Multicenter Quasi-Experimental Study.

The Global Antimicrobial Resistance Surveillance System (GLASS) is one of the pillars of the global action plan on antimicrobial resistance launched by the World Health Organization in 2015. This study was conducted to determine the feasibility and benefits of GLASS as a component of antimicrobial stewardship strategies in three provincial hospitals in Thailand. Data on the types of bacteria isolated and their antibiotic susceptibility during January-December 2019 and January-April 2020 were retrieved from the microbiology laboratory of each participating hospital. Laboratory-based antibiograms from 2019 and GLASS-based antibiograms from 2020 were created and compared. A total of 14,877 and 3580 bacterial isolates were obtained during January-December 2019 and January-April 2020, respectively. The common bacteria isolated in both periods were Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Staphylococcus aureus. Hospital-acquired infection (HAI)-related bacteria were observed in 59.0%, whereas community-acquired infection (CAI)-related bacteria were observed in 41.0% of isolates. Antibiotic resistance in CAIs was high and may have been related to the misclassification of colonized bacteria as true pathogens and HAIs as CAIs. The results of this study on AMR surveillance using GLASS methodology may not be valid owing to several inadequate data collections and the problem of specimen contamination. Given these considerations, related personnel should receive additional training on the best practices in specimen collection and the management of AMR surveillance data using the GLASS approach.

Impact of Antibiotic Authorisation at Three Provincial Hospitals in Thailand: Results from a Quasi-Experimental Study.

Implementing antimicrobial stewardship (AMS) at non-university hospitals is challenging. A quasi-experimental study was conducted to determine the impact of customised antibiotic authorisation implementation on antimicrobial consumption and clinical outcomes at three provincial hospitals in Thailand. Customised pre-authorisation of selected restricted antibiotics and post-authorisation of selected controlled antibiotics were undertaken and implemented at each hospital by the local AMS team with guidance from the AMS team at the university hospital. From January 2019−December 2020, there were 1802 selected patients (901 patients during the pre-implementation period and 901 patients during the post-implementation period). The most commonly used targeted antimicrobial was meropenem (49.61%), followed by piperacillin/tazobactam (36.46%). Comparison of the outcomes of the patients during the pre- and post-implementation periods revealed that the mean day of therapy of the targeted antimicrobials was significantly shorter during the post-implementation period (6.24 vs. 7.64 days; p < 0.001), the favourable clinical response (the improvement in all clinical and laboratory parameters at the end of antibiotic therapy) was significantly higher during the post-implementation period (72.70% vs. 68.04%; p = 0.03) and the mean length of hospital stay was significantly shorter during the post-implementation period (15.78 vs. 18.90 days; p < 0.001). In conclusion, implementation of antibiotic authorisation at provincial hospitals under experienced AMS team's guidance was feasible and useful. The study results could be a good model for the implementation of customised AMS strategies at other hospitals with limited resources.

Rat bite fever due to Streptobacillus notomytis complicated by meningitis and spondylodiscitis: a case report.

BACKGROUND: Only three other cases of rat bite fever caused by Streptobacillus notomytis in humans have been reported since this species was identified in 2015. Data specific to the differences in clinical features and geographic distribution between S. notomytis infection and S. moniliformis infection are scarce. All previous cases of human S. notomytis infection were reported from Japan. This is the first case of S. notomytis infection reported from outside of Japan. CASE PRESENTATION: A 72-year-old Thai woman was admitted to Siriraj Hospital (Bangkok, Thailand)-Thailand's largest university-based national tertiary referral center-in August 2020 with fever, myalgia, and polyarthralgia for 3 days, and gradually decreased consciousness for the past 1 day. Physical examination and laboratory investigations revealed septic arthritis of both knee joints, meningitis, and hepatitis. She was initially misdiagnosed as rheumatoid arthritis in the elderly since the initial investigations were unable to detect a causative pathogen. However, S. notomytis infection was later confirmed by polymerase chain reaction amplification of a part of the 16S rRNA gene and sequencing from synovial fluid. Her clinical course was also complicated by spondylodiscitis and epidural abscess caused by S. notomytis, which was detected from tissue biopsy. Therefore, rat bite fever in this patient manifested as meningitis, septic polyarthritis, hepatitis, and spondylodiscitis. The patient was treated with intravenous ceftriaxone then switched to oral amoxicillin with complete recovery. CONCLUSIONS: The clinical manifestations of S. notomytis infection are similar to those demonstrated in S. moniliformis infection. This case also showed that arthritis caused by S. notomytis mimics rheumatoid arthritis, and that meningitis and spondylodiscitis are potential coexisting complications that can be found in S. notomytis infection.

Optical DNA Mapping of Plasmids Reveals Clonal Spread of Carbapenem-Resistant Klebsiella pneumoniae in a Large Thai Hospital.

Carbapenem-resistant Klebsiella pneumoniae (CR-KP) in patients admitted to hospitals pose a great challenge to treatment. The genes causing resistance to carbapenems are mostly found in plasmids, mobile genetic elements that can spread easily to other bacterial strains, thus exacerbating the problem. Here, we studied 27 CR-KP isolates collected from different types of samples from 16 patients admitted to the medical ward at Siriraj Hospital in Bangkok, Thailand, using next generation sequencing (NGS) and optical DNA mapping (ODM). The majority of the isolates belonged to sequence type (ST) 16 and are described in detail herein. Using ODM, we identified the plasmid carrying the blaNDM-1 gene in the ST16 isolates and the plasmids were very similar, highlighting the possibility of using ODM of plasmids as a surrogate marker of nosocomial spread of bacteria. We also demonstrated that ODM could identify that the blaCTX-M-15 and blaOXA-232 genes in the ST16 isolates were encoded on separate plasmids from the blaNDM-1 gene and from each other. The other three isolates belonged to ST147 and each of them had distinct plasmids encoding blaNDM-1.

Epidemiology, clinical characteristics, and treatment outcomes of patients with COVID-19 at Thailand's university-based referral hospital.

BACKGROUND: The epidemiology and outcomes of COVID-19 patients in Thailand are scarce. METHODS: This retrospective cohort study included adult hospitalized patients who were diagnosed with COVID-19 at Siriraj Hospital during February 2020 to April 2020. RESULTS: The prevalence of COVID-19 was 7.5% (107 COVID-19 patients) among 1409 patients who underwent RT-PCR for SARS-CoV-2 detection at our hospital during the outbreak period. Patients with COVID-19 presented with symptoms in 94.4%. Among the 104 patients who were treated with antiviral medications, 78 (75%) received 2-drug regimen (lopinavir/ritonavir or darunavir/ritonavir plus chloroquine or hydroxychloroquine), and 26 (25%) received a 3-drug regimen with favipiravir added to the 2-drug regimen. Disease progression was observed in 18 patients (16.8%). All patients with COVID-19 were discharged alive. CONCLUSIONS: The prevalence of COVID-19 was 7.5% among patients who underwent RT-PCR testing, and 10% among those having risk factors for COVID-19 acquisition. Combination antiviral therapies for COVID-19 patients were well-tolerated and produced a favorable outcome.

Diagnostic and Prognostic Utility Compared Among Different Sepsis Scoring Systems in Adult Patients With Sepsis in Thailand: A Prospective Cohort Study.

BACKGROUND: The diagnostic and prognostic utility of various sepsis scores varied among different cohorts and settings. METHODS: A prospective cohort study in adult patients with sepsis at Siriraj Hospital (Bangkok, Thailand) was conducted during January to July 2019. The performance of sepsis assessments, including systemic inflammatory response syndrome (SIRS) score, sequential organ failure assessment (SOFA) score, quick sepsis-related organ failure assessment (qSOFA) score, modified early warning score (MEWS), and national early warning score (NEWS), for sepsis detection and mortality prediction were compared with agreement between 2 infectious disease (ID) specialists to determine their sepsis and septic shock status as the reference standard. RESULTS: Among the 470 subjects included in this study, 206 patients (43.8%) were determined by 2 ID specialists to have sepsis. Systemic inflammatory response syndrome ≥2, qSOFA ≥2, and NEWS ≥5 yielded the highest sensitivity (93.2%), specificity (81.3%), and accuracy (72.6%), respectively, for detecting sepsis. The SIRS ≥2 had the highest sensitivity (97.8%), whereas qSOFA ≥2 had the highest specificity (61%) and accuracy (69.7%) for predicting mortality among sepsis patients. Receiver operating characteristic (ROC) curve showed MEWS to have the highest discriminatory power for sepsis detection (area under the ROC curve [AUROC], 0.79; 95% confidence interval [CI], 0.74-0.83), whereas SOFA had the highest discriminatory power for predicting hospital mortality (AUROC, 0.76; 95% CI, 0.69-0.79). CONCLUSIONS: The NEWS ≥5 and qSOFA ≥2 were the most accurate scoring systems for sepsis detection and mortality prediction, respectively. Each scoring system is useful for different specific purposes relative to early detection and mortality prediction in sepsis patients.

Disseminated histoplasmosis in a kidney transplant patient.

Patients with impaired cell-mediated immunity have a higher risk of developing histoplasmosis; however, histoplasmosis after solid organ transplantation is rare. In Thailand, histoplasmosis cases are sporadic, and most cases are associated with human immunodeficiency virus (HIV) infection. Herein, we report a case of disseminated histoplasmosis in a kidney transplant Thai recipient diagnosed by fungal staining of fungal culture from bronchoalveolar lavage and bone marrow biopsy. Liposomal amphotericin B was given followed by oral itraconazole. The patient's clinical condition was improved; however, his graft function was irreversibly declined. The majority of histoplasmosis cases after solid organ transplant presented with disseminated disease with pulmonary involvement. Even in a non-endemic area of histoplasmosis, suspected cases should be early diagnosed and promptly managed in order to reduce morbidity and mortality, especially in cell-mediated immunity defect patients like solid organ transplant recipients.

Integrated one-day surveillance of antimicrobial use, antimicrobial consumption, antimicrobial resistance, healthcare-associated infection, and antimicrobial resistance burden among hospitalized patients in Thailand.

OBJECTIVES: Surveillance of antimicrobial use (AMU), antimicrobial consumption (AMC), antimicrobial resistance (AMR), healthcare-associated infection (HAI), and AMR burden are usually measured by time-consuming and expensive multiple separate longitudinal surveys. This study aimed to investigate feasibility and benefit of integrated one-day surveillance to estimate and monitor these parameters. METHODS: Integrated one-day surveillance of AMU, AMC, AMR, HAI, and AMR burden among hospitalized patients in 183 hospitals in Thailand was conducted. Parameter data was collected for each patient who received antibiotic on a survey day. RESULTS: AMU prevalence was 51.5% among 23,686 hospitalized patients. The most commonly used antibiotic for infection prophylaxis and treatment was cefazolin and ceftriaxone, respectively. The most common infection was pneumonia. Community-associated infection (CAI) was observed in 64.9%, and 34.1% had HAI. Prevalence of AMR was highest in A. baumannii infection. AMR in bacteria was more prevalent among HAI than among CAI. Consumption of all antibiotics was 18,103 defined daily doses. HAI prevalence was 14.0%. Health and economic burden were much higher in patients with antibiotic-resistant infection. CONCLUSIONS: Integrated one-day surveillance of these important parameters among hospitalized patients is feasible and can be used for estimation and monitoring from the facility-level to the national-level in resource-limited settings.

Lomentospora prolificans vertebral osteomyelitis with spinal epidural abscess in an immunocompetent woman: Case report and literature review.

Lomentospora prolificans is a rare cause of vertebral osteomyelitis. We report a case of L. prolificans thoracic vertebral osteomyelitis with spinal epidural abscess in a patient without apparent immunodeficiency. Clinical manifestations and radiographic findings could not distinguish from other etiologic agents. Treatment is also challenging because L. prolificans is usually resistant to antifungal agents. The patient underwent surgical debridement and has been receiving a prolonged combination of antifungal therapy to prevent an infection relapse.