Duration Of Antifungal Therapy Research Articles

Determining the usefulness of systematic 18F-FDG PET/CT for the management of invasive fungal infection (PETIFI project): a prospective national multicentre cohort study protocol

IntroductionThe evaluation of staging and activity of invasive fungal infection (IFI) is used to adjust the type and duration of antifungal therapy (AT). Typically anatomy-based imaging is used. Positron emission...

201. Utility of Incorporation of Beta-D-glucan Testing in Algorithms for Diagnosis and Treatment of Candidemia.

Abstract Background Candidemia is a common hospital acquired infection that is associated with significant morbidity and mortality. The optimal strategy for diagnosis remains unknown. Methods We evaluated 2 distinct diagnostic strategies in hospitalized patients with suspicion of Candida bloodstream infection, namely strategy #1 that included simultaneous blood cultures and T2Candida and strategy #2 that included blood cultures, T2Candida testing and Beta-D-glucan (BDG). We examined the consistency with which each diagnostic algorithm led to changes in antifungal prescribing, the overall rate of antifungal utilization and patients’ clinical outcomes. Flow Chart. Figure 1. Results Among 96 patients tested with strategy #1, 3 had a positive result. Of those 100% completed a 14-day antifungal course for candidemia or were on antifungals until hospital discharge. Of the 29 out 120 patients that tested positive with strategy #2, 55.2% received a complete 14-day course or were on antifungals until hospital discharge. The percentage of completed treatment increased to 75.0% and 80.0% when the threshold for BDG positivity was increased at 200 pg/ml and 500 pg/ml respectively. We observed a significant difference in the overall antifungal utilization with 268.5 days of antifungals per 1,000 patient days for strategy #1, as opposed to 371.9 days of antifungals for strategy #2, a 38.5% increase. Negative tests at both diagnostic strategies led to a similar rate of antifungal discontinuation 3 days after testing (36.8% and 37.0% for strategy #1 and #2 respectively). We did not find significant benefits in death and/or subsequent diagnosis of candidemia between the 2 diagnostic strategies. Sensitivity analyses performed based on indication for testing and severity of illness did not significantly alter results. Table 1.Characteristics of patients tested for suspicion of candidemia with the 2 diagnostic strategies. Figure 2. Duration of antifungal therapy among patients with positive BDG at different thresholds A. BDG<80 pg/ml, B. BDG<200 pg/ml, C. BDG<500 pg/ml. Figure 3. Percentage of patients who were taken off antifungals within 3 days of testing for different BDG thresholds, BDG<80 pg/ml, BDG<200 pg/ml, and BDG<500 pg/ml. Conclusion In summary, the addition of BDG in diagnostic algorithms for candidemia was interpreted variably by clinicians, was associated with a significant increase in antifungal utilization, and it did not appear to lead to measured clinical benefits for patients. Diagnostic strategies of common and serious infections that incorporate non-culture diagnostics need to be evaluated for added benefit. Table 2.Antifungal utilization among patients tested for suspicion of candidemia with the 2 diagnostic strategies. Table 3. Outcomes among patients tested for suspicion of candidemia with the two different diagnostic strategies. Disclosures All Authors: No reported disclosures.

Antifungal therapy in the management of fungal secondary infections in COVID-19 patients: A systematic review and meta-analysis.

The prevalence of fungal secondary infections among COVID-19 patients and efficacy of antifungal therapy used in such patients is still unknown. Hence, we conducted this study to find the prevalence of fungal secondary infections among COVID-19 patients and patient outcomes in terms of recovery or all-cause mortality following antifungal therapy (AFT) in such patients. We performed a comprehensive literature search in PubMed®, Scopus®, Web of Sciences™, The Cochrane Library, ClinicalTrial.gov, MedRxiv.org, bioRxiv.org, and Google scholar to identify the literature that used antifungal therapy for the management fungal secondary infections in COVID-19 patients. We included case reports, case series, prospective & retrospective studies, and clinical trials. Mantel Haenszel random-effect model was used for estimating pooled risk ratio for required outcomes. A total of 33 case reports, 3 case series, and 21 cohort studies were selected for final data extraction and analysis. The prevalence of fungal secondary infections among COVID-19 patients was 28.2%. Azoles were the most commonly (65.1%) prescribed AFT. Study shows that high survival frequency among patients using AFT, received combination AFT and AFT used for >28 days. The meta-analysis showed, no significant difference in all-cause mortality between patients who received AFT and without AFT (p = 0.17), between types of AFT (p = 0.85) and the duration of AFT (p = 0.67). The prevalence of fungal secondary infections among COVID-19 patients was 28.2%. The survival frequency was high among patients who used AFT for fungal secondary infections, received combination AFT and AFT used for >28 days. However, meta-analysis results found that all-cause mortality in COVID-19 patients with fungal secondary infections is not significantly associated with type and duration of AFT, mostly due to presence of confounding factors such as small number of events, delay in diagnosis of fungal secondary infections, presence of other co-infections and multiple comorbidities.

Clinical features of space occupying lesion due to fungal infections mimicking brain tumor: Case report

Diagnosis and treatment of masses due to fungal infection of the central nervous system is often difficult. Radiologic features are often non-specific and are often confused with malignant lesions so that a new diagnosis can be made by histological examination after resection. The combination of medical and surgical treatment of fungal infections of the central nervous system is optimal in shortening the duration of antifungal therapy, providing a definitive diagnosis and improving patient outcome. A 57-year-old male patient was conscious with complaints of weakness in the left half of the body, progressive chronic headache for 6 months and seizures, with physical examination results in the form of papilledema dextra, paresis N VI dextra et sinistra, paresis N VII S supranuclear, hemiparesis flaccid of left with grade 2/3, chronic progressive cephalgia and with a history of partial seizures become secondary common. Non-reactive HIV, CT scan of the head supporting a primary brain tumor with suspicion of intratumoral bleeding and cerebral edema. After surgery, histopathological examination results suitable for cerebral abscess, leading to fungal infection that is Cryptococcus neoformans. The patient was treated with 600 milligrams of Fluconazole every 12 hours intraoral for 6 months, the complaints improved and the head MRI was evaluated as normal. Conclusions. Diagnosis of fungal infection is still a challenge. The combination of surgical medical therapy in a mass fungal infection of the central nervous system is optimal in shortening the duration of antifungal treatment, providing a definitive diagnosis, and improving patient outcomes.

Mucormycosis as SARS-CoV2 sequelae in kidney transplant recipients: a single-center experience from India.

PurposeCoronavirus disease (COVID-19) sequelae in the transplant population are scarcely reported. Post-COVID-19 mucormycosis is one of such sequelae, which is a dreadful and rare entity. The purpose of this report was to study the full spectrum of this dual infection in kidney transplant recipients (KTR).MethodsWe did a comprehensive analysis of 11 mucormycosis cases in KTR who recovered from COVID-19 in IKDRC, Ahmedabad, Gujarat, India during the study period from Nov 2020 to May 2021. We also looked for the risk factors for mucormycosis with a historical cohort of 157 KTR who did not develop mucormycosis.ResultsThe median age (interquartile range, range) of the cohort was 42 (33.5–50, 26–60) years with 54.5% diabetes. COVID-19 severity ranged from mild (n = 10) to severe cases (n = 1). The duration from COVID-19 recovery to presentation was 7 (7–7, 4–14) days. Ten cases were Rhino-orbital-cerebral-mucormycosis (ROCM) and one had pulmonary mucormycosis. Functional endoscopic sinus surgery (FESS) was performed in all cases of ROCM. The duration of antifungal therapy was 28 (24–30, 21–62) days. The mortality rate reported was 27%. The risk factors for post-transplant mucormycosis were diabetes (18% vs 54.5%; p-value = 0.01), lymphopenia [12 (10–18) vs 20 (12–26) %; p-value = 0.15] and a higher neutrophil–lymphocyte ratio [7 (4.6–8.3) vs 3.85 (3.3–5.8); p-value = 0.5].ConclusionThe morbidity and mortality with post-COVID-19 mucormycosis are high. Post-transplant patients with diabetes are more prone to this dual infection. Preparedness and early identification is the key to improve the outcomes.

Impact of treatment duration on recurrence of chronic pulmonary aspergillosis

Limited data exist on the optimal treatment duration for chronic pulmonary aspergillosis (CPA). We investigated the treatment outcome and recurrence rate according to treatment duration in CPA patients. A total of 196 patients who completed at least 6 months of antifungal therapy (99% oral itraconazole) and achieved favorable treatment responses were analyzed. A Cox's proportional hazards regression model was used to adjust for potential confounding factors in the association between the duration of antifungal therapy (6-12 months vs. ≥12 months) and recurrence. All patients were treated with antifungal agents for at least 6 months (median: 12.5, interquartile range: 8.5-18.4 months) and categorized into 6-12 months group (79/196, 40%) and ≥12 months group (117/196, 60%). The 6-12 months group had significantly higher recurrence rates owing to CPA aggravation after the completion of treatment compared with the ≥12 months group (51% vs. 25%, P = 0.003). In a Cox's proportional hazards regression model, treatment duration ≥12 months was independently associated with a lower risk of recurrence (adjusted hazard ratio: 0.48, 95% confidence interval: 0.28-0.80). Our data suggest that prolonging antifungal therapy beyond 12 months could reduce the recurrence rate in CPA patients.

Epidemiological and Microbiological Study of Onychomycosis

Introduction: Onychomycosis is a common fungal infection of nail. It may be caused by dermatophytes, non-dermatophytic moulds or yeasts involving nail bed, nail plate or matrix of nail. As the fungi show variable susceptibility to antifungal drugs and treatment requires long duration of antifungal therapy, so it’s prevalence as well as proper laboratory diagnosis and antifungal susceptibility testing is essential for effective therapy. Aim: To find the prevalence of onychomycosis with demography along with various aetiology and the suitable antifungal drugs used for treatment. Materials and Methods: For this prospective study, over a period of two years a total of 300 nail samples were processed in the Department of Microbiology at IMS and SUM Hospital, Bhubaneswar, Odisha, India. The wet mount for microscopic examination was prepared using 20% Potassium Hydroxide (KOH) and examined after overnight incubation. Culture was done in duplicate in Sabouraud’s Dextrose Agar (SDA) tubes; one with actidione and another without it and both were incubated at 25°C in Biological Oxygen Demand (BOD) incubator. Culture tubes growing yeasts were further subjected to speciation by germ tube test, culture on Chromogenic (CHROM) agar and on cornmeal agar. In-vitro antifungal susceptibility testing was performed against Candida species using disc diffusion method on Muller Hinton agar. Chi-square test was used for statistical analysis of the results. Results: Onychomycosis can affect a wide age group though seen commonly at 31-40 years equally in both male and females. Fingernail infection was observed mostly in female cases. It was caused by Candida species (66%), moulds (24%) and dermatophytes (10%) and out of Candida sp. C.albicans was the main culprit. Although all the Candida strains were susceptible to amphotericin B, still some of them showed resistance to the commonly used antifungals like fluconazole and itraconazole. Conclusion:Candida albicans was the most common aetiological agent which contributed for onychomycosis and showed a variable resistance pattern to the commonly used antifungals. Proper laboratory diagnosis and selection of antifungal drug is essential prior to institution of therapy for successful treatment of this disease.

Aspergillus necrotizing otitis externa with temporomandibulozygomatic involvement

IntroductionAspergillus necrotizing otitis externa (NOE) is a rare disease, often associated with delayed diagnosis, the management of which is poorly defined. SummaryThe authors report a case of Aspergillus flavus necrotizing otitis externa with temporomandibular arthritis and temporozygomatic osteomyelitis with Staphylococcal coinfection in a diabetic patient. The diagnosis and discontinuation of treatment were guided by PET-CT scan. A favourable course without sequelae was observed after repeated surgical curettage and 3 months of antifungal therapy. DiscussionAspergillus flavus is the agent most commonly incriminated in NOE. Indirect diagnostic tests (serology) may be negative. The diagnosis is based on imaging-guided surgical biopsy with histological examination and standard and fungal microbiological culture. Treatment requires a combination of surgery and antifungal therapy. The duration of antifungal therapy is poorly defined and discontinuation of therapy can be guided by PET-CT scan.

Clinical characteristics and risk factors for complications of candidaemia in adults: Focus on endophthalmitis, endocarditis, and osteoarticular infections

ObjectivesThis study evaluated the incidence, risk factors, and clinical characteristics of complications of candidaemia in adults, with a focus on endophthalmitis, endocarditis, and osteoarticular infections. MethodsAll patients ≥18 years old with candidaemia in two Korean tertiary hospitals from 2007 to 2016 were investigated. Complications of candidaemia were defined as the presence of endophthalmitis, endocarditis, or osteoarticular infections documented in patients with candidaemia. The clinical characteristics and risk factors for candidaemia with complications were analysed in the patients who underwent ophthalmological examinations. ResultsOf 765 adult patients with candidaemia, 34 (4.4%) met the definition of complications, including endophthalmitis in 29 (3.8%), endocarditis in 4 (0.5%), and osteoarticular infections in 3 (0.4%). Of the 225 patients who underwent ophthalmological examinations, 29 (12.9%) had endophthalmitis. Candida albicans was an independent risk factor for complicated candidaemia (OR, 5.12; 95% CI, 2.17–12.09; P < 0.001). Although the mortality rate was no higher in complicated candidaemia, the duration of antifungal therapy was longer (23.1 ± 17.6 vs. 16.4 ± 10.8 days, P = 0.042), and 13 patients (39.3%) underwent additional procedures or surgery. ConclusionsComplications of candidaemia occurred in 4.4% of adult patients. C. albicans was an independent risk factor for complicated candidaemia in adults. Complications of candidaemia might need prolonged treatment and additional procedures or surgery. Therefore, careful evaluation and active treatment of candidaemia with complications should be encouraged.

Factors related to antibiotic-associated diarrhea in patients in the intensive care unit receiving antifungals: a single-center retrospective study.

ObjectiveTo analyze factors related to antibiotic-associated diarrhea (AAD) in patients in the intensive care unit (ICU) receiving antifungals with the aim of informing rational antibiotic use.MethodsSex, age, medical history, use of proton pump inhibitors, administration of parenteral nutrition, albumin level, occurrence of AAD, type of antibiotics, duration of ICU admission, and prognosis were retrospectively analyzed. The associations of age, sex, medical history, and other factors with AAD were associated by logistic regression.ResultsIn total, 284 patients were enrolled (antifungals, n = 110; no antifungals, n = 174). The total incidence of AAD was 32.39%. The incidence of AAD was significantly different between the groups (52.73% vs. 19.54%). The duration of proton pump inhibitor therapy, duration of antifungal therapy, enzyme inhibitor antibiotic use, and azithromycin use were associated with AAD in ICU patients receiving antifungal therapy. The mean duration of ICU admission was higher in patients receiving antifungal therapy (20.14 ± 11.50 vs. 14.48 ± 8.54 days). There was no significant difference in ICU mortality rates.ConclusionThe duration of proton pump inhibitor therapy, duration of antifungal therapy, use of enzyme inhibitor antibiotics, and use of azithromycins were associated with AAD in ICU patients receiving antifungal therapy.

Cutaneous Mucormycosis in Solid Organ Transplant Recipients after Hurricane Harvey: Short- and Long-term Management.

Summary:In the fall of 2017, Hurricane Harvey, one of the most costly hurricanes in American history, ravaged the Texas Gulf Coast, interrupting basic sanitation systems to hundreds of thousands of Texas residents. In the aftermath of Hurricane Harvey, our Houston hospitals noted an uptick in the incidence of cases of mucormycosis. Among the most vulnerable and affected have been immunocompromised transplant recipients. Here, we describe the successful management of 2 patients with atypical presentations of mucormycosis, 2 cutaneous infections after liver transplantation. Our comprehensive treatment strategy based upon guidelines and experience included coordinating aggressive surgical and medical therapies. We discuss our approach to surgical management including the extent and frequency of debridement, the methods of assessing disease-free margins, and minimizing the morbidity of radical debridement with temporary coverage and forethought to long-term reconstruction. Additionally, we describe the concurrent medical management, including type, route, and duration of antifungal therapy, minimizing suppression of the innate immune system, and optimizing the wound healing environment through maintaining nutritional status.

Candida arthritis: 18 cases report and literature review

Objective To analyze the clinical features of candida arthritis and to conduct literature review to improve diagnosis and treatment. Methods From January 2008 to June 2018, eighteen patients (5 females and 13 males) with candida arthritis were admitted to two hospitals. The mean age at diagnosis was 59±8 (range 48-71 years). The diagnosis was determined based on joint fluid aspirate in all cases and on intra-operative samples in 1 patients. Seventeen patients received MR examination, and on epatient who underwent total knee arthroplasty underwent knee X-ray examination. The clinical features, risk factors, clinical manifestations, etiology, treatment and prognosis are recorded. Results Knee joints were involved in all patients as infection sites. Seventeen patients had risk factors for candida infection, including diabetes mellitus in 2 patients, artificial joint replacement in 1, and glucocorticoid injection in the joint cavity in 16. Swelling and pain were presented in all cases. Peripheral blood leukocytes were increased or normal, while C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were increased. Magnetic resonance showed joint effusion and slip membrane hyperplasia. Joint turbidity and synovial hyperplasia were presented by arthroscopy. X-ray demonstrated swelling of soft tissue around the prosthesis and bone absorption around the prosthesis. The most frequent species was non-candida albicans. Susceptibility to antifungals was tested in all cases. Thirteen patients underwent surgery combined with antifungal therapy, while 4 patients only received antifungal therapy and 1 patient refused to treat. The duration of antifungal therapy was from 6 weeks to 52 weeks (median, 12 weeks). Twelve cases were treated with fluconazole and 1 with voriconazole, 1 with voriconazole and fluconazole, 1 with fluconazole combined with lipid formulation amphotericin B, 1 with terbinatine and fluconazole, 1 with flucytosine combined with fluconazole. Seventeen cases were followed up for 3 to 72 months. At final follow-up, twelve patients were healed, while 1 case was amputated and 4 patients relapsed and refused further treatment. Conclusion As a rare disease, candida arthritis is usually happened after artificial joint replacement and in high-risk patients with diabetes and immunosuppressant applications. In immunocompetent patients without surgery, infection may be related to multiple injections into the joint cavity with glucocorticoids. The infection may be difficult to be diagnosed and with poor prognosis. Surgery with long-term antifungal therapy is required. Key words: Knee joint; Arthritis; Prosthesis-related infections; Candidiasis

2054. Physician Responses to Positive Rapid Diagnostic Tests for Candida Fungemia in the Absence of Concomitant Positive Blood Cultures

Background Candida species are the fourth leading cause of nosocomial bloodstream infections in the United States. Unfortunately, detection, identification and susceptibility testing using standard instrumented blood culture systems and routine microbiological techniques may take 4–10 days. Moreover, sensitivity of routine blood cultures for candidemia is only ~50 to 75%. The T2 Candida Panel (T2CP) is an FDA-approved assay that rapidly detects the presence of five Candida species directly from whole blood in 3–5 hours. We examined mortality and antifungal therapy (AFT) decisions based on positive (pos) results of a T2CP in patients with negative (neg) blood cultures.MethodsWe performed a case series of all patients who had a pos T2CP with concomitant neg blood cultures at our institution from March 1, 2016 to March 1, 2018. If a patient had multiple valid T2CP, only the first pos result was used for analysis. Medical records were reviewed for demographics, comorbidities, risk factors for candida infection, length of stay, use and duration of AFT, and 14-day and in-hospital mortality from the time of the T2CP.ResultsFifteen patients were identified who met inclusion criteria. Eight patients were immunocompromised: four (26.7%) solid cancer malignancy, three (20%) hematologic malignancy, and one kidney transplant recipient. Pos T2CP results by species were as follows: 53.3% C. albicans/C. tropicalis, 40% C. parapsilosis, and 6.7% C. glabrata/C. krusei. Median SOFA, Charlson comorbidity index, and Candida scores were 6, 6, and 9, respectively. Fourteen-day mortality was 40% and in-hospital mortality was 53.3%. Only two patients were on prophylactic AFT due to an underlying hematologic malignancy at the time of T2CP; in both cases, azole AFT was replaced with an echinocandin in response to the pos T2CP. Of the remaining 13 patients who were not on prophylactic AFT, all were started on AFT after pos T2CP result.ConclusionPhysicians escalated or initiated AFT therapy based on pos T2CP in severely ill patients who had negative blood cultures. Unfortunately, the population had high severity index scores and high mortality despite initiation or escalation of AFT. We hypothesize that earlier testing and detection of Candida fungemia may lead to faster initiation of AFT and better outcomes.Disclosures All authors: No reported disclosures.

Outcome of Allogeneic Hematopoietic Stem Cell Transplantation in Patients with Prior Invasive Aspergillosis

Background: Introducing a new antifungals and diagnostic procedures has improved prognosis of the invasive aspergillosis (IA) in hematological patients. The number of patients with IA who are candidates for allogeneic hematopoietic stem cell transplantation (allo-HSCT) has increased. The influence of IA on survival and on allo-HSCT related complications has not been investigated in a prospective study.Aim: to estimate impact of prior proven and probable IA on outcome of allo-HSCT compared to patients without IA.Methods: In prospective observational single center study 362 allo-HSCT recipients (336 - first and 26 - second allo-HSCT) were included from Jan 2012 to Dec 2014. The median age was 34 y, males - 54%. Most of pts had high-risk acute leukemia (70%). Allo-HSCT with MUD were performed in 57%, MRD - 24%, haplo - 11%, MMUD - 8%, predominantly with RIC (80%). All patients with lesions in CT scan before allo-HSCT have undergone bronchoscopy with BAL microscopy, culture and GM test. EORTC/MSG 2008 criteria were used for the diagnosis of proven and probable IA as well as to evaluate response to therapy. "Active" invasive IA - IA diagnosed just before allo-HSCT. All patients were observed with the median 2 years follow up. We analyze status of pts before HSCT, donor types, source of HSCT, CMV status, conditioning regimens and type of immunosuppression, relapse or progression of IA, relapse of underlying disease, duration of antifungal therapy and prophylaxis, acute and chronic GvHD. The cumulative incidences were determined with cumulative incidence method. Differences between the two cohorts were verified with Gray test. Overall survival after allo-HSCT was estimated with Kaplan-Meier method and cohorts were compared by log-rank test.Results: Incidence of IA before allo-HSCT was 20% (n=72/362). According to EORTC/MSG 2008 criteria 92% of pts had probable IA and 8% - proven IA. The main sites of IA were lungs - 95%, central nervous system - 3%, and colon - 3%, other sites were observed in a combination with lungs involvement: sinuses - 5%, spleen - 3%, and liver - 3%. The median time from IA to allo-HSCT was 3 months (3 days - 30 months). Antifungal therapy before allo-HSCT was used in 69% pts (voriconazole - 95%, other - 5%) with the median duration of therapy - 2 months. Complete response to antifungal therapy was registered in 19 (26%) patients, partial response or stabilization - 31 (43%), and "active IA" - 22 (31%). After allo-HSCT all patients received antifungal therapy with voriconazole (first line - 31%, continuation of treatment - 43%, and secondary prophylaxis - 26%). Median length of treatment was 166 days (37 - 394) with the median duration to effect 99 days (31 - 217). No toxicity of the antifungal treatment was registered. Cumulative incidence of relapse or progression of IA at 2 year after allo-HSCT was 14% (n=10). "Active" underlying disease before D+100 post transplant was the only risk factor for the relapse or progression of IA after allo-HSCT (6% vs 33%, p=0,007). 100-days OS after allo-HSCT was 77%, 2-year OS after allo-HSCT was 62%. There was no significant difference in OS in patients with or without IA prior to allo-HSCT (57% vs 65%, p=0,3). Duration of antifungal therapy before HSCT (<90 days vs ≥90 days), status of IA at the moment of HSCT ("active" IA vs PR vs CR), relapse/progression of IA after HSCT was not affected on 2-year OS after allo-HSCT in patients with prior IA.Conclusions: Incidence of proven and probable invasive aspergillosis before allo-HSCT was 20%. Cumulative incidence of relapse or progression of the invasive aspergillosis after allo-HSCT was 14% and "active" underlying disease before D+100 post transplant was the only risk factor. Invasive aspergillosis prior to allo-HSCT did not impair the outcome of the procedure with effective diagnosis and prophylaxis being used. DisclosuresNo relevant conflicts of interest to declare.

Successful treatment of Candida osteoarticular infections with limited duration of antifungal therapy and orthopedic surgical intervention

Background: Current guidelines for treatment of Candida osteoarticular infections (COAIs) recommend a prolonged course of antifungal therapy (AFT) of 6–12 months. Based upon strategies developed at the Hospital for Special Surgery (HSS), we hypothesized that the duration of antifungal therapy may be substantially reduced for management of COAI. Methods: This was a retrospective chart review of cases of COAI treated at the HSS for the past 14 years. COAI was documented by open biopsy and direct culture in all cases. The mean (95% confidence interval, CI) duration of documented follow-up was 39 (16–61) months. Results: Among the 23 cases of COAI, the median age was 62 years (range 22–83 years) with 61% having no underlying condition. Orthopedic appliances, including joint prostheses and fracture hardware, were present in 74% of cases. All patients had COAI as the first proven site of candidiasis. Candida albicans and Candida parapsilosis were the most common species. Hip, knee, foot, and ankle were the most common sites. All patients received aggressive surgical intervention followed by AFT administered for a mean (95% CI) duration of 45 (38–83) days. Systemic AFT consisted principally of fluconazole alone (65%) or in combination with other agents (26%). Adjunctive intraoperative amphotericin B irrigation was used in 35%. Among eight cases of CAOI that required placement of a new prosthetic joint, all were successfully treated. There were no microbiologic failures. Conclusions: Candida osteoarticular infections may be successfully treated with substantially limited durations of AFT when combined with a thorough surgical approach.

Evaluation of antifungal use in a tertiary care institution: antifungal stewardship urgently needed

To assess the quality of antifungal use, to propose a point score for this evaluation and to estimate the potential economic savings of an antifungal stewardship programme. From December 2010 to January 2011, we identified 100 adult inpatients receiving systemic antifungals. Antifungal use was evaluated by means of a predefined score that considered indication, drug selection, dosage, adjustments after microbiology results, switching to an oral agent and length of treatment. Total antifungal prescriptions [in defined daily doses (DDDs) and days of therapy (DOTs)] and potential cost savings were calculated. Overall, 43% of prescriptions came from medical departments, 25% from haematology/oncology and 17% from intensive care units. The main reasons for starting antifungals were empirical (42%), pre-emptive (20%) and targeted treatment (20%). Antifungals were unnecessary in 16% of cases. Inadequacies in other aspects of antifungal prescription were: drug selection, 31%; dosing, 16%; no switch from intravenous to oral administration, 20%; no adjustment after microbiological results, 35%; and length of therapy, 27%. The number of antifungal DDDs per 1000 patient-days was 65.1. The total number of DOTs was 1556, which added a direct cost of €219 364. Only 51.3% of DOTs were considered optimal. The potential estimated savings would be €50 536. Major efforts should be made to improve the selection and duration of antifungal therapy. Our study demonstrated the potential cost savings that could be achieved by optimizing antifungal therapy. A stewardship programme should include an instrument to objectively evaluate the adequacy of antifungal use.

Current Epidemiology and Management of Invasive Candidiasis in Infants

Invasive candidiasis (IC) is common in premature infants and is associated with significant morbidity and mortality. Although the incidence of IC in infants is decreasing, there is marked variability in number of cases by center and geographical region, and current methods for diagnosis are suboptimal. Nonabsorbable antifungals, probiotics, and systemic antifungals have been shown to decrease IC in select populations. Although empirical antifungal therapy may provide benefit to infants with IC, prediction of the disease is difficult. While available antifungal agents appear to be effective in the treatment of IC in infants, knowledge of the optimal type, dose, and duration of antifungal therapy is limited by the low number of available infant studies.

Utility of (1–3)-β-d-Glucan Testing for Diagnostics and Monitoring Response to Treatment During the Multistate Outbreak of Fungal Meningitis and Other Infections

The 2012 outbreak of fungal meningitis associated with contaminated methylprednisolone produced by a compounding pharmacy has resulted in >750 infections. An important question facing patients and clinicians is the duration of antifungal therapy. We evaluated (1-3)-β-d-glucan (BDG) as a marker for monitoring response to treatment. We determined sensitivity and specificity of BDG testing using the Fungitell assay, by testing 41 cerebrospinal fluid (CSF) specimens from confirmed cases of fungal meningitis and 66 negative control CSF specimens. We also assessed whether BDG levels correlate with clinical status by using incident samples from 108 case patients with meningitis and 20 patients with serially collected CSF. A cutoff value of 138 pg/mL provided 100% sensitivity and 98% specificity for diagnosis of fungal meningitis in this outbreak. Patients with serially collected CSF were divided into 2 groups: those in whom BDG levels declined with treatment and those in whom BDG remained elevated. Whereas most patients with a decline in CSF BDG had clinical improvement, all 3 patients with continually elevated BDG had poor clinical outcomes (stroke, meningitis relapse, or development of new disease). Our data suggest that measuring BDG in CSF is a highly sensitive test for diagnosis of fungal meningitis in this outbreak. Analysis of BDG levels in serially collected CSF demonstrated that BDG may correlate with clinical response. Routine measurement of BDG in CSF may provide useful adjunctive data for the clinical management of patients with outbreak-associated meningitis.

Assessing Responses to Treatment of Opportunistic Mycoses and Salvage Strategies

Invasive fungal disease (IFD) in immunocompromised patients remains a major cause of morbidity and mortality and there is a pressing need for studies of novel antifungal agents and strategies to improve outcomes. Trial design details often determine not only the appropriate interpretation of the results, but also their translation into clinical practice. However, the conduct of IFD clinical trials remains challenging due to the rarity of IFD, heterogeneity of underlying diseases, and the lack of clear and standardized response criteria. Response assessments are influenced by host, underlying disease and treatment factors as well as eligibility criteria. In addition, the criteria used to assess response, when response is assessed and the type of antifungal therapy under study can impact response evaluations. This article will discuss recent trials of primary, salvage, empiric, and prophylactic antifungal therapy with specific attention to the design of these antifungal therapy trials and how their designs influence their interpretation. The potential role of surrogate markers, such as the galactomannan index, fungal deoxyribonucleic acid polymerase chain reaction assay, and (18F) fluorodeoxyglucose positron emission tomography scans in establishing the early diagnosis of IFD, as well as enhancing the ability to assess outcomes to antifungal therapy, and thereby the optimal duration of antifungal therapy, will be discussed.

INVASIVE RESPIRATORY ASPERGILLOSIS IS A TREATABLE DISEASE WITH EARLY DIAGNOSIS AND AGGRESSIVE THERAPY

This study aimed to document outcome of invasive respiratory aspergillosis (IRA) in pediatric malignancy patients. Patients with febrile neutropenia episodes followed between January 2003 and May 2007 were enrolled. Antifungal therapy was added to those who were still febrile on the 5th day of febrile neutropenia treatment. Patients were screened with computerized tomographies. IRA was identified in 22 of 98 patients. There were 13 males and the mean age was 97 months. Proven infection was established in 3, probable in 7, and possible in 12 patients. Liposomal amphotericin B was administered to all patients and was successful in 10 patients. Modifications with caspofungin or voriconazole were done in liposomal amphotericin B failures. The median duration of antifungal therapy was 5.5 months. The median follow-up time was 29 months. There was no evidence of IRA in 12 patients after completion of cancer chemotherapy. Six patients died due to underlying disease, whereas IRA was either in remission or stable disease. Four patients were lost due to IRA. The remission rate for IRA was 82%. Survival at 37 months was 55% (95% confidence ınterval 25–47 months). The amount of time that absolute neutrophil count after initiation of treatment for IRA remained at zero was found to be an independent prognostic factor on survival (P = .01). These results suggest that early diagnosis and aggressive treatment may increase the successful outcome of IRA.