Empiric Fluconazole Research Articles

Can Prolonged Incubation of Negative Blood Cultures Show Fungal Positivity?

Objective: Standard duration of one set blood culture (BC) is a maximum of 5-7 days. The aim of this study was to evaluate “culture-negative” vials with a prolonged incubation (max 30 days) time and to observe any mycological growth. Materials and Methods: Routine BCs optained from adult patients of Balıkesir Atatürk City Hospital for a year period were included. Render BC System BC128 (Render Biotech Co. Ltd., Shenzhen, China) were used. Randomly selected vials were re-incubated for additional three weeks by conventional methods. In case of any growth, identifications were done by PhoenixTM 100 system (Becton Dickinson, MA, USA) with cornmeal tween 80 agar (RTA Laboratories, Kocaeli, Turkey). Antifungal susceptibility testing was applied with CLSI disk diffusion method. Results: A total of 6047 BC sets were obtained and randomly chosen 1040+122 negative sets (A and B groups, respectively) were included. In group A, none of them had fungal growth. In B (ongoing empiric antifungal ≤48h), only 2 sets showed significant fungal growth, which were observed in 7±2 days, and all strains were identified as C.glabrata complex and these patients were on empiric fluconazole (200 mg/day). One isolate was susceptible dose dependent, the other one was resistant for fluconazole. Latter sets of these fungemia patients showed positive signals in routine incubation period. Conclusion: Invasive fungal infections are increasingly encountered and isolation capacity and optimization of BCs are crucial. In this study, it was obviously observed that standard incubation period is satisfactory in order to detect almost all fungemia.

10. Impact of Infectious Disease Consultation and Theoretical Management Bundle in Patients with Candidemia

BackgroundCandidemia is associated with significant morbidity and mortality. The impact of infectious diseases consultation (IDC) on clinical outcomes in patients with candidemia is not well established. We evaluated the impact of IDC and a management bundle on clinical outcomes in patients with candidemia.MethodsA retrospective chart review of adult (age ≥ 18 years) patients with at least 1 blood culture growing Candida species identified at Alberta Precision Laboratories between December 1, 2019 to November 30, 2020 and hospitalized at the University of Alberta Hospital, Edmonton, Canada were included. Patients who died within 48 hours and those who left against medical advice within 24 hours of initial positive blood culture result were excluded. Demographics, management, and outcome data were collected. A complete management bundle was defined as having all the following elements performed: IDC, repeat blood cultures, empiric echinocandin therapy, ophthalmology consult, and echocardiogram.ResultsThirty-one patients were included for study; mean age was 56 ± 17 years and 65% were male. 14 (45%) cases were admitted under critical care, 7 (23%) surgery, and 10 (32%) medicine. 3/17 (18%) required intensive care unit admission following candidemia diagnosis. Candida albicans was identified in more than half the cases. The primary source was intra-abdominal in 12 (39%), central-line associated in 8 (26%), and urinary in 6 (19%). IDC occurred in 27 cases (87%), echocardiogram in 22 (71%), ophthalmology consult in 10 (32%), and follow-up blood cultures in 30 (97%). 20 (65%) patients received empiric echinocandin. Of the remainder who received empiric fluconazole, 4 (36%) grew non albicans Candida species.Higher in-hospital mortality was observed in cases without IDC than those with IDC (4/4, 100% vs 8/27, 29.6%, p=0.016) and in those that did not have a complete bundle (12/25, 48% vs 0/6, p=0.059). However, IDC was not associated with the receipt of individual bundle components nor the complete bundle (p=NS).ConclusionIn patients with candidemia, lower in-hospital mortality was observed in patients who received IDC. Larger studies are required to confirm our findings and assess whether the implementation of a candidemia management bundle is beneficial. Disclosures Dima Kabbani, MD, AVIR Pharma (Grant/Research Support, Other Financial or Material Support, Speaker)Edesa Biotech (Scientific Research Study Investigator)Merck (Scientific Research Study Investigator)

AN UNUSUAL CASE OF SARCOIDOSIS PRESENTING AS A LUNG MASS AND CARDIAC TAMPONADE

TOPIC: Diffuse Lung Disease TYPE: Fellow Case Reports INTRODUCTION: Sarcoidosis is a multisystem granulomatous disease whose etiology remains elusive yet nevertheless has classic pulmonary and extrapulmonary findings that may aid in the diagnosis. The proceeding case demonstrates however the difficulty in diagnosing this masquerader when rare presentations instead form the clinical picture. CASE PRESENTATION: We present a 63-year-old male with a history of treated active tuberculosis who presented with abdominal pain and incidentally found to have innumerable bilateral pulmonary nodules accompanying a right hilar mass with confluent lymphadenopathy (Figs 1&2). Despite these findings, he denied cough, hemoptysis, dyspnea, fevers, chills, night sweats, and weight loss. He had a notable history of particulate exposure as a contractor but was otherwise a lifetime non-smoker. Diagnostic bronchoscopy with endobronchial ultrasound guidance revealed both necrotizing and non-necrotizing granulomata but no evidence of malignancy. Before additional studies could be performed, the patient was hospitalized at an outside facility for dyspnea and found to be in cardiac tamponade requiring a pericardial drain. Microbiology from his initial bronchoscopy grew Cryptococcus prompting empiric fluconazole at the outside facility. His parenchymal findings and dyspnea persisted however and with an interval discovery of pulmonary emboli (Fig 3), therapy was switched to prednisone and anticoagulation leading to near-resolution of his pulmonary nodularity and asymmetric lymphadenopathy. DISCUSSION: Pulmonary sarcoidosis generally manifests as symmetric, bilateral, hilar lymphadenopathy with micronodules along the peribronchovascular bundle and interlobular septa or in the upper and middle lobes when parenchymal involvement is present. Extrapulmonary sarcoidosis occurs much less frequently, often involving extrapulmonary lymphatics or presenting with dermatologic, ophthalmologic, and hepatic findings. Our patient's pulmonary sarcoid was unique in both its appearance as a basilar predominant nodularity seemingly randomly distributed with areas of confluence mimicking a malignant mass with hematogenous dissemination as well as the presence of asymmetric hilar lymphadenopathy without significant mediastinal involvement. Furthermore, the development of cardiac tamponade and unprovoked pulmonary embolism hints at highly atypical cardiac sarcoid and sarcoid-related thromboembolic disease that is only just gaining recognition in the nascent literature. CONCLUSIONS: In the correct epidemiologic and clinical context alongside radiographic and pathologic correlation, sarcoidosis can be diagnosed after the exclusion of etiologies like malignancy, infection, or autoimmune disease. However, as this case demonstrates, clinical suspicion remains the most powerful tool when synthesizing seemingly discordant data from rarely seen presentations of the disease. REFERENCE #1: Criado E, Sanchez M, Ramirez J et al. Pulmonary sarcoidosis: typical and atypical manifestation at high-resolution CT with pathologic correlation. Radiographics. 2010;30(6):1567-1586. REFERENCE #2: Ungprasert P, Crowson CS, Matteson EL. Association of sarcoidosis with increased risk of VTE: a population-based study, 1976-2013. CHEST. 2017;151(2):425-430. REFERENCE #3: Ungprasert P, Ryu JH, Matteson EL. Clinical manifestations, diagnosis, and treatment of sarcoidosis. Mayo Clin Proc Innov Qual Outcomes. 2019;3(3):358-375. DISCLOSURES: No relevant relationships by Christine Choi, source=Web Response No relevant relationships by Julien Nguyen, source=Web Response No relevant relationships by Janine Vintch, source=Web Response

Epidemiology and Antifungal Susceptibility in Patients with Candidemia in a University Hospital, Thailand

Background: Candidemia is the most common nosocomial invasive fungal infection that causes high mortality. Emergence of drug-resistant Candida is reported worldwide but there are few studies in Thailand. Objective: To determine the epidemiology, antifungal susceptibility of Candida, and outcomes among adult patients with candidemia. Materials and Methods: A prospective, observational study in adult patients with candidemia was conducted in 2015 at a university hospital. Demographic, microbiological, and outcome data were recorded. Results: Fifty-two patients with candidemia were identified, of whom 76.9% had an underlying disease and 69.2% had risks for candidemia. Sixty-four percent of candidemia patients contracted non-albicans Candida and 36% had Candida albicans. C. tropicalis was the most common non-albicans Candida species isolated (35%), followed by C. parapsilosis (19%), and C. glabrata (10%). Fluconazole resistance was found in 12.5% of C. albicans and in 11.1% of C. parapsilosis isolates. Reduced fluconazole susceptibility or high-level fluconazole resistance was found in 68.7% of C. tropicalis isolates. All except C. parapsilosis had excellent susceptibility to echinocandins. Seventy-three percent (38/52) of patients received antifungal treatment, of whom, 78.9% received empiric fluconazole therapy, and 89.7% were started on antifungal treatment 24 hours after the isolation of Candida. The overall mortality rate was 51.9%. Conclusion: Fluconazole-resistant Candida became more prevalent particularly in C. tropicalis, which was the predominant species among non-albicans Candida causing candidemia. Empiric treatment with either amphotericin B or echinocandins would be appropriate in high-risk patients with suspected candidemia. Trial registration: Thai Clinical Trials Registry, TCTR20150605001 Keywords: Candida, Fluconazole, Resistant, Thailand

Surgical infection prophylaxis prior to left ventricular assist device implantation: A survey of clinical practice

Short duration, antimicrobial prophylaxis that includes antistaphylococcal activity is recommended at the time of left ventricular assist device (LVAD) implantation to reduce infection-related complications. There continues to be wide variability in surgical infection prophylaxis (SIP) regimens among implantation centers. The aim of this study is to characterize current SIP regimens at different LVAD centers. A survey study was conducted from 26 September 2017 to 25 October 2017. Surveys were distributed electronically to LVAD coordinators and infectious diseases specialists at 75 US medical centers identified as having an LVAD program. Data collection included information about antimicrobial selection, duration, Staphylococcus aureus screening, and decolonization procedures. We received 29 survey responses. The majority of surveys were completed by infectious diseases physicians (72.4% [21 out of 29]). Most responding centers reported LVAD programs established for greater than 10 years (20 out of 29 [69%]). Cardiac transplantation was performed in 28 out of 29 (96%) centers. Of centers reporting a defined SIP regimen for non-penicillin allergic patients (96% [28 out of 29]), 17.9% (5 out of 28) reported a four-drug regimen, 35.7% (10 out of 28) reported a three-drug regimen, and 46.4% (13 out of 28) reported a two-drug regimen, while no centers reported a single-drug regimen. Empiric fluconazole was common (50% [14 out of 28]) and 96.4% (27 out of 28) of regimens included vancomycin. Duration of antimicrobial prophylaxis (24 hours to 5 days), S. aureus screening, decolonization procedures, and alterations due to drug allergies varied across participating centers. Our survey results indicate wide variation in SIP regimens among participating LVAD centers. These results highlight the need for studies evaluating the implications of SIP regimens, and whether clinical factors that prolong antimicrobial duration impact postoperative infection rates.

EPSTEIN-BARR–POSITIVE ULCERS OF THE ORAL CAVITY ASSOCIATED WITH IMMUNOSUPPRESSION IN A PATIENT WITH CANCER

A 24-year-old man with synovial sarcoma was hospitalized for neutropenic fever after chemotherapy, complaining of gingival pain for 1 day. No lymph node involvement was detected during neck palpation. Intraoral exam revealed a purple lesion involving the attached gingiva on the maxilla and mandible, of increased size and with a detachable overlying white plaque. There was rapid evolution to ulcerated lesions, causing an inability to feed. We performed an incisional biopsy and referred the patient for anatomopathologic examination, polymerase chain reaction (PCR), and culture for fungi and bacteria, a prescription of chlorhexidine 0.12%, and empiric fluconazole and acyclovir. PCR was positive for Epstein-Barr virus (EBV) with 1095 copies, so the patient was maintained on acyclovir for 15 days. The patient had significant improvement in pain and the oral lesions regressed after this period. This case demonstrated that EBV commonly occurs in immunosuppressed patients and underscores the importance of dentists in the diagnosis and control of oral complications in the multiprofessional hospital team. A 24-year-old man with synovial sarcoma was hospitalized for neutropenic fever after chemotherapy, complaining of gingival pain for 1 day. No lymph node involvement was detected during neck palpation. Intraoral exam revealed a purple lesion involving the attached gingiva on the maxilla and mandible, of increased size and with a detachable overlying white plaque. There was rapid evolution to ulcerated lesions, causing an inability to feed. We performed an incisional biopsy and referred the patient for anatomopathologic examination, polymerase chain reaction (PCR), and culture for fungi and bacteria, a prescription of chlorhexidine 0.12%, and empiric fluconazole and acyclovir. PCR was positive for Epstein-Barr virus (EBV) with 1095 copies, so the patient was maintained on acyclovir for 15 days. The patient had significant improvement in pain and the oral lesions regressed after this period. This case demonstrated that EBV commonly occurs in immunosuppressed patients and underscores the importance of dentists in the diagnosis and control of oral complications in the multiprofessional hospital team.

1176. Antibiotic Prophylaxis Strategies Prior to Left Ventricular Assist Device Implantation: A Survey of Practice

BackgroundShort duration, single-agent antimicrobial prophylaxis with anti-staphylococcal activity is recommended at the time of left ventricular assist device (LVAD) placement to prevent infection-related complications. Despite consensus guidelines, there continues to be wide variability in antimicrobial regimens among implantation centers. The aim of this study was to characterize current peri-operative antimicrobial prophylactic strategies at different LVAD implantation centers.MethodsA survey study was conducted from September 26, 2017 to October 25, 2017. Surveys were distributed electronically to both LVAD coordinators and infectious diseases specialists at 75 US medical centers identified as having an LVAD program. Data collection included information about antimicrobial selection, duration, MRSA screening and decolonization procedures.ResultsWe received 29 survey responses. The majority of surveys were completed by infectious diseases physicians [72.4% (21/29)]. Most responding centers reported LVAD programs established for >10 years [20/29 (69%)]. Cardiac transplantation was performed in 28/29 (96%) centers. Of centers reporting a defined antimicrobial prophylaxis regimen for nonpenicillin allergic patients [97% (28/29)], 17.9% (5/28) reported a four-drug regimen, 35.7% (10/28) reported a three-drug regimen, and 46.4% (13/28) reported a two-drug regimen, while no centers reported a single-drug regimen. Empiric fluconazole was common [50% (14/28)] and 96.4% (27/28) of regimens included Vancomycin. Duration of antimicrobial prophylaxis (24 h-5 d), MRSA screening, decolonization procedures, and alterations due to drug allergies varied significantly across participating centers.ConclusionOur survey results indicate a wide variation in the peri-operative antimicrobial prophylaxis regimens among participating LVAD centers. These results highlight the need for further studies evaluating the utility, toxicity, and stewardship implications of multi-drug regimens and whether specific clinical factors that prolong antimicrobial duration impact post-operative LVAD-related infection rates.DisclosuresRachel Miller, MD, Synexis: Research Grant.

374. Candidemia Management and Associated Clinical Outcomes in Hospitalized Patients: An Opportunity for Antifungal Stewardship

BackgroundThe incidence of candidemia has increased significantly over the past two decades and is a major cause of morbidity and mortality, prolonged hospital stays, and increased healthcare costs. This study aims to evaluate current practices of candidemia management and review associated clinical outcomes to identify potential targets for antifungal stewardship.MethodsA retrospective chart review of all patients with a positive blood culture for Candida spp. between July 2016 and June 2017 was conducted at a large academic medical center. The primary endpoint was time to effective therapy, defined as time from first positive blood culture to start of an antifungal with in vitro susceptibility. Secondary endpoints were time to clearance of candidemia and 30-day all-cause mortality. Data analysis was conducted and reported using descriptive statistics.ResultsA total of 36 patients with candidemia were included, a majority of whom were consulted by the Infectious Diseases (ID) team (81%). C. albicans and C. parapsilosis were the most common pathogens (36% and 25%, respectively) and sources of candidemia varied, with the most common being a line-related source (42%). Median time to effective therapy was 0.3 hours (IQR 0.12–9.95). Sixty-four percent of patients received a nonazole, primarily caspofungin, and 36% of patients received an azole as empiric antifungal therapy. Selection of empiric fluconazole was deemed suboptimal for 17% of patients, all of whom received delayed or no ID consult. Significantly more ID consult patients received an ophthalmology consult vs. non-ID consult patients (65% vs. 0%, P = 0.002). Additionally, echocardiograms were more frequent in ID consult vs. non-ID consult patients (52% vs. 29%, P = 0.408). Median time to candidemia clearance was 58 hours (IQR 46.4–95.6) and 30-day all-cause mortality was 25%.ConclusionMost patients were started on effective antifungal therapy once candidemia was identified. Patients with an ID consult were more likely to receive ophthalmology consults or echocardiograms to rule out optic or cardiac involvement, respectively. Antifungal stewardship efforts geared toward establishment of institutional guidelines, candidemia treatment bundles, or mandatory ID consult may be considered to improve current practices of candidemia management.Disclosures All authors: No reported disclosures.

Candida parapsilosis Candidemia Resistance Patterns and Treatment Outcomes: An Opportunity for Antifungal Stewardship

Background Candida parapsilosis has emerged as an important fungal pathogen with mortality rates up to 30%. Recent studies show no difference in treatment outcomes for patients treated both empirically and definitively with either echinocandins or fluconazole. However, the impact of antifungal susceptibility testing and opportunities for antifungal stewardship are less clear in this patient population. The purpose of this study was to assess antifungal susceptibility rates, treatment patterns, and outcomes among patients with C. parapsilosis candidemia.Methods This was a single-center, retrospective cohort review of adult patients with a positive blood culture for C. parapsilosis hospitalized at Baylor St. Luke’s Medical Center, between 2006 and 2016. Patients with mixed or breakthrough candidemia were excluded as well as patients who expired within 3 days of candidemia onset.ResultsEighty patients with C. parapsilosis candidemia were identified of which 48 met inclusion criteria. Nine patients had infections caused by fluconazole non-susceptible isolates (19%). The most common empiric treatment choice was an echinocandin (33/48, 69%), followed by fluconazole (9/48, 19%), and combination therapy (6/48, 13%). Of the 39 patients with fluconazole susceptible isolates, only 17 were treated with fluconazole definitively (44%). Among patients who received empiric echinocandin vs. fluconazole therapy, there was no difference in 14-day mortality (9% vs. 11%, P = 1.00) or in-hospital mortality (12% vs. 11%, P = 1.00). Empiric combination therapy was the only independent risk factor for treatment failure (OR, 13.8; 95% CI, 1.4–138.3; P = 0.03).Conclusion Treatment outcomes for patients receiving echinocandins were similar for those receiving fluconazole. At our institution, the increased incidence of fluconazole non-susceptible isolates warrants the use of echinocandins empirically. Patients were more likely to remain on echinocandin therapy even when fluconazole susceptible isolates were identified. This study reinforces the guideline suggestion that neither echinocandins nor fluconazole treatment leads to superior outcomes, but also identifies a cohort of patients in need of antifungal stewardship.Disclosures N. Beyda, Astellas: Grant Investigator and Scientific Advisor, Research grant

The Upside of Bias: A Case of Chronic Meningitis Due to Sporothrix Schenckii in an Immunocompetent Host.

Chronic meningitis of unknown etiology is a vexing illness for patients and clinicians. Identification of the correct pathogen can be challenging and time consuming, leading to delays in appropriate treatment. Although Sporothrix schenckii is a recognized and treatable cause of chronic meningitis, neurologists and infectious diseases physicians may not regularly evaluate for Sporothrix infection. We describe an immunocompetent patient with chronic meningitis who partially responded to empiric fluconazole. Prompted by a recent culture-confirmed case of meningeal sporotrichosis, we tested for S schenckii antibodies from the cerebrospinal fluid, which were positive. His clinical and functional status improved, and the S schenckii antibody titer decreased with itraconazole therapy. Clinicians should consider S schenckii in the differential diagnosis for chronic meningitis, even in immunocompetent patients, particularly when the clinical picture does not respond to standard empiric therapy.

A rare case of breakthrough fungal pericarditis due to fluconazole‐resistant Candida auris in a patient with chronic liver disease

Introduction: Candida pericarditis is a rare clinical entity with a high fatality, primarily attributed to difficulty in diagnosis. Unfortunately, the diagnosis is made post‐mortem in more than 50% of cases, and thus a high index of clinical suspicion is crucial. Case presentation: We report a rare case of fungal pericardial effusion caused by the recently recognized multidrug‐resistant Candida auris, which was cultured from pericardial fluid, blood, bronchoalveolar lavage and urine of a chronic liver disease patient while on empiric fluconazole therapy. The yeast was misidentified as Candida haemulonii by the VITEK2 commercial identification system, and was confirmed as C. auris by internal transcribed spacer and large ribosomal subunit sequencing. In addition, the VITEK2 AST card erroneously revealed a high amphotericin B MIC (16 µg ml−1) and low caspofungin MIC (0.25 µg ml−1) that did not correlate with results from the reference Clinical and Laboratory Standards Institute (CLSI) microbroth dilution method. Based on VITEK2 MIC data, the patient was administered caspofungin. However, in vitro antifungal susceptibility data for C. auris by the CLSI method exhibited high MICs to fluconazole (64 µg ml−1) and caspofungin MIC (1 µg ml−1) but low MICs to amphotericin B (MIC range, 0.125−0.5 µg ml−1). The patient’s repeat pericardial fluid culture, despite caspofungin therapy for 12 days, grew C. auris and he died on day 13 of therapy. Conclusion: C. auris is a recently reported agent of fungaemia and deep‐seated infections and is notable for its antifungal resistance. Although early species identification and rapid antifungal susceptibility testing are needed in cases of critical infections, the reporting of rare yeast isolates exhibiting high MICs to antifungals by automated systems needs a cautionary approach.

Background changing patterns of neonatal fungal sepsis in a developing country

Candida albicans is the predominant isolate in many neonatal fungal bloodstream infections (BSIs), so fluconazole is used as empiric antifungal therapy. To determine the predominant organisms, antifungal sensitivity patterns, clinical and demographic risk factors and crude mortality rate in neonatal fungal BSI cases. This is a review of all neonatal fungal BSI cases between January 2007 and December 2011. Fifty-nine patients were included in the study. Candida parapsilosis (54.2%) was isolated in majority of the cases, followed by C. albicans (27.1%). Fluconazole resistance was present in 16 of 32 cases of C. parapsilosis versus 1 of 16 cases of C. albicans (P = 0.003). Mortality rate was 45.8%. Surgical problems were present in 55.9%. Death was significantly associated with lower birth weight (P = 0.046) and necrotizing enterocolitis (P = 0.034). The increase in neonatal fungal BSI and resistant organisms highlights the need to review use of routine empiric fluconazole and to implement preventive measures.

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Case Reports: Candidemia is the fourth most common cause of nosocomial bloodstream infections in the United States. Guidelines recommend fluconazole or an echinocandin as initial empiric therapy for most non-neutropenic adult patients with candidemia. There is a lack of published data in morbidly obese patients and the optimal dose of fluconazole has not been described. A 28-year-old male with a BMI of 79 kg/m2 (295 kg) was admitted with acute respiratory distress. The patient was intubated on the second day of hospitalization and developed fevers and leukocytosis. The patient was started on empiric antimicrobial therapy. On Day 11 after admission, the urine culture showed Candida albicans. On Day 12, the patient was initiated on empiric fluconazole (800 mg loading dose followed by 400mg daily) therapy due to multiple risk factors for candidemia, worsening clinical status, and a suspected candidemia secondary to the central line. Preliminary laboratory findings indicated yeast in the blood on Day 15. Fluconazole was discontinued and empiric therapy with micafungin was initiated on Day 15 and the PICC line was removed. On Day 18, the blood culture results confirmed Candida albicans and a new PICC line was placed. Micafungin was changed to intravenous fluconazole 1200mg over 6 hours daily and continued for 12 days (total of 17 days of antifungal therapy). The dose of fluconazole used was based on a previously published case report of high dose fluconazole in a morbidly obese patient. The patient was successfully extubated at a tertiary care hospital and transferred back on BiPAP. All follow-up blood cultures (after the original Candida albicans culture on Day 15) were negative for fungal organisms. Clinical improvement was observed and no adverse effects attributable to fluconazole were observed.Data regarding fluconazole dosing in morbidly obese patients is lacking. We describe a case of candidemia in a 28-year-old male (BMI of 79 kg/m2) successfully treated with intravenous fluconazole 1200mg infused over 6 hours daily. Although there exists limited data for high dose fluconazole for other indications, this case report represents the second published report of high dose fluconazole used in a morbidly obese patient successfully and without any adverse effects despite high doses. Given the increasing prevalence of obesity and its recognition by the World Health Organization as a global pandemic, current dosing recommendations may be suboptimal for obese patients. Further studies are needed to evaluate antimicrobial dosing in the obese population.

Prophylactic Fluconazole Does Not Improve Outcome in Patients with Purulent and Fecal Peritonitis due to Lower Gastrointestinal Perforation

The benefit of anticandida treatment in addition to standard antibiotic therapy in the presence of perforation/leakage of the lower gastrointestinal tract (LGIT) is still controversial. We retrospectively assessed the clinical effects of empiric anticandida treatment in patients with LGIT perforation who had undergone exploratory laparotomy due to perforated/leaking bowel or appendix between 1999 and 2004, including generalized fecal/purulent peritonitis. Two groups of patients emerged: those receiving empiric anticandida treatment (fluconazole, n = 24) and those who did not (n = 77). All the fluconazole-treated and 40/77 nonfluconazole-treated patients required intensive care unit care and were the subject of this assessment. Postoperative candida infection and mortality rates were similar in the critically-ill fluconazole-treated and nontreated patients (4% vs 7%, 21% vs 22.5%, respectively, P = NS); resistant candidiasis rates were also similar. Hospital and intensive care unit stays were longer in the treated group, however not reaching statistical difference (26.5 +/- 18 vs 21.4 +/- 18.3 days, 14.8 +/- 14.2 vs 9.3 +/- 14.1 days, respectively). The rates of morbidity, pneumonia, and multiorgan failure were significantly higher (P < 0.05) in the treated patients (87% vs 63%, 37% vs 7.5%, and 58% vs 35%, respectively). Empiric fluconazole in patients with peritonitis associated with LGIT perforation did not improve patients' outcome compared with those without empiric treatment.

Index of Suspicion

Index of Suspicion

Empiric anti-Candida therapy for patients with sepsis in the ICU: how little is too little?

Prior analyses suggest that empiric fluconazole for ICU patients with sepsis is cost-effective. Using updated estimates of efficacy and cost, Zilberberg and colleagues compare the use of micafungin with that of fluconazole. The authors conclude that micafungin is an attractive alternative to fluconazole. This conclusion is driven by recent reduction in micafungin's cost and by better activity of micafungin against azole-resistant Candida species. Their results are limited by inflated estimates of efficacy, life expectancy and risk of Candida sepsis. This commentary explores the rationale for early anti-Candida strategies in the ICU and highlights the contribution and limitations of the article by Zilberberg and colleagues.

High- versus low-dose fluconazole therapy for empiric treatment of suspected invasive candidiasis among high-risk patients in the intensive care unit: a cost-effectiveness analysis

ABSTRACTBackground: High-dose fluconazole is an alternative for patients with candidemia caused by Candida glabrata or other Candida species with decreased fluconazole susceptibility. However, empiric high-dose fluconazole is not currently recommended and may result in higher drug costs and toxicity.Objective: To determine the cost-effectiveness of using empiric high-dose fluconazole in intensive care unit (ICU) with suspected invasive candidiasis.Design: Decision analytic model. Target population: ICU patients with suspected invasive candidiasis. Time horizon: Lifetime. Perspective: Societal.Interventions: Low-dose fluconazole (loading dose of 800 mg followed by 400 mg daily) vs. high-dose fluconazole (loading dose of 1600 mg followed by 800 mg daily). Generic fluconazole costs were used for the analysis. Outcome measures: Incremental life expectancy and incremental cost per discounted life year (DLY) saved.Result of base-case analysis: Based on current national levels of fluconazole resistance and ability to correctly identify patients with candidemia, high-dose fluconazole was the more effective but more expensive treatment strategy. Empiric high-dose fluconazole therapy decreased the mortality rate by 0.15% compared to low-dose strategy with a cost-effectiveness rate of $55 526 per DLY saved.Results of sensitivity analysis: Empirical high-dose fluconazole was an acceptable treatment strategy (using $100 000 per DLY saved as threshold) unless the physical age of an ICU survivor was 66 years or older. Empirical high-dose fluconazole was an acceptable treatment strategy using $50 000 per DLY saved with minor changes in parameters estimates.Limitations: The estimates of our model may not be applicable to all ICU patients. Other hospitals with differences in fluconazole resistance, prevalence of invasive candidiasis, or duration of fluconazole therapy may produce different results.Conclusion: These results suggest that empiric high-dose fluconazole therapy should reduce the mortality associated with invasive candidiasis at an acceptable cost.

Cunninghamella bertholletiae Endocarditis

Cunninghamella bertholletiae Endocarditis

A multicenter, randomized trial of fluconazole versus amphotericin B for empiric antifungal therapy of febrile neutropenic patients with cancer

purpose: To compare the efficacy and safety of fluconazole and amphotericin B as empiric antifungal therapy of febrile neutropenic patients with cancer. patients and methods: A total of 317 neutropenic patients (<500 cells/mm 3) with persistent or recrudescent fever despite 4 or more days of antibacterial therapy were randomly assigned to receive either fluconazole (400 mg intravenously once daily) or amphotericin B (0.5 mg/kg once daily). Patients were evaluated for the efficacy and safety of each drug by clinical criteria, frequent cultures and radiological procedures, and laboratory values. A response was classified as satisfactory at the end of therapy if the patient was afebrile, had no clinical or microbiological evidence of fungal infection, and did not require study termination due to lack of efficacy, drug toxicity, or death. results: A satisfactory response occurred in 68% of the patients treated with fluconazole (107 of 158 patients) and in 67% of patients treated with amphotericin B (106 of 159 patients). Progressive or new fungal infections during therapy occurred in 13 (8%) patients treated with fluconazole (8 with Candida, 5 with Aspergillus) and in 10 (6%) patients treated with amphotericin B (5 with Candida, 3 with Aspergillus, 2 with other fungi). Adverse events related to study drug (especially fever, chills, renal insufficiency, electrolyte disturbances, and respiratory distress) occurred more often in patients treated with amphotericin B (128 [81%] of 159 patients) than patients treated with fluconazole (20 [13%] of 158 patients, P = 0.001). Eleven (7%) patients treated with amphotericin B but only 1 (1%) patient treated with fluconazole were terminated from the study owing to an adverse event ( P = 0.005). Overall mortality (27 [17%] patients treated with fluconazole versus 34 [21%] patients treated with amphotericin B) and mortality from fungal infection (7 [4%] patients treated with fluconazole versus 5 [3%] patients treated with amphotericin B) were similar in each study group. conclusions: Intravenous fluconazole can be an effective and safe alternative to amphotericin B for empiric antifungal therapy in many febrile neutropenic patients. However, because fluconazole may be ineffective in the treatment of Aspergillus, patients at risk for that infection should be evaluated by chest radiograph, computed tomographic scanning, and cultures before the use of empiric fluconazole therapy.

Renal Allograft Dysfunction Associated with Rifampin–Tacrolimus Interaction

OBJECTIVE:To report an interaction between tacrolimus and rifampin with subsequent adverse effects on renal allograft function.CASE SUMMARY:A 61-year-old Chinese man received a cadaveric renal transplant in 1991. Progressive deterioration of allograft function developed during the following six years while the patient was receiving cyclosporine and prednisolone. In January 1998, tacrolimus was substituted for cyclosporine for late biopsy-proven graft rejection, with target trough blood concentrations between 5 and 8 ng/mL. After conversion, serum creatinine fell to 2.0 mg/dL; the nadir was reached within one year. At the same time, rifampin was instituted for controlling tuberculosis and empiric fluconazole was discontinued. Twelve days later, the patient's serum creatinine concentration rose to 2.9 mg/dL and tacrolimus concentration fell to 1.5 ng/mL, along with oliguria. These findings suggested acute rejection, which was successfully reversed by steroid therapy. However, more than a tenfold increase in the tacrolimus dosage was required to maintain the same concentrations during subsequent months, accompanied by an increase in serum creatinine (from 2.0 to 2.6 mg/dL) and decrease in urine excretion. Biopsy at this time demonstrated acute rejection (Banff I), chronic allograft nephropathy (Banff II), and suspected tacrolimus nephrotoxicity. After unsuccessful methylprednisolone recycling, mycophenolate mofetil was introduced to control rejection and facilitate reduction of the tacrolimus dosage to minimize its nephrotoxicity.CONCLUSIONS:As a potent CYP3A4 isoenzyme inducer, rifampin coadministration caused the abrupt decrease in tacrolimus blood concentrations, leading to an approximate tenfold increase in its daily dose, which may be important to subsequent allograft dysfunctions.