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Biomedical subjects

Luis Ostrosky-Zeichner

Publications and source records attributed to Luis Ostrosky-Zeichner.

At least 19 recordsLinked to original sources

Global guideline for the diagnosis and management of candidiasis: an initiative of the ECMM in cooperation with ISHAM and ASM.

Candida species are the predominant cause of fungal infections in patients treated in hospital, contributing substantially to morbidity and mortality. Candidaemia and other forms of invasive candidiasis primarily affect patients who are immunocompromised or critically ill. In contrast, mucocutaneous forms of candidiasis, such as oral thrush and vulvovaginal candidiasis, can occur in otherwise healthy individuals. Although mucocutaneous candidiasis is generally not life-threatening, it can cause considerable discomfort, recurrent infections, and complications, particularly in patients with underlying conditions such as diabetes or in those taking immunosuppressive therapies. The rise of difficult-to-treat Candida infections is driven by new host factors and antifungal resistance. Pathogens, such as Candida auris (Candidozyma auris) and fluconazole-resistant Candida parapsilosis, pose serious global health risks. Recent taxonomic revisions have reclassified several Candida spp, potentially causing confusion in clinical practice. Current management guidelines are limited in scope, with poor coverage of emerging pathogens and new treatment options. In this Review, we provide updated recommendations for managing Candida infections, with detailed evidence summaries available in the appendix.

Humans↗

Contemporary treatment and outcomes of zygomycosis in a non-oncologic tertiary care center.

BACKGROUND: Zygomycosis is an emerging mycosis of increasing relevance. Limited data exist for outcomes with contemporary therapies. METHODS: A 6-year retrospective chart review was performed in a non-oncological tertiary care center for patients with zygomycosis. RESULTS: Sixteen episodes of proven (EORTC/MSG criteria) zygomycosis were identified. The average age was 49.2 years. Sites of infection were surgical/traumatic wound [5], rhinocerebral [4], disseminated [2], pulmonary [2], peritoneal [2], and localized skin [1]. Associated conditions included diabetes [7], ketoacidosis [2], end-stage renal disease [4], surgery/trauma [4], steroids [3], solid organ transplant [2], neutropenia [1], and intravenous drug use [1]. Twelve patients had surgical debridement. Medical therapy included liposomal amphotericin B, conventional amphotericin B (CAB), and amphotericin B lipid complex. Overall mortality was 4/16 (25%), occurring in a patient each with rhinocerebral, pulmonary, surgical wound infection, and disseminated disease. Mortality with surgical treatment was 2/12 (17%) vs. 2/4 (50%) without surgery. Mortality for patients treated with CAB was 1/3 vs. 3/12 for those treated with any lipid preparation. Serious morbidity occurred in 7/12 survivors. CONCLUSIONS: In this limited study of contemporary therapies, patients with zygomycosis from a non-oncological tertiary care center have lower mortality than classically described. This disease and its treatments are still associated with severe morbidity, disfigurement, and disability.

Adult↗

Differences in beta-glucan levels in culture supernatants of a variety of fungi.

(1-->3)-beta-d-glucan is a well known cell wall constituent of fungal isolates that can be detected by assays in vivo and in vitro. Previous studies have shown that different fungal isolates may show different levels of reactivity with an assay for beta glucan. In this study we evaluated the in vitro reactivity of 127 clinical fungal isolates belonging to 40 different genera, with the Glucatell assay. The majority of the fungal isolates released high levels of beta glucan. Beta glucan test reactivity appears to be species-specific and this may reflect the beta glucan content of the organism.

Culture Media↗

Invasive candidiasis in the intensive care unit.

OBJECTIVE: To review epidemiologic trends, advances in diagnosis and susceptibility testing, therapeutic options and guidelines, and management strategies for invasive candidiasis as relevant to the intensive care unit physician. DATA SOURCES, STUDY SELECTION, DATA EXTRACTION, DATA SYNTHESIS: Nonstructured review of peer-reviewed original articles, review articles, abstracts, guidelines, and consensus statements appearing in Medline, major scientific journals, and conference proceedings. CONCLUSIONS: Invasive candidiasis is a problem associated with substantial morbidity and mortality that is highly prevalent in the intensive care unit setting. Recent epidemiologic studies have shown a trend toward increasing numbers of infections and a shift toward infections caused by non-albicans Candida species. Guidelines for the management of these diseases have been published and recommend amphotericin B, fluconazole, or caspofungin as the primary therapeutic option. The choice of agent should depend on local epidemiology and patient factors. The role of newer antifungal agents for this population, such as the new azoles and echinocandins, remains to be determined. Priority areas of research include diagnostics, risk identification, and management strategy assessment such as prophylactic, preemptive, and empirical therapy.

Antifungal Agents↗

Open-label, randomized comparison of itraconazole versus caspofungin for prophylaxis in patients with hematologic malignancies.

Invasive fungal infection remains the most common cause of infectious death in acute leukemia. In this open-label, randomized study, we compared the efficacy and safety of caspofungin with that of intravenous itraconazole for antifungal prophylaxis in patients undergoing induction chemotherapy for acute myelogenous leukemia or myelodysplastic syndrome. Of 200 patients, 192 were evaluable for efficacy (86 for itraconazole, 106 for caspofungin). Duration of prophylaxis (median, 21 days [range, 1 to 38 days]), demographics, and prognostic factors were similar in both groups. Ninety-nine patients completed antifungal prophylaxis without developing fungal infection (44 [51%] with itraconazole, 55 [52%] with caspofungin). Twelve patients developed documented invasive fungal infections, five in the itraconazole group (four with candidemia and one with Aspergillus pneumonia), and seven in the caspofungin group (two with candidemia, two with disseminated trichosporon species, two with Aspergillus pneumonia, and one with disseminated Fusarium spp). Two patients in the itraconazole group and four in the caspofungin group died of fungal infection (P = 0.57). Grade 3 to 4 adverse event rates were comparable between groups; the most common event in both was reversible hyperbilirubinemia. No evidence of cardiovascular toxicity from intravenous itraconazole was noted among patients older than 60. In conclusion, intravenous itraconazole and caspofungin provided similar protection against invasive fungal infection during induction chemotherapy, and both drugs were well tolerated.

Adolescent↗

Correlation between microdilution, E-test, and disk diffusion methods for antifungal susceptibility testing of posaconazole against Candida spp.

Agar-based antifungal susceptibility testing is an attractive alternative to the microdilution method. We examined the correlation between the microdilution, E-test, and disk diffusion methods for posaconazole against Candida spp. A total of 270 bloodstream isolates of Candida spp. with a broad range of posaconazole MICs were tested using the CLSI M27-A2 method for microdilution, as well as the M-44A method and E-test methods for agar-based testing on Mueller-Hinton agar supplemented with 2% glucose and 0.5 microg of methylene blue. MICs and inhibitory zone diameters at the prominent growth reduction endpoint were recorded at 24 and 48 h. The Candida isolates included Candida albicans (n = 124), C. parapsilosis (n = 44), C. tropicalis (n = 41), C. glabrata (n = 36), C. krusei (n = 20), C. lusitaniae (n = 3), and C. dubliniensis (n = 2). The overall concordance (i.e., the percentage of isolates within two dilutions) between the E-test and microdilution was 64.8% at 24 h and 82.6% at 48 h. When we considered an arbitrary breakpoint of < or = 1 microg/ml, the agreement between the E-test and microdilution methods was 87.8% at 24 h and 93.0% at 48 h. The correlation of MICs with disk diffusion zone diameters was better for the E-test than the microdilution method. Zone correlation for diameters produced by the disks of two manufacturers was high, with a Pearson test value of 0.941 at 24 h. The E-test and microdilution MICs show good concordance and interpretative agreement. The disk diffusion zone diameters are highly reproducible and correlate well with both the E-test and the microdilution method, making agar-based methods a viable alternative to microdilution for posaconazole susceptibility testing.

Antifungal Agents↗

Multicenter clinical evaluation of the (1-->3) beta-D-glucan assay as an aid to diagnosis of fungal infections in humans.

BACKGROUND: Measurement of (1-->3)-beta-D-Glucan (BG) has emerged as an adjunct diagnostic strategy for invasive fungal infections (IFI). METHODS: Subjects at 6 clinical sites in the United States were enrolled as either fungal infection-negative subjects (n = 170) or subjects with proven or probable IFI according to European Organization for the Research and Treatment of Cancer/Mycoses Study Group criteria (n = 163). A central laboratory and 4 sites performed assays. A single sample was obtained per patient and was evaluated using an assay to detect serum BG derived from fungal cell walls (range, 0 to > 7000 pg/mL). RESULTS: At a cutoff of 60 pg/mL, the sensitivity and specificity of the assay were 69.9% and 87.1%, respectively, with a positive predictive value (PPV) of 83.8% and a negative predictive value (NPV) of 75.1%. At a cutoff value of 80 pg/mL, the sensitivity and specificity were 64.4% and 92.4%, respectively, with a PPV of 89% and an NPV of 73%. Of the 107 patients with proven candidiasis, 81.3% had positive results at a cutoff value of 60 pg/mL, and 77.6% had positive results at a cutoff value of 80 pg/mL. Of the 10 patients with aspergillosis, 80% had positive results at cutoff values of 60 and 80 pg/mL. The 3 subjects diagnosed with Fusarium species had positive results at a cutoff value of 60 pg/mL. Patients infected with Mucor or Rhizopus species (both of which lack BG) had negative results at both cutoff values, and of the 12 patients with Cryptococcus infection, 3 had positive results at a cutoff value of 60 pg/mL, and 2 had positive results at a cutoff value of 80 pg/mL. Of the subjects with proven positive results who were receiving antifungal therapy (n = 118), 72.9% had results positive for BG at a cutoff value of 60 pg/mL, and 69.5% had results positive for BG at a cutoff value of 80 pg/mL. The interlaboratory sample test r2 was 0.93. CONCLUSION: Reproducible assay results with high specificity and high PPV in a multicenter setting demonstrate that use of an assay to detect serum BG derived from fungal cell walls is a useful diagnostic adjunct for IFI.

Adult↗

Successful use of amphotericin B lipid complex in the treatment of cryptococcosis.

The efficacy and renal safety of amphotericin B lipid complex (ABLC) injection were assessed in 106 patients with cryptococcal infection. Eighty-three patients (78%) had a central nervous system (CNS) infection. Of these patients, 20 initiated azole therapy concomitantly with ABLC therapy, and 7 had received prior azole therapy, which continued during administration of ABLC. Clinical response (cured or improved) was achieved in 67 (66%) of 101 patients whose results could be evaluated. Response rates were 65% (51/78) for patients with a CNS infection and 70% (16/23) for patients without a CNS infection. The response rate for patients with HIV infection was 58% (30/52). Response rates were 56% (19/34) for patients who were refractory to prior antifungal therapy, 65% (11/17) for patients who were intolerant of prior antifungal therapy, 60% (3/5) for patients with underlying renal disease who received prior antifungal therapy, 76% (25/33) for patients with underlying renal disease who did not receive prior antifungal therapy, and 73% (8/11) for patients with no renal disease who did not receive prior antifungal therapy. A mean serum creatinine level decrease of 0.02 mg/dL occurred. ABLC was an effective treatment for cryptococcal infection in immunocompromised patients.

Adult↗

Rules for identifying patients at increased risk for candidal infections in the surgical intensive care unit: approach to developing practical criteria for systematic use in antifungal prophylaxis trials.

The high rates of invasive candidiasis among intensive care unit (ICU) patients suggest that antifungal prophylaxis might be of value, but rules identifying patients who would best benefit are not established. Based on a retrospective study of 327 patients who stayed in a surgical ICU for > or = 4 days and had an 11.0% rate of invasive candidiasis, we sought to identify useful predictive rules. As prior work suggests that prompt initiation of prophylaxis is of value, we required our rules to be based on patient data routinely available during the week prior to ICU admission through the third day of the ICU stay. Patients with any combination of diabetes mellitus, new onset hemodialysis, use of total parenteral nutrition, or receipt of broad-spectrum antibiotics had an invasive candidiasis rate of 16.6% versus a 5.1% rate for patients lacking these characteristics (P = 0.001). Fifty-two percent of patients staying > or = 4 days in the ICU met this rule and the rule captured 78% of the patients who eventually developed invasive candidiasis. Risk-stratified antifungal prophylaxis in the ICU is possible. Validation of these results in other types of ICU is now needed.

Adolescent↗

Cost of a ventilator-associated pneumonia in a shock trauma intensive care unit.

BACKGROUND: Nosocomial pneumonia and especially ventilator-associated pneumonia (VAP) are costly complications for the hospitalized patient. Nosocomial pneumonia has been estimated to cost $5,000 per episode, but the specific cost for a VAP has not been well estimated. As part of a successful performance improvement program in decreasing VAP from 10 VAPs/100 ICU admissions to 2.5 VAPs/100 ICU admissions, we examined the costs associated with VAP. METHODS: From January 1, 2002, through September 30, 2003, Shock Trauma Intensive Care Unit patients and charts were reviewed concurrently by an infection control practitioner for development of VAP as defined by National Nosocomial Infection Surveillance (NNIS) guidelines. Costs were obtained from the hospital's cost accounting software Transition Systems version 3.1.01 (TSI). All patients requiring greater than one day of mechanical ventilation were evaluated. Seventy patients with VAP and 70 patients without VAP were matched according to age and Injury Severity Score. Differences were compared using Kruskal-Wallis and two sample T-tests. Significance was considered for p < 0.05. RESULTS: The ICU cost difference was significant (p < 0.05) between the case-controlled patients with VAP ($82,195) and those without VAP ($25,037). There was also a significant increase in ICU length of stay (21.6 versus 6.4 days) and the number of ventilator days (17.7 versus 5.8; both, p < 0.05). Mortality was not different in the case-controlled population. A substantial portion of the increased cost of a VAP was from the increase in ICU length of stay ($1,861/day). Pharmacy, respiratory and "other" also accounted for the increases when cost distribution was analyzed. This translates into a cost avoidance of approximately $428,685 per 100 admissions to the ICU. CONCLUSIONS: Ventilator-associated pneumonia not only leads to a significant increase in ventilator days and ICU length of stay, but adds substantially to hospital costs. In our ICU, an episode of VAP costs $57,000 per occurrence.

Adult↗

In vitro synergy testing of anidulafungin with itraconazole, voriconazole, and amphotericin B against Aspergillus spp. and Fusarium spp.

The in vitro interactions of anidulafungin with itraconazole, voriconazole, and amphotericin B were evaluated by using the checkerboard method. For Aspergillus spp., anidulafungin with amphotericin B showed indifference for 16/26 isolates, while anidulafungin with either azole showed a synergy trend for 18/26 isolates. All drug combinations showed indifference for 7/7 Fusarium sp. isolates.

Amphotericin B↗

Syscan3, a kit for detection of anti-Candida antibodies for diagnosis of invasive candidiasis.

Sera from 76 immunocompetent and 293 immunocompromised subjects were assayed for anti-Candida antibodies. The sensitivity, specificity, positive predictive value, and negative predictive value for invasive candidiasis were 74%, 75%, 62%, and 84% in the immunocompetent group and 15%, 60%, 1.7%, and 93% in the immunocompromised group, respectively. Syscan3 has high negative predictive value.

Antibodies, Fungal↗

Pharmacoeconomics of antifungal pharmacotherapy--challenges and future directions.

The frequency and severity of invasive fungal infections have been increasingly recognised and new antifungal therapies have expanded the therapeutic armamentarium available to manage such infections. Antifungal agents comprise a significant portion of antibiotic expenditures at major medical centres, prompting adoption of cost-containment measures and treatment guidelines. This paper reviews available data regarding the costs associated with managing fungal infections, including pharmacoeconomic analyses that have been performed in the setting of documented fungal infections, as well as prophylactic and empiric use of antifungal agents. The challenges of performing such studies are discussed, as well as the limitations of published investigations. Finally, recommendations are made regarding the design and implementation of future pharmacoeconomic analyses that can help establish the true costs of managing invasive fungal infections in at-risk patient populations.

Animals↗

Fatal amphotericin B overdose due to administration of nonlipid formulation instead of lipid formulation.

The toxicity of amphotericin B deoxycholate has led to increased preference for lipid formulations with more favorable safety profiles. However, the primary use of lipid formulations is cost prohibitive, and many hospital formularies list both lipid and nonlipid formulations. A dispensing and administration error that caused amphotericin B deoxycholate to be given instead of liposomal amphotericin B related in a fatality. Measures to prevent confusion and aid in understanding the differences between lipid and nonlipid formulations of amphotericin B should be implemented.

Adult↗

Beta-D-glucan as a diagnostic adjunct for invasive fungal infections: validation, cutoff development, and performance in patients with acute myelogenous leukemia and myelodysplastic syndrome.

The Glucatell (1-->3)- beta-D-glucan (BG) detection assay (Associates of Cape Cod) was studied as a diagnostic adjunct for invasive fungal infections (IFIs). On the basis of findings from a preliminary study of 30 candidemic subjects and 30 healthy adults, a serum BG level of >or=60 pg/mL was chosen as the cutoff. Testing was performed with serial serum samples obtained from 283 subjects with acute myeloid leukemia or myelodysplastic syndrome who were receiving antifungal prophylaxis. At least 1 serum sample was positive for BG at a median of 10 days before the clinical diagnosis in 100% of subjects with a proven or probable IFI. IFIs included candidiasis, fusariosis, trichosporonosis, and aspergillosis. Absence of a positive BG finding had a 100% negative predictive value, and the specificity of the test was 90% for a single positive test result and >or=96% for >or=2 sequential positive results. The Glucatell serum BG detection assay is highly sensitive and specific as a diagnostic adjunct for IFI.

Adult↗

Associations between antibiotic use and changes in susceptibility patterns of Pseudomonas aeruginosa in a private, university-affiliated teaching hospital: an 8-year-experience: 1995-2002.

Increasing resistance in Pseudomonas aeruginosa to multiple antibiotics has been observed and is posing therapeutic dilemmas. Antibiotic utilization is one factor that has been associated with the emergence of antimicrobial resistance. We examined the overall and specific antimicrobial use in relation to changes in susceptibility patterns in P. aeruginosa. Regression analysis was performed to explore the relationships between annual antibiotic use and the incidence of resistant P. aeruginosa. There were statistically significant relationships between increasing anti-pseudomonal cephalosporin and levofloxacin use and the increasing incidence of ciprofloxacin resistant P. aeruginosa. However, there was not an association between other fluoroquinolone or overall fluoroquinolone use and this change. In addition, there was no association between increasing anti-pseudomonal cephalosporin use and cefepime resistant P. aeruginosa. No statistical relationship was seen with overall antibiotic use and the development of resistance in P. aeruginosa, suggesting that the development of resistance is associated with the use of individual agents, rather than overall antibiotic consumption.

Anti-Bacterial Agents↗