[Pulmonary mucormycosis: report of 5 cases and review of 46 cases reported in China.]

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[Pulmonary mucormycosis: report of 5 cases and review of 46 cases reported in China.]

Zhonghua Jie He He Hu Xi Za Zhi. 2013 Aug;36(8):572-576

Authors: Yang YM, Fang BM, Xu XM, Fang F, Pan MM, Zhong XF, Sun TY

Abstract
OBJECTIVE: To describe the clinical manifestations and diagnosis of pulmonary mucormycosis.
METHODS: We presented 5 proven diagnosed cases of pulmonary mucormycosis in our hospital and reviewed all proven cases of pulmonary mucormycosis previously reported in mainland China. Publications in the form of case reports and articles between January 1982 and December 2011 were searched from Wan Fang Data and China Hospital Knowledge Database.
RESULTS: Of the 5 patients in our hospital, the main symptoms included cough, fever, and hemoptysis. Two cases were diagnosed by transbronchial lung biopsy (TBLB), 1 by surgery, 1 by CT-guided percutaneous lung biopsy, and 1 by blood culture. Three patients were cured by antifungal chemotherapy alone, 1 was cured by surgery, and 1 died. Forty-six proven diagnosed cases of pulmonary mucormycosis were retrieved from Wan Fang Data and China Hospital Knowledge Database using key word (pulmonary mucormycosis). Of the 51 patients in total, there were 31 males and 20 females, with a mean age of (47 ± 13)years. The most common risk factors for pulmonary mucormycosis were poorly controlled diabetes mellitus (18 cases), administration of immunosuppressants (7 cases), malignancy (5 cases) and kidney diseases (5 cases). Chest CT showed nodules (27 cases), infiltrates (21 cases), and cavities (18 cases). White blood cell count and neutrophil percentage were elevated in 26 patients. Eighteen cases were diagnosed by histological study of transbronchial biopsy or TBLB specimen. The diagnosis was proven with surgical specimen in 15 patients, CT-guided percutaneous lung biopsy specimen in 7 patients, autopsy in 4 patients, skin biopsy in 1 patient, and renal biopsy in one patient. Three cases were diagnosed by pleural effusion cultures and 2 were diagnosed by blood cultures. Administration of low-dose liposomal amphotericin B (AMB) alone or combined with posaconazole in 12 patients were effective and safe. Fourteen patients who had received surgical resection were cured.
CONCLUSIONS: There were no specific clinical features of pulmonary mucormycosis. Transbronchial biopsy and CT-guided percutaneous lung biopsy are useful diagnostic tools for pulmonary mucormycosis. Surgical resection and administration of low-dose liposomal AMB alone or combined with posaconazole were all effective and safe.

PMID: 24252732 [PubMed – as supplied by publisher]

Therapeutic efficacy of posaconazole in a murine model of disseminated trichosporonosis.

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Therapeutic efficacy of posaconazole in a murine model of disseminated trichosporonosis.

J Antimicrob Chemother. 2013 Nov 19;

Authors: Treviño-Rangel RD, López LJ, Palma-Nicolás JP, Hernández-Bello R, González JG, González GM

Abstract
OBJECTIVES: To study the effect of the initiation time of posaconazole treatment from 1 to 3 days after systemic infection by Trichosporon asahii in mice.
METHODS: BALB/c mice, 4-5 weeks old, were intravenously infected with 1 × 10(7) cfu/mouse of T. asahii. The onset of treatment varied from 1 to 3 days after infection. Orally administered posaconazole at 0.5, 1, 2, 5 or 10 mg/kg body weight/day was compared with orally administered fluconazole (at 10 mg/kg/day) and intraperitoneally administered amphotericin B (at 1 mg/kg) on alternating days. Livers, kidneys and spleens of mice that died or survived to day 25 were removed to determine fungal tissue burdens.
RESULTS: When therapy began 1 day after challenge, posaconazole at ≥1 mg/kg significantly prolonged survival of mice compared with that of the control group and considerably reduced the fungal tissue burden over the control group. On the other hand, when treatment was started 3 days after infection, regimens of 5 and 10 mg/kg posaconazole significantly prolonged mice survival over that of the control group and appreciably diminished the fungal load compared with untreated mice. In this model, as the severity of trichosporonosis increased, higher doses of posaconazole were required to achieve equivalent activity levels. Fluconazole and amphotericin B were ineffective in preventing mice death and in significantly reducing fungal tissue burden. Posaconazole displayed potent in vivo activity against the strain tested.
CONCLUSIONS: Posaconazole may be a suitable option in the treatment of disseminated T. asahii infection.

PMID: 24252752 [PubMed – as supplied by publisher]

Primary immunodeficiencies underlying fungal infections.

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Primary immunodeficiencies underlying fungal infections.

Curr Opin Pediatr. 2013 Dec;25(6):736-47

Authors: Lanternier F, Cypowyj S, Picard C, Bustamante J, Lortholary O, Casanova JL, Puel A

Abstract
PURPOSE OF REVIEW: We review the primary immunodeficiencies (PIDs) underlying an increasing variety of superficial and invasive fungal infections. We also stress that the occurrence of such fungal infections should lead physicians to search for the corresponding single-gene inborn errors of immunity. Finally, we suggest that other fungal infections may also result from hitherto unknown inborn errors of immunity, at least in some patients with no known risk factors.
RECENT FINDINGS: An increasing number of PIDs are being shown to underlie fungal infectious diseases in children and young adults. Inborn errors of the phagocyte NADPH oxidase complex (chronic granulomatous disease), severe congenital neutropenia (SCN) and leukocyte adhesion deficiency type I confer a predisposition to invasive aspergillosis and candidiasis. More rarely, inborn errors of interferon-γ immunity underlie endemic mycoses. Inborn errors of interleukin-17 immunity have recently been shown to underlie chronic mucocutaneous candidiasis (CMC), while inborn errors of caspase recruitment domain-containing protein 9 (CARD9) immunity underlie deep dermatophytosis and invasive candidiasis.
SUMMARY: CMC, invasive candidiasis, invasive aspergillosis, deep dermatophytosis, pneumocystosis, and endemic mycoses can all be caused by PIDs. Each type of infection is highly suggestive of a specific type of PID. In the absence of overt risk factors, single-gene inborn errors of immunity should be sought in children and young adults with these and other fungal diseases.

PMID: 24240293 [PubMed – in process]

Postoperative infections after cytoreductive surgery and HIPEC for peritoneal carcinomatosis: Proposal and results from a prospective protocol study of prevention, surveillance and treatment.

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Postoperative infections after cytoreductive surgery and HIPEC for peritoneal carcinomatosis: Proposal and results from a prospective protocol study of prevention, surveillance and treatment.

Eur J Surg Oncol. 2013 Nov 4;

Authors: Valle M, Federici O, Carboni F, Toma L, Gallo MT, Prignano G, Giannarelli D, Cenci L, Garofalo A

Abstract
The incidence of infectious complications due to several contributory causes is particularly elevated and life-threatening in patients undergoing peritonectomy and HIPEC procedure for peritoneal carcinomatosis. Following a previous experience, we started a prospective protocol study of preoperative screening, perioperative prophylaxis and postoperative surveillance and treatment. A total of 111 patients with peritoneal carcinomatosis of various origin underwent CRS with HIPEC between April 2004 and December 2012. The group was divided into a pilot group of 30 patients (04/04 to 05/08) and a main group of 81 patients (06/08 to 12/12). Overall postoperative morbidity rate was 44%, with 35.8% of symptomatic infections. No post-operative mortality was observed. Microorganisms were isolated in 24 patients (80.0%) in the first group and 54 (66.7%) in the second. They were symptomatic in 18 cases (75.0%) and 25 (46.3%) cases respectively. In addition, 7 invasive candidosis were recorded (25.9%). Colon resection (P = 0.01) and duration of surgery (P = 0.0008) were associated with infection at logistic regression model. Concerning symptomatic infections, only Infection Risk Index (P = 0.009) showed significance at multivariate analysis. Despite a significant incidence of infectious complications, establishment of a prevention, surveillance and treatment protocol lead to a zero mortality rate in the observed patients of our experience. Owing to the obtained results, we suggest the use of a standardized protocol for the prevention, monitoring and treatment in all patients enrolled for cytoreductive surgery and HIPEC.

PMID: 24246609 [PubMed – as supplied by publisher]

[Three Cases of Fungemia Caused by Blastoschizomyces capitatus].

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[Three Cases of Fungemia Caused by Blastoschizomyces capitatus].

Mikrobiyol Bul. 2013 Oct;47(4):734-41

Authors: Koç AN, Copur Çiçek A, Kaynar L, Sav H, Kasap Tekinşen FF, Atalay MA

Abstract
Blastoschizomyces capitatus is a rare fungal pathogen that may lead to severe and fatal systemic infections especially in immunosuppressive individuals. B.capitatus strains have also been reported as the cause of hospital-acquired infections and outbreaks. In this report, three fungemia cases caused by B.capitatus with hematologic malignancies have been presented. The first case was a 20-year-old female with acute lymphoblastic leukemia, the second was a 26-year-old female with B-cell malignant lymphoma and the third was a 7-year-old male with B-cell acute lymphoblastic leukemia. All of the patients have been receiving chemotherapy, and treated with antibacterial and antifungal agents due to neutropenia. The blood cultures obtained from the second and third patients yielded B.capitatus although they were under empirical caspofungin therapy. Those patients have been treated with voriconazole and amphotericin B after the identification of B.capitatus, and clinical improvement were noted during their follow-up. However the first patient who was also under caspofungin therapy had died just before the isolation of B.capitatus from her blood culture. Conventional mycological methods [macroscopic and microscopic morphology, germ tube test, urea hydrolysis, carbohydrate assimilation tests (API 20C AUX; BioMerieux, France), growth temperature, cycloheximide sensitivity] were used for the identification of the isolates. The strains were identified as B.capitatus with the characteristics of annelloconidia formation, urease negativity, carbohydrate utilization, growth at 45°C and resistance to cycloheximide. Antifungal susceptibilities of isolates were determined by using microdilution method (for amphotericin B, fluconazole, itraconazole, voriconazole, ketoconazole) and E-test (for caspofungin). Minimum inhibitory concentration (MIC) values of the three B.capitatus strains were detected as 0.25, 0.125, 0.032 µg/ml for amphotericin B; 2, 2, 16 µg/ml for fluconazole; 0.064, 0.032, 0.032 µg/ml for itraconazole and 0.125, 0.064, 0.064 µg/ml for ketoconazole, respectively, while MIC values of all strains were 0.032 µg/ml for voriconazole and > 32 µg/ml for caspofungin. Since B.capitatus strains were isolated from the cases within about 15 days -sequentially-, the genotypes of the isolates were determined by repetitive sequence-based PCR (DiversiLab System; BioMerieux, France) to investigate the similarity rates. The results of analysis indicated 97% similarity between two (case 1 and 2) strains and 94.9% similarity in one strain (case 3) of B.capitatus, however the transmission route could not be clarified due to the absence of environmental sampling. In conclusion, B.capitatus should also be considered as a cause of systemic fungal infections in immunocompromised patients. Determination of the in vitro antifungal susceptibilities of clinical B.capitatus strains may contribute to the therapeutic approaches and epidemiological data.

PMID: 24237444 [PubMed – in process]

Risk factors of mortality and comparative in-vitro efficacy of anidulafungin,caspofungin, and micafungin for candidemia.

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Risk factors of mortality and comparative in-vitro efficacy of anidulafungin,caspofungin, and micafungin for candidemia.

J Microbiol Immunol Infect. 2013 Nov 15;

Authors: Lee SC, Lee CW, Shih HJ, Huang SH, Chiou MJ, See LC

Abstract
BACKGROUND: Although echinocandins have high in vitro antifungal efficacy according to prior reports, comparative studies on the clinical cure rates of anidulafungin, caspofungin, and micafungin in systemic candida infections have not yet been reported.
METHODS: Interpretation of clinical and microbiological responses to anidulafungin, caspofungin, and micafungin in 109 cases of candidemia was done according to the published criteria. The clinical cure rates between patients treated with echinocandins and patients treated with fluconazole were also compared. The minimal inhibitory concentrations (MICs) of anidulafungin, caspofungin, micafungin, and fluconazole for these 109 blood isolates of candida were determined with the Clinical and Laboratory Standards Institute M27-A reference microdilution method. Logistic regression with forward selection was used to determine the important factors of prognosis with variables such as age, underlying diseases, acute physiology and chronic health evaluation (APACHE) III score, persistent candidemia, and antimicrobial therapy.
RESULTS: Among the 109 cases of candidemia, 70 were treated with echinocandins, azoles, or amphotericin B for ≥7 days. The clinical cure rate of cases treated with antifungal agents adequately (≥7 days) and inadequately (<7 days) were 44/70 (62.9%) and 4/39 (10.2%), respectively, with significant difference (p < 0.0001). Clinical cure rates of anidulafungin, caspofungin, micafungin, and fluconazole were 18/30 (60.0%), 6/9 (88.9%), 5/7 (71.4%), and 9/18 (50%), respectively. The difference in APACHE III score between treatment success and failure cases was significant. The MIC50/MIC90 of anidulafungin, caspofungin, and micafungin for all Candida spp. were 0.03/1 μg/mL, 0.06/0.5 μg/mL, and 0.008/1 μg/mL, respectively.
CONCLUSION: Adequate antifungal therapy and APACHE III score are both independent factors affecting the clinical outcome. The clinical cure rate of the echinocandins group was higher than that of the fluconazole group without significant difference. Although caspofungin had the best clinical cure rate in this study, there was no significant difference between the clinical cure rates among these three echinocandins. All Candida spp. were susceptible in vitro to these three echinocandins.

PMID: 24246191 [PubMed – as supplied by publisher]

In vitro susceptibility of Candida species to four antifungal agents assessed by the reference broth microdilution method.

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In vitro susceptibility of Candida species to four antifungal agents assessed by the reference broth microdilution method.

ScientificWorldJournal. 2013;2013:236903

Authors: Eksi F, Gayyurhan ED, Balci I

Abstract
This study was performed to determine the distribution of Candida species isolated from the blood cultures of the patients hospitalized in our hospital and to investigate their antifungal susceptibility. Candida strains were identified at species level by using classical methods and API ID 32C (bioMerieux, France) identification kits. The susceptibility of the strains to amphotericin B, fluconazole, voriconazole, and caspofungin was evaluated by using the reference broth microdilution method in document M27-A3 of the Clinical and Laboratory Standards Institute. Of the 111 Candida strains isolated, 47.7% were identified as C. albicans and 52.3% as non-albicans Candida strains. The MIC ranges were 0.03-1  μ g/mL for amphotericin B, 0.125-≥64  μ g/mL for fluconazole, 0.03-16  μ g/mL for voriconazole, and 0.015-0.25  μ g/mL for caspofungin. All Candida strains were susceptible to amphotericin B and caspofungin. 10.8% isolates were resistant to fluconazole and 8.1% isolates were dose-dependent susceptible. While 0.9% isolate was resistant to voriconazole, 0.9% isolate was dose-dependent susceptible. In our study, C. albicans and C. parapsilosis were the most frequently encountered agents of candidemia and it was detected that voriconazole with a low resistance rate might also be used with confidence in the treatment of infections occurring with these agents, primarily besides amphotericin B and caspofungin.

PMID: 24250260 [PubMed – in process]