Rhodotorula infection in haematological patient: Risk factors and outcome.

BACKGROUND: Rhodotorula spp are uncommon yeasts able to cause infections with high mortality rates. Rhodotorula infections have been associated with the presence of central venous catheter (CVC), immunosuppression, exposure to antifungals and the presence of either solid or haematologic malignancies. However, in this latter setting, only a few cases have so far been reported. OBJECTIVES: We have conducted a survey for Rhodotorula infections in haematologic patients. METHODS: Patients' clinical and microbiological data were collected and correlated to the outcome. RESULTS: A total of 27 cases were detected from 13 tertiary care hospitals. About 78% and 89% of patients had acute leukaemia and CVC. About 70% of patients were exposed to prophylaxis with azoles, mainly posaconazole (37%), 59% were severely neutropenic and 37% underwent allogeneic stem cell transplantation (alloSCT). The most frequent treatments were liposomal amphotericin B (L-AmB) and CVC removal in 17 and 16 patients, respectively. One month post-diagnosis, mortality was 26% and was associated with the presence of mucositis (P = 0.034). CONCLUSIONS: Our study shows that Rhodotorula spp should be considered as aetiologic agents of breakthrough infections in acute leukaemia patients with a CVC, mucositis, who receive prophylaxis with azoles, including posaconazole, and/or undergo alloSCT. Prompt measures, such as L-AmB administration and CVC removal, should be carried out to avoid the high mortality risk of Rhodotorula infections.

Burden of cytomegalovirus reactivation post kidney transplant with antithymocyte globulin use in Thailand: A retrospective cohort study.

Background: Cytomegalovirus (CMV) is an important cause of infectious complications after kidney transplantation (KT), especially among patients receiving antithymocyte globulin (ATG). CMV infection can result in organ dysfunction and indirect effects such as graft rejection, graft failure, and opportunistic infections . Prevention of CMV reactivation includes pre-emptive or prophylactic approaches. Access to valganciclovir prophylaxis is limited by high cost. Our objective is to determine the burden and cost of treatment for CMV reactivation/disease among KT recipients who received ATG in Thailand since its first use in our center. Methods: We conducted a single-center retrospective cohort study of KT patients who received ATG during 2010-2013. We reviewed patients' characteristics, type of CMV prophylaxis, incidence of CMV reactivation, and outcome (co-infections, graft function and death). We compared the treatment cost between patients with and without CMV reactivation. Results: Thirty patients included in the study had CMV serostatus D+/R+. Twenty-nine patients received intravenous ganciclovir early after KT as inpatients. Only three received outpatient valganciclovir prophylaxis. Incidence of CMV reactivation was 43%, with a median onset of 91 (range 23-1007) days after KT. Three patients had CMV end-organ disease; enterocolitis or retinitis. Infectious complication rate among ATG-treated KT patients was up to 83%, with a trend toward a higher rate among those with CMV reactivation ( P = 0.087). Patients with CMV reactivation/disease required longer duration of hospitalization ( P = 0.018). The rate of graft loss was 17%. The survival rate was 97%. The cost of treatment among patients with CMV reactivation was significantly higher for both inpatient setting ( P = 0.021) and total cost ( P = 0.035) than in those without CMV reactivation. Conclusions: Burden of infectious complications among ATG-treated KT patients was high. CMV reactivation is common and associated with longer duration of hospitalization and higher cost.

Deferiprone as adjunctive treatment for patients with invasive mucormycosis: A retrospective case series.

Mucormycosis is a life-threatening disease requiring multimodal treatment with antifungals and surgery. The mortality rate remains high, prompting consideration of alternative treatment strategies. Deferiprone has in vitro activity against Mucorales, but its efficacy has never been evaluated in humans. Here, we retrospectively analyzed patients with confirmed mucormycosis who received deferiprone from 2011 to 2017. Five patients had hematologic malignancies and one was diabetic. The sites of infection included sinus-orbit-cerebral (67%), lung (17%), and disseminated infection (17%). Surgery was performed in 83% of cases and achieved local control for 33% of patients. A combination regimen of polyenes plus echinocandins was administered with stepdown treatment using posaconazole. The median duration of antifungal treatment was 86 days (range: 46-435 days) days. Deferiprone was given as adjunctive treatment with a median dose and duration of 100 mg/kd/day (range: 86.2-100 mg/kg/day) and 25 days (range: 15-215 days), respectively. Overall, deferiprone was well-tolerated. Successful outcomes were observed at 12-week follow-up for 67% of patients. The mortality rate at 180- day follow-up was 50%. Adjunctive therapy with deferiprone showed safety and tolerability.

Disseminated extrapulmonary Legionella pneumophila infection presenting with panniculitis: case report and literature review.

BACKGROUND: Legionellosis is a well-known cause of pneumonia. Primary cutaneous and subcutaneous infection caused by Legionella pneumophila is rare and the diagnosis is challenging. CASE PRESENTATION: A 38-year-old Thai woman with systemic lupus erythematosus and myasthenia gravis treated with prednisolone and azathioprine presented to our hospital with low-grade fever, diarrhea, and indurated skin lesions on both thighs. Initial examination showed plaques on both inner thighs. Magnetic resonance imaging showed myositis and swelling of the skin and subcutaneous tissue. Diagnosis of panniculitis due to L. pneumophila was carried out by histopathology, Gram stain, and 16S rRNA gene sequencing method of tissue biopsy from multiple sites on both thighs. Myocarditis was diagnosed by echocardiography. The final diagnosis was disseminated extrapulmonary legionellosis. Treatment comprised intravenous azithromycin for 3 weeks and the skin lesions, myositis and myocarditis resolved. Oral azithromycin and ciprofloxacin were continued for 3 months to ensure eradication of the organism. The patient's overall condition improved. CONCLUSIONS: To our knowledge, we report the first case of L. pneumophila infection manifesting with panniculitis, possible myositis, and myocarditis in the absence of pneumonia. The diagnosis of extrapulmonary Legionella infection is difficult, especially in the absence of pneumonia. A high index of suspicion and appropriate culture with special media or molecular testing are required. Initiation of appropriate treatment is critical because delaying therapy was associated with progressive infection in our patient.

Treatment of mucormycosis in transplant patients: role of surgery and of old and new antifungal agents.

PURPOSE OF REVIEW: Mucormycosis is an opportunistic mold infection whose management is difficult, as there is a paucity of evidence-based data. We summarize the latest advances in diagnosis and management of mucormycosis in transplant recipients. RECENT FINDINGS: There is promise for improvement in nonculture-based diagnostics with new biomarkers of Mucorales DNA that can be used for early diagnosis, and monitoring of response. Antifungal treatment consists of high-dose lipid formulations of amphotericin B or isavuconazole as the first-line therapy and posaconazole as salvage therapy. The new, pharmacokinetically more reliable formulations of posaconazole (intravenous, extended-release tablets) are welcomed improvements. Yet, the role of combination therapy is still uncertain. Surgery had a significant role in selected cases, such as in patients with rhinosinusitis form of mucormycosis, which nowadays can be performed with minimal invasive technique. SUMMARY: Mucormycosis remain a life-threatening opportunistic mold infection among transplant patients. Early diagnosis, prompt treatment with effective antifungals in combination with surgery if feasible is essential. Immune adjunct therapy and improvement of early diagnostics are important areas for future research. There are good prospects of progress in diagnostics and management of mucormycosis in transplant patients.

A prospective observational study of CYP2C19 polymorphisms and voriconazole plasma level in adult Thai patients with invasive aspergillosis.

The aim of this study was to investigate the association of genetic variants of CYP2C19 (CYP2C19*2, CYP2C19*3 and CYP2C19*17 alleles) and voriconazole trough plasma concentrations in Thai patients with invasive fungal infection. A total of 285 samples from patients with invasive fungal infection and treated with voriconazole were prospectively enrolled. At steady state, trough voriconazole concentrations were measured using tandem mass spectrophotometry and high performance liquid chromatography. The genetic variants in the CYP2C19 gene were genotyped for CYP2C19*2 (G681A), CYP2C19*3 (G636A) and CYP2C19*17 (C-806T) on plasma voriconazole level. Voriconazole Ctrough levels were positively associated with CYP2C19*3. The median Ctrough level for patients with the 636GA genotype (2.109, IQR 1.054-4.166 µg/ml) was statistically significantly higher than those with the 636GG genotype (1.596, IQR 0.755-2.980 µg/ml), P = 0.046. The patients with a poor metabolizer (PM; CYP2C19*2/*2, *2/*3) had voriconazole Ctrough level of 1.900 (IQR, 1.130-3.673 µg/ml). This was statistically significantly higher than that seen with the extensive metabolizer phenotype (1.470; IQR, 0.632-2.720 µg/ml), P = 0.039. An association between CYP2C19 variant alleles and high voriconazole plasma level was identified. Therefore, determining the CYP2C19 genotype before initiation of voriconazole treatment may be useful in optimizing the dosing regimen in Thai patients with invasive fungal infections.

The 'cephalosporin era' of triazole therapy: isavuconazole, a welcomed newcomer for the treatment of invasive fungal infections.

INTRODUCTION: Invasive fungal infections remain frequent life-threatening complications in immunocompromised patients. Each of the currently available antifungals has limitations in terms of pharmacokinetic and pharmacodynamic profile, spectrum of efficacy, and tolerability. Isavuconazole (ISA) is a new generation, broad-spectrum triazole that has a favorable spectrum of efficacy and is available in both intravenous and oral forms. Recent Phase III clinical studies showed that ISA had comparable efficacy to voriconazole for the treatment of a variety of mould infections. AREAS COVERED: This review summarizes the literature on the use of ISA. PubMed was searched for publications in English from 2006 to December 2014 using the terms 'ISA', 'BAL4815', and 'BAL 8557'. Relevant publications were reviewed and reference lists were examined for further publications. Conference abstracts from the meeting during 2013 - 2014 were also reviewed. EXPERT OPINION: ISA is a new broad spectrum triazole antifungal for the treatment of invasive fungal disease available as oral and intravenous formulations, and the ability to be administered as a once-daily regimen. ISA has broad-spectrum in vitro activity, favorable pharmacokinetic profile, and good tolerability. ISA may be considered for primary treatment for a vast variety of invasive fungal infections. Further study of ISA given as prophylaxis, combination, or salvage therapy is warranted.

Rare opportunistic (non-Candida, non-Cryptococcus) yeast bloodstream infections in patients with cancer.

BACKGROUND: Rare opportunistic (non-Candida, non-Cryptococcus) yeast bloodstream infections (ROYBSIs) are rare, even in cancer patients. METHODS: We retrospectively reviewed all episodes of ROYBSIs occurring from 1998 to 2010 in our cancer center. RESULTS: Of 2984 blood cultures positive for Candida and non-Candida yeasts, 94 (3.1%) were positive for non-Candida yeasts, representing 41 ROYBSIs (incidence, 2.1 cases/100,000 patient-days). Catheter-associated fungemia occurred in 21 (51%) patients. Breakthrough ROYBSIs occurred in 20 (49%) patients. The yeast species distribution was Rhodotorula in 21 (51%) patients, Trichosporon in 8 (20%) patients, Saccharomyces cerevisiae in 8 (20%) patients, Geotrichum in 2 (5%) patients, Pichia anomala, and Malassezia furfur in 1 patient each. All tested Trichosporon, Geotrichum, and Pichia isolates were azole-susceptible, whereas the Rhodotorula isolates were mostly azole-resistant. We noted echinocandin nonsusceptibility (minimal inhibitory concentration ≥ 2 mg/L) in all but the S. cerevisiae isolates. Most of the isolates (28/33 [85%]) were susceptible to amphotericin B. The mortality rate in all patients at 30 days after ROYBSIs diagnosis was 34%. Multivariate survival analysis revealed increased risk of death in patients with S. cerevisiae infections (hazard ratio, 3.7), Geotrichum infections (hazard ratio, 111.3), or disseminated infections (hazard ratio, 33.4) and reduced risk in patients who had catheter removal (hazard ratio, 0.1). CONCLUSIONS: ROYBSIs are uncommon in patients with cancer, and catheters are common sources of them. Half of the ROYBSIs occurred as breakthrough infections, and in vitro species-specific resistance to echinocandins and azoles was common. Disseminated infections resulted in the high mortality rate.