Recent update in diagnosis and treatment of human pythiosis.

Human pythiosis is an infectious condition with high morbidity and mortality. The causative agent is the oomycete microorganism Pythium insidiosum. The pathogen inhabits ubiquitously in a wet environment, and direct exposure to the pathogen initiates the infection. Most patients with pythiosis require surgical removal of the affected organ, and many patients die from the disease. Awareness of pythiosis among healthcare personnel is increasing. In this review, we summarized and updated information on the diagnosis and treatment of human pythiosis. Vascular and ocular pythiosis are common clinical manifestations. Recognition of the typical clinical features of pythiosis is essential for early diagnosis. The definitive diagnosis of the disease requires laboratory testing, such as microbiological, serological, molecular, and proteomic assays. In vascular pythiosis, surgical intervention to achieve the organism-free margin of the affected tissue, in combination with the use of antifungal drugs and P. insidiosum immunotherapy, remains the recommended treatment. Ocular pythiosis is a serious condition and earliest therapeutic penetrating keratoplasty with wide surgical margin is the mainstay treatment. Thorough clinical assessment is essential in all patients to evaluate the treatment response and detect an early sign of the disease recurrence. In conclusion, early diagnosis and proper management are the keys to an optimal outcome of the patients with pythiosis.

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.

Vascular pythiosis of carotid artery with meningitis and cerebral septic emboli: A case report and literature review.

Vascular Pythiosis caused by Pythium insiodiosum rarely involves carotid artery. A case of concealed ruptured pseudoaneurysm of the carotid artery with neck abscesses, and cerebral septic emboli is described. Patient presented with large pulsatile neck mass that failed to response to surgery, antifungals and immunotherapeutic vaccine. Residual unresectable disease leads to death in the patient. Pythiosis should be considered as a differential diagnosis of head and neck infection.

Clinicopathological features and outcomes of pythiosis.

OBJECTIVES: Vascular pythiosis is a life-threatening infection caused by the oomycete Pythium insidiosum. This article reports the clinical presentation, serodiagnosis, pathology, and outcomes seen at the authors' institution. METHODS: The cases of patients with proven vascular pythiosis at Ramathibodi Hospital, Mahidol University, Bangkok, Thailand from January 2006 to December 2016 were analyzed retrospectively. RESULTS: Thirteen patients were analyzed, eight of whom had underlying thalassemias. Of the remaining five patients, one had aplastic anemia, one had myelodysplasia, one had acute leukemia, one had cirrhosis, and one had alcoholism. Neutropenic patients showed a rapid clinical deterioration. Atypical presentations including carotid arteritis, aneurysm, brain abscess, and stroke occurred in the non-thalassemic patients. Serology yielded positive results in all cases, with a rapid turnaround time. Serology has the advantage of providing a presurgical diagnosis, which allows prompt surgery and clinical cure to be achieved. Pathology revealed a neutrophilic response in the acute phase and a later shift to granuloma. Immunotherapy in combination with itraconazole and terbinafine was given. The amputation rate was 77%, and disease-free surgical margins were achieved in five cases (38%). The mortality rate was 31%. CONCLUSIONS: This study highlights new aspects of pythiosis, such as the unusual host, clinical presentation, serology as a marker for rapid diagnosis, histopathology, and outcomes. Early recognition of the disease with prompt multimodality treatment may improve survival.

A case report of Tubo-ovarian abscess caused by Burkholderia pseudomallei.

BACKGROUND: Melioidosis, the disease caused by Burkholderia pseudomallei is endemic in the Northeastern part of Thailand, South-East Asia, and Northern Australia. The pelvic involvement of disease is rare even in an endemic area. Therefore, we describe in this report the clinical presentation, management, and outcome of the patient with primary tubo-ovarian abscess due to melioidosis. CASE PRESENTATION: A 31-year-old Thai cassava farmer woman presented with fever and abdominal pain at left lower quadrant for one month. She also had pain, swelling, and redness of the genitalia without any ulcer. She had odorless whitish vaginal discharge. The pelvic examination revealed excitation pain on the left side of her cervix. Transvaginal ultrasonography revealed a large left tubo-ovarian abscess size 9.4 × 4.8 cm located at anterior of the uterus. Urgent exploratory laparotomy revealed left hydrosalpinx with a large amount of pus. The pus culture grew Burkholderia pseudomallei. The computer tomography of the abdomen revealed multiple hepatosplenic abscesses. The patient underwent left salpingo-oophorectomy and pus drainage. The pathological examination of excised left adnexa revealed chronic and acute suppurative inflammation with necrotic tissue. She was given intravenous ceftazidime for one month, and her clinical symptom improved. She was diagnosed with type 2 diabetes mellitus at this visit and treated with insulin injection. She continued to take oral co-trimoxazole for 20 weeks. The final diagnosis was disseminated melioidosis with left tubo-ovarian abscess and hepatosplenic abscesses in a newly diagnosed morbidly obese diabetic patient. CONCLUSION: Burkholderia pseudomallei should be considered as the causative organism of gynecologic infection among patient with risk factor resided in an endemic area who do not respond to standard antibiotics. The pus culture from the site of infection is the only diagnostic method of pelvic melioidosis, appropriate antibiotics, and adequate surgical drainage were the components of the successful outcome.

Prevalence and Outcome of Disseminated Varicella Zoster Infection Post Kidney Transplantation.

OBJECTIVE: Varicella zoster (VZV) is a potentially life-threatening infection after kidney transplantation (KT) but data on the incidence and outcome of late KT VZV infection is limited. MATERIAL AND METHOD: A retrospective study of disseminated VZV infection (D-VZV) in post KT patients was conducted between 2003 and 2013. Acyclovir prophylaxis was given routinely for six months after KT Statistical analyses were performed by SPSS software version 17.0. RESULTS: Prevalence of D-VZV was 2% [22/1,032 patients]. Patients median age were 40 (21-67) years old and 12 (55%) were male. Timing of the infection was mostly (68.2%) late (> 1 year) post KT The majority of maintenance immunosuppressive drug included prednisolone (95.5%), cyclosporine (77.3%), mycophenolate (68.2%). Two (9.1%) had a recent VZV exposure and four (18%) received intensified immunosuppression before the diagnosis. Common clinical presentations were lymphopenia (54.5%), generalized vesicular rash (50%), and multi-dermatomal distribution (50%) while liver involvement was infrequent (9.1%). None had pneumonitis or neurological involvement. All cases received systemic acyclovir with the median duration of 14 (3-31) days. One had received IVIG for fulminant hepatitis. Immunosuppressive drug/s was reduced in 59%. Median duration of hospitalization was seven (3-37) days. None of patients died. The median follow-up duration was 1939 (IQR 804-2440) days. Recurrent infection was uncommon (4.5%). Secondary prophylaxis was given only in one patient with fulminant VZV hepatitis. CONCLUSION: Incidence of D-VZV post KT was low. Treatments with intravenous acyclovir and reduction of immunosuppression without the use of VZV IgG provided favorable outcome in resource-limited settings.

EPIDEMIOLOGY AND CONTROL OF THE FIRST REPORTED VANCOMYCIN-RESISTANT ENTEROCOCCUS OUTBREAK AT A TERTIARY-CARE HOSPITAL IN BANGKOK, THAILAND.

This retrospective study described the first reported vancomycin-resistant enterococci (VRE) outbreak from June 2013 through January 2014 at a tertiary-care hospital in Bangkok, Thailand. After the index case was detected in an 18-bed medical intermediate care unit, a number of interventions was implemented, including targeted active surveillance for VRE, strict contact precautions, enhanced standard precautions, dedicated units for VRE cases, extensive cleaning of the environment and the restricted use of antibiotics. VRE isolates were evaluated by polymerase chain reaction and random amplified polymorphic DNA (RAPD) testing. A prevalence case-control study was conducted. Among 3,699 culture samples from 2,671 patients screened, 74 patients (2.8%) had VRE. The positivity rate declined from 15.1% during week 1 to 8.2% during week 2 and then 1.4% during week 3. By weeks 4-9, the prevalences were 0-2.7%. However, the prevalence rose to 9.4% during week 10 and then subsequently declined. All VRE isolates were Enterococcus faecium and had the vanA gene. RAPD analysis revealed a single predominant clone. Multivariate analysis showed mechanical ventilation for ≥ 7 days was a predictive factor for VRE colonization [odds ratio (OR) 11.47; 95% confidence interval (CI): 1.75-75.35; p = 0.011]. This experience demonstrates VRE can easily spread and result in an outbreak in multiple-bed units. Active surveillance, early infection control interventions and rapid patient cohorting were important tools for control of this outbreak. Patients requiring mechanical ventilator for ≥ 7 days were at higher risk for VRE acquisition.

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.

Disseminated Mycobacterium Simiae with Pelvic Malakoplakia in an AIDS Patient.

Malakoplakia in an acquired immunodeficiency syndrome (AIDS) patient with disseminated Mycobacterium simiae infection presented with a large pelvic mass that caused organ dysfunction from mimicking a tumor. Malakoplakia is a rare, chronic granulomatous abnormal host response toward infectious agents, presenting as a tumor-like lesion. This is the first report of pelvic malakoplakia after disseminated M. simiae infection in an AIDS patient.

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.