A cost-effectiveness analysis of the 13-valent pneumococcal conjugated vaccine and the 23-valent pneumococcal polysaccharide vaccine among Thai older adult.

Introduction: This study aims to assess the economic impact of introducing the 13-valent pneumococcal conjugate vaccine (PCV13) and 23-valent pneumococcal polysaccharide vaccine (PPSV23) to Thai older adult aged ≥ 65 years who are healthy or with chronic health conditions and immunocompromised conditions from a societal perspective in order to introduce the vaccine to Thailand's National Immunization Program for the older adult. Methods: A Markov model was adopted to simulate the natural history and economic outcomes of invasive pneumococcal diseases using updated published sources and Thai databases. We reported analyses as incremental cost-effectiveness ratios (ICER) in USD per quality-adjusted life year (QALY) gained. In addition, sensitivity analyses and budget impact analyses were conducted. Results: The base-case analysis of all interventions (no vaccinations [current standard of care in Thailand], PPSV23, and PCV13) showed that PPSV23 was extendedly dominated by PCV13. Among healthy individuals or those with chronic health conditions, ICER for PCV13 was 233.63 USD/QALY; meanwhile, among individuals with immunocompromised conditions, ICER for PCV13 was 627.24 USD/QALY. PCV13 are economical vaccine for all older adult Thai individuals when compared to all interventions. Conclusions: In the context of Thailand, PCV13 is recommended as the best buy and should be primarily prioritized when both costs and benefits are considered. Also, this model will be beneficial to the two-next generation pneumococcal vaccines implementation in Thailand.

Pneumococcal carriage among high-risk adults in a country with nonmandatory pneumococcal vaccination during the coronavirus disease 2019 pandemic.

BACKGROUND: Streptococcus pneumoniae carriage is a prerequisite for clinical infections and is used to make public health decisions on vaccine licensure. Pneumococcal carriage data among high-risk Thai adults are needed before national vaccine program introduction. The association between coronavirus disease 2019 (COVID-19) and pneumococcal carriage were also investigated. METHODS: During the COVID-19 pandemic, a multi-center cross-sectional study was conducted among high-risk Thai adults from September 2021 to November 2022. Pneumococcal carriage and serotypes were investigated using both conventional and molecular methods. Demographics and co-morbidities were determined for carriage while accounting for case clustering from various study sites. RESULTS: A total of 370 individuals were enrolled. The prevalence of pneumococcal carriage, as determined by the molecular method, was 30.8 % (95 % confidence interval (CI): 26.1-35.8), while after excluding non-typeable pneumococci from the oropharyngeal sample, the carriage prevalence was 20.8 % (95 % CI: 16.79-25.31). The serotype coverage rates by pneumococcal vaccine were 12.3 %, 13.1 %, and 16.4 % for PCV13, PCV15 or PCV20, and PPSV23, respectively, while the non-vaccine type was the majority (45.1 %). The most common serotype was 19B/C (35.5 %), followed by 6 A/B/C/D (10.7 %). The age group under 65 years was associated with a higher pneumococcal carriage rate than the age group 85 and older (odds ratio (OR): 5.01, 95 % CI: 1.75-14.36). There was no significant difference between SARS-CoV-2 and carriage status. CONCLUSIONS: The prevalence of pneumococcal carriage in Thais was high. The majority of serotypes were not covered by the vaccine. Further studies on the link between carriage serotypes and disease are required. The magnitude and serotype distribution of carriage were comparable in the SARS-CoV-2 positive and negative groups.

Impact of the Disk Diffusion Test on Fluconazole De-Escalation in Patients with Candidemia.

Disk diffusion (DD) is a simple antifungal susceptibility method for Candida. This study examined the impact of fluconazole DD testing on antifungal de-escalation. We enrolled patients with candidemia whose Candida isolates were tested for fluconazole susceptibility using DD between January 2019 and January 2020. The historical controls were patients with candidemia who underwent fluconazole susceptibility testing using the broth microdilution (BMD) method. Clinical data including antifungal therapy were analyzed. In total, 108 patients were enrolled. Most baseline characteristics were comparable between the groups. C. tropicalis was the predominant isolate (54.6%), followed by C. albicans (17.6%). The rates of antifungal de-escalation within 72 h were 25.9 and 9.3% in the DD and BMD groups, respectively (p = 0.023). The median time to de-escalation was 3 days in the DD group, versus 6 days in the BMD group (p = 0.037). The 14-day mortality rate and antifungal cost tended to be lower in the DD group. There were no differences in the length of hospital stay and treatment-related complications between the two groups. The agreement between the DD and BMD results was 90%. DD testing can be substituted for BMD to enhance antifungal de-escalation and antifungal stewardship.

The burden of carbapenem-resistant Enterobacterales infection in a large Thai tertiary care hospital.

Background: Carbapenem-resistant Enterobacterales (CRE) are resistant to several other classes of antimicrobials, reducing treatment options and increasing mortality. We studied the clinical characteristics and burden of hospitalized adult patients with CRE infections in a setting where treatment options are limited. Methods: A retrospective cohort study included adult inpatients between January 2015-December 2019 at Siriraj Hospital in Bangkok, Thailand. Clinical and microbiological data were reviewed. Results: Of 420 patients with CRE infections, the mean age was 65.00 ± 18.89 years, 192 (45.72%) were male, and 112 (26.90%) were critically ill. Three hundred and eighty (90.48%) had Klebsiella pneumoniae, and 40 (9.52%) had Escherichia coli infections. The mean APACHE II score was 14.27 ± 6.36. Nearly half had previous hospitalizations (48.81%), 41.2% received antimicrobials, and 88.1% had undergone medical procedures before the onset of infection. The median time of onset of CRE infection was 16 days after admission. Common sites of infection were bacteremia (53.90%) and pneumonia (45.47%). Most CRE-infected patients had septic shock (63.10%) and Gram-negative co-infections (62.85%). Colistin (29.95%) and non-colistin (12.91%) monotherapies, and colistin-based (44.78%) and non-colistin-based (12.36%) combination therapies were the best available antimicrobial therapies (BAAT). The median length of hospitalization was 31 days, and the median hospitalization cost was US$10,435. The in-hospital mortality rate was 68.33%. Septic shock [adjusted odds ratio (aOR) 10.73, 5.65-20.42, p <0 .001], coinfection (aOR 2.43, 1.32-4.47, p = 0.004), mechanical ventilation (aOR 2.33, 1.24-4.36, p = 0.009), and a high SOFA score at onset (aOR 1.18, 1.07-1.30, p <0 .001) were associated with mortality. Conclusion: CRE infection increases mortality, hospital stays, and healthcare costs. A colistin-based regimen was the BAAT in this study. Therefore, newer antimicrobial agents are urgently needed.

Genotyping, antifungal susceptibility testing, and biofilm formation of Trichosporon spp. isolated from urine samples in a University Hospital in Bangkok, Thailand.

The basidiomycetes yeast Trichosporon is widespread in the natural environment, but can cause disease, mainly in immunocompromised patients. However, there have been only few studies about this infection in Thailand. In this study, we characterized 53 Trichosporon spp. isolated from urine samples from patients admitted to a single hospital in Bangkok, Thailand over a one-year period from 2019 to 2020. The strains were identified using colony morphology, microscopy, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, and nucleotide sequence analysis of intergenic spacer 1 (IGS1). Fifty-one isolates were Trichosporon asahii, and the remaining isolates were Trichosporon inkin and other Trichosporon species. Three genotypes of IGS1-1, 3, and 7 were observed among T. asahii. The sensitivity of the yeasts to the antifungal drugs amphotericin B, fluconazole, and voriconazole ranged from 0.25 to >16 µg ml-1, 0.5-8 µg ml-1, and 0.01-0.25 µg ml-1, respectively. We investigated biofilm formation by the isolates, and no biofilm production was found in one isolate, low biofilm production in forty-four isolates, and medium biofilm production in six isolates. T. inkin produced biofilms at low levels, and Trichosporon spp. produced biofilms at medium levels. This research increases our understanding of the molecular epidemiology of Trichosporon spp. isolated from one university hospital in Bangkok, Thailand, and reveals their genetic diversity, antifungal susceptibility profiles, and capacity for in vitro biofilm production.

Characteristics and Outcomes of Patients with Invasive Pulmonary Aspergillosis and Respiratory Tract Aspergillus Colonization from a Tertiary University Hospital in Thailand.

Positive culture for Aspergillus spp. from respiratory specimens needs to be interpreted together with relevant clinical conditions/settings to differentiate invasive infection from colonization. In this study, we aimed to investigate the association between positive culture for Aspergillus spp. from respiratory specimens and the presence of invasive pulmonary aspergillosis. Hospitalized patients with positive culture for Aspergillus spp. from any respiratory sample were retrospectively recruited. Patients were classified into two groups: those with invasive pulmonary aspergillosis and those with non-invasive aspergillosis/colonization. Two hundred and forty-one patients (48.1% male; mean age: 59.8 ± 14.5 years) were included. The most common Aspergillus spp. was A. fumigatus (21.0%). The most common underlying condition was chronic lung disease (23.7%), followed by solid tumor (22.4%). Myeloproliferative disease (aOR: 69.2, 95% CI: 2.4-1991.9), neutropenia ≥ 10 days (aOR: 31.8; 95% CI: 1.10-920.53), and corticosteroid treatment (aOR: 42.8, 95% CI: 6.5-281.3) were independent predictors of the invasive form. Chronic lung disease was independently inversely related to invasive form (OR: 0.04; 95% CI: 0.003-0.49). Serum galactomannan was positive in 69.2% of patients with invasive aspergillosis (OR: 25.9, 95% CI: 5.2-127.8). All inappropriately treated patients with invasive form died. In conclusion, positive culture for Aspergillus spp. from respiratory specimens with coexisting myeloproliferative disease, neutropenia ≥ 10 days, corticosteroid treatment, or positive serum galactomannan is highly suggestive of invasive pulmonary aspergillosis.

Hematogenous dissemination of pulmonary mucormycosis manifested as multiple subcutaneous nodules: a case report and review of the literature.

BACKGROUND: Disseminated mucormycosis presenting with multiple subcutaneous nodules is a rare condition with a poor prognosis, and delayed diagnosis and treatment is common. CASE PRESENTATION: We report a case of 64-year-old Thai woman with colorectal cancer who initially presented with Acinetobacter baumannii pneumonia and respiratory failure. Following 10 days after her admission to the intensive care unit, she developed hospital-acquired pneumonia. Five days later, multiple subcutaneous nodules appeared on both arms and both legs. Bronchoalveolar lavage and skin biopsy cultures both grew Mucor spp. She was diagnosed with disseminated mucormycosis and was treated with liposomal amphotericin B at a dose of 5 mg/kg/day. Despite treatment, our patient succumbed to septic shock and multiorgan failure on the third day after definitive diagnosis. CONCLUSIONS: This case demonstrates that the subcutaneous nodules caused by hematogenously disseminated mucormycosis are unusual in a patient with a solid tumor. Clinicians should be aware of this atypical presentation of mucormycosis in patients with solid tumors.

Brain abscess mimicking acute stroke syndrome caused by dual Filifactor alocis and Porphyromonas gingivalis infections: A case report.

This case report is about a woman who had a brain abscess in the left parietal lobe that atypically presented as acute stroke-like syndrome. Pus samples from brain abscess aspiration revealed the periodontal pathogens Porphyromonas gingivalis and Filifactor alocis. After dental health care and 8 weeks of combined antimicrobial therapy, the patient recovered completely.

Risk Factors and Outcomes of Non-albicans Candida Bloodstream Infection in Patients with Candidemia at Siriraj Hospital-Thailand's Largest National Tertiary Referral Hospital.

This study aimed to investigate the risk factors for and the outcomes of patients with candidemia caused by non-albicans Candida. Candidemia patients treated at Siriraj Hospital (Bangkok, Thailand) during January 2016 to December 2017 were enrolled. A total of 156 patients (mean age: 65 years, 56.4% male) were included. The most prevalent underlying conditions were diabetes (32.1%), chronic cardiac disease (28.2%), chronic kidney disease (26.9%), and hematologic malignancies (21.2%). Candida species isolated from patient blood were C. tropicalis (49.4%), C. albicans (28.8%), C. glabrata (16.7%), and C. parapsilosis (5.1%). Fluconazole resistance was significantly increased in C. tropicalis (37.8%). No independent risk factors were associated with patients with non-albicans Candida candidemia compared to those with C. albicans candidemia. There was no significant difference in mortality between patients with non-albicans Candida candidemia and patients with C. albicans candidemia (OR: 1.35, 95% CI: 0.64-2.85). When compared with C. albicans candidemia, multivariate analysis revealed chronic liver disease (OR: 11.39, 95% CI: 1.38-94.02), neutropenia (OR: 4.31, 95% CI: 1.34-13.87), and male gender (OR: 2.34, 95% CI: 1.04-5.29) to be independent risk factors for C. tropicalis candidemia. The observed high resistance of C. tropicalis to fluconazole indicates that fluconazole should not be used for empirical antifungal treatment in these patients.

Identification and Biotyping of Pythium insidiosum Isolated from Urban and Rural Areas of Thailand by Multiplex PCR, DNA Barcode, and Proteomic Analyses.

Pythium insidiosum causes pythiosis, a fatal infectious disease of humans and animals worldwide. Prompt diagnosis and treatment are essential to improve the clinical outcome of pythiosis. Diagnosis of P. insidiosum relies on immunological, molecular, and proteomic assays. The main treatment of pythiosis aims to surgically remove all affected tissue to prevent recurrent infection. Due to the marked increase in case reports, pythiosis has become a public health concern. Thailand is an endemic area of human pythiosis. To obtain a complete picture of how the pathogen circulates in the environment, we surveyed the presence of P. insidiosum in urban (Bangkok) and rural areas of Thailand. We employed the hair-baiting technique to screen for P. insidiosum in 500 water samples. Twenty-seven culture-positive samples were identified as P. insidiosum by multiplex PCR, multi-DNA barcode (rDNA, cox1, cox2), and mass spectrometric analyses. These environmental strains of P. insidiosum fell into Clade-II and -III genotypes and exhibited a close phylogenetic/proteomic relationship with Thai clinical strains. Biodiversity of the environmental strains also existed in a local habitat. In conclusion, P. insidiosum is widespread in Thailand. A better understanding of the ecological niche of P. insidiosum could lead to the effective prevention and control of this pathogen.

Cryptococcal fungemia and Mycobacterium haemophilum cellulitis in a patient receiving ruxolitinib: a case report and literature review.

BACKGROUND: Ruxolitinib is a novel oral Janus kinase inhibitor that is used for treatment of myeloproliferative diseases. It exhibits potent anti-inflammatory and immunosuppressive effects, and may increase the risk of opportunistic infections. Here, we report a rare case of Cryptococcus neoformans and Mycobacterium haemophilum coinfection in a myelofibrosis patient who was receiving ruxolitinib. CASE PRESENTATION: A 70-year-old Thai man who was diagnosed with JAK2V617F-mutation-positive primary myelofibrosis had been treated with ruxolitinib for 4 years. He presented with cellulitis at his left leg for 1 week. Physical examination revealed fever, dyspnea, desaturation, and sign of inflammation on the left leg and ulcers on the right foot. Blood cultures showed positive for C. neoformans. He was prescribed intravenous amphotericin B deoxycholate with a subsequent switch to liposomal amphotericin B due to the development of acute kidney injury. He developed new onset of fever after 1 month of antifungal treatment, and the lesion on his left leg had worsened. Biopsy of that skin lesion was sent for mycobacterial culture, and the result showed M. haemophilum. He was treated with levofloxacin, ethambutol, and rifampicin; however, the patient eventually developed septic shock and expired. CONCLUSIONS: This is the first case of C. neoformans and M. haemophilum coinfection in a patient receiving ruxolitinib treatment. Although uncommon, clinicians should be aware of the potential for multiple opportunistic infections that may be caused by atypical pathogens in patients receiving ruxolitinib.

Disseminated histoplasmosis in a kidney transplant patient.

Patients with impaired cell-mediated immunity have a higher risk of developing histoplasmosis; however, histoplasmosis after solid organ transplantation is rare. In Thailand, histoplasmosis cases are sporadic, and most cases are associated with human immunodeficiency virus (HIV) infection. Herein, we report a case of disseminated histoplasmosis in a kidney transplant Thai recipient diagnosed by fungal staining of fungal culture from bronchoalveolar lavage and bone marrow biopsy. Liposomal amphotericin B was given followed by oral itraconazole. The patient's clinical condition was improved; however, his graft function was irreversibly declined. The majority of histoplasmosis cases after solid organ transplant presented with disseminated disease with pulmonary involvement. Even in a non-endemic area of histoplasmosis, suspected cases should be early diagnosed and promptly managed in order to reduce morbidity and mortality, especially in cell-mediated immunity defect patients like solid organ transplant recipients.

Continuous ambulatory peritoneal dialysis-associated Histoplasma capsulatum peritonitis: a case report and literature review.

BACKGROUND: Fungal peritonitis (FP) is a rare complication of peritoneal dialysis. We herein describe the second case in Asia of Histoplasma capsulatum peritonitis associated with continuous ambulatory peritoneal dialysis (CAPD). CASE PRESENTATION: An 85-year-old woman with end-stage renal disease (ESRD) who had been on CAPD for 3 years and who had a history of 3 prior episodes of peritonitis presented with intermittent abdominal pain for 2 weeks and high-grade fever for 3 days. Elevated white blood cell (WBC) count and rare small oval budding yeasts were found in her peritoneal dialysis (PD) fluid. From this fluid, a white mold colony was observed macroscopically after 7 days of incubation, and numerous large, round with rough-walled tuberculate macroconidia along with small smooth-walled microconidia were observed microscopically upon tease slide preparation, which is consistent with H. capsulatum. The peritoneal dialysis (PD) catheter was then removed, and it also grew H. capsulatum after 20 days of incubation. The patient was switched from CAPD to hemodialysis. The patient was successfully treated with intravenous amphotericin B deoxycholate (AmBD) for 2 weeks, followed by oral itraconazole for 6 months with satisfactory result. The patient remains on hemodialysis and continues to be clinically stable. CONCLUSION: H. capsulatum peritonitis is an extremely rare condition that is associated with high morbidity and mortality. Demonstration of small yeasts upon staining of PD fluid, and isolation of slow growing mold in the culture of clinical specimen should provide important clues for diagnosis of H. capsulatum peritonitis. Prompt removal of the PD catheter and empirical treatment with amphotericin B or itraconazole is recommended until the culture results are known.

Loop-mediated Isothermal Amplification (LAMP) for Identification of Pythium insidiosum.

OBJECTIVE: Pythium insidiosum causes a life-threatening condition called pythiosis. High morbidity and mortality of pythiosis are consequences of delayed diagnosis. We aimed to develop a loop-mediated isothermal amplification (LAMP) assay for the rapid detection of P. insidiosum for use in remote areas, where pythiosis is prevalent. METHODS: We designed four LAMP primers to amplify the rDNA sequence. A side-by-side comparison evaluated performances of LAMP and the previously-established multiplex PCR (M-PCR), using gDNA samples extracted from colonies of P. insidiosum (n = 28) and other fungi (n = 54), and tissues of animals with (n = 16) or without (n = 13) pythiosis. RESULTS: LAMP demonstrated a 50% shorter assay duration (1.5 h) and a 10-fold lower limit of detection (10-4 ng) than did M-PCR. Based on colony-extracted gDNAs, LAMP and M-PCR correctly reported P. insidiosum in all 28 samples, providing 100% sensitivity. While M-PCR did not amplify all fungal controls (100% specificity), LAMP falsely detected one organism (98% specificity). Based on the clinical samples, LAMP and M-PCR provided an equivalently-high specificity (100%). However, LAMP showed a markedly-higher sensitivity than that of M-PCR (88% vs. 56%). CONCLUSIONS: LAMP is a simple, useful, efficient assay for the detection of P. insidiosum in clinical specimens and pure cultures in resource-limited laboratories.

Case Report: Recovery of Pathogenic Leptospira spp. from Routine Aerobic Blood Culture Bottles.

Leptospira spp. are fastidious and slow-growing bacteria, making recovery difficult and diagnostic sensitivity in the clinical setting low. However, collection of Leptospira isolates is valuable for epidemiological and laboratory research. Severe leptospirosis cases may present as septic shock, and the differential diagnosis often includes bacterial septicemia, leading clinicians to collect blood cultures. Here, we report the successful isolation of pathogenic Leptospira spp. from blood culture bottles (targeting aerobic bacteria incubated at 37°C) from a 64-year-old man admitted with septic shock. The patient presented with 4 days of fever, severe hypotension, transient atrial fibrillation, jaundice, and oliguric renal failure. After admission, intravenous ceftriaxone plus azithromycin was given with fluid resuscitation, norepinephrine infusion, invasive mechanical ventilation, and renal replacement therapy. He was discharged from the hospital 16 days after admission. Using the blood sample obtained on admission, the diagnosis of leptospirosis was confirmed by multiplex real-time PCR (targeting bacterial 16S rRNA and LipL32 gene). We collected 200 µL from the blood culture bottle to inoculate a 5-mL Ellinghausen, McCullough, Johnson, and Harris media supplemented with 5% fetal bovine serum. After 2 weeks of incubation at 30°C, Leptospira strains were identified and confirmed by real-time PCR. Genotyping was undertaken using the multi-locus sequence typing (MLST) scheme#1. The isolate matched with ST50 isolates in the PUbMLST database. This case provides evidence that in tropical countries, severe leptospirosis should be considered in patients who present with symptoms of sepsis. Pathogenic Leptospira may be successfully isolated from aerobic blood cultures in routine clinical settings.

An Association of an eBURST Group With Triazole Resistance of Candida tropicalis Blood Isolates.

Candidemia, a bloodstream infection caused by genus Candida, has a high mortality rate. Candida albicans was previously reported to be the most common causative species among candidemia patients. However, during the past 10 years in Thailand, Candida tropicalis has been recovered from blood more frequently than C. albicans. The cause of this shift in the prevalence of Candida spp. remains unexplored. We conducted in vitro virulence studies and antifungal susceptibility profiles of 48 C. tropicalis blood isolates collected during 2015-2017. To compare to global isolates of C. tropicalis, multilocus sequence typing (MLST), a minimum spanning tree, and an eBURST analysis were also conducted. C. tropicalis and C. albicans were the most (47-48.7%) and second-most (21.5-33.9%) common species to be isolated from candidemia patients, respectively. Of the C. tropicalis blood isolates, 29.2, 0, 100, and 93.8% exhibited proteinase activity, phospholipase activity, hemolytic activity, and biofilm formation, respectively. Moreover, 20.8% (10/48) of the isolates were resistant to voriconazole and fluconazole, and also showed high minimum inhibitory concentrations (MICs) to posaconazole and itraconazole. In contrast, most of the isolates were susceptible to anidulafungin (97.9%), micafungin (97.9%), and caspofungin (97.9%), and showed low MICs to amphotericin B (100%) and 5-flucytosine (100%). The MLST identified 22 diploid sequence types. Based on the eBURST analysis and minimum spanning tree, 9 out of 13 members (69.2%) of an eBURST group 3 were resistant to voriconazole and fluconazole, and also showed high MICs to posaconazole and itraconazole. Association analysis revealed the eBURST group 3 was significantly associated with the four triazole resistance (p < 0.001). In conclusion, the eBURST group 3 was associated with the triazole resistance and resistance to many antifungal drugs might be collectively responsible for the prevalence shift.

Isolated pulmonary fusariosis caused by Neocosmospora pseudensiformis in a liver transplant recipient: A case report and review of the literature.

Neocosmospora pseudensiformis (formerly Fusarium pseudensiforme) is a hyaline mold in the Fusarium solani species complex that has been changed to the genus Neocosmospora. Invasive fusariosis is a rare fungal infection in solid organ transplantation. The most commonly reported manifestation of invasive fusariosis in this setting is localized cutaneous fusariosis. Here, we present the first case report of isolated N pseudensiformis pulmonary infection in a patient with non-alcoholic steatohepatitis cirrhosis who underwent orthotopic liver transplantation. A 67-year-old Thai woman developed acute graft rejection, dyspnea, and pulmonary consolidation 6 months after liver transplantation. N pseudensiformis was isolated from her sputum, and her clinical symptoms were improved with voriconazole treatment. However, she succumbed to Acinetobacter baumannii hospital-acquired pneumonia and acute coronary syndrome with cardiogenic shock after 10 days of treatment.

Cryptococcus neoformans/gattii Species Complexes from Pre-HIV Pandemic Era Contain Unusually High Rate of Non-Wild-Type Isolates for Amphotericin B.

INTRODUCTION: The Cryptococcus neoformans/gattii species complexes are a leading cause of fatality among HIV-infected patients. Despite the unavailability of clinical breakpoints (CBPs) for antifungal agents, epidemiological cutoff values (ECVs) were recently proposed, and non-wild-type isolates for polyenes and azoles are being increasingly reported. However, the distributions of the susceptibility patterns for pre-HIV-era isolates have not been studied. METHODS: We determined the in vitro antifungal susceptibility patterns of 233 Cryptococcus isolates, collected at the National Institutes of Health, USA, in pre-HIV pandemic era, to study minimum inhibitory concentrations (MICs) to the important drugs for cryptococcosis and to compare the results with strain genotypes. Amphotericin B susceptibility was compared to published ECV of C. neoformans. RESULTS: The 233 Cryptococcus strains consisted of 89.7% C. neoformans species complex and 10.3% C. gattii species complex. Most were from clinical sources (189, 81.1%), and the major molecular type was VNI (146, 62.7%). The highest geometric mean (GM) was observed for fluconazole (GM = 0.96 µg/mL) while the lowest was for itraconazole (GM = 0.10 µg/mL). MICs to fluconazole in C. gattii species complex were significantly higher than C. neoformans species complex (p < 0.001). Moreover, C. neoformans/VNI strains showed significantly higher MICs than others such as C. neoformans/VNII to fluconazole (p < 0.0001) and C. deneoformans/VNIV to amphotericin B (p = 0.022) and fluconazole (p = 0.008). In our collection of 167 clinical C. neoformans species complex strains, 85 (50.9%), 24 (14.4%), and 3 (1.8%) strains had an amphotericin B (AMB)-MIC of 1, 2, and 4 µg/mL, respectively. The high percentage (66.9%, 79/118 strains) of non-wild-type clinical C. neoformans VNI strains, using an AMB-ECV of 0.5 µg/mL, was found. Moreover, 25 of 28 (89.3%) C. neoformans VNI strains from environmental and veterinary sources also had AMB-MICs above 0.5 µg/mL. In general, there was no significant difference in GM AMB-MIC of the clinical strains isolated from patients with (35 patients) and without (78 patients) prior AMB treatment (0.85 vs 0.76; p = 0.624). GM MIC of the environmental strains was not significantly different from that of the prior AMB-treatment strains (0.98 vs 0.76, p = 0.159) and the post-AMB-treatment strains (0.98 vs 0.85, p = 0.488). CONCLUSION: The high rate of non-wild-type among these otherwise naive isolates to amphotericin B is unexpected. Confirmation with more strains from a later era is needed.

A case report of Talaromyces marneffei Oro-pharyngo-laryngitis: a rare manifestation of Talaromycosis.

BACKGROUND: The incidence of Taralomyces marneffei infection in HIV-infected individuals has been decreasing, whereas its rate is rising among non-HIV immunodeficient persons, particularly patients with anti-interferon-gamma autoantibodies. T. marneffei usually causes invasive and disseminated infections, including fungemia. T. marneffei oro-pharyngo-laryngitis is an unusual manifestation of talaromycosis. CASE PRESENTATION: A 52-year-old Thai woman had been diagnosed anti-IFNÉ£ autoantibodies for 4 years. She had a sore throat, odynophagia, and hoarseness for 3 weeks. She also had febrile symptoms and lost 5 kg in weight. Physical examination revealed marked swelling and hyperemia of both sides of the tonsils, the uvula and palatal arches including a swelling of the epiglottis, and arytenoid. The right tonsillar biopsy exhibited a few intracellular oval and elongated yeast-like organisms with some central transverse septum seen, which subsequently grew a few colonies of T. marneffei on fungal cultures. The patient received amphotericin B deoxycholate 45 mg/dayfor 1 weeks, followed by oral itraconazole 400 mg/day for several months. Her symptoms completely resolved without complication. CONCLUSION: In patients with anti-IFN-É£ autoantibodies, T. marneffei can rarely cause a local infection involving oropharynx and larynx. Fungal culture and pathological examination are warranted for diagnosis T. marneffei oro-pharyngo-laryngitis. This condition requires a long term antifungal therapy.

A Predominance of Clade 17 Candida albicans Isolated From Hemocultures in a Tertiary Care Hospital in Thailand.

Candida albicans is one of the most common human fungal pathogens. Candidemia has significant mortality globally. No epidemiological study of C. albicans based on multilocus sequence typing (MLST) has been conducted in Thailand. Therefore, MLST was used to study the molecular epidemiology of C. albicans blood strains in a large Thai teaching hospital. In vitro virulence phenotypes and antifungal susceptibility testing by broth microdilution were also conducted. Forty-six C. albicans blood strains from 37 patients were collected from the Department of Microbiology, Siriraj Hospital, in 2016 and 2017. Most patients (71.8%) were more than 60 years old, and the case fatality rate was 54.8%. The male-to-female ratio was 5:3. Thirty-four diploid sequence types (DSTs), including six new DSTs, were identified, with DST2514 (8.7%) and DST2876 (8.7%) as the most common DSTs. Strains were clustered into nine clades. Unlike other studies of C. albicans blood strains in Asia, clade 17 was the most common (13 strains, 28.3%). Sequential allelic changes were evident in sequential strains from one patient. All strains produced phospholipase and hemolysin, while none produced proteinase. The ability to form biofilm was found in 82.6% of the strains. Clade 17 strains showed significantly stronger hemolytic activity than non-clade 17 strains (69.2% versus 27.3%; p = 0.022). However, no significant association existed between clades and patient mortalities. All were susceptible or wild type to anidulafungin (MIC range = 0.015-0.12 and GM = 0.030), micafungin (MIC range = ≤ 0.008-0.015 and GM = 0.008), caspofungin (MIC range = 0.008-0.12 and GM = 0.036), and amphotericin B (MIC range = 0.25-0.5 and GM = 0.381). Only one strain was resistant to voriconazole (MIC range = ≤ 0.008 to ≥ 8 and GM = 0.010) and fluconazole (MIC range = 0.12-16 and GM = 0.398). In conclusion, a high prevalence of clade 17 C. albicans blood strains was found in Thailand, in contrast to other Asian countries. This unique finding might be explained by the strong hemolytic activity that is required for bloodstream infection of C. albicans.