Cryptococcus tetragattii Meningitis Associated with Travel, Taiwan.

Meningitis caused by Cryptococcus tetragattii fungus is rare and has been found in specific geographic regions. We report a case of meningitis caused by C. tetragattii (molecular type VGIV) in an immunocompetent patient in Taiwan. The patient had traveled to Egypt and was positive for granulocyte-macrophage colony-stimulating factor autoantibody.

Antifungal susceptibility of the clinical and environmental strains of Cryptococcus gattii sensu lato in Taiwan.

BACKGROUND: The rare occurrence of human cryptococcosis caused by Cryptococcus gattii sensu lato leads to difficulties in establishing the antifungal susceptibility profile between species of this potentially lethal pathogen, which may be crucial for treating cryptococcosis. OBJECTIVE: To establish an antifungal susceptibility profile of C. gattii s.l. in Taiwan. METHODS: A total of 104 environmental C. gattii s.l. strains (including multilocal sequence typing ST7, ST106, ST274, ST328, ST546, ST548 and ST630) and 21 previously collected clinical strains (including ST7, ST44, ST06, ST274, ST328 and ST329) were included in this study. We determined the minimum inhibitory concentrations (MICs) of six antifungal agents (itraconazole, fluconazole, voriconazole, posaconazole, flucytosine and amphotericin B) against environmental C. gattii s.l. strains and compared the antifungal susceptibility profiles of environmental strains with those of clinical strains. RESULTS: The antifungal susceptibility data demonstrated that the MICs of antifungal agents against environmental strains were comparable to those against clinical strains. Compared with strains of Cryptococcus deuterogattii, those of C. gattii sensu stricto were more susceptible to azoles and flucytosine. The differences in antifungal susceptibility between the strains of each sequence type (ST) were significant. Correlation analysis of MICs revealed cross-resistance between azoles in environmental strains of C. gattii s.l. Geographic differences in the antifungal susceptibility of C. gattii s.l. isolated from different cities in Taiwan were observed in this study. CONCLUSION: Clinical and environmental strains were indistinguishable in antifungal susceptibility. The antifungal susceptibility of C. gattii s.l. is associated with STs. Therefore, establishing an ST-oriented domestic antifungal susceptibility database may help treat C. gattii s.l.-induced cryptococcosis.

Cryptococcus gattii Infection as the Major Clinical Manifestation in Patients with Autoantibodies Against Granulocyte-Macrophage Colony-Stimulating Factor.

PURPOSE: Anti-granulocyte-macrophage colony-stimulating factor autoantibodies (anti-GM-CSF Abs) are a predisposing factor for pulmonary alveolar proteinosis (PAP) and Cryptococcus gattii cryptococcosis. This study aimed to investigate clinical manifestations in anti-GM-CSF Ab-positive patients with C. gattii cryptococcosis and analyze the properties of anti-GM-CSF Abs derived from these patients and patients with PAP. METHODS: Thirty-nine patients diagnosed with cryptococcosis (caused by C. neoformans or C. gattii) and 6 with PAP were enrolled in the present study. Clinical information was obtained from medical records. Blood samples were collected for analysis of autoantibody properties. We also explored the National Health Insurance Research Database (NHIRD) of Taiwan to investigate the epidemiology of cryptococcosis and PAP. RESULTS: High titers of neutralizing anti-GM-CSF Abs were identified in 15 patients with cryptococcosis (15/39, 38.5%). Most anti-GM-CSF Ab-positive cryptococcosis cases had central nervous system (CNS) involvement (14/15, 93.3%). Eleven out of 14 (78.6%) anti-GM-CSF Ab-positive CNS cryptococcosis patients were confirmed to be infected with C. gattii, and PAP did not occur synchronously or metachronously in a single patient from our cohort. Exploration of an association between HLA and anti-GM-CSF Ab positivity or differential properties of autoantibodies from cryptococcosis patients and PAP yielded no significant results. CONCLUSION: Anti-GM-CSF Abs can cause two diseases, C. gattii cryptococcosis and PAP, which seldom occur in the same subject. Current biological evidence regarding the properties of anti-GM-CSF Abs cannot provide clues regarding decisive mechanisms. Further analysis, including more extensive cohort studies and investigations into detailed properties, is mandatory to better understand the pathogenesis of anti-GM-CSF Abs.

Molecular epidemiology and phylogenetic analyses of environmental and clinical isolates of Cryptococcus gattii sensu lato in Taiwan.

BACKGROUND: The rare occurrence of cryptococcosis caused by Cryptococcus gattii sensu lato (C. gattii s.l.) leads to the difficulties in studying the molecular epidemiology of this globally emerging disease. OBJECTIVES: To establish the molecular epidemiological profile of C. gattii s.l. in Taiwan, and understand the genetic relationship between locally endemic and global isolates. METHODS: A nationwide survey on environmental C. gattii s.l. in Taiwan was conducted from 2017 to 2019. The geographic distribution and molecular epidemiology based on multilocus sequence typing (MLST) data of the environmental isolates were compared with 18 previously collected clinical isolates. Phylogenetic analysis was performed to elucidate the genetic relationship between the global isolates and the isolates endemic to Taiwan. RESULTS: From a total of 622 environmental samples, 104 (16.7%) were positive for C. gattii s.l.. Seven sequence types were identified among the environmental isolates. The genetic population structure showed that the environmental and clinical isolates were closely linked by sequence types and geographical locations. Phylogenetic analysis revealed the association between the C. gattii s.l. isolates in Taiwan and those from South America and South Asia. The recombination test suggested that, in Taiwan, the C. gattii sensu stricto (C. gattii s.s). isolates undergo clonal reproduction and sexual recombination, whereas C. deuterogattii isolates were clonal. CONCLUSIONS: The molecular epidemiology of environmental C. gattii s.l. isolates is closely linked to the clinical isolates. Phylogenetic analysis of the environmental isolates provides an insight into the mechanisms underlying reproduction and dispersal of C. gattii s.l. in Taiwan.

Sensitivity of Colletotrichum gloeosporioides species complex (CGSC) isolated from strawberry in Taiwan to benzimidazole and strobilurin.

Colletotrichum gloeosporioides species complex (CGSC) is the major pathogen causing strawberry anthracnose in Taiwan. Benzimidazoles and strobilurins are common fungicides used to control strawberry anthracnose. A total of 108 CGSC isolates were collected from five major strawberry-producing areas in Taiwan. The half-maximal effective concentration (EC50) values of most CGSC isolates for benomyl (59 isolates), carbendazim (70 isolates), and thiabendazole (63 isolates) were higher than 500 µg a.i./mL. Strobilurin tests showed that the EC50 values of most CGSC isolates for azoxystrobin (66 isolates), kresoxim-methyl (42 isolates), and trifloxystrobin (56 isolates) were higher than 500 µg a.i./mL. However, most CGSC isolates were sensitive to pyraclostrobin at 100 µg a.i./mL. Fungicide tests indicated that CGSC isolates show multi-resistance to benzimidazoles and strobilurins. Benzimidazole-resistant isolates were associated with a point mutation in codon 198 of the ß-tubulin gene, and strobilurin-resistant isolates did not correspond with mutation in the cyt b gene or alternative oxidase activity.

Two-step method for isolating Cryptococcus species complex from environmental material using a new selective medium.

Cryptococcosis is an opportunistic infection caused by the Cryptococcus species complex. An outbreak of cryptococcosis caused by Cryptococcus gattii (AFLP6/VGII) in North America has indicated the need for studies of this organism and its environmental niche. Difficulties in isolating the Cryptococcus spp. because of the overgrowth of filamentous fungi onto culture media and its low fungal population size under natural conditions limit studies of these pathogenic yeasts. We designed a selective medium that inhibits the growth of environmental filamentous fungi but does not inhibit that of Cryptococcus cells. After enrichment in acidified YPD media and inoculation onto selective media, Cryptococcus cells in brown-coloured colonies were isolated from environmental materials. This two-step method is useful for isolating environmental members of the Cryptococcus species complex, which is essential for further studies involving diversity and the microbe-environment relationship of this yeast.

Diabetes mellitus is associated with acquisition and increased mortality in HIV-uninfected patients with cryptococcosis: A population-based study.

OBJECTIVES: To disclose the association between diabetes mellitus (DM) and cryptococcosis in HIV-uninfected patients. METHODS: Case patients' diagnoses with cryptococcosis and cryptococcal meningitis were based on data from the Taiwan National Health Insurance Research Database from 2000 to 2010, and diagnoses were defined using the International Classification of Disease, Ninth Revision, Clinical Modification. A case-control study comprising inpatient and outpatient populations was conducted using 4 controls for each patient (4587 case patients and 18,348 controls) matched for age, sex, monthly income, and urbanization level. RESULTS: Human immunodeficiency virus (HIV)-uninfected patients with cryptococcosis were more likely to have diabetes than matched control patients (adjusted odds ratio [OR], 1.45; 95% confidence interval [95% CI], 1.36-1.64; p < 0.001). A diagnosis of DM was also associated with 1-year and overall mortality from cryptococcosis (hazard ratio [HR], 1.39; 95% CI, 1.17-1.65; p < 0.001, HR, 1.47; 95% CI, 1.29-1.67; p < 0.001; respectively) and cryptococcal meningitis (p = 0.018). CONCLUSIONS: Diabetes was associated with the occurrence of cryptococcosis and cryptococcal meningitis in HIV-uninfected patients. DM was also associated with 1-year and overall mortality for these patients.

Pseudomonas stutzeri necrotizing pneumonia in pre-existing pulmonary tuberculosis.

Pseudomonas stutzeri (P. stutzeri) is a Gram-negative, non-fermenting rod. It is a rare pathogen; therefore, its isolation is often associated with colonization or contamination. We herein describe the first reported case of necrotizing pneumonia caused by P. stutzeri in a non-HIV infected patient with previously undiagnosed pulmonary tuberculosis. The isolate was found to be antibiotic resistant, which led to the failure of the initial treatment. This case highlights the unique presentation of necrotizing pneumonia caused by P. stutzeri and the importance of emerging antimicrobial resistance in P. stutzeri.

Intraventricular antimicrobial therapy in postneurosurgical Gram-negative bacillary meningitis or ventriculitis: a hospital-based retrospective study.

BACKGROUND: Postneurosurgical Gram-negative bacillary meningitis (GNBM) or ventriculitis is a serious issue. Intraventricular (IVT) therapy has been applied; however, its effectiveness remains controversial, and the adverse drug effects are considerable. METHODS: The demographic data, treatment strategies, and clinical outcomes of patients with postneurosurgical GNBM or ventriculitis were recorded. RESULTS: From 2003 to 2011, data on 127 episodes of infection in 109 patients were collected, and 15 episodes in 14 patients were treated using a sequential combination of intravenous antibiotics and IVT therapy; others received intravenous antibiotics alone. The average age of patients who received a sequential combination with IVT therapy was 48.9 years, and 71.4% of the patients were men. The regimens used for IVT therapies included gentamicin (n = 4), amikacin (n = 7), and colistin (n = 4). After meningitis had been diagnosed, the average period that elapsed before initiation of IVT therapy was 25.4 days, and the average duration of IVT therapy was 13.3 days. The most frequently isolated pathogen from cerebrospinal fluid (CSF) was Acinetobacter baumannii, followed by Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae, and Serratia marcescens. The cure rate was 73.3%. Of note, the mean period to sterilize the CSF after appropriate IVT antibiotic treatment was 6.6 days. There were no incidents of seizure or chemical ventriculitis during this IVT therapy. CONCLUSION: The findings of this study suggest that IVT antibiotic therapy is a useful option in the treatment of postneurosurgical GNBM or ventriculitis, especially for those with a treatment-refractory state.

Report of a 63-case series of Candida empyema thoracis: 9-year experience of two medical centers in central Taiwan.

BACKGROUND: Candida empyema thoracis is a serious complication of invasive candidiasis with high mortality. However, the treatment for Candida empyema remains controversial. We conducted a 9-year retrospective study to analyze the treatments and factors associated with the mortality of patients with Candida empyema thoracis in two medical centers in central Taiwan. METHODS: The medical records of all patients with positive Candida culture from pleural effusion between October 2002 and September 2011 were reviewed. The demographic data, treatment regimens, and factors associated with mortality were analyzed. RESULTS: During the period of this study, 102 patients were identified. Sixty-three of these patients fulfilled the enrollment criteria, and their data were analyzed. Three-quarters of these patients were male, and the median age of these patients was 69. Thirty-five (55.6%) patients had contiguous infection. The crude mortality rate was 61.9%. Candida albicans was the most common isolate, and malignancy was the most common underlying disease. Patients with advanced age, a higher Charlson's score, shock status, respiratory failure, and noncontiguous infection had a higher mortality rate. Those who had received surgical intervention had a better outcome. In multivariate analysis, the shock status, respiratory failure, and noncontiguous infection source were associated with a higher mortality risk. CONCLUSION: Candida empyema thoracis is a severe invasive candidiasis with high mortality rate. Shock status, respiratory failure, and noncontiguous infection were factors associated with a higher mortality rate. Surgical intervention or drainage may improve the treatment outcome, especially in patients with contiguous infection.

Correlation of virulence genes to clinical manifestations and outcome in patients with Streptococcus dysgalactiae subspecies equisimilis bacteremia.

BACKGROUND/PURPOSE: Streptococcus dysgalactiae subsp. equisimilis (SDSE) is increasingly recognized as a human pathogen responsible for invasive infection and streptococcal toxic shock syndrome (STSS). The pathogen possesses virulence genes that resemble those found in Streptococcus pyogenes (GAS). We analyzed the association between these specific toxic genes, clinical presentations, and outcome in patients with SDSE infections. METHODS: Patients (older than 18 years) with community-acquired invasive bacteremia caused by SDSE bacteremia who were undergoing treatment at China Medical University Hospital from June 2007 to December 2010 were included in this study. Multiplex polymerase chain reaction was performed to identify virulence genes of the SDSE isolates. Demographic data, clinical presentations, and outcome in patients with SDSE infections were reviewed and analyzed. RESULTS: Forty patients with 41 episodes of SDSE bacteremia were reviewed. The median age of the patients with SDSE infection was 69.7 years; 55% were female and 78% had underlying diseases. Malignancy (13, 33%) and diabetes mellitus (13, 33%) were the most common comorbidities. The 30-day mortality rate was 12%. Compared with the survivors, the non-survivors had a higher rate of diabetes mellitus (80% vs. 26%), liver cirrhosis (60% vs.11%), shock (60% vs.17%), STSS (60% vs. 8%), and a high Pittsburgh bacteremia score >4 (40% vs. 6%). Most isolates had scpA, ska, saga, and slo genes, whereas speC, speG, speH, speI, speK, smez, and ssa genes were not detected. speA gene was identified only in one patient with STSS (1/6, 17%). All isolates were susceptible to penicillin, cefotaxime, levofloxacin, moxifloxacin, vancomycin, and linezolid. CONCLUSION: In invasive SDSE infections, most isolates carry putative virulence genes, such as scpA, ska, saga, and slo. Clinical SDSE isolates in Taiwan remain susceptible to penicillin cefotaxime, and levofloxacin.

Tuberculous arthritis--unexpected extrapulmonary tuberculosis detected by FDG PET/CT.

FDG PET/CT imaging has been used in various medical fields, including neoplastic and infectious diseases, for a long time. We reported a 62-year-old man with fever, chronic cough, arthralgia of the left side of the hip, and body weight loss. Chest radiograph showed increased infiltration in both upper lungs, and the acid-fast stain of sputum was positive. Whole-body PET/CT scan revealed a lesion with intense FDG uptake in the joint of the side left of the hip. Osteoarthritis of the hip was initially impressed by an orthopedist. However, tuberculous arthritis was subsequently confirmed by deep pus culture.