Fungal keratitis is a serious clinical infection on the cornea caused by fungi and is one of the leading causes of blindness in Asian countries. The treatment options are currently limited to a few antifungal agents. With the increasing incidence of drug-resistant infections, many patients fail to respond to antibiotics. Riboflavin-mediated corneal crosslinking (similar to photodynamic therapy (PDT)) for corneal ectasia was approved in the US in the early 2000s. Current evidence suggests that PDT could have the potential to inhibit fungal biofilm formation and overcome drug resistance by using riboflavin and rose bengal as photosensitizers. However, only a few clinical trials have been initiated in anti-fungal keratitis PDT treatment. Moreover, the removal of the corneal epithelium and repeated application of riboflavin and rose bengal are required to improve drug penetration before and during PDT. Thus, an improvement in trans-corneal drug delivery is mandatory for a successful and efficient treatment. In this article, we review the studies published to date using PDT against fungal keratitis and aim to enhance the understanding and awareness of this research area. The potential of modifying photosensitizers using nanotechnology to improve the efficacy of PDT on fungal keratitis is also briefly reviewed.

Background. Nontyphoid Salmonella (NTS) can cause fatal vascular infections. This study aims to establish a predictive scoring algorithm to identify adults aged ≥50 years with NTS bacteremia who are at risk for vascular infections. Methods. There were 358 adults aged ≥50 years with NTS bacteremia at 2 medical centers in southern Taiwan included in this study. Multiple logistic regression was used to identify risk factors for imaging-documented vascular infections. The prediction capability of the proposed scoring algorithm was indicated by a receiver operating characteristic curve and measures of sensitivity and specificity. Results. Sixty patients (16.8%) with vascular infections were noted. The 4 risk factors significantly associated with vascular infections—male sex, hypertension, coronary arterial disease, and serogroup C1 infections—were each assigned +1 point to form the NTS vascular infection (NTSVI) score. In contrast, malignancy and immunosuppressive therapy were each assigned −1 point, owing to their negative associations with vascular infections. Based on the proposed NTSVI scoring, the prevalence of vascular infections in patients with ≤0, 1, 2, 3, or 4 points was 2.2% (3 of 138 patients), 10.6% (13 of 123 patients), 39.4% (26 of 66 patients), 55.2% (16 of 29 patients), and 100% (2 of 2 patients), respectively (P < .0001). The scoring algorithm shows an area under the curve of 0.83 (95% confidence interval, .78–.89; P < .0001). A cutoff value of +1 represents a high sensitivity (95.0%) and an acceptable specificity (45.3%). Conclusions. This simple scoring algorithm can be used to identify patients with NTS bacteremia with a high risk of vascular infections. The cost-effectiveness of this algorithm should be further studied.

This study delineated the characteristics of 24 (11.2%) culture-positive, influenza-associated pulmonary aspergillosis (IAPA) patients out of 215 patients with severe influenza during 2016–2019 in a medical center in southern Taiwan. Twenty (83.3%) patients did not have EORTC/MSG-defined host factors. The mean time from influenza diagnosis to Aspergillus growth was 4.4 days, and 20 (83.3%) developed IAPA within seven days after influenza diagnosis. All patients were treated in intensive care units and all but one (95.8%) received mechanical ventilation. Aspergillus tracheobronchitis was evident in 6 (31.6%) of 19 patients undergoing bronchoscopy. Positive galactomannan testing of either serum or bronchoalveolar lavage was noted in all patients. On computed tomography imaging, IAPA was characterized by peribronchial infiltrates, multiple nodules, and cavities superimposed on ground-glass opacities. Pure Aspergillus growth without bacterial co-isolation in culture was found in 17 (70.8%) patients. A. fumigatus (15, 62.5%), A. flavus (6, 25.0%), and A. terreus (4, 16.7%) were the major causative species. Three patients had mixed Aspergillus infections due to two species, and two had mixed azole-susceptible and azole-resistant A. fumigatus infection. All patients received voriconazole with an all-cause mortality of 41.6%. Of 14 survivors, the mean duration of antifungal use was 40.5 days. In conclusion, IAPA is an early and rapidly deteriorating complication following influenza that necessitates clinical vigilance and prompt diagnostic workup.

Background: Epidemiological knowledge is important to guide antifungal therapy.Objective: This multicentre study aimed to investigate the species distribution and antifungal susceptibility of Aspergillus isolates in Taiwan.Method: Four hundred and ninety‐two clinical Aspergillus isolates, collected during 2016–2020, were identified by calmodulin sequencing and tested for antifungal susceptibility using CLSI M38‐A3. The Cyp51A sequences of azole‐resistant Aspergillus fumigatus and Aspergillus flavus isolates were analysed.Results: This collection comprised 30 species from eight Aspergillus sections—Flavi (33.5%), Nigri (26.0%), Fumigati (24.2%), Terrei (10.0%), Nidulantes (5.1%), Circumdati (0.8%), Restricti (0.2%) and Aspergillus (0.2%). Sections Fumigati, Flavi and Terrei were primarily represented by A. fumigatus (99.2%), A. flavus (95.8%) and A. terreus (100%), respectively. Section Nigri comprised nine species, mostly A. welwitschiae (60.2%), A. niger (12.5%), A. brunneoviolaceus (10.9%) and A. tubingensis (10.2%). A. fumigatus (39.6%) and A. flavus (26.4%) predominated among 53 isolates from lower respiratory samples, whereas section Nigri species (46.2%) and A. terreus (29.2%) predominated among 65 isolates from ear samples. Reduced susceptibility to amphotericin B (minimal inhibitory concentration (MIC) > 1 μg/mL) was noted in A. flavus (7.0%), A. terreus (6.1%), A. nidulans and section Circumdati (A. flocculosus, A. subramanianii and A. westerdijkiae) isolates. Acquired azole resistance was observed in seven A. fumigatus (5.9%), all of which carried TR₃₄/L98H or TR₃₄/L98H/S297T/F495I mutation, and three A. flavus (1.9%), one of which carried G441S mutation. Reduced susceptibility to itraconazole (MIC >1 μg/mL) was noted in 55.5% of section Nigri isolates, mainly in A. welwitschiae, A. niger and A. tubingensis, whereas A. brunneoviolaceus, A. aculeatinus and A. japonicus were hypersusceptible to azoles. Anidulafungin was active against all isolates except for one isolate.Conclusions: This study depicted the molecular epidemiology and species‐specific characteristics of Aspergillus in Taiwan, which aids in appropriate antifungal therapy and underlines the need of speciation and susceptibility testing of disease‐causing Aspergillus.

Background: Epidemiological knowledge of mucormycosis obtained from national population‐based databases is scarce.Objectives: This study aimed to depict the disease burden and demographics of mucormycosis in Taiwan by using the Taiwan National Health Insurance Research Database (NHIRD) and those of aspergillosis as a comparator.Methods: Data from patients with either mucormycosis or aspergillosis from 2006 to 2017 identified with the International Classification of Diseases (ICD) codes were extracted from the NHIRD. The incidence, demographics and clinical data of both diseases were analysed.Results: A total of 204 patients with mucormycosis and 2270 patients with aspergillosis who were hospitalised and treated with mould‐active antifungals between 2006 and 2017 were identified. The average annual incidence of aspergillosis (0.81 cases per 100,000 population [0.81/100,000]) was 11‐fold higher than that of mucormycosis (0.07/100,000). A significant increase in incidence was observed for aspergillosis (from 0.48/100,000 in 2006 to 1.19/100,000 in 2017, p < .0001) but not for mucormycosis (from 0.04/100,000 in 2006 to 0.11/100,000 in 2017, p = .07). The major underlying disease identified was diabetes mellitus (60.8%) for mucormycosis and malignant neoplasms (45.9%) for aspergillosis. The all‐cause 90‐day mortality rate was similar between mucormycosis and aspergillosis patients (39% vs. 37%, p = .60). For mucormycosis patients, multivariate analysis revealed that posaconazole use was associated with lower in‐hospital mortality (aOR 0.38; 95% CI 0.15–0.97; p = .04).Conclusions: Mucormycosis is an uncommon fungal disease in Taiwan, occurring mostly in diabetic patients. However, the incidence might be underestimated due to limited diagnostics. Continuous surveillance might aid in delineating the evolving features of mucormycosis.

This study aimed to investigate the prevalence and characteristics of Aspergillus lentulus clinical and environmental isolates in Taiwan. Aspergillus isolates obtained from patients at three hospitals and from 530 soil samples across Taiwan were screened. A. lentulus, confirmed by calmodulin sequencing, was subjected to antifungal susceptibility testing and cyp51A analyses. Soil samples yielding A. lentulus were analysed for residues of 25 azole fungicides. Nine A. lentulus isolates were identified, which included seven (1.2%, 7/601) isolates from three antifungal-naïve patients out of 601 Aspergillus section Fumigati clinical isolates and two (0.3%, 2/659) isolates out of 659 Aspergillus soil isolates. All isolates developed white colonies and failed to grow at 48°C. They were susceptible to anidulafungin but showed reduced susceptibility to amphotericin B (AmB), voriconazole and azole fungicides. One heart transplant recipient with proven invasive pulmonary aspergillosis (IPA) initially showed suboptimal response to voriconazole monotherapy but was cured with a combination of voriconazole–caspofungin, liposomal AmB (LAmB)–caspofungin, along with surgery, followed by voriconazole maintenance therapy. Among two critically ill patients with probable IPA, one survived with micafungin, while the other died of aspergillosis despite sequential isavuconazole and LAmB monotherapy. Clinical and environmental isolates sharing identical Cyp51A sequence are identified, matching the Cyp51A sequence of A. lentulus NIID0096. Flusilazole (0.0009 mg/kg) was detected in one soil sample. This study raises concerns about health threat posed by human pathogenic A. lentulus originating from natural environments and underscores the need for increased clinical and laboratory vigilance regarding A. lentulus infections.