Candida auris-associated hospitalizations and outbreaks, China, 2018-2023.

The emerging human fungal pathogen Candida auris has become a serious threat to public health. This pathogen has spread to 10 provinces in China as of December 2023. Here we describe 312 C. auris-associated hospitalizations and 4 outbreaks in healthcare settings in China from 2018 to 2023. Three genetic clades of C. auris have been identified during this period. Molecular epidemiological analyses indicate that C. auris has been introduced and local transmission has occurred in multiple instances in China. Most C. auris isolated from China (98.7%) exhibited resistance to fluconazole, while only a small subset of strains were resistant to amphotericin B (4.2%) and caspofungin (2.2%).

First report of Candida auris in Guangdong, China: clinical and microbiological characteristics of 7 episodes of candidemia.

Candida auris is an emerging multidrug-resistant fungal pathogen worldwide. To date, it has not been reported in Guangdong, China. For the first time, we reported 7 cases of C. auris candidemia from two hospitals in Guangdong. The clinical and microbiological characteristics of these cases were investigated carefully. Two geographic clades, i.e. III and I, were found popular in different hospitals by whole genome sequencing analyses. All C. auris isolates from bloodstream were resistant to fluconazole, 5 of which belonged to Clade III harbouring VF125AL mutation in the ERG11 gene. The isolates with Clade I presented Y132F mutation in the ERG11 gene as well as resistance to amphotericin B. All isolates exhibited strong biofilm-forming capacity and non-aggregative phenotype. The mean time from admission to onset of C. auris candidemia was 39.4 days (range: 12 - 80 days). Despite performing appropriate therapeutic regimen, 42.9% (3/7) of patients experienced occurrences of C. auris candidemia and colonization after the first positive bloodstream. C. auris colonization was still observed after the first C. auris candidemia for 81 days in some patient. Microbiologic eradication from bloodstream was achieved in 85.7% (6/7) of patients at discharge. In conclusion, this study offers a crucial insight into unravelling the multiple origins of C. auris in Guangdong, highlighting great challenges in clinical prevention and control.

Prevalence and molecular characteristics of ceftazidime-avibactam resistance among carbapenem-resistant Pseudomonas aeruginosa clinical isolates.

OBJECTIVES: Resistance against ceftazidime-avibactam (CZA) in carbapenem-resistant Pseudomonas aeruginosa (CRPA) is emerging. This study was aimed at detecting the prevalence and molecular characteristics of CZA-resistant CRPA clinical isolates in Guangdong Province, China. METHODS: The antimicrobial susceptibility profile of these strains was determined. A subset of 16 CZA-resistant CRPA isolates was analysed by whole-genome sequencing (WGS). Genetic surroundings of carbapenem resistance genes and pan-genome-wide association analysis were further studied. RESULTS: Of the 250 CRPA isolates, CZA resistance rate was 6.4% (16/250). The minimum inhibitory concentration (MIC) of CZA range was from 0.25 to >256 mg/L. MIC50 and MIC90 were 2/4 and 8/4 mg/L, respectively. Among the 16 CZA-resistant CRPA strains, 31.3% (5/16) of them carried class B carbapenem resistance genes, including blaIMP-4, blaIMP-45, and blaVIM-2, located on IncP-2 megaplasmids or chromosomes, respectively. Pan-genome-wide association analysis of accessory genes for CZA-susceptible or -resistant CRPA isolates showed that PA1874, a hypothetical protein containing BapA prefix-like domain, was enriched in CZA-resistant group significantly. CONCLUSIONS: Class B carbapenem resistance genes play important roles in CZA resistance. Meanwhile, the PA1874 gene may be a novel mechanism involving in CZA resistance. It is necessary to continually monitor CZA-resistant CRPA isolates.

Dynamic evolution of ceftazidime-avibactam resistance due to interchanges between blaKPC-2 and blaKPC-145 during treatment of Klebsiella pneumoniae infection.

Background: The emergence of ceftazidime-avibactam (CZA) resistance among carbapenem-resistant Klebsiella pneumoniae (CRKP) is of major concern due to limited therapeutic options. Methods: In this study, 10 CRKP strains were isolated from different samples of a patient with CRKP infection receiving CZA treatment. Whole-genome sequencing (WGS) and conjugation experiments were performed to determine the transferability of the carbapenem resistance gene. Results: This infection began with a KPC-2-producing K. pneumoniae (CZA MIC = 2 µg/mL, imipenem MIC ≥ 16 µg/mL). After 20 days of CZA treatment, the strains switched to the amino acid substitution of T263A caused by a novel KPC-producing gene, blaKPC-145, which restored carbapenem susceptibility but showed CZA resistance (CZA MIC ≥ 256 µg/mL, imipenem MIC = 1 µg/mL). The blaKPC-145 gene was located on a 148,185-bp untransformable IncFII-type plasmid. The subsequent use of carbapenem against KPC-145-producing K. pneumoniae infection led to a reversion of KPC-2 production (CZA MIC = 2 µg/mL, imipenem MIC ≥ 16 µg/mL). WGS analysis showed that all isolates belonged to ST11-KL47, and the number of SNPs was 14. This implied that these blaKPC-positive K. pneumoniae isolates might originate from a single clone and have been colonized for a long time during the 120-day treatment period. Conclusion: This is the first report of CZA resistance caused by blaKPC-145, which emerged during the treatment with CZA against blaKPC-2-positive K. pneumoniae-associated infection in China. These findings indicated that routine testing for antibiotic susceptibility and carbapenemase genotype is essential during CZA treatment.

Pharmacokinetics of Voriconazole in Peritoneal Fluid of Critically Ill Patients.

Data on the distribution of voriconazole (VRC) in the human peritoneal cavity are sparse. This prospective study aimed to describe the pharmacokinetics of intravenous VRC in the peritoneal fluid of critically ill patients. A total of 19 patients were included. Individual pharmacokinetic curves, drawn after single (first dose on day 1) and multiple (steady-state) doses, displayed a slower rise and lower fluctuation of VRC concentrations in peritoneal fluid than in plasma. Good but variable penetration of VRC into the peritoneal cavity was observed, and the median (range) peritoneal fluid/plasma ratios of the area under the concentration-time curve (AUC) were 0.54 (0.34 to 0.73) and 0.67 (0.63 to 0.94) for single and multiple doses, respectively. Approximately 81% (13/16) of the VRC steady-state trough concentrations (Cmin,ss) in plasma were within the therapeutic range (1 to 5.5 µg/mL), and the corresponding Cmin,ss (median [range]) in peritoneal fluid was 2.12 (1.39 to 3.72) µg/mL. Based on the recent 3-year (2019 to 2021) surveillance of the antifungal susceptibilities for Candida species isolated from peritoneal fluid in our center, the aforementioned 13 Cmin,ss in peritoneal fluid exceeded the MIC90 of C. albicans, C. glabrata, and C. parapsilosis (0.06, 1.00, and 0.25 µg/mL, respectively), which supported VRC as a reasonable choice for initial empirical therapies against intraabdominal candidiasis caused by these three Candida species, prior to the receipt of susceptibility testing results.

Species distribution and antifungal susceptibility of fungi originating from positive blood cultures in Guangdong, 2019-2021 / 中国热带医学

@#Abstract: Objective　To investigate the species distribution and the antifungal susceptibility of fungi originating from positive blood cultures in Guangdong, so as to provide a basis for the rational use of antifungal drugs in clinical fungal bloodstream infections. Methods All data were collected for retrospective study from monitoring units of the Guangdong Fungal Disease Surveillance Network between 2019-2021, including clinical characteristics, species distribution and antifungal susceptibility. Results A total of 3 589 fungi strains were isolated, most of which were Candida spp. (86.5%, 3 105/3 589). The most common species was Candida albicans (36.6%, 1 315/3 589), followed by Candida tropicalis (17.4%, 1 626/3 589) and Candida parapsilosis (14.5%, 520/3 589). There were 42.1%(1 512/3 589) of strains isolated from ICU. The proportions of Candida albicans strains were 40.0%-50.0% among ICU, general surgery, organ transplantation and emergency department. Candida tropicalis (60.0%, 144/240) was the most common species in hematology department. Both Cryptococcus neoformans (35.4%, 69/195) and Talaromyces marneffei (35.9%,70/195) were common in infection department. All of the Candida isolates were of wild-type (WT) phenotype to amphotericin B. Resistance rates of caspofungin and micafungin for Candida spp. ranged from 0.0% to 4.2%. The resistance rates of Candida tropicalis to fluconazole and voriconazole were 42.3% and 38.9%, which were significantly higher than other common Candida spp. The cryptococcus neoformans strains were totally of WT phenotype to fluconazole and voriconazole. Conclusions Candida albicans is the most common species originating from positive blood cultures in Guangdong Province. Common Candida strains are highly sensitive to echinocandins and amphotericin B. Candida tropicalis has a high resistance rate to triazole drugs.

In vitro characterization and molecular epidemiology of Cryptococcus spp. isolates from non-HIV patients in Guangdong, China.

Background: The burden of cryptococcosis in mainland China is enormous. However, the in vitro characterization and molecular epidemiology in Guangdong, a key region with a high incidence of fungal infection in China, are not clear. Methods: From January 1, 2010, to March 31, 2019, clinical strains of Cryptococcus were collected from six medical centres in Guangdong. The clinical information and characteristics of the strains were analysed. Furthermore, molecular types were determined. Results: A total of 84 strains were collected, mostly from male and young or middle-aged adult patients. Pulmonary and cerebral infections (82.1%) were most common. All strains were Cryptococcus neoformans, grew well at 37°C and had capsules around their cells. One melanin- and urea- and one melanin+ and urea- variants were found. Although most strains exhibited a low minimum inhibitory concentration (MIC) value for voriconazole (mean: 0.04 µg/mL) and posaconazole (mean: 0.12 µg/mL), the results for these isolates showed a high degree of variation in the MIC values of fluconazole and 5-fluorocytosine, and resistance was observed for 4 out of 6 drugs. A significant proportion of these strains had MIC values near the ECV values, particularly in the case of amphotericin B. The proportion of strains near the clinical breakpoints was as follows: fluconazole: 3.66%; voriconazole: 3.66%; itraconazole: 6.10%; posaconazole: 13.41%; amphotericin B: 84.15%; 5-fluorocytosine: 2.44%. These strains were highly homogeneous and were dominated by the Grubii variant (95.2%), VNI (94.0%), α mating (100%), and ST5 (89.3%) genotypes. Other rare types, including ST4, 31, 278, 7, 57 and 106, were also found. Conclusion: Phenotypically variant and non-wild-type strains were found in Guangdong, and a significant proportion of these strains had MIC values near the ECV values towards the 6 antifungal drugs, and resistance was observed for 4 out of 6 drugs. The molecular type was highly homogeneous but compositionally diverse, with rare types found. Enhanced surveillance of the aetiology and evolution and continuous monitoring of antifungal susceptibility are needed to provide references for decision-making in the health sector and optimization of disease prevention and control.

Comparison of molecular and MALDI-TOF MS identification and antifungal susceptibility of clinical Fusarium isolates in Southern China.

Background: Fusarium species are opportunistic causative agents of superficial and disseminated human infections. Fast and accurate identification and targeted antifungal therapy give help to improve the patients' prognosis. Objectives: This study aimed to evaluate the effectiveness of matrix-assisted laser desorption ionisation time of flight mass spectrometry (MALDI-TOF MS) for Fusarium identification, and investigate the epidemiology and antifungal susceptibility profiles of clinical Fusarium isolates in Southern China. Methods: There were 95 clinical Fusarium isolates identified by DNA sequencing of translation elongation factor 1-alpha (TEF1α) and MALDI-TOF MS, respectively. Antifungal susceptibility testing of isolates was performed by broth microdilution according to the CLSI approved standard M38-A3 document. Results: Seven species complexes (SC) with 17 Fusarium species were identified. The most prevalent SC was the F. solani SC (70.5%, 67/95), followed by the F. fujikuroi SC (16.8%, 16/95). F. keratoplasticum within the F. solani SC was the most prevalent species (32.6%, 31/95). There were 91.6% (87/95) of isolates identified by MALDI-TOF MS at the SC level. In most of species, amphotericin B and voriconazole showed lower MICs compared to itraconazole and terbinafine. The F. solani SC showed higher MICs to these antifungal agents compared to the other SCs. There were 10.5% (10/95) of strains with high MICs for amphotericin B (≥8 µg/ml), terbinafine (≥32 µg/ml) and itraconazole (≥32 µg/ml) simultaneously, mostly focusing on F. keratoplasticum (9/10). Conclusion: MALDI-TOF MS exhibited good performance on the identification of Fusarium strains at the SC level. The F. solani SC was the most prevalent clinical SC in Southern China. The MICs varied significantly among different species or SCs to different antifungal agents.

The Association of Organ Preservation Fluid Pathogens with Early Infection-Related Events after Kidney Transplantation.

(1) Background: The need to elucidate the microbial patterns in preservation fluid and explore their relationship with early infection-related events post kidney transplant and investigate antimicrobial resistance and the effects of preemptive antibiotic therapy. (2) Methods: This retrospective study analyzed the clinical data of 514 kidney transplant donors and 808 recipients from April 2015 to October 2020. Clinical data of donor and recipient characteristics, preservation fluid microbes, early infections (≤30 days), probable donor-derived infections (P-DDIs), antimicrobial resistance and preemptive antibiotic therapy was collected. (3) Results: The incidence of bloodstream (10.3% versus 5.2%, p = 0.006) and graft-site infections (9.7% versus 4.6%, p = 0.004) was significantly higher in recipients with culture-positive preservation fluid. In addition, recipients with ESKAPE pathogens or Candida species had a notably higher rate of bloodstream infections (14.1% versus 6.9%, p = 0.033) and graft-site infections (16.7% versus 3.5%, p < 0.01) than those with other positive pathogens. Preemptive antibiotic therapy decreased the bloodstream infection rate (11.8% versus 35.7%, p = 0.047) when preservation fluid was positive for ESKAPE pathogens. (4) Conclusions: Culture-positive preservation fluid has potential implications for kidney transplant recipients. ESKAPE pathogens or Candida species in preservation fluid as well as their antimicrobial resistance properties and non-preemptive antibiotic therapy could pose a risk of early infection-related events.

Risk factors and mortality for elderly patients with bloodstream infection of carbapenem resistance Klebsiella pneumoniae: a 10-year longitudinal study.

BACKGROUND: Bloodstream infection (BSI) caused by carbapenem resistant Klebsiella pneumoniae (CRKP), especially in elderly patients, results in higher morbidity and mortality. The purpose of this study was to assess risk factors associated with CRKP BSI and short-term mortality among elderly patients in China. METHODS: In this retrospective cohort study, we enrolled 252 inpatients aged ≥ 65 years with BSI caused by KP from January 2011 to December 2020 in China. Data regarding demographic, microbiological characteristics, and clinical outcome were collected. RESULT: Among the 252 BSI patients, there were 29 patients (11.5%) caused by CRKP and 223 patients (88.5%) by carbapenem-susceptible KP (CSKP). The overall 28-day mortality rate of elderly patients with a KP BSI episode was 10.7% (27/252), of which CRKP BSI patients (14 / 29, 48.3%) were significantly higher than CSKP patients (13 / 223, 5.83%) (P < 0.001). Hypertension (OR: 13.789, [95% CI: 3.883-48.969], P < 0.001), exposure to carbapenems (OR: 8.073, [95% CI: 2.066-31.537], P = 0.003), and ICU stay (OR: 11.180, [95% CI: 2.663-46.933], P = 0.001) were found to be associated with the development of CRKP BSI in elderly patients. A multivariate analysis showed that isolation of CRKP (OR 2.881, 95% CI 1.228-6.756, P = 0.015) and KP isolated in ICU (OR 11.731, 95% CI 4.226-32.563, P < 0.001) were independent risk factors for 28-day mortality of KP BSI. CONCLUSION: In elderly patients, hypertension, exposure to carbapenems and ICU stay were associated with the development of CRKP BSI. Active screening of CRKP for the high-risk populations, especially elderly patients, is significant for early detection and successful management of CRKP infection.

Thermosensitive Tri-Block Polymer Nanoparticle-Hydrogel Composites as Payloads of Natamycin for Antifungal Therapy Against Fusarium Solani.

Purpose: Fusarium Solani is the principal pathogen associated with fungal keratitis. As a sensitive drug to F. Solani, natamycin (NAT) was limited by the poor penetration and low bioavailability in clinical application. The aim of this study was to develop a new type of tri-block polymer nanoparticle-gel complex (Gel@PLGA-PEI-PEG@NAT) for delivering NAT and evaluate its physicochemical properties, antifungal activity, safety, penetrability, adhesion, and efficacy in treating fungal keratitis. Methods: PLGA-PEI-PEG@NAT was prepared and characterized with a nano-particle size analyzer, transmission electron microscopy (TEM), scanning electron microscopy (SEM), and Fourier transform infrared spectroscopy (FTIR). The minimum inhibitory concentration (MIC), cytotoxicity, penetrability of NAT (Natacyn® 5% ophthalmic suspension; Alcon) and PLGA-PEI-PEG@NAT with different concentrations were assessed. The eye surface retention time, ocular irritation, and curative effect of the NAT ophthalmic suspension and Gel@PLGA-PEI-PEG@NAT on a rabbit fungal keratitis model were evaluated. Results: PLGA-PEI-PEG@NAT had a particle size of 150 nm, a positive surface charge, and a sustained-release effect. The MIC for F. Solani was 2 µg/mL. A cytotoxicity test and ocular irritation test showed that PLGA-PEI-PEG@NAT and Gel@PLGA-PEI-PEG@NAT had good biocompatibility and no obvious irritation for rabbit corneas. Penetration experiments confirmed that PLGA-PEI-PEG@NAT can successfully enter corneal epithelial cells and through the cornea to enter the anterior chamber. Compared with NAT ophthalmic suspension, Gel@PLGA-PEI-PEG@NAT had stronger cornea permeation at the same concentration. The therapeutic effect and precorneal retention ability of the NAT ophthalmic suspension and Gel@PLGA-PEI-PEG@NAT on the fungal keratitis rabbit model were compared. Gel@PLGA-PEI-PEG@NAT achieved a better therapeutic effect at a lower drug concentration, and its eye surface retention time was significantly longer than that of the NAT ophthalmic suspension. Conclusion: Gel@PLGA-PEI-PEG@NAT was shown to be a safe and effective nanodrug delivery system for NAT. It has great potential to improve the cure rate of fungal keratitis, reduce the administration frequency during the treatment process, and improve patient compliance.

Population pharmacokinetic model-guided optimization of intravenous voriconazole dosing regimens in critically ill patients with liver dysfunction.

STUDY OBJECTIVES: This study aimed to establish a population pharmacokinetic (PPK) model of intravenous voriconazole (VRC) in critically ill patients with liver dysfunction and to explore the optimal dosing strategies in specific clinical scenarios for invasive fungal infections (IFIs) caused by common Aspergillus and Candida species. DESIGN: Prospective pharmacokinetics study. SETTING: The intensive care unit in a tertiary-care medical center. PATIENTS: A total of 297 plasma VRC concentrations from 26 critically ill patients with liver dysfunction were included in the PPK analysis. METHODS: Model-based simulations with therapeutic range of 2-6 mg/L as the plasma trough concentration (Cmin ) target and the free area under the concentration-time curve from 0 to 24 h (ƒAUC24 ) divided by the minimum inhibitory concentration (MIC) (ie, ƒAUC24 /MIC) ≥25 as the effective target were performed to optimize VRC dosing regimens for Child-Pugh class A and B (CP-A/B) and Child-Pugh class C (CP-C) patients. RESULTS: A two-compartment model with first-order elimination adequately described the data. Significant covariates in the final model were body weight on both central and peripheral distribution volume and Child-Pugh class on clearance. Intravenous VRC loading dose of 5 mg/kg every 12 h (q12h) for the first day was adequate for CP-A/B and CP-C patients to attain the Cmin target at 24 h. The maintenance dose regimens of 100 mg q12h or 200 mg q24h for CP-A/B patients and 50 mg q12h or 100 mg q24h for CP-C patients could obtain the probability of effective target attainment of >90% at an MIC ≤0.5 mg/L and achieve the cumulative fraction of response of >90% against C. albicans, C. parapsilosis, C. glabrata, C. krusei, A. fumigatus, and A. flavus. Additionally, the daily VRC doses could be increased by 50 mg for CP-A/B and CP-C patients at an MIC of 1 mg/L, with plasma Cmin monitored closely to avoid serious adverse events. It is recommended that an appropriate alternative antifungal agent or a combination therapy could be adopted when an MIC ≥2 mg/L is reported, or when the infection is caused by C. tropicalis but the MIC value is not available. CONCLUSIONS: For critically ill patients with liver dysfunction, the loading dose of intravenous VRC should be reduced to 5 mg/kg q12h. Additionally, based on the types of fungal pathogens and their susceptibility to VRC, the adjusted maintenance dose regimens with lower doses or longer dosing intervals should be considered for CP-A/B and CP-C patients.

Clinical characteristics and risk factors of Talaromyces marneffei infection in human immunodeficiency virus-negative patients: A retrospective observational study.

BACKGROUND: To investigate the clinical characteristics and risk factors of human immunodeficiency virus (HIV)-negative patients with Talaromyces marneffei (T. marneffei) infection. METHODS: We retrospectively collected the clinical information of HIV-negative patients with T. marneffei infection from January 1, 2010 to June 30, 2019, and analyzed the related risk factors of poor prognosis. RESULTS: Twenty-five cases aging 22 to 79 years were included. Manifestations of T. marneffei infection included fever, cough, dyspnea, chest pain or distress, lymphadenopathy, ear, nose, and throat (ENT) and/or skin lesions, bone or joint pain, edema and pain in the lower extremities, digestive symptoms, icterus, malaise, and hoarseness. Two cases had no comorbidity, while 23 cases suffered from autoimmune disease, pulmonary disease, cancer, and other chronic diseases. Sixteen cases had a medication history of glucocorticoids, chemotherapy or immunosuppressors. Pulmonary lesions included interstitial infiltration, nodules, atelectasis, cavitary lesions, pleural effusion or hydropneumothorax, bronchiectasis, pulmonary fibrosis, pulmonary edema, and consolidation. The incidence of osteolytic lesions was 20%. Eight patients received antifungal monotherapy, and 11 patients received combined antifungal agents. Fifteen patients survived and ten patients were dead. The Cox regression analysis showed that reduced eosinophil counts, higher levels of blood urea nitrogen (BUN), alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactic dehydrogenase (LDH), myoglobin (Mb), procalcitonin (PCT), and galactomannan were related to poor prognosis (hazard ratio [HR]>1, P<0.05). CONCLUSIONS: Bone destruction is common in HIV-negative patients with T. marneffei infection. Defective cell-mediated immunity, active infection, multiple system, and organ damage can be the risk factors of poor prognosis.

Identification and Antifungal Susceptibility Analysis of Stephanoascus ciferrii Complex Species Isolated From Patients With Chronic Suppurative Otitis Media.

BACKGROUND: Stephanoascus ciferrii is a heterothallic ascomycetous yeast-like fungus. Recently, the concept of S. ciferrii complex has been proposed and it consists of S. ciferrii, Candida allociferrii, and Candida mucifera. We aimed to identify 32 strains of S. ciferrii complex isolated from patients with chronic suppurative otitis media (CSOM) at the species level and analyze the morphology and antifungal susceptibility profiles of the three species. METHOD: The sequencing of the internal transcribed spacer (ITS) region and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) were used to identify S. ciferrii complex species. The SARAMIS software was used for cluster analysis of the mass spectra. All the strains were cultured on Sabouraud dextrose agar (SDA) and CHROM plates for 7 days. In the meantime, colonies of the 32 strains went through Gram staining. The Sensititre YeastOne YO10 colorimetric panel was used for the antifungal susceptibility analysis. RESULTS: There were 10 strains of C. allociferrii (31.25%), six strains of C. mucifera (18.75%), and 16 strains of S. ciferrii (50%) in the 32 strains of S. ciferrii complex according to the sequencing of the ITS region. MALDI-TOF MS could identify S. ciferrii but showed no results for C. allociferrii and C. mucifera. The cluster analysis of the mass spectra by SARAMIS indicated that the MALDI-TOF MS could distinguish the three species. The morphology characteristics of the three species were similar. As for antifungal susceptibility, S. ciferrii and C. mucifera tended to have high fluconazole MICs compared with C. allociferrii. C. mucifera and C. allociferrii had relatively low flucytosine MICs while S. ciferrii owned high flucytosine MICs. Besides, C. mucifera tended to have a higher MIC value than S. ciferrii for amphotericin B and C. allociferrii for anidulafungin, micafungin, and caspofungin. CONCLUSION: The antifungal susceptibility profiles of the three species of S. ciferrii complex had their own characteristics. Besides, more mass spectra of C. allociferrii and C. mucifera are needed to construct the reference database for S. ciferrii complex species, enabling MALDI-TOF MS to identify S. ciferrii complex at species level.

Vacuum-Assisted Closure and Skin Grafting Combined with Amphotericin B for Successful Treatment of an Immunocompromised Patient with Cutaneous Mucormycosis Caused by Mucor irregularis: A Case Report and Literature Review.

Cutaneous mucormycosis caused by Mucor irregularis (M. irregularis) is a rare condition that typically occurs in immunocompetent patients. Herein, we describe an immunocompromised patient with cutaneous M. irregularis infection who was successfully treated with debridement combined with vacuum assisted closure (VAC) negative pressure technique and split-thickness skin grafting. We present this case owing to its complexity and rarity and the successful treatment with surgical therapy. A 58-year-old man presented to our hospital with a history of skin ulcers and eschar on the right lower leg since two months. He had been receiving methylprednisolone therapy for bullous pemphigoid that occurred five months prior to the present lesions. Histopathological examination of a right leg lesion showed broad, branching hyphae in the dermis. Fungal culture and subsequent molecular cytogenetic analysis identified the pathogen as M. irregularis. After admission, methylprednisolone was gradually tapered and systemic treatment with amphotericin B (total dose 615 mg) initiated along with others supportive therapies. However, the ulcers showed no improvement, and amphotericin B had to be discontinued owing to development of renal dysfunction. After extensive surgical debridement combined with VAC and skin grafting, his skin ulcers were healed; subsequent fungal cultures of the lesions were negative. The patient exhibited no signs of recurrence at 36-month follow-up. Twenty-six cases with M. irregularis-associated cutaneous mucormycosis in literature were reviewed.

Investigation on Hydrate Growth at the Oil-Water Interface: In the Presence of Wax and Surfactant.

Natural gas hydrates can readily form in deep-water-oil production processes and pose a great threat to subsea pipeline flow assurance. The usage of surfactants and hydrate antiagglomerants is a common strategy to prevent hydrate hazards. In water/wax-containing oil systems, hydrate coexisting with wax could lead to more complex and risky transportation conditions. Moreover, the effectiveness of surfactants and hydrate antiagglomerants in the presence of wax should be further evaluated. In this work, for the purpose of investigating how wax and surfactants could affect hydrate growth at the oil-water interface, a series of microexperiments was conducted in an atmospheric visual cell where the nucleation and growth of hydrates took place on a water droplet surrounded by wax-containing oils. On the basis of the experimental phenomena observed using a microscope, the formation of a hydrate shell by lateral growth, the collapse of a water droplet after hydrate initial formation, and the formation of hollow-conical hydrate crystals were identified. These experimental phenomena were closely related to the concentration of wax and surfactant used in each case. In addition, it was shown that the effectiveness of the surfactant could be weakened by wax molecules. Moreover, there existed a critical wax content above which the effectiveness of the surfactant was greatly reduced and the critical wax content gradually increased with increasing surfactant concentration. This work could provide guidance for hydrate management in wax-containing systems.

Protective Effects of Chicken Egg Yolk Immunoglobulins (IgYs) against Vibrio vulnificus Infections.

Vibrio (V.) vulnificus infection is a rare disease whose death rates exceed 50% despite aggressive antibiotic treatment and surgical debridement. The aim of this study was to assess the ability of specific anti-V. vulnificus immunoglobulins Y (IgYs) for preventing and treating V. vulnificus infections. IgYs were produced by immunizing egg laying hens with inactivated whole cell bacteria. Peritoneal cytokines, blood's bacterial load, and survival curves were obtained from both prophylactic and therapeutic mouse models. The results showed that the specific IgYs (i) inhibited the growth of V. vulnificus in vitro, (ii) dramatically reduced the inflammatory response and blood's bacterial load, and (iii) improved the survival rate of V. vulnificus-infected mice. These results prove that anti-V. vulnificus IgYs can be markedly effective means for the prophylaxis and the therapy of V. vulnificus infections.

A case series of medically managed Candida parapsilosis complex prosthetic valve endocarditis.

BACKGROUND: In recent years, Candida parapsilosis is recognized as a species complex and is composed of Candida parapsilosis sensu stricto, Candida orthopsilosis and Candida metapsilosis. Candida parapsilosis complex prosthetic valve endocarditis (PVE) is rare and the survival rate is still low despite of optimal therapeutic strategies. In our report, it is novel to report cases as Candida parapsilosis complex PVE at species and identify Candida parapsilosis using MALDI-TOF MS. Case presentation A series of 4 cases of Candida parapsilosis complex PVE from our institution was reported. Three were infected by Candida parapsilosis sensu stricto and one was infected by Candida metapsilosis. The condition of two cases got better and the other died. CONCLUSIONS: More attention should be paid to Candida parapsilosis complex PVE and early diagnosis and prompt antibiotic therapy may play a role in the treatment for Candida parapsilosis complex PVE. It is recommended to identify Candida parapsilosis complex at species level and MALDI-TOF MS as an easy, fast and efficient identification method is worth promoting in clinical microbiology.

Genome- and Proteome-Wide Analysis of Lysine Acetylation in Vibrio vulnificus Vv180806 Reveals Its Regulatory Roles in Virulence and Antibiotic Resistance.

Infection with Vibrio vulnificus is notorious for its atypical clinical manifestations and irreversible disease progression. Lysine acetylation is a conserved post-translational modification (PTM) that plays a critical regulatory role in diverse cellular processes. However, little is known about the role of lysine acetylation on the pathogenesis of V. vulnificus. Here, we report the complete genome sequence and a global profile for protein lysine acetylation of V. vulnificus Vv180806, a highly cefoxitin resistant strain isolated from a mortality case. The assembled genome comprised two circular chromosomes and one circular plasmid; it contained 4,770 protein-coding genes and 153 RNA genes. Phylogenetic analysis revealed genetic homology of this strain with other V. vulnificus strains from food sources. Of all the proteins in this strain, 1,924 (40.34%) were identified to be acetylated at 6,626 sites. The acetylated proteins were enriched in metabolic processes, binding functions, cytoplasm, and multiple central metabolic pathways. Moreover, the acetylation was found in most identified virulence factors of this strain, suggesting its potentially important role in bacterial virulence. Our work provides insights into the genomic and acetylomic features responsible for the virulence and antibiotic resistance of V. vulnificus, which will facilitate future investigations on the pathogenesis of this bacterium.

Co-delivery of terbinafine hydrochloride and urea with an in situ film-forming system for nail targeting treatment.

Onychomycosis is a chronic nail disorder consisting of a fungal infection that causes physical and psychosocial discomfort to patients. However, its treatment remains challenging owing to the barrier of the highly keratinized nail plate and the short time that conventional formulations reside on nails. In this work, we developed an in situ film-forming system(IFFS) based on Eudragit® RLPO to co-deliver terbinafine hydrochloride (TBH) and urea, i.e., TBH-urea-RLPO IFFS, with the aim of overcoming the nail barrier, prolonging the residence time, and efficiently treating onychomycosis. The IFFS formulation formed a thin film with good appearance and adhesion upon application in situ. The physical states of TBH and urea in the film were evaluated with polarization microscopy and powder X-ray diffraction. TBH and urea were both amorphousmiscible components within the RLPO film. TBH release from TBH-urea-RLPO IFFS fitted to the Korsmeyer-Pappas model, and the cumulative release at 72 h was significantly higher than that from commercial preparations (Lamisil Pedisan® once). In vitro permeation of TBH from TBH-urea-RLPO IFFS through bovine hoof membranes was evaluated in comparison with the film containing TBH alone (TBH-RLPO) and commercial preparations. The retention and cumulative permeated amount of TBH were significantly enhanced for the TBH-urea-RLPO IFFS (170.80 ± 44.63 µg/cm2vs 75.49 ± 21.50 µg/cm2vs 60.25 ± 27.38 µg/cm2; 61.81 ± 16.09 µg/cm2vs 21.80 ± 11.56 µg/cm2vs 7.91 ± 1.03 µg/cm2, respectively), and the membranes treated with different formulations were observed with SEM and FTIR to identify the denaturing effect of urea on bovine hoof keratin. In vitro antifungal tests against Trichophyton rubrum,Microsporum canis, Fusarium, and Aspergillus fumigatus were cultured on Muller-Hinton agar; the findings indicated that TBH-urea-RLPO IFFS enhanced TBH antifungal activity. Overall, the results support that TBH-urea-RLPO IFFS is an efficient and promising approach for onychomycosis targeting treatment.