Elucidation of the mechanisms of fluconazole resistance and repurposing treatment options against urinary Candida spp. isolated from hospitalized patients in Alexandria, Egypt.

BACKGROUND: The incidence of fungal urinary tract infections (UTIs) has dramatically increased in the past decades, with Candida arising as the predominant etiological agent. Managing these infections poses a serious challenge to clinicians, especially with the emergence of fluconazole-resistant (FLC-R) Candida species. In this study, we aimed to determine the mechanisms of fluconazole resistance in urinary Candida spp. isolated from hospitalized patients in Alexandria, Egypt, assess the correlation between fluconazole resistance and virulence, and explore potential treatment options for UTIs caused by FLC-R Candida strains. RESULTS: Fluconazole susceptibility testing of 34 urinary Candida isolates indicated that 76.5% were FLC-R, with a higher prevalence of resistance recorded in non-albicans Candida spp. (88.9%) than in Candida albicans (62.5%). The calculated Spearman's correlation coefficients implied significant positive correlations between fluconazole minimum inhibitory concentrations and both biofilm formation and phospholipase production. Real-time PCR results revealed that most FLC-R isolates (60%) significantly overexpressed at least one efflux pump gene, while 42.3% significantly upregulated the ERG11 gene. The most prevalent mutation detected upon ERG11 sequencing was G464S, which is conclusively linked to fluconazole resistance. The five repurposed agents: amikacin, colistin, dexamethasone, ketorolac, and sulfamethoxazole demonstrated variable fluconazole-sensitizing activities in vitro, with amikacin, dexamethasone, and colistin being the most effective. However, the fluconazole/colistin combination produced a notable reduction (49.1%) in bladder bioburden, a 50% decrease in the inflammatory response, and tripled the median survival span relative to the untreated murine models. CONCLUSIONS: The fluconazole/colistin combination offers a promising treatment option for UTIs caused by FLC-R Candida, providing an alternative to the high-cost, tedious process of novel antifungal drug discovery in the battle against antifungal resistance.

Antifungal properties of abnormal cannabinoid derivatives: Disruption of biofilm formation and gene expression in Candida species.

Abnormal cannabinoids (including comp 3) are a class of synthetic lipid compounds with non-psychoactive properties and regioisomer configurations, but distinct from traditional cannabinoids since they do not interact with the established CB1 and CB2 receptors. Previous research showed the cardioprotective and anti-inflammatory potentials of comp 3 and more recently its antimicrobial effect on methicillin-resistant Staphylococcus aureus (MRSA). Given the escalating challenges posed by Candida infections and the rise of antifungal drug resistance, the exploration of novel therapeutic avenues is crucial. This study aimed to assess the anti-Candida properties of newly synthesized AbnCBD derivatives. AbnCBD derivatives were synthesized by acid catalysis-induced coupling and further derivatized. We evaluated the potential of the AbnCBD derivatives to inhibit the growth stages of various Candida species. By in vitro colorimetric assays and in vivo mice experiments, we have shown that AbnCBD derivatives induce differential inhibition of Candida growth. The AbnCBD derivatives, especially comp 3, comp 10, and comp 9 significantly reduced the growth of C. albicans, including FLC-resistant strains, and of C. tropicalis and C. parapsilosis but not of C auris compared to their controls (FLC and 0.5 % DMSO). Comp 3 also disrupted C. albicans biofilm formation and eradicated mature biofilms. Notably, other derivatives of AbnCBD disrupted the biofilm formation and maturation of C. albicans but did not affect yeast growth. In a murine model of VVC, comp 3 demonstrated significant fungal clearance and reduced C. albicans burden compared to vehicle and FLC controls. These findings highlight the potential of AbnCBDs as promising antifungal agents against Candida infections.

Higher doses of fluconazole are needed to ensure target attainment in critically ill adults on continuous Veno-venous hemodialysis.

BACKGROUND: Critically ill patients undergoing Continuous Renal Replacement Therapy (CRRT) are treated with higher doses of fluconazole based on the literature recommendations. However, clinical follow-up data demonstrating the effectiveness of this approach are lacking. PURPOSE: A retrospective cohort study was conducted to evaluate whether target attainment was achieved with higher doses of fluconazole. Additionally, the study focused on identifying factors that may contribute to variability in fluconazole exposure in these patients. METHODS: Critically ill patients undergoing Continuous Veno-Venous Hemodialysis (CVVHD) who received either standard or higher doses of intravenous fluconazole were included. Evaluation of target attainment was conducted for each dose regimen. RESULTS: Administering higher doses resulted in target attainment in 100 % of the patients, indicating that starting with at least 400 mg twice daily is an adequate dosing guideline. In this study, only the dose of fluconazole was found to significantly influence target attainment (p < 0.001), with no other predefined factors identified as having a significant impact. CONCLUSION: According to the results of the study, increasing the fluconazole dose to at least 400 mg twice daily is sufficient to reach the desired target in critically ill patients undergoing CVVHD.

Neonatal Fungemia by Non-Candida Rare Opportunistic Yeasts: A Systematic Review of Literature.

Fungal colonization poses a significant risk for neonates, leading to invasive infections such as fungemia. While Candida species are the most commonly identified pathogens, other rare yeasts are increasingly reported, complicating diagnosis and treatment due to limited data on antifungal pharmacokinetics. These emerging yeasts, often opportunistic, underscore the critical need for early diagnosis and targeted therapy in neonates. This systematic review aims to comprehensively analyze all published cases of neonatal fungemia caused by rare opportunistic yeasts, examining geographical distribution, species involved, risk factors, treatment approaches, and outcomes. Searching two databases (PubMed and SCOPUS), 89 relevant studies with a total of 342 cases were identified in the 42-year period; 62% of the cases occurred in Asia. Pichia anomala (31%), Kodamaea ohmeri (16%) and Malassezia furfur (15%) dominated. Low birth weight, the use of central catheters, prematurity, and the use of antibiotics were the main risk factors (98%, 76%, 66%, and 65%, respectively). 22% of the cases had a fatal outcome (80% in Asia). The highest mortality rates were reported in Trichosporon beigelii and Trichosporon asahii cases, followed by Dirkmeia churashimamensis cases (80%, 71%, and 42% respectively). Low birth weight, the use of central catheters, the use of antibiotics, and prematurity were the main risk factors in fatal cases (84%, 74%, 70%, and 67%, respectively). 38% of the neonates received fluconazole for treatment but 46% of them, died. Moreover, the rare yeasts of this review showed high MICs to fluconazole and this should be taken into account when planning prophylactic or therapeutic strategies with this drug. In conclusion, neonatal fungemia by rare yeasts is a life-threatening and difficult-to-treat infection, often underestimated and misdiagnosed.

Congenital Sepsis with Candida albicans-A Rare Event in the Neonatal Period: Report of Two Cases and Literature Review.

Candida spp. is rarely found in neonatal early-onset sepsis (EOS) etiology. However, candidemia is associated with increased mortality and morbidity, as in late-onset sepsis. Congenital candidiasis may present as a mucocutaneous infection or, more rarely, as a systemic infection in term and preterm infants. This paper presents case reports of two cases of congenital systemic candidiasis (CSC) caused by Candida albicans and a review of the data in the literature. An electronic search of PubMed, Scopus, and Google Scholar was performed to identify publications on congenital candidiasis. Both neonates were male, born vaginally, with risk factors for congenital candidiasis. One of the infants was born at term and presented with an almost generalized maculopapular rash at birth and congenital candidemia; parenteral fluconazole was used successfully. The other infant was born prematurely at 28 weeks of gestation; blood culture, gastric aspirate, and maternal vaginal cultures sampled at birth were positive for C. albicans. Liver and kidney involvement became apparent on the third day of life, while lung involvement was clinically evident on the fourth day. Prolonged parenteral fluconazole was administered due to multiple organ involvement and persistent candidemia. Our experience with the presented cases, similar to data in the literature, suggests that CSC may occur at any gestational age, with various clinical pictures, sometimes mimicking bacterial sepsis, and even in the absence of the rash. Careful anamnesis and a high index of suspicion are important for the prompt recognition and treatment of CSC, optimizing the short- and long-term outcomes. Further research should focus on CSC to improve its diagnosis.

Changes in fluconazole pharmacokinetics can impact on antifungal effectiveness in critically ill burn patients: a Pharmacokinetic-Pharmacodynamic (PK/PD) approach.

OBJECTIVES: The Fluconazole pharmacokinetic-pharmacodynamic relationship was investigated in a few clinical settings and only limited studies regarding burned patients are available. Thus, the authors aimed to investigate fluconazole pharmacokinetics changes and its impact on antifungal therapy coverage against dose-dependent Candida spp. applying the PK/PD approach in critically ill severely burned patients. METHODS: Fluconazole was administered as a one-hour intravenous infusion of 200 mg q12h. Doses were increased according to the coverage based on the PK/PD approach. Blood samples were collected at the end of the infusion (1st hour), two hours after (3rd hour), and before the next dose (12th or 24th hour). Serum concentrations were obtained by HPLC-UV. Pharmacokinetic parameters were estimated by noncompartmental analysis and compared with data described in healthy subjects. The effectiveness predictive index was based on the AUCss0-24h/MIC ratio, with a target above 25. RESULTS: Every pharmacokinetic parameter was reduced throughout all three sets of the study. Compared to healthy subjects, the volume of distribution was decreased about 3‒7 times, biological half-life was 2‒3 times shorter and total body clearance was slightly altered but statistically significant. Both half-life and total body clearance were correlated to the volume of distribution. Consequently, an increase in fluconazole daily dose was necessary to improve empiric coverage. CONCLUSIONS: Fluconazole pharmacokinetics is altered in critically ill severely burned patients, mainly related to the volume of distribution. Doses higher than usual may be necessary to reach the PK/PD target and guarantee antifungal coverage against dose-dependent Candida spp. up to MIC 32 mg/L.

Best Practices in Treatment of Fungal Urinary Tract Infections.

Fungal pathogens within the urine, specifically Candida species, are a common finding amongst hospitalized patients. Risk factors for the development of candiduria involve patients with indwelling urinary drainage devices, surgical patients, patients undergoing urologic instrumentation, and diabetic patients. Candiduria often presents with an asymptomatic course but can also be a severe life-threatening process. This article will review the epidemiology and risk factors associated with fungal urinary tract infections, and the diagnosis and categorization of these infections along with a review of current medical and surgical treatments for this condition.

Evaluation of amlodipine against strains of Candida spp. in planktonic cells, developing biofilms and mature biofilms.

Aim: To evaluate the antifungal activity of amlodipine against strains of Candida spp. and to its possible mechanism of action.Methods: Broth microdilution tests were used to determine the minimum inhibitory concentration, while the synergistic activity was evaluated by calculating the fractional inhibitory concentration index. The action of amlodipine against biofilms was determined using the MTT assay and its possible mechanism of action was investigated through flow cytometry tests.Results: Amlodipine showed MICs ranging from 62.5 to 250 µg/ml, in addition to action against pre-formed and forming biofilms, with reductions between 50 and 90%. Amlodipine increases the externalization of phosphatidylserine and reduces the cell viability of fungal cells, suggesting apoptosis.Conclusion: Amlodipine had good antifungal activity against planktonic cells and biofilms of Candida spp., by leading the cells to apoptosis.

Candida is a type of fungus that can cause diseases. This fungus became stronger over time and drugs can no longer kill them easily, so it is important to find new drugs. We decided to study whether amlodipine, a drug used for heart disease, has action against Candida. We discovered that amlodipine make fungi weaker. We still need to do more studies to find out if amlodipine can help prevent Candida diseases.

Parametric and nonparametric population pharmacokinetic analysis of fluconazole in critically ill patients and dosing simulations for Candida infections.

Large pharmacokinetic (PK) variability of fluconazole has been reported in critically ill patients, but the implications for fluconazole dosing remain unclear. The objectives of this study were to evaluate the population PK of fluconazole and identify appropriate dosage regimens by simulations. This was a retrospective analysis of fluconazole PK data from patients hospitalized in critical care and infectious disease departments. Both parametric and nonparametric population approaches were used. Various loading and maintenance fluconazole doses were evaluated by simulations, with computation of the probabilities of PK/pharmacodynamic (PD) target attainment (PTA) and cumulative fractions of response (CFR) based on international and local minimum inhibitory concentration (MIC) distributions of Candida sp. Data from 36 critically ill patients and 16 non-critically ill patients were available for model building (n = 202 concentrations). The final model adequately described the data, including the external data set (13 patients). After 24 h of therapy, 65% and 74% of patients had trough and area under the concentration-time curve values below the usual targets. Standard dosages were associated with low PTA for MIC >1 mg/L at 24 h. Higher loading doses administered two times daily improved PTA. CFR were >90% for C. albicans with standard dosages, while they were very low for C. glabrata, even with high dosages. Candida species and associated MIC distributions strongly influence fluconazole dosage requirements. Higher loading doses may be necessary for the achievement of PK/PD targets up to MIC breakpoints. The use of fluconazole for invasive C. glabrata infection should be discouraged because of poor PK/PD target attainment.

UPLC-MS/MS method for fluconazole determination in plasma and its application in Mexican patients with candidaemia.

Aim: An accurate and fast ultra-high performance liquid chromatography coupled with tandem mass spectrometry analytical method was developed and validated for quantifying fluconazole levels in human plasma according to the US FDA guidelines.Materials & methods: A simple protein precipitation by acetonitrile was employed for the sample preparation. The chromatographic separation was carried out using isocratic elution of water (0.1% formic acid) and acetonitrile on an Acquity ultra-high performance liquid chromatography HSS T3 column. Samples from ten adult patients diagnosed with candidemia who received fluconazole treatment were analyzed.Results & conclusion: The method demonstrated excellent linearity and stability within the 1-50 µg/ml range (r2 >0.999). The intraday and interday precision were determined with coefficient of variation values ranging from 1.4 to 4.38% and 2.8 to 6.6%, respectively. This rapid and selective method has successfully analyzed 27 plasma samples. The straightforward sample preparation in a single step and the reduced analysis time make this method suitable for adult patients with candidemia, leading to improved clinical outcomes.

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Now that griseofulvin is not available, what to do with tinea capitis treatments?

INTRODUCTION: Griseofulvin, discovered in 1939 and commercially available since 1959, was the first oral antifungal agent effective against dermatophytosis, particularly tinea capitis. Although it was eventually superseded by azole antifungals due to its long treatment duration and reliance on keratopoiesis, griseofulvin remains notable for its effectiveness and safety in treating tinea capitis, especially when caused by Microsporum canis. However, due to a decline in cases and commercial unavailability, alternative treatments are now required. AREAS COVERED: The following topics regarding to other treatments were discussed: (I) The efficacy of alternative antifungal agents such as terbinafine, itraconazole, and fluconazole, in the treatment of tinea capitis. (II) The use and role of topical therapies. (III) Experience in the management of tinea capitis. EXPERT OPINION: The usefulness of oral terbinafine as a replacement for griseofulvin in the treatment of tinea capitis and why it is the preferred drug in elderly patients was discussed. Challenges with Microsporum spp. and the use of fluconazole in pediatric patients were also analyzed. Support for the use of topical treatment as an adjunctive treatment for tinea capitis was highlighted.

Serial evaluation of liver enzyme activities in dogs with pulmonary coccidioidomycosis administered per os fluconazole.

Pulmonary coccidioidomycosis is a relatively common fungal disorder in dogs that have lived in or traveled to endemic regions and fluconazole is a common antifungal treatment. Liver enzymopathy can occur with fluconazole administration, but the frequency of occurrence nor potentially associative factors have been explored in dogs with pulmonary coccidioidomycosis. Therefore, our objectives were to describe the occurrence and magnitude of liver enzyme activity (LEA) elevation in dogs with pulmonary coccidioidomycosis during treatment with per os fluconazole and identify variables associated with liver enzymopathy. This was a retrospective observational study that analyzed serum biochemical data obtained from a separate prospective study that included 32 client-owned dogs with newly diagnosed pulmonary coccidioidomycosis from October 2020 to February 2021. Per os fluconazole administration (median dosage: 16.2 mg/kg/day) was initiated after diagnosis and dogs were evaluated once every 3 months thereafter until remission or for a maximum of 12 months. Recorded biochemical parameters at each visit (including baseline) included alanine transaminase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and gamma-glutamyl transferase (GGT). Magnitude of increased LEA was based on the fold increase above the upper limit of the reference interval and defined as mild (<5×), moderate (5-10×) or severe (>10×). Forty-seven percent (15/32) of dogs were documented to have elevations in one or more LEAs after initiation of fluconazole administration during the study period. Thirty-four percent and 25% of dogs had elevated ALP and ALT activities, respectively, at some point during treatment. Elevations in AST and GGT activities were rare. The magnitude of LEA elevation was mild in all cases. Logistic regression models did not identify associations between age, weight, sex, neutered status, prednisone administration, fluconazole dose or duration of treatment with the occurrence of liver enzymopathy. Approximately half of dogs with pulmonary coccidioidomycosis are expected to develop mild increases in activities of ALP and/or ALT with rare involvement of AST or GGT at some point during treatment with fluconazole up to 12 months.

Resistance and virulence genes characteristic of a South Asia Clade (I) Candida auris strain isolated from blood in Beijing.

INTRODUCTION: Candida auris is a globally disseminated invasive ascomycetous yeast, that imposes a substantial burden on healthcare systems. It has been documented to have spread to over 40 countries across six continents, necessitating in-depth comprehension through advanced techniques like Whole-Genome Sequencing. METHOD: This study entailed the isolation and Whole-Genome Sequencing of a fluconazole-resistant C. auris strain (CA01) obtained from a patient's blood in Beijing. Genome analysis was conducted to classify the strain, and molecular docking was performed to understand the impact of mutations on drug resistance. RESULTS: Genome analysis revealed that CA01 belongs to the South Asia Clade (I) and shares the closest genetic relationship with previously reported strains BJCA001 and BJCA002. Notably, unlike BJCA001, CA01 exhibits significant resistance to fluconazole primarily due to the A395T mutation in the ERG11 gene. Molecular docking studies demonstrated that this mutation leads to geometric changes in the active site where fluconazole binds, resulting in decreased binding affinity. Additionally, the present findings have identified several core virulence genes in C. auris, such as RBF1. DISCUSSION: The findings from this study expand the understanding of the genetic diversity and adaptive mechanisms of C. auris within the South Asia Clade (I). The observed fluconazole resistance driven by the ERG11 mutation A395T highlights the need for heightened awareness and adaptation in clinical treatment strategies in China. This study provides critical insights into drug resistance and virulence profiles at a genetic level, which could guide future therapeutic and management strategies for C. auris infections.

Nosocomial transmission of fluconazole-resistant Candida glabrata bloodstream isolates revealed by whole-genome sequencing.

The clonal transmission of fluconazole-resistant Candida glabrata isolates within hospitals has seldom been analyzed by whole-genome sequencing (WGS). We performed WGS on 79 C. glabrata isolates, comprising 31 isolates from three premature infants with persistent C. glabrata bloodstream infection despite antifungal treatment in the same neonatal intensive care unit (NICU) in 2022 and 48 (27 fluconazole-resistant and 21 fluconazole-susceptible dose-dependent) bloodstream isolates from 48 patients in 15 South Korean hospitals from 2010 to 2022. Phylogenetic analysis based on WGS single-nucleotide polymorphisms (SNPs) distinguished the 79 isolates according to multilocus sequence typing (MLST) (17 sequence type [ST]3, 13 ST7, two ST22, 41 ST26, four ST55, and two ST59 isolates) and unveiled two possible clusters of nosocomial transmission among ST26 isolates. One cluster from two premature infants with overlapping NICU hospitalizations in 2022 encompassed 15 fluconazole-resistant isolates harboring pleiotropic drug-resistance transcription factor (Pdr1p) P258L (13 isolates) or N1086I (two isolates), together with 10 fluconazole-susceptible dose-dependent isolates lacking Pdr1p SNPs. The other cluster indicated unforeseen clonal transmission of fluconazole-resistant bloodstream isolates among five patients (four post-lung transplantation and one with diffuse interstitial lung disease) in the same hospital over 8 months. Among these five isolates, four obtained after exposure to azole antifungals harbored distinct Pdr1p SNPs (N1091D, E388Q, K365E, and R376Q). The findings reveal the transmission patterns of clonal bloodstream isolates of C. glabrata among patients undergoing antifungal treatment, exhibiting different levels of fluconazole susceptibility or distinct Pdr1p SNP profiles. IMPORTANCE: The prevalence of fluconazole-resistant bloodstream infections caused by Candida glabrata is increasing globally, but the transmission of these resistant strains within hospitals has rarely been documented. Through whole-genome sequencing and epidemiological analyses, this study identified two potential clusters of C. glabrata bloodstream infections within the same hospital, revealing the transmission of clonal C. glabrata strains with different levels of fluconazole susceptibility or distinct transcription factor pleiotropic drug resistance protein 1 (Pdr1p) single-nucleotide polymorphism profiles among patients receiving antifungal therapy.

Revolutionizing treatment for topical fungal infections: evaluating penetration-enhancer-containing vesicles as a fluconazole delivery system: Ex-vivo and in-vivo dermal testing.

Fungal infections pose a significant challenge in numerous developing nations and worldwide, necessitating urgent solutions. Oral administration of antifungal medications often leads to severe adverse reactions. Hence, employing topical delivery systems is preferred to ensure efficient dermal delivery of antifungal agents while minimizing side effects. Furthermore, the incorporation of penetration enhancers into nanocarriers loaded with antifungal agents has demonstrated enhanced efficacy in combating mycotic infections. Consequently, ultra-deformable penetration enhancer-containing vesicles (PEVs) were developed to explore this promising approach. In this study, Labrasol® and Transcutol® were used as penetration enhancers in formulating ultra-deformable PEVs containing the antifungal agent Fluconazole (FCZ). The PEVs underwent comprehensive characterization, including measurements of particle size (PS), charge, and entrapment efficiency (EE%). The results revealed that the size of tested PEVs ranged from 100 to 762 nm. All particles exhibited a negative charge, with a minimum zeta potential (ZP) of -38.26 mV, and an intermediate entrapment efficiency (EE%) that reached approximately 40%w/w. Ex-vivo studies demonstrated the ability of PEVs to deliver FCZ to the dermis while minimizing transdermal delivery. The selected formula was tested in-vivo using candidiasis-induced rat model and showed a superiority in its antifungal effect against Candida Albicans compared to the drug control. Stability studies were executed for the selected formula, and revealed good stability shown by the insignificant change in the PS, ZP& EE% over a six-month period.

Invasive Candida Infections in Neonatal Intensive Care Units: Risk Factors and New Insights in Prevention.

Invasive Candida infections represent a significant cause of morbidity and mortality in neonatal intensive care units (NICUs), with a particular impact on preterm and low-birth-weight neonates. In addition to prematurity, several predisposing factors for Candida colonization and dissemination during NICU hospitalization have been identified, including prolonged exposure to broad-spectrum antibiotics, central venous catheters, parenteral nutrition, corticosteroids, H2 antagonist administration, and poor adherence to infection control measures. According to the literature, the implementation of antifungal prophylaxis, mainly fluconazole, in high-risk populations has proven to be an effective strategy in reducing the incidence of fungal infections. This review aims to provide an overview of risk factors for invasive Candida infections and current perspectives regarding antifungal prophylaxis use. Recognizing and reducing people's exposure to these modifiable risk factors, in conjunction with the administration of antifungal prophylaxis, has been demonstrated to be an effective method for preventing invasive candidiasis in susceptible neonatal populations.

Emergence of rare and uncommon yeast-like pathogens causing neonatal sepsis at a tertiary care center, North India.

Introduction: Neonatal candidemia is a life-threatening event in babies requiring ICU admission. Prompt diagnosis and appropriate treatment reduce mortality and morbidity. Worldwide, there is an emergence of drug-resistant rare Candida species causing neonatal sepsis that necessitates antifungal susceptibility testing in each case. Methods: We did a prospective study to isolate Candida species causing neonatal sepsis and to determine the predisposing risk factors and time to positivity for flagged positivity. We also determined fluconazole, itraconazole and amphotericin B minimum inhibitory concentration (MIC) against isolated Candida species by broth microdilution method using CLSI M27-A3 guidelines. Results: A total of 107 neonatal candidemia events were noted. Prematurity was the most common predisposing risk factor. Most isolates were non-albicans Candida. Candida utilis, C. pelliculosa, C. tropicalis and K. ohmeri were the predominant fungi causing neonatal candidemia. A varied antifungal MIC against isolated Candida species was noted. However, 90% of the isolated Candida strains had <8 µg/mL fluconazole MIC. Moreover, ≥8 and ≥2 µg/mL MIC for fluconazole and amphotericin B respectively were also noted. Conclusions: Rare Candida species having varied fluconazole and amphotericin B MIC cause neonatal candidemia. Therefore, culture isolation and antifungal susceptibility testing should be done in each case of neonatal candidemia.

Comparative efficacy of antifungal drugs for the treatment of oral candidiasis in HIV-positive patients: A Bayesian network meta-analysis.

Oral candidiasis infection is particularly prevalent among individuals in HIV-positive patients. Antifungal drugs have shown promising therapeutic effects in treating oral candidiasis in HIV-positive patients. However, the selection of specific antifungal drugs for the treatment of oral candidiasis in HIV-positive patients lacks evidence-based guidelines. This study aims to address this gap by conducting a comprehensive review of relevant randomized controlled trials (RCTs) and performing a network meta-analysis to assess the efficacy of different antifungal drugs in treating oral candidiasis in HIV-positive patients. A systematic search was conducted in databases including EMBASE, Web of Science, Medline, and Cochrane databases to identify relevant articles. Additionally, key pertinent sources in the literatures were also reviewed. All studies published prior to August 2023 were eligible for inclusion. Two researchers independently conducted the screening of literature, extraction of data, and evaluation of quality. Pairwise and network meta-analysis were then performed to assess the primary outcomes of the randomized controlled trials (RCTs) included. The protocol was registered on the PROSPERO database (CRD42024513912). Twenty-six RCTs were included in this meta-analysis, involving a total of 3145 patients and evaluating seven interventions (placebo, fluconazole, itraconazole, nystatin, clotrimazole, ketoconazole, miconazole). Pairwise meta-analysis and network meta-analysis showed fluconazole was significantly efficacy in increasing mycological cure rates when compared with placebo, clotrimazole, and nystatin. Ketoconazole and miconazole were significantly efficacy in increasing mycological cure rates when compared with nystatin. Network meta-analysis also suggested the efficacy of the seven interventions in increasing mycological cure rates was ranked as follows: placebo (35.3%), fluconazole (95.2%), itraconazole (61.6%), nystatin (17.0%), clotrimazole (52.7%), ketoconazole (69.2%), miconazole (69.1%). The available evidence indicates that fluconazole had the greatest possibility to increase mycological cure rates in HIV-positive patients, while, nystatin was the least effective antifungal drug in increasing mycological cure rates in HIV-positive patients.

Clinical characteristics and outcomes of patients with candidemia during the COVID-19 pandemic: Insights from experience in the Omicron era.

BACKGROUND: In Taiwan, COVID-19 outbreaks caused by the Omicron variant occurred in 2022. We investigated the incidence of candidemia during COVID-19 pandemic and the mortality of candidemia patients with COVID-19 in Taiwan. METHODS: The incidence of candidemia and fluconazole susceptibility of Candida species before (2015-2019) and during COVID-19 pandemic (2020-2023) at Kaohsiung Chang Gung Memorial Hospital were investigated. The associated factors with mortality in candidemia patients during COVID-19 pandemic were analyzed. Candidemia patients who had COVID-19 within the prior 90 days (case group, n = 34) were propensity-score matched for age, ICU admission, and abdominal surgery in a 1:4 ratio with candidemia patients without COVID-19 (control group, n = 136). RESULTS: Age (adjusted odds ratio [AOR] = 1.02, 95% CI: 1.01-1.03), ICU stay (AOR = 1.84, 95% CI: 1.29-2.62), higher Charlson comorbidity index (AOR = 1.08, 95% CI: 1.03-1.13), corticosteroid use (AOR = 1.50, 95% CI: 1.04-2.17) were associated with increased risk of mortality; abdominal surgery (AOR = 0.47, 95% CI: 0.29-0.74) and infected by Candida parapsilosis (AOR = 0.61, 95% CI: 0.38-0.98) were associated with decreased risk of mortality. After matching, there was no significant difference in mortality rates between the case and control groups. The incidence of candidemia increased from 196 to 278 patients/100,000 admissions during COVID-19 pandemic, while the causative species of candidemia and fluconazole susceptibility rates were similar. CONCLUSION: While the incidence of candidemia increased during COVID-19 pandemic, there was no significant difference in mortality between candidemia patients with and without COVID-19 in the Omicron era.