OBJECTIVES: To investigate the clinical characteristics and prognosis of chronic disseminated candidiasis (CDC) in children with acute leukemia (AL) following chemotherapy. METHODS: A retrospective analysis was conducted on children diagnosed with CDC (including confirmed, clinically diagnosed, and suspected cases) after AL chemotherapy from January 2015 to December 2023 at Fujian Medical University Union Hospital, Zhangzhou Municipal Hospital, and Quanzhou First Hospital Affiliated to Fujian Medical University. Clinical characteristics and prognosis were analyzed. RESULTS: The incidence of CDC in children with AL following chemotherapy was 1.92% (32/1 668). Among the children with acute lymphoblastic leukemia, the incidence of CDC in the high-risk group was significantly higher than in the low-risk group (P=0.002). All patients presented with fever unresponsive to antibiotics during the neutropenic period, with 81% (26/32) involving the liver. C-reactive protein (CRP) levels were significantly elevated (≥50 mg/L) in 97% (31/32) of the patients. The efficacy of combined therapy with liposomal amphotericin B and caspofungin or posaconazole for CDC was 66% (19/29), higher than with caspofungin (9%, 2/22) or liposomal amphotericin B (18%, 2/11) monotherapy. The overall cure rate was 72% (23/32). The proportion of patients with CRP ≥50 mg/L and/or a positive β-D-glucan test for more than 2 weeks and breakthrough infections during caspofungin treatment was significantly higher in the treatment failure group compared to the successful treatment group (P<0.05). CONCLUSIONS CDC in children with AL after chemotherapy may be associated with prolonged neutropenia due to intensive chemotherapy. Combination antifungal regimens based on liposomal amphotericin B have a higher cure rate, while persistently high CRP levels and positive β-D-glucan tests may indicate poor prognosis.
Adolescent ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Male ; Antifungal Agents/therapeutic use* ; Candidiasis/diagnosis* ; Chronic Disease ; Leukemia/complications* ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/complications* ; Prognosis ; Retrospective Studies

OBJECTIVE: To investigate the therapeutic efficacy of cinnamaldehyde (CA) on systemic Candida albicans infection in mice and to provide supportive data for the development of novel antifungal drugs. METHODS: Ninety BALB/c mice were randomly divided into 3 groups according to a random number table: CA treatment group, fluconazole (positive control) group, and Tween saline (negative control) group, with 30 mice in each group. Initially, all groups of mice received consecutive intraperitoneal injections of cyclophosphamide at 200 mg/kg for 2 days, followed by intraperitoneal injection of 0.25 mL C. albicans fungal suspension (concentration of 1.0 × 10⁷ CFU/mL) on the 4th day, to establish an immunosuppressed systemic Candida albicans infection animal model. Subsequently, the mice were orally administered CA, fluconazole and Tween saline, at 240, 240 mg/kg and 0.25 mL/kg respectively for 14 days. After a 48-h discontinuation of treatment, the liver, small intestine, and kidney tissues of mice were collected for fungal direct microscopic examination, culture, and histopathological examination. Additionally, renal tissues from each group of mice were collected for (1,3)- β -D-glucan detection. The survival status of mice in all groups was monitored for 14 days of drug administration. RESULTS: The CA group exhibited a fungal clearance rate of C. albicans above 86.7% (26/30), significantly higher than the fluconazole group (60.0%, 18/30, P<0.01) and the Tween saline group (30.0%, 9/30, P<0.01). Furthermore, histopathological examination in the CA group revealed the disappearance of inflammatory cells and near-normal restoration of tissue structure. The (1,3)-β-D-glucan detection value in the CA group (860.55 ± 126.73 pg/mL) was significantly lower than that in the fluconazole group (1985.13 ± 203.56 pg/mL, P<0.01) and the Tween saline group (5910.20 ± 320.56 pg/mL, P<0.01). The mouse survival rate reached 90.0% (27/30), higher than the fluconazole group (60.0%, 18/30) and the Tween saline group (30.0%, 9/30), with a significant difference between the two groups (both P<0.01). CONCLUSIONS CA treatment exhibited significant therapeutic efficacy in mice with systemic C. albicans infection. Therefore, CA holds potential as a novel antifungal agent for targeted treatment of C. albicans infection.
Animals ; Acrolein/pharmacology* ; Candida albicans/physiology* ; Mice, Inbred BALB C ; Candidiasis/pathology* ; Antifungal Agents/therapeutic use* ; Mice ; Fluconazole/therapeutic use* ; Kidney/drug effects* ; Female

OBJECTIVES: To explore the efficacy of low-intensity pulsed ultrasound (LIPUS) combined with nystatin for treatment of vaginal Candida albicans biofilm infection. METHODS: In vitro cultured Candida albicans biofilm were treated with LIPUS, nystatin, or both, and the minimum inhibitory concentration (MIC) of nystatin was determined. Crystal violet staining, confocal laser microscopy (CLSM) and scanning electron microscopy were used to quantify the biofilm and observe the activity and morphological changes of the biofilms; DCFH-DA was used to detect the changes in reactive oxygen species (ROS). Twenty female New Zealand White rabbits with vaginal inoculation of Candida albicans biofilm were randomized into 4 groups for treatment with normal saline, LIPUS, nystatin, or both LIPUS and nystatin. The changes in vulvar symptoms of the rabbits were observed, and the histopathological and ultrastructural changes of the vagina before and after treatment were observed using HE staining and transmission electron microscopy. RESULTS: In the combined treatment group, the MIC₅₀ and MIC₈₀ of nystatin in Candida albicans biofilms were both reduced by 50% compared with those in nystatin group, and the biofilm clearance rate increased by 26% and 68% compared with nystatin and LIPUS groups, respectively. Compared with nystatin and LIPUS treatment alone, the combined treatment produced stronger effects for inhibiting biofilm activity, causing structural disruption and promoting ROS production. In the rabbit models, the combined treatment more effectively improved vulvar symptoms and inflammatory infiltration, reduced residual vaginal hyphae/strains, and improved ultrastructure of the vaginal epithelium than LIPUS and nystatin treatment alone. CONCLUSIONS LIPUS combined with nystatin produces a significant synergistic antifungal effect against Candida albicans biofilm both in vitro and in vivo.
Animals ; Rabbits ; Female ; Biofilms/drug effects* ; Candida albicans/physiology* ; Nystatin/therapeutic use* ; Candidiasis, Vulvovaginal/microbiology* ; Ultrasonic Waves ; Antifungal Agents/therapeutic use* ; Vagina/microbiology* ; Ultrasonic Therapy ; Microbial Sensitivity Tests ; Combined Modality Therapy

Intra-abdominal candidiasis (IAC) is the most common invasive candidiasis, with a high incidence among critically ill patients, which can significantly increase medical costs and affect prognosis. In order to standardize the diagnosis and treatment of IAC in critically ill patients, experts in related fields were organized by the Peking University Critical Care Medicine (PKUCCM), Committee of Critical Care Medicine and Organ Support, China Association for Promotion of Health Science and Technology organized experts in related fields to initiate and form a working group. Expert writers drafted the consensus based on evidence-based medical evidence. A committee composed of critical care physicians, infectious disease physicians, surgeons, dermatologists specializing in antifungal fields, and clinical pharmacists discussed and revised the consensus draft through a standardized process, and finally formulated this consensus. This consensus contains a total of 20 core recommendations, mainly focusing on the epidemiology, high-risk factors, diagnostic techniques and methods (including traditional microbiological culture techniques, clinical risk prediction tools, serological tests, molecular biological tests, and histopathological examinations) of IAC, diagnostic criteria, stratified treatment strategies, antifungal drug selection, control the sources of infection, combined treatment, de-escalation strategies, drug treatment courses, prognosis, and special types of IAC. The aim is to provide expert guidance for the standardized clinical diagnosis and treatment of IAC in critically ill patients, with a view to improving prognosis of patients.
Humans ; Critical Illness ; Intraabdominal Infections/therapy* ; Antifungal Agents/therapeutic use* ; Consensus ; Candidiasis/drug therapy* ; Critical Care ; Candidiasis, Invasive/diagnosis*

Extracorporeal membrane oxygenation (ECMO) technology is an important life support method for critically ill patients. A large number of studies have found that ECMO can change the pharmacokinetic (PK) parameters of critically ill patients, thereby affecting the drug effect in vivo. However, there is still a lack of recommendations for the adjustment of commonly used drugs during ECMO support in China, and the selection or dosage adjustment of drugs during ECMO support is not clear. Therefore, a multidisciplinary group of domestic experts in clinical pharmacy and critical care medicine was established by Critical Care Medicine Committee of China International Exchange and Promotive Association for Medical and Health Care, and Hospital Pharmacy Committee of China Pharmaceutical Association, to develop the Expert consensus on drug adjustment during extracorporeal membrane oxygenation support (2025). Eight clinical issues of drug adjustment during ECMO support were discussed in this consensus: (1) Why does the patient's demand for drug dosage change during ECMO support? (2) What factors are related to the degree of drug loss during ECMO support? (3) Considering the features of drugs, which types of drugs may need to be adjusted during ECMO support? (4) How to adjust the dosage when using antibacterial drugs during ECMO support? (5) How to adjust antifungal drugs during ECMO support? (6) Does ECMO support change patients' dosage requirements for antiviral drugs? (7) How to adjust sedative and analgesic drugs during ECMO support? (8) Does ECMO support affect the dosage requirement of vasoactive agents? Eighteen consensus are elaborated based on the latest clinical evidence, aiming to provide recommendations for drug adjustment in critically ill patients receiving ECMO support to ensure the safety and effectiveness of medication.
Humans ; Critical Illness ; Extracorporeal Membrane Oxygenation ; Consensus ; Candidiasis/drug therapy* ; Intraabdominal Infections/therapy*

BACKGROUND

Invasive candidiasis is defined by the growth of Candida species in the bloodstream or other internal organs. It is a global concern due to increasing multidrug resistance and high mortality rates. This study aimed to update prevalence data on Candida infections in the Philippines, analyzing demographic factors (age, sex), specimen sources, and associated risk factors. We compared antifungal resistance patterns against CLSI epidemiological cutoff values (ECVs) and clinical breakpoints and examined MIC variations by underlying disease to inform potential standardized empiric therapies.

We conducted a retrospective analytical cross-sectional study (SLMC-IERC approval, minimal risk) reviewing one year of Candida speciation and susceptibility results from January 2024 to December 2024 at a private tertiary hospital. All aseptically collected samples that tested positive for Candida species were included. Respiratory and wound specimens required a Gram stain demonstrating yeasts and hyphae prior to culture, while urine cultures were included only if they yielded ≥100,000 CFU/mL. Identification and susceptibility testing were performed using the VITEK 2 system, with results interpreted using CLSI breakpoints and ECVs.

Among 266 patients with Candida infections, invasive candidiasis predominated in those aged ≥60 years (66.4%). Candida albicans (21.7%) and Candida tropicalis (13.5%) were more frequent in females, while Candida parapsilosis (13.2%) and Candida glabrata (5.3%) were more common in males. Blood and CSF samples strongly correlated with invasive disease and underlying risk factors. C. albicans was linked to infection-related conditions (13.9%), malignancy (9.0%), and cardiovascular disease (6.8%). C. parapsilosis(23.3%) and C. tropicalis (20.7%) were frequently associated with infection, malignancy, and metabolic disorders. C. glabrata (7.5%), noted for antifungal resistance, was isolated in patients with direct infections (3.4%) and malignancies (1.9%). Among azoles, fluconazole demonstrated greater susceptibility against Candida species, requiring lower concentrations for inhibition, despite a higher resistance rate (13.22%) compared to voriconazole (8.95%). Among echinocandins, micafungin showed better susceptibility than caspofungin. Amphotericin B demonstrated the highest overall susceptibilit y (93 –10 0%), though MICs approached ECV limits. Most susceptible MIC values were fluconazole 0.5 μg/mL for C. albicans and C. parapsilosis, 1.0 μg/mL for C. tropicalis; voriconazole and caspofungin 0.12 μg/mL; micafungin 0.06 μg/mL; amphotericin B 0.5 μg/mL; and flucytosine

These findings support a species-specific, risk-adapted approach to antifungal therapy, incorporating demographic and clinical variables. Continuous surveillance of invasive candidiasis prevalence and antifungal MIC trends, with periodic breakpoint updates, is crucial to preserve therapeutic efficacy. Effective management of multidrug-resistant Candidainfections also requires close collaboration between clinicians and pharmacists, as well as the development of new dosing strategies based on pharmacokinetic/pharmacodynamic (PK/PD) principles.

BACKGROUND

Candida infections range from oral candidiasis to candida endophthalmitis, peritonitis and candidemia. Invasive fungal disease or disseminated candidiasis is highly fatal among children. There are no studies done in the pediatric population to detect early candida infection to help identify those who will benefit from early and prompt medical treatment.

This study determined the value of Candida scoring (CS) as a predictive tool for invasive candidiasis among pediatric patients admitted in the intensive care units of a tertiary referral center.

This was a retrospective cross sectional study where 4184 charts of pediatric patients and admitted in the ICU between January 2018 to December 2020 were reviewed. Patients were scored upon admission, after 3 days, after 1 week and weekly thereafter until discharge or demise. The scoring tool used was developed by Leon et al., and uses four variables: presence of sepsis, use of total parenteral nutrition (TPN), presence of multifocal colonization and presence of surgery. Data collected for Candida scores were presented as frequencies and percentages.

There were 396 patients enrolled in this study and 25.7% were treated for candida infection. Majority were newborns where 78.7% had a CS >3, which is statistically significant, p =3 which is statistically significant. Among intubated patients, 84% had a CS of >3 and all patients on TPN had a CS of >3, both of which are significant. CS could correctly predict 64.6% of patients who will likely have candida infection.

Candida scoring is a tool that can be used in patients at high risk of developing Candida infection. In this study, a CS of >3 can be used to predict Candida infection in the ICU.

Background and Objectives: Oral candidiasis (OC) is a well-known local side effect of inhaled corticosteroid (ICS) therapy in patients with asthma and chronic obstructive pulmonary disease (COPD). This study aimed to determine the prevalence of OC and its association with ICS-related factors in out-patient asthma and COPD patients of the Departments of Pulmonology and Pediatric Pulmonology of the Philippine General Hospital (PGH). Methods: This is a cross-sectional study conducted from October 2019 to January 2020. Data was collected through a two-part questionnaire accomplished by doctors and patients with asthma or COPD. Results. A total of 67 patients were included in the study. Oral candidiasis was observed in 4 (5.97%) ICS users, and the prevalence was 1.65% to 14.59% (95% CI, SE: 0.028946). Conclusion This study determined the prevalence of oral candidiasis in asthma and COPD patients and its association with ICS-related factors, including the dosage, medication, device, and duration of therapy. The prevalence of OC in ICS users in PGH cannot be interpreted as high or low due to the small number of respondents, but is consistent with OC prevalence found in related literature. Increased prevalence was observed in adult females with asthma under low dose ICS therapy with Fluticasone/Salmeterol DPI for more than a year. There was no statistically significant correlation among OC prevalence, age, sex, and components of ICS-therapy including dosage, medication, device, frequency, and duration of therapy. A large-scale study is recommended for more accurate assessment of OC prevalence in the population and to determine statistically significant associations among the factors. It is also recommended to quantifiably measure patient compliance, inhalation technique and instruction, and its association to OC prevalence. Findings may be used to strengthen patient education, preventive measures, and disease management to facilitate improved compliance and effective treatment outcomes.
Candidiasis, Oral ; Adrenal Cortex Hormones ; Asthma ; Pulmonary Disease, Chronic Obstructive

Objective: To establish a nested recombinant enzyme-assisted polymerase chain reaction (RAP) technique combined with recombined mannose-binding lectin protein (M1 protein)-magnetic beads enrichment for the detection of Candida albicans (C. albicans) and Candida tropicalis (C. tropicalis) in blood samples for the early diagnosis of candidemia albicans and candidiemia tropicalis. Methods: The primer probes for highly conserved regions of the internal transcribed spacerregions of C. albicans and C. tropicalis were deigned to establish RAP assays for the detections of C. albicans and C. tropicalis; The sensitivity and reproducibility of nucleic acid tests with gradient dilutions of standard strains and specificity of nucleic acid tests with common clinical pathogens causing bloodstream infection were condcuted. M1 protein-magnetic bead enriched plasma C. albicans and C. tropicalis were used for RAP and PCR in with simulated samples and the results were compared. Results: The sensitivity of the established dual RAP assay was 2.4-2.8 copies/reaction, with higher reproducibility and specificity. M1 protein-magnetic bead enrichment of pathogen combined with the dual RAP assay could complete the detections of C. albicans and C. tropicalis in plasma within 4 hours. Fie the pathogen samples at concentration <10 CFU/ml, the number of the samples tested by RAP was higher than that tested by PCR after enrichment. Conclusion: In this study, a dual RAP assay for the detections of C. albicans and C. tropicalis in blood sample was developed, which has the advantages of accuracy, rapidity, and less contaminants and has great potential for rapid detection of Candidemia.
Humans ; Lectins ; Candida ; Candidemia ; Reproducibility of Results ; Polymerase Chain Reaction ; Nucleic Acids ; Magnetic Phenomena

This study aimed to explore the mechanism of n-butanol alcohol extract of Baitouweng Decoction(BAEB) in the treatment of vulvovaginal candidiasis(VVC) in mice based on the negative regulation of NLRP3 inflammasome via PKCδ/NLRC4/IL-1Ra axis. In the experiment, female C57BL/6 mice were divided randomly into the following six groups: a blank control group, a VVC model group, high-, medium-, and low-dose BAEB groups(80, 40, and 20 mg·kg~(-1)), and a fluconazole group(20 mg·kg~(-1)). The VVC model was induced in mice except for those in the blank control group by the estrogen dependence method. After modeling, no treatment was carried out in the blank control group. The mice in the high-, medium-, and low-dose BAEB groups were treated with BAEB at 80, 40, and 20 mg·kg~(-1), respectively, and those in the fluconazole group were treated with fluconazole at 20 mg·kg~(-1). The mice in the VVC model group received the same volume of normal saline. The general state and body weight of mice in each group were observed every day, and the morphological changes of Candida albicans in the vaginal lavage of mice were examined by Gram staining. The fungal load in the vaginal lavage of mice was detected by microdilution assay. After the mice were killed, the degree of neutrophil infiltration in the vaginal lavage was detected by Papanicolaou staining. The content of inflammatory cytokines interleukin(IL)-1β, IL-18, and lactate dehydrogenase(LDH) in the vaginal lavage was tested by enzyme-linked immunosorbent assay(ELISA), and vaginal histopathology was analyzed by hematoxylin-eosin(HE) staining. The expression and distribution of NLRP3, PKCδ, pNLRC4, and IL-1Ra in vaginal tissues were measured by immunohistochemistry(IHC), and the expression and distribution of pNLRC4 and IL-1Ra in vaginal tissues were detected by immunofluorescence(IF). The protein expression of NLRP3, PKCδ, pNLRC4, and IL-1Ra was detected by Western blot(WB), and the mRNA expression of NLRP3, PKCδ, pNLRC4, and IL-1Ra was detected by qRT-PCR. The results showed that compared with the blank control group, the VVC model group showed redness, edema, and white secretions in the vagina. Compared with the VVC model group, the BAEB groups showed improved general state of VVC mice. As revealed by Gram staining, Papanicolaou staining, microdilution assay, and HE staining, compared with the blank control group, the VVC model group showed a large number of hyphae, neutrophils infiltration, and increased fungal load in the vaginal lavage, destroyed vaginal mucosa, and infiltration of a large number of inflammatory cells. BAEB could reduce the transformation of C. albicans from yeast to hyphae. High-dose BAEB could significantly reduce neutrophil infiltration and fungal load. Low-and medium-dose BAEB could reduce the da-mage to the vaginal tissue, while high-dose BAEB could restore the damaged vaginal tissues to normal levels. ELISA results showed that the content of inflammatory cytokines IL-1β, IL-18, and LDH in the VVC model group significantly increased compared with that in the blank control group, and the content of IL-1β, IL-18 and LDH in the medium-and high-dose BAEB groups was significantly reduced compared with that in the VVC model group. WB and qRT-PCR results showed that compared with the blank control group, the VVC model group showed reduced protein and mRNA expression of PKCδ, pNLRC4, and IL-1Ra in vaginal tissues of mice and increased protein and mRNA expression of NLRP3. Compared with the VVC model group, the medium-and high-dose BAEB groups showed up-regulated protein and mRNA expression of PKCδ, pNLRC4, and IL-1Ra in vaginal tissues and inhibited protein and mRNA expression of NLRP3 in vaginal tissues. This study indicated that the therapeutic effect of BAEB on VVC mice was presumably related to the negative regulation of NLRP3 inflammasome by promoting PKCδ/NLRC4/IL-1Ra axis.
Female ; Animals ; Humans ; Mice ; Candidiasis, Vulvovaginal/drug therapy* ; Inflammasomes/genetics* ; Interleukin-18 ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; 1-Butanol/pharmacology* ; Fluconazole/therapeutic use* ; Interleukin 1 Receptor Antagonist Protein/therapeutic use* ; Mice, Inbred C57BL ; Candida albicans ; Cytokines ; Drugs, Chinese Herbal/pharmacology* ; Ethanol ; RNA, Messenger ; Calcium-Binding Proteins/therapeutic use*