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Acta Medica Indonesiana Oct 2019Tuberculosis (TB) remains a worldwide scourge and the most common cause of mortality from infectious disease. Around 95% of cases occur in developing country. Renal TB...
Tuberculosis (TB) remains a worldwide scourge and the most common cause of mortality from infectious disease. Around 95% of cases occur in developing country. Renal TB is a rare cases that complicates 3-4% of pulmonary TB patients and commonly overlooked in clinical practice due to its symptoms may mimic other diseases.A-39-year-old man was admitted to our institution due to flank pain. He had history of low grade fever and oligouria since 5 months prior. He had no complaint of cough, dyspnea, or night sweat. He was a non smoker and had no past medical history of tuberculosis. Previous 4 months abdominal ultrasound showed left pelvocaliectasis and ureteral dilatation with suspicion of left ureteral stenosis. Ureterolithiasis could not be excluded. No prostate enlargement or vesicolithiasis was seen. Intravenous pyelography (IVP) examination demonstrated similar finding. Initial laboratory blood examination showed anemia (10.7 g/dl), leukocytosis (14,080/ul), increased in serum creatinin (4.2 mg/dl), ureum (227 mg/dl), and calcium (6.78 mg/dl). Serology examinations were negative for HIV, HBsAg, anti HCV and blood culture had no growth. Urinary examination revealed severe leucocyturia, hematuria, and negative for bacteria, nitrite and cast. Urine culture was positive for Candida glabrata. Pulmonary X-ray suggested right pleural fibrotic. He was initially diagnosed as multiple myeloma with fungal infection. Nevertheless, additional peripheral blood smear showed neither rouleaux formation nor blast. He underwent percutaneous nephrostomy and got micafungin intravenously. Instead of improving, the patient deteriorated and transferred to intensive room. We then explored the possibility of TB infection. Further examination revealed positive for Mycobacterium tuberculosis in urinary polymerase chain reaction (PCR) test. Tracheal sputum examination was positive for acid fast bacilli staining. There was low level of serum vitamin D2 (5.8 ng/ml). He got TB treatment with rifampicin, isoniazid, pyrazinamide, and ethambutol. Unfortunately, the patient eventually succumbed.
Topics: Adult; Antitubercular Agents; Diagnosis, Differential; Humans; Male; Mycobacterium tuberculosis; Radiography, Thoracic; Tuberculosis, Pulmonary; Tuberculosis, Renal; Ultrasonography; Vitamin D Deficiency
PubMed: 32041921
DOI: No ID Found -
Current Medical Mycology Mar 2022Oral candidiasis has become a growing problem in hospitals worldwide, and the development of antifungal drug resistance in species constitutes a serious concern. This...
BACKGROUND AND PURPOSE
Oral candidiasis has become a growing problem in hospitals worldwide, and the development of antifungal drug resistance in species constitutes a serious concern. This study aimed to evaluate the efficacy of nystatin, and micafungin with chlorhexidine against fluconazole-resistant and fluconazole-sensitive () isolates.
MATERIALS AND METHODS
In this experimental-laboratory study, a total of 20 fluconazole-resistant (n=10) and fluconazole-susceptible (n=10) strains were obtained from the reference culture collection of the Invasive Fungi Research Center in Mazandaran University of Medical Sciences, Sari, Iran. combination of nystatin and micafungin with chlorhexidine was performed using a microdilution checkerboard method based on the Clinical and Laboratory Standards Institute guideline.
RESULTS
Micafungin had the highest antifungal activity against susceptible and resistant strains, with a Geometric mean of (GM) =0.008µg/ml and GM=0.008µg/ml, followed by nystatin with GM=0.06µg/ml and GM=0.042µg/ml and chlorhexidine with GM=0.25µg/ml and GM=0.165µg/ml against resistant and sensitive strains, respectively. The interaction of micafungin and nystatin with chlorhexidine showed a synergistic interaction against most strains. In addition, no antagonistic interaction was observed between micafungin, nystatin, and chlorhexidine against strains.
CONCLUSION
The synergistic interaction of micafungin with chlorhexidine against azole-resistant suggests an alternative approach to overcome antifungal drug resistance. However, further studies are needed for evaluation.
PubMed: 36340437
DOI: 10.18502/cmm.8.1.9208 -
Expert Opinion on Pharmacotherapy Dec 2022Invasive candidiasis remains a leading cause of morbidity and mortality in various categories of patients at risk. (Review)
Review
INTRODUCTION
Invasive candidiasis remains a leading cause of morbidity and mortality in various categories of patients at risk.
AREAS COVERED
Structure and mechanism of action, pharmacokinetics and pharmacodynamics, clinical studies, safety, and regulatory status of micafungin are explored in the present review, focusing on pediatric patients younger than 4 months old.
EXPERT OPINION
Although limited, the available data on the efficacy and safety of micafungin in pediatric patients younger than 4 months old support its use for the treatment of invasive candidiasis in this particular population, in line with the most updated recommendations from the European Medicines Agency and the US Food and Drug Administration. Additional study, especially of high-dose micafungin, could further optimize the use of this drug in pediatric patients younger than 4 months old with meningoencephalitis. The recent worrisome worldwide diffusion of , more frequently resistant to polyenes than to echinocandins and showing high rates of resistance to azoles, could render micafungin even more crucial for guaranteeing an efficacious antifungal treatment for invasive candidiasis in pediatric patients younger than 4 months old.
Topics: Humans; Child; Infant; Micafungin; Lipopeptides; Candidiasis, Invasive; Echinocandins; Antifungal Agents
PubMed: 36373395
DOI: 10.1080/14656566.2022.2147824 -
Clinical Laboratory Jun 2023This study assessed the potential effect of combining micafungin and tobramycin in vitro against biofilms of clinical Pseudomonas aeruginosa isolates.
BACKGROUND
This study assessed the potential effect of combining micafungin and tobramycin in vitro against biofilms of clinical Pseudomonas aeruginosa isolates.
METHODS
Nine biofilm-positive clinical isolates of P. aeruginosa were used in this study. The minimum inhibitory concentrations (MICs) of micafungin and tobramycin for planktonic bacteria were determined using the agar dilution method. The planktonic bacterial growth curve was plotted for micafungin treatment. Biofilms of these nine strains were treated with different concentrations of micafungin and combined with tobramycin in microtiter plates. Biofilm biomass was detected by crystal violet staining and spectrophotometry. Phenotypic reduction in biofilm formation and the eradication of mature biofilm were significant based on average optical density (p < 0.05). The kinetics of micafungin combined with tobramycin to eradicate mature biofilms was investigated in vitro using the time-kill method.
RESULTS
Micafungin exhibited no antibacterial effect on P. aeruginosa, and tobramycin minimum inhibitory concentrations (MICs) did not change in the presence of micafungin. Micafungin alone inhibited biofilm formation and eradicated established biofilms of all isolates in a dose-dependent manner, but the required minimum concentration varied. An increase in micafungin concentration resulted in an observed inhibition rate of 64.9% - 72.3% and achieved an eradication rate of 59.2% - 64.5%. Its combination with tobramycin exhibited synergistic effects, including inhibiting the biofilm formation of PA02, PA05, PA23, PA24, and PA52 isolates above 1/4 × MIC or 1/2 × MIC and eradicating mature biofilms of PA02, PA04, PA23, PA24, and PA52 above 32 × MIC, 2 × MIC, 16 × MIC, 32 × MIC, and 1 × MIC, respectively. Micafungin addition could eradicate biofilm-embedded bacterial cells more rapidly; at 32 mg/L, the biofilm eradication time lowered from 24 hours to 12 hours for the inoculum groups with 106 CFU/mL, and from 12 hours to 8 hours for 105 CFU/mL. Whereas at 128 mg/L, the time was lowered from 12 hours to 8 hours for the inoculum groups with 106 CFU/mL, and from 8 hours to 4 hours for 105 CFU/mL.
CONCLUSIONS
Micafungin showed good anti-biofilm activity at low concentrations. The combination of micafungin with tobramycin displayed a synergistic effect in controlling P. aeruginosa biofilm.
Topics: Humans; Tobramycin; Pseudomonas aeruginosa; Micafungin; Anti-Bacterial Agents; Biofilms
PubMed: 37307133
DOI: 10.7754/Clin.Lab.2022.220841 -
Mikrobiyoloji Bulteni Jan 2020Micafungin is recommended especially in patients with liver and kidney failure and in the presence of other side effects due to antifungals apart from its known priority...
Micafungin is recommended especially in patients with liver and kidney failure and in the presence of other side effects due to antifungals apart from its known priority indications such as invasive candidiasis. The aim of this study was to evaluate the children who have received micafungin treatment. In the study, 125 children who were hospitalized in the pediatric wards and intensive care units of our hospital and had used micafungin between November 2016 and January 2019 were analyzed retrospectively. Clinical data, micafungin indication, blood values on the first and fourth days of the treatment, side effects of the drug and efficacy were evaluated. Sixty percent (75/125) of the patients were male and the mean age of all the patients were 58 ± 67 (0-215, 30) months. Approximately half of the cases (48%) had malignancy and 13% of them were premature. Sixty-two percent (n= 37) of the malignencies were hematological (27 acute lymphocytic leukemia, nine acute myeloid leukemia, one myelodysplastic syndrome) and 38% (n= 23) were oncological (six neuroblastoma, four Hodgkin lymphoma, two Non-Hodgkin's lymphoma, five sarcomas, one hepatoblastoma, five others) malignencies. The major cause of hospitalization was sepsis (53%). The patients had several risk factors like immunosuppressive therapy (n= 68, 54%), neutropenia (n= 61, 49%), central venous catheter (n= 102, 82%), nasogastric tube (n= 63, 50%), endotracheal intubation tube (n= 49, 39%), urinary catheter (n= 14, 11%) and total parenteral nutrition (n= 81, 65%). Thirteen percent (n= 16) of the cases were post-operative patients. Candida species were cultivated in 97 clinical specimens (blood, endotracheal aspirate, sputum, urine, etc.) among 23 (18%) of the patients. Thirteen (10%) of the patients had candidemia and 62% of them were non-albicans strains. In all candidemias, strains were echinocandin susceptible, and blood cultures were negative within four days. When all the patients (n= 125) were evaluated, a significant decrease in C-reactive protein, an increase in sodium, and a decrease in alanine aminotransferase were observed on the fourth day of micafungin treatment (p<0.05). A total of 39 (31%) patients underwent various antifungal treatments for median seven (1-60) days prior to micafungin treatment. Fourteen (36%) of these 39 patients, had elevated liver function tests (LFT), 10 (26%) of them had hypokalemia, and five (13%) of them had elevated renal function tests. Ten (26%) patients had antifungal-induced hypokalemia previously; and potassium levels were normalized after micafungin treatment (p= 0.0001). The patients for which micafungin treatment was chosen due to elevated liver function tests (n= 47, 38%), whether the antifungalinduced or not; alanine aminotransferase and aspartate aminotransferase levels were decreased after micafungin treatment (p= 0.0001 and p= 0.0001, respectively). Nineteen (15%) of the patients have died within the first 30 days of micafungin treatment and one of them had candidemia. No micafungin treatment related significant side effects were observed in any of the patients. Our study showed that micafungin could be a safe and effective option in pediatric cases including newborns with high liver and kidney function tests.
Topics: Antifungal Agents; Child; Child, Preschool; Female; Humans; Infant; Infant, Newborn; Lipopeptides; Male; Micafungin; Retrospective Studies
PubMed: 32050883
DOI: 10.5578/mb.68832 -
American Journal of Health-system... Apr 2023Echinocandins are favored drugs for the treatment of fungal infections. There is growing evidence that obese patients treated with echinocandins have lower exposures due... (Review)
Review
PURPOSE
Echinocandins are favored drugs for the treatment of fungal infections. There is growing evidence that obese patients treated with echinocandins have lower exposures due to pharmacokinetic (PK) alterations. We conducted a scoping review to characterize, evaluate, and summarize the available evidence on echinocandins exposures in obese patients.
SUMMARY
A comprehensive search of PubMed, Embase, and Cochrane Library for studies on echinocandins published from database inception to October 28, 2022, was conducted using PRISMA-ScR methodology. A total of 25 studies comprising more than 3,174 subjects (8 micafungin studies, 7 caspofungin studies, 9 anidulafungin studies, and 1 rezafungin study) were included in this review. Seventeen studies reported lower echinocandins exposures in overweight and obese individuals compared with normal-weight individuals; the authors of these studies recommended dose adjustments. Conversely, 8 studies did not find significant differences in echinocandin exposure among subjects in varying body weight categories. Clinicians may consider dose adjustments of echinocandins in obese patients; however, there is limited evidence on the ideal dose adjustment strategy to overcome the low echinocandins exposures in obese patients.
CONCLUSION
This scoping review shed light on a growing body of evidence indicating that obese patients have lower echinocandin exposures relative to targeted PK indices, which may lead to negative therapeutic implications. Currently, a lack of high-quality evidence impedes reaching consensus on recommendations for echinocandin dosing adjustment in obese patients. Future research evaluating the optimal echinocandin dosing strategy for obese patients is needed.
Topics: Humans; Antifungal Agents; Body Weight; Echinocandins; Lipopeptides; Microbial Sensitivity Tests; Obesity; Overweight
PubMed: 36680786
DOI: 10.1093/ajhp/zxad021 -
Expert Review of Anti-infective Therapy Apr 2022Neonates and young infants with invasive candidiasis are particularly at increased risk of dissemination including hematogenous meningoencephalitis. The echinocandins... (Review)
Review
INTRODUCTION
Neonates and young infants with invasive candidiasis are particularly at increased risk of dissemination including hematogenous meningoencephalitis. The echinocandins including micafungin have emerged as a preferred agent in most cases of candidemia and invasive candidiasis but data in pediatric patients under 4 months of age are limited.
AREAS COVERED
In this report, we review the micafungin use in infants younger than 4 months of age. Animal studies as well as clinical data that support its use in neonatal candidiasis are reviewed. In addition, the status of FDA approval and the rationale of micafungin dosing recommendations in infants <4 months are discussed.
EXPERT OPINION
A dose of 4 mg/kg was approved for treatment of candidemia, peritonitis and abscesses excluding meningoencephalitis or ocular involvement in patients younger than 4 months of age. However, because of the risk of central nervous system dissemination as well as the difficulty in establishing this diagnosis, this dose is inadequate to treat ill infants with candidemia. More studies are needed to establish the safety and efficacy of micafungin daily dose of at least 10 mg/kg in infants younger than 4 months of age when hematogenous meningoencephalitis or ocular involvement cannot be excluded.
Topics: Animals; Antifungal Agents; Candida; Candidemia; Candidiasis; Candidiasis, Invasive; Child; Echinocandins; Humans; Lipopeptides; Meningoencephalitis; Micafungin
PubMed: 34882043
DOI: 10.1080/14787210.2022.2013807 -
Diagnostic Microbiology and Infectious... Oct 2022We investigated the neutralization performance of various automated blood culture systems for antifungal agents with regard to the most commonly isolated Candida species.
BACKGROUND
We investigated the neutralization performance of various automated blood culture systems for antifungal agents with regard to the most commonly isolated Candida species.
METHODS
In this study, we evaluated the time to detection (TTD) of simulated candidemia for 6 Candida spp. (C. albicans, C. auris, C. glabrata, C. krusei, C. parapsilosis, and C. tropicalis) in 3 automated blood culture systems (BACTEC™ FX, BACT/ALERT® 3D, and BACT/ALERT® VIRTUO®), with or without trough and peak levels of eight antifungal agents (amphotericin B, anidulafungin, caspofungin, fluconazole, itraconazole, micafungin, posaconazole, and voriconazole).
RESULTS
Caspofungin and micafungin significantly prolonged the TTDs for most of the tested strains in the 3 blood culture instruments, especially at peak concentrations.
CONCLUSION
Peak concentrations of caspofungin and micafungin influence the performance of blood culture detection systems. Therefore, one should be careful about the possibility of prolonged TTDs for candidemia when using the abovementioned antifungal agents.
Topics: Antifungal Agents; Candida; Candida albicans; Candida glabrata; Candida parapsilosis; Candida tropicalis; Candidemia; Caspofungin; Fluconazole; Humans; Micafungin; Microbial Sensitivity Tests
PubMed: 35944341
DOI: 10.1016/j.diagmicrobio.2022.115768 -
Brazilian Journal of Microbiology :... Dec 2022Candida auris is an emerging global public health threat. It is an opportunistic yeast that usually affects critically ill patients in healthcare settings and is...
Candida auris is an emerging global public health threat. It is an opportunistic yeast that usually affects critically ill patients in healthcare settings and is characterized by reduced susceptibility to multiple antifungal classes. Combination therapy with antifungals and repurposed drugs is a feasible alternative to overcome this problem. The aim of this study was to examine the in vitro interactions and potential synergy of micafungin (MFG) and voriconazole (VRC) plus the antidepressant sertraline (SRT) against clinical isolates of C. auris. Conventional antifungal testing was first performed with the three drugs according to the CLSI methodology. Drug interactions were determined by the checkerboard microdilution assay using the fractional inhibitory concentration (FIC) index. Synergistic interactions were noted with the combination of MFG and SRT plus VRC with FIC values of 0.37 to 0.49 for some strains. Indifferent interactions were observed when MFG was combined with SRT with just one exception (FIC 0.53). No antagonism was observed for any combination. The combination of VRC with MCF or SRT may be relevant for treating C. auris infections.
Topics: Humans; Voriconazole; Antifungal Agents; Micafungin; Sertraline; Candida auris; Candida; Microbial Sensitivity Tests
PubMed: 36036298
DOI: 10.1007/s42770-022-00817-y -
The Journal of Antimicrobial... Oct 2020We conducted a prospective study in ICU patients of two tertiary hospitals in order to determine basic pharmacokinetic (PK) parameters, associated variation and target...
BACKGROUND
We conducted a prospective study in ICU patients of two tertiary hospitals in order to determine basic pharmacokinetic (PK) parameters, associated variation and target attainment rates for anidulafungin, micafungin and caspofungin.
METHODS
Serum samples from patients treated for 7 days with the standard doses of anidulafungin (N = 13), micafungin (N = 14) or caspofungin (N = 7) were analysed by validated chromatographic methods. PK parameters determined with non-compartmental analysis were correlated with demographic, laboratory and disease severity characteristics. The percentages of patients attaining drug exposures described in the summary of product characteristics (SmPC) documents and preclinical PK/PD targets for stasis were estimated.
RESULTS
The median (range) AUC24 was 101.46 (54.95-274.15) mg·h/L for anidulafungin, 79.35 (28.00-149.30) mg·h/L for micafungin and 48.46 (19.44-103.69) mg·h/L for caspofungin. The interindividual variability of anidulafungin, micafungin and caspofungin AUC24 was 46%-58%, attributed mainly to variability in volume of distribution (V), clearance (CL) and in both V and CL, respectively. Significant correlations were found between anidulafungin AUC24 and BMI (rs = -0.670, P = 0.012) and liver enzymes (rs = 0.572-0.665, P = 0.013-0.041) and between caspofungin Cmin and transaminase levels (rs = -0.775 to -0.786, P = 0.036-0.041). Less than 50% of our patients attained the corresponding SmPC median AUC24s and none of the patients attained the PK/PD targets for Candida albicans and Candida parapsilosis.
CONCLUSIONS
Anidulafungin exposure in ICU patients was comparable with that reported in non-ICU patients and in healthy volunteers. Micafungin exposure was comparable to that of other patients but ∼30% lower than that in healthy volunteers, whereas caspofungin exposure was rather low (∼50% lower than in healthy volunteers). Larger interindividual variability (50%-60%) was recorded in ICU patients compared with other groups for all three echinocandins.
Topics: Anidulafungin; Antifungal Agents; Echinocandins; Humans; Intensive Care Units; Lipopeptides; Microbial Sensitivity Tests; Prospective Studies
PubMed: 32696036
DOI: 10.1093/jac/dkaa265