-
Infection and Drug Resistance 2023The emergence of resistance in to azoles and terbinafine has become increasingly evident in recent years, necessitating the development of novel antifungal drugs and...
INTRODUCTION
The emergence of resistance in to azoles and terbinafine has become increasingly evident in recent years, necessitating the development of novel antifungal drugs and the exploration of new indications for existing agents.
METHODS
In this study, we retrospectively evaluated the in vitro antifungal activity of 3 echinocandins (anidulafungin, caspofungin, and micafungin) against 73 clinical isolates of collected from a teaching hospital in Shanghai, China, using EUCAST E.DEF 9.3.1 with minor modification. We also reviewed the susceptibility of to echinocandins globally by literature searching.
RESULTS
Our findings revealed that micafungin exhibited the lowest modal minimum effective concentration (MEC) value (0.08 mg/L, n = 28) and the lowest geometric mean (GM) MEC value (0.014 mg/L) among the 73 isolates of tested, followed by anidulafungin with a modal MEC value of 0.016 mg/L (n = 67) and a GM of 0.018 mg/L. Caspofungin displayed a higher modal MEC value of 0.5 mg/L (n = 35) and a GM of 0.308 mg/L. Despite variations in methodologies, similar results were obtained from the review of five relevant studies included in our analysis.
DISCUSSION
Echinocandins exhibited excellent in vitro activity against isolates, with micafungin and anidulafungin demonstrating greater potency than caspofungin. These findings suggest that echinocandins could be considered as potential treatment options for managing recalcitrant dermatophytoses resulting from the emergence of resistance. However, it is important to note that the clinical efficacy of these in vitro findings has yet to be established and warrants further investigation.
PubMed: 37621698
DOI: 10.2147/IDR.S423735 -
Transplantation Jun 2024Ex situ normothermic liver perfusion (NMP) in a blood-based perfusate is associated with a risk of microbe growth, resulting in life-threatening posttransplant sepsis....
BACKGROUND
Ex situ normothermic liver perfusion (NMP) in a blood-based perfusate is associated with a risk of microbe growth, resulting in life-threatening posttransplant sepsis. Antibiotics are widely used, but the pharmacokinetics of these agents are unknown as is their efficacy. We wished to assess the perfusate concentrations of the meropenem and fluconazole that we use and to audit the incidence of infection with this antimicrobial therapy.
METHODS
Fluconazole and meropenem (100 mg each) were added to the perfusate before NMP began, and serial samples were taken and assayed for drug concentrations. Perfusate cultures were available from 210 of the 242 perfusions performed between February 1, 2018, and April 6, 2023; these were reviewed.
RESULTS
Following administration of 100 mg fluconazole, levels fell slightly from a median of 24.9 mg/L at 1 h to 22.6 mg/L at 10 h. In contrast, meropenem concentrations fell over time, from a median of 21.8 mg/L at 1 h to 9.4 mg/L at 10 h. There were 4 significant microorganisms grown in the perfusions, including 3 Candida species and an Enterococcus faecium . All the Candida -infected livers were transplanted with no adverse consequences, the recipients being treated with anidulafungin upon identification of the infecting organism; the Enterococcus -infected liver was not transplanted.
CONCLUSIONS
Serious infection is a risk with NMP but appears to be mitigated with a protocol combining fluconazole and meropenem. This combination may not be appropriate in areas where resistance is prevalent. Routine culture of NMP perfusate is essential to identify breakthrough organisms early and enable recipient treatment.
Topics: Humans; Perfusion; Meropenem; Liver Transplantation; Fluconazole; Incidence; Male; Female; Middle Aged; Anti-Bacterial Agents; Antifungal Agents; Organ Preservation; Antibiotic Prophylaxis; Retrospective Studies; Liver; Candidiasis
PubMed: 38196099
DOI: 10.1097/TP.0000000000004897 -
Journal of Fungi (Basel, Switzerland) Aug 2023Echinocandins, used for the prevention and treatment of invasive fungal infections, have led to a rise in breakthrough infections caused by resistant species. Among...
Echinocandins, used for the prevention and treatment of invasive fungal infections, have led to a rise in breakthrough infections caused by resistant species. Among these species, those belonging to the complex are rare multidrug-resistant (MDR) yeasts that are frequently misidentified but have emerged as significant healthcare-associated pathogens causing invasive infections. The objectives of this study were to investigate the evolutionary pathways of echinocandin resistance in by identifying mutations in the gene and evaluating the impact of resistance on fitness. After subjecting a MDR clinical isolate of (named Ch4) to direct selection using increasing caspofungin concentrations, we successfully obtained an isolate (designated ) that exhibited a high level of resistance, with MIC values exceeding 16 mg/L for all tested echinocandin drugs (caspofungin, micafungin, and anidulafungin). Sequence analysis revealed a specific mutation in the resistant strain, leading to an arginine-histidine amino acid substitution (R1354H), occurring at the G4061A position of the HS2 region of the gene. Compared to the wild-type strain, exhibited significantly reduced growth proliferation, biofilm formation capability, and phagocytosis ratio, indicating a decrease in fitness. Transmission electron microscopy analysis revealed alterations in cell wall components, with a notable increase in cell wall thickness. The resistant strain also exhibited higher amounts (2.5-fold) of chitin, a cell wall-located molecule, compared to the wild-type strain. Furthermore, the resistant strain demonstrated attenuated virulence in the larval model. The evolved strain maintained its resistance profile in vivo since the treatment with either caspofungin or micafungin did not improve larval survival or reduce the fungal load. Taken together, our findings suggest that the acquisition of pan-echinocandin resistance occurred rapidly after drug exposure and was associated with a significant fitness cost in . This is particularly concerning as echinocandins are often the first-line treatment option for MDR species.
PubMed: 37623630
DOI: 10.3390/jof9080859 -
Medical Mycology Case Reports Mar 2024is emerging as a highly resistant species of the complex causing invasive and mucocutaneous infections. In this study, three cases of vulvovaginal candidiasis caused...
is emerging as a highly resistant species of the complex causing invasive and mucocutaneous infections. In this study, three cases of vulvovaginal candidiasis caused by are described and identified by Internal Transcribed Spacer 1-2 sequencing. All isolates were susceptible in vitro to anidulafungin, micafungin, caspofungin, 5-flucytosine, posaconazole, voriconazole, itraconazole, amphotericin B, and showed dose-dependent susceptibility to fluconazole. In two patients, three doses of oral fluconazole were effective, while one patient developed clinical fluconazole resistance with a new relapse after 6 months. Increasing the weekly dose of fluconazole showed to be effective in this patient.
PubMed: 38444800
DOI: 10.1016/j.mmcr.2024.100640 -
Journal of Fungi (Basel, Switzerland) May 2024The incidence of infections has increased in the last decade, posing a serious threat to public health. Appropriately facing this challenge requires precise...
The incidence of infections has increased in the last decade, posing a serious threat to public health. Appropriately facing this challenge requires precise epidemiological data on species and antimicrobial resistance incidence, but many countries lack appropriate surveillance programs. This study aims to bridge this gap for Morocco by identifying and phenotyping a year-long collection of clinical isolates (n = 93) from four clinics in Tetouan. We compared the current standard in species identification with molecular methods and assessed susceptibility to fluconazole and anidulafungin. Our results identified limitations in currently used diagnostics approaches, and revealed that ranks as the most prevalent species with 60 strains (64.52%), followed by with 14 (15.05%), with 6 (6.45%), and with 4 (4.30%). In addition, we report the first identification of in Morocco. Susceptibility results for fluconazole revealed that some isolates were approaching MICs resistance breakpoints in (2), and (1). Our study also identified anidulafungin resistant strains in (1), (1), and (2), rendering the two strains from the latter species multidrug-resistant due to their innate resistance to fluconazole. These results raise concerns about species identification and antifungal resistance in Morocco and highlight the urgent need for more accurate methods and preventive strategies to combat fungal infections in the country.
PubMed: 38921360
DOI: 10.3390/jof10060373 -
Biomedicines Jan 2024The aim of the present study was to characterize biofilms formed by spp. clinical isolates (n = 19), isolated from the oral mucosa of HIV-positive patients. For...
The aim of the present study was to characterize biofilms formed by spp. clinical isolates (n = 19), isolated from the oral mucosa of HIV-positive patients. For characterizing the biofilms formed by several sp. strains, isolated from HIV-positive patients, in terms of formed biomass, matrix composition and antifungal susceptibility profile, clinical isolates (n = 19) were collected from oral mucosa and identified. The biofilm of the samples was cultured with fluconazole (1250 mg/L), voriconazole (800 mg/L), anidulafungin (2 mg/L) or amphotericin B (2 mg/L). Afterwards, the quantification of the total biomass was performed using crystal violet assay, while the proteins and carbohydrates levels were quantified in the matrix. The results showed a predominance of , followed by . Around 58% of the spp. biofilm had susceptibility to fluconazole and voriconazole (800 mg/L), 53% to anidulafungin and 74% to amphotericin B. presented both the lowest and the highest biofilm matrix contents in polysaccharides and proteins. The low resistance to antifungal agents reported here was probably due to the fact that none of the participants had a prolonged exposure to these antifungals. A predominance of less virulent spp. strains with low or no resistance to antifungals was observed. This can be attributed to a low fungal selective pressure. This most probably happened due to a low fungal selective pressure but also due to a good adherence to HAART therapy, which guarantees a stable and stronger immune patient response.
PubMed: 38397912
DOI: 10.3390/biomedicines12020310 -
IDCases 2024is an emerging opportunistic yeast in the Mediterranean region typically isolated from immunocompromised patients, usually affected by blood malignancies. We reported a...
is an emerging opportunistic yeast in the Mediterranean region typically isolated from immunocompromised patients, usually affected by blood malignancies. We reported a rare case of infection, isolated from a drainage fluid in a patient affected by lung cancer recovered in the University Hospital of Campania "Luigi Vanvitelli", Naples, Italy. The isolate was identified by phenotypic methods, i.e., Gram and Lactophenol cotton blue (LCB) staining, and matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) analysis. We identified on the third day from Sabouraud Dextrose Agar supplemented with chloramphenicol and gentamicin. Antifungal susceptibility test revealed that 5-fluorocytosine was the most active drug against , followed by itraconazole and voriconazole, micafungin, amphotericin B and fluconazole, posaconazole, anidulafungin, and caspofungin. Our data showed the importance of an early cultural and fast microbiology diagnosis based on the characteristic morphologic features observed in Gram-stained smears of blood culture positive bottles, and the validation via MALDI-TOF MS. This dual approach has significant impact in the clinical management of infectious diseases and antibiotic stewardship, by integrating sample processing, fluid handling, and detection for rapid bacterial diagnosis.
PubMed: 38681078
DOI: 10.1016/j.idcr.2024.e01959 -
Access Microbiology 2024stands as the predominant fungal genus in the airways of cystic fibrosis (CF) patients, significantly contributing to their morbidity and mortality. represents the...
stands as the predominant fungal genus in the airways of cystic fibrosis (CF) patients, significantly contributing to their morbidity and mortality. represents the primary causative species for infections, though the emergence of rare species within the section has become noteworthy. Among these, is particularly significant due to its frequent misidentification and intrinsic resistance to azole antifungal agents. In the management of invasive aspergillosis and resistant infections, combination antifungal therapy has proven to be an effective approach. This report documents a case involving the death of a CF patient due to a pulmonary exacerbation linked to the colonization of multiple species, including , , and , and treated with Itraconazole (ITC) monotherapy. We delineated the procedures used to characterize the isolates in clinical settings and simulated the impact of the combination antifungal therapy on the isolates obtained from the patient. We evaluated three different combinations: Amphotericin B (AMB)+Voriconazole (VRC), AMB+Anidulafungin (AND), and VRC+AND. Notably, all strains isolated from the patient exhibited a significant decrease in their minimum inhibitory concentration (MIC) or minimum effective concentration (MEC) values when treated with all antifungal combinations. The VRC+AMB combination demonstrated the most synergistic effects. This case report emphasizes the critical importance of susceptibility testing and precise identification of species to enhance patient prognosis. It also underscores the potential benefits of combined antifungal treatment, which, in this case, could have led to a more favourable patient outcome.
PubMed: 38737802
DOI: 10.1099/acmi.0.000758.v3 -
Antibiotics (Basel, Switzerland) Apr 2024Patients undergoing extracorporeal membrane oxygenation (ECMO) often require therapy with anti-infective drugs. The pharmacokinetics of these drugs may be altered during...
Patients undergoing extracorporeal membrane oxygenation (ECMO) often require therapy with anti-infective drugs. The pharmacokinetics of these drugs may be altered during ECMO treatment due to pathophysiological changes in the drug metabolism of the critically ill and/or the ECMO therapy itself. This study investigates the latter aspect for commonly used anti-infective drugs in an ex vivo setting. A fully functional ECMO device circulated an albumin-electrolyte solution through the ECMO tubes and oxygenator. The antibiotic agents cefazolin, cefuroxim, cefepime, cefiderocol, linezolid and daptomycin and the antifungal agent anidulafungin were added. Blood samples were taken over a period of four hours and drug concentrations were measured via high-pressure liquid chromatography (HPLC) with UV detection. Subsequently, the study analyzed the time course of anti-infective concentrations. The results showed no significant changes in the concentration of any tested anti-infectives throughout the study period. This ex vivo study demonstrates that the ECMO device itself has no impact on the concentration of commonly used anti-infectives. These findings suggest that ECMO therapy does not contribute to alterations in the concentrations of anti-infective medications in severely ill patients.
PubMed: 38667049
DOI: 10.3390/antibiotics13040373 -
Medicina 2024Acute cholangitis is a bile duct infection associated with bile duct obstruction. Bile culture is positive in most cases, and the most frequent etiological agent is...
Acute cholangitis is a bile duct infection associated with bile duct obstruction. Bile culture is positive in most cases, and the most frequent etiological agent is Escherichia coli. Candida sp acute cholangitis is a rare finding, which is more common in patients with immunosuppression, use of corticosteroids, prolonged antibiotic treatment or surgical procedures of the bile duct. We present the case of a 67-year-old woman with none of the above-mentioned history who consulted for fever, abdominal pain and jaundice. MRI of the abdomen revealed a lithiasic image in the common bile duct with dilation. It required endoscopic drainage of the biliary tract. Direct microscopic examination of the bile fluid revealed gram-negative bacilli and yeast, and in the culture of bile fluid Klebsiella pneumoniae producing extended spectrum beta-lactamase (ESBL) and Candida glabrata were isolated. The patient completed the antibiotic treatment with piperacillin tazobactam and anidulafungin with good evolution. Bile duct infection by association of Gram-negative bacilli and Candida sp is a rare entity, more in patients without underlying diseases.
Topics: Female; Humans; Aged; Klebsiella pneumoniae; Candida glabrata; Cholangitis; Anti-Bacterial Agents; Bile; Gram-Negative Bacteria; Escherichia coli
PubMed: 38271946
DOI: No ID Found