colistin and Candidiasis

Topics: Amphotericin B; Animals; Antifungal Agents; Aspergillosis; Blastomycosis; Candicidin; Candidiasis; Coccidioidomycosis; Colistin; Cryptococcosis; Dermatomycoses; Drug Resistance, Microbial; Emetine; Flucytosine; Griseofulvin; Histoplasmosis; Humans; Imidazoles; Minocycline; Natamycin; Nystatin; Polyenes; Tolnaftate

Antifungal combination is an interesting approach for the treatment of several fungal infections but there is currently little evidence to support combined therapy in Candida auris infections. The antibacterial colistin has recently been shown to interact synergistically with antifungals against Candida spp., including azole-resistant isolates. The current study evaluated the in vitro interaction between colistin and either caspofungin or micafungin against 15 C. auris isolates by a checkerboard methodology based on the European Committee on Antimicrobial Susceptibility Testing (EUCAST) reference method. Results were analysed by two approaches: calculation of the fractional inhibitory concentration index (FICI) and response surface analysis based on the Bliss model. The minimum inhibitory concentration (MIC) range (geometric mean [Gmean]) of caspofungin and micafungin was 0.25 to 1 µg/mL (0.691 µg/mL) and 0.03 to 0.125 µg/mL (0.114 µg/mL), respectively. No activity was observed for colistin alone with MIC of >64 µg/mL for all the isolates. When colistin was combined with caspofungin, synergistic interactions were observed for all strains with FICI values of 0.08 to 0.14. In contrast, indifferent interactions were observed for the combination of colistin with micafungin with FICI values of 0.51 to 1.01. Synergy was also demonstrated using the Bliss model against all isolates for the colistin-caspofungin combination and in 60% of isolates for the colistin-micafungin combination. Antagonism was not observed for any combination.

Topics: Anti-Bacterial Agents; Antifungal Agents; Candida; Candidiasis; Caspofungin; Colistin; Drug Synergism; Echinocandins; Humans; Micafungin

The in vitro interactions of isavuconazole with colistin were evaluated against 15 clinical Candida auris isolates by a microdilution checkerboard technique based on the EUCAST reference method for antifungal susceptibility testing and by agar diffusion using isavuconazole gradient concentration strips with or without colistin incorporated RPMI agar. Interpretation of the checkerboard results was done by the fractional inhibitory concentration index and by response surface analysis based on the Bliss model. By checkerboard, combination was synergistic for 93% of the isolates when interpretation of the data was done by fractional inhibitory concentration index, and for 80% of the isolates by response surface analysis interpretation. By agar diffusion test, although all MICs in combination decreased compared to isavuconazole alone, only 13% of the isolates met the definition of synergy. Essential agreement of EUCAST and gradient concentration strip MICs at +/- 2 log

Topics: Agar; Antifungal Agents; Candida; Candidiasis; Colistin; Colony Count, Microbial; Drug Synergism; Humans; Microbial Sensitivity Tests; Nitriles; Pyridines; Triazoles

To evaluate the antifungal activity of a fixed antibiotic combination (AC) containing tetracycline (TET), chloramphenicol (CAF), and colistimethate sodium (CS).. In vitro: Candida ATCC and clinical strains were used. The minimum inhibitory concentrations (MICs) of AC and of each antibiotic were determined. Fluconazole (FLC) was tested for comparison. Time-killing curves of selected strains were performed. Ex vivo keratitis: corneas were injected intrastromally with the selected strains. After the injection, corneas were divided into groups of treatments: AC, FLC, or saline. Then, the tissues were analyzed for colony-forming units per gram (CFU/g). Propidium iodide (PI) and MitoTracker (MTR) staining were used to investigate the mode of action.. Values of MIC required to inhibit the growth of 90% of organisms for the antibiotics alone were higher than FLC. However, their activity was enhanced when used in combination against Candida yeasts. Time-killing curves showed that at 24 hours, AC reduced the load of both strains of approximately 1 Log10 CFU/g compared with the initial inoculum (P < 0.0001). This effect was also significant versus FLC. In ex vivo, AC was effective in decreasing the loads of both strains by 4 Log10 CFU/g with respect to the control. Moreover, it showed higher activity than FLC against Candida albicans ATCC 10231 (1 Log10 CFU/g, P < 0.01 versus control). PI staining demonstrated that CS changed the membrane's permeability, whereas MTR staining demonstrated that TET or CAF altered mitochondrial function. The cells treated with AC and stained showed both effects.. In this study, AC showed antifungal efficacy versus Candida spp.; this activity can be due to the synergistic effects of antibiotics in it.

Topics: Animals; Anti-Bacterial Agents; Candida albicans; Candidiasis; Chloramphenicol; Colistin; Colony Count, Microbial; Corneal Ulcer; Drug Combinations; Drug Resistance, Fungal; Drug Synergism; Eye Infections, Fungal; Microbial Sensitivity Tests; Ophthalmic Solutions; Rabbits; Tetracycline; Treatment Outcome

Candida albicans is the most prevalent fungal pathogen of humans, causing a wide range of infections from harmless superficial to severe systemic infections. Improvement of the antifungal arsenal is needed since existing antifungals can be associated with limited efficacy, toxicity and antifungal resistance. Here we aimed to identify compounds that act synergistically with echinocandin antifungals and that could contribute to a faster reduction of the fungal burden.. A total of 38 758 compounds were tested for their ability to act synergistically with aminocandin, a β-1,3-glucan synthase inhibitor of the echinocandin family of antifungals. The synergy between echinocandins and an identified hit was studied with chemogenomic screens and testing of individual Saccharomyces cerevisiae and C. albicans mutant strains.. We found that colistin, an antibiotic that targets membranes in Gram-negative bacteria, is synergistic with drugs of the echinocandin family against all Candida species tested. The combination of colistin and aminocandin led to faster and increased permeabilization of C. albicans cells than either colistin or aminocandin alone. Echinocandin susceptibility was a prerequisite to be able to observe the synergy. A large-scale screen for genes involved in natural resistance of yeast cells to low doses of the drugs, alone or in combination, identified efficient sphingolipid and chitin biosynthesis as necessary to protect S. cerevisiae and C. albicans cells against the antifungal combination.. These results suggest that echinocandin-mediated weakening of the cell wall facilitates colistin targeting of fungal membranes, which in turn reinforces the antifungal activity of echinocandins.

Topics: Animals; Antifungal Agents; Candida; Candidiasis; Cell Membrane Permeability; Cell Wall; Chitin; Colistin; Coloring Agents; Drug Synergism; Echinocandins; Gene Library; Genetic Fitness; Genotype; Indicator Dilution Techniques; Lipopeptides; Mice; Mice, Inbred BALB C; Microbial Sensitivity Tests; Mutation; Propidium; Saccharomyces cerevisiae; Sphingolipids

Recent exposure to azoles is an important risk factor for infection with fluconazole-resistant Candida spp., but little is known about the role of antibacterial drug exposure in the emergence of drug-resistant Candida. We did a prospective nationwide surveillance study of candidemia in Israel and analyzed the propensity score-adjusted association between antifungal and antibacterial drug exposure and bloodstream infection with C. glabrata and fluconazole-resistant Candida isolates. Four hundred forty-four episodes of candidemia (450 Candida isolates, 69 [15%] C. glabrata isolates, and 38 [8.5%] fluconazole-resistant isolates) from 18 medical centers in Israel were included. C. glabrata bloodstream infection was strongly associated with recent metronidazole exposure (odds ratio [OR], 3.2; P < 0.001). Infection with a fluconazole-resistant isolate was associated with exposure to carbapenems, trimethoprim-sulfamethoxazole, clindamycin, and colistin (odds ratio, 2.8; P = 0.01). The inclusion of antibacterial drug exposure in a multivariable model significantly enhanced the model's predictive accuracy for fluconazole-resistant Candida bloodstream infection. Our findings may be relevant to the selection of empirical antifungal treatment and broaden the scope of antibiotic-associated collateral damage.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Antifungal Agents; Bacteria; Bacterial Infections; Candida glabrata; Candidemia; Candidiasis; Carbapenems; Clindamycin; Coinfection; Colistin; Drug Resistance, Fungal; Female; Fluconazole; Humans; Israel; Microbial Sensitivity Tests; Middle Aged; Odds Ratio; Prospective Studies; Risk Factors; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adolescent; Adult; Aerobiosis; Bacterial Infections; Candida; Candidiasis; Child; Colistin; Gentamicins; Gram-Negative Bacteria; Humans; Intestines; Liver Transplantation; Nystatin; Pharynx; Postoperative Complications; Rectum

Topics: Adult; Aged; Antitubercular Agents; Bronchial Diseases; Candidiasis; Colistin; Humans; Lung Abscess; Lung Diseases, Fungal; Male; Middle Aged; Nystatin; Tuberculosis, Pulmonary

Topics: Amphotericin B; Bronchopneumonia; Candidiasis; Child; Colistin; Female; Humans; Iatrogenic Disease; Infant; Infant, Newborn; Infant, Newborn, Diseases; Infusions, Parenteral; Male; Meningitis; Sepsis; Sterilization; Vaccination

Topics: Abscess; Amphotericin B; Brain Abscess; Candidiasis; Carrier State; Child; Chloramphenicol; Colistin; Deoxyribonucleases; DNA; Empyema; Enteritis; Humans; Kanamycin; Meningitis; Methicillin; Penicillins; Peritonitis; Phlebitis; Pneumonia; Pneumothorax; Pseudomonas Infections; Sepsis; Staphylococcal Infections; Sulfadiazine; Troleandomycin

Topics: Candida albicans; Candidiasis; Colistin; Humans; Infections; Klebsiella; Oxytetracycline; Sepsis; Streptomycin

Topics: Candidiasis; Colistin; Diarrhea; Diarrhea, Infantile; Enterocolitis; Escherichia coli Infections; Humans; Infant; Intestines; Toxicology

Topics: Anti-Bacterial Agents; Candidiasis; Chloramphenicol; Colistin; Colitis, Ulcerative; Erythromycin; Escherichia coli Infections; Gastrointestinal Hemorrhage; Humans; Intestines; Penicillins; Peptic Ulcer Perforation; Polyps; Proteus Infections; Staphylococcal Infections; Streptomycin; Tetracycline

Topics: Anti-Bacterial Agents; Candidiasis; Chronobiology Phenomena; Colistin; Humans; Tetracycline

Topics: Anti-Bacterial Agents; Candidiasis; Colistin; Humans; Leukocytes; Tetracycline; Transendothelial and Transepithelial Migration