scholarly journals Head-to-Head Comparison of Inhibitory and Fungicidal Activities of Fluconazole, Itraconazole, Voriconazole, Posaconazole, and Isavuconazole against Clinical Isolates of Trichosporon asahii

2013 ◽  
Vol 57 (10) ◽  
pp. 4841-4847 ◽  
Author(s):  
Gulsen Hazirolan ◽  
Emilia Canton ◽  
Selma Sahin ◽  
Sevtap Arikan-Akdagli

ABSTRACTTreatment of disseminatedTrichosporoninfections still remains difficult. Amphotericin B frequently displays inadequate fungicidal activity and echinocandins have no meaningful antifungal effect against this genus. Triazoles are currently the drugs of choice for the treatment ofTrichosporoninfections. This study evaluates the inhibitory and fungicidal activities of five triazoles against 90 clinical isolates ofTrichosporon asahii. MICs (μg/ml) were determined according to Clinical and Laboratory Standards Institute microdilution method M27-A3 at 24 and 48 h using two endpoints, MIC-2 and MIC-0 (the lowest concentrations that inhibited ∼50 and 100% of growth, respectively). Minimum fungicidal concentrations (MFCs; μg/ml) were determined by seeding 100 μl of all clear MIC wells (using an inoculum of 104CFU/ml) onto Sabouraud dextrose agar. Time-kill curves were assayed against four clinicalT. asahiiisolates and theT. asahiiATCC 201110 strain. The MIC-2 (∼50% reduction in turbidity compared to the growth control well)/MIC-0 (complete inhibition of growth)/MFC values that inhibited 90% of isolates at 48 h were, respectively, 8/32/64 μg/ml for fluconazole, 1/2/8 μg/ml for itraconazole, 0.12/0.5/2 μg/ml for voriconazole, 0.5/2/4 μg/ml for posaconazole, and 0.25/1/4 μg/ml for isavuconazole. The MIC-0 endpoints yielded more consistent MIC results, which remained mostly unchanged when extending the incubation to 48 h (98 to 100% agreement with 24-h values) and are easier to interpret. Based on the time-kill experiments, none of the drugs reached the fungicidal endpoint (99.9% killing), killing activity being shown but at concentrations not reached in serum. Statistical analysis revealed that killing rates are dose and antifungal dependent. The lowest concentration at which killing activity begins was for voriconazole, and the highest was for fluconazole. These results suggest that azoles display fungistatic activity and lack fungicidal effect againstT. asahii. By rank order, the most active triazole is voriconazole, followed by itraconazole ∼ posaconazole ∼ isavuconazole > fluconazole.

2011 ◽  
Vol 56 (3) ◽  
pp. 1247-1252 ◽  
Author(s):  
James A. Karlowsky ◽  
Andrew J. Walkty ◽  
Heather J. Adam ◽  
Melanie R. Baxter ◽  
Daryl J. Hoban ◽  
...  

ABSTRACTClinical isolates of theBacteroides fragilisgroup (n= 387) were collected from patients attending nine Canadian hospitals in 2010-2011 and tested for susceptibility to 10 antimicrobial agents using the Clinical and Laboratory Standards Institute (CLSI) broth microdilution method.B. fragilis(59.9%),Bacteroides ovatus(16.3%), andBacteroides thetaiotaomicron(12.7%) accounted for ∼90% of isolates collected. Overall rates of percent susceptibility were as follows: 99.7%, metronidazole; 99.5%, piperacillin-tazobactam; 99.2%, imipenem; 97.7%, ertapenem; 92.0%, doripenem; 87.3%, amoxicillin-clavulanate; 80.9%, tigecycline; 65.9%, cefoxitin; 55.6%, moxifloxacin; and 52.2%, clindamycin. Percent susceptibility to cefoxitin, clindamycin, and moxifloxacin was lowest forB. thetaiotaomicron(n= 49, 24.5%),Parabacteroides distasonis/P. merdae(n= 11, 9.1%), andB. ovatus(n= 63, 31.8%), respectively. One isolate (B. thetaiotaomicron) was resistant to metronidazole, and two isolates (bothB. fragilis) were resistant to both piperacillin-tazobactam and imipenem. Since the last published surveillance study describing Canadian isolates ofB. fragilisgroup almost 20 years ago (A.-M. Bourgault et al., Antimicrob. Agents Chemother. 36:343–347, 1992), rates of resistance have increased for amoxicillin-clavulanate, from 0.8% (1992) to 6.2% (2010-2011), and for clindamycin, from 9% (1992) to 34.1% (2010-2011).


2019 ◽  
Vol 64 (3) ◽  
Author(s):  
Ian Morrissey ◽  
Stephen Hawser ◽  
Sibylle H. Lob ◽  
James A. Karlowsky ◽  
Matteo Bassetti ◽  
...  

ABSTRACT Eravacycline is a novel, fully synthetic fluorocycline antibiotic being developed for the treatment of serious infections, including those caused by resistant Gram-positive pathogens. Here, we evaluated the in vitro activities of eravacycline and comparator antimicrobial agents against a recent global collection of frequently encountered clinical isolates of Gram-positive bacteria. The CLSI broth microdilution method was used to determine in vitro MIC data for isolates of Enterococcus spp. (n = 2,807), Staphylococcus spp. (n = 4,331), and Streptococcus spp. (n = 3,373) isolated primarily from respiratory, intra-abdominal, urinary, and skin specimens by clinical laboratories in 37 countries on three continents from 2013 to 2017. Susceptibilities were interpreted using both CLSI and EUCAST breakpoints. There were no substantive differences (a >1-doubling-dilution increase or decrease) in eravacycline MIC90 values for different species/organism groups over time or by region. Eravacycline showed MIC50 and MIC90 results of 0.06 and 0.12 μg/ml, respectively, when tested against Staphylococcus aureus, regardless of methicillin susceptibility. The MIC90 values of eravacycline for Staphylococcus epidermidis and Staphylococcus haemolyticus were equal (0.5 μg/ml). The eravacycline MIC90s for Enterococcus faecalis and Enterococcus faecium were 0.06 μg/ml and were within 1 doubling dilution regardless of the vancomycin susceptibility profile. Eravacycline exhibited MIC90 results of ≤0.06 μg/ml when tested against Streptococcus pneumoniae and beta-hemolytic and viridans group streptococcal isolates. In this surveillance study, eravacycline demonstrated potent in vitro activity against frequently isolated clinical isolates of Gram-positive bacteria (Enterococcus, Staphylococcus, and Streptococcus spp.), including isolates collected over a 5-year period (2013 to 2017), underscoring its potential benefit in the treatment of infections caused by common Gram-positive pathogens.


2019 ◽  
Vol 63 (4) ◽  
Author(s):  
Dandan Yin ◽  
Shi Wu ◽  
Yang Yang ◽  
Qingyu Shi ◽  
Dong Dong ◽  
...  

ABSTRACT The in vitro activities of ceftazidime-avibactam (CZA), ceftolozane-tazobactam (C-T), and comparators were determined for 1,774 isolates of Enterobacteriaceae and 524 isolates of Pseudomonas aeruginosa collected by 30 medical centers from the China Antimicrobial Surveillance Network (CHINET) in 2017. Antimicrobial susceptibility testing was performed by the CLSI broth microdilution method, and blaKPC and blaNDM were detected by PCR for all carbapenem-resistant Enterobacteriaceae (CRE). Ceftazidime-avibactam demonstrated potent activity against almost all Enterobacteriaceae (94.6% susceptibility; MIC50, ≤0.25 mg/liter; MIC90, ≤0.25 to >32 mg/liter) and good activity against P. aeruginosa (86.5% susceptibility; MIC50/90, 2/16 mg/liter). Among the CRE, 50.8% (189/372 isolates) were positive for blaKPC-2, which mainly existed in ceftazidime-avibactam-susceptible Klebsiella pneumoniae isolates (92.1%, 174/189). Among the CRE, 17.7% (66/372 isolates) were positive for blaNDM, which mainly existed in strains resistant to ceftazidime-avibactam (71.7%, 66/92). Ceftolozane-tazobactam showed good in vitro activity against Escherichia coli and Proteus mirabilis (MIC50/90, ≤0.5/2 mg/liter; 90.5 and 93.8% susceptibility, respectively), and the rates of susceptibility of K. pneumoniae (MIC50/90, 2/>64 mg/liter) and P. aeruginosa (MIC50/90, 1/8 mg/liter) were 52.7% and 88.5%, respectively. Among the CRE strains, 28.6% of E. coli isolates and 85% of K. pneumoniae isolates were still susceptible to ceftazidime-avibactam, but only 7.1% and 1.9% of them, respectively, were susceptible to ceftolozane-tazobactam. The rates of susceptibility of the carbapenem-resistant P. aeruginosa isolates to ceftazidime-avibactam (65.7%) and ceftolozane-tazobactam (68%) were similar. Overall, both ceftazidime-avibactam and ceftolozane-tazobactam were highly active against clinical isolates of Enterobacteriaceae and P. aeruginosa recently collected across China, and ceftazidime-avibactam showed activity superior to that of ceftolozane-tazobactam against Enterobacteriaceae, whereas ceftolozane-tazobactam showed a better effect against P. aeruginosa.


2017 ◽  
Vol 62 (1) ◽  
Author(s):  
Meredith A. Hackel ◽  
Olga Lomovskaya ◽  
Michael N. Dudley ◽  
James A. Karlowsky ◽  
Daniel F. Sahm

ABSTRACT Vaborbactam (formerly RPX7009) is a novel inhibitor of serine β-lactamases, including Ambler class A carbapenemases, such as KPCs. The current study evaluated the in vitro activity of the combination agent meropenem-vaborbactam against a global collection of 991 isolates of KPC-positive Enterobacteriaceae collected in 2014 and 2015 using the Clinical and Laboratory Standards Institute (CLSI) standard broth microdilution method. The MIC90 of meropenem (when tested with a fixed concentration of 8 μg/ml of vaborbactam) for isolates of KPC-positive Enterobacteriaceae was 1 μg/ml, and MIC values ranged from ≤0.03 to >32 μg/ml; 99.0% (981/991) of isolates had meropenem-vaborbactam MICs of ≤4 μg/ml, the U.S. FDA-approved MIC breakpoint for susceptibility to meropenem-vaborbactam (Vabomere). Vaborbactam lowered the meropenem MIC50 from 32 to 0.06 μg/ml and the MIC90 from >32 to 1 μg/ml. There were no differences in the activity of meropenem-vaborbactam when the isolates were stratified by KPC variant type. We conclude that meropenem-vaborbactam demonstrates potent in vitro activity against a worldwide collection of clinical isolates of KPC-positive Enterobacteriaceae collected in 2014 and 2015.


2006 ◽  
Vol 50 (3) ◽  
pp. 1096-1099 ◽  
Author(s):  
Hua Quan ◽  
Ying-Ying Cao ◽  
Zheng Xu ◽  
Jing-Xia Zhao ◽  
Ping-Hui Gao ◽  
...  

ABSTRACT In vitro interaction of fluconazole and berberine chloride was investigated against 40 fluconazole-resistant clinical isolates of Candida albicans. Synergism in fungistatic activity was found with the checkerboard microdilution assay. The findings of agar diffusion tests and time-kill curves confirmed the synergistic interaction, but no antagonistic action was observed.


2014 ◽  
Vol 58 (10) ◽  
pp. 6255-6257 ◽  
Author(s):  
Marta Sanchis ◽  
Francisco Javier Pastor ◽  
Javier Capilla ◽  
Deanna A. Sutton ◽  
Annette W. Fothergill ◽  
...  

ABSTRACTWe evaluated thein vitrokilling activity of voriconazole (VRC) and posaconazole (PSC) against two clinical isolates ofCandida guilliermondii. The two drugs showed fungistatic activity against both isolates and were effective in reducing kidney fungal burden in a neutropenic murine model of disseminated candidiasis in infected mice. PSC was significantly more effective than VRC against one of the strains. The serum levels of PSC and VRC were above the corresponding MICs for these isolates.


2018 ◽  
Vol 57 (2) ◽  
Author(s):  
Patricia J. Simner ◽  
Yehudit Bergman ◽  
Marisol Trejo ◽  
Ava A. Roberts ◽  
Remy Marayan ◽  
...  

ABSTRACT Limited methods for colistin MIC determination are available to clinical microbiology laboratories. The purpose of this study was to evaluate the accuracy of the colistin broth disk elution (CBDE) test compared to that of broth microdilution (BMD) for identifying colistin MICs. CBDE was compared to colistin BMD using a collection of Gram-negative bacilli tested at two U.S. microbiology laboratories. The isolates tested included 121 retrospective clinical isolates, 45 prospective clinical isolates, and 6 mcr-1-positive Escherichia coli isolates. CBDE was performed with four 10-ml cation-adjusted Mueller-Hinton broth tubes per isolate, to which 0, 1, 2, and 4 colistin 10-µg disks were added, generating final concentrations in the tubes of 0 (growth control), 1, 2, and 4 µg/ml, respectively. MICs were evaluated visually and interpreted using Clinical and Laboratory Standards Institute breakpoints. Site 2 also compared CBDE to the reference broth macrodilution (BMAD) method (n = 110 isolates). Overall, CBDE yielded a categorical agreement (CA) and essential agreement (EA) of 98% and 99%, respectively, compared to the results of colistin BMD. Very major errors occurred for mcr-1-producing strains, with MICs fluctuating from 2 to 4 µg/ml on repeat testing. The results for all other isolates were in CA with those of BMD. CBDE versus BMAD had an EA of 100% and a CA of 100%. Compared to currently used techniques, CBDE is an easy and practical method to perform colistin MIC testing. Some mcr-1-producing isolates yielded MICs of 2 µg/ml by CBDE and 4 µg/ml by BMD. As such, the results for isolates with colistin MICs of 2 µg/ml by CBDE should be confirmed by the reference BMD method, and isolates with MICs of ≥2 µg/ml should be evaluated for the presence of mcr genes.


Author(s):  
Yinjuan Guo ◽  
Xingwei Cao ◽  
Jinghui Yang ◽  
Xiaocui Wu ◽  
Yin Liu ◽  
...  

Introduction. Resistance to rifampin (RIF) in Mycobacterium tuberculosis infection is associated with mutations in the rpoB gene coding for the β-subunit of RNA polymerase. The contribution of various rpoB mutations to the development and level of RIF resistance remains elusive. Hypothesis/Gap Statement. Various rpoB mutations may be associated with differential levels of RIF resistance. Aim. This study aimed to investigate the relationship between specific rpoB mutations and the MICs of RIF and rifabutin (RFB) against M. tuberculosis . Methodology. Of the 195 clinical isolates, 105 and 90 isolates were randomly selected from isolates resistant to RIF and sensitive to RIF, respectively. The MICs of 12 agents for M. tuberculosis isolates were determined using commercial Sensititre M. tuberculosis MIC plates and the broth microdilution method. Strains were screened for rpoB mutations by DNA extraction, rpoB gene amplification and DNA sequence analysis. Results. One hundred isolates (95.24 %) were found to have mutations in the RIF-resistance-determining region (RRDR) of the rpoB gene. Three rpoB mutations were identified in 90 RIF-susceptible isolates. Out of 105 isolates, 86 (81.90 %) were cross-resistant to both RIF and RFB. The most frequent mutation occurred at codons 450 and 445. We also found a novel nine-nucleotide (ATCATGCAT) deletion (between positions 1543 and 1551) in the rpoB gene in two strains (1.90 %) with resistance to RIF, but susceptibility to RFB. In addition, the mutation frequency at codon 450 was significantly higher in RIF-resistant/RFB-resistant (RIFR/RFBR) strains than in RIFR/RFBS strains (75.58 % versus 21.05 %, P<0.01), whereas the mutation frequency at codon 435 was significantly lower in RIFR/RFBR strains than in RIFR/RFBS strains (1.16 % versus 26.32 %, P<0.01). Conclusion. Our data support previous findings, which reported that various rpoB mutations are associated with differential levels of RIF resistance. The specific mutations in the rpoB gene in RIFR/RFBR isolates differed from those in the RIFR/RFBS isolates. A novel deletion mutation in the RRDR might be associated with resistance to RIF, but not to RFB. Further clinical studies are required to investigate the efficacy of RFB in the treatment of infections caused by M. tuberculosis strains harbouring these mutations.


2013 ◽  
Vol 58 (3) ◽  
pp. 1284-1293 ◽  
Author(s):  
Alessandra Oliva ◽  
Ulrika Furustrand Tafin ◽  
Elena Maryka Maiolo ◽  
Safaa Jeddari ◽  
Bertrand Bétrisey ◽  
...  

ABSTRACTEnterococcal implant-associated infections are difficult to treat because antibiotics generally lack activity against enterococcal biofilms. We investigated fosfomycin, rifampin, and their combinations against planktonic and adherentEnterococcus faecalis(ATCC 19433)in vitroand in a foreign-body infection model. The MIC/MBClogvalues were 32/>512 μg/ml for fosfomycin, 4/>64 μg/ml for rifampin, 1/2 μg/ml for ampicillin, 2/>256 μg/ml for linezolid, 16/32 μg/ml for gentamicin, 1/>64 μg/ml for vancomycin, and 1/5 μg/ml for daptomycin. In time-kill studies, fosfomycin was bactericidal at 8× and 16× MIC, but regrowth of resistant strains occurred after 24 h. With the exception of gentamicin, no complete inhibition of growth-related heat production was observed with other antimicrobials on early (3 h) or mature (24 h) biofilms. In the animal model, fosfomycin alone or in combination with daptomycin reduced planktonic counts by ≈4 log10CFU/ml below the levels before treatment. Fosfomycin cleared planktonic bacteria from 74% of cage fluids (i.e., no growth in aspirated fluid) and eradicated biofilm bacteria from 43% of cages (i.e., no growth from removed cages). In combination with gentamicin, fosfomycin cleared 77% and cured 58% of cages; in combination with vancomycin, fosfomycin cleared 33% and cured 18% of cages; in combination with daptomycin, fosfomycin cleared 75% and cured 17% of cages. Rifampin showed no activity on planktonic or adherentE. faecalis, whereas in combination with daptomycin it cured 17% and with fosfomycin it cured 25% of cages. Emergence of fosfomycin resistance was not observedin vivo. In conclusion, fosfomycin showed activity against planktonic and adherentE. faecalis. Its role against enterococcal biofilms should be further investigated, especially in combination with rifampin and/or daptomycin treatment.


2014 ◽  
Vol 13 (7) ◽  
pp. 933-946 ◽  
Author(s):  
Erin M. Vasicek ◽  
Elizabeth L. Berkow ◽  
Stephanie A. Flowers ◽  
Katherine S. Barker ◽  
P. David Rogers

ABSTRACTInCandida albicans, the transcription factor Upc2 is central to the regulation of ergosterol biosynthesis.UPC2-activating mutations contribute to azole resistance, whereas disruption increases azole susceptibility. In the present study, we investigated the relationship ofUPC2to fluconazole susceptibility, particularly in azole-resistant strains. In addition to the reduced fluconazole MIC previously observed withUPC2disruption, we observed a lower minimum fungicidal concentration (MFC) for aupc2Δ/Δ mutant than for its azole-susceptible parent, SC5314. Moreover, theupc2Δ/Δ mutant was unable to grow on a solid medium containing 10 μg/ml fluconazole and exhibited increased susceptibility and a clear zone of inhibition by Etest. Time-kill analysis showed higher fungistatic activity against theupc2Δ/Δ mutant than against SC5314.UPC2disruption in strains carrying specific resistance mutations also resulted in reduced MICs and MFCs.UPC2disruption in a highly azole resistant clinical isolate containing multiple resistance mechanisms likewise resulted in a reduced MIC and MFC. This mutant was unable to grow on a solid medium containing 10 μg/ml fluconazole and exhibited increased susceptibility and a clear zone of inhibition by Etest. Time-kill analysis showed increased fungistatic activity against theupc2Δ/Δ mutant in the resistant background. Microarray analysis showed attenuated induction by fluconazole of genes involved in sterol biosynthesis, iron transport, or iron homeostasis in the absence ofUPC2. Taken together, these data demonstrate that theUPC2transcriptional network is universally essential for azole resistance inC. albicansand represents an attractive target for enhancing azole antifungal activity.


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