Minimum inhibitory concentrations of commonly used antibiotics against Helicobacter Pylori: A multicenter study in South China

Aim To determine the minimum inhibitory concentrations (MICs) of commonly used antibiotics against Helicobacter Pylori (H. pylori) in South China and compare their resistance rates by using EUCAST breakpoints and other breakpoints. Methods Patients who had not previously received H. pylori treatment in clinical centers in South China were enrolled in this study from 2017 to 2020. Gastric biopsies were obtained for H. pylori culture. The MICs of amoxicillin (AMX), clarithromycin (CLA), metronidazole (MTZ), levofloxacin (LEV), tetracycline (TET) and furazolidone (FZD) were tested by broth microdilution method and assessed by two different breakpoints. ATCC43504 standard strain served as a control. Results A total of 208 H. pylori strains were isolated from patients’ biopsy samples. The MICs of AMX, CLA, MTZ, LEV, TET and FZD for H. pylori were 0.0156-256mg/L (MIC50 0.125mg/L, MIC90 4mg/L), 0.0156- >256 mg/L (MIC50 0.0312mg/L, MIC90 64mg/L), 0.0156- >256mg/L (MIC50 8mg/L, MIC90 256mg/L), 0.0156-256mg/L (MIC50 0.25mg/L, MIC90 16mg/L), 0.0156-256mg/L (MIC50 0.0625mg/L, MIC90 4mg/L), and 0.0156- >256mg/L (MIC50 0.0312mg/L, MIC90 2mg/L), respectively. The MICs of AMX, CLA, MTZ, LEV, TET and FZD for ATCC43504 strain were 0.25mg/L, 0.0625mg/L, 64mg/L, 0.5mg/L, 1mg/L and 0.25mg/L, respectively. The resistance rate of FZD was 11.05%. The overall resistance rates according to EUCAST breakpoints and other breakpoints were 57.21% and 14.90% for AMX (p<0.001), 38.94% and 38.94% for CLA (p = 1), 39.42% and 50.96% for MTZ (p<0.001), 12.98% and 10.58% for TET (p = 0.025), 35.10% and 35.10% for LEV (p = 1), respectively. Conclusions Our results demonstrate that AMX, FZD, and TET, but not MTZ, CLR or LEV, showed good anti-H. pylori activity in vitro in South China. When different breakpoints were used, similar results were found with CLA, and LEV, but not with AMX, MTZ, or TET.

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Antimicrobial-ResistantStreptococcus pneumoniaein Canadian Hospitals: Results from the 2007 CANWARD Study

Canadian Journal of Infectious Diseases and Medical Microbiology ◽

10.1155/2009/286823 ◽

2009 ◽

Vol 20 (suppl a) ◽

pp. 37A-42A

Author(s):

Aleksandra K Wierzbowski ◽

Franil Tailor ◽

Kim Nichol ◽

James A Karlowsky ◽

Daryl J Hoban ◽

...

Keyword(s):

Antimicrobial Agents ◽

Macrolide Resistance ◽

Minimum Inhibitory Concentrations ◽

Microdilution Method ◽

Broth Microdilution Method ◽

Amoxicillin Clavulanic Acid ◽

Resistance To Penicillin ◽

Overall Resistance ◽

Blood Specimens ◽

Resistance Rates

BACKGROUND: The Canadian Ward Surveillance Study (CANWARD 2007) tested isolates collected from January to December 2007 from 12 Canadian hospitals to a range of antimicrobial agents. The present paper focuses on antimicrobial resistance inStreptococcus pneumoniaein Canadian hospitals, with an emphasis on macrolide resistance. MEtHODS: Minimum inhibitory concentrations of antimicrobial agents were determined using the broth microdilution method and interpreted according to Clinical and Laboratory Standards Institute breakpoints. Macrolide-nonsusceptible strains (clarithromycin minimum inhibitory concentrations 0.5 μg/mL or greater) were analyzed by multiplex polymerase chain reaction for the presence ofmefA andermB genes. RESULTS:S pneumoniaerepresented 9.0% (706 of 7881) of all isolates collected in CANWARD 2007. Of the 706S pneumoniaeisolates collected, 33.1% (234) were from blood and 66.9% (472) were from respiratory specimens. The overall resistance (resistant and intermediate) rates forS pneumoniaeisolated from respiratory and blood specimens, respectively, were: penicillin (23.9%, 14.4%), clarithromycin (22.1%, 12.6%), trimethoprim-sulfamethoxazole (14.7%, 11.5%), doxycycline (7.8%, 5.1%) and clindamycin (7.1%, 3.3%). Multidrug resistance (resistance to penicillin, clarithromycin and trimethoprimsulfamethoxazole) accounted for 2% (n=9) and 0.5% (n=1) of respiratory and blood isolates, respectively. Susceptibility of 95% or greater was found with amoxicillin-clavulanic acid (99.5%, 99.3%), ceftriaxone (99.5%, 100%), cefuroxime (95.0%, 96.8%), ertapenem (99.8%, 100%), meropenem (96.1%, 99.5%) and levofloxacin (99.1%, 100%) for respiratory and blood specimens, respectively. No resistance to vancomycin, tigecycline, cethromycin or telithromycin was found. mefA was present in 53.6% (52 of 97) of respiratory and 59.3% (16 of 27) of blood macrolide-nonsusceptibleS pneumoniae, while ermB was present in 38.1% (37 of 97) of respiratory and 37% (10 of 27) of blood isolates. Eight of 97 (8.2%) respiratory and one of 27 (3.7%) blood isolates contained both mefA and ermB genes. CONCLUSIONS:S pneumoniaeis a common organism isolated from clinical specimens in Canadian hospitals. Resistance was highest to penicillin and clarithromycin, while ceftriaxone and levofloxacin susceptibility were both greater than 99%. No isolates resistant to vancomycin, tigecycline, linezolid or the ketolides were found. Resistance rates were higher among respiratory tract isolates ofS pneumoniaethan among blood isolates. Macrolide efflux,mefA, was the predominant mechanism of macrolide resistance among both respiratory and blood clarithromycin-nonsusceptible isolates.

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Comparison of In Vitro Activities of ABT-773 and Telithromycin against Macrolide-Susceptible and -Resistant Streptococci and Staphylococci

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.46.3.783-786.2002 ◽

2002 ◽

Vol 46 (3) ◽

pp. 783-786 ◽

Cited By ~ 51

Author(s):

Virginia D. Shortridge ◽

Ping Zhong ◽

Zhensheng Cao ◽

Jill M. Beyer ◽

Laurel S. Almer ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Streptococcus Pneumoniae ◽

Ribosomal Protein ◽

Streptococcus Pyogenes ◽

Clinical Isolates ◽

Broth Microdilution ◽

Minimum Inhibitory Concentrations ◽

Microdilution Method ◽

Broth Microdilution Method

ABSTRACT The activity of a new ketolide, ABT-773, was compared to the activity of the ketolide telithromycin (HMR-3647) against over 600 gram-positive clinical isolates, including 356 Streptococcus pneumoniae, 167 Staphylococcus aureus, and 136 Streptococcus pyogenes isolates. Macrolide-susceptible isolates as well as macrolide-resistant isolates with ribosomal methylase (Erm), macrolide efflux (Mef), and ribosomal mutations were tested using the NCCLS reference broth microdilution method. Both compounds were extremely active against macrolide-susceptible isolates, with the minimum inhibitory concentrations at which 90% of the isolates tested were inhibited (MIC90s) for susceptible streptococci and staphylococci ranging from 0.002 to 0.03 μg/ml for ABT-773 and 0.008 to 0.06 μg/ml for telithromycin. ABT-773 had increased activities against macrolide-resistant S. pneumoniae (Erm MIC90, 0.015 μg/ml; Mef MIC90, 0.12 μg/ml) compared to those of telithromycin (Erm MIC90, 0.12 μg/ml; Mef MIC90, 1 μg/ml). Both compounds were active against strains with rRNA or ribosomal protein mutations (MIC90, 0.12 μg/ml). ABT-773 was also more active against macrolide-resistant S. pyogenes (ABT-773 Erm MIC90, 0.5 μg/ml; ABT-773 Mef MIC90, 0.12 μg/ml; telithromycin Erm MIC90, >8 μg/ml; telithromycin Mef MIC90, 1.0 μg/ml). Both compounds lacked activity against constitutive macrolide-resistant Staphylococcus aureus but had good activities against inducibly resistant Staphylococcus aureus (ABT-773 MIC90, 0.06 μg/ml; telithromycin MIC90, 0.5 μg/ml). ABT-773 has superior activity against macrolide-resistant streptococci compared to that of telithromycin.

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Broad spectrum resistance in Helicobacter pylori isolated from gastric biopsies of patients with dyspepsia in Cameroon and efflux-mediated multiresistance detection in MDR isolates

BMC Infectious Diseases ◽

10.1186/s12879-019-4536-8 ◽

2019 ◽

Vol 19 (1) ◽

Cited By ~ 3

Author(s):

Laure Brigitte Kouitcheu Mabeku ◽

Bertrand Eyoum Bille ◽

Cromwell Tepap Zemnou ◽

Lionel Danny Tali Nguefack ◽

Hubert Leundji

Keyword(s):

Helicobacter Pylori ◽

Efflux Pump ◽

Resistance Rate ◽

Diffusion Method ◽

Multi Drug Resistance ◽

Resistance Pattern ◽

Broth Microdilution Method ◽

Gastric Biopsies ◽

H Pylori ◽

Multiple Drugs

Abstract Background Antibiotic resistance is a leading cause of treatment failure in Helicobacter pylori infection. In Africa, there are very little data concerning the susceptibility of Helicobacter pylori isolates to antibiotics. The purpose of this study was to evaluate the resistance prevalence of Helicobacter pylori strains circulating in Cameroon, and to assess overexpression of efflux pump as a possible multi-drug resistance mechanisms. Methods A total of 140 H. pylori isolates were recovered from gastric biopsies of dyspeptic patients in two reference hospitals in Cameroon and analyzed for their antimicrobial susceptibility to amoxicillin, co-amoxiclav, ampicillin, penicillin, imipenem, metronidazole, rifabutin, erythromycin, clarithromycin, azithromycin, levofloxacin, ciprofloxacin, norfloxacin, tetracycline, doxycycline and minocycline. Antibiotic sensitivity was tested by disk diffusion method. Phe-Arg-naphthylamide (PAßN) was used as efflux pump inhibitor. INT broth microdilution method in supplemented Brain Heart Infusion broth was used to determine the MIC of ampicillin, amoxicillin, metronidazole, erythromycin, clarithromycin and doxycycline in the absence and the presence of PAßN against 32 selected MDR isolates. Results Overall H. pylori resistance rate was 100% to ampicillin, penicillin and co-amoxiclav; 97.14% to amoxicillin, 97.85% to metronidazole, 47.85% to erythromycin, 13.57% to clarithromycin; 5, 2.86 and 0.71% to doxycycline, tetracycline and minocycline respectively. No resistance to azithromycin, rifabutin, imipenem, ciprofloxacin, norfloxacin and levofloxacin was detected among H. pylori isolates. Seventy percent (70%) of the tested isolates elicited a multiple drugs resistance pattern; 42.57% double, 15.71% triple and 5.71% quadruple drugs resistance. Metronidazole and amoxicillin were more concerned with double resistance pattern (86.76%). The spectrum of activity recorded with metronidazole, doxycycline, clarithromycin and erythromycin ranged from 0 to 100% in the absence to the presence of PAßN against the tested MDR isolates. An 8 to 128-fold increase in potency was also noticed with these antibiotics in the presence of PAßN. Conclusion With regard to the high resistance rate to both amoxicillin and metronidazole, these drugs should be avoided as components of triple therapy in our milieu. In contrast, ciprofloxacin, norfloxacin, levofloxacin and tetracyclines could be used to achieve a better eradication rate and to reduce the risk of selection of H. pylori resistant strains.

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In Vitro Susceptibility ofCandidaSpecies to Four Antifungal Agents Assessed by the Reference Broth Microdilution Method

The Scientific World JOURNAL ◽

10.1155/2013/236903 ◽

2013 ◽

Vol 2013 ◽

pp. 1-6 ◽

Cited By ~ 14

Author(s):

Fahriye Eksi ◽

Efgan Dogan Gayyurhan ◽

Iclal Balci

Keyword(s):

Amphotericin B ◽

Antifungal Agents ◽

Antifungal Susceptibility ◽

Resistance Rate ◽

Broth Microdilution ◽

In Vitro Susceptibility ◽

Microdilution Method ◽

Broth Microdilution Method ◽

Dose Dependent

This study was performed to determine the distribution ofCandidaspecies isolated from the blood cultures of the patients hospitalized in our hospital and to investigate their antifungal susceptibility.Candidastrains were identified at species level by using classical methods and API ID 32C (bioMerieux, France) identification kits. The susceptibility of the strains to amphotericin B, fluconazole, voriconazole, and caspofungin was evaluated by using the reference broth microdilution method in document M27-A3 of the Clinical and Laboratory Standards Institute. Of the 111Candidastrains isolated, 47.7% were identified asC. albicansand 52.3% as non-albicansCandidastrains. The MIC ranges were 0.03–1 μg/mL for amphotericin B, 0.125–≥64 μg/mL for fluconazole, 0.03–16 μg/mL for voriconazole, and 0.015–0.25 μg/mL for caspofungin. AllCandidastrains were susceptible to amphotericin B and caspofungin. 10.8% isolates were resistant to fluconazole and 8.1% isolates were dose-dependent susceptible. While 0.9% isolate was resistant to voriconazole, 0.9% isolate was dose-dependent susceptible. In our study,C. albicansandC. parapsilosiswere the most frequently encountered agents of candidemia and it was detected that voriconazole with a low resistance rate might also be used with confidence in the treatment of infections occurring with these agents, primarily besides amphotericin B and caspofungin.

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Evaluation of Antimicrobial, Antioxidant, and Cytotoxic Activity of Phenolic Preparations of Diverse Composition, Obtained from Elaeagnus rhamnoides (L.) A. Nelson Leaf and Twig Extracts

Molecules ◽

10.3390/molecules26102835 ◽

2021 ◽

Vol 26 (10) ◽

pp. 2835

Author(s):

Anna Stochmal ◽

Bartosz Skalski ◽

Rostyslav Pietukhov ◽

Beata Sadowska ◽

Joanna Rywaniak ◽

...

Keyword(s):

Chemical Composition ◽

Plasma Lipids ◽

Biological Properties ◽

Sea Buckthorn ◽

Phenolic Antioxidants ◽

Microdilution Method ◽

Solid Media ◽

Broth Microdilution Method ◽

Markers Of Oxidative Stress

Although the major components of various organs of sea buckthorn have been identified (particularly phenolic compounds), biological properties of many of these phytochemicals still remain poorly characterized. In this study, we focused on the chemical composition and biological activity of preparations that were obtained from sea buckthorn twigs and leaves. The objective was to investigate cytotoxicity of these preparations against human fibroblast line HFF-1, using MTT reduction assay, their anti- or pro-oxidant activities against the effects of a biological oxidant -H2O2/Fe—on human plasma lipids and proteins in vitro (using TBARS and carbonyl groups as the markers of oxidative stress). Antimicrobial activity of the tested preparations against Gram-positive (Staphylococcus aureus, S. epidermidis, Enterococcus faecalis) and Gram-negative bacteria (Escherichia coli, Pseudomonas aeruginosa), as well as against fungi (Candida albicans, C. glabrata) by the EUCAST-approved broth microdilution method, followed by growth on solid media, were also assessed. Our analysis showed significant differences in chemical composition and biological properties of the tested preparations (A–F). All tested preparations from sea buckthorn twigs (D–F) and one preparation from sea buckthorn leaves (preparation C) may be a new source of phenolic antioxidants for pharmacological and cosmetic applications.

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In Vitro Antibacterial Effect of the Methanolic Extract of the Korean Soybean Fermented Product Doenjang against Staphylococcus aureus

Animals ◽

10.3390/ani11082319 ◽

2021 ◽

Vol 11 (8) ◽

pp. 2319

Author(s):

Klara Lalouckova ◽

Lucie Mala ◽

Petr Marsik ◽

Eva Skrivanova

Keyword(s):

Staphylococcus Aureus ◽

High Performance ◽

Methanolic Extract ◽

Bioactive Substances ◽

Microdilution Method ◽

Antibacterial Compound ◽

Fermented Product ◽

Broth Microdilution Method

Ultra-high performance liquid chromatography/mass spectrometry showed soyasaponin I and the isoflavones daidzein, genistein, and glycitein to be the main components of the methanolic extract of the Korean soybean fermented product doenjang, which is known to be a rich source of naturally occurring bioactive substances, at average contents of 515.40, 236.30, 131.23, and 29.00 ng/mg, respectively. The antimicrobial activity of the methanolic extract of doenjang against nine Staphylococcusaureus strains was determined in vitro by the broth microdilution method to investigate its potential to serve as an alternative antibacterial compound. The results suggest that the extract is an effective antistaphylococcal agent at concentrations of 2048–4096 µg/mL. Moreover, the tested extract also showed the ability to inhibit the growth of both methicillin-sensitive and methicillin-resistant animal and clinical S. aureus isolates. The growth kinetics of the chosen strains of S. aureus at the minimum inhibitory concentration of the methanolic extract of doenjang support the idea that the tested extract acts as an antibacterial compound. To the best of our knowledge, this is the first report on the antistaphylococcal action of the methanolic extract of doenjang thus, additional studies including in vivo testing are necessary to confirm this hypothesis.

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Activity of Ceftazidime-Avibactam against Fluoroquinolone-Resistant Enterobacteriaceae and Pseudomonas aeruginosa

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.05136-14 ◽

2015 ◽

Vol 59 (6) ◽

pp. 3059-3065 ◽

Cited By ~ 14

Author(s):

C. Pitart ◽

F. Marco ◽

T. A. Keating ◽

W. W. Nichols ◽

J. Vila

Keyword(s):

Pseudomonas Aeruginosa ◽

Resistant Mutant ◽

Fluoroquinolone Resistance ◽

Cross Resistance ◽

Content Type ◽

E Coli ◽

Microdilution Method ◽

Broth Microdilution Method ◽

The Impact

ABSTRACTCeftazidime-avibactam and comparator antibiotics were tested by the broth microdilution method against 200Enterobacteriaceaeand 25Pseudomonas aeruginosastrains resistant to fluoroquinolones (including strains with the extended-spectrum β-lactamase [ESBL] phenotype and ceftazidime-resistant strains) collected from our institution. The MICs and mechanisms of resistance to fluoroquinolone were also studied. Ninety-nine percent of fluoroquinolone-resistantEnterobacteriaceaestrains were inhibited at a ceftazidime-avibactam MIC of ≤4 mg/liter (using the susceptible CLSI breakpoint for ceftazidime alone as a reference). Ceftazidime-avibactam was very active against ESBLEscherichia coli(MIC90of 0.25 mg/liter), ESBLKlebsiella pneumoniae(MIC90of 0.5 mg/liter), ceftazidime-resistant AmpC-producing species (MIC90of 1 mg/liter), non-ESBLE. coli(MIC90of ≤0.125 mg/liter), non-ESBLK. pneumoniae(MIC90of 0.25 mg/liter), and ceftazidime-nonresistant AmpC-producing species (MIC90of ≤0.5 mg/liter). Ninety-six percent of fluoroquinolone-resistantP. aeruginosastrains were inhibited at a ceftazidime-avibactam MIC of ≤8 mg/liter (using the susceptible CLSI breakpoint for ceftazidime alone as a reference), with a MIC90of 8 mg/liter. Additionally, fluoroquinolone-resistant mutants from each species tested were obtainedin vitrofrom two strains, one susceptible to ceftazidime and the other a β-lactamase producer with a high MIC against ceftazidime but susceptible to ceftazidime-avibactam. Thereby, the impact of fluoroquinolone resistance on the activity of ceftazidime-avibactam could be assessed. The MIC90values of ceftazidime-avibactam for the fluoroquinolone-resistant mutant strains ofEnterobacteriaceaeandP. aeruginosawere ≤4 mg/liter and ≤8 mg/liter, respectively. We conclude that the presence of fluoroquinolone resistance does not affectEnterobacteriaceaeandP. aeruginosasusceptibility to ceftazidime-avibactam; that is, there is no cross-resistance.

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In VitroSynergistic Effect of Curcumin in Combination with Third Generation Cephalosporins against Bacteria Associated with Infectious Diarrhea

BioMed Research International ◽

10.1155/2014/561456 ◽

2014 ◽

Vol 2014 ◽

pp. 1-8 ◽

Cited By ~ 15

Author(s):

Nishanth Kumar Sasidharan ◽

Sreerag Ravikumar Sreekala ◽

Jubi Jacob ◽

Bala Nambisan

Keyword(s):

Synergistic Effect ◽

New Combination ◽

Normal Fibroblast ◽

Infectious Diarrhea ◽

Combination Drug ◽

Microdilution Method ◽

Broth Microdilution Method ◽

Time Kill ◽

Third Generation Cephalosporins

Diarrhea is one of the leading causes of morbidity and mortality in humans in developed and developing countries. Furthermore, increased resistance to antibiotics has resulted in serious challenges in the treatment of this infectious disease worldwide. Therefore, there exists a need to develop alternative natural or combination drug therapies. The aim of the present study was to investigate the synergistic effect of curcumin-1 in combination with three antibiotics against five diarrhea causing bacteria. The antibacterial activity of curcumin-1 and antibiotics was assessed by the broth microdilution method, checkerboard dilution test, and time-kill assay. Antimicrobial activity of curcumin-1 was observed against all tested strains. The MICs of curcumin-1 against test bacteria ranged from 125 to 1000 μg/mL. In the checkerboard test, curcumin-1 markedly reduced the MICs of the antibiotics cefaclor, cefodizime, and cefotaxime. Significant synergistic effect was recorded by curcumin-1 in combination with cefotaxime. The toxicity of curcumin-1 with and without antibiotics was tested against foreskin (FS) normal fibroblast and no significant cytotoxicity was observed. From our result it is evident that curcumin-1 enhances the antibiotic potentials against diarrhea causing bacteria inin vitrocondition. This study suggested that curcumin-1 in combination with antibiotics could lead to the development of new combination of antibiotics against diarrhea causing bacteria.

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In Vitro Activities of the Novel Oxazolidinones DA-7867 and DA-7157 against Rapidly and Slowly Growing Mycobacteria

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00763-06 ◽

2006 ◽

Vol 50 (12) ◽

pp. 4027-4029 ◽

Cited By ~ 18

Author(s):

Lucio Vera-Cabrera ◽

Barbara A. Brown-Elliott ◽

Richard J. Wallace ◽

Jorge Ocampo-Candiani ◽

Oliverio Welsh ◽

...

Keyword(s):

Mycobacterium Tuberculosis ◽

Clinical Isolates ◽

Nontuberculous Mycobacterium ◽

The Novel ◽

Broth Microdilution ◽

Reference Species ◽

Microdilution Method ◽

Broth Microdilution Method ◽

Aerobic Actinomycetes

ABSTRACT DA-7867 and DA-7157 are oxazolidinones active against pathogenic aerobic actinomycetes including Nocardia spp. and Mycobacterium tuberculosis. However, the activity of these drugs against nontuberculous mycobacterium (NTM) species is not known. In this work, we compared the susceptibilities of 122 clinical isolates and 29 reference species of both rapidly growing and slowly growing mycobacteria to linezolid, DA-7867, and DA-7157 by the broth microdilution method. The MICs for 50 and 90% of the strains tested (MIC50s and MIC90s, respectively) of DA-7867 and DA-7157 were lower than those of linezolid. In all of the cases, a MIC90 of <8 μg/ml was observed for all of the species tested in both groups of NTM. For M. kansasii and M. marinum isolates, the MIC90s of both DA-7867 and DA-7157 were less than 0.5 μg/ml. These results demonstrate the potential of these compounds to treat NTM infections.

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In Vitro Activities of Voriconazole in Combination with Three Other Antifungal Agents against Candida glabrata

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.48.9.3317-3322.2004 ◽

2004 ◽

Vol 48 (9) ◽

pp. 3317-3322 ◽

Cited By ~ 21

Author(s):

Francesco Barchiesi ◽

Elisabetta Spreghini ◽

Monia Maracci ◽

Annette W. Fothergill ◽

Isabella Baldassarri ◽

...

Keyword(s):

Candida Glabrata ◽

Antifungal Agents ◽

Beneficial Effects ◽

Synergistic Interactions ◽

Microdilution Method ◽

Broth Microdilution Method ◽

Disk Diffusion Assay ◽

Combination Regimens

ABSTRACT Candida glabrata has recently emerged as a significant pathogen involved in both superficial and deep-seated infections. In the present study, a checkerboard broth microdilution method was performed to investigate the in vitro activities of voriconazole (VOR) in combination with terbinafine (TRB), amphotericin B (AMB), and flucytosine (5FC) against 20 clinical isolates of C. glabrata. Synergy, defined as a fractional inhibitory concentration (FIC) index of ≤0.50, was observed in 75% of VOR-TRB, 10% of VOR-AMB, and 5% of VOR-5FC interactions. None of these combinations yielded antagonistic interactions (FIC index > 4). When synergy was not achieved, there was still a decrease in the MIC of one or both drugs used in the combination. In particular, the MICs were reduced to ≤1.0 μg/ml as a result of the combination for all isolates for which the AMB MIC at the baseline was ≥2.0 μg/ml. By a disk diffusion assay, the halo diameters produced by antifungal agents in combination were greater that those produced by each drug alone. Finally, killing curves showed that VOR-AMB exhibited synergistic interactions, while VOR-5FC sustained fungicidal activities against C. glabrata. These studies demonstrate that the in vitro activity of VOR against this important yeast pathogen can be enhanced upon combination with other drugs that have different modes of action or that target a different step in the ergosterol pathway. Further studies are warranted to elucidate the potential beneficial effects of such combination regimens in vivo.

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