scholarly journals In vitro activity of ceftazidime/avibactam against isolates of carbapenem-non-susceptible Enterobacteriaceae collected during the INFORM global surveillance programme (2015–17)

2019 ◽  
Vol 75 (2) ◽  
pp. 384-391 ◽  
Author(s):  
Iris Spiliopoulou ◽  
Krystyna Kazmierczak ◽  
Gregory G Stone
Keyword(s):  
Antimicrobial Activity ◽  
In Vitro Activity ◽  
Broth Microdilution ◽  
Gene Encoding ◽  
Surveillance Programme ◽  
Genes Encoding ◽  
The Usa ◽  
Report Data ◽  
Pcr Assays

Abstract Objectives To report data for ceftazidime/avibactam and comparators against meropenem-non-susceptible Enterobacteriaceae collected globally (excluding centres in the USA) from 2015 to 2017 as part of the International Network For Optimal Resistance Monitoring (INFORM) surveillance programme. Methods MICs and susceptibility were determined using EUCAST broth microdilution methodology and EUCAST breakpoints. Isolates were screened to detect genes encoding β-lactamases using multiplex PCR assays. MBL-positive isolates were those in which one or more of the IMP, VIM and/or NDM genes were detected. Results A total of 1460 meropenem-non-susceptible isolates were collected and, of the agents on the panel, susceptibility was highest to ceftazidime/avibactam, colistin and tigecycline [73.0%, 77.0% (1081/1403) and 78.1%, respectively]. Ceftazidime/avibactam was not active against MBL-positive isolates (n=367); these isolates showed the highest rates of susceptibility to colistin (92.1%, 303/329), tigecycline (71.9%) and amikacin (46.6%). A total of 394 isolates were resistant to ceftazidime/avibactam and, of the 369 isolates that were screened, 98.4% were found to carry a gene encoding an MBL enzyme. Among isolates that were identified as carbapenemase positive and MBL negative (n=910), susceptibility was highest to ceftazidime/avibactam (99.8%). Susceptibility was also highest to ceftazidime/avibactam among isolates that were carbapenemase negative and MBL negative (94/98, 95.9%). Conclusions These data highlight the need for continued surveillance of antimicrobial activity as well as the need for new antimicrobials to treat infections caused by meropenem-non-susceptible Enterobacteriaceae, for which the options are extremely limited.

Murepavadin antimicrobial activity against and resistance development in cystic fibrosis Pseudomonas aeruginosa isolates

2020 ◽  
Author(s):  
María Díez-Aguilar ◽  
Marta Hernández-García ◽  
María-Isabel Morosini ◽  
Ad Fluit ◽  
Michael M Tunney ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Antimicrobial Activity ◽  
Spontaneous Mutation ◽  
Lung Surfactant ◽  
Vitro Activity ◽  
In Vitro Activity ◽  
Broth Microdilution ◽  
Agar Dilution

Abstract Background Murepavadin, a novel peptidomimetic antibiotic, is being developed as an inhalation therapy for treatment of Pseudomonas aeruginosa respiratory infection in people with cystic fibrosis (CF). It blocks the activity of the LptD protein in P. aeruginosa causing outer membrane alterations. Objectives To determine the in vitro activity of murepavadin against CF P. aeruginosa isolates and to investigate potential mechanisms of resistance. Methods MIC values were determined by both broth microdilution and agar dilution and results compared. The effect of artificial sputum and lung surfactant on in vitro activity was also measured. Spontaneous mutation frequency was estimated. Bactericidal activity was investigated using time–kill assays. Resistant mutants were studied by WGS. Results The murepavadin MIC50 was 0.125 versus 4 mg/L and the MIC90 was 2 versus 32 mg/L by broth microdilution and agar dilution, respectively. Essential agreement was >90% when determining in vitro activity with artificial sputum or lung surfactant. It was bactericidal at a concentration of 32 mg/L against 95.4% of the strains within 1–5 h. Murepavadin MICs were 2–9 two-fold dilutions higher for the mutant derivatives (0.5 to >16 mg/L) than for the parental strains. Second-step mutants were obtained for the PAO mutS reference strain with an 8×MIC increase. WGS showed mutations in genes involved in LPS biosynthesis (lpxL1, lpxL2, bamA2, lptD, lpxT and msbA). Conclusions Murepavadin characteristics, such as its specific activity against P. aeruginosa, its unique mechanism of action and its strong antimicrobial activity, encourage the further clinical evaluation of this drug.

In vitro activity of ampicillin and ceftriaxone against ampicillin-susceptible Enterococcus faecium

2019 ◽  
Vol 74 (8) ◽  
pp. 2269-2273 ◽  
Author(s):  
Michael P Lorenzo ◽  
James M Kidd ◽  
Stephen G Jenkins ◽  
David P Nicolau ◽  
Seth T Housman
Keyword(s):  
Enterococcus Faecium ◽  
Susceptibility Testing ◽  
Diffusion Time ◽  
Disc Diffusion ◽  
In Vitro Activity ◽  
Broth Microdilution ◽  
Gradient Diffusion ◽  
The Usa ◽  
Time Kill

AbstractObjectivesTo assess activity of the combination of ceftriaxone and ampicillin against clinical isolates of ampicillin-susceptible Enterococcus faecium.MethodsAmpicillin-susceptible E. faecium (n = 29) and Enterococcus faecalis (n = 10) collected from locations in the USA and France were used for this analysis. Susceptibility testing was performed by gradient diffusion strip (GDS) and broth microdilution (BMD). Synergy with the combination of ceftriaxone and ampicillin was assessed in all isolates using GDS crossing and double disc diffusion methods. Selected isolates (nine E. faecium and three E. faecalis) were assessed for synergy in time–kill studies using ampicillin alone and in combination with ceftriaxone.ResultsIn isolates of E. faecium, the median (range) ampicillin MIC by BMD was 0.5 (0.25–4) mg/L and by GDS it was 2 (1–8)  mg/L. In E. faecalis, the median (range) ampicillin MIC by BMD was 0.5 (0.5–1) mg/L and by GDS it was 2 (0.75–3) mg/L. A total of 24/29 (82.8%) isolates of E. faecium displayed synergy by GDS and 22/29 (75.9%) by double disc diffusion. Seven of 10 (70%) isolates of E. faecalis displayed synergy by GDS and 4/10 (40%) by double disc diffusion. Time–kill studies found synergy in 3/9 (33.3%) E. faecium and 3/3 (100%) E. faecalis.ConclusionsIn contrast to the demonstrated synergy in time–kill models of ceftriaxone and ampicillin for E. faecalis, this combination does not appear to provide uniform synergy in E. faecium. Antagonism was not observed. Clinical correlation is necessary and caution should be used when considering ampicillin and ceftriaxone for the treatment of infections caused by ampicillin-susceptible E. faecium.

scholarly journals PRO: Carbapenems should be used for ALL infections caused by ceftriaxone-resistant Enterobacterales

2021 ◽  
Vol 3 (1) ◽  
Author(s):  
David L Paterson ◽  
Burcu Isler ◽  
Patrick N A Harris
Keyword(s):  
Antibiotic Resistance ◽  
Observational Studies ◽  
Randomized Trials ◽  
Antibiotic Resistance Genes ◽  
Definitive Treatment ◽  
In Vitro Activity ◽  
Genes Encoding ◽  
Amoxicillin Clavulanate ◽  
Trial Outcomes

Abstract Ceftriaxone resistance in the Enterobacterales is typically the result of production of ESBLs or AmpC β-lactamases. The genes encoding these enzymes are often co-located with other antibiotic resistance genes leading to resistance to aminoglycosides, quinolones and trimethoprim/sulfamethoxazole. Carbapenems are stable to ESBLs and AmpC giving them reliable in vitro activity against producers of these β-lactamases. In contrast, piperacillin/tazobactam and amoxicillin/clavulanate are compromised by co-production of OXA-1, which is not inhibited by tazobactam or clavulanate. These in vitro findings provide an explanation for the MERINO trial outcomes, where 3.7% (7/191) randomized to meropenem died compared with 12.3% (23/187) randomized to piperacillin/tazobactam as definitive treatment of bloodstream infection due to ceftriaxone-resistant organisms. No randomized trials have yet put cefepime and carbapenems head to head, but some observational studies have shown worse outcomes with cefepime. We argue that carbapenems are the antibiotics of choice for ceftriaxone-resistant Enterobacterales.

scholarly journals In Vitro Activity of Ibrexafungerp, a Novel Glucan Synthase Inhibitor against Candida glabrata Isolates with FKS Mutations

2019 ◽  
Vol 63 (11) ◽  
Author(s):  
Natalie S. Nunnally ◽  
Kizee A. Etienne ◽  
David Angulo ◽  
Shawn R. Lockhart ◽  
Elizabeth L. Berkow
Keyword(s):  
Candida Glabrata ◽  
Vitro Activity ◽  
Good Activity ◽  
In Vitro Activity ◽  
Broth Microdilution ◽  
Glucan Synthase ◽  
Content Type ◽  
Synthase Inhibitor

ABSTRACT Ibrexafungerp is a first-in-class glucan synthase inhibitor. In vitro activity was determined for 89 Candida glabrata isolates with molecularly identified FKS1 or FKS2 mutations conferring resistance to the echinocandins. All isolates were resistant to at least one echinocandin (i.e., anidulafungin, caspofungin, or micafungin) by broth microdilution. Results for ibrexafungerp were compared with those for each echinocandin. Ibrexafungerp had good activity against all echinocandin-resistant C. glabrata isolates.

scholarly journals In Vitro Activities of Daptomycin against 2,789 Clinical Isolates from 11 North American Medical Centers

2001 ◽  
Vol 45 (6) ◽  
pp. 1919-1922 ◽  
Author(s):  
Arthur L. Barry ◽  
Peter C. Fuchs ◽  
Steven D. Brown
Keyword(s):  
Clinical Isolates ◽  
In Vitro Activity ◽  
Broth Microdilution ◽  
In Vitro Susceptibility ◽  
Medical Centers ◽  
Mueller Hinton ◽  
Calcium Cations ◽  
Important Exception ◽  
Mueller Hinton Broth

ABSTRACT The in vitro activity of daptomycin is affected by the concentration of calcium cations in the test medium. Mueller-Hinton broth is currently adjusted to contain 10 to 12.5 mg of magnesium per liter and 20 to 25 mg of calcium per liter, but for testing of daptomycin, greater concentrations of calcium (50 mg/liter) are recommended to better resemble the normal concentration of ionized calcium in human serum. Two levels of calcium were used for broth microdilution tests of 2,789 recent clinical isolates of gram-positive bacterial pathogens. MICs of daptomycin were two- to fourfold lower when the broth contained additional calcium. For most species, however, the percentages of strains that were inhibited by 2.0 μg of daptomycin per ml were essentially identical with the two broth media. Enterococci were the important exception; i.e., 92% were inhibited when tested in calcium-supplemented broth but only 35% were inhibited by 2.0 μg/ml without the additional calcium. This type of information should be considered when selecting criteria for defining in vitro susceptibility to daptomycin.

scholarly journals In Vitro Activities of the New Antifungal Triazole SCH 56592 against Common and Emerging Yeast Pathogens

2000 ◽  
Vol 44 (1) ◽  
pp. 226-229 ◽  
Author(s):  
Francesco Barchiesi ◽  
Daniela Arzeni ◽  
Annette W. Fothergill ◽  
Luigi Falconi Di Francesco ◽  
Francesca Caselli ◽  
...  
Keyword(s):  
Clinical Laboratory ◽  
Clinical Development ◽  
National Committee ◽  
In Vitro Activity ◽  
Broth Microdilution ◽  
Microdilution Method ◽  
Broth Microdilution Method ◽  
Vitro Data ◽  
In Vitro Data

ABSTRACT A broth microdilution method performed in accordance with the National Committee for Clinical Laboratory Standards guidelines was used to compare the in vitro activity of the new antifungal triazole SCH 56592 (SCH) to that of fluconazole (FLC), itraconazole (ITC), and ketoconazole (KETO) against 257 clinical yeast isolates. They included 220 isolates belonging to 12 different species of Candida, 15 isolates each of Cryptococcus neoformans andSaccharomyces cerevisiae, and seven isolates ofRhodotorula rubra. The MICs of SCH at which 50% (MIC50) and 90% (MIC90) of the isolates were inhibited were 0.06 and 2.0 μg/ml, respectively. In general, SCH was considerably more active than FLC (MIC50 and MIC90 of 1.0 and 64 μg/ml, respectively) and slightly more active than either ITC (MIC50 and MIC90 of 0.25 and 2.0 μg/ml, respectively) and KETO (MIC50 and MIC90 of 0.125 and 4.0 μg/ml, respectively). Our in vitro data suggest that SCH has significant potential for clinical development.

scholarly journals In Vitro Antimicrobial Activity of the Siderophore Cephalosporin Cefiderocol against Acinetobacter baumannii Strains Recovered from Clinical Samples

Antibiotics ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 1309
Author(s):  
Davide Carcione ◽  
Claudia Siracusa ◽  
Adela Sulejmani ◽  
Roberta Migliavacca ◽  
Alessandra Mercato ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Acinetobacter Baumannii ◽  
Inhibition Zone ◽  
Broth Microdilution ◽  
Large Variability ◽  
Gold Standard Method ◽  
Disk Diffusion Test ◽  
In Vitro Antimicrobial Activity ◽  
Broth Microdilution Method

Background: Cefiderocol is a siderophore cephalosporin that exhibits antimicrobial activity against most multi-drug resistant Gram-negative bacteria, including Enterobacterales, Pseudomonas aeruginosa, Acinetobacter baumannii, and Stenotrophomonas maltophilia. Methods: A total of 20 multidrug-resistant A. baumannii strains were isolated from 2020 to 2021, molecularly characterized and tested to assess the in vitro antibacterial activity of cefiderocol. Thirteen strains were carbapenem-hydrolysing oxacillinase OXA-23-like producers, while seven were non-OXA-23-like producers. Minimum inhibitory concentrations (MICs) were determined by broth microdilution, considered as the gold standard method. Disk diffusion test was also carried out using iron-depleted CAMHB plates for cefiderocol. Results: Cefiderocol MICs ranged from 0.5 to 1 mg/L for OXA-23-like non-producing A. baumannii strains and from 0.25 to >32 mg/L for OXA-23-like producers, using the broth microdilution method. Cefiderocol MIC90 was 8 mg/L. Diameter of inhibition zone of cefiderocol ranged from 18 to 25 mm for OXA-23-like non-producers and from 15 to 36 mm for OXA-23-like producers, using the diffusion disk method. A large variability and a low reproducibility were observed during the determination of diameter inhibition zone. Molecular characterization showed that all isolates presented the ISAba1 genetic element upstream the blaOXA-51. Among OXA-23-like non-producers, four were blaOXA-58 positive and two were negative for all the resistance determinants analyzed. Conclusions: Cefiderocol showed in vitro antimicrobial activity against both carbapenem-susceptible and non-susceptible A. baumannii strains, although some OXA-23-like producers were resistant. Further clinical studies are needed to consolidate the role of cefiderocol as an antibiotic against MDR A. baumannii.

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