<i>In Vitro</i>
            Activity of Ceftazidime-Avibactam against Isolates in a Phase 3 Open-Label Clinical Trial for Complicated Intra-Abdominal and Urinary Tract Infections Caused by Ceftazidime-Nonsusceptible Gram-Negative Pathogens

Stone, Gregory G.; Bradford, Patricia A.; Newell, Paul; Wardman, Angela

doi:10.1128/aac.01820-16

Cited by 25 publications

(15 citation statements)

References 9 publications

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“…Ceftazidime-avibactam (87.4% susceptible) was the second most potent agent tested against isolates of P. aeruginosa from six Latin American countries in 2012 to 2015, after colistin (94.9% susceptible). Based on the in vitro susceptibilities and proven clinical efficacy (30,31,(38)(39)(40)(41), ceftazidime-avibactam should be considered in the treatment of indicated infections caused by susceptible Enterobacteriaceae and P. aeruginosa strains.…”

Section: Discussionmentioning

confidence: 99%

In Vitro Activity of Ceftazidime-Avibactam against Clinical Isolates of Enterobacteriaceae and Pseudomonas aeruginosa Collected in Latin American Countries: Results from the INFORM Global Surveillance Program, 2012 to 2015

Karlowsky¹,

Kazmierczak²,

Bouchillon³

et al. 2019

Antimicrob Agents Chemother

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The International Network for Optimal Resistance Monitoring (INFORM) global surveillance program collected clinical isolates of Enterobacteriaceae (n ϭ 7,665) and Pseudomonas aeruginosa (n ϭ 1,794) from 26 medical centers in six Latin American countries from 2012 to 2015. The in vitro activity of ceftazidime-avibactam and comparators was determined for the isolates using the Clinical and Laboratory Standards Institute (CLSI) reference broth microdilution method. Enterobacteriaceae were highly susceptible (99.7%) to ceftazidime-avibactam, including 99.9% of metallo-␤-lactamase (MBL)-negative isolates; 87.4% of all P. aeruginosa isolates and 92.8% of MBL-negative isolates were susceptible to ceftazidime-avibactam. Susceptibility to ceftazidime-avibactam ranged from 99.4% to 100% for Enterobacteriaceae and from 79.1% to 94.7% for P. aeruginosa when isolates were analyzed by country of origin. Ceftazidime-avibactam inhibited 99.6% to 100% of Enterobacteriaceae isolates that carried serine ␤-lactamases, including extended-spectrum ␤-lactamases (ESBLs), AmpC cephalosporinases, and carbapenemases (KPC and OXA-48-like) as well as 99.7%, 99.6%, 99.5%, and 99.2% of MBL-negative isolatesdemonstratingceftazidime-nonsusceptible,multidrug-resistant(MDR),meropenem-nonsusceptible, and colistin-resistant phenotypes, respectively. Among carbapenem-nonsusceptible isolates of P. aeruginosa (n ϭ 750), 14.7% carried MBLs with or without additional acquired serine ␤-lactamases, while in the majority of isolates (70.0%), no acquired ␤-lactamase was identified. Ceftazidime-avibactam inhibited 89.5% of carbapenem-nonsusceptible P. aeruginosa isolates in which no acquired ␤-lactamase was detected. Overall, clinical isolates of Enterobacteriaceae collected in Latin America from 2012 to 2015 were highly susceptible to ceftazidime-avibactam, including isolates that exhibited resistance to ceftazidime, meropenem, colistin, or an MDR phenotype. Country-specific variations were noted in the susceptibility of P. aeruginosa isolates to ceftazidime-avibactam.

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Section: Discussionmentioning

confidence: 99%

In Vitro Activity of Ceftazidime-Avibactam against Clinical Isolates of Enterobacteriaceae and Pseudomonas aeruginosa Collected in Latin American Countries: Results from the INFORM Global Surveillance Program, 2012 to 2015

Karlowsky¹,

Kazmierczak²,

Bouchillon³

et al. 2019

Antimicrob Agents Chemother

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“…However, our findings were comparable to that of Stone et al who showed that the CAZ and CZA MIC 50/90 values for 27 P. aeruginosa isolates were 64/> 64

and 8/64

, respectively, versus 64/128

and 32/64

in the present study. Higher MIC 90 values were assessed to be due to the possession of either a class B or a class D enzyme as those strains which lacked these enzymes had a MIC 90 value of 8

[ 40 ].…”

Section: Discussionmentioning

confidence: 99%

In Vitro Activity of Newer and Conventional Antimicrobial Agents, Including Fosfomycin and Colistin, against Selected Gram-Negative Bacilli in Kuwait

Nicolau

2018

Pathogens

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Limited data are available on susceptibilities of these organisms to some of the recently made accessible antimicrobial agents. The in vitro activities of newer antibiotics, such as, ceftolozane/tazobactam (C/T) and ceftazidime/avibactam (CZA) along with some “older” antibiotics, for example fosfomycin (FOS) and colistin (CL) were determined against selected strains (resistant to ≥3 antimicrobial agents) of Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa. Minimum inhibitory concentrations (MIC) were determined by Clinical and Laboratory Standards Institute microbroth dilution. 133 isolates: 46 E. coli, 39 K. pneumoniae, and 48 P. aeruginosa were tested. Results showed that E. coli isolates with MIC50/90, 0.5/1 sans-serifμnormalg/mL for CL; 4/32 sans-serifμnormalg/mL for FOS; 0.25/32 sans-serifμnormalg/mL for C/T; 0.25/8 sans-serifμnormalg/mL for CZA, exhibited susceptibility rates of 95.7%, 97.8%, 76.1%, and 89.1%, respectively. On the other hand, K. pneumoniae strains with MIC50/90, 0.5/1 sans-serifμnormalg/mL for CL; 256/512 sans-serifμnormalg/mL for FOS; 2/128 sans-serifμnormalg/mL for C/T; 0.5/128 sans-serifμnormalg/mL for CZA showed susceptibility rates of 92.3%, 7.7%, 51.3%, and 64.1%, respectively. P. aeruginosa isolates with MIC50/90, 1/1 sans-serifμnormalg/mL for CL; 128/128 sans-serifμnormalg/mL for C/T; 32/64 sans-serifμnormalg/mL for CZA presented susceptibility rates of 97.9%, 33.3%, and 39.6%, respectively. Higher MICs were demonstrated against most of the antibiotics. However, CL retained efficacy at low MICs against most of the isolates tested.

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“…avibactam studies in which baseline pathogen samples were obtained from patients with cIAI and cUTI, including isolates that were nonsusceptible to ceftazidime (33)(34)(35).…”

Section: Discussionmentioning

confidence: 99%

In Vitro Activity of Ceftazidime-Avibactam against Isolates from Respiratory and Blood Specimens from Patients with Nosocomial Pneumonia, Including Ventilator-Associated Pneumonia, in a Phase 3 Clinical Trial

Stone

Bradford

Tawadrous

et al. 2020

Antimicrob Agents Chemother

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Nosocomial pneumonia (NP), including ventilator-associated pneumonia (VAP), is increasingly associated with multidrug-resistant Gram-negative pathogens. This study describes the in vitro activity of ceftazidime-avibactam, ceftazidime, and relevant comparator agents against bacterial pathogens isolated from patients with NP, including VAP, enrolled in a ceftazidime-avibactam phase 3 trial. Gram-positive pathogens were included if coisolated with a Gram-negative pathogen. In vitro susceptibility was determined at a central laboratory using Clinical and Laboratory Standards Institute broth microdilution methods. Of 817 randomized patients, 457 (55.9%) had ≥1 Gram-negative bacterial pathogen(s) isolated at baseline, and 149 (18.2%) had ≥1 Gram-positive pathogen(s) coisolated. The most common isolated pathogens were Klebsiella pneumoniae (18.8%), Pseudomonas aeruginosa (15.8%), and Staphylococcus aureus (11.5%). Ceftazidime-avibactam was highly active in vitro against 370 isolates of Enterobacteriaceae, with 98.6% susceptible (MIC90, 0.5 μg/ml) compared with 73.2% susceptible for ceftazidime (MIC90, >64 μg/ml). The percent susceptibility values for ceftazidime-avibactam and ceftazidime against 129 P. aeruginosa isolates were 88.4% and 72.9% (MIC90 values of 16 μg/ml and 64 μg/ml), respectively. Among ceftazidime-nonsusceptible Gram-negative isolates, ceftazidime-avibactam percent susceptibility values were 94.9% for 99 Enterobacteriaceae and 60.0% for 35 P. aeruginosa. MIC90 values for linezolid and vancomycin (permitted per protocol for Gram-positive coverage) were within their respective MIC susceptibility breakpoints against the Gram-positive pathogens isolated. This analysis demonstrates that ceftazidime-avibactam was active in vitro against the majority of Enterobacteriaceae and P. aeruginosa isolates from patients with NP, including VAP, in a phase 3 trial. (This study has been registered at ClinicalTrials.gov under identifier NCT01808092.)

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In Vitro Activity of Ceftazidime-Avibactam against Isolates in a Phase 3 Open-Label Clinical Trial for Complicated Intra-Abdominal and Urinary Tract Infections Caused by Ceftazidime-Nonsusceptible Gram-Negative Pathogens

Cited by 25 publications

References 9 publications

In Vitro Activity of Ceftazidime-Avibactam against Clinical Isolates of Enterobacteriaceae and Pseudomonas aeruginosa Collected in Latin American Countries: Results from the INFORM Global Surveillance Program, 2012 to 2015

In Vitro Activity of Ceftazidime-Avibactam against Clinical Isolates of Enterobacteriaceae and Pseudomonas aeruginosa Collected in Latin American Countries: Results from the INFORM Global Surveillance Program, 2012 to 2015

In Vitro Activity of Newer and Conventional Antimicrobial Agents, Including Fosfomycin and Colistin, against Selected Gram-Negative Bacilli in Kuwait

In Vitro Activity of Ceftazidime-Avibactam against Isolates from Respiratory and Blood Specimens from Patients with Nosocomial Pneumonia, Including Ventilator-Associated Pneumonia, in a Phase 3 Clinical Trial

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