Ceftazidime-avibactam activity when tested against ceftazidime-nonsusceptible Citrobacter spp., Enterobacter spp., Serratia marcescens, and Pseudomonas aeruginosa from Unites States medical centers (2011–2014)

Sader, Hélio S.; Castanheira, Mariana; Farrell, David J.; Flamm, Robert K.; Jones, Ronald N.

doi:10.1016/j.diagmicrobio.2015.06.008

Cited by 30 publications

(16 citation statements)

References 20 publications

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“…The high level of in vitro activity observed for ceftazidimeavibactam against P. aeruginosa was corroborated by an additional study that showed similar activity (67.4% susceptible to ceftazidime-avibactam) against 396 P. aeruginosa isolates, obtained between 2011 and 2014, with nonsusceptibility to ceftazidime, cefepime, meropenem, and piperacillin-tazobactam (15).…”

supporting

confidence: 51%

In Vitro Activity of Ceftazidime-Avibactam against Contemporary Pseudomonas aeruginosa Isolates from U.S. Medical Centers by Census Region, 2014

Huband

Castanheira

Flamm

et al. 2016

Antimicrob Agents Chemother

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The in vitro antibacterial activities of ceftazidime-avibactam and comparator agents were evaluated using reference broth microdilution methods against 1,743 Pseudomonas aeruginosa isolates collected in 2014 from 69 U.S. medical centers, representing each of the nine census regions. Ceftazidime-avibactam demonstrated potent activity against P. aeruginosa, including many isolates not susceptible to ceftazidime, meropenem, and piperacillin-tazobactam. In each of the nine census regions, ceftazidimeavibactam demonstrated the highest percentage of susceptible isolates. Increasing occurrence of antimicrobial resistance in Gram-negative bacilli, including Enterobacteriaceae and Pseudomonas aeruginosa, has complicated the treatment of serious nosocomial infections. ␤-Lactam antibacterials, which were once highly effective against these pathogens, have been compromised by isolates that harbor resistance due to the production of extended-spectrum ␤-lactamases (ESBLs) and carbapenemases (1-4), along with other resistance mechanisms, including efflux and porin loss (5, 6) and the recent emergence of plasmid-mediated resistance to colistin (7). The spread of ␤-lactamases is particularly problematic due to the potential for additional mutations that can broaden their spectrum of hydrolysis, as well as their ability to disseminate to other pathogens. Ceftazidime-avibactam is the combination of the established third-generation cephalosporin ceftazidime and the novel non-␤-lactam ␤-lactamase inhibitor avibactam. Avibactam inhibits a broad range of serine ␤-lactamases, including Ambler class A (ESBL and Klebsiella pneumoniae carbapenemase), class C (AmpC), and some class D (OXA-48) enzymes. When used in combination with ceftazidime, avibactam restores the activity of ceftazidime against a number of clinically relevant ␤-lactamase-producing Gram-negative pathogens that cause serious infections (8). We evaluated the in vitro antibacterial activities and susceptibility patterns of ceftazidime-avibactam and comparator compounds against P. aeruginosa surveillance isolates obtained in 2014 from a variety of infection types (skin and soft tissue, urinary tract, intra-abdominal, and others) from each of the nine census regions within the United States.A total of 1,743 P. aeruginosa isolates collected in 2014 from 69 medical centers within the nine U.S. census regions were included in the International Network for Optimal Resistance Monitoring (INFORM) surveillance program. Broth microdilution susceptibility testing for ceftazidime-avibactam, ceftazidime, cefepime, meropenem, piperacillin-tazobactam, ciprofloxacin, levofloxacin, amikacin, gentamicin, and colistin was performed according to Clinical and Laboratory Standards Institute (CLSI) guidelines (9) using validated MIC panels produced by Thermo Fisher Scientific (Cleveland, OH). Susceptibility interpretive criteria for comparator compounds included both CLSI (10) and EUCAST (European Committee on Antimicrobial Susceptibility Testing) (11) breakpoint criteria, when available. The rec...

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supporting

confidence: 51%

In Vitro Activity of Ceftazidime-Avibactam against Contemporary Pseudomonas aeruginosa Isolates from U.S. Medical Centers by Census Region, 2014

Huband

Castanheira

Flamm

et al. 2016

Antimicrob Agents Chemother

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“…In vitro studies showed that the combination of ceftazidime-avibactam is highly effective against Enterobacteriaceae producing KPCs, ESBLs OXA and AmpC enzymes. However, the drug has no activity against metallo-beta lactamases (MBL, VIM and NDM) and avibactam offers no enhanced activity against P. aeruginosa [ 116 – 119 ]. The effectiveness of ceftazidime-avibactam against VAP has been analyzed in a phase III studies comparing this new drug with meropenem (NTC01808092) [ 120 ].…”

Section: New Systemic Drugsmentioning

confidence: 99%

How to manage Pseudomonas aeruginosa infections

Bassetti

Vena

Croxatto

et al. 2018

DIC

610

489

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Infections with Pseudomonas aeruginosa have become a real concern in hospital-acquired infections, especially in critically ill and immunocompromised patients. The major problem leading to high mortality lies in the appearance of drug-resistant strains. Therefore, a vast number of approaches to develop novel anti-infectives is currently pursued. Diverse strategies range from killing (new antibiotics) to disarming (antivirulence) the pathogen. In this review, selected aspects of P. aeruginosa antimicrobial resistance and infection management will be addressed. Many studies have been performed to evaluate the risk factors for resistance and the potential consequences on mortality and attributable mortality. The review also looks at the mechanisms associated with resistance – P. aeruginosa is a pathogen presenting a large genome, and it can develop a large number of factors associated with antibiotic resistance involving almost all classes of antibiotics. Clinical approaches to patients with bacteremia, ventilator-associated pneumonia, urinary tract infections and skin soft tissue infections are discussed. Antibiotic combinations are reviewed as well as an analysis of pharmacokinetic and pharmacodynamic parameters to optimize P. aeruginosa treatment. Limitations of current therapies, the potential for alternative drugs and new therapeutic options are also discussed.

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“…The restoration of in vitro activity translates to restoration of ceftazidime efficacy against ceftazidime-resistant P. aeruginosa in vivo (13)(14)(15). The restoration by avibactam of the in vitro activity of ceftazidime described above has extended to collections of unselected clinical isolates of P. aeruginosa in surveillance studies (16)(17)(18)(19)(20)(21)(22)(23)(24).…”

mentioning

confidence: 99%

“…Surveillance studies are an important tool to monitor the activity of agents on a local and global level and to detect the possible emergence of resistance that might compromise therapy, as has been observed for ceftazidime-avibactam in vitro (13,26). In the present work, the activity of ceftazidimeavibactam against P. aeruginosa was assessed through the Interna-tional Network for Optimal Resistance Monitoring (INFORM) global surveillance study across four regions for 3 years (2012 to 2014), by (i) comparing the relative in vitro activities of ceftazidime and ceftazidime-avibactam, in order to understand what extra proportion of susceptible isolates is provided by the inhibition of ␤-lactamases by avibactam in vitro; (ii) examining the potential clinical value that ceftazidime-avibactam might represent based on its in vitro activity compared to the activities of other important antipseudomonal agents, such as meropenem, imipenem, doripenem, cefepime, piperacillin-tazobactam, amikacin, and colistin; and (iii) placing this study of recent clinical isolates into context with other recent surveillance studies (16)(17)(18)(19)(20)(21)(22)(23)(24) and studies that were confined to subpopulations of isolates of P. aeruginosa selected as being resistant to ceftazidime or other ␤-lactams (27)(28)(29).…”

mentioning

confidence: 99%

In Vitro Susceptibility of Global Surveillance Isolates of Pseudomonas aeruginosa to Ceftazidime-Avibactam (INFORM 2012 to 2014)

Nichols

Jonge

Kazmierczak³

et al. 2016

Antimicrob Agents Chemother

143

115

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, meropenem (MIC 90 , >8 g/ml; 64.9 to 77.4% susceptible), and piperacillin-tazobactam (MIC 90 , >128 g/ml; 62.3 to 71.3% susceptible). Compared to the overall population, susceptibility to ceftazidime-avibactam of isolates that were nonsusceptible to ceftazidime (n ‫؍‬ 1,627) was reduced to between 56.8% (Middle East/Africa; MIC 90 , 64 g/ml) and 68.9% (Asia/South Pacific; MIC 90 , 128 g/ml), but these percentages were higher than susceptibilities to other ␤-lactam agents (0 to 44% susceptible, depending on region and agent; meropenem MIC 90 , >8 g/ml; 26.5 to 43.9% susceptible). For this subset of isolates, susceptibilities to amikacin (MIC 90 , >32 g/ml; 53.2 to 80.0% susceptible) and colistin (MIC 90 , 1 g/ml; 98.5 to 99.5% susceptible) were comparable to or higher than that of ceftazidime-avibactam. A similar observation was made with isolates that were nonsusceptible to meropenem (n ‫؍‬ 1,926), with susceptibility to ceftazidime-avibactam between 67.8% (Middle East/Africa; MIC 90 , 64 g/ ml) and 74.2% (Europe; MIC 90 , 32 g/ml) but again with reduced susceptibility to comparators except for amikacin (MIC 90 , >32 g/ml; 56.8 to 78.7% susceptible) and colistin (MIC 90 , 1 g/ml; 98.9 to 99.3% susceptible). Of the 8% of isolates not susceptible to ceftazidime-avibactam, the nonsusceptibility of half could be explained by their possession of genes encoding metallo-␤-lactamases. The data reported here are consistent with results from other country-specific and regional surveillance studies and show that ceftazidime-avibactam demonstrates in vitro activity against globally collected clinical isolates of P. aeruginosa, including isolates that are resistant to ceftazidime and meropenem.

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Ceftazidime-avibactam activity when tested against ceftazidime-nonsusceptible Citrobacter spp., Enterobacter spp., Serratia marcescens, and Pseudomonas aeruginosa from Unites States medical centers (2011–2014)

Cited by 30 publications

References 20 publications

In Vitro Activity of Ceftazidime-Avibactam against Contemporary Pseudomonas aeruginosa Isolates from U.S. Medical Centers by Census Region, 2014

In Vitro Activity of Ceftazidime-Avibactam against Contemporary Pseudomonas aeruginosa Isolates from U.S. Medical Centers by Census Region, 2014

How to manage Pseudomonas aeruginosa infections

In Vitro Susceptibility of Global Surveillance Isolates of Pseudomonas aeruginosa to Ceftazidime-Avibactam (INFORM 2012 to 2014)

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