Abstract
Pseudomonas aeruginosa is an opportunistic Gram-negative pathogen that causes a range of serious infections that are often challenging to treat, as this pathogen can express multiple resistance mechanisms, including multidrug-resistant (MDR) and extensively drug-resistant (XDR) phenotypes. Ceftazidime–avibactam is a combination antimicrobial agent comprising ceftazidime, a third-generation semisynthetic cephalosporin, and avibactam, a novel non-β-lactam β-lactamase inhibitor. This review explores the potential role of ceftazidime–avibactam for the treatment of P. aeruginosa infections. Ceftazidime–avibactam has good in vitro activity against P. aeruginosa relative to comparator β-lactam agents and fluoroquinolones, comparable to amikacin and ceftolozane–tazobactam. In Phase 3 clinical trials, ceftazidime–avibactam has generally demonstrated similar clinical and microbiological outcomes to comparators in patients with complicated intra-abdominal infections, complicated urinary tract infections or hospital-acquired/ventilator-associated pneumonia caused by P. aeruginosa. Although real-world data are limited, favourable outcomes with ceftazidime–avibactam treatment have been reported in some patients with MDR and XDR P. aeruginosa infections. Thus, ceftazidime–avibactam may have a potentially important role in the management of serious and complicated P. aeruginosa infections, including those caused by MDR and XDR strains.
Highlights
Ceftazidime–avibactam was generally effective in treating hospitalized adults with complicated urinary tract infection (cUTI), complicated IAI (cIAI) and hospital-acquired pneumonia (HAP)/ventilator-associated pneumonia (VAP) caused by P. aeruginosa, as assessed by clinical cure and favourable microbiological response rates at the TOC visit [112,113,114,115,116]
P. aeruginosa is relatively common in infections in healthcare settings, causing around 10–20% of skin, lower respiratory and urinary tract infections in hospitalized patients, and is associated with severe and critical illness, such as in intensive care unit (ICU) and haematological patients
Patients with acute P. aeruginosa infections are at significantly greater risk of 30-day mortality when receiving inappropriate initial antimicrobial therapy (IAT) vs. those receiving appropriate IAT; selection of appropriate IAT in some settings and regions is challenged by increasing antimicrobial resistance, including MDR and DTR P. aeruginosa [135,136]
Summary
The Surgical Infection Society guidelines for management of IAIs (2017) include stratification of empiric antimicrobial treatment recommendations based on the risk of pseudomonal involvement [65]. Third- or fourth-generation cephalosporins (e.g., cefotaxime, ceftriaxone, ceftizoxime, ceftazidime and cefepime) in combination with metronidazole, β-lactam/β-lactamase inhibitors (e.g., piperacillin/tazobactam and ticarcillin/clavulanic acid) and carbapenems (e.g., meropenem and imipenem/cilastatin) are commonly used [69]. For patients with complicated IAI (cIAI) considered at risk for infection with MDR, XDR or pandrug-resistant P. aeruginosa, combinations of a β-lactam antibiotic, including ceftolozane–tazobactam, an aminoglycoside and/or a polymyxin are recommended [65]. The World Society for Emergency Surgery guidelines (2017) provide similar recommendations and, recognize ceftolozane–tazobactam and ceftazidime–avibactam as approved treatments for cIAI caused by P. aeruginosa [64]
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