Ceftolozane/tazobactam and ceftazidime/avibactam for the treatment of complicated intra-abdominal infections

Abstract

Complicated intra-abdominal infections (cIAI) represent a large proportion of all hospital admissions and are a major cause of morbidity and mortality in the intensive care unit. Rising rates of multidrug resistant organisms (MDRO), including extended-spectrum β-lactamase producing Enterobacteriaceae and carbapenem-nonsusceptible Pseudomonas spp., for which there are few remaining active antimicrobial agents, pose an increased challenge to clinicians. Patients with frequent exposures to the health care system or multiple recurrent IAIs are at increased risk for MDRO; however, treatment options have traditionally been limited, in some cases necessitating the utilization of last-line agents with unfavorable side-effect profiles. Ceftolozane/tazobactam and ceftazidime/avibactam are two new cephalosporin and β-lactamase inhibitor combinations with recent US Food and Drug Administration approvals for the treatment of cIAI in combination with metronidazole. Ceftolozane/tazobactam has demonstrated excellent in vitro activity against MDR and extensively drug-resistant Pseudomonas spp., including carbapenem-nonsusceptible strains, while ceftazidime/avibactam effectively inhibits a broad range of β-lactamases, making it an excellent option for the treatment of carbapenem-resistant Enterobacteriaceae. Both agents were shown to be noninferior to meropenem for treatment of cIAI in Phase III trials; however, reduced responses in patients with renal impairment at baseline highlight the importance of routine serum creatinine monitoring and ongoing dose adjustments. This review highlights in vitro and in vivo data of these two agents and suggests their proper place in cIAI treatment to ensure adequate therapy in our most at-risk patients while sparing unnecessary use in patients without MDRO risk factors.

Comparison of antimicrobial activity between ceftolozane–tazobactam and ceftazidime–avibactam against multidrug-resistant isolates of Escherichia coli , Klebsiella pneumoniae , and Pseudomonas aeruginosa

“…Antimicrobial resistance in Gram-negative bacteria, particularly among those of the Enterobacteriaceae family and nonfermenters, has become a leading cause of morbidity and mortality and a serious public health concern worldwide (Yezli et al, 2015;Goodlet et al, 2016). Gram-negative bacteria carrying extendedspectrum beta-lactamase (ESBL) enzymes now represent a significant proportion of all bacteria isolated from different countries worldwide (Yezli et al, 2015;Aly and Balkhy, 2012;Zahedi-bialvaei et al, 2015;Zowawi et al, 2013;Sonnevend et al, 2013).…”

“…Ceftolozane is a novel third-generation cephalosporin that has been combined with tazobactam, a betalactamase inhibitor, for broader activity against many aerobic and facultative anaerobic Gram-negative bacteria, including those of the Enterobacteriaceae family and Pseudomonas aeruginosa. Ceftolozane-tazobactam (Zerbaxa; Merck & Co., Kenilworth, NJ, USA) was approved on December 19, 2014 for the treatment of complicated intra-abdominal infections (in combination with metronidazole) and complicated urinary tract infections, including pyelonephritis (Goodlet et al, 2016;Liscio et al, 2015). Ceftazidime-avibactam (Avycaz; Allergen, Inc., Irvine, CA, USA) is another third-generation cephalosporin and beta-lactamase inhibitor combination that was approved on February 25, 2015 for the same clinical indications mentioned above (Goodlet et al, 2016;Liscio et al, 2015).…”

“…Ceftolozane-tazobactam (Zerbaxa; Merck & Co., Kenilworth, NJ, USA) was approved on December 19, 2014 for the treatment of complicated intra-abdominal infections (in combination with metronidazole) and complicated urinary tract infections, including pyelonephritis (Goodlet et al, 2016;Liscio et al, 2015). Ceftazidime-avibactam (Avycaz; Allergen, Inc., Irvine, CA, USA) is another third-generation cephalosporin and beta-lactamase inhibitor combination that was approved on February 25, 2015 for the same clinical indications mentioned above (Goodlet et al, 2016;Liscio et al, 2015). Ceftazidime-avibactam has the same spectrum of activity as ceftazidime (e.g., against Enterobacteriaceae and P. aeruginosa), but the addition of avibactam expands its activity against many resistant strains carrying certain betalactamases (Goodlet et al, 2016).…”

Emergence of Antimicrobial Resistance among Pseudomonas aeruginosa: Implications for Therapy

“…332,333,336,338 However, while ceftazidime/avibactam has activity against organisms that produce KPC CPEs, ceftolozane/tazobactam does not, and neither drug has activity against organisms that produce NDM-1. 333 Both agents are Food and Drug Administration approved to treat complicated UTIs and complicated IAI 339,340 ; studies to treat VAP are in progress.…”

A multirezisztens infekciók rizikófaktorainak vizsgálata két intenzív osztályon

“…Jelen vizsgálatunk a klinikai végpontokat nem rögzítette. Ugyan rendelkezünk néhány új, akár a komplikált infekciókat okozó, rezisztens baktériumok egy részére is hatékony antibiotikummal is, mint például a ceftolozan [19], de nincs okunk feltételezni, hogy rövid időn belül az eszköztárunk jelentős bővülése lenne várható. A multirezisztens törzsek terjedésének kedvező feltételek azonosítása így alapvető lenne.…”