Combinatorial Pharmacodynamics of Ceftolozane-Tazobactam against Genotypically Defined β-Lactamase-Producing Escherichia coli: Insights into the Pharmacokinetics/Pharmacodynamics of β-Lactam–β-Lactamase Inhibitor Combinations

Soon, Rachel L.; Lenhard, Justin R.; Bulman, Zackery P.; Holden, Patricia N.; Kelchlin, Pamela; Steenbergen, Judith N.; Friedrich, Lawrence V.; Forrest, Alan; Tsuji, Brian T.

doi:10.1128/aac.02635-15

Cited by 12 publications

(8 citation statements)

References 36 publications

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“…Comparator antibiotics performed poorly as well; only 57.1% of MDR isolates were susceptible to meropenem, and only tigecycline and colistin with susceptibilities >90% 13. These results are concordant with other in vitro studies, which show excellent activity of ceftolozane/tazobactam against E. coli (the most common organism associated with cIAI), though with higher MICs against CTX-M-15 β-lactamase producers; however, activity against K. pneumoniae in vitro was more variable than E. coli , with SHV-5 and CTX-M-15 producing strains demonstrating higher MICs despite the presence of tazobactam 21–23. It is important to note that overall susceptibilities and ESBL prevalence and resistance patterns may vary widely by geographic region.…”

Section: Ceftolozane/tazobactamsupporting

confidence: 90%

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

Goodlet¹,

Nicolau²,

Nailor³

2016

TCRM

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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.

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Section: Ceftolozane/tazobactamsupporting

confidence: 90%

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

Goodlet¹,

Nicolau²,

Nailor³

2016

TCRM

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“…1), an inoculum effect due to AmpC overexpression cannot be excluded for clinical isolates. The amplification of a ceftolozaneresistant subpopulation was previously suggested in time-kill assays performed with Escherichia coli (21). Therefore, 24-h colonies obtained after regrowth were plated on brain heart infusion (BHI) agar with increasing concentrations of ceftolozanetazobactam.…”

mentioning

confidence: 99%

In Vitro Activity of Ceftolozane-Tazobactam against Multidrug-Resistant Nonfermenting Gram-Negative Bacilli Isolated from Patients with Cystic Fibrosis

Grohs

Taieb

Morand

et al. 2017

Antimicrob Agents Chemother

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Ceftolozane-tazobactam was tested against 58 multidrug-resistant nonfermenting Gram-negative bacilli (35 Pseudomonas aeruginosa, 11 Achromobacter xylosoxydans, and 12 Stenotrophomonas maltophilia isolates) isolated from cystic fibrosis patients and was compared to ceftolozane alone, ceftazidime, meropenem, and piperacillin-tazobactam. Ceftolozane-tazobactam was the most active agent against P. aeruginosa but was inactive against A. xylosoxydans and S. maltophilia. In time-kill experiments, ceftolozane-tazobactam had complete bactericidal activity against 2/6 clinical isolates (33%).

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“…No information is available on the extent of ceftolozane activity as monotherapy, as all bacteria regrowth was observed even at the highest concentration tested. On a per drug weight basis, ceftolozane activity is comparable with aztreonam or ceftazidime in monotherapy against MDR E. coli that expresses CTX-M-15 b-lactamases [10]. At 16 and 64 mg/L tazobactam, bactericidal effect was observed in most of the tested ceftolozane concentrations except 1 mg/L where regrowth occurred.…”

Section: In Vitro Time-kill Kinetic Studies and Experimental Design Of Two-drug Combinationsmentioning

confidence: 93%

“…Examples of agile versus fixed matrices are shown in Fig. 1 for aztreonam-avibactam (top graph) and ceftolozane-tazobactam (bottom graph), respectively [10,14]. The corresponding MICs of BL at each tested BLI concentration are shown in Table 2.…”

Section: In Vitro Time-kill Kinetic Studies and Experimental Design Of Two-drug Combinationsmentioning

confidence: 99%

Experimental design and modelling approach to evaluate efficacy of β-lactam/β-lactamase inhibitor combinations

Derendorf

2018

Clinical Microbiology and Infection

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Combinatorial Pharmacodynamics of Ceftolozane-Tazobactam against Genotypically Defined β-Lactamase-Producing Escherichia coli: Insights into the Pharmacokinetics/Pharmacodynamics of β-Lactam–β-Lactamase Inhibitor Combinations

Abstract: 8 CFU/ml were 2.81 to 66.5 times greater than the EC 50 s at 10 6 CFU/ml (median, 10.7-fold increase; P ‫؍‬ 0.002). These promising results indicate that ceftolozane-tazobactam achieves bactericidal activity against a wide range of ␤-lactamase-producing E. coli strains.

Cited by 12 publications

References 36 publications

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

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

In Vitro Activity of Ceftolozane-Tazobactam against Multidrug-Resistant Nonfermenting Gram-Negative Bacilli Isolated from Patients with Cystic Fibrosis

Experimental design and modelling approach to evaluate efficacy of β-lactam/β-lactamase inhibitor combinations

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