Multicenter Evaluation of Ceftolozane/Tazobactam for Serious Infections Caused by Carbapenem-Resistant Pseudomonas aeruginosa

Munita, José M.; Aitken, Samuel L; Miller, William R.; Pérez, Federico; Rosa, Rossana; Shimose, Luis; Lichtenberger, Paola N.; Abbo, Lilian M.; Jain, Rupali; Nigo, Masayuki; Wanger, Audrey; Araos, Rafael; Tran, Truc T.; Adachi, Javier A.; Rakita, Robert M.; Shelburne, Samuel A.; Bonomo, Robert A.; Arias, César A.

doi:10.1093/cid/cix014

Cited by 128 publications

(121 citation statements)

References 13 publications

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“…In contrast, ceftolozanetazobactam susceptibilities were sufficient to allow empirical monotherapy; in addition, ceftolozane-tazobactam had a more favorable side effect profile than either the aminoglycosides or fluoroquinolones. Robust clinical data assessing the efficacy of ceftolozane-tazobactam for the treatment of nosocomial pneumonia are still needed; however, early data from a retrospective study are promising (28). Currently, a phase 3 randomized controlled trial (ClinicalTrials.gov registration number NCT02070757) of ceftolozane-tazobactam versus meropenem is in the recruitment phase and should help to further define ceftolozane-tazobactam's efficacy for this indication.…”

Section: Discussionmentioning

confidence: 99%

In Vitro Comparison of Ceftolozane-Tazobactam to Traditional Beta-Lactams and Ceftolozane-Tazobactam as an Alternative to Combination Antimicrobial Therapy for Pseudomonas aeruginosa

Goodlet

Nicolau

Nailor

2017

Antimicrob Agents Chemother

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Guidelines for the treatment of sepsis, febrile neutropenia, and hospitalacquired pneumonia caused by Pseudomonas aeruginosa include empirical regimens incorporating two antibiotics from different classes with activity against P. aeruginosa for select at-risk patients to increase the likelihood that the organism will be susceptible to at least one agent. The activity against P. aeruginosa and the rates of cross-resistance of ceftolozane-tazobactam were compared to those of the ␤-lactam comparators cefepime, ceftazidime, piperacillin-tazobactam, and meropenem alone and cumulatively with ciprofloxacin or tobramycin. Nonurine P. aeruginosa isolates were collected from adult inpatients at 44 geographically diverse U.S. hospitals. MICs were determined using reference broth microdilution methods. Of the 1,257 isolates collected, 29% were from patients in intensive care units and 39% were from respiratory sites. The overall rate of susceptibility to ceftolozane-tazobactam was high at 97%, whereas it was 72 to 76% for cefepime, ceftazidime, piperacillin-tazobactam, and meropenem. The rate of nonsusceptibility to all four comparator ␤-lactams was 11%; of the isolates nonsusceptible to the four comparator ␤-lactams, 80% remained susceptible to ceftolozane-tazobactam. Among the isolates nonsusceptible to the tested ␤-lactam comparators, less than half were susceptible to ciprofloxacin. By comparison, approximately 80% of the ␤-lactam-nonsusceptible isolates were susceptible to tobramycin, for overall cumulative susceptibility rates of 94 to 95%, nearly 10% higher than that of the ciprofloxacin-␤-lactam combinations and approaching that of ceftolozane-tazobactam as a single agent. The rates of susceptibility to ceftolozane-tazobactam were consistently high, with little observable crossresistance. Ceftolozane-tazobactam monotherapy performed at or above the level of commonly utilized combination therapies on the basis of in vitro susceptibilities. Ceftolozane-tazobactam should be considered for use in patients at high risk for resistant P. aeruginosa infection and as an alternative to empirical combination therapy, especially for patients unable to tolerate aminoglycosides.KEYWORDS Pseudomonas aeruginosa, antimicrobial resistance, ceftolozanetazobactam, combination treatment, resistance P seudomonas aeruginosa is a notorious cause of nosocomial infection both within the United States and around the world. The CDC's National Healthcare Safety Network lists P. aeruginosa as the seventh most common cause of health careassociated infection, accounting for 8% of all reported cases (1), while other surveillance

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Section: Discussionmentioning

confidence: 99%

In Vitro Comparison of Ceftolozane-Tazobactam to Traditional Beta-Lactams and Ceftolozane-Tazobactam as an Alternative to Combination Antimicrobial Therapy for Pseudomonas aeruginosa

Goodlet

Nicolau

Nailor

2017

Antimicrob Agents Chemother

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“…In fact, only the approved dose of 1.5 g was found to result in success in some cases. Munita and colleagues were also challenged by this debate as they reported variations in their dosing 9. Ultimately, our decision was made to continue 1.5 g every 8 hours, given the patient's weight of 40 kg and poor nutritional status.…”

Section: Discussionmentioning

confidence: 99%

“…Notably, these trials are evaluating a higher dose of 3 g IV every 8 hours. Several case reports have also described successful use of ceftolozane‐tazobactam in pneumonia, secondary to multi‐drug resistant P. aeruginosa (MDRPA) 7, 8, 9, 10…”

Section: Introductionmentioning

confidence: 99%

“…Several case reports have also described successful use of ceftolozane-tazobactam in pneumonia, secondary to multi-drug resistant P. aeruginosa (MDRPA). [7][8][9][10] Failures have been observed with ceftolozane-tazobactam when used off-label. Caston and colleagues studied 6 patients with pneumonia, 2 resulting in deaths and one resulting in a clinical cure but microbiological persistence at 30 days.…”

Section: Introductionmentioning

confidence: 99%

“…Munita and colleagues studied 18 patients with pneumonia, 7 of whom were considered treatment failures. 9 We report our experience and lessons learned with a treatment failure in a patient treated for pneumonia complicated by lung abscess.…”

Section: Introductionmentioning

confidence: 99%

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Failure of ceftolozane‐tazobactam salvage therapy in complicated pneumonia with lung abscess

Lewis

Cluck

Tharp

et al. 2018

Clinical Case Reports

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Key Clinical MessageTreatment of Pseudomonas aeruginosa remains challenging, despite the availability ceftolozane‐tazobactam. We report a treatment failure with ceftolozane‐tazobactam salvage therapy for pneumonia complicated by lung abscess. Drug resistance, dose selection, and source control are possible contributing factors. Ceftolozane‐tazobactam susceptibility testing should precede therapy and consideration should be given to dosing selection.

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Approach to the Treatment of Patients with Serious Multidrug‐Resistant Pseudomonas aeruginosa Infections

2020

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Multidrug resistance(MDR) among Pseudomonas aeruginosa (PSA) isolates presents a significant clinical challenge and can substantially complicate the approach to selection of optimal antibiotic therapy. This review addresses major considerations in antibiotic selection for patients with suspected or documented serious MDR‐PSA infections. Common mechanisms contributing to MDR among clinical PSA isolates are summarized. Empiric and definitive therapy considerations are addressed including the potential role of combination therapy. Newer agents with in vitro activity against MDR‐PSA (e.g., ceftolozane‐tazobactam, ceftazidime‐avibactam, imipenem‐relebactam, and cefiderocol) and their potential roles in clinical settings are discussed. Although these newer agents are promising options for the treatment of MDR‐PSA, clinical data remain generally limited. Future studies are needed to determine optimal agents for the empiric and definitive treatment of MDR‐PSA.

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Multicenter Evaluation of Ceftolozane/Tazobactam for Serious Infections Caused by Carbapenem-Resistant Pseudomonas aeruginosa

Cited by 128 publications

References 13 publications

In Vitro Comparison of Ceftolozane-Tazobactam to Traditional Beta-Lactams and Ceftolozane-Tazobactam as an Alternative to Combination Antimicrobial Therapy for Pseudomonas aeruginosa

In Vitro Comparison of Ceftolozane-Tazobactam to Traditional Beta-Lactams and Ceftolozane-Tazobactam as an Alternative to Combination Antimicrobial Therapy for Pseudomonas aeruginosa

Failure of ceftolozane‐tazobactam salvage therapy in complicated pneumonia with lung abscess

Approach to the Treatment of Patients with Serious Multidrug‐Resistant Pseudomonas aeruginosa Infections

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