Ceftolozane/tazobactam in the treatment of osteomyelitis and skin and soft-tissue infections due to extensively drug-resistant Pseudomonas aeruginosa : clinical and microbiological outcomes

Dietl, Beatriz; Sánchez, I.; Arcenillas, Paula; Cuchí, Eva; Gómez, Lucía; Molina, F.J. González de; Boix-Palop, Lucía; Nicolás, José M.

doi:10.1016/j.ijantimicag.2017.11.003

Cited by 32 publications

(24 citation statements)

References 11 publications

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“…Although it is difficult to make comparisons across studies due to differences in study design and case mix, the rates of clinical failure (37.6%) and 30-day mortality (17.3%) in the present study are broadly comparable to previous observational studies describing the use of C/T for MDR P. aeruginosa infections and suggest meaningful progress for patients compared with historical controls (16,(21)(22)(23)(24)(25). Clinical outcomes among patients with a respiratory tract infection in this study were remarkably similar to those reported for the recently completed ASPECT-NP study, a randomized controlled phase 3 study comparing C/T to meropenem in patients with ventilated nosocomial pneumonia (14).…”

Section: Discussionsupporting

confidence: 69%

“…Published data on the use of C/T for the treatment of MDR infections is slowly accumulating in the form of case reports, case series. and uncontrolled retrospective cohort studies (21)(22)(23)(24)(25)(26). We sought to add to these data and describe the prescribing practices, clinical characteristics, microbiology, and outcomes of a large cohort of U.S. patients treated with C/T for confirmed or suspected MDR Gram-negative bacterial infections.…”

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confidence: 99%

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Real-World Experience with Ceftolozane-Tazobactam for Multidrug-Resistant Gram-Negative Bacterial Infections

Jorgensen

Trinh

Zasowski

et al. 2020

Antimicrob Agents Chemother

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Our objective was to describe the prescribing practices, clinical characteristics, and outcomes of patients treated with ceftolozane-tazobactam (C/T) for multidrug-resistant (MDR) Gram-negative infections. This was a multicenter, retrospective, cohort study at eight U.S. medical centers (2015 to 2019). Inclusion criteria were age ≥18 years and receipt of C/T (≥72 hours) for suspected or confirmed MDR Gram-negative infection. The primary efficacy outcome, evaluated among patients with MDR Pseudomonas aeruginosa infections, was composite clinical failure, namely, 30-day all-cause mortality, 30-day recurrence, and/or failure to resolve or improve infection signs or symptoms after C/T treatment. In total, 259 patients were included, and P. aeruginosa was isolated in 236 (91.1%). The MDR and extremely drug-resistant phenotypes were detected in 95.8% and 37.7% of P. aeruginosa isolates, respectively. The most common infection source was the respiratory tract (62.9%). High-dose C/T was used in 71.2% of patients with a respiratory tract infection (RTI) overall but in only 39.6% of patients with an RTI who required C/T renal dose adjustment. In the primary efficacy population (n = 226), clinical failure and 30-day mortality occurred in 85 (37.6%) and 39 (17.3%) patients, respectively. New C/T MDR P. aeruginosa resistance was detected in 3 of 31 patients (9.7%) with follow-up cultures. Hospital-acquired infection and Acute Physiological and Chronic Health Evaluation II (APACHE II) score were independently associated with clinical failure (adjusted odds ratio [aOR], 2.472 and 95% confidence interval [CI], 1.322 to 4.625; and aOR, 1.068 and 95% CI, 1.031 to 1.106, respectively). Twenty-five (9.7%) patients experienced ≥1 adverse effect (9 acute kidney injury, 13 Clostridioides difficile infection, 1 hepatotoxicity, 2 encephalopathy, and 2 gastrointestinal intolerance). C/T addresses an unmet medical need in patients with MDR Gram-negative infections.

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Section: Discussionsupporting

confidence: 69%

mentioning

confidence: 99%

Real-World Experience with Ceftolozane-Tazobactam for Multidrug-Resistant Gram-Negative Bacterial Infections

Jorgensen

Trinh

Zasowski

et al. 2020

Antimicrob Agents Chemother

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“…The main indication in these series was respiratory tract infection, and different doses of ceftolozane-tazobactam were used, sometimes in combination therapy. Cure rates were close to 70%, with emergence of resistance of 4 to 14% in some studies and mortality rates, measured at different times, ranging from 0% (in small series of cases) to 27% (26,62,165,(281)(282)(283)(284)(285)(286)(287)(288).…”

Section: Ceftolozane-tazobactammentioning

confidence: 83%

“…Most publications have analyzed patients treated with colistin (180-188, 299, 300) and, more recently, with ceftolozane-tazobactam (26,62,165,(281)(282)(283)(284)(285)(286)(287). There are some articles about patients treated with polymyxin B (207)(208)(209), ceftazidime-avibactam (163,308), and aminoglycosides (250) or with different combinations of antimicrobials (203,204,206,258).…”

Section: Critical Evaluation Of Clinical Studies Providing Informatiomentioning

confidence: 99%

Epidemiology and Treatment of Multidrug-Resistant and Extensively Drug-Resistant Pseudomonas aeruginosa Infections

et al. 2019

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SUMMARYIn recent years, the worldwide spread of the so-called high-risk clones of multidrug-resistant or extensively drug-resistant (MDR/XDR)Pseudomonas aeruginosahas become a public health threat. This article reviews their mechanisms of resistance, epidemiology, and clinical impact and current and upcoming therapeutic options.In vitroandin vivotreatment studies and pharmacokinetic and pharmacodynamic (PK/PD) models are discussed. Polymyxins are reviewed as an important therapeutic option, outlining dosage, pharmacokinetics and pharmacodynamics, and their clinical efficacy against MDR/XDRP. aeruginosainfections. Their narrow therapeutic window and potential for combination therapy are also discussed. Other “old” antimicrobials, such as certain β-lactams, aminoglycosides, and fosfomycin, are reviewed here. New antipseudomonals, as well as those in the pipeline, are also reviewed. Ceftolozane-tazobactam has clinical activity against a significant percentage of MDR/XDRP. aeruginosastrains, and its microbiological and clinical data, as well as recommendations for improving its use against these bacteria, are described, as are those for ceftazidime-avibactam, which has better activity against MDR/XDRP. aeruginosa, especially strains with certain specific mechanisms of resistance. A section is devoted to reviewing upcoming active drugs such as imipenem-relebactam, cefepime-zidebactam, cefiderocol, and murepavadin. Finally, other therapeutic strategies, such as use of vaccines, antibodies, bacteriocins, anti-quorum sensing, and bacteriophages, are described as future options.

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“…In another recent study, C/T was successful in treating 15/21 patients with various MDR P. aeruginosa infections (71%), although it should be noted that resistance to C/T conferred by de novo mutations occurred in 14% of cases (3/21) [43]. Regarding case reports and small case series, they also mainly reported on the successful off-label use of C/T for treating infections due MDR P. aeruginosa (mostly pneumonia, bloodstream infections, osteomyelitis, and acute pulmonary exacerbation of cystic fibrosis) [54,[93][94][95][96][97][98][99][100][101][102][103][104][105][106][107][108][109][110][111][112]. More reports will come in the near future, that remain critical to enrich our knowledge about the effectiveness of C/T for all these indications.…”

Section: C/t In Mdr-p Aeruginosa In Many Countries Approximately 2mentioning

confidence: 99%

Ceftolozane/tazobactam: place in therapy

Giacobbe

Bassetti

Rosa

et al. 2018

Expert Review of Anti-infective Therapy

113

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Ceftolozane/tazobactam (C/T) is a new antibiotic resulting from the combination of a novel cephalosporin, structurally similar to ceftazidime, with tazobactam, a well-known beta-lactamase inhibitor. C/T remains active against extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae and multi-drug resistant (MDR) P. aeruginosa, and has been recently approved for the treatment of complicated intra-abdominal infections (cIAI) and complicated urinary tract infections (cUTI). A trial on hospital-acquired pneumonia is ongoing. Areas covered: The place in therapy of C/T is delineated by addressing the following main topics: (i) antimicrobial properties; (ii) pharmacological properties; (iii) results of clinical studies. Expert commentary: C/T is approved for cIAI and cUTI. However, the drug has a special value for clinicians in any kind of infectious localization for two main reasons. The first is that C/T is especially valuable in suspected or documented severe infections due to MDR P. aeruginosa, which is not a rare occurrence in many countries. The second is that C/T may provide an alternative to carbapenems for the treatment of infections caused by ESBL-producers, thus allowing a carbapenem-sparing strategy. Reporting of off-label use is mandatory to increase the body of evidence and the clinicians' confidence in using it for indications other than cIAI and cUTI.

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Ceftolozane/tazobactam in the treatment of osteomyelitis and skin and soft-tissue infections due to extensively drug-resistant Pseudomonas aeruginosa : clinical and microbiological outcomes

Cited by 32 publications

References 11 publications

Real-World Experience with Ceftolozane-Tazobactam for Multidrug-Resistant Gram-Negative Bacterial Infections

Real-World Experience with Ceftolozane-Tazobactam for Multidrug-Resistant Gram-Negative Bacterial Infections

Epidemiology and Treatment of Multidrug-Resistant and Extensively Drug-Resistant Pseudomonas aeruginosa Infections

Ceftolozane/tazobactam: place in therapy

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