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Laura Puzniak
Merck & Co Inc
Corresponding Author
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Background: Antibacterial-resistant gram-negative infections are a serious risk to global public health. Resistant Enterobacterales and Pseudomonas aeruginosa are highly prevalent, particularly in healthcare settings, and there are limited effective treatment options. Patients with infections caused by resistant pathogens have considerably worse outcomes, and significantly higher costs, relative to patients with susceptible infections. Ceftolozane/tazobactam (C/T) has established efficacy in clinical trials. This review aimed to collate data on C/T use in clinical practice.
Methods: This systematic literature review searched online biomedical databases for real-world studies of C/T for gram-negative infections. Relevant study, patient, and treatment characteristics, microbiology, and efficacy outcomes were captured.
Results: There were 83 studies comprising 3,701 patients were identified. The most common infections were respiratory infections (52.9% of reported infections), urinary tract infections (UTIs; 14.9%), and intra-abdominal infections (IAIs; 10.1%). Most patients included were seriously ill and had multiple comorbidities. The majority of patients had infections caused by P. aeruginosa (90.7%), of which 86.0% were antimicrobial-resistant. C/T was used as both a 1.5 g q8h and 3 g q8h dose, for a median duration of 7–56 days (varying between studies). Outcome rates were comparable between studies: clinical success rates ranged from 45.7–100.0%, with 27 studies (69%) reporting clinical success rates of >70%; microbiological success rates ranged from 31–100%, with 14 studies (74%) reporting microbiological success rates of >70%. Mortality rates ranged from 0–50%, with 31 studies (69%) reporting mortality rates of ≤20%. In comparative studies, C/T was as effective as aminoglycoside- or polymyxin-based regimens, and in some instances, significantly more effective.
Conclusions: The studies identified in this review demonstrate that C/T is effective in clinical practice, despite the diverse group of seriously ill patients, different levels of resistance of the pathogens treated, and varying dosing regimens used. Furthermore, comparative studies suggest that C/T offers a successful alternative to standard of care (SoC).
Keywords
Ceftolozane/tazobactam, Pseudomonas aeruginosa, antibacterial resistance, real-world evidence
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View the published article at Antimicrobial Resistance & Infection Control.
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Posted 30 Dec, 2020
No community comments so far
Editorial decision: Major revision
On 02 Feb, 2021
Review #3 received
Received 01 Feb, 2021
Review #2 received
Received 22 Jan, 2021
Review #1 received
Received 17 Jan, 2021
Review #4 received
Received 15 Jan, 2021
Reviewer #4 agreed
On 10 Jan, 2021
Reviewer #3 agreed
On 10 Jan, 2021
Reviewer #2 agreed
On 07 Jan, 2021
Reviewer #1 agreed
On 06 Jan, 2021
Reviewers invited
Invitations sent on 05 Jan, 2021
Editor assigned
On 22 Dec, 2020
Submission checks complete
On 22 Dec, 2020
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On 22 Dec, 2020
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On 20 Dec, 2020
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A new preprint design is coming!
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See the published version of this preprint at Antimicrobial Resistance & Infection Control.
This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research
Laura Puzniak
Merck & Co Inc
Corresponding Author
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Published
View the published article at Antimicrobial Resistance & Infection Control.
Version 1
Posted 30 Dec, 2020
No community comments so far
Editorial decision: Major revision
On 02 Feb, 2021
Review #3 received
Received 01 Feb, 2021
Review #2 received
Received 22 Jan, 2021
Review #1 received
Received 17 Jan, 2021
Review #4 received
Received 15 Jan, 2021
Reviewer #4 agreed
On 10 Jan, 2021
Reviewer #3 agreed
On 10 Jan, 2021
Reviewer #2 agreed
On 07 Jan, 2021
Reviewer #1 agreed
On 06 Jan, 2021
Reviewers invited
Invitations sent on 05 Jan, 2021
Editor assigned
On 22 Dec, 2020
Submission checks complete
On 22 Dec, 2020
Editor invited
On 22 Dec, 2020
First submitted
On 20 Dec, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published article at Antimicrobial Resistance & Infection Control.
Background: Antibacterial-resistant gram-negative infections are a serious risk to global public health. Resistant Enterobacterales and Pseudomonas aeruginosa are highly prevalent, particularly in healthcare settings, and there are limited effective treatment options. Patients with infections caused by resistant pathogens have considerably worse outcomes, and significantly higher costs, relative to patients with susceptible infections. Ceftolozane/tazobactam (C/T) has established efficacy in clinical trials. This review aimed to collate data on C/T use in clinical practice.
Methods: This systematic literature review searched online biomedical databases for real-world studies of C/T for gram-negative infections. Relevant study, patient, and treatment characteristics, microbiology, and efficacy outcomes were captured.
Results: There were 83 studies comprising 3,701 patients were identified. The most common infections were respiratory infections (52.9% of reported infections), urinary tract infections (UTIs; 14.9%), and intra-abdominal infections (IAIs; 10.1%). Most patients included were seriously ill and had multiple comorbidities. The majority of patients had infections caused by P. aeruginosa (90.7%), of which 86.0% were antimicrobial-resistant. C/T was used as both a 1.5 g q8h and 3 g q8h dose, for a median duration of 7–56 days (varying between studies). Outcome rates were comparable between studies: clinical success rates ranged from 45.7–100.0%, with 27 studies (69%) reporting clinical success rates of >70%; microbiological success rates ranged from 31–100%, with 14 studies (74%) reporting microbiological success rates of >70%. Mortality rates ranged from 0–50%, with 31 studies (69%) reporting mortality rates of ≤20%. In comparative studies, C/T was as effective as aminoglycoside- or polymyxin-based regimens, and in some instances, significantly more effective.
Conclusions: The studies identified in this review demonstrate that C/T is effective in clinical practice, despite the diverse group of seriously ill patients, different levels of resistance of the pathogens treated, and varying dosing regimens used. Furthermore, comparative studies suggest that C/T offers a successful alternative to standard of care (SoC).
Figure 1
Figure 2
Figure 3
This is a list of supplementary files associated with this preprint. Click to download.
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