Ceftolozane/tazobactam for the treatment of bacteremia: a systematic literature review (SLR)

Abstract Background Bloodstream infections (BSIs), or bacteremia, are responsible for considerable disease burden. Increasing rates of antibiotic resistance and delays in selection of appropriate treatment lead to increased morbidity, mortality, and costs. Due to limitations of current standard trea...

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Main Authors: Z. S. Khankhel, R. J. Dillon, M. Thosar, C. Bruno, L. Puzniak
Format: Article
Language:English
Published: BMC 2022-10-01
Series:Annals of Clinical Microbiology and Antimicrobials
Subjects:
Online Access:https://doi.org/10.1186/s12941-022-00528-0
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author Z. S. Khankhel
R. J. Dillon
M. Thosar
C. Bruno
L. Puzniak
author_facet Z. S. Khankhel
R. J. Dillon
M. Thosar
C. Bruno
L. Puzniak
author_sort Z. S. Khankhel
collection DOAJ
description Abstract Background Bloodstream infections (BSIs), or bacteremia, are responsible for considerable disease burden. Increasing rates of antibiotic resistance and delays in selection of appropriate treatment lead to increased morbidity, mortality, and costs. Due to limitations of current standard treatments, especially for bacteremia caused by resistant pathogens, a systematic literature review (SLR) was conducted to understand the utilization of ceftolozane/tazobactam (C/T) in bacteremia. Methods Electronic database searches of EMBASE®, MEDLINE®, CCTR and Northern Lights, as well as hand searches of conference proceedings from the last two annual meetings (i.e., 2018, 2019) of the European Congress of Clinical Microbiological and Infectious Diseases (ECCMID) and the Infectious Diseases Society of America’s annual meeting (IDWeek) were conducted. A total of 23 studies reporting on patients with bacteremia receiving C/T were included in the review. Results Most studies were observational (k = 20 studies), though few interventional studies were also identified (k = 3). Heterogeneity was ubiquitous with respect to source of bacteremia (i.e., primary or secondary), source of infection (for secondary bacteremia), pathogen type, antibiotic resistance, C/T dose, and outcome definitions. This heterogeneity, along with limited data, and small sample sizes (n = 1 to 31) made it difficult to draw any substantial conclusions, though overall results were favorable to C/T with respect to the outcomes of interest. Nineteen studies reported clinical cure or success (primary bacteremia: k = 6, reported range: 33.3% to 100%; secondary bacteremia: k = 8, 60% to 100%; mixed/unspecified bacteremia: k = 10, 50% to 91.7%). Eight studies reported microbiological cure or eradication rates (primary: k = 3, all reporting 100%; secondary: k = 4, 68% to 80%; mixed/unspecified: k = 5, 60% to 80%). Thirteen studies reported mortality (primary: k = 4, 0% to 14%; secondary: k = 7, 0% to 100%; or mixed/unspecified bacteremia: k = 7, 0% to 51.6%). One study each also reported composite clinical response, relapse, hospital re-admission, and hospital length of stay. Conclusions Although the available evidence and observed trends for C/T in bacteremia should be interpreted with caution, the direction of effect would support the utilization of C/T for these difficult to treat infections. Future research should supplement the existing evidence by considering the impact of key treatment effect modifiers without contributing to the observed heterogeneity.
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spelling doaj.art-defe028665bb485ba8d9454ceba20b322022-12-22T03:38:37ZengBMCAnnals of Clinical Microbiology and Antimicrobials1476-07112022-10-0121112110.1186/s12941-022-00528-0Ceftolozane/tazobactam for the treatment of bacteremia: a systematic literature review (SLR)Z. S. Khankhel0R. J. Dillon1M. Thosar2C. Bruno3L. Puzniak4PrecisionHEORMerck & Co., IncPrecisionHEORMerck & Co., IncMerck & Co., IncAbstract Background Bloodstream infections (BSIs), or bacteremia, are responsible for considerable disease burden. Increasing rates of antibiotic resistance and delays in selection of appropriate treatment lead to increased morbidity, mortality, and costs. Due to limitations of current standard treatments, especially for bacteremia caused by resistant pathogens, a systematic literature review (SLR) was conducted to understand the utilization of ceftolozane/tazobactam (C/T) in bacteremia. Methods Electronic database searches of EMBASE®, MEDLINE®, CCTR and Northern Lights, as well as hand searches of conference proceedings from the last two annual meetings (i.e., 2018, 2019) of the European Congress of Clinical Microbiological and Infectious Diseases (ECCMID) and the Infectious Diseases Society of America’s annual meeting (IDWeek) were conducted. A total of 23 studies reporting on patients with bacteremia receiving C/T were included in the review. Results Most studies were observational (k = 20 studies), though few interventional studies were also identified (k = 3). Heterogeneity was ubiquitous with respect to source of bacteremia (i.e., primary or secondary), source of infection (for secondary bacteremia), pathogen type, antibiotic resistance, C/T dose, and outcome definitions. This heterogeneity, along with limited data, and small sample sizes (n = 1 to 31) made it difficult to draw any substantial conclusions, though overall results were favorable to C/T with respect to the outcomes of interest. Nineteen studies reported clinical cure or success (primary bacteremia: k = 6, reported range: 33.3% to 100%; secondary bacteremia: k = 8, 60% to 100%; mixed/unspecified bacteremia: k = 10, 50% to 91.7%). Eight studies reported microbiological cure or eradication rates (primary: k = 3, all reporting 100%; secondary: k = 4, 68% to 80%; mixed/unspecified: k = 5, 60% to 80%). Thirteen studies reported mortality (primary: k = 4, 0% to 14%; secondary: k = 7, 0% to 100%; or mixed/unspecified bacteremia: k = 7, 0% to 51.6%). One study each also reported composite clinical response, relapse, hospital re-admission, and hospital length of stay. Conclusions Although the available evidence and observed trends for C/T in bacteremia should be interpreted with caution, the direction of effect would support the utilization of C/T for these difficult to treat infections. Future research should supplement the existing evidence by considering the impact of key treatment effect modifiers without contributing to the observed heterogeneity.https://doi.org/10.1186/s12941-022-00528-0BacteremiaBlood stream infectionClinical cureMicrobiological cureMortality
spellingShingle Z. S. Khankhel
R. J. Dillon
M. Thosar
C. Bruno
L. Puzniak
Ceftolozane/tazobactam for the treatment of bacteremia: a systematic literature review (SLR)
Annals of Clinical Microbiology and Antimicrobials
Bacteremia
Blood stream infection
Clinical cure
Microbiological cure
Mortality
title Ceftolozane/tazobactam for the treatment of bacteremia: a systematic literature review (SLR)
title_full Ceftolozane/tazobactam for the treatment of bacteremia: a systematic literature review (SLR)
title_fullStr Ceftolozane/tazobactam for the treatment of bacteremia: a systematic literature review (SLR)
title_full_unstemmed Ceftolozane/tazobactam for the treatment of bacteremia: a systematic literature review (SLR)
title_short Ceftolozane/tazobactam for the treatment of bacteremia: a systematic literature review (SLR)
title_sort ceftolozane tazobactam for the treatment of bacteremia a systematic literature review slr
topic Bacteremia
Blood stream infection
Clinical cure
Microbiological cure
Mortality
url https://doi.org/10.1186/s12941-022-00528-0
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