Single-drug versus combination antimicrobial therapy in critically ill patients with hospital-acquired pneumonia and ventilator-associated pneumonia due to Gram-negative pathogens: a multicenter retrospective cohort study
In this study including 391 critically ill patients with nosocomial pneumonia due to Gram-negative pathogens, combination therapy was not associated with a reduced hazard of death at Day 28 or a greater likelihood of clinical cure at Day 14. No over-risk of AKI was observed in patients receiving com...
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| Veröffentlicht in: | Critical care (London, England) England), 2024-01, Vol.28 (1), p.10-10, Article 10 |
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| creator | Barbier, François Dupuis, Claire Buetti, Niccolò Schwebel, Carole Azoulay, Élie Argaud, Laurent Cohen, Yves Hong Tuan Ha, Vivien Gainnier, Marc Siami, Shidasp Forel, Jean-Marie Adrie, Christophe de Montmollin, Étienne Reignier, Jean Ruckly, Stéphane Zahar, Jean-Ralph Timsit, Jean-François |
| description | In this study including 391 critically ill patients with nosocomial pneumonia due to Gram-negative pathogens, combination therapy was not associated with a reduced hazard of death at Day 28 or a greater likelihood of clinical cure at Day 14. No over-risk of AKI was observed in patients receiving combination therapy.
The benefits and harms of combination antimicrobial therapy remain controversial in critically ill patients with hospital-acquired pneumonia (HAP), ventilated HAP (vHAP) or ventilator-associated pneumonia (VAP) involving Gram-negative bacteria.
We included all patients in the prospective multicenter OutcomeRea database with a first HAP, vHAP or VAP due to a single Gram-negative bacterium and treated with initial adequate single-drug or combination therapy. The primary endpoint was Day-28 all-cause mortality. Secondary endpoints were clinical cure rate at Day 14 and a composite outcome of death or treatment-emergent acute kidney injury (AKI) at Day 7. The average effects of combination therapy on the study endpoints were investigated through inverse probability of treatment-weighted regression and multivariable regression models. Subgroups analyses were performed according to the resistance phenotype of the causative pathogens (multidrug-resistant or not), the pivotal (carbapenems or others) and companion (aminoglycosides/polymyxins or others) drug classes, the duration of combination therapy ( |
| doi_str_mv | 10.1186/s13054-023-04792-0 |
| format | Article |
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The benefits and harms of combination antimicrobial therapy remain controversial in critically ill patients with hospital-acquired pneumonia (HAP), ventilated HAP (vHAP) or ventilator-associated pneumonia (VAP) involving Gram-negative bacteria.
We included all patients in the prospective multicenter OutcomeRea database with a first HAP, vHAP or VAP due to a single Gram-negative bacterium and treated with initial adequate single-drug or combination therapy. The primary endpoint was Day-28 all-cause mortality. Secondary endpoints were clinical cure rate at Day 14 and a composite outcome of death or treatment-emergent acute kidney injury (AKI) at Day 7. The average effects of combination therapy on the study endpoints were investigated through inverse probability of treatment-weighted regression and multivariable regression models. Subgroups analyses were performed according to the resistance phenotype of the causative pathogens (multidrug-resistant or not), the pivotal (carbapenems or others) and companion (aminoglycosides/polymyxins or others) drug classes, the duration of combination therapy (< 3 or ≥ 3 days), the SOFA score value at pneumonia onset (< 7 or ≥ 7 points), and in patients with pneumonia due to non-fermenting Gram-negative bacteria, pneumonia-related bloodstream infection, or septic shock.
Among the 391 included patients, 151 (38.6%) received single-drug therapy and 240 (61.4%) received combination therapy. VAP (overall, 67.3%), vHAP (16.4%) and HAP (16.4%) were equally distributed in the two groups. All-cause mortality rates at Day 28 (overall, 31.2%), clinical cure rate at Day 14 (43.7%) and the rate of death or AKI at Day 7 (41.2%) did not significantly differ between the groups. In inverse probability of treatment-weighted analyses, combination therapy was not independently associated with the likelihood of all-cause death at Day 28 (adjusted odd ratio [aOR], 1.14; 95% confidence interval [CI] 0.73-1.77; P = 0.56), clinical cure at Day 14 (aOR, 0.79; 95% CI 0.53-1.20; P = 0.27) or death or AKI at Day 7 (aOR, 1.07; 95% CI 0.71-1.63; P = 0.73). Multivariable regression models and subgroup analyses provided similar results.
Initial combination therapy exerts no independent impact on Day-28 mortality, clinical cure rate at Day 14, and the hazard of death or AKI at Day 7 in critically ill patients with mono-bacterial HAP, vHAP or VAP due to Gram-negative bacteria.</description><identifier>ISSN: 1364-8535</identifier><identifier>EISSN: 1466-609X</identifier><identifier>EISSN: 1364-8535</identifier><identifier>EISSN: 1366-609X</identifier><identifier>DOI: 10.1186/s13054-023-04792-0</identifier><identifier>PMID: 38172969</identifier><language>eng</language><publisher>England: BioMed Central Ltd</publisher><subject>Anti-infective agents ; Antibiotics ; Bacteria ; Blood ; Body temperature ; Control ; Disease control ; Dosage and administration ; Drug resistance ; Drug resistance in microorganisms ; Drug therapy ; Gram-negative bacteria ; Health aspects ; Identification and classification ; Infections ; Life Sciences ; Medical research ; Medicine, Experimental ; Mortality ; Pathogenic microorganisms ; Pathogens ; Pneumonia ; Prevention ; Risk factors ; Sepsis ; Septic shock ; Ventilators</subject><ispartof>Critical care (London, England), 2024-01, Vol.28 (1), p.10-10, Article 10</ispartof><rights>2024. The Author(s).</rights><rights>COPYRIGHT 2024 BioMed Central Ltd.</rights><rights>2024. This work is licensed under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>Attribution</rights><rights>The Author(s) 2024</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c483t-9868780b74580074cf1f25dde4b06c6f42fd24f7111170899088e053604dc0733</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC10765858/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC10765858/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38172969$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://u-paris.hal.science/hal-04592467$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Barbier, François</creatorcontrib><creatorcontrib>Dupuis, Claire</creatorcontrib><creatorcontrib>Buetti, Niccolò</creatorcontrib><creatorcontrib>Schwebel, Carole</creatorcontrib><creatorcontrib>Azoulay, Élie</creatorcontrib><creatorcontrib>Argaud, Laurent</creatorcontrib><creatorcontrib>Cohen, Yves</creatorcontrib><creatorcontrib>Hong Tuan Ha, Vivien</creatorcontrib><creatorcontrib>Gainnier, Marc</creatorcontrib><creatorcontrib>Siami, Shidasp</creatorcontrib><creatorcontrib>Forel, Jean-Marie</creatorcontrib><creatorcontrib>Adrie, Christophe</creatorcontrib><creatorcontrib>de Montmollin, Étienne</creatorcontrib><creatorcontrib>Reignier, Jean</creatorcontrib><creatorcontrib>Ruckly, Stéphane</creatorcontrib><creatorcontrib>Zahar, Jean-Ralph</creatorcontrib><creatorcontrib>Timsit, Jean-François</creatorcontrib><creatorcontrib>OutcomeRéa Study Group</creatorcontrib><creatorcontrib>the OutcomeRéa Study Group</creatorcontrib><title>Single-drug versus combination antimicrobial therapy in critically ill patients with hospital-acquired pneumonia and ventilator-associated pneumonia due to Gram-negative pathogens: a multicenter retrospective cohort study</title><title>Critical care (London, England)</title><addtitle>Crit Care</addtitle><description>In this study including 391 critically ill patients with nosocomial pneumonia due to Gram-negative pathogens, combination therapy was not associated with a reduced hazard of death at Day 28 or a greater likelihood of clinical cure at Day 14. No over-risk of AKI was observed in patients receiving combination therapy.
The benefits and harms of combination antimicrobial therapy remain controversial in critically ill patients with hospital-acquired pneumonia (HAP), ventilated HAP (vHAP) or ventilator-associated pneumonia (VAP) involving Gram-negative bacteria.
We included all patients in the prospective multicenter OutcomeRea database with a first HAP, vHAP or VAP due to a single Gram-negative bacterium and treated with initial adequate single-drug or combination therapy. The primary endpoint was Day-28 all-cause mortality. Secondary endpoints were clinical cure rate at Day 14 and a composite outcome of death or treatment-emergent acute kidney injury (AKI) at Day 7. The average effects of combination therapy on the study endpoints were investigated through inverse probability of treatment-weighted regression and multivariable regression models. Subgroups analyses were performed according to the resistance phenotype of the causative pathogens (multidrug-resistant or not), the pivotal (carbapenems or others) and companion (aminoglycosides/polymyxins or others) drug classes, the duration of combination therapy (< 3 or ≥ 3 days), the SOFA score value at pneumonia onset (< 7 or ≥ 7 points), and in patients with pneumonia due to non-fermenting Gram-negative bacteria, pneumonia-related bloodstream infection, or septic shock.
Among the 391 included patients, 151 (38.6%) received single-drug therapy and 240 (61.4%) received combination therapy. VAP (overall, 67.3%), vHAP (16.4%) and HAP (16.4%) were equally distributed in the two groups. All-cause mortality rates at Day 28 (overall, 31.2%), clinical cure rate at Day 14 (43.7%) and the rate of death or AKI at Day 7 (41.2%) did not significantly differ between the groups. In inverse probability of treatment-weighted analyses, combination therapy was not independently associated with the likelihood of all-cause death at Day 28 (adjusted odd ratio [aOR], 1.14; 95% confidence interval [CI] 0.73-1.77; P = 0.56), clinical cure at Day 14 (aOR, 0.79; 95% CI 0.53-1.20; P = 0.27) or death or AKI at Day 7 (aOR, 1.07; 95% CI 0.71-1.63; P = 0.73). Multivariable regression models and subgroup analyses provided similar results.
Initial combination therapy exerts no independent impact on Day-28 mortality, clinical cure rate at Day 14, and the hazard of death or AKI at Day 7 in critically ill patients with mono-bacterial HAP, vHAP or VAP due to Gram-negative bacteria.</description><subject>Anti-infective agents</subject><subject>Antibiotics</subject><subject>Bacteria</subject><subject>Blood</subject><subject>Body temperature</subject><subject>Control</subject><subject>Disease control</subject><subject>Dosage and administration</subject><subject>Drug resistance</subject><subject>Drug resistance in microorganisms</subject><subject>Drug therapy</subject><subject>Gram-negative bacteria</subject><subject>Health aspects</subject><subject>Identification and classification</subject><subject>Infections</subject><subject>Life Sciences</subject><subject>Medical research</subject><subject>Medicine, Experimental</subject><subject>Mortality</subject><subject>Pathogenic 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Ha, Vivien ; Gainnier, Marc ; Siami, Shidasp ; Forel, Jean-Marie ; Adrie, Christophe ; de Montmollin, Étienne ; Reignier, Jean ; Ruckly, Stéphane ; Zahar, Jean-Ralph ; Timsit, Jean-François</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c483t-9868780b74580074cf1f25dde4b06c6f42fd24f7111170899088e053604dc0733</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Anti-infective agents</topic><topic>Antibiotics</topic><topic>Bacteria</topic><topic>Blood</topic><topic>Body temperature</topic><topic>Control</topic><topic>Disease control</topic><topic>Dosage and administration</topic><topic>Drug resistance</topic><topic>Drug resistance in microorganisms</topic><topic>Drug therapy</topic><topic>Gram-negative bacteria</topic><topic>Health aspects</topic><topic>Identification and classification</topic><topic>Infections</topic><topic>Life Sciences</topic><topic>Medical 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England)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Barbier, François</au><au>Dupuis, Claire</au><au>Buetti, Niccolò</au><au>Schwebel, Carole</au><au>Azoulay, Élie</au><au>Argaud, Laurent</au><au>Cohen, Yves</au><au>Hong Tuan Ha, Vivien</au><au>Gainnier, Marc</au><au>Siami, Shidasp</au><au>Forel, Jean-Marie</au><au>Adrie, Christophe</au><au>de Montmollin, Étienne</au><au>Reignier, Jean</au><au>Ruckly, Stéphane</au><au>Zahar, Jean-Ralph</au><au>Timsit, Jean-François</au><aucorp>OutcomeRéa Study Group</aucorp><aucorp>the OutcomeRéa Study Group</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Single-drug versus combination antimicrobial therapy in critically ill patients with hospital-acquired pneumonia and ventilator-associated pneumonia due to Gram-negative pathogens: a multicenter retrospective cohort study</atitle><jtitle>Critical care (London, England)</jtitle><addtitle>Crit Care</addtitle><date>2024-01-03</date><risdate>2024</risdate><volume>28</volume><issue>1</issue><spage>10</spage><epage>10</epage><pages>10-10</pages><artnum>10</artnum><issn>1364-8535</issn><eissn>1466-609X</eissn><eissn>1364-8535</eissn><eissn>1366-609X</eissn><abstract>In this study including 391 critically ill patients with nosocomial pneumonia due to Gram-negative pathogens, combination therapy was not associated with a reduced hazard of death at Day 28 or a greater likelihood of clinical cure at Day 14. No over-risk of AKI was observed in patients receiving combination therapy.
The benefits and harms of combination antimicrobial therapy remain controversial in critically ill patients with hospital-acquired pneumonia (HAP), ventilated HAP (vHAP) or ventilator-associated pneumonia (VAP) involving Gram-negative bacteria.
We included all patients in the prospective multicenter OutcomeRea database with a first HAP, vHAP or VAP due to a single Gram-negative bacterium and treated with initial adequate single-drug or combination therapy. The primary endpoint was Day-28 all-cause mortality. Secondary endpoints were clinical cure rate at Day 14 and a composite outcome of death or treatment-emergent acute kidney injury (AKI) at Day 7. The average effects of combination therapy on the study endpoints were investigated through inverse probability of treatment-weighted regression and multivariable regression models. Subgroups analyses were performed according to the resistance phenotype of the causative pathogens (multidrug-resistant or not), the pivotal (carbapenems or others) and companion (aminoglycosides/polymyxins or others) drug classes, the duration of combination therapy (< 3 or ≥ 3 days), the SOFA score value at pneumonia onset (< 7 or ≥ 7 points), and in patients with pneumonia due to non-fermenting Gram-negative bacteria, pneumonia-related bloodstream infection, or septic shock.
Among the 391 included patients, 151 (38.6%) received single-drug therapy and 240 (61.4%) received combination therapy. VAP (overall, 67.3%), vHAP (16.4%) and HAP (16.4%) were equally distributed in the two groups. All-cause mortality rates at Day 28 (overall, 31.2%), clinical cure rate at Day 14 (43.7%) and the rate of death or AKI at Day 7 (41.2%) did not significantly differ between the groups. In inverse probability of treatment-weighted analyses, combination therapy was not independently associated with the likelihood of all-cause death at Day 28 (adjusted odd ratio [aOR], 1.14; 95% confidence interval [CI] 0.73-1.77; P = 0.56), clinical cure at Day 14 (aOR, 0.79; 95% CI 0.53-1.20; P = 0.27) or death or AKI at Day 7 (aOR, 1.07; 95% CI 0.71-1.63; P = 0.73). Multivariable regression models and subgroup analyses provided similar results.
Initial combination therapy exerts no independent impact on Day-28 mortality, clinical cure rate at Day 14, and the hazard of death or AKI at Day 7 in critically ill patients with mono-bacterial HAP, vHAP or VAP due to Gram-negative bacteria.</abstract><cop>England</cop><pub>BioMed Central Ltd</pub><pmid>38172969</pmid><doi>10.1186/s13054-023-04792-0</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1364-8535 |
| ispartof | Critical care (London, England), 2024-01, Vol.28 (1), p.10-10, Article 10 |
| issn | 1364-8535 1466-609X 1364-8535 1366-609X |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_10765858 |
| source | SpringerLink Journals; EZB-FREE-00999 freely available EZB journals; PubMed Central; Alma/SFX Local Collection; Springer Nature OA Free Journals |
| subjects | Anti-infective agents Antibiotics Bacteria Blood Body temperature Control Disease control Dosage and administration Drug resistance Drug resistance in microorganisms Drug therapy Gram-negative bacteria Health aspects Identification and classification Infections Life Sciences Medical research Medicine, Experimental Mortality Pathogenic microorganisms Pathogens Pneumonia Prevention Risk factors Sepsis Septic shock Ventilators |
| title | Single-drug versus combination antimicrobial therapy in critically ill patients with hospital-acquired pneumonia and ventilator-associated pneumonia due to Gram-negative pathogens: a multicenter retrospective cohort study |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-29T00%3A18%3A04IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Single-drug%20versus%20combination%20antimicrobial%20therapy%20in%20critically%20ill%20patients%20with%20hospital-acquired%20pneumonia%20and%20ventilator-associated%20pneumonia%20due%20to%20Gram-negative%20pathogens:%20a%20multicenter%20retrospective%20cohort%20study&rft.jtitle=Critical%20care%20(London,%20England)&rft.au=Barbier,%20Fran%C3%A7ois&rft.aucorp=OutcomeR%C3%A9a%20Study%20Group&rft.date=2024-01-03&rft.volume=28&rft.issue=1&rft.spage=10&rft.epage=10&rft.pages=10-10&rft.artnum=10&rft.issn=1364-8535&rft.eissn=1466-609X&rft_id=info:doi/10.1186/s13054-023-04792-0&rft_dat=%3Cgale_pubme%3EA778212317%3C/gale_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2914285409&rft_id=info:pmid/38172969&rft_galeid=A778212317&rfr_iscdi=true |