Difficult-to-Treat Resistance in Gram-negative Bacteremia at 173 US Hospitals: Retrospective Cohort Analysis of Prevalence, Predictors, and Outcome of Resistance to All First-line Agents
Abstract Background Resistance to all first-line antibiotics necessitates the use of less effective or more toxic "reserve" agents. Gram-negative bloodstream infections (GNBSIs) harboring such difficult-to-treat resistance (DTR) may have higher mortality than phenotypes that allow for ≥1 a...
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| Veröffentlicht in: | Clinical infectious diseases 2018-11, Vol.67 (12), p.1803-1814 |
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| creator | Kadri, Sameer S Adjemian, Jennifer Lai, Yi Ling Spaulding, Alicen B Ricotta, Emily Prevots, D Rebecca Palmore, Tara N Rhee, Chanu Klompas, Michael Dekker, John P Powers, John H Suffredini, Anthony F Hooper, David C Fridkin, Scott Danner, Robert L |
| description | Abstract
Background
Resistance to all first-line antibiotics necessitates the use of less effective or more toxic "reserve" agents. Gram-negative bloodstream infections (GNBSIs) harboring such difficult-to-treat resistance (DTR) may have higher mortality than phenotypes that allow for ≥1 active first-line antibiotic.
Methods
The Premier Database was analyzed for inpatients with select GNBSIs. DTR was defined as intermediate/resistant in vitro to all ß-lactam categories, including carbapenems and fluoroquinolones. Prevalence and aminoglycoside resistance of DTR episodes were compared with carbapenem-resistant, extended-spectrum cephalosporin-resistant, and fluoroquinolone-resistant episodes using CDC definitions. Predictors of DTR were identified. The adjusted relative risk (aRR) of mortality was examined for DTR, CDC-defined phenotypes susceptible to ≥1 first-line agent, and graded loss of active categories.
Results
Between 2009-2013, 471 (1%) of 45011 GNBSI episodes at 92 (53.2%) of 173 hospitals exhibited DTR, ranging from 0.04% for Escherichia coli to 18.4% for Acinetobacter baumannii. Among patients with DTR, 79% received parenteral aminoglycosides, tigecycline, or colistin/polymyxin-B; resistance to all aminoglycosides occurred in 33%. Predictors of DTR included urban healthcare and higher baseline illness. Crude mortality for GNBSIs with DTR was 43%; aRR was higher for DTR than for carbapenem-resistant (1.2; 95% confidence interval, 1.0-1.4; P = .02), extended-spectrum cephalosporin-resistant (1.2; 1.1-1.4; P = .001), or fluoroquinolone-resistant (1.2; 1.0-1.4; P = .008) infections. The mortality aRR increased 20% per graded loss of active first-line categories, from 3-5 to 1-2 to 0.
Conclusion
Nonsusceptibility to first-line antibiotics is associated with decreased survival in GNBSIs. DTR is a simple bedside prognostic measure of treatment-limiting coresistance.
Resistance to all first-line agents or difficult-to-treat resistance (DTR) was observed in 1% of gram-negative bacteremias. DTR was identified at half the hospitals; nearly 80% of patients with DTR received "reserve" agents. Mortality risk increased with decreasing active first-line categories. |
| doi_str_mv | 10.1093/cid/ciy378 |
| format | Article |
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Background
Resistance to all first-line antibiotics necessitates the use of less effective or more toxic "reserve" agents. Gram-negative bloodstream infections (GNBSIs) harboring such difficult-to-treat resistance (DTR) may have higher mortality than phenotypes that allow for ≥1 active first-line antibiotic.
Methods
The Premier Database was analyzed for inpatients with select GNBSIs. DTR was defined as intermediate/resistant in vitro to all ß-lactam categories, including carbapenems and fluoroquinolones. Prevalence and aminoglycoside resistance of DTR episodes were compared with carbapenem-resistant, extended-spectrum cephalosporin-resistant, and fluoroquinolone-resistant episodes using CDC definitions. Predictors of DTR were identified. The adjusted relative risk (aRR) of mortality was examined for DTR, CDC-defined phenotypes susceptible to ≥1 first-line agent, and graded loss of active categories.
Results
Between 2009-2013, 471 (1%) of 45011 GNBSI episodes at 92 (53.2%) of 173 hospitals exhibited DTR, ranging from 0.04% for Escherichia coli to 18.4% for Acinetobacter baumannii. Among patients with DTR, 79% received parenteral aminoglycosides, tigecycline, or colistin/polymyxin-B; resistance to all aminoglycosides occurred in 33%. Predictors of DTR included urban healthcare and higher baseline illness. Crude mortality for GNBSIs with DTR was 43%; aRR was higher for DTR than for carbapenem-resistant (1.2; 95% confidence interval, 1.0-1.4; P = .02), extended-spectrum cephalosporin-resistant (1.2; 1.1-1.4; P = .001), or fluoroquinolone-resistant (1.2; 1.0-1.4; P = .008) infections. The mortality aRR increased 20% per graded loss of active first-line categories, from 3-5 to 1-2 to 0.
Conclusion
Nonsusceptibility to first-line antibiotics is associated with decreased survival in GNBSIs. DTR is a simple bedside prognostic measure of treatment-limiting coresistance.
Resistance to all first-line agents or difficult-to-treat resistance (DTR) was observed in 1% of gram-negative bacteremias. DTR was identified at half the hospitals; nearly 80% of patients with DTR received "reserve" agents. Mortality risk increased with decreasing active first-line categories.</description><identifier>ISSN: 1058-4838</identifier><identifier>EISSN: 1537-6591</identifier><identifier>DOI: 10.1093/cid/ciy378</identifier><identifier>PMID: 30052813</identifier><language>eng</language><publisher>US: Oxford University Press</publisher><subject>Adolescent ; Adult ; Aged ; and Commentaries ; Anti-Bacterial Agents - therapeutic use ; Bacteremia - drug therapy ; Bacteremia - epidemiology ; Carbapenems - therapeutic use ; Databases, Factual ; Drug Resistance, Multiple, Bacterial ; Editor's Choice ; Female ; Fluoroquinolones - therapeutic use ; Gram-Negative Bacteria - drug effects ; Gram-Negative Bacterial Infections - drug therapy ; Gram-Negative Bacterial Infections - mortality ; Hospitals ; Humans ; Male ; Microbial Sensitivity Tests ; Middle Aged ; Prevalence ; Prognosis ; Retrospective Studies ; Treatment Outcome ; United States - epidemiology ; Young Adult</subject><ispartof>Clinical infectious diseases, 2018-11, Vol.67 (12), p.1803-1814</ispartof><rights>Published by Oxford University Press for the Infectious Diseases Society of America 2018. 2018</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c408t-1d9789489c1856eb1ccac204bed4c5548b5199e158f09e2024af199a43f5ae0c3</citedby><cites>FETCH-LOGICAL-c408t-1d9789489c1856eb1ccac204bed4c5548b5199e158f09e2024af199a43f5ae0c3</cites><orcidid>0000-0002-4420-9004</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,1578,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30052813$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kadri, Sameer S</creatorcontrib><creatorcontrib>Adjemian, Jennifer</creatorcontrib><creatorcontrib>Lai, Yi Ling</creatorcontrib><creatorcontrib>Spaulding, Alicen B</creatorcontrib><creatorcontrib>Ricotta, Emily</creatorcontrib><creatorcontrib>Prevots, D Rebecca</creatorcontrib><creatorcontrib>Palmore, Tara N</creatorcontrib><creatorcontrib>Rhee, Chanu</creatorcontrib><creatorcontrib>Klompas, Michael</creatorcontrib><creatorcontrib>Dekker, John P</creatorcontrib><creatorcontrib>Powers, John H</creatorcontrib><creatorcontrib>Suffredini, Anthony F</creatorcontrib><creatorcontrib>Hooper, David C</creatorcontrib><creatorcontrib>Fridkin, Scott</creatorcontrib><creatorcontrib>Danner, Robert L</creatorcontrib><creatorcontrib>National Institutes of Health Antimicrobial Resistance Outcomes Research Initiative (NIH–ARORI)</creatorcontrib><title>Difficult-to-Treat Resistance in Gram-negative Bacteremia at 173 US Hospitals: Retrospective Cohort Analysis of Prevalence, Predictors, and Outcome of Resistance to All First-line Agents</title><title>Clinical infectious diseases</title><addtitle>Clin Infect Dis</addtitle><description>Abstract
Background
Resistance to all first-line antibiotics necessitates the use of less effective or more toxic "reserve" agents. Gram-negative bloodstream infections (GNBSIs) harboring such difficult-to-treat resistance (DTR) may have higher mortality than phenotypes that allow for ≥1 active first-line antibiotic.
Methods
The Premier Database was analyzed for inpatients with select GNBSIs. DTR was defined as intermediate/resistant in vitro to all ß-lactam categories, including carbapenems and fluoroquinolones. Prevalence and aminoglycoside resistance of DTR episodes were compared with carbapenem-resistant, extended-spectrum cephalosporin-resistant, and fluoroquinolone-resistant episodes using CDC definitions. Predictors of DTR were identified. The adjusted relative risk (aRR) of mortality was examined for DTR, CDC-defined phenotypes susceptible to ≥1 first-line agent, and graded loss of active categories.
Results
Between 2009-2013, 471 (1%) of 45011 GNBSI episodes at 92 (53.2%) of 173 hospitals exhibited DTR, ranging from 0.04% for Escherichia coli to 18.4% for Acinetobacter baumannii. Among patients with DTR, 79% received parenteral aminoglycosides, tigecycline, or colistin/polymyxin-B; resistance to all aminoglycosides occurred in 33%. Predictors of DTR included urban healthcare and higher baseline illness. Crude mortality for GNBSIs with DTR was 43%; aRR was higher for DTR than for carbapenem-resistant (1.2; 95% confidence interval, 1.0-1.4; P = .02), extended-spectrum cephalosporin-resistant (1.2; 1.1-1.4; P = .001), or fluoroquinolone-resistant (1.2; 1.0-1.4; P = .008) infections. The mortality aRR increased 20% per graded loss of active first-line categories, from 3-5 to 1-2 to 0.
Conclusion
Nonsusceptibility to first-line antibiotics is associated with decreased survival in GNBSIs. DTR is a simple bedside prognostic measure of treatment-limiting coresistance.
Resistance to all first-line agents or difficult-to-treat resistance (DTR) was observed in 1% of gram-negative bacteremias. DTR was identified at half the hospitals; nearly 80% of patients with DTR received "reserve" agents. Mortality risk increased with decreasing active first-line categories.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Aged</subject><subject>and Commentaries</subject><subject>Anti-Bacterial Agents - therapeutic use</subject><subject>Bacteremia - drug therapy</subject><subject>Bacteremia - epidemiology</subject><subject>Carbapenems - therapeutic use</subject><subject>Databases, Factual</subject><subject>Drug Resistance, Multiple, Bacterial</subject><subject>Editor's Choice</subject><subject>Female</subject><subject>Fluoroquinolones - therapeutic use</subject><subject>Gram-Negative Bacteria - drug effects</subject><subject>Gram-Negative Bacterial Infections - drug therapy</subject><subject>Gram-Negative Bacterial Infections - mortality</subject><subject>Hospitals</subject><subject>Humans</subject><subject>Male</subject><subject>Microbial Sensitivity Tests</subject><subject>Middle Aged</subject><subject>Prevalence</subject><subject>Prognosis</subject><subject>Retrospective Studies</subject><subject>Treatment Outcome</subject><subject>United States - epidemiology</subject><subject>Young Adult</subject><issn>1058-4838</issn><issn>1537-6591</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kc1OGzEUhS0E4q9seIDKGzYVBns8znhYVEpDCUhIqdqwHt147gRXM-PIdiLl1fp0OKREsGFh-V77u-dYPoScC34leCmvja3TWstC75FjoWTBBqoU-6nmSrNcS31ETkL4y7kQmqtDciQ5V5kW8pj8u7VNY82yjSw6NvUIkf7GYEOE3iC1PR176FiPc4h2hfQHmIgeOws0kaKQ9OkPvXdhYSO04SbNRp86NK_0yD07H-mwh3adNKlr6C-PK2gxiV9u6tqa6Hy4pNDXdLKMxnW4wd69ITo6bFt6Z32IrLU90uEc-xi-kIMmeeLZ__2UPN39nI7u2eNk_DAaPjKTcx2ZqMtCl7kujdBqgDNhDJiM5zOsc6NUrmdKlCUKpRteYsazHJp0ALlsFCA38pR83-oulrMOa5O8PbTVwtsO_LpyYKuPN719ruZuVQ2yAReFSALftgImfU3w2OxmBa82CVYpwWqbYIK_vnfboW-RJeBiC7jl4jOhF8OBqIA</recordid><startdate>20181128</startdate><enddate>20181128</enddate><creator>Kadri, Sameer S</creator><creator>Adjemian, Jennifer</creator><creator>Lai, Yi Ling</creator><creator>Spaulding, Alicen B</creator><creator>Ricotta, Emily</creator><creator>Prevots, D Rebecca</creator><creator>Palmore, Tara N</creator><creator>Rhee, Chanu</creator><creator>Klompas, Michael</creator><creator>Dekker, John P</creator><creator>Powers, John H</creator><creator>Suffredini, Anthony F</creator><creator>Hooper, David C</creator><creator>Fridkin, Scott</creator><creator>Danner, Robert L</creator><general>Oxford University Press</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-4420-9004</orcidid></search><sort><creationdate>20181128</creationdate><title>Difficult-to-Treat Resistance in Gram-negative Bacteremia at 173 US Hospitals: Retrospective Cohort Analysis of Prevalence, Predictors, and Outcome of Resistance to All First-line Agents</title><author>Kadri, Sameer S ; Adjemian, Jennifer ; Lai, Yi Ling ; Spaulding, Alicen B ; Ricotta, Emily ; Prevots, D Rebecca ; Palmore, Tara N ; Rhee, Chanu ; Klompas, Michael ; Dekker, John P ; Powers, John H ; Suffredini, Anthony F ; Hooper, David C ; Fridkin, Scott ; Danner, Robert L</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c408t-1d9789489c1856eb1ccac204bed4c5548b5199e158f09e2024af199a43f5ae0c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Aged</topic><topic>and Commentaries</topic><topic>Anti-Bacterial Agents - therapeutic use</topic><topic>Bacteremia - drug therapy</topic><topic>Bacteremia - epidemiology</topic><topic>Carbapenems - therapeutic use</topic><topic>Databases, Factual</topic><topic>Drug Resistance, Multiple, Bacterial</topic><topic>Editor's Choice</topic><topic>Female</topic><topic>Fluoroquinolones - therapeutic use</topic><topic>Gram-Negative Bacteria - drug effects</topic><topic>Gram-Negative Bacterial Infections - drug therapy</topic><topic>Gram-Negative Bacterial Infections - mortality</topic><topic>Hospitals</topic><topic>Humans</topic><topic>Male</topic><topic>Microbial Sensitivity Tests</topic><topic>Middle Aged</topic><topic>Prevalence</topic><topic>Prognosis</topic><topic>Retrospective Studies</topic><topic>Treatment Outcome</topic><topic>United States - epidemiology</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kadri, Sameer S</creatorcontrib><creatorcontrib>Adjemian, Jennifer</creatorcontrib><creatorcontrib>Lai, Yi Ling</creatorcontrib><creatorcontrib>Spaulding, Alicen B</creatorcontrib><creatorcontrib>Ricotta, Emily</creatorcontrib><creatorcontrib>Prevots, D Rebecca</creatorcontrib><creatorcontrib>Palmore, Tara N</creatorcontrib><creatorcontrib>Rhee, Chanu</creatorcontrib><creatorcontrib>Klompas, Michael</creatorcontrib><creatorcontrib>Dekker, John P</creatorcontrib><creatorcontrib>Powers, John H</creatorcontrib><creatorcontrib>Suffredini, Anthony F</creatorcontrib><creatorcontrib>Hooper, David C</creatorcontrib><creatorcontrib>Fridkin, Scott</creatorcontrib><creatorcontrib>Danner, Robert L</creatorcontrib><creatorcontrib>National Institutes of Health Antimicrobial Resistance Outcomes Research Initiative (NIH–ARORI)</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Clinical infectious diseases</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kadri, Sameer S</au><au>Adjemian, Jennifer</au><au>Lai, Yi Ling</au><au>Spaulding, Alicen B</au><au>Ricotta, Emily</au><au>Prevots, D Rebecca</au><au>Palmore, Tara N</au><au>Rhee, Chanu</au><au>Klompas, Michael</au><au>Dekker, John P</au><au>Powers, John H</au><au>Suffredini, Anthony F</au><au>Hooper, David C</au><au>Fridkin, Scott</au><au>Danner, Robert L</au><aucorp>National Institutes of Health Antimicrobial Resistance Outcomes Research Initiative (NIH–ARORI)</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Difficult-to-Treat Resistance in Gram-negative Bacteremia at 173 US Hospitals: Retrospective Cohort Analysis of Prevalence, Predictors, and Outcome of Resistance to All First-line Agents</atitle><jtitle>Clinical infectious diseases</jtitle><addtitle>Clin Infect Dis</addtitle><date>2018-11-28</date><risdate>2018</risdate><volume>67</volume><issue>12</issue><spage>1803</spage><epage>1814</epage><pages>1803-1814</pages><issn>1058-4838</issn><eissn>1537-6591</eissn><abstract>Abstract
Background
Resistance to all first-line antibiotics necessitates the use of less effective or more toxic "reserve" agents. Gram-negative bloodstream infections (GNBSIs) harboring such difficult-to-treat resistance (DTR) may have higher mortality than phenotypes that allow for ≥1 active first-line antibiotic.
Methods
The Premier Database was analyzed for inpatients with select GNBSIs. DTR was defined as intermediate/resistant in vitro to all ß-lactam categories, including carbapenems and fluoroquinolones. Prevalence and aminoglycoside resistance of DTR episodes were compared with carbapenem-resistant, extended-spectrum cephalosporin-resistant, and fluoroquinolone-resistant episodes using CDC definitions. Predictors of DTR were identified. The adjusted relative risk (aRR) of mortality was examined for DTR, CDC-defined phenotypes susceptible to ≥1 first-line agent, and graded loss of active categories.
Results
Between 2009-2013, 471 (1%) of 45011 GNBSI episodes at 92 (53.2%) of 173 hospitals exhibited DTR, ranging from 0.04% for Escherichia coli to 18.4% for Acinetobacter baumannii. Among patients with DTR, 79% received parenteral aminoglycosides, tigecycline, or colistin/polymyxin-B; resistance to all aminoglycosides occurred in 33%. Predictors of DTR included urban healthcare and higher baseline illness. Crude mortality for GNBSIs with DTR was 43%; aRR was higher for DTR than for carbapenem-resistant (1.2; 95% confidence interval, 1.0-1.4; P = .02), extended-spectrum cephalosporin-resistant (1.2; 1.1-1.4; P = .001), or fluoroquinolone-resistant (1.2; 1.0-1.4; P = .008) infections. The mortality aRR increased 20% per graded loss of active first-line categories, from 3-5 to 1-2 to 0.
Conclusion
Nonsusceptibility to first-line antibiotics is associated with decreased survival in GNBSIs. DTR is a simple bedside prognostic measure of treatment-limiting coresistance.
Resistance to all first-line agents or difficult-to-treat resistance (DTR) was observed in 1% of gram-negative bacteremias. DTR was identified at half the hospitals; nearly 80% of patients with DTR received "reserve" agents. Mortality risk increased with decreasing active first-line categories.</abstract><cop>US</cop><pub>Oxford University Press</pub><pmid>30052813</pmid><doi>10.1093/cid/ciy378</doi><tpages>12</tpages><orcidid>https://orcid.org/0000-0002-4420-9004</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | Clinical infectious diseases, 2018-11, Vol.67 (12), p.1803-1814 |
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| source | Jstor Complete Legacy; Oxford University Press Journals All Titles (1996-Current); MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| subjects | Adolescent Adult Aged and Commentaries Anti-Bacterial Agents - therapeutic use Bacteremia - drug therapy Bacteremia - epidemiology Carbapenems - therapeutic use Databases, Factual Drug Resistance, Multiple, Bacterial Editor's Choice Female Fluoroquinolones - therapeutic use Gram-Negative Bacteria - drug effects Gram-Negative Bacterial Infections - drug therapy Gram-Negative Bacterial Infections - mortality Hospitals Humans Male Microbial Sensitivity Tests Middle Aged Prevalence Prognosis Retrospective Studies Treatment Outcome United States - epidemiology Young Adult |
| title | Difficult-to-Treat Resistance in Gram-negative Bacteremia at 173 US Hospitals: Retrospective Cohort Analysis of Prevalence, Predictors, and Outcome of Resistance to All First-line Agents |
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