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Attributable mortality from extensively drug-resistant gram-negative infections using propensity-matched tracer antibiotic algorithms

Published:February 27, 2019DOI:https://doi.org/10.1016/j.ajic.2019.01.010

      Highlights

      • Antibiotic algorithms allow estimation of attributable mortality (AM) from resistance.
      • Estimated AM for extensively drug-resistant (XDR) gram-negative infections was 12.6%.
      • AM of XDR gram-negative infections varied by site, onset, and severity of infection.
      • Direct hospitalization costs attributed to XDR infection exceed $35,000 per encounter.

      Background

      Tracer antibiotic algorithms using administrative data were investigated to estimate mortality attributable to extensively drug-resistant gram-negative infections (GNIs).

      Methods

      Among adult inpatients coded for GNIs, colistin cases and 2 comparator cohorts (non-carbapenem β-lactams or carbapenems) treated for ≥4 consecutive days, or died while receiving the antibiotic, were separately propensity score-matched (1:2). Attributable mortality was the in-hospital mortality difference among propensity-matched groups. Infection characteristics and sepsis severity influences on attributable mortality were examined. Algorithm accuracy was assessed by chart review.

      Results

      Of 232,834 GNIs between 2010 and 2013 at 79 hospitals, 1,023 per 3,350 (30.5%) colistin and 9,188 per 105,641 (8.7%) β-lactam (non-carbapenem) comparator cases died. Propensity-matched colistin and β-lactam case mortality was 29.2% and 16.6%, respectively, for an attributable mortality of 12.6% (95% confidence interval 10.8-14.4%). Attributable mortality varied from 11.0% (7.5%-14.7%) for urinary to 15.5% (12.6%-18.4%) for respiratory (P < .0001), and 4.6% (2.1%-7.4%) for early (≤4 days) to 16.6% (14.3%-18.9%) for late-onset infections (P < .0001). Attributable mortality decreased to 7.5% (5.6%-9.4%) using a carbapenem comparator cohort but increased 9-fold in patients coded for severe sepsis or septic shock (P < .0001). Our colistin algorithm had a positive predictive value of 60.4% and sensitivity of 65.3%.

      Conclusions

      Mortality attributable to treatment-limiting resistance during GNIs varied considerably by site, onset, and severity of infection.

      Key Words

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      References

        • Muscedere JG
        • Day A
        • Heyland DK.
        Mortality, attributable mortality, and clinical events as end points for clinical trials of ventilator-associated pneumonia and hospital-acquired pneumonia.
        Clin Infect Dis. 2010; 51: 120-125
        • Borer A
        • Saidel-Odes L
        • Riesenberg K
        • Eskira S
        • Peled N
        • Nativ R
        • et al.
        Attributable mortality rate for carbapenem-resistant Klebsiella pneumoniae bacteremia.
        Infect Control Hosp Epidemiol. 2009; 30: 972-976
        • de Gouvea EF
        • Martins IS
        • Halpern M
        • Ferreira AL
        • Basto ST
        • Goncalves RT
        • et al.
        The influence of carbapenem resistance on mortality in solid organ transplant recipients with Acinetobacter baumannii infection.
        BMC Infect Dis. 2012; 12: 351
        • Kwon KT
        • Oh WS
        • Song JH
        • Chang HH
        • Jung SI
        • Kim SW
        • et al.
        Impact of imipenem resistance on mortality in patients with Acinetobacter bacteraemia.
        J Antimicrob Chemother. 2007; 59: 525-530
        • Pena C
        • Suarez C
        • Gozalo M
        • Murillas J
        • Almirante B
        • Pomar V
        • et al.
        Prospective multicenter study of the impact of carbapenem resistance on mortality in Pseudomonas aeruginosa bloodstream infections.
        Antimicrob Agents Chemother. 2012; 56: 1265-1272
        • Hoxha A
        • Karki T
        • Giambi C
        • Montano C
        • Sisto A
        • Bella A
        • et al.
        Attributable mortality of carbapenem-resistant Klebsiella pneumoniae infections in a prospective matched cohort study in Italy, 2012-2013.
        J Hosp Infect. 2016; 92: 61-66
        • Lemos EV
        • de la Hoz FP
        • Einarson TR
        • McGhan WF
        • Quevedo E
        • Castaneda C
        • et al.
        Carbapenem resistance and mortality in patients with Acinetobacter baumannii infection: systematic review and meta-analysis.
        Clin Microbiol Infect. 2014; 20: 416-423
        • Falagas ME
        • Tansarli GS
        • Karageorgopoulos DE
        • Vardakas KZ.
        Deaths attributable to carbapenem-resistant Enterobacteriaceae infections.
        Emerg Infect Dis. 2014; 20: 1170-1175
        • Liu Q
        • Li X
        • Li W
        • Du X
        • He JQ
        • Tao C
        • et al.
        Influence of carbapenem resistance on mortality of patients with Pseudomonas aeruginosa infection: a meta-analysis.
        Sci Rep. 2015; 5: 11715
        • Roberts RR
        • Hota B
        • Ahmad I
        • Scott RD
        • Foster SD
        • Abbasi F
        • et al.
        Hospital and societal costs of antimicrobial-resistant infections in a Chicago teaching hospital: implications for antibiotic stewardship.
        Clin Infect Dis. 2009; 49: 1175-1184
      1. Centers for Disease Control and Prevention. Antibiotic Resistance Threats in the United States, 2013; 2013. Available at: https://www.cdc.gov/drugresistance/pdf/ar-threats-2013-508.pdf. Accessed February 6, 2019.

        • Nelson RE
        • Slayton RB
        • Stevens VW
        • Jones MM
        • Khader K
        • Rubin MA
        • et al.
        Attributable mortality of healthcare-associated infections due to multidrug-resistant gram-negative bacteria and methicillin-resistant Staphylococcus aureus.
        Infect Control Hosp Epidemiol. 2017; 38: 848-856
        • Kadri SS
        • Adjemian J
        • Lai YL
        • Spaulding AB
        • Ricotta E
        • Prevots DR
        • et al.
        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.
        Clin Infect Dis. 2018; 67: 1803-1814
      2. World Health Organization. Extensively drug-resistant tuberculosis (XDR-TB): recommendations for prevention and control.
        Wkly Epidemiol Rec. 2006; 81: 430-432
        • Falagas ME
        • Karageorgopoulos DE.
        Pandrug resistance (PDR), extensive drug resistance (XDR), and multidrug resistance (MDR) among gram-negative bacilli: need for international harmonization in terminology.
        Clin Infect Dis. 2008; 46: 1121-1122
        • Magiorakos AP
        • Srinivasan A
        • Carey RB
        • Carmeli Y
        • Falagas ME
        • Giske CG
        • et al.
        Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: an international expert proposal for interim standard definitions for acquired resistance.
        Clin Microbiol Infect. 2012; 18: 268-281
        • Kadri SS
        • Hohmann SF
        • Orav EJ
        • Bonne SL
        • Moffa MA
        • Timpone JG
        • et al.
        Tracking colistin-treated patients to monitor the incidence and outcome of carbapenem-resistant gram-negative infections.
        Clin Infect Dis. 2015; 60: 79-87
        • Ruppe E
        • Woerther PL
        • Barbier F.
        Mechanisms of antimicrobial resistance in gram-negative bacilli.
        Ann Intensive Care. 2015; 5: 61
        • Kumar A
        • Ellis P
        • Arabi Y
        • Roberts D
        • Light B
        • Parrillo JE
        • et al.
        Initiation of inappropriate antimicrobial therapy results in a fivefold reduction of survival in human septic shock.
        Chest. 2009; 136: 1237-1248
        • Shields RK
        • Potoski BA
        • Haidar G
        • Hao B
        • Doi Y
        • Chen L
        • et al.
        Clinical outcomes, drug toxicity, and emergence of ceftazidime-avibactam resistance among patients treated for carbapenem-resistant Enterobacteriaceae infections.
        Clin Infect Dis. 2016; 63: 1615-1618
        • Fraile-Ribot PA
        • Mulet X
        • Cabot G
        • Del Barrio-Tofino E
        • Juan C
        • Perez JL
        • et al.
        In vivo emergence of resistance to novel cephalosporin-beta-lactamase inhibitor combinations through the duplication of the amino acid D149 from OXA-2 beta-lactamase (OXA-539) in ST235 Pseudomonas aeruginosa.
        Antimicrob Agents Chemother. 2017; 61 (:e01117-17)
        • Eichacker PQ
        • Gerstenberger EP
        • Banks SM
        • Cui X
        • Natanson C.
        Meta-analysis of acute lung injury and acute respiratory distress syndrome trials testing low tidal volumes.
        Am J Respir Crit Care Med. 2002; 166: 1510-1514
        • Christensen KL
        • Holman RC
        • Steiner CA
        • Sejvar JJ
        • Stoll BJ
        • Schonberger LB.
        Infectious disease hospitalizations in the United States.
        Clin Infect Dis. 2009; 49: 1025-1035
      3. 3M Health Information Systems. All patient refined diagnosis related groups (APR–DRGs), version 15.0, methodology overview. 1998.

        • Geisinger E
        • Isberg RR.
        Interplay between antibiotic resistance and virulence during disease promoted by multidrug-resistant bacteria.
        J Infect Dis. 2017; 215(Suppl 1): 9-17
        • Bjorkman J
        • Nagaev I
        • Berg OG
        • Hughes D
        • Andersson DI.
        Effects of environment on compensatory mutations to ameliorate costs of antibiotic resistance.
        Science. 2000; 287: 1479-1482
        • Patel G
        • Huprikar S
        • Factor SH
        • Jenkins SG
        • Calfee DP.
        Outcomes of carbapenem-resistant Klebsiella pneumoniae infection and the impact of antimicrobial and adjunctive therapies.
        Infect Control Hosp Epidemiol. 2008; 29: 1099-1106
        • Ben-David D
        • Kordevani R
        • Keller N
        • Tal I
        • Marzel A
        • Gal-Mor O
        • et al.
        Outcome of carbapenem resistant Klebsiella pneumoniae bloodstream infections.
        Clin Microbiol Infect. 2012; 18: 54-60
      4. CDC federal engagement in antimicrobial resistance. 2017. Available at: https://www.who.int/antimicrobial-resistance/publications/global-action-plan/en/. Accessed February 6, 2019.

      5. WHO global action plan on antimicrobial resistance. 2015. Available at: https://www.who.int/antimicrobial-resistance/publications/global-action-plan/en/. Accessed February 6, 2019.

      6. The Lancet Infectious Diseases. Editorial: A better pathway to approval of 21st century cures?.
        Lancet Infect Dis. 2017; 17: 117
        • Prestinaci F
        • Pezzotti P
        • Pantosti A.
        Antimicrobial resistance: a global multifaceted phenomenon.
        Pathog Glob Health. 2015; 109: 309-318
        • Friedman ND
        • Temkin E
        • Carmeli Y.
        The negative impact of antibiotic resistance.
        Clin Microbiol Infect. 2016; 22: 416-422
        • Cosgrove SE
        • Carmeli Y.
        The impact of antimicrobial resistance on health and economic outcomes.
        Clin Infect Dis. 2003; 36: 1433-1437
        • Rhee C
        • Dantes R
        • Epstein L
        • Murphy DJ
        • Seymour CW
        • Iwashyna TJ
        • et al.
        Incidence and trends of sepsis in US hospitals using clinical vs claims data, 2009-2014.
        JAMA. 2017; 318: 1241-1249
        • Lee BY.
        Digital decision making: computer models and antibiotic prescribing in the twenty-first century.
        Clin Infect Dis. 2008; 46: 1139-1141