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Clinical Therapeutics

Risk Factors and Outcomes of Endocarditis Due to Non-HACEK Gram-Negative Bacilli: Data from the Prospective Multicenter Italian Endocarditis Study Cohort

Marco Falcone, Giusy Tiseo, Emanuele Durante-Mangoni, Veronica Ravasio, Francesco Barbaro, Maria Paola Ursi, Maria Bruna Pasticci, Matteo Bassetti, Paolo Grossi, Mario Venditti, Marco Rizzi
Marco Falcone
aDepartment of Public Health and Infectious Diseases, Sapienza University of Rome, Rome, Italy
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Giusy Tiseo
bDepartment of Internal Medicine and Medical Specialties, Sapienza University of Rome, Rome, Italy
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Emanuele Durante-Mangoni
cDipartimento di Internistica Clinica e Sperimentale, Università della Campania L. Vanvitelli, UOC Medicina Infettivologica e dei Trapianti, AORN dei Colli-Monaldi, Naples, Italy
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Veronica Ravasio
dASST Papa Giovanni XXIII, Infectious Diseases, Bergamo, Italy
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Francesco Barbaro
eInfectious Diseases, University Hospital, Padua, Italy
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Maria Paola Ursi
cDipartimento di Internistica Clinica e Sperimentale, Università della Campania L. Vanvitelli, UOC Medicina Infettivologica e dei Trapianti, AORN dei Colli-Monaldi, Naples, Italy
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Maria Bruna Pasticci
fInfectious Diseases Section, Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy
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Matteo Bassetti
gInfectious Diseases Clinic, Department of Medicine, University of Udine and Azienda Sanitaria Universitaria Integrata, Udine, Italy
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Paolo Grossi
hInfectious Diseases Unit, University of Insubria and University Hospital ASST Sette Laghi, Varese, Italy
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Mario Venditti
aDepartment of Public Health and Infectious Diseases, Sapienza University of Rome, Rome, Italy
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Marco Rizzi
dASST Papa Giovanni XXIII, Infectious Diseases, Bergamo, Italy
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DOI: 10.1128/AAC.02208-17
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    FIG 1

    Flow diagram of the study.

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    FIG 2

    Kaplan-Meier plots showing in-hospital (A) and 1-year (B) survival of patients with IE caused by GNB according to multidrug-resistant etiology.

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  • TABLE 1

    Etiologies of IE due to non-HACEK GNB

    EtiologyNo. of patients (% of totala)
    Enterobacteriaceae
        Escherichia coli18 (31)
        Klebsiella pneumoniae6 (10.3)
        Citrobacter koseri3 (5.2)
        Proteus mirabilis2 (3.5)
        Serratia marcescens2 (3.5)
        Enterobacter spp.2 (3.5)
        Yersinia enterocolitica1 (1.7)
        Total34 (58.6)
    Nonfermenting bacteria
        Pseudomonas spp.11 (19)
        Acinetobacter baumannii1 (1.7)
    Other bacteria
        Campylobacter fetus2 (3.5)
        Fusobacterium spp.2 (3.5)
        Achromobacter xylosoxidans1 (1.7)
        Brucella spp.1 (1.7)
        Prevotella buccae1 (1.7)
        Raoultella spp.1 (1.7)
        Sphingomonas paucimobilis1 (1.7)
    GNB coinfectionsb3 (5.2)
    MDR etiology16 (27.6)
    • ↵a A total of 58 patients with IE due to non-HACEK GNB were studied.

    • ↵b Comprising one case with E. coli and Proteus mirabilis, one with Pseudomonas aeruginosa and Pseudomonas fluorescens, and one with Pseudomonas aeruginosa and Stenotrophomonas maltophilia.

  • TABLE 2

    Comparison between patients with IE due to GNB (cases) and patients with IE due to other etiologies

    VariableaValueb for patients with IE due to:P
    GNB (n = 58)Other etiologies (n = 174)
    Demographic data
        Males39 (67.2)117 (67.6)1.0
        Median (range) age (yr)69.5 (57.75–77)69.5 (60–76)1.0
    Type of endocarditis
        NVE34 (58.6)118 (67.8)0.202
        PVE16 (27.6)48 (27.6)1.0
        Device-related IE8 (13.8)8 (4.6)0.017
    Comorbidities
        Diabetes19 (32.8)30 (17.2)0.012
        Hemodialysis1 (1.7)5 (2.9)0.633
        Malignancies10 (17.2)16 (9.2)0.093
        HIV infection2 (3.4)4 (2.3)0.633
    Risk factors
        IVDU5 (8.6)15 (8.6)1.0
        Dental procedures3 (5.2)13 (7.5)0.537
        CVC12 (20.7)16 (10)0.021
        CIED15 (25.9)19 (10.9)0.005
        Congenital heart disease4 (6.9)10 (5.7)0.758
        Immunosuppression9 (15.5)7 (4)0.003
        Pre-existing valvular disease18 (31)57 (32.8)0.808
    Invasive procedures within 180 days
        Dental procedures3 (5.2)13 (7.5)0.537
        Esophagogastroscopy1 (1.7)5 (2.9)0.633
        Colonoscopy4 (6.9)6 (3.4)0.263
        Cystoscopy3 (5.2)3 (1.7)0.152
    Route of acquisition
        Community acquired32 (55.2)116 (66.7)0.115
        Healthcare associated24 (41.4)49 (28.2)0.060
        Nosocomially acquired2 (3.4)9 (5.2)0.593
    Complications
        Stroke7 (12.1)27 (15.5)0.520
        Embolism14 (24.1)64 (36.8)0.078
        Heart failure15 (25.9)72 (41.4)0.030
        Septic shock2 (3.4)3 (1.7)0.434
        Arrhythmias5 (8.6)27 (15.5)0.187
    Echocardiographic findings
        Evidence of vegetation50 (86.2)155 (89.1)0.555
        Median (range) size of vegetation (mm)14 (6.5–20)10 (8–15)0.027
        Cardiac abscess3 (5.2)17 (9.8)0.280
        Perforation4 (6.9)8 (4.6)0.494
        Dehiscence6 (10.3)9 (5.2)0.165
        New regurgitation10 (17.2)63 (36.2)0.007
        Fistula0 (0)4 (2.3)0.244
    Presumed source of infection
        Genitourinary tract16 (27.6)6 (3.4)<0.001
        Skin8 (13.8)28 (16.1)0.675
        Nonoral gastrointestinal tract9 (15.5)37 (21.3)0.342
        Oral3 (5.2)18 (10.3)0.234
        Other or unknown24 (41.4)81 (46.6)0.493
    Treatment (surgery plus antibiotic therapy)25 (43.1)79 (45.4)0.760
    Outcomes
        All-cause in-hospital mortality8 (13.8)23 (13.2)0.911
        IE-related in-hospital mortality8 (13.8)21 (12.1)0.731
        Cumulative all-cause 1-yr mortalityc15 (30.6)NA
        Cumulative IE-related 1-yr mortalityc11 (22.4)NA
    • ↵a NVE, native valve endocarditis; PVE, prosthetic valve endocarditis; IVDU, intravenous drug user; CVC, central venous catheter (including any of the following: arteriovenous fistula, chronic intravenous catheter, or acute central catheter); CIED, cardiac implantable electronic device (12 permanent pacemakers and 3 cardioverter defibrillators in patients with endocarditis due to GNB; 17 permanent pacemakers and 2 cardioverter defibrillators in patients with other causes of endocarditis).

    • ↵b Values are numbers (percentages) of patients except where otherwise indicated.

    • ↵c Cumulative 1-year mortality was calculated for 49 patients (8 patients who died during the hospital stay and 41 patients with available follow-up after 1 year). NA, not available.

  • TABLE 3

    Multivariate analysis of factors independently associated with Gram-negative IE

    FactoraUnivariate analysisMultivariate analysis
    OR95.0% CIPOR95.0% CIP
    LowerUpperLowerUpper
    Genitourinary tract10.673.9328.92<0.00113.604.6339.93<0.001
    Immunosuppression4.381.5512.370.0035.161.616.620.006
    CIED2.851.336.060.0053.601.558.200.003
    New regurgitation0.370.170.770.0070.390.170.900.027
    Device-related endocarditis3.321.199.300.017
    CVC2.561.135.800.021
    Heart failure0.480.250.940.003
    • ↵a CIED, cardiac implantable electronic device; CVC: central venous catheter (including any of the following: arteriovenous fistula, chronic intravenous catheter, or acute central catheter).

  • TABLE 4

    Treatment strategies for IE due to non-HACEK GNB

    Antibiotic therapyaNo. (% of totalb)
    Noncarbapenem β-lactamc ± aminoglycosides ± fluoroquinolones29 (50)
        Penicillin or cephalosporin only5
        Non-carbapenem β-lactam + aminoglycosides14
        Non-carbapenem β-lactam + fluoroquinolones8
        Non-carbapenem β-lactam + aminoglycosides + fluoroquinolones2
    Carbapenem ± aminoglycosides ± fluoroquinolones8 (13.8)
        Carbapenem only3
        Carbapenem + aminoglycosides1
        Carbapenem + fluoroquinolones3
        Carbapenem + aminoglycosides + fluoroquinolones1
    Noncarbapenem β-lactam +carbapenem ± aminoglycosides ± fluoroquinolones13 (22.4)
        Non-carbapenem β-lactam + carbapenem4
        Non-carbapenem β-lactam + carbapenem + aminoglycosides3
        Non-carbapenem β-lactam + carbapenem + fluoroquinolones4
        Non-carbapenem β-lactam + carbapenem + aminoglycosides + fluoroquinolones2
    Colistin-containing regimens3 (5.2)
        Colistin + carbapenem + rifampin2
        Colistin + penicillin or cephalosporin + carbapenem + rifampin1
    Other regimens5 (8.6)
        Non-carbapenem β-lactam + rifampin1
        Non-carbapenem β-lactam + tobramycin + clindamycin1
        Aminoglycosides + rifampin1
        Aminoglycosides + fluoroquinolones + rifampin2
    • ↵a ±, with or without.

    • ↵b A total of 58 patients with IE due to non-HACEK GNB were studied.

    • ↵c Includes penicillin alone, penicillin–penicillinase inhibitor combinations, and third-generation cephalosporins.

  • TABLE 5

    Cox regression analysis investigating the effect of MDR etiology on in-hospital and 1-year mortality among patients with IE due to non-HACEK GNB

    MDR etiology on:Cox regression analysis
    HR95.0% CIP
    LowerUpper
    In-hospital mortality21.8492.672178.6830.004
    1-yr mortality4.4081.58112.2870.005

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Risk Factors and Outcomes of Endocarditis Due to Non-HACEK Gram-Negative Bacilli: Data from the Prospective Multicenter Italian Endocarditis Study Cohort
Marco Falcone, Giusy Tiseo, Emanuele Durante-Mangoni, Veronica Ravasio, Francesco Barbaro, Maria Paola Ursi, Maria Bruna Pasticci, Matteo Bassetti, Paolo Grossi, Mario Venditti, Marco Rizzi
Antimicrobial Agents and Chemotherapy Mar 2018, 62 (4) e02208-17; DOI: 10.1128/AAC.02208-17

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Risk Factors and Outcomes of Endocarditis Due to Non-HACEK Gram-Negative Bacilli: Data from the Prospective Multicenter Italian Endocarditis Study Cohort
Marco Falcone, Giusy Tiseo, Emanuele Durante-Mangoni, Veronica Ravasio, Francesco Barbaro, Maria Paola Ursi, Maria Bruna Pasticci, Matteo Bassetti, Paolo Grossi, Mario Venditti, Marco Rizzi
Antimicrobial Agents and Chemotherapy Mar 2018, 62 (4) e02208-17; DOI: 10.1128/AAC.02208-17
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KEYWORDS

Gram-negative bacteria
infective endocarditis
multidrug resistance

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