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Clinical Therapeutics

Importance of Site of Infection and Antibiotic Selection in the Treatment of Carbapenem-Resistant Pseudomonas aeruginosa Sepsis

Nicholas S. Britt, David J. Ritchie, Marin H. Kollef, Carey-Ann D. Burnham, Michael J. Durkin, Nicholas B. Hampton, Scott T. Micek
Nicholas S. Britt
aDepartment of Pharmacy, Barnes-Jewish Hospital, St. Louis, Missouri, USA
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David J. Ritchie
aDepartment of Pharmacy, Barnes-Jewish Hospital, St. Louis, Missouri, USA
bDepartment of Pharmacy Practice, St. Louis College of Pharmacy, St. Louis, Missouri, USA
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Marin H. Kollef
cDepartment of Medicine, Division of Pulmonary and Critical Care Medicine, Washington University School of Medicine, St. Louis, Missouri, USA
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Carey-Ann D. Burnham
dDepartment of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA
eDepartment of Pediatrics, Washington University School of Medicine, St. Louis, Missouri, USA
fDepartment of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri, USA
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Michael J. Durkin
gDepartment of Medicine, Division of Infectious Diseases, Washington University School of Medicine, St. Louis, Missouri, USA
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Nicholas B. Hampton
hCenter for Clinical Excellence, BJC HealthCare, St. Louis, Missouri, USA
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Scott T. Micek
aDepartment of Pharmacy, Barnes-Jewish Hospital, St. Louis, Missouri, USA
bDepartment of Pharmacy Practice, St. Louis College of Pharmacy, St. Louis, Missouri, USA
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DOI: 10.1128/AAC.02400-17
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  • TABLE 1

    Characteristics associated with all-cause in-hospital mortality among patients with sepsis due to carbapenem-resistant Pseudomonas aeruginosa

    Characteristica (n = 215)Survivor (n = 169)Nonsurvivor (n = 46)P value
    Age, median (yr [IQR])58 (44–67)61 (52–70)0.060
        Age ≥65 yr (n [%])59 (34.9)19 (41.3)0.424
    Yr of infection (n [%])0.224
        201259 (34.9)17 (37.0)0.797
        201342 (24.9)7 (15.2)0.167
        201428 (16.6)13 (28.3)0.073
        201540 (23.7)9 (19.6)0.556
    ICU admission (n [%])86 (50.9)31 (67.4)0.046
    Length of stay (median days [IQR])b3 (1–18)10 (1–29)0.034
    Hospital-acquired infection (n [%])c93 (55.0)33 (71.7)0.041
    Time to appropriate treatment (mean ± SD h)d16.3 ± 27.628.5 ± 77.50.302
    Antibiotic treatment (n [%])e,f0.089
        Aminoglycoside monotherapy24 (14.2)15 (32.6)0.004
        Colistin monotherapy13 (7.7)1 (2.2)0.311
        Cefepime monotherapy74 (43.8)14 (30.4)0.102
        Fluoroquinolone monotherapy10 (5.9)4 (8.7)0.505
        Piperacillin-tazobactam monotherapy38 (22.5)8 (17.4)0.455
        Aztreonam monotherapy1 (0.6)1 (2.2)0.383
        Ceftolozane/tazobactam monotherapy1 (0.6)0 (0.0)>0.999
        Combination therapy8 (4.7)3 (6.5)0.705
    Infection site (n [%])0.081
        Intraabdominal9 (5.3)3 (6.5)0.754
        Respiratory tract74 (43.8)30 (65.2)0.010
        Bloodstream/endovascular17 (10.1)4 (8.7)>0.999
        Urinary tract43 (25.4)3 (6.5)0.004
        Skin/soft tissue/osteomyelitis26 (15.4)6 (13.0)0.692
    Previous hospitalization (n [%])g151 (89.3)46 (100)0.015
    Invasive surgical procedure (n [%])h86 (50.9)23 (50.0)0.915
    Central venous catheter (n [%])h133 (78.7)32 (69.6)0.194
    Urinary catheter (n [%])h107 (63.3)32 (69.6)0.432
    Other invasive device (n [%])h37 (21.9)11 (23.9)0.771
    Mechanical ventilation (n [%])105 (62.1)43 (93.5)<0.001
    Previous antibiotic exposure (n [%])i131 (77.5)42 (91.3)0.036
        Carbapenemi81 (47.9)27 (58.7)0.195
    Vasopressor requirement (n [%])70 (41.4)41 (89.1)<0.001
    Immunosuppression (n [%])56 (33.1)28 (60.9)0.001
        Solid organ transplantation14 (8.3)7 (15.2)0.160
        Stem cell transplantation18 (10.7)5 (10.9)>0.999
    Acute kidney injury (n [%])j48 (28.4)13 (28.3)0.985
    SIRS criteria (median [IQR])3 (2–3)3 (2–3)0.541
    Charlson comorbidity index (median [IQR])6 (3–8)7 (5–11)0.007
    APACHE II score (median [IQR])13 (10–17)15 (12–19)0.030
    • ↵a IQR, interquartile range; SD, standard deviation; APACHE II, Acute Physiology and Chronic Health Evaluation II.

    • ↵b Before index culture.

    • ↵c Hospitalized >48 h before index culture without previous evidence of infection.

    • ↵d Treatment with an agent to which the organism was phenotypically susceptible in vitro.

    • ↵e Monotherapy defined as receipt of <2 antibiotics to which the organism was susceptible in vitro as definitive therapy for ≥48 h.

    • ↵f Combination therapy defined as receipt of ≥2 antibiotics to which the organism was susceptible in vitro as definitive therapy for ≥48 h.

    • ↵g Within the preceding 6 months.

    • ↵h During the index hospitalization before index culture.

    • ↵i Within the preceding 3 months.

    • ↵j Determined by diagnosis code as recorded by a treating physician.

  • TABLE 2

    Multivariable log-binomial regression model of variables associated with all-cause in-hospital mortality among patients with carbapenem-resistant Pseudomonas aeruginosa sepsis

    VariableCrude RRa (95% CI)P valueAdjusted RRa (95% CI)P value
    Aminoglycoside monotherapya1.35 (1.04–1.75)0.0031.72 (1.03–2.85)0.037
    Vasopressor requirement7.68 (3.16–18.69)<0.0016.85 (2.71–17.35)<0.001
    Charlson comorbidity index1.15 (1.04–1.96)0.0051.16 (1.05–1.90)0.001
    APACHE II score1.07 (1.01–1.13)0.0361.01 (0.98–1.04)0.394
    • ↵a RR, risk ratio. Comparator: all other monotherapies.

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Importance of Site of Infection and Antibiotic Selection in the Treatment of Carbapenem-Resistant Pseudomonas aeruginosa Sepsis
Nicholas S. Britt, David J. Ritchie, Marin H. Kollef, Carey-Ann D. Burnham, Michael J. Durkin, Nicholas B. Hampton, Scott T. Micek
Antimicrobial Agents and Chemotherapy Mar 2018, 62 (4) e02400-17; DOI: 10.1128/AAC.02400-17

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Importance of Site of Infection and Antibiotic Selection in the Treatment of Carbapenem-Resistant Pseudomonas aeruginosa Sepsis
Nicholas S. Britt, David J. Ritchie, Marin H. Kollef, Carey-Ann D. Burnham, Michael J. Durkin, Nicholas B. Hampton, Scott T. Micek
Antimicrobial Agents and Chemotherapy Mar 2018, 62 (4) e02400-17; DOI: 10.1128/AAC.02400-17
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KEYWORDS

carbapenem resistance
Pseudomonas aeruginosa
multidrug resistance
sepsis

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