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Clinical Therapeutics

Bloodstream Infections Caused by Antibiotic-Resistant Gram-Negative Bacilli: Risk Factors for Mortality and Impact of Inappropriate Initial Antimicrobial Therapy on Outcome

Cheol-In Kang, Sung-Han Kim, Wan Beom Park, Ki-Deok Lee, Hong-Bin Kim, Eui-Chong Kim, Myoung-don Oh, Kang-Won Choe
Cheol-In Kang
1Departments of Internal Medicine
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Sung-Han Kim
1Departments of Internal Medicine
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Wan Beom Park
1Departments of Internal Medicine
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Ki-Deok Lee
1Departments of Internal Medicine
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Hong-Bin Kim
1Departments of Internal Medicine
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Eui-Chong Kim
2Laboratory Medicine, Seoul National University College of Medicine
3Clinical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea
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Myoung-don Oh
1Departments of Internal Medicine
3Clinical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea
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  • For correspondence: mdohmd@snu.ac.kr
Kang-Won Choe
1Departments of Internal Medicine
3Clinical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea
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DOI: 10.1128/AAC.49.2.760-766.2005
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    FIG. 1.

    Survival curve using the Kaplan-Meier method for patients with antibiotic-resistant gram-negative bacteremia who received appropriate initial antimicrobial therapy compared to those who received inappropriate therapy. The inappropriate therapy group has the lower probability of survival than the appropriate therapy group. The 30-day mortality rate of the appropriate initial antimicrobial therapy group was 27.4%, whereas that of the inappropriate therapy group was 38.4% (P = 0.049).

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  • TABLE 1.

    Demographic characteristics of study populationa

    CharacteristicValue for groupbP value
    Appropriate initial antibiotics (n = 135)Inappropriate initial antibiotics (n = 151)
    No. of males83 (61.5)100 (66.2)NS
    Age (yr) (mean ± SD, range)53 ± 16, 16-8656 ± 16, 16-95NS
    APACHE II score (mean ± SD, range)11.39 ± 4.85, 0-2511.02 ± 5.15, 0-24NS
    Underlying disease
        Leukemia20 (14.8)21 (13.9)NS
        Malignant lymphoma3 (2.2)4 (2.6)NS
        Solid organ transplantation7 (5.2)7 (4.6)NS
        Liver cirrhosis13 (9.6)14 (9.3)NS
        End-stage renal disease6 (4.4)6 (4.0)NS
        Pancreaticobiliary tract disease13 (9.6)20 (13.2)NS
        Solid tumor51 (37.8)59 (39.1)NS
        Others22 (16.3)20 (13.2)NS
    Comorbid condition
        Neutropenia27 (20)29 (19.2)NS
        Presentation with septic shock33 (24.4)42 (27.8)NS
        Long hospital stay (> 14 days)79 (58.5)76 (50.3)NS
        ICU care27 (20)26 (17.2)NS
        Postoperative state19 (14.1)21 (13.9)NS
        Polymicrobial18 (13.3)25 (16.6)NS
    Primary site of infection
        Catheter related3 (2.2)5 (3.3)NS
        Pancreaticobiliary tract50 (37)59 (39.1)NS
        Urinary tract14 (10.4)18 (11.9)NS
        Lung4 (3)12 (7.9)NS
        Peritoneum18 (13.3)21 (13.9)NS
        Unknown45 (33.3)32 (21.1)NS
    Microorganism
        E. coli30 (22.2)31 (20.5)NS
        K. pneumoniae42 (31.1)23 (15.2)0.001
        Enterobacter species49 (36.3)37 (24.5)0.030
        P. aeruginosa14 (10.4)60 (39.7)<0.001
    • ↵ a NS, not significant (P > 0.05); SD, standard deviation.

    • ↵ b Number and percentage (in parentheses) of patients with each characteristic are shown.

  • TABLE 2.

    Reasons for inappropriate initial antimicrobial therapy

    Reasons for inappropriate therapyNo. of patients
    E. coli (n = 31)K. pneumoniae (n = 23)Enterobacter (n = 37)P. aeruginosa (n = 60)
    Cephalosporin use and resistance to druga111221
    Combination therapy and resistance to multiple drugs1710115
    Monotherapy and resistance to drugb31117
    Monotherapy with aminoglycoside in Pseudomonasc33
    No therapy0045
    • ↵ a Applied to bloodstream infections caused by E. coli, K. pneumoniae, and Enterobacter spp.

    • ↵ b Patients who received cephalosporin monotherapy for bloodstream infections caused by E. coli, K. pneumoniae, or Enterobacter spp. were not included. Those were classified under cephalosporin use and resistance to drug.

    • ↵ c Applied to P. aeruginosa bacteremia.

  • TABLE 3.

    Risk factors associated with 30-day mortality in bloodstream infections caused by antimicrobial-resistant gram-negative bacilli based on univariate analysis

    Risk factorNo. of survivors (n = 191) (%)No. of nonsurvivors (n = 95) (%)OR (95% CI)P value
    Inappropriate initial empirical antimicrobial therapy93 (48.7)58 (61.1)1.65 (1.001-2.73)0.049
    Old age (>65 yrs)49 (25.7)28 (24.2)0.93 (0.52-1.64)0.791
    Long hospital stay (>14 days)a87 (45.5)68 (71.6)3.01 (1.77-5.11)<0.001
    Immunosuppressive therapy14 (7.3)16 (16.8)2.56 (1.19-5.50)0.013
    Corticosteroid use30 (15.7)32 (33.7)2.73 (1.53-4.85)0.001
    Care in ICU20 (10.5)33 (34.7)4.55 (2.43-8.52)<0.001
    High-risk source of bacteremia62 (32.5)70 (73.7)5.83 (3.37-10.08)<0.001
    Neutropenic state30 (15.7)26 (27.4)2.02 (1.11-3.67)0.019
    Postoperative state24 (12.6)16 (16.8)1.41 (0.71-2.00)0.326
    Polymicrobial23 (12)20 (21.1)1.95 (1.01-3.76)0.045
    Presentation with septic shock10 (5.2)65 (68.4)39.22 (18.16-84.68)<0.001
    APACHE II score
        ≤766 (34.6)6 (6.3)
        8-15109 (57.1)44 (46.3)<0.001
        ≥1616 (8.4)45 (47.4)
    Microorganism
        E. coli48 (25.1)13 (13.7)0.47 (0.24-0.92)0.026
        K. pneumoniae44 (23)21 (22.1)0.95 (0.53-1.71)0.859
        Enterobacter species57 (29.8)29 (30.5)1.03 (0.61-1.77)0.906
        P. aeruginosa42 (22)32 (33.7)1.80 (1.04-3.11)0.033
    • ↵ a Hospital stay prior to onset of bacteremia.

  • TABLE 4.

    Independent risk factors for mortality in bloodstream infections caused by antimicrobial-resistant gram-negative bacilli based on multivariate analysisa

    Risk factorAdjusted OR (95% CI)P value
    All patients of study population (n = 286)
        High-risk source of bacteremia3.95 (1.66-9.41)0.002
        Presentation with septic shock40.99 (15.30-109.82)<0.001
        APACHE II score (per 1-point increment)1.29 (1.16-1.44)<0.001
        P. aeruginosa bacteremia3.07 (1.21-7.79)0.018
    Patients with low-risk source of bacteremia (n = 154)b
        Presentation with septic shock23.01 (6.42-82.49)<0.001
        APACHE II score (per 1-point increment)1.25 (1.09-1.43)0.001
        P. aeruginosa bacteremia4.27 (1.33-13.67)0.015
    Patients with high-risk source of bacteremia (n = 132)c
        Presentation with septic shock100.87 (17.98-565.89)<0.001
        APACHE II score (per 1-point increment)1.348 (1.13-1.61)0.001
        Inappropriate initial antimicrobial therapy3.64 (1.13-11.72)0.030
    • ↵ a Variables with a P value of <0.05 in the univariate analysis were candidates for multivariate analysis as well as the main variable of interest (i.e., inappropriate initial antimicrobial therapy).

    • ↵ b Multivariate analysis using a logistic regression model included the following variables: a long hospital stay, ICU care, neutropenia, polymicrobial, septic shock, APACHE II score, Pseudomonas infection, and inappropriate initial antimicrobial therapy.

    • ↵ c Multivariate analysis included ICU care, septic shock, APACHE II score, Pseudomonas infection, old age, and inappropriate initial antimicrobial therapy.

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Bloodstream Infections Caused by Antibiotic-Resistant Gram-Negative Bacilli: Risk Factors for Mortality and Impact of Inappropriate Initial Antimicrobial Therapy on Outcome
Cheol-In Kang, Sung-Han Kim, Wan Beom Park, Ki-Deok Lee, Hong-Bin Kim, Eui-Chong Kim, Myoung-don Oh, Kang-Won Choe
Antimicrobial Agents and Chemotherapy Jan 2005, 49 (2) 760-766; DOI: 10.1128/AAC.49.2.760-766.2005

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Bloodstream Infections Caused by Antibiotic-Resistant Gram-Negative Bacilli: Risk Factors for Mortality and Impact of Inappropriate Initial Antimicrobial Therapy on Outcome
Cheol-In Kang, Sung-Han Kim, Wan Beom Park, Ki-Deok Lee, Hong-Bin Kim, Eui-Chong Kim, Myoung-don Oh, Kang-Won Choe
Antimicrobial Agents and Chemotherapy Jan 2005, 49 (2) 760-766; DOI: 10.1128/AAC.49.2.760-766.2005
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KEYWORDS

anti-infective agents
bacteremia
Gram-negative bacterial infections

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