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Clinical Therapeutics

Proteus mirabilis Bloodstream Infections: Risk Factors and Treatment Outcome Related to the Expression of Extended-Spectrum β-Lactamases

Andrea Endimiani, Francesco Luzzaro, Gioconda Brigante, Mariagrazia Perilli, Gianluigi Lombardi, Gianfranco Amicosante, Gian Maria Rossolini, Antonio Toniolo
Andrea Endimiani
1Laboratorio di Microbiologia, Ospedale di Circolo and Università dell'Insubria, I-21100 Varese
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Francesco Luzzaro
1Laboratorio di Microbiologia, Ospedale di Circolo and Università dell'Insubria, I-21100 Varese
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Gioconda Brigante
1Laboratorio di Microbiologia, Ospedale di Circolo and Università dell'Insubria, I-21100 Varese
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Mariagrazia Perilli
2Dipartimento di Scienze e Tecnologie Biomediche, Università di L'Aquila, I-67100 L'Aquila
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Gianluigi Lombardi
1Laboratorio di Microbiologia, Ospedale di Circolo and Università dell'Insubria, I-21100 Varese
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Gianfranco Amicosante
2Dipartimento di Scienze e Tecnologie Biomediche, Università di L'Aquila, I-67100 L'Aquila
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Gian Maria Rossolini
3Dipartimento di Biologia Molecolare, Sezione di Microbiologia, Università di Siena, I-53100 Siena, Italy
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Antonio Toniolo
1Laboratorio di Microbiologia, Ospedale di Circolo and Università dell'Insubria, I-21100 Varese
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  • For correspondence: antonio.toniolo@ospedale.varese.it aendimiani@tin.it
DOI: 10.1128/AAC.49.7.2598-2605.2005
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Tables

  • TABLE 1.

    MICs and molecular results for all P. mirabilis isolates causing BSI during the study period (January 1997 to June 2004)

    IsolateMIC of antimicrobial agent (μg/ml)aType of enzymes produced
    AMPSAMAMCFOXPIPTZPCROCTXCTLCAZTZLFEPIPMMEMATMCIPLVXAMKGENTOB
    43/97>256243>2560.75380.03220.06441.50.1250.1254449616TEM-52, TEM-1
    1/98>256463>2560.5480.03220.064430.0640.094>3283>2566TEM-52
    405/01>256864>2560.5380.03240.25030.50.0940.38>32>324>25624TEM-92
    130/02>256262>2560.388320.09410.032320.0470.064>32163>2568TEM-92, TEM-1
    629/02>2568124>2560.75440.03220.064810.0940.094>32>324>25624TEM-92
    139/03b>256484>2560.5480.03220.0643210.0640.125>32>324>25624TEM-92
    309/03b>256484>2560.5480.03220.0643210.0640.125>32>324>25624TEM-92
    463/03b>256484>2560.5480.03220.0643210.0640.125>32>324>25624TEM-92
    601/03>256244>2561280.03220.064320.0940.19>32>321.5644TEM-92, TEM-1
    A19/03>256821.5>2560.75240.03220.064220.0470.0470.7523968TEM-92
    A68/03>256446>25611.560.09440.12540.250.0320.12516>321644TEM-92
    65/99>25640.510.1250.125<0.016<0.016<0.016<0.016<0.0160.0640.50.023<0.0160.0160.0321.50.50.75TEM-1
    1289/01>256431.50.50.19<0.016<0.016<0.016<0.016<0.0160.0470.750.032<0.016141.5122TEM-1
    2501/010.50.50.3820.1250.125<0.016<0.016<0.016<0.016<0.016<0.01610.032<0.0160.0160.03210.50.75None
    2512/010.50.50.3810.1250.125<0.016<0.016<0.016<0.016<0.016<0.0160.50.032<0.0160.0160.03210.50.75None
    108/02>25681.51.50.50.19<0.016<0.016<0.016<0.016<0.0160.03210.023<0.0160.0160.032210.5TEM-1
    461/020.50.50.3810.1250.125<0.016<0.016<0.016<0.016<0.016<0.0160.750.032<0.0160.0320.0471.50.50.5None
    683/020.750.50.3810.1250.125<0.016<0.016<0.016<0.016<0.0160.09410.032<0.0160.0160.03220.50.75None
    794/02>25620.510.1250.125<0.016<0.016<0.016<0.016<0.0160.0640.50.023<0.0160.0160.032612832TEM-1
    85/03110.3810.1250.125<0.016<0.016<0.016<0.016<0.0160.03210.032<0.0160.0160.0321.548None
    654/03>25620.520.380.19<0.016<0.016<0.016<0.016<0.0160.0320.750.032<0.0160.0160.0320.510.5TEM-1
    753/030.50.50.3810.1250.125<0.016<0.016<0.016<0.016<0.016<0.01610.032<0.0160.0160.03220.50.75None
    A48/0310.750.3810.750.75<0.016<0.016<0.016<0.016<0.016<0.0160.50.016<0.0160.0160.0321.521None
    134/04>25640.3810.1250.094<0.016<0.016<0.016<0.016<0.0160.04710.032<0.0160.0320.06421284TEM-1
    634/04110.3810.250.125<0.016<0.016<0.016<0.016<0.0160.02310.032<0.016240.520.75None
    • ↵ a Abbreviations for antimicrobial agents follow (NCCLS 2004 breakpoints for susceptibility [S] and resistance [R] [in micrograms per milliliter] are given in parentheses): AMP, ampicillin (S ≤ 8, R ≥ 32); SAM, ampicillin plus sulbactam (S ≤ 8/4, R ≥ 32/16); AMC, amoxicillin plus clavulanate (S ≤ 8/4, R ≥ 32/16); FOX, cefoxitin (S ≤ 8, R ≥ 32); PIP, piperacillin (S ≤ 16, R ≥ 128); TZP, piperacillin plus tazobactam (S ≤ 16/4, R ≥ 128/4); CRO, ceftriaxone (S ≤ 8, R ≥ 64); CTX, cefotaxime (S ≤ 8, R ≥ 64); CTL, cefotaxime plus clavulanate; CAZ, ceftazidime (S ≤ 8, R ≥ 32); TZL, ceftazidime plus clavulanate; FEP, cefepime (S ≤ 8, R ≥ 32); IPM, imipenem (S ≤ 4, R ≥ 16); MEM, meropenem (S ≤ 4, R ≥ 16); ATM, aztreonam (S ≤ 8, R ≥ 32); CIP, eiprofloxacin (S ≤ 1, R ≥ 4); LVX, levofloxacin (S ≤ 2, R ≥ 8); AMK, amikacin (S ≤ 16, R ≥ 32); GEN, gentamicin (S ≤ 4, R ≥ 8); TOB, tobramycin (S ≤ 4, R ≥ 8).

    • ↵ b These strains caused three different BSI in the same patient.

  • TABLE 2.

    Demographic and clinical parameters of patients with BSI due to Proteus mirabilis strains and differences between ESBL-P-PM and ESBL-N-PM isolates

    Demographic and clinical parametersNo. (%) of patientsaP valueb
    ESBL-P-PMESBL-N-PM
    No. of BSI patients9c14ND
    No. of BSI episodes11c14ND
    Age (yr) (mean ± SD)70.9 ± 17.567.3 ± 18.2NS
    Sex (male/female)7/27/7ND
    McCabe and Jackson groupsd
        Nonfatal5 (55.6)8 (57.1)NS
        Ultimately fatal3 (33.3)4 (28.6)NS
        Rapidly fatal1 (11.1)2 (14.3)NS
    Charlson weighted index (mean ± SD)e4.0 ± 2.54.1 ± 2.6NS
    Severity of septicemia
        Sepsis6 (66.7)11 (78.6)NS
        Severe sepsis2 (22.2)2 (14.3)NS
        Septic shock1 (11.1)1 (7.1)NS
    Previous hospitalizations (during the last 12 months)6 (66.7)8 (57.1)NS
    Previous hospitalization in nursing home5 (55.6)3 (21.4)0.04
    Hospital-acquired BSI3 (33.3)6 (42.9)NS
    Hospital stay before BSI diagnosis (days) (mean ± SD)16.8 ± 30.36.0 ± 6.90.10
    Length of hospital stay (days) (mean ± SD)86.2 ± 193.419.4 ± 8.00.10
    Empirical treatment
        Provided9 (100.0)12 (85.7)NS
        Adequate5 (55.6)12 (85.7)0.04
    Adequate treatment after ID/AST results4 (44.4)12 (85.7)0.04
    Predisposing factors
        Bladder catheter9 (100.0)8 (57.1)0.01
        Previous use of antibiotics4 (44.4)3 (21.4)0.09
        Intravascular catheter4 (44.4)3 (21.4)0.09
        Corticosteroids or antineoplastic therapy2 (22.2)4 (28.6)NS
        Previous surgery0 (0.0)3 (21.4)NS
        Drainages0 (0.0)3 (21.4)NS
        Intubation1 (11.1)1 (7.1)NS
    Secondary BSI
        All patients4 (44.4)3 (21.4)0.09
        Urinary tract4 (44.4)f3 (21.4)g0.09
        Other0 (0.0)0 (0.0)NS
    Overall mortality3 (33.3)2 (14.3)NS
    Mortality attributable to BSI3 (33.3)0 (0.0)0.04
    • ↵ a Data are number (%) of patients, unless otherwise indicated.

    • ↵ b NS, not significant; ND, not determined.

    • ↵ c One patient had three different BSI; therefore, statistical analysis was performed considering only 9 BSI patients.

    • ↵ d McCabe and Jackson groups used to classify the severity of the underlying disease (22).

    • ↵ e Comorbidity scores determined according to the Charlson weighted index (6).

    • ↵ f Three from bladder catheter.

    • ↵ g One from bladder catheter.

  • TABLE 3.

    Clinical parameters, antimicrobial regimens, and treatment outcome of patients with BSI due to ESBL-N-PM and ESBL-P-PM strains

    IsolateAge (yr)SexaMcCabe and Jackson groupbCharlson weighted indexcSeverity of septicemiaEmpirical antimicrobial treatmentdAntimicrobial therapy administered after ID and AST resultsdTreatment outcomePatient outcome and comments
    Agent (daily dose)AdequateAgentTiming from BSI onsetDuration (days)Daily dose
    43/97 ESBL83FNonfatal2SepsisCRO (1,000 mg × 2)NoCRO4 days before81,000 mg × 2Partial responseTransferred on day 8 to nursing home
    GENFirst day52,000 mg
    1/98 ESBL91MNonfatal3SepsisCRO (1,000 mg)NoN.c.First day6N.c.FailureDeath on day 6 for causes attributable to BSI
    405/01 ESBL43MNonfatal0SepsisAMC (1,000 mg × 3)YesN.c.First day9N.c.RelapseTransferred on day 12 to clinic for rehabilitation
    130/02 ESBL77MNonfatal5SepsisSAM (1,500 mg × 3)YesMEM3 days after211,000 mg × 3Complete responseDischarged on day 46
    AMK3 days after21500 mg
    629/02 ESBL65MRapidly7SepsisSAM (3,000 mg × 3)YesN.c.2 day before6N.c.FailureDeath on day 4 for causes attributable to BSI
    AMK (500 mg × 3)
    139/03 ESBLe45MNonfatal0SepsisCRO (2,000 mg)NoN.c.First day12N.c.RelapseNew BSI on day 12
    309/03 ESBLe45MNonfatal0SepsisCRO (1,000 mg × 2)NoSAM3 days after121,500 mg × 4Partial responseRecurrent UTIf; new BSI on day 42
    463/03 ESBLe45MNonfatal0SepsisFEP (1,000 mg × 3)NoN.c.First day10N.c.FailureComplete response when AMK (500 mg × 2) added on day 53 for 6 days
    601/03 ESBL81MUltimately4Septic shockTZP (2,250 mg × 3)YesN.c.2 days before6N.c.FailureDeath on day 4 for causes attributable to BSI
    A19/03 ESBL84FUltimately6Severe sepsisCAZ (2,000 mg × 3)YesIPM4 days after121,000 mg × 3Complete responseTransferred on day 21 to nursing home
    CIP (400 mg × 3)
    A68/03 ESBL71MUltimately7Severe sepsisCAZ (1,000 mg × 3)NoCAZ1 day before132,000 mg × 2Complete responseDischarged on day 13
    AMK2 days after10500 mg × 2
    65/9977FNonfatal2SepsisCRO (2,000 mg)YesN.c.1 day before10N.c.Complete responseTransferred on day 11 to nursing home
    1289/0161FRapidly9SepsisCRO (2,000 mg)YesCIP5 days after9400 mg × 3Partial responseComplete response after IMP (1,000 mg × 3) use; death on day 24
    2501/0192FUltimately7Severe sepsisSAM (1,500 mg × 3)YesN.c.First day9N.c.Complete responseDischarged on day 10
    AMK (500 mg)
    2512/0152MRapidly5SepsisSAM (3,000 mg × 3)YesN.c.1 day before8N.c.Complete responseDischarged on day 10
    108/0262MNonfatal2Septic shockIPM (1,000 mg × 4)YesN.c.10 days before19N.c.Complete responseDischarged on day 90
    AMK (1,000 mg)
    461/0263FUltimately6Severe sepsisCRO (2,000 mg)YesIPM5 days after81,000 mg × 2Complete responseDischarged on day 26
    LVX (500 mg × 3)
    683/0216MNonfatal0SepsisCRO (1,000 mg × 2)YesN.c.First day6N.c.Complete responseDischarged on day 6
    794/0269MNonfatal5SepsisNoneNoIPM1 day after7500 mg × 2Complete responsePatient submitted to day hospital for dialysis
    85/0373MNonfatal2SepsisTZP (2,250 mg × 3)YesCAZ2 days after162,000 mg × 3Complete responseDischarged on day 20
    654/0361FUltimately8SepsisTZP (2,250 mg × 3)YesN.c.1 day before15N.c.Complete responseDischarged on day 25
    753/0377MNonfatal3SepsisTZP (2,250 mg × 3)YesN.c.1 day after12N.c.Complete responseDischarged on day 8
    A48/0378FNonfatal2SepsisCRO (2,000 mg)YesN.c.First day7N.c.Complete responseTransferred on day 15 to clinic for rehabilitation
    134/0477MUltimately4SepsisNoneNoNoneNoneNoneNoneNot assessableDeath on day 1
    634/0484FNonfatal3SepsisTZP (2,250 mg × 3)N.c.1 day before9N.c.Complete responseDischarged on day 10
    • ↵ a F, female; M, male.

    • ↵ b McCabe and Jackson groups used to classify the severity of the underlying disease (22).

    • ↵ c Comorbidity scores determined according to the Charlson weighted index (6).

    • ↵ d Antimicrobial agent abbreviations: CRO, ceftriaxone; GEN, gentamicin; AMC, amoxicillin plus clavulanate; SAM, ampicillin plus sulbactam; MEM, meropenem; AMK, amikacin; FEP, cefepime; TZP, piperacillin plus tazobactam; CAZ, ceftazidime; CIP, ciprofloxacin; IPM, imipenem; LVX, levofloxacin. 1,000 mg × 2, two 1,000-mg doses. N.c., not changed.

    • ↵ e These cases occurred in the same patient.

    • ↵ f UTI, urinary tract infection.

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Proteus mirabilis Bloodstream Infections: Risk Factors and Treatment Outcome Related to the Expression of Extended-Spectrum β-Lactamases
Andrea Endimiani, Francesco Luzzaro, Gioconda Brigante, Mariagrazia Perilli, Gianluigi Lombardi, Gianfranco Amicosante, Gian Maria Rossolini, Antonio Toniolo
Antimicrobial Agents and Chemotherapy Jun 2005, 49 (7) 2598-2605; DOI: 10.1128/AAC.49.7.2598-2605.2005

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Proteus mirabilis Bloodstream Infections: Risk Factors and Treatment Outcome Related to the Expression of Extended-Spectrum β-Lactamases
Andrea Endimiani, Francesco Luzzaro, Gioconda Brigante, Mariagrazia Perilli, Gianluigi Lombardi, Gianfranco Amicosante, Gian Maria Rossolini, Antonio Toniolo
Antimicrobial Agents and Chemotherapy Jun 2005, 49 (7) 2598-2605; DOI: 10.1128/AAC.49.7.2598-2605.2005
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KEYWORDS

Anti-Bacterial Agents
bacteremia
Proteus Infections
Proteus mirabilis
beta-lactamases

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