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Experimental Therapeutics

Impact of Cethromycin (ABT-773) Therapy on Microbiological, Histologic, Immunologic, and Respiratory Indices in a Murine Model of Mycoplasma pneumoniae Lower Respiratory Infection

Ana María Ríos, Asunción Mejías, Susana Chávez-Bueno, Mónica Fonseca-Aten, Kathy Katz, Jeanine Hatfield, Ana María Gómez, Hasan S. Jafri, George H. McCracken Jr., Octavio Ramilo, Robert Doug Hardy
Ana María Ríos
1Departments of Pediatrics
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  • For correspondence: ana.rios@utsouthwestern.edu
Asunción Mejías
1Departments of Pediatrics
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Susana Chávez-Bueno
1Departments of Pediatrics
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Mónica Fonseca-Aten
1Departments of Pediatrics
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Kathy Katz
1Departments of Pediatrics
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Jeanine Hatfield
1Departments of Pediatrics
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Ana María Gómez
2Pathology, University of Texas Southwestern Medical Center, Dallas, Texas
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Hasan S. Jafri
1Departments of Pediatrics
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George H. McCracken Jr.
1Departments of Pediatrics
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Octavio Ramilo
1Departments of Pediatrics
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Robert Doug Hardy
1Departments of Pediatrics
3Internal Medicine
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DOI: 10.1128/AAC.48.8.2897-2904.2004
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  • FIG. 1.
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    FIG. 1.

    Mean CFU of M. pneumoniae (Mp) in BAL cultures of infected mice treated with either cethromycin (25 mg/kg/day subcutaneously) or placebo for 10 days (therapy was started 1 day after infection). Error bars represent standard deviations. *, P < 0.05; ***, P < 0.001. n = 5 to 10 mice per cethromycin treatment group and 5 to 15 mice per placebo group.

  • FIG. 2.
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    FIG. 2.

    Median HPS of mice infected with M. pneumoniae (Mp) and treated with either cethromycin or placebo. Error bars represent 75th to 25th percentiles. *, P < 0.05; **, P < 0.01. n = 5 to 10 mice per cethromycin treatment group and 5 to 15 mice per placebo group.

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    FIG. 3.

    (a to j) Mean and median cytokine and chemokine concentrations in BAL fluid of mice infected with M. pneumoniae (Mp) and treated with either cethromycin or placebo. Error bars represent standard deviations when variables have a normal distribution and 75th to 25th percentiles when variables do not have a normal distribution. *, P < 0.05; **, P < 0.01; ***, P < 0.001. n = 5 to 10 mice per cethromycin treatment group and 5 to 15 mice per placebo group.

  • FIG. 4.
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    FIG. 4.

    Median Penh of mice infected with M. pneumoniae (Mp) and treated with either cethromycin or placebo. Error bars represent 75th to 25th percentiles. *, P < 0.05. n = 5 to 10 mice per cethromycin treatment group and 5 to 15 mice per placebo group.

  • FIG. 5.
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    FIG. 5.

    Mean post-methacholine exposure Penh of mice infected with M. pneumoniae (Mp) and treated with either cethromycin or placebo. Error bars represent standard deviations. *, P < 0.05. n = 5 to 10 mice per cethromycin treatment group and 5 to 15 mice per placebo group.

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  • TABLE 1.

    Correlations among outcome variables at day 4

    VariableCorrelation with:
    HPSAOaAHRbCethromycin therapy
    rPnrPnrPnrPn
    M. pneumoniae culture0.20.3190.40.1180.10.618−0.20.319
    HPS0.50.03200.50.0420−0.6<0.00123
    AO0.7<0.00120−0.60.00720
    AHR−0.40.0820
    • ↵ a AO, airway obstruction.

    • ↵ b AHR, airway hyperreactivity.

  • TABLE 2.

    Correlations of cytokines and chemokines in BAL samples at day 4

    Cytokine or chemokineCorrelation with:
    M. pneumoniae culturesHPSAOaAHRbCethromycin therapy
    rPnrPnrPnrPnrPn
    IL-1β0.20.4150.50.05190.30.2160.60.0216−0.50.0319
    IL-20.30.3150.50.01190.40.2160.40.116−0.40.0919
    TNF-α0.20.3190.7<0.001230.40.09200.30.220−0.60.00523
    IL-120.50.06150.50.02190.60.01160.40.216−0.70.00219
    IFN-γ0.70.004150.7<0.001190.7<0.001160.60.0116−0.60.00819
    IL-40.030.9150.40.1190.30.2160.40.116−0.10.519
    GM-CSF0.020.9150.30.1190.080.7160.30.2160.050.819
    IL-80.20.4190.30.1230.40.1200.40.0420−0.40.00323
    MCP-10.30.3190.60.001230.60.005200.40.0720−0.8<0.00123
    MIP-1α0.20.3190.60.007220.50.05190.20.319−0.8<0.00122
    • ↵ a AO, airway obstruction.

    • ↵ b AHR, airway hyperreactivity.

  • TABLE 3.

    Correlations of cytokines and chemokines in BAL samples at day 4

    Cytokine or chemokineCorrelation with:
    IL-1βIL-2TNF-αIL-12INF-γ
    rPnrPnrPnrPnrPn
    IL-1β0.70.002190.40.06190.40.06190.50.0119
    IL-20.50.04190.50.01190.50.0219
    TNF-α0.20.3190.50.0119
    IL-120.70.00119
    MCP-10.070.7190.30.1190.50.01190.8<0.001190.8<0.00119
    MIP-1α0.30.2190.30.2190.50.02190.7<0.001190.60.0119
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Impact of Cethromycin (ABT-773) Therapy on Microbiological, Histologic, Immunologic, and Respiratory Indices in a Murine Model of Mycoplasma pneumoniae Lower Respiratory Infection
Ana María Ríos, Asunción Mejías, Susana Chávez-Bueno, Mónica Fonseca-Aten, Kathy Katz, Jeanine Hatfield, Ana María Gómez, Hasan S. Jafri, George H. McCracken Jr., Octavio Ramilo, Robert Doug Hardy
Antimicrobial Agents and Chemotherapy Jul 2004, 48 (8) 2897-2904; DOI: 10.1128/AAC.48.8.2897-2904.2004

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Impact of Cethromycin (ABT-773) Therapy on Microbiological, Histologic, Immunologic, and Respiratory Indices in a Murine Model of Mycoplasma pneumoniae Lower Respiratory Infection
Ana María Ríos, Asunción Mejías, Susana Chávez-Bueno, Mónica Fonseca-Aten, Kathy Katz, Jeanine Hatfield, Ana María Gómez, Hasan S. Jafri, George H. McCracken Jr., Octavio Ramilo, Robert Doug Hardy
Antimicrobial Agents and Chemotherapy Jul 2004, 48 (8) 2897-2904; DOI: 10.1128/AAC.48.8.2897-2904.2004
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KEYWORDS

cephalosporins
erythromycin
ketolides
Mycoplasma pneumoniae
Pneumonia, Mycoplasma
Respiratory Mechanics
respiratory tract infections

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