Abstract
Doxycycline is a broad-spectrum antibacterial drug. It is used widely to treat diseases caused by Mycoplasma species. We investigated the antibacterial activity of doxycycline against the Mycoplasma hyopneumoniae strain ATCC25934. The minimum inhibitory concentration (MIC) of doxycycline against M. hyopneumoniae determined by a microdilution method was 0.125 μg/ml. Static time–kill curves with constant drug concentrations (0–64 MIC) showed that a bacteriostatic effect occurred if the doxycycline concentration reached 4 MIC. Doxycycline produced a maximum antimycoplasmal effect (reduction of 2.76 log10CFU/ml) at 64 MIC within 48 h. The effect of doxycycline against M. hyopneumoniae was analyzed by a sigmoid E max model, and there was high correlation between the kill rate and doxycycline concentration (R 2 = 0.986). A one-compartment open model with first-order absorption was adopted and was used to simulate doxycycline pharmacokinetics in porcine plasma. The dynamic time–concentration curve showed that the area under the curve at 24 h (AUC24 h) and C max (peak concentration) after each drug administration was 1.78–48.4 μg h/ml and 0.16–3.41 μg/ml, respectively. The reduction of M. hyopneumoniae (log10CFU/ml) for 1, 2.5, 5, 7.5, 10, 15, 20, and 30 mg/kg body weight was 0.16, 1.29, 1.75, 2.94, 3.35, 3.91, 4.35, and 5.77, respectively, during the entire experiment, respectively. When the dose was >10 mg/kg body weight, continuous administration for 3 days could achieve a bactericidal effect. The correlation coefficient of AUC24 h/MIC, C max/MIC, and %T > MIC (the cumulative percentage of time over a 24-h period that the drug concentration exceeds the MIC) with antibacterial effect was 0.917, 0.923, and 0.823, respectively. Doxycycline showed concentration-dependent activity, and the value of AUC24 h/MIC and C max/MIC required to produce a drop of 1 log10CFU/ml was 164 h and 9.89, respectively.
Highlights
Mycoplasma hyopneumoniae is the primary etiologic agent of enzootic pneumonia and is widespread in pig populations (Rebaque et al, 2018)
M. hyopneumoniae is resistant to antimicrobial agents that interfere with the metabolism of folic acid and cell-wall synthesis, such as sulfonamides, trimethoprim, and the β-lactam class of antibiotics
Limited information is available on the PK/ pharmacodynamic (PD) interactions of antibacterial agents against Mycoplasma species, including doxycycline
Summary
Mycoplasma hyopneumoniae is the primary etiologic agent of enzootic pneumonia and is widespread in pig populations (Rebaque et al, 2018). M. hyopneumoniae possesses a limited number of genes, low guanine and cytosine content and has simple metabolic pathways, so it cannot synthesize some essential compounds (Weber Sde et al, 2012). This microorganism is found primarily on PK/PD Integration of Doxycycline Against M. hyopneumoniae the mucosal surface of the trachea, bronchi, and bronchioles. If M. hyopneumoniae is present with other pathogens, such as Actinobacillus pleuropneumoniae, Pasteurella multocida, Streptococcus suis, or Haemophilus parasuis, respiratory infections are aggravated and leads to porcine respiratory disease complex, which can cause considerable economic losses to the pig industry (Sibila et al, 2009). Macrolides, tetracyclines, fluoroquinolones, lincosamides, and pleuromutilins are active agents against M. hyopneumoniae (Hannan et al, 1997; Maes et al, 2008)
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