Abstract
Mycoplasma gallisepticum is one of the most important pathogens that cause chronic respiratory disease in chicken. This study investigated the antibacterial activity of doxycycline against M. gallisepticum strain S6. In static time–killing studies with constant antibiotic concentrations [0–64 minimum inhibitory concentration (MIC)], M. gallisepticum colonies were quantified and kill rates were calculated to estimate the drug effect. The half-life of doxycycline in chicken was 6.51 ± 0.63 h. An in vitro dynamic model (the drug concentrations are fluctuant) was also established and two half-lives of 6.51 and 12 h were simulated. The samples were collected for drug concentration determination and viable counting of M. gallisepticum. In static time–killing studies, doxycycline produced a maximum antimycoplasmal effect of 5.62log10 (CFU/mL) reduction and the maximum kill rate was 0.11 h−1. In the in vitro dynamic model, doxycycline had a mycoplasmacidal activity in the two regimens, and the maximum antimycoplasmal effects were 4.1 and 4.75log10 (CFU/mL) reduction, respectively. Furthermore, the cumulative percentage of time over a 48-h period that the drug concentration exceeds the MIC (%T > MIC) was the pharmacokinetic–pharmacodynamic index that best correlated with antimicrobial efficacy (R2 = 0.986, compared with 0.897 for the peak level divided by the MIC and 0.953 for the area under the concentration–time curve over 48 h divided by the MIC). The estimated %T > MIC values for 0log10 (CFU/mL) reduction, 2log10 (CFU/mL) reduction and 3log10 (CFU/mL) reduction were 32.48, 45.68, and 54.36%, respectively, during 48 h treatment period of doxycycline. In conclusion, doxycycline shows excellent effectiveness and time-dependent characteristics against M. gallisepticum strain S6 in vitro. Additionally, these results will guide optimal dosing strategies of doxycycline in M. gallisepticum infection.
Highlights
Mycoplasma gallisepticum belongs to the class Mollicutes, order Mycoplasmatales, family Mycoplasmataceae which is characterized by lacking a cell wall (Athamna et al, 1997; Uilenberg et al, 2006)
Mitchell et al (2013b) have evaluated the antimicrobial activity against M. mycoides subspecies mycoides Small Colony in in vitro dilution PK/PD model. They have evaluated a series of antimicrobials activity in vitro, but in the in vitro model, the dilution was simulated by increasing volume
Whereas our dynamic model provided the continuous flow without increasing volume, and eliminated the agent through an outlet; Xiao et al (2015a,b) have studied the PK/PD relationship of valnemulin against M. gallisepticum by ex vivo model and in vivo model with the target species
Summary
Mycoplasma gallisepticum belongs to the class Mollicutes, order Mycoplasmatales, family Mycoplasmataceae which is characterized by lacking a cell wall (Athamna et al, 1997; Uilenberg et al, 2006). Similar to many other pathogenic mycoplasmas, this microorganism colonizes its host via the mucosal surface of the respiratory tract and the most paramount process to develop an infection is the adhesion of M. gallisepticum to its host target cell initially. M. gallisepticum colonizes the respiratory tract usually as a risk factor for subsequent systemic infection, such as salpingitis and arthritis (Winner et al, 2000; Nascimento et al, 2005). This infectious disease spreads vertically through infected eggs and horizontally by close contact, which result in worldwide prevalence of M. gallisepticum infection. Even though viable count estimation is complicated by strict nutritional conditions of M. gallisepticum cell, the CFU determination is an accurate measure for quantifying the number of M. gallisepticum clone, and resistant M. gallisepticum stains could be selected from the agar plate
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