Research articleImpact of early versus later fluoroquinolone treatment on the clinical; microbiological and resistance outcomes in a mouse-lung model of Pasteurella multocida infection
Introduction
The use of antimicrobial agents in veterinary medicine is regarded as a serious concern for the emergence of bacterial resistance (Aarestrup and Wegener, 1999, Phillips et al., 2004) and the antimicrobial treatments should not only aim at curing the diseased animals but also at limiting the resistance. To preserve individuals in situations at risk, a choice has to be made between two strategies: (i) an early collective treatment, also called control or metaphylaxis, in which all the animals of a group that are actually exposed to a pathogen are treated even if, at the time of treatment, only few animals show symptoms of infection or (ii) a later individual treatment in which only the animals of the group showing clinical symptoms of the disease are treated. The advantages and limitations of these two strategies need to be scientifically documented in a framework of risk–benefit analysis. The first strategy is challenged by the argument that the treatment of all the animals of a group is an overuse of antibiotics which is suspected to favour the emergence of resistant bacteria, especially in the digestive commensal flora. However, these collective treatments are launched very early after the start of the infection and consequently the bacterial load targeted by the antibiotic is supposedly lower than for the second strategy of the late treatment of animals with clinical symptoms. Therefore, the assessment of the impact of the bacterial load on the clinical and microbiological outcomes may be a key factor in making a decision between the two strategies. Indeed, previous studies have shown that the eradication of the targeted bacterial population needed lower concentrations of antibiotic (Mizunaga et al., 2005, Morrissey and George, 1999, Udekwu et al., 2009) and that the selection of resistant subpopulations of the pathogen was less frequent when a low bacterial inoculum was compared to a high inoculum (Ferran et al., 2007, Ferran et al., 2009, Kesteman et al., 2009).
In the present study, we assessed the impact of early versus late curative administration of marbofloxacin, a fluoroquinolone extensively used in veterinary medicine, on the survival of mice, the eradication of bacteria and the prevention of resistance during the natural course of a lung infection with Pasteurella multocida, a bacterium responsible for pneumonia in cattle and swine.
Section snippets
Bacteria and antibiotic
A strain of P. multocida isolated from the trachea of a pig with clinical symptoms of a bacterial lung infection was used as the test bacteria. Marbofloxacin, a third generation fluoroquinolone, was used as the test antibiotic.
MIC determination
The MICs were determined in triplicate according to the CLSI reference methods (CLSI, 2006).
Determination of the Mutant Prevention Concentration (MPC)
The MPC was determined as previously described (Blondeau et al., 2001). Briefly, an overnight culture of the test bacteria in Mueller Hinton broth (MHB) was concentrated 100 times
Susceptibility studies
The MIC and the MPC of marbofloxacin for P. multocida were 0.016 and 0.256 μg/mL respectively. The term “resistant bacteria” in the present paper should be understood as bacteria growing in the presence of 0.128 μg/mL marbofloxacin, the first dilution step below the MPC.
Pharmacokinetics
The observed (total) and the predicted (total) plasma concentrations of marbofloxacin following single intraperitoneal doses of 20 mg/kg in mice treated 10 (early administration) or 32 (late administration) hours after the
Discussion
In veterinary medicine, to preserve the health of a herd or a flock, collective antimicrobial treatments can be administered to all the animals after the observation of symptoms in only few animals of the group. This practice is referred to as metaphylaxis which corresponds to the administration of antibiotics to animals experiencing any level of bacterial disease before overt disease (Young, 1995). According to this definition, metaphylaxis is launched after (meta) the start of the infectious
Acknowledgements
We thank Sylvie Puel and Marlène Lacroix for performing analytical assays.
References (18)
- et al.
The effects of antibiotic usage in food animals on the development of antimicrobial resistance of importance for humans in Campylobacter and Escherichia coli
Microbes Infect.
(1999) - et al.
Comparative pharmacokinetics of marbofloxacin in healthy and Mannheimia haemolytica infected calves
Res. Vet. Sci.
(2007) - et al.
Mutant prevention concentrations of fluoroquinolones for clinical isolates of Streptococcus pneumoniae
Antimicrob. Agents Chemother.
(2001) Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically. Approved Standard, Document M7-A7
(2006)- et al.
Influence of inoculum size on the selection of resistant mutants of Escherichia coli in relation to mutant prevention concentrations of marbofloxacin
Antimicrob. Agents Chemother.
(2007) - et al.
Pharmacokinetic/pharmacodynamic analysis of the influence of inoculum size on the selection of resistance in Escherichia coli by a quinolone in a mouse thigh bacterial infection model
Antimicrob. Agents Chemother.
(2009) - et al.(1982)
- et al.
Human health hazards from antimicrobial-resistant Escherichia coli of animal origin
Clin. Infect. Dis.
(2009) - et al.
Application of a mathematical model to prevent in vivo amplification of antibiotic-resistant bacterial populations during therapy
J. Clin. Invest.
(2003)
Cited by (45)
Resistance to colistin: what is the fate for this antibiotic in pig production?
2016, International Journal of Antimicrobial AgentsCitation Excerpt :We consider that the major use of colistin in pig production worldwide is metaphylactically through the oral route [26,27,35], which involves treatment of clinically healthy animals belonging to the same pen as animals with clinical symptoms [73,74]. It has been demonstrated that treatment of an early infection with low pathogenic inoculum in an animal model (metaphylactically) with certain antibiotics (marbofloxacin, cefquinome) was able to fully cure an infection without any measurable amplification of intestinal Enterobacteriaceae resistance [74–76]. However, no study has shown this effect for CS that could justify the efficiency of CS metaphylactic use in pig production.
The origin of Pasteurella multocida impacts pathology and inflammation when assessed in a mouse model
2016, Research in Veterinary ScienceA Systematic Review of Bovine Respiratory Disease Diagnosis Focused on Diagnostic Confirmation, Early Detection, and Prediction of Unfavorable Outcomes in Feedlot Cattle
2015, Veterinary Clinics of North America - Food Animal PracticeMarbofloxacin Influence on Haemato-biochemical Alterations in Diarrheic Calves Infected with Salmonella spp
2023, Journal of Advanced Veterinary Research