[Gyrase inhibitors, a new class of therapeutic drugs]

Abstract

Fluorinated inhibitors of gyrase open a new field in chemotherapy. For veterinary purposes one drug, enrofloxacin (Baytril), has been registered hitherto in Germany. Well known disadvantages of the old gyrase blockers (e.g. nalidixic acid and others) have been their limited clinical application (compounds were useful only for therapy of infections of kidney cavities) and their deficits in antimicrobial efficacy regarding Gram-positive bacteria, pseudomonas and mycoplasmas. Fluorinated 4-quinolones, however, exhibit broad antibiotic effects in addition to their useful pharmacokinetic properties. The compounds are indicated in therapy of infections by E. coli, Salmonella, Pasteurella, Mycoplasma and Haemophilus species as well as against CRD (chronic respiratory disease). Development of resistance is markedly slowed down compared with nalidixic acid due to a multi-step resistance. Resistance is unstable and may revert in bacteria. Nevertheless, resistant bacteria in the veterinary field are exceptions. Cross-resistance includes only compounds belonging to 4-quinolones. Adult animals show few side effects to gyrase blockers. In young animals a deficit in biotransformation and renal clearance has been observed. Most prominent are dose dependent irreparable deformations of joint cartilages which have forced to contraindicate the use of Baytril in growing dogs.