Quinolone Antibiotics - Antibiotic Misuse and Bacterial Resistances

Antibiotic Misuse and Bacterial Resistances

Resistance to quinolones can evolve rapidly, even during a course of treatment. Numerous pathogens, including Staphylococcus aureus, enterococci, and Streptococcus pyogenes now exhibit resistance worldwide. Widespread veterinary usage of quinolones, in particular in Europe, has been implicated.

Fluoroquinolones have been recommended to be reserved for the use in patients who are seriously ill and may soon require immediate hospitalization. Though considered to be very important and necessary drugs required to treat severe and life-threatening bacterial infections, the associated antibiotic misuse remains unchecked, which has contributed to the problem of bacterial resistance. The overuse of antibiotics such as happens with children suffering from otitis media (ear infections) has given rise to a breed of super bacteria that are resistant to antibiotics entirely.

For example, the use of the fluoroquinolones had increased threefold in an emergency room environment in the United States between 1995 and 2002, while the use of safer alternatives, such as macrolides, declined significantly. Fluoroquinolones had become the most commonly prescribed class of antibiotics to adults in 2002. Nearly half (42%) of these prescriptions were for conditions not approved by the FDA, such as acute bronchitis, otitis media, and acute upper respiratory tract infection, according to a study supported in part by the Agency for Healthcare Research and Quality. In addition, they are commonly prescribed for medical conditions, such as acute respiratory illness, that are usually caused by viral infections.

Within a recent study concerning the proper use of this class in the emergency rooms of two academic hospitals, 99% of these prescriptions were revealed to be in error. Out of the 100 total patients studied, 81 received a fluoroquinolone for an inappropriate indication. Out of these cases, 43 (53%) were judged to be inappropriate because another agent was considered first line, 27 (33%) because there was no evidence of a bacterial infection to begin with (based on the documented evaluation), and 11 (14%) because of the need for such therapy was questionable. Of the 19 patients who received a fluoroquinolone for an appropriate indication, only one patient of 100 received both the correct dose and duration of therapy.

Three mechanisms of resistance are known. Some types of efflux pumps can act to decrease intracellular quinolone concentration. In Gram-negative bacteria, plasmid-mediated resistance genes produce proteins that can bind to DNA gyrase, protecting it from the action of quinolones. Finally, mutations at key sites in DNA gyrase or topoisomerase IV can decrease their binding affinity to quinolones, decreasing the drugs' effectiveness.