Pefloxacin - Antibiotic Misuse and Bacterial Resistance

Antibiotic Misuse and Bacterial Resistance

See also: Antibiotic misuse and Antibiotic resistance

Resistance to pefloxacin and other fluoroquinolones may 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 the fluoroquinolones, in particular over in Europe, has been implicated. The ever increasing bacterial resistance to pefloxacin, (which is a major concern) together with an unacceptable safety profile, may very well threaten its future viability to treat serious and life threatening bacterial infections. Years ago the FDA had added warnings regarding the proper use of the fluoroquinolones drugs within the package inserts to combat such scripting abuse. Advising physicians that fluoroquinolones: "...should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria..."(See the monographs for this class)

Normally pefloxacin should only be used in patients who have failed at least one prior therapy. Reserved for the use in patients who are seriously ill and may soon require immediate hospitalization. Though considered to be a very important and necessary drug required to treat severe and life threatening bacterial infections, the associated scripting abuse of pefloxacin remains unchecked, which has contributed to the problem of bacterial resistance. The overuse of antibiotics such as happens with children suffering from otitis media has given rise to a breed of super bacteria which are resistant to antibiotics entirely.

For example the use of the fuoroquinolones 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.

Within a recent study concerning the proper use of this class in the emergency room it was revealed that 99% of these prescriptions were in error. Out of the one hundred total patients studied, eighty one received a fluoroquinolone for an inappropriate indication. Out of these cases, forty three (53%) were judged to be inappropriate because another agent was considered first line, twenty seven (33%) because there was no evidence of a bacterial infection to begin with (based on the documented evaluation), and eleven (14%) because of the need for such therapy was questionable. Out of the nineteen patients who received a fluoroquinolone for an appropriate indication, only one patient out of one hundred received both the correct dose and duration of therapy.

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 regulatory agencies, such as acute bronchitis, otitis media, and acute upper respiratory tract infection, according to a study that was supported in part by the Agency for Healthcare Research and Quality. Additionally they are commonly prescribed for medical conditions that are not even bacterial to begin, with such as viral infections, or those to which no proven benefit exist.

There are three known mechanisms of resistance. 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 drug's effectiveness.