1. The safety in everyday clinical usage of three
4-quinolone antibiotics, (
ciprofloxacin,
norfloxacin and
ofloxacin), was compared with similar data for
azithromycin and
cefixime, each agent being examined by Prescription-Event Monitoring (PEM) during the early post-marketing period. 2. In PEM the exposure data are derived from general practitioner prescriptions confidentially provided by the Prescription Pricing Authority. Outcome data are provided by questionnaires (green forms) on which the prescribing medical practitioner records event data. When necessary, further information is obtained from a number of sources which include follow-up of all pregnancies and the patients' life-time medical record. 3. The main outcome measures were demographic information, including the patient's date of birth and sex; the indication for prescribing the
drug being monitored; the reason for stopping treatment; the start and stop dates of treatment and the events recorded during and
after treatment. 4. The final cohort for each of the five
antibiotics exceeded 11000 patients. The only event significantly related to the use of all five
antibiotics was
nausea/
vomiting. This was also the most frequent adverse event causing treatment to be discontinued with
norfloxacin,
ofloxacin and
azithromycin (relevant information was not requested in the studies of
ciprofloxacin and
cefixime). Vaginal
candidiasis was significantly more frequently associated with the use of the three
4-quinolones than with
azithromycin and
cefixime but it was frequently delayed until the week or two after the cessation of
therapy. Within each event, as recorded in these studies, the highest event rates (the number of events per 1000 patients) in the week following the start of
therapy were: 9.2 for diarrhoea with
cefixime; 4.9 for
nausea/
vomiting with
ofloxacin; 2.4 for
rash with
azithromycin; 2.2 for
abdominal pain with
norfloxacin; 1.5 for
headache/migraine with
ofloxacin; 1.4 for malaise/
lassitude with
ofloxacin; 1.2 for
dizziness with
norfloxacin. Uncommon events (reported in less than 1:1000 patients) included rare cases of allergic phenomena, convulsions and
pseudomembranous colitis. There were no reports of
tendinitis,
tenosynovitis or tendon
rupture in children but tendon disorders were reported in the two months following the start of treatment in 20 adults. A total of 307 pregnancies were reported. Thirty-eight of the 55 women who received these drugs during the first trimester of pregnancy gave birth to healthy babies. No
congenital abnormalities were reported. Apart from one case of unconfirmed
pseudomembranous colitis, none of the other 2468 deaths that occurred in these studies was attributed to the
antibiotics. 5. These five
antibiotics are acceptably safe
antimicrobial agents when used in general medical practice. PEM is an effective method for monitoring the safety of recently introduced
antimicrobial agents.