Professor Acar presented results from five randomised, controlled trials that helped to differentiate the safety profile of levofloxacin with commonly used agents in respiratory tract infections. The comparators included ceftriaxone, cefuroxime axetil, clarithromycin and amoxicillin-clavulanic acid. The ADR rate for levofloxacin ranged from 5.8 to 22.7%. For the comparator agents, the risk of ADRs was higher, ranging from 8.5 to 39.3%.

Gastrointestinal symptoms occured in 1.7% of patients in the File study, compared to 4% for the ceftriaxone plus cefuroxime axetil group. The incidence of levofloxacin-associated diarrhoea was 1.4% versus 3.8% for the comparators.Greater tolerability of levofloxacin was confirmed by the Norrby study, with levofloxacin-associated diarrhoea occurring in 1.9% compared to 4.6% for ceftriaxone.

Levofloxacin (500 mg once daily) was also much better tolerated than clarithromycin (500 mg twice daily). Nausea was low for levofloxacin and diarrhoea much lower at 0.9% compared to 5.6% for clarithromycin. Taste perversion was a noted adverse event associated with clarithromycin at 12%, but was negligible in the levofloxacin arm.In another trial, levofloxacin-associated GI events were approximately half that of clarithromycin. Taste perversion was very low for levofloxacin, but high in the comparator arm.

Four of the studies also reported differences in CNS-related adverse events such as dizziness, insomnia, and headache. Rates for levofloxacin ranged from 0.6 to 6.7%, for ceftriaxone 1.3%, for clarithromycin 2.8 and 4.3%, and 0.3% for amoxicillin-clavulanic acid. These differences were not statistically significant.

The effect of various agents on the oral microflora showed the total numbers of streptococci were not affected by levofloxacin. Neisseria species were reduced and peptostreptococci were partly suppressed.Most importantly, there was no colonisation with resistant strains following levofloxacin therapy.

The effect of a seven-day course of 500 mg levofloxacin on the intestinal flora was compared to other agents. After the 4th day of levofloxacin treatment, Enterobacteriacae decreased, as was seen with ceftriaxone and ampicillin, but not with amoxicillin-clavulanic acid. Aerobic Gram-positive cocci and anaerobes were all similarly decreased.

However, ampicillin and amoxicillin-clavulanic acid selected for resistant strains of Enterococcus species. While ceftriaxone had a similar effect on the intestinal microflora compared to levofloxacin, it was adversely associated with the selection of resistant strains of Clostridium difficile and Candida species.

Microflora effects also favoured levofloxacin over macrolides and tetracyclines. While Enterobacter levels decreased more following levofloxacin treatment, the effect on aerobic Gram-positive cocci was similar among the agents. Clindamycin was shown to have a greater effect than levofloxacin on anaerobic microflora.

Clarithromycin was associated with resistant Enterococcus species, doxycycline to both Enterococcus and Candida species, and clindamycin to Clostridium difficile. There was no colonisation with levofloxacin giving it an important advantage over other agents.