Exposure to antibacterial agents with QT liability in 14 European countries: trends over an 8-year period

Abstract

Aims: (i) To classify antibacterial agents with QT liability on the basis of the available evidence, and (ii) to assess trends in their consumption over an 8-year period (1998-2005) in 14 European countries.

Methods: Current published evidence on QT liability of antibiotics was retrieved through MEDLINE search and joined to official warnings from regulatory agencies. Each drug was classified according to an already proposed algorithm based on the strength of evidence: from group A (any evidence) to group E (clinical reports of torsades de pointes and warnings on QT liability). Consumption data were provided by the European Surveillance of Antibacterial Consumption (ESAC) project and were expressed as defined daily doses per 1000 inhabitants per day (DID).

Results: Among 21 detected compounds, nine [six fluoroquinolones (FQs) and three macrolides (MACs)] belonged to group E. Use of group E drugs ranged from 1.3 (Sweden) to 4.1 DID (Italy) in 1998 and from 1.2 (Sweden) to 6.5 DID (Italy) in 2005. Significant exposure was observed in Italy and Spain (6.5 and 3.8 DID, respectively, in 2005). Only Denmark, Sweden and UK showed a slight decrease in use. Exposure to clarithromycin increased in 10 out of 14 countries, with a marked increment in Italy (3 DID in 2005).

Conclusions: Notwithstanding regulatory measures, in 2005 there was still significant exposure to antibacterials with strong evidence of QT liability and, in most countries, it was even increased. This warrants further investigation of appropriateness of use and suggests closer monitoring of group E drugs. Physicians should be aware when prescribing them to susceptible patients.

Figure 1

Consumption of antibacterial agents grouped by the strength of evidence on QT liability: comparison between 1998 and 2005 based on information available as of December 2007. Most countries showed an increase of population exposure both in terms of absolute value and as a fraction of overall antibacterial use. Countries were ranked by magnitude of total antibacterial consumption in 1998. Total consumption of antibacterials without evidence on QT-liability (□); Total consumption of antibacterials with QT-liability except for compounds listed in group E (); Group E, strongest level of evidence on QT-liability (▪). Percentage: antibacterial agents labeled as group E/total consumption of antibacterials. In parenthesis changes in use of group E compounds (absolute values); + = increment in consumption; − = decrease in consumption

Figure 2

Consumption of each antibacterial drug with documented QT liability country by country: comparison between 1998 and 2005 [abscissa: defined daily doses per 1000 inhabitants per day (DID)]. Antibacterial agents with DID ≤0.1 were not included. Relevant consumption (≥2 DID) of some compounds have been outlined. Mtd, metronidazole; Mox, moxifloxacin; Prx, prulifloxacin; Lvx, levofloxacin; Lmx, lomefloxacin; Gpx, grepafloxacin; Nox, norfloxacin; Cpx, ciprofloxacin; Ofx, ofloxacin; Clim, clindamycin; Try, telithromycin; Azy, azithromycin; Cly, clarithromycin; Joy, josamycin; Rxy, roxithromycin; Ery, erythromycin; Cox, cotrimoxazole. 2005 (▪); 1998 ()