Fluoroquinolone-associated anaphylaxis in spontaneous adverse drug reaction reports in Germany: differences in reporting rates between individual fluoroquinolones and occurrence after first-ever use.

BACKGROUND: The frequency of fluoroquinolone-associated anaphylaxis has been estimated to be 1.8-23 per 10 million days of treatment based on spontaneous reports. It is unknown whether there are differences between the reporting rates of anaphylaxis with individual fluoroquinolones. According to pathophysiology, anaphylaxis may be immune mediated (anaphylactic) or not (anaphylactoid). The latter may occur after first-ever intake since no sensitisation phase is necessary. OBJECTIVE: To analyse spontaneous reports of fluoroquinolone-associated anaphylaxis contained in the spontaneous adverse drug reaction database of the Federal Institute for Drugs and Medical Devices in Germany with regard to differences in reporting rates between various fluoroquinolones, the previous intake and the time to onset of the reaction. METHODS: All fluoroquinolone-associated cases of anaphylaxis, anaphylactic shock, and anaphylactic/anaphylactoid reaction spontaneously reported to the Federal Institute for Drugs and Medical Devices between 1 January 1993 and 31 December 2004 were identified and assessed with regard to the correctness of the diagnosis of anaphylaxis, the causal relationship with the drug, the previous intake of fluoroquinolones and the time to onset of the reaction. RESULTS: In 166 of 204 cases identified, the diagnosis of anaphylaxis and a causal relationship with the drug were considered at least possible. Moxifloxacin, levofloxacin, ciprofloxacin and ofloxacin accounted for 90 (54%), 25 (15%), 21 (13%) and 16 (10%) of the 166 cases, respectively. The corresponding reporting rates per 1 million defined daily doses based on crude estimates of exposure were 3.3, 0.6, 0.2 and 0.2 for moxifloxacin, levofloxacin, ciprofloxacin and ofloxacin, respectively. The occurrence of anaphylaxis after the first dose or within the first three days was reported in 71 of 166 (43%) cases, but no information on prior exposure with this or any other fluoroquinolone was provided with these reports. In 21 of 166 (13%) cases, the reaction occurred within the first 3 days and it was stated that the particular fluoroquinolone had never been taken before. CONCLUSIONS: Anaphylaxis appears to be associated with the fluoroquinolone class of antibacterials. Observed differences in reporting rates should be further investigated. Fluoroquinolone-associated anaphylaxis may occur after first-ever intake of the agent.

Pharmacological indices in antibiotic therapy.

After 60 years of antibiotic treatment, attempts to rationalize it have culminated in the use of pharmacological indices. These indices facilitate comparison of the activity of different antibiotics and serve as a sound basis for antibiotic dosing. Pharmacokinetic parameters (e.g. AUC, Cmax) and pharmacodynamic parameters (mostly MIC) are used for this purpose. For the so-called concentration-dependent antibiotics, the pharmacological indices AUC/MIC and Cmax/MIC are used, whereas for time-dependent antibiotics, the pharmacological index T>MIC is used. Some authors believe that the index AUC/MIC can be used as a universal index, but, not all experts accept this generalization. As the various pharmacological indices have been defined inconsistently in the literature, the International Society for Anti-Infective Pharmacology (ISAP) has published a paper on the terminology of pharmacokinetic and pharmacodynamic parameters and the pharmacological indices. This paper will help to ensure uniform use of terminology. In addition, we point out that the use of pharmacological indices should consider the differences in pharmacokinetics (patient characteristics and localization of the infection) and the differences in pharmacodynamics of antibiotics (beyond MICs) with different pathogens (e.g. Gram-positive and Gram-negative).