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This therapeutic drug monitoring (TDM) grand round describes a patient with serious valproic acid intoxication. A total valproic acid level of 844 mg/L and an unbound valproic acid level of 604 mg/L were observed. Meropenem was administered to enhance the clearance of valproic acid. This off-label usage of meropenem is based on the drug–drug interaction between carbapenems and valproic acid, which reduced the level of valproic acid within 24 hours after administration.

AbstractObjective:To reduce the use of amoxicillin-clavulanate after high-resistance rates in Escherichia coliwere detected.Design:Intervention study; the interventions were introduced successively over a 4-year period while closely monitoring the resistance patterns.Setting:A 260-bed acute-care hospital in Switzerland.Interventions:Introduction of therapeutic guidelines for specific departments or indications, which proposed alternative antibiotics to amoxicillin-clavulanate. The perioperative prophylactic use of amoxicillin-clavulanate was eliminated completely.Results:The absolute amount of amoxicillin-clavulanate consumed decreased by 23%, from 24.8 g per 100 patient days in 1992 to 18.5 g per 100 patient days in 1995. The number of courses, a parameter that takes the prophylactic use into account, decreased by 62% from 2.3 per 100 patient days in 1992 to 0.9 per 100 patient days in 1995. The percentage of sensitive strains increased from 54.9% (n=512) in 1992 and 54.0% (n=506) in 1993 to 72.1% (n=546) in 1994 and 83.1% (n=668) in 1995. No major changes were detected for other antimicrobials, such as cotrimoxazole, tetracycline, or cefuroxime, used in this 4-year period.Conclusions:A decrease in the use of amoxicillin-clavulanate was followed by an increase in susceptibility of E colito it. It was not possible to prove a causative relationship. Only a temporal association was discovered. The reduction of the use of amoxicillin-clavulanate was achieved through the implementation of treatment guidelines, facilitated through a close collaboration among the clinical pharmacists, the infection control practitioner, the microbiology laboratory, and the physicians in charge of the respective departments.

OBJECTIVE: To report two cases of anaphylactic reactions to proton-pump inhibitors (PPIs).CASE SUMMARIES: A 54-year-old woman who had taken omeprazole in the past was treated with omeprazole 40 mg and developed periorbital edema, edema of the skin, pruritus, nausea, and vomiting about 45 minutes after taking one capsule. Five months later, she was treated with lansoprazole 30-mg capsules. Again, within 45 minutes she developed an even more serious reaction, with pruritus and urticaria on her whole body, increased sweating, facial edema, and loss of consciousness. A 61-year-old man took one tablet of pantoprazole 40 mg one year after first being treated with the drug. Within hours after ingestion, he developed malaise, generalized pruritus and urticaria, a swollen tongue and eyes, and diffuse sweating; his blood pressure decreased to 75/50 mm Hg.DISCUSSION: Because of the acute onset of symptoms and close temporal association with exposure to the drug, as well as previous exposure to it, the reactions can be classified as anaphylactic shock to PPIs. These benzimidazole derivatives are chemically related; observations in a few patients, such as the first case above, suggest that cross-sensitivity may occur. The Uppsala Monitoring Centre (UMC) has received a total of 42 reports of anaphylactic reactions or anaphylactic shock in association with PPIs. These reports account for 0.2% of the total of reported suspected adverse drug reactions to PPIs, compared with 0.8% anaphylactic reactions in the UMC database as a whole.CONCLUSIONS: These findings suggest that the chemically related PPIs can, as a group, cause anaphylactic reactions; however, the rate is comparatively low. Since anaphylaxis is a potentially serious reaction, more precise information is needed regarding its frequency, and healthcare professionals need to be aware of this possibility when prescribing these agents.