Reactions Weekly | 2021
Amoxicillin/clavulanic-acid and clarithromycin
Abstract
Antibiomania following interaction: case report A 50-year-old man developed antibiomania following drug-drug pharmacodynamic interaction between amoxicillin/clavulanicacid and clarithromycin for pneumonia [routes not stated]. This case had been reported to the national pharmacovigilance center of Switzerland. The man was diagnosed with left basal pneumonia, and subsequently started receiving amoxicillin/clavulanic-acid [Augmentin; a β-lactamase inhibitor antibiotic therapy] 1g thrice daily. However, he returned to the hospital the day after due to persistent respiratory symptoms. Therefore, the treatment was switched to clarithromycin (a macrolide antibiotic) 500mg twice daily. Two days after initiation of clarithromycin, a progressive change in his behavior was noted by the family members, charectorised by unusual logorrhoea, irritability, increased physical activity, elevated mood and ideas of being in contact with God. Thus, he was admitted to the hospital and transferred to the emergency department (ED). He had no known allergies, no tobacco, alcohol and illicit substance use. At the first psychiatric evaluation, he reported that he had experienced a feeling of dying and developed auditory hallucinations during the same the night when the first antibiotic (amoxicillin/clavulanic-acid) was initiated. The psychiatric examination revealed a familiar attitude, a lightly increased psychomotor activity, irritability, logorrhoea, elevated mood, difficulty falling asleep, as well as auditory hallucinations and mystic mood-congruent delusions. The man’s treatment with clarithromycin was therefore immediately stopped, and he was treated received lorazepam for psychomotor agitation along with psychopharmacotherapy. Moreover, 12h after clarithromycin cessation, amelioration was rapidly observed with the progressively gained insight of delusions and cessation of auditory hallucinations. These symptoms lasted in total about 36h. The Young Mania Rating Scale (YMRS) score was 28, indicating a manic episode. He remained hospitalised for one night. Thereafter, a diminution of other manic symptoms was observed expect logorrhoea. The YMRS score was found to be 13, equivalent of hypomanic symptomatology. He was then discharged with two tablets of lorazepam and consulted for a psychiatric evaluation a week later. Given the clinical presentation, the diagnosis of clarithromycin-induced manic episode was suspected. The Naranjo algorithm score of 5, was indicative of a probable causal relation between clarithromycin and manic episode. The man’s therapy with amoxicillin/clavulanic-acid was reintroduced at 625mg twice daily for the pneumonia. One week later, at the psychiatric follow-up evaluation, he presented the subjective impression of a mildly elevated mood and talkativeness and an YMRS score of 3, the equivalent of a euthymic state. He reported a worsening of the psychiatric symptomatology the evening after the reintroduction of amoxicillin/clavulanic-acid. As he left the hospital, he received two doses of amoxicillin/clavulanic-acid as prescribed. At the midnight, he started hearing voices again, felt persecuted, anxious and was again partially nosognosic. The next day, he presented symptoms similar to the first manic episode, with logorrhoea, difficulties sleeping, familiar attitude, and dysphoria. He received two tablets of lorazepam. Consequently, amoxicillin/clavulanic-acid was stopped, as it was suspected that the manic episode was related to the antibiotic, consistent with antibiomania. It was concluded that a pharmacodynamic drug-drug interaction between clarithromycin and amoxicillin/clavulanic-acid (because of the common mechanism of increasing neuron excitability) might have occurred, leading to antibiomania [final outcome of the reaction not stated].