Antibacterial and mutagenic activity of inhaled bronchodilators on the respiratory pathogen Haemophilus influenzae

The U.K. prevalence of non-beta-lactamase-mediated resistance to ampicillin among Haemophilus influenzae reached 4% in 1986. The majority (70%) of isolates of this type come from sputa of patients with chronic obstructive airways disease. This study investigated whether bronchodilator drugs delivered directly to the respiratory tract have any antibacterial activity and/or play a role in promoting selection of organisms with this type of resistance. Antibacterial activity was detected in two out of six pharmaceutical preparations for nebulization examination but was entirely attributable to the preservative (benzalkonium chloride) in them. Exposure of ampicillin-susceptible H. influenzae (minimum inhibitory concentration 0.25 mg l-1) to concentrations of salbutamol, fenoterol and beclomethasone theoretically attainable in vivo resulted, after 48 h, in isolation of colonies with reduced susceptibility to ampicillin (minimum inhibitory concentration 1-4 mg l-1) but reversion to beta-lactam susceptibility occurred following serial subculture on chocolate agar. Organisms with stable reduced susceptibility to ampicillin were obtained when exposure to one of these three bronchodilators in broth was followed by serial subculture on agar containing the same preparations at equivalent concentrations and when the period of exposure to salbutamol at 100 mg l-1 in broth was extended to 5 days. The occurrence of these phenomena in vivo might be contributing to failures in treatment of exacerbations with ampicillin and to an increasing prevalence of beta-lactamase-negative, ampicillin-resistant H. influenzae.