Benzalkonium Chloride Resistance in Staphylococcus epidermidis on the Ocular Surface of Glaucoma Patients Under Long-Term Administration of Eye Drops

Purpose: We previously reported the presence of multidrug-resistant staphylococci on the ocular surface of glaucoma patients using prostaglandin analog drops for more than 1 year. Here, we investigated the effect of benzalkonium chloride (BAC) on these multidrug-resistant staphylococci.

Methods: Staphylococcus epidermidis was isolated from the conjunctival sacs of 32 eyes of 32 patients comprised of 13 eyes treated with 0.005% latanoprost (Xalatan; Xa group) and 19 eyes treated with 0.004% travoprost (Travatan Z; Tz group). The minimum inhibitory concentrations (MICs) of prostaglandin analogs and BAC were measured. The presence of efflux pump genes was analyzed using polymerase chain reaction.

Results: No difference was found in the MIC values of prostaglandin analogs. In contrast, the MIC values of BAC were significantly higher for the isolates from the Xa group than for those from the Tz group (2.02 vs. 1.02 µg/mL; P = 0.001). One proton-motive efflux gene, qacC/smr, was detected more frequently in the Xa isolates than in the Tz isolates (P < 0.001). The prevalence of methicillin resistance was correlated with the presence of qacC/smr (P = 0.010), and the MIC of BAC was significantly correlated with the detection of qacA/B and qacC/smr sequences (P = 0.03 and P < 0.001, respectively).

Conclusions: The long-term use of eye drops containing BAC might select BAC-resistant S. epidermidis harboring qacC/smr.

Translational relevance: These findings suggest that the long-term use of eye drops containing BAC might be inappropriate in terms of avoiding antimicrobial resistance.