Levofloxacin in eye drops: a case of lung damage

Cataract surgery is the most commonly performed medical surgical procedure in the EU states each year. Although it is an effective and safe procedure, an extremely serious complication that can occur following surgery is endophthalmitis. 

For this reason, it is common practice in cataract and vitreous body surgery to administer antibiotics prophylactically, in order to sterilise the surgical field pre-operatively. With this in mind, antibiotic ophthalmic solutions, such as quinolones, are routinely used. However, this class of antibiotics can cause significant side effects. 

Levofloxacin: a case of serious adverse reaction 

Levofloxacin is one of the third-generation quinolones (fluoroquinolones) used in ophthalmic surgery. Most of the adverse effects caused by levofloxacin ophthalmic solutions described in the literature are local reactions. Drug-induced lung damage due to quinolones is generally rare and only a few cases associated with tablet or injection administration have previously been reported. However, one studio described the first case of drug-induced lung damage due to the administration of levofloxacin eye drops. An outcome that, although rare, represents a serious adverse event. 

This was a 78-year-old man who, following the administration of levofloxacin eye drops as a perioperative prophylactic antibacterial agent for cataract surgery, developed pyrexia and dyspnoea, followed by respiratory failure. Drug-induced lung damage due to levofloxacin was diagnosed and symptoms improved after administration of corticosteroids and discontinuation of levofloxacin eye drops.

Lung damage induced by levofloxacin eye drops has been demonstrated through various evidences:

• negative test results for infections and autoimmune diseases;
• improvement after steroid administration and discontinuation of levofloxacin;
• positive results in drug-induced lymphocyte stimulation (DLST) with eye drops alone and levofloxacin injection, even during steroid administration. 

In previous reports of quinolone-induced lung damage, three out of five cases had a positive DLST. 

The patient in this study presented with severe respiratory failure and radiographic findings showed thickening of the bronchovascular bundles, pleural effusion and mild lymphadenopathy. Analysis of bronchoalveolar lavage fluid (BALF) revealed a higher number of lymphocytes than eosinophils. An increased serum total IgE level was also found. 

In addition to the pulmonary damage, based on the elevation of BNP (B-type natriuretic peptide) values and radiographic changes, it was assumed that concomitant diastolic heart failure also occurred in the patient.

Drug-induced lung damage: what possible mechanism?

The pathophysiological mechanism of drug-induced lung damage is mostly unknown, with the exception of a small number of molecules. Basically, it is believed that drugs can exert direct toxicity, act as a haptene or mimic an antigen and activate immune cells. 

Levofloxacin ophthalmic solution is absorbed into the systemic circulation by the nasal mucosa via the conjunctival blood vessels and nasolacrimal ducts after ocular administration, but its plasma concentration is extremely low compared to oral administration. One possibility of the mechanism acting in the patient considered in this study is that he was sensitised by an extremely small amount of levofloxacin in the systemic circulation, although the patient showed no local symptoms after ocular instillation. Underlying the adverse effect may therefore have been a delayed allergy due to cellular immunity.

Conclusions

The incidence of levofloxacin-induced lung damage is a rare occurrence compared to the frequency with which the drug is prescribed. However, one must be aware that, even in the form of eye drops, levofloxacin can be a source of important side effects, such as the drug-induced lung damage described in this patient. This observation is all the more important when one considers that safer and equally effective alternatives are available. For instance, fixed steroid/antibiotic combinations have several advantages over the use of single components, such as better compliance, lower costs and reduction of the potential wash-out effect.

One of the combinations available for the control of inflammation and bacterial infections after cataract surgery is that of dexamethasone/netilmicin.

The use of dexamethasone after cataract surgery is now well-established and the added value of this combination lies in the presence of netilmycin, a broad-spectrum antibiotic that also covers methicillin-resistant strains, ensuring complete sterilisation of the ocular surface in the immediate post-operative period, with negligible toxicity.

1. Hosogaya N, Toida K, Ishihara H, Kugiyama K. A case of drug induced lung injury caused by levofloxacin eye drops. Respir Med Case Rep. 2018 Mar 16;24:12-15. 
2. Caporossi A, Alessio G, Fasce F, Marchini G, Rapisarda A, Papa V. Short-Term Use of Dexamethasone/Netilmicin Fixed Combination in Controlling Ocular Inflammation After Uncomplicated Cataract Surgery. Clin Ophthalmol. 2021 Jun 30;15:2847-2854.