Fluoroquinolone Efficacy? How effective are the old antibiotics compared with the new fourth-generation fluoroquinolones? By Thomas John, MD
				Interest in topical antibiotics will endure because ophthalmologists frequently observe patients with ocular infections in their practice.1,2 Because patients with a red eye secondary to an ocular infection visit a variety of “frontline” physicians for their initial treatment, they receive different ocular antibiotics, both old and new, for treatment. These antibiotics may range from trimethoprim/sulfamethoxazole, or other antibiotics as prescribed by an ER physician, to fourth-generation fluoroquinolones, such as moxifloxacin or gatifloxacin, as prescribed by an ophthalmologist or a corneal specialist. A family-practice physician, internist, or pediatrician may use other antibiotics, including erythromycin, tobramycin, or ciprofloxacin. Currently, there is no published study that compares the efficacy of the old to that of the new antibiotics. Thus, my colleagues (A.W. Dvorak, MD; J. Clark, MD; and J. Lyzak, MD) and I conducted a study (without any corporate support) to attempt to answer the question: are the old ophthalmic antibiotics still effective against infectious micro-organisms compared with the new, fourth-generation fluoroquinolones? CLINICAL INVESTIGATION In this study, my co-investigators and I used the E-test method to determine the minimum inhibitory concentrations of vancomycin, gentamicin, tobramycin, ceftriaxone, erythromycin, trimethoprim/sulfamethoxazole, trovafloxacin, moxifloxacin, gatifloxacin, levofloxacin, ciprofloxacin, and ofloxacin for ocular isolates of the most common bacterial causes of conjunctivitis and keratitis. We used ocular isolates of Staphylococcus aureus (n=10), Staphylococcus epidermidis (n=11), Streptococcus pneumoniae (n=10), Streptococcus viridans group (n=11), Enterococcus species (n=9), Bacillus species (n=11), Pseudomonas aeruginosa (n=9), Serratia marcescens (n=11), and Haemophilus influenza (n=8). SURPRISING FINDINGS We were surprised to discover that, when treating gram-negative and gram-positive organisms separately, old antibiotics such as gentamicin and vancomycin performed better than new fourth-generation fluoroquinolones such as moxifloxacin or gatifloxacin. Both gram-positive and gram-negative organisms cause ocular bacterial infections. Yet, gram-positive organisms outnumber gram-negatives when considering eye infections from the front to the back of the eye—namely, blepharitis, conjunctivitis, keratitis, and ulceration, as well as endophthalmitis. Because gram-positive organisms exist in high numbers and represent the majority of infection-causing organisms, ophthalmologists certainly need an antibiotic that has excellent coverage against those organisms. When we compared gram-positive infections, one of the old antibiotics, vancomycin, outperformed the fourth-generation fluoroquinolones moxifloxacin and gatifloxacin. Vancomycin had 97% coverage versus moxifloxacin’s 89% and gatifloxacin’s 90%. We cannot, however, ignore the smaller group of gram-negative organisms that invade the eye, because those such as P. aeruginosa can perforate the cornea within 72 hours if not appropriately managed. Here, too, gentamicin out-performed moxifloxacin and gatifloxacin. Gentamicin displayed 100% coverage versus 86% with moxifloxacin and 89% with gatifloxacin. Although older antibiotics, namely gentamicin and vancomycin, are limited in systemic treatment due to such toxicity as nephrotoxicity and ototoxicity when it comes to the eye, these systemic toxicity factors are removed from the equation because very little systemic absorption of these medications takes place after the topical application of these eye drops. In the absence of any serious systemic side effects, and because of the effectiveness of these old antibiotics for gram-positive and gram-negative organisms, these old antibiotics can be used for the effective treatment of ocular infections. RESISTANCE When my colleagues and I examined resistance to S. aureus, we observed a 40% resistance for every fluoroquinolone tested, including moxifloxacin and gatifloxacin. P. aeruginosa was the next most resistant species, with resistance to moxifloxacin and ofloxacin reaching 33%. Considering the prevalence of staphylococcal and pseudomonal resistance to the fourth-generation fluoroquinolones, one might question the wisdom of their use as monotherapy, especially in serious sight-threatening corneal infections. Additionally, an increased incidence of corneal perforation after fluoroquinolone use for the treatment of bacterial keratitis has been reported.3 An ophthalmologist who initiates monotherapy with these medications has to follow cases very closely; if the ocular infection does not improve or it deteriorates, then he must try a combination therapy or change the antibiotics as needed based upon the patient’s clinical response to the treatment and the sensitivity results of the cultured organisms. IN CONCLUSION Although the fourth-generation fluoroquinolones afford ease of use as monotherapy and provide a broad spectrum of antimicrobial coverage, this study showed that the old antibiotics, vancomycin and gentamicin, outperformed the new ones, including the fourth-generation fluoroquinolones, against gram-positive and gram-negative organisms isolated from eye infections. Hence, properly chosen old antibiotics covering both gram-positive and gram-negative organisms can be safely used for the effective management of ocular infections. As with any eye infections, the clinician should be vigilant for deterioration in the clinical condition, should rely largely on the clinical response to treatment, and should be ready to use alternative medication whenever it is warranted.  Thomas John, MD, is Clinical Associate Professor at Loyola University at Chicago in Maywood, Illinois, and has offices in Tinley Park and Oak Lawn, Illinois, and in Merrillville, Indiana. He states that he holds no financial interest in any of the products mentioned herein. Dr. John may be reached at (708) 429-2223 and (219) 769-3555; cornea999@aol.com. 1. Mah FS. New antibiotics for bacterial infections. Ophthalmol Clin North Am. 2003;16:11-27. 2. Benson WH, Lanier JD. Current diagnosis and treatment of corneal ulcers. Curr Opin Ophthalmol. 1998;9:45-49. 3. Mallari P, McCarty DJ, Daniel M, Taylor H. Increased incidence of corneal perforation after topical fluoroquinolone treatment for microbial keratitis. Am J Ophthalmol. 2001;13:131-133.
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