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New and old drugs help in preventing endophthalmitis
A fourth generation of fluoroquinolones might allow surgeons to reduce prophylaxis to topical-only treatment.
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NAPLES – Careful prophylaxis with established drugs — and possibly with agents now in the pipeline — may be a surgeon’s best defense against endophthalmitis. Forthcoming fluoroquinolone drugs hold promise to simplify prophylactic regimens, according to presentations here at Rome 2002.
Postoperative endophthalmitis is rare, but it is the most feared postop complication of cataract surgery. The ophthalmic literature shows that most cases are a consequence of cataract surgery, and incidence varies from 0.07% to 0.21%, according to Vincenzo Orfeo, MD. This variability is mostly related to the type of prophylaxis used, he said.
Dr. Orfeo stressed the importance of taking into account all possible risk factors and addressing them with appropriate safety measures.
“A sterile environment, correct surgical maneuvers and attention to all details concerning prevention of bacterial transmission from the surgeon and everybody else in the operating room are essential,” he said.
However, because the causative organisms of endophthalmitis have been found to be in most cases genetically identical to the patients’ own flora, the most attention must be given to the patients’ own sources of infection.
“An accurate preoperative examination of the eyelids, eyelashes and conjunctiva is crucial, because it’s there that most of the infectious agents are hiding. Prevention of endophthalmitis is mainly a matter of reducing with effective prophylactic methods the bacterial flora on and around the eye,” Dr. Orfeo said.
Methods of prevention
Dr. Orfeo described the difference made by a change in prophylactic regimen at his clinic. At the Mediterranean Clinic, located here, from 1997 through 2001, 7,800 cataract cases were treated with phacoemulsification, he said.
“From 1997 to 1999, the protocol for the prevention of postoperative endophthalmitis entailed disinfection of the palpebral and periorbital skin with 10% povidone iodine solution, systemic antibiotic therapy for 5 days and instillation of tobramycin and dexamethazone drops for 15 days. In this situation, we had five cases of endophthalmitis in 4,500 patients, which amounted to 0.11%,” said Dr. Orfeo, director of the clinic’s department of ophthalmology.
From January 2000 to December 2001, a different protocol was adopted.
“We still did a thorough disinfection of the periorbital area, but also instilled 5% povidone-iodine in the conjunctival sac at the beginning and at the end of surgery,” Dr. Orfeo said.
As he explained, this was done to prolong the action of this antimicrobial agent for a further 12 to 24 hours.
“We also injected vancomycin at a dose of 1 mg in 0.2 mL into the anterior chamber, just after IOL implantation and aspiration of residual viscoelastic. This topical antibiotic has an effect for 2 hours, which is useful in the very early postop period,” he said.
Topical antibiotic and corticosteroid therapy was maintained, and levofloxacin 500 mg was administered systemically for 4 days.
“This new prophylaxis proved effective in cutting down the rate of endophthalmitis to 0.009%. We had only one case in 3,300” with the altered regimen, he said.
Best antibiotics
The role of antibiotics, especially fluoroquinolones, in preventing endophthalmitis was central in the presentation of Harold R. Katz, MD, an assistant professor at Johns Hopkins University.
According to Dr. Katz, fluoroquinolones are a good choice because they are broad spectrum, act rapidly, have minimal toxicity and resistance is low.
Among the fluoroquinolones currently available, which include ciprofloxacin, ofloxacin, norfloxacin and levofloxacin, Dr. Katz said he prefers ciprofloxacin due to its potency against bacteria that cause endophthalmitis and because it kills bacteria rapidly.
His own in vivo studies on human eyes confirmed that, compared to ofloxacin, ciprofloxacin was able to eradicate more organisms in the first 15 minutes and to achieve a statistically significantly higher eradication of organisms at all the time points examined.
“Therefore, the ideal combination to reduce ocular surface flora is, at present, instillation of ciprofloxacin 0.3% before and after surgery and instillation of 5% povidone-iodine into the conjunctival sac,” he said.
Another point covered by Dr. Katz was the inability of recently available topical antibiotics to penetrate the anterior chamber.
“Many people are under the misconception that the application of an antibiotic drop can achieve therapeutic levels inside the eye, but this is not true,” he said.
New generation
Dr. Katz explained that in order for fluoroquinolone antibiotics to be effective, the maximum concentration of the antibiotic should be about 10 times the minimum inhibitory concentration (MIC) of the organism causing or potentially causing an infection. Also, there needs to be a sustained therapeutic concentration of antibiotic over time.
“There is no study indicating in any way that this concentration can be achieved with the currently available fluoroquinolones,” he said.
However, a fourth generation of quinolones is in the pipeline, and the new antibiotics gatifloxacin and moxifloxacin are undergoing clinical trials.
“I have been involved in clinical studies with both antibiotics, and they both have a number of advantages compared to what is currently available,” he said.
First, they are more potent against gram-positive organisms and against anaerobes and are effective against organisms that are already resistant to other available fluoroquinolone.
They are also extremely soluble, with good tissue penetration, Dr. Katz said.
“There is evidence that they might actually penetrate at therapeutic levels into intraocular tissue, maybe even into the anterior chamber. This is a great step forward, because topical prophylaxis alone could become the only necessary step to reduce ocular surface flora and achieve a therapeutic intraocular level of antibiotics,” he said.
For Your Information:
- Vincenzo Orfeo, MD, can be reached at Clinica Mediterranea, Via Orazio 2, Naples 80122, Italy; +(39) 081-725-9206; fax: +(39) 081-546-3151; e-mail: vincenzorfeo@tin.it. Dr. Orfeo has no direct financial interest in the products mentioned in this article, nor is he a paid consultant for any companies mentioned.
- Harold R. Katz, MD, can be reached at Sinai Hospital of Baltimore, 2411 Belvedere Ave., Baltimore, MD 21215 U.S.A.; +(1) 410-601-5991; fax: +(1) 410-601-6284; e-mail: hal1999@aol.com. Dr. Katz is a paid consultant for Alcon.