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Clinical Update: Pediatrics
Kids and Conjunctivitis: When to Treat, What to Use
By Gurney Williams III, Contributing Writer
 
 

Here’s a switch on an old joke about the common cold. If you don’t treat conjunctivitis, the infection will last a week. If you do treat it, it will last seven days.

Ophthalmologists still tell that one, according to Sherwin J. Isenberg, MD, professor of ophthalmology and pediatrics and vice chairman of ophthalmology at the University of California, Los Angeles. But "studies show it’s not true," he said. "Antibiotics do speed up the healing of a normally self-limited bacterial infection, with usual resolution in one to five days."

Antimicrobials: big and bigger. The studies of a comparatively new and more expensive generation of fluoroquinolones—moxifloxacin (Vigamox) and gatifloxacin (Zymar)—show that these drugs are even more potent than their predecessors in an already strong class of topical antibiotics. And they allay some of the concerns about growing bacterial resistance to the other workhorse quinolones, including ciprofloxacin (Ciloxan), ofloxacin (Ocuflox) and the more-recent levofloxacin (Quixin).

But they also lead some clinicians to question whether their use is like uprooting a dandelion with a bulldozer. "I think clearance of bacterial conjunctivitis is excellent with almost any antibiotic," said David G. Morrison, MD, assistant professor of ophthalmology and pediatrics at Vanderbilt University in Nashville, Tenn. "And reserving the quinolone drugs for the more significant infections, such as bacterial keratitis, is a better plan when an inexpensive nonquinolone drop will clear conjunctivitis very nicely." Others argue that enlisting the strongest medications—despite their higher cost—is the best strategy for preventing mutations that might turn "dandelions" into more dangerous flora.

Rising Drug Resistance

No one disagrees that the newest quinolones (moxifloxacin and gatifloxacin were approved in 2003) may help meet the challenge of resistance to earlier generations that researchers have monitored with apprehension since the late 1980s.

One in vitro study, published in 1999, from the University of Pittsburgh, suggested that resistance of Staphylococcus aureus to ciprofloxacin increased significantly, from 5.8 percent in 1993 to 35 percent in 1997.1 More recently, laboratory analysis of other isolates also indicated that resistance to cipro and levofloxacin among S. aureus isolates from keratitis and conjunctivitis cases was on the rise.

A study published in 2004 from the Bascom Palmer Eye Institute focused on methicillin-sensitive S. aureus (MSSA). MSSA is responsible for a sizable proportion of eye infections. Researchers found that the average annual cipro resistance rate for MSSA rose from two percent in the years following its introduction, 1990 through 1995, to five percent on average for the years 1996 to 2001. Zeroing in just on the period from January 2000 to December 2001, they found that the cipro resistance rate had leapt to 11.9 percent, a sixfold increase compared with the drug’s early years.

The comparable levofloxacin resistance rate was a more-comfortable 4.7 percent in the latest year studied. But the researchers caution that any new quinolone may follow the same pattern, trending toward weakness, as its predecessors.2

Mutations vs. mechanisms. "There has been some fear that bacteria would defeat us," Dr. Isenberg said, "because of their mutations and developing resistance." The newer drugs "keep us one step ahead" of resistance, he said, "or maybe two steps."

He was referring to one of the strongest selling points for moxifloxacin and gatifloxacin. Both attack bacterial cells in different ways compared with earlier quinolones. Like their predecessors, they bind strongly to topoisomerase IV, a key enzyme involved in bacterial replication. The extra protection comes from the fact that the newer drugs also bind strongly to a second critical enzyme, DNA gyrase (topoisomerase II), left mainly unbound by others in the drug class. The bonus is that any pathogen would have to undergo two mutations to become resistant to these newer quinolones.

Such a "double mutation" is unlikely, but not impossible, in the opinion of ophthalmic microbiologist Regis P. Kowalski, MS, [M.] ASCP, at the University of Pittsburgh. His laboratory work often focuses on antibiotic potencies and weaknesses. When a pathogen becomes resistant to an older fluoroquinolone, "one mutation is already in place," he said. So "just one more mutation" would convey resistance to the latest-generation fluoroquinolones.

A Very Wide Array of Antibiotics

That’s why, in theory, it makes sense to preempt resistance by enlisting the medications—moxifloxacin and gatifloxacin—that appear most effective, Mr. Kowalski said. But in practice, several other antibiotics generally perform just as well for conjunctivitis without undue risk of resistance.

The most recent in vitro research does indicate that the two newer quinolones offer some potency advantages over older fluoroquinolones for covering the gram-positive pathogens S. aureus and Streptococcus pneumoniae. These bacteria are believed to be common culprits in pediatric conjunctivitis, although physicians rarely collect cultures from young patients.

There is no distinct advantage favoring the stronger drugs over earlier quinolones for another bacterium, Haemophilus influenzae. All of the quinolones are about equally effective against this erstwhile menace to children, the laboratory research suggests.3 Today, H. influenzae appears to play a smaller role in pediatric conjunctivitis thanks to vaccines, available since 1987, offering early protection against this gram-negative pathogen. "It’s not as common in children as it once was," said Michael X. Repka, MD, professor of ophthalmology at Johns Hopkins in Baltimore.

In practice, clinicians enjoy a wide choice of antibiotics that can effectively shorten the course of conjunctivitis. "Here’s the bottom line," Mr. Kowalski said. "Just about anything you use would work," at least based on in vitro studies. Clinicians can draw reassurance from these studies because much of the lab research is based on standards that apply to systemic antibiotics.

Eyedrops, commonly used for pediatric cases, act directly on a superficial infection. "When you put the drug right there, you get really high concentrations in the conjunctiva. So [even] resistant bacteria will probably respond, as long as they’re not that resistant." Clinically, Dr. Morrison said, "Clearance of bacterial conjunctivitis is equally efficacious with almost any topical antibiotic."

For uncomplicated pediatric conjunctivitis, Dr. Isenberg suggests an ophthalmic solution of neomycin, polymyxin B and gramicidin, now available as a generic.

Pressure to Prescribe Something

All such options are irrelevant, of course, in the setting of viral or allergic conjunctivitis. Under salvos of warnings about overprescription, pediatricians are a bastion against parents’ false belief that antibiotics are a cure-all. Still, physicians including ophthalmologists sometimes surrender to ardent pleas for medication.

Unscientific school policies. Parental demand for antibiotics is fueled by ill-advised school policies "that as soon as they’re on drops, children can go back to the classroom, even if the policy doesn’t make a whole lot of sense," said Dr. Repka. Parents are under pressure, according to Dr. Repka, "to have their child get back to school. And oftentimes the only way they can do that is to get them on topical antibiotics even if they have a viral infection." Ophthalmologists can provide an antidote to overprescription by talking with the pediatricians who, in most communities, are the first-responders to conjunctivitis.

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1 Goldstein, M. H. et al. Ophthalmology 1999; 106(7):1313–1318.
2 Marangon, F. B. et al. Am J Ophthalmol 2004; 137(3):453–458.
3 Kowalski, R. P. et al. Ophthalmology 2005; 112(11):1987–1991.

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Mr. Kowalski has conducted contract research for Alcon and Allergan, and is a consultant for both. Drs. Isenberg, Morrison and Repka report no financial conflicts of interest.

The Crux of Conjunctivitis

How to evaluate antimicrobials. Don’t rely on just one descriptive statistic for evaluating in vitro antibiotic data. Sales materials sometimes highlight minimum inhibitory concentrations (MICs) as if they were the case-closed data when it comes to choosing one drug over another. "But you have to look at the whole picture," said Mr. Kowalski, who with coauthors laid out some of the subtleties in a recent article in Ophthalmology.3 Example: MIC data may indicate that one antibiotic appears far more potent (that is, with lower MICs) than another. But both may be more than sufficiently effective against a particular pathogen.

How to diagnose the cause. A thick, mucopurulent discharge with injection of the bulbar and palpebral conjunctiva is characteristic of a bacterial infection. Alternatively, a stringy discharge with minimal redness may also indicate an allergic condition for which other medications such as epinastine (Elestat), olopatadine (Patanol) or ketotifen (Zaditor) might be appropriate. Swelling in the preauricular lymph nodes, easily discovered by palpating the facial area between the ear and the cheek, indicates a viral infection. The differential diagnosis also includes sexually transmitted diseases—chlamydia and gonorrhea—most commonly acquired during birth.

When should children go back to school? "When the redness is almost gone," Dr. Isenberg said. Often the risk of contagion from a bacterial infection abates within a day or so after a child starts an antibiotic. Viral infections usually resolve more slowly, requiring three days to two weeks at home.