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Therapeutic Drugs What's Your IQ?
Fluoroquinolones work quickly and efficiently to subdue the most common ocular microbes. Here's how you use this weapon in your own practice. by John A. McGreal, O.D., St. Louis A 48-year-old black female, with no significant
ocular history, presented with a painful, red eye and decreased vision in the right eye. She did not wear contact lenses. The clinical findings showed a keratitis with hypopyon. The management was straightforward. We did not
culture this patient, but told her to instill Ocuflox (ofloxacin) every 15 minutes for six hours, followed by every 30 minutes for six hours, then taper until the condition resolved. This is just one example of how optometrists
use fluoroquinolones to combat corneal infections. This class of antibiotics came onto the scene in the early 1990s to give us another powerful weapon in the battle against bacterial infections, specifically bacterial keratitis.
Fluoroquinolones inhibit DNA gyrase, a bacterial-specific enzyme that allows the DNA to coil and replicate. These drugs are available in topical, oral and intravenous forms. The oral forms have become standard for treating
urinary tract, lower respiratory and intestinal infections, including those caused by Salmonella.1 They are effective in treating sexually transmitted diseases caused by Neisseria gonorrhoeae and Chlamydia, and in treating septic
arthritis and osteomyelitis. With their broad spectrum of activity, low toxicity and minimum resistance, clinicians are prescribing fluoroquinolones for a greater variety of systemic illnesses and ocular diseases. This article
explores how fluoroquinolones work and evaluates their effectiveness in treating bacterial keratitis, either alone or in combination with other antibiotics. Broad Spectrum The
current topical formulations—each in 0.3 percent concentrations—include Ciloxan (ciprofloxacin) and Chibroxin (norfloxacin), besides Ocuflox. Each has distinct clinical characteristics, differences in solubility and precipitate
formation. Of the three, Ocu-flox is the most soluble.3 This solubility enables more of the active agent to penetrate the deep corneal layers and anterior chamber.4 Precipitate formation most commonly occurs with Ciloxan.5 The
precipitate is a chemically pure fluoroquinolone and, as such, may act as a pharmacologic depot. While the precipitate is highly bactericidal, it does slow corneal reepithelialization. Ciloxan is particularly effective against
gram-negative organisms, and is the drug of choice for treating pseudomonal infections, common in contact lens-related bacterial keratitis. In comparing the absorption rate and activity of these three drugs, it's helpful to
understand the inhibitory quotient, or IQ. The IQ is an attempt by ocular infectious disease specialists to combine laboratory bacterial sensitivity data with ocular penetration to compare the effectiveness of drugs 6 Though uncommon, adverse ocular reactions to flouoroquinolones include transient
burning or discomfort upon instillation, possibly related to the benzalkonium chloride preservative found in the drug. Non-ocular reactions include skin rash, gastrointesitnal disturbance, central nervous system problems (such as
dizziness, insomnia and confusion) and, rarely, tendonitis or tendon rupture. Bacterial Keratitis Besides Pseudomonas aeru-ginosa, other organisms commonly responsible for corneal ulcers include Staphylococcus aureus, Staphylococcus epidermatis, Streptococcus pneumonia,
Hemo-philis influenza, Serratia, Proteus and Enterobacter. Less common causes: Neisseria, Moraxella, Mycobacterium and anaerobes.9 In many cases, external forces predispose the cornea to infection. These can include epithelial
trauma, topical steroid use, ocular surface disease, a history of penetrating keratoplasty and problems with the immune system. These patients typically complain of pain and sharply demarcated epithelial ulceration, with stromal
infiltration. Adherent mucopurulent exudate with liqui-factive stromal necrosis is a sign of pseudomonal infection. Diffuse epithelial edema and stromal cellular infiltrate in the distant cornea can also be present. There may be an
iritis or a hypopyon associated with significant infection. Diagnosis and Treatment We still
must take cultures, however, in certain cases, such as an ulcer with an infiltrate larger than 2mm or one in the middle to deep stroma. Any ulcer that is either chronic or doesn't respond to conventional antibiotic therapy also
requires a culture.9 The value of culturing remains controversial. You must weigh your decision to culture against other factors, such as cost, feasibility and patient considerations.10 Treatment of bacterial keratitis begins
with immediate and aggressive antimicrobial therapy. Once you get the culture results and see how the patient responds, you can modify this therapy. Contemporary treatment can be separated into three distinct protocols:
• Fortified topical tobramycin (14mg/ml) and fortified cephazolin (50mg/ml).11 This culture-directed treatment has long been the standard of institutional referral-based practices, which often treat microbial keratitis that has
failed to respond to initial antibiotic therapy. • Topical fluoroquinolone monotherapy. You don't need to take a culture with this treatment. It's best reserved for small, non-severe peripheral ulcers. • Topical fluoroquinolone
combined with a fortified antibiotic.6 Substitute the tobramycin with a fluoroquinolone, and combine this with the fortified cephazolin. This type of therapy is indicated for large, severe, central ulcers. Culturing is an important
part of this disease management plan. Adjunctive therapies in treating bacterial keratitis include oral tetracycline or doxycycline, which inhibit collagenase activity. I've found that topical corticosteroids rarely have a place
in managing corneal ulcers because they neither eradicate the infection nor hasten wound healing,9 although many clinicians would disagree. The role of non-steroidal anti-inflammatories (NSAIDs) hasn't yet been fully determined,
but they may have some role in managing pain. It's important to note that like other antibiotics, fluoroquinolones have recently shown an increased laboratory resistance to some pathogens. This in-vitro resistance, however, tends
to be greater than the "clinical" resistance experienced in daily practice. Clinical resistance occurs more often with Streptococ-cus pneumonia and coagulase-negative Staphylococcus. For this reason, bear in mind that
fluoroquinolones are not effective in all cases.12 Perioperative Therapy Patients who develop postoperative endophthalmitis and who have a visual acuity of better than light perception should
undergo anterior chamber paracentesis (in which 0.1cc of aqueous is removed), together with a vitreous tap (in which 0.3cc are aspirated with a needle or vitrector through the pars plana). They should receive intravitreal
vancomycin combined with either Ciloxan or ceftazidime. If the patient has a visual acuity of light perception, the surgeon would remove at least 50 percent of the vitreous by the standard three-port pars plana vitrectomy. This
treatment consists of a 0.1cc intravitreal injection of vancomycin 1mg, along with amikacin 0.4mg in a 0.1cc intravitreal injection, plus fluoroquinolone therapy. Growing numbers of surgeons are substituting ceftazidime 2.25mg in
a 0.1cc intravitreal injection in place of the amikacin.13 Like Ciloxan, ceftazidime also performs well against Pseudomonas. This approach has proven to be substantially more effective than systemic intravenous antibiotics.14 In
studied eyes, 53 percent of cases had visual acuity outcomes of better than 20/40, and 74 percent had outcomes better than 20/100. Fluoroquinolones have also demonstrated their effectiveness in post-refractive surgery. In
clinical studies of post-LASIK eyes, Ocuflox demonstrated twice the penetration of Ciloxan. New Horizons We also anticipate the development of new molecular diagnostic
techniques to more rapidly identify microbial organisms. Also on the horizon: new techniques in drug delivery systems to replace current treatment modalities. These include drug administration via contact lenses, collagen
shields, liposomes, iontophoreses, sustained-release formulations and bioerodable polymers. Given the effectiveness of fluoroquinolones and their ease of administration, it's easy to see why more doctors are turning to them in
the war against ocular and systemic antimicrobials. Dr. McGreal is center director of the Missouri Eye Institute comanagement center. He lectures frequently on
clinical and practice management topics. 1. The choice of antibacterial drugs. The Medical Letter. 1996;38(issue 971) 25-34. |
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What's Your IQ? The IQ integrates the peak tissue concentration with the minimum inhibitory concentration (MIC) of the pathogen. The higher a drug's IQ score, the more effective it will probably be. Ocuflox achieves higher tissue
concentrations than Ciloxan because it has significantly higher MICs than the latter. There are limitations in using this equation, however. For example, a drug's IQ doesn't consider variability in tissue levels or the synergy
or antagonism among several drugs. Nor does it take into account the length of time it takes for a drug to achieve maximum therapeutic levels. And, the IQ equation becomes less important when dealing with epithelial defects and
inflammation. Lastly, be aware that a drug with an IQ of greater than 1 doesn't necessarily guarantee a cure. |
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Case Report I A 14-year-old black female presented with a painful, red eye and decreased vision. She had a history of Marcus Gunn phenomenon and eyelid surgery. She did not wear contact
lenses. Clinical findings revealed an unusual keratitis with an endothelial ring and a second peripheral lesion in the left eye. The culture findings showed the infectious agent was Kingella kingae, known to be sensitive to
tobramycin. The patient was treated with fortified tobramycin and fortified cephazolin every hour, alternating the medications on the half hour. |
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Case Report II A 37-year-old white male with a history of RGP contact lens use presented a painful, red eye and decreased vision in his left eye. The clinical findings showed a central, severe
keratitis with mucopurulent discharge. I consulted with a corneal specialist on this case, and the patient was then admitted for treatment. The culture confirmed a Pseudomonas infection. The patient was treated with Ciloxan
every 15 minutes for six hours, then for every 30 minutes afterward, and fortified cephazolin every 30 minutes. |
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