Is Antibiotic Resistance a Problem in the Treatment of Ophthalmic Infections?

Regis P Kowalski

Disclosures

Expert Rev Ophthalmol. 2013;8(2):119-126. 

In This Article

Abstract and Introduction

Abstract

Antibiotic resistance is a world-wide problem of systemic medicine, but it appears to be less problematic in the treatment of ophthalmic infections. The use of topical administration and intraocular injection of antibiotics provides very high antibiotic concentrations in the ocular tissues. These high concentrations are effective in treating bacteria that are deemed resistant using standard interpretations of susceptibility. Although in vitro bacterial resistance, based on serum standard interpretation, is reported for ocular bacteria, these isolates are generally not spread from patient-to-patient and there are antibiotics available to effectively treat and overcome the false resistance.

Introduction

The discussion of ocular bacterial resistance to antibiotics must take into account the type of bacterial pathogens encountered and the mode of treatment. Figures 1–3 depict the key bacterial pathogens from our clinical laboratory that are isolated from endophthalmitis (intraocular infections generally associated with postoperative complications), keratitis (infections of the cornea) and conjunctivitis/blepharitis (infections of the conjunctiva and eyelid margin). Gram-positive bacteria are the predominant isolate over Gram-negative bacteria. The key pathogens of endophthalmitis are coagulase-negative Staphylococci and Staphylococcus aureus followed by Streptococcus species. Gram-negative bacteria are an infrequent cause of endophthalmitis that is generally implicated through trauma or endogenous infection. Bacterial keratitis is frequently due to S. aureus, Pseudomonas aeruginosa, various Streptococcus species and Gram-negative bacteria, while bacterial conjunctivitis are generally associated with S. aureus, Streptococcus pneumoniae and Haemophilus influenzae. Other areas of the eye can be infected, but these are generally grouped based on treatment within the three main descriptions (endophthalmitis [i.e., blebitis], keratitis [i.e., dacryocystitis, canaliculitis and scleritis] and conjunctivitis/blepharitis [i.e., orbital cellulitis]).[101]

Figure 1.

Distribution of bacteria isolated from endophthalmitis (1993–2011).

Figure 2.

Distribution of bacteria isolated from keratitis (1993–2011).

Figure 3.

Distribution of bacteria isolated from conjunctivitis/blepharitis (1993–2011).

In contrast to systemic therapy, bacterial keratitis and conjunctivitis are treated topically with eye drops, while endophthalmitis is treated with a direct injection of antibiotics into the vitreous humor. Systemic antibiotics, as a rule, are not considered effective in the treatment of ocular infections, but this route is sometimes used in the treatment of preseptal and orbital cellulitis, scleritis and abscesses.

As a general definition in this article, 'problematic resistance' occurs concurrently when intrinsically susceptible bacteria become resistant to antibiotics (i.e., resistance of Gram-positive bacteria to vancomycin); resistant bacteria spread from patient to patient and effective antibiotics are not available to treat the resistance.

The pertinent question is whether 'problematic resistance' occurs in the treatment of ocular infections.

The first important point to address is whether systemic in vitro susceptibility standards accurately interpret susceptibility and resistance.[1,2] There are no antibiotic susceptibility standards for bacterial isolates from infections that are treated topically or by direct injection, which includes ocular infections. The systemic standards can be used if it is assumed that antibiotic concentrations in the ocular tissue are equal to or greater than the antibiotic concentrations in the blood serum.[3] Intuitively, administration directly to the site of infection would be more advantageous than relying on the circulatory system to deliver high concentrations of antibiotic. For example, injecting 1 mg of vancomycin into the vitreous to obtain an approximate concentration of 200 µg/ml could never be achieved with systemic therapy. Since the antibiotic concentrations are much higher in the ocular tissue by topical therapy, interpretation with the systemic standards results in the overreporting of resistance, which is widely evident in the literature, but not completely discussed in this article. The overreporting of resistance does provide a safety factor for predicting a susceptible interpretation, although bacteria deemed resistant to an antibiotic may also be truly susceptible. In support of this safety factor, we were able to demonstrate in our rabbit keratitis and endophthalmitis models, that the fluoroquinolone anti-infectives were able to overcome in vitro resistance by successfully eradicating serum interpreted resistant bacteria.[4–6]

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