eMedicine Specialties > Ophthalmology > Cornea

Keratitis, Bacterial: Treatment & Medication

Author: Fernando H Murillo-Lopez, MD, Senior Surgeon, Unidad Privada de Oftalmologia CEMES
Contributor Information and Disclosures

Updated: Apr 18, 2006

Treatment

Medical Care

If no organisms are identified on the slide smear, initiate broad-spectrum antibiotics with the following: tobramycin (14 mg/mL) 1 drop every hour alternating with fortified cefazolin (50 mg/mL) 1 drop every hour.

If the corneal ulcer is small, peripheral and no impending perforation is present, intensive monotherapy with fluoroquinolones is an alternative treatment. Other antimicrobials can be used, depending on the clinical progress and laboratory findings.

The fourth-generation ophthalmic fluoroquinolones include moxifloxacin (VIGAMOX, Alcon Laboratories, Inc, Fort Worth, TX) and gatifloxacin (Zymar, Allergan, Irvine, CA), and they are now being used for the treatment of bacterial conjunctivitis. Both antibiotics have better in vitro activity against gram-positive bacteria than ciprofloxacin or ofloxacin. Moxifloxacin penetrates better into ocular tissues than gatifloxacin and older fluoroquinolones; in vitro activity of moxifloxacin and gatifloxacin against gram-negative bacteria is similar to that of older fluoroquinolones. Moxifloxacin also has better mutant prevention characteristics than other fluoroquinolones. These findings support the use of the newer fluoroquinolones for the prevention and treatment of serious ophthalmic infections (eg, keratitis, endophthalmitis) caused by susceptible bacteria.

In view of these findings, moxifloxacin or gatifloxacin may be a preferred alternative to ciprofloxacin as the first-line monotherapy in bacterial keratitis.

Additionally, 0.5% moxifloxacin and, to a lesser extent, levofloxacin and ciprofloxacin have demonstrated significant effectiveness for reducing the number of Mycobacterium abscessus in vivo, suggesting the potential use of these agents in prevention of M abscessus keratitis.

The frequency of antibiotic administration should be tapered off according to the clinical course using some of the following parameters:

• Blunting of the perimeter of the stromal infiltrate
• Decreased density of the stromal infiltrate
• Decreased stromal edema and endothelial inflammatory plaque
• Decreased anterior chamber inflammation
• Reepithelialization of the corneal epithelial defect
• Improvement in painful symptoms

Surgical Care

The most common cause of corneal perforation is infection by bacteria, virus, or fungus, accounting for 24-55% of all perforations, with bacterial infections being the most common. PK, sclerocorneal patch, or application of cyanoacrylate tissue adhesive may be necessary in cases of corneal perforation or imminent perforation, following the guidelines provided below.

• Systemic intravenous antibiotics (alternatively ciprofloxacin 500 mg PO bid) should be started once an infected corneal ulcer has perforated and for 3 days following the PK.
• A clear plastic shield should be placed over the eye.
• The use of general anesthesia usually is preferred for keratoplasty surgery. Topical anesthesia can be used for application of tissue adhesive.
• The size of the transplant should be the smallest trephine capable of incorporating the perforation site and any infected or ulcerated border. Donor generally is oversized by 0.5 mm.
• Cataract removal is left for a subsequent procedure because of the risk of expulsive hemorrhage and endophthalmitis.
• Posterior and anterior synechiae should be lysed gently.
• The anterior chamber should be irrigated to remove any necrotic or inflammatory debris.
• The donor cornea should be secured with 16 interrupted 10-0 nylon sutures.
• Subconjunctival injections of antibiotics can be given without depot steroid injection.
• Postoperative use of frequent topical fortified antibiotics. Corticosteroids 4 times a day can be used immediately after surgery if it is believed that the infection was excised completely. Alternatively, steroids can be withheld for several days to monitor for infection. Once the acute postoperative period is over, long-term care is similar as that for uncomplicated PK.

Consultations

Consultation with vitreoretinal colleagues may be helpful if the diagnosis of endophthalmitis is considered.

Medication

Topical antibiotics constitute the mainstay of treatment in cases of bacterial keratitis, with subconjunctival antibiotics used only under unusual circumstances, and systemic antibiotics used only in cases of perforation or specific organisms (eg, N gonorrhoeae). The use of topical corticosteroids remains controversial; however, when they are used, strict guidelines and close follow-up care are mandatory to ensure the best ultimate outcome of these patients.

Antibiotics

Aminoglycosides have a broad range of bactericidal activity against many bacterial species, particularly gram-negative rods. They have a selective affinity to bacterial 30S and 50S ribosomal subunits to produce a nonfunctional 70S initiation complex that results in inhibition of bacterial cell protein synthesis. Unlike other antibiotics that impair protein synthesis, they are bactericidal. Their clinical activity is limited severely in anaerobic conditions. They have a low therapeutic/toxic ratio.

Cephalosporins have a broad spectrum of activity, including effective action against Haemophilus species. They contain a beta-lactam ring similar to penicillins, and a dihydrothiazine ring that makes them resistant to the action of penicillinases produced by staphylococci. They inhibit the third and final stage of bacterial cell wall formation by preferentially binding to one or more penicillin-binding proteins that are in the cytoplasmic membrane beneath the cell walls of susceptible bacteria. They are well tolerated topically.

Chloramphenicol usually is reserved for specific infections such as those associated with H influenzae. Its use has been limited by toxicity, including a dose-dependent bone marrow depression.

Macrolides are bacteriostatic agents (eg, erythromycin, tetracycline) that can suppress the growth of susceptible gram-positive cocci. This class of drugs works by inhibition of bacterial protein synthesis.

Glycopeptides have activity against gram-positive bacteria, and methicillin and penicillin-resistant staphylococci. They inhibit the biosynthesis of peptidoglycan polymers during the second stage of bacterial cell wall formation, at a different site of action from that of the beta-lactam antibiotics. They also have an excellent activity against a variety of gram-positive bacilli.

Sulfonamides have a structure similar to para -aminobenzoic acid (PABA), a precursor required by bacteria for folic acid synthesis. They competitively inhibit the synthesis of dihydropteroic acid, the immediate precursor of dihydrofolic acid from PABA pteridine. This inhibition does not affect mammalian cells because they lack the ability to synthesize folic acid and require preformed folic acid. They are active against gram-positive and gram-negative bacteria, and they are the preferred drugs against Nocardia keratitis.

Fluoroquinolones variably inhibit the action of bacterial DNA gyrase an enzyme essential for bacterial DNA synthesis. They have activity against most aerobic gram-negative bacteria and some gram-positive bacteria. Concern has been generated regarding the emerging resistance to fluoroquinolones among staphylococci. Emerging resistance to these antimicrobials has been reported in nonocular and ocular isolates. They have limited efficacy against streptococci, enterococci, non-aeruginosa Pseudomonas, and anaerobes. Two multicenter trials compared the efficacy of ciprofloxacin 0.3% and ofloxacin 0.3% solution versus fortified cefazolin and tobramycin showing favorable efficacy for a single agent fluoroquinolone therapy.

They also have a record for low toxicity, good ocular surface penetration, and prolonged tear film penetration. Monotherapy for bacterial keratitis using these classes of antibiotics has been proved to be effective in large clinical trials. However, emerging resistance to the fluoroquinolones is now being reported in nonocular and ocular isolates.

Fortified tobramycin 14 mg/mL (AKTob, Tobrex)

Interferes with bacterial protein synthesis by binding to 30S and 50S ribosomal subunits, which results in a defective bacterial cell membrane. Add 2 mL of parenteral tobramycin (40 mg/cc) to 5 mL commercial 0.3% tobramycin solution. Refrigerate (expires in 7 d)

Amikacin 20 mg/mL (Amikin)

When mycobacteria are suspected. Irreversibly binds to 30S subunit of bacterial ribosomes; blocks recognition step in protein synthesis; causes growth inhibition.

Fortified cefazolin 50 mg/mL (Ancef, Kefzol, Zolicef)

First-generation cephalosporin with excellent gram-positive but narrow gram-negative activity. To prepare for topical use, dilute 500 mg parenteral cefazolin powder in sterile water to form 10 mL solution. Refrigerate (preparation expires in 7 d).

Ceftazidime 50 mg/mL (Fortaz, Ceptaz)

Third-generation cephalosporin has slightly less activity against gram-positive pathogens but more activity against gram-negative bacteria compared to a first-generation cephalosporin. To prepare, add 1 g parenteral ceftazidime powder to 9.2 cc of artificial tears. Add 5 cc of dilution to 5 cc of artificial tears, and shake well.

Chloramphenicol (Chloromycetin)

Acts by inhibiting bacterial protein synthesis. Binds reversibly to the 50S subunit of bacterial 70S ribosome and prevents attachment of the amino acid-containing end of the aminoacyl-tran to acceptor site on ribosome. Active in vitro against a wide variety of bacteria, including gram-positive, gram-negative, aerobic, and anaerobic organisms.

Erythromycin (E-Mycin)

Ophthalmic ointment applied hs can be used in combination with a fluoroquinolone to improve coverage against streptococci and other gram-positive bacteria when dealing with small ulcers and outpatient treatment.

Vancomycin 50 mg/mL (Vancocin)

To prepare for topical administration, dilute 500 mg of parenteral vancomycin powder in 10 mL sterile water, artificial tears, or normal saline (0.9%). Refrigerate (preparation expires in 4 d). The 25 mg/mL concentration appears to be just as effective as the 50 mg/mL concentration but is much better tolerated by patients.

Sulfa

Laboratory diagnosis of Nocardia keratitis. Exerts bacteriostatic action by competitive antagonism of PABA, an essential component of folic acid synthesis.

Ciprofloxacin 0.3% (Ciloxan)

Fluoroquinolone with activity against pseudomonads, streptococci, MRSA, S epidermidis, and most gram-negative organisms, but no activity against anaerobes. Inhibits bacterial DNA synthesis, and consequently growth.

Ofloxacin 0.3% (Floxin)

A pyridine carboxylic acid derivative with broad-spectrum bactericidal effect.

Gatifloxacin

Quinolone that has antimicrobial activity based on ability to inhibit bacterial DNA gyrase and topoisomerases, which are required for replication, transcription, and translation of genetic material. Quinolones have broad activity against gram-positive and gram-negative aerobic organisms. Differences in chemical structure between quinolones have resulted in altered levels of activity against different bacteria. Altered chemistry in quinolones result in toxicity differences.

Topical corticosteroids

Anti-inflammatory agents that may impair host defenses and enhance microbial proliferation, but can reduce host inflammatory response that contributes to conjunctival or corneal scarring. Should not be used until specific antimicrobial therapy has controlled microbial proliferation, and clear clinical improvement is evident. Judicious corticosteroid use entails dosage adjustment according to severity of ocular inflammation and occurrence of side effects. Discontinuation should be gradual to minimize rebound of inflammation.

Prednisolone acetate 1% (AK-Pred, Pred Forte)

Decreases inflammation by suppressing migration of polymorphonuclear leukocytes and reversing increased capillary permeability.
As the keratitis is controlled with antimicrobials, increase corticosteroids and decrease antibiotics.

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