There are several classes of topical and oral antibiotics available in the treatment and management of ocular disease. As optometrists, we often need these medications for the lid and ocular surface conditions.
This review will only focus on antibiotics from an ophthalmic point of view and will not list all types; it will not review drug mechanisms.
Brief overview of antibiotics
Let’s start from the beginning! There are a few things that need to be reviewed before diving deeper into the various kinds of antibiotics and their profiles.
Drug function1,2
- Bactericidal: Agents that KILL all microorganisms by inhibiting cell wall synthesis. Examples include penicillin derivatives, cephalosporins, and vancomycin.
- Bacteriostatic: Agents that ARREST the growth and replication of bacteria, limiting spread while our immune system does the work. Examples include aminoglycosides, augmentin, quinolones, and tetracyclines.
Antibiotic spectrum of therapy
- Narrow: Single or limited group of organisms. Used when you know what kind of bacteria you’re dealing with. Examples include bacitracin against gram-positive bacteria and polymyxin against gram-negative bacteria.
- Broad: Effective against gram-positive and gram-negative microorganisms. Examples include tetracyclines, fluoroquinolones, and 3rd and 4th generation cephalosporins.
What ODs need to know about bacteria
Gram-positive bacteria are the most common cause of ocular bacterial infections.1 Staphylococcus aureus, coagulase-negative staphylococci (CoNS), Streptococcus pneumoniae, and Pseudomonas aeruginosa are leading isolates in ocular infections.1,2
Table 1 lists some bacteria that we may see in the optometry clinic.2
| Gram-Positive Bacteria | Pathogen |
|---|---|
| Staphylococcus (Staph) | Methicillin-sensitive S. aureus (MSSA), methicillin-resistant S. aureus (MRSA), S. epidermidis, coagulase-negative S. aureus (CNSA) |
| Streptococcus | S. pneumoniae, S. pyogenes, S. viridians |
| Enterococcus | Enterococcus species |
| Spore Forming (bacilli) | Bacillus species, MSSA, MRSA, Clostridium species |
| Gram-Negative Bacteria | Pathogen |
|---|---|
| Neisseria (cocci) | N. meningitidis, N. gonorrhoeae |
| Enterics (bacilli) | E. coli, Klebsiella pneumoniae, Serratia species, Proteus species, Helicobacter pylori, P. aeruginosa |
| Respiratory bacilli | Haemophilus influenzae |
Table 1: Courtesy of Huda Minhas, OD.
Bacteria linked with ophthalmic conditions
Other bacteria to be aware of include Chlamydia trachomatis, mycobacteria, and spirochetes.
Here are some of the common pathogens related to ophthalmic conditions:
- Blepharitis: Staph, S. pyogenes, and P. aeruginosa
- Conjunctivitis: Staph, S. pneumoniae, P. aeruginosa, K. pneumoniae, E. coli, and H. influenzae
- H. influenzae is most common in children
- Keratitis: CNSA, P. aeruginosa, and S. aureus
- Contact lens-related keratitis is typically Pseudomonas, especially if it is severe and central
- Peripheral ulcers are commonly from Staphylococcus spp.
- Dacryocystitis: Staph, P. aeruginosa, and E. coli
- Endophthalmitis: S. viridans, S. pneumoniae, and CNSA
- CNSA and Bacillus spp. are common in post-operative/trauma causes
- Endogenous endophthalmitis: K. pneumoniae
- This endophthalmitis is caused by metastatic spread from a primary site of infection, ex: systemic factors, such as diabetes, urinary tract infection (UTI), etc.
Tip: Remember “FAT PAC” for pregnant women:
- Never use FAT (fluoroquinolones, aminoglycosides, and tetracyclines)
- You can use PAC (penicillins, azithromycin, and cephalosporin)
Download the Reference Guide for Systemic and Topical Ocular Antibiotics here
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Reference Guide for Systemic and Topical Ocular Antibiotics
Optometrists can use this cheat sheet that outlines topical and systemic antibiotics by class, with details on pathogen targets, uses, and recommended dosing, for quick reference when treating patients.
Penicillins
These are the most common oral ocular antibiotics prescribed as they are effective bactericidal agents for infections around the ocular adnexa.4,5
Penicillinase-resistant penicillin
When treating eyelid infections, it is important to use a penicillinase-resistant penicillin since bacteria produce an enzyme called penicillinase, which renders penicillin ineffective.6 These drugs work great against S. aureus.
As an example, for lid infections, dicloxacillin is dosed at 125mg QID for mild to moderate cases or 500mg BID for severe cases.
Amoxicillin
There are several synthetic derivatives with a broad spectrum of coverage that we are familiar with as well—amoxicillin, for example! Amoxicillin is categorized under aminopenicillins—this class is active against gram-negative rods, such as E. coli and H. influenzae.
Further, amoxicillin is useful for treating periocular infections (i.e., preseptal cellulitis, orbital cellulitis, and dacryocystitis). But, in order to make it penicillinase-resistant, it is combined with clavulanic acid to make Augmentin. A typical dose would be 500mg BID to TID; for more serious infections, it is 875mg BID.
Cephalosporins
Cephalosporins are also bactericidal and similar in structure to penicillins. They share a beta-lactam ring, which means there’s a possibility of cross-reactivity between these two compounds.4 So, if a patient has a true anaphylactic reaction to penicillin, we do not prescribe cephalosporins.
This class of medication is also used commonly in eyelid infections. They are classified into generations with effective coverage against gram-positive bacteria, such as S. aureus and S. epidermidis. Higher generations have expanded coverage for gram-negative bacteria.4,7
Table 2 classifies cephalosporins in more detail.
| Type of Cephalosporin | Spectrum of Activity | Clinical Usefulness |
|---|---|---|
| First generation: Cefazolin, Cephalexin (Keflex) | Gram-positive cocci (except enterococci), H. influenzae, E. coli, Klebsiella species, Proteus species, and methicillin-susceptible staphylococci. | Frequent use in skin and soft tissue infections. |
| Second generation: Cefaclor, Cefuroxime (Ceftin) | Gram-positive cocci (except Enterococci), H. influenzae, E. coli, Klebsiella species, Proteus species, M. catarrhalis, and anaerobes such as Bacteroides and Clostridium. | Oral cefaclor can be used for preseptal cellulitis. Parenteral cefuroxime with ampicillin is a recommended treatment for severe orbital cellulitis. |
| Third generation: Ceftriaxone, Cefdinir (Omnicef), Cefpodoxime (Vantin) | Gram-positive cocci (except enterococci), H. influenzae, E. coli, Klebsiella species, Proteus species. These are more active against gram-negative bacteria. | Ceftriaxone combined with vancomycin can be used to treat severe orbital cellulitis. Intramuscular ceftriaxone is also recommended for treatment of gonococcal infections and a good option for treatment of syphilitic uveitis. |
| Fourth generation: Cefepime | Extended spectrum of activity against both gram-positive (methicillin-sensitive S. aureus) and gram-negative (Pseudomonas) organisms. | Not prescribed orally, but I listed it to distinguish the 4th generation of cephalosporins. I have seen some reports of it used intravenously for cataract surgery. |
Table 2: Courtesy of Huda Minhas, OD.
One of the most commonly prescribed cephalosporin is cephalexin (Keflex) for infectious eyelid conditions such as internal hordeolum and mild preseptal cellulitis, typically at 500mg BID for 1 week. For more severe infections, you can prescribe it TID.
The November 2018 issue of the Journal of the American Medical Association (JAMA) published that fewer than 10% of people with allergies to penicillins are actually allergic. A true anaphylactic reaction includes hypotension, laryngeal edema, wheezing, angioedema, or urticaria.
Among those with true allergic reactions, 80% can lose this sensitivity within 10 years. Most often, people consider stomach upset as an allergy to this drug. Sorting out these reactions is important so we can consider using these antibiotics instead of misclassifying our patients.8
Fluoroquinolones
Fluoroquinolones are broad-spectrum antibiotics that are concentration-dependent bactericidal agents.9 They are currently the most popular topical antibiotic used for the treatment of ocular infections due to their safety, penetration into the aqueous and vitreous, and long duration of tear concentration.
Oral fluoroquinolones are typically used for serious bacterial infections such as endophthalmitis, severe bacterial keratitis, and prophylactic agents in trauma.
Table 3 lists fluoroquinolones classified by generation.4,10 *There is alternative literature that classifies moxifloxacin and gatifloxacin in the fourth generation.
| Spectrum of Activity | |
|---|---|
| First Generation: Nalidixic Acid Cinobac | Gram-negative (except Pseudomonas). I have not come across these ophthalmically due to its poor coverage overall compared to the other widely available quinolones. |
| Second Generation: Ofloxacin Ciprofloxacin | Gram-negative including Pseudomonas, some gram-positive (including S. aureus, but not S. pneumoniae). For conjunctivitis: 1 to 2 drops q2 to 4hr x 2 days, QID x 5 days. For corneal ulcer: Loading dose 1 to 2 days (q30 to q60 mins while awake); days 3+: 1 to 2 drops q1hr while awake; after signs of improvement, complete with 1 drop QID. |
| Third Generation: Levofloxacin, Gatifloxacin*, Moxifloxacin* | Same as 2nd generation with expanded gram-positive coverage. For conjunctivitis: Gatifloxacin 1 drop q2hr x 1 day (up to 8 tmes), BID to QID x 6 days; Levofloxacin: 1 to 2 drops q2 to q4hr x 2 days, QID x 5 days; Moxifloxacin 1 drop TID x 7 days. For corneal ulcer: Low risk of vision loss 1 drop q1 to q2hr (and optional addition of tobramycin or ciprofloxacin ointment QHS; moderate risk of vision loss loading dose q5min for 5 doses, then q30min until midnight, then q1hr; vision-threatening consider fortified tobramycin or gentamicin (15mg/mL) q1hr, alternating with fortified vancomycin (25mg/mL) q1hr. |
| Fourth Generation: Besifloxacin | Same as 3rd generation with broad anaerobic coverage, MRSA, and MRSE (same as gatifloxacin). |
Table 3: Courtesy of Huda Minhas, OD.
Second-generation fluoroquinolones hold well against gram-negative bacteria, but are not used as much due to their high rate of resistance versus gram-positive microbes. You’ll see ciprofloxacin used commonly to combat Pseudomonas sp. Ofloxacin has a widely available generic, which is why it is an inexpensive option for bacterial conjunctivitis.
The third- and fourth-generation fluoroquinolones are typically more popular due to their potency against gram-positive and gram-negative bacteria.10 Unfortunately, there is also increased bacterial resistance against the higher generations.
Besivance is a unique suspension that has a broad spectrum of coverage, administered TID for 5 days for acute bacterial conjunctivitis in adults and children.11 For severe infections such as bacterial keratitis, it is safe to give as a loading dose.
Check out the Reference Guide for Systemic and Topical Ocular Antibiotics
Macrolides
They are bacteriostatic with a spectrum of activity against gram-positive cocci and bacilli, Mycoplasma, Borrelia, Chlamydia, and Rickettsia. It is a great alternative to penicillin and cephalosporin hypersensitivity. The newer macrolides, such as azithromycin and clarithromycin, also have better tolerance against H. influenzae.12
Erythromycin
Erythromycin ointment is commonly used for blepharitis.13,14 It has a very good safety profile but poor resistance. Erythromycin can also be used in chlamydial infections caused by gram-positive organisms.
Conjunctivitis in a newborn can be treated with oral erythromycin suspension at 50mg/kg per day divided into four doses for at least 2 weeks. You can also use it as an alternative to tetracyclines to treat phlyctenular keratoconjunctivitis.
Azithromycin
This medication has a high tissue penetration, which makes it an excellent choice for sexually transmitted infections and it has shown success with relieving the signs and symptoms of meibomian gland dysfunction (MGD).15 It is less effective against gram-positive bacteria than erythromycin, but useful against H. influenzae, atypical Mycobacteria, and Toxoplasma gondii.
A single 1g dose of azithromycin is effective for treating chlamydial conjunctivitis and trachoma in adults, and is typically prescribed as two 500mg tablets.
You’re probably familiar with “Z-pak,” a pack of five pills prescribed two 250mg on day one followed by one 250mg tablet each day for 4 days. This antibiotic has excellent coverage even after its short course.
Topical azithromycin can also be used for conjunctivitis. Azasite is popular not only for bacterial conjunctivitis but also to stabilize meibomian gland expression.
Clarithromycin
This antibiotic is actually derived from erythromycin. It is used for systemic treatment of chronic endophthalmitis, and infectious keratitis post-laser assisted in situ keratomileusis (LASIK).
Tetracyclines
These are also bacteriostatic, with a spectrum of activity against Chlamydia, Rickettsia, Mycoplasma, and Spirochetes. It is toxic for children under the age of 12 and pregnant/nursing women. But, they are a good option for patients with allergies to penicillin and sulfa.
In addition to their antibiotic properties, they also inhibit corneal matrix metalloproteinase-9 (MMP-9), which improves corneal epithelium irregularity, MGD, and ocular rosacea-associated blepharitis and tear film stability.16
These antibiotics are divided based on the duration of action, with doxycycline being preferred due to better absorption and long action. Due to its dichotomous nature, you can prescribe it as an anti-infective at a high dosage or an anti-inflammatory at a low dosage.
For chronic MGD, you can dose it as 50mg once or twice a day for a few weeks, and then maintain it at 50mg daily for subsequent weeks. As an alternative to cephalosporin, you can dose at 100mg BID for 1 week for an internal hordeolum.17
As I mentioned above, it’s also a great medication for recurrent corneal erosions (50mg x 1 month) in conjunction with a topical corticosteroid and artificial tear ointment. Doxycycline hyclate and doxycycline monohydrate are well tolerated, but monohydrate is preferred.4 Oral tetracycline and levofloxacin are also available choices.
Peptides
Polypeptides
Bacitracin and polymyxin belong in this class, but they differ in their function and antimicrobial spectrum. Bacitracin is bacteriostatic in action but may reach bacteriocidal levels based on the concentration and susceptibility to the organism.
It is strictly against gram-positive cocci, and commonly used in staphylococcal blepharitis cases. It is also often used in combination with other antibiotics (ex., polysporin, see below). You may also use it in ointment form overnight for severe ulcerative keratitis. However, normally, a combination of fourth-generation quinolones and polysporin provides broader coverage.18
On the other hand, polymyxin B is a bactericidal agent that counteracts gram-negative organisms, P. aeruginosa in particular. Due to systemic toxicity, it is mostly used as a topical drug.
Polymyxin B combinations
- Neosporin (polymyxin B/neomycin/bacitracin)
- Dosage: Apply ointment into conjunctival sac q3 to 4hrs for 7 to 10 days, depending on the severity of infection
- Polytrim (polymyxin B/trimethoprim)
- Dosage: 1 drop q3+hrs for 7 to 10 days (maximum of six doses per day)
- Polysporin (polymyxin B/bacitracin) - only in an ointment form
- Dosage: Apply ointment q3 to q4hrs for 7 to 10 days depending on the severity of infection
Glycopeptides
These are bactericidal agents that work on gram-positive cocci and bacilli bacteria. They have little effect on gram-negative species.
Vancomycin falls under this category—because of its toxicity levels, it’s typically only used for infections caused by MRSA and penicillin-resistant S. pneumoniae.19
It is most commonly used for treatment of endophthalmitis after cataract surgery, infectious cavernous sinus thrombosis, open globe, etc. It is also used to fortify drops for severe corneal ulcers.
Aminoglycosides
These bactericidal agents include gentamicin, tobramycin, neomycin, and amikacin. Due to their poor absorption in the gastrointestinal tract, systemic agents are given parenterally.
We come across them topically, although with a poor reputation of being corneotoxic. This can be reduced by prescribing for a shorter duration.
Aminoglycosides are broad-spectrum antibiotics, including S. aureus, and gram-negative bacteria including Pseudomonas, Proteus, Klebsiella, E. coli, Enterobacter, and Serratia. They work poorly against anaerobes, and streptococci, enterococci, and MRSA. Because of this, fluoroquinolones are more often used.20,21
Dosing tobramycin
To manage mild to moderate disease, tobramycin can be prescribed 1 to 2 drops q4h; severe disease requires two drops qh until improvement, and reduced dosage until resolution.
These antibiotics can be combined with polymyxin B or another drug to expand bacterial coverage against gram-negative organisms (ex., Neosporin - polymyxin B/neomycin/bacitracin).
You may also see them combined with steroids to eradicate bacteria and decrease conjunctival hyperemia.
Steroid Combinations
- Zylet (loteprednol/tobramycin)
- Dosing: For mild to moderate ocular inflammation and/or infection 1 to 2 drops q4 to q6hrs, 1 drop QID x 7 days to treat recurrence.
- For severe inflammation/infection: Loading dose 1 to 2 drops q1 to q2hr (for 1 to 2 days). Frequency should be gradually decreased as warranted by clinical signs.
- Tobradex (dexamethasone/tobramycin)
- Dosing: Same as Zylet.
- Maxitrol (dexamethasone/neomycin/polymyxin B)
- Dosing: For mild bacterial infection 1 to 2 drops QID x 5 to 7 days.
- For severe infection: 1 to 2 drops q1hr, then taper as inflammation subsides.
- Can also be applied as ½-inch ointment BID to QID in the conjunctival sac.
- For blepharitis: Apply to eyelashes BID to TID x 7 days.
Conclusion
This review is a basic outline to understand the different kinds of antibiotics available, their classifications, and some clinical settings to apply them.
It is important to heed dosing, contraindications, adverse and drug reactions, along with your patient criteria when prescribing. Taking careful medical history is important.
You may also consider consulting with primary care physicians (PCPs) or pharmacists. There are many apps available at our fingerprints to access information. I personally use Epocrates on my iPhone. You can also reference prescribing methods in Wills Eye Manual, Sanford Guide to Antimicrobial Therapy, and Monthly Prescribing Reference.
As the need for medically-based optometric care continues to grow, it is important for today’s ODs to be knowledgeable on the myriad options for antibiotics. Providing satisfactory treatment options for patients can help avoid sight-threatening eye infections while also building doctor-patient rapport.
Don’t miss this opportunity to serve your patients while also growing your practice.
