Conjunctivitis, which is defined as inflammation of the bulbar and/or palpebral conjunctiva (the transparent lubricating mucous membrane that covers both the surface of the eye and lining of the undersurface of the eyelids), has many etiologies, including infection from various bacteria, fungi, and viruses, as well as toxic and allergic insults. Conjunctivitis, which is also known as pink eye, is common; about 1% of all primary care office visits in the United States are related to conjunctivitis, affecting about 6 million people annually.[1, 2]
Only about 30% of primary care patients with infectious conjunctivitis are confirmed to have bacterial conjunctivitis, although 80% are treated with antibiotics.[3] The bacterial etiology often depends on geography and age, but the most common include Staphylococcus, Streptococcus, Corynebacterium, Haemophilus, Pseudomonas, and Moraxella species.
Complications can range from mild corneal irritation to severe visual loss, which develops in cases caused by extremely pathogenic bacteria, such as Chlamydia trachomatis or Neisseria gonorrhoeae. Bacterial conjunctivitis has been estimated to account for between $377 and $875 million annually in healthcare costs in the United States.[4]
Signs and symptoms
Signs and symptoms of bacterial conjunctivitis, beyond injected and edematous (inflamed) conjunctiva, include the following:
See Clinical Presentation for more detail.
Diagnosis
Routine bacterial culture is indicated for specific cases of clinically suspected bacterial disease. These are best obtained with a commercially available sterile red-top culturette using applicators that contain artificial fiber, rather than cotton-tip applicators, which have bacteriostatic properties. Although most routine cases of bacterial conjunctivitis should not require culture confirmation, certain presentations, such as the following, suggest utility to the astute clinician:
Conjunctival scrapings are often used in the diagnosis of bacterial conjunctivitis; they can be collected with topical anesthetic and gentle use of a platinum spatula or similar blunt metallic object.
Gram stain is useful for identifying bacterial characteristics, including a rough bacterial titer, a rough estimate of white blood cell (WBC) count, and the presence of chains, clusters, or intracytoplasmic inclusions.
Giemsa stain is helpful in screening for intracellular inclusion bodies of Chlamydia.
Cultures can be completed for chlamydial and other bacterial organisms, as well as for viral agents. Fungal culture would be unusual except in the setting of a corneal ulcer, a vegetative or gardening injury, or in the case of known contamination of a contact lens solution. The cellular response in conjunctivitis differs according to the cause, as follows:
See Workup for more detail.
Management
The mainstay of treatment for bacterial conjunctivitis is topical (administered as eye drops or ointment) antibiotic therapy. Systemic antibiotics are indicated for gonorrhea and chlamydial infections. Under certain circumstances, topical antibiotics may be considered of limited benefit and, considering the risks of widespread antibiotic resistance, should be withheld while the disease course resolves without treatment.[5, 6, 7]
Steroid use is controversial (see Treatment for more details).
Povidone-iodine 1.25% ophthalmic solution may be a safe and viable alternative to topical antibiotics for treating bacterial conjunctivitis,[8] especially in resource-poor countries, where antibiotics may be scarce and/or expensive. A product that contains both povidone iodide 1% and dexamethasone 0.1% is in phase III clinical trials for the treatment of viral and bacterial conjunctivitis (Shire, Dublin, Ireland).
Conjunctivitis of the bulbar and/or palpebral conjunctiva can be caused by allergies, toxins, fungi, viruses, or bacteria.
Bacterial conjunctivitis due to gram-positive bacteria such as Staphylococcus aureus or Streptococcus pneumoniae is generally milder than conjunctivitis caused by gram-negative bacteria. Mild conjunctivitis is usually benign and self-limited and can be monitored without treatment or easily treated with antibiotics. Gram-negative conjunctivitis is caused by bacteria such as Pseudomonas, Serratia marcescens, Haemophilus influenzae, Moraxella, C trachomatis, and N gonorrhoeae. Gram-negative causes of conjunctivitis are especially virulent and can lead to severe infections of the cornea and possible ocular perforation within 24-48 hours of infection. Severe conjunctivitis can cause blindness and can signify a severe underlying systemic disease.
The purpose of this article is to (1) help the practitioner recognize the characteristics and significance of bacterial conjunctivitis, (2) avoid pitfalls in diagnosis, and (3) convey appropriate treatment modalities.
Conjunctival scrapings and cultures are commonly used to guide treatment choices and confirm the microbe in severe bacterial conjunctivitis and cases that are resistant to antibiotic treatment (see Workup). The mainstay of treatment of bacterial conjunctivitis is topical antibiotic therapy. Systemic antibiotics are indicated for N gonorrhoeae and chlamydial infections. Surgical intervention is required only if the cornea is involved and results in corneal opacification (see Treatment).
See the following for more information regarding the differential diagnoses of bacterial conjunctivitis:
The surface tissues of the eye and the ocular adnexa are colonized by normal flora such as streptococci, staphylococci, and corynebacteria. Alterations in the host defense, in the bacterial titer, or in the species of bacteria can lead to clinical infection. Alteration in the flora can also result from external contamination (eg, contact lens wear, swimming), the use of topical or systemic antibiotics, or spread from adjacent infectious sites (eg, rubbing of the eyes).
The primary defense against infection is the epithelial layer covering the conjunctiva. Disruption of this barrier can lead to infection. Secondary defenses include hematologic immune mechanisms carried by the conjunctival vasculature, tear film immunoglobulins, and lysozyme and the rinsing action of lacrimation and blinking.
Bacterial conjunctivitis most often occurs in otherwise healthy individuals. Risk factors include exposure to infected individuals, fomite contact (eg, towels, napkins, pillow cases, slit-lamp chin rests and handles), contact lens wear, sinusitis, immunodeficiency states, prior ocular disease, trauma, and exposure to agents of sexually transmitted disease at birth.
Contact lens use is commonplace and thus deserves special consideration. It is known that contact lens wear, especially sleeping while wearing the lenses, is a common risk factor for bacterial corneal infection, especially in developed countries where contact lens use is more prevalent.[9] Risks for bacterial corneal infection in contact lens wearers are also known to increase with improperly maintaining contact lens integrity and contact lens case hygiene, failing to discard the contact lenses in a timely manner, and exposing the contact lenses to water (eg, swimming, showering, tap water). Allergic conjunctivitis in contact lens users is also common, and differentiation is important for appropriate treatment. It is usually prudent to treat suspected bacterial conjunctivitis in contact lens users, including discontinuing use of lenses and prescribing topical antibiotics.
Bacterial conjunctivitis is common worldwide. The estimated incidence of bacterial conjunctivitis in the United States is 135 cases per 10,000 population annually,[4] constituting approximately 1% of all primary care consultations.[10] Internationally, isolated epidemics can be devastating in areas affected by blinding infections of newborns, especially in areas heavily affected by C trachomatis,[11] which can cause blindness in up to 8% of the population.[12] Staphylococcal infection was the most common etiology in Paraguay,[13] Pseudomonas in Thailand,[14] and streptococci in India.[15]
Bacterial conjunctivitis occurs in persons of all races, although differences in frequencies may be reflected by geographical variations of pathogen prevalence.
Males and females have equal natural resistance to bacterial conjunctivitis. Differences in infection rates may reflect environmental and behavioral patterns, such as the higher rate of contact lens use among women.
Age is a relevant factor in the prevalence of bacterial conjunctivitis. In the United States, bacterial conjunctivitis is more prevalent in children than in adults; 23% of cases are reported in children aged 0-2 years, 28% in children aged 3-9 years, and 13% in children aged 10-19 years. Adults account for 36% of cases.[4, 16] H influenzae is the most common pathogen in children, followed by S pneumoniae, S aureus, and Moraxella catarrhalis. In adults, S aureus, H influenzae, S pneumoniae, and Moraxella species are the most common pathogens; MRSA prevalence has been increasing in nursing homes.
The practitioner must be vigilant in considering sexually transmitted diseases caused by N gonorrhoeae and Chlamydia in sexually active age groups and in newborns who may have been exposed during birth. Tactful and confidential history taking are a necessary skill in order to avoid violating HIPAA regulations. In an ethical or medicolegal situation, obtaining advice from administration and/or colleagues is recommended.
The prognosis for complete recovery without sequelae is excellent in bacterial conjunctivitis, as long as the cornea is not involved. Most benign cases are treated with topical antibiotics or self-resolve.[17] Bacterial conjunctivitis generally resolves within 1-2 weeks without treatment. Complications are expected to develop only in cases caused by extremely pathogenic bacteria, such as C trachomatis or N gonorrhoeae.
Mortality in the setting of bacterial conjunctivitis is related to the failure to recognize and treat the underlying disease. Sepsis and meningitis caused by N gonorrhoeae can be life-threatening.[18] Chlamydial infection in the newborn can lead to pneumonia and/or otitis media.[19]
Signs and symptoms of discomfort, mucopurulent ocular discharge, and conjunctival redness are common in benign cases and often lead to absence from work and school to minimize the risk of infection to others. Morbidity can be associated with misdiagnosis. Since many eye diseases cause the eye to be red, it is beneficial to have a solid clinical approach to differential diagnoses of the red eye, as well as an effective referral paradigm in the primary care setting. Diagnoses often missed by non–eye-care providers (providers other than ophthalmologists and optometrists) include acute glaucoma; iritis; bacterial, fungal, and parasitic keratitis; corneal foreign bodies; conjunctival and tarsal foreign bodies; herpetic dendritic keratitis; scleritis; and subconjunctival hemorrhage, among others.
To prevent bacterial conjunctivitis, patient education should include good hygiene (eg, washing hands with soap and water) and avoidance of touching the eyes, especially after exposure to potentially infectious sources. Proper contact lens care includes avoidance of contact lens wear while sleeping and proper cleaning and discarding of both lenses and contact lens cases.
Patients with bacterial conjunctivitis should be instructed not to touch their eyes and to avoid sharing fomites. They should also be educated regarding their infectious nature to prevent transmission and the importance of finishing their antibiotic regimen. Patients with bacterial conjunctivitis who wear contact lenses should be instructed to discontinue contact lens use and to discard their used contact lenses, open contact lens solutions, used contact lens cases, and used makeup and makeup brushes.
The choice of questions to ask when eliciting a clinical history from the patient is influenced by such factors as age, occupation, and social habits. It may occasionally focus on sensitive issues that can be embarrassing to discuss.
Most cases of bacterial conjunctivitis are bilateral, although the time of onset may vary. Most cases of bacterial conjunctivitis occur in otherwise healthy individuals. In these cases, the history should take the following factors into consideration:
Venereal diseases should be considered in patients at a sexually active age. Consider the following:
Conjunctival injection may be present segmentally or diffusely. The everted inferior or superior palpebral conjunctival pattern may hold clues to the etiology.
Using slit-lamp biomicroscopy and everting both the upper and lower eyelids, follicles or papillae can be identified on the inflamed conjunctiva. Follicles, more common in the lower lid conjunctiva, have blood vessels that circumscribe the base of tiny elevated lesions. Follicles are characteristic of a hypersensitivity conjunctivitis (eg, due to brimonidine [Alphagan] or trifluorothymidine [Viroptic] drops), viral conjunctivitis, or chlamydial conjunctivitis or allergy to contact lens solution preservatives. Papillae, seen commonly in the conjunctiva of the upper lid, have vessels coming up the center of the tiny elevated lesion and are characteristic of bacterial or allergic conjunctivitis.
The discharge in bacterial conjunctivitis is typically more purulent than the watery discharge of viral or allergic conjunctivitis. Thus, there is more "mattering" of the lid margins and associated difficulty in prying the lids open following sleep. The mucopurulent discharge can appear white, yellow, or even greenish in color.
In uncomplicated bacterial conjunctivitis, slit lamp examination reveals a quiet anterior chamber that is devoid of cells and flare. The vitreous is also unaffected.
A preauricular lymph node is unusual in bacterial conjunctivitis but can be present in severe conjunctivitis caused by N gonorrhoeae. This key finding is also strongly associated with viral ocular syndromes, typically herpes simplex keratitis and epidemic keratoconjunctivitis.
Eyelid edema is often present, but it is mild in most cases of bacterial conjunctivitis. Severe lid edema in the presence of copious purulent discharge raises the suspicion for N gonorrhoeae infection.
Visual acuity is preserved in bacterial conjunctivitis as long as the cornea is intact, except for the expected mild blur secondary to the discharge and debris in the tear film. Some patients may inadvertently abrade their own corneas out of symptomatic frustration, leading to worse vision, even more discomfort, and increased morbidity. Rarely, topical anesthetic abuse can initiate or exacerbate this complication.
The pupil reacts normally in bacterial conjunctivitis. Anisocoria or a fixed pupil in the setting of a red eye should raise the suspicion for angle-closure glaucoma or iritis with posterior synechiae.[5]
Extreme unilateral dilation and tortuosity of the major conjunctival blood vessels suggests a cavernous sinus-carotid artery fistula rather than conjunctivitis.
Bacterial conjunctivitis, as long as the cornea is not affected, seldom leads to complications.
General concerns include membrane formation, severe postrecovery dry eye, and subsequent scarring of the punctum; corneal ulcer when the epithelium is not intact; and symblepharon from severe inflammation. Organisms most commonly associated with membrane formation and conjunctival scarring include adenovirus (epidemic keratoconjunctivitis [EKC]), N gonorrhea, and exotoxin-producing S pneumoniae.
In eyes with previous intraocular surgery, particularly with filtering blebs, endophthalmitis could result.
A medical and detailed ocular history includes questions about the onset and duration of the red eye, the quality and quantity of discharge, presence or absence of pain, photophobia, trauma, blurry vision, foreign body sensation, ocular itch, contact lens use, history of previous ocular infections, and current and recent medication use. An eye evaluation should be performed with particular attention to reductions in best corrected vision in either eye, gross evaluation of lid margins and both bulbar and tarsal conjunctivae (presence or absence of a ciliary flush), any ocular discharge, pupillary reactions, any pain with eye movements, slit lamp biomicroscope evaluation of the cornea (with adjunctive fluorescein stain), IOP, and anterior chamber flare or cell. If only one eye has bacterial conjunctivitis, examine the unaffected eye first to prevent cross-infection.
Many astute eye-care providers use a long-wooded cotton-tipped applicator while examining patients. Thus, the ocular tissues are never touched by the examiner’s fingers. This approach can markedly reduce the potential for cross-contamination between eyes, as well as transmission to the examining physician and subsequent patients.
Traditional teaching suggests that significant eye pain, loss of vision, and photophobia are indications of serious eye disease. Anisocoria and ocular pain during pupillary constriction (even during a pencil push-up test) can also indicate serious eye diseases.[5] However, note that the absence of photophobia and anisocoria does not rule out the possibility of such serious diseases. Conversely, complete redness of the conjunctiva obscuring the tarsal vessels, purulent discharge, matting of both eyes in the morning, and onset during winter or spring all increase the probability of bacterial conjunctivitis.[5] If the patient has symptoms of itchy eyes and recurrent conjunctivitis, bacterial conjunctivitis is unlikely.[21] Dense deep-red to violaceous coloring of the conjunctiva that does not blanche with topical sympathomimetics (eg, phenylephrine 2.5%) indicates scleritis in the context of significant pain.
Conjunctival scrapings and cultures are frequently obtained in severe bacterial conjunctivitis or if there is corneal involvement, especially when the central cornea is affected, multiple keratitis lesions are present, any corneal ulcer is 2 mm or larger in diameter, or antibacterial therapy is ineffective. Gram staining and cultures should be grown in blood agar, chocolate agar, Sabouraud dextrose agar, and thioglycollate broth.
Imaging studies do not play a significant role in the workup of bacterial conjunctivitis unless an underlying condition is suspected. For example, MRA, CT scan, and orbital color Doppler may play a role in a suspected cavernous sinus fistula. Orbital CT scan may be indicated to rule out an orbital abscess or pansinusitis, when the conjunctivitis is coincident to orbital cellulitis.
Certain procedures may address a known or suspected underlying cause for conjunctivitis or conditions that mimic it. Removal of offending lashes with epilation forceps or by electrolysis may be indicated for trichiasis. Nasolacrimal duct irrigation may be attempted to see if an obstruction that predisposes to infection is present. An obstruction should be suspected in chronic and intermittent purulent conjunctivitis. Eversion of the eyelid at the slit lamp is indicated when a foreign body is suspected.
Conjunctival scrapings can be performed with topical anesthetic and gentle use of a platinum spatula or similar blunt metallic object. This should precede antibiotic therapy. Gram stain is useful to identify bacterial characteristics. Giemsa stain is helpful to screen for intracellular inclusion bodies of Chlamydia. Cultures can be completed for viral, chlamydial and bacterial agents. If testing for N gonorrhoeae, specific procedures should be followed to optimize the yield. The anesthetic agent should be preservative-free, in order to limit false-negative culture results (Tetracaine, Alcon).Fungal culture is usually unnecessary, except in the setting of a corneal ulcer or in the case of known contamination of a specific contact lens solution, such as occurred in the contamination epidemic of early 2006.[22]
Additionally, the nature of the inflammatory reaction is reflected in the cellular response. Lymphocytes predominate in viral infections, neutrophils in bacterial infections and eosinophils in allergic reactions.
Bacterial conjunctivitis generally last 1-2 weeks and is usually self-limiting. The mainstay of treatment for bacterial conjunctivitis is topical antibiotic therapy, with the intent of significantly reducing the duration of symptoms and likelihood of contagion. Ideally, the antibiotic should be specific for the causative organism. Unfortunately, bacterial culturing, although recommended, is not always available nor cost-effective for routine cases, and Gram stain may take several days to yield results.
For mild and non–vision-threatening bacterial conjunctivitis, older-generation antibiotics should be used. Later-generation antibiotics should be reserved for more serious infections to minimize creation of bacterial resistance in the ocular surface flora.[23] For moderate to severe bacterial conjunctivitis, the latest-generation fluoroquinolones provide excellent gram-negative and some gram-positive bacterial coverage. Fortified antibiotics are also used in severe cases. Systemic antibiotics are indicated for N gonorrhoeae and chlamydial infections. Surgical intervention is required only when indicated for the treatment of causative conditions, such as hordeolum, nasolacrimal duct obstruction, or sinusitis.
Steroid use in combination with antibiotics is controversial, and results are mixed in terms of decreasing corneal scarring.[24, 25] Unfortunately, steroids may slow the rate of healing, increase the risk of corneal melting, and increase the risk of elevated IOP.
Povidone-iodine solution 1.25% ophthalmic solution may be a safe and viable alternative to topical antibiotics for treating bacterial conjunctivitis,[8] especially in resource-poor countries, where antibiotics may be hard to come by and/or expensive.
Inpatient care for bacterial conjunctivitis is highly unusual and would be provided only if hospitalization is indicated for other reasons or if antibiotic treatment is required every 15 minutes around the clock (severe cases). It is important to realize that, in the inpatient setting, the differential diagnoses must be carefully considered through internal medicine consultation since these patients tend to be ill. Therefore, it is more common to see a red eye due to endogenous endophthalmitis, hyperacute gonorrheal conjunctivitis, orbital cellulitis, or a perforated corneal ulcer in this population.
Serious consideration should be given to admitting patients with hyperacute bacterial conjunctivitis if the entire cornea cannot be visualized, as there may be an early peripheral corneal ulceration threatening perforation, especially in Neisseria infections.[18] Topical antibiotic, proper hygiene, and isolation are considerations for these patients.
Be aware of drug alerts, such as the Fusarium keratitis outbreak related to ReNu with MoistureLoc (Bausch & Lomb) in 2006 and the Acanthamoeba keratitis outbreak in 2003-2006 related to Complete Moisture Plus (AMO).[22]
Also of special concern is trachoma, a devastating disease common in third-world countries characterized by chronic infection during youth and potentially blinding corneal and conjunctival scarring in mid-life. Although acute hospitalization is uncommon for trachoma, hospital-based preventive lid surgeries are central to trachoma management paradigms. See Trachoma.
Instruct patients to return for follow-up in a timely manner or if they do not recover completely, so that therapy can be reassessed. Consider culture and conjunctival scrapings for resistant cases.
Please see the following for more information:
Practice patterns for prescribing topical antibiotics vary. For routine mild cases of bacterial conjunctivitis, most practitioners prescribe a broad-spectrum agent on an empirical basis without obtaining a culture. Always be aware of the differential diagnosis by taking thorough case histories and careful evaluation of the ocular surface. Instruct patients to seek follow-up care if the expected improvement does not occur or if vision becomes affected.
For mild and non–vision-threatening bacterial conjunctivitis, older-generation antibiotics should be used. Later-generation antibiotics and the latest fluoroquinolones should be reserved for more serious infections to minimize the risk of developing microbial resistance.[23] The following are older topical antibiotics that remain efficacious:
For moderate and severe bacterial conjunctivitis, the latest fluoroquinolones, including moxifloxacin, besifloxacin, and levofloxacin, are generally effective. Rare severe infections may also require patient hospitalization to ensure consistent administration of fortified aminoglycoside-cephalosporin combination therapy, fortified topical vancomycin, or topical fluoroquinolone monotherapy treatment every 15 minutes to hourly. All are effective treatments, although fortified antibiotics must be prepared without preservatives in compounding pharmacies and must remain refrigerated because of their shorter shelf life.
Bacterial culture is the recommended method of diagnosing chlamydial and gonococcal infections in newborns. RNA probe technology and immunoassays developed for the obstetrical industry are also potentially useful.
Chlamydial infection of the newborn requires systemic treatment of the neonate, the mother, and at-risk contacts. The neonate may be treated with erythromycin orally in liquid form 50 mg/kg/d in 4 divided doses for 2 weeks. Some newborns also require a second dose. These patients are also susceptible to chlamydial pneumonitis and otitis media. The mother and at-risk contacts may be treated with doxycycline 100 mg orally twice daily for 7 days.
N gonorrhoeae infection of the newborn also requires systemic treatment of the neonate, the mother, and at-risk contacts. The neonate may be treated with intravenous aqueous penicillin G 100 units/kg/d in 4 divided doses for 1 week. The mother and at-risk contacts may be treated with a single dose of intramuscular ceftriaxone 125 mg followed by oral doxycycline 100 mg twice daily for 7 days. Strict daily attention to the peripheral cornea, conjunctival scarring, and membrane formation allows timely surgical action: corneal cyanoacrylate glue for corneal melts and glass rod lysis of the conjunctival membranes destined to become symblepharons without intervention. Amniotic membrane therapy may also be beneficial in more extreme cases.
Prophylaxis against ophthalmia neonatorum is a major force in the worldwide effort to prevent blindness.[26] Common regimens are the instillation of 1% silver nitrate solution, 1% tetracycline ointment, or 0.5% erythromycin ointment. Relatively inexpensive povidone iodide is also gaining popularity in this role.[8]
Hygiene and avoidance of close patient contact and fomites deter bacterial conjunctivitis with infected individuals. Patients and household members should be educated to pay attention to hygiene and the avoidance of close proximity with the infected individual. It is customary to advise the infected individual to avoid sharing napkins, towels, pillow cases, and linens.
A patient with bacterial conjunctivitis should wash hands often and avoid contaminating public swimming pools. Workers and students often are excused from work or school during the first several days of treatment to decrease the possibility of spread.
Consultations with an infectious disease specialist and/or a pediatrician may be indicated in suspected or proven chlamydial or N gonorrhoeae infections.
An experienced ophthalmic pathologist can be an excellent resource in determining the cause of a resistant conjunctivitis by interpreting conjunctival scrapings.
Most bacterial conjunctivitides are self-limiting,[10] although topical antibiotics are recommended[27] because they can shorten the duration of the disease[28] and prevent the spread of infection. Broad-spectrum antibiotics are generally used empirically as first-line therapy for bacterial conjunctivitis. Topical as opposed to oral antibiotics are recommended to deliver high levels of the drug directly to the site of infection, exceeding what is normally achieved in body tissues by oral or parenteral routes. Therefore, the antibiotic action of the individual drug is enhanced.
For severe conjunctivitis marked by copious purulent discharge and eye inflammation, cultures are needed to guide the choice of antibiotic. Fortified antibiotics such as combination aminoglycosides and cephalosporins have a similar efficacy profile to fluoroquinolones. However, resistance to early-generation fluoroquinolones, moxifloxacin, and levofloxacin has been increasing, while some resistance profiles, particularly in multidrug-resistant staphylococci, appear to be more favorable for besifloxacin.[29, 30] Oral antibiotics are recommended for gonococcal and chlamydial infections.
Clinical Context: Besifloxacin is a broad-spectrum fluoroquinolone antimicrobial ophthalmic suspension indicated for bacterial conjunctivitis approved for both children and adults to be used tid for 7 days. This agent is available as a 0.6% ophthalmic suspension. It has no human systemic formulation or animal use, thereby lowering the rate of bacterial resistance. Susceptible bacteria include CDC coryneform group G (Corynebacterium pseudodiphtheriticum, Corynebacterium stratum), H influenzae, Moraxella lacunata, S aureus, Staphylococcus epidermidis, Staphylococcus hominis, Staphylococcus lugdunensis, Streptococcus mitis, Streptococcus oralis, S pneumoniae, Pseudomonas aeruginosa, and Streptococcus salivarius.
Clinical Context: A so-called fourth-generation fluoroquinolone ophthalmic indicated for bacterial conjunctivitis, gatifloxacin elicits a dual mechanism of action by possessing an 8-methoxy group, thereby inhibiting the enzymes DNA gyrase and topoisomerase IV. DNA gyrase is involved in bacterial DNA replication, transcription, and repair. Topoisomerase IV is essential in chromosomal DNA partitioning during bacterial cell division.
Gatifloxacin is indicated for bacterial conjunctivitis due to Corynebacterium propinquum, S aureus, S epidermidis, S mitis, S pneumoniae, or H influenzae.
Clinical Context: Moxifloxacin is another fourth-generation fluoroquinolone indicated for bacterial conjunctivitis due to H influenzae, S pneumoniae, and anaerobic bacteria. Compared to earlier-generation fluoroquinolones such as levofloxacin and ciprofloxacin, it is more effective against gram-positive bacteria and anaerobes. Moxifloxacin is self-preserved and, as such, contains no benzalkonium chloride (BAK) or other preservatives.
Clinical Context: Levofloxacin is a third-generation fluoroquinolone and an S (-) enantiomer of ofloxacin. It inhibits DNA gyrase in susceptible organisms, thereby inhibiting relaxation of supercoiled DNA and promoting breakage of DNA strands. It has enhanced activity against S pneumoniae relative to earlier fluoroquinolone derivatives such as ciprofloxacin but is less effective than ciprofloxacin against gram-negative bacteria, especially P aeruginosa. It may also not be as effective against MRSA compared to moxifloxacin or gatifloxacin.
Clinical Context: Ciprofloxacin is a second-generation fluoroquinolone that inhibits bacterial growth by inhibiting DNA gyrase. It is very commonly prescribed for a wide variety of systemic, cutaneous, respiratory, and genitourinary infections. It is indicated for superficial ocular infections of the conjunctiva or cornea caused by strains of microorganisms susceptible to this agent. It is effective in most cases of routine conjunctivitis, including those caused by S aureus, group A streptococci, H influenzae, and P aeruginosa. It may not cover all cases of S pneumoniae infection. Ciprofloxacin is the most effective of all fluoroquinolones against P aeruginosa infections, both superficial and systemic. Owing to its solubility profile, Ciloxan may leave precipitates because of its relative insolubility in corneal ulcers or epithelial defects, often imitating an infiltrate to the unaware observer. Ciprofloxacin is available as a topical ophthalmic, topical external auditory, and oral and IV preparation.
Clinical Context: Ofloxacin is a second-generation fluoroquinolone. A pyridine carboxylic acid derivative with broad-spectrum bactericidal effect, ofloxacin inhibits bacterial growth by inhibiting DNA gyrase. It is indicated for superficial ocular infections of the conjunctiva or cornea caused by susceptible strains of microorganisms. Generic preparations are generally readily available.
Clinical Context: Tobramycin is an aminoglycoside antibiotic that interferes with bacterial protein synthesis by binding to 30S and 50S ribosomal subunits, which results in a defective bacterial cell membrane. It has a narrow spectrum but is effective against gram-negative organisms, especially P aeruginosa, as well as many strains of MRSA and MRSE. It is available as a solution, ointment, and lotion and has been combined with steroids for combination antibiotic/steroid drops.
Clinical Context: Gentamicin is another commonly prescribed generic topical aminoglycoside antibiotic used for gram-negative bacterial coverage, including Pseudomonas and gram-positive Staphylococcus. Gentamicin is commercially available in solution or ointment form. Long-term or repeated use of topical aminoglycoside antibiotics can produce significant corneal toxicity, as well as resistant ocular-surface flora.
Clinical Context: Polymyxin B is primarily used systemically for multidrug-resistant gram-negative organisms including P aeruginosa and is very ineffective against gram-positive organisms. In topical form, it is useful for broader gram-negative coverage. The trimethoprim component is generally effective against staphylococci and most gram-positive organisms, as well as some gram-negative aerobic bacilli and Escherichia coli. Because it is particularly effective against S pneumoniae and H influenzae, which affect primarily children, it is the antibiotic of choice in pediatric patients. The combination is an ophthalmic drop to be used q4h for 7-10 days.
Clinical Context: Neomycin is an aminoglycoside antibiotic used for treatment of minor infections; it inhibits bacterial protein synthesis and growth. Polymyxin B disrupts the bacterial cytoplasmic membrane, permitting leakage of intracellular constituents and causing inhibition of bacterial growth. Neosporin is available as an ophthalmic ointment and a drop to be used q4h for 7-10 days.
Clinical Context: Neomycin has excellent activity against gram-negative organisms and partial activity against gram-positive bacteria. The combination with polymyxin B and bacitracin covers a broad spectrum of gram-positive, gram-negative, and anaerobic micro-organisms. This combination is available in ointment form because of the insolubility of the bacitracin constituent.
Clinical Context: This second-generation ophthalmic macrolide antibiotic is indicated for bacterial conjunctivitis caused by CDC coryneform group G bacteria, H influenzae, S aureus, S mitis group, and S pneumoniae. It is especially effective against pediatric conjunctivitis owing to its efficient dosage regimen requiring only 9 drops of medication over 7 days. Clinical trials demonstrate superior efficacy with azithromycin in comparison to tobramycin. Its highly viscous mucoadhesive vehicle (Durasite) allows bid dosing the first 2 days and then qd for 5 more days. The decreased dosing allows for better patient compliance and hence quicker resolution of the conjunctivitis. Systemic and topical azithromycin have also exhibited anti-inflammatory properties through inhibition of the matrix metalloprotease 9 (MMP-9) pathway.
Clinical Context: Topical erythromycin ointment is indicated for infections caused by susceptible strains of primarily gram-positive microorganisms and for prevention of corneal and conjunctival infections. It is effective in most cases of bacterial conjunctivitis, including those caused by S aureus, group A streptococci, S pneumoniae, and H influenzae. Because of the high level of bacterial resistance to this antibiotic, it has limited clinical use and is available only in ointment form because of its insolubility.
Clinical Context: Bacitracin prevents transfer of mucopeptides into growing cell wall, inhibiting bacterial growth. It a mixture of cyclic peptides that are effective against both gram-positive and gram-negative bacteria. Most cases of routine bacterial conjunctivitis will respond to bacitracin, including those caused by group A streptococci, S aureus, S pneumoniae, and H influenzae. It is a highly effective against gram-positive pathogens. Because it is available only in an ointment form because of its insolubility, the blurring of vision often limits its practical use to primarily off-label night-time–only prophylactic administration. It is not available systemically owing to nephrotoxicity.
Clinical Context: A 1-gram single dose, generally in combination with IM or IV ceftriaxone to cover N gonorrhea, is an effective treatment, as the drug of choice for adult inclusion (chlamydial) conjunctivitis concomitant to genitourinary chlamydial infection. Because chlamydial conjunctivitis must always be assumed to accompany genitourinary infection, systemic therapy is always indicated. This includes diagnostic confirmatory testing, as well as epidemiologic pursuit of all sexual contacts. Azithromycin has broad but shallow antibacterial activity effective against some gram-positive bacteria, some gram-negative bacteria, and many atypical bacteria. Systemic azithromycin is also widely used to treat routine upper and lower respiratory infections, usually in the form of the 5-day 6-pill Z-pack.
Clinical Context: Doxycycline inhibits protein synthesis and thus bacterial growth by binding to 30S and possibly 50S ribosomal subunits of susceptible bacteria. Doxycycline is a tetracycline antibiotic that is effective in the treatment of adult chlamydial infections, Lyme disease, and a wide variety of respiratory and cutaneous infections. The dosage is 100 mg orally twice a day for 7 days for routine infections and 100 mg PO BID for one month to treat primary Lyme disease. In addition, doxycycline is frequently used for its anti-inflammatory, anti-MMP-9, and meibomian liquification properties in patients with cutaneous diseases such as rosacea, as well as for chronic blepharitis. Long-term administration in doses as low as 20 mg or 50 mg PO daily is often sufficient to control inflammation. Patients prescribed doxycycline and other tetracycline derivatives should always understand photosensitivity, gastrointestinal, and pregnancy precautions.
Clinical Context: Erythromycin inhibits bacterial growth, possibly by blocking dissociation of peptidyl t-RNA from ribosomes, causing RNA-dependent protein synthesis to arrest. Oral erythromycin is effective in the treatment of chlamydial infections. Erythromycin base 500 mg orally four times a day for 7 days or erythromycin ethylsuccinate 800 mg orally four times a day for 7 days are effective treatments for chlamydial infections. Gastrointestinal side effects render erythromycin a secondary choice for chlamydial disease.
Clinical Context: Levofloxacin inhibits bacterial topoisomerase IV and DNA gyrase, which are required for bacterial DNA replication and transcription. This is the L stereoisomer of the D/L parent compound ofloxacin, the D form being inactive. Administer 500 mg orally once daily for 7 days for chlamydial infection. Levaquin is available in generic form and, along with ciprofloxacin, is among the most frequently prescribed oral fluoroquinolones used for respiratory and genitourinary infections.
Clinical Context: Used to treat complicated and uncomplicated skin and skin structure infections, ofloxacin and other fluoroquinolones have an exceptional safety profile. Ofloxacin provides good monotherapy with extended coverage against Pseudomonas species, as well as excellent activity against pneumococcus. This agent acts by inhibition of DNA gyrase activity. The oral form has a reported bioavailability of 99%. Administer 300 mg orally twice daily for 7 days for chlamydial infections.
Clinical Context: Ceftriaxone is a third-generation cephalosporin that arrests bacterial growth by binding to one or more penicillin-binding proteins. It has lower efficacy against gram-positive organisms but has excellent activity against susceptible pneumococcal organisms. It exerts an antimicrobial effect by interfering with the synthesis of peptidoglycan, a major structural component of the bacterial cell wall. It is highly effective against N gonorrhea as a single 1-gram dose. It is used IM and IV for a wide variety of cutaneous, respiratory, and genitourinary infections.
Clinical Context: Penicillin interferes with synthesis of cell wall mucopeptide during active multiplication, resulting in bactericidal activity against susceptible microorganisms. It is used in the hospital setting for neonatal gonorrheal infections.
Most cases of routine bacterial conjunctivitis respond to the commercially available combination of antibiotics, artificial tears, lid scrubs, oral analgesics, and, often, a topical antihistamine to relieve itching and discomfort.
Although the aminoglycosides are used in other fields of medicine primarily to treat gram-negative bacteria, the spectrum of efficacy expands to include gram-positive bacteria when used topically for conjunctivitis. Aminoglycosides are not used orally and hence have lower rates of systemic bacterial resistance. They are especially effective against gram-negative organisms. These are also useful in mild bacterial conjunctivitis. Polymyxin B with trimethoprim is also efficacious for mild conjunctivitis, especially in pediatric patients, but it may blur visions because it is in an ointment form. Both aminoglycosides and polymyxin B/trimethoprim are significantly more effective against methicillin-resistant staphylococci than most fluoroquinolones or sulfonamides.
Fluoroquinolones inhibit bacterial DNA gyrase and topoisomerase IV. They offer broad-spectrum coverage for bacterial conjunctivitis; however, owing to antibiotic overuse and misuse, bacterial resistance is increasing for this class of antibiotics, especially among older-generation fluoroquinolones. Fluoroquinolones have gained popularity in ocular therapy owing to their efficacy in the treatment of bacterial corneal ulcers, although many bacterial-resistant strains are also emerging in keratitis. Later-generation fluoroquinolones should be reserved for more severe cases of conjunctivitis. Older fluoroquinolones are effective for milder infections.
Regardless of the topical antibiotic regimen chosen, start off with a higher frequency of dosing (eg, q2h) for the first 1-2 days before decreasing the dosage (eg, qid) for the subsequent 5-7 days. Reiterate to the patient the importance of compliance with antibiotic drugs to ensure conjunctivitis resolution and especially to prevent bacterial resistance.
Neonatal chlamydial infection is treated with oral erythromycin. Doxycycline is used to treat the mother of a neonate with chlamydial infection as well as her at-risk contacts.
Intravenous penicillin G is used for neonatal gonorrhea infections. Third-generation cephalosporins are used in the treatment of adult gonorrhea infections.