Conjunctivitis

Bacterial conjunctivitis, commonly referred to as “pink eye,” is the most common type of ocular infection and may be caused by allergies or bacterial or viral infection. The principal causes of acute conjunctivitis in the normal host are listed in Table 72-1. Age-related factors are key in the identification of the etiologic agent. In neonates, neisserial and chlamydial infections are frequent and are acquired during passage through an infected vaginal canal. With the common practice of instilling antibiotic drops into the eyes of newborns in the United States, the incidence of gonococcal and chlamydial conjunctivitis has dropped dramatically. However, Chlamydia trachomatis remains responsible for one of the most important types of conjunctivitis, trachoma, one of the leading causes of blindness in the world, primarily in underdeveloped countries.

In children the most common causes of bacterial conjunctivitis includes Haemophilus influenzae, S. pneumoniae, and perhaps S. aureus. S. pneumoniae and H. aegyptius have been isolated from conjunctivitis epidemics. Inflammation of the conjunctiva is characterized by redness, itching, and discharge, and the condition is highly contagious; it can be transferred from one eye to the other by rubbing the infected eye and can easily be transferred to other individuals.

Numerous other bacteria may also cause conjunctivitis. For example, diphtheritic conjunctivitis may occur in conjunction with diphtheria elsewhere in the body. Moraxella lacunata produces a localized conjunctivitis with little discharge from the eye. Distinctive clinical pictures may also occur with conjunctivitis caused by Mycobacterium tuberculosis, Francisella tularensis, Treponema pallidum, and Yersinia enterocolitica.

Fungi may be responsible for this type of infection as well, often in association with a foreign body that has been introduced into the eye or an underlying host immunologic problem. However, these infections are infrequently encountered.

In adults, the etiology of conjunctivitis is usually viral, with adenovirus being the most common viral cause; 20% of such infections in children resulted from adenoviruses in one large U.S. study and 14% of infections in adult patients in another study. Adenoviruses types 4, 3, and 7A are common. Most viral conjunctivitis is self-limited but is highly contagious, with the potential to cause major outbreaks. Worldwide, enterovirus 70 and Coxsackie virus A24 are responsible for outbreaks and epidemics of acute hemorrhagic conjunctivitis.

Keratitis

Keratitis (corneal infection) may be caused by a variety of infectious agents, usually following some type of trauma to the ocular surface. Keratitis should be regarded as an emergency, because corneal perforation and loss of the eye can occur within 24 hours when organisms such as Pseudomonas aeruginosa, Staphylococcus aureus, or HSV are involved. Bacteria account for 65% to 90% of corneal infections.

In the United States, S. aureus, S. pneumoniae, and P. aeruginosa account for more than 80% of all bacterial corneal ulcers. Many culture-positive cases are now being recognized as polymicrobial. A toxic factor known as exopeptidase has been implicated in the pathogenesis of corneal ulcer produced by S. pneumoniae. With P. aeruginosa, proteolytic enzymes (Neisseria gonorrhoeae) are responsible for the corneal destruction. Gonococcus may cause keratitis in the course of inadequately treated conjunctivitis. Acinetobacter, which may look identical microscopically to gonococcus and is resistant to penicillin and many other antimicrobial agents, can cause corneal perforation. Many other bacteria, several viruses other than HSV, and many fungi may cause keratitis. Fungal keratitis is usually a complication of trauma.

Although still unusual, a previously rare etiologic agent of corneal infections has become more common in users of soft and extended-wear contact lenses. Acanthamoeba spp., free living amebae, can survive in improperly sterilized cleaning fluids and be introduced into the eye with the contact lens. The fungus, Fusarium, is emerging as an infectious disease associated with contact lens use or contact lens solutions. This genus of fungus is ubiquitous and can be found in soil and tap water and on many plants; fungal keratitis is rare but usually associated with trauma to the eye from an object contaminated with plant matter. This infection can be serious and can lead to the loss of vision. Other bacterial and fungal causes of infections have also been traced to inadequate cleaning of lenses.

Endophthalmitis

Surgical trauma, nonsurgical trauma (infrequently), and hematogenous spread from distant sites of infection are the typical routes of transmission for endophthalmitis. The infection may be limited to specific tissues within the eye or may involve all of the intraocular contents. Bacteria are the most common infectious agents responsible for endophthalmitis.

After surgery or trauma, evidence of the disease is usually identified within 24 to 48 hours. Postoperative infection involves primarily normal flora bacteria from the ocular surface. Although Staphylococcus epidermidis and S. aureus are responsible for the majority of cases of endophthalmitis following cataract removal, any bacterium, including those considered to be saprophytic, may cause endophthalmitis. In hematogenous endophthalmitis, a septic focus elsewhere is usually evident before onset of the intraocular infection. Bacillus cereus has caused endophthalmitis in people addicted to narcotics and following transfusion with contaminated blood. Endophthalmitis associated with meningitis may involve various organisms, including Haemophilus influenzae, streptococci, and Neisseria meningitidis. Nocardia endophthalmitis may follow pulmonary infection with this organism.

Mycotic infection of the eye has increased significantly since the 1980s because of the increased use of antibiotics, corticosteroids, antineoplastic chemotherapy, addictive drugs, and hyperalimentation (overeating). Fungi generally considered to be saprophytic are important causes of postoperative endophthalmitis (see Table 72-1). Endogenous mycotic endophthalmitis is most often caused by Candida albicans. High-risk patients include those with diabetes or some other chronic underlying disease. Other causes of hematogenous ocular infection include Aspergillus, Cryptococcus, Coccidioides, Sporothrix, and Blastomyces.

Endophthalmitis may be a result of viral or parasitic infections. Viral causes of endophthalmitis include HSV, varicella (herpes) zoster virus (VZV), cytomegalovirus, and measles viruses. The most common parasitic agent associated with endophthalmitis is Toxocara. Toxoplasma gondii is a well-known cause of chorioretinitis. Thirteen percent of patients with cysticercosis (Taenia solium) have ocular involvement. Onchocerca usually produces keratitis, but intraocular infection also occurs.

Periocular

Canaliculitis, one of three infections of the lacrimal apparatus (see Table 72-1), is an inflammation of the lacrimal canal and is usually caused by Actinomyces or Propionibacterium propionicum (formerly Arachnia). Infection of the lacrimal sac (dacryocystitis) may involve numerous bacterial and fungal agents; the major causes are listed in Table 72-1. Dacryoadenitis is an uncommon infection of the lacrimal gland characterized by pain of the upper eyelid with erythema and often involves pyogenic bacteria such as S. aureus and streptococci. Chronic infections of the lacrimal gland occur in tuberculosis, syphilis, leprosy, and schistosomiasis. Acute inflammation of the gland may occur during the course of the mumps and infectious mononucleosis.

Orbital cellulitis is an acute infection of the orbital contents and is most often caused by bacteria. This is a potentially serious infection because it may spread posteriorly to produce central nervous system complications. Most cases involve spread from contiguous sources such as the paranasal sinuses. In children, blood-borne bacteria, notably Haemophilus influenzae, may lead to orbital cellulitis. S. aureus is the most common etiologic agent; Streptococcus pyogenes and S. pneumoniae are also common. Anaerobes may cause a cellulitis secondary to chronic sinusitis, primarily in adults. Mucormycosis of the orbit is a serious, invasive fungal infection seen particularly in patients with diabetes who have poor control of their disease, patients with acidosis from other causes, and patients with malignant disease receiving cytotoxic and immunosuppressive therapy. Aspergillus may produce a similar infection in the same settings but also can cause mild, chronic infections of the orbit.

Newer surgical techniques involving the ocular implantation of prosthetic or donor lenses have resulted in increasing numbers of iatrogenic (resulting from the activities of a physician) infections. Isolation of Propionibacterium acnes may have clinical significance in such situations, in contrast to many other sites in which it is usually considered to be a contaminant. Nontuberculous mycobacterial pericocular infections have become increasingly important in patients with systemic disease. These infections are more prevalent in immunocompromised patients.

Other Infections

Opportunistic infections in human immunodeficiency virus (HIV)-infected individuals can involve the eye. Ocular manifestations were previously reported in up to 70% of HIV-infected patients. Systemic infections that involve the eye included cytomegalovirus, Pneumocystis jiroveci, Cryptococcus neoformans, Mycobacterium avium complex, and Candida spp. Most often the retina, choroid, and optic nerve may be infected with these agents, resulting in significant visual morbidity (unhealthy condition) if left untreated. However, because of widespread use of highly active antiretroviral therapy capable of assisting in immune system recovery and lowering the viral load in patients with HIV infection, the incidence of acquired immunodeficiency syndrome (AIDS) and related ophthalmic infections has declined sharply.

Direct Visual Examination

All material submitted for culture should be smeared and examined directly by Gram stain or other appropriate microscopic techniques. In bacterial conjunctivitis, polymorphonuclear leukocytes predominate; in viral infection, the host cells are primarily lymphocytes and monocytes. Specimens in which Chlamydia is suspected can be stained immediately with monoclonal antibody conjugated to fluorescein for the detection of elementary bodies or inclusions. Using histologic stains, basophilic intracytoplasmic inclusion bodies are seen in epithelial cells. Cytologists and anatomic pathologists usually perform these tests. Direct examination of conjunctivitis specimens using histologic methods (Tzanck smear; a scraping from the lesion for collection of cells) may reveal multinucleated epithelial cells typical of herpes group viral infections. However, DFA stains available for both HSV and VZV are recommended for rapid diagnosis of viral infections. In patients with keratitis, scrapings may be examined using Gram, Giemsa, periodic acid-Schiff (PAS), and methenamine silver stains. If Acanthamoeba or other amebae are suspected, a direct wet preparation should be examined for motile trophozoites, and a trichrome stain should be added to the regimen. For this diagnosis, however, culture is by far the most sensitive detection method for the identification of the organism. In patients with endophthalmitis, the specimen is examined using Gram, Giemsa, periodic acid-schiff (PAS), and methenamine silver stains. When submitted in large volumes of fluid, ophthalmic specimens must be concentrated by centrifugation before additional studies are performed.

Culture

Because of the constant washing action of the tears, the number of organisms recovered from cultures of eye infections may be relatively low. Unless the clinical specimen is obviously purulent, using a relatively large inoculum and a variety of media is recommended to ensure recovery of the etiologic agent. Conjunctival scrapings placed directly onto media yield the best results. At a minimum, blood and chocolate agar plates should be inoculated and incubated under increased carbon dioxide tension (5% to 10% CO₂). Because potential pathogens may be present in an eye without causing infection, it may be very helpful to culture both eyes. If a potential pathogen grows in cultures of the infected and the uninfected eye, the organism may not be causing the infection; however, if the organism only grows in culture from the infected eye, it is most likely the causative agent. When Moraxella lacunata is suspected, Loeffler’s medium may prove useful; the growth of the organism often leads to proteolysis and pitting of the medium, although nonproteolytic strains may be isolated. If diphtheritic conjunctivitis is suspected, Loeffler’s or cystine-tellurite medium should be used. For more serious eye infections, such as keratitis, endophthalmitis, and orbital cellulitis, one should always include a reduced anaerobic blood agar plate, a medium for the isolation of fungi, and a liquid medium such as thioglycolate broth. Blood cultures are also important in serious eye infections.

Specimen cultures for chlamydia and viruses should be inoculated to appropriate media from transport broth.

For Chlamydia isolation use cycloheximide-treated McCoy cells; for viral isolation the use of human embryonic kidney, primary mondey kidney and Hep-2 cell lines is recommended.

Nonculture Methods

Although acute and convalescent serologic tests for viral agents might be used in the event of epidemic conjunctivitis, they typically are not performed because the infections are self-limited. Enzyme-linked immunosorbent assay (ELISA) tests and DFA staining are available for the detection of Chlamydia trachomatis. An ELISA test of aqueous humor is available for the diagnosis of Toxocara infection. Finally, single and multiplex polymerase chain reaction (PCR) assays including both conventional and real-time formats have been used to diagnose viral and chlamydial keratoconjunctivitis and other ophthalmic infections including uveitis (inflammation in the middle layer of the eye).

Otitis Media (Middle Ear Infections)

In children (in whom otitis media is most common), pneumococci (33% of cases) and Haemophilus influenzae (20%) are the usual etiologic agents in acute disease. Group A streptococci (Streptococcus pyogenes) are the third most frequently encountered agents, found in 8% of cases. Other organisms, encountered in 1% to 6% of cases, include Moraxella catarrhalis, Staphylococcus aureus, gram-negative enteric bacilli, and anaerobes; in one recent study, M. catarrhalis, S. pneumoniae, and H. influenzae were the most common bacterial pathogens. Viruses, chiefly respiratory syncytial virus (RSV) and influenza virus, have been recovered from the middle ear fluid of 4% of children with acute or chronic otitis media. Chlamydia trachomatis and Mycoplasma pneumoniae have occasionally been isolated from middle ear aspirates. Otitis media with effusion (fluid) is considered a chronic sequela of acute otitis media. A slowly growing organism, Alloiococcus otitis is a pathogen that has been isolated from patients with otitis media with effusion.

Chronic otitis media yields a predominantly anaerobic flora, with Peptostreptococcus spp., Bacteroides fragilis group, Prevotella melaninogenica (pigmented, anaerobic, gram-negative rods), Porphyromonas, other Prevotella spp., and Fusobacterium nucleatum as the principal pathogens; less frequently present are S. aureus, Pseudomonas aeruginosa, Proteus spp., and other gram-negative facultative bacilli. Table 72-2 summarizes the major causes of ear infections.

The mastoid is a portion of the temporal bone (lower sides of the skull) containing the mastoid sinuses (cavities). Mastoiditis is a complication of chronic otitis media in which organisms find their way into the mastoid sinuses. To prevent the further spread of this infection to the central nervous system, a mastoidectomy is performed.

Direct Visual Examination

Material aspirated from the middle ear or mastoid is also examined directly for bacteria and fungi. The calcofluor white or PAS stains can reveal fungal elements. Methenamine silver stains have the added efficiency of staining most bacterial, fungal, and several parasitic species.

Culture and Nonculture Methods

Ear specimens submitted for culture should be inoculated to blood, MacConkey, and chocolate agars. Anaerobic cultures should also be set up on those specimens obtained by tympanocentesis or those obtained from patients with chronic otitis media or mastoiditis. Because cultures of middle ear effusions are culture positive for only 20% to 30% of patients, conventional and real-time PCR assays have been used to detect the common middle ear pathogens.