Infections due to anaerobic bacteria are common in children. The recent increased recovery of these organisms from children has led to greater appreciation of the role anaerobes play in pediatric infections at all body sites, including the eye.
Anaerobes are the predominant components of the normal bacterial flora of human skin and mucous membranes, and are therefore a common cause of bacterial infections of endogenous origin.1 Because of their fastidious nature, these organisms are difficult to isolate from infectious sites and are often overlooked. Their exact frequency is difficult to ascertain because of the inconsistent use of adequate methods for their isolation and identification. The lack of directing adequate therapy against these organisms may lead to clinical failures. Their isolation requires appropriate methods of collection, transportation, and cultivation of specimens. Treatment of anaerobic infection is complicated by the slow growth of these organisms, their polymicrobial nature, and the growing resistance of anaerobic bacteria to antimicrobials.
This review describes the microbiology and management of ocular infections due to anaerobic bacteria in children.
Conjunctivitis is defined as redness of the conjunctivae associated with hyperemia and congestion of the blood vessels, with varying severity of ocular exudate. Preauricular adenopathy may be present.
Although many infective agents can cause conjunctivitis, recognition of acute bacterial conjunctivitis is of utmost importance because of the rapidity of its development and its potential to cause irreversible ocular damage. Viruses, chlamydiae, rickettsiae, fungi, parasites, and numerous noninfectious agents and metabolic diseases may all cause conjunctivitis. Therefore, it is important to arrive at a specific diagnosis for selection of appropriate antimicrobial therapy.
The most common aerobic bacteria causing conjunctivitis in children are Haemophilus influenzae (mostly non-typable), Streptococcus pneumoniae, Streptococcus pyogenes, other streptococci (mostly Streptococcus mitis), Moraxella spp., Staphylococcus aureus, and Staphylococcus epidermidis. Others include Neisseria gonorrhoeae, Neisseria meningitidis, gram-negative rods such as Pseudomonas and Proteus, and Corynebacterium spp.2–4 The pneumococci, Pseudomonas spp., and Peptostreptococcus spp. have a high tendency for corneal ulceration. The most common viral causes are adenovirus, herpes simplex, and picornavirus. The organisms associated with illness were found in a study of 99 children to be H. influenzae (42% of patients), S. pneumoniae (12%), and adenoviruses (20%).2 Another study of 95 children found 78% to have bacterial etiology and 13% viral cause.3
We described the recovery of gram-positive anaerobic cocci in statistically significant higher numbers from inflamed conjunctivae of adults and children compared to recovery from uninflamed conjunctivae in two studies.5,6 Since the conclusion of these studies, we have recovered anaerobes from 95 more cases of conjunctivitis. The predominant organisms recovered were Clostridium spp. (14 isolates), gram-negative anaerobic bacilli (12 isolates), and Peptostreptococcus spp. (13 isolates).
In the pediatric population that was studied,6 aerobic and anaerobic cultures and clinical data were obtained from 126 patients with acute conjunctivitis. Similar cultures were obtained from 66 children who did not have conjunctival inflammation. Anaerobes were isolated from 47 patients (37.3%). They were in mixed cultures with aerobes in 26 patients (20.6%) and they were the only isolates in 21 patients (16.7%). Aerobes alone were recovered from 72 patients (57.1%). No bacterial growth was noted in 7 patients (5.6%). The organisms recovered from eyes with conjunctivitis in statistically significant numbers were S. aureus, S. pneumoniae, H. influenzae, and anaerobic gram-positive cocci.
Other anaerobes occasionally found in the infected eyes were Bacteroides fragilis, pigmented Prevotella and Porphyromonas, fusobacteria, and bifidobacteria. Of special note is that 38% of inflamed conjunctivae contained more than one organism. Anaerobes were reported in a case of chronic conjunctivitis in which Prevotella intermedia and Peptostreptococcus micros were the causative organisms.7
Aggarwal et al.8 processed 138 eye specimens in children and adults for aerobic and anaerobic cultures. Clinical data were obtained from 50 patients with unilateral ophthalmic infection. Cultures from the uninfected eye of 38 of these 50 patients were also processed for comparison. In addition, 50 cultures were obtained from one or both eyes of 30 healthy control subjects who had no eye infection.
In their study, anaerobes and aerobes were isolated from infected eyes of 6 (12%) and 37 (74%) patients, respectively. No growth was observed in the infected eye of 8 (16%) patients. A mixture of aerobes and anaerobes were recovered in only 2 cases. Of the total 47 aerobic isolates from infected eye specimens, S. aureus (11), S. epidermidis (12), and S. pneumoniae (9) were the predominant isolates. Six anaerobe isolates included gram-positive nonspore-forming anaerobic bacilli (4 including P. acnes) as predominant isolates. Clostridium perfringens was isolated from a case of postoperative endophthalmitis. Although the number and types of aerobic bacteria were similar in the uninfected eye of the same patients, no cultures grew any anaerobes. Aerobic and anaerobic bacteria were isolated in 70% and 6% of eye swabs, respectively, from the healthy control subjects.
We have also recovered anaerobic bacteria from 6 patients (2 of whom were children) who wore contact lenses and developed conjunctivitis.9 The 10 anaerobes recovered included Peptostreptococcus spp. (3 isolates), Bacteroides spp. (2 isolates), and Fusobacterium spp. (2 isolates).
Organisms can be transmitted to the ocular surface through a variety of modes, but direct contamination by the fingers is the most common. Most bacterial pathogens are also found in the nasopharynx. Microorganisms can also be inoculated by airborne droplets (eg, by sneezing and coughing) or by contact with fomites. Most studies of the bacterial flora of acute conjunctivitis have failed to record the presence of anaerobic bacteria. Appropriate culture media and proper anaerobic techniques were not employed in these studies, although occasional reports document anaerobes as part of the normal flora in conjunctivitis and other minor eye infections and in panophthalmitis.10,11 A higher incidence of anaerobes was also found in patients with acquired immunodeficiency syndrome.11Clostridium spp.,12–14 nonspore-forming anaerobic organisms,15Actinomyces spp.,16 and anaerobic gram-positive cocci were recovered from various infections of the eye.
Gram-positive anaerobic cocci are well-documented pathogens. They are commonly isolated from pulmonary infections,17 infections of the female genital tract,18 and soft-tissue infections.19 Although the findings of increased numbers of gram-positive anaerobic cocci in inflamed conjunctivae may be due to their active role in the inflammatory process, it also could be incidental, resulting from inflammation from other causes.
Studies conducted in adults11,20 demonstrated the presence of P. acnes in the conjunctival sac of uninflamed eyes and an increased rate of recovery of peptostreptococci from patients with conjunctivitis. A statistically significant increase in the numbers of anaerobic gram-positive cocci in inflamed eyes also was demonstrated in the pediatric study group.6
The recovery of anaerobes in the normal flora of the conjunctival sac does not exclude their ability to become pathogenic under the right circumstances. This can occur when foreign bodies, injuries, and underlying noninfectious diseases favor the establishment of conjunctival infections, thus allowing the resident organisms to become pathogenic. The anaerobes recovered from children with conjunctivitis are all part of the normal oral and skin flora.
Children often introduce saliva and its oral flora into their conjunctival sac. This can be done inadvertently while rubbing the eyes or wetting contact lenses with saliva. Five of the six patients we described who had conjunctivitis associated with wearing contact lenses reported routinely wetting their lenses with saliva. Because anaerobes are present in the saliva in high numbers10 (up to 109 organisms/mL), the recovery of anaerobes in this group of patients is not surprising.
Typically, the palpebral conjunctiva is more inflamed than the bulbar and the area around the cornea is spared. A bacterial etiology is suspected when severe conjunctivitis is present, and many polymorphonuclear leukocytes are found in conjunctival swab specimens. Severe infection, copious exudate, and matting of the eyelids are more likely to occur with bacterial or chlamydial infection than with viral infection. Preauricular lymphadenitis is generally associated with viral infections. The presence of follicles on the palpebral conjunctivae is indicative of viral or chlamydial infections in children older than 3 months. Conjunctival scraping can be helpful when they contain conjunctival epithelial cells that may harbor intracellular pathogens.
Conjunctivitis associated with anaerobes is indistinguishable from inflammation caused by other bacteria, although patients wearing contact lenses may be at higher risk of developing infections caused by these organisms. Gram and Giemsa stains and aerobic and anaerobic cultures are necessary for correct diagnosis. The presence of lymphocytes suggests viral infection, eosinophils and basophils suggest an allergic etiology, and intranuclear inclusions implicate herpes virus or adenoviruses. Intracytoplasmic inclusions suggest chlamydial agents.
The infection is often self-limited. Treatment of bacterial conjunctivitis facilitates the resolution21 and includes application of proper topical antibiotics selected according to the antimicrobial susceptibility of the infecting organism. Conjunctival infection caused by anaerobes should be treated by antimicrobial agents effective against these organisms. Bacitracin is active against pigmented Prevotella and Porphyromonas and Peptostreptococcus spp. but is generally inactive against B. fragilis and Fusobacterium nucleatum.9 Erythromycin shows good activity against pigmented Prevotella and Porphyromonas, microaerophilic and anaerobic streptococci, and gram-positive nonspore-forming anaerobic bacilli.9 Erythromycin has relatively good activity against Clostridium spp. but poor and inconsistent activity against gram-negative anaerobic bacilli.9 Chloramphenicol has the greatest in vitro activity against anaerobes, but occasional resistance has been observed.
Anaerobic gram-positive cocci are the anaerobes most frequently recovered from inflamed conjunctivae and are susceptible to penicillins, erythromycin, and chloramphenicol. The penicillins should not be used topically because they are highly sensitizing in the conjunctival sac. Chloramphenicol should be used cautiously because it is absorbed from the conjunctivae. Anaerobic bacteria may be relatively resistant to sulfonamide, quinolones, polymyxin B, and aminoglycoside preparations that are commonly applied to inflamed conjunctiva. Because anaerobes may be involved in severe cases of conjunctivitis and especially with the most serious complications of bacterial conjunctivitis, such as a penetrating corneal ulcer or orbital cellulitis, special coverage for these organisms should be considered. In such instances, administration of parenteral antimicrobial agents should supplement the frequent topical application of medications.
Microbial keratitis is a serious ocular infection that can be caused by a variety of organisms and can cause corneal scarring and opacification.
Infective keratitis can be viral, bacterial, fungal, and due to Acanthamoeba. The main viruses are herpes simplex, varicella-zoster, measles, mumps, rubella, adenovirus, coxsackievirus A24, and enterovirus 70. Fungal causes are rare and include Aspergillus, Fusarium solani, and Candida albicans.
A variety of aerobic and gram-positive and gram-negative bacteria can cause keratitis. These include S. pneumoniae, S. aureus, and S. epidermidis, which is commonly recovered in cooler climate zones. Pseudomonas aeruginosa is common in contact lens wearers. H. influenzae and Moraxella catarrhalis cause ulcerative keratitis, and enteric organisms (ie, Shigella) can be transferred by contaminated hands.22–24
Anaerobic bacteria have also been reported in cases of keratitis. C. perfringens, the etiologic agent of gas gangrene, is a well-known ocular pathogen that causes a fulminant endophthalmitis associated with perforating ocular injuries. Tsutsui25 reported corneal infection with Clostridium tetani. Pringle26 described three cases of C. perfringens infection of the cornea associated with ocular trauma. Majekodunmi and Odugbemi27 reported a case of C. perfringens corneal ulcer that was not related to trauma, and Stern et al.28 described a case of nontraumatic C. perfringens corneal ulcer complicating Sjögren’s syndrome.
Jones and Robinson29 reported five cases of non-spore-forming anaerobic keratitis. Anaerobic bacteria were mixed with aerobic and facultative bacteria in three instances. The organisms isolated were P. acnes (3 isolates), Propionibacterium avidum (1 isolate), S. epidermidis (2 isolates), microaerophilic streptococci (2 isolates), and Enterobacter aerogenes (1 isolate).
O’Brien and Green30 isolated P. acnes from 16 of 140 (11%) patients with keratitis whose culture showed bacterial growth. However, adequate techniques for recovery of anaerobic bacteria were not used in this study, which may account in part for the lack of recovery of any organisms in 108 of the 248 (44%) patients.
We conducted a retrospective review of the microbiological records of samples collected for aerobic and anaerobic bacteria, as well as fungus, from 148 patients, including 22 children with keratitis.31 A total of 173 organisms (1.2 per specimen)—98 aerobic or facultative aerobic, 68 anaerobic, and 7 fungi—were recovered.
The predominant aerobic and facultative organisms were S. aureus (35 isolates), S. epidermidis (26 isolates), Pseudomonas spp. (9 isolates), Serratia marcescens (6 isolates), and S. pneumoniae (5 isolates). The most frequently recovered anaerobes were Propionibacterium spp. (31 isolates), Peptostreptococcus spp. (15 isolates), Clostridium spp. (11 isolates), Prevotella spp. (6 isolates), and Fusobacterium spp. (3 isolates). The predominant fungus was C. albicans (4 isolates).
Use of contact lenses was associated with the recovery of Pseudomonas spp., S. marcescens, Peptostreptococcus spp., Fusobacterium spp., and P. acnes. The recovery of Staphylococcus spp., P. acnes, and P. aeruginosa was associated with more predisposing conditions than was that of other isolates.
The susceptibility of the cornea to infection is due to its exposure, avascularity, and limited inflammatory response because it lacks white cells.32 The only barrier to infection is the epithelium and its basement membrane. Predisposing conditions include trauma (eg, foreign body, corneal laceration, or contact lens), corneal exposure (facial palsy, sedated or moribund state, globe proptosis, or congenital abnormalities of the eyelids), immune deficiency (immunodeficiency syndrome, immunosuppressive therapy, or topical steroids), and abnormalities of the ocular surface (dryness, mucin deficiency, vitamin A deficiency, malnutrition, or corneal anesthesia).
The patient presents with severe pain, reflex tearing, eye redness, decreased vision, and photophobia. Grayish corneal opacification is characteristic, the light reflex is dulled, and the cornea can be stained with fluorescein. A hypopyon can be observed in the anterior chamber. Corneal scraping of the leading edge and base of the ulcer for smears and culture is necessary.32,33 The material should be inoculated immediately onto solid media supportive of both aerobic and anaerobic bacteria and thioglycollate broth. Viral cultures are obtained using tissue cultures. For bacteria, Gram and Giemsa staining is obtained and methenamine-silver, acridine orange, and calcofluor white staining are used for detecting fungi and Acanthamoeba.34,35Chlamydia, viruses, and some fungi can be detected using recombinant DNA methods, enzyme-linked immunofluorescent assays, and fluorescein-labeled monoclonal antibodies.
Topical anti-infective agents are the major therapy. These include a combination of a cephalosporin plus a fortified aminoglycoside36,37 or a quinolone (norfloxacin, ciprofloxacin, or ofloxacin).38,39 However, because these quinolones have poor activity against gram-positive aerobes, adding a cephalosporin may be advised. Frequent administration of topical therapy is important because they are cleared rapidly. For coverage for anaerobes, see the section on conjunctivitis in this article.
After an initial application of five consecutive single drops every minute and then every 15 minutes for four doses, the drops are given every 30 to 60 minutes for at least 2 days. Treatment is continued for 7 to 14 days.40
Fungi are treated with frequently administered topical flucytosine, natamycin, amphotericin B, or miconazole41,42 for 6 to 12 weeks. Parenteral therapy and excisional keratoplasty is considered when the response is inadequate to prevent deep fungal keratitis and endophthalmitis. Viral infections, excluding herpes virus, are self-limited and there is currently no effective therapy. Herpes virus infection can be treated with frequently administered (every hour during the first week, every 2 hours during the second week) topical antivirals such as vidarabine or trifluorothymidine. Debridement is also an option. Herpes zoster is managed with topical steroids. Acanthamoeba keratitis is treated with the combination of imidazole, propamide isothiocyanate, neomycin, and polyhexamethylene biguanide.43,44
The corneal transparency may be lost and refractive changes and central corneal scars (leukomas) may occur. Corneal grafting may be necessary.
Dacryocystitis is a bacterial infection of the lacrimal sac. It can occur at any age as a bacterial complication of a viral upper respiratory tract infection.45
S. aureus, S. epidermidis, and, rarely, P. aeruginosa and Escherichia coli have been reported in older patients,46 whereas S. pneumoniae, H. influenzae, Streptococcus agalactiae, and anaerobes are common in neonates.45–48
Anaerobic bacteria were rarely recovered and their role was demonstrated in a previous study.48 A review of 62 cases with dacryocystitis (including 7 children) reported the isolation of aerobic and facultative bacteria in 32 cases (52%), anaerobic bacteria only in 20 cases (32%), mixed aerobic and anaerobic bacteria in 7 cases (11%), and fungi in 3 cases (5%). A total of 94 organisms (1.5 per specimen), which included 56 aerobic or facultative anaerobic organisms, 35 anaerobic organisms, and 3 fungi, were recovered.
The predominant aerobic and facultative bacteria were S. aureus (15 isolates), S. epidermidis (13 isolates), and Pseudomonas spp. (7 isolates). The most frequently recovered anaerobes were Peptostreptococcus spp. (13 isolates), Propionibacterium spp. (12 isolates), Prevotella spp. (4 isolates), and Fusobacterium spp. (3 isolates). The predominant fungus was C. albicans (2 isolates). Polymicrobial infection was present in 28 cases (45%).
The infection can occur as a result of tear stagnation in the lacrimal sac secondary to obstruction of the normal drainage of the tears through the nasolacrimal duct due to trauma, infection or inflammation, tumor infiltration, and after surgery. Delayed opening, inspissated secretion, or anatomical abnormality is a common etiology in infants.
Dacryocystitis often follows a viral respiratory infection, and the patient presents with fever and significant erythema, edema, and tenderness over the triangular area below the medial canthus. Purulent material can be expressed from the lacrimal puncta.
Obstruction to drainage can be documented by the dye disappearance test done by instilling 2% sodium fluorescein in the lower conjunctival sac and observing its disappearance after 5 minutes. An alternative method is to irrigate the lacrimal excretory system. However, probing and irrigation should not be done until the inflammation has resolved. Other tests include dacryocystography, computed tomography, and magnetic resonance imaging.49 A specimen of the pus obtained from the puncta or intraoperatively should be Gram-stained and cultured for aerobic and anaerobic bacteria.
Admission to the hospital and parenteral antimicrobial therapy is indicated in acute cases because of the potential for extension of the infection (eg, cavernous sinus or thrombosis). The choice of therapy depends on the identification of the causative organisms. A first-generation cephalosporin or a beta-lactamase–resistant penicillin (eg, nafcillin) is adequate for S. aureus. Vancomycin or clindamycin are appropriate in individuals who are allergic to penicillin and vancomycin for S. aureus resistant to methicillin. Clindamycin, a combination of penicillin plus beta-lactamase inhibitor (eg, amoxicillin–clavulanate), chloramphenicol, metronidazole (plus a penicillin), or a carbapenem is adequate for anaerobes. When the infection has improved, oral therapy can be substituted for a total of 10 to 14 days.
Incision and drainage plus direct application of antibiotics into the sac has been employed in adults who had a pointed lacrimal sac abscess.50 Surgical drainage is not necessary for most patients, but probing is helpful in neonates.47 Most neonatal nasolacrimal duct obstructions open spontaneously. In those who develop dacryocystitis, probing of the lacrimal excretory system is sufficient to open the localized membranous obstruction. Definite surgery is done in adults on resolution of the infection.
Chronic ipsilateral conjunctivitis and corneal ulcers can develop and spread into the orbit, causing orbital abscess. Intraorbital complications should be treated surgically without delay. Failure to do that can lead to visual compromise and life-threatening complications.