CHAPTER 5

Infectious Diseases of the External Eye: Microbial

and Parasitic Infections

A detailed history and physical examination are essential to proper diagnosis of external eye infections. The patient’s chief concern should be noted and a complete systemic and ocular history, eliciting specific risk factors for infections of the external eye, should be obtained. A complete eye examination should note conjunctival discharge as well as corneal and conjunctival morphology, but it should focus on the ocular adnexa, which include facial skin, eyelids, lacrimal drainage apparatus, and preauricular lymph nodes, and which can effect or be affected by external ocular infections. Diagnostic tests are chosen to differentiate between likely diagnostic entities and to assist in therapy (eg, antimicrobial sensitivity testing in microbial keratitis), when needed.

Bacteriology

A basic understanding of bacteriology is important in the diagnosis of external eye infections and for effective, appropriate use of antibiotics. Bacteria are prokaryotes, defined as organisms in which the genetic material is not separated from the cytoplasm by a nuclear membrane. Rather, DNA, RNA, and protein in an amorphous matrix are enclosed in a single cytoplasmic compartment without membrane-bound cellular organelles, surrounded by a plasma membrane. Most bacterial genes exist as part of a single circular chromosome, but some are present on smaller extrachromosomal circles called plasmids, which typically determine inheritance of 1 or a few characteristics. Plasmid DNA is passed between bacterial strains and species more easily than is chromosomal DNA and represents an important mechanism in the rapid proliferation of mutations such as antibiotic resistance. Classification of bacteria is determined by the International Committee for Systemic Bacteriology (ICSB) and is based on microscopic morphology (round or elongated) and colony morphology, enzyme activity, biochemical tests, DNA fingerprinting, and genomic sequence (when known).

The prokaryote cell wall imparts shape and rigidity to the cell and also mediates interactions with other bacteria, bacterial viruses, and the environment, including therapeutic drugs. The reaction of a bacterium to the Gram stain classifies the bacterial cell wall as either gram-positive (blue) or gramnegative (red) and provides critical information on the structure and biochemical composition of the cell wall that can be predictive of the bacteria’s antibiotic susceptibility (Table 5-1). Thick grampositive bacterial cell walls contain predominantly peptidoglycan, the primary target of penicillin,

and teichoic acid, whereas gram-negative cell walls have a thin peptidoglycan layer that is covered by an external lipopolysaccharide membrane (endotoxin), which excludes certain antibiotics. Some bacteria stain poorly with Gram stain, including Mycobacteria and Nocardia asteroides, but they can be visualized with acid-fast stain.

Table5-1

Structures external to the cell wall facilitate bacterial interactions, including flagella (motility), pili (bacterial conjugation [transfer of bacterial DNA from one bacterial cell to another]), fimbriae (bacterial adherence), and adhesins (mucosal surface adhesion). The rapid replication times of bacteria, combined with both plasmid-mediated and chromosomal-mediated mutations as well as biofilm formation, favor bacterial survival and make it largely inevitable that bacteria will develop resistance to antibiotics.

Gram-positive Cocci

Staphylococcus species

Staphylococci inhabit the skin, skin glands, and mucous membranes of healthy mammals. They grow in grapelike clusters in culture but may be seen singly, in pairs, or in short chains on smears from ocular specimens. Staphylococci produce an external biofilm that interferes with phagocytosis and secrete a variety of extracellular proteins—including toxins, enzymes, and enzyme activators—that facilitate both colonization and disease. Staphylococci also produce lantibiotics, small polypeptides that exert antibacterial effects on other bacteria competing for the same natural habitat. Staphylococci adapt quickly and effectively to administered antibacterial agents and may develop resistance to β- lactams, macrolides, tetracyclines, and quinolones. Methicillin-resistant Staphylococcus aureus (MRSA) is an increasing problem for both ocular and nonocular infections and has led to the common use of vancomycin, which continues to provide reliable gram-positive coverage. Resistance to vancomycin is emerging, however (see the section “Enterococcus species”), requiring the development and introduction of newer drugs.

Streptococcus species

Streptococci inhabit the mucous membranes of the normal upper respiratory tract and female genital tract (Fig 5-1). They grow in pairs and chains. The historical classification of streptococci based on their ability to hemolyze blood-containing agar media is useful for initial recognition of clinical isolates. Another historical means of classification was serologic grouping based on cell-wall carbohydrates (Lancefield groups). These methods are used less often today, given the availability of genetic sequence data.

Figure 5-1 Gram-positive cocci (Streptococcus pneumoniae). (Gram ×1000.) (Courtesy of James Chodosh, MD.)

Disease-causing factors of the highly pathogenic β-hemolytic Streptococcus pyogenes and other pyogenic streptococci include the M and M-like proteins, pyrogenic exotoxins, streptolysin, C5a peptidase, and hyaluronidase. M proteins anchor in the cytoplasmic membrane and extend externally through the bacterial cell wall to help the organism resist phagocytosis by neutrophils. Streptolysin lyses erythrocytes, platelets, and neutrophils. C5a peptidase cleaves and destroys the function of C5a, an important chemoattractant of neutrophils. Hyaluronidase is believed to act as a tissue invasion factor.

Streptococcus pneumoniae appear in smears as lancet-shaped diplococci and express a polysaccharide capsule that resists phagocytosis by macrophages and neutrophils. The toxin pneumolysin is liberated by autolysis and inhibits neutrophil chemotaxis, phagocytosis, lymphocyte proliferation, and antibody synthesis.

Enterococcus species

Enterococci are gram-positive cocci that may be seen in pairs or in short chains. They are capable of survival in harsh environments but, in humans, are commensal in the gastrointestinal and genitourinary tracts. Enterococcus faecalis, an important cause of endophthalmitis, uses a unique mechanism of plasmid exchange involving the expression of sex pheromones. These chemicals, when expressed on the surface of enterococci, induce a bacterial mating response and exchange of genetic material, a means by which enterococci acquire antibiotic resistance, one prominent example being vancomycin-resistant enterococci (VRE). Enterococci also produce a cytolysin with potent effects on eukaryotic cell membranes.

Gram-negative Cocci

Neisseria species

Neisseria gonorrhoeae causes urogenital, rectal, and pharyngeal infections, as well as hyperacute conjunctivitis, and can invade intact corneal epithelium, induce keratolysis of the corneal stroma, and perforate the cornea. N gonorrhoeae is always a pathogen, whereas the closely related species Neisseria meningitidis may be commensal in the pharynx without causing disease. N gonorrhoeae is a bean-shaped, gram-negative diplococcus usually seen within neutrophils on a clinical smear from ocular or genital sites (Fig 5-2).