Staphylococcal Infections of the Skin

Staphylococcus species are commonly found on the skin, with S. epidermidis and S. hominis being prevalent in the normal microbiota. S. aureus is also commonly found in the nasal passages and on healthy skin, but pathogenic strains are often the cause of a broad range of infections of the skin and other body systems.

S. aureus is quite contagious. It is spread easily through skin-to-skin contact, and because many people are chronic nasal carriers (asymptomatic individuals who carry S. aureus in their nares), the bacteria can easily be transferred from the nose to the hands and then to fomites or other individuals. Because it is so contagious, S. aureus is prevalent in most community settings. This prevalence is particularly problematic in hospitals, where antibiotic-resistant strains of the bacteria may be present, and where immunocompromised patients may be more susceptible to infection. Resistant strains include methicillin-resistant S. aureus (MRSA), which can be acquired through health-care settings (hospital-acquired MRSA, or HA-MRSA) or in the community (community-acquired MRSA, or CA-MRSA). Hospital patients often arrive at health-care facilities already colonized with antibiotic-resistant strains of S. aureus that can be transferred to health-care providers and other patients. Some hospitals have attempted to detect these individuals in order to institute prophylactic measures, but they have had mixed success (see Eye on Ethics: Screening Patients for MRSA).

When a staphylococcal infection develops, choice of medication is important. As discussed above, many staphylococci (such as MRSA) are resistant to some or many antibiotics. Thus, antibiotic sensitivity is measured to identify the most suitable antibiotic. However, even before receiving the results of sensitivity analysis, suspected S. aureus infections are often initially treated with drugs known to be effective against MRSA, such as trimethoprim-sulfamethoxazole (TMP/SMZ), clindamycin, a tetracycline (doxycycline or minocycline), or linezolid.

The pathogenicity of staphylococcal infections is often enhanced by characteristic chemicals secreted by some strains. Staphylococcal virulence factors include haemolysins called staphylolysins, which are cytotoxic for many types of cells, including skin cells and white blood cells. Virulent strains of S. aureus are also coagulase-positive, meaning they produce coagulase, a plasma-clotting protein that is involved in abscess formation. They may also produce leukocidins, which kill white blood cells and can contribute to the production of pus and Protein A, which inhibits phagocytosis by binding to the constant region of antibodies. Some virulent strains of S. aureus also produce other toxins, such as toxic shock syndrome toxin-1 (see Virulence Factors of Bacterial and Viral Pathogens).

To confirm the causative agent of a suspected staphylococcal skin infection, samples from the wound are cultured. Under the microscope, gram-positive Staphylococcus species have cellular arrangements that form grape-like clusters; when grown on blood agar, colonies have a unique pigmentation ranging from opaque white to cream. A catalase test is used to distinguish Staphylococcus from Streptococcus, which is also a genus of gram-positive cocci and a common cause of skin infections. Staphylococcus species are catalase-positive while Streptococcus species are catalase-negative.

Other tests are performed on samples from the wound in order to distinguish coagulase-positive species of Staphylococcus (CoPS) such as S. aureus from common coagulase-negative species (CoNS) such as S. epidermidis. Although CoNS are less likely than CoPS to cause human disease, they can cause infections when they enter the body, as can sometimes occur via catheters, indwelling medical devices, and wounds. Passive agglutination testing can be used to distinguish CoPS from CoNS. If the sample is coagulase-positive, the sample is generally presumed to contain S. aureus. Additional genetic testing would be necessary to identify the particular strain of S. aureus.

Another way to distinguish CoPS from CoNS is by culturing the sample on mannitol salt agar (MSA). Staphylococcus species readily grow on this medium because they are tolerant of the high concentration of sodium chloride (7.5% NaCl). However, CoPS such as S. aureus ferment mannitol (which will be evident on a MSA plate), whereas CoNS such as S. epidermidis do not ferment mannitol but can be distinguished by the fermentation of other sugars such as lactose, malonate, and raffinose (Figure 22.9).

Streptococcal Infections of the Skin

Streptococcus are gram-positive cocci with a microscopic morphology that resembles chains of bacteria. Colonies are typically small (1–2 mm in diameter), translucent, entire edge, with a slightly raised elevation that can be either nonhaemolytic, alpha-hemolytic, or beta-haemolytic when grown on blood agar (Figure 22.13). Additionally, they are facultative anaerobes that are catalase-negative.

The genus Streptococcus includes important pathogens that are categorized in serological Lancefield groups based on the distinguishing characteristics of their surface carbohydrates. The most clinically important streptococcal species in humans is S. pyogenes, also known as group A streptococcus (GAS). S. pyogenes produces a variety of extracellular enzymes, including streptolysins O and S, hyaluronidase, and streptokinase. These enzymes can aid in transmission and contribute to the inflammatory response.^[1] S. pyogenes also produces a capsule and M protein, a streptococcal cell wall protein. These virulence factors help the bacteria to avoid phagocytosis while provoking a substantial immune response that contributes to symptoms associated with streptococcal infections.

S. pyogenes causes a wide variety of diseases not only in the skin, but in other organ systems as well. Examples of diseases elsewhere in the body include pharyngitis and scarlet fever, which will be covered in later chapters.

Pseudomonas Infections of the Skin

Another important skin pathogen is Pseudomonas aeruginosa, a gram-negative, oxidase-positive, aerobic bacillus that is commonly found in water and soil as well as on human skin. P. aeruginosa is a common cause of opportunistic infections of wounds and burns. It can also cause hot tub rash, a condition characterized by folliculitis that frequently afflicts users of pools and hot tubs (recall the Clinical Focus case in Microbial Biochemistry). P. aeruginosa is also the cause of otitis externa (swimmer’s ear), an infection of the ear canal that causes itching, redness, and discomfort, and can progress to fever, pain, and swelling (Figure 22.16).

Wounds infected with P. aeruginosa have a distinctive odour resembling grape soda or fresh corn tortillas. This odour is caused by the 2-aminoacetophenone that is used by P. aeruginosa in quorum sensing and contributes to its pathogenicity. Wounds infected with certain strains of P. aeruginosa also produce a blue-green pus due to the pigments pyocyanin and pyoverdin, which also contribute to its virulence. Pyocyanin and pyoverdin are siderophores that help P. aeruginosa survive in low-iron environments by enhancing iron uptake. P. aeruginosa also produces several other virulence factors, including phospholipase C (a haemolysin capable of breaking down red blood cells), exoenzyme S (involved in adherence to epithelial cells), and exotoxin A (capable of causing tissue necrosis). Other virulence factors include a slime that allows the bacterium to avoid being phagocytized, fimbriae for adherence, and proteases that cause tissue damage. P. aeruginosa can be detected through the use of cetrimide agar, which is selective for Pseudomonas species (Figure 22.17).

Pseudomonas spp. tend to be resistant to most antibiotics. They often produce β-lactamases, may have mutations affecting porins (small cell wall channels) that affect antibiotic uptake, and may pump some antibiotics out of the cell, contributing to this resistance. Polymyxin B and gentamicin are effective, as are some fluoroquinolones. Otitis externa is typically treated with ear drops containing acetic acid, antibacterials, and/or steroids to reduce inflammation; ear drops may also include antifungals because fungi can sometimes cause or contribute to otitis externa. Wound infections caused by Pseudomonas spp. may be treated with topical antibiofilm agents that disrupt the formation of biofilms.

One of the most ubiquitous skin conditions is acne. Acne afflicts nearly 80% of teenagers and young adults, but it can be found in individuals of all ages. Higher incidence among adolescents is due to hormonal changes that can result in overproduction of sebum.

Acne occurs when hair follicles become clogged by shed skin cells and sebum, causing non-inflammatory lesions called comedones. Comedones (singular “comedo”) can take the form of whitehead and blackhead pimples. Whiteheads are covered by skin, whereas blackhead pimples are not; the black colour occurs when lipids in the clogged follicle become exposed to the air and oxidize (Figure 22.18).

Often comedones lead to infection by Propionibacterium acnes, a gram-positive, non-spore-forming, aerotolerant anaerobic bacillus found on skin that consumes components of sebum. P. acnes secretes enzymes that damage the hair follicle, causing inflammatory lesions that may include papules, pustules, nodules, or pseudocysts, depending on their size and severity.

Treatment of acne depends on the severity of the case. There are multiple ways to grade acne severity, but three levels are usually considered based on the number of comedones, the number of inflammatory lesions, and the types of lesions. Mild acne is treated with topical agents that may include salicylic acid (which helps to remove old skin cells) or retinoids (which have multiple mechanisms, including the reduction of inflammation). Moderate acne may be treated with antibiotics (erythromycin, clindamycin), acne creams (e.g., benzoyl peroxide), and hormones. Severe acne may require treatment using strong medications such as isotretinoin (a retinoid that reduces oil buildup, among other effects, but that also has serious side effects such as photosensitivity). Other treatments, such as phototherapy and laser therapy to kill bacteria and possibly reduce oil production, are also sometimes used.

Anthrax

The zoonotic disease anthrax is caused by Bacillus anthracis, a gram-positive, endospore-forming, facultative anaerobe. Anthrax mainly affects animals such as sheep, goats, cattle, and deer, but can be found in humans as well. Sometimes called wool sorter’s disease, it is often transmitted to humans through contact with infected animals or animal products, such as wool or hides. However, exposure to B. anthracis can occur by other means, as the endospores are widespread in soils and can survive for long periods of time, sometimes for hundreds of years.

The vast majority of anthrax cases (95–99%) occur when anthrax endospores enter the body through abrasions of the skin.^[3] This form of the disease is called cutaneous anthrax. It is characterized by the formation of a nodule on the skin; the cells within the nodule die, forming a black eschar, a mass of dead skin tissue (Figure 22.19). The localized infection can eventually lead to bacteraemia and septicaemia. If untreated, cutaneous anthrax can cause death in 20% of patients.^[4] Once in the skin tissues, B. anthracis endospores germinate and produce a capsule, which prevents the bacteria from being phagocytized, and two binary exotoxins that cause oedema and tissue damage. The first of the two exotoxins consists of a combination of protective antigen (PA) and an enzymatic lethal factor (LF), forming lethal toxin (LeTX). The second consists of protective antigen (PA) and an oedema factor (EF), forming oedema toxin (EdTX).

Less commonly, anthrax infections can be initiated through other portals of entry such as the digestive tract (gastrointestinal anthrax) or respiratory tract (pulmonary anthrax or inhalation anthrax). Typically, cases of non-cutaneous anthrax are more difficult to treat than the cutaneous form. The mortality rate for gastrointestinal anthrax can be up to 40%, even with treatment. Inhalation anthrax, which occurs when anthrax spores are inhaled, initially causes influenza-like symptoms, but mortality rates are approximately 45% in treated individuals and 85% in those not treated. A relatively new form of the disease, injection anthrax, has been reported in Europe in intravenous drug users; it occurs when drugs are contaminated with B. anthracis. Patients with injection anthrax show signs and symptoms of severe soft tissue infection that differ clinically from cutaneous anthrax. This often delays diagnosis and treatment, and leads to a high mortality rate.^[5]

B. anthracis colonies on blood agar have a rough texture and serrated edges that eventually form an undulating band (Figure 22.19). Broad spectrum antibiotics such as penicillin, erythromycin, and tetracycline are often effective treatments.

Unfortunately, B. anthracis has been used as a biological weapon and remains on the United Nations’ list of potential agents of bioterrorism.^[6] Over a period of several months in 2001, a number of letters were mailed to members of the news media and the United States Congress. As a result, 11 individuals developed cutaneous anthrax and another 11 developed inhalation anthrax. Those infected included recipients of the letters, postal workers, and two other individuals. Five of those infected with pulmonary anthrax died. The anthrax spores had been carefully prepared to aerosolize, showing that the perpetrator had a high level of expertise in microbiology.^[7]

A vaccine is available to protect individuals from anthrax. However, unlike most routine vaccines, the current anthrax vaccine is unique in both its formulation and the protocols dictating who receives it.^[8] The vaccine is administered through five intramuscular injections over a period of 18 months, followed by annual boosters. The US Food and Drug Administration (FDA) has only approved administration of the vaccine prior to exposure for at-risk adults, such as individuals who work with anthrax in a laboratory, some individuals who handle animals or animal products (e.g., some veterinarians), and some members of the United States military. The vaccine protects against cutaneous and inhalation anthrax using cell-free filtrates of microaerophilic cultures of an avirulent, non-encapsulated strain of B. anthracis.^[9] The FDA has not approved the vaccine for routine use after exposure to anthrax, but if there were ever an anthrax emergency in the United States, patients could be given anthrax vaccine after exposure to help prevent disease.

DISEASE PROFILE: Bacterial Infections of the Skin

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Bacterial infections of the skin can cause a wide range of symptoms and syndromes, ranging from the superficial and relatively harmless to the severe and even fatal. Most bacterial skin infections can be diagnosed by culturing the bacteria and treated with antibiotics. Antimicrobial susceptibility testing is also often necessary because many strains of bacteria have developed antibiotic resistance. Table 22.3 summarizes the characteristics of some common bacterial skin infections.

Table 22.3. Bacterial Infections of the Skin

 

Bacterial Conjunctivitis

Like the skin, the surface of the eye comes in contact with the outside world and is somewhat prone to infection by bacteria in the environment. Bacterial conjunctivitis (pinkeye) is a condition characterized by inflammation of the conjunctiva, often accompanied by a discharge of sticky fluid (described as acute purulent conjunctivitis) (Figure 22.20). Conjunctivitis can affect one eye or both, and it usually does not affect vision permanently. Bacterial conjunctivitis is most commonly caused by Haemophilus influenzae, but can also be caused by other species such as Moraxella catarrhalis, S. pneumoniae, and S. aureus. The causative agent may be identified using bacterial cultures, Gram stain, and diagnostic biochemical, antigenic, or nucleic acid profile tests of the isolated pathogen. Bacterial conjunctivitis is very contagious, being transmitted via secretions from infected individuals, but it is also self-limiting. Bacterial conjunctivitis usually resolves in a few days, but topical antibiotics are sometimes prescribed. Because this condition is so contagious, medical attention is recommended whenever it is suspected. Individuals who use contact lenses should discontinue their use when conjunctivitis is suspected. Certain symptoms, such as blurred vision, eye pain, and light sensitivity, can be associated with serious conditions and require medical attention.

Trachoma

Trachoma, or granular conjunctivitis, is a common cause of preventable blindness that is rare in the Canada, but widespread in developing countries, especially in Africa and Asia. The condition is caused by the same species that causes neonatal inclusion conjunctivitis in infants, Chlamydia trachomatis. C. trachomatis can be transmitted easily through fomites such as contaminated towels, bed linens, and clothing and also by direct contact with infected individuals. C. trachomatis can also be spread by flies that transfer infected mucous containing C. trachomatis from one human to another.

Infection by C. trachomatis causes chronic conjunctivitis, which leads to the formation of necrotic follicles and scarring in the upper eyelid. The scars turn the eyelashes inward (a condition known as trichiasis) and mechanical abrasion of the cornea leads to blindness (Figure 22.22). Antibiotics such as azithromycin are effective in treating trachoma, and outcomes are good when the disease is treated promptly. In areas where this disease is common, large public health efforts are focused on reducing transmission by teaching people how to avoid the risks of the infection.

Bacterial Keratitis

Keratitis can have many causes, but bacterial keratitis is most frequently caused by Staphylococcus epidermidis and/or Pseudomonas aeruginosa. Contact lens users are particularly at risk for such an infection because S. epidermidis and P. aeruginosa both adhere well to the surface of the lenses. Risk of infection can be greatly reduced by proper care of contact lenses and avoiding wearing lenses overnight. Because the infection can quickly lead to blindness, prompt and aggressive treatment with antibiotics is important. The causative agent may be identified using bacterial cultures, Gram stain, and diagnostic biochemical, antigenic, or nucleic acid profile tests of the isolated pathogen.

Biofilms and Infections of the Skin and Eyes

When treating bacterial infections of the skin and eyes, it is important to consider that few such infections can be attributed to a single pathogen. While biofilms may develop in other parts of the body, they are especially relevant to skin infections (such as those caused by S. aureus or P. aeruginosa) because of their prevalence in chronic skin wounds. Biofilms develop when bacteria (and sometimes fungi) attach to a surface and produce extracellular polymeric substances (EPS) in which cells of multiple organisms may be embedded. When a biofilm develops on a wound, it may interfere with the natural healing process as well as diagnosis and treatment.

Because biofilms vary in composition and are difficult to replicate in the lab, they are still not thoroughly understood. The extracellular matrix of a biofilm consists of polymers such as polysaccharides, extracellular DNA, proteins, and lipids, but the exact makeup varies. The organisms living within the extracellular matrix may include familiar pathogens as well as other bacteria that do not grow well in cultures (such as numerous obligate anaerobes). This presents challenges when culturing samples from infections that involve a biofilm. Because only some species grow in vitro, the culture may contain only a subset of the bacterial species involved in the infection.

Biofilms confer many advantages to the resident bacteria. For example, biofilms can facilitate attachment to surfaces on or in the host organism (such as wounds), inhibit phagocytosis, prevent the invasion of neutrophils, and sequester host antibodies. Additionally, biofilms can provide a level of antibiotic resistance not found in the isolated cells and colonies that are typical of laboratory cultures. The extracellular matrix provides a physical barrier to antibiotics, shielding the target cells from exposure. Moreover, cells within a biofilm may differentiate to create subpopulations of dormant cells called persister cells. Nutrient limitations deep within a biofilm add another level of resistance, as stress responses can slow metabolism and increase drug resistance.

DISEASE PROFILE: Bacterial Infections of the Eyes

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A number of bacteria are able to cause infection when introduced to the mucosa of the eye. In general, bacterial eye infections can lead to inflammation, irritation, and discharge, but they vary in severity. Some are typically short-lived, and others can become chronic and lead to permanent eye damage. Prevention requires limiting exposure to contagious pathogens. When infections do occur, prompt treatment with antibiotics can often limit or prevent permanent damage. Table 22.4 summarizes the characteristics of some common bacterial infections of the eyes.

Table 22.4. Bacterial Infections of the Eyes

Key Takeaways

• Staphylococcus and Streptococcus cause many different types of skin infections, many of which occur when bacteria breach the skin barrier through a cut or wound.
• S. aureus are frequently associated with purulent skin infections that manifest as folliculitis, furuncles, or carbuncles. S. aureus is also a leading cause of staphylococcal scalded skin syndrome (SSSS).
• S. aureus is generally drug resistant and current MRSA strains are resistant to a wide range of antibiotics.
• Community-acquired and hospital-acquired staphyloccocal infections are an ongoing problem because many people are asymptomatic carriers.
• Group A streptococci (GAS), S. pyogenes, is often responsible for cases of cellulitis, erysipelas, and erythema nosodum. GAS are also one of many possible causes of necrotizing fasciitis.
• P. aeruginosa is often responsible for infections of the skin and eyes, including wound and burn infections, hot tub rash, otitis externa, and bacterial keratitis.
• Acne is a common skin condition that can become more inflammatory when Propionibacterium acnes infects hair follicles and pores clogged with dead skin cells and sebum.
• Cutaneous anthrax occurs when Bacillus anthracis breaches the skin barrier. The infection results in a localized black eschar on skin. Anthrax can be fatal if B. anthracis spreads to the bloodstream.
• Common bacterial conjunctivitis is often caused by Haemophilus influenzae and usually resolves on its own in a few days. More serious forms of conjunctivitis include gonococcal ophthalmia neonatorum, inclusion conjunctivitis (chlamydial), and trachoma, all of which can lead to blindness if untreated.
• Keratitis is frequently caused by Staphylococcus epidermidis and/or Pseudomonas aeruginosa, especially among contact lens users, and can lead to blindness.
• Biofilms complicate the treatment of wound and eye infections because pathogens living in biofilms can be difficult to treat and eliminate.