Review of Medical Microbiology and Immunology, 13th Edition

6. Normal Flora

CHAPTER CONTENTS

Concept of Normal Flora

Normal Flora of the Skin

Normal Flora of the Respiratory Tract

Normal Flora of the Intestinal Tract

Normal Flora of the Genitourinary Tract

Pearls

Self-Assessment Questions

Practice Questions: USMLE & Course Examinations

Normal flora is the term used to describe the various bacteria and fungi that are permanent residents of certain body sites, especially the skin, oropharynx, colon, and vagina (Tables 6–1 and 6–2). Viruses and parasites (protozoa and helminths), which are the other major groups of microorganisms, are usually not considered members of the normal flora, although they can be present in asymptomatic individuals. The normal flora organisms are often referred to as commensals. Commensals are organisms that derive benefit from another host but do not damage that host.

TABLE 6–1 Summary of the Members of Normal Flora and Their Anatomic Locations

TABLE 6–2 Medically Important Members of the Normal Flora

The term human microbiome is often used to describe the normal flora. Using sophisticated molecular diagnostic techniques, many new bacteria have been identified as members of the microbiome. The role of these bacteria in immune system function and as the cause of disease is being investigated.

The members of the normal flora vary in both number and kind from one site to another. Although the normal flora extensively populates many areas of the body, the internal organs usually are sterile. Areas such as the central nervous system, blood, lower bronchi and alveoli, liver, spleen, kidneys, and bladder are free of all but the occasional transient organism.

There is a distinction between the presence of these organisms and the carrier state. In a sense, we all are carriers of microorganisms, but that is not the normal use of the term in the medical context. The term carrier implies that an individual harbors a potential pathogen and therefore can be a source of infection of others. It is most frequently used in reference to a person with an asymptomatic infection or to someone who has recovered from a disease but continues to carry the organism and may shed it for a long period.

There is also a distinction to be made between members of the normal flora, which are the permanent residents, and the colonization of the individual with a new organism. In a sense, we are all colonized by the normal flora organisms, but the term colonization typically refers to the acquisition of a new organism. After the new organism colonizes (i.e., attaches and grows, usually on a mucosal membrane), it may cause an infectious disease, or it may be eliminated by our host defenses. Furthermore, the person colonized by a new organism can transmit that organism to others (i.e., act as a reservoir of infection for others).

The members of the normal flora play a role both in the maintenance of health and in the causation of disease in three significant ways:

(1) They can cause disease, especially in immunocompromised and debilitated individuals. Although these organisms are nonpathogens in their usual anatomic location, they can be pathogens in other parts of the body.

(2) They constitute a protective host defense mechanism. The nonpathogenic resident bacteria occupy attachment sites on the skin and mucosa that can interfere with colonization by pathogenic bacteria. The ability of members of the normal flora to limit the growth of pathogens is called colonization resistance. If the normal flora is suppressed, pathogens may grow and cause disease. For example, antibiotics can reduce the normal colonic flora that allows Clostridium difficile, which is resistant to the antibiotics, to overgrow and cause pseudomembranous colitis.

(3) They may serve a nutritional function. The intestinal bacteria produce several B vitamins and vitamin K. Poorly nourished people who are treated with oral antibiotics can have vitamin deficiencies as a result of the reduction in the normal flora. However, since germ-free animals are well-nourished, the normal flora is not essential for proper nutrition.

The predominant organism is Staphylococcus epidermidis, which is a nonpathogen on the skin but can cause disease when it reaches certain sites, such as artificial heart valves and prosthetic joints. It is found on the skin much more frequently than its pathogenic relative Staphylococcus aureus (Table 6–2). There are about 10³–10⁴ organisms/cm² of skin. Most of them are located superficially in the stratum corneum, but some are found in the hair follicles and act as a reservoir to replenish the superficial flora after hand washing. Anaerobic organisms, such as Propionibacterium and Peptococcus, are situated in the deeper follicles in the dermis, where oxygen tension is low. Propionibacterium acnes is a common skin anaerobe that is implicated in the pathogenesis of acne.

The yeast Candida albicans is also a member of the normal flora of the skin. It can enter a person’s bloodstream when needles pierce the skin (e.g., in patients with intravenous catheters or in those who use intravenous drugs). It is an important cause of systemic infections in patients with reduced cell-mediated immunity.

A wide spectrum of organisms colonize the nose, throat, and mouth, but the lower bronchi and alveoli typically contain few, if any, organisms. The nose is colonized by a variety of streptococcal and staphylococcal species, the most significant of which is the pathogen S. aureus. Occasional outbreaks of disease due to this organism, particularly in the newborn nursery, can be traced to nasal, skin, or perianal carriage by health care personnel.

The throat contains a mixture of viridans streptococci, Neisseria species, and S. epidermidis (Table 6–2). These nonpathogens occupy attachment sites on the pharyngeal mucosa and inhibit the growth of the pathogens Streptococcus pyogenes, Neisseria meningitidis, and S. aureus, respectively.

In the mouth, viridans streptococci make up about half of the bacteria. Streptococcus mutans, a member of the viridans group, is of special interest since it is found in large numbers (10¹⁰/g) in dental plaque, the precursor of caries. The plaque on the enamel surface is composed of gelatinous, high-molecular-weight glucans secreted by the bacteria. The entrapped bacteria produce a large amount of acid, which demineralizes the enamel and initiates caries. The viridans streptococci, such as S. sanguinis, are also the leading cause of subacute bacterial (infective) endocarditis. These organisms can enter the bloodstream at the time of dental surgery and attach to damaged heart valves.

Eikenella corrodens, also part of the normal oral flora, causes skin and soft tissue infections associated with human bites and “clenched-fist” injuries (i.e., injuries to the hand that occur during fist fights).

Anaerobic bacteria, such as species of Bacteroides, Prevotella, Fusobacterium, Clostridium, and Peptostreptococcus, are found in the gingival crevices, where the oxygen concentration is very low. If aspirated, these organisms can cause lung abscesses, especially in debilitated patients with poor dental hygiene. In addition, the gingival crevices are the natural habitat of Actinomyces israelii—an anaerobic actinomycete that can cause abscesses of the jaw, lungs, or abdomen.

In normal fasting people, the stomach contains few organisms, primarily because of its low pH. The small intestine usually contains small numbers of streptococci, lactobacilli, and yeasts, particularly C. albicans. Larger numbers of these organisms are found in the terminal ileum.

The colon is the major location of bacteria in the body. Roughly 20% of the feces consists of bacteria, approximately 10¹¹ organisms/g. The major bacteria found in the colon are listed in Table 6–3. Note that more than 90% of the fecal flora are anaerobes, the most important of which is Bacteroides fragilis. The most abundant facultative bacteria are the coliforms, of which Escherichia coli is the most important.

TABLE 6–3 Major Bacteria Found in the Colon

The normal flora of the intestinal tract plays a significant role in extraintestinal disease. For example, E. coli is the leading cause of urinary tract infections, and B. fragilis is an important cause of peritonitis associated with perforation of the intestinal wall following trauma, appendicitis, or diverticulitis. Other important anaerobic pathogens include Fusobacterium and Peptostreptococcus, and other important facultative bacteria include Enterococcus faecalis, which causes urinary tract infections and endocarditis, and Pseudomonas aeruginosa, which can cause various infections, particularly in hospitalized patients with decreased host defenses. P. aeruginosa is present in 10% of normal stools, as well as in soil and water.

Antibiotic therapy (e.g., with clindamycin) can suppress the predominant normal flora, thereby allowing a rare organism such as the toxin-producing Clostridium difficile to overgrow and cause severe colitis. Administration of certain antibiotics, such as neomycin orally, prior to gastrointestinal surgery to “sterilize” the gut leads to a significant reduction of the normal flora for several days, followed by a gradual return to normal levels.

The vaginal flora of adult women consists primarily of Lactobacillus species (Table 6–2). Lactobacilli are responsible for producing the acid that keeps the pH of the adult woman’s vagina low. Before puberty and after menopause, when estrogen levels are low, lactobacilli are rare and the vaginal pH is high. Lactobacilli appear to prevent the growth of potential pathogens, since their suppression by antibiotics can lead to overgrowth by C. albicans. Overgrowth of this yeast can result in Candida vaginitis.

The vagina is located close to the anus and can be colonized by members of the fecal flora. For example, women who are prone to recurrent urinary tract infections harbor organisms such as E. coli and Enterobacter in the introitus. About 15% to 20% of women of childbearing age carry group B streptococci in the vagina. This organism is an important cause of sepsis and meningitis in the newborn and is acquired during passage through the birth canal. The vagina is colonized by S. aureus in approximately 5% of women, which predisposes them to toxic shock syndrome.

Urine in the bladder is sterile in the healthy person, but during passage through the outermost portions of the urethra, it often becomes contaminated with S. epidermidis, coliforms, diphtheroids, and nonhemolytic streptococci. The area around the urethra of women and uncircumcised men contains secretions that carry Mycobacterium smegmatis, an acid-fast organism. The skin surrounding the genitourinary tract is the site of Staphylococcus saprophyticus, a cause of urinary tract infections in women.

PEARLS

• Normal flora are those microorganisms that are the permanent residents of the body that everyone has. Some people can be colonized, either transiently or for long periods, with certain organisms, but those are not considered members of the normal flora. Carriers (also called chronic carriers) are those individuals in whom pathogenic organisms are present in significant numbers and therefore are a source of infection for others.

• Normal flora organisms are either bacteria or yeasts. Viruses, protozoa, and helminths are not considered to be members of the normal flora (but humans can be carriers of some of these organisms).

• Normal flora organisms inhabit the body surfaces exposed to the environment, such as the skin, oropharynx, intestinal tract, and vagina. Members of the normal flora differ in number and kind at various anatomic sites.

• Members of the normal flora are low-virulence organisms. In their usual anatomic site, they are nonpathogenic. However, if they leave their usual anatomic site, especially in an immunocompromised individual, they can cause disease.

• Colonization resistance occurs when members of the normal flora occupy receptor sites on the skin and mucosal surfaces, thereby preventing pathogens from binding to those receptors.

Important Members of the Normal Flora

• Skin. The predominant member of the normal flora of the skin is S. epidermidis. It is an important cause of infections of prosthetic heart valves and prosthetic joints. Candida albicans, a yeast also found on the skin, can enter the bloodstream and cause disseminated infections, such as endocarditis in intravenous drug users. S. aureus is also present on the skin, but its main site is in the nose. It causes abscesses in the skin and in many other organs.

• Oropharynx. The main members of the normal flora of the mouth and throat are the viridans streptococci, such as S. sanguinis and S. mutans. Viridans streptococci are the most common cause of subacute endocarditis.

• Gastrointestinal tract. The stomach contains very few organisms because of the low pH. The colon contains the largest number of normal flora and the most diverse species, including both anaerobic and facultative bacteria. There are both gram-positive and gram-negative rods and cocci. The members of the colonic normal flora are an important cause of disease outside of the colon. The two most important members of the colonic flora that cause disease are the anaerobe Bacteroides fragilis and the facultative Escherichia coli. Enterococcus faecalis, a facultative, is also a very important pathogen.

• Vagina. Lactobacilli are the predominant normal flora organisms in the vagina. They keep the pH of the vagina low, which inhibits the growth of organisms such as C. albicans, an important cause of vaginitis.

• Urethra. The outer third of the urethra contains a mixture of bacteria, primarily S. epidermidis. The female urethra can become colonized with fecal flora such as E. coli, which predisposes to urinary tract infections.

1. The colon is the site of the largest number of normal flora bacteria. Which one of the following bacteria is found in the greatest number in the colon?

(A) Bacteroides fragilis

(B) Clostridium perfringens

(C) Enterococcus faecalis

(D) Escherichia coli

(E) Lactobacillus species

2. A 76–year–old woman with a prosthetic (artificial) hip comes to you complaining of fever and pain in that joint. You are concerned about an infection by S. epidermidis. Using your knowledge of normal flora, what is the most likely source of this organism?

(A) Dental plaque

(B) Mouth

(C) Skin

(D) Stomach

(E) Vagina

3. Your patient is a 30-year-old woman with a previous history of rheumatic fever who has had fever for the past 2 weeks. On examination, you find a new heart murmur. You suspect endocarditis and do a blood culture, which grows a viridans group streptococcus later identified as S. sanguinis. Using your knowledge of normal flora, what is the most likely source of this organism?

(A) Duodenum

(B) Skin

(C) Throat

(D) Urethra

(E) Vagina

4. An outbreak of postsurgical wound infections caused by S. aureus has occurred in the hospital. The infection control team was asked to determine whether the organism could be carried by one of the operating room personnel. Using your knowledge of normal flora, which one of the following body sites is the most likely location for this organism?

(A) Colon

(B) Gingival crevice

(C) Mouth

(D) Nose

(E) Throat

1. (A)

2. (C)

3. (C)

4. (D)

Questions on the topics discussed in this chapter can be found in the Basic Bacteriology section of PART XIII: USMLE (National Board) Practice Questions starting on page 689. Also see PART XIV: USMLE (National Board) Practice Examination starting on page 731.