CHAPTER CONTENTS
Bacteria of Minor Medical Importance
Abiotrophia
Achromobacter
Acinetobacter
Actinobacillus
Aeromonas
Alcaligenes
Anaplasma
Arachnia
Arcanobacterium
Arizona
Bartonella quintana & Bartonella bacilliformis
Bifidobacterium
Bradyrhizobium
Branhamella
Calymmatobacterium
Capnocytophaga
Cardiobacterium
Chromobacterium
Chryseobacterium
Citrobacter
Corynebacterium jeikeium
Corynebacterium minutissimum
Edwardsiella
Ehrlichia
Eikenella
Erwinia
Erysipelothrix
Eubacterium
Fusobacterium
Gardnerella
HACEK Group
Haemophilus aegyptius
Haemophilus ducreyi
Hafnia
Kingella
Lactobacillus
Micrococcus
Mobiluncus
Moraxella
Peptococcus
Peptostreptococcus
Plesiomonas
Porphyromonas
Propionibacterium
Pseudomonas pseudomallei
Rhodococcus
Sarcina
Spirillum
Streptobacillus
Streptococcus suis
Tropheryma
Veillonella
Wolbachia
Yersinia enterocolitica & Yersinia pseudotuberculosis
Self-Assessment Questions
Summaries of Organisms
Practice Questions: USMLE & Course Examinations
BACTERIA OF MINOR MEDICAL IMPORTANCE
The bacterial pathogens of lesser medical importance are briefly described in this chapter. Experts may differ on their choice of which organisms to put in this category. Nevertheless, separating the minor from the major pathogens should allow the reader to focus on the more important pathogens while providing at least some information about the less important ones.
These organisms are presented in alphabetical order. Table 27–1 lists the organisms according to their appearance on Gram stain.
TABLE 27–1 Minor Bacterial Pathogens
Abiotrophia
Abiotrophia species were formerly known as nutritionally deficient streptococci. They are members of the normal flora of the mouth and can cause subacute bacterial endocarditis.
Achromobacter
Achromobacter species are gram-negative coccobacillary rods found chiefly in water supplies. They are opportunistic pathogens and are involved in sepsis, pneumonia, and urinary tract infections.
Acinetobacter
Acinetobacter species are gram-negative coccobacillary rods found commonly in soil and water, but they can be part of the normal flora. They are opportunistic pathogens that readily colonize patients with compromised host defenses. Acinetobacter baumannii, the species usually involved in human infection, causes disease chiefly in a hospital setting usually associated with respiratory therapy equipment (ventilator-associated pneumonia) and indwelling catheters. Sepsis, pneumonia, and urinary tract infections are the most frequent manifestations. A. baumannii is remarkably antibiotic resistant, and some isolates are resistant to all known antibiotics. Imipenem is the drug of choice for infections caused by susceptible strains. Colistin is useful in carbapenem-resistant strains. Previous genus names for this organism include Herellea and Mima.
Actinobacillus
Actinobacillus species are gram-negative coccobacillary rods. Actinobacillus actinomycetemcomitans is found as part of the normal flora in the upper respiratory tract. It is a rare opportunistic pathogen, causing endocarditis on damaged heart valves and sepsis.
Aeromonas
Aeromonas species are gram-negative rods found in water, soil, food, and animal and human feces. Aeromonas hydrophila causes wound infections, diarrhea, and sepsis, especially in immunocompromised patients.
Alcaligenes
Alcaligenes species are gram-negative coccobacillary rods found in soil and water and are associated with water-containing materials such as respirators in hospitals. Alcaligenes faecalis is an opportunistic pathogen, causing sepsis and pneumonia.
Anaplasma
Anaplasma phagocytophilum is a member of the Rickettsia family that causes human granulocytic anaplasmosis (HGA). Disease is endemic in northeastern and north central states (e.g., Connecticut and Wisconsin). Distribution is similar to that of Lyme disease. Ixodes ticks are the main vectors. Rodents and dogs are important reservoirs. In HGA, granulocytes rather than mononuclear cells are infected, but the disease is clinically indistinguishable from that caused by Ehrlichia chaffeensis. The organism forms an inclusion body called a morula in the cytoplasm of infected cells. The morula, which is shaped like a mulberry, is indistinguishable from that formed by Ehrlichia. The diagnosis is made serologically by detecting a rise in antibody titer. Doxycycline is the treatment of choice. This organism was formerly known as Ehrlichia equi, and the disease it caused was formerly known as human granulocytic ehrlichiosis (HGE).
Arachnia
Arachnia species are anaerobic gram-positive rods that form long, branching filaments similar to those of Actinomyces. They are found primarily in the mouth (associated with dental plaque) and in the tonsillar crypts. Arachnia propionica, the major species, causes abscesses similar to those of Actinomyces israelii, including the presence of “sulfur granules” in the lesions.
Arcanobacterium
Arcanobacterium haemolyticum is a club-shaped gram-positive rod that closely resembles corynebacteria. It is a rare cause of pharyngitis and chronic skin ulcers. The pharyngitis can be accompanied by a rash resembling the rash of scarlet fever.
Arizona
Arizona species are gram-negative rods in the family Enterobacteriaceae; they ferment lactose slowly. Arizona hinshawii is found in the feces of chickens and other domestic animals and causes diseases similar to those caused by Salmonella, such as enterocolitis and enteric fevers. The organism is usually transmitted by contaminated food (e.g., dried eggs).
Bartonella quintana & Bartonella bacilliformis
Bartonella quintana is the cause of trench fever and also is implicated as the cause of some cases of bacillary angiomatosis. Trench fever is transmitted by body lice, and humans are the reservoir for the organism. B. bacilliformis causes two rare diseases: Oroya fever and verruga peruana, both of which are stages of Carrión’s disease. The disease occurs only in certain areas of the Andes Mountains, and an animal reservoir is suspected.
Bifidobacterium
Bifidobacterium eriksonii is a gram-positive, filamentous, anaerobic rod found as part of the normal flora in the mouth and gastrointestinal tract. It occurs in mixed anaerobic infections.
Bradyrhizobium
Bradyrhizobium enterica is a gram-negative rod that is thought to be the cause of cord colitis. Cord colitis manifests as nonbloody diarrhea in patients who have received an allogeneic hematopoietic stem-cell transplant of umbilical cord cells. It was identified by using DNA sequencing and polymerase chain reaction (PCR) assays on infected tissue from biopsies of the colon.
Bradyrhizobium species are common soil bacteria that fix nitrogen in leguminous plants. B. enterica is the first member of the genus to be identified as a human opportunistic pathogen.
Branhamella
Branhamella catarrhalis has been renamed Moraxella catarrhalis (see Moraxella, later).
Calymmatobacterium
Calymmatobacterium granulomatis is a gram-negative rod that causes granuloma inguinale (also known as donovanosis), a sexually transmitted disease characterized by genital ulceration and soft tissue and bone destruction. The diagnosis is made by visualizing the stained organisms (Donovan bodies) within large macrophages from the lesion. Tetracycline is the treatment of choice for this disease, which is rare in the United States but endemic in many developing countries. C. granulomatis is also known as Klebsiella granulomatis.
Capnocytophaga
Capnocytophaga gingivalis is a gram-negative fusiform rod that is associated with periodontal disease, but it can also be an opportunistic pathogen, causing sepsis and mucositis in immunocompromised patients. Capnocytophaga canimorsus is a member of the oral flora of dogs and causes infections following dog bites. It also can cause sepsis in immunocompromised patients, especially those without a spleen and those who abuse alcohol.
Cardiobacterium
Cardiobacterium hominis is a gram-negative pleomorphic rod. It is a member of the normal flora of the human colon, but it can be an opportunistic pathogen, causing mainly endocarditis.
Chromobacterium
Chromobacterium violaceum is a gram-negative rod that produces a violet pigment. It is found in soil and water and can cause wound infections, especially in subtropical parts of the world.
Chryseobacterium
Chryseobacterium species are gram-negative rods found in soil and water. Chryseobacterium meningosepticum, the major pathogen in this genus, is an opportunistic pathogen, causing meningitis and sepsis, especially in premature infants. In adults, it causes outbreaks of nosocomial pneumonia, especially in intubated patients. It is resistant to most antibiotics but is noteworthy as the only gram-negative bacterium that is susceptible to vancomycin. The genus Chryseobacterium was formerly called Flavobacterium.
Citrobacter
Citrobacter species are gram-negative rods (members of the Enterobacteriaceae) related to Salmonella and Arizona. They occur in the environment and in the human colon and can cause sepsis in immunocompromised patients.
Corynebacterium jeikeium
Corynebacterium jeikeium is a small gram-positive rod primarily found on the skin of hospitalized patients. It causes sepsis in immunocompromised patients, most often those who are neutropenic. Infections are often associated with indwelling catheters and prosthetic heart valves. The drug of choice is vancomycin. Hospital-acquired strains are resistant to many other antibiotics.
Corynebacterium minutissimum
Corynebacterium minutissimum is a small gram-positive rod that causes erythrasma. Erythrasma is characterized by pruritic, scaly, brownish macules on the skin of the genital region. The diagnosis is usually made by visualizing a coral-red fluorescence with a Wood’s lamp rather than by culturing the organism. The drug of choice is oral erythromycin.
Edwardsiella
Edwardsiella species are gram-negative rods (members of the Enterobacteriaceae) resembling Salmonella. They can cause enterocolitis, sepsis, and wound infections.
Ehrlichia
Ehrlichia chaffeensis is a member of the Rickettsia family and causes human monocytic ehrlichiosis (HME). This disease resembles Rocky Mountain spotted fever, except that the typical rash usually does not occur. High fever, severe headache, and myalgias are prominent symptoms. The organism is endemic in dogs and is transmitted to humans by ticks, especially the dog tick, Dermacentor, and the Lone Star tick, Amblyomma. Ticks of the genus Ixodes are also vectors. E. chaffeensis primarily infects mononuclear leukocytes and forms characteristic morulae in the cytoplasm. (A morula is an inclusion body that resembles a mulberry. It consists of many E. chaffeensis cells.) Lymphopenia, thrombocytopenia, and elevated liver enzyme values are seen. In the United States, the disease occurs primarily in the southern states, especially Arkansas. The diagnosis is usually made serologically by detecting a rise in antibody titer. Doxycycline is the treatment of choice.
Eikenella
Eikenella corrodens is a gram-negative rod that is a member of the normal flora in the human mouth. It causes skin and bone infections associated with human bites and “clenched fist” injuries. It also causes sepsis and soft tissue infections of the head and neck, especially in immunocompromised patients and in drug abusers who lick needles prior to injection. E. corrodens is also called Bacteroides ureolyticus.
Erwinia
Erwinia species are gram-negative rods (members of the Enterobacteriaceae) found in soil and water and are rarely involved in human disease.
Erysipelothrix
Erysipelothrix rhusiopathiae is a gram-positive rod that causes erysipeloid, a skin infection that resembles erysipelas (caused by streptococci). Erysipeloid usually occurs on the hands of persons who handle meat and fish.
Eubacterium
Eubacterium species are gram-positive, anaerobic, non–spore-forming rods that are present in large numbers as part of the normal flora of the human colon. They rarely cause human disease.
Fusobacterium
Fusobacterium species are anaerobic gram-negative rods with pointed ends. They are part of the human normal flora of the mouth, colon, and female genital tract and are isolated from brain, pulmonary, intra-abdominal, and pelvic abscesses. They are frequently found in mixed infections with other anaerobes and facultative anaerobes. Fusobacterium nucleatum occurs, along with various spirochetes, in cases of Vincent’s angina (trench mouth), which is characterized by a necrotizing ulcerative gingivitis. F. nucleatum and Fusobacterium necrophorum also cause Lemierre’s disease, which is an anaerobic infection of the posterior pharyngeal space accompanied by thrombophlebitis of the internal jugular vein and metastatic infectious emboli to the lung. The drug of choice for Fusobacterium infections is either penicillin G or metronidazole.
Gardnerella
Gardnerella vaginalis is a facultative gram-variable rod associated with bacterial vaginosis, characterized by a malodorous vaginal discharge and clue cells, which are vaginal epithelial cells covered with bacteria. The “whiff” test, which consists of treating the vaginal discharge with 10% KOH and smelling a pungent, “fishy” odor, is often positive. However, trichomoniasis, which can also cause a positive whiff test, must be ruled out before a diagnosis of bacterial vaginosis can be made. The drug of choice is metronidazole. Mobiluncus (see later), an anaerobic rod, is often found in this disease as well. Women with bacterial vaginosis have a higher incidence of preterm deliveries and, consequently, a higher incidence of morbidity and mortality occurs in their newborn children.
HACEK Group
This is a group of small gram-negative rods that have in common the following: slow growth in culture, the requirement for high CO2 levels to grow in culture, and the ability to cause endocarditis. They are members of the human oropharyngeal flora and can enter the bloodstream from that site. The name “HACEK” is an acronym of the first letters of the genera of the following bacteria: Haemophilus aphrophilus and Haemophilus paraphrophilus, Actinobacillus actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens, and Kingella kingae.
Haemophilus aegyptius
Haemophilus aegyptius (Koch-Weeks bacillus) is a small gram-negative rod that is an important cause of conjunctivitis in children. Certain strains of H. aegyptius cause Brazilian purpuric fever, a life-threatening childhood infection characterized by purpura and shock. This organism is also known as Haemophilus influenzae biogroup aegyptius.
Haemophilus ducreyi
This small gram-negative rod causes the sexually transmitted disease chancroid (soft chancre), which is common in tropical countries but uncommon in the United States. The disease begins with penile lesions, which are painful; nonindurated (soft) ulcers; and local lymphadenitis (bubo). The diagnosis is made by isolating H. ducreyi from the ulcer or from pus aspirated from a lymph node. The organism requires heated (chocolate) blood agar supplemented with X factor (heme) but, unlike H. influenzae, does not require V factor (NAD). Chancroid can be treated with erythromycin, azithromycin, or ceftriaxone. Because many strains of H. ducreyi produce a plasmid-encoded penicillinase, penicillins cannot be used.
Hafnia
Hafnia species are gram-negative rods (members of the Enterobacteriaceae) found in soil and water and are rare opportunistic pathogens.
Kingella
K. kingae is a gram-negative rod in the normal flora of the human oropharynx. It is a rare cause of opportunistic infection and endocarditis.
Lactobacillus
Lactobacilli are gram-positive non–spore-forming rods found as members of the normal flora in the mouth, colon, and female genital tract. In the mouth, they may play a role in the production of dental caries. In the vagina, they are the main source of lactic acid, which keeps the pH low. Lactobacilli are rare causes of opportunistic infection.
Micrococcus
Micrococci are gram-positive cocci that are part of the normal flora of the skin. They are rare human pathogens.
Mobiluncus
Mobiluncus species are anaerobic gram-positive, curved rods that often stain gram-variable. They are associated with bacterial vaginosis in women. Gardnerella (see above), a facultative rod, is often found in this disease as well.
Moraxella
Moraxella species are gram-negative coccobacillary rods resembling neisseriae. M. catarrhalis is the major pathogen in this genus. It causes otitis media and sinusitis, primarily in children, as well as bronchitis and pneumonia in older people with chronic obstructive pulmonary disease. It is found only in humans and is transmitted by respiratory aerosol. Trimethoprim-sulfamethoxazole or amoxicillin-clavulanate can be used to treat these infections. Most clinical isolates produce β-lactamase. Moraxella nonliquefaciens is one of the two common causes of blepharitis (infection of the eyelid); Staphylococcus aureus is the other. The usual treatment is local application of antibiotic ointment, such as erythromycin.
Peptococcus
Peptococci are anaerobic gram-positive cocci, resembling staphylococci, found as members of the normal flora of the mouth and colon. They are also isolated from abscesses of various organs, usually from mixed anaerobic infections.
Peptostreptococcus
Peptostreptococci are anaerobic gram-positive cocci found as members of the normal flora of the mouth and colon. They are also isolated from abscesses of various organs, usually from mixed anaerobic infections.
Plesiomonas
Plesiomonas shigelloides is a gram-negative rod associated with water sources. It causes self-limited gastroenteritis, primarily in tropical areas, and can cause invasive disease in immunocompromised individuals.
Porphyromonas
Porphyromonas gingivalis and Porphyromonas endodontalis are anaerobic gram-negative rods found in the mouth. They cause periodontal infections, such as gingivitis and dental abscesses.
Propionibacterium
Propionibacteria are pleomorphic, anaerobic gram-positive rods found on the skin and in the gastrointestinal tract. Propionibacterium acnes is part of the normal flora of the skin and can cause catheter and shunt infections. It is involved in mixed infections associated with cat and dog bites and in head and neck abscesses.
P. acnes is also involved in the pathogenesis of acne, a condition that affects more than 85% of teenagers. The pathogenesis of acne involves impaction of the sebaceous gland followed by inflammation caused by the presence of P. acnes. The pustules of acne are composed of sebum, inflammatory cells such as neutrophils and lymphocytes, and the organism. Antibiotics, such as erythromycin, administered either topically or orally, are effective especially when coupled with other agents such as benzoyl peroxide or retinoids.
Pseudomonas pseudomallei
Pseudomonas pseudomallei (also known as Burkholderia pseudomallei) is a gram-negative rod that causes melioidosis, a rare disease found primarily in Southeast Asia. The organism is found in soil and is transmitted most often when soil contaminates skin abrasions. This disease has been seen in the United States, because infections acquired by members of the armed forces during the Vietnam War have reactivated many years later. The acute disease is characterized by high fever and bloody, purulent sputum. Untreated cases can proceed to sepsis and death. In the chronic form, the disease can appear as pneumonia or lung abscess or may resemble tuberculosis. Diagnosis is made by culturing the organism from blood or sputum. The treatment of choice is ceftazidime, which is administered for several weeks.
Rhodococcus
Rhodococcus equi is a gram-positive bacterium whose shape varies from a coccus to a club-shaped rod. It is a rare cause of pneumonia and cavitary lung disease in patients whose cell-mediated immunity is compromised. The diagnosis is made by isolating the organism on laboratory agar and observing salmon-pink colonies that do not ferment most carbohydrates. It may appear acid-fast and, if so, can be confused with Mycobacterium tuberculosis. The treatment of choice is a combination of rifampin and erythromycin. (R. equi used to be called Corynebacterium equi.)
Sarcina
Sarcina species are anaerobic gram-positive cocci grouped in clusters of four or eight. They are minor members of the normal flora of the colon and are rarely pathogens.
Spirillum
Spirillum minor is a gram-negative, spiral-shaped rod that causes rat-bite fever (“sodoku”). The disease is characterized by a reddish brown rash spreading from the bite, accompanied by fever and local lymphadenopathy. The diagnosis is made by a combination of microscopy and animal inoculation.
Streptobacillus
Streptobacillus moniliformis is a gram-negative rod that causes another type of rat-bite fever (see Spirillum, preceding paragraph).
Streptococcus suis
In August 2005, it was reported that S. suis caused the death of 37 farmers in China. The illness is characterized by the sudden onset of hemorrhagic shock. This species is known to cause disease in pigs but only rarely in people prior to this outbreak. Spread of the bacteria from the index case to others has not occurred.
Tropheryma
Tropheryma whipplei is the cause of Whipple’s disease, a rare disease characterized by prolonged weight loss, diarrhea, and polyarthritis. Without antibiotic treatment, it is ultimately fatal. Infiltrates of “foamy” macrophages in affected tissue, especially in the small intestine, are commonly seen. The reservoir of the organism, its mode of transmission, and pathogenesis are unknown.
The nature of this organism was unknown for many years. In 1992, it was identified as an actinomycete when ribosomal RNA taken from bacilli seen in duodenal lesions was compared with ribosomal RNA of other bacteria. Tropheryma is an intracellular organism that has been grown in human cell culture, but that procedure is not used to diagnose the disease. Laboratory diagnosis is typically made by periodic acid-Schiff (PAS) staining of biopsy specimens of the small bowel in which inclusions are seen in the macrophages. PAS staining, however, is nonspecific, and PCR assays, which are more specific, are used to confirm the diagnosis. The drug of choice is trimethoprim-sulfamethoxazole.
Veillonella
Veillonella parvula is an anaerobic gram-negative diplococcus that is part of the normal flora of the mouth, colon, and vagina. It is a rare opportunistic pathogen that causes abscesses of the sinuses, tonsils, and brain, usually in mixed anaerobic infections.
Wolbachia
Wolbachia species are Rickettsia-like bacteria found intracellularly within filarial nematodes such as Wuchereria and Onchocerca (see Chapter 56). Wolbachia release endotoxin-like molecules that are thought to play a role in the pathogenesis of Wuchereria and Onchocerca infections. Treatment of patients with Wuchereria and Onchocerca infections with doxycycline to kill Wolbachia results in a significant decrease in the number of filarial worms in the patient. Wolbachia themselves are not known to cause human disease but do infect many species of insects worldwide.
Yersinia enterocolitica & Yersinia pseudotuberculosis
Y. enterocolitica and Y. pseudotuberculosis are gram-negative, oval rods that are larger than Yersinia pestis. The virulence factors produced by Y. pestis are not made by these species. These organisms are transmitted to humans by contamination of food with the excreta of domestic animals such as dogs, cats, and cattle. Yersinia infections are relatively infrequent in the United States, but the number of documented cases has increased during the past few years, perhaps as a result of improved laboratory procedures.
Y. enterocolitica causes enterocolitis that is clinically indistinguishable from that caused by Salmonella or Shigella. Both Y. enterocolitica and Y. pseudotuberculosis can cause mesenteric adenitis that clinically resembles acute appendicitis. Mesenteric adenitis is the main finding in appendectomies in which a normal appendix is found. Rarely, these organisms are involved in bacteremia or abscesses of the liver or spleen, mainly in persons with underlying disease.
Yersinia infection is associated with two autoimmune diseases: reactive arthritis and Reiter’s syndrome. Other enteric pathogens such as Salmonella, Shigella, and Campylobacter also trigger these diseases. Reactive arthritis and Reiter’s syndrome are described further in Chapter 66.
Y. enterocolitica is usually isolated from stool specimens and forms a lactose-negative colony on MacConkey’s agar. It grows better at 25°C than at 37°C; most biochemical test results are positive at 25°C and negative at 37°C. Incubation of a stool sample at 4°C for 1 week, a technique called cold enrichment, increases the frequency of recovery of the organism. Y. enterocolitica can be distinguished from Y. pseudotuberculosis by biochemical reactions.
The laboratory is usually not involved in the diagnosis of Y. pseudotuberculosis; cultures are rarely performed in cases of mesenteric adenitis, and the organism is rarely recovered from stool specimens. Serologic tests are not available in most hospital clinical laboratories.
Enterocolitis and mesenteric adenitis caused by the organisms do not require treatment. In cases of bacteremia or abscess, either trimethoprim-sulfamethoxazole or ciprofloxacin is usually effective. There are no preventive measures except to guard against contamination of food by the excreta of domestic animals.
SELF-ASSESSMENT QUESTIONS
1. Regarding Fusobacterium nucleatum, which one of the following is most accurate?
(A) Its natural habitat is the soil.
(B) It is an anaerobic gram-negative rod with pointed ends.
(C) The drug of choice for infections caused by F. nucleatum is azithromycin.
(D) Laboratory diagnosis is based on detecting the ability of the exotoxin to kill cells in tissue culture.
2. Regarding Haemophilus ducreyi, which one of the following is most accurate?
(A) It requires both X and V factors to grow on MacConkey’s agar.
(B) Gram stain of exudate from the lesion shows large gram-positive rods.
(C) Penicillin G is the drug of choice to treat infections caused by H. ducreyi.
(D) It causes chancroid, which is characterized by a painful ulcer on the genitals.
3. Regarding Yersinia enterocolitica, which one of the following is most accurate?
(A) It causes mesenteric adenitis, which can mimic appendicitis.
(B) It is a gram-negative diplococcus found primarily within neutrophils.
(C) It is the most common cause of enterocolitis in the United States.
(D) Its natural habitat is the human oropharynx, and there is no animal reservoir.
4. Regarding Ehrlichia chaffeensis, which one of the following is most accurate?
(A) It is transmitted primarily by mosquito bite.
(B) It forms beta-hemolytic colonies on blood agar.
(C) Its most common clinical presentation is acute meningitis.
(D) It is endemic on the islands off the coast of Massachusetts (e.g., Nantucket).
(E) It forms an inclusion body called a morula in the cytoplasm of infected cells.
ANSWERS
1. (B)
2. (D)
3. (A)
4. (E)
SUMMARIES OF ORGANISMS
Brief summaries of the organisms described in this chapter begin on page 663. Please consult these summaries for a rapid review of the essential material.
PRACTICE QUESTIONS: USMLE & COURSE EXAMINATIONS
Questions on the topics discussed in this chapter can be found in the Clinical Bacteriology section of PART XIII: USMLE (National Board) Practice Questions starting on page 693. Also see PART XIV: USMLE (National Board) Practice Examination starting on page 731.