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image The genus Vibrio includes several human pathogens that do not cause cholera. Abundant in coastal waters throughout the world, noncholera vibrios can reach high concentrations in the tissues of filter-feeding mollusks. As a result, human infection commonly follows the ingestion of seawater or of raw or undercooked shellfish (Table 163-5). Most noncholera vibrios can be cultured on blood or MacConkey agar, which contains enough salt to support the growth of these halophilic species. In the microbiology laboratory, the species of noncholera vibrios are distinguished by standard biochemical tests. The most important of these organisms are Vibrio parahaemolyticus and Vibrio vulnificus.

TABLE 163-5Features of Selected Noncholera Vibrioses

The two major types of syndromes for which these noncholera vibrios are responsible are gastrointestinal illness (due to V. parahaemolyticus, non-O1/O139 V. cholerae, Vibrio mimicus, Vibrio fluvialis, Vibrio hollisae, and Vibrio furnissii) and soft tissue infections (due to V. vulnificus, Vibrio alginolyticus, and Vibrio damselae). V. vulnificus is also a cause of primary sepsis in some compromised individuals.

SPECIES ASSOCIATED PRIMARILY WITH GASTROINTESTINAL ILLNESS

V. parahaemolyticus

image Widespread in marine environments, the halophilic V. parahaemolyticus is the leading seafood-borne bacterial cause of enteritis worldwide. This species was originally implicated in enteritis in Japan in 1953, accounting for 24% of reported cases in one study—a rate that presumably was due to the common practice of eating raw seafood in that country. In the United States, common-source outbreaks of diarrhea caused by this organism have been linked to the consumption of undercooked or improperly handled seafood or of other foods contaminated by seawater. Since the mid-1990s, the incidence of V. parahaemolyticus infections has increased in several countries, including the United States. Serotypes O3:K6, O4:K68, and O1:K-untypable, which are genetically related to one another, account in part for this increase. The enteropathogenicity of V. parahaemolyticus is linked to its ability to cause hemolysis on Wagatsuma agar (i.e., the Kanagawa phenomenon) via a thermostable direct hemolysin (Vp-TDH). Although the mechanisms by which the organism causes diarrhea are not fully defined, the genome sequence of V. parahaemolyticus contains two type III secretion systems, which directly inject toxic bacterial proteins into host cells. The activity of one of these secretion systems is required for intestinal colonization and virulence in animal models. V. parahaemolyticus should be considered a possible etiologic agent in all cases of diarrhea that can be linked epidemiologically to seafood consumption or to the sea itself. The incidence of V. parahaemolyticus infection in the United States may be increasing, with this species accounting for almost half of all Vibrio isolates reported in this country in 2014.

Infections with V. parahaemolyticus can result in two distinct gastrointestinal presentations. The more common of the two presentations (including nearly all cases in North America) is characterized by watery diarrhea, usually occurring in conjunction with abdominal cramps, nausea, and vomiting and accompanied in ~25% of cases by fever and chills. After an incubation period of 4 h to 4 days, symptoms develop and persist for a median of 3 days. Dysentery, the less common presentation, is characterized by severe abdominal cramps, nausea, vomiting, and bloody or mucoid stools. V. parahaemolyticus also causes rare cases of wound infection and otitis and very rare cases of sepsis.

Most cases of V. parahaemolyticus–associated gastrointestinal illness, regardless of the presentation, are self-limited. Fluid replacement should be stressed. The role of antimicrobial agents is uncertain, but they may be of benefit in moderate or severe disease. Doxycycline, fluoroquinolones, macrolides, or third-generation cephalosporins are usually used. Deaths are extremely rare among immunocompetent individuals. Severe infections are associated with underlying diseases, including diabetes, preexisting liver disease, iron-overload states, or immunosuppression.

Non-O1/O139 (Noncholera) V. cholerae

The heterogeneous non-O1/O139 V. cholerae organisms cannot be distinguished from V. cholerae O1 or O139 by routine biochemical tests but do not agglutinate in O1 or O139 antiserum. Non-O1/O139 strains have caused several well-studied food-borne outbreaks of gastroenteritis and have also been responsible for sporadic cases of otitis media, wound infection, and bacteremia; non-O1/O139 V. cholerae strains do not cause epidemics of cholera. Like other vibrios, non-O1/O139 V. cholerae organisms are widely distributed in marine environments. In most instances, recognized cases in the United States have been associated with the consumption of raw oysters or with recent travel. The broad clinical spectrum of diarrheal illness caused by these organisms is probably due to the group’s heterogeneous virulence attributes.

In the United States, about half of all non-O1/O139 V. cholerae isolates are from stool samples. The typical incubation period for gastroenteritis due to these organisms is <2 days, and the illness lasts for ~2–7 days. Patients’ stools may be copious and watery or may be partly formed, less voluminous, and bloody or mucoid. Diarrhea can result in severe dehydration. Many cases include abdominal cramps, nausea, vomiting, and fever. Like those with cholera, patients who are seriously dehydrated should receive oral or IV fluids; the value of antibiotics is not clear.

Extraintestinal infections due to non-O1/O139 V. cholerae commonly follow occupational or recreational exposure to seawater. Around 10% of non-O1/O139 V. cholerae isolates come from cases of wound infection, 10% from cases of otitis media, and 20% from cases of bacteremia (which is particularly likely to develop in patients with liver disease). Extraintestinal infections should be treated with antibiotics. Information to guide antibiotic selection and dosing is limited, but most strains are sensitive in vitro to tetracycline, ciprofloxacin, and third-generation cephalosporins.

SPECIES ASSOCIATED PRIMARILY WITH SOFT TISSUE INFECTION OR BACTEREMIA

(See also Chap. 124)

V. vulnificus

Infection with V. vulnificus is rare, but this organism is the most common cause of severe Vibrio infections in the United States. Like most vibrios, V. vulnificus proliferates in the warm summer months and requires a saline environment for growth. In the United States, infections in humans typically occur in coastal states between May and October and most commonly affect men >40 years of age. V. vulnificus has been linked to two distinct syndromes: primary sepsis, which usually occurs in patients with underlying liver disease, and primary wound infection, which generally affects people without underlying disease. (Vulnificus is Latin for “wound maker.”) Some authors have suggested that V. vulnificus also causes gastroenteritis independent of other clinical manifestations. V. vulnificus is endowed with a number of virulence attributes, including a capsule that confers resistance to phagocytosis and to the bactericidal activity of human serum as well as a cytolysin. Measured as the 50% lethal dose in mice, the organism’s virulence is considerably increased under conditions of iron overload; this observation is consistent with the propensity of V. vulnificus to infect patients who have hemochromatosis.

Primary sepsis most often develops in patients who have cirrhosis or hemochromatosis. However, V. vulnificus bacteremia can also affect individuals who have hematopoietic disorders or chronic renal insufficiency, those who are using immunosuppressive medications or alcohol, or (in rare instances) those who have no known underlying disease. After a median incubation period of 16 h, the patient develops malaise, chills, fever, and prostration. One-third of patients develop hypotension, which is often apparent at admission. Cutaneous manifestations develop in most cases (usually within 36 h of onset) and characteristically involve the extremities (the lower more often than the upper). In a common sequence, erythematous patches are followed by ecchymoses, vesicles, and bullae. In fact, sepsis and hemorrhagic bullous skin lesions suggest the diagnosis in appropriate settings. Necrosis and sloughing may also be evident. Laboratory studies reveal leukopenia more often than leukocytosis, thrombocytopenia, or elevated levels of fibrin-split products. V. vulnificus can be cultured from blood or cutaneous lesions. The mortality rate approaches 50%, with most deaths due to uncontrolled sepsis (Chap. 297). Accordingly, prompt treatment is critical and should include empirical antibiotic administration, aggressive debridement, and general supportive care. V. vulnificus is sensitive in vitro to a number of antibiotics, including tetracycline, fluoroquinolones, and third-generation cephalosporins. Data from animal models suggest that either a fluoroquinolone or the combination of a tetracycline and a third-generation cephalosporin should be used in the treatment of V. vulnificus septicemia.

V. vulnificus–associated soft tissue infection can complicate either a fresh or an old wound that comes into contact with seawater; the patient may or may not have underlying disease. After a short incubation period (4 h to 4 days; mean, 12 h), the disease begins with swelling, erythema, and (in many cases) intense pain around the wound. These signs and symptoms are followed by cellulitis, which spreads rapidly and is sometimes accompanied by vesicular, bullous, or necrotic lesions. Metastatic events are uncommon. Most patients have fever and leukocytosis. V. vulnificus can be cultured from skin lesions and occasionally from the blood. Prompt antibiotic therapy and debridement are usually curative.

V. alginolyticus

First identified as a pathogen of humans in 1973, V. alginolyticus occasionally causes eye, ear, and wound infections. This species is the most salt-tolerant of the vibrios and can grow in salt concentrations of >10%. Most clinical isolates come from superinfected wounds that presumably become contaminated at the beach. Although its severity varies, V. alginolyticus infection tends not to be serious and generally responds well to antibiotic therapy and drainage. A few cases of otitis externa, otitis media, and conjunctivitis due to this pathogen have been described. Tetracycline treatment usually results in cure. V. alginolyticus is a rare cause of bacteremia in immunocompromised hosts.

ACKNOWLEDGMENT

The authors gratefully acknowledge the valuable contributions of Drs. Robert Deresiewicz and Gerald T. Keusch, coauthors of this chapter for previous editions.

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