Updated: Mar 30, 2009
Vibrio infections are largely classified into two distinct groups: Vibrio cholera infections and noncholera Vibrio infections. Historically, the noncholera Vibrio species are classified as halophilic or nonhalophilic, depending on their requirement of sodium chloride for growth.
Because most Vibrio infections are associated with the consumption of contaminated food, these infections are often considered a foodborne disease. The prevalence of noncholera Vibrio infections in the United States appears to have increased in recent years. The combination of increased water temperature and salinity where shellfish are harvested may contribute to increased contamination rates of shellfish. Although many foodborne diseases are not reportable in the United States, the Centers for Disease Control and Prevention (CDC) estimates that approximately 76 million cases of foodborne illnesses occur annually, with 5200 deaths.1,2
Since 1988, the CDC has maintained a voluntary surveillance system for culture-confirmed Vibrio infections in Alabama, Florida, Louisiana, Mississippi, and Texas. Cases of culture-confirmed noncholera Vibrio infections from these states accounted for 39% of the 462 cases reported to the CDC in 2003. Noncholera Vibrio species in the United States cause an estimated 8000 illnesses yearly.3
While the estimated incidence of infection with Shiga toxin–producing Escherichia coli O157:H7 (STEC O157) and species of Campylobacter, Cryptosporidium, Listeria, Salmonella, and Yersinia significantly decreased from 1996-1998 to 2004, the incidence of Vibrio infections during this period increased 47% (95% CI, 7%-102%).3,4
Although Vibrio parahaemolyticus is the most common noncholera Vibrio species reported to cause infection, Vibrio vulnificus is associated with 94% of reported deaths. Because clinical laboratories do not routinely use the selective medium thiosulfate-citrate-bile salts-sucrose (TCBS) for stool culture, many cases of Vibrio gastroenteritis are not identified.5,6
In the event of a natural disaster, the disturbance to the environment may increase the risk of infectious diseases such as Vibrio infections. During the 2 weeks following Hurricane Katrina in August 2005, the CDC reported 22 new cases of Vibrio infections in Louisiana and Mississippi. V vulnificus accounted for most (82%) of these wound-associated infections. The increased incidence of Vibrio wound infections in the residents of Gulf Coast states was most likely associated with the exposure of skin and soft-tissue injuries to the contaminated floodwaters.7
The Vibrionaceae family includes the genera Vibrio, Plesiomonas, and Aeromonas. Members of the family Vibrionaceae are natural inhabitants of sea water but can also be found in fresh water. Vibrio species are oxidase-positive, gram-negative bacilli. With the exception of nonhalophilic Vibrio species, such as Vibrio cholerae and Vibrio mimicus, all Vibrio species require saline for growth.
Vibrio species can produce multiple extracellular cytotoxins and enzymes that are associated with extensive tissue damage and that may play a major role in the development of sepsis (see Table 1).
Table 1. Noncholera Vibrio Species and Associated Clinical Presentations
| Infection Type | Noncholera Vibrio Species | Cytotoxins/Enzymes |
|---|---|---|
| Gastroenteritis | V parahaemolyticus Non-01 V cholerae Vibrio fluvialis V mimicus Vibrio furnissii Vibrio hollisae Vibrio alginolyticus V vulnificus | Cytotoxin Hemolysin |
| Wound infection | V alginolyticus V vulnificus Non-01 V cholerae Vibrio damsela Vibrio carchariae V fluvialis V parahaemolyticus V mimicus | Protease Hemolysin Lipase DNAase Cytolysin |
| Septicemia | V vulnificus V fluvialis V damsela Non-01 V cholerae Vibrio cincinnatiensis | Proteases Endotoxic lipopolysaccharide |
V vulnificus lives in areas where the temperature exceeds 18°C. In the United States, it is found in the coastal waters of the Gulf of Mexico, New England, and the northern Pacific. Low-to-moderate salinity (15-25 parts per thousand) provides the most favorable growing condition for V vulnificus, and, conversely, high salinity (>25 parts per thousand) adversely affects its survival. Similar to the effect of high salinity, low seawater temperature (<10°C) significantly inhibits the growth of V vulnificus. V vulnificus is ingested by filter-feeding mollusks such as oysters, mussels, clams, and scallops. During the warmer months, the concentration of bacteria can be as high as 1 X 106 bacteria per gram of oyster.8
Several mechanisms contribute to the virulence of V vulnificus. Iron is an important growth factor. However, because free iron is virtually absent in humans, the organism produces siderophores that acquire iron from transferrin or lactoferrin and deliver it to the bacteria. Conversely, the inability to produce siderophores leads to reduction of virulence. Hepcidin, a natural cysteine-rich peptide, has recently been suggested to possess important antibacterial activity. It is possible that inadequate expression of hepcidin in patients with liver disease predisposes them to serious infections, including those caused by Vibrio species.9,10
Clinical conditions associated with increased free iron, such as hemochromatosis or hemolytic anemia, represent a major risk factor for disseminated Vibrio infections. In addition, V vulnificus produces several other virulence factors, including proteases, hemolysins, and cytolysins. One in particular, a thermolysin-like metalloprotease, activates the bradykinin pathway, causing an increase in vascular permeability. This metalloprotease is far more efficient at activating human enzymes than those of other Vibrio species, possibly explaining why V vulnificus causes severe skin damage and necrotizing fasciitis.11
Recently, the gene pyrH has been demonstrated as essential for in vivo survival and growth of V vulnificus in infected mice and is likely associated with its virulence. Clinical isolates of V vulnificus, but not environmental isolates , caused extensive damage to macrophages in animal models, possibly explaining the lethal effects of this infection. One of the major virulence factors in pathogenic V haemolyticus strains is a thermostable direct hemolysin (TDH). This beta-hemolysin has both enterotoxic and cytotoxic effects; it is detoxified at 60-70°C but reactivated at 80°C (Arrhenius effect).
For additional information on cutaneous V vulnificus infections, see the article Vibrio Vulnificus in eMedicine’s Dermatology volume.
Between 1996 and 2001, the incidence of Vibrio infections increased by more than 80%. More importantly, despite a significant decline (30-45%) in the incidence of most bacterial foodborne infections in the United States in 2004, the incidence of Vibrio infections increased by 47% over the baseline period of 2001-2002.12 The CDC estimates that 8000 Vibrio infections and approximately 60 deaths related to Vibrio infections may occur annually in the United States. Vibrio infections are acquired through consumption of contaminated raw or undercooked shellfish such as oysters, clams, mussels, or crabs. Exposure of wounds to contaminated sea water, injury caused by contaminated seashells, and shark and alligator bites are potential alternative sources of infection (see Table 2).
V parahaemolyticus is the leading cause of seafood-associated gastroenteritis in the United States. During a large outbreak of gastroenteritis in July 2004 in the Gulf of Alaska, V parahaemolyticus caused illness in almost one third of cruise ship passengers who consumed Vibrio -contaminated oysters. From May to July 2006, health departments of New York City, New York state, Oregon, and Washington state reported a total of 177 cases of V parahaemolyticus gastroenteritis. Of these reported cases, 113 (64%) involved residents of Washington state. 13| Vibrio Species | Gastroenteritis (%) | Wound Infection (%) | Septicemia (%) | Miscellaneous (%) |
|---|---|---|---|---|
| V parahaemolyticus | 59 | 34 | 5 | 2 |
| V vulnificus | 5 | 45 | 43 | 7 |
| Non-01 V cholerae | 67 | 9 | 15 | … |
| V alginolyticus | 5-12 | 71 | 1 | 10-15 |
| V mimicus | 85 | 3 | 3 | … |
| V fluvialis | 73 | 10 | 6 | … |
| V damsela | Rare | >95 | Rare | … |
| V furnissii | >90 | Rare | Rare | … |
| Vibrio metschnikovii | Common | Rare | Rare | … |
| V hollisae | 85 | 7 | 5 | … |
| V cincinnatiensis | Rare | Rare | Rare | Meningitis |
Noncholera Vibrio infections are commonly reported in areas such as Japan, Taiwan, China, Hong Kong, Korea, Italy, and Israel. The high prevalence of hepatitis B infections in areas such as China and Taiwan may also contribute to the high incidence of severe noncholera Vibrio infections.
Contrary to epidemiologic patterns of Vibrio infections, only sporadic cases were reported among survivors and injured individuals following the tsunami that devastated Thailand, Indonesia, and India in December 2004.
Despite a high annual estimated incidence of V vulnificus septicemia in Japan (425 cases; 95% CI, 238-752), a survey of registered emergency physicians in Japan surprisingly revealed that only 15.7% (95% CI, 11.3-21.0) of responding physicians had a basic knowledge of this frequently fatal infection.14
According to CDC estimates, foodborne diseases cause approximately 76 million illnesses, 325,000 hospitalizations, and 5200 deaths annually in the United States.14
Vibrio infections have no racial predilection.
Vibrio infections can occur in all persons, regardless of sex. V vulnificus infections were reported in women who engaged in sexual intercourse in brackish water of the Gulf of Mexico. In general, V vulnificus infections are more common in males (82%), according to most reports.
Most patients with noncholera Vibrio infections report having recently consumed raw seafood such as oysters, clams, crabs, or mussels. With the exception of a dramatic clinical progression in wound infection and septicemia, no characteristic signs and symptoms of early-stage noncholera Vibrio infections exist (see Table 3).
Table 3. Clinical Signs and Symptoms of Vibrio Infections
| Clinical Presentation | Symptoms (Frequency) |
|---|---|
| Gastroenteritis | Diarrhea (100%) Abdominal cramps (89%) Nausea (76%) Vomiting (55%) Fever (47%) Bloody stools (29%) Headache (24%) Myalgia (24%) |
| Wound infection | Swelling (100%) Pain (100%) Erythema (100%) Bullae (30-50%) Necrosis (30-50%) Gangrene (<10%) |
| Septicemia | Fever (>90%) Hypothermia (<10%) Hypotension (100%) Tachycardia (80-90%) Shock (50-70%) Bullae (80-100%) Acute respiratory distress syndrome (<5%) Multiple organ dysfunction (30-50%) |
The physical findings of Vibrio infections vary according to clinical presentations.
| Aeromonas Infections | Gastroenteritis, Bacterial |
| Cholera | Multisystem Organ Failure of Sepsis |
| Clostridial Gas Gangrene | Sepsis, Bacterial |
| Disseminated Intravascular Coagulation | Septic Shock |
| Gas Gangrene |
Clostridial necrotizing fasciitis
Aeromonas necrotizing fasciitis
Findings on histologic examination of the skin and/or soft tissue in patients with noncholera Vibrio wound infection frequently demonstrate gram-negative bacilli, acute inflammatory reaction with extensive tissue necrosis, and fat infarction. In patients with rapidly progressing illness, examination of biopsy specimens of the skin may demonstrate an absence of cellular response.
Medical care depends on the clinical presentation and the presence of underlying medical conditions.
A team effort is required to ensure successful therapy in patients with noncholera Vibrio wound infection or septicemia.
For noncholera Vibrio infections other than gastroenteritis, the combination of ceftazidime and doxycycline or an antipseudomonal penicillin (eg, ticarcillin and clavulanate, piperacillin and tazobactam) is the therapy of choice. Alternative antibiotics include cefotaxime or fluoroquinolones. Although in vitro testing demonstrates that Vibrio species are sensitive to aminoglycosides, the use of aminoglycosides may be associated with toxicities above those observed with other agents.
In a retrospective chart review of 93 patients hospitalized with serious Vibrio infections, the combination of a third-generation cephalosporin and tetracycline or its analogue was an independent factor for lower mortality (OR, 0.337; 95% CI, 0.007-0.192; P <0.001).
Tigecycline, a novel glycylcycline, has a potent in vitro antimicrobial effect against Vibrio species. Other newer antibiotics such as daptomycin and linezolid that were approved for the treatment of serious skin and soft-tissue infections have not been studied in serious Vibrio infections. Therefore, the authors do not currently recommend the use of these antibiotics in the treatment of serious Vibrio infections.
Adjuvant therapy: Recombinant human activated protein C (drotrecogin alfa activated) has been used as an adjuvant therapy in patients with severe sepsis who scored 25 or more on the Acute Physiology and Chronic Health Evaluation (APACHE II). A few patients with V vulnificus sepsis who were successfully treated with antibiotics, surgical debridement, and recombinant human activated protein C were reported. In view of serious bleeding associated with the continuous infusion of recombinant human activated protein C and the potential requirement for repeated surgical debridement in patients with V vulnificus sepsis, routine use of this adjuvant therapy is not recommended.20
Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting. Antibiotic combinations are usually recommended for serious gram-negative bacillary infections. This approach ensures coverage for a broad range of organisms and polymicrobial infections. In addition, resistance from bacterial subpopulations is prevented, and additive or synergistic effects are provided. Once organisms and sensitivities are known, the use of antibiotic monotherapy is recommended.
Inhibits protein synthesis and, thus, bacterial growth by binding to 30S and possibly 50S ribosomal subunits of susceptible bacteria.
200 mg PO/IV q12h for 3 d, then 100-200 mg PO q12h for 14 d
<8 years: Not recommended
>8 years: 2-5 mg/kg/d PO/IV qd or divided bid; not to exceed 200 mg/d
Bioavailability decreases minimally with antacids containing aluminum, calcium, magnesium, iron, or bismuth subsalicylate; tetracyclines can increase hypoprothrombinemic effects of anticoagulants; tetracyclines can decrease effects of oral contraceptives, causing breakthrough bleeding and increased risk of pregnancy
Documented hypersensitivity; severe hepatic dysfunction
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Photosensitivity may rarely occur; use during tooth development (last half of pregnancy through age 8 y) can cause permanent discoloration of teeth
Antipseudomonal penicillin plus beta-lactamase inhibitor. Inhibits biosynthesis of cell wall mucopeptide and is effective during stage of active multiplication.
4.5 g IV q8h
<6 months: Not established
>6 months: 75 mg/kg IV q6h
Tetracyclines may decrease effects of piperacillin; high concentrations in vivo or in vitro of piperacillin may chemically inactivate aminoglycosides; synergistic effect occurs when administered concurrently with aminoglycosides; probenecid may increase penicillin levels
Documented hypersensitivity
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Perform CBC prior to initiation of therapy and at least weekly during therapy; adjust dose in renal dysfunction; monitor for liver and renal function abnormalities
Inhibits biosynthesis of cell wall mucopeptide and is effective during stage of active growth. Antipseudomonal penicillin plus beta-lactamase inhibitor provides coverage against most gram-positive, gram-negative, and anaerobic bacteria.
3.1 g IV q4-6h
75 mg/kg IV q6h
Tetracyclines may decrease effects of ticarcillin; high concentrations of ticarcillin in vivo or in vitro may chemically inactivate aminoglycosides; synergistic effect occurs when administered concurrently with aminoglycosides; probenecid may increase penicillin levels
Documented hypersensitivity
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Perform CBC prior to initiation of therapy and at least weekly during therapy; monitor for liver function abnormalities by measuring AST and ALT during therapy; exercise caution in patients diagnosed with hepatic insufficiencies; perform urinalysis, BUN, and creatinine determinations during therapy and adjust dose if values become elevated
Fluoroquinolone with activity against pseudomonads, streptococci, MRSA, Staphylococcus epidermidis, and most gram-negative organisms but no activity against anaerobes. Inhibits bacterial DNA synthesis and, consequently, growth.
400 mg IV bid for 7-14 d, may switch to 500 mg PO to complete therapy when oral intake is normalized
<18 years: Not recommended
>18 years: Administer as in adults
Antacids, iron salts, and zinc salts may reduce serum levels; administer antacids 2-4 h before or after fluoroquinolones; cimetidine may interfere with metabolism of fluoroquinolones; ciprofloxacin reduces therapeutic effects of phenytoin; probenecid may increase ciprofloxacin serum concentrations; may increase toxicity of theophylline, caffeine, cyclosporine, and digoxin (monitor digoxin levels); may increase effects of anticoagulants (monitor PT)
Documented hypersensitivity
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
In prolonged therapy, perform periodic evaluations of organ system functions (eg, renal, hepatic, hematopoietic); adjust dose in renal function impairment; superinfections may occur with prolonged or repeated antibiotic therapy; CNS and GI disturbances have been observed
For septicemia and treatment of gynecologic infections caused by susceptible organisms. Arrests bacterial cell wall synthesis, which in turn inhibits bacterial growth. Third-generation cephalosporin with gram-negative spectrum. Lower efficacy against gram-positive organisms.
2 g IV q6h
Infants to <12 years: 50-180 mg/kg/d IV divided q4-6h
>12 years: Administer as in adults
Probenecid may increase cefotaxime levels; coadministration with furosemide and aminoglycosides may increase nephrotoxicity
Documented hypersensitivity
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Adjust dose in severe renal impairment; has been associated with severe colitis
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Olsen SJ, MacKinnon LC, Goulding JS, Bean NH, Slutsker L. Surveillance for foodborne-disease outbreaks--United States, 1993-1997. MMWR CDC Surveill Summ. Mar 17 2000;49(1):1-62. [Medline].
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Daniels NA, MacKinnon L, Bishop R. Vibrio parahaemolyticus infections in the United States, 1973-1998. J Infect Dis. May 2000;181(5):1661-6. [Medline].
Marano NN, Daniels NA, Easton AN, McShan A, Ray B, Wells JG. A survey of stool culturing practices for vibrio species at clinical laboratories in Gulf Coast states. J Clin Microbiol. Jun 2000;38(6):2267-70. [Medline].
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Anand RG, Lopez FA, deBoisblanc B. Vibrio vulnificus sepsis successfully treated with antibiotics, surgical debridement, and recombinant human activated protein C. J La State Med Soc. May-Jun 2004;156(3):130-3; quiz 133. [Medline].
Mouzin E, Mascola L, Tormey MP. Prevention of Vibrio vulnificus infections. Assessment of regulatory educational strategies. JAMA. Aug 20 1997;278(7):576-8. [Medline].
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Hollis DG, Weaver RE, Baker CN. Halophilic Vibrio species isolated from blood cultures. J Clin Microbiol. Apr 1976;3(4):425-31. [Medline].
Vibrio infections, Vibrio cholera infections, noncholera Vibrio infections, halophilic Vibrio species, nonhalophilic Vibrio species, Vibrio parahaemolyticus, Vibrio vulnificus, V parahaemolyticus, V vulnificus, Vibrionaceae family, vibriosis, vibrioses, Vibrio gastroenteritis, Vibrio wound infection, Vibrio septicemia, Vibrio sepsis, Vibrio cholerae, Vibrio mimicus, Vibrio fluvialis, Vibrio furnissii, Vibrio hollisae, Vibrio alginolyticus, Vibrio damsela, Vibrio carchariae, Vibrio cincinnatiensis, Vibrio metschnikovii, V cholerae, V mimicus, V fluvialis, V furnissii, V hollisae, V alginolyticus, V damsela, V carchariae, V cincinnatiensis, V metschnikovii
Hoi Ho, MD, Associate Dean for Faculty Affairs and Development, Professor, Department of Internal Medicine, Director, Clinical Skills and Clinical Simulation Center, Paul L Foster School of Medicine, Texas Tech University Health Sciences Center; Consulting Staff, Thomason Hospital
Hoi Ho, MD is a member of the following medical societies: Alpha Omega Alpha, American Association for the Advancement of Science, American College of Forensic Examiners, American College of Physicians, American Society for Microbiology, and Infectious Diseases Society of America
Disclosure: Nothing to disclose.
Thong Huy Do, MD, Staff Physician, Department of Internal Medicine, Thomason Hospital, Texas Tech University
Thong Huy Do, MD is a member of the following medical societies: American College of Physicians
Disclosure: Nothing to disclose.
Tony Tran Ho, MS, Texas Tech University School of Medicine
Tony Tran Ho, MS is a member of the following medical societies: American Medical Association and Texas Medical Association
Disclosure: Nothing to disclose.
Mary Nettleman, MD, MS, Chair, Department of Medicine, Michigan State University
Mary Nettleman, MD, MS is a member of the following medical societies: American College of Physicians, Association of Professors of Medicine, Central Society for Clinical Research, Infectious Diseases Society of America, and Society of General Internal Medicine
Disclosure: Nothing to disclose.
Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment
Richard B Brown, MD, FACP, Chief, Division of Infectious Diseases, Baystate Medical Center; Professor, Department of Internal Medicine, Tufts University School of Medicine
Richard B Brown, MD, FACP is a member of the following medical societies: Alpha Omega Alpha, American College of Chest Physicians, American College of Physicians, American Medical Association, American Society for Microbiology, Infectious Diseases Society of America, and Massachusetts Medical Society
Disclosure: Nothing to disclose.
Eleftherios Mylonakis, MD, Clinical and Research Fellow, Department of Internal Medicine, Division of Infectious Diseases, Massachusetts General Hospital
Eleftherios Mylonakis, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Physicians, American Society for Microbiology, and Infectious Diseases Society of America
Disclosure: Nothing to disclose.
Burke A Cunha, MD, Professor of Medicine, State University of New York School of Medicine at Stony Brook; Chief, Infectious Disease Division, Winthrop-University Hospital
Burke A Cunha, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, and Infectious Diseases Society of America
Disclosure: Nothing to disclose.