Chapter 196 Aeromonas and Plesiomonas
Aeromonas and Plesiomonas are pathogenic gram-negative bacilli that commonly cause enteritis and less frequently cause skin and soft tissue infections and septicemia. They are common in fresh and brackish water and colonize animals and plants in these niches.
196.1 Aeromonas
Aeromonas is a member of the family Aeromonadaceae. These organisms are oxidase-positive, facultatively anaerobic, gram-negative bacilli that ferment glucose. At least 17 phenotypic species are known, including 8 that are recognized as human pathogens. A. hydrophila, A. veronii biotype sobria, and A. caviae are the species most often associated with human infection. A. trota is being isolated with increasing frequency from human stool.
Aeromonas infects many cold- and warm-blooded animals. There are 2 major groups of Aeromonas isolates: the nonmotile psychrophilic organisms that infect cold-blooded animals, including fish, and the motile mesophilic organisms that infect humans and other warm-blooded animals.
Aeromonas organisms are ubiquitous and are found in fresh and brackish aquatic sources, including rivers and streams, well water, and sewage. They are most often cultivated from aquatic sources during warm weather months when they can attain large populations. The prevalence of human infection may or may not exhibit seasonality, depending on local conditions. Some species can resist chlorination of water and show tolerance to high salt. Aeromonas has been isolated from meats, milk, seafood, seaweed, and vegetables consumed by humans. Most human infections with Aeromonas are associated with exposure to contaminated water. Asymptomatic colonization occurs in humans and is more common in inhabitants of tropical regions. A systematic review of cases of traveler’s diarrhea worldwide implicated Aeromonas in 0.8-3.3% of infections, with highest frequencies in travelers to Southeast Asia and Africa. Aeromonas infections have been acquired at sites of natural disasters. A. hydrophila has been isolated from ticks and cockroaches. Prophylaxis against A. hydrophila should be used in conjunction with therapy with medicinal leeches, which carry symbiotic A. hydrophila.
Clinical and epidemiologic data support that Aeromonas organisms are enteric pathogens, although adult volunteers can ingest 104-1010 colony-forming units without developing diarrhea or becoming colonized. Aeromonas isolates possess a variety of potential virulence factors, including constitutive polar and inducible lateral flagella, fimbriae, outer membrane proteins, an S-layer, endotoxin (lipopolysaccharide), capsules, collagenase, elastase, nuclease, gelatinase, lipase, chitinase, enterotoxins, hemolysins, and multiple secretion systems. Polar flagella provide motility in liquid media, and lateral flagella act as adhesins. There are various hemolysins and heat labile and heat stable enterotoxins. Aeromonas cytotoxic enterotoxin (aerolysin) is secreted by a type II secretion system and is able to lyse erythrocytes, inhibit phagocytosis, and induce cytotoxicity in eukaryotic cells. Aeromonas also has a type III secretion system with an effector protein that causes actin reorganization and eventual apoptosis in vitro. A type VI secretion system was identified in a clinical isolate. A. sombria is the most enterotoxic among clinical isolates, and cytotoxic activity with cytopathic and intracellular effects is found in 89% of isolates. A few strains produce Shiga toxin. Aeromonas has serine proteases that can cause a cascade of inflammatory mediators leading to vascular leakage, and in vitro studies show induction of apoptosis in murine macrophages by human isolates of Aeromonas. Aeromonas also has enzyme systems and efflux pumps that enable it to develop resistance to antibiotics.
Human serum generally promotes phagocytosis and intracellular killing of Aeromonas. Absence of this serum action has been associated with a poor prognosis.
Colonization with Aeromonas may be asymptomatic or cause illness, including enteritis, focal invasive infection, and septicemia. Apparently immunologically normal individuals may present with each manifestation, but invasive disease is more common among immunocompromised persons.
The most common clinical manifestation of infection with Aeromonas is enteritis, which occurs primarily among children <3 yr of age. Aeromonas is the 3rd or 4th most common cause of childhood bacterial diarrhea and has been isolated from 2-10% of patients with diarrhea and 1-5% of asymptomatic control subjects. One study showed isolation from hospitalized neonates with diarrhea at rates of 0-19% depending on season. Diarrhea is often watery and self-limited, although a dysentery-like syndrome with blood and mucus in the stool has also been described. Fever, abdominal pain, and vomiting are common in children. Enteritis caused by A. hydrophila and A. sobria tends to be acute and self-limited, whereas 30% of the patients with A. caviae enteritis have chronic or intermittent diarrhea that may last 4-6 wk. A. sobria and A. caviae are most frequently associated with traveler’s diarrhea. Complications of Aeromonas enteritis include intussusception, failure to thrive, hemolytic-uremic syndrome, bacteremia, and strangulated intestinal hernia. A. caviae infection may mimic inflammatory bowel disease.
A. hydrophila is the predominant species associated with skin and soft tissue infections, with peak incidence during the summer months. Skin and soft tissue infection is the 2nd most common presentation of Aeromonas. Predisposing factors include local trauma and exposure to contaminated fresh water. Aeromonas soft tissue infections have been reported to result from alligator, tiger, bear, tick, and snake bites; sports injuries; and medicinal leech therapy. The spectrum of skin and soft tissue infections is broad, ranging from a localized skin nodule to life-threatening necrotizing fasciitis, myonecrosis, and gas gangrene. Aeromonas cellulitis is indistinguishable from that due to other bacterial pathogens that cause cellulitis but should be suspected in wounds following contact with a water source, especially during the summer.
Aeromonas septicemia is the 3rd most frequent presentation of infection and is associated with a mortality rate of 27-73%. Aeromonas septicemia usually occurs in patients with underlying conditions such as hepatobiliary disease or malignancy but may occur in apparently immunocompetent persons. Aeromonas may be the only organism isolated or may be part of a polymicrobial bacteremic illness. A. sobria bacteremia has resulted in disseminated intravascular gas production and subsequent acute death in the absence of any underlying condition.
Aeromonas is a rare cause of necrotizing gastroenteritis, endocarditis, meningitis, osteomyelitis, pyogenic arthritis, endophthalmitis, keratitis, orbital cellulitis, ear infections, urinary tract infection, peritonitis, pyomyositis, cellulitis, necrotizing fasciitis, cholecystitis, septic embolism, pneumonia, empyema, appendicitis, surgical wound infections, pelvic inflammatory disease, lymphadenitis, epiglottitis, and lung, liver, and pancreatic abscess. Aeromonas has been associated with tracheobronchitis and aspiration pneumonia after near-drowning. Aeromonas can cause hot tub folliculitis.
Diagnosis is established by culture isolation of Aeromonas. The organism is easily grown on standard media when the source material is normally sterile. Isolation of the organism from samples containing numerous bacteria is more difficult, presumably because competing bacteria outgrow Aeromonas. Use of selective media such as a blood agar supplemented with ampicillin or MacConkey agar containing Tween 80 and ampicillin enhances isolation. Most (∼90%) strains produce β-hemolysis on blood agar. However, lack of hemolysis is not a reliable indicator of lack of hemolysin in the isolate. Lactose-fermenting strains of Aeromonas may be overlooked in stool specimens if the clinical laboratory does not routinely perform oxidase tests on lactose fermenters isolated on MacConkey or does not routinely use selective media for the isolation of Aeromonas.
While the mainstay of Aeromonas laboratory identification remains culture on selective media, numerous molecular techniques are coming into use and new selective media are being tested.
Aeromonas enteritis is usually self-limited, and antimicrobial therapy may not be indicated. Data from uncontrolled trials does suggest that antimicrobial therapy shortens the course of the illness. Antimicrobial therapy is reasonable to consider in patients with protracted diarrhea, dysentery-like illness, or underlying conditions such as hepatobiliary disease or an immunocompromised state. There is near uniform resistance to ampicillin. Septicemia should be treated with a 3rd generation cephalosporin or an aminoglycoside. Other options include aztreonam, imipenem, meropenem, chloramphenicol, trimethoprim-sulfamethoxazole (TMP-SMZ), and quinolones. Many species have developed multidrug resistance, especially to quinolones. Rarely, extended-spectrum β-lactamase–producing Aeromonas are found.
Reducing contact with contaminated environmental fresh and brackish water and contaminated foods should reduce the risk for Aeromonas infections. Aeromonas expresses LamB-like outer membrane proteins (OMPs) that facilitate bacterial adherence to extracellular matrix components. OMPs are strongly immunogenic and have been target antigens for vaccine development.
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196.2 Plesiomonas shigelloides
Plesiomonas shigelloides is most commonly associated with acute enteritis and rarely with extraintestinal infections. The organism is a facultative, anaerobic, gram-negative non–spore forming bacillus with over 100 serotypes (100 somatic [O] and 50 flagellar [H] antigens). It is catalase and oxidase positive, able to ferment xylose, and motile, with 2-5 polar flagella.
P. shigelloides is a member of the Enterobacteriaceae. A high level of diversity has been recognized within P. shigelloides strains, reflecting the frequency of homologous recombination and differing from other members of the Enterobacteriaceae.
P. shigelloides is ubiquitous in fresh water and can be found in estuarine water. Historically it has been found most often in warmer and tropical waters, although there are increasing reports of isolation from colder regions. P. shigelloides colonizes numerous cold- and warm-blooded animals, may cause disease in cats, and has been isolated from fish and seafood. Infection of humans is thought to be the result of consumption of contaminated water or raw seafood and possibly through contact with colonized animals. The role that colonized animals play in the ecology of human infection is poorly understood. A majority of symptomatic patients in North America report exposure to potentially contaminated water or seafood or have traveled abroad. In general, enteric infections with Plesiomonas occur more commonly in areas where development and hygiene are inadequate.
Epidemiologic evidence indicates that P. shigelloides is an enteropathogen. However, the diarrheagenic capacity of P. shigelloides has not been confirmed when volunteers have been fed the organism. The mechanism of enteritis is not known, but it appears that the species can commonly cause secretory and less commonly invasive disease. In vitro studies show that isolates of P. shigelloides are capable of invading and inducing apoptosis in cells of enteric origin. Most strains of P. shigelloides secrete a β-hemolysin, which is thought to be a major virulence factor. They also produce a β-lactamase, which renders them resistant to the penicillins. Studies show evidence of modulation of host defenses through inhibition of cathepsins involved in antigen processing and presentation.
Clinical disease in humans begins 1-4 days after contact with the organism. Enteritis is commonly secretory/watery and less often invasive dysentery. Infrequently, disease may last 2 wk to 3 mo. The frequency of secretory vs dysenteric diarrhea clusters by outbreak report, suggesting that either human populations or bacterial populations associate with type of presentation. Symptoms include diarrhea (100%), vomiting (70%), fever (50%), headache, abdominal cramping (more common with increased age), nausea, and transient arthralgias. Frequently diarrhea is mild and watery without significant dehydration. Blood, mucus, or both may be passed with stool, and white blood cells may be visualized in stained preparations of stool.
Extraintestinal infections are rare and usually occur in patients with underlying conditions, such as immunodeficiency (including HIV), malignancy, sickle cell disease, thalassemia, splenectomy, or cirrhosis. Traumatic wounds sustained in aquatic environments less commonly contain P. shigelloides. Rarely, bacteremia accompanying enteritis has been documented in apparently otherwise normal children. Extraintestinal disease includes septicemia, pneumonia, meningitis, osteomyelitis, septic arthritis, reactive arthritis, cellulitis, cutaneous abscess, endophthalmitis, cholecystitis, pseudoappendicitis, pseudomembranous colitis, proctitis, epididymo-orchitis, and pyosalpinx. Early-onset neonatal sepsis and meningitis are rare but comprise most of the reported cases of P. shigelloides meningitis and have a very high mortality rate (80%). Septicemia has a high mortality rate in adults.
A history of foreign travel, ingestion of raw seafood, or exposure to contaminated water or an animal with diarrhea suggests possible P. shigelloides infection. Mixed infection with Salmonella, Aeromonas, or rotavirus may occur in up to 50% of patients. Culture and isolation of the organism from stool or sterile body fluids is essential for diagnosis. P. shigelloides is a non–lactose fermenter and grows well on traditional enteric media, although selective techniques may be required to isolate the organism from mixed cultures and to differentiate P. shigelloides from Shigella species. It may be underrecognized by clinical laboratories that do not routinely perform an oxidase test. Molecular methodology is available for phylogenetic analyses and detection of organisms in some food products but is not a standard diagnostic procedure.
Enteritis due to P. shigelloides is usually self-limited. In cases associated with dehydration, patients respond favorably to oral rehydration solution. Antimicrobial therapy is reserved for those patients with prolonged or bloody diarrhea. Data from uncontrolled trials suggest that antimicrobial therapy decreases the duration of symptoms. Most strains of P. shigelloides are susceptible to TMP-SMZ, cephalosporins, carbapenems, and quinolones. In the USA quinolones are not approved for use in children <18 yr of age. P. shigelloides is commonly resistant to broad-spectrum penicillins, streptomycin, and azithromycin. In some strains resistance has also been found to TMP-SMZ, quinolones, and tetracyclines. Resistance to gentamicin, chloramphenicol, and nalidixic acid has been demonstrated in strains of P shigelloides from tilapia.
Antibiotics are essential for therapy of extraintestinal disease. Empirical therapy with a 3rd-generation cephalosporin is reasonable, because most isolates are susceptible in vitro. There are no definitive guidelines; imipenem, aztreonam, β-lactam/β-lactamase inhibitor combinations, and quinolones can be considered as alternatives to 3rd-generation cephalosporins. Definitive therapy should be guided by the susceptibility of the individual isolate.
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