Erysipelothrix rhusiopathiae

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MICROBIOLOGY

Erysipelothrix rhusiopathiae is a slender, pleomorphic, non-sporulating, gram-positive rod.

EPIDEMIOLOGY

Erysipelothrix rhusiopathiae is found worldwide. It has been reported as a commensal or a pathogen in a wide variety of vertebrate and invertebrate species including swine, sheep, turkeys, ducks, and fish but also dogs, cats, chickens and rodents. It has been isolated from flies, mites, lice and ticks. The risk of human infection with E. rhusiopathiae is closely related to the opportunity for exposure to the organism. Most human cases are related to occupational exposure (25). Those at greatest risk include fishermen, butchers, slaughterhouse workers, veterinarians and housewives (27, 48, 49). The organism is communicable from animals to humans generally by direct cutaneous contact (5). There are a few reports of bacteremia that have occurred after ingestion of undercooked pork. The occurrence of systemic infection that doesn't have an occupational link (predominantly in immunocompromised hosts) suggests that oropharyngeal or gastrointestinal colonization may occur. Recent reports of erysipeloid following cat and dog bites suggest that E. rhusiopathiae may rarely be part of the oral flora of these household pets (43).

CLINICAL MANIFESTATION

There are 3 well-defined clinical entities described in humans: 1) A localized cutaneous form known as erysipeloid; 2) A generalized cutaneous form; 3) A bacteremic form which is often associated with endocarditis (17, 34). Erysipeloid is the most common form of infection (18). Because of its mode of acquisition (i.e., contact with infected animals, fish, or their products, with organisms gaining entrance via cuts or abrasions on the skin), lesions are usually confined to the hands and fingers (7). Erysipeloid is painful and may have a throbbing or burning quality. The incubation period is approximately five to seven days. The lesion is violaceous in color and slightly elevated with well-defined borders (3). As it spreads peripherally, the central area clears. Lymphadenopathy and lymphangitis occur in approximately 20% cases. Systemic symptoms are uncommon, with low grade fevers and arthralgias occurring in only 10% of cases (47). Features which help to distinguish erysipeloid from staphylococcal or streptococcal cellulitis include the absence of suppuration, the violaceous color, the lack of pitting edema, and the disproportionate pain seen with erysipeloid (28)

The diffuse cutaneous form is rare. In this situation, the cutaneous lesion progresses proximally from the site of inoculation or appears at remote areas. Vesicles and bullae may be present. There are often systemic manifestations such as fever and arthralgias, but blood cultures are usually negative. The clinical course is much more protracted than in erysipeloid, and recurrences are not unusual.

Systemic infection with Erysipelothrix is uncommon. It rarely develops from localized infection. Over 90 cases of bacteremia with E. rhusiopathiae have been reported, with a very high incidence of endocarditis among them (15, 33). Bacteremia, without endocarditis, is being reported more frequently. It tends to occur in immunocompromised patients, whereas endocarditis usually occurs in immunocompromised patients. Although most reported cases of endocarditis have involved native valves, prosthetic valve endocarditis has been reported(16). Erysipelothrix endocarditis correlates highly with occupation (animal exposure), effects more males than females (which probably reflects occupational exposure), exhibits a peculiar aortic valve trophism, and is associated with significant mortality. Approximately a third of patients have had a history of an antecedent skin lesion or a concurrent characteristic skin lesion of erysipeloid (15). In nearly 60% of patients, Erysipelothrix endocarditis apparently developed on previously normal heart valves. The clinical picture with respect to fever, emboli, peripheral skin stigmata of endocarditis, splenomegaly, hematuria, and mycotic aneurysm are similar for cases of Erysipelothrix endocarditis, and for those of endocarditis caused by other bacteria. The most common complication of Erysipelothrix endocarditis, congestive heart failure, was present in approximately 80% of patients (15). Acute renal failure has also been reported as a complication (12). Focal infections such as brain abscess, meningitis, epidural abscess, paravertebral abscess, endophthalmitis, pneumonia, osteomyelitis, septic arthritis, prosthetic joint infection, necrotizing fasciitis, liver abscess, intra-abdominal abscess, and peritonitis have also been reported (2, 10, 11, 17, 19, 20, 21, 23, 26, 36, 40, 44). Some of these infections occurred as complications of bacteremia or endocarditis (35).

LABORATORY DIAGNOSIS

Routine blood culture techniques are adequate for specimen collection and organism growth in suspected cases of bacteremia or endocarditis. Since organisms are located only in deeper parts of the skin in cases of erysipeloid, aspirates or biopsy specimens from the edge of the lesion are needed to recover the organism. Biopsies should be of the entire thickness of the dermis (32). Because of the classical clinical presentation and rapid response to treatment, skin biopsy is rarely necessary to establish the diagnosis. Erysipelothrix rhusiopathiae will need to be differentiated from other gram-positive bacilli, in particular from Actinomyces (Corynebacterium) pyogenes andArcanobacterium (Corynebacterium) haemolyticum, and from Listeria monocytogenes. The first two organisms are b-hemolytic on blood agar and do not produce hydrogen sulfide in the butt of triple sugar iron agar slants, whereas, E. rhusiopathiae may be a-hemolytic but is never b-hemolytic and the majority of Erysipelothrix strains produce hydrogen sulfide which causes a blackened butt on triple sugar iron agar slants (9). The catalase test should be performed and motility examined to distinguish E. rhusiopathiae from L. monocytogenes. E. rhusiopathiae is catalase- negative and non-motile while L. monocytogenes is catalase- positive and motile. The neomycin susceptibility test can also be used to distinguish the two organisms. E. rhusiopathiae is resistant to neomycin, whereas L. monocytogenes is susceptible (31). E. rhusiopathiae has occasionally been misidentified as a viridans streptococcus, and since it decolonizes readily, as a gram-negative rod. It has also been dismissed as a contaminant. Molecular techniques, including PCR with primers specific for E. rhusiopathiae, have been developed and improve detection and identification (4).

PATHOGENESIS

The virulence of E. rhusiopathiae is associated, in part, with resistance to phagocytosis by polymorphonuclear leukocytes, but even if phagocytized, it is able to replicate intracellularly. The antiphagocytic ability of this organism likely results from its possession of a capsule (38, 39). Other virulence factors include enzymes, such as neuraminidase and hyaluronidase, and surface proteins (1, 6).

SUSCEPTIBILITY IN VITRO AND IN VIVO

Single Drug

Because of the small number of reported cases of systemic human infection with E. rhusiopathiae, antibiotic susceptibility data are limited. E. rhusiopathiae is highly susceptible to penicillins and to cephalosporins (25, 41, 42, 46). Penicillin and imipenem were the most active of 16 agents tested by a macrodilution method in cation-supplemented Mueller-Hinton broth with 5% horse blood (45). Additional blood was required because some E. rhusiopathiae strains showed poor growth in Mueller-Hinton broth in preliminary testing. Penicillin and imipenem were inhibitory or bactericidal for all ten isolates tested at concentrations of 0.01 and 0.06 mg/ml, respectively. The next most active antibiotics were cefotaxime and piperacillin, which were bactericidal at concentrations of 0.12 and 0.25 mg/ml, respectively. Clindamycin, linezolid, daptomycin, and fluoroquinolones are also active against E. rhusiopathiae (22, 30). Although clindamycin was inhibitory for all isolates tested with an MIC range of 0.01-1 mg/ml, it was usually not bactericidal. Of the fluoroquinolones, only pefloxacin and ciprofloxacin were tested (45). Ciprofloxacin was superior to pefloxacin and showed MIC and MBC results similar to those obtained with b-lactam antibiotics. Chloramphenicol, erythromycin, and tetracycline are inhibitory for many E. rhusiopathiae isolates. Emergence of E. rhusiopathiae strains that are resistant to these three antibiotics is arising as a consequence of animals eating antibiotic-containing feed (42).

Susceptibility of E. rhusiopathiae to vancomycin has been determined by disk diffusion or by MIC testing in eight isolates from systemic human infection reported in the medical literature and nine isolates from swine (15, 16, 45, 46). Virtually all isolates of E. rhusiopathiae are resistant to vancomycin (MIC 25 mg/ml). Teicoplanin and daptomycin appear to be somewhat more active than vancomycin. These agents were inhibitory for a human isolate at 4 and 2 mg/ml respectively (30, 45, 46). They were not bactericidal. Trimethoprim-sulfamethoxazole and aminoglycosides are inactive against E. rhusiopathiae. Mechanisms of resistance are unknown although E. rhusiopathiae is known to have plasmids. There are no data from comparative clinical trials.

Combination Drugs

Synergy with aminoglycosides has not been demonstrated.

ANTIMICROBIAL THERAPY

General

Despite being ubiquitous in nature, infection with Erysipelothrix is rare. In humans, E. rhusiopathiae manifests itself primarily as a skin disease. Except for one case of erysipeloid in a sheep farmer with coexisting orf, all other reported cases have been monomicrobial (4, 8). Based on in vitro susceptibility data and on clinical experience reported in the literature, penicillin G is the drug of choice for infections caused by E. rhusiopathiae (15, 17, 33).

Specific Infections

Erysipeloid

Erysipeloid usually resolves without treatment within three to four weeks. Intramuscular penicillin has been shown to shorten the course of erysipeloid from an average of 17.4 to 2 days (24). The optimum dosage and duration of penicillin therapy for erysipeloid have not been defined; oral penicillin V at a dose of one to two grams per day for five to seven days is probably adequate for most uncomplicated cases.

Bacteremia/Endocarditis

Because of the high rate of endocarditis among cases of bacteremia, most of the cases of bacteremia reported in the literature have been treated with at least two weeks of parenteral penicillin G at doses of 12-20 million units per day often followed by one to two weeks of oral penicillin or amoxicillin (14,29). Patients with the diffuse cutaneous form of E. rhusiopathiae should be treated like bacteremic patients with at least two weeks of intravenous penicillin G (12 million units daily).

The recommended antibiotic therapy for endocarditis is 12 to 20 million units of penicillin G per day in divided doses or Ceftriaxone, one gram intravenously daily for 4 to 6 weeks. Shorter causes consisting of 2 weeks of IV therapy followed by 2-4 weeks of oral penicillin have been reported to be successful (32, 33).

Other Focal Infections

There is a paucity of data in the literature on the treatment of serious focal infections such as brain abscess, meningitis, and bone and joint infections. Brain abscess should be treated with high dose intravenous penicillin or Ceftriaxone for at least six weeks and until resolution by CT scan. The author recommends a fluoroquinolone orally for six weeks for treatment of osteomyelitis.

Underlying Diseases

Cases of systemic infection with Erysipelothrix have been reported in persons with HIV infection, systemic lupus erythematosus, acute leukemia, and oropharyngeal cancer, and in neonates. Most of these had no history of animal or occupational exposure. Very few cases of endocarditis have occurred in immunocompromised patients, but a history of ethanol abuse was present in one third (37). There has been a recent suggestion that bacteremia due to E. rhusiopathiae without endocarditis occurs more frequently than was previously believed, and that bacteremia may be occurring with increased frequency in immunocompromised patients, while endocarditis usually occurs in immunocompetent patients (14).

Alternative Therapy

Alternatives to penicillin have seldom been used in therapy. Cephalosporins or imipenem are alternatives for the penicillin-allergic patient who does not have an immediate hypersensitivity reaction. Use of fluoroquinolones,daptomycin, and linezolid should be considered in Erysipelothrix infections when the patient is allergic to b-lactams. Although data on the fluoroquinolones and Erysipelothrix infections are limited, fluoroquinolones have been successful in curing erysipeloid (13). Tricuspid valve infective endocarditis due to Erysipelothrix was successfully treated with high doses of ciprofloxacin. Oral linezolid has been used to complete therapy in a case of bacteremia complicated by endophthalmitis (10). Clindamycin may be used if the patient does not have endocarditis. Tetracycline and erythromycin are other alternatives if susceptibility is documented and the patient doesn't have endocarditis. Bacteremia in penicillin-allergic immunocompromised hosts has been treated successfully with either clindamycin alone for two weeks or erythromycin for six weeks in combination with rifampin for three weeks. Resistance to vancomycin and to gentamicin is important because these agents are often used empirically to treat bacteremia due to gram-positive organisms or in those who are allergic to b-lactams.

ADJUNCTIVE THERAPY

Over one third of the patients with endocarditis reported in the literature required valve replacement (15). The presence of a paravalvular abscess would be an indication for surgical intervention. Infected prosthetic devices should be removed. Abscesses should be drained whenever possible.

ENDPOINTS FOR MONITORING THERAPY

Because of the limited clinical experience with this organism, therapeutic response should be monitored clinically.

VACCINES

Commercial vaccines are currently used for vaccination of swine. There are no vaccines for use in humans.

PREVENTION

The incidence of human infection with Erysipelothrix may be declining because of technological advances in animal industries. Cleaning and disinfection of work surfaces and tools, hand hygiene, and use of gloves reduce the risk of infection when working with animals or animal products. Protective apparel such as gloves should be worn by those working in slaughterhouses or fisheries.

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