Other Coryneform Bacteria, Arcanobacterium haemolyticum, and Rhodococci

Corynebacterium ulcerans and Corynebacterium pseudotuberculosis

C. ulcerans and C. pseudotuberculosis are members of the C. diphtheriae group and are known primarily as animal pathogens, although disease in humans has been reported as zoonotic infections. Both C. ulcerans and C. pseudotuberculosis may elaborate diphtheria-like toxin.

Increasingly, C. ulcerans has been implicated in causing diseases such as exudative pharyngitis and cutaneous ulcers in humans indistinguishable from C. diphtheriae . In the United Kingdom, C. ulcerans exceeded C. diphtheriae as the causative agent in diphtheria infection; in total, 59 cases of toxigenic C. ulcerans infection were reported from 1986 to 2008, and 12 cases from 2007 to 2013. The European-based Diphtheria Surveillance Network reported an increase in diphtheria cases attributable to C. ulcerans during a 9-year surveillance period. C. ulcerans has been implicated in human infection because of contact with domesticated animals; the use of multilocus sequence typing has allowed for rapid confirmation of zoonotic transmission. This has made the identification of the causative organism important for epidemiology, and guidelines for laboratory diagnosis of diphtheria cases have been published; molecular testing with techniques such as real-time polymerase chain reaction (PCR) facilitates identification of toxigenic corynebacteria. The spectrum of illness with C. ulcerans is similar to that with C. diphtheriae. Fatalities have been reported, including sudden death from toxin-induced cardiac injury and a case of fatal necrotizing sinusitis. Skin infection with C. ulcerans mimics that with C. diphtheriae. Infection of the lower respiratory tract may occur, causing pneumonia and pulmonary nodules. One case of possible human-to human transmission of C. ulcerans has been reported. Treatment of pharyngitis caused by C. ulcerans is similar to treatment of diphtheria, including the use of antibiotics such as erythromycin and diphtheria antitoxin when appropriate.

C. pseudotuberculosis is a significant pathogen in animals, particularly sheep, in which it causes caseous lymphadenitis. Human disease is rare, manifesting as granulomatous lymphadenitis, found mainly in farm workers and veterinarians who have had exposure to infected animals. It has been reported to cause a diphtheria-like illness and pneumonia, and has also been isolated from soft tissue abscesses in a young butcher. Management of C. pseudotuberculosis infection includes excision of affected lymph nodes and treatment with β-lactam antibiotics, macrolides, or tetracyclines.

Corynebacterium xerosis

C. xerosis is a colonizer of the human nasopharynx, conjunctiva, and skin. Historically, C. xerosis has been described in the literature as a pathogen that causes serious human disease, especially in immunocompromised hosts, including sepsis, endocarditis, pneumonia, peritonitis, ventriculoperitoneal shunt infection, and postoperative sternal wound infection. Subsequent investigations have questioned the reliability of identification of C. xerosis in the microbiology laboratory. In one study, all isolates originally identified as C. xerosis were in actuality C. amycolatum. This calls into question preceding case reports attributing disease to C. xerosis because true C. xerosis isolates apparently are quite rare. C. xerosis infections in humans have included blepharitis, a brain abscess, and a case of sepsis in a pediatric patient with sickle cell disease. True C. xerosis strains are susceptible to most antibiotics, which helps to distinguish them from C. amycolatum, which demonstrates multiple antibiotic resistances.

Corynebacterium striatum

C. striatum has been one of the more commonly isolated coryneform bacteria in the clinical microbiology laboratory. As with other nonlipophilic fermentative corynebacteria, a high degree of misidentification of C. striatum has occurred in the past in microbiology laboratories, and investigators have found many isolates to be C. amycolatum on detailed retesting.

C. striatum is ubiquitous and colonizes the skin and mucous membranes of normal hosts and hospitalized patients. Historically, C. striatum was not routinely identified to the species level and was often considered a contaminant. With the use of analytic tests such as MALDI-TOF, C. striatum is increasingly being recognized as an emerging pathogen. Reports of true infection confirmed with isolation of C. striatum have increased in frequency and have been described in patients with indwelling devices, chronic pulmonary disease, and immunosuppression. In addition, significant C. striatum infection has been reported in immunocompetent hosts. Case reports in the literature include native and prosthetic valve endocarditis, meningitis, pulmonary nodules, necrotizing fasciitis, septic arthritis, tubo-ovarian abscess, empyema, and osteomyelitis. There is evidence for patient-to-patient transmission of C. striatum in hospital settings, which may account for the frequency with which it is isolated in hospitalized patients. C. striatum has the ability to produce biofilm and has been implicated in a nosocomial outbreak of a multidrug-resistant strain. Nosocomial outbreaks of C. striatum have been reported in patients with chronic obstructive pulmonary disease.

Historically, C. striatum has been shown to be uniformly susceptible to vancomycin and other antimicrobials with broad gram-positive activity. Resistance has been demonstrated to penicillin, ciprofloxacin, erythromycin, clindamycin, and tetracyclines, limiting potential oral antimicrobial options for therapy. Increasingly, resistance to daptomycin has been reported; specifically in the setting of prior daptomycin therapy and during therapy in patients with infections of left ventricular assist devices.

Corynebacterium minutissimum

Defined in 1983 by Collins, C. minutissimum is a colonizer of human skin, particularly moist intertriginous areas. As with other members of this group, C. amycolatum has been misidentified as C. minutissimum in the past. Although C. minutissimum historically has been considered the causative agent in erythrasma, that association has been questioned because cultures tend to show polymicrobial infection. Erythrasma is a superficial skin infection that occurs in intertriginous areas between skin folds, axillae, groin, and fingers and toes. It causes reddened scaling patches that may be accompanied by pruritus. Skin patches glow coral-red under a Wood lamp. Diagnosis is made by means of clinical appearance and symptoms and by culture of skin scrapings. Colonies also appear coral-red under ultraviolet light. Treatment includes topical and oral antibiotics. Recurrences are frequent.

Other rare infections attributed to C. minutissimum include septicemia and endocarditis in immunocompromised patients and patients with indwelling central venous catheters, peritonitis in patients undergoing continuous ambulatory peritoneal dialysis (CAPD), pyelonephritis, costochondral abscess, breast abscess, postoperative abdominal infection, and vascular graft infection. One case of bacteremia and meningitis has been reported, in addition a case of an infected pseudomeningocele.

Corynebacterium amycolatum

Defined as a new species in 1988 by Collins, C. amycolatum was first isolated from the skin of healthy humans. Noted for its lack of mycolic acids, the species corresponds to the CDC coryneform groups F-2 and I-2. It is the nonlipophilic coryneform bacterial species most frequently isolated from clinical specimens. C. amycolatum forms small dry nonhemolytic colonies of 1 to 2 mm in diameter when cultured at 37°C. The organisms are pleomorphic and vary from single organisms to an array of Chinese letters. Because of variability in biochemical reactions, C. amycolatum had been misidentified previously as C. minutissimum, C. xerosis, and C. striatum. Currently, the API Coryne system can correctly identify C. amycolatum, but confirmatory tests should be performed.

Although case reports of infections attributed to C. amycolatum are rare, many previously reported infections by other members of the nonlipophilic fermentative group were most likely caused by C. amycolatum. Reports with reliable information on organism identification include nosocomial endocarditis after intravenous catheter–related infection, septic arthritis, a case of native valve endocarditis with aorta–left atrial fistula, and sepsis in pediatric oncology patients. C. amycolatum has been implicated in ear infections and orbital implant infections. Susceptibility testing has shown resistance to penicillins, cephalosporins, macrolides, and fluoroquinolones, and susceptibility to vancomycin, daptomycin, and linezolid. There is variable resistance to aminoglycosides and tetracyclines. Reports of successful treatment of endovascular infection include the use of vancomycin and daptomycin in combination with rifampin.

Corynebacterium glucuronolyticum

C. glucuronolyticum was defined in 1995; since 2000, the species has included isolates previously identified as Corynebacterium seminale that had been defined by Riegel and coworkers. Although it has been primarily isolated from the genitourinary tract of animals, in humans it may be included in the normal flora of the genitourinary tract. It is commonly isolated from males with genitourinary tract infections and is associated with chronic prostatitis; a case of encrusted cystitis due to C. glucuronolyticum has been reported. C. glucuronolyticum strains are susceptible to β-lactam antibiotics, gentamicin, and vancomycin but demonstrate variable resistance to fluoroquinolones, macrolides, and tetracyclines.

Other Nonlipophilic, Fermentative Corynebacteria

Corynebacterium argentoratense has been isolated from the throats of healthy volunteers and from mucosal biofilms on adenoid tissue from children with chronic or recurrent otitis media. The clinical significance of this finding is unclear. Corynebacterium matruchotii is identified by its characteristic “whip handle” appearance on Gram staining. It was previously identified as Bacterionema matruchotii until 1983, when it was reclassified as a Corynebacterium species by Collins. Mainly an inhabitant of the oral cavity of humans and animals, C. matruchotii has been rarely associated with human disease.

In 1998, Funke and colleagues identified a new species of Corynebacterium isolated from female patients with symptomatic urinary tract infections. Given the name Corynebacterium riegelii, it is nonlipophilic, weakly fermentative, and facultatively anaerobic. Similar to the lipophilic C. urealyticum, it demonstrates strong urease activity. It is susceptible to penicillins, cephalosporins, gentamicin, fluoroquinolones, and tetracyclines.

Corynebacterium confusum was defined in 1998 by Funke and colleagues ; it is nonlipophilic and very slowly fermentative. C. confusum has been isolated from a blood culture, foot infections, and a breast abscess. Additional nonlipophilic fermentative Corynebacterium spp. identified from human clinical specimens include C. simulans, C. sundsvallense, C. thomssenii, C. freneyi, C. aurimucosum, C. tuscaniae, C. coyleae, C. canis, C. falsenii, C. freiburgense, C. massiliense, C. pilbarense, C. stationis, and C. timonense.

Corynebacterium afermentans subsp. afermentans

C. afermentans subsp. afermentans was included in the CDC coryneform group ANF-1 until 1993, when Riegel and coworkers defined the species as C. afermentans with two subspecies: C. afermentans subsp. afermentans and C. afermentans subsp. lipophilum. C. afermentans subsp. afermentans is a rare human pathogen but has been reported to cause septicemia in immunocompromised patients.

Corynebacterium auris

As in the case of Turicella otitidis, C. auris was initially isolated from middle ear fluid of pediatric patients with otitis media and was presumed to be among the pathogens that cause otitis media. Subsequent studies have cultured C. auris from the external ear canal and cerumen of healthy subjects, both children and adults, and its role as a pathogen has been discounted. C. auris is resistant to penicillins, clindamycin, and erythromycin and susceptible to fluoroquinolones, gentamicin, tetracyclines, and vancomycin.

Corynebacterium pseudodiphtheriticum

C. pseudodiphtheriticum is included in the normal bacterial flora of the human upper respiratory tract. Lehmann and Neumann described the organism in 1896, giving it the name Bacillus pseudodiphtheriticum. Since 1925, it has been known as C. pseudodiphtheriticum. Historically, C. pseudodiphtheriticum was associated with endocarditis of native and prosthetic valves. The first cases of infections at other sites attributable to C. pseudodiphtheriticum became known in 1982, and since then, C. pseudodiphtheriticum has been associated primarily with respiratory infections, particularly in immunocompromised hosts and in patients with chronic lung disease. It has been isolated from patients with pneumonia and advanced acquired immunodeficiency syndrome (AIDS), and from children with cystic fibrosis and respiratory infections. Other sites of infections have been the eye, intervertebral disks, joints, lymph nodes, urine, peritoneal fluid, intravenous catheters, and surgical wounds. Although C. pseudodiphtheriticum does not elaborate toxins, it has been isolated from patients with exudative pharyngitis with pseudomembrane formation, not unlike C. diphtheriae. Corneal scrapings from patients with bacterial keratitis due to C. pseudodiphtheriticum were evaluated for host immune response to infection; elevated expression of Toll-like receptors and proinflammatory cytokines interleukin (IL)-6 and Il-1β were noted. Isolates of C. pseudodiphtheriticum have demonstrated resistance to macrolides and lincosamides but have maintained susceptibility to penicillins, cephalosporins, doxycycline, and glycopeptides. One large case series of 113 C. pseudodiphtheriticum strains from a single institution showed moderate levels of resistance to β-lactams, imipenem, tetracycline, erythromycin, ciprofloxacin, aminoglycosides, and clindamycin; all strains were susceptible to vancomycin.

Corynebacterium propinquum

Before 1994, C. propinquum was known as CDC coryneform group ANF-3; it is primarily isolated from the human respiratory tract. C. propinquum has been implicated in native and prosthetic valve endocarditis; species identification was confirmed with 16s rRNA gene sequencing and MALDI-TOF. C. propinquum has also been isolated from a pulmonary pleural effusion, an infected orthopedic device, and a plaque associated with keratitis in a diabetic patient who used a therapeutic contact lens; a case of nongonococcal urethritis due to C. propinquum has been reported.