- Email: [email protected]
Other Corynebacteria
PART III Etiologic Agents of Infectious Diseases SECTION A Bacteria
131 Other Corynebacteria Denise F. Bratcher
Corynebacterium species, which are recognized as members of the normal human flora, are isolated from the skin, mucous membranes, and gastrointestinal tract. Although frequently dismissed as contaminants in clinical specimens, corynebacteria are recognized more often as pathogens, particularly in immunocompromised people.1,2 Infections caused by Corynebacterium species have occurred predominantly among patients with prosthetic and other medical devices. Currently, 88 valid studies have been published on Corynebacterium species, and further definition of the pathogenic role of these species in human infections and of the mechanisms of pathogenesis continues to be elucidated. Many case reports have questionable validity because of the limitations of commercial identification systems, use of inappropriate identifica-
tion methods, significant changes in taxonomy, and lack of distinction between colonization and infection.1 Identification of significant clinical isolates of Corynebacterium spp. and antimicrobial susceptibility and synergy testing are warranted; identification is enhanced by the combination of biochemical testing using commercially available panels, sequence-based methods using 16S (small subunit) ribosomal RNA (rRNA) gene sequencing, and matrix-assisted laser desorption ionization–time of flight (MALDITOF) mass spectrometry.3 Characteristics of reported infections caused by Corynebacterium species are outlined in Table 131.1. Corynebacterium infections among children rarely cause severe symptoms or mortality.4
TABLE 131.1 Characteristics of Infection and Habitats of Frequently Reported Corynebacterium Species Infection Species C. afermentans
Normal Flora Human Animal
C. amycolatum
C. bovis
Animal
C. coyleae
C. glucuronolyticum
778
Normal Host
Compromised Hosta
Brain abscess Hepatic abscess
BSI Endocarditis Pulmonary infections
Septic arthritis Endocarditis
BSI Endocarditis Peritonitis
Skin infection Meningitis Mastoiditis
BSI Endocarditis Glomerulonephritis Meningitis Septic arthritis Ascites Sepsis Skin/soft tissue infection
Human Animal
Prostatitis Genitourinary infections
Children
Antibiotic Susceptibilityb
Unusual Features
c
33–37
MDR
BSI
BSI
References
S: Vanc, Teico, V: Amg, Dap, Lin, Tet R: MDRc
Often nosocomial
1,4,24– 26,38–40
S: Ery, Rif V: Pcn
Causes rancidity of milk
1,41,42
S: Pcn, Vanc, Tet, Rif, Lin V: Ery R: MDRc
Diagnostic procedures main risk; commercial identification challenging
43
S: Pcn, Ceph, Amg, Rif, Vanc V: FQ, Ery, Tet R: MDRc
44–46
Other Corynebacteria
131
TABLE 131.1 Characteristics of Infection and Habitats of Frequently Reported Corynebacterium Species—cont’d Infection Species
Normal Flora
C. jeikeium
Human
Normal Host BSI Cardiac device infections Otitis media Septic arthritis
C. macginleyi
Compromised Hosta
Children
Antibiotic Susceptibilityb
Abscess BSI Endocarditis Enteritis Meningitis Osteomyelitis Peritonitis Pneumonia Pyelonephritis Septic arthritis Skin infections Transverse myelitis Urinary tract infection Ventriculitis
Abscess BSI Endocarditis Meningitis Pulmonary infection
S: Vanc, Lin, Tig V: Dap, Ery, FQ, Rif, Tet R: MDRc
Catheter-related infection Conjunctivitis Endocarditis Endophthalmitis Keratitis Sepsis Urinary tract infection
S: Multiple V: FQ R: Ery
Almost exclusively from eye specimens
Unusual Features
References
Most common cause of diphtheroid endocarditis; removal of prosthetic device usually required for cure; major nosocomial pathogen
1,4,6–22, 47–59
60–67
C. minutissimumd
Human
BSI Cellulitis Erythrasma (polymicrobial) Meningitis
BSI Abscess Endocarditis Erythrasma Peritonitis
Erythrasma Pyelonephritis
S: Ery, Tet, T/S, Vanc V: 2G Ceph, Chloro, Pcn R: MDRc
C. propinquum
Human
Endocarditis
Pulmonary infection
Endocarditis
S: Pen, Ceph, T/S R: Clin
C. pseudodiphtheriticum Human (Corynebacterium hofmannii)
Conjunctivitis/ keratitis Discitis Endocarditis Lymphadenitis Pharyngitis (membranous) Pulmonary infections Skin infections
BSI Endocarditis Peritonitis Pulmonary infections Septic arthritis Surgical site infection Urinary tract infectiond
BSI Endocarditis Lymphadenitis Otitis media Pharyngitis (membranous) Pulmonary infections Surgical site infection Urinary tract infection
S: Amg, Vanc, Lin, Rif, Tet V: 1G & 2G Ceph, Pcn, Chloro, Clin, FQ, Tet, Tig, T/S R: MDRc
Commensal of human nasopharynx; Gram staining shows parallel rows of bacilli
1,78–92
C. pseudotuberculosis (Corynebacterium ovis)
Animal
Lymphadenitis Pneumonia
Abscess Lymphadenitis Pneumonia
Lymphadenitis Septic arthritis
S: Amg, Ery, Clin, Pcn, Tet, Vanc,e Chloro, Rif
Produces dermonecrotic toxin; usually associated with animal contact
1,93,94
C. striatumd
Human
Endocarditis BSI Central line infection Chorioamnionitis Meningitis Osteomyelitis Peritonitis Pulmonary infections Septic arthritis Skin/soft tissue infection
BSI Ventriculitis
S: Vanc, Teico, Imip, Tig V: Clin, Dapto, Ery, Lin, Pcn, Amg, Tet R: MDRc
Nosocomial infections
1,4,17,95– 114
Involved skin fluoresces coral red with Wood light
1,68–75
76–77
Continued
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PART III Etiologic Agents of Infectious Diseases SECTION A Bacteria
TABLE 131.1 Characteristics of Infection and Habitats of Frequently Reported Corynebacterium Species—cont’d Infection Species
Normal Flora
C. ulcerans
Animal
C. urealyticum (group D2)
Human
C. xerosisd
Human
Normal Host Pharyngitis (membranous) Sinusitis Skin ulcers
Endocarditis
Compromised Hosta
Children
Antibiotic Susceptibilityb
Pharyngitis Pneumonia Pulmonary nodules
Pharyngitis (membranous) Otitis media
BSI Endocarditis Osteomyelitis Pericarditis Pneumonia Urinary tract infection (encrusted) Wound infection BSI Central nervous system infections Endocarditis Keratitis (postoperative) Osteomyelitis Peritonitis Pulmonary infections Septic arthritis
Unusual Features
References
S: multiple drugs; Ery (drug of choice)
Produces exotoxins of C. diphtheriae and C. pseudotuberculosis; associated with raw milk; treatment includes antitoxin
1,15–125
Soft tissue infection Urinary tract infection
S: Teico, Vanc V: FQ, Rif, Ery, Tet R: MDRc
Urease activity produces alkaline urine; leads to crystal formation
1,126–132
BSI Endocarditis Meningitis Pericarditis Ventriculitis
S: Vanc, 3G Ceph, FQ V: Amg, Clin, Ery, Pcn
Nosocomial infections
1,133–140
a
Compromised hosts include immunodeficient patients, neutropenic patients, those with indwelling devices, and postsurgery and trauma patients. There are no reports of controlled clinical trials using different antimicrobial agents in the treatment of infections with Corynebacterium species. Notation is based on antimicrobial susceptibilities reported in cases and laboratory evaluations. c MDR: Multidrug resistance has been reported; the only drugs active against these strains are glycopeptides, linezolid, quinupristin/dalfopristin, daptomycin, and tigecycline. d Some reports likely represent misidentification of Corynebacterium amycolatum or another Corynebacterium strain.1 e Surgical excision after parenteral antibiotic therapy is necessary for cure. BSI, bloodstream infection; Amg, aminoglycosides; Ceph, cephalosporins; 1G Ceph, first-generation cephalosporins; 2G Ceph, second-generation cephalosporins; 3G Ceph, third-generation cephalosporins; Chloro, chloramphenicol; Clin, clindamycin; Dapto, daptomycin; Ery, erythromycin; Imip, imipenem; Lin, linezolid; Pcn, penicillin; FQ, fluoroquinolones; R, resistant; Rif, rifampin; S, susceptible; Teico, teicoplanin; Tet, tetracyclines; Tig, tigecycline; T/S, trimethoprim-sulfamethoxazole; V, variable; Vanc, vancomycin. b
CORYNEBACTERIUM JEIKEIUM Corynebacterium jeikeium, formerly known as Centers for Disease Control and Prevention (CDC) group JK, was identified as a distinct group in 1976, and a pathogenic role in endocarditis after cardiovascular surgery has been noted since 1963. C. jeikeium increasingly has been identified in association with a variety of clinical entities, predominantly in immunocompromised people, and it is recognized as a significant nosocomial pathogen. C. jeikeium is the most frequently recovered medically significant corynebacterial species in patients in intensive care units.5 Only pathogenic for humans, C. jeikeium is found in soil and water and is part of normal human skin flora. The colonization rate increases with hospitalization; it has been reported in hospital personnel and in up to 40% of hospitalized patients, especially on the skin of the perirectal area, groin, and axilla.6 Infection is thought to occur when C. jeikeium invades through mucosal breaks and colonizes prosthetic devices. Risk factors for C. jeikeium infection include prolonged hospitalization; profound, extended granulocytopenia; multiple or prolonged courses of antibiotic therapy; disruption of mucocutaneous barriers; and presence of a medical device. In one study C. jeikeium was recognized as the most frequent cause of bloodstream infection (BSI) among patients who had received a bone marrow transplant6; BSI also has been reported among immunocompetent and immunosuppressed patients. C. jeikeium is the most common cause of diphtheroid endocarditis of prosthetic valves,7 and it also can infect native valves. C. jeikeium infection is the corynebacteria infection
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most likely to require valve replacement.8 Other infections attributed to C. jeikeium include skin and wound infections, catheter-related infection, enteritis, meningitis, osteomyelitis, peritonitis, pneumonia, prosthetic joint infection, pyelonephritis, and liver abscess in a patient with AIDS.9–17 Several infections caused by C. jeikeium have been reported in children, including meningitis associated with a ventriculoperitoneal shunt, BSI, endocarditis, and a localized skin abscess at a puncture site.18–20 Most cases were associated with immunosuppression, a medical device, or trauma. C. jeikeium is a nonmotile, gram-positive bacillus that can appear to be coccobacillary. Growth appears as discrete, pinpoint, smooth white colonies that take on a characteristic metallic sheen after 24 to 48 hours of incubation. The bacterium ferments glucose but does not produce urease or reduce nitrate. Identification frequently is confirmed on the basis of resistance to many antibiotics, including β-lactams, aminoglycosides, erythromycin, and tetracycline. Vancomycin generally is the most active antibiotic against C. jeikeium and is the drug of choice for the treatment of these infections, although vancomycin resistance has been reported.21 Telithromycin, linezolid, and quinupristin/dalfopristin have good in vitro activity.22 Although some have suggested that removal of a central venous catheter may not always be necessary, removal of involved prosthetic devices usually is required for cure. Corynebacterium species form biofilms that are refractory to vancomycin therapy.6,23 Prevention of nosocomial transmission of C. jeikeium depends on meticulous handwashing and aseptic technique. Further elucidation of the modes of transfer of C. jeikeium in healthcare settings may suggest additional methods of infection control.
OTHER CORYNEBACTERIUM SPECIES The frequency of corynebacteria infections has been increasing over the past 20 years; in addition, many new Corynebacterium species have been established, and more new identifications are expected.1 Corynebacteria are diverse morphologically, metabolically, and structurally. Multiple changes and improvements in the taxonomic framework for coryneform bacteria have facilitated clinical associations. C. amycolatum, a species established in 1988, probably accounted for many previously reported infections that had been misidentified as C. kutscheri, C. minutissimum, C. striatum, and C. xerosis.1 C. amycolatum, one of the species most commonly isolated from clinical specimens,1 has been reported as a cause of septicemia in a patient with diabetes24 and a premature infant,25 and also as a cause of pyogenic arthritis.26 C. amycolatum typically is resistant to multiple antibiotics but is susceptible to vancomycin and teicoplanin. Other newly identified Corynebacterium spp. have been reported in association with human disease in rare cases; these include C. accolens, C. afermentans, C. argentoratense, C. auris, C. falsenii, C. glucuronolyticum, C. kroppenstedtii, C. lipophiloflavum, C. macginleyi, C. propinquum, C. resistens, C. riegelli, C. simulans, C. tuberculostearicum, and C. ureicelerivorans.27–30 Current methods of identification of Corynebacterium species, especially those relying on commercial identification systems, may be inadequate because a limited number of species are represented. Similarly, numerous differences within reference strains of Corynebacterium species have been noted.1 Referral of isolates to a reference laboratory may be necessary. Standardized guidelines for susceptibility testing of Corynebacterium species were updated in 2010 and 2012.31,32 Variable susceptibility to antimicrobial agents mandates specific testing of each clinical isolate. In general, Corynebacterium species are susceptible to vancomycin and linezolid.3 Vancomycin is recommended for empiric
Key Points: Corynebacterium Species • Corynebacterium species often are dismissed as contaminants in clinical specimens; however, they increasingly are recognized as pathogens, especially in immunocompromised people. • Newer molecular and protein fingerprinting methods of identification have led to clarification of the taxonomy of Corynebacterium species and have corrected some previous, misleading reports. • Corynebacterium species have been associated with a variety of infections; the propensity for certain infections varies by species. • Variable susceptibility of corynebacteria to antimicrobial agents, including some multidrug-resistant strains, requires specific susceptibility testing of each isolate.
therapy of suspected Corynebacterium infections. Multidrug-resistant strains have been identified, primarily C. jeikeium, C. striatum, and C. urealyticum. All references are available online at www.expertconsult.com.
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Other Corynebacteria
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Corynebacterium minutissimum bacteremia and meningitis: a case report and review of the literature. J Infect 2008;56:77. 76. Kawasaki Y, Matsubara K, Ishihara H, et al. Corynebacterium propinquum as the first cause of infective endocarditis in childhood. J Infect Chemother 2014;20:317. 77. Petit PL, Bok JW, Thompson J, et al. Native-valve endocarditis due to CDC coryneform group ANF-3: report of a case and review of corynebacterial endocarditis. Clin Infect Dis 1994;19:897. 78. Morris A, Guild I. Endocarditis due to Corynebacterium pseudodiphtheriticum: five case reports, review, and antibiotic susceptibilities of nine strains. Rev Infect Dis 1991;13:887. 79. Bittar F, Cassagne C, Bosdure E, et al. Outbreak of Corynebacterium pseudodiphtheriticum infection in cystic fibrosis patients, France. Emerg Infect Dis 2010;16:1231. 80. Colt HG, Morris JF, Marston BJ, et al. Necrotizing tracheitis caused by Corynebacterium pseudodiphtheriticum: unique case and review. Rev Infect Dis 1991;13:73. 81. Manzella JP, Kellogg JA, Parsey KS. Corynebacterium pseudodiphtheriticum: a respiratory tract pathogen in adults. Clin Infect Dis 1995;20:37. 82. Chiner E, Arriero JM, Signes-Costa J, et al. Demonstration by PCR and DNA: sequencing of Corynebacterium pseudodiphtheriticum as a cause of joint infection and isolation of the same organism from a surface swab specimen from the patient. J Med Microbiol 2005;54:689. 83. Hemsley C, Abraham S, Rowland-Jones S. Corynebacterium pseudodiphtheriticum: a skin pathogen. Clin Infect Dis 1999;29:938. 84. Izurieta HS, Strebel PM, Youngblood T, et al. Exudative Corynebacterium pseudodiphtheriticum, a new challenge in the differential diagnosis of diphtheria. Emerg Infect Dis 1997;3:65. 85. Li A, Lai S. Corynebacterium pseudodiphtheriticum keratitis and conjunctivitis: a case report. Clin Exp Ophthalmol 2000;28:60. 86. Simonet M, DeBriel D, Boucot I, et al. Coryneform bacteria isolated from middle ear fluid. J Clin Microbiol 1993;31:1667. 87. Cimolai N, Rogers P, Seear M. Corynebacterium pseudodiphthericum in a leukemic child. Thorax 1992;47:838. 88. Kemp M, Holtz K, Andresen K, et al. Demonstration by PCR and DN of Corynebacterium pseudodiphtheriticum of the same organism from a surface swab specimen from the patient. J Med Microbiol 2005;54:689. 89. Ahmed K, Kawakami K, Watanabe K, et al. Corynebacterium pseudodiphtheriticum: a respiratory tract pathogen. Clin Infect Dis 1995;20:41. 90. Camello TCF, Souza MC, Martins CAS, et al. Corynebacterium pseudodiphtheriticum isolated from relevant clinical sites of infections: a human pathogen overlooked in emerging countries. Lett Appl Microbiol 2009;48:458. 91. Nhan TX, Parient JJ, Badiou G, et al. Microbiological investigation and clinical significance of Corynebacterium spp. in respiratory specimens. Diagn Microbiol Infect Dis 2012;74:236. 92. Bittar F, Cassagne C, Bosdure E, et al. Outbreak of Corynebacterium pseudodiphtheriticum infection in cystic fibrosis patients, France. Emerg Infect Dis 2010;16:1231. 93. Peel MM, Palmer GG, Stacpoole AM, et al. Human lymphadenitis due to Corynebacterium pseudotuberculosis: report of ten cases from Australia and review. Clin Infect Dis 1997;24:185. 94. Mills AE, Mitchell RD, Lim EK. Corynebacterium pseudotuberculosis human necrotising granulomatous lymphadenitis. Pathology 1997;29:231. 95. Rufael DW, Cohn SE. Native valve endocarditis due to Corynebacterium striatum: case report and review. Clin Infect Dis 1994;19:1054. 96. Bhandari S, Meigh JA, Sellars L. CAPD peritonitis due to Corynebacterium striatum. Perit Dial Int 1995;15:88. 97. Martínez-Martínez L, Suárez AI, Winstanley J, et al. Phenotypic characteristics of 31 strains of Corynebacterium striatum isolated from clinical samples. J Clin Microbiol 1991;33:2458. 98. Superti SV, Martins DDS, Caierao J, et al. Corynebacterium striatum infecting a malignant cutaneous lesion: the emergence of an opportunistic pathogen. Rev Inst Med Trop Sao Paulo 2009;51:115. 99. Boltin D, Katzir M, Bugoslavsky V, et al. Corynebacterium striatum: a classic pathogen eluding diagnosis. Eur J Intern Med 2009;20:e49. 100. Renom F, Garau M, Rubi M, et al. Nosocomial outbreak of Corynebacterium striatum infection in patients with chronic obstructive pulmonary disease. J Clin Microbiol 2007;45:2064. 101. Hoy DM, Kerr K, Livingston JH. Cerebrospinal fluid-shunt infection due to Corynebacterium striatum. Clin Infect Dis 1997;25:1486. 102. Cone LA, Curry N, Wuestoff MA, et al. Septic synovitis and arthritis due to Corynebacterium striatum following an accidental scalpel injury. Clin Infect Dis 1998;27:1532. 103. Scholle D. A spontaneous joint infection with Corynebacterium striatum. J Clin Microbiol 2007;45:656. 104. Tattevin P, Crémieux AC, Muller-Serieys CM, et al. Native valve endocarditis due to Corynebacterium striatum: first reported case of medical treatment alone. Clin Infect Dis 1996;23:1330.
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105. Campanile F, Carretto E, Barbarini D, et al. Clonal multidrug-resistant Corynebacterium striatum strains, Italy. Emerg Infect Dis 2009;15:75. 106. Shah M, Murillo JL. Successful treatment of Corynebacterium striatum endocarditis with daptomycin plus rifampin. Ann Pharmacother 2005;39:1741. 107. Lee PP, Ferguson DA, Sarubbi FA. Corynebacterium striatum community and nosocomial pathogen. J Infect 2005;50:338. 108. Houghton T, Kaye GC, Meigh RE. An unusual case of infective endocarditis. Postgrad Med J 2002;78:290. 109. Martin MC, Melón O, Celada MM, et al. Septicemia due to Corynebacterium striatum: molecular confirmation of entry via skin. J Med Microbiol 2003;52:599. 110. Fernandez-Ayala M, Nan DN, Farinas MC. Vertebral osteomyelitis due to Corynebacterium striatum. Am J Med 2001;111:167. 111. Tran TT, Jaijakul S, Lewis CT, et al. Native valve endocarditis caused by Corynebacterium striatum with heterogeneous high-level daptomycin resistance: collateral damage from daptomycin therapy? Antimicrob Agents Chemother 2012;56:3461. 112. Iaria C, Stassi G, Costa GB, et al. Outbreak of multi-resistant Corynebacterium striatum infection in an Italian general intensive care unit. J Hosp Infect 2007;67:102. 113. Savini V, Gherardi G, Favaro M, et al. About a bloodstream Corynebacterium striatum isolate. Folia Microbiol 2013;58:451. 114. Wang J, Du X, Cui J, et al. Drug susceptibility and homologous analysis on Corynebacterium striatum strains isolated from inpatients. Zhonghua Yi Xue Za Zhi 2014;94:2501. 115. Barrett NJ. Communicable disease associated with milk and dairy products in England and Wales, 1983–1984. J Infect 1986;12:265. 116. Wagner KS, White JM, Crowcroft NS, et al. Diphtheria in the United Kingdom, 1986–2008: the increasing role of Corynebacterium ulcerans. Epidemiol Infect 2010;138:1519. 117. Centers for Disease Control and Prevention. Respiratory diphtheria caused by Corynebacterium ulcerans – Terre Haute, Indiana, 1996. MMWR Morb Mortal Wkly Rep 1997;46:330. 118. Dessau RB, Brandt-Christensen M, Jensen OJ, et al. Pulmonary nodules due to Corynebacterium ulcerans. Eur Respir J 1995;8:651. 119. Wagner J, Ignatius R, Voss S, et al. Infection of the skin caused by Corynebacterium ulcerans and mimicking classical cutaneous diphtheria. Clin Infect Dis 2001;33:1598. 120. Lartique MF, Monnet X, LeFleche A, et al. Corynebacterium ulcerans in an immunocompromised patient with diphtheria and her dog. J Clin Microbiol 2005;43:999. 121. Schuhegger F, Kugler R, Sing A. Pitfalls with diphtheria-like illness due to toxigenic Corynebacterium ulcerans. Clin Infect Dis 2008;46:395. 122. Taylor J, Saveedra-Campos M, Harwood D, et al. Toxigenic Corynebacterium ulcerans infection in a veterinary student in London, United Kingdom, May 2010. Euro Surveill 2010;15:1. 123. DeZoysa A, Hawkey PM, Engler K, et al. Characterization of toxigenic Corynebacterium ulcerans strains isolated from humans and domestic cats in the United Kingdom. J Clin Microbiol 2005;43:4377. 124. Centers for Disease Control and Prevention. Notes from the field: respiratory diphtheria-like illness caused by toxigenic Corynebacterium ulcerans – Idaho, 2010. MMWR Morb Mortal Wkly Rep 2011;60:77. 125. Wagner KS, White JM, Crowcroft NS, et al. Screening for Corynebacterium diphtheriae and Corynebacterium ulcerans in patients with upper respiratory tract infections 2007–2008: a multicentre European study. Clin Microbiol Infect 2011; 17:519. 126. Aguado JM, Morales JM, Salto E, et al. Encrusted pyelitis and cystitis by Corynebacterium urealyticum (CDC group D2): a new and threatening complication following renal transplant. Transplantation 1993;56:617. 127. Soriano F, Ponte C, Ruiz P, et al. Non-urinary tract infections caused by multiply antibiotic-resistant Corynebacterium urealyticum. Clin Infect Dis 1993;17:890. 128. Soriano F, Tauch A. Microbiological and clinical features of Corynebacterium urealyticum: urinary tract stones and genomics as the Rosetta Stone. Clin Microbiol Infect 2008;14:632. 129. Saavedra J, Rodriguez JN, Fernandez-Jurado A, et al. A necrotic soft-tissue lesion due to Corynebacterium urealyticum in a neutropenic child. Clin Infect Dis 1996;22:851. 130. Mendizabal S, Estorhell F, Zamora I, et al. Renal transplantation in children with severe bladder dysfunction. J Urol 2005;6:560. 131. Meria P, Margaryan M, Haddad E, et al. Encrusted cystitis and pyelitis in children: an unusual condition with potentially severe consequences. Urology 2004; 64:569. 132. Ojeda-Vargas M, Gonzalez-Fernandez MA, Romero D, et al. Pericarditis caused by Corynebacterium urealyticum. Clin Microbiol Infect 2000;6:560. 133. Arisoy ES, Demmler GJ, Dunne WM. Corynebacterium xerosis ventriculoperitoneal shunt infection in an infant: report of a case and review of the literature. Pediatr Infect Dis J 1993;12:536. 134. Berkowitz FE, Dansky R. Infective endocarditis in black South African children: report of 10 cases with some unusual features. Pediatr Infect Dis J 1989;8:787. 135. Malik AS, Johari MR. Pneumonia, pericarditis, and endocarditis in a child with Corynebacterium xerosis septicemia. Clin Infect Dis 1995;20:191. 136. Wooster SL, Qamruddin A, Clarke R, et al. Brain abscess due to Corynebacterium xerosis. J Infect 1999;38:55. 137. Gaskin PR, St John MA, Cave CT, et al. Cerebrospinal fluid shunt infection due to Corynebacterium xerosis. J Infect 1994;28:323. 138. King CT. Sternal wound infection due to Corynebacterium xerosis. Clin Infect Dis 1994;19:1171. 139. Robins E, Haile-Selassie T. Corynebacterium xerosis sepsis in a pediatric patient with sickle cell disease (a case report). Clin Pediatr (Phila) 2001;40:181. 140. de Oliveira GC, Solari HP, Ciola FB, et al. Corneal infiltrates after excimer laser photorefractive keratectomy and LASIK. J Refract Surg 2006;22:159.
131 Other Corynebacteria Denise F. Bratcher
Corynebacterium species, which are recognized as members of the normal human flora, are isolated from the skin, mucous membranes, and gastrointestinal tract. Although frequently dismissed as contaminants in clinical specimens, corynebacteria are recognized more often as pathogens, particularly in immunocompromised people.1,2 Infections caused by Corynebacterium species have occurred predominantly among patients with prosthetic and other medical devices. Currently, 88 valid studies have been published on Corynebacterium species, and further definition of the pathogenic role of these species in human infections and of the mechanisms of pathogenesis continues to be elucidated. Many case reports have questionable validity because of the limitations of commercial identification systems, use of inappropriate identifica-
tion methods, significant changes in taxonomy, and lack of distinction between colonization and infection.1 Identification of significant clinical isolates of Corynebacterium spp. and antimicrobial susceptibility and synergy testing are warranted; identification is enhanced by the combination of biochemical testing using commercially available panels, sequence-based methods using 16S (small subunit) ribosomal RNA (rRNA) gene sequencing, and matrix-assisted laser desorption ionization–time of flight (MALDITOF) mass spectrometry.3 Characteristics of reported infections caused by Corynebacterium species are outlined in Table 131.1. Corynebacterium infections among children rarely cause severe symptoms or mortality.4
TABLE 131.1 Characteristics of Infection and Habitats of Frequently Reported Corynebacterium Species Infection Species C. afermentans
Normal Flora Human Animal
C. amycolatum
C. bovis
Animal
C. coyleae
C. glucuronolyticum
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Normal Host
Compromised Hosta
Brain abscess Hepatic abscess
BSI Endocarditis Pulmonary infections
Septic arthritis Endocarditis
BSI Endocarditis Peritonitis
Skin infection Meningitis Mastoiditis
BSI Endocarditis Glomerulonephritis Meningitis Septic arthritis Ascites Sepsis Skin/soft tissue infection
Human Animal
Prostatitis Genitourinary infections
Children
Antibiotic Susceptibilityb
Unusual Features
c
33–37
MDR
BSI
BSI
References
S: Vanc, Teico, V: Amg, Dap, Lin, Tet R: MDRc
Often nosocomial
1,4,24– 26,38–40
S: Ery, Rif V: Pcn
Causes rancidity of milk
1,41,42
S: Pcn, Vanc, Tet, Rif, Lin V: Ery R: MDRc
Diagnostic procedures main risk; commercial identification challenging
43
S: Pcn, Ceph, Amg, Rif, Vanc V: FQ, Ery, Tet R: MDRc
44–46
Other Corynebacteria
131
TABLE 131.1 Characteristics of Infection and Habitats of Frequently Reported Corynebacterium Species—cont’d Infection Species
Normal Flora
C. jeikeium
Human
Normal Host BSI Cardiac device infections Otitis media Septic arthritis
C. macginleyi
Compromised Hosta
Children
Antibiotic Susceptibilityb
Abscess BSI Endocarditis Enteritis Meningitis Osteomyelitis Peritonitis Pneumonia Pyelonephritis Septic arthritis Skin infections Transverse myelitis Urinary tract infection Ventriculitis
Abscess BSI Endocarditis Meningitis Pulmonary infection
S: Vanc, Lin, Tig V: Dap, Ery, FQ, Rif, Tet R: MDRc
Catheter-related infection Conjunctivitis Endocarditis Endophthalmitis Keratitis Sepsis Urinary tract infection
S: Multiple V: FQ R: Ery
Almost exclusively from eye specimens
Unusual Features
References
Most common cause of diphtheroid endocarditis; removal of prosthetic device usually required for cure; major nosocomial pathogen
1,4,6–22, 47–59
60–67
C. minutissimumd
Human
BSI Cellulitis Erythrasma (polymicrobial) Meningitis
BSI Abscess Endocarditis Erythrasma Peritonitis
Erythrasma Pyelonephritis
S: Ery, Tet, T/S, Vanc V: 2G Ceph, Chloro, Pcn R: MDRc
C. propinquum
Human
Endocarditis
Pulmonary infection
Endocarditis
S: Pen, Ceph, T/S R: Clin
C. pseudodiphtheriticum Human (Corynebacterium hofmannii)
Conjunctivitis/ keratitis Discitis Endocarditis Lymphadenitis Pharyngitis (membranous) Pulmonary infections Skin infections
BSI Endocarditis Peritonitis Pulmonary infections Septic arthritis Surgical site infection Urinary tract infectiond
BSI Endocarditis Lymphadenitis Otitis media Pharyngitis (membranous) Pulmonary infections Surgical site infection Urinary tract infection
S: Amg, Vanc, Lin, Rif, Tet V: 1G & 2G Ceph, Pcn, Chloro, Clin, FQ, Tet, Tig, T/S R: MDRc
Commensal of human nasopharynx; Gram staining shows parallel rows of bacilli
1,78–92
C. pseudotuberculosis (Corynebacterium ovis)
Animal
Lymphadenitis Pneumonia
Abscess Lymphadenitis Pneumonia
Lymphadenitis Septic arthritis
S: Amg, Ery, Clin, Pcn, Tet, Vanc,e Chloro, Rif
Produces dermonecrotic toxin; usually associated with animal contact
1,93,94
C. striatumd
Human
Endocarditis BSI Central line infection Chorioamnionitis Meningitis Osteomyelitis Peritonitis Pulmonary infections Septic arthritis Skin/soft tissue infection
BSI Ventriculitis
S: Vanc, Teico, Imip, Tig V: Clin, Dapto, Ery, Lin, Pcn, Amg, Tet R: MDRc
Nosocomial infections
1,4,17,95– 114
Involved skin fluoresces coral red with Wood light
1,68–75
76–77
Continued
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PART III Etiologic Agents of Infectious Diseases SECTION A Bacteria
TABLE 131.1 Characteristics of Infection and Habitats of Frequently Reported Corynebacterium Species—cont’d Infection Species
Normal Flora
C. ulcerans
Animal
C. urealyticum (group D2)
Human
C. xerosisd
Human
Normal Host Pharyngitis (membranous) Sinusitis Skin ulcers
Endocarditis
Compromised Hosta
Children
Antibiotic Susceptibilityb
Pharyngitis Pneumonia Pulmonary nodules
Pharyngitis (membranous) Otitis media
BSI Endocarditis Osteomyelitis Pericarditis Pneumonia Urinary tract infection (encrusted) Wound infection BSI Central nervous system infections Endocarditis Keratitis (postoperative) Osteomyelitis Peritonitis Pulmonary infections Septic arthritis
Unusual Features
References
S: multiple drugs; Ery (drug of choice)
Produces exotoxins of C. diphtheriae and C. pseudotuberculosis; associated with raw milk; treatment includes antitoxin
1,15–125
Soft tissue infection Urinary tract infection
S: Teico, Vanc V: FQ, Rif, Ery, Tet R: MDRc
Urease activity produces alkaline urine; leads to crystal formation
1,126–132
BSI Endocarditis Meningitis Pericarditis Ventriculitis
S: Vanc, 3G Ceph, FQ V: Amg, Clin, Ery, Pcn
Nosocomial infections
1,133–140
a
Compromised hosts include immunodeficient patients, neutropenic patients, those with indwelling devices, and postsurgery and trauma patients. There are no reports of controlled clinical trials using different antimicrobial agents in the treatment of infections with Corynebacterium species. Notation is based on antimicrobial susceptibilities reported in cases and laboratory evaluations. c MDR: Multidrug resistance has been reported; the only drugs active against these strains are glycopeptides, linezolid, quinupristin/dalfopristin, daptomycin, and tigecycline. d Some reports likely represent misidentification of Corynebacterium amycolatum or another Corynebacterium strain.1 e Surgical excision after parenteral antibiotic therapy is necessary for cure. BSI, bloodstream infection; Amg, aminoglycosides; Ceph, cephalosporins; 1G Ceph, first-generation cephalosporins; 2G Ceph, second-generation cephalosporins; 3G Ceph, third-generation cephalosporins; Chloro, chloramphenicol; Clin, clindamycin; Dapto, daptomycin; Ery, erythromycin; Imip, imipenem; Lin, linezolid; Pcn, penicillin; FQ, fluoroquinolones; R, resistant; Rif, rifampin; S, susceptible; Teico, teicoplanin; Tet, tetracyclines; Tig, tigecycline; T/S, trimethoprim-sulfamethoxazole; V, variable; Vanc, vancomycin. b
CORYNEBACTERIUM JEIKEIUM Corynebacterium jeikeium, formerly known as Centers for Disease Control and Prevention (CDC) group JK, was identified as a distinct group in 1976, and a pathogenic role in endocarditis after cardiovascular surgery has been noted since 1963. C. jeikeium increasingly has been identified in association with a variety of clinical entities, predominantly in immunocompromised people, and it is recognized as a significant nosocomial pathogen. C. jeikeium is the most frequently recovered medically significant corynebacterial species in patients in intensive care units.5 Only pathogenic for humans, C. jeikeium is found in soil and water and is part of normal human skin flora. The colonization rate increases with hospitalization; it has been reported in hospital personnel and in up to 40% of hospitalized patients, especially on the skin of the perirectal area, groin, and axilla.6 Infection is thought to occur when C. jeikeium invades through mucosal breaks and colonizes prosthetic devices. Risk factors for C. jeikeium infection include prolonged hospitalization; profound, extended granulocytopenia; multiple or prolonged courses of antibiotic therapy; disruption of mucocutaneous barriers; and presence of a medical device. In one study C. jeikeium was recognized as the most frequent cause of bloodstream infection (BSI) among patients who had received a bone marrow transplant6; BSI also has been reported among immunocompetent and immunosuppressed patients. C. jeikeium is the most common cause of diphtheroid endocarditis of prosthetic valves,7 and it also can infect native valves. C. jeikeium infection is the corynebacteria infection
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most likely to require valve replacement.8 Other infections attributed to C. jeikeium include skin and wound infections, catheter-related infection, enteritis, meningitis, osteomyelitis, peritonitis, pneumonia, prosthetic joint infection, pyelonephritis, and liver abscess in a patient with AIDS.9–17 Several infections caused by C. jeikeium have been reported in children, including meningitis associated with a ventriculoperitoneal shunt, BSI, endocarditis, and a localized skin abscess at a puncture site.18–20 Most cases were associated with immunosuppression, a medical device, or trauma. C. jeikeium is a nonmotile, gram-positive bacillus that can appear to be coccobacillary. Growth appears as discrete, pinpoint, smooth white colonies that take on a characteristic metallic sheen after 24 to 48 hours of incubation. The bacterium ferments glucose but does not produce urease or reduce nitrate. Identification frequently is confirmed on the basis of resistance to many antibiotics, including β-lactams, aminoglycosides, erythromycin, and tetracycline. Vancomycin generally is the most active antibiotic against C. jeikeium and is the drug of choice for the treatment of these infections, although vancomycin resistance has been reported.21 Telithromycin, linezolid, and quinupristin/dalfopristin have good in vitro activity.22 Although some have suggested that removal of a central venous catheter may not always be necessary, removal of involved prosthetic devices usually is required for cure. Corynebacterium species form biofilms that are refractory to vancomycin therapy.6,23 Prevention of nosocomial transmission of C. jeikeium depends on meticulous handwashing and aseptic technique. Further elucidation of the modes of transfer of C. jeikeium in healthcare settings may suggest additional methods of infection control.
OTHER CORYNEBACTERIUM SPECIES The frequency of corynebacteria infections has been increasing over the past 20 years; in addition, many new Corynebacterium species have been established, and more new identifications are expected.1 Corynebacteria are diverse morphologically, metabolically, and structurally. Multiple changes and improvements in the taxonomic framework for coryneform bacteria have facilitated clinical associations. C. amycolatum, a species established in 1988, probably accounted for many previously reported infections that had been misidentified as C. kutscheri, C. minutissimum, C. striatum, and C. xerosis.1 C. amycolatum, one of the species most commonly isolated from clinical specimens,1 has been reported as a cause of septicemia in a patient with diabetes24 and a premature infant,25 and also as a cause of pyogenic arthritis.26 C. amycolatum typically is resistant to multiple antibiotics but is susceptible to vancomycin and teicoplanin. Other newly identified Corynebacterium spp. have been reported in association with human disease in rare cases; these include C. accolens, C. afermentans, C. argentoratense, C. auris, C. falsenii, C. glucuronolyticum, C. kroppenstedtii, C. lipophiloflavum, C. macginleyi, C. propinquum, C. resistens, C. riegelli, C. simulans, C. tuberculostearicum, and C. ureicelerivorans.27–30 Current methods of identification of Corynebacterium species, especially those relying on commercial identification systems, may be inadequate because a limited number of species are represented. Similarly, numerous differences within reference strains of Corynebacterium species have been noted.1 Referral of isolates to a reference laboratory may be necessary. Standardized guidelines for susceptibility testing of Corynebacterium species were updated in 2010 and 2012.31,32 Variable susceptibility to antimicrobial agents mandates specific testing of each clinical isolate. In general, Corynebacterium species are susceptible to vancomycin and linezolid.3 Vancomycin is recommended for empiric
Key Points: Corynebacterium Species • Corynebacterium species often are dismissed as contaminants in clinical specimens; however, they increasingly are recognized as pathogens, especially in immunocompromised people. • Newer molecular and protein fingerprinting methods of identification have led to clarification of the taxonomy of Corynebacterium species and have corrected some previous, misleading reports. • Corynebacterium species have been associated with a variety of infections; the propensity for certain infections varies by species. • Variable susceptibility of corynebacteria to antimicrobial agents, including some multidrug-resistant strains, requires specific susceptibility testing of each isolate.
therapy of suspected Corynebacterium infections. Multidrug-resistant strains have been identified, primarily C. jeikeium, C. striatum, and C. urealyticum. All references are available online at www.expertconsult.com.
KEY REFERENCES 1. Funke G, von Graevenitz A, Clarridge JE III, et al. Clinical microbiology of coryneform bacteria. Clin Microbiol Rev 1997;10:125. 2. Martins CAS, Faria LMD, Souza MC, et al. Microbiological and host features associated with corynebacteriosis in cancer patients: a five-year study. Mem Inst Oswaldo Cruz 2009;104:905. 3. Bernard K. The genus Corynebacterium and other medically relevant coryneform-like bacteria. J Clin Microbiol 2012;50:3152.
Other Corynebacteria
REFERENCES 1. Funke G, von Graevenitz A, Clarridge JE III, et al. Clinical microbiology of coryneform bacteria. Clin Microbiol Rev 1997;10:125. 2. Martins CAS, Faria LMD, Souza MC, et al. Microbiological and host features associated with corynebacteriosis in cancer patients: a five-year study. Mem Inst Oswaldo Cruz 2009;104:905. 3. Bernard K. The genus Corynebacterium and other medically relevant coryneformlike bacteria. J Clin Microbiol 2012;50:3152. 4. Adderson EE, Boudreaux JW, Hayden RT. Infections caused by coryneform bacteria in pediatric oncology patients. Pediatr Infect Dis J 2008;27:136. 5. Tauch A, Kaiser O, Hain T, et al. Complete genome sequence and analysis of the multiresistant nosocomial pathogen Corynebacterium jeikeium K411, a lipidrequiring bacterium of the human skin flora. J Bacteriol 2005;187:4671. 6. Riebel W, Frantz N, Adelstein D, et al. Corynebacterium JK: a cause of nosocomial device-related infection. Rev Infect Dis 1986;8:42. 7. Allen KD, Green HT. Infections due to a “group JK” Corynebacterium. J Infect 1986;13:41. 8. Belmares J, Detterline S, Pak JB, et al. Corynebacterium endocarditis species-specific risk factors and outcomes. BMC Infect Dis 2007;7:4. 9. Ordónez-Palau S, Boquet D, Gil-Garcia M, et al. Chronic osteomyelitis of the metatarsal sesamoid due to Corynebacterium jeikeium in a patient with rheumatoid arthritis. Joint Bone Spine 2007;74:516. 10. Chao CT, Huang JW, Yen CJ. A rare and under-recognized pathogen in peritoneal dialysis peritonitis: Corynebacterium jeikeium. Perit Dial Int 2013;33:580. 11. Waters BL. Pathology of culture-proven JK Corynebacterium pneumonia. Am J Clin Pathol 1989;91:616. 12. Turett GS, Fazal BA, Johnston BE, et al. Liver abscess due to Corynebacterium jeikeium in a patient with AIDS. Clin Infect Dis 1993;17:514. 13. Greene KA, Clark RJ, Zabramski JM. Ventricular CSF shunt infections associated with Corynebacterium jeikeium: report of three cases and review. Clin Infect Dis 1993;16:139. 14. 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