Cluster of invasive infections, including endocarditis, caused by nontoxigenic Corynebacterium diphtheriae.

To the Editor: Nontoxigenic Corynebacterium diphtheriae is an unusual cause of deep infections such as endocarditis. We encountered a cluster of three deep infections caused by nontoxigenic C diphtheriae during a ten week period in Oakland, California. A 42-year-old, homeless, alcoholic male presented on May 14, 1999, complaining of chills, cough, weight loss, arthralgias, and night sweats. Examination revealed fever, poor hygiene, a swollen and tender right wrist, and II/VI apical systolic murmur. Three blood cultures yielded C diphtheriae biotype gravis. Transthoracic echocardiograms showed mitral valve and aortic valve vegetations. After penicillin treatment for six weeks, he underwent mitral and aortic valve replacement for congestive heart failure, and then was lost to follow-up.

A 20-year-old female crack cocaine smoker presented on July 21, 1999, with fever and systemic symptoms. One of two blood cultures grew C diphtheriae biotype gravis. Transthoracic echocardiogram showed mitral valve vegetation. Her course was complicated by systemic emboli and nosocomial infections, but she usually received vancomycin, penicillin, or ceftriaxone without aminoglycoside. She underwent mitral valve replacement for congestive heart failure on August 6, 1999. The Gram stain of the mitral valve vegetation showed Gram positive bacilli, but culture was sterile. The patient was presumed well when last seen on May 31, 2000, in the dental clinic and was subsequently lost to follow-up.

A 49-year-old, alcoholic male sustained a fibula and medial malleolus fracture to his left ankle in October of 1998, treated by open reduction and internal fixation at that time, followed by transient wound dehiscence. On June 7, 1999, he presented with fever and a swollen red left ankle. Twenty milliliters of purulent fluid thought to be synovial was aspirated; fluid analysis demonstrated a white cell count of 95,500 (98% polymorphonuclear leukocytes), Gram stain showed no organisms, and culture yielded two colonies of C diphtheriae biotype gravis; anaerobic culture were sterile. Surgical exploration on June 9,1999, demonstrated a soft tissue abscess not involving the joint or hardware. The infection responded to cefazolin and cephalexin, and he was last seen on June 15, 2000, for a wrist fracture without notation of ankle complaints.

The isolates were confirmed as nontoxigenic C diphtheriae by the California State Department of Public Health Microbial Diseases Laboratory (Berkeley, CA), using both PCR and the Elek immunodiffusion test. Antimicrobial susceptibility testing (E-test) yielded identical MICs for all three isolates: penicillin G, 0.019 [muicro]g/mL; ceftriaxone, 1.0 [micro]g/mL: vancomycin 0.75 [micro]g/mL; gentamicin 2 [micro]g/mL. All three isolates had identical BstEII ribotypes, performed at the Centers for Disease Control and Prevention.

Diphtheria due to toxigenic C diphtheriae has become rare in the United States due to vaccination with diphtheria toxoid, yet vaccination does not eliminate carriage of either toxigenic or nontoxigenic C diphtheriae and outbreaks have been occasionally reported, with disease usually cutaneous. (1) In Europe and Australia, epidemiologic and/or molecular clusters of nontoxigenic Corynebacterium diphtheriae endocarditis and other infections have been reported, (2-4) often involving drug abusers. A recent report (5) from Vancouver, Canada, related seven patients with bacteremia with a nontoxigenic strain of C diphtheriae, six of which were subtype mitis and one gravis. These patients were encountered during a five year period in three hospitals: two died, and one had tricuspid valve endocarditis. Our report herein demonstrates a small cluster in the Western Hemisphere linked by geography, time of presentation, subtyping, and molecular analysis. Clinicians and microbiologists must be attentive to the possibility of "diphtheroids" causing significant infection, rather than automatically dismissing them as contaminants.

Anthony Kakis, DPM

Beth Hartung, MD

Larry Lambert, MPH

Robert McCabe, MD

Alameda County Medical Center

Atlanta, GA

Chung K. Marston, BS

Tanja Popovic, MD, PhD

Centers for Disease Control and Prevention

Atlanta, GA

References

1. Harnisch JP, Tronca E, Nolan CM, et al. Diphtheria among alcoholic urban adults. A decade of experience in Seattle. Ann Intern Med 1989;111:71-82.

2. Gubler J, Huber-Schneider C, Gruner E, et al. An outbreak of nontoxigenic Corynebacterium diphtheriae infection: single bacterial clone causing invasive infection among Swiss drug users. Clin Infect Dis 1998;27:1295-1298.

3. Tiley SM, Kociuba KR, Heron LG, et al. Infective endocarditis due to nontoxigenic Corynebacterium diphtheriae: report of seven cases and review. Clin Infect Dis 1993 16:271-275.

4. Patey O, Bimet F, Riegel P, et al. Clinical and molecular study of Corynebacterium diphtheriae systemic infections in France. Coryne Study Group. J Clin Microbiol 1997;35:441-445.

5. Romney MG, Roscoe DL, Bernard K, et al. Emergence of an invasive clone of nontoxigenic Corynebacterium diphtheriae in the urban poor population of Vancouver, Canada. J Clin Microbiol 2006;44:1625-1629.