Nosocomial endocarditis caused by Corynebacterium amycolatum and other nondiphtheriae corynebacteria. (Dispatches).
The nondiphtheriae corynebacteria are uncommon but increasingly recognized as agents of endocarditis endocarditis (ĕn'dōkärdī`tĭs), bacterial or fungal infection of the endocardium (inner lining of the heart) that can be either acute or subacute. in patients with underlying structural heart disease or prosthetic valves. We describe three cases of nosocomial nosocomial /noso·co·mi·al/ (nos?o-ko´me-il) pertaining to or originating in a hospital.
1. Of or relating to a hospital.
2. endocarditis caused by nondiphtheriae corynebacteria, including the first reported case of Corynebacterium Corynebacterium /Co·ry·ne·bac·te·ri·um/ (-bak-ter´e-um) a genus of bacteria including C. ac´nes, a species present in acne lesions, C. diphthe´riae, the etiologic agent of diphtheria, C. amycolatum endocarditis. These all occurred in association with indwelling indwelling /in·dwell·ing/ (in´dwel-ing) pertaining to a catheter or other tube left within an organ or body passage for drainage, to maintain patency, or for the administration of drugs or nutrients. intravascular intravascular /in·tra·vas·cu·lar/ (in?trah-vas´ku-lar) within a vessel.
Within one or more blood vessels. devices.
The nondiphtheriae corynebacteria, major components of the normal flora of human skin and mucous membranes, are commonly isolated from clinical specimens. As such, they are frequently dismissed as contaminants. Recently, however, the microbiologic classification of this group of organisms and their role in clinical disease are being more clearly defined (1). In particular, Corynebacterium amycolatum, which was first described in 1988 (2), is becoming widely recognized as an important pathogen, although it has been underreported in part because of its misidentification as C. xerosis xerosis /xe·ro·sis/ (ze-ro´sis) abnormal dryness, as of the eye, skin, or mouth.xerot´ic
xerosis generalisa´ta (3,4), an established human pathogen.
These organisms are causes of community-acquired endocarditis in patients who have underlying structural heart disease or are immunocompromised immunocompromised /im·mu·no·com·pro·mised/ (-kom´pro-mizd) having the immune response attenuated by administration of immunosuppressive drugs, by irradiation, by malnutrition, or by certain disease processes (e.g., cancer). , as well as of prosthetic-valve endocarditis. Cases in previously healthy patients are rarely described (5,6). Hospital-acquired bacterial endocarditis accounts for 7.5% to 29% of cases of endocarditis in tertiary-care hospitals and is strongly associated with infection of indwelling intravascular lines (7). Common causative organisms include Staphylococcus aureus, enterococci enterococci
bacteria in the genus Enterococcus. , and coagulase-negative staphylococci. Corynebacterium species are rarely reported as agents of hospital-acquired endocarditis.
We describe three cases of endocarditis caused by three different species of corynebacteria in our hospital within an 18-month period, all associated with indwelling intravascular devices (IID IID Imperial Irrigation District (California)
IID Interface Identifier (Component Object Model)
IID Ignition Interlock Device (automotive security system) ). These accounted for 3 of 10 cases of hospital-acquired endocarditis identified during this period and include the first reported case of endocarditis caused by C. amycolatum. Two of the Corynebacterium species were resistant to multiple antibiotics. These cases highlight the importance of the nondiphtheriae corynebacteria as emerging multiresistant nosocomial pathogens in the growing population of patients with IID.
A 74-year-old woman was hospitalized with a diagnosis of antineutrophil cytoplasmic antibody antineutrophil cytoplasmic antibody ANCA Immunology Any autoantibody directed against certain components of granulocytes, myeloid-specific lysosomal enzymes; ANCAs are most commonly found in systemic vasculitides–eg, necrotizing vasculitis, active generalized (ANCA ANCA Armenian National Committee of America
ANCA Anti-Neutrophil Cytoplasmic Antibody (medical)
ANCA Australian National Choral Association
ANCA Australian Nature Conservation Agency
ANCA Airport Noise and Capacity Act )-positive vasculitis Vasculitis Definition
Vasculitis refers to a varied group of disorders which all share a common underlying problem of inflammation of a blood vessel or blood vessels. The inflammation may affect any size blood vessel, anywhere in the body. . Her treatment included daily plasma exchanges via a right internal jugular vascular catheter that was placed on the 5th hospital day. On day 21 of admission, she had a low-grade fever that resolved after removal of the catheter, the tip of which produced a culture of diphtheroids. Blood cultures were sterile.
The patient was discharged after 1 month but was readmitted 4 weeks later for control of vasculitis. On admission she was anemic (hemoglobin 7.0 g/dL) and had persistent microscopic hematuria and elevated C-reactive protein. She had no new vasculitic manifestations and, as previously, a grade II systolic murmur was noted at the left sternal sternal /ster·nal/ (ster´n'l) of or relating to the sternum.
Of, relating to, or occurring near the sternum.
pertaining to the sternum. edge. She had a fever of 38 [degrees] C 48 hours after admission. Four sets of blood cultures were positive for C. amycolatum (Table 1). Transesophageal echocardiogram ech·o·car·di·o·gram
A visual record produced by echocardiography.
A non-invasive ultrasound test that shows an image of the inside of the heart. (TOE) showed a large mobile vegetation on the mitral valve, with prolapse prolapse
Protrusion of an internal organ out of its normal place, usually of the rectum or uterus outside the body when supporting muscles weaken. The membrane lining the rectum can push out through the anus, most often in old people with constipation who strain during and mild to moderate mitral regurgitation. A transthoracic transthoracic /trans·tho·rac·ic/ (-thah-ras´ik) through the thoracic cavity or across the chest wall.
Across or through the thoracic cavity or chest wall. echocardiogram on her previous admission had shown no mitral valve abnormality. A combination of intravenous vancomycin and oral rifampicin rifampicin /rif·am·pi·cin/ (rif´am-pi-sin) rifampin.
a derivative of rifamycin; an antibacterial and antifungal agent used in the treatment of mycobacterial infections, actinomycosis and histoplasmosis. was begun, and the fever resolved within 48 hours. The patient refused surgical intervention, and dual antibiotic therapy was continued indefinitely. A follow-up TOE at 15 months showed improvement in mitral valve features and no vegetations. The antibiotics were stopped after 16 months, and 5 months later the patient had no clinical evidence of disease recurrence.
A 69-year-old woman with hemodialysis-dependent chronic renal failure chronic renal failure Chronic kidney failure Nephrology A slow decline in renal function, which may be 2º to chronic HTN, DM, CHF, SLE, or sickle cell anemia and, if extreme, leads to ESRD, mandating kidney dialysis; an abrupt decline in renal function may be secondary to ANCA-positive vasculitis was admitted after acute thrombosis of a GoreTex dialysis fistula fistula (fĭs`chlə), abnormal, usually ulcerous channellike formation between two internal organs or between an internal organ and the skin. in her left arm. She had required temporary vascular access for hemodialysis for the preceding 12 days. On examination she was unwell and feverish. She had a grade I systolic murmur over the cardiac apex; no previous echocardiogram was available. Two sets of blood cultures grew C. striatum striatum /stri·a·tum/ (stri-a´tum) corpus striatum.stria´tal
n. pl. stri·a·ta (Table 1), as did the tip of her vascular catheter on removal. A TOE revealed a large vegetation on her mitral valve. Because of penicillin allergy, intravenous vancomycin and oral rifampicin were begun. The prosthetic arteriovenous fistula could not be removed completely, although it was considered a potential reservoir of infection. The patient had a mitral valve replacement Mitral valve replacement is a cardiac surgery procedure in which a patient’s mitral valve is replaced by a different valve. Mitral valve replacement is typically performed robotically or manually, when the valve becomes too tight (mitral valve stenosis) for blood to flow into 22 days into medical therapy, on the 29th hospital day. Her valve was completely destroyed, but on culture was sterile. Antibiotics were continued for another 15 days; however, the patient had postoperative complications and died 4 weeks later.
A 53-year-old man underwent mitral valve replacement with a Starr Edwards metal valve. His postoperative course was complicated by acute renal failure acute renal failure Acute kidney failure Nephrology An abrupt decline in renal function, triggered by various processes–eg, sepsis, shock, trauma, kidney stones, drug toxicity-aspirin, lithium, substances of abuse, toxins, iodinated radiocontrast. , for which he required temporary hemodialysis by vascular catheter for 36 days. The maximum time a single line was in place was 13 days. Cultures of four vascular catheter tips after their removal grew both diphtheroids and coagulase-negative staphylococci, which were considered to be normal skin flora. During this time, a low-grade fever developed that resolved after a change of lines. Blood cultures remained sterile. Serial echocardiograms over the following 2 weeks, however, showed a worsening paraprosthetic leak. Subsequently, five sets of blood cultures grew C. jeikeium (Table 1). The patient completed 6 weeks of intravenous vancomycin and oral rifampicin for prosthetic valve endocarditis prosthetic valve endocarditis,
n See endocarditis, infective. and was well on discharge. At follow-up, TOE studies showed no further increase in the paraprosthetic leak, and the patient had no clinical evidence of relapse of infection. He died 7 months later from noninfective causes.
Interest in the taxonomy of the nondiphtheriae corynebacteria has increased, with a resultant reclassification Reclassification
The process of changing the class of mutual funds once certain requirements have been met. These requirements are generally placed on load mutual funds. Reclassification is not considered to be a taxable event. of earlier defined taxa taxa: see taxon. and discovery of new pathogens in the group (1,8). One of the more commonly reported human infections with these organisms is infectious endocarditis. Since 1966, several case reports and reviews have described 191 cases of nondiphtheriae corynebacterial endocarditis on both prosthetic and native valves. In only six (3.1%) of these cases was association with an indwelling intravascular device specifically documented: two patients in association with chronic hemodialysis (6), one case attributed to an infected permanent pacemaker wire (9), two in connection with ventriculo-peritoneal shunts (6), and one in association with a ventriculo-atrial shunt (10). Of reports pertaining to hospital-acquired endocarditis in particular, in four case series totaling 80 cases, Corynebacterium species were not identified as causative agents (7,11-13). In another series, Corynebacterium species accounted for 1 (3.3%) of 30 cases (14), this case occurring postcardiac catheterization catheterization
Threading of a flexible tube (catheter) through a channel in the body to inject drugs or a contrast medium, measure and record flow and pressures, inspect structures, take samples, diagnose disorders, or clear blockages. . A further series of 14 cases of hospital-acquired endocarditis describes 3 (21.4%) cases due to coryneform coryneform /co·ry·ne·form/ (-form) denoting or resembling organisms of the family Corynebacteriaceae.
denoting or resembling organisms of the family Corynebacteriaceae. See also diphtheroid. species but gives no species identification or source of infection (15).
We have described three cases of nondiphtheriae corynebacterial nosocomial endocarditis associated with IID, all occurring in a single hospital, accounting for one third of 10 cases occurring in an 18-month period. These cases include the first reported case of endocarditis caused by C. amycolatum. Of the remaining seven cases, two were due to methicillin-resistant S. aureus and five to methicillin-sensitive S. aureus.
Since Lehmann and Neumann proposed in 1896 that bacteria morphologically resembling the diphtheria bacillus be incorporated with it into the genus Corynebacterium, the classification of the coryneform bacteria has been drastically altered (8). This change has, in turn, increased the difficulty of identifying these organisms, as methods that reliably differentiate related species, such as mycolic acid chromatography, gas liquid chromatography, and molecular amplification techniques, cannot easily be used in the routine laboratory setting. During 1987 to 1995, 11 new Corynebacterium species were described (1). Commercial identification systems need to be updated to include those species relevant in human disease. C. amycolatum has only recently been included in the updated API Coryne database 2.0 (4), which, as illustrated by our case, may still lead to misidentification if used alone. That there have been no previous reports of C. amycolatum causing endocarditis may be due to its misidentification as other nonlipophilic fermentative fer·men·ta·tive
1. Causing or having the ability to cause fermentation.
2. Relating to or of the nature of fermentation. corynebacteria species such as C. xerosis and C. minutissimum (3,16), both of which are associated with human disease.
Published material provides useful schema for differentiating C. amycolatum, C. minutissimum, and C. striatum by using colonial morphology, carbohydrate assimilation tests, and sensitivity to amoxycillin amoxicillin, amoxycillin
an aminopenicillin, similar in action to ampicillin and susceptible to ß-lactamase, but more efficiently absorbed from the gastrointestinal tract and with a longer duration of action. and the vibriostatic compound O/129, in conjunction with the API Coryne and API 20NE systems (17). Antibiotic sensitivity patterns may support identification, with C. amycolatum and C. jeikeium generally resistant to multiple antibiotics (18). In contrast, C. striatum, C. minutissimum, and C. xerosis generally are sensitive to a wide range of antibiotics.
Funke et al. (1) have published guidelines for identifying the coryneform bacteria, including simple phenotypic characteristics but also recommending more complex chemotaxonomic investigations and molecular genetic analysis if phenotypic characteristics do not differentiate between species. These guidelines are intended to facilitate the establishment of true disease associations of these organisms. In our experience, morphologic features combined with antibiogram profiles and the Coryne API allowed identification of two out of three corynebacteria (Table 2). As the colonial morphology and the Coryne API profile did not match in the isolate from Case 1, the organism was sent to our reference laboratory, where identification as C. amycolatum was confirmed by gas liquid chromatography (Microbial Identification System, Microbial ID, Newark, DE).
Treatment regimens described include penicillin alone, beta-lactam antibiotics or erythromycin erythromycin (ĭrĭth'rōmī`sĭn), any of several related antibiotic drugs produced by bacteria of the genus Streptomyces (see antibiotic). plus gentamicin gentamicin /gen·ta·mi·cin/ (jen?tah-mi´sin) an aminoglycoside antibiotic complex isolated from bacteria of the genus Micromonospora, , and vancomycin. Our three patients all received dual therapy with vancomycin and rifampicin. This combination has not previously been described but was effective in two of the three patients (including the case of prosthetic valve endocarditis), who were both free from infection at least 5 months after cessation of therapy. In a review of 19 patients with prosthetic valve endocarditis due to diphtheroids (19), 4 (57.1%) of 7 patients treated with antibiotics alone were reported as cured at least 1 year posttreatment. Of 12 patients treated both medically and surgically, 7 (58.3%) were reported as having a microbiologic cure (19).
This study highlights the importance of the nondiphtheriae corynebacteria in severe human disease. Specifically, clinicians and microbiologists must be aware of the potential risk factors for nondiphtheriae corynebacterial endocarditis in the hospital setting and the danger of overlooking positive longline long·line
A heavy fishing line usually several miles long and having a series of baited hooks.
long tip cultures as normal skin flora or contaminants. Stringent identification of clinical isolates will be required to define the role of the nondiphtheriae corynebacteria in human disease.
Table 1. Patient characteristics, heart valve affected, source of Corynebactedum infection and organism cultured, London Underlying disease Case Age(y)/sex process Site of endocarditis 1 74/F ANCA + Native mitral valve vasculitis 2 69/F ANCA + Native vasculitis mitral valve 3 53/M Postoperative Prosthetic mitral acute renal failure valve (Starr Edwards) Case Age(y)/sex Associated IID (a) Therapy 1 74/F Vascular catheter Vancomycin i.v. + for HD oral rifampicin, 16 months (b) 2 69/F Gortex AV fistula, Vancomycin i.v. + vascular catheter oral rifampicin, 37 for HD days; mitral valve replacement 3 53/M Vascular catheter Vancomycin i.v. + for HD CVC oral rifampicin, 42 days Case Age(y)/sex Outcome 1 74/F Resolved at 21 months postdiagnosis 2 69/F Died of unrelated causes 9 weeks after diagnosis 3 53/M Died of unrelated causes 8.5 months postdiagnosis (a) IID = indwelling intravascular device; ANCA = anti-neutrophil cytoplasmic antibody; HD = hemodialysis; AV = arteriovenous; CVC = central venous catheter. (b) Patient refused surgery and follow-up echocardiograms. Table 2. Identification and antibiograms of the Corynebacteria species in three cases of endocarditis, London Organism: gram-positive rod, nonmotile, Further catalase positive Colonial morphology identification Corynebacterium amycolatum Case 1 Dry, gray (a) Coryne API GLC (b) C. striatum Case 2 Moist, white, smooth (a) Coryne API C. jeikeiun Case 3 Gray, nonhemolytic (a) Coryne API (aerobic growth) Antibiotic sensitivity pattern (Stokes plate) Organism: gram-positive rod, nonmotile, Sensitive Resistant catalase positive Corynebacterium Cip, Ery, F, Gent, amycolatum Case 1 Rif, Teic, Vanc Pen, Trim C. striatum Case 2 Cip, Ery, F, Gent, Rif, Pen Trim, Teic, Vanc C. jeikeiun Case 3 Rif, Teic, Vanc Cip, Ery, F, Gent, Pen, Trim (a) Horse blood agar at 37 [degrees] C. (b) API = analytical profile index; GLC = gas liquid chromatography; Cip = ciprofloxacin; Ery = erythromycin; F = fucidin; Gent = gentamicin; Pen = penicillin; Rif = rifampicin; Teic = teicoplanin; Trim = Trimethoprim; Vanc = vancomycin.
We thank H. Malnick and his team in the laboratory of Hospital Infection at the Public Health Laboratory Service, Colindale, London.
Dr. Knox is a specialist registrar in clinical microbiology at St. George's Hospital, London. Her research interests include nosocomial infection and antibiotic resistance.
Dr. Holmes is an infectious diseases specialist, the senior lecturer in hospital epidemiology and infection control at Imperial College London History
Imperial College was founded in 1907, with the merger of the City and Guilds College, the Royal School of Mines and the Royal College of Science (all of which had been founded between 1845 and 1878) with these entities continuing to exist as "constituent colleges". , based at the Hammersmith Hospitals Trust. She is also codirector of the International Health Unit, Imperial College, London.
(1.) Funke G, von Graevenitz A, Clarridge JE, Bernard KA. Clinical microbiology of coryneform bacteria. Clin Microbiol Rev 1997; 10:125-59.
(2.) Collins MD, Burton RA, Jones D. Corynebacterium amycolatum sp. nov., a new mycolic acid-less Corynebacterium species from human skin. FEMS Microbiol Lett 1988;49:349-52.
(3.) Funke G, Lawson PA, Bernard KA, Collins MD. Most Corynebacterium xerosis strains identified in the routine clinical laboratory correspond to Corynebacterium amycolatum. J Clin Microbiol 1996;34:1124-8.
(4.) Wayters SG, Van Bosterhaut B, Janssens M, Verhaegen J. Identification of Corynebacterium amycolatum and other nonlipophilic fermentative corynebacteria of human origin. J Clin Microbiol 1998;36:1430-2.
(5.) Malik AS, Johari MR. Pneumonia, pericarditis Pericarditis Definition
Pericarditis is an inflammation of the two layers of the thin, sac-like membrane that surrounds the heart. This membrane is called the pericardium, so the term pericarditis means inflammation of the pericardium. , and endocarditis in a child with Corynebacterium xerosis septicaemia septicaemia or septicemia
an infection of the blood which develops in a wound [Greek sēptos decayed + haima blood]
septicemia, septicaemia [letter]. Clin Infect Dis 1995;20:191-2.
(6.) Rufael DW, Cohn SE. Native valve endocarditis due to Corynebacterium striatum: case report and review. Clin Infect Dis 1994; 19:1054-61.
(7.) Fernandez-Guerro ML, Verdejo C, Azofra J, de Gorgolas M. Hospital-acquired infectious endocarditis not associated with cardiac surgery: an emerging problem. Clin Infect Dis 1995;20:16-23.
(8.) Lipsky BA, Goldberger AC, Tompkins LS, Plorde JJ. Infections caused by non-diphtheriae corynebacteria. Rev Intact Dis 1982;4:1220-35.
(9.) Melero-Bascones M, Munoz P, Rodrigues-Creixems M, Bouza E. Corynebacterium striatum: an undescribed agent of pacemaker-related endocarditis. Clin Infect Dis 1996;22:576-7.
(10.) Tattevin P, Cremieux A-C A-C Air Conditioning , Muller-Serieys C, Carbon C. Native valve endocarditis due to Corynebacterium striatum: first reported case of medical treatment alone. Clin Infect Dis 1996;23:1330-1.
(11.) Saiman L, Prince A, Gersong WM. Pediatric pediatric /pe·di·at·ric/ (pe?de-at´rik) pertaining to the health of children.
Of or relating to pediatrics. infective endocarditis in the modern era. J Pediatr 1993;122:847-53.
(12.) Lamas CC, Eykyn SJ. Hospital acquired native valve endocarditis: analysis of 22 cases presenting over 11 years. Heart 1998;79:442-7.
(13.) Terpenning MS, Buggy BP, Kauffman CA. Hospital-acquired infective endocarditis. Arch Intern Med 1988; 148:1601-3.
(14.) Chen SCA (Single Connector Attachment) An 80-pin plug and socket used to connect peripherals. With a SCSI drive, it rolls three cables (power, data channel and ID configuration) into one connector for fast installation and removal. , Dwyer DE, Sorrell TC. A comparison of hospital and community acquired infective endocarditis. Am J Cardiol 1992;70:1449-52.
(15.) Von-Reyn CF, Levy BS, Arbeit RD, Friedland G, Crumpacker CS. Infective endocarditis: an analysis based on strict case definitions. Ann Intern Med 1981;94:505-18.
(16.) Zinkernagel AS, von Graevenitz A, Funke G. Heterogeneity within Corynebacterium minutissimum strains is explained by misidentified C. amycolatum strains. Am J Clin Pathol 1996;106:378-83.
(17.) Renaud FNR FNR False Negative Rate
FnR Find and Replace
FNR Ford Nuclear Reactor
FNR Future Net Revenue
FNR For No Reason
FNR Flexible Numbering Register
FNR Fixed Network Reconfiguration
FNR Frequency Normalization Response , Dutaur M, Daoud S, Aubel D, Reigel P, Monget D, et al. Differentiation of Corynebacterium amycolatum, C. minutissimum and C. striatum by carbon assimilation tests. J Clin Microbiol 1998;36:3698-702.
(18.) Funke G, Punter V, von Graevenitz A. Antimicrobial susceptibility patterns of some recently established coryneform bacteria. Antimicrob Agents Chemother 1996;40:2874-8.
(19.) Murray BE, Karchmer AW, Moellering RC. Diphtheroid diphtheroid /diph·the·roid/ (dif´the-roid)
1. resembling diphtheria or the diphtheria bacillus.
2. any member of Corynebacterium other than C. diphtheriae.
3. pseudodiphtheria. prosthetic valve endocarditis. A study of clinical features and infecting organisms. Am J Med 1980;69:838-48.
Karen L. Knox * and Alison H. Holmes ([dagger])
* St. George's Hospital, London, United Kingdom; and ([dagger]) Imperial College School of Medicine The Imperial College School of Medicine is the medical school of Imperial College London in England. The Faculty of Medicine was established in 1997, bringing together all the major West London medical schools into one world-class institution (see infra). , Hammersmith Hospital, London, United Kingdom
Address for correspondence: Karen L. Knox, Department of Microbiology, 1st Floor, Jenner Wing, St George's Hospital St George's Hospital, founded in 1733, is a teaching hospital in London, England. It has continuously trained medical students since that date. History
In 1716 Henry Hoare, William Wogan, Robert Witham and Patrick Cockburn decided to open the Westminster Public Infirmary , Cranmer Terrace, Tooting, London SW17 0RE, United Kingdom; fax: 44-208-725-5694; e-mail: email@example.com