Journal of Neuro-Oncology 11: 65-69, 1991. © 1991KluwerAcademic Publishers. Printedin the Netherlands. Clinical Study

Corynebacterium JK: A new pathogen in ventriculostomy infections Vicki A. Morrison, Eric L. Weinshel and Sharon D. Luikart Department of Medicine, Division of Medical Oncology, University of Minnesota Health Sciences Center, Minneapolis, MN55455, USA

Key words: Corynebacterium JK, ventriculostomy, cerebrospinal fluid shunts, prosthetic device infections Summary

In the past decade, Corynebacterium JK has emerged as a pathogen in several distinct clinical settings, including sepsis in immunocompromised patients and prosthetic valve endocarditis. It is also recognized as a nosocomial pathogen in infections of prosthetic devices. We present a case of a patient with carcinomatous meningitis who developed a Corynebacterium JK infection of an internal ventriculostomy which was used for intraventricular chemotherapy. Treatment with systemic and intraventriculostomy vancomycin for three weeks resulted in bacteriologic resolution of the infection. Removal of the prosthetic device was not essential for cure in this patient. The clinical spectrum of infection with this organism and aspects of therapy are reviewed. As a greater awareness of the pathogenic nature of this organism develops, it is likely to be implicated as a causative agent in a variety of infections.

Internal ventriculostomies have been in use for many years for a multiplicity of purposes. Antimicrobial agents may be instilled in these devices to treat infections such as ventriculitis or meningitis of either bacterial or fungal etiology. These devices also have a role in the care of oncology patients. Treatment of primary and secondary neoplasms of the central nervous system (CNS), carcinomatous and lymphomatous meningitis, and the acute leukemias can involve intraventricular administration of chemotherapeutic agents. However, like cerebrospinal fluid (CSF) internal shunts, these devices are at risk of infection [1]. These infections may be nosocomial in origin, acquired at the time of surgical placement of the device or via repeated accession of the device for administration of drugs. A break in the local host defense system occurs in either setting. The majority of these infections are due to coagulase negative staphylococci [2]. Not only are these organisms common skin commensuals, but they also are frequently found in in-

fections involving implanted prosthetic devices. This is related to several factors including: 1) protection of the organism from host defenses and antimicrobials by the prosthesis, itself, 2) production of a mucoid material by coagulase negative staphylococci which facilitates colonization of prosthetic surfaces, and 3) potential alterations of the prosthesis surface by these organisms [3]. Other organisms have also been identified as pathogens in this setting, including Staphylococcus aureus, Gram-negative enteric pathogens, Pseudomonas species, anaerobes such as Propionibacterium species, and rarely, fungi. Corynebacterium JK, although better known for causing sepsis in immunocompromised hosts [4, 8] and prosthetic heart valve endocarditis [9-14], may also cause infection of internal ventriculostomies [15, 16]. We report a case of a Corynebacterium JK Ommaya ® reservoir infection in a patient with metastatic malignant melanoma and carcinomatous meningitis, and review the clinical spectrum of infection, in-

66 cluding CSF shunt infections due to this organism, and appropriate antimicrobial therapy of these infections.

ized deterioration ensued until the patient's death three months later.

Discussion Case report JS was a 47 year old male who was diagnosed in July, 1988 with an intraocular melanoma. Despite treatment with involved field radiation therapy, he recurred with cutaneous disseminated disease three months later, and subsequently underwent autologous bone marrow transplantation (BMT). Four months after BMT, an intraocular recurrence prompted enucleation. This was followed by metastatic disease involving the liver, which was treated with combination chemotherapy (cyclophosphamide, doxorubicin, and DTIC), resulting in a complete remission for four months. He then developed carcinomatous meningitis, with no other evidence of disease recurrence. An Ommaya ® reservoir was implanted, and therapy with oral decadron and intraventricular thiotepa was begun. With persistance of malignant cells on cerebrospinal fluid (CSF) cytology, chemotherapy was changed to intrathecal methotrexate. One month later, the patient was noted to have persistent headache and intermittent confusion. On physical examination he was afebrile, and had no focal neurologic abnormalities. A peripheral white blood cell count was 4900 cells//~L, with 77% neutrophils on differential count. Blood cultures revealed no growth. A head CT scan was unremarkable. A CSF sample from the Ommaya ®reservoir revealed 0 wbc, 0 rbc, glucose 72mg/dl, protein 21mg/dl; a Gram stain showed rare diphtheroids but no white cells. Serial CSF cultures were significant for the growth of Corynebacterium JK (Table 1). Treatment, including intravenous vancomycin (1 gm every 12 hours) and intra-Ommaya ® vancomycin (5 mg every 48 hours), was instituted, and continued for three weeks. The patient had symptomatic improvement. All CSF cultures obtained after ten days of therapy were sterile, including a culture done two weeks after antimicrobial therapy was discontinued. However, the carcinomatous meningitis persisted despite chemotherapy; progressive general-

A report by Hande et al. in 1976 of four cases of sepsis due to a new Corynebacterium species brought the organism to the attention of those caring for compromised hosts [4]. This isolate was subsequently found to be a cause of sepsis in cancer [5] and bone marrow transplant patients [6] at other institutions across the country. In 1979, the Centers for Disease Control characterized 95 diphtheroid isolates from various clinical specimens (mainly blood cultures), and designated them as Corynebacterium 'group JK' [17]. This organism, which is a normal human commensual, appears on Gram stain as a tiny beaded gram-positive rod, which is often present in a cuneiform or 'picketfence' pattern. Tiny colonies with a distinct metallic sheen grow readily at 24 to 48 hours on blood agar. It grows poorly, if at all, anaerobically. The organism is catalase positive but is otherwise biochemically inert, which is another distinctive laboratory feature. Sepsis in immunocompromised patients is a common presentation of Corynebacterium JK infection. More than 100 cases have been reported since the mid 1970's [18]. Most cases have occurred in patients with prolonged periods of neutropenia, as in bone marrow transplant and leukemia patients. Three-fourths of the patients have been male, most greater than 16 years of age. This predisposition is Table 1. Antimierobial sensitivities of Corynebacterium JK isolate Antimicrobial

MIC (mcg/ml)

Interpretation

Ampicillin Cefaclor Cefazolin Cefuroxine Chloramphenicol Erythromycin Penicillin Vancomycin

> 8.00 8.00 > 32.00 4.00 4.00 0.25 > 2.00 0.50

Resistant Intermediate Resistant Sensitive Sensitive Sensitive Resistant Sensitive

67 thought to be due to higher skin free fatty acid levels due to circulating androgens, which favors the growth of lipophilic diphtheroids on the skin [18]. The organism, which can be a nosocomial isolate [6], is found colonizing the skin, most commonly the inguinal region, rectum, and axilla [19]. Risk factors for infection with this organism include: 1) cutaneous colonization, 2) prolonged granulocytopenia, 3) concurrent broad spectrum antimicrobial therapy with consequent alteration of the host's normal flora, and 4) mucocutaneous defects, such as rectal fissures, skin and mucosal ulcerations, and bone marrow biopsy and IV catheter sites [5-7]. Recovery from infection is dependent upon vancomycin therapy; catheter removal is necessary in some cases. Diphtheroid endocarditis usually occurs in the setting of prosthetic heart valves, although occasional cases of native valve involvement have been reported, as in intravenous drug abusers [10, 20]. Twenty-six confirmed cases of diphtheroid prosthetic valve endocarditis have been reported, with the majority occurring within 60 days of surgery [18[. Antimicrobial therapy is successful in uncomplicated cases; however, if myocardial or annular invasion occur, surgical intervention is often required. Overall survival is approximately 50%, being comparable in the medically and surgically treated groups [18]. Various nosocomial device-related infections due to this organism in patients with normal immune function have been anecdotally reported [21]. Corynebacterium JK has been cultured from central venous access device catheter tips, chest tube sites, peritoneal dialysate [22], an epicardial pacemaker site abscess [23], and a Kfintschernailed tibial fracture site [24]. Two infections involving cerebrospinal fluid shunts have been previously described [15, 16]. In one case [15], a ventriculo-atrial (VA) shunt was placed for hydrocephalus which occurred after surgical excision of a medulloblastoma. Three days after VA shunt placement, cultures from the blood and the proximal and distal ends of the shunt grew Corynebacterium JK. Clinical resolution occurred after VA shunt removal and treatment with chloramphenicol and metronidazole. A ventriculo-peritoneal (VP)

shunt was subsequently inserted. However, one year later when the peritoneal end of the VP shunt dehisced through the abdominal wall, Corynebacterium JK was again isolated from the distal tubing and the cerebrospinal fluid (CSF) in the shunt. The VP shunt was removed; no antimicrobial therapy was given, and the patient was well five months later. In the second case [16], a VP shunt was implanted to decompress the cerebral ventricles after an intracerebral bleed. A week later, when the patient developed a low-grade fever and peripheral leukocytosis, a culture of the reservoir CSF grew Corynebacterium JK. The shunt was subsequently externalized and the tubing changed. Intravenous vancomycin was given for one month, in addition to daily instillation (times three) of vancomycin into the shunt reservoir. The shunt was later removed with a new one inserted while the patient was on intravenous vancomycin. No further CSF cultures grew Corynebacterium JK. Other types of infection due to Corynebacterium JK have been reported. Cutaneous lesions have been described, most often in granulocytopenic patients at localized sites (catheter insertion site, bone marrow biopsy site, etc); the lesions would often precede septicemia [25]. Interstitial lung infiltrates have been described in association with perirectal inflammation, cutaneous lesions, and septicemia in a patient with acute leukemia [26]. Nosocomial outbreaks have also been reported [27]. Corynebacterium JK is characteristically resistant to multiple antimicrobial agents. The mechanism of this resistance is not known, although it may be related to cell wall permeability [6]. No plasmid accounting for this resistance has been demonstrated. The majority of isolates are resistant to penicillin and its derivatives, cephalosporins, chloramphenicol, and clindamycin. Characteristically, these organisms are sensitive to vancomycin, which is considered the therapy of choice. Occasional isolates will be sensitive to erythromycin or tetracycline. Activity has also been demonstrated with newer antimicrobials such as teichomycin [28] and ciprofloxacin [29]. In some cases of diphtheroid prosthetic valve endocarditis, aminoglycosides have also been used [10, 14].

68 It is not clear whether removal of an associated prosthetic device is mandatory for effective treatment of these infections. Indwelling catheters have been removed as part of treatment in some cases of Corynebacterium JK sepsis in immunocompromised patients [6]. Likewise, treatment of shunt (VA or VP) infections has involved removal of part or all of the prosthetic device [15, 16, 21]. Instillation of vancomycin into the shunt or CSF reservoir may also be used in this setting. Although prosthetic device removal in addition to systemic vancomycin therapy may not be necessary in all infected patients, it is clear that CorynebacteriumJK has a predilection to persist on prosthetic material, and if infection persists despite appropriate antimicrobial therapy, removal of the prosthetic device may be necessary for resolution of the infection. The case presented here has several interesting aspects. Infections due to CorynebacteriumJK may be acute in presentation, with high fever and systemic toxicity, or may be more indolent and subtle in presentation, as in our case and in the previously described VA and VP shunt infection cases. Findings on the CSF Gram stain may also be misleading. The presence of occasional diphtheroids with no pleocytosis may be misinterpreted as representing contamination. The isolate in our case was sensitive to several antimicrobial agents, (erythromycin, chloramphenicol, cefuroxime, vancomycin), which is not a typical sensitivity pattern. Prolonged systemic and intra-Ommaya ® vancomycin therapy was successful in eradicating our patient's infection; removal of the internal ventriculostomy was not required for bacteriologic cure. In the past decade, Corynebacterium JK has been recognized as a cause of prosthetic valve endocarditis and sepsis in patients with prolonged immunosuppression, such as leukemia and bone marrow transplant patients. However, it is now gaining prominence as a nosocomial pathogen, especially in association with implanted prosthetic devices, in patients who are not immunocompromised. The Gram stain and/or culture finding of diphtheroids from a normally sterile site in these patients should not be dismissed as a contaminant. Appropriate therapy of Corynebacterium JK infections consists of systemic vancomycin (with or

without local vancomycin instillation), with removal of a catheter or prosthesis if clinical resolution does not ensue. As a greater awareness of the pathogenic potential of this organism develops, it is likely that CorynebacteriumJK will be implicated as the etiologic agent in a greater number and greater variety of infections.

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69 13. Hook, III EW, Johnson Jr WD: Vancomycin therapy of bacterial endocarditis. Am J Med 65: 411-415, 1978 14. Murray BE, Karchmer AW, Moellering Jr RC: Diphtheroid prosthetic valve endocarditis. A study of clinical features and infecting organisms. Am J Med 69: 838-848, 1980 15. Allen KD, Green HT: Infections due to a 'Group JK' corynebacterium. J Infect 13: 41-44, 1986 16. Fisher RA, Rodziewicz G, Selman W, White R, Vibhaker S: Liver abscess: complication of a ventriculoperitoneal shunt. Neurosurgery 14: 480-482, 1984 17. Riley PS, Hollis DG, Utter GB, Weaver RE, Baker CN: Characterization and identification of 95 diphtheroid (Group JK) cultures isolated from clinical specimens. J Clin Microbiol 9: 418-424, 1979 18. Locksley RM: The lowly diphtheroid: Nondiphtheria corynebacterial infections in humans. West J Med 137: 45-52, 1982 19. Gill VJ, Manning C, Lamson M, Woltering P, Pizzo PA: Antibiotic-resistant group JK bacteria in hospitals. J Clin Microbiol 13: 472-477, 1981 20. Levine DP, Crane LR, Zervos MJ: Bacteremia in narcotic addicts at the Detroit Medical Center. II. Infectious endocarditis: A prospective comparative study. Rev Infect Dis 8: 374-396, 1986 21. Riebel W, Frantz N, Adelstein D, Spagnuolo PJ: Corynebacterium JK: A cause of nosocomial device-related infection. Rev Infect Dis 8: 42-49, 1986 22. Pierard D, Lauwers S, Mouton M-C, Sennesael J, Verbeelen D: Group JK Corynebacterium peritonitis in a patient

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Address for offprints: V.A. Morrison, University of Minnesota Health Sciences Center, Division of Medical Oncology, Box 286, Minneapolis, MN 55455, USA

Corynebacterium JK: a new pathogen in ventriculostomy infections.

In the past decade, Corynebacterium JK has emerged as a pathogen in several distinct clinical settings, including sepsis in immunocompromised patients...
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