Successful management of central nervous system infection due to Propionibacterium acnes with vancomycin and doxycycline.

Abstract: Propionibacterium acnes is an infrequent but increasingly recognized cause of neurosurgical infections. In this setting, it has been most commonly reported as complicating neurosurgical shunt procedures. The optimum therapy for central nervous system infections caused by P acnes has not been established. The authors report on a patient who had development of P acnes central nervous system infection after craniotomy for subdural hematoma. This case was successfully treated with prolonged therapy with vancomycin and doxycycline. Neurologic symptom improvement and radiographic resolution were documented on this regimen, and neurosurgical intervention was not required.

Key Words: craniotomy, neurosurgical infections, Propionibacterium acnes

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Propionibacterium acnes is an infrequent but increasingly recognized cause of neurosurgical infections. In this setting, it has been most commonly reported as complicating neurosurgical shunt procedures. (1) The optimum therapy for central nervous system (CNS) infections caused by P acnes has not been established. We report a patient who had development of P acnes CNS infection after craniotomy for subdural hematoma (SDH). This case was successfully treated with prolonged therapy with vancomycin and doxycycline. Neurologic symptom improvement and radiographic resolution were documented on this regimen.

P acnes is a Gram-positive pleomorphic rod that grows best under anaerobic conditions. (2) It is usually found either as a skin saprophyte or associated with acne but has occasionally been implicated in infections in neurosurgical patients. The ideal medical and surgical treatment of neurosurgical patients with P acnes infection has not been established. Our microbiologic laboratory does not routinely perform antibiotic sensitivity tests on this anaerobic organism, and optimal antibiotic selection for these patients is not clear. We report a patient who had development of P acnes CNS infection after craniotomy for subdural hematoma, and who was successfully treated with a prolonged course of doxycycline and vancomycin.

Case Report

In December 2002, a 72-year-old male was admitted to the hospital for progressively worsening headaches and altered mental status since having a fall several weeks earlier. Evaluation revealed a left frontoparietal chronic SDH (Fig. 1). The patient was taken to the operating room for burr hole drainage of his SDH, with improvement of neurologic symptoms during the immediate postoperative period. He was readmitted 1 week after discharge, when a subsequent computed tomographic (CT) scan showed recurrence of the SDH. He returned to the operating room urgently for a left-sided craniotomy for evacuation of the SDH. He did well and was discharged but was again readmitted 2 months later, complaining of memory difficulties and malaise. When repeat CT scanning showed reaccumulation of the hematoma, a revision of his previous craniotomy was performed for re-evacuation of the SDH. Subsequent CT scan did not reveal reaccumulation of the hematoma, but the patient continued to have memory difficulties and malaise, and began to have expressive aphasia. His symptoms initially were subtle and appeared over several days to weeks. They appeared to his physicians to be slowly worsening.

Because of the patient's continuing neurologic symptoms, he underwent a magnetic resonance imaging scan that showed pia and dural enhancement, and changes compatible with cerebritis (Fig. 2). An infectious cause was suspected, and he was again admitted to the hospital and given empiric vancomycin and ceftriaxone therapy. Cultures of subdural fluid obtained at the time of the repeat craniotomy grew P acnes. Pending results of blood cultures that were ordered to help address the possibility of mixed infection, the decision was made to discontinue ceftriaxone (one day of therapy was administered) and add ceftazidime (as empiric Gram-negative coverage) while continuing vancomycin (as empiric methicillin-resistant Staphylococcus aureus coverage, as well as coverage for the P acnes). Doxycycline was also added because of the P acnes. The patient's neurologic status stabilized during this 2-week hospital stay, and he was not found to be bacteremic. Because of the improvement in his neurologic status and no re-accumulation of the subdural empyema with the use of antibiotics alone, no further surgical intervention was indicated. At discharge, the decision was made to discontinue ceftazidime and continue the patient on a 4-week course of vancomycin and doxycycline as an outpatient. During this treatment period, the patient reported resolution of his malaise and memory problems. His expressive aphasia also gradually resolved. After 4 weeks, the vancomycin was discontinued. He was empirically continued on doxycycline for another month. A CT scan with contrast was performed that did not show fluid collection or changes consistent with infection, and the patient's doxycycline was discontinued (Fig. 3). He has subsequently done well, with no further neurologic problems.

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Discussion

Propionibacterium acnes is a normal inhabitant of skin and sebaceous glands. The literature includes a number of dermatologic articles about the microbiologic characteristics of the organism as well as its importance in clinical dermatology. (3,4) This bacterium was originally thought to be a contaminant when it appeared in clinical cultures, but came to be recognized as an important cause of postoperative neurosurgical infections in the 1970s. In 1978, Skinner and coworkers reported a series of nine neurosurgical patients who had P acnes isolated from various CNS sites. Several of these patients had postoperative fever or symptoms suggestive of meningitis. These patients were treated with various antibiotics including chloramphenicol, gentamicin, ampicillin, erythromycin, and cloxacillin. Their clinical courses were reviewed, and the special relation between P acnes and CNS shunts was discussed. The indolent nature of the CNS infection produced by this organism was mentioned as well, and is of interest in a consideration of our patient (who also had a relatively indolent clinical expression of CNS infection). (5)

Since the 1970s, P acnes infections have been infrequently but consistently encountered by neurosurgeons. The organism has been implicated in glomerulonephritis after CNS shunt placement, (1) neurosurgical wound infection with contiguous osteomyelitis, (6) CNS infection after craniotomy for evacuation of subdural hematoma, (7) and subdural empyema. (8) P acnes-related problems have also emerged in disciplines other than neurosurgery. It has been implicated in ocular surface inflammation, (9) granulomatous colitis, (10) endocarditis, (11) endophthalmitis, (12) and the contamination of blood components at a blood donation center. (13) In addition to the association of the bacterium with infections involving surgically implanted foreign material (neurosurgical shunts), possible links between the organism and several immunologic diseases have recently been described. There have been reports of P acnes complicating immune deficiency (chronic granulomatous disease), (14) and as a possible causal agent in sarcoidosis. (15,16)

Perhaps the most challenging aspect of our patient's case was the decision regarding his antibiotic therapy. Although P acnes appears to demonstrate susceptibility to a wide number of antibiotics, including tetracycline, carbenicillin, penicillin, chloramphenicol, erythromycin, (5) and vancomycin and doxycycline, (14) no clear-cut recommendations exist in the literature with regard to therapeutic treatment. (6) Many neurosurgical patients have been successfully treated with a combination of penicillin and surgical drainage, (6,7) but there are also reports of successful treatment of these patients with levofloxacin, (2) chloramphenicol, and intrathecal gentamicin (1) and vancomycin (as an initial part of combination therapy with penicillin). (6) Routine anaerobic bacterial antibiotic sensitivity testing in clinical laboratories is problematic because of lack of standardization, failure of anaerobes to grow on various media, and other technical difficulties. (17) The antibiotic susceptibility profile of P acnes is not reported in our laboratory, so antibiotic selection for our patient was empiric. After our patient stabilized on his initial regimen of vancomycin, ceftazidime, and doxycycline, the decision was made to discontinue ceftazidime and continue to administer vancomycin along with doxycycline as prolonged outpatient therapy. Vancomycin was selected (as opposed to penicillin) because of the relative ease of parenteral dosing (once per day as opposed to multiple daily doses of penicillin or penicillin administration via continuous infusion pump), and doxycycline was selected because of the known susceptibility of this organism to tetracycline and doxycycline. The marked clinical improvement of the patient on this regimen and the fact that repeat neurosurgical intervention was not required in this case were believed to be of particular importance.

The object of war is not to die for your country but to make the other
bastard die for his.
--General George Patton

Accepted September 21, 2004.

References

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2. Jallo GI, Koslow M, Hanna BA, Carson LA. Propionibacterium as a cause of postneurosurgical infection in patients with dural allografts: report of three cases. Neurosurgery 1999;44:1138-1141.

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8. Yoshikawa TT, Chow AW, Guze LB. Role of anaerobic bacteria in subdural empyema. Am J Med 1975;58:99-104.

9. Suzuki T, Sano Y, Sasaki O, Kinoshita S. Ocular surface inflammation induced by Propionibacterium acnes. Cornea 2002;21:812-817.

10. Wada R, Kawamura C, Inoue S, et al. Granulomatous colitis associated with botryomycosis of Propionibacterium acnes. Arch Pathol Lab Med 2001;125:1491-1493.

11. Vandenbos F, Roger PM, Mondain-Miton V, et al. Ventricular patch endocarditis caused by Propionibacterium acnes: advantages of gallium scanning. J Infect 2001;43:249-251.

12. Gutierrez-Diaz E, Montero-Rodriguez M, Mencia-Gutierrez E, et al. Propionibacterium acnes endophthalmitis in Ahmed glaucoma valve. Eur J Ophthalmol 2001;11:383-385.

13. Kunishima S, Inoue C, Kamiya T, Ozawa K. Presence of Propionibacterium acnes in blood components. Transfusion 2001;41:1126-1129.

14. Bourdeaut F, Quartier P, Alkaer G, et al. Propionibacterium acnes chest infections in patients with chronic granulomatous disease: case reports. CID 2002;34:853-854.

15. Ichiyasu H, Suga M, Iyonaga K, Ando M. Role of monocyte chemoattractant protein-1 in Propionibacterium acnes-induced pulmonary granulomatosis. Microsc Res Tech 2001;53:288-297.

16. Yamada T, Eishi Y, Ikeda S, et al. In situ localization of Propionibacterium acnes DNA in lymph nodes from sarcoidosis patients by signal amplification with catalysed reporter deposition. J Pathol 2002;198:541-547.

17. Engelkirk PG, Duben-Engelkirk J. Anaerobes of clinical importance, in Mahon CR, Manuselis G (eds): Textbook of Diagnostic Microbiology. Philadelphia, WB Saunders, 2000, pp 565-622.

RELATED ARTICLE: Key Points

* Propionibacterium acnes infection can follow craniotomy.

* Treatment of central nervous system Propionibacterium acnes infection is discussed.

* Use of antibiotics for treatment of cerebral empyema is described.

Michael E. Fincher, MD, Mary Forsyth, MD, and Scott Y. Rahimi, MD

From the Section of Infectious Diseases, the Department of Internal Medicine, and the Department of Neurosurgery, Medical College of Georgia, Augusta, GA; and VA Medical Center, Augusta, GA.

Reprint requests to Dr. Michael E. Fincher, Medical College of Georgia, 1120 15th Street, Augusta, GA 30312. Email: [e-mail]