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Infections Caused by Propionibacterium Species Itzhak Brook and Edith H. Frazier

From the Departments of Pediatrics and Laboratory Medicine, National Naval Medical Center, Bethesda, Maryland

Eight hundred and sixteenisolatesof Propionibacterium species(725 of whichwere Propionibacterium acnes) were isolated from 3,971 specimens submitted for the identification of anaerobic bacteria over the course of 10 years. A total of 94 Propionibacterium isolates (12%) identified

Propionibacterium acnes and other Propionibacterium species are nonsporeforming, anaerobic gram-positive bacilli that normally inhabit the conjunctiva [1], external ear canal [2], skin [3], mouth and upper respiratory tract, and, occasionally, intestine. The organisms are common contaminants of cultures of blood and body fluids and have traditionally been considered nonpathogenic for humans [4]. Although unusual pathogens, Propionibacterium species have been identified with or without other aerobic or anaerobic bacteria as causes of brain abscesses [5, 6], subdural empyema [7-9], parotid and dental infections [10], conjunctivitis associated with a contact lens [11],pulmonary infections [12], and peritonitis [13]. The organisms have been identified in pure culture in specimens taken from patients with or without artificial heart valves who have endocarditis [14, 15]/from patients with CNS shunt infections [14, 16], and from those with other serious infections [17, 18]. This report describes our experience over a period of 10 years in the recovery of Propionibacterium species from patients with significant infections.

Materials and Methods Records from the clinical microbiology laboratory fgr June 1978-June 1988 were reviewed to identify patients infected

Received 3 May 1990; revised 30 October 1990. The opinions and assertions contained herein are the opinions of the authors and are not to be construed as official or reflecting the views of the U.S. Department of Navy or the Naval Service at large. Reprints and correspondence; Dr. Itzhak Brook, Armed Forces Radiobiology Research Institute, Bethesda, Maryland 20889-5145. Reviews of Infectious Diseases 1991;13:819-22 This article is in the public domain.

with Propionibacterium species. Anyone of the following criteria defined a case of significant infection: (1) isolation of a Propionibacterium species in a pure culture of a surgical specimen obtained during an open surgical procedure as well as clinical evidence of infection at that site (i.e., local tenderness or swelling on examination or obvious purulence noted at surgery); (2) an isolate from a normally sterile body site and at least one blood culture positive for a Propionibacterium species; or (3) at least two separately obtained positive blood cultures. Only specimens that were properly collected and submitted in transport media appropriate for anaerobic bacteria were accepted by the microbiology laboratory. Most specimens, except blood, were submitted in Port-a-Cul transport swab or liquid systems (BBL, Cockeysville, MD). However, no exact record of the transport media used is available. Blood was collected aseptically from patients suspected of having bacteremia and was inoculated (10%, vol/vol) into one bottle each of two commercially obtained broth media, both under vacuum and with C02. The specimen material was inoculated onto prereduced vitamin Ki-enriched Brucella blood agar, an anaerobic blood agar plate containing kanamycin and vancomycin, an anaerobic blood plate containing colistin sulfate and naladixic acid, and an enriched thioglycolate broth (containing hemin, sodium carbonate, and vitamin K 1) [19]. It was then incubated in GasPak jars (BBL) and examined at 48 and 96 hours. Anaerobes were identified by techniques previously described [19-21].

Results A total of 3,971 specimens were examined for anaerobic bacteria during the study period. Eight hundred and sixteen

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in 92 patients were considered to cause infection. The rest of the isolates were determined to be contaminants or of uncertain pathogenic significance. Significant infectionscaused by Propionibacterium species were associated with the blood in 15 patients, central nervous system in 11, lymph glands in 10, abscesses in eight, joints in seven, wounds in seven, cysts in six, and sinuses in five. Predisposing or underlying conditions were noted in 66 patients (70%). The most common conditions werethe presence of foreignbodies (29 patients), diabetes (12), previous surgery (10), trauma (seven), malignancy (seven), immunodeficiency (seven), and steroid therapy (four). Antimicrobial therapy was administered to 83 patients; for 47 patients this therapy was given in conjunction with surgical drainage or correction. Surgical drainage alone was performed in nine patients. Five patients (5%) died. These data illustrate that although Propionibacterium species are rarely associated with infections, these organisms can occasionallycause serious infections.

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Table 1. Recovery of Propionibacterium species from sites of infection.

Site of infection

Total

315 728 59 7 478 35 208 178 201 19 48 26 10 58 59 781 87 52 580 42 3,971

P. acnes

Other

Total

3/21 6/40 1/6 0/2 12/202 2/8 10/141 3/45 4/15 1/6 2/31 0/3 3/5 6/29 8/38 2/14 5/30 4/19 6/54 2/16

0/0 2/11 1/3 0/0 3/16 0/1 1/9 0/3 2/7 011 0/2 0/0 0/0 1/5 2/6 1/10 0/5 0/1 1/9 0/2

3/21 (14) 8/51 (16) 2/9 (23) 0/2 (0) 15/218 (7) 2/9 (22) 11/150 (7) 3/48 (6) 6/22 (27) 1/7 (14) 2/33 (6) 0/3 (0) 3/5 (60) 7/34 (21) 10/44 (23) 3/24 (12) 5/35 (14) 4120 (20) 7/63 (11) 2/18 (11)

1 2 0 0 2 1 0 0 1 0 0 0 0 0 1 1 1 0 2 0

Propionibacterium species isolated*

80/725 (11)

14/91 (15)

94/816 (12)

12/94 (13)

* Number of Propionibacterium isolates causing true infection/total number of Propionibacterium isolates (%). t OBG = obstetric and gynecologic.

Propionibacterium organisms were isolated, and 725 of them were identified as P. acnes (table 1). According to the data from the clinical microbiology laboratory, 118isolates recovered from 116patients met the criteria set for significant infection. However, clinical records were available for only 94 isolates recovered from 92 patients. These 94 isolates accounted for 12 % of all Propionibacterium isolates. Significant infection was less often associated with isolates from blood than with isolates from all other sites (table 1). In 12 instances, clinically significant Propionibacterium species were recovered with other flora. Two of the patients had two concomitant infections: one had bacteremia and osteomyelitis, and another had endocarditis and osteomyelitis. The rest of the Propionibacterium isolates were considered contaminants or of uncertain pathogenic significance. The ages of the 92 patients ranged from 7 months to 69 years (mean, 38 years) .and 71 were males. Significant infections caused by Propionibacterium species were associated with the blood in 15 patients, CNS in 11, lymph glands in 10, abscesses in eight, joints in seven, wounds in seven, cysts in six, and sinuses in five. Predisposing or underlying conditions were noted in 66 patients (70 %). One predisposing condition was observed in 50 instances and two such conditions were found in 16. The conditions noted in these 66 patients were the presence of for-

eign bodies, including intravascular, intrathecal, and prosthetic devices (29 patients); diabetes (12); previous surgery (10); trauma (seven); malignancy (seven); immunodeficiency(seven); steroid therapy (four); intravenous drug use (three); and sickle cell anemia (three). Of the three patients with intraabdominal infection, two had peritonitis (associated with diabetes and peritoneal dialysis in one and occurring after trauma in the other) and the third patient had an abscess (etiology unknown). Of the eight isolates recovered from specimens from abscesses, two were from a breast abscess (one from a patient on steroids), two were recovered from skin (one from a drug addict), and one isolate each was found in abscesses of the neck (in a diabetic), hip, parotid gland (in an immunodeficient patient), and nose (also in an immunodeficient patient). The two bile isolates were from patients with cholecystitis (one patient had bile stones). Ofthe 15 isolates recovered from blood, 11 were associated with the presence of a foreign body. The foreign bodies included seven prosthetic valves and four vascular catheters. Endocarditis was diagnosed in two patients with prosthetic valves. The two isolates from patients with osteomyelitis were recovered from the humerus and femur after surgical implantation of foreign bodies to correct fractures. Of the 11 isolates from the CNS, seven were recovered from

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Abdomen Abscess Bile Bites Blood Bone CNS Chest Cysts Ear Eye Genitourinary tract Grafts Joints Lymph glands OBGt Sinuses Tumors Wounds Miscellaneous

Total no. of specimens

Instances of infection due to Propionibacterium species mixed with other flora

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Propionibacterium Infection

Discussion The data presented illustrate the recovery of Propionibacterium species over a period of 10 years from 92 patients with significant infections. The 94 isolates recovered from 92 patients represent 12 % of all Propionibacterium isolates recovered during the study period. These organisms were especially prevalent in infections associated with foreign bodies, diabetes, previous surgery, immunodeficiency, and malignancy. Our findings confirm the previous recovery and incrimination of these organisms as causative agents in patients with endocarditis associated with implanted cardiac valves [15], meningitis associated with CNS shunts [14, 16], skin infection [22], endophthalmitis [23], septic arthritis [24], and osteomyelitis [25]. P. acnes is known to be associated with the inflammatory process in acne lesions [26]. Propionibacterium species are known to possess immunostimulatory mechanisms that have been previously studied. These include activation of complement [27], stimulation of lysosomal enzyme release from human neutrophils [28], and production of serum-independent neutrophil chemotactic factors [29, 30]. Under certain circumstances, many organisms with relatively low pathogenicity such as Propionibacterium spec~es may be involved in infections. Infections were observed WIth Bacillus species [31], alpha and gamma streptococci [32], Moraxella catarrhalis [33], and aerobic diphtheroids [17, 18]. Propionibacterium species are generally susceptible to most antibiotics used for the treatment of anaerobic infections, including (j-Iactam antibiotics (penicillins and cephalosporins) and macrolides (erythromycin, lincomycin, and clindamycin). However, Propionibacterium species are generally resistant to imidazoles (such as metronidazole). It is imperative that agents other than imidazoles be used [34] whene~er Pr~pi­ onibacterium species are suspected as the causes of infection, Since Propionibacterium species are capable of inducing significant infections, especially in some high-risk patient~, efforts should be made to obtain specimens free of contamination by the normal flora of the mucous membrane and skin, where Propionibacterium species reside. Determination of the clinical significance of each isolate must be made with caution, since such determinations influence the need to direct therapy against that isolate. Acknowledgments

The authors acknowledge the efforts of the staffs of the hospital and the clinical microbiology laboratory services, the editorial assistance of M. Greenville, and the secretarial assistance of Marianne Owens. References 1. Brook I, Pettit TH, Martin WJ, Finegold SM. Aerobic and anaerobic bacteriology of acute conjunctivitis. Ann OphthalmoI1978;11:13-6

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patients with meningoventriculitis associated. with i~fected shunts (six ventriculoatrial shunts and one ventnculopentoneal shunt), and two were recovered following trauma. Four isolates were recovered from brain abscesses, two were of unknown etiology, and one each was associated with frontal sinusitis and otitis media. Ofthe three chest isolates, two were recovered from pleural fluid (one from a patient after trauma and implantation of a drainage tube and the other after placement of a drainage tube) and another was recovered following diagnostic surgery. Of the six isolates from cysts, three were recovered from sebaceous cysts and one each was found in scrotal, abdominal, and neck cysts. Two of the patients with cysts had diabetes. The two isolates from infected eyes were from patients with endophthalmitis. One of these patients suffered from immunodeficiency. Of the seven isolates fromjoints, three were recovered from the hip (one from a patient after surgery and two from patients with implants), two were recovered from the wrist (one after implantation and one from an immunodeficient patient), and one each was recovered from a disk of a diabetic patient and a knee of a patient after trauma. The three isolates from grafts were recovered from femoral grafts (one such isolate was from a diabetic patient). Of the 10 isolates from lymph glands, four were recovered from cervical glands, three from inguinal nodes, and one each from submandibular, abdominal, and mediastinal glands. Concomitant malignancy in the nodes occurred in two patients. Three isolates were recovered from obstetric and gynecologic sources; two isolates were found in the amni~tic fl~id (one from a diabetic patient and the other from a patient WIth sickle cell anemia), and the other was recovered from a pelvic aspirate. Of the five isolates from sinuses, three were from the frontal sinus and two from the maxillary sinus. Of the four isolates from tumors, three were recovered from lymphatic tumors in the neck and one from a mediastinal malignancy. Two patients had prior surgical resection. Of the seven isolates from wounds, three were recovered from postsurgical wounds (one from a diabetic immunodeficient patient, one from an immunodeficient patient, and one from a patient with malignancy). Three of the wounds occurred in the face, two in the abdomen, one in the scalp, and one in the fingers. The two miscellaneous isolates were from a pericardial infection and a thyroid infection. Antimicrobial therapy was administered to 83 patients altogether and in conjunction with surgical drainage or eorrection in 47 of these. The antimicrobial agents administered were a penicillin in 44 cases, a cephalosporin in 23, clindamycin in 15, and erythromycin in six.· Surgical drainage only was performed in nine patients. Five patients (5 %) died of infection. These included three patients with endocarditis (complicated with cardiac failure in two) and two with CNS sh~nt infection. The other patients' infections resolved following therapy.

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19. Holdeman LV, Cato EP, Moore WEC, eds. Anaerobe laboratory manual. 4th ed. Blacksburg, VA: Anaerobe Laboratory, Virginia Polytechnic Institute and State University, 1977 20. Sutter VL, Citron DM, Edelstein MAC, Finegold SM. Wadsworth bacteriology manual. 4th ed. Belmont, CA: Star Publishing Company, 1985 21. Lennette EH, Ballows A, Hausler W Jr, Shadomy HJ. Manual of clinical microbiology. 4th ed. Washington, DC: American Society for Microbiology, 1985 22. Maibach HI. Scalp pustules due to Corynebacterium acnes. Arch Dermatol 1967;96:453-5 23. Friedman E, Peyman GA, May DR. Endophthalmitis caused by Propionibacterium acnes. Can J Ophthalmol 1978;13:50-2 24. Yocum RC, McArthur J, Petty BG, Diehl AM, Moench TR. Septic arthritis caused by Propionibacterium acnes. JAMA 1982;248:1740-1 25. Newman JH, Mitchell RG. Diphtheroid infection ofthe cervical spine. Acta Orthop Scand 1975;46:67-70 26. Strauss JS, Kligman AM. The pathologic dynamics of acne vulgaris. Arch Dermatol 1960;82:779-90 27. Webster GF, Leyden 11, Norman ME, Nilsson UR. Complement activation in acne vulgaris. In vitro studies with Propionibacterium acnes and Propionibacterium granulosom. Infect Immun 1978;22:523-9 28. Webster GF, Leyden 11, Tsai C-C, Baehni P, McArthur WP. Polymorphonuclear leukocyte lysosomal release in response to Propionibacterium acnes in vitro and its enhancement by sera from inflammatory acne patients. J Invest Dermatol 1980;74:398-401 29. Puhvel SM, Sakamoto MI. The chemoattractant properties of comedonal components. J Invest Dermatol 1978;71:324-9 30. Webster GF, Leyden 11. Characterization of serum-independent polymorphonuclear leukocyte chemotactic factors produced by Propionibacterium acnes. Inflammation 1980;4:261-9 31. Sliman R, Rehm S, Shlaes DM. Serious infections caused by Bacillus species. Medicine 1987;66:218-23 32. Swensen FJ, Rubin SF. Clinical significance of streptococci isolates from blood cultures. J Clin Microb 1982;15:752-7 33. Brook 1. Direct and indirect pathogenicity of Branhamella catarrhalis. Drugs 1986;31(Suppl 3):97-102 34. Denys GA, Jerris RC, Swenson JM, Thornsberry C. Susceptibility of Propionibacterium acnes clinical isolates to 22 antimicrobial agents. Antimicrob Agents Chemother 1983;23:335-7

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2. Brook 1. Microbiological studies of the bacterial flora of the external auditory canal in children. Acta Otolaryngol (Stockh) 1981;91:285-7 3. McGinley 10, Webster GF, Leyden J1. Regional variations of cutaneous propionibacteria. Appl Environ Microbiol 1978;35:62-6 4. Finegold SM. Anaerobic bacteria in human disease. New York: Academic Press, 1977, 18, 29, 70, 437, 456, 577-8 5. Heineman HS, Braude AI. Anaerobic infection of the brain. Observations on eighteen consecutive cases of brain abscess. Am J Med 1963;35:682-97 6. Mathisen GE, Meyer RD, George WL, Citron DM, Finegold SM. Brain abscess and cerebritis. Rev Infect Dis 1984;6(Suppl 1):101-6 7. Davidson RI. Intracranial epidural suppuration. The occult empyema. Neurosurgery 1882;11:390-4. 8. Kaufman DM, Miller MH, Steigbigel NH. Subdural empyema: analysis of 17 recent cases and review of the literature. Medicine (Baltimore) 1975;54:485-98 9. Yoshikawa TT, Chow AW, Guze LB. Role of anaerobic bacteria in subdural empyema. Report of four cases and review of 327 cases from the English literature. Am J Med 1975;58:99-104 10. Goldberg MH. Corynebacterium: an oral-systemic pathogen. Report of cases. J Oral Surg 1971;29:349-51 11. Brook 1. Presence of anaerobic bacteria in conjunctivitis associated with wearing contact lenses. Ann Ophthalmol 1988;20:397-9 12. Finegold SM, Bartlett JG. Anaerobic pleuropulmonary infections. Cleve Clin J Med 1975;42:101-11 13. Dunkle LM, Brotherton TJ, Feigin RD. Anaerobic infections in children: a prospective study. Pediatrics 1976;57:311-20 14. Everett ED, Eickhoff Te, Simon RH. Cerebrospinal fluid shunt infections with anaerobic diphtheroids (Propionibacterium species). J Neurosurg 1976;44:580-4 15. WJ.1son WR, Martin WJ, Wilkowske CJ, Washington JA. Anaerobic bacteremia. Mayo Clin Proc 1972;47:639-46 16. Beeler BA, Crowder JG, Smith JW, White A. Propionibacterium acnes: pathogen in central nervous system shunt infection. Report of three cases including immune complex glomerulonephritis. Am J Med 1976;61:935-8 17. Johnson WD, Kaye D. Serious infections caused by diphtheroids. Ann N Y Acad Sci 1970;174:568-76 18. Kaplan K, Weinstein L. Diphtheroid infections of man. Ann Intern Med 1969;70:919-29

RID 1991;13 (September-October)

Infections caused by Propionibacterium species.

Eight hundred and sixteen isolates of Propionibacterium species (725 of which were Propionibacterium acnes) were isolated from 3,971 specimens submitt...
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