Propionibacterium acnes
Authors: Itzhak Brook, MD, MSc
Microbiology
Propionibacteria are pleomorphic, sometimes branching bacilli. Propionibacterium acnes is the most commonly isolated species and is often a contaminant in blood cultures along with other Propionibacterium spp.
Epidemiology
Propionibacterium spp. are part of the normal flora of the skin (38), conjunctiva (4), external ear canal (6), mouth, and upper respiratory tract, and, occasionally, intestine, urethra, and vagina (38).
Clinical Manifestations
Propionibacterium acnes is associated with the inflammatory process in acne lesions (2). Uncommonly, Propionibacterium spp. have been identified with or without other aerobic or anaerobic bacteria as causes of infections, including brain abscesses, subdural empyema, parotid and dental infections, conjunctivitis associated with contact lens, pulmonary infections, peritonitis, and osteomyelitis (3-5, 8). The organisms have been identified in device-related infections include those of joint prostheses, shunts and prosthetic heart valves. It has also been recovered from specimens obtained from patients with endocarditis, with artificial or native valves, with central nervous system shunt infections, intravenous catheters, and with septic arthritis, especially in prosthetic joints and from other serious infections (3-5, 8, 9, 18, 30).
P. acnes may play a role in other conditions, including inflammation of the prostate leading to cancer, SAPHO (synovitis, acne, pustulosis, hyperostosis, osteitis) syndrome, sarcoidosis and sciatica. (30,31)
Laboratory Diagnosis
The organisms are common contaminants of cultures of blood and body fluids and have traditionally been considered nonpathogenic for humans (8, 18). Therefore, interpretation of the significance of an isolate must be undertaken with caution. Propionibacteria are the most commonly isolated anaerobic gram-positive non-sporulating bacilli, accounting for 15% to 20% of all anaerobes isolated in some studies (9,18).
Pathogenesis
P. acnes secretes several proinflammatory products, which play an important role in the development of acne inflammation. These include lipases, proteases, hyaluronidases, and chemotactic factors. Immune response to P. acnes includes humoral and cell-mediated immunity as well as complement activation. Recent results indicate that keratinocytes and sebocytes, as major components of pilosebaceous unit, may act as immune cells and may be activated by P. acnes via toll-like receptors (TLRs) and CD14, and through CD1 molecules may recognize altered lipid content in sebum, followed by the production of inflammatory cytokines (26).
Propionibacterium spp. possess immunostimulatory mechanisms that have been extensively studied (10, 39, 40). These include activation of complement (40), stimulation of lysosomal enzyme release from human neutrophils (40), and production of serum-independent neutrophil chemotactic factors (40). These organisms can be differentiated phenotypically according to their metabolic end products by the use of gas liquid chromatography (25). Propionibacterium spp. typically produce large amounts of propionic acid and all Propionibacterium spp. are indole positive. The pathogenicity and potential for synergy with aerobic bacteria was studied in a subcutaneous abscess model in mice (7). Single and mixed infections with 11 clinical isolates of Propionibacterium acnes and three facultative bacteria (Staphylococcus aureus,Escherichia coli, and Klebsiella pneumoniae) were studied. Abscesses were induced by pure cultures of six of 11 strains of P. acnes and by the three facultative bacteria. The abscesses produced by each of the six virulent P. acnes isolated mixed with S. aureus, E. coli, or K. pneumoniae were larger than those induced by the single organisms in 16 of the 18 combinations. There was a significant increase in the numbers of the six P. acnes strains in 13 of the 18 bacterial mixtures and in the numbers of the facultative bacteria in 17 of the 18 combinations. These data illustrate the potential virulence of some P. acnes strains and their synergic capacity with facultative bacteria.
SUSCEPTIBILITY IN VITRO AND IN VIVO
The susceptibility of P. acnes needs to be monitored to verify current susceptibility. Incases of serious infections, susceptibility tests of P. acnes isolates should be performed, to assure the proper use of antimicrobials (32).
Single Drugs
P. acnes, as well as most other Propionibacterium .spp. are generally (but not universally) susceptible to penicillin-G, amoxicillin, ticarcillin, ticarcillin/sulbactam, piperacillin/tazobactam, cefazolin, cefoxitin, cefotetan, third-generation cephalosporins (e.g., ceftriaxone, cefotaxime), chloramphenicol, clindamycin, erythromycin, imipenem, meropenem, tetracycline, vancomycin, rifampin, fluoroquinolones (e.g., ciprofloxacin, ofloxacin, levofloxacin, gatifloxacin, moxifloxacin, trovafloxacin) and the combinations of penicillins and β-lactamase inhibitors (1, 11, 13, 14, 15, 16, 17, 19, 20, 22, 33, 36, 37). Propionibacterium spp. are generally resistant to the 5-nitroimidazole agents, including metronidazole, tinidazole, and ornidazole (MIC90 > 16 µg/mL) and the aminoglycosides (9, 10, 22, 23, 24, 32,).
Resistant strains have developed to erythromycin, especially in individuals who used this agent for topical therapy of acne (33, 34). Most erythromycin-resistant isolates (MIC90 51 2 µg/mL) were cross-resistant to clindamycin and B-type streptogramins. Tetracycline resistant strains have also been recovered from patients with acne who attended dermatology clinics (33, 34). Tetracycline-resistant isolates displayed varying degrees of cross-resistance to doxycycline and minocycline.
The overall incidence of P. acnes antibiotic resistance among isolates recovered from patients with acnes vulgaris has increased from 20% in 1978 to 62% in 1996 (28). Resistance to specific antibiotics varied and was most commonly reported with erythromycin, clindamycin, tetracycline, doxycycline, and trimethoprim. Resistance to minocycline is rare. Repeated use of topical clindamycin was associated with increased resistance to clindamycin (28). Topical clindamycin phosphate and nadifloxacin were bacteriostatic against P. acnes in a mouse burn model (27). However, emergence of resistance occurred with the organisms when they were passaged in vitro.
Recent susceptibility testing of P .acnes isolates recovered from patients with acnes illustrated in-vitro resistance to erythromycin ( 12.5-35%), azithromycin (82%), clindamycin ( 7.5-30%), tetracycline (8%), minocycline (1%), doxycycline (9%), and trimethoprim-sulfamethoxazole ( 26-46%) (21, 29, 35).
Combinations of Drugs
No known synergistic combination is thought to benefit treatment of Propionibacterium spp. infection (27).
ANTIMICROBIAL THERAPY
Penicillin-G in a dose ranging from 1.2 million units to as high as 20 million units per day in adults and 100 to 250,000 units/kg/d every four hours in children is the treatment of choice for serious infections, including bacteremia, central nervous system, and soft tissue infections. In cases of penicillin allergy or concern about resistance, other antibiotics should be considered. All isolates of serious infections should be tested for in vitro efficacy because of the possible recovery of resistant strains. Alternative treatments to penicillin are listed in Table 1.
In clinical situations that involve polymicrobial infections, coverage against the other potential pathogens, aerobic and anaerobic, should be included. This can be achieved by choosing single therapy with an antimicrobial that possesses wider coverage (e.g., imipenem) or by additional agents that cover other organisms (e.g., aminoglycoside or fluoroquinolone for Enterobacteriaceae, or a penicillinase-resistant penicillin for Staphylococcus aureus). Treatment of central nervous system infection requires the use of antimicrobials with good penetration through the blood-brain barrier (8).
ENDPOINTS FOR MONITORING THERAPY
Improvements and resolution of the infections are determined through a variety of clinical and laboratory tests. In the case of bacteremia, the lack of recovery of organisms from the blood is an important endpoint. The reduction in the number of white blood cells are important signs of improvement. Improvement in intraabdominal, biliary tract, genital and pulmonary infections can be judged through clinical and radiographic resolution of the infection-returns the gastrointestinal and pulmonary system to normal function, and disappearance of purulence. Central nervous system infection can be followed by repeated lumbar punctures and radiography. In the case of subcutaneous tissue infection, return of the tissue to normal color and blood perfusion and resolution of the purulent inflammation are desired.
VACCINES
Currently, there are no vaccines available.
CONTROVERSIES, CAVEATS, AND COMMENTS
Removal of foreign bodies, surgery and debridements when indicated, and fluid management are important and integral components to any therapy of Propionibacterium spp. infection.
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Tables
Table 1. Antimicrobials for the Treatments of Probionibacteria Infections
| Agent | Dose | Route | Comment |
|---|---|---|---|
| Penicillin * | 1.2 to 20 million units per day (100,000 to 250,000 units/kg/d for children) every 4 to 6 hours | oral, intravenous | First-line therapy for propionibacteria infection |
| Ampicillin/amoxicillin | 2 to 3 g/d (40 to 80 mg/kg/d for children) every 8 hours | oral, intravenous (ampicillin) | |
| Chloramphenicol | 12.5 to 25 mg/kg/d every 6 hours | oral, intravenous, intramuscular | maximum daily dose for adults is 4 g |
| Clindamycin | 150 to 450 mg every 6 hours (25 to 40 mg/kg/d every 6 to 8 hours for children) | oral, intravenous, intramuscular | |
| Tetracycline | 250 to 500 mg every 6 hours (15 to 20 mg/kg/d intravenous or 25 to 50 mg/kg/d oral every 6 hours for children) | oral, intravenous | maximum daily dose for adults is 2 g; do not use for children younger than 9 years |
| Erythromycin | 250 to 500 mg every 6 hours (10 mg/kg every 6 hours for children) | oral, intravenous | |
| Vancomycin | 15 mg/kg every 12 hours or 6 to 8 mg/kg every 6 hours (10 mg/kg every 6 hours for children) | intravenous | |
| Imipenem | 0.5 to 1 g every 6 to 8 hours(15 to 24 mg/kg every 6 to 8 hours for children) | intravenous or intramuscular | maximum daily dose for adults is 2 g |
| Meropenem | 0.5 to 1 g every 8 hours (40 mg/kg/d every 8 hours for children) | intravenous | |
| Gatifloxacin | 400 mg daily | oral or intravenous | not approved for use in children |
| Moxifloxacin | 400 mg daily | oral | not approved for use in children |
* = drug of choice
What's New
Ghosh M, Talwani R, et al. Propionibacterium skull osteomyelitis treated with daptomycin. Clin Neurol Neurosurg. 2009 May 16. [Epub ahead of print]