Orthopedics

Feature Article Supplemental Data

Cutibacterium acnes Infection in Orthopedics: Microbiology, Clinical Findings, Diagnostic Strategies, and Management

Zilan X. Lin, MD; Lisa L. Steed, PhD; Camelia E. Marculescu, MD, MSCR; Harris S. Slone, MD; Shane K. Woolf, MD

Abstract

Cutibacterium (formerly called Propionibacterium) acnes is a human skin flora often implicated in orthopedic infections. The unique characteristics of this microorganism make the diagnosis of infection difficult. The diagnosis often is made based on clinical evidence, radiographic signs, and laboratory and/or surgical findings combined. Treatment often involves both pharmacologic and surgical methods. In addition, formation of biofilms and increased resistance to drugs exhibited by the microorganism can require combined antimicrobial therapy. Prophylactic measures are particularly important, but no single method has been shown to fully eliminate the risk of C acnes infections. Previous reports have focused on C acnes infections involving surgical implants or after certain orthopedic procedures, particularly in the shoulder and spine. This article reviews current clinical, diagnostic, and treatment principles for C acnes in orthopedics in general. [Orthopedics. 2020; 43(1):52–61.]

Abstract

Cutibacterium (formerly called Propionibacterium) acnes is a human skin flora often implicated in orthopedic infections. The unique characteristics of this microorganism make the diagnosis of infection difficult. The diagnosis often is made based on clinical evidence, radiographic signs, and laboratory and/or surgical findings combined. Treatment often involves both pharmacologic and surgical methods. In addition, formation of biofilms and increased resistance to drugs exhibited by the microorganism can require combined antimicrobial therapy. Prophylactic measures are particularly important, but no single method has been shown to fully eliminate the risk of C acnes infections. Previous reports have focused on C acnes infections involving surgical implants or after certain orthopedic procedures, particularly in the shoulder and spine. This article reviews current clinical, diagnostic, and treatment principles for C acnes in orthopedics in general. [Orthopedics. 2020; 43(1):52–61.]

Numerous factors may contribute to postoperative orthopedic infections, including specific area of the body, type of procedure, and characteristics of the host patient. Staphylococcus epidermidis and S aureus are the most frequently encountered bacteria on human skin.1Cutibacterium acnes, formerly known as Propionibacterium acnes, is another organism that has been studied with increasing interest due to its unique characteristics and identification in specific orthopedic infections. Each of these pathogens has distinct characteristics (Table A, available in the online version of this article).

Characteristics of common skin flora

Table A.

Characteristics of common skin flora

Insidious infections are often difficult to diagnose, which can be the case with C acnes. Previous reports have focused on C acnes infections associated with surgical implants or after orthopedic procedures in the shoulder and spine. This article reviews current clinical, diagnostic, and treatment principles for C acnes in orthopedics in general.

Microbiology

C acnes is a low virulence, anaerobic, gram-positive, non–spore-forming bacillus (Figure 1) normally found on human skin. It tends to reside in lipid-rich hair follicles and sebaceous glands. Due to the denser concentration of these structures in the neck, chest, shoulder, and back, C acnes is more common in these locations.2,3C acnes grows slowly on routine microbiologic media. A mean time of 10 to 15 days for detection in culture has been reported.3–6

Composite Gram stain showing Cutibacterium acnes in various presentations of pleomorphic, non–spore-forming, gram-positive bacilli. The arrow indicates the most characteristic morphology (original magnification, ×100).

Figure 1:

Composite Gram stain showing Cutibacterium acnes in various presentations of pleomorphic, non–spore-forming, gram-positive bacilli. The arrow indicates the most characteristic morphology (original magnification, ×100).

The organism can easily be distinguished from other Cutibacterium species by catalase and indole positivity. It is categorized into phylotypes I, II, and III with sub-phylotypes IA and IB based on gene sequences. These phylotypes show differences in virulence and inflammatory capability.4C acnes forms mature biofilms on the surface of prosthetic materials within 96 hours,4,7,8 which is of particular importance for the management of orthopedic infections. Although it is often considered a contaminant in routine operative cultures, C acnes can be a true pathogen when isolated from surgical specimens in certain clinical scenarios.

Incidence and Etiology of Infection

Overall, C acnes infections are relatively rare, being associated with less than 10% of orthopedic infections.9–13 The bacteria tend to colonize implants and are thought to be inoculated at the time of surgery. Common factors in infections are history of previous surgery or trauma and presence of surgical implants or foreign material.14 Evidence suggests that a delayed C acnes infection is rare in the absence of an implant.15

Although the shoulder is a common site of C acnes infection, the pathogen is also implicated in infections in the elbow, hand, spine, knee, and hip.9,16–28C acnes and Staphylococcus species are the two most prevalent pathogens in shoulder surgeries,1,4,29–32 and C acnes is isolated as a bacterial pathogen about the shoulder more often than other sites (Table B, available in the online version of this article). Patel et al1 showed that the prevalence of C acnes was greater around the acromion and in the axilla than in the knee and the hip. This correlates with a greater density of hair follicles and sebaceous glands in the shoulder and axilla. These authors further reported that C acnes was most prevalent at the anterior acromion followed by the posterior, whereas the prevalence of Staphylococcus species was greater at the axilla than the acromial areas.1

Relevance of C. acnes infections in orthopaedic surgery.Relevance of C. acnes infections in orthopaedic surgery.

Table B.

Relevance of C. acnes infections in orthopaedic surgery.

In addition, sex is a risk factor for C acnes infections.1,31,33–35C acnes prosthetic shoulder joint infections are more common in males, who have a higher concentration of hair follicles and sebaceous glands.36 Athwal et al33 reported that 19 of 33 (58%) males with deep infection after rotator cuff repair had confirmed C acnes infections, whereas the rate in females was only 20%.

Colonization of the skin and dermis is common, particularly in shoulders. Because C acnes can reside in the dermal layer, it has been hypothesized that incision through the skin might release and spread the bacterium to surrounding tissues. This would not be prevented by standard skin surgical preparation techniques. In a controlled study of primary shoulder arthroscopy with 2 skin swabs, synovial fluid, and 3 tissue sample cultures, Sethi et al34 found that 56% of patients had at least one positive culture and 22% of all harvested cultures were positive for C acnes at 14 days of growth. Another shoulder arthroscopy study showed 73% superficial and 20% deep layer colonization at 21 days in Brucella medium.37

C acnes may be difficult to eradicate with standard skin preparation. A study using dermal punch biopsy on the upper back showed C acnes persistence in skin at a rate of 70% despite standard skin preparation with chlorhexidine (Chlora-Prep; Becton, Dickinson and Co, Franklin Lakes, New Jersey).38 Similar data were published for lumbar spine surgery prepped with both ChloraPrep and Dura-Prep (3M, St Paul, Minnesota).39

Procedure duration is likely a factor associated with positive cultures. Among patients who had at least 3 positive C acnes samples, 11.1% were noted to have positive cultures when surgical time was less than 60 minutes compared with 40.0% after procedures of 60 minutes or longer.34 The percentage of positive C acnes cultures from superficial skin swabs increased from 15.8% before incision to 40.4% at wound closure during primary shoulder arthroscopy (from 31.3% to 63.0% in the male cohort).34

Clinical Findings

Generally, the diagnosis of C acnes infection can be difficult, so clinical suspicion must be high. Due to its unique biology, the bacterium is ordinarily associated with low-grade, chronic, sub-acute, or delayed infections, but it can also cause acute infections. Postoperative C acnes infections often appear in a delayed fashion. In one small case series, the average time from shoulder surgery to the diagnosis of occult C acnes infection was 1.8 years.40 However, another study showed that the median period between surgery and acute presentation of C acnes infection was 5.0 weeks (range, 2.0–78.0 weeks) in 15 cases.14 The difference between the findings was likely due to the different patient populations studied.

Persistent pain is an important presenting complaint.3,9,14,18,29,31,40–45 In the acute stage, it can often be confused with normal postoperative pain. Zeller et al13 observed that pain and joint dysfunction were the two major symptoms of C acnes prosthetic joint infections. Specifically in shoulders, the most common presenting symptoms of C acnes infections are persistent pain and stiffness.3,29,31,40,41 Fever and other classic signs of inflammation, such as erythema, swelling, sinus tract, and drainage, are rarely observed.3,9,16,29,30,40,44 Another manifestation of C acnes infection is presumed aseptic loosening of implants, especially in shoulder arthroplasty.38,41,45

Other risk factors must also be considered. In 193 revision arthroplasties performed due to pain, stiffness, or loosening, it was found that cloudy joint fluid (12 times), humeral osteolysis on radiographs (10 times), male sex (6 times), glenoid wear (4 times), membrane formation (4 times), and humeral loosening (3 times) were all associated with increased likelihood of a positive C acnes culture.41

The infection rate about the elbow after primary elbow arthroplasty is reported to be approximately 4%.21 One study of 16 revision elbow arthroplasties with unexpected positive intraoperative cultures found C acnes to be the second most common pathogen after S epidermidis. All C acnes specimens in that study grew in broth only and were identified initially as contaminants.21

Diagnostic Tools and Techniques

The diagnosis of C acnes infection is challenging, and the average time to definitive diagnosis can be longer than that for other pathogens.9,40,46 Criteria proposed for establishing the diagnosis of C acnes infection include deep tissue cultures, physical manifestations, perioperative findings, and a history of previous surgery and orthopedic implants. The most valuable criterion is two or more positive deep samples.47

Formation of a draining fistula is a strong indication for infection with most pathogens, but it is rarely seen with C acnes infection.11,43 Prosthesis failure requiring revision within 2 years of implantation highly supports infection, even if other clinical signs are absent.45 Zeller et al13 proposed that symptom manifestation within 2 years is more likely to indicate C acnes infection, with beyond 2 years suggesting colonization instead of true infection as the cause of aseptic loosening. They suggested that colonization would increase the local inflammatory response and could ultimately induce presumed aseptic implant loosening, which could eventually lead to true infection.13

Plain radiographs are an important diagnostic tool. However, with C acnes infections, radiographs can be normal, especially in early stages, or may show only presumed aseptic loosening of the prosthesis.3,10,29 In cases of delayed infection, radiographs may show osteopenia, prosthetic component lucency, or pseudosubluxation.3 In addition, computed tomography, magnetic resonance imaging, and ultrasound may be helpful but do not typically confirm the diagnosis.1,44

A laboratory workup, including inflammatory biomarkers and peripheral blood tests, is less useful. C-reactive protein and erythrocyte sedimentation rate are not dependable.3,12,13,18,29,40,41,44,46,48 Just 13% of C-reactive protein and 17% of erythrocyte sedimentation rate results were elevated in patients with positive C acnes cultures undergoing revision shoulder arthroplasty.41 Peripheral white blood cell counts are often normal and even less reliable than erythrocyte sedimentation rate and C-reactive protein.1,14,29,40,44 White blood cell counts and neutrophil counts are both within normal limits 75% of the time in non-selective C acnes infections.14 Although synovial fluid cell counts, especially from the knee, have higher sensitivity and specificity for prosthetic joint infections,43,49,50 studies specific to C acnes are lacking.

Other diagnostic methods have been investigated. Synovial fluid interleukin-6 is an infectious biomarker with likely better sensitivity and specificity than erythrocyte sedimentation rate and C-reactive protein in patients with shoulder prosthetic joint infections.51 Conversely, the sensitivity of serum interleukin-6 was lower in revision shoulder arthroplasty related to prosthetic joint infection and it was not found to be cost-effective.52 Further studies are needed to clarify the utility of both serum and synovial fluid inter-leukin-6 levels. In a study of 33 shoulder revision arthroplasty surgeries, synovial fluid alpha-defensin (ie, Synovasure [Zimmer Biomet, Warsaw, Indiana]), a relatively new biomarker found to have high specificity for infection in general, was shown to be significantly elevated when C acnes culture was positive.53

Aspiration of synovial fluid prior to or during surgery and direct collection (ie, biopsy) of tissue, bone, or synovial fluid from joints are the preferred methods for diagnostic samples. With preoperative aspiration, patients with overt signs of infection typically have cultures positive for the growth of microorganisms other than C acnes,14 but low-grade infections frequently demonstrate high false-negative rates.21,29,54 Several surgical tissue specimens collected from various locations are optimal because biofilms are unevenly distributed along the implant and multiple samples help rule out contamination. According to the Infectious Diseases Society of America guidelines, at least 3, and optimally up to 6, intraoperative specimens are needed for culture to diagnose prosthetic joint infection.55 The collected samples are sent for cell count, frozen section, and aerobic and anaerobic bacterial culture. Due to their poor sensitivity, swab specimens should never be submitted for culture.

Histopathology from frozen section collected during surgery may demonstrate inflammation as a surrogate for infection. Definitive results from histopathology through paraffin-embedded sections require 2 days on average to return but have better quality. Generally for frozen histologic sections, 5 or more neutrophils in at least 5 high-power (×400) microscopic fields (Feldman's criteria) or 1 or more neutrophils in 10 high-power microscopic fields (Athanasou's criteria) are indicative of acute inflammation and useful for diagnosing infection,14,30,54,56 although no consensus on method exists. Grosso et al57 asserted that using a criterion of 10 instead of 5 neutrophils in 5 high-power fields could increase the sensitivity of frozen section in C acnes infections while keeping the specificity high in revision shoulder arthroplasty.51 However, the findings from C acnes infections may be minimal, with only chronic inflammatory changes and no evidence of acute inflammation.19,21,29,30,58 Peri-implant tissue histopathology is a positive predictor of infection in only 18% to 27% of C acnes cases.16,48 Thus, histology may have poor utility in C acnes cases.

The incubation period for C acnes is longer than that of most other common bacteria due to its indolent growth. The recommended incubation period for C acnes is up to 15 days.1,3,5,30,35,40,58 Sethi et al34 reported that 21.8% (81 of 371) of samples obtained from primary shoulder arthroplasties were positive for C acnes in the first 14 days, while 25.1% (93 of 371) were positive at 28 days. Butler-Wu et al58 suggest that a minimum 13-day incubation period is necessary for both aerobic and anaerobic cultures. A premature final reporting of the culture can result in a false-negative rate of up to 10% to 20%11,19 and can cause under-reporting of C acnes infections. On the other hand, a longer incubation period can increase laboratory costs as well as the likelihood of detecting contamination from the environment and/or skin. Probable true-positive C acnes cultures were more likely to have a shorter growth time than probable contaminated cultures, with means of 5 days and 9 days, respectively.59 Moreover, in addition to being embedded in a biofilm matrix that renders it slow growing, the bacterium can dwell in a dormant state, creating further difficulty for accurate culture.1

Specimen handling methods are important. An anaerobic culture environment can be difficult to maintain. A common practice in diagnosing C acnes infections is to inoculate both aerobic and anaerobic agar plates and also an enriched liquid medium, such as thioglycollate broth. Figure 2 and Figure 3 illustrate the growth of C acnes on blood agar plates and in chopped meat broth, respectively. Table C (available in the online version of this article) lists key recommendations on culture and specimen handling.

Small (1 to 2 mm), white colonies of Cutibacterium acnes growing on anaerobic blood agar (Centers for Disease Control and Prevention media).

Figure 2:

Small (1 to 2 mm), white colonies of Cutibacterium acnes growing on anaerobic blood agar (Centers for Disease Control and Prevention media).

Close up of Cutibacterium acnes growing as a white film on top of the chopped meat in chopped meat broth.

Figure 3:

Close up of Cutibacterium acnes growing as a white film on top of the chopped meat in chopped meat broth.

Recommendations for C. acnes specimen handling to optimize cultures

Table C.

Recommendations for C. acnes specimen handling to optimize cultures

Improved culture quality may facilitate pathogen detection and shorten the incubation time for C acnes. Better recovery of anaerobes can be achieved by inoculation intraoperatively with Rosenow's broth, an enriched liquid medium.60 A hemolytic phenotype determined by growth on Brucella blood agar plates might indicate a more aggressive infection. Use of anaerobic thioglycollate broth with strict anaerobic collection and transportation plus an incubation period of at least 7 days has been shown to be an effective culture strategy.61

Recent studies have focused on bio-film sampling. Sonication of the implant itself has shown more promise than direct peri-implant tissue culture because it dislodges bacteria from bio-films more efficiently, and the sonication fluid can be analyzed by culture, polymerase chain reaction, immunofluorescence, and fluorescence in situ hybridization.11,19,20,27,36,62,63 Sampedro et al20 tested this technology by sonicating and vortexing spinal implants followed by polymerase chain reaction analysis and found increased sensitivity for infection, although antibiotics administered within 14 days of surgery might reduce the sensitivity for specimens of both tissue and sonicate fluid.64 Sonication was still shown to be more sensitive.65 Sonication has been advocated for clinical use in shoulder prosthetic joint infections36 and was found to be superior to scraping for titanium and steel surfaces.63 To optimize the efficacy of sonication, specific techniques must be applied.65 However, the utility of culturing sonication fluid for revision shoulder arthroplasty has recently been refuted.66 Further, this specialized technique is not routinely available and thus is not widely adopted.

DNA analysis has been used to confirm certain infections but may have less utility with C acnes, as most polymerase chain reaction kits do not contain primers for C acnes.67,68 Further, polymerase chain reaction has poor sensitivity due to difficulty extracting DNA through the cell wall.40,69 A promising experimental technique has recently been described that uses a polymerase chain reaction–restriction fragment length polymorphism assay with C acnes–specific primers. It optimizes the sensitivity of polymerase chain reaction with the specificity of restriction fragment length polymorphism mapping for testing of fresh surgical specimens suspicious for C acnes. Results are available within 24 hours with this method, which might enable earlier definitive treatment decisions.70

Immunofluorescence microscopy is a technique that could help differentiate C acnes contamination from infection. Single cells were found in patients undergoing non-infectious spine surgery, likely indicating contamination, whereas large aggregates were found in cases of prosthetic hip loosening, possibly related to biofilm formation.2

Treatment

Treatment of C acnes implant-associated infections may often require surgical debridement and/or antimicrobial therapy. Intravenous beta-lactam antibiotics, such as penicillin, and ceftriaxone are considered the first choice pharmacotherapy against C acnes in surgical infections, while vancomycin and daptomycin are used in cases of beta-lactam allergy or antimicrobial resistance.3,9,11,19 Routine susceptibilities are typically not done because the organism is susceptible to penicillins and usually to clindamycin and tetracyclines. However, resistance to tetracyclines has been increasingly reported.71 Aminoglycosides have very low activity, and C acnes is resistant to metronidazole.3,5,9,11,12,14,19,30,72–74 Although C acnes has historically been susceptible to multiple antibiotics, bacterial resistance is increasing.

Moreover, studies have shown that biofilm formation enhances C acnes resistance to cefamandole, ciprofloxacin, vancomycin, and gentamicin.7 In theory, bacteria that can form biofilms are more resistant to antimicrobial agents and thus more difficult to eradicate.11,14 Therefore, sharp surgical debridement and/or implant removal is often necessary in addition to pharmacologic therapy. Antibiotic spacers and antibiotic-impregnated cement can be adjunct treatment options following implant removal. There may be an additive effect with combined oral or parenteral antibiotic therapy.74 Increased activity against C acnes has been shown when rifampin is used along with daptomycin.75 Although rifampin is believed to be active against C acnes biofilms,11,19,75 Aubin et al11 reported a 0.7% resistance rate for C acnes. As with most orthopedic infections, when there is deep involvement, parenteral antibiotics are usually necessary and typically administered for 4 to 6 weeks. Table D (available in the online version of this article) summarizes the efficacy of various commonly used antibiotic agents.

Antibiotic efficacy in C. acnes infectionsAntibiotic efficacy in C. acnes infections

Table D.

Antibiotic efficacy in C. acnes infections

The significance of a single positive C acnes culture in an otherwise benign-appearing environment is unknown, making treatment decisions difficult. With inconsistent culture results and no specific clinical signs of infection, it is unclear whether antibiotics are needed. In a retrospective series, C acnes was isolated in 6 of 8 positive intraoperative cultures from 28 revision shoulder arthroplasties that were presumed to be aseptic and had only received perioperative antibiotic treatment. Among them, only 1 of the 3 cases with just 1 positive culture developed subsequent infection. None of the 3 cases with 2 positive cultures developed infection at 1 year.76 In another series of 17 one-stage revision shoulder arthroplasties without obvious infection and with at least 1 positive intraoperative culture, C acnes grew in 10 patients (56%). None of them had subsequent infection at 2 years after routine 24-hour postoperative intravenous antibiotics.51 Zeller et al13 proposed in their cohort study that when positive samples are obtained during a surgery for presumed aseptic prosthetic loosening, and the patient did not show initial clinical symptoms until many years after the implantation, antibiotic treatment would be advisable to prevent possible colonization from evolving into prosthetic joint infection.13 Patients with suspected C acnes infection, if untreated, should be followed for a longer period because symptoms may take longer to manifest.

Current literature has recommended that treatment of definite C acnes prosthetic joint infection should combine exchange arthroplasty and prolonged parenteral antibiotic therapy.13 However, opinions vary on this topic. Some surgeons prefer one-stage exchange revision surgery,3 while others favor two or more stages.19 No standard protocol has been established. Benefits of one-stage revision include preservation of tissue planes, less scarring, reduced risk associated with additional surgery, and lower costs.3,44 Conversely, a clear reason for two-stage exchange is that prosthesis loosening compromises retention of components and immediate reimplantation is sometimes not possible due to bone or tissue quality.19 In addition, definitive confirmation of eradication of the existing infection has been advised before reimplantation. Zhang et al77 found that 22% of open biopsies were still positive after incision and debridement, antibiotic spacer placement, and a 6-week antibiotic therapy course for shoulder prosthetic joint infection. Among the treated C acnes infections, 38% recurred. Therefore, they recommended considering open biopsy and culture before reim-plantation.77

Prophylaxis

Given the potential impact of C acnes on implant survival, prophylaxis is paramount. Various interventions have been advocated for prevention of C acnes infections. A satisfactory sterile surgical field is critical. Various methods, including preoperative skin treatment, hair clipping, perioperative antibiotics, antimicrobial irrigation solutions, proper draping and ventilation flow, and antimicrobial dressings, are used to kill bacterium on the superficial skin.

Prehospital skin cleansing and preparation protocols have been implemented. However, preoperative home use of a 2% chlorhexidine gluconate cloth before shoulder surgery does not significantly reduce the rate of positive C acnes cultures compared with a shower with soap and water, although it does reduce overall bacterial and coagulase-negative Staphylococcus rates.78 Chlorhexidine gluconate was found to be less effective than benzoyl peroxide in reducing C acnes colonization at the shoulder.79 A benzoyl peroxide–clindamycin topical skin preparation was found to dramatically reduce both superficial and deep C acnes colonization in shoulder arthroscopy patients,80 but it may not effectively reduce C acnes growth over standard chlorhexidine gluconate skin preparation.81,82 However, preoperative treatment with either oral or topical doxycycline alone does not significantly reduce C acnes colonization.83,84 A 5-minute preoperative application of topical 3% hydrogen peroxide has shown promise in reducing C acnes preoperative skin burden.85,86

Laminar air flow in the operating room may reduce bacterial contamination and surgical site infections.87–89 Given the deeper residency of C acnes around hair follicles and glands, specific surgical methods have been proposed. Separate scalpel blades for skin and deeper tissue may be beneficial.90 Use of cyanoacrylate microbial sealant, an adhesive skin barrier, may reduce the rate of positive C acnes cultures.91 Contaminated light handles may be a reservoir, so dipping surgical gloves in a chlorhexi-dine splash-basin every 10 minutes has been advocated.92

Axillary hair clipping had no effect on C acnes burden either before or after skin preparation in cases using ChloraPrep.93 No significant difference was found among ChloraPrep, DuraPrep, and regular povidone-iodine for reducing C acnes in shoulder surgery.94

Perioperative antibiotic prophylaxis is the accepted standard of care to reduce general infection risk. Besides perioperative intravenous antibiotics, some surgeons use wound irrigation or coating with antibiotics during surgery. This is not yet widely accepted as an evidence-based practice. Some researchers have studied the use of vancomycin powder in spine surgery, reporting conflicting results.95–97 The practice of using antibiotics in daptomycin-impregnated polymethylmethacrylate cement for prophylaxis remains controversial.98–102 Its routine use should be reserved for only high-risk patients, such as immunocom-promised patients, those with a history of native septic arthritis, or those who receive revision after infection. Further, indiscriminate use of antibiotics can increase antibiotic resistance and is clearly problematic.

Finally, operative wound dressing may help further reduce infection risk. Silver-based dressings at the surgical site are effective against a broad spectrum of bacteria, including methicillin-resistant S aureus.103–108 However, data on efficacy against C acnes are limited. An in vitro study concluded that silver-impregnated wound dressings used postoperatively might decrease C acnes surgical site infections.42 The available evidence-based preventive interventions discussed above are listed in Table E (available in the online version of this article).

Evidence-based information on perioperative measures to lower C. acnes infection risk.Evidence-based information on perioperative measures to lower C. acnes infection risk.

Table E.

Evidence-based information on perioperative measures to lower C. acnes infection risk.

Conclusion

C acnes is a low virulence bacterium that lives in human hair follicles and sebaceous glands. It can cause chronic, insidious infection. The shoulder and neck/back are the most common sites, but difficult or unusual presentations may involve other areas, such as the elbow, hand, hip, and knee. The clinical presentation is often more benign than that seen with more virulent pathogens. Routine laboratory testing may not be sensitive. Proper tissue handling and prolonged culture growth can increase the likelihood of confirming C acnes infection. Management often mandates both surgical and pharmacologic methods, with thoughtful selection of appropriate agents. Removal of prostheses may be necessary, even when minimal clinical signs other than pain, stiffness, or aseptic loosening of components are apparent. Due to the complexity and ambiguity of diagnosis and treatment, prevention is essential. Numerous evidence-based interventions are available that may help reduce the risk of postoperative C acnes infection.

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Characteristics of common skin flora

C. acnesS. epidermidisS. aureus
Location regard to skin layersuperficial and deepsuperficialsuperficial
Gram Staingram + / purplegram + / purplegram + / purple
Morphologybacillusclusters of cocciclusters of cocci
Aerobic / Anaerobicanaerobic-aerotolerantfacultative anaerobicfacultative anaerobic
Spore Productionnonono
Coagulase Positivityn/acoagulase −coagulase +
Biofilm Formationyesyesyes
Gender Preferencemaleneitherneither
Pathogenicityopportunisticopportunisticoften pathogenic

Relevance of C. acnes infections in orthopaedic surgery.

LocationStudy Findings
GeneralAmong 61 C. acnes isolates (62 patients), C. acnes caused definite implant infections in shoulder (80%), spine (50%), hip (15.4%), and knee (8.3%).16
Pain and joint dysfunction were the two major symptoms of C. acnes PJI discovered within 2 years of implantation, while other signs of infection were observed less often with the prosthetic hip (34), knee (10) or shoulder (6) infections.13
ShoulderThe prevalence of C. acnes was found to be greater around the acromion and axilla than in the hip and knee.1
C. acnes was the most common pathogen in 39 rotator cuff repair cases with deep infections; the prevalence was significantly higher in males.33
Cloudy joint fluid, humeral osteolysis on radiographs, male gender, glenoid wear, membrane formation, and humeral loosening were associated with increased likelihood of positive C. acnes culture.41
C. acnes was the most common pathogen in 75 revision shoulder arthroplasty cases with positive intraoperative cultures.32
C. acnes was the most common pathogen in 2-stage exchange shoulder arthroplasty done for infection in 18 patients.77
SpinePositive C. acnes culture was found more frequently after spinal fusion when > 1 year than < 1 year.22
C. acnes was found in 6 of 7 patients with late implant infections after adolescent scoliosis surgery.18
C. acnes was a major pathogen in posterior pediatric spinal deformity surgery and was seen only in children 11 years or older with back acne.23
The most common pathogens involved in late postoperative infections after spine surgery were C. acnes and coagulase-negative Staphylococci.20
The most common site of C. acnes infections in 15 reported orthopaedic infection cases was the spine.36
C. acnes identified in the intervertebral disk material of patients undergoing microdiscectomy.24
C. acnes implicated in spondylodiscitis in 29 patients, and previous surgery was the most frequent risk factor.9
HandC. acnes has been identified in metacarpophalangeal arthroplasty infection.17
Hip and KneeThe incidence rate ratio of C. acnes infections in 395 total hip and 390 total knee arthroplasties was 1.21, with an increasing trend over years.25
One of 31 patients after one stage revision of total hip prosthesis had a positive C. acnes culture and this was detected with sonicate fluid only.26
Positive C. acnes culture was identified in 19% of 63 arthroplasty revision procedures for aseptic loosening, including 44 knees and 19 hips.45
16 of 26 hip revision arthroplasty with culture-positive implants after ultrasonication were C. acnes positive.28
ElbowC. acnes was the second most common pathogen in 16 revision elbow arthroplasties with unexpected positive intraoperative cultures, although all grew in broth only and were identified initially as contaminants.21

Recommendations for C. acnes specimen handling to optimize cultures

Recommendations
Diagnostic RequirementTwo or more positive cultures from tissue and/or synovial fluid specimens (not swabs).47
Specimen CountAt least 3 and up to 5–6 specimens 57
PreparationStop antibiotics 14 days before surgery if feasible.64,74
Sonication or vortexing of the explant may improve response,63,65 but has not been shown to be efficacious in revision TSA.66
Culture MediumUse both aerobic and anaerobic agars and also an enriched liquid
medium, such as thioglycollate broth58,61
Rosenow's broth is also a suggested medium.60
Incubation periodMinimum culture period of 10 – 15 days3–6,40,44,58
Utilization of strict anaerobic collection and transportation with an anaerobic thioglycollate broth may reduce the incubation period to 7 days.58,61
An experimental technique using a PCR-RFLP assay, which combines the sensitivity of PCR with the specificity of RFLP mapping, has been described for identifying C. acnes in fresh surgical specimens. Results are available within 24 hours with this method.70

Antibiotic efficacy in C. acnes infections

AntibioticsSusceptibilityComments
β–lactam (penicillin, ampicillin), ceftriaxonesusceptiblefirst choice in surgical infections if β–lactam tolerant
vancomycin, daptomycinsusceptibleused in case of β–lactam allergy or antimicrobial resistance
amoxicillinsusceptible
aminoglycosideweakly susceptible
clindamycin, erythromycin, tetracycline, doxycycline, moxifloxacin, cotrimoxazoleoccasionally resistantResistance to tetracyclines increasingly reported71
metronidazole, fosfomycinresistant100% resistance to metronidazole reported74
rifampinsusceptibleactive against biofilms but should not be used alone as it is prone to rapid development of resistance
a 0.7% resistance has been noticed.11
Biofilm formation has been implicated in increased resistance to cefamandole, ciprofloxacin, clindamycin, vancomycin, and inconsistently to gentamicin.7,72–75
Combined antibiotic therapy has been advocated:
rifampin and daptomycinsusceptibleincreased activity against C. acnes compared with vancomycin/rifampin 75

Evidence-based information on perioperative measures to lower C. acnes infection risk.

InterventionDescription/EfficacyBeneficial
preoperative measuresThree consecutive preoperative days of topical Benzoyl peroxide 5% was superior to chlorhexidine gluconate 4% in reducing C. acnes skin burden in shoulders.79+
Application of 3% topical hydrogen peroxide before a standard surgical prep has been shown to reduce preoperative C acnes skin burden.85,86+
Topical Benzoyl peroxide/clindamycin was effective at reducing superficial and deep C. acnes colonization, with dose dependent effect favoring more than 1 application,80 but this may not control C acnes growth over 14 days.81,82+/−
Preoperative oral or parenteral doxycycline is not effective at reducing C. acnes skin colonization.83,84
antimicrobial solutionsChloraPrepTM, DuraPrepTM, and regular povidone-iodine scrub and paint had no significant difference in efficacy toward reducing C. acnes in shoulder surgery.94
hair clippingAxillary hair clipping had no effect on C. acnes burden either before or after skin preparation with ChloraPrepTM.93+/−
proper drapingThe use of cyanoacrylate microbial sealant, an adhesive skin barrier may help reduce C. acnes infections.91+
proper ventilation flowLaminar air flow in the operating room reduces bacterial contamination.87–89+
surgical techniquesSeparate scalpel blade for the skin and deeper tissue given dermal colonization.90+
Submerging surgical gloves in a chlorhexidine splash-basin every 10 minutes reduces transfer of bacteria, including C. acnes.92+
implant preparationCoating surgical field or implants with antimicrobial power has been used for general antimicrobial prophylaxis.95–97+/−
Use of antibiotic impregnated cement in selective cases98–100,102 but may not be efficacious in primary total joints101+/−
Take caution as indiscriminate use of antibiotics can increase antibiotic resistance.
appropriate postoperative wound careSilver-impregnated operative wound dressings can potentially decrease C. acnes surgical site infection risk.42+
Authors

The authors are from the Department of Orthopaedics and Physical Medicine (ZXL, HSS, SKW), the Department of Pathology and Laboratory Medicine (LLS), and the Department of Internal Medicine, Division of Infectious Diseases (CEM), Medical University of South Carolina, Charleston, South Carolina.

The authors have no relevant financial relationships to disclose.

Correspondence should be addressed to: Shane K. Woolf, MD, Department of Orthopaedics and Physical Medicine, Medical University of South Carolina, CSB 708, MSC 622, 96 Jonathan Lucas St, Charleston, SC 29425 ( woolfsk@musc.edu).

Received: June 20, 2019
Accepted: September 30, 2019

10.3928/01477447-20191213-02

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