Version May 2024
INTRODUCTION — Cutibacteria (formerly propionibacteria) are part of the normal flora of human skin and mucosal surfaces. Occasionally they cause clinically significant infections, particularly in the setting of shoulder surgery, orthopedic hardware, endovascular devices, and cerebrospinal shunts. It can be difficult to determine whether positive culture results for cutibacteria reflect contamination or true infection.
Infections with Cutibacterium species can be classified into three categories:
●Acne in teenagers and young adults (when caused by C. acnes)
●Surgical wound infections
●Invasive deep seated infections, usually in the setting of implantable devices (eg, pacemakers, shunts, etc)
This topic discusses the clinical manifestations, diagnosis, and treatment of invasive Cutibacterium infections in patients with implantable devices. Issues related to acne are discussed in detail separately. (See "Pathogenesis, clinical manifestations, and diagnosis of acne vulgaris" and "Acne vulgaris: Overview of management".)
MICROBIOLOGY AND PATHOGENESIS — Cutibacteria are normally present on human skin and in sebaceous glands and hair follicles; they can also be recovered from the conjunctiva, external ear, nasopharynx, oral cavity, and genitourinary tract [1]. In addition, C. acnes is a common environmental surface contaminant [2,3]. Therefore, it is often difficult to determine whether positive culture results for cutibacteria reflect contamination or true infection.
Cutibacterium species are members of the Actinobacteria class of microorganisms. They are slow-growing, gram-positive, nonmotile, anaerobic bacilli of relatively low virulence. The organisms can occur singly, in pairs, or in groups. They produce lactic, propionic, and acetic acids, and, unlike most other anaerobic gram-positive bacilli, they are catalase positive. These organisms may be difficult to identify initially because of their slow growth, especially in clinical specimens that also contain other common, readily recovered organisms. Therefore, identification of cutibacteria may be overlooked if cultures are not rechecked or if cultures are discarded after three to five days of incubation. Cutibacteria are more likely to represent true pathogens if they are isolated in pure culture from multiple specimens (particularly in the setting of consistent Gram stain morphology between specimens) or from a deep intraoperative specimen. One study found that the time to positive culture is shorter among patients with true infection group than among those with probable contamination (5 days versus 9 days) [4]. A polymerase chain reaction–restriction fragment length polymorphism assay has been used in surgical biopsy specimens with a turnaround time of 24 hours and with high sensitivity and specificity for the detection of C. acnes [5].
Most clinical infections due to Cutibacterium are due to C. acnes; other less common species of possible clinical significance include C. granulosum, C. avidum, and C. propionicum. However, most laboratories do not routinely speciate cutibacterial species. Clinical suspicion for infection should prompt request for speciation of the organism if available from a local microbiology laboratory and if the significance of an isolate is questionable. In the absence of clinical signs of infection, the relevance of unexpected positive cultures during orthopedic surgeries is unclear [6]. In one study including 117 primary shoulder surgical procedures without signs of infection, there was at least one positive pericapsular tissue culture after prolonged incubation in 18 percent of cases, with most cultures growing C. acnes [7]. C. acnes is thought to be a commensal in deeper tissue layers and that some of these positive cultures may represent culture contamination and a false-positive result. Therefore, the diagnosis of true low-grade infection is quite challenging. A combination of clinical, microbiologic, and histopathologic evidence is important.
C. acnes is of relatively low virulence but is capable of adherence and biofilm formation; this characteristic plays an important role in pathogenesis of infection due to this organism. In the majority of patients with Cutibacterium prosthetic joint infections, infiltration of the glycocalyx with adherence to the implant surface has been observed [8-10]. In one report, C. acnes was associated with chronic low-grade infection of implanted biomaterials as frequently as Staphylococcus spp [8]. C. acnes strains exhibiting the hemolytic phenotype appear to be more pathogenic, whereas nonhemolytic strains are more likely to represent contamination [11].
Three types of C. acnes have been proposed: type I C. acnes (known as C. acnes subsp acnes, subdivided into type IA and IB), type II C. acnes (known as C. acnes subsp defendens), and type III C. acnes (known as C. acnes subsp elongatum) [12,13]. These types colonize different areas of the human body [14] and have varying degrees of virulence. In one study, type IB strains were more frequently associated with prosthesis infection than type IA strains [15].
CLINICAL MANIFESTATIONS — Cutibacterium infections are usually characterized by a paucity of classical symptoms of infection or inflammation. Invasive Cutibacterium infection typically occurs in the setting of prior surgery. Given the low virulence of cutibacteria, infections with these organisms are usually indolent. In some cases, clinical manifestations may be delayed for months and, rarely, for years [16].
C. acnes tends to inhabit the deep crevices of the skin where surgical antiseptic solutions may penetrate poorly [17,18]. Flushing the wound during surgery may facilitate transmission of the organism from the surrounding skin into the wound.
The ability of C. acnes to adhere and form biofilm facilitates development of infection in patients with surgically implanted foreign material [8,17-26]. Cutibacterium species have been implicated in a variety of serious infections related to implantable devices:
●Orthopedic implants (including prosthetic joints as well as spinal hardware) [19,20,27]
●Endovascular devices (including prosthetic valves and pacemakers) [28,29]
●Central nervous system devices (including shunts, reservoirs, and drains) [30-33]
Infection may present with evidence of device malfunction; in some circumstances, infection is detected at the time of removal of a malfunctioning device.
Orthopedic infection — Most orthopedic Cutibacterium infections develop within the first two years after surgery [19-21,27,34-36]. Early infections present with local and systemic inflammatory signs and symptoms (joint effusion, fever, sinus tract formation with purulent discharge) [20]. In late presentations, these findings may be absent; in such cases, manifestations may include pain, joint stiffness, or prosthesis dysfunction [37].
Some patients who developed loosened prostheses ≥2 years after implantation have positive cultures with Cutibacterium species when the hardware is removed. In such cases, it may be impossible to determine if the positive cultures represent true infection or contamination secondary to the removal and processing of samples for culture.
Risk factors for C. acnes orthopedic infection include prolonged surgery, multiple surgeries, and male sex [2,16,21]. In a retrospective analysis of 52 cases of C. acnes bone or joint infections, 71 percent of cases occurred in men [19,20,38]. Men may be at increased risk for cutibacteria infection because they have more sebaceous glands and hair follicles than women. Neither perioperative topical antisepsis nor intravenous cefazolin is effective in eliminating C. acnes colonization [39].
Cutibacteria have been implicated in a variety of orthopedic infections, including prosthetic joint infection (3.6 to 5.7 percent of cases) [19,40], native joint infection following arthroscopy [26,41,42], and vertebral osteomyelitis following spine surgery [27,34,43-46].
Cutibacteria appear to have greater predilection for infection involving the shoulder joint than other joints [7,16,26,41,42,47,48]. This may be related to the observation that C. acnes colonization rates for the shoulder appear to be greater than colonization of the knee or hip [49]. In general, the infection rate is 0.9 to 1.9 percent following implantation [16,50,51]. Infections present with pain and stiffness of the shoulder, followed by local swelling or erythema. A peculiar bruising appearance along the surgical incision should raise suspicion for Cutibacterium infection of shoulder prostheses (picture 1). In one series including 17 shoulder prosthetic joint infections caused by C. acnes, the time to infection after surgery was <3 months [50].
Issues related to prosthetic joint infection are discussed further separately. (See "Prosthetic joint infection: Epidemiology, microbiology, clinical manifestations, and diagnosis".)
Endovascular infection — Cutibacterium may cause infections of endovascular devices such as prosthetic valves, pacemakers, and defibrillators [28,29,52]. Infection can be divided into local infection (pocket infection) and device-related bloodstream infections, including device-related endocarditis. Endocarditis caused by C. acnes has been associated with both native and prosthetic valves but more often develops on valve prostheses, most commonly the aortic valve [53,54]. Symptoms of endocarditis are often subtle due to the low virulence and slow growth of C. acnes [55,56]. The mortality rate is 15 to 27 percent due to valvular and perivalvular destruction associated with delayed diagnosis of infection [54,55].
In one series of 15 cases of Cutibacterium endocarditis, 13 patients had a prosthetic valve [28]. The mean onset of infection was four years following surgery. Central nervous system emboli, congestive heart failure, cardiac abscess, and valve dehiscence may complicate such infections [55].
Late-onset prosthetic valve infections due to Cutibacterium may be difficult to diagnose, as clinical manifestations may be limited to valve dysfunction with few symptoms suggestive of infection. Furthermore, histological examination of excised paravalvular tissues in such cases may demonstrate minimal evidence of acute inflammation [57].
Central nervous system infection — C. acnes is a well-known cause of cerebrospinal fluid (CSF) shunt infections. In a retrospective analysis of 78 cases, C. acnes was the third most common causative organism following coagulase-negative staphylococci and S. aureus, even though it only caused 8 percent of all infections [58].
When compared with patients with shunt infections due to other organisms, patients with Cutibacterium shunt infections were older and more often had low body temperature, few CSF leukocytes, and high CSF/blood glucose ratios [59]. In addition, in contrast to infections due to other common organisms, Cutibacterium shunt infections in children have been associated with CSF eosinophilia [60].
One small case-control study noted risk factors for C. acnes infection after neurosurgery included craniotomy, malignancy, and prolonged duration of surgery [61].
In a case-control study including 13 patients with postoperative central nervous system (CNS) infections due to C. acnes and 13 controls (patients with CNS infection caused by other bacteria), symptoms of infection due to C. acnes manifested later than infection due to aerobic bacteria (median 22 days versus 15 days) [62]. In addition, the time to positive cultures was longer in the C. acnes group versus control group (median 8 days versus 2 days).
Vertebral osteomyelitis — C. acnes infection should be considered when patients with history of back surgery present with back pain, even when blood cultures are negative. A long interval between surgery and onset of symptoms or diagnosis of infection has been observed (up to 34 months) [63]. (See "Vertebral osteomyelitis and discitis in adults".)
In one case-control study including 59 patients with spinal implant-associated infection (SIAI) due to C. acnes, 93 patients with SIAI due to other organisms, and 302 controls who underwent spinal instrumentation without subsequent infection, factors associated with C. acnes infection included age <54 years, body mass index <22 kg/m2, and thoracic instrumentation [64]. (See "Vertebral osteomyelitis and discitis in adults".)
Breast implant infection — C. acnes is an important pathogen in breast implant infection [52,65]. (See "Breast implant infections", section on 'Microbiology and epidemiology of infection'.)
Other infections — Cutibacteria have also been implicated in other serious infections such as brain abscess, subdural empyema, sinusitis, peritonitis, and respiratory infections [28,66-70].
DIAGNOSIS — Cutibacterium infection frequently poses a diagnostic challenge because it is often difficult to discern whether isolation of Cutibacterium from clinical specimens represents true infection or contamination [71]. Growth of Cutibacterium species in superficial specimens and isolation with other skin flora such as coagulase-negative staphylococci usually suggest contamination. In some cases, delayed growth of Cutibacterium may lead to false-negative results. Thus, when cultures are negative and the clinical suspicion of infection is high, prolonged specimen incubation should be requested (at least seven days).
Cutibacterium infection should be considered in the following settings:
●Following Cutibacterium isolation from the joint or wound of a patient with signs of postoperative infection following shoulder surgery [47]
●In a patient with a prosthetic joint with other clinical signs of joint infection (see "Prosthetic joint infection: Epidemiology, microbiology, clinical manifestations, and diagnosis")
●In a patient with a central nervous system shunt, signs compatible with shunt infection, and central nervous system eosinophilia
●In a patient with prosthetic valve dysfunction and findings compatible with endocarditis (such as a vegetation or a valve ring abnormality), even when other classical signs of endocarditis, such as fever, are absent
Diagnosis of orthopedic infections — Microbiological criteria proposed for the diagnosis of prosthetic joint infections due to cutibacteria include ≥3 operative cultures (out of 5 to 6 specimens) growing biochemically and microbiologically identical organisms [21,72]. Other measures that may increase the sensitivity and specificity of intraoperative cultures include sonication of removed implants and prolonged incubation period of culture specimens [19,40,73]. Sonication is useful for removing biofilm bacteria and is more sensitive than vortex alone [74,75].
Molecular methods, such as polymerase chain reaction (PCR), have been evaluated for the diagnosis of Cutibacterium infections. At present, PCR results must be interpreted carefully and correlated with Gram stains and clinical and epidemiologic findings, since small amounts of contaminating bacterial material can lead to false-positive results [76]. In a study of 41 prosthetic joint infections caused by various organisms, a multiplex PCR assay correctly identified Cutibacterium in all five culture-confirmed cutibacteria infections and exhibited 95 percent concordance with cultures from all 41 infected cases (two cases were PCR-positive for Cutibacterium but grew staphylococcal species on culture) [77]. PCR assays for cutibacteria are not yet available for widespread use.
Besides microbiological methods, a variety of preoperative diagnostic tools and markers have been evaluated to aid in the diagnosis of joint infections. These include synovial IL-6, IL-2, TNF-alpha, alpha-defensin, and calprotectin, which have been studied alone and in various combinations [78]. Results suggest that these tests may be useful for lowering or elevating the level of suspicion for a C. acnes shoulder infection, but their value beyond culture and other synovial markers (such as cell count) is uncertain. More detail regarding synovial markers of infection is found separately. (See "Prosthetic joint infection: Epidemiology, microbiology, clinical manifestations, and diagnosis", section on 'Synovial fluid analysis'.)
TREATMENT
Overview — The approach to antibiotic therapy should be guided by antimicrobial susceptibility. Treatment should be individualized depending on the clinical circumstances. The choice, duration, and route of antimicrobial therapy depend on the site of infection.
Cutibacterium isolates are usually highly susceptible to penicillins, clindamycin, cephalosporins, and carbapenems [79]. Most Cutibacterium species are also susceptible to vancomycin [80], tetracyclines [81], rifampin [9], macrolides [81], and gentamicin [8] but resistant to metronidazole [79]. Daptomycin has also been used for successful treatment of Cutibacterium osteomyelitis [82].
Antibiotic-resistant C. acnes strains have been recovered from the skin of patients with moderate to severe acne (37 percent of antibiotic-treated patients versus 13 percent of non-treated patients) [83]. Among 304 C. acnes isolates collected from various human infections, 17 percent of isolates were resistant to erythromycin and 15 percent to clindamycin [84]. C. acnes isolates embedded in biofilms demonstrate greater resistance than those in the planktonic phase [8]. In an in vitro model of C. acnes biofilm, biofilm was successfully eradicated by penicillin and linezolid/rifampin (14 days) [9].
Susceptibility testing for Cutibacterium species is not performed routinely in all laboratories. Therefore, clinicians may have to rely on the local epidemiology; suspicion for resistance should be increased in patients with history of antibiotic treatment for acne.
Orthopedic infection — Issues related to management of osteomyelitis and prosthetic joint infection are discussed further separately. (See "Nonvertebral osteomyelitis in adults: Treatment" and "Prosthetic joint infection: Treatment".)
Hardware removal — Given the role of biofilm formation in the pathogenesis of Cutibacterium infections associated with orthopedic hardware or other implanted devices, device removal is often required in order to achieve cure [8-10]. Often, such infections are associated with evidence of device malfunction; in other circumstances, infection is detected at the time of removal of a malfunctioning device.
In a series of 52 patients with orthopedic implant infections due to cutibacteria, all patients undergoing partial hardware removal had clinical failure [20]. Complete removal of prosthetic material is particularly important in the setting of device dysfunction, delayed onset infection, and chronic infection [21,24]. Spinal hardware infection should prompt removal of all components when feasible [27,34,45]. The decision to remove prosthetic material must be made in the context of individual patient circumstances.
It appears that single-stage revision is effective in the setting of failed shoulder arthroplasties growing Cutibacterium without obvious signs of infection [85]. A two-stage revision in these cases may therefore not be necessary, particularly if biofilm-active antimicrobial agents are used.
Antibiotic therapy — Initial management should consist of parenteral therapy; penicillin is the drug of choice based on in vitro susceptibility data. The optimal duration is uncertain and in various reports has ranged from two weeks to several months [19-21,34,38,86]. If, upon transition from acute to long-term care, the administration of penicillin is not practical, reasonable alternatives include cephalosporins such as cefazolin or ceftriaxone.
In the setting of clinical improvement following an initial course of parenteral therapy (minimum two weeks), treatment may be continued with oral antibiotics; we favor an oral beta-lactam agent such as a first-generation oral cephalosporin for a minimum duration of two weeks. In the setting of retained hardware (eg, because removal is not feasible), long-term oral suppressive therapy with a first-generation cephalosporin may be warranted [86]. Clindamycin and an oxazolidinone-class antibiotic (such as linezolid or tedizolid) are also acceptable choices for oral therapy; however, clindamycin is associated with increased risk for Clostridioides difficile infection and oxazolidinones are costly. Thus, these agents are best reserved for patients who cannot tolerate oral beta-lactam agents.
The assessment of treatment response can be difficult in the absence of inflammatory signs (including elevated erythrocyte sedimentation rate) and other overt symptoms of infection. Important indicators of treatment failure include recurrent joint pain or prostheses dysfunction.
The use of rifampicin in the adjunctive treatment of C. acnes orthopedic infections is of controversial value; its use should be weighed against potential risks and adverse events. One study including 60 patients with prosthetic joint infection due to C. acnes noted similar success rates among patients treated with and without rifampicin [87].
Endocarditis — In the setting of prosthetic valve endocarditis due to Cutibacterium, valve replacement is frequently necessary, particularly in the setting of congestive heart failure, cardiac abscess, or valve dehiscence [28,55]. (See "Surgery for prosthetic valve endocarditis", section on 'Indications for surgery'.)
Infected cardiovascular implantable devices require complete removal [88]. (See "Infections involving cardiac implantable electronic devices: Epidemiology, microbiology, clinical manifestations, and diagnosis".)
Parenteral penicillin is the drug of choice for treatment of Cutibacterium endocarditis based on in vitro susceptibility data and case series [28,55]. Other options include cephalosporins, vancomycin, and daptomycin, although clinical data are scarce. Prosthetic valve endocarditis (PVE) should be treated with parenteral antibiotics for six weeks. In addition, many of the reported cases of PVE due this organism have required surgical intervention [56]. (See "Antimicrobial therapy of prosthetic valve endocarditis".)
Central nervous system device infection — Issues related to hardware removal in the setting of central nervous system device infections are discussed separately. (See "Infections of cerebrospinal fluid shunts", section on 'Device removal'.)
Treatment should include an agent with good cerebrospinal fluid penetration. Penicillin G is the agent of choice; alternative agents include third-generation cephalosporins (ceftriaxone, cefotaxime), vancomycin, daptomycin, and linezolid. Device removal coupled with parenteral therapy (10 to 14 days) is usually appropriate [89]. This issue is discussed in detail separately. (See "Infections of cerebrospinal fluid shunts", section on 'Treatment'.)
PREVENTION OF SURGICAL SITE INFECTIONS — Standard operative infection control measures should be employed to prevent post-operative C. acnes infections. In addition, specific interventions can reduce prosthetic joint infections. Details are found elsewhere. (See "Overview of control measures for prevention of surgical site infection in adults" and "Prevention of prosthetic joint and other types of orthopedic hardware infection".)
Preoperative antibiotics are one of the most effective interventions for reducing prosthetic joint infections. The most commonly used preoperative regimen is cefazolin, which has been found to be more effective than alternative agents, including vancomycin and clindamycin. In one observational study of over 7700 shoulder arthroplasty procedures, the use of cefazolin was found to decrease C. acnes infections compared with preoperative alternatives consisting mainly of vancomycin or clindamycin (HR 0.22; 95% CI 0.11 to 0.42) [90].
However, studies suggest that standard peri-operative practices, such as preoperative antibiotics and skin preps, may not kill C. acnes bacteria and other skin flora on and beneath the surface of the skin. Additional intraoperative measures have been evaluated to reduce the risk of C. acnes infection following shoulder surgery. In a randomized clinical trial, disinfection of the subcutaneous tissue with povidone-iodine as an adjunct to standard disinfection procedures for shoulder arthroplasty decreased C. acnes culture-positivity of the operating field [91]. In another study, application of skin acne cream (benzoyl peroxide–miconazole nitrate) for seven days before shoulder surgery reduced intraoperative culture-positivity [92]. The clinical significance of these studies remains unproven, and at present we continue to recommend the routine use of chlorhexidine-based skin antiseptics.
SUMMARY AND RECOMMENDATIONS
●Overview – Cutibacteria (formerly propionibacteria) are part of the normal flora of human skin and mucosal surfaces but can cause clinically significant infection in some circumstances, particularly in the setting of shoulder surgery, orthopedic hardware, endovascular devices, and cerebrospinal shunts. (See 'Introduction' above.)
●Pathogenesis – Cutibacteria are of relatively low virulence but are capable of adherence and biofilm formation; this characteristic plays an important role in the pathogenesis of infection due to this organism. (See 'Microbiology and pathogenesis' above.)
●Microbiology and diagnosis – In general, cutibacteria are not usually pathogenic. Therefore, it can be difficult to determine whether positive culture results reflect contamination or true infection. Cutibacteria are more likely to represent a true pathogen if isolated in culture from multiple specimens or from a deep intraoperative specimen. (See 'Microbiology and pathogenesis' above and 'Diagnosis' above.)
●Clinical manifestations – Infections are usually indolent and clinical manifestations may be delayed for months or, rarely, years. In addition, Cutibacterium infections are usually characterized by a paucity of classical symptoms of infection or inflammation. (See 'Clinical manifestations' above.)
●Management of infection – Treatment includes antimicrobial therapy coupled with surgical intervention, if appropriate.
•Antimicrobial therapy – The choice and duration of antibiotic therapy should be individualized depending on the clinical circumstances. In general, we suggest parenteral penicillin for initial management of invasive Cutibacterium infections (Grade 2C). (See 'Overview' above.)
•Surgical management – Given the role of biofilm formation in the pathogenesis of Cutibacterium infection, eradication of Cutibacterium infections is difficult without removal of infected devices. We suggest hardware removal except when this intervention would result in joint or spine instability (in the case of orthopedic infections) or when the overall condition of the patient makes the procedure unsafe (Grade 2B). (See 'Orthopedic infection' above.)
●Prevention of surgical site infection – Standard operative infection control measures should be employed to prevent post-operative C. acnes infections. In addition, specific interventions can reduce prosthetic joint infections, including those due to C. acnes. (See "Overview of control measures for prevention of surgical site infection in adults" and "Prevention of prosthetic joint and other types of orthopedic hardware infection".)
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