9
CASE SERIES ABSTRACT One or more authors have potential conflicts of interest related to this work. The complete Disclosure of Po- tential Conflicts of Interest submitted by the authors is available with the online version of the article. THE ORTHOPAEDIC JOURNAL AT HARVARD MEDICAL SCHOOL 66 Proprionibacterium acnes Infection Complicating the Operative Treatment of Clavicle Fractures Arvind G. von Keudell, MD 1 Sandra B. Nelson MD 2 Jesse B. Jupiter, MD 1 AUTHOR AFFILIATIONS 1 Massachusetts General Hospital, Depart- ment of Orthopaedic Surgery, Harvard Medical School Boston, MA 2 Massachusetts General Hospital, Division of Infectious Disease, Harvard Medical School Boston 02114, MA CORRESPONDING AUTHOR Arvind G. von Keudell, MD Hand and Upper Extremity Service Massachusetts General Hospital Department of Orthopaedic Surgery Yawkey Center for Outpatient Care 55 Fruit Street, YAW-2-2C Boston, Massachusetts 02114 Phone: 617-726-5100 [email protected] ©2015 by The Orthopaedic Journal at Harvard Medical School BACKGROUND Management of failed surgical fixation of clavicle fractures resulting in nonunion is a challenging entity and warrants suspicion for indolent infection. Propionibacterium acnes (P. acnes) and other Proprionibacterium species have been recognized as one of the major sources of infection of the shoulder girdle. This study reviews a series of patients diagnosed with P. acnes infection after nonunion of a surgically treated clavicle fracture. METHODS From 2002 to 2014, six patients were diagnosed with P. acnes infection after a failed surgical fixation of a clavicle fracture and were retrospectively analyzed. Clinical outcome was measured using pre- and post-operative outcome scores. RESULTS All patients had an initial diagnosis of clavicle fracture that was treated with open reduction and internal fixation (ORIF). Four patients subsequently developed chronic nonunion and wound cul- tures revealed P. acnes at the time of revision ORIF or irrigation and debridement and were subsequently treated with intravenous anti- biotics followed by a course of oral antibiotics. Two patients devel- oped an acute infection after clavicle fixation within 3 months of the initial fixation and went on to nonunion. All six patients ultimately demonstrated union and had significantly improved physical func- tion and reduction of pain. CONCLUSION Failure of surgical fixation of clavicle fractures result- ing in nonunion should raise suspicion for infection and cultures should be obtained. P. acnes has been recognized as a source of in- fection in the shoulder girdle; when recognized and treated appro- priately, excellent functional outcome and union can be achieved. Clavicle fractures represent a common injury of the shoulder girdle. 14 Various treatment options have been proposed, ranging from nonsurgical treatment with a sling to surgical treatment using a variety of forms of inter- nal fixation depending on location of the fracture. McKee et al. 13 conducted a meta-analysis analyzing the current evidence of operative versus nonop-

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Page 1: Proprionibacterium acnes Infection Complicating the ... · Proprionibacterium acnes Infection Complicating the Operative Treatment of Clavicle Fractures ... tures revealed P. acnes

CASE SERIES

ABSTRACT

One or more authors have potential conflicts of interest related to thiswork. The complete Disclosure of Po-tential Conflicts of Interest submittedby the authors is available with the online version of the article.

THE ORTHOPAEDIC JOURNAL AT HARVARD MEDICAL SCHOOL66

Proprionibacterium acnes Infection Complicating the Operative Treatment of Clavicle Fractures

Arvind G. von Keudell, MD1

Sandra B. Nelson MD2

Jesse B. Jupiter, MD1

AUTHOR AFFILIATIONS1Massachusetts General Hospital, Depart-ment of Orthopaedic Surgery, Harvard Medical School Boston, MA2Massachusetts General Hospital, Division of Infectious Disease, Harvard Medical School Boston 02114, MA

CORRESPONDING AUTHORArvind G. von Keudell, MDHand and Upper Extremity Service Massachusetts General Hospital Department of Orthopaedic Surgery Yawkey Center for Outpatient Care55 Fruit Street, YAW-2-2CBoston, Massachusetts 02114Phone: [email protected]

©2015 by The Orthopaedic Journal at Harvard Medical School

BACKGROUND Management of failed surgical fixation of clavicle fractures resulting in nonunion is a challenging entity and warrants suspicion for indolent infection. Propionibacterium acnes (P. acnes) and other Proprionibacterium species have been recognized as one of the major sources of infection of the shoulder girdle. This study reviews a series of patients diagnosed with P. acnes infection after nonunion of a surgically treated clavicle fracture.

METHODS From 2002 to 2014, six patients were diagnosed with P. acnes infection after a failed surgical fixation of a clavicle fracture and were retrospectively analyzed. Clinical outcome was measured using pre- and post-operative outcome scores.

RESULTS All patients had an initial diagnosis of clavicle fracture that was treated with open reduction and internal fixation (ORIF). Four patients subsequently developed chronic nonunion and wound cul-tures revealed P. acnes at the time of revision ORIF or irrigation and debridement and were subsequently treated with intravenous anti-biotics followed by a course of oral antibiotics. Two patients devel-oped an acute infection after clavicle fixation within 3 months of the initial fixation and went on to nonunion. All six patients ultimately demonstrated union and had significantly improved physical func-tion and reduction of pain.

CONCLUSION Failure of surgical fixation of clavicle fractures result-ing in nonunion should raise suspicion for infection and cultures should be obtained. P. acnes has been recognized as a source of in-fection in the shoulder girdle; when recognized and treated appro-priately, excellent functional outcome and union can be achieved.

Clavicle fractures represent a common injury of the shoulder girdle.14 Various treatment options have been proposed, ranging from nonsurgical treatment with a sling to surgical treatment using a variety of forms of inter-nal fixation depending on location of the fracture. McKee et al.13 conducted a meta-analysis analyzing the current evidence of operative versus nonop-

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erative treatment of displaced midshaft clavicular frac-tures. Operative treatment was found to result in earlier return to function, a reduced rate of nonunion, and an overall decreased complication rate when compared to nonoperative treatment. The complication rate (includ-ing nonunion, symptomatic malunion, infection, hard-ware removal, neurologic symptoms and refracture) was reported to occur in 29% in the operative group versus 42% in the nonoperative group. Postoperative pin site or wound infections occurred in 4% (9 of the 212 patients) treated operatively.

In the past decade, Proprionibacterium acnes (P. acnes) has been recognized as one of the major sourc-es of infection after surgical interventions around the shoulder girdle.17 This study reviews a series of patients who were either from our institution or referred to our institution and diagnosed with P. acnes infection after either chronic nonunion or acute infection of a surgically treated clavicle fracture. The primary goal

is to report on (1) radiographic union and (2) clinical outcome (Quick DASH, VAS and Range of motion) af-ter the various treatment options applied for infection control or eradication of infected clavicle nonunions. Further goals are to (3) report on re- operations and (4) complications of all treated patients. Three exemplary cases will be discussed in further detail.

MATERIALS & METHODS

This case series was approved by the institutional review board. We retrospectively reviewed all patients seen for infections after surgically repaired clavicle fractures and treated at the Upper Extremity or Or-thopaedic Trauma Department. Additionally, patients were identified using the Infectious Disease Outpatient Parenteral Antimicrobial Therapy registry. The retro-spective review identified six patients who were treated between January 2002 and April 2014 (Table 1). Clin-

Patient Age (yrs) Gender Type of Initial

FractureInitial

Treatment(s)

Location and Type of Nonunion

Nonunion Duration

(mos)

Secondary Sur-geries Final Fixation Method

Time to Evidence of Healing of Nonunion

(wks)

1 52 F Distal third, type 2

Coracoclavicu-lar screw

Distal third clavicle, atrophic 3

2 (Hook plate/removal of hook plate)

Iliac crest bone graft, dorsal lateral locking compression plate & anterior non locking plate

6

2 59 M Mid-shaft fracture

ORIF (unkonwn implant)

Mid-shaft clavicle, hypertrophic

8

3 (Two Revision ORIF with allograft, Revision ORIF with autogenous graft)

Superior (3.5mm) and anterior (2.7mm) double plating with intercalary metatarsal allograft

8

3 21 FMid-shaft with comminution

8-hole plate with 6 3.5 mm cortical screws and 1 lag screw

Mid-shaft, atrophic 4

2 (Removal of hardware and Irri-gation& Debride-ment and VAC placement)

Superior and anterior double non- locking reconstruction plating

6

4 49 FSegmental mid- shaft fracture

ORIF 3.5mm pelvic recon-struction plate

Mid-shaft, atrophic with a 4.5 cm defect

10

3 (Revision ORIF and Removal of hardware and irrigation and debridement)

9-hole non-locking pelvic reconstruction plating with 5cm iliac crest bone graft

4

5 49 M

Mid- shaft clavicle frac-ture with mild comminution

ORIF (unknown implant)

Mid-shaft, atrophic 12

2 (ORIF revision with intercalary bone graft, un-known implant)

Iliac crest bone graft, LCDC anterior plate and 2.7mm superior plate

12

6 51 MDistal third calvicle frac-ture, Type 2

Hook plate and screws Distal third 3

2 (Irrigation and Debridement, Removal of hard-ware)

None 12

Patient demographic data and information on surgical treatmentsTABLE 1

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von Keudell et al.

ical outcome was measured by radiologic outcomes as well as patient rated factors including Quick DASH Score,3 Range of motion and Visual Pain Analogue.

Four patients presented with a diagnosis of a non-union of a clavicle fracture following surgical treatment and two patients developed acute infection following primary fracture fixation at our institution.

Two patients developed a symptomatic postopera-tive infection within 3 months following surgical treat-ment while the other four patients developed positive cultures at a later date obtained at the revision surgery (mean 23.6 months, range 6-71 months). In all, the pri-mary causative agent was P. acnes. Coagulase negative staphylococcus was also found in two patients.

In two out of the four patients, P. acnes had been cul-tured during a second surgery prior to referral to our ser-vice. The organisms that grew on culture were initially interpreted as contaminants, and prior to revision surgery at our institution no antibiotic treatment was provided.

Antibiotic therapy after surgical debridement and revision consisted of six to eight weeks of an intrave-nous antibiotic regimen including cefazolin, penicillin, ceftriaxone, clindamycin, vancomycin or daptomycin for an average of 7 weeks (range 6-11 weeks). This was followed by an oral regimen with one agent (clinda-mycin, amoxicillin, or cefadroxil) or a combination of

one of these drugs with rifampin. Oral antibiotics were continued for an average of 21 weeks (range 2 and 6 months; one individual was placed on life long antibi-otic suppression). The parenteral antibiotics were tai-lored towards the sensitivities of the bacterium when available (Table 2).

Case 1

A 52-year-old woman and avid triathlete sus-tained a closed, displaced distal clavicle fracture of her non-dominant limb. She initially underwent cora-co-clavicular screw fixation with a 4.5 mm cannulat-ed screw. Three weeks postoperatively, the screw was noted to have migrated superiorly. She returned to the operating room, where the fracture was internally fixed with a hook plate and screws. Two months lat-er, radiographs suggested the fracture had united and the plate was removed due to hardware irritation. Fol-low-up radiographs at eight weeks following plate re-moval demonstrated a nonunion, and the patient was referred for reconstruction. A third operation was per-formed four months following hook plate removal us-ing a dorsolateral plate with four locking screws in the distal piece in addition to a 2.4mm anterior plate with five screws along with 3 cm autogenous iliac crest bone

Patient Time to Growth Culture Sensitivities Initial Antibiotic Treatment

(Duration)Suppressive Antibiotic

Treatment

1 7 daysP. acnes in anaerobic culture, one colony of Coagulase-negative Staphylococcus

Stapylococcus resistant only to Penicillin

IV Cefazolin and oral Rifampin (6 weeks)

Doxycycline (8 weeks)Rifampin (4 weeks)

2 5 days P. acnes in anaerobic culture Sensitivities were not obtained Penicillin (6 weeks)Amoxicillin (lifelong sup-pression)Rifampin (1 year)

3 11 days P. acnes in anaerobic culture Sensitivities were not obtainedIV Ceftriaxone and oral Rifampin (6 weeks) Amoxicillin and rifampin

(4 months)

4 9 days P. acnes in anaerobic culture Unknown Clindamycin (unknown) Clindamycin (unknown)

5 8 days P. acnes in anaerobic culture Sensitivities were not obtained IV Vancomycin (3 weeks), IV Dapto-mycin (8 weeks) Clindamycin (8 weeks)

6 8 daysP. acnes in anaerobic culture, one colony of Coagulase-negative Staphylococcus

Staphylococcus resistant to Penicllin and Clindamycin IV Cefazolin (6 weeks) Cefadroxil (6 months)

Culture data and antibiotic therapyTABLE 2

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graft. Cultures revealed one colony of Coagulase-nega-tive staphylococcus and moderate P. acnes.

She was treated with intravenous cefazolin in com-bination with oral rifampin for a total of six weeks, fol-lowed by eight weeks of oral doxycycline.

At thirty-four months status post revision surgery,

she reported 0/10 pain on VAS, and an improvement from 66 to 9 points on the short Disability Arm, Shoul-der and Hand Score (DASH). Physical examination demonstrated full range of motion of her shoulder. The patient was able to return to her competitive athletic lifestyle (Figure 1).

Initial trauma CT scan 3D reconstructionFIGURE 1

A

C

B

D

(A) Evidence of failure of fixation with a 4.5mm coraco-clavicular screw (B). Subsequent fixation with a hook plate and screws (C) and radiographs taken after removal of hardware demonstrating nonunion (D). Final clavicle radiographs (E/F) demonstrating healing of nonunion status post superior & anterior plating and screw fixation.

E F

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Case 2

A 59-year-old male sustained a closed midshaft frac-ture of his right dominant clavicle from a fall. Surgery was performed at an outside institution with a plate and screws, which failed to heal. Two subsequent sur-gical attempts to achieve union with plate and screws and allograft bone graft followed.

A fourth attempt at our institution included au-togenous iliac crest graft plus plate and screw fixation, which also proved to be unsuccessful. Intraoperative cultures demonstrated P. acnes, which was thought to be a contaminant due to multiple prior surgeries. The patient was referred to the senior author. Physical ex-amination revealed a painful shoulder girdle motion with his pain scale on the VAS being 10/10 and DASH score of 95 points. The erythrocyte sedimentation rate was 16 mm/hr and C-reactive Protein 10.4 mg/L. Ra-diographs revealed an obvious non-union in addition to loose internal fixation.

Surgery was performed using a dual plate fixation including a 6-hole 2.7mm plate on the dorsal sur-face and 9- hole 3.5 mm on the anterior surface. A metatarsal allograft was used to bridge the defect at the nonunion site following debridement. Intraop-erative cultures again revealed P. acnes. Parenteral penicillin was given for total of 8 weeks followed by oral amoxicillin and rifampin, which was anticipated to be lifelong. At three months post-op, radiographs demonstrated that his nonunion to have healed. At 43 months following his last revision surgery, his VAS score was 3/10, and his DASH improved from 95 to 61 points with full shoulder range of motion (Figure 2).

Case 3

A 21-year old college soccer player sustained a displaced midshaft clavicle fracture in her non-dom-inant extremity while playing soccer and underwent surgical fixation with a 3.5mm plate. Six weeks post-operatively, wound dehiscence occurred. Radio-graphs did not show any evidence of bony healing. She was taken to the operating room for irrigation and debridement of the surgical site. The plate was left in place. Cultures were obtained and grew P. acnes. Intravenous ceftriaxone in addition to rifam-

pin was administered for six weeks followed by oral amoxicillin with rifampin. Four months status post irrigation and debridement, the plate was removed and revision internal fixation with double plating us-ing a 5-hole 3.5mm anterior plate and 8-hole 3.5mm superior plate was performed. Cancellous bone graft-ing from the iliac crest was used to fill the 2cm gap from the apparent nonunion site. Cultures that were obtained at the revision operation remained without growth. Antibiotics were discontinued when bony union was evident on CT scan four months after the revision procedure. At five months following her re-vision surgery, the patient report 0/10 on VAS with a DASH score of 2 and returned to playing soccer.

RESULTS

After eradicating the infectious organism, all six patients demonstrated healing of the infected non-union on follow-up radiographs.

All six patients improved in regards to their Quick DASH Score, functional motion, and pain scale when the treatment was completed. The DASH Score improved from 54±32 (n=5) to 22±72 (n=5) points at final follow-up (25±19 months, range 3- 43months). The range of motion (n=5) of the af-fected shoulder postoperatively demonstrated on average abduction of 160±35 degrees, forward flex-ion of 153±46 degrees, external rotation of 75± 26 degrees and VAS pain scale decreased from 4.8±3.1 to 1±1.7 (Table 3).

Overall, two patients underwent four procedures, three patients underwent three operations and one patient underwent two operations to achieve healing of their infected non-unions. All patients demonstrated union at final follow-up. Evidence of bony healing following revision surgery was appar-ent in less than 3 months in all patients (8± 3 weeks, range 4-12 weeks).

Complications included an initial cortical screw backing out slightly in one patient, which remained mildly symptomatic but did not interfere with func-tional activities. Two patients had allergic reactions to the antibiotic therapy. Upon change of the antibiotic, the symptoms subsided.

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Patient Final Follow-up (mos) Preoperative VAS (0-10) Preoperative DASH Postoperative VAS Postoperative DASH Final ROM

1 37 4 66 0 9 Full

2 43 10 96 3 61 Full

3 5 5 64 0 2 Full

4 3 3 9 n/a n/a n/a

5 36 2 36 0 18 Full

6 14 n/a n/a 2 20 Full

Final outcome scoresTABLE 3

Case 2FIGURE 2

A

C

B

D

(A/B) Initial presentation demonstrating hardware breakage and nonunion of mid shaft clavicle fracture. (C/D) Radiographs demonstrating revision fixation of the clavicle fracture and nonunion. (E/F) Imaging of the re-revision fixation with double plating and screw fixation demonstrating healed nonunion.

E F

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von Keudell et al.

DISCUSSION

Infection after surgery about the shoulder girdle is an uncommon condition but can have devastating impact on the shoulder function.17 P. acnes was once thought to be a contaminant but now is recognized as one of the most common and important pathogens causing infection after surgical procedures about the shoulder girdle.10, 16, 20 With the increase in operative treatment of clavicle fractures, there is a potential for an increase in surgical complications such as infec-tions.

Duncan et al.6 were the first to report on P. acnes in-fection after surgical treatment of the clavicle. In their series of six patients, three patients were found to have P. acnes inoculation. All three patients were noted to have pain even after eradication of the infection. Liu et al.11 reported on seven patients with clavicle frac-ture who developed postoperative infection, although none were caused by P. acnes.

P. acnes is a gram-positive anaerobic bacillus that is found on the skin, especially in sebum excreting seba-ceous follicles. It was first noted to be the source of in-fection in shoulder surgery in 1999,19 with an increas-ing incidence reported in subsequent studies.2, 7 The explanation for why the shoulder appears to be the most commonly affected area after surgical interven-tion by this bacterium remains not fully understood. The shoulder area has the highest density of sebaceous glands and most lipophilic skin, which may be a pre-disposing factor. P. acnes is notorious for having slow growth in a culture medium (requiring a minimum of 6 days) and can be difficult to detect.

Lutz et al. found that it took an average of 11 days for this bacteria to grow from specimens associated with arthroplasty and osteosynthesis infections. In their study, early infections resulted in a slightly short-er duration until cultures were positive in comparison to late infections. (8.4 and 13.5 days, respectively)12 It should be noted that ESR and CRP concentration are insensitive indicators for Propionibacterium os-teosynthetic shoulder infection. It is rare for P. acnes to present itself with a sinus tract communicating with the osteosynthetic material and similarly rare to demonstrate visible purulence at the implant site. However, it is prudent to have a high suspicion for infection, in particular P. acnes, in chronic nonunion

after surgically reconstructed clavicle fractures. It is advisable to obtain at least three samples of anaerobic cultures, which should be held for at least 14 days to increase the diagnostic value of detecting the patho-gen.1, 4, 9, 18 Asseray et al.1 determined different criteria to improve the probability of diagnosing infection. They found that a probability of >90% was achieved if at least two positive deep cultures were present with one of the following criteria: intraoperative signs of infection, the presence of an orthopaedic implant or revision surgery. If only one positive deep culture was present, the diagnosis of P. acnes required three of the following criteria: local signs of infections, inflamma-tory biological markers, orthopaedic device and revi-sion surgery to achieve >90% probability of an actual P. acnes infection.

Osmon et al.15 published guidelines on the treat-ment of prosthetic joint infection and recommended parenteral penicillin or ceftriaxone for P. acnes in-fection. The optimal choice of antibiotic medication, however, has not been established due to the paucity of the data for osteosynthetic infections with P. acnes. Thus, a few authors have used a variety of antibiot-ics such clindamycin, vancomycin, cephalosporins or linezolid. Rifampin appears to offer synergy in the eradication of P. acnes biofilms,2, 5, 7 though the role of this antibiotic in treatment is not clear yet due to the paucity of the available data, and drug interactions complicate its use. Rifampin should only be used in combination with another antibiotic, as it is thought to aid in antibiotic penetration into the bone architec-ture. Due to the limited number of patients in this se-ries we are not able to give general recommendations on the antibiotic treatment therapy.

Currently there is no treatment algorithm for man-aging P. acnes infection of clavicular nonunion. Con-trolled clinical research is necessary to identify the op-timal antimicrobial approach to these infections. Two general approaches appear feasible for chronic non-unions (>3 months post-op), which can be amenable to either single-stage revision plating versus two-stage revision including irrigation and debridement and re-vision fixation.8 This decision should be made on an individualized basis. Based upon the senior author’s experience, we suggest a staged procedure if there is suspicion for chronic infection or massive bone loss in comparison to chronic infection with mild to

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moderate bone loss. Double plating with intercala-ry bone graft either from the iliac crest or allograft may be required to provide the stability to counter-act the inherent rotational forces across the clavicle. Parenteral antibiotics should be started as soon as the pathogen is identified. Acute infection (<3 months post-op) should be treated either with local irrigation and debridement with retaining hardware until union is observed with subsequent removal of hardware or revision fixation with plate and screw fixation. It is advisable to keep three samples of cultures obtained during a revision procedure for at least 2 weeks if there is suspicion for P. acnes infection.

CONCLUSION

This is the first series of P. acnes infection after clav-icle fracture ORIF. It is difficult to diagnose and when unrecognized can result in significant long-term im-pairment of the patient. It is necessary to have high suspicion of infection in clavicle nonunion after sur-gical fixation. No clinical guidelines currently exist. Single stage or two stage procedures in combination with long-term parenteral antibiotic therapy may lead to union and good outcomes.

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