Stop Adding Antibiotics to Irrigation Solutions
The rate of adoption of knowledge gleaned from multiple well-done randomized clinical trials into medical practice is disappointingly slow. This has been well-documented in cardiovascular medicine, and the examples in orthopaedic surgery are embarrassingly similar. A corollary phenomenon exists with the slow rate of transfer of information from basic science studies to orthopaedic clinical practice.
These “disconnects” occur largely because we tend to adopt the practices of our residency faculty, often without any rational inquiry. Having been an oral examiner for the Part II ABOS Oral Boards, I frequently asked, “Why did you decide on that approach to the patient’s problem?” And I often heard in response, “That’s the way it was done in my residency.”
In the September 18, 2019 issue of The Journal, Goswami et al,. report findings from a well-designed in vitro study demonstrating that the common practice of adding the antibiotics polymyxin and bacitracin to irrigation solution to lower the risk of infection is not based on sound evidence. While adding antibiotics might make intuitive sense, according to these authors, it is “a futile exercise.”
After testing 8 different irrigation solutions for efficacy against S. aureus and E. coli and for toxicity to musculoskeletal cells, Goswami et al. concluded that “our results provide further support for the use of dilute povidone-iodine because of its bactericidal properties, relatively limited toxicity,… and modest cost.” They go on to say that their findings bring into question the widespread usage of polymyxin-bacitracin.
Certainly, we need to assemble more evidence from additional research to identify the optimal irrigation solution for orthopaedic surgery, but in the interim, we should probably stop using polymyxin-bacitracin. Doing so would have the added benefits of lowering costs and not exacerbating the serious problem of antimicrobial resistance. There are many areas of clinical practice where we have no evidence either for against a particular approach. But when we do have solid evidence, even if it’s from an in vitro study, we should work together to improve the rates of adoption into clinical practice.
Marc Swiontkowski, MD
JBJS Editor-in-Chief
Rabbit Study Suggests Antibiotic-Releasing Implant Coating Could Cut Infection Risk
A study by Miller et al. in the February 20, 2019 issue of JBJS provides preclinical proof of concept that antibiotic-loaded coatings on orthopaedic implants could eventually reduce the incidence of implant-associated infection.
The researchers used in vivo bioluminescence imaging (BLI) and ex vivo analysis of colony-forming units (CFUs) to show the efficacy of an implant coating that released linezolid-rifampin over a 7-day period. Through a parapatellar arthrotomy, researchers reamed the femoral canal of 12 rabbits and inoculated the canals with a bioluminescent strain of MRSA. They then inserted a surgical grade titanium peg into each canal. All of the pegs were coated with a nanofiber coating; 6 of the pegs were loaded with the antibiotic coating and 6 were not.
Implants coated without antibiotics were associated with significantly increased in vivo BLI signals and significantly increased knee width, relative to implants with the antibiotic-releasing coatings. The animals were killed on day 7, and ex vivo analysis of CFUs isolated from soft tissue, bone, and implant specimens showed significantly increased CFUs in the specimens without the antibiotic-releasing coating, while CFUs were undetectable in the implants with antibiotics.
This larger-animal model to assess bacterial burden employed a clinically used orthopaedic implant and replicated a medial parapatellar arthrotomy in humans. According to the authors, the coating used is “highly versatile, and the polymers or drug concentrations could be modified for more rapid or longer release.” This rabbit model should be amenable to studying additional antibiotic-releasing strategies for possible translation to clinical research in humans.
Musculoskeletal Infections: Oral Antibiotics Not Inferior to IV
OrthoBuzz occasionally receives posts from guest bloggers. In response to a recent New England Journal of Medicine study, the following commentary comes from Daniel Leas, MD and Joseph R. Hsu, MD.
Deep infections continue to be one of the most resource-intensive problems that orthopaedic surgeons face. Long-standing dogma has favored 6 or more weeks of intravenous (IV) antibiotics, resulting in increased healthcare costs during both the inpatient and outpatient treatment periods.
To explore the possibility of utilizing targeted oral antibiotics as an alternative, effective treatment for musculoskeletal infections, the OVIVA (Oral versus Intravenous Antibiotics) multicenter research collaboration conducted a prospective, randomized controlled trial. A total of 1,054 patients with deep musculoskeletal infections were randomized to oral or IV arms for 6 weeks of antibiotic treatment and followed for 1 year to determine treatment efficacy. The primary end point was treatment failure within 1 year, defined as the presence of predefined clinical symptoms of deep infection, microbiologic evidence of continued infection, or histologic presence of microorganisms or inflammatory tissue. Secondary outcomes included catheter-associated complications, discontinuation of therapy, and Clostridium difficile diarrhea.
Of the 1,054 patients enrolled, 909 patients were included in the final analysis. Treatment failure occurred in 14.6% of patients treated with IV antibiotics and 13.2% of patients in the oral-therapy group. This -1.4% difference indicated noninferiority based on the predetermined 7.5% noninferiority margin. Secondary outcomes between the groups differed only in catheter-related complications being more common in the IV group (9.4% vs 1.0% in the oral group).
These findings and conclusions should challenge us to re-evaluate the basis for extended IV antibiotics to treat complex musculoskeletal infections, and to consider a greater role for oral antibiotics for such infections. Further study of this question focused on patients with retained hardware is warranted.
Daniel P. Leas, MD is a PGY-5 orthopaedic resident at Carolinas Medical Center.
Joseph R. Hsu, MD is a Professor of Orthopaedic Trauma and Vice Chair of Quality at the Atrium Health Musculoskeletal Institute.
Surgical Infection Prevention: Local Antibiotic Powders Beat IV Agents in Rats
When it comes to preventing infections associated with orthopaedic procedures, the question of which antibiotic to use is only one of several concerns. How and where to administer antibiotics is another relevant question, not only in terms of infection-fighting effectiveness but also in terms of combatting the proliferation of antibiotic-resistant microbes.
In the September 19, 2018 issue of The Journal of Bone & Joint Surgery, Sweet et al. report on findings from a study in rats that compared the infection-prevention efficacy of intravenous (IV) cefazolin (n = 20) and IV vancomycin (n = 20) with local application of 4 antimicrobials—vancomycin powder (n = 20), cefazolin powder (n = 20), tobramycin powder (n = 20), and dilute Betadine lavage (n = 20).
The researchers induced infection by surgically implanting a polytetrafluoroethylene vascular graft near each rat’s thoracic spine and inoculating it with methicillin-sensitive Staphylococcus aureus (MSSA). After 7 days, all of the rats in each of the IV cefazolin, IV vancomycin, and Betadine lavage groups had grossly positive cultures for MSSA, “with bacterial colonies too numerous to count.” Ninety percent of the rats in the local cefazolin-powder group also had positive cultures, but the infection rates with vancomycin and tobramycin powder were much lower than those with the other four approaches (p <0.000001).
In addition to the main “disclaimer” about this study (namely, that its findings cannot be extrapolated to clinical practice in humans), the authors caution that “the effect of locally applied antibiotics on the emergence of resistant organisms is unknown,” while citing evidence that systemic administration of antibiotics is “associated with the emergence of resistant organisms at an alarming rate.”
Sweet et al. say they plan to follow up this study with a similar model to investigate the efficacy of local antimicrobials against the more problematic methicillin-resistant Staphylococcus aureus (MRSA)—and they suggest further that “clinical studies should be considered to determine the relative clinical efficacy of local versus systemic antibiotics for surgical infection prophylaxis in humans.”
Use Data, Guidelines, and Intuition to Manage Infection after Toe/Forefoot Amputation
The number of articles published each year in orthopaedics that evaluate infections seems to approach, if not exceed, 1,000. Yet, despite all of these publications, consensus statements, and guidelines, we seem to have very few concrete recommendations about which every surgeon will say, “This is what needs to be done.” So we send out samples, run cultures, sonicate implants, and sometimes even perform DNA sequencing, and then we mix the data with selected recommendations and intuition to make our final treatment decisions. Foolproof? No, but it is the best we can do in many situations.
The article by Mijuskovic et al. in the September 5, 2018 edition of The Journal helps simplify this type of decision making in the setting of residual osteomyelitis after toe or forefoot amputation. The authors evaluated 51 consecutive patients with gangrene and/or infection who underwent either digit or partial foot amputations. They found that, after surgery, 41% of the patients without histological evidence of osteomyelitis (which the authors considered the reference, “true positive” analysis) had a positive culture from the same sample. In addition, only 12 patients (24%) had both positive histological findings and positive cultures, the criteria set forth by the Infectious Disease Society of America for the definitive diagnosis of osteomyelitis.
As interesting as the main findings of the study are, some of the “minor” results are even more curious. The decision regarding which patients received antibiotics after amputation seemed largely arbitrary, with 10 of the 14 patients who had a positive histological result not receiving any postoperative antibiotics. (Five of those patients ended up needing a secondary procedure.) In addition, because of the need for decalcification prior to analysis, the median time to receiving histological results was almost a week. Based on the findings in this study, in many instances patients are sent home or to a rehabilitation facility with antibiotics based only on the results of a potentially “false-positive” culture.
The authors conclude that their results “cast doubt on the strategy of relying solely on culture of bone biopsy specimens when deciding whether antibiotic treatment for osteomyelitis is necessary after toe or forefoot amputation.” But this paper also highlights the fact that we are still looking for definitive answers about which data to use and which to disregard when it comes to the detection and treatment of post-amputation osteomyelitis. We surgeons decide on which side to err, and we need to appreciate all three facets—data, guidelines, and patient factors—when discussing treatment options with patients.
Chad A. Krueger, MD
JBJS Deputy Editor for Social Media
What’s New in Musculoskeletal Infection
Every month, JBJS publishes a Specialty Update—a review of the most pertinent and impactful studies published in the orthopaedic literature during the previous year in 13 subspecialties. Click here for a collection of all OrthoBuzz Specialty Update summaries.
This month, Arvind Nana, MD, co-author of the July 19, 2017 Specialty Update on musculoskeletal infection, selected the five most compelling findings from among the more than 120 studies cited in the Specialty Update.
Periprosthetic Joint Infection
–Much of the discussion around treating periprosthetic joint infections (PJIs) centers around comparing one-stage versus two-stage exchange arthroplasty. Two-stage exchange arthroplasty requires the use of a temporary cement spacer, and one study1 found that debris from articulating spacers may induce CD3, CD20, CD11(c), and IL-17 changes, raising the possibility of associated immune modulation.
–When performing debridement to treat a PJI, instead of an irrigation solution containing antibiotics, a 20-minute antiseptic soak with 0.19% vol/vol acetic acid reduced the risk of reinfection.2
Spine
–Four studies helped bolster evidence that surgical-site infections are the leading cause of reoperations after spine surgery, both early (within 30 days)3, 4 and late (after 2 years).5, 6
Trauma
–A 100-patient prospective cohort study found that posttraumatic osteomyelitis treated with a 1-stage protocol and host optimization in Type B hosts resulted in 96% infection-free outcomes.7
Shoulder
–As in lower-extremity procedures, the risk of infection after shoulder arthroplasty and arthroscopy is higher when the surgeries are performed less than 3 months after a corticosteroid injection. This finding suggests elective shoulder procedures should be delayed for at least 90 days after such injections.8
References
- Singh G, Deutloff N, Maertens N, Meyer H, Awiszus F, Feuerstein B, Roessner A, Lohmann CH. Articulating polymethylmethacrylate (PMMA) spacers may have an immunomodulating effect on synovial tissue. Bone Joint J. 2016 ;98-B(8):1062–8.
- Williams RL, Ayre WN, Khan WS, Mehta A, Morgan-Jones R. Acetic acid as part of a debridement protocol during revision total knee arthroplasty. J Arthroplasty. 2017 ;32(3):953–7. Epub 2016 Sep 28.
- Medvedev G, Wang C, Cyriac M, Amdur R, O’Brien J. Complications, readmissions, and reoperations in posterior cervical fusion. Spine (Phila Pa 1976). 2016 ;41(19):1477–83.
- Hijas-Gómez AI, Egea-Gámez RM, Martínez-Martín J, González-Díaz RC, Losada-Viñas JI, Rodríguez-Caravaca G. Surgical wound infection rates and risk factors in spinal fusion in a university teaching hospital in Madrid, Spain. Spine. November 2016.
- Ohya J, Chikuda H, Takeshi O, Kato S, Matsui H, Horiguchi H, Tanaka S, Yasunaga H. Seasonal variations in the risk of reoperation for surgical site infection following elective spinal fusion surgery: a retrospective study using the Japanese diagnosis procedure combination database. Spine (Phila Pa 1976). 2016 . Epub 2016 Nov 22.
- Ahmed SI, Bastrom TP, Yaszay B, Newton PO; Harms Study Group. 5-year reoperation risk and causes for revision after idiopathic scoliosis surgery. Spine (Phila Pa 1976). 2016 . Epub 2016 Nov 9.
- McNally MA, Ferguson JY, Lau ACK, Diefenbeck M, Scarborough M, Ramsden AJ, Atkins BL. Single-stage treatment of chronic osteomyelitis with a new absorbable, gentamicin-loaded, calcium sulphate/hydroxyapatite biocomposite: a prospective series of 100 cases. Bone Joint J. 2016 ;98-B(9):1289–96.
- Werner BC, Cancienne JM, Burrus MT, Griffin JW, Gwathmey FW, Brockmeier SF. The timing of elective shoulder surgery after shoulder injection affects postoperative infection risk in Medicare patients. J Shoulder Elbow Surg. 2016 ;25(3):390–7. Epub 2015 Nov 30.
What’s New in Musculoskeletal Infection: Update on Biofilms
Every month, JBJS publishes a Specialty Update—a review of the most pertinent and impactful studies published in the orthopaedic literature during the previous year in 13 subspecialties. Click here for a collection of all OrthoBuzz Specialty Update summaries.
This month, Arvind Nana, MD, co-author of the July 20, 2016 Specialty Update on musculoskeletal infection, selected the three most compelling discoveries from among the more than 100 studies cited in the Specialty Update, which focused on biofilms.
Dr. Nana and his co-authors provide a concise primer on the biology of biofilms, the network of microorganisms that adhere to implant surfaces and form a complex structure surrounded by a self-generated extracellular polymeric matrix. This matrix not only anchors bacteria to orthopaedic implants, but also provides a nearly impenetrable defense mechanism against the host immune system. Staphylococci are the most common biofilm-forming bacteria found in orthopaedics.
Persister Cells in Biofilms
So-called persister cells have an inherent tolerance to antimicrobial agents. Misconceptions about persisters have permeated the literature. The authors provide clarification about persisters:
- Persister cells CAN be reliably killed when the antimicrobial concentration is high enough. The minimum biofilm eradication concentration (MBEC) is lower when antimicrobial exposure is continuous and prolonged.1
- Decreasing the number of microorganisms with antimicrobial intervention is NOT good enough. Cure requires the total elimination of all viable microbes.
Biofilm in Orthopaedic Trauma
Biofilm formation in the setting of open fractures is concerning because biofilm can develop on bone and in soft tissues in a matter of hours. The assumption is that appropriate surgical techniques for open fractures, including therapeutic antibiotic administration, can decrease bioburden and provide fracture stability, thus modulating the acute, local inflammatory response and minimizing biofilm formation.2 However, current technology does not enable noninvasive quantification of biofilm activity and presence in a stable open fracture following wound closure.
Biofilm in Total Joint Arthroplasty
Traditionally, prosthesis-related biofilm infections in the US have been treated by a 2-stage exchange arthroplasty. Although biofilm from the implant is removed by extraction of the components, the potential exists for persistence of biofilm in the surrounding soft tissues. Most patients treated for periprosthetic joint infections also receive intravenous antibiotics, but a recent in vitro study demonstrated that administering cefazolin even at increased concentrations still resulted in persistent Staphylococcus biofilm on cobalt-chromium, polymethylmethacrylate, and polyethylene,3 which supports the need for explantation.
There is still room to develop novel treatment methods for eradicating biofilm in periprosthetic joint infections. Future novel treatment methods for eradicating implant biofilm will help minimize the morbidity associated with current accepted periprosthetic joint infection treatment options.
References
- Castaneda P, McLaren A, Tavaziva G, Overstreet D. Biofilm antimicrobial susceptibility increases with antimicrobial exposure time. Clin Orthop Relat Res. 2016 Jan 21.
- Pfeifer R, Darwiche S, Kohut L, Billiar TR, Pape HC. Cumulative effects of bone and soft tissue injury on systemic inflammation: a pilot study. Clin Orthop Relat Res. 2013 Sep;471(9):2815-21.
- Urish KL, DeMuth PW, Kwan BW, Craft DW, Ma D, Haider H, Tuan RS, Wood TK, Davis CM 3rd..Antibiotic-tolerant Staphylococcus aureus biofilm persists on arthroplasty materials. Clin Orthop Relat Res.2016 Feb 1.
What’s New in Orthopaedic Trauma
Every month, JBJS publishes a Specialty Update—a review of the most pertinent and impactful studies published in the orthopaedic literature during the previous year in 13 subspecialties. Click here for a collection of all OrthoBuzz Specialty Update summaries.
This month, David Teague, MD, co-author of the July 7, 2016 Specialty Update on orthopaedic trauma, selected the eight most clinically compelling findings from among the 35 studies summarized in the Specialty Update.
Shoulder
–The randomized PROFHER trial found that surgical treatment of acute displaced proximal humeral fractures (with either ORIF or hemiarthroplasty) yielded no difference in patient outcomes compared with nonsurgical sling treatment at time points up to 2 years. Surgery was also significantly more expensive.1
Wrist
–A randomized trial of 461 patients with an acute dorsally displaced distal radial fracture found no difference at one year in primary or secondary outcomes between a group that received ORIF and a group that received Kirschner-wire fixation. K-wire fixation was also more cost-effective.2
Tibia
–A retrospective study of 137 type-III open tibial fractures concluded that both antibiotic prophylaxis and definitive wound coverage should occur as soon as possible for severe open tibial fractures. Prehospital antibiotic administration should be considered when transport is expected to take longer than one hour. 3
Ankle
–A randomized trial of 214 patients who received either supervised physical therapy or engaged in self-directed home exercise after six weeks of immobilization treatment for an ankle fracture found no difference in activity and quality-of-life outcomes at 1, 3, and 6 months.4
Managing Thromboembolism
–A registry study examining the incidence of deep venous thrombosis (DVT)/pulmonary embolism (PE) after surgery for a fracture distal to the knee identified the following risk factors for a thromboembolic event: previous DVT or PE, oral contraceptive use, and obesity.
Wound Care
–A randomized controlled trial of 2,447 patients compared irrigation with normal saline solution at various pressures to castile soap irrigation. Saline was superior in terms of reoperation rates after 12 months but irrigation pressure did not influence the reoperation rate.5
–A retrospective cohort study involving 104 patients who required a fasciotomy found that hospital stays were shorter among patients who underwent delayed primary closure (DPC) or a split-thickness skin graft on the first post-fasciotomy surgery. The authors noted limited utility of repeat surgeries to achieve DPT if fasciotomy wounds were not closed primarily on the first return trip.6
Obesity
–A prospective observational study of 376 trauma patients requiring orthopaedic surgery found that those with a BMI of >30 kg/m2 had an overall complication rate of 38% and had longer hospital stays, longer delays to definitive fixation, and higher infection rates than nonobese patients.7
References
- Rangan A, Handoll H, Brealey S, Jefferson L, Keding A, Martin BC, Goodchild L, Chuang LH, Hewitt C,Torgerson D; PROFHER Trial Collaborators. Surgical vs nonsurgical treatment of adults with displaced fractures of the proximal humerus: the PROFHER randomized clinical trial. JAMA. 2015 Mar 10;313(10):1037-47.
- Costa ML, Achten J, Plant C, Parsons NR, Rangan A, Tubeuf S, Yu G, Lamb SEUK. UK DRAFFT: a randomised controlled trial of percutaneous fixation with Kirschner wires versus volar locking-plate fixation in the treatment of adult patients with a dorsally displaced fracture of the distal radius. Health Technol Assess.2015 Feb;19(17):1-124: v-vi
- Lack WD, Karunakar MA, Angerame MR, Seymour RB, Sims S, Kellam JF, Bosse MJ. Type III open tibia fractures: immediate antibiotic prophylaxis minimizes infection. J Orthop Trauma. 2015 Jan;29(1):1-6.
- Moseley AM, Beckenkamp PR, Haas M, Herbert RD, Lin CW; EXACT Team. Rehabilitation after immobilization for ankle fracture: the EXACT randomized clinical trial. JAMA. 2015 Oct 6;314(13):1376-85.
- Bhandari M, Jeray KJ, Petrisor BA, Devereaux PJ, Heels-Ansdell D, Schemitsch EH, Anglen J, Della RoccaGJ, Jones C, Kreder H, Liew S, McKay P, Papp S, Sancheti P, Sprague S, Stone TB, Sun X, Tanner SL,Tornetta P 3rd., Tufescu T, Walter S, Guyatt GH; FLOW Investigators. A trial of wound irrigation in the initial management of open fracture wounds. N Engl J Med. 2015 Dec 31;373(27):2629-41. Epub 2015 Oct 8.
- Weaver MJ, Owen TM, Morgan JH, Harris MB. Delayed primary closure of fasciotomy incisions in the lower leg: do we need to change our strategy? J Orthop Trauma. 2015 Jul;29(7):308-11.
- Childs BR, Nahm NJ, Dolenc AJ, Vallier HA. Obesity is associated with more complications and longer hospital stays after orthopaedic trauma. J Orthop Trauma. 2015 Nov;29(11):504-9.
“Smart” Implant Coating Delivers Antibiotics in Presence of Bacteria
Despite advances in sterile techniques and evidence-based use of perioperative antibiotics, periprosthetic joint infections still occur in 1% of primary and 3% to 7% of revision total joint arthroplasties. But a “smart” antimicrobial polymer coating, described in the July 20, 2016 Journal of Bone & Joint Surgery, has great potential to cut those percentages.
Stavrakis et al. devised a nontoxic, biodegradable polymer coating (called PEG-PPS for short) that locally delivers antibiotics (vancomycin and tigecycline in this study) both passively and actively, with the active release initiated by the presence of bacteria.
The authors tested the efficacy of the coating both in vitro and in vivo. In vitro, the release of antibiotics from the coating was enhanced in the presence of an oxidative environment, as would occur during a periprosthetic joint infection, demonstrating the coating’s “smartness.”
In vivo, using a mouse model of post-arthroplasty infection caused by Staphylococcus aureus, the authors showed radiographically that implants coated with PEG-PPS alone had a dramatic degree of periprosthetic osteolysis by postoperative day 7, compared with antibiotic-encapsulated PEG-PPS implants, which showed no detectable osteolysis. Similarly, the number of colony forming units of S. aureus cultured from implants on postoperative day 21 was significantly lower in the antibiotic-encapsulated implants than in the PEG-PPS-alone implants. (Interestingly, the tigecycline coating was more effective than the vancomycin coating in preventing bacterial colonization.)
While acknowledging that this proof-of-concept study needs to be replicated with other infectious organisms and in larger animals and humans, the authors conclude that PEG-PPS delivery of antibiotics has “great potential to minimize the incidence of postoperative infection following arthroplasty.”
JBJS Webinar: How to Prevent and Treat MSK Infections
Musculoskeletal (MSK) infections are highly prevalent and potentially serious, and orthopaedists are frequently faced with preventing and treating them. Wherever or however they are acquired, these pathogen-based conditions are among the most challenging to address effectively.
On Monday, May 23, 2016 at 8:00 pm EDT, The Journal of Bone & Joint Surgery will present a complimentary webinar that includes findings from two recent JBJS studies that explore how best to prevent deep infections in lower-grade open fractures, and the most effective antibiotics for treating community-acquired hand infections.
Richard Jenkinson, MD will discuss findings from a cohort study that compared deep infection rates in patients with lower-grade open fractures who were treated with either immediate wound closure or delayed wound closure. Rick Tosti, MD will examine resistance patterns of specific antibiotics to MRSA infections of the hand in an urban population.
Moderated by musculoskeletal-infection expert Jonathan Schoenecker, MD, PhD, the webinar will also feature commentaries on the studies by Lawrence Marsh, MD and Isaac Thomsen, MD.
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