The prompt administration of prophylactic antibiotics is considered a critical component of open-fracture management. In 2011, the Eastern Association for the Surgery of Trauma (EAST) recommended updates to traditional antibiotic administration, including gram-positive coverage for Gustilo Type-I and Type-II fractures, the addition of gram-negative coverage for Type-III, and additional penicillin for the presence of fecal or clostridial contamination. Concerns regarding the side effects of antibiotics, along with changing patterns in bacteria resistance, have led many treating physicians to consider alternative antibiotic choices.
In a recent JBJS article, Lin et al. report on the level of adherence to open-fracture antibiotic guidelines (both traditional and EAST recommendations), analyzing data collected as part of 2 large, ongoing, multicenter trials. They also evaluated the association of Gustilo type, wound contamination, and multifracture injuries with antibiotic choice and duration.
Included were 1,234 patients from 24 medical centers in the US and Canada, all of whom received antibiotics on the day of admission. While cefazolin monotherapy was the most commonly prescribed regimen (53.6%), 54 different combinations of prophylactic antibiotics were prescribed. Lin et al. found moderate adherence to traditional antibiotic treatment guidelines for Gustilo Types-I and II fractures and low adherence for Type-III, and less-than-optimal compliance with the EAST recommendations: 31% of Gustilo Type-I and Type-II fractures received gram-negative coverage, and 54.9% of Type-III fractures did not.
The authors offer many plausible reasons for low compliance, including increased incidence of methicillin-resistant S. aureus infections, concerns regarding the nephrotoxicity of aminoglycosides, and the more frequent use of intraoperative topical antibiotics.
The median duration of antibiotic use following wound closure in this study was 2 days. The authors note that the most widely recommended duration in the literature is 3 days after wound closure, which they add, contradicts the <24 hours recommended by the EAST guidelines (for Type-III fractures, discontinuation within 72 hours post-injury or 24 hours after soft-tissue coverage).
The study provides helpful insight into the sometimes contradictory and confusing guidelines for open-fracture antibiotic prophylaxis and the variations that exist in current practice patterns. It also begs the question: is it time for a stringent new look at the guidelines and more high-quality research into which practices help ensure the best patient outcomes and the most sensible antibiotic stewardship?
Matthew R. Schmitz, MD
JBJS Deputy Editor for Social Media
Under one name or another, The Journal of Bone & Joint Surgery has published quality orthopaedic content spanning three centuries. In 1919, our publication was called the Journal of Orthopaedic Surgery, and the first volume of that journal was Volume 1 of what we know today as JBJS.
Thus, the 24 issues we turn out in 2018 will constitute our 100th volume. To help celebrate this milestone, throughout the year we will be spotlighting 100 of the most influential JBJS articles on OrthoBuzz, making the original content openly accessible for a limited time.
Unlike the scientific rigor of Journal content, the selection of this list was not entirely scientific. About half we picked from “JBJS Classics,” which were chosen previously by current and past JBJS Editors-in-Chief and Deputy Editors. We also selected JBJS articles that have been cited more than 1,000 times in other publications, according to Google Scholar search results. Finally, we considered “activity” on the Web of Science and The Journal’s websites.
We hope you enjoy and benefit from reading these groundbreaking articles from JBJS, as we mark our 100th volume. Here are two more:
Prevention of Infection in Treatment of 1,025 Open Fractures of Long Bones
R B Gustilo and J T Anderson: JBJS, 1976 June; 58 (4): 453
While “best practices” for managing open long-bone fractures have changed since this landmark study was published, the Gustilo-Anderson classification still correlates well with the risk of infection in patients with comorbid medical illnesses and other complications. It remains widely accepted for research and training purposes, and it provides commonly used basic language for communicating about open fractures.
Rates and Outcomes of Primary and Revision Total Hip Replacement in the US Medicare Population
N N Mahomed, J A Barrett, J N Katz, C B Phillips, E Losina, R A Lew, E Guadagnoli, W H Harris, R Poss, J A Baron: JBJS, 2003 January; 85 (1): 27
Analyzing Medicare claims data between July 1, 1995 and June 30, 1996, the authors of this prognostic study claimed it was “the first population-based study of the rates of revision total hip replacement and its short-term outcomes.” In the last 10 years alone, more than 5,000 studies on revision THA have been published in PubMed-indexed journals, including this 2012 JBJS study, which examined THA revision risk in the same Medicare cohort over 12 years.
Basic science investigations into clinically relevant orthopaedic conditions are very common—and often very fruitful. What’s not very common is seeing results from large, multicenter randomized trials published in the same time frame as high-quality in vivo basic-science research on the same clinical topic.
But the uncommon has occurred. In the November 1, 2017 issue of The Journal, Chiaramonti et al. present research on the effects of 20-psi pulsatile lavage versus 1-psi bulb-syringe irrigation on soft tissue in a rat model of blast injuries. With support from the US Department of Defense, Chiaramonti et al. developed an elegant animal study that found radiological and histological evidence that lavage under pressure—previously thought to be critical to removing contamination in high-energy open fractures—results in muscle necrosis and wound complications.
Although none of the rats developed heterotopic ossification during the 6-month study period, the authors plausibly suggest that the muscle injury and dystrophic calcification they revealed “may potentiate the formation of heterotopic ossification by creating a favorable local environment.” Heterotopic ossification is an unfortunately common sequela in patients who suffer blast-related limb amputations.
The aforementioned rare alignment between basic-research findings and clinical findings in people relates to a large multicenter randomized clinical trial recently published in The New England Journal of Medicine. That study found that one-year reoperation rates among nearly 2,500 patients treated surgically for open-fracture wounds were similar whether high, low, or very low irrigation pressures were used. This is a case where the clinical advice from basic-study authors Chiaramonti et al. to keep “delivery device irrigation pressure below the 15 to 20-psi range” when managing open fractures is based on very solid ground.
Marc Swiontkowski, MD
Injuries to the musculoskeletal system are among the most common wounds of war. Compared with extremity injuries in the civilian population, injuries sustained in combat tend to be due to high-energy explosions and are associated with a greater degree of contamination and a longer timeline for recovery and healing. Importantly, the sequelae of musculoskeletal injuries sustained during combat tend to lead to more long-term disability than those affecting other organ systems.
In this month’s Editor’s Choice article, Rivera et al. review the current literature on combat injuries of the lower extremity and suggest that explosions are the most common mechanism of injury encountered by deployed service members. While exposure to an explosion does not necessarily result in a specific limb injury, the explosion mechanism does contribute to more severe injuries. Moreover, among service members who sustain open fractures of the tibia, foot, and ankle, infection is a common complication and is associated with more severe soft-tissue injury. As a result, surgeons who are deployed in combat settings are now performing more fasciotomies for limbs that are at risk. However, the outcomes and complication rates associated with these procedures are not well established, and the causes of late amputations are not always clear.
As part of a comprehensive review of this topic, Rivera et al. pose 3 important clinical questions that are ideal for translational research investigation. First, they ask, “What is the best way to manage and transport patients who have severe open fractures in order to minimize infection?” Indeed, while negative-pressure wound therapy (NPWT) appears to be a promising wound-care technique, additional study is needed in order to know how to best augment the standard of care for battlefield medicine. Second, “What is the best way to treat fasciotomy wounds and the late sequelae of the compartment syndrome?” In order to answer this question, a broader understanding of compartment syndrome detection and the indications for surgical treatment are needed. Finally, “What is the best way to select limbs for salvage and to optimize the reconstruction of injured tissues?” This question must explore not only the patient’s perspective but also the multitude of causes that lead to late amputation.
Thomas A. Einhorn, MD
Editor, JBJS Reviews
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.
–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
–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
–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
–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
–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.
–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
–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
- 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.
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.
OrthoBuzz regularly brings you a current commentary on a “classic” article from The Journal of Bone & Joint Surgery. These articles have been selected by the Editor-in-Chief and Deputy Editors of The Journal because of their long-standing significance to the orthopaedic community and the many citations they receive in the literature. Our OrthoBuzz commentators highlight the impact that these JBJS articles have had on the practice of orthopaedics. Please feel free to join the conversation about these classics by clicking on the “Leave a Comment” button in the box to the left.
From the time of Hippocrates until after the American Civil War, open fractures and other wounds prone to sepsis were fatal injuries in approximately 50% of patients, and amputation of the affected limb was recognized as lifesaving treatment. With the adoption of antisepsis and formal surgical débridement in the late 19th century, improved stabilization techniques in the 20th century, and the introduction of antibiotics, death as an outcome was virtually eliminated, but nonunion with or without infection remained challenging complications.
In the 1960s, reports concluding that in open fracture care “prophylactic antibiotics were of questionable value” created great debate and controversy among surgeons. The pioneering 1974 JBJS study by Patzakis et al., titled “The Role of Antibiotics in the Management of Open Fractures,” addressed this controversy by asking and answering three key questions:
- Is antibiotic prophylaxis worthwhile in open fractures?
- Which organisms cause the infections?
- Which antibiotics are effective?
The study demonstrated that nearly two-thirds of wounds caused by direct injury and an even higher rate of gunshot wounds were contaminated. That finding, along with the fact that several days must elapse before a culture can be considered truly sterile, makes true “prophylaxis” in open fractures practicable only if antibiotics are applied to all patients. Patzakis et al. also stressed that antibiotic treatment is not a substitute for the critically important practice of extensive surgical debridement of all devitalized tissue. Urgent surgical irrigation and debridement remain the mainstay of infection eradication, although questions persist regarding the optimal irrigation solution, volume, and delivery pressure.
I agree with the authors of this classic article that the term “prophylaxis” is not appropriate because these wounds should presumptively be considered contaminated and treated with effective antibiotics. Wound sampling has a poor predictive value in determining subsequent infections, so a first-generation cephalosporin should be administered as soon as possible, with or without coverage for gram-negative bacteria. In addition, as Lawing et al. found in a 2015 JBJS study, local aqueous aminoglycoside administration as an adjunct to systemic antibiotics may be effective in lowering infection rates in open fractures.
This classic prospective study by Patzakis et al. in the 1970s has prompted us to ask and pursue answers to many more clinical questions regarding open-fracture infections. For example, the optimal duration of antibiotic administration has not been well defined, but they should be continued for more than 24 hours. The evidence to support either extending the duration or broadening the antibiotic protocol for Gustilo type III wounds remains inconclusive, and more investigation into this question with higher-level research methods is needed.
Konstantinos Malizos, MD, PhD
JBJS Deputy Editor
In the November 18, 2015 edition of JBJS, Lawing et al. present a well-documented cohort study comparing the outcomes of open-fracture management with local administration of aminoglycoside antibiotics plus systemic antibiotics, versus systemic antibiotics alone. The impact of this intervention on the ultimate rate of deep infection is eye-catching. The deep-infection rate in the local-antibiotic group was 6%, compared to 14.2% in the control group (p = 0.011). Moreover, locally administered aminoglycosides did not have a negative impact on nonunion rates, as one might expect due to the osteocyte toxicity reportedly associated with some aminoglycosides.
There are, however, issues of administrator bias with this study, because the use of local antibiotics was based on attending-surgeon preference. In addition, surgeons make other individual judgments about open-fracture management, such as debridement technique, that were not controlled for in this study. We also went through a period of using local antibiotic drips and catheter pumps in the 1990s that did not seem to yield reproducible results.
Lawing et al. conclude with the hope that their study “will provide support for future prospective, blinded, and randomized trials” focused on this intervention. I believe the data here are compelling enough for one of our trauma clinical-trials networks to plan and conduct an adequately powered trial complete with prospective criteria and blinded outcome adjudication. One reason we publish cohort studies in The Journal is to stimulate just that sort of response in the orthopaedic-research community. It is my hope that within a few years, JBJS editors will be reviewing an RCT manuscript that completes the investigative cycle on this important clinical question.
Marc Swiontkowski, MD
Irrigation and debridement of open fractures have been standard practices since the late 1800s. However, the finer details have not been agreed upon. For example, should we use higher pressures with pulsatile lavage devices? And will adding soap to standard saline irrigation solution get better results? Answers to those two questions from lab and animal studies over the years have been limited and contradictory. The goal of the recently reported FLOW study (Fluid Lavage of Open Wounds) was to answer those questions definitively.
Initially, a pilot study with just over 100 patients suggested that using soap might yield fewer adverse events requiring a return to the OR. Little difference was noted between high and low pressures using a pulsatile lavage device. Most importantly, the pilot showed that a definitive study was feasible.
FLOW investigators, of which I was one, then began pursuing a multicenter, international, randomized, controlled study to evaluate the effects of irrigation pressure and solutions on open fractures. The US Department of Defense (DoD), the Canadian Institutes of Health Research, and others supported us in the definitive trial. From what we learned in the pilot study and from DoD input, we added a third arm to the pressure investigation and included gravity flow, which is essentially a bag of fluid run through quarter-inch tubing into the wound.
We collected data for five years from 2,447 patients at 41 sites worldwide and achieved a 90% 12-month follow-up. The results demonstrated that reoperation rates for the three different pressures were similar. But unlike the size-limited data from the pilot study, using soap in the irrigation solution resulted in a significantly higher reoperation rate than normal saline.
This second finding should convince us that saline is the irrigation solution of choice and that by avoiding soap, adverse outcomes can be diminished and costs lowered for institutions. The discrepancy between the soap findings in the pilot data and the full study may simply reflect the need for larger numbers. Intuitively, we might think that soap, which we use all the time for hand-washing, would be better because it helps remove debris and bacteria. However, the FLOW findings suggest that soap may have a negative impact on soft tissues and bone, making reoperation rates significantly higher. In regard to pressures, the use of a pulsatile lavage with high or low pressures offered no apparent benefit compared to irrigation with gravity flow. This should allow sites to avoid the cost of using pulsatile lavage devices.
Taken together, these findings should reassure institutions worldwide that do not have access to soap or pulsatile lavage devices that their wound-irrigation practices are not compromised and may indeed be the standard of care based on the FLOW data.
Kyle Jeray, MD
Greenville Health System
Vice-Chairman of Academics, Department of Orthopaedic Surgery
JBJS Associate Editor
Most surgeons believe that an open fracture of an extremity is an indication for antibiotic prophylaxis. However, few are familiar with the evidence to support this practice, and the optimum duration of treatment is unknown. In the June 2015 issue of JBJS Reviews, Chang et al. report the results of a systematic review of randomized controlled trials to help shed light on this question. The investigators performed a review of different antibiotic regimens, including antibiotic prophylaxis versus no prophylaxis, longer versus shorter durations of treatment, and the use of alternative drugs.
Using systematic review and meta-analysis methodology, the investigators identified 329 potentially eligible articles, of which seventeen were found to be eligible for inclusion in the analysis. Four randomized controlled trials that involved 472 patients demonstrated significantly lower rates of infection in patients who received antibiotic prophylaxis compared with those who did not receive antibiotic prophylaxis. Three studies involving 1104 patients demonstrated no difference in the infection rate when a longer duration of antibiotic prophylaxis was compared with a shorter duration (three to five days versus one day).
However, confidence in the estimates for both of these questions was low to moderate, and individual comparisons of alternate drugs yielded only low to very low confidence. The investigators concluded that the results of randomized controlled trials performed to date provide evidence that antibiotic prophylaxis reduces infection and that treatment for as short as one day is as effective as treatment for three to five days. Although the evidence warrants only low to moderate confidence, these findings provide support for the design and execution of a large, multicenter, randomized controlled trial to address the question of how antibiotics may be best used in the treatment of open extremity fractures.
Thomas A. Einhorn, MD
Editor, JBJS Reviews