|Year : 2019 | Volume
| Issue : 3 | Page : 110-112
Infection prevention for open fractures: Is antibiotic monotherapy equivalent to multitherapy?
Andrew C Miller1, Stanislaw P Stawicki2
1 Department of Emergency Medicine, East Carolina University Brody School of Medicine, Greenville, North Carolina, USA
2 Department of Research and Innovation, St. Luke's University Health Network, Bethlehem, Pennsylvania, USA
|Date of Web Publication||30-Sep-2019|
Dr. Andrew C Miller
Department of Emergency Medicine, East Carolina University Brody School of Medicine, 600 Moye Blvd, Mailstop 625, Greenville, North Carolina 27834
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Miller AC, Stawicki SP. Infection prevention for open fractures: Is antibiotic monotherapy equivalent to multitherapy?. Int J Crit Illn Inj Sci 2019;9:110-2
|How to cite this URL:|
Miller AC, Stawicki SP. Infection prevention for open fractures: Is antibiotic monotherapy equivalent to multitherapy?. Int J Crit Illn Inj Sci [serial online] 2019 [cited 2020 Jan 18];9:110-2. Available from: http://www.ijciis.org/text.asp?2019/9/3/110/268355
Open extremity fractures (OEFx) continue to exact a disproportionately heavy toll on trauma victims across the world. Among the populations most susceptible to the most severe sequelae of OEFx – such as severe infection, compartment syndrome, disability, amputation, and mortality – are patients from vulnerable populations, limited-resource environments, and disaster-stricken regions.,,,,,,, Given the critical nature of early recognition, timely and appropriate antimicrobial therapy, and prompt surgical treatment of OEFx, various national and international organizations advocate for protocolized, multidisciplinary, evidence-based approaches aimed at improving clinical outcomes for the affected patients.,,,, Within this broader context, the research continues into the most optimal approaches toward antibiotic prophylaxis for patients with OEFx , – the focus of both our Editorial and the Original Article by Depcinski et al. in the current issue of the International Journal of Critical Illness and Injury Science (IJCIIS).
The Gustilo and Anderson classification is the most widely used classification for OEFx. They categorized open injuries into three categories: based on wound size, contamination level, and osseous damage as follows: (i) wound ≤1 cm, minimal contamination or muscle damage; (ii) wound 1–10 cm, moderate soft-tissue injury (without extensive soft-tissue damage, flaps, or avulsions); (iiia) wound usually >10 cm, high energy, extensive soft-tissue damage, contaminated, adequate tissue for flap coverage, and farm injuries; (iiib) extensive periosteal stripping, wound requires soft-tissue coverage (rotational or free flap); and (iiic) vascular injury requiring vascular repair, regardless of degree of soft-tissue injury. The incidence of wound infection correlates directly with the grade of fracture: type I (0%–2%); Type II (2%–7%); Type IIIA (7%); Type IIIB (10%–50%); and Type IIIC (25%–50%). Infection rates for OEFx involving the hand and upper extremity are lower compared with those of the lower extremity.
The theoretical basis for the effective antibiotic prophylactic in the setting of OEFx was established in the late 1950s., The use of antibiotics has been a standard management tool to either prevent or treat infection of OEFx; however, based on the existing practice guidelines and clinical trials, the optimal antibiotic prophylaxis for Type III open fractures remains uncertain. Experts propose preoperative prophylactic antibiotics for OEFx to be started “as soon as possible after injury., Initiating antibiotic prophylaxis within 1 h  or even 3 h  of injury has been shown to reduce infection rates. Furthermore, the participation of a pharmacist during the initial trauma resuscitation may further improve door-to-antibiotic administration times.
Regarding the duration of therapy, the guidelines make a Level III recommendation for antibiotics to be discontinued 24 h after wound closure for Grade I and II fractures. For Grade III fractures, the guidelines recommend antibiotics to be continued for the earliest of either 72 h after the time of injury or 24 h after soft-tissue coverage of the wound. This is based on the evidence showing that shorter antibiotic regimens (<72 h) were equivalent to longer regimens (<72 h) in preventing infection.,,
Although narrow-spectrum antimicrobial prophylaxis is recommended by the evidence-based guidelines, many trauma centers use broad-spectrum antibiotics. There is substantial morbidity related to the use of broad-spectrum antibiotics in the OEFx population, including potential acute kidney injury with the use of aminoglycosides, development of antimicrobial resistance, and superinfections with multidrug-resistant organisms.,,
In this issue of IJCIIS, Depcinski et al. set out to compare the merits of single-agent cefazolin versus cefazolin + gentamycin. Although there are intrinsic limitations to the retrospective approach, and the study was not adequately powered to assess for noninferiority, there are important insights to be gained from their efforts. This has been a controversial topic in recent years. In another study using a retrospective cohort design (n = 167), the authors reported no difference in infection rates between those patients treated with or without the addition of a systemic aminoglycoside. Moreover, in a before and after study (n = 174) where aminoglycosides were removed from the treatment protocol, no difference was observed in per fracture event rate of resistant Gram-positive or Gram-negative organisms or in methicillin-resistant Staphylococcus aureus.
Important to note, however, is that many of the studies did not distinguish between deep and superficial infections. Those that have focused on deep infections have often looked at the addition of locally administered (rather than systemic) aminoglycosides. Several studies have reported lower deep infection rates with locally administered aminoglycosides. Meanwhile, critics of the adding aminoglycosides have argued that a small benefit with expanded Gram-negative coverage may not extend to a decreased risk of osteomyelitis, rates of hardware removal, nonunion rates, and may not outweigh the additional costs in terms of increased antibiotic resistance and adverse effects. Changes in rates of acute kidney injury with addition of an aminoglycoside are controversial, and studies have been conflicting in the findings.,
Despite growing evidence that antibiotic monotherapy may be similarly efficacious as multitherapy for preventing infectious complications of OEFx, the data are incomplete. This movement has been largely based on underpowered retrospective studies utilizing varied endpoints. We encourage investigators to move forward to a randomized controlled study design to more definitively clarify this issue.
| References|| |
Saeb M, Yaghoubi M, Bagheri N, Dkabiri SS. Musculoskeletal injuries of the kermanshah earthquake and orthopedic management at trauma center of Kermanshah, West Iran. Trauma Mon 2019;24:e83464.
Rush RM Jr., Arrington ED, Hsu JR. Management of complex extremity injuries: Tourniquets, compartment syndrome detection, fasciotomy, and amputation care. Surg Clin North Am 2012;92:987-1007, ix.
Bertol MJ, Van den Bergh R, Trelles Centurion M, Kenslor Ralph DH, Basimuoneye Kahutsi JP, Qayeum Qasemy A, et al.
Saving life and limb: Limb salvage using external fixation, a multi-centre review of orthopaedic surgical activities in médecins sans frontières. Int Orthop 2014;38:1555-61.
Mock C, MacKenzie E, Jurkovich G, Burgess A, Cushing B, deLateur B, et al.
Determinants of disability after lower extremity fracture. J Trauma 2000;49:1002-11.
Woolf AD, Pfleger B. Burden of major musculoskeletal conditions. Bull World Health Organ 2003;81:646-56.
Ding R, McCarthy ML, Houseknecht E, Ziegfeld S, Knight VM, Korehbandi P, et al.
The health-related quality of life of children with an extremity fracture: A one-year follow-up study. J Pediatr Orthop 2006;26:157-63.
Naghii MR. Public health impact and medical consequences of earthquakes. Rev Panam Salud Publica 2005;18:216-21.
Mock CN, Denno D, Adzotor ES. Paediatric trauma in the rural developing world: Low cost measures to improve outcome. Injury 1993;24:291-6.
Hudak PL, Amadio PC, Bombardier C. Development of an upper extremity outcome measure: The DASH (disabilities of the arm, shoulder and hand) [corrected]. The upper extremity collaborative group (UECG) Am J Ind Med 1996;29:602-8.
WHO Scientific Group on the Burden of Musculoskeletal Conditions at the Start of the New Millennium. The burden of musculoskeletal conditions at the start of the new millennium. World Health Organ Tech Rep Ser 2003;919:i-x, 1-218.
Bach JA, Leskovan JJ, Scharschmidt T, Boulger C, Papadimos TJ, Russell S, et al.
The right team at the right time – Multidisciplinary approach to multi-trauma patient with orthopedic injuries. Int J Crit Illn Inj Sci 2017;7:32-7.
] [Full text]
Depcinski SC, Nguyen KH, Ender PT. Cefazolin and an aminoglycoside compared with cefazolin aline for the antimicrobial prophylaxis of type III open orthopedic fractures. Int J Crit Illn Inj Sci 2019;9:119-23.
Barton CA, McMillian WD, Crookes BA, Osler T, Bartlett CS 3rd
. Compliance with the Eastern association for the surgery of trauma guidelines for prophylactic antibiotics after open extremity fracture. Int J Crit Illn Inj Sci 2012;2:57-62. [Full text]
Gustilo RB, Anderson JT. Prevention of infection in the treatment of one thousand and twenty-five open fractures of long bones: Retrospective and prospective analyses. J Bone Joint Surg Am 1976;58:453-8.
Isaac SM, Woods A, Danial IN, Mourkus H. Antibiotic prophylaxis in adults with open tibial fractures: What is the evidence for duration of administration? A systematic review. J Foot Ankle Surg 2016;55:146-50.
Warrender WJ, Lucasti CJ, Chapman TR, Ilyas AM. Antibiotic management and operative debridement in open fractures of the hand and upper extremity: A systematic review. Hand Clin 2018;34:9-16.
Miles AA, Miles EM, Burke J. The value and duration of defence reactions of the skin to the primary lodgement of bacteria. Br J Exp Pathol 1957;38:79-96.
Burke JF. The effective period of preventive antibiotic action in experimental incisions and dermal lesions. Surgery 1961;50:161-8.
Lack WD, Karunakar MA, Angerame MR, Seymour RB, Sims S, Kellam JF, et al.
Type III open tibia fractures: Immediate antibiotic prophylaxis minimizes infection. J Orthop Trauma 2015;29:1-6.
Harvey S, Brad Hall A, Wilson K. Impact of an emergency medicine pharmacist on initial antibiotic prophylaxis for open fractures in trauma patients. Am J Emerg Med 2018;36:290-3.
Gosselin RA, Roberts I, Gillespie WJ. Antibiotics for preventing infection in open limb fractures. Cochrane Database Syst Rev 2004;1:CD003764.
Messner J, Papakostidis C, Giannoudis PV, Kanakaris NK. Duration of administration of antibiotic agents for open fractures: Meta-analysis of the existing evidence. Surg Infect (Larchmt) 2017;18:854-67.
Dunkel N, Pittet D, Tovmirzaeva L, SuvÁ D, Bernard L, Lew D, et al.
Short duration of antibiotic prophylaxis in open fractures does not enhance risk of subsequent infection. Bone Joint J 2013;95-B: 831-7.
Dellinger EP, Caplan ES, Weaver LD, Wertz MJ, Droppert BM, Hoyt N, et al.
Duration of preventive antibiotic administration for open extremity fractures. Arch Surg 1988;123:333-9.
Hauser CJ, Adams CA Jr. Eachempati SR; Council of the Surgical Infection Society. Surgical infection society guideline: Prophylactic antibiotic use in open fractures: An evidence-based guideline. Surg Infect (Larchmt) 2006;7:379-405.
Rodriguez L, Jung HS, Goulet JA, Cicalo A, Machado-Aranda DA, Napolitano LM, et al.
Evidence-based protocol for prophylactic antibiotics in open fractures: Improved antibiotic stewardship with no increase in infection rates. J Trauma Acute Care Surg 2014;77:400-7.
Gerlach AT, Stawicki SP, Cook CH, Murphy C. Risk factors for aminoglycoside-associated nephrotoxicity in surgical intensive care unit patients. Int J Crit Illn Inj Sci 2011;1:17-21.
] [Full text]
Tessier JM, Moore B, Putty B, Gandhi RR, Duane TM. Prophylactic gentamicin is not associated with acute kidney injury in patients with open fractures. Surg Infect (Larchmt) 2016;17:720-3.
Lawing CR, Lin FC, Dahners LE. Local injection of aminoglycosides for prophylaxis against infection in open fractures. J Bone Joint Surg Am 2015;97:1844-51.
Bankhead-Kendall B, Gutierrez T, Murry J, Holland D, Agrawal V, Almahmoud K, et al.
Antibiotics and open fractures of the lower extremity: Less is more. Eur J Trauma Emerg Surg 2019;45:125-9.
Lloyd BA, Murray CK, Shaikh F, Carson ML, Blyth DM, Schnaubelt ER, et al.
Early infectious outcomes after addition of fluoroquinolone or aminoglycoside to posttrauma antibiotic prophylaxis in combat-related open fracture injuries. J Trauma Acute Care Surg 2017;83:854-61.