Clínical Audit of Primary Treatment of Open Fractures: Antibiotic Treatment and Tetanus Prophylaxis^[*]

Keywords

open fracture - antibiotic prophylaxis - infection - tetanus

Introduction

Open fractures (OFs) are characterized by a communication between the fracture focus and the external environment or contaminated cavities through a soft tissue injury, which favors contamination and impairs healing. As a result, the clinical approach to these fractures is difficult and their prognosis is worse.[1] In major urban centers, OFs are mostly caused by traffic accidents, affecting men from the economically active age group.[2] [3]

There are several classifications for OF according to lesion severity and contamination degree, which affects prognosis and therapeutic choices.[1] Gustilo et al[4] propose a system considering trauma energy, soft tissue injury degree and contamination degree to classify OFs as types I, II and III.[1] [5] Higher classification levels are associated with greater extent, severity, soft tissue involvement and contamination, and, therefore, higher risk of infections.[6]

An antimicrobial treatment, preferably starting in the first hours after OF occurrence, is advocated to minimize the incidence of infectious complications.[5] [7] The intravenous administration of an antibiotic agent has a protective role against infections,[8] and the earlier its institution, the better the outcomes.[9]

The primary treatment of OFs must also include tetanus prophylaxis;[5] [9] although this is a life-threatening infectious disease, tetanus is preventable through immunization. Transmission often occurs by the Clostridium tetani bacillus introduction in puncturing wounds contaminated with soil, dust, animal or human feces. Clinically, the disease presents with neurotoxic symptoms resulting from the action of the bacillus-produced toxin.[10]

At Fundação Hospitalar do Estado de Minas Gerais (FHEMIG, in the Portuguese acronym), the guidelines for initial OF care are established by the Clinical Protocol (CP) “Primary Treatment of Exposed Fractures” (“Tratamento Primário das Fraturas Expostas”). One of the goals of this Protocol is to reduce the incidence of infections.[11] To do so, several approaches were standardized, including the initial treatment of open fractures with antimicrobial agents and tetanus prophylaxis. Both antimicrobial treatment and tetanus prophylaxis must be used rationally to ensure the efficacy and safety of antibiotic drugs and immunobiological products and to improve resources management in patient care.[12]

However, the mere elaboration and publication of protocols are not enough to ensure proper assistance. Strategies are required to assess adherence to agreed behaviors. One of these strategies is a Clinical Audit (CA), a structured process for clinical practice evaluation according to established guidelines, followed by educational measures and implementation of necessary changes.[13]

Thus, the present study, in the form of a CA, aims to evaluate whether the antimicrobial treatment and tetanus prophylaxis in the initial care of patients with open fracture have been performed according to the guidelines established by the CP adopted by the institution.

Methods

The present CA was performed through a descriptive and retrospective study analyzing the initial consultations for OF surgical treatment from June to December 2016 in a state public hospital specialized in urgency and trauma. Both male and female patients, > 18 years old with appendicular skeleton fracture were selected. Patients with hand fractures were excluded because these injuries have their own protocol.

Data were obtained in medical records, medication prescriptions from the Hospital Management System (SIGH, in the Portuguese acronym), reports of patients admitted to the Surgical Department for emergency OF surgery and tetanus prophylaxis requests.

Patients were characterized according to gender, age and origin. The OF was evaluated according to the trauma mechanism, affected limb and the Gustilo classification. Osteomyelitis and soft tissue infection, the infectious complications investigated, were identified through a conclusive medical diagnosis included in the patient records by physicians from the traumatology team.

The initial antimicrobial treatment was evaluated based on the antimicrobial regimen used, doses, prescribed treatment duration, time elapsed between admission and antimicrobial treatment initiation and waiting time for surgery. These data were compared with CP recommendations detailed in [Box 1].

Box 1

ANTIMICROBIAL AGENTS	RECOMMENDATIONS
Starting time	Treatment must start at the preoperative period
Choice of antimicrobial agents	Type I fractures: cefazolin, 1 g IV every 6 hours
	Type II fractures: cefazolin, 1 g IV every 6 hours + gentamycin, 240 mg IV every 24 hours
	Alternative regimen for type I and II fractures: clindamicina 600 mg EV de 6/6 hours + gentamycin, 240 mg IV every 24 hours
	Type III fractures: cefazolin, 1 g IV every 6 hours + gentamycin, 240 mg IV every 24 hours + metronidazole, 500 mg every 6 hours
	For fractures occurring in rural environment and with gross contamination, add metronidazole, 500 mg every 6 hours
Treatment duration	Type I and II: 24 hours
	Type III: 72 hours
TETANUS PROPHYLAXIS	RECOMMENDATIONS
	Evaluate requirement based on the vaccination history of the patient
	In case of doubt regarding previous tetanus prophylaxis: add metronidazole, 500 mg every 6 hours

The indication for tetanus prophylaxis was evaluated according to the vaccination history of the patient detailed at the medical record. In addition, the length of stay for OF initial approach and treatment, as well as the care flow within the hospital network, were investigated.

Frequencies, measures of central tendency and dispersion measures were obtained for statistical analysis. The association between categorical variables was assessed using the Pearson chi-squared test (χ²) with a 5% significance level (p < 0.05). The study was approved by the institutional Research Ethics Committee under the protocol number 2.211.687/2017.

Results

During the study period, 241 patients with OF were identified, predominantly male (81.7%), young adults (64.3%), victims of motorcycle accidents (53.5%). Lower limbs were the most affected anatomical segment (82.6%) ([Table 1]).

Table 1

Variables	Patients primarily treated for open fractures
	(n = 241)
	n	(%)
Gender
Male	197	81.7
Female	44	18.3
Age group (37.2 ± 16.0 years old; 18–86 years-old)
18–39 years-old	155	64.3
40–59 years-old	62	25.7
≥ 60 years-old	24	10.0
Origin
Belo Horizonte Metropolitan Region	192	79.7
Minas Gerais State, except for RMBH	48	19.9
Not informed	1	0.4
Trauma mechanism
Car accident	15	6.2
Bicycle accident	5	2.1
Machinery accident	10	4.1
Motorcycle accident	129	53.5
Physical assault	5	2.1
Running over	33	13.7
Firearm or knife assault	8	3.3
Fall	32	13.3
Other	4	1.7
Affected anatomical segment
Lower limb	199	82.6
Upper limb	38	15.8
Lower + upper limbs	4	1.6

According to the Gustilo classification, 48 (20.0%) fractures were type I, 46 (19.0%) were type II, and 52 (21.6%) were type III. This classification was not recorded in medical records of 39.4% patients with OF. After the initial approach, infectious complications occurred in 18.7% patients, most often in those with type III fractures (36.5%).

The average waiting time for emergency surgery was 4 hours and 12 minutes ± 3 hours and 18 minutes, ranging from 38 minutes to 21 hours and 7 minutes; 199 (82.6%) patients were operated on within 6 hours of admission. Preoperative antimicrobial treatment was prescribed for 221 (91.7%) patients; in addition, for 172 subjects (71.7%), antimicrobial treatment was prescribed within 3 hours of admission. There was a statistically significant association between infectious complications and type III fractures (p = 0.0014), postoperative antimicrobial treatment (p = 0.0362) and antimicrobial treatment starting 3 hours after admission (p = 0.0350); these data are presented in [Table 2].

Table 2

Variables	Patients with open fracture (n = 241)		Infectious complications				p-value [*]
			YES (n = 45)		NO (n = 196)
	n	(%)	n	(%)	n	(%)
Open fracture classification
Type I	048	(20.0)	05	(10.4)	043	(89.6)	p = 0.0014
Type II	046	(19.0)	04	(08.7)	042	(91.3)
Type III	052	(21.6)	19	(36.5)	033	(63.5)
Unclassified	095	(39.4)	17	(17.9)	078	(82.1)
Time from patient admission to surgery
≤ 6 hours	199	(82.6)	37	(18.6)	162	(81.4)	p = 0.4621
> 6 hours	042	(17.4)	08	(19.0)	034	(81.0)
Time from patient admission to antimicrobial treatment start
Preoperative	221	(91.7)	38	(17.2)	183	(82.8)	p = 0.0362
Postoperative	020	(08.3)	07	(35.0)	013	(65.0)
≤ 3 hours after admission	172	(71.7)	27	(15.7)	145	(84.3)	p = 0.0350
> 3 hours after admission	069	(28.3)	18	(26.1)	051	(73.9)
TOTAL	241	(100)	45	(18.7)	196	(81.3)

From the total sample of 241 patients, 74 (30.7%) were excluded from the antimicrobial treatment evaluation because of the lack of fracture classification record and the lack of criteria for antimicrobial treatment in type III fractures from trauma cases occurred > 6 hours before.

Inadequacies regarding the choice of antimicrobial regimen, prescribed doses and antimicrobial treatment duration outweighed adequacies, as shown in [Figure 1].

Fig. 1 Distribution of antimicrobial regimens, prescribed doses and treatment duration adequacies and inadequacies according to the Clinical Protocol “Primary Treatment of Exposed Fractures” - FHEMIG guidelines from June to December 2016, Hospital João XXIII, Belo Horizonte, Minas Gerais, Brazil.

Regarding antimicrobial agents, 59.3% of the patients were exposed to associations not recommended by the CP. The highest percentage of inadequacies was observed in patients with type III OFs and/or trauma occurred > 6 hours before (75.0%) and in those with type II OFs (40.0%). The main inadequacies were, respectively, the absence of the metronidazole prescription for anaerobic bacteria coverage (55.5%) and the absence of the gentamicin prescription for extended gram-negative coverage (87.4%) ([Table 3]).

Table 3

ANTIMICROBIAL TREATMENT	Patients (n = 167)
	n	(%)
Type I
Adequate	20	(645)
Inadequate	11	(35.5)
Trauma occurred in rural environment and/or contamination with dirt with no coverage for anaerobic organisms	03	(27.3)
Increased coverage for gram-negative organisms is unrequired	03	(27.3)
Increased coverage for gram-negative and anaerobic organisms is unrequired	04	(36.3)
Alternative regimen: Clindamycin not associated with gentamycin	01	(09.1)
Type II
Adequate	24	(60.0)
Inadequate	16	(40.0)
Trauma occurred in rural environment and/or contamination with dirt with no coverage for anaerobic organisms	01	(06.3)
No increased coverage for gram-negative organisms	14	(87.4)
Coverage for anaerobic agents is not required	01	(06.3)
Type III and/or trauma over 6 hours before
Adequate	24	(25.0)
Inadequate	72	(75.0)
No coverage for gram-negative organisms	40	(55.5)
No increased coverage for gram-negative and anaerobic organisms	21	(29.2)
No increased coverage for gram-negative organisms	06	(08.3)
Use of not recommended antimicrobial agent (ceftriaxone)	05	(06.9)
Adequacies	68	(040.7)
Inadequacies	99	(059.3)

Considering the total of 438 antimicrobial agents prescribed for the evaluated treatment regimens, daily doses of 254 (58.0%) drugs were inconsistent with the CP. Most inadequacies occurred in prescriptions of cefazolin (93.0%) and clindamycin (86.0%). In contrast, most of the prescribed doses of metronidazole (65.0%) were adequate. All gentamicin dosages agreed with the CP ([Figure 2]).

Fig. 2 Adequacy and inadequacy analysis of prescribed antimicrobial doses according to the Clinical Protocol “Primary Treatment of Exposed Fractures” - FHEMIG guidelines from June to December 2016, Hospital João XXIII, Belo Horizonte, Minas Gerais, Brazil.

As for duration, 63.5% of antimicrobial treatments were prescribed for an inadequate period. Most significant results were obtained in patients with OF type I and II (95.6%), who were exposed to antimicrobial treatment for > 24 hours ([Figure 3]).

Fig. 3 Adequacy and inadequacy analysis of prescribed antimicrobial treatment duration according to the Clinical Protocol “Primary Treatment of Exposed Fractures” - FHEMIG guidelines from June to December 2016, Hospital João XXIII, Belo Horizonte, Minas Gerais, Brazil.

The average duration of antimicrobial treatment in patients with type I and II OF was 4 days, ranging from 1 to 10 days; the CP, however, recommends treatment for only 1 day. In patients with type III OF and/or trauma occurring > 6 hours before, the average treatment duration was 3 days, ranging from 1 to 9 days, while the CP recommends it for 3 days. Overall, the average duration of antimicrobial treatment was longer in patients transferred to other units from the hospital network (4 days, ranging from 1 to 10 days) than in patients who remained at the primary care hospital (3 days, ranging from 1 to 8 days).

Regarding tetanus prophylaxis, the vaccination history from 207 (85.9%) OF patients were not found in the medical records, and no immunization was prescribed for them. Only 34 (14.1%) patients were immunized, of which 28 (82.3%) were at the Intensive Care Unit (ICU).

As for the care flow, 124 (51.4%) OF patients were transferred to other units from the hospital network, 91 (37.8%) completed treatment at the primary care hospital, 21 (8.7 %) were transferred to private hospitals, and 5 (2.1%) died. The average length of stay at the hospital network was 16 days, being longer in patients with type III OF (25 days) and in those with infectious complications (37 days), as shown in [Table 4].

Table 4

Variables	Length of stay (Days)
	Primary care hospital			Other unit from the hospital network			Total time at the hospital network
	Mean	Median	Range	Mean	Median	Range	Mean	Median	Range
Fracture classification
Type I	10	04	1–35	11	08	1–41	15	09	1–137
Type II	05	02	1–42	09	05	1–48	10	06	1–60
Type III	17	09	1–93	14	13	1–72	25	19	1–107
Unclassified	07	04	1–79	09	07	1–50	13	08	1–77
Infectious complication
Without infection	07	04	1–079	07	04	1–41	12	07	1–77
With infection o	21	15	1–135	16	12	1–72	37	30	4–137
Total	0 9	04	1–135	11	8	1–72	16	09	1–137

Discussion

With technological development and the increased diversity of existing diagnostic and therapeutic options, CPs have emerged to reduce the variability of adopted behaviors and to assist health professionals in the decision-making process to assure the quality and safety of patient care. The CPs are elaborated based on a comprehensive study of the best scientific evidence and consensus available in the literature on a given subject.[14]

The CP guiding this CA standardized antimicrobial treatment in the first care of OF patients according to fracture classification, which helps to choose the best treatment and predict the prognosis. Nevertheless, the study showed a significant frequency of fractures with no reported classification in the medical record. This inadequacy made it impossible to evaluate antimicrobials use in these fractures, except for those with trauma occurring > 6 hours before, because its recommended regimen is the same as for type III fractures.

The epidemiological profile of the participants of the study was similar to that found in the literature, with young males mostly affected.[15] [16] [17] [18] This finding can be explained by the greater exposure of young men to traffic accidents, especially with motorcycles.

The infection rate (18.7%) was consistent with the results from a study at an emergency hospital located in Canoas, state of Rio Grande do Sul, Brazil (18.8%).[18] However, other studies, one Brazilian[16] and one international,[19] found lower rates, of 10.0% and 13.2%, respectively. The significant association between infectious complications and type III fracture revealed by this CA is a well-established relationship in the literature.[18] [19]

The CA also showed that the average waiting time for emergency surgery was 4 hours and 12 minutes, which is below the 6-hour limit recommended by the CP. In a Canadian study, the average waiting time was 9 hours and 15 minutes.[17] As in other publications, the present CA did not show any association between the waiting time for emergency surgery and the presence of infectious complications.[16] [17]

The positive association between lower frequency of infectious complications and time from admission to antimicrobial treatment initiation was also observed in the descriptive study performed by Lack et al.[20] Although the CP recommends the preoperative institution of antimicrobial therapy without establishing a time limit between admission and treatment initiation, studies have shown that a delay in antimicrobial administration beyond 3 hours is related to a higher risk of infections.[21]

The fact that the highest rates of inadequate antimicrobial use occurred in type II and III OFs is worrisome, since these fractures are the most prone to infectious complications.[22]

The CP defined antimicrobial agent dosages based on OF epidemiological profile in the study scenario, that is, individuals with an average weight of 70 kg, and considering the predominance of otherwise healthy young adults. This standardization intends to facilitate antimicrobials management in emergency situations, as well as to ensure their rational use, avoiding inappropriate doses, frequencies and/or treatment durations. However, the CP does not predict situations with other patient profiles with OF, such as obese subjects, whose antimicrobial dose should be individualized and calculated according to body weight. As such, antimicrobial doses not standardized by the CP were considered inadequate even when they were within the therapeutic range established in the literature according to the body weight of the patient. Thus, it is important that these cases are predicted in the CP, increasing the flexibility of antimicrobial doses according to individual characteristics of the patients.[23] [24]

The prolonged prescribed antimicrobial treatment duration was a surprising result, especially in type I and II OFs, when the average treatment time was four times longer compared to the CP recommendation. It is also worth mentioning that the longest antimicrobial treatment duration occurred in the transition from primary care to other units from the hospital network, probably due to a failure in consulting medical records about the time of antimicrobial use at the first hospital. Despite controversies among several authors about the appropriate duration of antimicrobial treatment, current studies show that increased exposure does not reduce infectious complications rates.[25] [26] A retrospective case-control study comparing infection rates in OF patients undergoing antimicrobial treatment for periods ranging from 1 to > 5 days did not indicate significant differences in the risk of infection, including in type III OF.[25] In addition to not being beneficial, prolonged antimicrobial treatment is related to an increased risk of adverse events, development of bacterial resistance, increased length of hospital stay and increased care-related costs.[5] [6]

Regarding tetanus prophylaxis, the CP only mentions that it must be performed, without detailing the procedures, which should be based on national guidelines.[11] The CP only recommends the association of metronidazole for patients with unknown or uncertain vaccination history due to its antianaerobic activity, which reduces bacterial loads at the inoculation focus and prevents the production of tetanus toxin.[27] However, metronidazole administration does not exclude the need for immunoprophylaxis. During the audited period, there was no vaccination history records for all OF patients, which was considered a serious inadequacy given the probable missed opportunities for immunization. Thus, in all OF cases, it is necessary to verify and register the vaccination of the patient in the medical record, allowing adoption of the appropriate strategies.

The role of the clinical pharmacist in the ICU to review the basic care applicable to critically ill patients, including the investigation of vaccine status, may explain why most immunized OF patients were those admitted to this unit. Other studies reported the positive results of the participation of the pharmacist in trauma teams, reinforcing the significance of this professional as a member of the multidisciplinary healthcare team.[28]

A major limitation of the present study was the fact that the research evaluated only CP compliance by the traumatology team during the initial care of OF patients, not considering other comorbidities or injuries. This fact may have influenced our results, as subjects in more severe conditions could have their first orthopedic approach postponed to focus on most urgent issues, influencing the criteria evaluated in the study, such as waiting time for the first surgical approach, length of stay and incidence of infectious complications.

Conclusion

The present study identified divergences from the institutional clinical protocol; the most significant inadequacies were observed in the choice of antimicrobial regimens, doses and treatment duration, as well as in tetanus prophylaxis.

• Referências

• 1 Gliglio PN, Cristante AF, Pécora JR, Helito CP, Lima ALL, Silva JS. Avanços no tratamento das fraturas expostas. Rev Bras Ortop 2015; 50 (02) 125-130
• 2 Müller SS, Sadenberg T, Pereira GJ, Sadatsune T, Kimura EE, Novelli Filho JL. Estudo epidemiológico, clínico e microbiológico prospectivo de pacientes portadores de fraturas expostas atendidos em hospital universitário. Acta Ortop Bras 2003; 11 (03) 158-169
• 3 Arruda LR, Silva MA, Malerba FG, Fernandes MC, Turibio FM, Matsumoto MH. Fraturas expostas: estudo epidemiológico e prospectivo. Acta Ortop Bras 2009; 17 (06) 326-330
• 4 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 (04) 453-458
• 5 Rodriguez L, Jung HS, Goulet JA, Cicalo A, Machado-Aranda DA, Napolitano LM. 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 (03) 400-407
• 6 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 (01) 146-150
• 7 Hauser CJ, Adams Jr CA, 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 (04) 379-405
• 8 Cotta AMA, Peres CF, Ribeiro DAM. , et al. Antibioticoterapia e imunoprofilaxia do tétano no trauma perfurocortante. Rev Med Minas Gerais. 2009; 19 (02) 96-103
• 9 Gonzalez VL, Santin E, Arsego FV. , et al. Diagnóstico e manejo das lesões ortopédicas em pacientespolitraumatizados. Rev HCPA. 2009; 29 (02) 153-160
• 10 Brasil. Ministério da Saúde. Guia de Vigilância Epidemiológica/Fundação Nacional de Saúde [acesso em 2018 Fev 20]. 5° ed. Brasília: FUNASA; 2002 . Disponível em: http://bvsms.saude.gov.br/bvs/publicacoes/funasa/guia_vig_epi_vol_ll.pdf
• 11 Fundação Hospitalar do Estado de Minas Gerais. Diretrizes clinicas Protocolos clínicos. Tratamento primário das fraturas expostas. Revisado 2014 [acesso em 2018 Fev 20]. Disponível em: http://www.fhemig.mg.gov.br/index.php/docman/Protocolos_Clinicos-1/70-019-tratamento-primario-das-fraturas-expostas-07082014/file
• 12 Araujo RQ. Antibióticoprofilaxia em cirurgias ortopédicas: resultado da implantação de um protocolo [tese]. São Paulo: Universidade Estadual de Campinas, Faculdade de Ciências Medicas; 2000
• 13 Bazzanella NA, Slob E. A auditoria como ferramenta de analise para a melhoria da qualidade do serviço prestado. Cad Saude Desenvolv. 2013; 3 (02) 50-65
• 14 Mahmud SDP. Protocolos clínicos: adesão e aplicabilidade numa instituição hospitalar [tese]. Rio Grande do Sul: Universidade Federal do Rio Grande do Sul, Escola de Administração; 2002
• 15 Villa PEA, Nunes TR, Gonçalves FP, Martins JS, Lemos GSP, Moraes FB. Avaliação clinica de pacientes com osteomielite crônica após fraturas expostas tratadas no Hospital de Urgências de Goiânia, Goiás. Rev Bras Ortop 2013; 48 (01) 22-28
• 16 Fernandes MC, Peres LR, Queiroz Neto AC, Lima Neto JQ, Turíbio FM, Matisumoto MH. Fraturas expostas e a incidência de infecções no desbridamento cirúrgico 6 horas após o trauma. Acta Ortop Bras 2015; 23 (01) 38-42
• 17 Weber D, Dulai SK, Bergman J, Buckley R, Beaupre LA. Time to initial operative treatment following open fracture does not impact development of deep infection: a prospective cohort study of 736 subjects. J Orthop Trauma 2014; 28 (11) 613-619
• 18 Guerra MTE, Gregio FM, Bernardi A, Castro CC. Taxa de infecção em pacientes adultos com fratura exposta atendidos no hospital de pronto socorro e no hospital universitário Ulbra do município de Canoas, Rio Grande do Sul. Rev Bras Ortop 2017; 52 (05) 541-548
• 19 Chen AF, Schreiber VM, Washington W, Rao N, Evans AR. What is the rate of methicillin-resistant Staphylococcus aureus and Gram-negative infections in open fractures?. Clin Orthop Relat Res 2013; 471 (10) 3135-3140
• 20 Lack WD, Karunakar MA, Angerame MR. , et al. Type III open tibia fractures: immediate antibiotic prophylaxis minimizes infection. J Orthop Trauma 2015; 29 (01) 1-6
• 21 Patzakis MJ, Wilkins J. Factors influencing infection rate in open fracture wounds. Clin Orthop Relat Res 1989; (243) 36-40
• 22 Hoff WS, Bonadies JA, Cachecho R, Dorlac WC. East Practice Management Guidelines Work Group: update to practice management guidelines for prophylactic antibiotic use in open fractures. J Trauma 2011; 70 (03) 751-754
• 23 DynaMed Plus [database online]. Ipswich (MA): EBSCO Information Services [acesso em 2018 Feb 23]. Disponível em: http://www.dynamed.com
• 24 Halawi MJ, Morwood MP. Acute management of open fractures: an evidence-based review. Orthopedics 2015; 38 (11) e1025-e1033
• 25 Dunkel N, Pittet D, Tovmirzaeva L. , et al. Short duration of antibiotic prophylaxis in open fractures does not enhance risk of subsequent infection. Bone Joint J 2013; 95-B [phone]
• 26 Messner J, Papakostidis C, Giannoudis PV, Kanakaris NK. Duration of administration of antibiotic agentes for open fractures; meta- analysis of the existing evidence. Surg Infect (Larchmt) 2017; 18 (08) 854-867
• 27 Lisboa T, Ho YL, Henriques Filho GT. , et al. Diretrizes para o manejo do tétano acidental em pacientes adultos. Rev Bras Ter Intensiva 2011; 23 (04) 394-409
• 28 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 (02) 290-293