Antibiotic Treatment What Can Be Learned from Point of Injury Experience?

Transcription

1 MILITARY MEDICINE, 183, 3/4:466, 2018 Antibiotic Treatment What Can Be Learned from Point of Injury Experience? LTC Avi Benov, MD* ; Ben Antebi, PhD ; Joseph C. Wenke, PhD ; Andriy I. Batchinsky, MD ; COL Clinton K. Murray, MC, USA ; MAJ Dean Nachman, MD* ; Paran Haim, MD ; BG Bader Tarif, MD* ; COL Elon Glassberg, MD*; COL Avi Yitzhak, MD* ABSTRACT Introduction: Early antibiotic administration after trauma reduces infection rates of open wounds. A clinical practice guideline (CPG) was created to ensure that wounded personnel who are not expected to arrive at the hospital within an hour receive antibiotic treatment in the field. This study evaluated how well-advanced life saver (ALS) providers complied with Israeli Defense Force (IDF) CPG. Materials and Methods: A retrospective review of all trauma patients between November 2011 and January 2015 was conducted. All casualties who suffered from penetrating injuries with evacuation times greater than 60 min were examined. Casualties who should have received antibiotic treatment in accordance with the IDF CPG were further divided into those who received antibiotics (i.e., Antibiotic group) and those who did not receive antibiotic treatment (i.e., No Antibiotics group). Results: For a 3-yr period, a total of 5,142 casualties occurred in the pre-hospital environment. According to parameters established in the CPG, 600 casualties should have received antibiotic treatment. Of these patients, only 49 (8.2%) received antibiotic treatment. Comparative analysis between these groups revealed no significant differences in regards to gender, age, and time to MTF; however, significant differences were found in regards to injury severity score (ISS) (p < 0.01), care under fire (i.e., treatment at a combat zone) criteria (p < ), and life-saving interventions (p < 0.005). Discussion: Although the reasons for poor adherence to IDF CPG s are not entirely clear, the data suggest that the severity of the injuries sustained by these casualties requiring a greater number of LSIs, longer evacuation distances, and a more hostile battlefield environment may each contribute to poor adherence. Since this has been identified as a training gap, the importance of antibiotic administration at point of injury in delayed evacuation scenarios has been reinforced. INTRODUCTION Injuries inflicted on the battlefield may lead to infectious complications and increase the risk of sepsis and death among casualties. 1 3 Early evidence of wound management techniques from Sumerian origin are dated over 4,000 yr ago; yet, until the twentieth century, wound infections have resulted in more deaths than the direct battle-related injuries. 4 The discovery of penicillin by Alexander Fleming in *Israel Defense Forces, Medical Corps, Tel Hasomer, Ramat Gan 02718, Israel. Department of Surgery A, Meir Medical Center, 59 Tesernikovski st, Kfar Saba and the Sackler School of Medicine, Tel-Aviv University, , Israel. U.S. Army Institute of Surgical Research, 3698 Chambers Pass, Bldg 3611, JBSA, Fort Sam Houston, TX San Antonio Military Medical Center, 3551 Roger Brooke Dr, JBSA, Fort Sam Houston, TX Institute for Research in Military Medicine, The Hebrew University, Kiryt Hadassah, Jerusalem 91120, Israel. Department of Military Medicine, The Hebrew University, Kiryt Hadassah, Jerusalem 91120, Israel. Avi Benov and Ben Antebi contributed equally to the manuscript and are co-first authors The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the U.S. Department of the Army or the U.S. Department of Defense. doi: /milmed/usx144 Association of Military Surgeons of the United States All rights reserved. For permissions, please journals.permissions@oup.com. 1928, as well as advancements in wound management, reversed this trend in the twentieth century, steadily decreasing the mortality rate resulting from combat-related wound infections in each successive war involving the United States (U.S.). However, with the increased use (and misuse) of antibiotics, pathogens have become increasingly resistant, making the ability to manage wound infections more challenging. 5,6 Several studies performed in the civilian setting have shown that early administration of the appropriate type and/or combination of antibiotics, along with irrigation and proper debridement of wounds, is of the utmost importance in the prevention of complications and reduction in long-term morbidity and mortality Although only minimal data exist regarding the effects of antibiotic treatment immediately after sustaining injury during combat, 15 medical organizations worldwide as well as The Committee of Trauma Combat Casualty Care recommends antibiotic use in the settings of delayed evacuation and prolonged field care. 16,17 The selection of antibiotics in the pre-hospital setting is based on ease of administration, spectrum of coverage, drug stability, and other logistical considerations. These recommendations are not applicable to injured casualties who can be rapidly evacuated from the battlefield or to those who have already reached a medical treatment facility (MTF) that can provide definitive care. The Israel Defense Forces Medical Corps (IDF-MC) Clinical Practice Guideline (CPG), last updated on November 466 MILITARY MEDICINE, Vol. 183, March/April Supplement 2018

2 2011, instructs advanced life saver (ALS: physician or a paramedic) providers to administer antibiotics to casualties with penetrating injuries whose estimated evacuation time is over 1 hr. The CPG also instructs that wounds be copiously irrigated with a sterile solution and dressed. The purpose of this study is to evaluate the IDF experience with the use of antibiotics at point of injury (POI) with respect to IDF-MC CPG and propose certain recommendations that may potentially increase future adherence to CPGs by medical providers at large. MATERIALS AND METHODS IDF Clinical Practice Guidelines for Antibiotic Administration The IDF CPG instructs ALS providers to treat casualties with penetrating injuries as soon as possible after injury. To remove any debris and dilute any existing contaminants, wounds should be irrigated using a minimum of 2 L of any available sterile solution (preferably saline or Hartmann s solution). To avoid delays in evacuation, this approach is to be performed en route to the MTF if possible. The IDF-MC antibiotic of choice is a single dose of intravenous (IV) moxifloxacin (fluoroquinolone) 400 mg/d for trunk injuries, oral administration (PO) of moxifloxacin for extremity wounds, and a single dose of IV ceftriaxone (cephalosporin; 2 g/d) in combination with IV metronidazole 500 mg every 8 hr for head injuries (Fig. 1). In circumstances of multiple penetrating injuries, the choice of antibiotic is determined according to the predominant (i.e., most severe) injury. IDF Trauma Registry In 1997, the IDF-MC launched a centralized pre-hospital trauma registry (ITR) administered by the Trauma and Combat Medicine Branch (TCMB) at the Surgeon General s Headquarters. In this registry, data are gathered from casualty cards. The data include demographics, information concerning mechanism and anatomic distribution of injury, vital signs and interventions (e.g., procedures, use of medications, and administration of fluids), as well as information regarding the injury scenario and identity of the medical providers, which facilitates data collection throughout the different roles of care Upon arrival at the hospital, the casualty card is scanned and later conveyed to the TCMB. Subsequently at the TCMB, the recorded data are verified for consistency and registered at the ITR. One recent improvement in the ITR is an interface that allows for direct online input of information as soon as treatment is completed (i.e., real-time data flow). Study Design The data collection for the analysis was conducted under the approval of the IDF-MC as a process review and improvement project. All trauma cases documented in the ITR between November 2011 and January 2015 were retrieved and evaluated. All casualties (military personnel and civilians including non-israeli citizens) who suffered from penetrating injuries with evacuation times to hospitals greater than 60 min were extracted. Descriptive statistics included demographics, wound distribution, mechanism of injury (MOI), antibiotics administered, and pre-hospital life-saving interventions (LSIs). Demographics included the following: gender, age, time to MTF, injury severity score (ISS), and scenario of injury (i.e., battlefield/care under fire or scenarios not involving hostile fire). Regional wound distribution was demarcated based on projected body surface area, as previously described, and grouped into three main body regions: (1) head and neck, (2) trunk, and (3) extremities. MOI was grouped into three main categories: (1) explosion (to include improvised explosive device, landmine, mortar, shrapnel, bomb, and grenade), (2) gunshot wound (GSW, to include shrapnel originating from gunshots), and (3) unknown. The LSIs were defined according to IDF-MC CPGs to include endotracheal intubation, cricothyroidotomy, needle thoracostomy, chest tube thoracostomy, application of tourniquets and hemostatic dressings, concurrent use FIGURE 1. Decision criteria for antibiotic administration at point of injury as recommended by the Israeli Defense Forces clinical practice guidelines. MILITARY MEDICINE, Vol. 183, March/April Supplement

3 of crystalloids, tranexamic acid (TXA), and reconstituted freeze-dried plasma (FDP) For comparison purposes, the casualties who were designated to receive antibiotic administration as set out by the CPG were further divided into two groups: those who received antibiotics (i.e., Antibiotic group) and those who did not receive antibiotic treatment (i.e., No Antibiotics group). Overall adherence to CPG regarding antibiotic administration immediately following injury was evaluated. Statistical Analysis Continuous data are presented as medians and interquartile ranges (IQR; difference between the upper and lower quartiles); categorical data are presented as absolute numbers and percentiles. Categorical data were analyzed using chi-square test or Fisher s exact test when appropriate. Continuous variables were evaluated using a two-tailed Student s t-test for normally distributed data or a Wilcoxon/Kruskal Wallis test for skewed data. Significance was set at an α < RESULTS Patient Demographics From November 2011 to January 2015, a total of 5,142 casualties were recorded in the ITR. All casualties were from different IDF pre-hospital combat environments. Per IDF CPG, 600 casualties (11.7%) should have received pre-hospital antibiotic treatment and are the focus of the present study. Of these 600 patients, a total of 49 (8.2%) received antibiotic treatment as recommended by the CPG. Comparative analysis between the two groups (i.e., Antibiotics and No Antibiotics ) revealed no significant differences in regards to gender, age, and time to MTF; however, significant differences were found in regards to ISS (p < 0.01) and care under fire (i.e., treatment at a combat zone) criteria (p < ), as shown in Table I. Injury Characteristics Mechanism of injury was similar between groups; explosions accounted for 68.2% (n = 376) of injuries in patients who did not receive antibiotics and 65.3% (n = 32) of injuries in those receiving treatment. Similarly, 30.1% and 28.6% of patients were injured from GSWs in the No Antibiotics and Antibiotics groups, respectively. In regards to distribution of wounds, the predominant injured body regions were the lower and upper extremities followed by head and neck and trunk (Table II). As in MOI, no significant differences were found between the two groups. Antibiotic Administration Of the 49 patients receiving antibiotic treatment, 32 (65.3%) were treated by moxifloxacin IV, 16 (32.6%) were treated with moxifloxacin PO, and 1 patient (2.1%) was treated with ceftriaxone IV; no casualties were treated with metronidazole. In regards to IDF CPG, 31 (63.3%) patients received the correct antibiotic treatment as set out by the CPG with the following distribution: 16 patients were treated with moxifloxacin PO for extremity and superficial injuries and 15 patients were treated with moxifloxacin IV for truncal injuries. The 18 patients (36.7%) who were not treated according to the CPG included 14 casualties treated with moxifloxacin IV instead of moxifloxacin PO, 3 casualties treated with moxifloxacin IV instead of a combination of ceftriaxone and metronidazole for head injury, and 1 casualty with head injury that was treated with moxifloxacin only. Correlation between injuries and administered antibiotics is shown in Table III. Life-saving Interventions Among the 600 patients that should have received antibiotic treatment, a total of 281 LSIs were performed on 170 (28.3%) patients with the application of a tourniquet being the predominant intervention. Comparison between the two groups, with and without antibiotic treatment, in terms of LSIs performed at the pre-hospital settings revealed significant differences in patients treated with endotracheal intubation (p < 0.01) and tube thoracostomy (p < 0.05) procedures (Table IV). Comparison of total LSIs revealed significant TABLE I. Demographics of Patients Eligible to Receive Antibiotics at Point of Injury According to Israeli Defense Forces Clinical Practice Guidelines Criteria Antibiotics No Antibiotics p Patient Number (%) 49 (8.2%) 551 (91.8%) N/A Male (%) 45 (91.8 %) 524 (95.1 %) 0.98 Age, median (IQR) 22 (20 26) 22 (20 26) NS Care under fire (%) 2 (4) 202 (36.7) < Time to MTF (IQR) 80 (70 120) 80 (72 125) NS ISS, median (IQR) 9 (3 13) 4 (2 9) <0.001 Note. Population is divided into two groups: those who received antibiotic treatment and those eligible who were not rendered treatment. NS, no significance; IQR, interquartile ranges (difference between the upper and lower quartiles). TABLE II. Injury Characteristics Injury Characteristics of Patients Eligible to Receive Antibiotic Treatment Antibiotics (n = 49) No Antibiotics (n = 551) Mechanism of injury (MOI) Explosion (%) 32 (65.3) 376 (68.2) Gunshot wound (%) 14 (28.6) 166 (30.1) Unknown (%) 3 (6.1) 9 (1.6) Anatomical distribution of wounds Head and neck (%) 17 (34.7) 208 (37.7) Trunk (%) 20 (40.8) 214 (38.9) Extremity (%) 42 (85.7) 402 (72.9) Total (region per casualty) 79 (1.6) 824 (1.5) Note. Percentages for anatomical distribution are shown as casualties suffering from an injury to a body region. Due to multiple injuries on a single patient, total regions are greater than total number of patients. 468 MILITARY MEDICINE, Vol. 183, March/April Supplement 2018

4 TABLE III. Types of Antibiotics Administered at Point of Injury Correlated with the Corresponding Injured Body Region Antibiotics at POI TABLE IV. Moxifloxacin PO Pre-hospital LSI Performed on 170 Patients of the Study Cohort Number of Casualties Undergoing Pre-hospital LSIs Moxifloxacin IV Antibiotics (n = 49) Ceftriaxone + Metronidazole Head a Trunk Extremities Superficial injuries Total patients (%) 16 (32.6) 32 (65.3) 1 a (2.1) a Ceftriaxone treatment only (without metronidazole as instructed by the CPG). No Antibiotics (n = 551) p Total patients (%) 10 (20) 160 (29) 0.2 Tourniquet (%) 3 (30) 82 (30.3) 0.09 Hemostatic dressing (%) 3 (30) 53 (19.6) 0.42 Endotracheal intubation (%) 1 (10) 60 (22.1) <0.01 Cricothyrotomy (%) 1 (10) 22 (8.1) 0.5 Needle decompression (%) 2 (20) 20 (7.4) 0.87 Tube thoracotomy (%) 0 (0) 34 (12.5) <0.05 Total LSI (LSI per casualty) 10 (1) 271 (1.7) <0.01 differences between the two groups as more LSIs per casualty were needed in casualties with no antibiotic treatment (p < 0.005). CONCLUSION Early antibiotic administration after injury is believed to prevent wound infection and subsequent overall morbidity and mortality, but this is primarily based on expert opinion, and evidence-based data regarding this important approach are still lacking. In a recent study, Lack et al provided evidence that immediate antibiotic prophylaxis minimizes infection in type III open tibia fractures. This retrospective study consisted of 137 patients admitted to a civilian level 1 trauma center and demonstrated that there was a progressive rise in the infection rate when antibiotics were delayed: 7% when antibiotics were given within an hour, 18% with antibiotics given between 60 and 90 min, and 28% when antibiotics given beyond 90 min. 7 Yet, this evidence of improved outcome is specific to open fractures and only limited to the civilian sector. Similarly, in a combat-related scenario during the 1982 Falkland Campaign, antibiotic treatment within 3 hr was associated with a lower incidence of infection in casualties with extremity injuries when compared with casualties who received antibiotics after the 3-h window. 32,33 Conversely, a wound infection study from the Yom Kippur War in 1973 reported that 91% of infections (from a total of 88 episodes) occurred in spite of antibiotic therapy. 34 In that study, Klein et al concluded that antibiotic prophylaxis may be a contributing factor to the overall incidence of infection on the battlefield. 31 Thus, the concept that antibiotic administration within an hour of battlefield injury truly has a favorable effect on casualty outcome rather than treatment in a hospital setting (within 2 4 hr after injury) remains to be proven. In this study, we evaluated the use of antibiotics at prehospital scenarios with emphasis on adherence to IDF CPG. Analysis of results revealed that overall adherence to CPG was poor, with less than 10% of casualties receiving proper medical treatment by IDF ALS providers, compared with higher rates of antibiotic administration shown in other militaries. 35 In that study, adherence to the CPG was classified as receipt of recommended antimicrobials within 48 hr of injury. A total of 1,106 military personnel eligible for CPG assessment were identified and 74% received antimicrobial prophylaxis. Overall, CPG compliance within 48 hr of injury was 75%. Lack of antimicrobial prophylaxis contributed 2 22% to noncompliance varying by injury category, whereas receipt of antibiotics other than preferred ranged from 11% to 30%. For extremity injuries, antimicrobial prophylaxis adherence was 60 83%, whereas it was 80% for closed injuries and 68% for penetrating abdominal injuries. The reason for this poor compliance is most likely multifactorial; thus, factors such as care under fire, time to MTF, and ISS that may be potentially related to this phenomenon were initially evaluated. A significantly higher percentage of patients who were not given antibiotics were treated in the battlefield or under fire, where most efforts are aimed at LSI and evacuation. Confounding these results, however, is the fact that patients receiving antibiotics were more severely injured; it is assumed that patients with severe injuries will not receive antibiotic treatment since it is not considered a life-saving intervention, and as shown these patients received more LSIs. Time to MTF was similar between groups, although we would expect a longer time to MTF in patients receiving antibiotics due to the instructions set out by the CPG and the availability of en route care time that can be used to administer such treatment. Another probable reason to the low adherence rate could stem from the novelty of the CPG, which was only introduced in November Furthermore, antibiotic treatment, according to CPG, is not part of basic medical training rendered to the ALS provider, as opposed to basic LSIs, such as airway management and chest tubes. Therefore, as antibiotic treatment is not considered an LSI and the immediate outcome is not seen by the provider, unlike hemorrhage prevention after tourniquet application or a rise in oxygen saturation after intubation, the importance of such treatment is not inherently obvious. As this low compliance is identified as a training gap, this will be addressed and reinforced in training of antibiotic administration at POI as instructed by the CPGs. Another possible factor for the poor compliance is that ALS MILITARY MEDICINE, Vol. 183, March/April Supplement

5 providers may leave treatment to hospitals due to the typical short evacuation times in Israel. Mechanism of injury and anatomical wound distribution were also examined to reveal any potential links to compliance with the CPG. To this end, the category of explosion was the predominant MOI, and the category of extremities described the body region sustaining the most injuries; these epidemiological data are consistent with those reported in other military conflicts engaged in war against terror worldwide ,36 38 The MOI of injury in these reports was predominantly due to explosions ranging between 74.4% to 78%, and extremities being the body region sustaining most injuries ranging between 49.4% and 54%. In terms of MOI, no significant differences were found between the two groups (i.e., Antibiotics and No Antibiotics ) in this study. Analysis regarding the type of antibiotics administered revealed that of the 49 patients (8.2%) receiving treatment, 18 (36.7%) did not receive the correct treatment, receiving the wrong treatment or receiving only part of the antibiotics. Preference to the IV route could stem from uninformed decisions due to unfamiliarity with the CPG, as well as a tendency to choose the standard option and administer one medication instead of two. Finally, LSIs were investigated in relation to CPG to determine whether urgent care may delay or thwart antibiotic administration. Significantly more patients who did not receive antibiotics were treated with endotracheal intubation and tube thoracotomy, which may elucidate the low compliance to CPG. In terms of total LSIs, however, no significant difference was found between the groups. A limitation of this study is the small sample proportion of the population that received antibiotic treatment. One possible approach to mitigate this is widening the study period in future studies. Moreover, increased adherence to CPGs by medical providers will inevitability lead to larger number of patients receiving antibiotic treatment in the pre-hospital environment. Another limitation concerns the retrospective nature of the study. To circumvent this challenge, future efforts should focus at collecting these data via prospective studies. The third limitation concerns the challenge of data collection from the battlefield under combat situations that might lead to missing data. This challenge is difficult to overcome due to the inherent nature of the battlefield environment, which includes scenarios of care under fire; however, with technological advancements and the increased efforts by the IDF (and other militaries) to collect viable medical data at early roles of care, we envision that future studies will benefit from data collection that is more comprehensive. The concept of early antibiotic therapy is yet to be an accepted paradigm. This work contains data regarding antibiotic treatment at POI and emphasizes the importance of proper education and training of medical providers as well as the significance of ongoing data collection and analysis as they serve as the basis for lessons learned in combat casualty care. Further research is needed to determine the outcome of those patients who required antibiotic administration but were not rendered treatment at POI. Importantly, short-term and long-term outcomes should be looked into in this patient population to determine the effects of early antibiotic therapy. Irrespective of the patient s clinical outcome, the etiology of such poor compliance to current guidelines must be further investigated and emphasis must be placed to address and promote this important issue. It is the author s opinion that the low adherence to CPGs can be potentially mitigated by proper training, education, and the involvement of high-level command. Training for various pre-hospital scenarios that require the use of antibiotics in accordance with the CPGs will instill the provider with the mindset to follow the CPGs when rendering care. Emphasis on the importance of antibiotic treatment through proper education is also instrumental in increasing future adherence to CPGs. Finally, further research is needed to finding a single antibiotic that can target all pre-hospital scenarios. A single antibiotic will reduce the burden of selecting the appropriate antibiotic in challenging battlefield scenarios and is therefore likely to increase the adherence to CPGs. PRESENTATIONS The work was presented at the Military Health System Research Symposium, FL, USA. CONFLICT OF INTEREST The authors have no conflicts of interest to disclose. REFERENCES 1. 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