Prophylaxis and Treatment of Infections Associated with Penetrating Traumatic Injury

Kyle Petersen; Paige Waterman

Expert Rev Anti Infect Ther. 2011;9(1):81-96.

Expert Commentary & Five-year View

Penetrating trauma, particularly HE injuries, are likely to increase in the future as military assault weapons are increasingly penetrating the civilian sector via the illegal narcotics trade, and terrorist bombings are becoming more commonplace. The actual cause of infection in penetrating trauma injury remains unclear but is likely multifactorial, to include impaired host immune response, the environment of the injury, mechanism of injury and anatomic location. A prospective trial is not feasible in military patients owing to dangerous conditions of injury but a trial examining infection pathogenesis and bacterial pathogen-specific outcomes by evaluating host immune response using modern genomic and proteomic molecular techniques would provide valuable information and could be carried out at a large academic trauma center.

Gram-positive organisms, for example, Streptococcus pyogenes and S. aureus, historically were major causes of morbidity and mortality following penetrating trauma in the pre-antibiotic era and remain initial pathogens for many infection types. As a result, prophylactic antibiotic regimens are mandatory during penetrating trauma surgical management and must prevent these organisms. While multidrug-resistant infections are clearly on the rise, the cause remains unclear. Surgical providers should be cognizant that infections in this population are inevitable, and numerous studies prove the use of broader spectrum agents or prolonging prophylactic therapy does not further mitigate infection risk. Unfortunately, prophylactic antibiotic use asserts selective pressure on host and hospital flora, leading to resistance. An excellent example is the recent demonstration of substantially higher ampicillin/sulbactam resistance in a center where abdominal trauma patients repeatedly received ampicillin/sulbactam.^[69] Utilizing practice guidelines will help minimize this phenomenon. Over time, we may see first-generation cephalosporins lose their prophylactic effect in traumatic injury. Novel nonantibiotic approaches such as immunoaugmentation with antibodies, or limiting antimicrobials to topical applications might reduce selective pressure to develop antibiotic resistance in the host microbiome that is currently thought to be caused by perioperative agents.

Duration of prophylactic antibiotic therapy remains problematic. There are few quality studies comparing duration to any objective measures of infection. Prospective randomized trials to find the best prophylactic agent and duration to reduce penetrating injury infections of all the areas we examined (CNS, maxillofacial, thorax, abdomen and orthopedic) are desperately needed and could easily be performed at large trauma centers. Trials optimizing timing of antibiotic administration with regard to known antimicrobial pharmacokinetic/pharmacodynamic properties (e.g., prolonging infusion times of β-lactams to reduce bacterial resistance) should also assist in improving outcomes in penetrating traumatic infections, which are increasingly antibiotic resistant.

In summary, large advances in morbidity and mortality have been achieved by coupling antimicrobial therapy with aggressive surgical management following penetrating traumatic injury, however, many exciting opportunities exist for providers in the field to improve care and outcomes for patients suffering these terrible injuries.

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Acknowledgements
The authors would like to thank Diana Temple for her assistance in preparation of the manuscript.

Financial & competing interests disclosure
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
No writing assistance was utilized in the production of this manuscript.

Cite this: Prophylaxis and Treatment of Infections Associated with Penetrating Traumatic Injury - Medscape - Jan 01, 2011.

Table 1. Strength of recommendation and quality of evidence.
Assessment	Type of evidence
*Strength of recommendation*
Grade A	Good evidence to support a recommendation for use
Grade B	Moderate evidence to support a recommendation for use
Grade C	Poor evidence to support a recommendation
*Quality of evidence*
Level I	Evidence from at least one properly designed, randomized controlled trial
Level II	Evidence from at least one well-designed clinical trial, without randomization; from cohort or case-controlled analytic studies (preferably from >one center); from multiple time series; or from dramatic results of uncontrolled experiments
Level III	Evidence from opinions of respected authorities, based on clinical experience, descriptive studies or reports of expert committees

Table 2. Epidemiology and recommended prophylaxis and empiric treatment for CNS infection following penetrating trauma.
Seminal papers (type)	Pathogens described	Prophylactic antibiotic of choice (level of evidence)	Duration of prophylaxis (level of evidence)	Empiric treatment of choice^† (level of evidence)	Duration of treatment (level of evidence)
No controlled trials of prophylaxis or therapy exist	Scalp wound: Coagulase-negative Staphylococcus Meningitis: Coagulase-negative Staphylococcus Staphylococcus aureus Gram-negative facultative aerobes Anaerobes^‡ Rapidly growing mycobacteria^§	Cefazolin 1 g iv. q 8 h or ceftriaxone 2 g q 24 h^¶ Penicillin allergic: Vancomycin 15 mg/kg divided q 6 h plus ciprofloxacin 400 mg iv. q 12 h (BIII)	5 days (BII)	Vancomycin 15 mg/kg divided q 6 h plus cefepime or ceftazidime or meropenem 2g q 8 h^# (BIII)	21 days (BIII)

^†Empiric antimicrobials should be 'de-escalated' to target susceptibility of pathogens isolated from culture as soon as possible.
^‡If oral injury or soil contamination occurs.
^§Rarely found.
^¶Consider adding gentamicin and penicillin prophylaxis if wound grossly contaminated.
^#Consider ciprofloxacin for β-lactam allergy.
iv.: Intravenously; q: Every.

Table 3. Epidemiology and recommended prophylaxis and empiric treatment for maxillofacial infection following penetrating trauma.
Seminal papers (type)	Pathogens described	Prophylactic antibiotic of choice(level of evidence)	Duration of prophylaxis (level of evidence)	Empiric treatment of choice^† (level of evidence)	Duration of treatment (level of evidence)	Ref.
Chole and Yee (prospective randomized trial) Andreasen et al. (meta-analysis)	Pseudomonas spp. Staphylococcus aureus Escherichia coli and Klebsiella spp. Candida spp. Proteus mirabilis Bacteroides fragilis Peptococcus Peptostreptococcus	Cefazolin 2 g iv. q 8 h Or Clindamycin 900 mg iv. q 8 h^‡ (BI)	24 h (AI)	Ampicillin/sulbactam 2 g iv. q 6 h Or Clindamycin 600 mg iv. q 8 h plus moxifloxacin 400 mg every day^‡ (BIII)	10–14 days or 2–3 days after wound closed 6 weeks for mandibular osteomyelitis (BIII)	[38] [39]

^†Empiric antimicrobials should be 'de-escalated' to target susceptibility of pathogens isolated from culture as soon as possible.
^‡Consider clindamycin regimen for β-lactam allergy.
iv.: Intraveniously; q: Every.

Table 4. Epidemiology and recommended prophylaxis and empiric treatment for thoracic infections following penetrating trauma.
Seminal papers (type)	Pathogens described	Prophylactic antibiotic of choice (level of evidence)	Duration of prophylaxis (level of evidence)	Empiric treatment of choice^† (level of evidence)	Duration of treatment (level of evidence)	Ref.
Maxwell et al. (prospective, randomized) Sanabria et al. (meta-analysis)	Empyema with tube thoracostomy: Coagulase-negative Staphylococcus Delayed onset (>48 h after admission): Coagulase-negative Staphylococcus MRSA Gram-negative facultative aerobes Anaerobes Abdominal contamination: Enterococcus spp. Candida spp.	Cefazolin 1 g iv. q 8 h (BII)^‡	24 h (BII)	Vancomycin 15 mg/kg divided q 6 h plus cefepime or ceftazidime or meropenem 2 g q 8 h^‡ (BIII)	21 days (BIII)^§	[60] [59]

^†Empiric antimicrobials should be 'de-escalated' to target susceptibility of pathogens isolated from culture as soon as possible.
^‡Aminoglycosides should be avoided.
^§Could be shortened if adequate drainage achieved earlier.
iv.: Intravenously; MRSA: Methicillin-resistant Staphylococcus aureus; q: Every.

Table 5. Epidemiology and recommended prophylaxis and empiric treatment for abdominal infection following penetrating trauma.
Seminal papers (type)	Pathogens described	Prophylactic antibiotic of choice (level of evidence)	Duration of prophylaxis (level of evidence)	Empiric treatment of choice^† (level of evidence)	Duration of treatment (level of evidence)	Ref.
Fullen et al. (retrospective cohort) Fabian et al. (prospective randomized) Griswold et al. (prospective randomized) Velmahos et al. (prospective observational) Brand et al. (Cochrane review)	Escherichia coli Enterobacter cloacae Klebsiella spp. Proteus mirabilis Bacteroides spp.	Cefoxitin 2 g iv. q 6 h Or Moxifloxacin 400 mg iv. daily or ciprofloxacin 400 mg iv. q 24 h Plus Metronidazole 500 mg q 8 h^‡ (AI)	24 h (AI)	Moderate injury: Ticarcillin/clavulanate 3.1 g q 4–6 h or cefoxitin 2 g iv. q 6 h or ertapenem 1 g iv. q 24 h or moxifloxacin 400 mg iv. q 24 h^‡ Severe injury:carbapenem or piperacillin/tazobactam 4.5 g iv. q 6 h (AII)	4–7 days (BIII)	[71] [73] [74] [76] [70]

^†Several other regimens possible [58].
^‡Empiric antimicrobials should be 'de-escalated' to target susceptibility of pathogens isolated from culture as soon as possible.
iv.: Intravenously; q: Every.

Table 6. Epidemiology and recommended prophylaxis and empiric treatment for extremity infections following penetrating trauma.
Seminal papers (type)	Pathogens described	Prophylactic antibiotic of choice (level of evidence)	Duration of prophylaxis (level of evidence)	Empiric treatment of choice^† (level of evidence)	Duration of treatment (level of evidence)	Ref.
Johnson et al. (retrospective review) Mody et al. (retrospective review) Ostermann et al. (retrospective cohort) Gosselin et al. (Cochrane review) Dellinger et al. (prospective randomized) Patzakis et al. (prospective, randomized)	Soft tissue: Coagulase-negative Staphylococcus Streptococcus spp. Acinetobacter spp.^‡ Escherichia coli ^‡ Pseudomonas aeruginosa ^‡ Osteomyelitis: Staphylococcus aureus (often MRSA) Orthopedic hardware: S. aureus (often MRSA) Acinetobacter spp.	Penicillin 2–4 mu q 4 h or cefazolin 1 g iv. q 8 h^§ β-lactam allergy: Clindamycin 900 mg iv. q 6 h (BII) Local: Consider cefazolin or tobramycin beads especially in Grade III fractures (BII)	1–5 days (AI)	Gram positive: Vancomycin 15 mg/kg divided q 6 h or Daptomycin 4–6 mg/kg iv. q 24 h or linezolid 600 mg q 24 h^¶# Gram negative: Cefepime 2 g q 8 h or ceftazidime 2 g q 12 h or carbapenem (BIII)	Soft tissue: 7–14 days (BII) Osteomyelitis: 4–6 weeks (BII) Hardware: 4–6 weeks (BII)^††	[96] [99] [111] [107] [110] [109]

Empiric antimicrobials should be de-escalated to target susceptibility of pathogens isolated from culture as soon as possible.
^†Seen after 5 days of initial injury.
^‡Metronidazole added when infections develop after 72 h.
^¶Linezolid toxicity limits utility when used for >2 weeks duration.
^#Rifampin (± quinolone) may improve outcomes.
^††Duration depends upon removal of hardware.
iv.: Intravenously; MRSA: Methicillin-resistant Staphylococcus aureus; mu: Million units; q: Every.

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