Prophylaxis and Treatment of Infections Associated with Penetrating Traumatic Injury

Kyle Petersen; Paige Waterman

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

Infections of the Thorax

Epidemiology

Mortality for thoracic injury in the pre-antibiotic era was 63%^[45] but decreased to 2% during the Korean conflict, reflecting benefits of surgery and antibiotics.^[45] Thoracic trauma mortality rates in Vietnam and Bosnia were 3–4%.^[46,47] Body armor has further decreased mortality from thoracic wounds.^[10] However, in past conflicts, the majority of HE trauma reprised gunshot and grenade injuries, while currently, fragmentation devices (IEDs and rocket propelled grenades) predominate.^[48] Between 2002 and 2008, 4.9% of HE injuries in Iraq and Afghanistan were sustained thoracic injury, half civilians and half combatants.^[49] Penetrating trauma accounted for 40% of all injuries, second only to blast (45.8%). Civilian penetrating trauma rates exceeded combatants (64 vs 36%), probably due to the lack of protective body armor.^[49]

Historically, HE thoracic injuries of war have had higher infection rates (5–9%) than LE civilian injuries (3%). Delayed treatment and polytrauma (additional blast and burn components) may contribute this the discrepancy. Thoracic infections accounted for 5–10% of HE injuries in World War II (primarily empyema), as penicillin was being introduced, dropping to 2% during the Vietnam War.^[50] A recent single-center review of all HE trauma infections from Iraq revealed 14% with thoracic injuries, 23% with associated infection.^[50,51] LE (58.8%) and VLE (41.2%) penetrating trauma represented the primary causes of the 1.5% of civilian patients with post-traumatic empyema in a Turkish hospital.^[52] Pathogens commonly described include coagulase-negative Staphylococcus if a tube thoracostomy is in place.^[53] In infection developing over 48 h after injury, coagulase-negative Staphylococcus, S. aureus (including methicillin-resistant), Gram-negative facultative aerobes and anaerobes are all know to cause infection.^[53] Both Enterococcus and Candida spp. have been described when the abdominal compartment is involved.^[50]

Perioperative Prophylaxis

Historically, the greatest risk of infection in penetrating thoracic injury is retained hemothorax.^[50,54,55] Consequently, tube thoracostomy is used most often in the management of thoracic trauma to promote lung expansion and remove blood to minimize infection.^[50] Some studies cite conditions of tube insertion (prehospital vs hospital) as having a negative effect on infection,^[56] while a more recent study found no difference.^[57] Bacterial causes of infection in penetrating thoracic injury include Gram-positive, Gram-negative and anaerobic organisms, with S. aureus most commonly cited.^[53] Antimicrobial prophylaxis has not definitively improved outcomes when used before, during or after tube thoracostomy, probably because bacterial contamination occurs long before thoracostomy placement.^[58]

Prophylactic antibiotics ideally should reduce empyema and pneumonia, while inhibiting the emergence of antimicrobial resistance. Six randomized placebo-controlled trials failed to show that prophylactic antibiotics statistically reduced infection rates.^[50] A study of post-thoracostomy cefazolin administration demonstrated no reduction in empyema or pneumonia incidence. However, a recent meta-analysis (including the cited study), demonstrated an overall reduction in empyema when primarily cephalosporins were administered for 24 h following thoracostomy placement. Duration of therapy remains in question, however; if adequate source control and drainage is achieved, 24 h is likely adequate.^[59] In summary, for thoracic injury (Table 4), based upon consensus opinion,^[50] one prospective trial^[60] and a meta-analysis^[59] (BII level of evidence), we recommend cefazolin for use with empyema in the presence of tube thoracostomy. In addition, aminoglycosides should be avoided in this setting. Duration of therapy based upon one prospective trial^[60] and a meta-analysis,^[59] should be no longer than 24 h (BII).

Antibiotic Therapy for Infection

Empyema is often present and is caused by skin flora which are probably introduced by tube thoracostomy placement or immediately following trauma. Furthermore, pneumonia is also often present as a complication of injury or concomitant ventilatory support.^[60] Source control and drainage of fluid is appropriate for all empyemas, as is performing a pH test, Gram stain and culture of available fluid. Although Maxwell et al. found no benefit in terms of reduced incidence of empyema or pneumonia in their small study, first-generation cephalosporin is preferred in this setting or when staining indicates Gram-positive organisms.^[60] Gram-negative coverage should be added if Gram stain is indicative, or for infections developing over 48 h after hospital admission.^[50] Enteric contamination, including B. fragilis, can occur in the polytrauma patient, and should be treated with fluoroquinolones or third-generation cephalosporins with metronidazole; alternatively ticarcillin/clavulanic acid, piperacillin/tazobactam or moxifloxacin monotherapy can be used.^[50] Nosocomial pathogens should be targeted in any patient with sepsis or receiving antimicrobials after 48 h or with signs of systemic inflammatory response syndrome over 48 h following surgery. In these cases, carbapenems, advanced cephalosporins (ceftazidime and cefepime) with metronidazole, or aztreonam with metronidazole provide good coverage.^[50] Clindamycin, while useful for thoracic cavity infections, may not be adequate for B. fragilis owing to resistance.^[61] Coverage for Enterococcus spp. and Candida spp. should also be considered for contaminated IAIs penetrating into the thoracic cavity.^[50] Hospital-specific antibiograms can also aid in empiric antimicrobial selection. Guidelines regarding duration of therapy recommend 3 weeks, although if adequate drainage is achieved earlier, courses may be shortened.^[62] In summary, or empiric treatment of infections of the thorax in the setting of traumatic injury (Table 4) or for infections that develop greater than 48 h after admission and tube thoracostomy (i.e., delayed), based upon consensus opinion^[50] and meta-analysis^[59] (BIII level of evidence), we recommend vancomycin combined with an antipseudomonal third-generation cephalosporin or carbapenem with treatment for 21 days (BIII level of evidence).

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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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