Cefazolin

• Mechanism of Action: Bactericidal; inhibition of bacterial cell wall synthesis
• Dose: Intravenous, 2g (3g if >120 kg), q8h
• Pharmacokinetics: Half-life is approximately 1.8 hours following IV administration
• Contraindications: Cephalosporin hypersensitivity or cephamycin hypersensitivity
• Adverse Effects: Hypersensitivity reactions, C. difficile-associated diarrhea, central line infections, nosocomial pneumonia secondary to resistant and/or Gram-negative bacteria, white patches or sores in the mouth or lips
• Pearls: Preferred initial antibiotic for open fractures; Duration: 24 hours
• Spectrum of Activity
  • Gram-positive aerobes
    • Staphylococcus aureus (including beta-lactamase producing strains)
    • Staphylococcus epidermidis
    • Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus pneumoniae and other strains of streptococci
  • Gram-negative bacteria
    • Moraxella catarrhalis, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis

Metronidazole

• Mechanism of Action: Bactericidal; inhibition of bacterial cell wall synthesis
• Dose: Intravenous, 500mg, q8h
• Pharmacokinetics: Half-life is 7.3 ± 1.0 after a single 500mg IV dose in healthy subjects
• Contraindications: Hypersensitivity to metronidazole or other nitroimidazole derivatives
• Adverse Effects: Hypersensitivity reactions, irritability, sleep problems, depression, headache, rash, constipation, nausea, mouth sores
• Pearls: Preferred antibiotic for Type I and II open fracture with soil or feces contamination (with or without Penicillin G 4 million units IV, q4h); Duration: 24 hours
• Spectrum of Activity
  • Anaerobic Gram-negative bacilli:  Bacteroides fragilis, Bacteroides species, Fusobacterium spp., Porphyromonas spp., Prevotella spp.
  • Anaerobic Gram-positive bacilli:  Clostridium spp.
  • Anaerobic cocci:  Peptostreptococcus species, Veillonella species
  • Protozoa:  Blastocystis hominis, Entamoeba histolytica, Giardia lamblia, Trichomonas vaginalis

Clindamycin

• Mechanism of Action: Bacteriostatic; binds to the 50s ribosomal subunit of bacteria
• Dose: Intravenous, 900 mg, q8h
• Pharmacokinetics: Elimination half-life of clindamycin is about 3 hours in adults and 2.5 hours in children
• Contraindications: Hypersensitivity to preparations containing clindamycin or lincomycin, Myasthenia gravis, Crohn’s disease, ulcerative colitis, severe liver and renal impairment
• Adverse Effects: Hypersensitivity reactions, C. difficile-associated diarrhea, nausea, vomiting, stomach pain, mild skin rash, vaginal itching or discharge
• Pearls: Preferred antibiotic for severe beta-lactam allergy
• Spectrum of Activity
  • Streptococcus spp., Staphylococcus spp., H. influenzae, M. catarrhalis, Bacteroides spp., (Clostridia spp.of variable susceptibility) Prevotella spp., Fusobacterium spp., Veillonella spp., Chlamydia trachomatis

Vancomycin

• Mechanism of Action: Bactericidal; Inhibits cell wall synthesis by binding to the D-Ala-D-Ala terminal of the growing peptide chain during cell wall synthesis
• Dose: Intravenous, 15mg/kg, q12h
• Pharmacokinetics: Half-life is approximately 1.8 hours following IV administration
• Contraindications: Systemic mastocytosis, low levels of neutrophils, patients with kidney disease
• Adverse Effects: Hypersensitivity reactions, bitter taste to the tongue, reddish rash on face and upper body (red neck or red man syndrome related to infusion rate), low blood pressure, eosinophilia, rash, bloody urine or stool, tinnitus
• Pearls: Preferred initial antibiotic for patients with known MRSA colonization and/or severe PCN allergy
• Spectrum of Activity
  • Staphylococcus aureus (vancomycin susceptible), Coagulase negative Staphylococci, Streptococcus pneumoniae, Streptococcus spp., Enterococcus spp. (Vancomycin-susceptible), C. jeikeium, Clostridium spp., L. monocytogenes, Actinomyces

Type III Open Fractures with No Gross Contamination

Ceftriaxone

• Mechanism of Action: Bactericidal; inhibits the mucopeptide synthesis in the bacterial cell wall
• Dose: Intravenous, 2g, q24h
• Pharmacokinetics: Elimination half-life of ceftriaxone is 5.8-8.7 hours
• Contraindications: Hemolytic anemia, liver problems, diseases of the gal bladder, severe renal impairment
• Adverse Effects: Hypersensitivity reactions, black or tarry stools caused by C. difficile-associated diarrhea, chest pain, shortness of breath, unusual tiredness or weakness, sores or white spots on the lips or mouth, swollen glands
• Pearls: Duration: 24-72 hours but not more than 24 hours after wound closure
• Spectrum of Activity:
  • Staphylococcus aureus (methicillin susceptible), Coagulase negative Staphylococci, Streptococcus pneumoniae (penicillin susceptible), Streptococcus spp., Haemophilus influenzae, Moraxella catarrhalis, Neisseria meningitides, Neisseria gonorrhoeae, Enterobacteriaceae, E.coli

Or

Administer Cefazolin 2g IV, q8h + Gentamicin 5mg/kg IV q24h

• For Severe PCN allergy, administer:

Clindamycin 900mg IV q8h + Levofloxacin 500mg IV q24h

Type III Open Fractures with Standing Water Contamination

Piperacillin-Tazobactam

• Mechanism of Action: Bacteriostatic; inhibition of bacterial cell wall synthesis by binding to penicillin binding proteins
• Dose: Intravenous, dosed per policy and is adjusted based on renal function
• Pharmacokinetics: Half-lives are 1.14 hours for Piperacillin and 0.92 hours for Tazobactam
• Contraindications: Low blood potassium, low seizure threshold, low neutrophil count
• Adverse Effects: Hypersensitivity reactions, diarrhea – most common, bladder pain, burning upper abdominal or stomach pain, changes in urination, fever or sweating, blurred vision, pain or burning sensation on extremities, nausea, inconsistent heartbeat
• Pearls: Duration: 24-72 hours but not more than 24 hours after wound closure; Consider infectious diseases consult
• Spectrum of Activity
  • Staphylococcus aureus (methicillin susceptible), Coagulase negative Staphylococci, Streptococcus pneumoniae (penicillin susceptible), Streptococcus spp., Haemophilus influenzae, Moraxella catarrhalis, Neisseria meningitides, Neisseria gonorrhoeae, Enterobacteriaceae, E. coli, Pseudomonas aeruginosa, Clostridium sp, Prevotella bivia(Bacteroides), fusobacterium necrophorum, Prevotella intermedius.

• For Severe PCN allergy, administer:

Levofloxacin 500mg IV q24h + Metronidazole 500mg IV, q8h

• For Acutely intoxicated patients with Severe PCN allergy, administer:

Clindamycin 900mg IV, q8h + Levofloxacin 500mg IV, q24h

• For patients with known MRSA colonization in injury, administer:

+ Vancomycin 15mg/kg IV, q12h