Cefazolin

Mechanism of Action

First-generation semisynthetic cephalosporin that binds to 1 or more penicillin-binding proteins, thereby arresting bacterial cell-wall synthesis and inhibiting bacterial replication; has poor capacity to cross blood-brain barrier; primarily active against skin flora, including S aureus

Absorption

Peak plasma time: 0.5-2 hr (IM); 5 min (IV)

Distribution

Crosses placenta; penetrates CSF poorly

Protein bound: 74-86%

Metabolism

Minimally metabolized in liver

Elimination

Half-life: 90-150 min

Excretion: Urine (80-100% as unchanged drug)

IV and IM dosing regimens are similar; drug is primarily active against skin flora, including S aureus, and is typically used alone for skin and skin-structure coverage

IV Incompatibilities

Additive: Amikacin, gentamicin

Syringe: Cimetidine, lidocaine

Y-site: Amiodarone(?), amphotericin B

Not specified: Erythromycin, norepinephrine, pentobarbital, tetracycline

IV Compatibilities

Additive: Cimetidine, verapamil

Y-site: Aminophylline, amiodarone(?), calcium gluconate, lidocaine, vitamins B and C

Not specified: Ampicillin, diazepam, hydrocortisone, potassium chloride

IV Preparation

Reconstitute 500 mg or 1 g with 2 mL or 2.5 mL SWI, respectively, to provide solutions containing approximately 225 or 330 mg/mL

IV push: Further dilute in approximately 5 mL of SWI or according to manufacturer's directions

Infusion: Dilute reconstituted 500 mg or 1 g solution in 50-100 mL NS or D5W

IM Preparation

Reconstitute 500 mg or 1 g with 2 mL or 2.5 mL SWI, respectively, to provide solutions containing approximately 225 or 330 mg/mL

IV Administration

IV push

• Administer directly into vein, and infuse over 3-5 minutes or slowly into tubing of compatible IV infusion solution
• Solution is usually light-yellow to yellow
• Discard if precipitate is present

Infusion: volume control set or piggyback container

• IV infusion stable for 24 hours at room temperature and 96 hours refrigerated

IM Administration

Inject deep into large muscle mass

Cefazolin is a prescription medication used to treat bacterial infections, including lung, skin, bone, joint, stomach, blood, heart valve, and urinary tract infections. It is also used to prevent infection before, during, and after surgery. Cefazolin belongs to a group of drugs called cephalosporin antibiotics. These work by stopping the growth of bacteria in the body.

This medication is available in an injectable form to be given directly into a vein (IV) or into a muscle (IM) by a healthcare professional.

Common side effects of cefazolin include diarrhea and upset stomach.

Tell your doctor if you are pregnant or plan to become pregnant.

The FDA categorizes medications based on safety for use during pregnancy. Five categories - A, B, C, D, and X - are used to classify the possible risks to an unborn baby when a medication is taken during pregnancy.

Cefazolin falls into category B. There are no well-done studies that have been done in humans with cefazolin. In animal studies, pregnant animals were given this medication, and the babies did not show any medical issues related to this medication.

If you take too much cefazolin, call your healthcare provider or local Poison Control Center, or seek emergency medical attention right away.

If cefazolin is administered by a healthcare provider in a medical setting, it is unlikely that an overdose will occur. However, if overdose is suspected, seek emergency medical attention.

(sef A zoe lin)

• Antibiotic, Cephalosporin (First Generation)

Catheter-related bloodstream infections (adults)

IDSA clinical practice guidelines state that the use of cefazolin in catheter-related bloodstream infections may be appropriate when the infection is due to methicillin-susceptible S. aureus or methicillin-susceptible, coagulase-negative Staphylococcus species.

Community-acquired pneumonia (children)

Following clinical guideline recommendations on the management of CAP reduces the incidence of morbidity and mortality related to pneumonia. IV cefazolin is a preferred agent for treatment of children with CAP due to MSSA. To potentially reduce morbidity and mortality, therapy should be initiated in the inpatient setting.

Infective endocarditis (prophylaxis)

Based on the American Heart Association (AHA) guidelines for the prevention of infective endocarditis, cefazolin is effective and recommended for administration to patients with certain cardiac conditions who are unable to take oral medication or are allergic to penicillins or ampicillin and unable to take oral medication to provide prophylaxis against infective endocarditis associated with dental or respiratory tract procedures.

Prophylaxis in patients with prosthetic joint implants undergoing dental procedures which produce bacteremia

Although currently not recommended for routine use prior to dental procedures in patients with prosthetic joint implants to prevent prosthetic joint infection as stated within the American Academy of Orthopaedic Surgeons/American Dental Association Prevention of Orthopaedic Implant Infection in Patients Undergoing Dental Procedures guidelines and a subsequent report of the American Dental Association Council on Scientific Affairs, if deemed to be necessary for select patients at risk for prosthetic joint infection (eg, history of complications associated with joint replacement surgery), antibiotic prophylaxis may be considered. Dentists planning invasive oral procedures should therefore consult with the patient's orthopedic surgeon to determine the risk associated with infection and the need for antibiotics. Based on a retired advisory statement from the American Dental Association and American Academy of Orthopaedic Surgeons, the use of cefazolin (or ampicillin) was suggested for patients not allergic to penicillin and unable to take oral medications [ADA/AAOS 2003].

Skin and soft tissue necrotizing infections

Based on the Infectious Diseases Society of America (IDSA) guidelines for the diagnosis and management of skin and soft tissue infections (SSTI), cefazolin, is an effective and recommended alternative for treatment of necrotizing infections of the skin, fascia, and muscle due to methicillin-sensitive S. aureus.

Surgical site infection

Based on the Infectious Diseases Society of America (IDSA) guidelines for the diagnosis and management of skin and soft tissue infections (SSTI), cefazolin is an effective and recommended option for treatment of surgical site infections occurring after surgery of the trunk or extremity (away from axilla or perineum). Systemic antibacterials are not routinely indicated for surgical site infections, but may be beneficial (in conjunction with suture removal plus incision and drainage) in patients with significant systemic response (eg, temperature >38.5ºC, heart rate >110 beats per minute, erythema/induration extending >5 cm from incision, WBC >12,000/mm3).

Adults:

CrCl ≥55 mL/minute: No dosage adjustment necessary

CrCl 35 to 54 mL/minute: Administer full dose in intervals of ≥8 hours

CrCl 11 to 34 mL/minute: Administer 50% of usual dose every 12 hours

CrCl ≤10 mL/minute: Administer 50% of usual dose every 18 to 24 hours

Intermittent hemodialysis (IHD) (administer after hemodialysis on dialysis days): Dialyzable (20% to 50%): 500 mg to 1 g every 24 hours or use 1 to 2 g every 48 to 72 hours (Heintz 2009) or 15 to 20 mg/kg (maximum dose: 2 g) after dialysis 3 times weekly (Ahern 2003; Sowinski 2001) or 2 g after dialysis if next dialysis expected in 48 hours or 3 g after dialysis if next dialysis is expected in 72 hours (Stryjewski 2007).

Note: Dosing dependent on the assumption of 3 times weekly, complete IHD sessions.

Peritoneal dialysis (PD): IV: 500 mg every 12 hours

Continuous renal replacement therapy (CRRT) (Heintz 2009; Trotman 2005): Drug clearance is highly dependent on the method of renal replacement, filter type, and flow rate. Appropriate dosing requires close monitoring of pharmacologic response, signs of adverse reactions due to drug accumulation, as well as drug concentrations in relation to target trough (if appropriate). The following are general recommendations only (based on dialysate flow/ultrafiltration rates of 1 to 2 L/hour and minimal residual renal function) and should not supersede clinical judgment:

CVVH: Loading dose of 2 g followed by 1 to 2 g every 12 hours

CVVHD/CVVHDF: Loading dose of 2 g followed by either 1 g every 8 hours or 2 g every 12 hours. Note: Dosage of 1 g every 8 hours results in similar steady-state concentrations as 2 g every 12 hours and is more cost effective (Heintz 2009).

Infants >1 month, Children, and Adolescents:

CrCl >70 mL/minute: No dosage adjustment necessary.

CrCl 40 to 70 mL/minute: 60% of usual daily dose divided every 12 hours

CrCl 20 to 40 mL/minute: 25% of usual daily dose divided every 12 hours

CrCl 5 to 20 mL/minute: 10% of usual daily dose every 24 hours

Intermittent hemodialysis (IHD): 25 mg/kg per dose every 24 hours (Aronoff 2007)

Peritoneal dialysis (PD): 25 mg/kg per dose every 24 hours (Aronoff 2007)

Continuous renal replacement therapy (CRRT): 25 mg/kg per dose every 8 hours (Aronoff 2007)

Dilute 500 mg vial with 2 mL SWFI and 1 g vial with 2.5 mL SWFI; reconstituted solution may be directly injected after further dilution with 5 mL SWFI or further diluted for IV administration in 50 to 100 mL compatible solution (eg, D5W, NS); 10 g vial may be diluted with 45 mL to yield 1 g/5 mL or 96 mL to yield 1 g/10 mL.

IM: Inject deep IM into large muscle mass.

IV: Inject direct IV over 3 to 5 minutes or may infuse as an intermittent infusion over 30 to 60 minutes.

Some penicillins (eg, carbenicillin, ticarcillin and piperacillin) have been shown to inactivate aminoglycosides in vitro. This has been observed to a greater extent with tobramycin and gentamicin, while amikacin has shown greater stability against inactivation. Concurrent use of these agents may pose a risk of reduced antibacterial efficacy in vivo, particularly in the setting of profound renal impairment. However, definitive clinical evidence is lacking. If combination penicillin/aminoglycoside therapy is desired in a patient with renal dysfunction, separation of doses (if feasible), and routine monitoring of aminoglycoside levels, CBC, and clinical response should be considered.