VA Class:AM115

AHFS Class:

• First Generation Cephalosporins 8:12.06.04

Generic Name(s):

• ceFAZolin Sodium

Associated Monographs

• Cephalosporins General Statement

Cefazolin sodium is a semisynthetic, first generation cephalosporin antibiotic.

Biliary Tract Infections

Cefazolin is used for the treatment of biliary tract infections caused by susceptible Escherichia coli ,100,115,116,117,119 Klebsiella ,115,116 Proteus mirabilis ,100,115,116,117,119 Staphylococcus aureus ,100,115,116,117,119 or various streptococci.100,115,116,117,119

Bone and Joint Infections

Cefazolin is used for the treatment of bone and joint infections caused by susceptible S. aureus .100,115,116,117,119

Endocarditis

Treatment

Staphylococcal Endocarditis

Cefazolin is used as an alternative to nafcillin or oxacillin for the treatment of staphylococcal endocarditis, including infections caused by coagulase-positive strains ( S. aureus )114,115,116,117,119 or coagulase-negative strains (e.g., S. epidermidis , S. lugdunensis )100,113,114 in penicillin-allergic patients (nonanaphylactoid type only). Cefazolin should not be used in patients with a history of immediate-type penicillin hypersensitivity (urticaria, angioedema, anaphylaxis).100,113,114,115,116,117

For the treatment of native valve endocarditis caused by oxacillin-susceptible (methicillin-susceptible) staphylococci, the American Heart Association (AHA) and Infectious Diseases Society of America (IDSA) recommend a regimen of IV nafcillin or oxacillin with or without IV or IM gentamicin.113,114 For penicillin-allergic patients (nonanaphylactoid type only), a regimen of IV cefazolin with or without IV or IM gentamicin is recommended.113,114 In patients with complicated right-sided staphylococcal endocarditis or with left-sided staphylococcal endocarditis, a 6-week regimen of the β-lactam should be used and gentamicin given concomitantly during the first 3-5 days of treatment.113 In those with uncomplicated right-sided staphylococcal endocarditis (i.e., patients with no evidence of renal failure, extrapulmonary metastatic infections, aortic or mitral valve involvement, meningitis, or oxacillin-resistant strains), a 2-week regimen that includes both the β-lactam and gentamicin can be considered.113

Staphylococcal endocarditis in patients with prosthetic valves or other prosthetic material usually is caused by oxacillin-resistant staphylococci, especially when endocarditis develops within 1 year after surgery, and is associated with high morbidity and mortality rates.113 Unless susceptibility to oxacillin has been demonstrated using in vitro susceptibility testing, it should be assumed that patients with staphylococcal prosthetic valve endocarditis have oxacillin-resistant strains.113 If prosthetic valve endocarditis is known to be caused by oxacillin-susceptible staphylococci, the AHA and IDSA recommend at least 6 weeks of IV nafcillin or oxacillin in conjunction with IV or oral rifampin and concomitant use of IV or IM gentamicin during the initial 2 weeks of treatment.113 If the strain is known to be penicillin susceptible (i.e., penicillin MIC 0.1 mcg/mL or less) and does not produce β-lactamase, IV penicillin G sodium can be substituted for nafcillin or oxacillin in this regimen; for penicillin-allergic patients (nonanaphylactoid type only), IV cefazolin can be substituted for nafcillin or oxacillin.113

Cefazolin and other cephalosporins should not be used for the treatment of endocarditis caused by oxacillin-resistant staphylococci, despite the fact that in vitro testing may indicate the strains are susceptible.113 If the strain is known or presumed to be oxacillin-resistant, the AHA and IDSA recommend at least 6 weeks of IV vancomycin in conjunction with IV or oral rifampin and concomitant use of IV or IM gentamicin during the initial 2 weeks of treatment.113

Streptococcal Endocarditis

Cefazolin is used as an alternative to penicillin G sodium for the treatment of endocarditis caused by susceptible Streptococcus pyogenes (group A β-hemolytic streptococci),100,113,115,116,117,119 or S. pneumoniae †.113

For the treatment of endocarditis caused by highly penicillin-susceptible S. pneumoniae †, the AHA and IDSA recommend a 4-week regimen of penicillin G sodium, cefazolin, or ceftriaxone.113 Vancomycin should only be used in patients who cannot receive a β-lactam.113 It has been suggested that high-dose treatment with penicillin G sodium or a third-generation cephalosporin can be used in patients with endocarditis caused by penicillin-resistant S. pneumoniae provided meningitis is not present.113 However, penicillin-resistant S. pneumoniae often are cross-resistant to cephalosporins, and consultation with an infectious disease specialist is recommended whenever decisions are being made regarding treatment of pneumococcal endocarditis.113

For the treatment of endocarditis caused by S. pyogenes , the AHA and IDSA recommend a 4-week regimen of IV penicillin G sodium.113 In penicillin-allergic patients (nonanaphylactoid type only), cefazolin or ceftriaxone are acceptable alternatives.113 Vancomycin should only be used in patients who cannot receive a β-lactam.113

For the treatment of endocarditis caused by groups B, C, or G streptococci, the AHA and IDSA recommend 4-6 weeks of IV penicillin G sodium or, alternatively, a cephalosporin; some clinicians recommend that gentamicin be added to the regimen for at least the first 2 weeks.113 Consultation with an infections disease specialist is recommended.113

Prevention

Cefazolin is used for the prevention of α-hemolytic (viridans group) streptococcal endocarditis† in penicillin-allergic individuals undergoing certain dental or upper respiratory tract procedures who have cardiac conditions that put them at highest risk.104 Oral amoxicillin is the usual drug of choice for such prophylaxis.104 Cefazolin is an alternative in penicillin-allergic individuals or when an oral anti-infective cannot be used.104 Cefazolin should not be used in those with immediate-type penicillin hypersensitivity (e.g., urticaria, angioedema, anaphylaxis).104

For information on which cardiac conditions are associated with the highest risk of endocarditis and which procedures require prophylaxis, see Prevention under Uses: Endocarditis, in the Cephalosporins General Statement 8:12.06. When selecting anti-infectives for prophylaxis of bacterial endocarditis, the current recommendations published by the AHA should be consulted.104

Respiratory Tract Infections

Cefazolin is used for the treatment of respiratory tract infections caused by susceptible S. pneumoniae ,100,115,116,117,119 S. pyogenes (group A β-hemolytic streptococci),100,115,116,117,119 S. aureus (including penicillin-resistant strains),100,115,116,117,119 Klebsiella ,115,116 or Haemophilus influenzae .115,116

Septicemia

Cefazolin is used for the treatment of septicemia caused by susceptible S. pneumoniae ,100,115,116,117,119 S. aureus (including penicillinase-producing strains),100,115,116,117,119 E. coli ,100,115,116,117,119 Klebsiella ,115,116 or P. mirabilis .100,115,116,117,119

Skin and Skin Structure Infections

Cefazolin is used for the treatment of skin or skin structure infections caused by susceptible S. aureus (including penicillinase-producing strains),100,115,116,117,119 S. pyogenes ,100,115,116,117,119 or other streptococci.100,115,116,117,119

Urinary Tract and Urogenital Infections

Cefazolin is used for the treatment of urinary tract infections caused by susceptible E. coli ,100,115,116,117,119 P. mirabilis ,115,116,117,119 Klebsiella ,115,116 some strains of Enterobacter ,115,116 or some strains of enterococci.115,116

Cefazolin is used for the treatment of prostatitis or epididymitis caused by susceptible E. coli ,100,115,116,117,119 Klebsiella ,115,116 P. mirabilis ,100,115,116,117,115,116,119 or some strains of enterococci.115,116

Prevention of Perinatal Group B Streptococcal Disease

In certain penicillin-allergic women, cefazolin is used as an alternative to penicillin G or ampicillin for prevention of perinatal group B streptococcal (GBS) disease†.111

Pregnant women who are colonized with GBS in the genital or rectal areas can transmit GBS infection to their infants during labor and delivery resulting in invasive neonatal infection that can be associated with substantial morbidity and mortality.111 Intrapartum anti-infective prophylaxis for prevention of early-onset neonatal GBS disease is administered selectively to women at high risk for transmitting GBS infection to their neonates.111 The US Centers for Disease Control and Prevention (CDC), American Academy of Pediatrics (AAP), and other experts recommend routine universal prenatal culture-based screening for GBS colonization (vaginal and rectal cultures) in all pregnant women at 35-37 weeks of gestation, unless GBS bacteriuria is known to be present during the current pregnancy or the woman had a previous infant with invasive GBS disease.111 These experts state that anti-infective prophylaxis to prevent perinatal GBS disease is indicated in pregnant women identified as GBS carriers during the routine prenatal GBS screening performed at 35-37 weeks during the current pregnancy, in women with GBS bacteriuria identified at any time during the current pregnancy, and in women who had a previous infant diagnosed with invasive GBS disease.111 Anti-infective prophylaxis to prevent perinatal GBS disease also is indicated in women with unknown GBS status at the time of onset of labor (i.e., culture not done, incomplete, or results unknown) if delivery is at less than 37 weeks of gestation, the duration of amniotic membrane rupture is 18 hours or longer, intrapartum temperature is 38°C or higher, or an intrapartum nucleic acid amplification test (NAAT) was positive for GBS.111

When intrapartum prophylaxis is indicated in the mother to prevent GBS disease in the neonate, it should be given at onset of labor or rupture of membranes.111 The CDC, AAP, and other experts recommend penicillin G as the drug of choice and ampicillin as the preferred alternative for such prophylaxis.111 If intrapartum prophylaxis is indicated in a penicillin-allergic woman who is not at high risk for anaphylaxis (i.e., does not have a history of anaphylaxis, angioedema, respiratory distress, or urticaria after receiving a penicillin or cephalosporin), IV cefazolin is recommended.111 If intrapartum prophylaxis is indicated in a penicillin-allergic woman who is at high risk for anaphylaxis (e.g., history of anaphylaxis, angioedema, respiratory distress, or urticaria after receiving a penicillin or cephalosporin), IV clindamycin is recommended if the GBS isolate is susceptible to the drug;111 alternatively, IV vancomycin can be used if the isolate is resistant to clindamycin,111

For additional information regarding prevention of perinatal group B streptococcal disease, the current CDC guidelines available at [Web] should be consulted.111

Perioperative Prophylaxis

Cefazolin is used perioperatively to reduce the incidence of infection in patients undergoing certain cardiac surgery (e.g., coronary artery bypass, placement of cardiac devices), noncardiac thoracic surgery (e.g., lobectomy), vascular surgery (arterial surgery involving the abdominal aorta, a prosthesis, or a groin incision or lower extremity amputation for ischemia), head and neck surgery involving incisions through oral or pharyngeal mucosa, neurosurgery (e.g., craniotomy, spinal surgery), orthopedic surgery (e.g., total joint replacement, surgical repair of closed fractures, internal fixation of compound or open fractures), GI surgery (gastroduodenal, esophageal, biliary tract, colorectal, appendectomy, bariatric), genitourinary surgery (e.g., open or laparoscopic surgery including percutaneous renal surgery, procedures with entry into the urinary tract or implantation of a prosthesis), and gynecologic and obstetric surgery (cesarean section or vaginal, abdominal, or laparoscopic hysterectomy).100,102,103,106,107,108,109,110,115,116,117,119 Published guidelines and protocols for perioperative prophylaxis should be consulted for recommendations regarding specific procedures.102,103

Because cefazolin has a narrow spectrum of activity that covers the most likely surgical site pathogens, has a moderately long serum half-life, and has been shown to be effective, it is considered by many clinicians to be the drug of choice for perioperative prophylaxis for a wide variety of contaminated or potentially contaminated procedures.102,103 Cefazolin also is recommended as a drug of choice for perioperative prophylaxis in patients undergoing heart, lung, heart-lung, pancreas, and pancreas-kidney transplantation.103

If cefazolin is used for perioperative prophylaxis in patients undergoing certain GI procedures (e.g., colorectal surgery, appendectomy) that might involve exposure to Bacteroides fragilis or other anaerobic bowel bacteria or in patients undergoing head and neck surgery involving incisions through oral or pharyngeal mucosa, it should be used in conjunction with metronidazole to provide anaerobic coverage.102,103 (See Uses: Perioperative Prophylaxis, in the Cephalosporins General Statement 8:12.06.)

Reconstitution and Administration

Cefazolin sodium is administered by IV injection or infusion100,115,116,117,119 or by deep IM injection.100,115 The drug also has been administered intraperitoneally in dialysis solutions†.

Prior to administration, cefazolin solutions should be inspected visually for particulate matter; if particulate matter is evident, the solution should be discarded.100,115,116,117,119

Intermittent IV Injection

For direct IV injection, vials labeled as containing 500 mg or 1 g of cefazolin should be reconstituted with 2 or 2.5 mL, respectively, of sterile water for injection to provide solutions containing approximately 225 or 330 mg/mL, respectively.100,115 These solutions should be further diluted in approximately 5 mL of sterile water for injection, or according to the manufacturers' directions.100,115

The appropriate dose should then be injected over a period of 3-5 minutes directly into a vein or the tubing of a freely flowing compatible IV solution.100,115

Intermittent or Continuous IV Infusion

For intermittent IV infusion, vials labeled as containing 500 mg or 1 g of cefazolin should be reconstituted with 2 or 2.5 mL, respectively, of sterile water for injection to provide solutions containing approximately 225 or 330 mg/mL, respectively.100,115 The reconstituted solutions should be further diluted in 50-100 mL of a compatible IV solution.100,115

Alternatively, the commercially available Duplex^® drug delivery system containing 1 or 2 g of cefazolin and 50 mL of dextrose 4 or 3% injection, respectively, in separate chambers should be reconstituted (activated) according to the manufacturer's directions and administered by IV infusion.117

Cefazolin pharmacy bulk vials should be reconstituted according to the manufacturer's directions and then further diluted in a compatible IV solution prior to IV infusion.100,116 The reconstituted solutions should be used promptly; the pharmacy bulk vial should be discarded within 4 hours after initial entry.100,116

Thawed solutions of the commercially available frozen premixed cefazolin sodium injection in dextrose should be given only by intermittent or continuous IV infusion.119 The frozen injection should be thawed at room temperature (25°C) or under refrigeration (5°C); the injection should not be thawed by warming in a water bath or by exposure to microwave radiation.119 Precipitates that may have formed in the frozen injection usually will dissolve with little or no agitation when the injection reaches room temperature; potency is not affected.119 After thawing to room temperature, the injection should be agitated and the container checked for minute leaks by firmly squeezing the bag.119 The injection should be discarded if container seals or outlet ports are not intact or leaks are found or if the solution is cloudy or contains an insoluble precipitate.119 Additives should not be introduced into the injection container.119 The injection should not be used in series connections with other plastic containers, since such use could result in air embolism from residual air being drawn from the primary container before administration of fluid from the secondary container is complete.119

IM Injection

IM injections of cefazolin sodium are prepared by reconstituting vials labeled as containing 500 mg or 1 g of cefazolin with 2 or 2.5 mL, respectively, of sterile water for injection to provide solutions containing approximately 225 or 330 mg/mL, respectively.100,115

IM injections of cefazolin should be made deeply into a large muscle mass.100,115

Dosage

Dosage of cefazolin sodium is expressed in terms of cefazolin and is identical for IM or IV administration.110,115,116,117,119

To avoid unintentional overdosage, the commercially available Duplex^® drug delivery system containing cefazolin and dextrose injection and the commercially available frozen premixed cefazolin injection in dextrose should not be used in patients who require less than the entire 1- or 2-g dose in the container.117,119

Adult Dosage

General Adult Dosage

The usual adult dosage of cefazolin for the treatment of mild infections caused by susceptible gram-positive cocci is 250-500 mg every 8 hours.100,115,116,117,119

The usual adult dosage of cefazolin for the treatment of moderate to severe infections is 0.5-1 g every 6-8 hours.100,115,116,117,119

The usual adult dosage of cefazolin for the treatment of severe, life-threatening infections (e.g., endocarditis, septicemia) is 1-1.5 g every 6 hours.100,115,116,117,119 In rare instances, up to 12 g daily has been used.100,115,116,117,119

Endocarditis Treatment

For the treatment of endocarditis caused by staphylococci or Streptococcus pneumoniae , the manufacturers recommend that adults receive 1-1.5 g of cefazolin every 6 hours.100,115,116,117,119 Dosage up to 12 g daily has been used.100,115,116,117,119

If IV cefazolin is used for the treatment of native valve staphylococcal endocarditis in penicillin-allergic patients (nonanaphylactoid type only) with oxacillin-susceptible (methicillin-susceptible) strains, the American Heart Association (AHA) and Infectious Diseases Society of America (IDSA) recommend that adults receive 6 g daily given in 3 equally divided doses; cefazolin should be given for 6 weeks and may be used with or without IM or IV gentamicin (3 mg/kg daily in 3 equally divided doses given during the first 3-5 days of the cefazolin regimen).113

If IV cefazolin is used for the treatment of prosthetic valve staphylococcal endocarditis in penicillin-allergic patients (nonanaphylactoid type only) with oxacillin-susceptible strains, the AHA and IDSA recommend that adults receive 6 g daily given in 3 equally divided doses; cefazolin should be given for 6 weeks or longer and used in conjunction with IV or IM gentamicin (3 mg/kg daily given in 2 or 3 equally divided doses during the first 2 weeks of treatment) and IV or oral rifampin (900 mg daily given in 3 equally divided doses for 6 weeks or longer).113

If cefazolin is used for the treatment of endocarditis caused by susceptible S. pyogenes or S. pneumoniae †, the AHA recommends a treatment duration of 4 weeks.113

If cefazolin is used for the treatment of endocarditis caused by groups B, C, or G streptococci†, a treatment duration of 4-6 weeks is recommended and some clinicians also include gentamicin during at least the first 2 weeks.113 Consultation with an infectious disease specialist is recommended.113

Endocarditis Prevention

If cefazolin is used as an alternative for prevention of α-hemolytic (viridans group) streptococcal endocarditis† in individuals considered to be at highest risk for bacterial endocarditis following certain dental or upper respiratory tract procedures, adults should receive a single 1-g IM or IV dose administered 0.5-1 hour prior to the procedure.104 Cefazolin should not be used for such prophylaxis in individuals with a history of immediate-type hypersensitivity reactions to penicillin.104

Respiratory Tract Infections

The usual adult dosage of cefazolin for the treatment of pneumonia caused by S. pneumoniae is 500 mg every 12 hours.100,115,116,117,119

Septicemia

The usual adult dosage of cefazolin for the treatment of septicemia is 1-1.5 g every 6 hours.100,115,116,117,119 Dosage up to 12 g daily has been used.100,115,116,117,119

Urinary Tract Infections

The usual adult dosage of cefazolin for the treatment of acute, uncomplicated urinary tract infections is 1 g every 12 hours.100,115,116,117,119

Prevention of Perinatal Group B Streptococcal Disease

If cefazolin is used for intrapartum anti-infective prophylaxis for prevention of perinatal group B streptococcal (GBS) disease in women with penicillin hypersensitivity who are not at risk for anaphylaxis, the US Centers for Disease Control and Prevention (CDC) recommends that an initial 2-g IV dose of cefazolin be given at the time of onset of labor or rupture of membranes followed by 1 g IV every 8 hours until delivery.111 (See Uses: Prevention of Perinatal Group B Streptococcal Disease.)

Perioperative Prophylaxis

For perioperative prophylaxis in contaminated or potentially contaminated surgery, the manufacturers recommend that adults receive 1 or 2 g of cefazolin IM or IV 30-60 minutes prior to surgery and state that additional doses of 0.5-1 g may be given IM or IV during the procedure.100,115,116,117,119 Although the manufacturers state that 0.5-1 g may be given IM or IV every 6-8 hours for 24 hours postoperatively and, when the occurrence of infection may be particularly devastating (e.g., open-heart surgery, prosthetic arthroplasty), prophylaxis may be continued for 3-5 days postoperatively,100,115,116,117,119 most clinicians state that the duration of prophylaxis should be less than 24 hours for most procedures.102

For perioperative prophylaxis in adults undergoing certain cardiac surgery, noncardiac thoracic surgery, vascular surgery, head and neck surgery, neurosurgery, orthopedic surgery, GI surgery, genitourinary surgery, or gynecologic and obstetric surgery (see Uses: Perioperative Prophylaxis), cefazolin should be given within 60 minutes before surgical incision to ensure adequate serum and tissue concentrations.102,103 Some experts recommend a cefazolin dose of 1 g in adults weighing less than 80 kg and 2 g in those weighing 80 kg or more and suggest that morbidly obese patients may need higher dosage.102 Other experts recommend a cefazolin dose of 2 g for most adults and 3 g in those weighing 120 kg or more.103

During prolonged procedures (longer than 4 hours) or if major blood loss occurs, additional intraoperative doses of cefazolin should be given every 4 hours.102,103 The duration of prophylaxis should be less than 24 hours for most procedures;102 there is no evidence to support continuing prophylaxis after wound closure or until all indwelling drains and intravascular catheters are removed.102,103

If cefazolin is used for perioperative prophylaxis in patients undergoing certain GI procedures (e.g., colorectal surgery, appendectomy) that might involve exposure to Bacteroides fragilis or other anaerobic bowel bacteria or in patients undergoing head and neck surgery involving incisions through oral or pharyngeal mucosa, the usual cefazolin dose should be given in conjunction with IV metronidazole (0.5 g) within 60 minutes before surgical incision.102,103

Pediatric Dosage

General Dosage for Neonates

The manufacturers state that safety and efficacy of cefazolin have not been established in premature infants or neonates 1 month of age or younger.100,115,116

The American Academy of Pediatrics (AAP) recommends that neonates 7 days of age or younger† receive IV or IM cefazolin in a dosage of 25 mg/kg every 12 hours, regardless of weight.105 For neonates 8-28 days of age†, the AAP recommends a dosage of 25 mg/kg every 12 hours for those weighing 2 kg or less and 25 mg/kg every 8 hours for those weighing more than 2 kg.105

General Dosage for Infants and Children

The usual dosage of cefazolin recommended by the manufacturers for the treatment of mild to moderately severe infections in pediatric patients older than 1 month of age is 25-50 mg/kg daily given in 3 or 4 equally divided doses.100,115,116,119 The manufacturers state that dosage may be increased to 100 mg/kg daily in divided doses for the treatment of severe infections.100,115,116,119

The AAP recommends that pediatric patients beyond the neonatal period receive IV or IM cefazolin in a dosage of 25-50 mg/kg daily given in 3 equally divided doses for the treatment of mild to moderate infections or 100-150 mg/kg daily given in 3 equally divided doses for the treatment of severe infections.105

Endocarditis Treatment

If IV cefazolin is used for the treatment of native valve staphylococcal endocarditis in penicillin-allergic patients (nonanaphylactoid type only) with oxacillin-susceptible strains, the AHA and IDSA recommend that pediatric patients receive 100 mg/kg daily (up to 6 g daily) given in 3 or 4 equally divided doses; cefazolin should be given for 6 weeks and may be used with or without IM or IV gentamicin (3 mg/kg daily in 3 equally divided doses given during the first 3-5 days of the cefazolin regimen).113,114

If IV cefazolin is used for the treatment of prosthetic valve staphylococcal endocarditis in penicillin-allergic patients (nonanaphylactoid type only) with oxacillin-susceptible strains, the AHA and IDSA recommend that pediatric patients receive 100 mg/kg daily (up to 6 g daily) given in 3 or 4 equally divided doses; cefazolin should be given for 6 weeks or longer and used in conjunction with IV or IM gentamicin (3 mg/kg daily given in 2 or 3 equally divided doses during the first 2 weeks of treatment) and IV or oral rifampin (20 mg/kg daily in 3 equally divided doses given for 6 weeks or longer).113,114

If cefazolin is used for the treatment of endocarditis caused by susceptible S. pyogenes or S. pneumoniae †, the AHA recommends a treatment duration of 4 weeks.113

Endocarditis Prevention

If cefazolin is used as an alternative for prevention of α-hemolytic (viridans group) streptococcal endocarditis† in individuals considered to be at highest risk for bacterial endocarditis following certain dental or upper respiratory tract procedures, pediatric patients should receive a single dose of 50 mg/kg given IM or IV 0.5-1 hour prior to the procedure.104 Cefazolin should not be used for such prophylaxis in individuals with a history of immediate-type hypersensitivity reactions to penicillin.104

Perioperative Prophylaxis

For perioperative prophylaxis in pediatric patients undergoing certain cardiac surgery, noncardiac thoracic surgery, vascular surgery, head and neck surgery, neurosurgery, orthopedic surgery, GI surgery, or genitourinary surgery (see Uses: Perioperative Prophylaxis), some experts recommend that cefazolin should be given in a dose of 30 mg/kg103 within 60 minutes before surgical incision to ensure adequate serum and tissue concentrations.102,103

During prolonged procedures (longer than 4 hours) or if major blood loss occurs, additional intraoperative doses of cefazolin should be given every 4 hours.102,103 The duration of prophylaxis should be less than 24 hours for most procedures;102 there is no evidence to support continuing prophylaxis after wound closure or until all indwelling drains and intravascular catheters are removed.102,103

If cefazolin is used for perioperative prophylaxis in patients undergoing certain GI procedures (e.g., colorectal surgery, appendectomy) that might involve exposure to B. fragilis or other anaerobic bowel bacteria or in patients undergoing head and neck surgery involving incisions through oral or pharyngeal mucosa, pediatric patients should receive the usual cefazolin dose in conjunction with IV metronidazole (15 mg/kg)103 within 60 minutes before surgical incision.102,103

Dosage in Renal Impairment

In patients with impaired renal function, doses and/or frequency of administration of cefazolin must be modified in response to the degree of impairment, severity of the infection, susceptibility of the causative organism, and serum concentrations of the drug.

The manufacturers recommend an initial loading dose appropriate for the severity of the infection followed by dosage based on the degree of renal impairment.100 (See Table 1 and Table 2.)

Cefazolin shares the toxic potentials of other cephalosporins, and the usual cautions, precautions, and contraindications associated with cephalosporin therapy should be observed. (See Cautions in the Cephalosporins General Statement 8:12.06.)

Spectrum

Based on its spectrum of activity, cefazolin is classified as a first generation cephalosporin. For information on the classification of cephalosporins and closely related β-lactam antibiotics based on spectra of activity, see Spectrum in the Cephalosporins General Statement 8:12.06. Like other first generation cephalosporins (e.g., cefadroxil, cephalexin), cefazolin is active in vitro against many gram-positive aerobic cocci but has limited activity against gram-negative bacteria.

In Vitro Susceptibility Testing

Strains of staphylococci resistant to penicillinase-resistant penicillins (oxacillin-resistant [methicillin-resistant] staphylococci) should be considered resistant to cefazolin, although results of in vitro susceptibility tests may indicate that the organisms are susceptible to the drug.118

For information on interpreting results of in vitro susceptibility testing (disk susceptibility tests, dilution susceptibility tests) when cefazolin susceptibility testing is performed according to the standards of the Clinical and Laboratory Standards Institute (CLSI; formerly National Committee for Clinical Laboratory Standards [NCCLS]), see Spectrum: In Vitro Susceptibility Testing, in the Cephalosporins General Statement 8:12.06.

Pharmacokinetics

Absorption

Cefazolin sodium is not appreciably absorbed from the GI tract and must be administered parenterally. Following IM administration of cefazolin sodium in healthy adults with normal renal function, peak serum cefazolin concentrations are attained within 1-2 hours and average 17 mcg/mL following a single 250-mg dose, 30-44 mcg/mL following a single 500-mg dose, and 64-76 mcg/mL following a single 1-g dose. Following a single 1-g IV dose in adults with normal renal function, serum concentrations of cefazolin average 188 mcg/mL at 5 minutes, 74 mcg/mL at 1 hour, and 46 mcg/mL at 2 hours. In one study in adults with normal renal function, steady-state serum concentrations of cefazolin were reached 3 hours after IV infusion of 3.5 mg/kg over 1 hour followed by 1.5 mg/kg over 2 hours.

In one study in children, peak serum concentrations of cefazolin occurred at 30 minutes and averaged 28 mcg/mL after a single cefazolin IM dose of 5-6.25 mg/kg and 42 mcg/mL after a single IM dose of 10-12.5 mg/kg.

Elimination

The serum half-life of cefazolin is 1.2-2.2 hours in adults with normal renal function. In one study, half-life was 6.8 hours in 1 adult with a creatinine clearance of 26 mL/minute, 12 hours in 3 adults with creatinine clearances of 12-17 mL/minute, and 57 hours in 3 adults with creatinine clearances less than 5 mL/minute.

Cefazolin is excreted unchanged in urine. Approximately 60% of a single IM or IV dose of cefazolin is excreted within 6 hours and 80-100% of the dose is excreted within 24 hours in adults with normal renal function. In adults with normal renal function, peak urinary cefazolin concentrations of about 2 or 4 mg/mL may be attained following a single 500-mg or 1-g IM dose, respectively, of the drug.

Chemistry and Stability

Chemistry

Cefazolin sodium is a semisynthetic cephalosporin antibiotic. Cefazolin sodium occurs as a white to off-white, crystalline powder which may have a faint odor or as a white to off-white lyophilized solid. The drug is freely soluble in water and very slightly soluble in alcohol. Each gram of cefazolin as the sodium salt contains 48 mg of sodium.100,117

When the commercially available cefazolin sodium powder for injection is reconstituted as directed, solutions containing 225 or 330 mg/mL are light yellow to yellow100,115,116 and have a pH of 4.5-6.115

When the commercially available Duplex^® delivery system containing 1 or 2 g of cefazolin and 50 mL of dextrose 4 or 3% injection, respectively, in separate chambers is reconstituted (activated) according to the manufacturer's directions, the resultant solution is iso-osmotic and has an osmolality of approximately 290 mOsm/kg.117

Commercially available frozen premixed cefazolin sodium injection in dextrose containing 1 g of cefazolin is a sterile, nonpyrogenic, iso-osmotic solution of the drug provided in a plastic container fabricated from specially formulated multilayered plastic (PL 2040).119 The 1-g frozen injection of cefazolin contains approximately 2 g of dextrose to adjust osmolality and contains sodium bicarbonate to adjust pH.119

Stability

Cefazolin sodium powder for injection should be stored at 20-25°C and protected from light.100,115,116 Following reconstitution of the commercially available powder for injection with sterile water for injection, solutions containing approximately 225 or 330 mg of cefazolin per mL are pale yellow to yellow in color and are stable for 24 hours at room temperature or 10 days at 5°C.100,115 Reconstituted solutions have a pH of approximately 4.5-6; rapid hydrolysis of the drug occurs when pH exceeds 8.5, and precipitation of the insoluble free acid may occur when pH is below 4.5.

Reconstituted solutions containing approximately 225 or 330 mg of cefazolin per mL may be frozen in their original containers immediately after reconstitution with sterile water for injection and are stable for 12 weeks when stored at -20°C. If the solutions are warmed to facilitate thawing, care should be taken to avoid heating after thawing has been completed. Once thawed, solutions should not be refrozen.

The commercially available Duplex^® delivery system containing 1 or 2 g of cefazolin and 50 mL of dextrose injection in separate chambers should be stored at 20-25°C, but may be exposed to temperatures ranging from 15-30°C.117 Following reconstitution (activation), these IV solutions must be used within 24 hours if stored at room temperature or within 7 days if stored in a refrigerator and should not be frozen.117

The commercially available frozen premixed cefazolin sodium injection in dextrose should be stored at -20°C or lower.119 The frozen injection should be thawed at room temperature (25°C) or under refrigeration (5°C) and, once thawed, should not be refrozen.119 Thawed solutions of the commercially available frozen injection are stable for 48 hours at room temperature (25°C) or 30 days under refrigeration (5°C).119 The commercially available frozen injection of the drug is provided in plastic containers fabricated from specially formulated multilayered plastic PL 2040 (Galaxy^® containers).119 Solutions in contact with PL 2040 can leach out some of its chemical components in very small amounts within the expiration period of the injection; however, safety of the plastic has been confirmed in tests in animals according to USP biological tests for plastic containers as well as by tissue culture toxicity studies.119

Cefazolin sodium powder and solutions of the drug tend to darken, depending on storage conditions; however, such discoloration does not indicate loss of potency.100,115,117

Additional Information

For further information on chemistry, mechanism of action, spectrum, resistance, pharmacokinetics, uses, cautions, drug interactions, laboratory test interferences, and dosage and administration of cefazolin, see the Cephalosporins General Statement 8:12.06.

Only references cited for selected revisions after 1984 are available electronically.

100. GlaxoSmithKline. Ancef^® (cefazolin) for injection prescribing information. Research Triangle Park, NC; 2005 Apr.

102. . Antimicrobial prophylaxis for surgery. Treat Guidel Med Lett . 2012; 10:73-8; quiz 79-80. [PubMed 22996382]

103. Bratzler DW, Dellinger EP, Olsen KM et al. Clinical practice guidelines for antimicrobial prophylaxis in surgery. Am J Health Syst Pharm . 2013; 70:195-283. [PubMed 23327981]

104. Wilson W, Taubert KA, Gewitz M et al. Prevention of infective endocarditis: guidelines from the American Heart Association: a guideline from the American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee, Council on Cardiovascular Disease in the Young, and the Council on Clinical Cardiology, Council on Cardiovascular Surgery and Anesthesia, and the Quality of Care and Outcomes Research Interdisciplinary Working Group. Circulation . 2007; 116:1736-54. [PubMed 17446442]

105. American Academy of Pediatrics. Red Book: 2012 Report of the Committee on Infectious Diseases. 29th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2012.

106. Mangram AJ, Horan TC, Pearson ML et al. Guideline for prevention of surgical site infection, 1999. Infect Control Hosp Epidemiol . 1999; 20:250-78. [PubMed 10219875]

107. Noyes N, Berkeley AS, Freedman K et al. Incidence of postpartum endomyometritis following single-dose antibiotic prophylaxis with either ampicillin/sulbactam, cefazolin, or cefotetan in high-risk cesarean section patients. Infect Dis Obstet Gynecol . 1998; 6:220-3. [PubMedCentral][PubMed 9894177]

108. Gonzalez RP, Holevar MR. Role of prophylactic antibiotics for tube thoracostomy in chest trauma. Am Surg . 1998; 64:617-20. [PubMed 9655270]

109. Aznar R, Mateu M, Miro JM et al. Antibiotic prophylaxis in non-cardiac thoracic surgery: cefazolin versus placebo. Eur J Cardiothorac Surg . 1991; 5:515-8. [PubMed 1756043]

110. Scher KS. Studies on the duration of antibiotic administration for surgical prophylaxis. Am Surg . 1997; 63:59-62. [PubMed 8985073]

111. Verani JR, McGee L, Schrag SJ et al. Prevention of perinatal group B streptococcal disease--revised guidelines from CDC, 2010. MMWR Recomm Rep . 2010; 59(RR-10):1-36. [PubMed 21088663]

113. Baddour LM, Wilson WR, Bayer AS et al. Infective endocarditis: diagnosis, antimicrobial therapy, and management of complications: a statement for healthcare professionals from the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease of the Young, and the Councils on Clinical Cardiology, Stroke, and Cardiovascular Surgery and Anesthesia, American Heart Association: endorsed by the Infectious Diseases Society of America. Circulation . 2005; 111:e394-433. [PubMed 15956145]

114. Ferrieri P, Gewitz MH, Gerber MA et al and the Committee on Rheumatic Fever et al. Unique features of infective endocarditis in childhood. Circulation . 2002; 105:2115-27. [PubMed 11980694]

115. Sandoz Inc. Cefazolin for injection, USP (500 mg and 1 g vials) prescribing information. Princeton, NJ; 2013 Feb.

116. West-Ward Pharmaceutical Corp. Cefazolin for injection, USP (10 g and 20 g pharmacy bulk vials) prescribing information. Eatontown, NJ; 2012 Jan.

117. B Braun Medical. Cefazolin for injection USP and dextrose injection USP in Duplex^® container prescribing information. Irvine, CA; 2012 May.

118. Clinical and Laboratory Standards Institute. Performance standards for antimicrobial susceptibility testing: Twenty-first informational supplement. CLSI document M100-S21. Wayne, PA; 2011.

119. Baxter Healthcare. Cefazolin sodium injection, solution (frozen) prescribing information. Deerfield, IL; 2013 Jan.

120. Cohen SH, Gerding DN, Johnson S et al. Clinical practice guidelines for Clostridium difficile infection in adults: 2010 update by the Society for Healthcare Epidemiology of America (SHEA) and the Infectious Diseases Society of America (IDSA). Infect Control Hosp Epidemiol . 2010; 31:431-55. [PubMed 20307191]