Bloodstream infection:
Pathogen-directed therapy for methicillin-susceptible staphylococci:
IV: 2 g every 8 hours (Fowler 2021; IDSA [Mermel 2009]; Li 2014); treat uncomplicated Staphylococcus aureus bacteremia for ≥14 days starting from day of first negative blood culture, with longer courses warranted for endocarditis or metastatic sites of infection (IDSA [Mermel 2009]).
Pathogen-directed therapy for susceptible Enterobacteriaceae:
IV: 2 g every 8 hours (Hsieh 2016; Turnidge 2011). Usual duration is 7 to 14 days; individualize depending on source and extent of infection as well as clinical response. A 7-day duration is recommended for patients with uncomplicated Enterobacteriaceae infection who respond appropriately to antibiotic therapy (Moehring 2019; Yahav 2018).
Antibiotic lock technique (catheter-salvage strategy): Note: For infections caused by susceptible organisms when the catheter cannot be removed; use in addition to systemic antibiotics. Catheter salvage is not recommended for S. aureus.
Intracatheter: Prepare lock solution to final concentration of cefazolin 5 to 10 mg/mL (may be combined with heparin). Instill into each lumen of the catheter access port using a volume sufficient to fill the catheter (2 to 5 mL), with a dwell time of up to 72 hours depending on frequency of catheter use and solution stability. Withdraw lock solution prior to catheter use; replace with fresh cefazolin lock solution after catheter use. Antibiotic lock therapy is given for the same duration as systemic antibiotics (Bookstaver 2009; Girand 2020; IDSA [Mermel 2009]).
Endocarditis, prophylaxis (dental or invasive respiratory tract procedures) (alternative agent for patients with nonsevere, non-IgE-mediated penicillin allergy who cannot take oral therapy) (off-label use):
IM, IV: 1 g as a single dose 30 to 60 minutes before procedure; if inadvertently not given prior to the procedure, may be administered up to 2 hours after the procedure. Note: Reserve for select situations (cardiac condition with the highest risk of adverse endocarditis outcomes and procedure likely to result in bacteremia with an organism that can cause endocarditis) (AHA [Wilson 2007]; AHA [Wilson 2021]).
Endocarditis, treatment:
Note: Cefazolin should not be used in patients with concomitant CNS infections (eg, brain abscess) (AHA [Baddour 2015]).
Pathogen-directed therapy for methicillin-susceptible staphylococci (alternative agent for patients with nonsevere, non-IgE-mediated penicillin allergy):
Native valve: IV: 2 g every 8 hours for 6 weeks (AHA [Baddour 2015]).
Prosthetic valve: IV: 2 g every 8 hours for ≥6 weeks (combine with rifampin for entire duration of therapy and gentamicin for the first 2 weeks) (AHA [Baddour 2015]).
Intra-abdominal infection, mild to moderate, community-acquired in patients without risk factors for resistance or treatment failure:
Note: Reserve for patients with low risk for resistant pathogens (eg, local Enterobacteriaceae resistance rate to cefazolin <10% and no recent antibiotic exposure) (Barshak 2021).
Cholecystitis, acute: IV: 1 to 2 g every 8 hours; continue for 1 day after gallbladder removal or until clinical resolution in patients managed nonoperatively (SIS/IDSA [Solomkin 2010]; Vollmer 2021). Note: The addition of anaerobic therapy (eg, metronidazole) is recommended if biliary-enteric anastomosis is present (SIS/IDSA [Solomkin 2010]).
Other intra-abdominal infections (eg, perforated appendix, appendiceal abscess, diverticulitis) (off-label use): IV: 1 to 2 g every 8 hours in combination with metronidazole. Total duration of therapy (which may include transition to oral antibiotics) is 4 to 5 days following adequate source control (Sawyer 2015; SIS [Mazuski 2017]); for diverticulitis or uncomplicated appendicitis managed without intervention, duration is 7 to 10 days (Barshak 2021; Pemberton 2021; Salminen 2015).
Osteomyelitis and/or discitis:
Treatment, pathogen-directed therapy for methicillin-susceptible S. aureus:
IV: 2 g every 8 hours for ≥6 weeks depending on extent of infection, debridement, and clinical response (IDSA [Berbari 2015]; Osmon 2019).
Prevention, following open fractures:
IV: 2 g for patients <120 kg or 3 g for patients ≥120 kg every 8 hours; ideally administer within 6 hours of injury. For type I or II fractures (no more than moderate comminution or contamination, no or minimal periosteal stripping, adequate soft tissue coverage), discontinue 24 hours following wound closure. For type III fractures (severe contamination or comminution), use as part of an appropriate combination regimen and continue for 72 hours after injury or up to 24 hours after wound closure (EAST [Hoff 2011]; Schmitt 2020). Note: For patients with risk for methicillin-resistant S. aureus (MRSA), potential water exposure, or fecal or clostridial contamination, alternative or additional antibiotics are recommended (Schmitt 2020).
Peritonitis, treatment (peritoneal dialysis patients) (off-label use):
Note: As a component of empiric therapy in patients at low risk for MRSA or as pathogen-directed therapy. Intraperitoneal administration is preferred to IV administration. Duration of therapy is ≥2 to 3 weeks, depending on organism, for patients with adequate clinical response (Burkart 2019; ISPD [Li 2016]). Consider a 25% dose increase in patients with significant residual renal function (urine output >100 mL/day) (ISPD [Li 2010]; ISPD [Li 2016]; Mancini 2018; Szeto 2018).
Intermittent: Intraperitoneal: 15 to 20 mg/kg added to one exchange of dialysis solution once daily (allow to dwell for ≥6 hours). For patients on continuous ambulatory peritoneal dialysis, add cefazolin to the overnight dwell. Note: Some experts recommend adding cefazolin to each exchange in patients on automated peritoneal dialysis as nighttime intraperitoneal levels of cefazolin may fall below the minimum inhibitory concentration of most organisms (ISPD [Li 2016]).
Continuous (with every exchange) (dose is per liter of dialysate): Intraperitoneal: Loading dose: 500 mg/L of dialysate added to first exchange of dialysate; maintenance dose: 125 mg/L of dialysate with each subsequent exchange of dialysate (ISPD [Li 2016]).
Pneumonia: Pathogen-directed therapy for methicillin-susceptible S. aureus: IV: 2 g every 8 hours (Klompas 2022; Miller 2018). Minimum duration is generally 5 days for community-acquired pneumonia and 7 days for hospital-acquired or ventilator-associated pneumonia; patients should be clinically stable with normal vital signs before therapy is discontinued (IDSA/ATS [Kalil 2016]; IDSA/ATS [Metlay 2019]).
Prostatitis, acute bacterial: Pathogen-directed therapy for susceptible organisms: IV: 1 g every 8 hours; may switch to oral therapy 24 to 48 hours after improvement in fever and clinical symptoms. Total duration of therapy is 4 to 6 weeks (Meyrier 2020).
Prosthetic joint infection: Pathogen-directed therapy for methicillin-susceptible S. aureus: IV: 2 g every 8 hours. Duration ranges from 2 to 6 weeks depending on prosthesis management, use of rifampin, and other patient-specific factors. Note: In select cases (eg, debridement and retention of prosthesis or one-stage arthroplasty), combine with oral rifampin and give oral suppressive antibiotic therapy following completion of IV treatment (Berbari 2019; IDSA [Osmon 2013]).
Septic arthritis, without prosthetic material: Pathogen-directed therapy for methicillin-susceptible S. aureus: IV: 2 g every 8 hours. Duration is 3 to 4 weeks (in the absence of osteomyelitis), including oral step-down therapy (Goldenberg 2019; Ross 2017). Some experts recommend 4 weeks of parenteral therapy for patients with concomitant bacteremia (Goldenberg 2019).
Skin and soft tissue infection:
Erysipelas or nonpurulent cellulitis in patients without risk for methicillin-resistant S. aureus: IV: 1 to 2 g every 8 hours. Total duration of therapy ≥5 days (including oral step-down therapy); may extend to 14 days depending on severity and clinical response (IDSA [Stevens 2014]; Spelman 2019).
Pathogen-directed therapy for methicillin-susceptible S. aureus: IV: 1 to 2 g every 8 hours. Total duration of therapy is 5 to 14 days (including oral step-down therapy) depending on severity of infection, need for debridement, and clinical response (IDSA [Stevens 2014]; Spelman 2019). Note: For necrotizing infections, antibiotic therapy must be used in conjunction with early and aggressive surgical exploration and debridement of necrotic tissue; continue until further debridement is not necessary and the patient has clinically improved and is afebrile for 48 to 72 hours (IDSA [Stevens 2014]).
Surgical site incisional infection (trunk or extremity surgery, not involving axilla or perineum): IV: 1 g every 8 hours; duration is dependent upon severity, need for debridement, and clinical response (IDSA [Stevens 2014]).
Streptococcus (group B), maternal prophylaxis for prevention of neonatal disease (alternative agent) (off-label use):
IV: 2 g as a single dose at onset of labor or prelabor rupture of membranes, then 1 g every 8 hours until delivery. Use of cefazolin should be reserved for penicillin-allergic patients at low risk for anaphylaxis (eg, rash without urticaria and no systemic symptoms, family history of penicillin allergy but no personal history, patients who report penicillin allergy but have no recollection of symptoms or treatment) (ACOG 2020).
Surgical prophylaxis: IV: 2 g for patients <120 kg or 3 g for patients ≥120 kg; administer within 60 minutes of surgical incision. Use in combination with metronidazole for procedures requiring anaerobic coverage (eg, colorectal and clean-contaminated head and neck procedures). May repeat dose intraoperatively in 4 hours if procedure is lengthy or if there is excessive blood loss (ASHP/IDSA/SIS/SHEA [Bratzler 2013]); maximum dose: 12 g/day (manufacturer's labeling). In cases where an extension of prophylaxis is warranted postoperatively, total duration should be ≤24 hours (Anderson 2014). Postoperative prophylaxis is not recommended in clean and clean-contaminated surgeries (CDC [Berríos-Torres 2017]).
Toxic shock syndrome (off-label use): Pathogen-directed therapy for group A streptococcus or methicillin-susceptible S. aureus (alternative agent for patients with nonsevere, non-IgE-mediated penicillin allergy) (off-label use): IV: 2 g every 8 hours in combination with clindamycin. In the absence of bacteremia, treat for a total of ≥10 days, including oral step-down therapy (Chu 2019; Stevens 2021).
Urinary tract infection, complicated (pyelonephritis or urinary tract infection with systemic signs/symptoms): Pathogen-directed therapy for susceptible organisms: IV: 1 g every 8 hours (Millar 1995; Wing 1998). Switch to an appropriate oral regimen once symptoms improve, if culture and susceptibility results allow. Total duration of therapy ranges from 5 to 14 days and depends on clinical response and the antimicrobial chosen to complete the regimen (IDSA/ESCMID [Gupta 2011]; IDSA [Hooton 2010]).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
Note: The following dose adjustments are for the usual recommended dosing of 1 to 2 g IV every 8 hours.
Altered kidney function (Bellouard 2019; expert opinion; manufacturer's labeling): IV:
Note: Consider an initial unadjusted dose appropriate to the severity of the infection before reducing the dose.
CrCl ≥50 mL/minute: 1 to 2 g every 8 hours.
CrCl 30 to <50 mL/minute: 1 to 2 g every 8 to 12 hours.
CrCl >10 to <30 mL/minute: 500 mg to 1 g every 12 hours (some experts give 2 g every 12 hours for severe infections in patients with CrCl 10 to <30 mL/minute [Aronoff 2007]).
CrCl ≤10 mL/minute: 500 mg to 1 g every 24 hours.
Augmented renal clearance (measured urinary CrCl ≥130 mL/minute/1.73 m2): Augmented renal clearance (ARC) is a condition that occurs in certain critically ill patients without organ dysfunction and with normal serum creatinine concentrations. Young patients (<55 years of age) admitted post trauma or major surgery are at highest risk for ARC, as well as those with sepsis, burns, or hematologic malignancies. An 8- to 24-hour measured urinary CrCl is necessary to identify these patients (Bilbao-Meseguer 2018; Udy 2010).
IV: 2 g every 6 hours (Roberts 2015; Wong 2018).
Hemodialysis, intermittent (thrice weekly): Dialyzable (45% to 60% [Marx 1998]):
IV:
Daily dosing: 500 mg to 1 g every 24 hours (when scheduled dose falls on a dialysis day, administer after dialysis).
or
Thrice weekly (post dialysis) dosing: 2 g after dialysis 3 times weekly (Heintz 2009; Kuypers 1999) or 20 mg/kg (maximum dose: 2 g) after dialysis 3 times weekly (Ahern 2003; Sowinski 2001) or 2 g after dialysis if next dialysis is expected in 48 hours or 3 g after dialysis if next dialysis is expected in 72 hours (Stryjewski 2007).
Peritoneal dialysis: IV: 500 mg every 12 hours or 1 g every 24 hours (Aronoff 2007; Bunke 1983; Levison 1973; expert opinion).
CRRT: Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement. Recommendations are based on high-flux dialyzers and effluent flow rates of 20 to 25 mL/kg/hour (or ~1,500 to 3,000 mL/hour) unless otherwise noted. Appropriate dosing requires consideration of adequate drug concentrations (eg, site of infection), organism MIC, residual kidney function, and consideration of initial loading doses. Close monitoring of response and adverse reactions (eg, neurotoxicity [Schliamser 1991]) due to drug accumulation is important.
CVVH/CVVHD/CVVHDF: IV: 2 g loading dose followed by either 1 g every 8 hours or 2 g every 12 hours (Heintz 2009; expert opinion).
PIRRT (eg, sustained, low-efficiency diafiltration): Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement. Appropriate dosing requires consideration of adequate drug concentrations (eg, site of infection), organism MIC, residual kidney function, and consideration of initial loading doses. Close monitoring of response and adverse reactions (eg, neurotoxicity [Schliamser 1991]) due to drug accumulation is important.
IV: 2 g loading dose followed by either 1 g every 8 hours or 2 g every 12 hours (expert opinion).
There are no dosage adjustments provided in the manufacturer's labeling.
(For additional information see "Cefazolin: Pediatric drug information")
General dosing, susceptible infection (Bradley 2019; Red Book [AAP 2018]): Infants, Children, and Adolescents: IM, IV:
Mild to moderate infections: 25 to 100 mg/kg/day divided every 8 hours; maximum daily dose: 6 g/day
Severe infections (eg, bone/joint infections): 100 to 150 mg/kg/day divided every 6 to 8 hours; maximum daily dose: 12 g/day
Endocarditis, bacterial:
Prophylaxis for dental and upper respiratory procedures: Infants, Children, and Adolescents: IM, IV: 50 mg/kg 30 to 60 minutes before procedure; maximum dose: 1,000 mg/dose (AHA [Wilson 2007]). Note: AHA guidelines (Baltimore 2015) limit the use of prophylactic antibiotics to patients at the highest risk for infective endocarditis (IE) or adverse outcomes (eg, prosthetic heart valves, patients with previous IE, unrepaired cyanotic congenital heart disease, repaired congenital heart disease with prosthetic material or device during first 6 months after procedure, repaired congenital heart disease with residual defects at the site or adjacent to site of prosthetic patch or device, and heart transplant recipients with cardiac valvulopathy).
Treatment: Children and Adolescents: IV: 100 mg/kg/day in divided doses every 8 hours; usual adult dose: 2,000 mg/dose; maximum daily dose: 12 g/day; treat for at least 4 weeks; longer durations may be necessary; may use with or without gentamicin (AHA [Baltimore 2015])
Peritonitis (peritoneal dialysis) (ISPD [Warady 2012]): Limited data available: Infants, Children, and Adolescents:
Prophylaxis:
Touch contamination of PD line: Intraperitoneal: 125 mg per liter
Invasive dental procedures: IV: 25 mg/kg administered 30 to 60 minutes before procedure; maximum dose: 1,000 mg/dose
Gastrointestinal or genitourinary procedures: IV: 25 mg/kg administered 60 minutes before procedure; maximum dose: 2,000 mg/dose
Treatment: Intraperitoneal:
Intermittent: 20 mg/kg every 24 hours in the long dwell
Continuous: Loading dose: 500 mg per liter of dialysate; maintenance: 125 mg per liter of dialysate
Pneumonia, community-acquired pneumonia (CAP), S. aureus , methicillin susceptible: Infants >3 months, Children, and Adolescents: IV: 50 mg/kg/dose every 8 hours (Bradley 2011); usual maximum dose for severe infections: 12 g/day (Red Book [AAP 2018])
Skin and soft tissue infections, S. aureus, methicillin susceptible (mild to moderate): (IDSA [Stevens 2014]): Infants, Children, and Adolescents:
S. aureus, methicillin susceptible skin and soft tissue infections including pyomyositis: IV: 50 mg/kg/day divided every 8 hours; maximum dose: 1,000 mg/dose; higher doses may be required in severe cases; duration of therapy at least 5 days, but longer may be necessary in some cases, eg, febrile and neutropenic patients: 7 to 14 days; pyomyositis: 14 to 21 days
S. aureus, methicillin susceptible necrotizing infection of skin, fascia, or muscle: IV: 100 mg/kg/day divided every 8 hours; maximum dose: 1,000 mg/dose; continue therapy until surgical debridement no longer necessary, clinical improvement and afebrile for 48 to 72 hours
Streptococcal, nonpurulent skin infection (cellulitis): IV: 100 mg/kg/day divided every 8 hours; maximum dose: 1,000 mg/dose; duration of therapy at least 5 days, but longer may be necessary in some cases
Surgical prophylaxis: Infants, Children, and Adolescents: IV: 30 mg/kg within 60 minutes prior to procedure, may repeat in 4 hours for prolonged procedure or excessive blood loss (eg, >1,500 mL in adults); maximum dose dependent upon patient weight: Weight <120 kg: 2,000 mg/dose; weight ≥120 kg: 3,000 mg/dose (ASHP/IDSA [Bratzler 2013]; Red Book [AAP 2018])
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Note: Dosing is based on pharmacokinetic parameters, limited pediatric studies, adult studies, and expert opinion (Aronoff 2007; Heintz 2009; Hiner 1980; Nahata 1991; Salvador 2021; Trotman 2005; Veltri 2004).
The following dose adjustments assume a usual recommended dose of 25 to 50 mg/kg/dose every 8 hours.
Altered kidney function:
Infants, Children, and Adolescents (expert opinion): IV, IM:
GFR ≥50 mL/minute/1.73 m2: No dosage adjustment necessary.
GFR 30 to <50 mL/minute/1.73 m2: 25 to 30 mg/kg/dose every 12 hours; doses up to 50 mg/kg/dose may be needed for severe infections; maximum dose: 2,000 mg/dose.
GFR 10 to 30 mL/minute/1.73 m2: 25 to 30 mg/kg/dose every 24 hours; doses up to 50 mg/kg/dose may be needed for severe infections; maximum dose: 2,000 mg/dose.
GFR ≤10 mL/minute/1.73 m2: 25 to 30 mg/kg/dose every 48 hours; doses up to 50 mg/kg/dose may be needed for severe infections; maximum dose: 2,000 mg/dose.
Hemodialysis, intermittent: Dialyzable: 35% to 65% (Hiner 1980).
Note: Appropriate dosing requires consideration of drug penetration to site of infection, minimum inhibitory concentration (MIC) of bacteria, severity of illness, residual kidney function, and interval between dialysis sessions.
Infants, Children, and Adolescents (expert opinion):
Intermittent dosing (eg, 3 times weekly): IV: 25 to 50 mg/kg/dose after dialysis; maximum dose: 2,000 mg/dose. Note: Children with residual kidney function may require higher or more frequent dosing.
Peritoneal dialysis:
Infants, Children, Adolescents (expert opinion): IV, IM: 25 to 30 mg/kg/dose every 24 to 48 hours; maximum dose: 1,000 mg/dose.
CRRT:
Note: Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement. Recommendations are based on high-flux dialyzers and effluent flow rates of ≥1,500 mL/m2/hour) unless otherwise noted; flow rates vary widely in pediatric patients. Appropriate dosing requires consideration of drug penetration to site of infection, MIC of bacteria, and severity of illness. Close monitoring of response and adverse reactions due to drug accumulation (eg, neurotoxicity) is important. Due to minimal data in pediatric patients receiving CRRT, consider monitoring serum concentrations (eg, trough concentration) if available. Dosing based on limited adult information and expert opinion (Heintz 2009; Trotman 2005; Veltri 2004).
CVVH/CVVHD/CVVHDF: Infants, Children, and Adolescents (expert opinion): IV: 25 to 50 mg/kg/dose IV every 8 to 12 hours. Maximum dose: 2,000 mg/dose.
Augmented renal clearance (ARC):
Note: ARC is a condition that occurs in certain critically ill patients without organ dysfunction and with normal serum creatinine concentrations that results in increased drug elimination. An 8- to 24-hour measured urinary CrCl is necessary to identify these patients (Bilbao-Meseguer 2018; Udy 2010).
Infants, Children, and Adolescents:
GFR ≥200 mL/minute/1.73 m2:
Continuous infusion: 150 mg/kg/day as a continuous infusion; maximum daily dose: 12 g/day. May give an initial loading dose of 30 mg/kg (maximum dose: 2,000 mg/dose) before starting the continuous infusion if rapid attainment of therapeutic drug concentrations is desired (eg, sepsis). Dosing is based on a pharmacokinetic modeling study; additional dosages (eg, lower daily doses, every-6-hour dosing) may be appropriate depending on the clinical situation (Salvador 2021).
There are no dosage adjustments provided in the manufacturer's labeling.
Refer to adult dosing.
Refer to indication-specific dosing for obesity-related information (may not be available for all indications).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Solution, Intravenous [preservative free]:
Generic: 1 g/50 mL in Dextrose 4% (50 mL); 2 g/100 mL in Dextrose 4% (100 mL)
Solution Reconstituted, Injection:
Generic: 500 mg (1 ea [DSC]); 10 g (1 ea)
Solution Reconstituted, Injection [preservative free]:
Generic: 500 mg (1 ea); 1 g (1 ea); 10 g (1 ea); 20 g (1 ea [DSC]); 100 g (1 ea); 300 g (1 ea)
Solution Reconstituted, Intravenous [preservative free]:
Generic: 1 g (1 ea); 1 g and Dextrose 4% (1 ea); 2 g and Dextrose 3% (1 ea)
Yes
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Solution Reconstituted, Injection:
Generic: 500 mg (1 ea); 1 g (1 ea); 10 g (1 ea); 20 g (1 ea); 100 g (1 ea)
Solution Reconstituted, Intravenous:
Generic: 1 g ([DSC])
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.
Parenteral:
IM: Deep IM injection into a large muscle mass.
IV: May be administered IVP over 3 to 5 minutes or IV intermittent infusion over 10 to 60 minutes.
Biliary tract infection: Treatment of biliary tract infections due to Escherichia coli, various strains of streptococci, Proteus mirabilis, Klebsiella species, and Staphylococcus aureus.
Bloodstream infection: Treatment of bloodstream infection due to methicillin-susceptible staphylococci, E. coli, P. mirabilis, and Klebsiella species.
Bone and joint infection: Treatment of bone and joint infections due to S. aureus.
Endocarditis, treatment: Treatment of endocarditis due to methicillin-susceptible staphylococci and group A beta-hemolytic streptococci (Streptococcus pyogenes).
Genital infection: Treatment of genital infections (ie, prostatitis, epididymitis) due to E. coli, P. mirabilis, and Klebsiella species.
Respiratory tract infection: Treatment of respiratory tract infections due to Streptococcus pneumoniae, Klebsiella species, methicillin-susceptible S. aureus, and group A beta-hemolytic streptococci.
Skin and soft tissue infection: Treatment of skin and soft tissue infections due to methicillin-susceptible S. aureus, group A beta-hemolytic streptococci, and other strains of streptococci.
Surgical prophylaxis: To reduce the incidence of certain postoperative infections in adults and pediatric patients 10 to 17 years of age undergoing surgical procedures.
Urinary tract infection: Treatment of urinary tract infections due to E. coli, P. mirabilis, and Klebsiella species.
Endocarditis, prophylaxis; Peritonitis, treatment (peritoneal dialysis patients); Streptococcus (group B), maternal prophylaxis for prevention of neonatal disease; Toxic shock syndrome
CeFAZolin may be confused with cefoTEtan, cefOXitin, cefprozil, cefTAZidime, cefTRIAXone, cephalexin.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
Frequency not defined:
Cardiovascular: Hypotension, syncope
Dermatologic: Pruritus (including genital pruritus), skin rash, Stevens-Johnson syndrome, urticaria
Gastrointestinal: Abdominal cramps, anorexia, Clostridioides difficile colitis, diarrhea, epigastric pain, flatulence, heartburn, nausea, oral candidiasis, oral mucosal ulcer, pruritus ani, vomiting
Genitourinary: Vaginitis, vulvovaginal candidiasis, vulvovaginal pruritus
Hematologic & oncologic: Eosinophilia, leukopenia, neutropenia, thrombocythemia, thrombocytopenia
Hepatic: Hepatitis, increased serum alanine aminotransferase, increased serum alkaline phosphatase, increased serum aspartate aminotransferase
Hypersensitivity: Anaphylaxis
Local: Induration at injection site, injection site phlebitis, pain at injection site
Nervous system: Confusion, dizziness, drowsiness, drug fever, fatigue, headache
Neuromuscular: Asthenia
Renal: Increased blood urea nitrogen, increased serum creatinine, renal failure syndrome
Postmarketing:
Dermatologic: Acute generalized exanthematous pustulosis
Gastrointestinal: Clostridioides difficile associated diarrhea
Hypersensitivity: Serum sickness
Renal: Acute interstitial nephritis
Hypersensitivity to cefazolin, other cephalosporin antibiotics, penicillins, other beta-lactams, or any component of the formulation.
Concerns related to adverse effects:
• Elevated INR: May be associated with increased INR, especially in nutritionally-deficient patients, prolonged treatment, hepatic or renal disease.
• Hypersensitivity reactions: Hypersensitivity reactions, including anaphylaxis, may occur. If an allergic reaction occurs, discontinue treatment and institute appropriate supportive measures.
• Penicillin allergy: Use with caution in patients with a history of penicillin allergy.
• Superinfection: Prolonged use may result in fungal or bacterial superinfection, including Clostridioides difficile-associated diarrhea (CDAD) and pseudomembranous colitis; CDAD has been observed >2 months postantibiotic treatment.
Disease-related concerns:
• Gastrointestinal disease: Use with caution in patients with a history of gastrointestinal disease, particularly colitis.
• Renal impairment: Use with caution in patients with renal impairment; dosage adjustment required.
• Seizure disorders: Use with caution in patients with a history of seizure disorder; high levels, particularly in the presence of renal impairment, may increase risk of seizures.
None known.
Aminoglycosides: Cephalosporins may enhance the nephrotoxic effect of Aminoglycosides. Cephalosporins may decrease the serum concentration of Aminoglycosides. Risk C: Monitor therapy
BCG (Intravesical): Antibiotics may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination
BCG Vaccine (Immunization): Antibiotics may diminish the therapeutic effect of BCG Vaccine (Immunization). Risk C: Monitor therapy
Cholera Vaccine: Antibiotics may diminish the therapeutic effect of Cholera Vaccine. Management: Avoid cholera vaccine in patients receiving systemic antibiotics, and within 14 days following the use of oral or parenteral antibiotics. Risk X: Avoid combination
Fosphenytoin: CeFAZolin may decrease the protein binding of Fosphenytoin. Risk C: Monitor therapy
Immune Checkpoint Inhibitors: Antibiotics may diminish the therapeutic effect of Immune Checkpoint Inhibitors. Risk C: Monitor therapy
Lactobacillus and Estriol: Antibiotics may diminish the therapeutic effect of Lactobacillus and Estriol. Risk C: Monitor therapy
Phenytoin: CeFAZolin may decrease the protein binding of Phenytoin. Risk C: Monitor therapy
Probenecid: May increase the serum concentration of Cephalosporins. Risk C: Monitor therapy
RifAMPin: CeFAZolin may enhance the adverse/toxic effect of RifAMPin. Specifically, the risk for bleeding may be increased. Management: Avoid concomitant use of rifampin with cefazolin when possible. If combined, closely monitor prothrombin time or other coagulation tests and administer vitamin K as needed. Risk D: Consider therapy modification
Sodium Picosulfate: Antibiotics may diminish the therapeutic effect of Sodium Picosulfate. Management: Consider using an alternative product for bowel cleansing prior to a colonoscopy in patients who have recently used or are concurrently using an antibiotic. Risk D: Consider therapy modification
Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Management: Avoid use of live attenuated typhoid vaccine (Ty21a) in patients being treated with systemic antibacterial agents. Postpone vaccination until 3 days after cessation of antibiotics and avoid starting antibiotics within 3 days of last vaccine dose. Risk D: Consider therapy modification
Vitamin K Antagonists (eg, warfarin): Cephalosporins may enhance the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy
Cefazolin crosses the placenta.
Based on available data, cephalosporin antibiotics are generally considered compatible for use during pregnancy (Ailes 2016; Bookstaver 2015; Crider 2009; Czeizel 2001; Lamont 2014; Muanda 2017a; Muanda 2017b). Adverse events have not been reported in the fetus following administration of cefazolin prior to cesarean delivery.
Due to pregnancy-induced physiologic changes, some pharmacokinetic parameters of cefazolin may be altered (Allegaert 2009; Elkomy 2014; Philipson 1987). In addition to pregnancy, obesity has been found to influence the pharmacokinetics of cefazolin (Ahmadzia 2015; Duff 2019; Eley 2020; Groff 2017; Kram 2017; Pevzner 2011; Stitely 2013; Young 2015). Higher doses are recommended in obese patients; however, additional studies are needed to determine the ideal dose, especially in pregnant patients with extreme obesity (ACOG 2018; Dallmann 2019; La Rosa 2020).
A targeted antibiotic such as cefazolin is recommended prior to all cesarean deliveries unless the patient is already receiving an appropriate antibiotic. A single dose administered within 60 minutes prior to the delivery is recommended unless drug allergies are present. Dose adjustments of cefazolin may be considered based on maternal weight (ACOG 2018).
Cefazolin is recommended as an alternative antibiotic for group B streptococcus (GBS) prophylaxis in pregnant patients who are penicillin allergic and at low risk for anaphylaxis. Treatment is intended to prevent early-onset disease in newborns. Prophylaxis is reserved for pregnant patients with a positive GBS vaginal or rectal screening in late gestation; GBS bacteriuria during the current pregnancy; history of birth of an infant with early-onset GBS disease; and unknown GBS culture status with any of the following: birth <37 0/7 weeks gestation, intrapartum fever, prolonged rupture of membranes, known GBS positive in a previous pregnancy, or intrapartum nucleic acid amplification testing positive for GBS (ACOG 2020).
Cefazolin is one of the recommended antibiotics that may be used prior to vaginal delivery in patients at high risk for endocarditis. This includes patients with congenital heart disease, prosthetic valves, previous infective endocarditis, or cardiac transplant. Cefazolin is given 30 to 60 minutes prior to a vaginal delivery; the endocarditis prophylactic dose is the same as nonpregnant patients (ACOG 2018).
Cefazolin is present in breast milk.
Based on limited information, the relative infant dose (RID) of cefazolin is <1% following a single maternal dose of 2 g (Yoshioka 1979).
In general, breastfeeding is considered acceptable when the RID of a medication is <10% (Anderson 2016; Ito 2000).
The RID of cefazolin was calculated using a milk concentration of 1.51 mcg/mL, providing an estimated daily infant dose via breast milk of 0.2265 mcg/kg/day. This milk concentration was obtained 3 hours following maternal administration cefazolin 2 g IV to 20 postpartum women (Yoshioka 1979).
In general, antibiotics that are present in breast milk may cause non-dose-related modification of bowel flora (WHO 2002). The manufacturer recommends that caution be exercised when administering cefazolin to breastfeeding women.
Some products may contain sodium.
Renal function periodically, hepatic function tests, CBC; monitor for signs of anaphylaxis during first dose
Inhibits bacterial cell wall synthesis by binding to one or more of the penicillin-binding proteins (PBPs) which in turn inhibits the final transpeptidation step of peptidoglycan synthesis in bacterial cell walls, thus inhibiting cell wall biosynthesis. Bacteria eventually lyse due to ongoing activity of cell wall autolytic enzymes (autolysins and murein hydrolases) while cell wall assembly is arrested.
Distribution: Widely into most body tissues and fluids including gallbladder, liver, kidneys, bone, sputum, bile, pleural, and synovial; CSF penetration is poor.
Vd:
Preterm neonates (GA: 25 to <32 weeks): 0.39 L/kg (range 0.31 to 0.52 L/kg) (Balevic 2019).
Preterm and term neonates (GA: 30 to 40 weeks; PNA: 2 to 28 days): 0.212 to 0.373 L/kg (Deguchi 1988).
Children 3 to 12 years of age: 0.133 ± 0.015 L/kg (Koshida 1987).
Adults: 0.193 ± 0.064 L/kg (Scheld 1981).
Bone:serum concentration ratio: Median: 0.25 (range: 0.06 to 0.41) (Zeller 2009).
Protein binding: 80% (Marshall 1999).
Half-life elimination: IM or IV:
Neonates: 3 to 5 hours.
Infants ≥9 months of age and children ≤10 years of age: 1.7 ± 0.6 hours (Nahata 1991).
Children 10 to 12 years of age: 1.95 hours (range 1.44 to 2.88 hours) (Schmitz 2015).
Adults: 1.8 hours (IV); ~2 hours (IM) (prolonged with renal impairment).
Time to peak, serum: IM: 0.5 to 2 hours; IV: Within 5 minutes.
Excretion: Urine (70% to 80% as unchanged drug).
Anti-infective considerations:
Parameters associated with efficacy: Time dependent, associated with time free drug concentration (fT) > minimum inhibitory concentration (MIC).
Organism specific:
S. aureus (methicillin-susceptible [MSSA]): Goal: ≥ ~24% to 55% fT > MIC (bacteriostatic) (Turnidge 1998; Zelenitsky 2018); ≥ ~55% to 100% fT > MIC (bacteriocidal) (Vogelman 1988; Zelenitsky 2018).
E. coli: Goal: ≥60% fT > MIC (bacteriostatic); ≥100% fT > MIC (2-log kill) (Vogelman 1988).
Population specific:
Critically ill patients in the ICU: Minimum goal: ≥50% fT > MIC; preferred goal: ≥100% fT > MIC (Roberts 2015); some experts favor ≥100% fT ≥4 times the MIC (Guilhaumou 2019).
Expected drug concentrations in patients with normal renal function:
Infants ≥9 months of age and children ≤10 years of age: Cmax (peak), single dose: Mean dose: 22.7 mg/kg ± 4 mg/kg: 137 ± 87.9 mg/L (Nahata 1991).
Adults: Cmax (peak), steady state: 1 g every 8 hours: 94 ± 30.33 mg/L (Bhalodi 2013).
Postantibiotic effect: Generally little to no postantibiotic effect (<1 hour) for streptococci and gram-negative bacilli; for S. aureus: ~4 hours (Craig 1993; Craig 1998).
Solution (ceFAZolin Sodium-Dextrose Intravenous)
1GM/50ML 4% (per mL): $0.13
2GM/100ML 4% (per mL): $0.11
Solution (reconstituted) (ceFAZolin Sodium Injection)
1 g (per each): $1.08 - $7.50
10 g (per each): $7.20 - $60.00
100 g (per each): $120.00
300 g (per each): $348.00
500 mg (per each): $1.01 - $9.74
Solution (reconstituted) (ceFAZolin Sodium Intravenous)
1 g (per each): $3.28
Solution (reconstituted) (ceFAZolin Sodium-Dextrose Intravenous)
1GM 4%(50ML) (per each): $13.62
2GM 3%(50ML) (per each): $15.32
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