Cefazolin

J01D - Other beta-lactam antibacterials ATC J01DB24 Small molecule approved 1973 Parenteral Natural product

🧬 Cross-allergy: Cephalosporins

JFDA label: Cefazoline Sandoz

Mechanism of Action

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.

Indications

Approved

Biliary tract infections
Bone and joint infections
Endocarditis, treatment
Genital infections
Perioperative prophylaxis
Respiratory tract infections
Septicemia
Skin and skin structure infections
Urinary tract infections

Off-label

Catheter-related bloodstream infections (adults)
Community-acquired pneumonia (children)
Endocarditis, prophylaxis
Prophylaxis in patients with prosthetic joint implants undergoing dental procedures which produce bacteremia
Skin and soft tissue necrotizing infections
Surgical site infection

Antimicrobial Spectrum

Expected / intrinsic spectrum (EUCAST breakpoints & labels) — not local resistance. Source: curated · openfda-label.

Bacteria

Organism	Activity	MIC
Escherichia coli	Susceptible	8.0 mg/L
Klebsiella pneumoniae	Susceptible	8.0 mg/L
Morganella morganii	Active	—
Proteus mirabilis	Active	—
Proteus vulgaris	Active	—
Providencia rettgeri	Active	—
Staphylococcus aureus	Susceptible	2.0 mg/L
Staphylococcus epidermidis	Active	—
Streptococcus agalactiae	Active	—
Streptococcus pneumoniae	Active	—
Streptococcus pyogenes	Active	—
Staphylococcus aureus	Resistant	4.0 mg/L

Class profile

gramStatus	Both
spectrumBreadth	Moderate
atypicalCoverage	No
isBactericidal	1
moaCategory	Cell wall synthesis inhibitor (beta-lactam, 1st generation cephalosporin)
pdIndex	Time-dependent
postAntibioticEffect	None
mrsaCoverage	0
resistanceMechanisms	Beta-lactamase production,PBP mutations

Contraindications

Source: Lexicomp

Hypersensitivity to cefazolin, other cephalosporin antibiotics, penicillins, other beta-lactams, or any component of the formulation Absolute

Adverse Reactions

Very Common >10%Common 1–10%Uncommon 0.1–1% Rare 0.01–0.1%Very Rare <0.01%Not Known

Cardiac disorders (1)

Not Known Localized phlebitis

Nervous system disorders (1)

Not Known Seizure

Hepatobiliary disorders (2)

Not Known Hepatitis · increased serum transaminases

Renal and urinary disorders (4)

Not Known Increased blood urea nitrogen · increased serum creatinine · renal failure · Vaginitis

Blood and lymphatic system disorders (5)

Not Known Eosinophilia · leukopenia · neutropenia · thrombocythemia · thrombocytopenia

Immune system disorders (1)

Not Known Anaphylaxis

Gastrointestinal disorders (7)

Not Known Abdominal cramps · anorexia · diarrhea · nausea · oral candidiasis · pseudomembranous colitis · vomiting

Skin and subcutaneous tissue disorders (3)

Not Known Pruritus · skin rash · Stevens-Johnson syndrome

General disorders and administration site conditions (2)

Not Known Fever · Pain at injection site

Dosing

Source: Lexicomp

Usual dosage range: IM, IV: 1 to 1.5 g every 8 hours, depending on severity of infection; maximum: 12 g daily Catheter-related bloodstream infections (off-label use): IV: 2 g every 8 hours (IDSA [Mermel 2009]) Cholecystitis, mild-to-moderate: IV: 1 to 2 g every 8 hours for 4 to 7 days (provided source controlled) Endocar ditis, prophylaxis (off-label use): Dental and upper respiratory procedures: IM, IV: 1 g 30 to 60 minutes before procedure. Intramuscular injections should be avoided in patients who are receiving anticoagulant therapy. In these circumstances, orally administered regimens should be given whenever possible. Intravenously administered antibiotics should be used for patients who are unable to tolerate or absorb oral medications. Note: American Heart Association (AHA) guidelines now recommend prophylaxis only in patients undergoing invasive procedures and in whom underlying cardiac conditions may predispose to a higher risk of adverse outcomes should infection occur. As of April 2007, routine prophylaxis for GI/GU procedures is no longer recommended by the AHA. Endocarditis, treatment: IV: Manufacturer’s labeling: 1 to 1.5 g every 6 hours Alternate dosing (AHA [Baddour 2015]): MSSA in penicillin-allergic (nonanaphylactoid) patients: Native valve: 2 g every 8 hours for 6 weeks Prosthetic valve: 2 g every 8 hours for a minimum of 6 weeks (in combination with rifampin for entire course of therapy and gentamicin for the first 2 weeks) Group B streptococcus (neonatal prophylaxis): IV: 2 g once, then 1 g every 8 hours until delivery (CDC 2010) Intra-abdominal infection, complicated, community-acquired, mild-to-moderate (in combination with metronidazole): IV: 1 to 2 g every 8 hours for 4 to 7 days (provided source controlled) Moderate to severe infections: IV: 500 mg to 1 g every 6 to 8 hours Mild infection with gram-positive cocci: IV: 250 to 500 mg every 8 hours Osteomyelitis, native vertebral (off-label dose): Staphylococci (oxacillin-susceptible): IV: 1 to 2 g every 8 hours for 6 weeks (IDSA [Berbari 2015]) Perioperative prophylaxis: Manufacturer’s labeling: IM, IV: 1 to 2 g initiated 30 to 60 minutes prior to surgery; may repeat after 2 hours if procedure is lengthy with 500 mg to 1 g intraoperatively, followed by 500 mg to 1 g every 6 to 8 hours for 24 hours postoperatively. Guideline recommendations (off-label): IV: Note: For most surgical procedures, joint clinical practice guidelines from the American Society of Health-System Pharmacists, Infectious Diseases Society of America, Surgical Infection Society, and Society for Healthcare Epidemiology of America (ASHP/IDSA/SIS/SHEA) recommend a dose of 2 g within 60 minutes prior to surgical incision (for nonobese patients weighing Obesity: The ASHP/IDSA/SIS/SHEA guidelines recommend that for patients weighing ≥120 kg, a dose of 3 g within 60 minutes prior to surgical incision should be administered (Bratzler 2013). Alternatively, for patients with BMI >40 kg/m2, a single 2 g dose may be

(For additional information see "Cefazolin: Pediatric drug information") Usual dosage range: IM, IV: Infants >1 month, Children, and Adolescents: 25 to 100 mg/kg/day divided every 6 to 8 hours; maximum: 6 g daily Community-acquired pneumonia (CAP) (IDSA/PIDS 2011), moderate-to-severe infection, S. aureus (methicillin-susceptible) (preferred): Infants >3 months and Children: IM, IV: 150 mg/kg/day divided every 8 hours Endocarditis, prophylaxis (off-label use): 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 (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). Endocarditis, treatment (off-label): 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]) Perioperative prophylaxis (off-label use): Children ≥1 year: IV: Note: For most surgical procedures, joint clinical practice guidelines from the American Society of Health-System Pharmacists, Infectious Diseases Society of America, Surgical Infection Society, and Society for Healthcare Epidemiology of America (ASHP/IDSA/SIS/SHEA) recommend a dose of 30 mg/kg (maximum dose: 2,000 mg) administered within 60 minutes prior to surgical incision. For procedures requiring anaerobic coverage (eg, appendectomy, small bowel surgery with intestinal obstruction, colon procedures), combine cefazolin with metronidazole as an alternative to a second generation cephalosporin with anaerobic activity (eg, cefoxitin or cefotetan). Cefazolin doses may be repeated intraoperatively in 4 hours if procedure is lengthy or if there is excessive blood loss (Bratzler 2013). Peritonitis, treatment (off-label route; Warady 2012): Infants, Children, and Adolescents: Intraperitoneal: Intermittent exchange: 20 mg/kg every 24 hours in the long dwell Continuous exchange: Loading dose: 500 mg per liter of dialysate. Maintenance: 125 mg per liter of dialysate. Skin and soft tissue infection due to MSSA, including pyomyositis: Infants and Children: IV: 50 mg/kg/day divided every 8 hours for 7 to 14 days; treat pyomyositis for 14 to 21 days (IDSA [Stevens 2014]) Skin and soft tissue necrotizing infections due to MSSA (off-label use): Infants and Children: IV: 33 mg/kg every 8 hours; continue until further debridement is not n

Refer to adult dosing.

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)

There are no dosage adjustments provided in the manufacturer's labeling.

Warnings & Precautions

Source: Lexicomp

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 C. 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. Concurrent drug therapy issues:

Drug-drug interactions

Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Pregnancy & Lactation

Pregnancy

FDA category B

Adverse effects have not been observed in animal reproduction studies. Cefazolin crosses the placenta. Adverse events have not been reported in the fetus following administration of cefazolin prior to cesarean section. Cefazolin is recommended for group B streptococcus prophylaxis in pregnant patients with a nonanaphylactic penicillin allergy. It is also one of the antibiotics recommended for prophylactic use prior to cesarean delivery and may be used in certain situations prior to vaginal delivery in women at high risk for endocarditis. Due to pregnancy-induced physiologic changes, the pharmacokinetics of cefazolin are altered. The half-life is shorter, the AUC is smaller, and the clearance and volume of distribution are increased.

Lactation

Small amounts of cefazolin are excreted in breast milk. The manufacturer recommends that caution be exercised when administering cefazolin to nursing women. Nondose-related effects could include modification of bowel flora.

Monitoring

Efficacy	Culture and susceptibility testing; clinical resolution (temperature, WBC, CRP, procalcitonin)
Toxicity	Renal function (dose adjustment in renal impairment); hepatic function for hepatically cleared agents; signs of C. difficile infection (diarrhoea)
Clinical pearl	Culture results guide de-escalation to narrower-spectrum therapy. Review antibiotic appropriateness at 48–72 h (antimicrobial stewardship).
Counseling	Complete the full course. Report persistent diarrhoea, rash, or lack of improvement after 48–72 h.

Chemistry & Properties

Formula	C14H14N8O4S3
Molecular weight	454.52 g/mol
IUPAC name	(6R,7R)-3-[(5-methyl-1,3,4-thiadiazol-2-yl)sulfanylmethyl]-8-oxo-7-[[2-(tetrazol-1-yl)acetyl]amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid
CAS	25953-19-9
PubChem CID	33255
InChIKey	`MLYYVTUWGNIJIB-BXKDBHETSA-N`
logP	-0.64 (XLogP -0.4)
Polar surface area	156.09 Å²
H-bond acceptors / donors	12 / 2
Drug-likeness (QED)	0.41
Lipinski violations	1

SMILES

Cc1nnc(SCC2=C(C(=O)O)N3C(=O)[C@@H](NC(=O)Cn4cnnn4)[C@H]3SC2)s1

Biology & Pharmacokinetics

Pharmacokinetics

BBB penetrant	No

Transporters

BCRP (Inhibitor)BSEP (Inhibitor)BSEP (Inhibitor)MATE1 (Inhibitor)MATE2 (Inhibitor)MRP1 (Inhibitor)MRP2 (Inhibitor)MRP3 (Inhibitor)MRP4 (Inhibitor)OAT1 (Inhibitor)OAT2 (Inhibitor)OAT3 (Inhibitor)OAT4 (Inhibitor)OATP1B1 (Inhibitor)OATP1B1 (Inhibitor)OATP1B3 (Inhibitor)OATP1B3 (Inhibitor)P-gp (Inhibitor)PEPT1 (Inhibitor)MATE2 (Substrate)MRP4 (Substrate)OAT (Substrate)OAT1 (Substrate)OAT2 (Substrate)OAT3 (Substrate)OATP1B1 (Substrate)OATP1B3 (Substrate)P-gp (Substrate)PEPT1 (Substrate)

Drug–drug interactions (14, DDInter)

Interacting drug	Severity	Management
Amikacin	moderate
Amikacin (liposome)	moderate
Chloramphenicol	moderate
Dicoumarol	moderate
Ethinylestradiol	moderate
Gentamicin	moderate
Kanamycin	moderate
Mycophenolic acid	moderate
Neomycin	moderate
Pemetrexed	moderate
Picosulfuric acid	moderate
Streptomycin	moderate
Warfarin	moderate
Heparin	minor

Registered Products (10)

Brand	Form / strength	Pack	Agent	Citizen (JOD)
Hikma Cefazolin 250 IM Injection	Powder for Injection 250 mg	1 vial	Hikma Pharmaceuticals Co.Ltd/Jordan	0.800
Hikma Cefazolin 500 IV Injection	Powder for Injection 500 mg	1 vial pack varies	Hikma Pharmaceuticals Co.Ltd/Jordan	1.220
Hikma Cefazolin 500 IM Injection	Powder for Injection 500 mg	1 ampoule pack varies	Hikma Pharmaceuticals Co.Ltd/Jordan	1.350
Hikma Cefazolin 1000 IV Injection	Powder for Injection (as Sodium) 1000 mg	1 vial	Hikma Pharmaceuticals Co.Ltd/Jordan	1.890
Hikma Cefazolin 1000 IM Injection	Powder for Injection 1000 mg	1 vial pack varies	Hikma Pharmaceuticals Co.Ltd/Jordan	2.080
Hikma Cefazolin 500 IM Injection	Powder for Injection 500 mg	1 ampoule pack varies	Hikma Pharmaceuticals Co.Ltd/Jordan	9.000
Hikma Cefazolin 1000 IV Injection	Powder for Injection (as Sodium)1000 mg	10 vial	Hikma Pharmaceuticals Co.Ltd/Jordan	15.070
Hikma Cefazolin 1000 IM Injection	Powder for Injection 1000 mg	10 vial pack varies	Hikma Pharmaceuticals Co.Ltd/Jordan	18.720
Cefazoline Sandoz	Tablet 0.5 g	50 tab	Nabulsi Drug Store	57.260
Cefazolin Sandoz	Vial 1 g	50	Nabulsi Drug Store	100.530