Cefazolin (Ancef)
cefazolin sodium
Indications
| Indication | Approved Population | Therapy Type | Status |
|---|---|---|---|
| Respiratory tract infections (S. pneumoniae, S. aureus [MSSA], Klebsiella spp., H. influenzae, GAS) | Adults & pediatric ≥1 month | Monotherapy | FDA Approved |
| Urinary tract infections (E. coli, P. mirabilis, Klebsiella spp.) | Adults & pediatric ≥1 month | Monotherapy | FDA Approved |
| Skin & skin structure infections (S. aureus [MSSA], GAS, S. agalactiae) | Adults & pediatric ≥1 month | Monotherapy | FDA Approved |
| Biliary tract infections (E. coli, Streptococcus spp., P. mirabilis, Klebsiella spp., MSSA) | Adults & pediatric ≥1 month | Monotherapy | FDA Approved |
| Bone & joint infections (S. aureus [MSSA]) | Adults & pediatric ≥1 month | Monotherapy | FDA Approved |
| Genital infections (prostatitis, epididymitis — E. coli, P. mirabilis, Klebsiella spp.) | Adults & pediatric ≥1 month | Monotherapy | FDA Approved |
| Septicemia (S. pneumoniae, S. aureus [MSSA], E. coli, P. mirabilis, Klebsiella spp.) | Adults & pediatric ≥1 month | Monotherapy | FDA Approved |
| Endocarditis (S. aureus [MSSA], GAS) | Adults & pediatric ≥1 month | Monotherapy or combination | FDA Approved |
| Perioperative prophylaxis (contaminated/potentially contaminated surgery) | Adults | Prophylaxis | FDA Approved |
Cefazolin is the only parenteral first-generation cephalosporin available in the United States and remains the cornerstone of surgical antimicrobial prophylaxis and empiric MSSA therapy. It has strong activity against gram-positive cocci (MSSA, streptococci) and modest gram-negative coverage (E. coli, Klebsiella, P. mirabilis). It lacks activity against MRSA, enterococci, Pseudomonas, Enterobacter, and anaerobes. Current AHA/IDSA guidelines recommend cefazolin as a preferred alternative to antistaphylococcal penicillins for MSSA bacteremia and native valve endocarditis based on comparable efficacy and better tolerability.
MSSA bacteremia — first-line definitive therapy: AHA/IDSA endocarditis guidelines recommend cefazolin 2 g IV q8h as a preferred alternative to nafcillin/oxacillin for MSSA native valve endocarditis. Multiple observational studies demonstrate non-inferior or superior outcomes compared with antistaphylococcal penicillins. Evidence quality: High.
Cesarean section prophylaxis: ACOG and ASHP/IDSA/SIS/SHEA guidelines recommend cefazolin as the preferred agent for cesarean delivery prophylaxis (2 g IV; 3 g if ≥120 kg). Evidence quality: High.
Weight-based surgical prophylaxis (≥120 kg): ASHP/IDSA/SIS/SHEA 2013 guideline recommends 3 g for patients ≥120 kg, with re-dosing at 4-hour intervals for prolonged procedures. Evidence quality: High.
Dosing
Adult Dosing by Clinical Scenario (CrCl ≥55 mL/min)
| Clinical Scenario | Starting Dose | Maintenance Dose | Maximum Dose | Notes |
|---|---|---|---|---|
| Mild infection — susceptible gram-positive cocci | 250–500 mg IV Q8H | 250–500 mg IV Q8H | 1.5 g/day | Step down to oral cephalexin when clinically stable |
| Moderate-severe infection (SSSI, UTI, biliary) | 500 mg–1 g IV Q6–8H | 500 mg–1 g IV Q6–8H | 6 g/day | Majority of treatment infections Adjust frequency based on severity and site |
| Uncomplicated UTI | 1 g IV Q12H | 1 g IV Q12H | 2 g/day | Step down to oral agent when culture data available |
| Pneumococcal pneumonia | 500 mg IV Q12H | 500 mg IV Q12H | 1 g/day | For penicillin-susceptible S. pneumoniae only |
| MSSA bacteremia / endocarditis / septicemia | 1–1.5 g IV Q6H | 2 g IV Q8H | 12 g/day (rare) | NVE: 6 weeks; bacteremia: 2–6 weeks per source AHA/IDSA prefer cefazolin 2 g Q8H for MSSA NVE |
| Osteomyelitis / septic arthritis (MSSA) | 1–2 g IV Q8H | 1–2 g IV Q8H | 6 g/day | 4–6 weeks total; step down to oral cephalexin Preferred IV agent for MSSA bone/joint infection |
| Surgical prophylaxis — standard weight (<120 kg) | 1–2 g IV | 500 mg–1 g Q6–8H × 24 h | 2 g preop | Give ½–1 h before incision; re-dose Q4H intraop Discontinue within 24 h; cardiac/prosthetic: up to 3–5 days |
| Surgical prophylaxis — high weight (≥120 kg) | 3 g IV | 1 g Q6–8H × 24 h | 3 g preop | ASHP/IDSA/SIS/SHEA 2013 weight-based guideline Re-dose 1–2 g intraop Q4H for prolonged surgery |
Pediatric Dosing (≥1 month, CrCl ≥70 mL/min)
| Clinical Scenario | Starting Dose | Maintenance Dose | Maximum Dose | Notes |
|---|---|---|---|---|
| Mild-moderate infection | 25–50 mg/kg/day IV | Divided Q6–8H | 50 mg/kg/day | Per FDA PI Table 2 |
| Severe infection | Up to 100 mg/kg/day IV | Divided Q6–8H | 100 mg/kg/day | Do not exceed adult dose |
Renal Dose Adjustment — Adults (CrCl <55 mL/min)
| CrCl (mL/min) | Dosage Recommendation | Notes | Source |
|---|---|---|---|
| 35–54 | Full recommended dose Q8H or longer | After initial loading dose | FDA PI |
| 11–34 | Half recommended dose Q12H | After initial loading dose | FDA PI |
| ≤10 | Half recommended dose Q18–24H | After initial loading dose | FDA PI |
The FDA label and ASHP/IDSA/SIS/SHEA guidelines emphasise that the preoperative dose must be given within 30–60 minutes of surgical incision to ensure adequate tissue concentrations at the time of the first cut. For prolonged procedures exceeding 2 hours (approximately two half-lives), intraoperative re-dosing with 500 mg–1 g is recommended. Prophylaxis should be discontinued within 24 hours after surgery for most procedures, with an exception for cardiac and prosthetic arthroplasty surgery where up to 3–5 days may be justified. Cefazolin’s longer half-life compared with cefoxitin or cefuroxime makes it particularly practical for this role.
Pharmacology
Mechanism of Action
Cefazolin is a bactericidal beta-lactam antibiotic that disrupts bacterial cell wall synthesis by binding to penicillin-binding proteins (PBPs). This binding inhibits the transpeptidation step in peptidoglycan cross-linking, weakening the cell wall and leading to osmotic lysis and bacterial death. As a first-generation cephalosporin, cefazolin has strong affinity for PBPs in gram-positive organisms, particularly MSSA and streptococci, making it the parenteral agent of choice for MSSA infections. Its bactericidal activity is time-dependent, with efficacy correlating to the percentage of the dosing interval during which free drug concentrations exceed the MIC (% fT > MIC). Given its high protein binding (~85%), the unbound fraction drives antimicrobial activity, a consideration particularly important in hypoalbuminaemic patients where free drug levels are higher.
ADME Profile
| Parameter | Value | Clinical Implication |
|---|---|---|
| Absorption | Not orally bioavailable; given IV (or IM with some formulations); Cmax ~185 mcg/mL after 1 g IV | Parenteral administration only; IV bolus (2 g vial, over 3–5 min for 1 g) or infusion over 30 min; switch to oral cephalexin for step-down |
| Distribution | Vd ~10 L/1.73 m² (~0.12 L/kg); ~85% protein bound (concentration-dependent, non-linear); penetrates bile (up to 5× serum in non-obstructed), synovial fluid, bone, placenta | Small Vd concentrates drug in intravascular space; high protein binding is saturable at peak concentrations — higher free fraction at Cmax; poor CSF penetration limits CNS use |
| Metabolism | No hepatic metabolism; does not affect CYP450 enzymes | No drug-drug interactions via hepatic pathways; no hepatic dose adjustment |
| Elimination | t½ ~1.8 h; excreted unchanged in urine via glomerular filtration; ~60% in first 6 h, ~100% within 24 h; renal clearance 64 mL/min/1.73 m² | Dose reduction required when CrCl <55 mL/min; longer half-life than cephalothin (~0.5 h) makes Q8H dosing practical for many infections |
Side Effects
The cefazolin FDA PI does not report specific percentage incidence rates for individual adverse reactions. It lists reactions descriptively from clinical trials. The estimates below are derived from published literature, surgical prophylaxis studies, and class-effect data for first-generation cephalosporins.
| Adverse Effect | Estimated Incidence | Clinical Note |
|---|---|---|
| Diarrhea | 2–5% | Most common GI reaction; distinguish from C. difficile |
| Nausea / vomiting | 1–3% | Usually self-limiting |
| Phlebitis / injection site reactions | 1–5% | More common with bolus injection; pain associated with IV bolus reported in FDA PI |
| Rash | 1–2% | Evaluate for evolving hypersensitivity; distinguish from drug fever |
| Adverse Effect | Estimated Incidence | Clinical Note |
|---|---|---|
| Transient AST/ALT/ALP elevation | <2% | Usually resolves without intervention; monitor if prolonged therapy |
| Eosinophilia | <2% | May indicate drug hypersensitivity |
| Oral candidiasis | <2% | Class effect from disruption of normal flora |
| Genital / vulvovaginal pruritus | <2% | May include vaginitis and candidiasis |
| Drug fever | <1% | Distinguish from infection-related fever; resolves upon discontinuation |
| Dizziness / confusion / somnolence | <1% | More common with renal impairment when dose is not adjusted |
| Adverse Effect | Estimated Frequency | Typical Onset | Required Action |
|---|---|---|---|
| Anaphylaxis / severe hypersensitivity | Rare | Minutes to hours | Discontinue immediately; epinephrine; emergency care |
| Stevens-Johnson syndrome | Very rare | 1–3 weeks | Discontinue; dermatology referral; supportive care |
| Clostridioides difficile colitis | Uncommon | During or up to 2 months post-therapy | Test for C. difficile toxin; discontinue cefazolin; treat with vancomycin or fidaxomicin |
| Seizures | Rare (renal impairment) | Variable; risk with drug accumulation | Discontinue or dose-adjust; anticonvulsant therapy as indicated |
| Hemolytic anemia (positive Coombs’ test) | Rare | During therapy | Discontinue; hemolysis workup; transfuse if needed |
| Neutropenia / thrombocytopenia | Rare | Prolonged therapy | Monitor CBC; discontinue if significant cytopenias |
| Acute tubulointerstitial nephritis | Very rare (postmarketing) | Days to weeks | Discontinue; evaluate renal function; usually reversible |
| Serum sickness-like reaction | Very rare (postmarketing) | 1–2 weeks | Discontinue; supportive care |
Drug Interactions
Cefazolin undergoes no hepatic metabolism and does not affect CYP450 enzymes, giving it an exceptionally favourable drug interaction profile. The only FDA-labelled pharmacokinetic interaction involves renal tubular secretion blockade by probenecid.
Monitoring
- Renal FunctionBaseline; periodically
RoutineAssess CrCl before and during therapy. Dose reduction required when CrCl <55 mL/min (adults) or <70 mL/min (pediatric). Elderly patients especially likely to have impaired renal function. - Clinical Response48–72 h
RoutineEvaluate for clinical improvement. If no response, reassess cultures and coverage. For bacteremia, repeat blood cultures at 48–72 hours to document clearance. - CBCWeekly if therapy >14 days
Trigger-basedMonitor for neutropenia, thrombocytopenia, and eosinophilia during prolonged courses (e.g., endocarditis, osteomyelitis). - Hepatic FunctionPeriodically if prolonged therapy
Trigger-basedTransient AST/ALT/ALP elevations reported; check if signs of hepatotoxicity develop. - PT/INRIf on anticoagulants
Trigger-basedMonitor prothrombin time in patients on warfarin, with renal/hepatic impairment, or poor nutritional status. Administer vitamin K as indicated. - IV SiteEach dose
RoutineInspect for phlebitis and induration. Rotate sites as needed. Pain with IV bolus injection has been reported. - Stool AssessmentIf diarrhea develops
Trigger-basedTest for C. difficile toxin if diarrhea is persistent, watery, or bloody, during or up to 2 months after therapy.
Contraindications & Cautions
Absolute Contraindications
- History of immediate hypersensitivity reactions (anaphylaxis, serious skin reactions) to cefazolin, other cephalosporins, penicillins, or other beta-lactams
Relative Contraindications (Specialist Input Recommended)
- Non-immediate penicillin allergy — cross-hypersensitivity may occur in up to 10% of penicillin-allergic patients; evaluate risk-benefit and consider allergy testing
- MRSA infection — cefazolin has no activity; confirm susceptibility before definitive therapy
Use with Caution
- Renal impairment (CrCl <55 mL/min) — dose reduction required; risk of drug accumulation and seizures
- Known seizure disorder — seizures reported particularly with renal impairment when dosage not adjusted
- Elderly patients — more likely to have decreased renal function; verify CrCl
- Patients on anticoagulants — monitor PT/INR; may be associated with prothrombin time prolongation
- Premature infants and neonates <1 month — safety and effectiveness not established
- History of GI disease (especially colitis) — increased risk of C. difficile
Serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported in patients receiving beta-lactam antibacterial drugs. Cross-hypersensitivity among beta-lactam agents may occur in up to 10% of patients with a history of penicillin allergy. Careful inquiry about prior reactions is essential before initiating cefazolin therapy. If an allergic reaction occurs, the drug should be discontinued immediately and appropriate treatment instituted (FDA PI, revised December 2024).
Patient Counselling
Purpose of Therapy
Cefazolin is a prescription antibiotic given through a vein (intravenously) to treat or prevent bacterial infections. It is effective against many common bacteria, including those causing skin, bone, blood, heart, urinary, and abdominal infections. It is also widely used to prevent infection during surgery. Cefazolin does not work against viral infections.
How It Is Given
Cefazolin is administered by a healthcare professional as an intravenous infusion or injection. It cannot be taken by mouth. Treatment duration depends on the type and severity of infection — typically 7 to 14 days for most infections, and up to 6 weeks for endocarditis or bone infections. When clinically appropriate, your prescriber may switch you to an oral antibiotic (such as cephalexin) to complete the course at home.
Sources
- Cefazolin for Injection prescribing information. Hikma Pharmaceuticals USA Inc. Revised December 2024. FDA LabelPrimary source for all approved indications, dosing tables (including renal adjustment), adverse reactions, PK data, and contraindications cited in this monograph.
- Cefazolin for Injection and Dextrose Injection prescribing information. B. Braun Medical Inc. Revised August 2024. FDA LabelPremixed bag formulation label with identical clinical data and additional pediatric PK study results for perioperative prophylaxis.
- Lee S, Choe PG, Song KH, et al. Is cefazolin inferior to nafcillin for treatment of methicillin-susceptible Staphylococcus aureus bacteremia? Antimicrob Agents Chemother. 2011;55(11):5122-5126. doi:10.1128/AAC.00485-11Retrospective cohort demonstrating non-inferior outcomes with cefazolin vs nafcillin for MSSA bacteremia, supporting its role as first-line alternative.
- Li J, Echevarria KL, Hughes DW, et al. Comparison of cefazolin versus oxacillin for treatment of complicated bacteremia caused by methicillin-susceptible Staphylococcus aureus. Antimicrob Agents Chemother. 2014;58(9):5117-5124. doi:10.1128/AAC.02800-14Supports cefazolin as effective alternative to oxacillin for MSSA complicated bacteremia with comparable outcomes and fewer adverse events.
- Bratzler DW, Dellinger EP, Olsen KM, et al. Clinical practice guidelines for antimicrobial prophylaxis in surgery. Am J Health Syst Pharm. 2013;70(3):195-283. doi:10.2146/ajhp120568ASHP/IDSA/SIS/SHEA guideline recommending cefazolin as preferred agent for most surgical prophylaxis, including weight-based dosing (3 g for ≥120 kg).
- Baddour LM, Wilson WR, Bayer AS, et al. Infective endocarditis in adults: diagnosis, antimicrobial therapy, and management of complications. Circulation. 2015;132(15):1435-1486. doi:10.1161/CIR.0000000000000296AHA guideline for infective endocarditis management; recommends cefazolin as alternative to nafcillin/oxacillin for MSSA native valve endocarditis.
- Stevens DL, Bisno AL, Chambers HF, et al. Practice guidelines for the diagnosis and management of skin and soft tissue infections: 2014 update by the IDSA. Clin Infect Dis. 2014;59(2):e10-e52. doi:10.1093/cid/ciu296IDSA SSTI guideline supporting cefazolin for parenteral treatment of nonpurulent MSSA cellulitis.
- Tamma PD, Aitken SL, Bonomo RA, et al. IDSA 2023 guidance on the treatment of antimicrobial-resistant gram-negative infections. Clin Infect Dis. 2023;ciad428. doi:10.1093/cid/ciad428IDSA AMR guidance referencing cefazolin’s position in the empiric and definitive treatment of susceptible gram-negative infections.
- Tipper DJ. Mode of action of beta-lactam antibiotics. Pharmacol Ther. 1985;27(1):1-35. doi:10.1016/0163-7258(85)90062-2Foundational review of beta-lactam mechanism of action through PBP binding and cell wall synthesis inhibition.
- Kirby WMM, Regamey C. Pharmacokinetics of cefazolin compared with four other cephalosporins. J Infect Dis. 1973;128(Suppl 2):S341-S346. doi:10.1093/infdis/128.Supplement_2.S341Classic PK study confirming cefazolin half-life (1.8 h), protein binding (~86%), Vd (10 L/1.73 m²), and renal clearance (64 mL/min/1.73 m²).
- Welling PG, Tse FLS, Craig WA, et al. Pharmacokinetics of cefazolin in normal and uremic subjects. Clin Pharmacol Ther. 1974;15(4):344-353. doi:10.1002/cpt1974154344PK study demonstrating prolonged half-life and elevated levels in uremic patients, supporting renal dose adjustment recommendations.
- van Kralingen S, Taks M, Diepstraten J, et al. Pharmacokinetics and protein binding of cefazolin in morbidly obese patients. Eur J Clin Pharmacol. 2011;67(10):985-992. doi:10.1007/s00228-011-1048-xPK study in obese patients (112–260 kg) confirming adequate unbound concentrations above MSSA MIC90 for at least 4 hours after 2 g IV dose; saturable protein binding ~79%.