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Cefazolin
Cefazolin
Cefazolin
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Cefazolin
Clinical data
Pronunciation/səˈfæzələn/[1]
Trade namesAncef, Cefacidal, other
AHFS/Drugs.comMonograph
Pregnancy
category
  • AU: B1
Routes of
administration		intravenous, intramuscular
Drug classFirst-generation cephalosporin
ATC code
Legal status
Legal status
  • In general: ℞ (Prescription only)
Pharmacokinetic data
BioavailabilityNA
Metabolism?
Elimination half-life1.8 hours (given IV)
2 hours (given IM)
Excretionkidney, unchanged
Identifiers
  • (6R,7R)-3-{[(5-methyl-1,3,4-thiadiazol-2-yl)thio]methyl}-8-oxo-7-[(1H-tetrazol-1-ylacetyl)amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.043.042 Edit this at Wikidata
Chemical and physical data
FormulaC14H14N8O4S3
Molar mass454.50 g·mol−1
3D model (JSmol)
Melting point198 to 200 °C (388 to 392 °F) (decompose.)
  • O=C2N1/C(=C(\CS[C@@H]1[C@@H]2NC(=O)Cn3nnnc3)CSc4nnc(s4)C)C(=O)O
  • InChI=1S/C14H14N8O4S3/c1-6-17-18-14(29-6)28-4-7-3-27-12-9(11(24)22(12)10(7)13(25)26)16-8(23)2-21-5-15-19-20-21/h5,9,12H,2-4H2,1H3,(H,16,23)(H,25,26)/t9-,12-/m1/s1 checkY
  • Key:MLYYVTUWGNIJIB-BXKDBHETSA-N checkY
  (verify)

Cefazolin, also known as cefazoline and cephazolin, is a first-generation cephalosporin antibiotic used for the treatment of a number of bacterial infections.[2] Specifically it is used to treat cellulitis, urinary tract infections, pneumonia, endocarditis, joint infection, and biliary tract infections.[2] It is also used to prevent group B streptococcal disease around the time of delivery and before surgery.[2] It is typically given by injection into a muscle or vein.[2]

Common side effects include diarrhea, vomiting, yeast infections, and allergic reactions.[2] Historically, it was thought to be contraindicated in patients with allergies to penicillin, although several recent studies have refuted this and it is proven to be safe in almost all patients, including those with known penicillin allergies.[3] It is relatively safe for use during pregnancy and breastfeeding.[2][4] Cefazolin is in the first-generation cephalosporin class of medication and works by interfering with the bacteria's cell wall.[2]

Cefazolin was patented in 1967 and came into commercial use in 1971.[5][6] It is on the World Health Organization's List of Essential Medicines.[7] It is available as a generic medication.[2]

Medical uses

[edit]

Cefazolin is used in a variety of infections provided that susceptible organisms are involved. It is indicated for use in the following infections:[8]

It can also be used peri-operatively to prevent infections post-surgery, and is often the preferred drug for surgical prophylaxis.[8]

There is no penetration into the central nervous system and therefore cefazolin is not effective in treating meningitis.[9]

Cefazolin has been shown to be effective in treating methicillin-susceptible Staphylococcus aureus (MSSA) but does not work in cases of methicillin-resistant Staphylococcus aureus (MRSA).[8] In many instances of staphylococcal infections, such as bacteremia, cefazolin is an alternative to penicillin in patients who are allergic to penicillin.[9] However, there is still potential for a reaction to occur with cefazolin and other cephalosporins in patients allergic to penicillin.[8] Resistance to cefazolin is seen in several species of bacteria, such as Mycoplasma and Chlamydia, in which case different generations of cephalosporins may be more effective.[10] Cefazolin does not fight against Enterococcus, anaerobic bacteria, or atypical bacteria, among others.[9]

Bacterial susceptibility

[edit]

As a first-generation cephalosporin antibiotic, cefazolin and other first-generation antibiotics are very active against gram-positive bacteria and some gram-negative bacteria.[8] Their broad spectrum of activity can be attributed to their improved stability to many bacterial beta-lactamases compared to penicillins.[9]

Spectrum of activity

[edit]

Gram-positive aerobes:[8][9]

Gram-Negative Aerobes:[11]

Non susceptible

[edit]

The following are not susceptible:[8][9]

Special populations

[edit]

Pregnancy

[edit]

Cefazolin is pregnancy category B, indicating general safety for use in pregnancy. Caution should be used in breastfeeding as a small amount of cefazolin enters the breast milk.[8] Cefazolin can be used prophylactically against perinatal Group B streptococcal infection (GBS). Although penicillin and ampicillin are the standard of care for GBS prophylaxis, penicillin-allergic women with no history of anaphylaxis can be given cefazolin instead. These patients should be closely monitored as there is a small chance of an allergic reaction due to the similar structure of the antibiotics.[12]

Newborns

[edit]

There has been no established safety and effectiveness for use in premature infants and neonates.[8]

Elderly

[edit]

No overall differences in safety or effectiveness were observed in clinical trials comparing elderly and younger subjects, however the trials could not eliminate the possibility that some older individuals may have a higher level of sensitivity.[8]

Additional considerations

[edit]

People with kidney disease and those on hemodialysis may need the dose adjusted.[8] Cefazolin levels are not significantly affected by liver disease.

As with other antibiotics, cefazolin may interact with other medications being taken. Some important drugs that may interact with cefazolin such as probenecid.[9]

Side effects

[edit]

Side effects associated with use of cefazolin therapy include:[8]

  • Common (1–10%): diarrhea, stomach pain or upset stomach, vomiting, and rash.
  • Uncommon (<1%): dizziness, headache, fatigue, itching, transient hepatitis.[13]

Patients with penicillin allergies could experience a potential reaction to cefazolin and other cephalosporins.[8] As with other antibiotics, patients experiencing watery and/or bloody stools occurring up to three months following therapy should contact their prescriber.[8]

Like those of several other cephalosporins, the chemical structure of cefazolin contains an N-methylthiodiazole (NMTD or 1-MTD) side-chain. As the antibiotic is broken down in the body, it releases free NMTD, which can cause hypoprothrombinemia (likely due to inhibition of the enzyme vitamin K epoxide reductase) and a reaction with ethanol similar to that produced by disulfiram (Antabuse), due to inhibition of aldehyde dehydrogenase.[14] Those with an allergy to penicillin may develop a cross sensitivity to cefazolin.[15][16]

Mechanism of action

[edit]

Cefazolin inhibits cell wall biosynthesis by binding penicillin-binding proteins which stops peptidoglycan synthesis. Penicillin-binding proteins are bacterial proteins that help to catalyze the last stages of peptidoglycan synthesis, which is needed to maintain the cell wall. They remove the D-alanine from the precursor of the peptidoglycan. The lack of synthesis causes the bacteria to lyse because they also continually break down their cell walls. Cefazolin is bactericidal, meaning it kills the bacteria rather than inhibiting their growth.[9]

Cost

[edit]

Cefazolin is relatively inexpensive.[17]

Trade names

[edit]

It was initially marketed by GlaxoSmithKline under the trade name Nostof.[18]

Other trade names include: Cefacidal, Cefamezin, Cefrina, Elzogram, Faxilen, Gramaxin, Kefol, Kefzol, Kefzolan, Kezolin, Novaporin, Reflin, Zinol, and Zolicef.

References

[edit]
[edit]
Revisions and contributorsEdit on WikipediaRead on Wikipedia

Cefazolin

View on Grokipedia
from Grokipedia
Cefazolin is a semisynthetic first-generation that acts as a bactericidal agent against a range of gram-positive and some . It is administered primarily via intravenous or and is commonly used to treat infections of the , and soft tissues, urinary tract, bones and joints, , and bloodstream, as well as for perioperative prophylaxis to prevent surgical site infections in adults and pediatric patients. Cefazolin works by binding to in bacterial cell walls, inhibiting the final step of peptidoglycan synthesis and leading to cell lysis and death. It exhibits good activity against pathogens such as Staphylococcus aureus (methicillin-susceptible), Streptococcus species, and certain Enterobacteriaceae, but resistance can occur through beta-lactamase production or altered . The drug achieves peak serum concentrations of approximately 185 mcg/mL after a 1 g intravenous dose, with a of about 1.8 hours, and is primarily excreted unchanged in the urine. Developed in the 1960s, patented in 1967, and approved by the FDA in 1973, cefazolin is included on the World Health Organization's Model List of (23rd list, 2023; updated 2025). It continues to be widely used due to its efficacy and safety when appropriate. Common adverse effects include gastrointestinal upset, injection site pain, and reactions, with contraindications for those with known allergies to cephalosporins or penicillins. Dosage adjustments are necessary for patients with renal impairment to avoid toxicity.

Medical uses

Indications

Cefazolin is indicated for the treatment of respiratory tract infections due to susceptible strains of Streptococcus pneumoniae, Staphylococcus aureus, and Streptococcus pyogenes. It is also approved for urinary tract infections caused by Escherichia coli or Proteus mirabilis, skin and skin structure infections from S. aureus or S. pyogenes, biliary tract infections involving E. coli, various streptococci, P. mirabilis, or S. aureus, bone and joint infections due to S. aureus, genital infections by E. coli or P. mirabilis, septicemia from S. pneumoniae, S. aureus, P. mirabilis, or E. coli, and endocarditis caused by S. aureus or S. pyogenes. For community-acquired pneumonia and empyema, cefazolin may be used when susceptibility is confirmed, particularly in hospitalized patients. In surgical settings, cefazolin serves as a first-line agent for perioperative prophylaxis to prevent surgical site infections in procedures such as (e.g., open-heart operations), orthopedic interventions (e.g., prosthetic ), and abdominal surgeries (e.g., colorectal or contaminated cases) in adults and pediatric patients aged 10 to 17 years for whom appropriate dosing can be achieved. According to ASHP/IDSA/SIS/SHEA clinical practice guidelines, cefazolin is recommended for prophylaxis in these clean-contaminated or contaminated procedures, with administration within 60 minutes before incision to achieve adequate tissue concentrations (strength of evidence: A). For endocarditis prophylaxis in high-risk patients undergoing dental procedures that involve gingival manipulation, cefazolin 1 g IV or may be used as an alternative for those with non-severe penicillin allergies unable to take oral medications, per AHA guidelines. For skin and soft tissue infections such as or wound infections caused by methicillin-susceptible S. aureus (MSSA) or streptococci, cefazolin is recommended as an intravenous option for hospitalized patients or severe cases, per IDSA guidelines. In urinary tract infections like or cystitis due to susceptible , and biliary tract infections, it provides targeted therapy when oral options are unsuitable. Adult dosing regimens vary by indication and severity: for moderate to severe infections (e.g., skin/soft tissue, , urinary tract, or biliary), 500 mg to 1 g IV every 6–8 hours; for mild infections caused by gram-positive cocci, 250–500 mg every 8 hours; for acute uncomplicated urinary tract infections, 1 g every 12 hours; and for severe life-threatening infections (e.g., or septicemia), 1–1.5 g every 6 hours, not exceeding 12 g daily. In perioperative prophylaxis, a 1–2 g dose is given 30– preoperatively, with 500 mg to 1 g redosing during procedures longer than 4 hours or significant blood loss, followed by 500 mg to 1 g every 6–8 hours for 24 hours postoperatively (extendable to 3–5 days in high-risk cases). For patients weighing ≥120 kg, guidelines recommend an initial 3 g dose for prophylaxis to optimize . All doses are administered intravenously over 30 minutes, with adjustments for renal impairment.

Spectrum of activity

Cefazolin, a first-generation and beta-lactam , exhibits a spectrum of activity primarily focused on , with limited coverage of certain Gram-negative organisms. It demonstrates time-dependent bactericidal activity by inhibiting bacterial synthesis through binding to , leading to cell lysis. The drug shows strong activity against many Gram-positive aerobes, particularly cocci such as methicillin-susceptible Staphylococcus aureus (excluding MRSA), Streptococcus pyogenes, and Streptococcus agalactiae. It is effective against most Staphylococcus and Streptococcus species, making it suitable for infections caused by these pathogens. Cefazolin provides moderate activity against some Gram-negative aerobes, including , , and . However, it lacks activity against anaerobes, atypical bacteria, and most other Gram-negative pathogens, such as . Compared to other cephalosporins, cefazolin has a narrower spectrum, with enhanced Gram-positive coverage but reduced efficacy against relative to second- and third-generation agents like or .

Bacterial susceptibility

Bacterial susceptibility to cefazolin is determined through standardized antimicrobial susceptibility testing (AST) methods that measure the minimum inhibitory concentration (MIC) or inhibition zone diameters, allowing categorization of isolates as susceptible (S), intermediate (I), or resistant (R). These tests are essential for predicting clinical efficacy, particularly for common indications like skin and soft tissue infections or urinary tract infections caused by susceptible organisms such as methicillin-susceptible Staphylococcus aureus (MSSA) or certain Enterobacterales. For S. aureus, cefazolin susceptibility is not directly tested; MSSA (oxacillin-susceptible) isolates are considered susceptible to cefazolin based on PK/PD data, with caution for inoculum effects. The primary methods for testing cefazolin susceptibility include , which provides quantitative MIC values by serial dilutions in broth; disk (Kirby-Bauer method), which assesses qualitative zone diameters on plates; and the E-test, a gradient strip method combining aspects of and dilution for precise MIC estimation. follows CLSI M07 guidelines, using Mueller-Hinton broth with a standardized inoculum of 5 × 10^5 CFU/mL, incubated at 35 ± 2°C for 16-20 hours. Disk adheres to CLSI M02, employing 30 μg cefazolin disks on Mueller-Hinton , with zones measured after 16-18 hours of incubation. The E-test uses a plastic strip with a cefazolin gradient (0.016-256 μg/mL) placed on , where the MIC is read at the intersection of the inhibition ellipse. Standardized breakpoints from CLSI and EUCAST guide interpretation, though they differ slightly by organism and indication. For in uncomplicated urinary tract infections, CLSI (M100, 35th ed., 2025) defines susceptible as MIC ≤ 2 μg/mL (disk zone ≥ 23 mm), intermediate at MIC 4 μg/mL (20-22 mm), and resistant at MIC ≥ 8 μg/mL (≤ 19 mm). EUCAST (v 15.0, 2025) sets susceptible at MIC ≤ 1 mg/L, intermediate 2 mg/L, resistant > 2 mg/L. These breakpoints are derived from pharmacokinetic/pharmacodynamic data, clinical outcomes, and wild-type MIC distributions to ensure reliable predictions of therapeutic success.
OrganizationOrganismMIC (μg/mL) SusceptibleMIC (μg/mL) IntermediateMIC (μg/mL) ResistantDisk Zone (mm) Susceptible
CLSI (2025)Enterobacterales (UTI)≤ 24≥ 8≥ 23
EUCAST (2025) (UTI)≤ 12> 2Not specified
Factors such as inoculum size and production can influence results, potentially leading to higher MICs (inoculum effect) in high-density infections, particularly with type A -producing MSSA, where MICs may increase 4- to 32-fold at 10^7 CFU/mL compared to standard 10^5 CFU/mL. Laboratories mitigate this by using standardized inocula and confirming via nitrocefin tests or . In clinical practice, susceptible results support cefazolin as a first-line option for de-escalation from broad-spectrum , such as switching from in MSSA bacteremia if MIC ≤ 2 μg/mL, while resistant or intermediate results prompt alternatives like . These interpretations align with guidelines emphasizing AST to optimize and reduce resistance pressure.

Limitations and resistance

Cefazolin, a first-generation , lacks activity against several inherently non-susceptible organisms due to intrinsic resistance mechanisms. These include species, which exhibit low-affinity (PBPs) that prevent effective binding and inhibition; (MRSA), which produces an altered PBP2a that confers resistance to all beta-lactam antibiotics, including cefazolin; , which possesses outer membrane impermeability and efflux pumps limiting drug entry; and , an anaerobe that produces constitutive beta-lactamases hydrolyzing the beta-lactam ring. Acquired resistance to cefazolin primarily arises through production, where enzymes such as extended-spectrum s (ESBLs) in like and hydrolyze the drug, rendering it ineffective. Additionally, alterations in PBPs can emerge in susceptible strains, further reducing binding affinity, though this is more prevalent in staphylococci. Susceptibility testing is essential to identify resistance, as phenotypic methods can detect activity and guide alternatives when cefazolin fails. Resistance prevalence remains a significant concern, with MRSA comprising nearly 50% of isolates in U.S. hospitals as of 2022, though hospital-onset MRSA bacteremia has declined by 78% from 2005 to 2019 and continued decreasing; making cefazolin unsuitable for in high-prevalence settings. For E. coli, resistance rates to first-generation cephalosporins like cefazolin have risen, driven by ESBL producers; CDC data indicate a 20% increase in hospital-onset ESBL-producing infections from 2019 to 2022, with community-onset cases also escalating post-pandemic. To address these challenges, antimicrobial stewardship programs promote judicious cefazolin use through prospective audit, education on local resistance patterns, and prioritization of susceptibility-guided , which has been shown to reduce overall beta-lactam resistance rates without compromising outcomes. Combination therapies, such as cefazolin with inhibitors in select non-ESBL cases, may enhance efficacy, though remains the cornerstone. Recent post-2020 studies highlight rising community MRSA and ESBL trends, exacerbated by COVID-19-related overuse of broad-spectrum antibiotics, underscoring the need for ongoing .

Pharmacology

Mechanism of action

Cefazolin, a first-generation , exerts its bactericidal action by binding to (PBPs) in the bacterial , particularly PBP-1 and PBP-3, thereby inhibiting the transpeptidase activity essential for cross-linking during synthesis. This disruption weakens the structural integrity of the layer, preventing the formation of a rigid necessary for bacterial survival. The core structure of cefazolin features a beta-lactam ring fused to a dihydrothiazine ring, which is critical for its antimicrobial activity as it mimics the D-alanyl-D-alanine substrate of PBPs, forming a stable acyl-enzyme complex that halts further peptidoglycan assembly. Cefazolin's specific R1 side chain at the 7-position ((1H-tetrazol-1-yl)acetamido) and R2 side chain at the 3-position ([(5-methyl-1,3,4-thiadiazol-2-yl)thio]methyl) enhance its binding affinity and confer relative stability against hydrolysis by some staphylococcal beta-lactamases, allowing effective activity against methicillin-susceptible Staphylococcus aureus. In actively dividing bacteria, this inhibition activates endogenous autolysins, proteolytic enzymes that degrade the existing cell wall, leading to osmotic lysis and cell death. As a time-dependent , cefazolin's efficacy is primarily determined by the of the dosing interval during which free concentrations remain above the (fT>MIC), with optimal bacterial killing achieved when this exceeds 40-50% for susceptible pathogens. Unlike against Gram-positive organisms, cefazolin demonstrates no significant post-antibiotic effect against , necessitating sustained exposure to maintain suppression of regrowth.

Pharmacokinetics

Cefazolin is administered intravenously or intramuscularly due to its poor oral , with intravenous administration being the preferred route for achieving rapid and reliable systemic exposure. Following intravenous , peak plasma concentrations are attained at the end of the , with nearly 100% , while results in peak levels within 1 to 2 hours. The drug exhibits a small of approximately 0.09 L/kg, indicating limited distribution primarily to . Cefazolin penetrates well into tissues such as , , , and pleural fluid, achieving concentrations comparable to plasma levels, which supports its use in and orthopedic infections. However, penetration into is poor, typically less than 1% of plasma concentrations in the absence of meningeal . Cefazolin undergoes minimal hepatic and is primarily excreted unchanged in the , with 70% to 80% recovery via glomerular filtration and active tubular secretion. In individuals with normal renal function, approximately 60% is eliminated within the first 6 hours and 70% to 80% within 24 hours. The plasma of cefazolin is approximately 1.8 hours following intravenous administration and 2 hours after intramuscular dosing in adults with normal renal function. This is prolonged in renal impairment, necessitating dosing adjustments when clearance is below 50 mL/min to avoid accumulation. Cefazolin is moderately bound to plasma proteins, with binding ranging from 74% to 86%, which influences the unbound fraction available for distribution and activity.

Adverse effects

Common adverse effects

Cefazolin is generally well-tolerated, with common adverse effects primarily mild and self-limiting, affecting less than 10% of patients overall and leading to drug discontinuation in fewer than 5% of cases in clinical studies. Gastrointestinal disturbances are the most frequent, including diarrhea (1-10%), nausea (1-10%), and vomiting (1-10%), often resulting from disruption of normal gut flora by the antibiotic. These effects are typically managed supportively, with antiemetics for and or to mitigate , though severe cases warrant evaluation for . Local injection site reactions occur in 1-10% of patients receiving intravenous administration, manifesting as , induration, or (0.1-1%), which can be minimized by proper dilution, slow , and site rotation. Mild reactions, such as pruritus or , are reported in approximately 1-2% of patients, usually resolving upon discontinuation without further intervention. Hematologic changes are uncommon, with transient or mild elevations in liver enzymes (e.g., AST/ALT) occurring in less than 1% of cases, monitored via routine labs and generally requiring no specific management beyond observation.

Serious adverse effects

Serious reactions, including , have been reported with cefazolin use and can be fatal, occurring rarely in patients receiving beta-lactam antibiotics. Recent studies have noted an increasing incidence of cefazolin-specific worldwide. These reactions necessitate immediate discontinuation of the drug and may require interventions such as epinephrine, oxygen, intravenous fluids, and antihistamines. with penicillins affects approximately 1-10% of patients with a history of penicillin , though recent studies indicate a lower true rate of 0.7-2%. Cefazolin is contraindicated in individuals with known immediate to cephalosporins or severe penicillin due to this risk. Clostridium difficile-associated (CDAD), including , is a serious complication that can range from mild to fatal and has been associated with cefazolin, particularly with prolonged or repeated use. Risk factors include antibiotic exposure duration, with cefazolin linked to increased CDAD incidence compared to non-use, and median onset around 6 days after initiation. Treatment may involve discontinuation of cefazolin and administration of anti-CDI , with evaluation recommended for any during or shortly after . Cephalosporins like cefazolin contribute to this risk by disrupting , though the exact incidence varies by factors and exposure. Hematologic adverse effects, such as and , are rare but reversible complications of cefazolin therapy, often requiring (CBC) monitoring during prolonged treatment. These effects have been documented in case reports and post-marketing surveillance, with cephalosporins implicated in immune-mediated platelet and neutrophil reductions. typically resolves upon drug cessation, but severe cases may necessitate supportive care. Renal toxicity, including acute interstitial nephritis (AIN), is uncommon with cefazolin and is often linked to high doses or mechanisms. presents with elevated serum creatinine, , and , and may progress to renal failure if untreated; it is reversible with prompt discontinuation and supportive measures like corticosteroids. Monitoring renal function is advised, especially in patients with pre-existing impairment or concurrent nephrotoxic agents. Neurologic effects, particularly seizures, can occur with cefazolin overdose or in patients with renal failure due to drug accumulation, as the is primarily renally excreted. High plasma levels in renal dysfunction increase risk, manifesting as , , or , which typically resolve with and drug withdrawal. Dose adjustment is critical in such populations to prevent these events. Adverse events should be reported to the FDA's MedWatch program to facilitate post-marketing surveillance and safety updates for cefazolin. Clinicians are encouraged to monitor patients for signs of serious reactions, including , CDAD, hematologic changes via CBC, renal function tests, and neurologic symptoms, with early intervention improving outcomes.

Use in special populations

and

Available from published prospective cohort studies, case series, and case reports over several decades with use, including cefazolin, during do not suggest an increased of major birth defects, , or adverse maternal or fetal outcomes. It is commonly administered for surgical prophylaxis during cesarean sections to prevent postoperative infections, with guidelines recommending a 2 g intravenous dose prior to incision, or 3 g for patients weighing over 120 kg. from cohort studies and case reports spanning decades show no increased of major congenital malformations associated with use, including cefazolin, during the first trimester, with observed rates aligning with the general population baseline of less than 3%. Cefazolin readily crosses the following maternal administration, achieving therapeutic concentrations in fetal blood and , which supports its efficacy for intrauterine infection prophylaxis. Studies in early confirm transplacental passage even in the first trimester, with fetal levels sufficient for antibacterial activity against susceptible pathogens. Regarding breastfeeding, cefazolin is considered compatible, as it is excreted into in low concentrations, typically less than 1 mg/L after standard doses, representing less than 0.5% of the maternal dose adjusted for infant weight. The rates cephalosporins like cefazolin as compatible with nursing, with no expected adverse effects on breastfed infants, though monitoring for potential gastrointestinal disturbances such as is advised. Dosing during and follows standard adult regimens of 1-2 g intravenously every 8 hours for most indications, with no specific adjustments required unless renal impairment is present, in which case dose reduction is necessary to avoid accumulation.

Pediatrics and neonates

Cefazolin is used in neonates for the treatment of early-onset , particularly in term infants, with a typical dosage of 50 mg/kg/day administered intravenously and divided every 12 hours. In preterm neonates, dosing is often reduced to 25 mg/kg/dose every 12 hours due to pharmacokinetic differences, aiming to achieve therapeutic concentrations while minimizing exposure. For pediatric patients beyond the neonatal period, standard dosing for susceptible infections ranges from 50 to 100 mg/kg/day, divided every 8 hours intravenously or intramuscularly, with a maximum daily dose of 6 g to avoid in older children. Higher doses within this range are reserved for severe infections, such as or , guided by susceptibility testing and clinical response. In neonates at risk for group B (GBS) early-onset disease, cefazolin demonstrates efficacy as part of intrapartum prophylaxis when administered to penicillin-allergic mothers, significantly reducing and rates to less than 1 per 1,000 live births in screened populations. Direct neonatal administration may be considered in cases of suspected GBS where is unavailable, providing comparable coverage to first-line agents. Safety considerations in and neonates include monitoring for gastrointestinal upset, such as and , which occur in up to 5% of treated children and may necessitate supportive care or discontinuation. Pharmacodynamic adjustments are essential owing to immature renal function in neonates, which prolongs cefazolin's to approximately 3 to 5 hours in preterm infants compared to 1.8 hours in adults, necessitating extended dosing intervals to maintain efficacy without accumulation. Postmenstrual age influences clearance, with preterm infants requiring dose reductions based on gestational and postnatal age to optimize unbound concentrations above the for target pathogens.

Geriatrics

In geriatric patients, cefazolin dosing requires adjustment due to age-related declines in (GFR), which commonly result in reduced clearance (CrCl). For patients with CrCl 35–54 mL/min, the recommended dose is 1–2 g every 12 hours, while for CrCl 11–34 mL/min, it is 0.5–1 g every 12 hours; these modifications help prevent accumulation and toxicity in the context of impaired renal function, which affects up to 30–50% of individuals over 65 years. Older adults face heightened risks from cefazolin use, primarily due to physiological changes and comorbidities. is a concern, exacerbated by —a common issue in the elderly that can lead to prerenal and amplify the drug's renal effects—necessitating vigilant hydration and renal monitoring. Additionally, cephalosporins like cefazolin increase the incidence of *, with elderly patients over 65 years exhibiting a 7- to 10-fold higher baseline risk compared to younger individuals. , including and , may also occur, particularly in those with renal impairment or disorders, prompting close observation for cognitive changes. Cefazolin remains effective for common geriatric infections such as urinary tract infections and and infections, with clinical trials demonstrating similar efficacy rates in patients aged 65 and older compared to younger adults. However, rates may be elevated by 15–25% in this population due to pharmacokinetic alterations and frailty, as observed in outpatient parenteral antimicrobial therapy studies. further complicates use, as concurrent diuretics like can potentiate through additive renal stress, underscoring the need for comprehensive medication reviews in older patients.

Renal and hepatic impairment

In patients with renal impairment, cefazolin dosing must be adjusted based on creatinine clearance (CrCl) to prevent drug accumulation, as the is primarily eliminated by glomerular filtration. For mild impairment (CrCl 35-55 mL/min), the standard dose of 1-2 g every 8 hours can often be maintained, but for moderate impairment (CrCl 11-34 mL/min), the dose should be reduced to 500 mg to 1 g every 12 hours. In severe renal impairment (CrCl ≤10 mL/min), administration of 500 mg every 18-24 hours is recommended to avoid . Cefazolin is significantly removed by , with approximately 70% of the drug eliminated during a typical session, necessitating a supplemental dose of 500 mg to 1 g immediately post-dialysis to maintain therapeutic levels. Pharmacokinetic studies in end-stage renal disease demonstrate a markedly prolonged of up to 32 hours in the interdialytic period, compared to the normal 1.8 hours, underscoring the need for these adjustments. No dosage adjustment is required for hepatic impairment alone, given cefazolin's minimal hepatic and primary renal . However, in patients with , monitoring for is advised, as it can reduce protein binding and potentially alter free drug concentrations, though clinical impact is generally limited. Routine monitoring of serum creatinine and (BUN) is essential in all patients with renal impairment receiving cefazolin to guide dosing and detect worsening function. Cefazolin should be avoided or used with extreme caution in severe renal impairment without appropriate adjustments, as accumulation can lead to , including seizures.

History

Development

Cefazolin was developed by Fujisawa Pharmaceutical Co., Ltd. (now part of ) in during the late as a semi-synthetic first-generation derived from cephalosporin C, aiming to create an injectable antibiotic with enhanced antibacterial properties. The synthesis involved modifying the core cephalosporin structure to improve its spectrum and stability, with the initial chemical properties and preparation methods detailed in a publication by Fujisawa researchers. A key innovation in cefazolin's structure was the incorporation of a ring in the 7-position , which conferred greater resistance to beta-lactamases and superior pharmacokinetic profile, including better tissue penetration and longer half-life, compared to contemporaries like cephalexin. This modification addressed limitations in earlier cephalosporins, enabling effective parenteral administration for systemic infections. Preclinical evaluations highlighted cefazolin's potent activity against , particularly staphylococci, with minimum inhibitory concentrations (MICs) of 0.25–1.0 mcg/mL against . safety studies in animal models demonstrated low toxicity, with an oral LD50 exceeding 10 g/kg in rats, supporting its progression to human testing. The compound was protected by U.S. Patent No. 3,516,997, issued on June 23, 1970, to Fujisawa Pharmaceutical Co., Ltd., covering 3,7-disubstituted derivatives including cefazolin. Following promising preclinical data, phase I–III clinical trials in the early evaluated its tolerability and efficacy across various infections, notably demonstrating reduced postoperative infection rates in surgical prophylaxis settings, such as abdominal procedures, with success rates over 90% in preventing wound infections. Cefazolin received its first regulatory approval in in 1971.

Regulatory approval and availability

Cefazolin received initial approval from the U.S. (FDA) in 1973 under the trade name Ancef for intravenous and intramuscular administration to treat infections, urinary tract infections, and infections, infections, and joint infections, , septicemia, and perioperative prophylaxis. Indications were expanded in the 1980s to include additional uses such as treatment of genitourinary infections and further perioperative applications based on post-marketing studies and clinical data. In the , cefazolin has been available since the 1970s through national regulatory approvals rather than centralized (EMA) authorization, and it is currently marketed as a generic across member states. The (WHO) added cefazolin to its in 2007, recognizing its role in treating surgical site infections and later adding in 2017, underscoring its importance for global access to basic healthcare needs. Following the expiry of its original patents in the , cefazolin transitioned to generic status worldwide, enabling widespread production and distribution by multiple manufacturers. Cefazolin is broadly available as an affordable generic antibiotic in most countries, though periodic supply disruptions have occurred due to manufacturing challenges. In the United States, notable shortages affected availability in the and persisted into the , including a significant event in 2021 that prompted shifts to alternative therapies. Shortages have continued into 2025, with some manufacturers reporting backorders until the fourth quarter of 2025. Although not formally approved for all applications, cefazolin is endorsed as an alternative therapy in the 2015 (AHA) and Infectious Diseases of America (IDSA) guidelines for treating due to methicillin-susceptible . No withdrawals or bans have been imposed on cefazolin globally, but ongoing surveillance for may lead to future restrictions on its use in certain contexts.

Society and culture

Cost

In the United States, the wholesale acquisition cost for generic cefazolin intravenous 1 g vials typically ranges from $1 to $5 as of 2025, reflecting its status as a long-established generic with multiple manufacturers. Hospitals often apply markups, resulting in charged prices of $20 to $50 per dose, though acquisition costs for institutions remain low due to and contracts. Globally, cefazolin generics are available at significantly lower prices in low- and middle-income countries, often under $1 per gram through international procurement and WHO-prequalified suppliers, enhancing for essential uses like surgical prophylaxis. Bulk production primarily occurs in and , which accounts for over 80% of global active pharmaceutical ingredient supply for generics like cefazolin, driving down costs through . Cefazolin's cost-effectiveness is particularly evident in surgical prophylaxis, where a typical course (1-2 doses) costs $20-50 in drug expenses alone, compared to over $500 for a equivalent course when factoring in administration and monitoring. This preference contributes to overall savings, with studies showing vancomycin alternatives increase per-patient prophylaxis costs by up to 250% in procedures like total knee arthroplasty. In the , cefazolin is classified as a Tier 1 generic on most insurance formularies, minimizing out-of-pocket expenses. Post-2020 shortages, which disrupted supply and temporarily elevated prices due to reliance on concentrated , cefazolin has generally improved by 2025, though intermittent shortages and recalls persist, supported by diversified generic production, without major . In 2025, additional supply disruptions occurred due to voluntary recalls for packaging errors by manufacturers like .

Trade names and formulations

Cefazolin is the generic name and (INN) for the drug, typically administered as its sodium salt form, cefazolin sodium. In the United States, it was historically marketed under brand names such as Ancef and Kefzol, though Ancef was discontinued in following its divestiture to . Internationally, brand names have included Zolicef (by Bristol-Myers Squibb), Elzogram (by Lilly), Anzolin (in ), Basocef (in ), and Cefamezin (in , often combined with lidocaine). Following the expiry of key patents in 1987, generic versions of cefazolin have dominated the market worldwide since the late 1980s. Cefazolin is primarily formulated as a sterile for injection in single-dose vials, available in strengths such as 500 mg, 1 g, 2 g, 3 g, 5 g, 10 g, and 20 g, which is reconstituted with a for intravenous (IV) or intramuscular () administration. IM use as a suspension is possible but uncommon in clinical practice, with IV administration preferred for most indications. Premixed ready-to-use IV solutions are also available, typically in iso-osmotic dextrose formulations such as 1 g per 50 mL or 2 g per 100 mL in single-dose plastic containers.

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