Cefazolin: A Comprehensive Monograph

I. Executive Summary

Cefazolin is a parenteral, first-generation cephalosporin antibiotic that has served as a workhorse agent in clinical medicine for decades. It functions as a bactericidal agent by irreversibly inhibiting bacterial cell wall synthesis, leading to cell lysis and death. Its primary utility lies in the treatment of infections caused by susceptible Gram-positive cocci, most notably methicillin-susceptible Staphylococcus aureus (MSSA) and Streptococcus species, as well as certain clinically relevant Gram-negative pathogens such as Escherichia coli and Klebsiella pneumoniae. Cefazolin's most prominent role is as the drug of choice for surgical prophylaxis across a vast array of procedures, a status earned through its ideal antimicrobial spectrum, established efficacy, and low cost.

Recent clinical evidence has highlighted a significant paradigm shift in the management of serious MSSA infections, such as bacteremia. Comparative studies consistently demonstrate that Cefazolin possesses a more favorable safety profile than traditional antistaphylococcal penicillins (e.g., nafcillin, oxacillin), with a markedly lower incidence of nephrotoxicity and hepatotoxicity. This superior safety, combined with less frequent dosing requirements and lower cost, increasingly positions Cefazolin as a preferred first-line agent for these infections.

The clinical use of Cefazolin is, however, critically dependent on patient renal function. The drug is eliminated almost exclusively unchanged by the kidneys, and its half-life can be prolonged more than 25-fold in patients with renal failure. Consequently, failure to implement appropriate and significant dose adjustments in patients with renal impairment can lead to toxic drug accumulation and severe adverse events, including seizures. Conversely, its pharmacokinetic profile can be therapeutically manipulated; co-administration with probenecid blocks its renal secretion, prolonging its half-life and enabling convenient once-daily dosing regimens for outpatient therapy. Cefazolin remains an indispensable tool in the antimicrobial armamentarium, but its safe and effective use demands a nuanced understanding of its pharmacology, a vigilant approach to dosing in special populations, and an awareness of its evolving role in modern infectious disease practice.

II. Drug Identification and Physicochemical Properties

This section establishes the fundamental identity of Cefazolin, consolidating its chemical, nomenclature, and physical data into a standardized reference format.

2.1 Nomenclature and Identifiers

Cefazolin is a semi-synthetic small molecule antibiotic belonging to the cephalosporin class.[1] It is also known by the alternative spellings cefazoline and cephazolin.[3] As a cornerstone antibiotic, it is cataloged across numerous international chemical and pharmacological databases under a set of standardized identifiers.

• DrugBank ID: DB01327 [1]
• CAS Number: 25953-19-9 [1]
• 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 [1]
• Other Key Identifiers:
• InChI: 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 [1]
• InChIKey: MLYYVTUWGNIJIB-BXKDBHETSA-N [1]
• SMILES: CC1=NN=C(S1)SCC2=C(N3C@@HSC2)C(=O)O
• European Community (EC) Number: 247-362-8
• UNII: IHS69L0Y4T
• ChEBI ID: CHEBI:474053

2.2 Chemical Structure and Formula

Cefazolin's chemical structure is based on the 7-aminocephalosporanic acid nucleus, which it shares with other cephalosporins. Its unique properties are conferred by two specific side chains attached to this core.

• Molecular Formula: The chemical formula for the cefazolin acid form is C14​H14​N8​O4​S3​. For parenteral administration, it is formulated as a sodium salt, with the formula C14​H13​N8​NaO4​S3​.
• Molecular Weight: The molecular weight of the acid form is approximately 454.5 g/mol. The sodium salt has a molecular weight of 476.5 g/mol.
• Structural Description: Cefazolin is a beta-lactam antibiotic characterized by a core 5-thia-1-azabicyclo[4.2.0]oct-2-ene structure. It is distinguished by two side groups: a [(5-methyl-1,3,4-thiadiazol-2-yl)sulfanyl]methyl group at position 3 and a (1H-tetrazol-1-ylacetyl)amino group at position 7. These specific chemical moieties are responsible for defining its antimicrobial spectrum and pharmacokinetic behavior.

2.3 Physical and Chemical Properties

The physical properties of Cefazolin, particularly its sodium salt, are critical for its formulation as a parenteral drug.

• Physical Description: It is a white to yellowish-white, odorless crystalline powder. It may present a bitter, salty taste and can be crystallized from aqueous acetone to form needles.
• Solubility: The solubility profile dictates its administration route. The acid form is practically insoluble in water, chloroform, and benzene, but soluble in organic solvents like dimethylformamide (DMF) and pyridine. In contrast, the sodium salt form is easily soluble in water, which is essential for creating aqueous solutions for injection. It is only slightly soluble in methanol and ethanol.
• Melting Point: Cefazolin decomposes upon heating, with a melting point range of 197-200 °C.
• Stability: Both the dry powder and reconstituted solutions may darken in color over time, from pale yellow to yellow, without a significant loss of potency. Reconstituted solutions are stable for 24 hours at room temperature and for 10 days when refrigerated at 5°C.

Table 1: Cefazolin Key Identifiers and Properties

Property	Value	Source(s)
Common Name	Cefazolin
DrugBank ID	DB01327
CAS Number	25953-19-9
Molecular Formula	C14​H14​N8​O4​S3​ (Acid Form)
Molecular Weight	454.51 g/mol (Acid Form)
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
Physical Form	White to yellowish-white crystalline powder
Solubility (Sodium Salt)	Easily soluble in water

III. Pharmacology

This section details the pharmacological profile of Cefazolin, covering both its mechanism of action against bacteria (pharmacodynamics) and its absorption, distribution, metabolism, and excretion within the human body (pharmacokinetics).

3.1 Pharmacodynamics

Pharmacodynamics describes how a drug affects the body. For Cefazolin, this encompasses its bactericidal mechanism, its specific molecular targets, and its spectrum of antimicrobial activity.

3.1.1 Mechanism of Action

Cefazolin is a bactericidal antibiotic, a classification indicating that it actively kills susceptible bacteria rather than simply inhibiting their proliferation. Its mechanism is characteristic of the β-lactam class of antibiotics, targeting the synthesis of the bacterial cell wall, a structure essential for bacterial integrity and survival but absent in human cells.

The process unfolds in several steps:

1. Cefazolin penetrates the outer layers of the bacterial cell.
2. It covalently binds to and inactivates its molecular targets, the Penicillin-Binding Proteins (PBPs).
3. This binding action inhibits the transpeptidation reaction, which is the final and critical step in the synthesis of peptidoglycan, the primary structural polymer of the bacterial cell wall. The transpeptidation step involves the cross-linking of peptide chains, which gives the cell wall its strength and rigidity.
4. The inhibition of cell wall synthesis, coupled with the unabated activity of bacterial autolytic enzymes (autolysins) that continuously remodel the cell wall, leads to a structurally compromised and weakened wall.
5. Ultimately, this structural failure results in cell lysis and bacterial death.

3.1.2 Interaction with Penicillin-Binding Proteins (PBPs)

PBPs are a group of bacterial enzymes, specifically DD-transpeptidases, that catalyze the final stages of peptidoglycan synthesis. Because they are vital for bacterial reproduction and structural maintenance, and are unique to bacteria, they represent an ideal target for selective toxicity.

Cefazolin's efficacy is derived from its ability to inhibit a range of these essential proteins. In model organisms such as Escherichia coli, Cefazolin has been shown to be an effective inhibitor of several key PBPs :

• Penicillin-binding proteins 1A, 1B, and 1C: These are high-molecular-weight PBPs involved in the primary synthesis and elongation of the peptidoglycan cell wall.
• Peptidoglycan D,D-transpeptidase MrdA (PBP-2): This enzyme is crucial for maintaining the characteristic rod shape of the bacterium.
• Peptidoglycan D,D-transpeptidase FtsI (PBP-3): This enzyme is essential for cell division, as it catalyzes peptidoglycan synthesis at the division septum.

By binding to this diverse set of PBPs, Cefazolin effectively disrupts multiple facets of cell wall maintenance and cell division, contributing to its potent bactericidal activity.

3.1.3 Antimicrobial Spectrum of Activity

Cefazolin is classified as a first-generation cephalosporin. This class is defined by its strong activity against Gram-positive bacteria and more limited, but clinically significant, activity against certain Gram-negative bacteria. Its chemical structure provides improved stability against many staphylococcal β-lactamases compared to older penicillins, broadening its useful spectrum.

• Gram-Positive Aerobes (High Activity): Cefazolin is highly effective against many of the most common Gram-positive pathogens. This includes methicillin-susceptible Staphylococcus aureus (MSSA) and Staphylococcus epidermidis, even strains that produce penicillinase enzymes. It is also highly active against various streptococcal species, including Streptococcus pyogenes (Group A β-hemolytic streptococci), Streptococcus agalactiae (Group B streptococci), and Streptococcus pneumoniae.
• Gram-Negative Aerobes (Moderate Activity): The Gram-negative coverage of Cefazolin is narrow but includes several important pathogens often responsible for community-acquired infections. It is active against Escherichia coli, Proteus mirabilis, and Klebsiella pneumoniae.
• Non-Susceptible Organisms (Key Gaps in Coverage): Understanding the organisms against which Cefazolin is not effective is crucial for appropriate clinical use. There are several significant gaps in its coverage. Cefazolin is inactive against methicillin-resistant Staphylococcus aureus (MRSA), Enterococcus species, and Listeria monocytogenes. It also lacks activity against most indole-positive Proteus species (e.g., Proteus vulgaris), Enterobacter species, Serratia species, Pseudomonas species, and anaerobic bacteria.

3.1.4 Mechanisms of Bacterial Resistance

Bacterial resistance to Cefazolin, like other β-lactam antibiotics, primarily arises from two major mechanisms. The first is the alteration of the target PBPs through genetic mutation, which reduces the binding affinity of the drug and renders it less effective. The second, and more common, mechanism is the production of β-lactamase enzymes. These enzymes hydrolyze the amide bond in the β-lactam ring of the antibiotic, inactivating it before it can reach its PBP target. While Cefazolin is stable against many common staphylococcal penicillinases, it is susceptible to hydrolysis by other types of β-lactamases, such as extended-spectrum beta-lactamases (ESBLs), which are often produced by Gram-negative bacteria.

Table 2: Cefazolin Antimicrobial Spectrum

Category	Organism	Clinical Note	Source(s)
Gram-Positive Aerobes	Staphylococcus aureus (MSSA)	Includes beta-lactamase producing strains. A primary target for Cefazolin.
	Staphylococcus epidermidis	Includes beta-lactamase producing strains.
	Streptococcus pyogenes (Group A)	Common cause of skin infections and pharyngitis.
	Streptococcus agalactiae (Group B)	Important pathogen in neonatal infections and in adults with comorbidities.
	Streptococcus pneumoniae	A common cause of pneumonia, meningitis, and otitis media.
Gram-Negative Aerobes	Escherichia coli	A primary cause of urinary tract infections.
	Proteus mirabilis	Common cause of urinary tract infections.
	Klebsiella pneumoniae	Can cause pneumonia and urinary tract infections.
Non-Susceptible Organisms	Methicillin-resistant S. aureus (MRSA)	Uniformly resistant. A critical gap in coverage.
	Enterococcus species	Important gap in coverage for this common nosocomial pathogen.
	Pseudomonas aeruginosa	No activity. Important for nosocomial pneumonia and infections in immunocompromised hosts.
	Anaerobic Bacteria (e.g., Bacteroides fragilis)	No significant activity. Requires addition of agents like metronidazole for mixed infections.
	Atypical Bacteria (e.g., Mycoplasma, Chlamydia)	No activity.

3.2 Pharmacokinetics

Pharmacokinetics describes the journey of a drug through the body, encompassing its absorption, distribution, metabolism, and excretion (ADME). The pharmacokinetic profile of Cefazolin is straightforward and dominated by its handling by the kidneys.

3.2.1 Absorption

Cefazolin is not significantly absorbed from the gastrointestinal tract and therefore must be administered parenterally, either via intravenous (IV) or intramuscular (IM) injection. Following IM administration, peak serum concentrations are typically reached within 1 to 2 hours. After a 1-gram IV dose, peak serum concentrations reach approximately 185 mcg/mL, while a 1-gram IM dose results in a peak of about 64 mcg/mL at 1 hour.

3.2.2 Distribution

Once in the bloodstream, Cefazolin is widely distributed into most body tissues and fluids. It achieves therapeutic concentrations in bone, synovial fluid, and bile, making it effective for infections in these sites. Cefazolin is moderately bound to plasma proteins, with reported binding of 74–86%. It is known to cross the placenta, resulting in detectable concentrations in fetal cord blood. However, it is distributed into the milk of nursing mothers only in very low concentrations. A key limitation is its poor penetration into the cerebrospinal fluid (CSF), making it unsuitable for the treatment of meningitis.

3.2.3 Metabolism

Cefazolin is not appreciably metabolized in the body. This is a significant pharmacokinetic feature. The absence of a 3-ester linkage in its chemical structure, a group present on other cephalosporins like cephalothin, makes it resistant to degradation by esterase enzymes found in the liver and other tissues. This lack of metabolism means that hepatic function has a negligible impact on its clearance, and there is no concern for the formation of active or toxic metabolites.

3.2.4 Route of Elimination

The drug's pharmacokinetic profile is dominated by its near-exclusive reliance on renal elimination. Cefazolin is excreted almost entirely unchanged in the urine, primarily through a combination of glomerular filtration and active tubular secretion. In individuals with normal renal function, approximately 60% of an administered dose is excreted in the urine within the first 6 hours, with 70–80% eliminated within 24 hours.

3.2.5 Biological Half-Life

In patients with normal renal function, the serum half-life of Cefazolin is relatively short, approximately 1.8 hours following IV administration and 2.0 hours after IM administration. This short half-life necessitates relatively frequent dosing intervals (e.g., every 6 to 8 hours) to maintain serum concentrations above the minimum inhibitory concentration (MIC) for target pathogens.

The drug's reliance on renal clearance has profound implications for its use in patients with impaired kidney function. As renal function declines, the elimination of Cefazolin is severely hampered, leading to a dramatic increase in its half-life. In patients with severe renal impairment or who are anuric (anephric), the half-life can be prolonged from its normal value of approximately 1.6-2.0 hours to as long as 42 to 69 hours. This represents a 25- to 40-fold increase in the drug's persistence in the body. This pharmacokinetic vulnerability is the direct cause of the dose-dependent neurological adverse events, such as seizures, observed in patients with renal failure who receive unadjusted doses, as the drug accumulates to toxic levels in the central nervous system. This direct link between pharmacokinetics and toxicity underscores why assessment of renal function and appropriate dose adjustment is the single most critical factor in ensuring the safe use of Cefazolin.

Table 3: Key Pharmacokinetic Parameters of Cefazolin

Parameter	Value / Description	Source(s)
Administration Route	Parenteral (Intravenous or Intramuscular) only
Bioavailability	Not applicable (parenteral administration)
Plasma Protein Binding	74–86%
Metabolism	Not metabolized
Route of Elimination	>90% renal, excreted unchanged in urine
Half-life (Normal Renal Function)	IV: ~1.8 hours; IM: ~2.0 hours
Half-life (Anephric Patients)	~42–69 hours

IV. Clinical Applications and Therapeutic Efficacy

This section translates the fundamental pharmacology of Cefazolin into its practical applications in clinical medicine, detailing its approved indications, its vital role in surgical prophylaxis, and its comparative standing against alternative antibiotic therapies.

4.1 Approved Therapeutic Indications

Cefazolin is approved by regulatory agencies for the treatment of a wide array of bacterial infections, provided they are caused by susceptible organisms identified through culture and susceptibility testing. Its use should be guided by these results whenever possible to ensure efficacy and promote antimicrobial stewardship.

Key indications include:

• Respiratory Tract Infections: Treatment of pneumonia caused by susceptible pathogens like S. pneumoniae and K. pneumoniae.
• Urinary Tract Infections (UTIs): Effective for acute, uncomplicated UTIs caused by susceptible E. coli, P. mirabilis, and Klebsiella species.
• Skin and Skin Structure Infections: A primary indication for Cefazolin, used extensively for cellulitis and other skin infections caused by S. aureus (MSSA) and Streptococcus species.
• Biliary Tract Infections: Used for infections such as cholecystitis when caused by susceptible organisms.
• Bone and Joint Infections: A standard treatment for osteomyelitis and septic arthritis caused by susceptible S. aureus.
• Genital Infections: Indicated for prostatitis and epididymitis caused by susceptible Gram-negative organisms.
• Serious Systemic Infections: Used in the treatment of life-threatening infections such as sepsis (bacteremia) and endocarditis caused by susceptible staphylococci and streptococci.

4.1.1 The Role in Surgical Prophylaxis

Perhaps the most critical and widespread use of Cefazolin is in the prevention of surgical site infections (SSIs). It is firmly established as the drug of choice for perioperative prophylaxis in a majority of surgical procedures. This status is based on an ideal combination of factors:

• Optimal Spectrum: Its activity is perfectly targeted against the most common pathogens responsible for SSIs, which are typically skin flora such as Staphylococcus aureus and Streptococcus species.
• Proven Efficacy: Decades of clinical use and numerous studies have demonstrated its effectiveness in reducing postoperative infection rates.
• Favorable Safety Profile: It is generally well-tolerated.
• Low Cost: Its availability as a generic medication makes it a highly cost-effective intervention.

Guidelines from leading professional organizations, including the Infectious Diseases Society of America (IDSA) and the American Society of Health-System Pharmacists (ASHP), recommend its administration shortly before surgical incision for procedures classified as contaminated or potentially contaminated. This includes a vast range of surgeries such as orthopedic (e.g., prosthetic arthroplasty), cardiac, vascular, gynecologic (e.g., hysterectomy), and certain gastrointestinal procedures.

A significant point of clinical discussion and ongoing research is the optimal prophylactic dose for obese patients. While a 2-gram dose has been standard, pharmacokinetic studies have raised concerns that this may result in inadequate antibiotic concentrations in the tissues of obese individuals. Consequently, many guidelines now recommend an increased dose of 3 grams for patients weighing 120 kg or more. However, the evidence driving this recommendation is largely based on these pharmacokinetic models rather than robust clinical outcome data. A retrospective study found that while there was a trend toward a higher rate of SSIs in obese patients who received a 2-gram dose compared to non-obese patients (8.6% vs 4.6%), this difference did not reach statistical significance. This highlights an important area of clinical uncertainty where large-scale randomized trials are needed to definitively establish whether the higher 3-gram dose provides a meaningful reduction in infection risk for this patient population.

4.1.2 Special Indications

Beyond routine infection treatment and surgical prophylaxis, Cefazolin has several other important uses:

• Prevention of Perinatal Group B Streptococcal (GBS) Disease: It serves as a recommended alternative to penicillin or ampicillin for intrapartum prophylaxis in GBS-colonized pregnant women with a history of penicillin allergy (but not a history of anaphylaxis), to prevent early-onset GBS disease in the newborn.
• Endocarditis Prophylaxis and Treatment: The American Heart Association (AHA) recommends Cefazolin as an alternative agent for prophylaxis against infective endocarditis in high-risk patients undergoing certain dental or respiratory tract procedures. It is also a key alternative to antistaphylococcal penicillins for the treatment of native valve endocarditis caused by MSSA in patients with a non-anaphylactic penicillin allergy.

4.2 Comparative Efficacy and Safety Analysis

A crucial aspect of modern pharmacotherapy is understanding how a drug compares to its alternatives. Cefazolin's position in the therapeutic landscape has been solidified and, in some cases, elevated based on extensive comparative data.

4.2.1 Versus Antistaphylococcal Penicillins (ASPs) for MSSA Bacteremia

A major evolution in infectious disease practice involves the comparison between Cefazolin and the traditional antistaphylococcal penicillins (ASPs), such as nafcillin, oxacillin, and flucloxacillin, for the treatment of serious MSSA infections like bacteremia. While ASPs have historically been considered the gold standard, a growing body of evidence suggests Cefazolin is an equivalent, and often superior, alternative.

• Efficacy: Despite some early theoretical concerns about a potential "inoculum effect"—whereby a large bacterial burden might overwhelm the drug's activity—numerous observational studies and meta-analyses have found that Cefazolin is associated with clinical outcomes, including mortality, that are similar or even superior to those of ASPs for MSSA bacteremia. Ongoing randomized controlled trials are expected to provide definitive evidence of non-inferiority.
• Safety: The most compelling argument for Cefazolin over ASPs lies in its significantly better safety profile. Multiple large-scale analyses have consistently and robustly demonstrated that treatment with Cefazolin is associated with a substantially lower risk of key adverse events. Compared to nafcillin, Cefazolin use results in significantly lower rates of nephrotoxicity (including acute kidney injury and acute interstitial nephritis) and hepatotoxicity. For example, one study reported an incidence of acute kidney injury of 33% in patients receiving nafcillin versus only 13% in those receiving Cefazolin. This pronounced safety advantage, combined with its lower cost and less frequent dosing schedule (every 8 hours vs. every 4-6 hours for ASPs), is driving a clear paradigm shift toward the preferential use of Cefazolin as a first-line agent for the treatment of many MSSA infections.

4.2.2 Versus Other Cephalosporins

• vs. Cephalexin (First-Generation, Oral): Cefazolin and Cephalexin are both first-generation cephalosporins but are not interchangeable due to fundamental differences in administration route and clinical application. Cefazolin is administered parenterally and is reserved for hospitalized patients, surgical prophylaxis, and more severe infections. Cephalexin is an oral agent used for less severe infections in the outpatient setting, such as uncomplicated UTIs or skin infections. In terms of spectrum, Cefazolin exhibits greater potency against S. aureus and a slightly broader spectrum against common Gram-negative pathogens like E. coli and K. pneumoniae when compared to Cephalexin.
• vs. Cefuroxime (Second-Generation) and Ceftriaxone (Third-Generation): As a first-generation agent, Cefazolin has a narrower spectrum of activity than second- and third-generation cephalosporins. This is often a clinical advantage. For uncomplicated cellulitis, where the most likely pathogens are Staphylococcus and Streptococcus, Cefazolin is the preferred agent because it provides targeted therapy without the unnecessary broad-spectrum pressure of an agent like Ceftriaxone, which can contribute to antibiotic resistance. Ceftriaxone's broader Gram-negative coverage and long half-life make it a better choice for more complicated infections or when once-daily outpatient IV therapy is desired. In the context of surgical prophylaxis, a meta-analysis involving over 12,000 patients concluded that Cefazolin is as effective as both Cefuroxime and Ceftriaxone in preventing SSIs. This finding strongly reinforces Cefazolin's position as the preferred agent for this indication, as it provides equivalent efficacy with a narrower, more appropriate spectrum and at a lower cost.

V. Dosage, Administration, and Special Populations

This section provides a practical, clinically-focused guide to the safe and effective use of Cefazolin, detailing its formulations, administration procedures, and recommended dosing for various patient populations and clinical scenarios, with a critical emphasis on dose adjustments for organ impairment.

5.1 Formulations and Administration

• Formulations: Cefazolin is commercially available as Cefazolin sodium, a powder for injection supplied in vials of various strengths (e.g., 500 mg, 1 g, 2 g, and larger pharmacy bulk packages). It is also available in convenient premixed frozen solutions and dual-chamber container systems (e.g., Duplex®) designed for direct IV infusion.
• Administration Routes: Cefazolin is for parenteral use only and must be administered by either Intravenous (IV) or Intramuscular (IM) injection. It is not absorbed orally and should never be given by that route.
• Reconstitution and Dilution: Vials containing the dry powder must first be reconstituted with a compatible sterile diluent, such as Sterile Water for Injection, to create a concentrated solution. For IV infusion, this reconstituted solution must then be further diluted in a larger volume (typically 50–100 mL) of a compatible IV fluid, such as 0.9% Sodium Chloride (Normal Saline) or 5% Dextrose in Water (D5W).
• Rate of Administration: When given as a direct IV injection (bolus), the solution should be administered slowly over a period of 3 to 5 minutes. When given as an intermittent IV infusion, it is typically administered over approximately 30 minutes.

5.2 Dosing Regimens

Dosage of Cefazolin is expressed in terms of the cefazolin base and varies based on the patient's age, weight, renal function, and the severity and type of infection.

Table 4: Recommended Dosing Regimens for Cefazolin

Patient Population	Indication / Severity	Dose	Route	Frequency	Max Dose / Notes	Source(s)
Adult	Mild Infections	250–500 mg	IV/IM	Every 8 hours
	Moderate to Severe Infections	500 mg–1 g	IV/IM	Every 6–8 hours
	Severe, Life-threatening	1–1.5 g	IV	Every 6 hours	12 g/day (rarely)
	Surgical Prophylaxis (<120 kg)	2 g	IV	Once, 30-60 min pre-op	Redose q4h for long procedures
	Surgical Prophylaxis (≥120 kg)	3 g	IV	Once, 30-60 min pre-op	Redose q4h for long procedures
Pediatric (>1 month)	Mild to Moderate Infections	25–50 mg/kg/day	IV/IM	Divided every 6-8 hours	6 g/day
	Severe Infections	100 mg/kg/day	IV/IM	Divided every 6-8 hours	6 g/day
Neonate	≤7 days old	25 mg/kg	IV/IM	Every 12 hours
	>7 days old, >2 kg	25 mg/kg	IV/IM	Every 8 hours

5.3 Dosing in Special Populations

Adjusting Cefazolin dosage in specific patient populations is essential to ensure both efficacy and safety, particularly in patients with renal impairment.

5.3.1 Renal Impairment: A Critical Consideration

As established in the pharmacokinetics section, Cefazolin's elimination is almost entirely dependent on renal function. The dramatic prolongation of its half-life in patients with kidney disease necessitates mandatory dosage adjustments to prevent the accumulation of the drug to toxic levels. This is a direct clinical application of pharmacokinetic principles to mitigate a known safety risk. The standard approach is to administer a normal initial loading dose appropriate for the infection's severity, followed by a modified maintenance regimen that either reduces the dose amount, extends the dosing interval, or both.

Table 5: Cefazolin Dosage Adjustments in Renal Impairment

Creatinine Clearance (CrCl)	Recommended Adult Dose Adjustment	Recommended Pediatric Dose Adjustment	Source(s)
35–54 mL/min	Give usual dose every ≥8 hours	60% of usual daily dose, divided q12h (for CrCl 40-70)
11–34 mL/min	Give 50% of usual dose every 12 hours	25% of usual daily dose, divided q12h (for CrCl 20-39)
≤10 mL/min	Give 50% of usual dose every 18–24 hours	10% of usual daily dose, q24h (for CrCl 5-19)
Hemodialysis	Give 0.5–1 g supplemental dose post-dialysis	Give supplemental dose post-dialysis
Peritoneal Dialysis	500 mg every 12 hours (intermittent) or specific intraperitoneal loading/maintenance doses	No supplement needed

5.3.2 Other Special Populations

• Geriatric Use: While no specific age-based dose adjustments are required, clinicians should exercise caution. Elderly patients are more likely to have a decline in renal function, even with normal serum creatinine levels. Therefore, it is prudent to select doses at the lower end of the range and consider monitoring renal function, as the risk of toxicity is greater in this population.
• Hepatic Impairment: No dosage adjustments are defined or necessary, as Cefazolin is not metabolized by the liver.
• Obesity: For the specific indication of surgical prophylaxis, a higher dose is recommended to ensure adequate tissue penetration. Patients weighing 120 kg or more should receive a 3-gram preoperative dose instead of the standard 2 grams.
• Pregnancy: Cefazolin is classified as Pregnancy Category B. Animal studies have not shown evidence of harm, but there are no adequate and well-controlled studies in pregnant women. It should be used during pregnancy only if clearly needed.
• Lactation: Cefazolin is distributed into breast milk in very low concentrations. Caution should be exercised when administering to a nursing mother.

VI. Safety Profile and Risk Management

This section provides a comprehensive review of Cefazolin's safety profile, detailing its adverse effects, contraindications, warnings, and clinically significant interactions.

6.1 Adverse Drug Reactions

Cefazolin is generally well-tolerated, but like all medications, it is associated with a range of potential adverse effects.

• Common (1–10% incidence):
• Gastrointestinal: The most frequently reported side effects are gastrointestinal in nature, including diarrhea, nausea, vomiting, and abdominal pain or cramps.
• Local Site Reactions: Pain, swelling, redness, and induration (a hard lump) at the site of IM or IV injection are also common. Phlebitis can occur with IV administration.
• Uncommon (<1% incidence):
• General: Dizziness, headache, and fatigue have been reported.
• Dermatologic: Rash and itching (pruritus).
• Hepatic: Transient, asymptomatic elevations in liver enzymes (AST, ALT, alkaline phosphatase) may occur.
• Infectious: Oral candidiasis (thrush), particularly with prolonged use.
• Serious Adverse Events (Rare):
• Hypersensitivity Reactions: Severe allergic reactions can occur, ranging from drug fever and urticaria (hives) to life-threatening anaphylaxis. Severe skin reactions, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), have been reported with cephalosporins.
• Clostridioides difficile-Associated Diarrhea (CDAD): Cefazolin carries a significant warning for CDAD. By disrupting the normal gut flora, the antibiotic can allow for the overgrowth of the toxin-producing bacterium C. difficile. This can lead to a spectrum of illness from mild diarrhea to severe, life-threatening pseudomembranous colitis. Symptoms can begin during therapy or manifest up to several months after treatment has been discontinued.
• Hematologic Effects: Blood dyscrasias such as neutropenia (low neutrophils), leukopenia (low white blood cells), and thrombocytopenia (low platelets) have been reported. Additionally, cephalosporins can interfere with vitamin K metabolism and may be associated with a fall in prothrombin activity, which can increase the risk of bleeding, especially in at-risk patients.
• Renal Effects: While safer than ASPs, Cefazolin can cause renal toxicity. This may manifest as elevations in blood urea nitrogen (BUN) and serum creatinine. In rare cases, acute interstitial nephritis (AIN) and renal failure have occurred.
• Neurologic Effects: Seizures are a known, serious adverse effect. This neurotoxicity is strongly linked to the accumulation of the drug to toxic levels and occurs almost exclusively in patients with significant renal impairment who have received inappropriately high, unadjusted doses.

6.2 Contraindications, Warnings, and Precautions

• Contraindications: Cefazolin is strictly contraindicated in patients with a known, documented hypersensitivity (allergy) to Cefazolin or any other antibiotic in the cephalosporin class.
• Warnings: Penicillin Cross-Reactivity: A critical area of clinical nuance involves the risk of cross-reactivity in patients with a penicillin allergy. Official FDA-approved labeling carries a stern warning, stating that cross-hypersensitivity among beta-lactam antibiotics is well-documented and may occur in up to 10% of patients with a history of penicillin allergy. This warning necessitates caution. However, it is important to recognize that this "10%" figure is now widely considered by experts to be an overestimation, likely stemming from older studies involving early cephalosporin preparations that may have been contaminated with penicillin, and from a failure to differentiate between types of allergic reactions and the chemical structures of the antibiotic side chains. Current clinical guidelines and a large body of evidence suggest that the true rate of cross-reactivity is much lower, likely in the range of 1-4%, and is primarily a concern for patients with a history of a severe, immediate (IgE-mediated) reaction like anaphylaxis to penicillin. For patients with a history of a mild, delayed rash to penicillin, Cefazolin can often be administered safely under observation. This discrepancy requires clinicians to perform a careful risk-benefit analysis, weighing the conservative official warning against modern evidence to avoid the unnecessary use of broader-spectrum or more toxic antibiotics.
• Precautions:
• Gastrointestinal Disease: Use with caution in individuals with a history of GI disease, particularly colitis, due to the risk of CDAD.
• Superinfection: Prolonged use of Cefazolin may disrupt normal flora and lead to the overgrowth of non-susceptible organisms, such as fungi (Candida) or resistant bacteria, resulting in a superinfection.
• Antimicrobial Stewardship: To limit the development of drug-resistant bacteria, Cefazolin should be prescribed only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria.

6.3 Drug-Drug and Laboratory Interactions

Cefazolin can interact with several other drugs and laboratory tests, some of which are clinically significant.

Table 6: Clinically Significant Drug Interactions with Cefazolin

Interacting Drug/Class	Effect of Interaction	Mechanism	Clinical Management / Recommendation	Source(s)
Probenecid	Increases and prolongs Cefazolin serum concentrations and half-life.	Competitive inhibition of renal tubular secretion.	This interaction is often used therapeutically to achieve once-daily dosing. Monitor for signs of Cefazolin toxicity. Not recommended for routine co-administration unless this effect is intended.
Anticoagulants (e.g., Warfarin)	Increases anticoagulant effect, leading to an elevated INR and increased risk of bleeding.	May alter gut flora responsible for Vitamin K synthesis; may also directly inhibit prothrombin activity.	This is a serious interaction. Monitor INR frequently when starting, stopping, or changing the dose of Cefazolin. Adjust warfarin dose as needed. Counsel patient on signs of bleeding.
Aminoglycosides (e.g., Gentamicin)	Increased risk of nephrotoxicity (kidney damage).	Additive or synergistic nephrotoxic effects.	Avoid concomitant use if possible. If required, monitor renal function (BUN, creatinine) closely.
Loop Diuretics (e.g., Furosemide)	Potential for increased risk of nephrotoxicity.	Pharmacodynamic synergism leading to increased renal stress.	Use with caution and monitor renal function.

• Laboratory Test Interactions:
• Urine Glucose Tests: Cefazolin can cause a false-positive result for glucose in the urine when using tests based on copper reduction methods (e.g., Clinitest®, Benedict's solution). This can lead to incorrect management of diabetic patients. Tests based on enzymatic glucose oxidase reactions (e.g., Clinistix®) are not affected and should be used instead.
• Direct Coombs' Test: Cefazolin can cause a positive direct antiglobulin (Coombs') test. This is important in hematologic workups, as it can be misinterpreted as evidence of hemolytic anemia.

6.4 Special Topic: Nephrotoxicity Profile

While Cefazolin is notably less nephrotoxic than its common alternatives, the antistaphylococcal penicillins, it still carries a risk of kidney injury.

• Mechanisms of Renal Injury: The primary mechanisms by which Cefazolin can harm the kidneys are through direct toxic effects on the renal tubules and, less commonly, through a hypersensitivity reaction known as acute interstitial nephritis (AIN). Case reports have documented Cefazolin-induced AIN, which can sometimes present with severe proteinuria (nephrotic-range proteinuria) and eosinophiluria.
• Comparative Risk of Acute Kidney Injury (AKI): The key safety advantage of Cefazolin lies in its relative renal safety compared to ASPs. Meta-analyses and cohort studies have consistently shown a significantly lower incidence of AKI with Cefazolin. One study comparing Cefazolin to nafcillin for MSSA bacteremia found an AKI incidence of 13% in the Cefazolin group versus 33% in the nafcillin group. Another large study reported similar findings, with AKI occurring in 14.8% of patients receiving Cefazolin compared to 29.2% of those on nafcillin. This two-fold or greater reduction in the risk of kidney injury is a primary factor driving the clinical shift towards Cefazolin for MSSA infections.
• Clinical Management and Prevention: Prevention of nephrotoxicity relies on appropriate dosing, especially in at-risk populations such as the elderly and those with pre-existing renal disease. Regular monitoring of renal function (serum creatinine) is recommended during therapy for these patients. If signs of AKI develop (e.g., rising creatinine, decreased urine output), the drug should be discontinued or the dose significantly reduced, and concomitant use of other nephrotoxic agents should be avoided.

VII. Regulatory and Commercial Landscape

This section covers the regulatory history, branding, and commercial aspects of Cefazolin.

7.1 FDA Approval History and Key Milestones

Cefazolin has a long history of clinical use. It was first patented in 1967 and introduced for commercial use in 1971. Its

initial U.S. approval by the Food and Drug Administration (FDA) occurred in 1973. Over the subsequent decades, numerous manufacturers have received approval for generic versions and different formulations. For example, an Abbreviated New Drug Application (ANDA) for a generic Cefazolin for Injection was approved in 1998 , and a formulation of Cefazolin in Dextrose Injection was approved in 2000. This long history and generic availability have cemented its place as a cost-effective staple in hospitals worldwide.

7.2 Brand Names and Generic Availability

Cefazolin is widely available as an inexpensive generic medication, which is a key factor in its extensive use, particularly for surgical prophylaxis. It has been marketed under a multitude of brand names across the globe. In the United States, the most recognized trade names are

Ancef and Kefzol. It was initially brought to market by GlaxoSmithKline under the brand name Nostof. Other international brand names include Cefacidal, Cefamezin, Cefrina, Elzogram, Gramaxin, Kefol, Novaporin, Reflin, Zinol, and Zolicef.

7.3 Recent Regulatory Actions and Recalls

While Cefazolin itself has a well-established safety profile, its supply chain is not immune to manufacturing and quality control issues. This was highlighted by a significant regulatory action in 2025. Sandoz, Inc. initiated a voluntary nationwide recall of specific lots of Cefazolin for Injection. The recall was prompted by a customer complaint that cartons of Cefazolin were found to contain vials that were incorrectly labeled as Penicillin G Potassium.

This type of mislabeling error poses a grave and direct threat to patient safety. The inadvertent administration of penicillin to a patient with a known, severe penicillin allergy could trigger a life-threatening anaphylactic reaction. Conversely, administering Cefazolin to a patient who requires penicillin for a specific infection could lead to treatment failure due to differences in antimicrobial spectrum. This incident underscores that the safety of a drug product extends beyond its intrinsic pharmacological properties and is critically dependent on rigorous quality control throughout the manufacturing, labeling, and distribution processes.

VIII. Conclusion and Expert Recommendations

Cefazolin remains a cornerstone first-generation cephalosporin, valued for its efficacy, safety, and cost-effectiveness. Its clinical utility is extensive, ranging from the treatment of common skin, soft tissue, and urinary tract infections to its indispensable, guideline-recommended role as the agent of choice for surgical prophylaxis. The drug's well-defined antimicrobial spectrum, which is highly active against key Gram-positive pathogens like MSSA and streptococci, combined with predictable pharmacokinetics and decades of clinical experience, solidifies its place in modern medicine.

A key development in contemporary infectious disease practice is the emerging paradigm shift favoring Cefazolin over traditional antistaphylococcal penicillins for the treatment of MSSA bacteremia. This shift is driven by compelling evidence demonstrating a superior safety profile, most notably a significantly lower risk of nephrotoxicity and hepatotoxicity, without compromising clinical efficacy. This makes Cefazolin not just an alternative, but often a more prudent first-line choice.

Based on this comprehensive analysis, the following expert recommendations are provided for clinicians:

1. Embrace Cefazolin as a First-Line Agent for MSSA Infections: For infections caused by susceptible MSSA, clinicians should strongly consider Cefazolin as a primary therapeutic option over antistaphylococcal penicillins. The proven benefits in safety and cost generally outweigh the largely theoretical concern of an "inoculum effect" in most clinical scenarios.
2. Prioritize Renal Function Assessment and Dose Adjustment: The single most critical step to ensure the safe use of Cefazolin is the assessment of a patient's renal function (i.e., calculation of creatinine clearance) prior to initiating therapy. The recommended dosage adjustments for renal impairment must be applied scrupulously to prevent drug accumulation and the associated risk of severe neurotoxicity.
3. Leverage Pharmacokinetic Knowledge for Outpatient Therapy: Clinicians should be aware of the therapeutically beneficial interaction between Cefazolin and probenecid. The co-administration of these agents to prolong Cefazolin's half-life is a well-validated strategy that facilitates effective and cost-efficient once-daily outpatient IV therapy for conditions like cellulitis.
4. Practice Nuanced Allergy Assessment: While exercising appropriate caution, clinicians should move beyond the outdated "10% cross-reactivity" dogma. A careful allergy history should be taken to distinguish between severe, immediate reactions to penicillin (where Cefazolin should be avoided) and mild, delayed reactions (where Cefazolin can often be used safely). This practice prevents the unnecessary use of broader-spectrum or more toxic alternatives.
5. Uphold Principles of Antimicrobial Stewardship: The value of Cefazolin lies in its targeted spectrum. It should be used judiciously for its established indications, guided by culture and susceptibility data whenever possible. This responsible use is essential to preserve its long-term efficacy and limit the emergence of antibiotic resistance.

Works cited

1. Cefazolin | C14H14N8O4S3 | CID 33255 - PubChem, accessed July 31, 2025, https://pubchem.ncbi.nlm.nih.gov/compound/CEFAZOLIN
2. Cefazolin: Uses, Interactions, Mechanism of Action | DrugBank Online, accessed July 31, 2025, https://go.drugbank.com/drugs/DB01327
3. Cefazolin - Wikipedia, accessed July 31, 2025, https://en.wikipedia.org/wiki/Cefazolin
4. Cefazolin - LKT Labs, accessed July 31, 2025, https://lktlabs.com/product/cefazolin/
5. Cefazolin for Injection, USP, accessed July 31, 2025, https://labeling.pfizer.com/ShowLabeling.aspx?id=7006
6. Cefazolin | CAS 25953-19-9 | SCBT - Santa Cruz Biotechnology, accessed July 31, 2025, https://www.scbt.com/p/cefazolin-25953-19-9
7. Cefazolin Side Effects: Common, Severe, Long Term - Drugs.com, accessed July 31, 2025, https://www.drugs.com/sfx/cefazolin-side-effects.html
8. Cefazolin (injection route) - Side effects & uses - Mayo Clinic, accessed July 31, 2025, https://www.mayoclinic.org/drugs-supplements/cefazolin-injection-route/description/drg-20073267
9. Penicillin-binding proteins - Wikipedia, accessed July 31, 2025, https://en.wikipedia.org/wiki/Penicillin-binding_proteins
10. CeFAZolin Monograph for Professionals - Drugs.com, accessed July 31, 2025, https://www.drugs.com/monograph/cefazolin.html
11. Is cefazolin (Cefazolin) or cephalexin (Cephalexin) more broad-spectrum? - Dr.Oracle AI, accessed July 31, 2025, https://www.droracle.ai/articles/40706/is-cefazolin-or-cefalexin-more-broad-spectrum-
12. Systematic Review and Meta-analysis of the Safety of Antistaphylococcal Penicillins Compared to Cefazolin - PubMed Central, accessed July 31, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC5913998/
13. Cefazolin for Injection, USP - Pfizer, accessed July 31, 2025, https://labeling.pfizer.com/ShowLabeling.aspx?id=10527
14. Pharmacodynamics of Cefazolin in the Presence of Normal and Impaired Renal Function - ASM Journals, accessed July 31, 2025, https://journals.asm.org/doi/pdf/10.1128/aac.4.3.366
15. Cefazolin for Injection, USP, accessed July 31, 2025, https://labeling.pfizer.com/ShowLabeling.aspx?id=4380
16. Is cefazolin (a first-generation cephalosporin antibiotic) nephrotoxic? - Dr.Oracle AI, accessed July 31, 2025, https://www.droracle.ai/articles/208701/is-cefazolin-nephrotoxic
17. Cefazolin Dosage Guide + Max Dose, Adjustments - Drugs.com, accessed July 31, 2025, https://www.drugs.com/dosage/cefazolin.html
18. Prophylactic Cefazolin Dosing and Surgical Site Infections: Does the Dose Matter in Obese Patients? - PMC, accessed July 31, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC6320352/
19. Cephalosporins - StatPearls - NCBI Bookshelf, accessed July 31, 2025, https://www.ncbi.nlm.nih.gov/books/NBK551517/
20. (PDF) Meta-Analysis of Clinical Trials Comparing Cefazolin to Cefuroxime, Ceftriaxone, and Cefamandole for Surgical Site Infection Prevention - ResearchGate, accessed July 31, 2025, https://www.researchgate.net/publication/365115889_Meta-Analysis_of_Clinical_Trials_Comparing_Cefazolin_to_Cefuroxime_Ceftriaxone_and_Cefamandole_for_Surgical_Site_Infection_Prevention
21. Cefazolin versus Antistaphylococcal Penicillins for the Treatment of Methicillin-Susceptible Staphylococcus aureus Bacteremia: A Systematic Review and Meta-Analysis | medRxiv, accessed July 31, 2025, https://www.medrxiv.org/content/10.1101/2025.02.17.25322429v1.full-text
22. The Safety and Economic Impact of Cefazolin versus Nafcillin for the Treatment of Methicillin-Susceptible Staphylococcus aureus Bloodstream Infections - PubMed Central, accessed July 31, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC5446361/
23. Systematic Review and Meta-analysis of the Safety of Antistaphylococcal Penicillins Compared to Cefazolin | Antimicrobial Agents and Chemotherapy - ASM Journals, accessed July 31, 2025, https://journals.asm.org/doi/abs/10.1128/aac.01816-17
24. Nephrotoxicity and Clinical Outcomes in Patients Treated With Nafcillin or Cefazolin | Open Forum Infectious Diseases | Oxford Academic, accessed July 31, 2025, https://academic.oup.com/ofid/article/3/suppl_1/302/2636428
25. Compare Cefazolin vs. Cephalexin - GoodRx, accessed July 31, 2025, https://www.goodrx.com/compare/cefazolin-vs-cephalexin
26. Are cefazolin and Keflex (cephalexin) the same antibiotic? - Dr.Oracle, accessed July 31, 2025, https://www.droracle.ai/articles/147331/is-cefazolin-same-thing-as-keflex
27. What is the comparison between Cefazolin (a first-generation cephalosporin antibiotic) and Ceftriaxone (a third-generation cephalosporin antibiotic) for the treatment of cellulitis? - Dr.Oracle AI, accessed July 31, 2025, https://www.droracle.ai/articles/139399/cefazolin-va-ceftriaxone-for-cellulitis
28. Cefazolin - WikEM, accessed July 31, 2025, https://wikem.org/wiki/Cefazolin
29. Ancef, Kefzol (cefazolin) dosing, indications, interactions, adverse effects, and more, accessed July 31, 2025, https://reference.medscape.com/drug/ancef-kefzol-cefazolin-342492
30. Cefazolin in chronic hemodialysis patients: a safe, effective alternative to vancomycin - PubMed, accessed July 31, 2025, https://pubmed.ncbi.nlm.nih.gov/9740155/
31. Cefazolin injection Uses, Side Effects & Warnings - Drugs.com, accessed July 31, 2025, https://www.drugs.com/mtm/cefazolin-injection.html
32. Reference ID: 3997330 This label may not be the latest approved by FDA. For current labeling information, please visit https:// - accessdata.fda.gov, accessed July 31, 2025, https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/207131s003lbl.pdf
33. Cefazolin Interactions Checker - Drugs.com, accessed July 31, 2025, https://www.drugs.com/drug-interactions/cefazolin.html
34. Cefazolin-Related Acute Interstitial Nephritis with Associated Nephrotic, accessed July 31, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC5891510/
35. Cefazolin: Side Effects, Uses, Dosage, Interactions, Warnings - RxList, accessed July 31, 2025, https://www.rxlist.com/cefazolin/generic-drug.htm
36. Cephalosporins: A Focus on Side Chains and β-Lactam Cross-Reactivity - PubMed Central, accessed July 31, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC6789778/
37. Cellulitis Referral and Treatment in Hospital in the Home, accessed July 31, 2025, https://www.canberrahealthservices.act.gov.au/__data/assets/word_doc/0011/1981190/Cellulitis-Referral-and-Treatment-in-Hospital-in-the-Home.docx
38. Cefazolin and probenecid Interactions - Drugs.com, accessed July 31, 2025, https://www.drugs.com/drug-interactions/cefazolin-with-probenecid-541-0-1941-0.html?professional=1
39. cefazolin and Coumadin (warfarin) - Interactions - Drugs.com, accessed July 31, 2025, https://www.drugs.com/drug-interactions/cefazolin-with-coumadin-541-0-2311-1529.html
40. www.drugs.com, accessed July 31, 2025, https://www.drugs.com/drug-interactions/cefazolin-with-coumadin-541-0-2311-1529.html#:~:text=Interactions%20between%20your%20drugs&text=CeFAZolin%20may%20increase%20the%20effects,blood%20thinner%20dosage%20if%20necessary.
41. Cefazolin Injection - Cleveland Clinic, accessed July 31, 2025, https://my.clevelandclinic.org/health/drugs/18038-cefazolin-injection
42. Cefazolin-Related Acute Interstitial Nephritis with Associated Nephrotic-Range Proteinuria: A Case Report - ResearchGate, accessed July 31, 2025, https://www.researchgate.net/publication/324362187_Cefazolin-Related_Acute_Interstitial_Nephritis_with_Associated_Nephrotic-Range_Proteinuria_A_Case_Report
43. Cefazolin - FDA Drug Approval Details - MedPath, accessed July 31, 2025, https://trial.medpath.com/drug/approvals/fda/73f30a70945be4e1
44. Label: CEFAZOLIN- cefazolin sodium injection, solution - DailyMed, accessed July 31, 2025, https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d91a8d13-99a0-4d87-88dc-71cbd37922b4
45. Drug Approval Package: Cefazolin NDA #64-170 - accessdata.fda.gov, accessed July 31, 2025, https://www.accessdata.fda.gov/drugsatfda_docs/anda/98/64170.cfm
46. Drug Approval Package: Cefazolin NDA #50-779 - accessdata.fda.gov, accessed July 31, 2025, https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/50779_Cefazolin.cfm
47. Cefazolin - brand name list from Drugs.com, accessed July 31, 2025, https://www.drugs.com/ingredient/cefazolin.html
48. en.wikipedia.org, accessed July 31, 2025, https://en.wikipedia.org/wiki/Cefazolin#:~:text=It%20was%20initially%20marketed%20by,Reflin%2C%20Zinol%2C%20and%20Zolicef.
49. Update – Sandoz Inc. Issues Voluntary Nationwide Recall Expansion of One Additional Lot of Cefazolin for Injection Due to Vials Being Potentially Mislabeled as Penicillin G Potassium for Injection | FDA, accessed July 31, 2025, https://www.fda.gov/safety/recalls-market-withdrawals-safety-alerts/update-sandoz-inc-issues-voluntary-nationwide-recall-expansion-one-additional-lot-cefazolin
50. FDA Drug Recall Alert - UPDATE - Cefazolin for Injection, USP, 1 gm vial, accessed July 31, 2025, https://www.hpsj.com/fda-drug-recall-alert-update-cefazolin-for-injection-usp-1-gm-vial/
51. Sandoz Inc. Issues Voluntary Nationwide Recall of One Lot of Cefazolin for Injection Due to Product Mispackaging | FDA, accessed July 31, 2025, https://www.fda.gov/safety/recalls-market-withdrawals-safety-alerts/sandoz-inc-issues-voluntary-nationwide-recall-one-lot-cefazolin-injection-due-product-mispackaging