Cefuroxime

Introduction Overview

Generic Name

Cefuroxime

Brand Name

Ceftin, Zinacef

Dosage Form

Oral tablets, oral suspension, parenteral injection (IV, IM)

Drug Class

Second Generation Cephalosporins

Pharmacokinetics

Absorption:
Cefuroxime axetil, the oral prodrug form, is absorbed in the gastrointestinal tract where it is rapidly hydrolyzed by nonspecific esterases in the intestinal mucosa to active cefuroxime. The oral suspension and tablets are not bioequivalent and should not be interchanged on a mg-to-mg basis. The bioavailability of cefuroxime axetil tablets is approximately 37% when administered fasting and increases to 52% if given with food, particularly with milk or infant formula, which enhance absorption by increasing extent but not rate. Peak serum concentrations after oral dosing are typically attained between 2 to 3 hours in adults and 2.7 to 3.6 hours in children. Cefuroxime sodium administered parenterally is not absorbed orally and must be given IV or IM; peak serum levels occur within 15 to 60 minutes following IM administration. Injection into the thigh results in higher serum levels than gluteal injections in women.

Distribution:
Following IV or IM administration, cefuroxime distributes widely into body tissues and fluids, including pleural fluid, joint fluid, bile, sputum, bone, aqueous humor, and cerebrospinal fluid (CSF) especially in the setting of inflamed meninges where therapeutic concentrations may be achieved. It crosses the placenta and is excreted into breast milk. Plasma protein binding is moderate, ranging from 33% to 50%, which facilitates a relatively extensive tissue penetration and effective antibacterial action.

Metabolism:
Cefuroxime axetil is a prodrug that undergoes enzymatic hydrolysis by nonspecific esterases in intestinal mucosa and blood to produce the active cefuroxime. The active drug itself is not further metabolized but is eliminated unchanged, which minimizes variability due to metabolic enzyme activity or drug-drug interactions through metabolic pathways.

Elimination:
Excretion of cefuroxime occurs predominantly via the kidneys through glomerular filtration and tubular secretion, with the drug eliminated almost entirely unchanged in urine. The elimination half-life in healthy adults after oral administration ranges from approximately 1.2 to 1.6 hours and 1 to 2 hours following parenteral administration. In neonates and young children, the half-life is longer and inversely proportional to age due to immature renal function. In patients with impaired renal function, particularly those with creatinine clearance below 20 mL/min, elimination is significantly delayed with reported half-lives extending up to 15 to 22 hours in anuric patients. Dose adjustment is necessary in renal impairment to prevent accumulation and toxicity.

Dosage Forms

Available Dosage Forms:
Cefuroxime formulations include oral tablets, oral suspensions, and injectable preparations. Specifically, the oral forms consist of film-coated tablets in strengths of 125 mg, 250 mg, and 500 mg of cefuroxime axetil and oral suspensions providing 125 mg or 250 mg of cefuroxime per 5 mL. Injectable forms include cefuroxime sodium for injection in vials of 750 mg, 1.5 g, and a 7.5 g pharmacy bulk package. Additionally, the drug is available as dual-chambered Duplex drug delivery system vials (750 mg or 1.5 g cefuroxime with dextrose injection) and frozen injections intended for intravenous infusion.

Dosages for Adults and Adolescents:
For adults and adolescents, cefuroxime dosing varies by indication and severity. Oral tablets are typically given as 250 mg twice daily for mild to moderate infections such as pharyngitis, sinusitis, or uncomplicated skin infections, with doses up to 500 mg twice daily for more severe infections. For parenteral administration, 750 mg to 1.5 g every 8 hours is standard, with doses as high as 1.5 g every 6 hours for life-threatening infections. Specific regimens include 1 g single oral dose for uncomplicated gonorrhea (although not recommended by CDC as first-line), and 500 mg twice daily for 14 to 20 days in Lyme disease treatment.

Specific Patient Populations:
Pediatric dosing is carefully titrated by weight and age. Neonates require adjusted dosing intervals reflecting renal immaturity (e.g., 50 mg/kg every 12 hours for ≤7 days old). Children beyond neonatal age typically receive 20–30 mg/kg daily orally in divided doses for mild infections and up to 100–200 mg/kg daily IV or IM for severe infections, with special consideration to administration route. Oral suspension is preferred in children unable to swallow tablets. Renal impairment necessitates parenteral dose interval extension and reduced frequency; for example, 750 mg every 12 to 24 hours in adults with severe renal dysfunction. Tablets should not be crushed for pediatric use due to persistent bitter taste; oral suspension is recommended.

Summary of Available Dosage Forms with Strengths:
- Oral tablets (film-coated): 125 mg, 250 mg, 500 mg cefuroxime axetil
- Oral suspension: 125 mg/5 mL, 250 mg/5 mL cefuroxime axetil
- Injection (IM/IV): 750 mg, 1.5 g, 7.5 g cefuroxime sodium
- Duplex drug delivery systems (IV infusion): 750 mg and 1.5 g cefuroxime with dextrose injection
- Frozen injections for IV infusion: 1.5 g (30 mg/mL solution)

Mechanism Of Action

Cefuroxime is a β-lactam antibiotic belonging to the second generation cephalosporin class, exhibiting bactericidal activity by inhibiting bacterial cell wall synthesis. The primary molecular mechanism involves binding to penicillin-binding proteins (PBPs) located on the bacterial cell membrane. These PBPs catalyze the cross-linking of peptidoglycan strands, which provide the cell wall structural integrity. By irreversibly binding to PBPs, cefuroxime interrupts the transpeptidation step, thereby inhibiting the formation of cross-links essential for cell wall strength and rigidity.

At the cellular level, the inhibition of PBPs leads to a weakened cell wall, which cannot withstand the osmotic pressure within the bacterial cell. This disruption results in cell wall instability and renders the bacteria susceptible to osmotic lysis. The bactericidal effect is most effective during bacterial growth and division when cell wall synthesis is maximal. Cefuroxime's binding affinity is broad, targeting multiple PBPs in susceptible gram-positive and gram-negative bacteria, extending its spectrum of activity.

Biochemically, cefuroxime resists hydrolysis by many β-lactamases, enzymes produced by bacteria to deactivate β-lactam antibiotics, owing to its structural modifications at the 7-aceylamino side chain. This confers potency against certain β-lactamase producing strains such as Haemophilus influenzae and Moraxella catarrhalis. However, resistance may still occur in bacteria producing extended-spectrum β-lactamases (ESBLs) or altered PBPs, such as in methicillin-resistant Staphylococcus aureus (MRSA).

Clinically, cefuroxime's mode of action translates to efficacy against a diverse range of infections caused by susceptible bacteria, including respiratory tract infections, skin infections, urinary tract infections, and Lyme disease. Compared to first generation cephalosporins, cefuroxime provides extended gram-negative coverage due to enhanced stability against certain β-lactamases. However, it does not have significant activity against MRSA or anaerobic bacteria harboring resistant mechanisms.

Research studies highlight cefuroxime's role as a valuable antibiotic offering effective penetration into bone, cerebrospinal fluid during meningitis with inflamed meninges, and respiratory secretions. Its bactericidal action contributes to rapid bacterial eradication, reducing infection severity and complications. Comparative clinical trials have demonstrated its advantages in treating penicillin-allergic patients and as an alternative in empiric therapy of community-acquired infections when susceptibility patterns favor its use.

Pharmacological Actions

Bactericidal activity through inhibition of bacterial cell wall synthesis by targeting penicillin-binding proteins.
Broad-spectrum activity including effective coverage against many gram-positive cocci and an expanded range of gram-negative bacteria compared to first-generation cephalosporins.
Resistant to hydrolysis by beta-lactamases produced by some bacteria, enhancing its usefulness against beta-lactamase producing Haemophilus influenzae and Moraxella catarrhalis.
Effective against Staphylococcus aureus (penicillinase-producing strains), Streptococcus pneumoniae, group A Streptococcus pyogenes, and various Enterobacteriaceae species.
Maintains activity in cerebrospinal fluid in the presence of inflamed meninges, allowing use in some meningitis cases.
Exhibits moderate plasma protein binding (33-50%), facilitating distribution into tissues including bone, joints, and respiratory secretions.
Bactericidal effect maximized during bacterial active growth phase.
Inactive against methicillin-resistant strains (MRSA), limited activity against anaerobes and certain resistant gram-negative pathogens like Pseudomonas.
Pharmacokinetic properties allow for flexible dosing routes including oral and parenteral administration.
Not metabolized; eliminated unchanged primarily by renal excretion.
Perform additive or synergistic antibacterial effects with aminoglycosides in vitro against some Enterobacteriaceae.
Displays reduced efficacy against beta-lactamase negative ampicillin-resistant H. influenzae (BLNAR strains).
Effective replacement antibiotic in penicillin-allergic patients without severe hypersensitivity history.
Induces killing by weakening the bacterial cell wall leading to osmotic lysis.

Therapeutic Or Clinical Uses

Treatment of acute otitis media caused by Streptococcus pneumoniae, Haemophilus influenzae (including beta-lactamase producing strains), Moraxella catarrhalis, and Streptococcus pyogenes.
Management of pharyngitis and tonsillitis due to Streptococcus pyogenes as an alternative in penicillin-allergic individuals.
Parenteral treatment of bone and joint infections caused by susceptible Staphylococcus aureus including penicillinase-producing strains.
Parenteral therapy for meningitis caused by susceptible S. pneumoniae, H. influenzae (including ampicillin-resistant strains), Neisseria meningitidis, and S. aureus, with caution due to slower bacteriological response.
Treatment of respiratory tract infections including acute maxillary sinusitis, secondary bacterial infections of acute bronchitis, acute exacerbations of chronic bronchitis, and community-acquired pneumonia caused by susceptible pathogens.
Treatment of septicemia caused by susceptible S. aureus, S. pneumoniae, E. coli, H. influenzae (including resistant strains), and Klebsiella species.
Management of uncomplicated skin and soft tissue infections caused by susceptible strains of S. aureus and S. pyogenes.
Oral treatment of uncomplicated urinary tract infections caused by susceptible E. coli and K. pneumoniae.
Used in treatment of uncomplicated gonorrhea and disseminated gonococcal infections, although not currently CDC first-line treatment.
First-line oral therapy for early localized or early disseminated Lyme disease manifested as erythema migrans and certain neurologic Lyme disease presentations without meningitis.
Perioperative prophylaxis in cardiac surgery, clean head and neck surgery involving placement of prosthesis, and select other surgical procedures.
Used empirically in combination regimens for community-acquired pneumonia in adults and children with risk factors for resistant pathogens.
Treatment of acute bacterial maxillary sinusitis in pediatric and adult patients caused by susceptible strains.
Provides antimicrobial coverage for several gram-negative bacilli and gram-positive cocci, making it versatile for polymicrobial infections.
Alternative antibiotic in patients with mild beta-lactam allergies needing cephalosporin therapy.

Side Or Adverse Effects

Gastrointestinal disturbances including nausea, vomiting, diarrhea, and abdominal discomfort.
Hypersensitivity reactions ranging from mild rash, pruritus, fever, eosinophilia, and urticaria to severe anaphylaxis, Stevens-Johnson syndrome, toxic epidermal necrolysis.
Local reactions at injection sites such as pain, inflammation, and thrombophlebitis during IV administration.
Superinfection risk including Clostridium difficile-associated diarrhea (CDAD), which can range from mild diarrhea to fatal colitis.
Prolongation of prothrombin time, particularly in patients with poor nutritional status, hepatic or renal impairment.
Transient elevation of liver enzymes and rare cases of hepatotoxicity.
Rare nephrotoxicity, especially when co-administered with other nephrotoxic agents such as aminoglycosides or potent diuretics.
Mild to moderate hearing loss reported rarely in pediatric patients treated for meningitis.
Central nervous system effects including headache, dizziness, or rarely seizures in those with renal impairment.
Allergic cross-reactivity risks with other beta-lactams including penicillins necessitating caution in hypersensitive individuals.
Injection site adverse events may include sterile abscess formation after IM injection.
Phenylketonurics must be cautious due to aspartame in oral suspensions providing metabolized phenylalanine.
Sodium content in parenteral formulations may be relevant in sodium-restricted patients.
Potential for hematologic effects such as eosinophilia or thrombocytopenia.
Rare instances of serum sickness-like reactions.

Precautions

Use only for treating or preventing infections proven or strongly suspected to be caused by susceptible bacteria to reduce resistance development.
Assess patient history for hypersensitivity to cephalosporins, penicillins, or other beta-lactams before administration.
Close monitoring in patients with history of gastrointestinal disease, particularly colitis, due to risk of Clostridium difficile-associated diarrhea.
Renal function should be monitored during therapy, especially in seriously ill or elderly patients and those on concomitant nephrotoxic drugs.
Adjust parenteral dosage in patients with renal impairment to avoid accumulation and toxicity.
Cefuroxime oral tablets should not be crushed for pediatric administration due to bitter taste and risk of vomiting; oral suspension is preferred.
Maintain vigilant observation for superinfection with resistant organisms or fungi during prolonged therapy.
Monitor prothrombin time in patients with risk factors such as hepatic or renal impairment, poor nutrition, or concomitant anticoagulant therapy.
Use with caution during pregnancy and lactation; classified as pregnancy category B but distributed into milk.
Use cautiously in geriatric patients due to potential for decreased renal clearance.
Avoid concomitant administration with incompatible drugs; administer separate IV lines if combined with aminoglycosides.
Patients with phenylketonuria should be informed about phenylalanine content in oral suspensions.
Be cautious in patients with a history of anaphylaxis to beta-lactams; cefuroxime generally suitable for those without severe penicillin allergy.
Discontinue therapy if serious hypersensitivity or severe adverse reactions occur.
Complete full course of therapy even if symptoms improve to prevent bacterial resistance.

Warnings

Risk of Clostridium difficile-associated diarrhea (CDAD), which can be severe and sometimes fatal; onset may be delayed up to several weeks after therapy.
Serious hypersensitivity reactions including anaphylaxis have been reported; emergency treatment should be available.
Partial cross-reactivity with penicillins means patients with immediate-type hypersensitivity to penicillins should avoid cefuroxime.
Use cautiously in patients with renal impairment; dosage adjustment necessary to prevent toxicity.
Prolonged use may result in bacterial or fungal superinfection; monitor accordingly.
Potential for prolongation of prothrombin time; monitor in patients with risk factors.
Injection site inflammation or pain may occur with parenteral administration.
Mild to moderate hearing loss has been reported rarely in pediatric meningitis treatment with cefuroxime.
Not the drug of choice for meningitis due to slower bacteriologic response compared with third generation cephalosporins; risk of neurologic sequelae.
Avoid use for gonorrhea as first-line therapy due to rising resistance; CDC does not recommend cefuroxime for this indication.
Use with caution in patients with history of gastrointestinal diseases such as colitis.
Oral suspension contains aspartame; caution in phenylketonuric patients.
Do not use Duplex drug delivery system formulations in pediatric patients unless entire dose is required due to risk of overdose.
Avoid sodium overload in patients on sodium-restricted diets; parenteral formulations contain significant sodium.
Avoid forced thawing of frozen IV infusion solutions to prevent precipitation and loss of potency.

Contraindication

Known hypersensitivity to cefuroxime or other cephalosporins.
Patients with a history of immediate-type (anaphylactic) hypersensitivity to penicillins should avoid cefuroxime due to risk of cross-reactivity.
Severe allergic reactions to beta-lactam antibiotics.
Known hypersensitivity to any component of the formulated product.

Drug Interactions

Concurrent use with aminoglycosides may increase risk of nephrotoxicity; these drugs should be administered separately and not admixed.
Potent diuretics concomitantly used with cefuroxime may elevate nephrotoxicity risk; use with caution and monitor renal function.
Probenecid decreases renal tubular secretion of cefuroxime leading to increased serum concentrations and prolonged half-life.
Oral contraceptives containing estrogen and progestin may have reduced efficacy when used with cefuroxime due to alteration of gut flora affecting estrogen reabsorption.
Glucose urine tests using Clinitest, Benedict's, or Fehling's solutions may yield false-positive results with cefuroxime; recommend glucose oxidase based tests such as Clinistix or Tes-Tape.
Potential additive antimicrobial effects with aminoglycosides against certain Enterobacteriaceae, but requires separate administration lines.
Cefuroxime is incompatible with ciprofloxacin and ranitidine HCl when mixed in solution; avoid co-administration through same IV line.
Variable compatibility and potential precipitation with gentamicin sulfate; co-administration should be carefully managed.
Incompatibility noted with azithromycin, clarithromycin, filgrastim, fluconazole, and vinorelbine tartrate when administered via Y-site or admixture.
Compatible with clindamycin phosphate, furosemide, metronidazole, midazolam HCl (but variable on Y-site), and other commonly co-administered agents.
Drugs affecting renal function may alter cefuroxime pharmacokinetics requiring dosage adjustments.
Discontinuing or initiating agents that affect gut flora can impact the microbiologic environment and potentially alter efficacy or adverse event profiles.
Use with caution when combined with other antibiotics to minimize development of resistance and adverse effects.
Monitoring when given with anticoagulants recommended due to possible PT prolongation.

Preparations Of The Drug

Oral Suspensions: Cefuroxime axetil oral suspensions available in 125 mg/5 mL and 250 mg/5 mL formulations (marketed as Ceftin by GlaxoSmithKline). Contains aspartame; caution in phenylketonurics.
Oral Tablets: Film-coated tablets in strengths of 125 mg, 250 mg, and 500 mg (Ceftin by GlaxoSmithKline), designed for oral administration; tablets should not be crushed or chewed, especially in pediatric patients due to bitter taste.
Parenteral Injections: Cefuroxime sodium for injection available as 750 mg, 1.5 g, and 7.5 g pharmacy bulk packages (Zinacef by Covis).
Dual Chamber Systems: Duplex drug delivery system vials containing 750 mg or 1.5 g cefuroxime sodium with dextrose injections for IV infusion (Zinacef TwistVial by Covis, and products by B Braun).
Frozen Injection for IV Infusion: 30 mg/mL cefuroxime sodium solution (1.5 g per vial), stable under frozen conditions before thawing for use.
Powder for Injection: Require reconstitution with sterile water for injection to prepare injectable suspensions or solutions for IV infusion or IM injection.
Im Injection Suspensions: Prepared by reconstituting powder with sterile water to approximate 220 mg/mL concentration; administered deeply into large muscle masses.
Adjunct Formulations: Cefuroxime for injection may be supplied with diluents including sterile water or dextrose injection solutions with specified compatibility.
Excipients: Include stabilizers, flavoring agents and aspartame in oral suspensions; specific ingredients vary by manufacturer.
Packaging: Available from multiple manufacturers and distributors in vials, bottles, bottles with powder for reconstitution, and ready-to-use premixed formulations.
Storage Recommendations: Tablets stored at 20–25°C or 15–30°C in tight containers; suspensions require refrigeration post reconstitution and discard within 10 days.
Parenteral preparations protected from light and stored at 15–30°C; reconstituted solutions stable for specified durations depending on storage temperature.
Injection vials should not be frozen except specific frozen formulations; thawed injections discarded if precipitation or seal damage is evident.