Cefuroxime (cefuroxime axetil)

Cefuroxime is a semisynthetic, second generation cephalosporin antibiotic.

Cefuroxime is usually bactericidal in action. Like other cephalosporins, the antibacterial activity of the drug results from inhibition of mucopeptide synthesis in the bacterial cell wall. Based on its spectrum of activity, cefuroxime is classified as a second generation cephalosporin.

Susceptibility to cefuroxime will vary with geography and time; consult local susceptibility data if available.

Like other available second generation cephalosporins (e.g., cefaclor, cefamandole, cefprozil), cefuroxime generally is more active in vitro against gram-negative bacteria than first generation cephalosporins but has a narrower spectrum of activity against gram-negative bacteria than third generation cephalosporins. The spectrum of activity of cefuroxime resembles that of cefamandole and, to a lesser extent, that of cefoxitin. Cefuroxime has activity in the presence of some beta-lactamases, both penicillinases and cephalosporinases, of gram-negative and gram-positive bacteria.

Cefuroxime is more resistant to hydrolysis by beta-lactamases than cefamandole and is active against some strains of gram-negative bacteria (e.g., Escherichia coli, Enterobacter, Klebsiella, Neisseria) that are resistant to cefamandole. Cefoxitin is active against several organisms that generally are resistant to cefuroxime (e.g., Serratia marcescens, Proteus vulgaris, Bacteroides fragilis).

Parenteral cefuroxime is active in vitro and in clinical infections against Staphylococcus aureus, Streptococcus pneumoniae, and S. pyogenes (group A beta-hemolytic streptococci). Cefuroxime axetil is active in vitro and in clinical infections against S. aureus (methicillin-susceptible isolates only), S. pneumoniae, and S. pyogenes. Parenteral cefuroxime is active in vitro against Staphylococcus epidermidis, but clinical efficacy has not been established.

Cefuroxime axetil is active in vitro against S. epidermidis (methicillin-susceptible isolates only), Staphylococcus saprophyticus (methicillin-susceptible isolates only), and Streptococcus agalactiae, but clinical efficacy has not been established.

Strains of staphylococci resistant to penicillinase-resistant penicillins (oxacillin-resistant (methicillin-resistant) staphylococci) should be considered resistant to cefuroxime and cefuroxime axetil, although results of in vitro susceptibility tests may indicate that the organisms are susceptible to the drug. In addition, beta-lactamase-negative, ampicillin-resistant (BLNAR) strains of H. influenzae should be considered resistant to cefuroxime and cefuroxime axetil despite the fact that results of in vitro susceptibility tests may indicate that the organisms are susceptible to the drug. Most extended spectrum beta-lactamase (ESBL)-producing and carbapenemase-producing isolates are resistant to cefuroxime axetil.

In vitro, cefuroxime concentrations of 0.5-1 mcg/mL inhibit most strains of S. aureus (including penicillinase-producing and nonpenicillinase-producing strains) and concentrations of 1-2 mcg/mL inhibit most strains of S. epidermidis. Most strains of staphylococci resistant to penicillinase-resistant penicillins also are resistant to cefuroxime. In vitro, alpha-hemolytic and beta-hemolytic streptococci are usually inhibited by cefuroxime concentrations of 0.05-0.5 mcg/mL and S. pneumoniae is usually inhibited by concentrations of 0.01-0.13 mcg/mL.

Most strains of enterococci, including E. faecalis, are generally resistant to cefuroxime. Listeria monocytogenes generally is resistant to cefuroxime.

Cefuroxime is active in vitro against most gram-negative aerobic cocci and many gram-negative aerobic bacilli including Enterobacteriaceae. Pseudomonas aeruginosa is resistant to cefuroxime. Acinetobacter calcoaceticus is also usually resistant to the drug.

Parenteral cefuroxime is active in vitro and in clinical infections against Enterobacter, Escherichia coli, Haemophilus influenzae (including ampicillin-resistant strains), Klebsiella (including K. pneumoniae ), Neisseria gonorrhoeae, and N. meningitidis. Cefuroxime axetil is active in vitro and in clinical infections against E. coli, K. pneumoniae, H. influenzae, Haemophilus parainfluenzae, Moraxella catarrhalis, and N. gonorrhoeae. Parenteral cefuroxime is active in vitro against Citrobacter, Providencia rettgeri, H. parainfluenzae, Proteus mirabilis, M. catarrhalis, Morganella morganii, Salmonella, and Shigella, but clinical efficacy has not been established.

Cefuroxime axetil is active in vitro against M. morganii, Proteus inconstans, P. mirabilis, and P. rettgeri,but clinical efficacy has not been established.

Generally, cefuroxime is active in vitro against the following Enterobacteriaceae: Citrobacter diversus, C. freundii, Enterobacter aerogenes, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Salmonella, and Shigella. Although cefuroxime is active in vitro against some strains of Morganella morganii (formerly Proteus morganii), Providencia rettgeri (formerly Proteus rettgeri), and Proteus vulgaris, most strains of these organisms are resistant to the drug. Most susceptible Enterobacteriaceae are inhibited in vitro by cefuroxime concentrations of 1-12.5 mcg/mL.

In vitro on a weight basis, the activity of cefuroxime against susceptible Enterobacteriaceae is approximately equal to that of cefoxitin but less than that of cefotaxime. Cefuroxime may be active in vitro against some strains of E. aerogenes that are resistant to cefoxitin; however, cefotaxime and, to a lesser extent, cefoxitin may be active in vitro against some strains of P. vulgaris and Serratia resistant to cefuroxime.

Cefuroxime is active in vitro against H. influenzae (including ampicillin-resistant strains) and H. parainfluenzae. Most susceptible strains of H. influenzae are inhibited in vitro by cefuroxime concentrations of 0.1-2 mcg/mL.

Cefuroxime is active in vitro and in clinical infections against N. gonorrhoeae (including both penicillinase-producing and nonpenicillinase-producing strains) and N. meningitidis. The MIC90 (minimum inhibitory concentration of the drug at which 90% of strains tested are inhibited) of cefuroxime reported for N. gonorrhoeae (including both penicillinase-producing and nonpenicillinase-producing strains) is 0.1-0.5 mcg/mL.

Cefuroxime is active in vitro against some anaerobic bacteria, including Actinomyces, Eubacterium, Fusobacterium, Lactobacillus, Peptococcus, Peptostreptococcus, Propionibacterium, and Veillonella. Cefuroxime axetil is active in vitro against Peptococcus niger. Cefuroxime is active in vitro against some strains of Clostridioides, but clinical efficacy has not been established; however, C. difficile is usually resistant to the drug.

Most susceptible anaerobes are inhibited in vitro by cefuroxime concentrations of 0.5-16 mcg/mL. Although cefuroxime concentrations of 16 mcg/mL inhibit some strains of Bacteroides fragilis in vitro, most strains of the organism are resistant to the drug.

Cefuroxime is active in vitro and in vivo against Borrelia burgdorferi, the causative organism of Lyme disease. In vitro, the MIC of cefuroxime for B. burgdorferireportedly is 0.13 mcg/mL and the minimum bactericidal concentration (MBC) is 1 mcg/mL.

Because cefuroxime contains a methoxyimino group that protects the beta-lactam ring from hydrolysis by many penicillinases and cephalosporinases, the drug is more resistant to hydrolysis by beta-lactamases than are first generation cephalosporins or cefamandole. Cefuroxime is generally resistant to hydrolysis by beta-lactamases classified as Richmond-Sykes types I, II, III, IV, and V and most beta-lactamases produced by N. gonorrhoeae, H. influenzae, and staphylococci. However, cefuroxime is hydrolyzed by beta-lactamases produced by B. fragilis, and some type I beta-lactamases produced by Serratia, P. vulgaris, and P. rettgeri.

Results of one in vitro study indicate that cefuroxime is hydrolyzed more rapidly than cefotaxime by beta-lactamases produced by P. vulgaris and B. fragilis. Although cefuroxime is resistant to hydrolysis by beta-lactamases produced by P. aeruginosa, these organisms are resistant to cefuroxime because the drug cannot penetrate their cell wall.

Resistance to cefuroxime is primarily through hydrolysis by beta-lactamase, alteration of penicillin-binding proteins (PBPs), decreased permeability, and the presence of bacterial efflux pumps.

Following oral administration of cefuroxime axetil, the drug is absorbed from the GI tract and rapidly hydrolyzed to cefuroxime. Cefuroxime axetil has little, if any, microbiologic activity until hydrolyzed in vivo to cefuroxime.

In adults receiving cefuroxime axetil film-coated tablets, peak serum concentrations are attained approximately 2-3 hours after the dose.

In adults, bioavailability following oral administration of film-coated tablets averages about 37% when given in the fasting state and 52% when given with or shortly after food. Absorption is increased when cefuroxime axetil is given with milk or infant formula. The extent (but not the rate) of absorption is substantially greater when cefuroxime axetil is administered concomitantly with milk compared with applesauce or fasting.

Cefuroxime sodium is not appreciably absorbed from the GI tract and must be given parenterally. Following IM administration of cefuroxime sodium in healthy adults, peak serum concentrations are attained within 15-60 minutes. In women, serum cefuroxime concentrations are lower when IM injections are given into the gluteus maximus rather than into the thigh.

Following IM or IV administration, cefuroxime is widely distributed into body tissues and fluids including pleural fluid, joint fluid, bile, sputum, bone, and aqueous humor. Therapeutic concentrations may be attained in CSF following IV administration in patients with inflamed meninges. Cefuroxime readily crosses the placenta and is distributed into milk.

Cefuroxime is 33-50% bound to serum proteins.

Following oral administration, cefuroxime axetil is rapidly hydrolyzed to cefuroxime by nonspecific esterases in the intestinal mucosa and blood; the axetil moiety (the 1-(acetyloxy)ethyl ester)is metabolized to acetaldehyde and acetic acid. Cefuroxime is not metabolized and is excreted unchanged principally in urine by both glomerular filtration and tubular secretion.

In adults with normal renal function, 90-100% of a single IM or IV dose of cefuroxime is excreted unchanged in urine within 24 hours; most of the dose is excreted within the first 6 hours following administration.

In adults, the serum or plasma half-life of cefuroxime following oral administration of commercially available cefuroxime axetil tablets or oral suspension (no longer commercially available in the US) ranges from 1.2-1.6 hours. In adults with normal renal function, the serum half-life of cefuroxime following IM or IV administration reportedly ranges from 1-2 hours. In adults, approximately 50% of an administered dose of cefuroxime axetil is recovered in the urine within 12 hours.

In patients with renal impairment, the serum half-life of the drug is prolonged and generally ranges from 1.9-16.1 hours depending on the degree of impairment. In one study, the serum half-life of cefuroxime was 1 hour in patients with creatinine clearances of 50-79 mL/minute, 2.55 hours in patients with creatinine clearances of 25-46 mL/minute, 5.1 hours in patients with creatinine clearances of 10-24 mL/minute, and 14.8 hours in patients with creatinine clearances less than 10 mL/minute. A serum half-life of 15-22 hours has been reported in anuric patients.

In neonates and children, the serum half-life of cefuroxime is inversely proportional to age. Following oral administration of cefuroxime axetil oral suspension (no longer commercially available) in children 3 months to 12 years of age, the serum half-life of cefuroxime averages 1.4-1.9 hours. The serum half-life of cefuroxime following IM or IV administration is reportedly 5.1-5.8 hours in neonates 3 days of age or younger, 2-4.2 hours in neonates 6-14 days of age, and 1-1.5 hours in neonates 3-4 weeks of age.

The manufacturers of cefuroxime axetil state that the urinary pharmacokinetics of cefuroxime axetil have not been determined in children and that the renal pharmacokinetics of oral cefuroxime axetil as established in the adult population should not be extrapolated to children.

Cefuroxime axetil is used orally for the treatment of mild to moderate respiratory tract infections (i.e., acute maxillary sinusitis, acute bacterial exacerbations of chronic bronchitis) caused by susceptible bacteria; acute bacterial otitis media; mild to moderate pharyngitis and tonsillitis caused by Streptococcus pyogenes (group A beta-hemolytic streptococci); uncomplicated skin and skin structure infections caused by Staphylococcus aureus (including beta-lactamase-producing strains) or S. pyogenes; and uncomplicated urinary tract infections caused by Escherichia coli or Klebsiella pneumoniae. Cefuroxime axetil also is used orally for the treatment of Lyme disease and has been used for the treatment of uncomplicated gonorrhea.

Generic name: cefuroxime axetil
Pronunciation: (seff-you-ROX-eem)
Drug class: Beta-Lactams
Therapeutic class: Anti-Infective Agents

The following indications are listed for Cefuroxime:

• Acute Bacterial Maxillary Sinusitis
• Acute Bacterial Otitis Media
• Acute Maxillary Haemophilus Influenzae Sinusitis
• Acute Maxillary Streptococcus Pneumoniae Sinusitis
• Bacterial Urinary Tract Infection
• Chronic Bronchitis With Bacterial Exacerbation
• E. Coli Urinary Tract Infection
• Haemophilus Influenzae Acute Otitis Media
• Haemophilus Influenzae Bronchitis
• Haemophilus Influenzae Chronic Bronchitis
• Haemophilus Parainfluenzae Bronchitis
• Haemophilus Parainfluenzae Chronic Bronchitis
• Impetigo
• Klebsiella Urinary Tract Infection
• Lower Respiratory Infection
• Lyme Disease
• Moraxella Catarrhalis Acute Otitis Media
• Pharyngitis Due To Streptococcus Pyogenes
• Skin And Skin Structure Infection
• Skin And Skin Structure Streptococcus Pyogenes Infection
• Staphylococcus Aureus Skin And Skin Structure Infection
• Streptococcus Acute Otitis Media
• Streptococcus Pneumoniae Bronchitis
• Streptococcus Pneumoniae Chronic Bronchitis
• Tonsillitis Due To Streptococcus Pyogenes

Also known as: Acute Bacterial Exacerbation Of Chronic Bronchitis, Acute Maxillary Sinusitis Due To Diplococcus Pneumoniae, Acute Maxillary Sinusitis Due To Fraenkel's Pneumococcus, Acute Maxillary Sinusitis Due To H. Flu, Acute Maxillary Sinusitis Due To Haemophilus Influenzae, Acute Maxillary Sinusitis Due To Hemophilus Influenzae, Acute Maxillary Sinusitis Due To Influenza Bacillus, Acute Maxillary Sinusitis Due To Pfeiffer's Bacillus, Acute Maxillary Sinusitis Due To Pneumococcus, Acute Maxillary Sinusitis Due To Pneumonococcus, Acute Maxillary Sinusitis From Streptococcus Pneumoniae, Acute Otitis Media Due To H. Flu, Acute Otitis Media Due To Haemophilus Influenzae, Acute Otitis Media Due To Hemophilus Influenzae, Acute Otitis Media Due To Influenza Bacillus, Acute Otitis Media Due To Moraxella Catarrhalis, Acute Otitis Media Due To Pfeiffer's Bacillus, Acute Otitis Media Due To Streptococcus Species, Bacterial Exacerbation Of Chronic Bronchitis, Bacterial Otitis Media, Bronchitis Due To Diplococcus Pneumoniae, Bronchitis Due To Fraenkel's Pneumococcus, Bronchitis Due To Fraenkel-Weichselbaum Pneumococcus, Bronchitis Due To H. Flu, Bronchitis Due To H. Influenzae, Bronchitis Due To Haemophilus Influenzae, Bronchitis Due To Haemophilus Parainfluenzae, Bronchitis Due To Hemophilus Influenzae, Bronchitis Due To Hemophilus Parainfluenzae, Bronchitis Due To Influenzae Bacillus, Bronchitis Due To Pfeiffer's Bacillus, Bronchitis Due To Pneumococcus, Bronchitis Due To Pneumonococcus, Bronchitis Due To Streptococcus Pneumoniae, Chronic Bronchitis Due To Diplococcus Pneumoniae, Chronic Bronchitis Due To Fraenkel's Pneumococcus, Chronic Bronchitis Due To H. Flu, Chronic Bronchitis Due To H. Influenzae, Chronic Bronchitis Due To Haemophilus Influenzae, Chronic Bronchitis Due To Haemophilus Parainfluenzae, Chronic Bronchitis Due To Hemophilus Influenzae, Chronic Bronchitis Due To Hemophilus Parainfluenzae, Chronic Bronchitis Due To Influenza Bacillus, Chronic Bronchitis Due To Pfeiffer's Bacillus, Chronic Bronchitis Due To Pneumococcus, Chronic Bronchitis Due To Pneumonococcus, Chronic Bronchitis Due To Streptococcus Pneumoniae, E. Coli Uti, Epidemic Sore Throat, Fraenkel-Weichselbaum Pneumococcal Chronic Bronchitis, Impetigo Contagiosa, Impetigo Vulgaris, Infection Of Skin And/Or Subcutaneous Tissue, Klebsiella Uti, Lower Respiratory Tract Infection, Pharyngitis Due To Group A Beta-Hemolytic Streptococci, Pharyngitis Due To Streptococcus Epidemicus, Septic Sore Throat, Skin & Skin Soft Tissue Streptococcus Pyogenes Infection, Skin And Skin Soft Tissue Staphylococcus Aureus Infection, Skin And Soft Tissue Skin Infection, Streptococcal Pharyngitis, Streptococcus Pyogenes Tonsillitis, Urinary Tract Infection Due To Escherichia Coli, Urinary Tract Infection Due To Klebsiella Species.