Cefixime

Class: Third Generation Cephalosporins
Chemical Name: [6R-[6α,7β(Z)]]-7-[[(2-Amino-4-thiazoyl)[(carboxymethoxy)imino]acetyl]amino]-3-ethenyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid
CAS Number: 79350-37-1
Brands: Suprax

Introduction

Antibacterial; β-lactam antibiotic; third generation cephalosporin.¹ ² ³ ⁴ ⁶ ⁷ ¹³ ²³ ⁵⁷ ⁶⁰ ⁷⁵ ⁸³

Uses for Cefixime

Acute Otitis Media (AOM)

Treatment of AOM¹ ² ³ ⁵ ²³ ⁴³ ⁵⁶ ⁶¹ ⁶² ⁶³ ⁷⁵ ¹³⁸ ¹⁶⁴ ¹⁶⁵ caused by Haemophilus influenzae,¹ ² ²³ ⁶¹ ⁶² ⁶³ Moraxella catarrhalis,¹ ² ²³ ⁶¹ ⁶² ⁶³ or Streptococcus pyogenes (group A β-hemolytic streptococci).¹ ² ²³ ⁶² ⁶³

When anti-infectives indicated, AAP recommends high-dose amoxicillin or amoxicillin and clavulanate as drugs of choice for initial treatment of AOM; certain cephalosporins (cefdinir, cefpodoxime, cefuroxime, ceftriaxone) recommended as alternatives for initial treatment in penicillin-allergic patients without a history of severe and/or recent penicillin-allergic reactions.¹⁸⁴

Pharyngitis and Tonsillitis

Treatment of pharyngitis and tonsillitis caused by susceptible S. pyogenes (group A β-hemolytic streptococci).¹ ² ³ ⁵ ²³ ⁴⁴ ⁵⁶ ⁶⁴ ⁷⁵ Generally effective in eradicating S. pyogenes from nasopharynx; efficacy in prevention of subsequent rheumatic fever not established to date.¹

AAP, IDSA, AHA, and others recommend a penicillin regimen (10 days of oral penicillin V or oral amoxicillin or single dose of IM penicillin G benzathine) as treatment of choice for S. pyogenes pharyngitis and tonsillitis;⁸² ⁸⁶ ¹⁰⁴ ¹⁵² other anti-infectives (oral cephalosporins, oral macrolides, oral clindamycin) recommended as alternatives in penicillin-allergic patients.⁸² ⁸⁶ ¹⁰⁴ ¹⁵²

If an oral cephalosporin used, 10-day regimen of first generation cephalosporin (cefadroxil, cephalexin) preferred instead of other cephalosporins with broader spectrums of activity (e.g., cefaclor, cefdinir, cefixime, cefpodoxime, cefuroxime).⁸² ⁸⁶ ¹⁵²

Respiratory Tract Infections

Treatment of acute exacerbations of chronic bronchitis caused by S. pneumoniae,¹ ² ²³ ⁴⁴ ⁷⁰ ⁷² ¹⁰³ H. influenzae,¹ ² ²³ ⁴⁴ ⁷⁰ ⁷² ¹⁰³ or M. catarrhalis†.² ⁴⁴ ⁷⁰ ⁷² ¹⁰³

Treatment of mild to moderate community-acquired pneumonia† (CAP) caused by S. pneumoniae,² ²³ ⁴⁴ ⁷⁰ ⁷² ¹⁰³ H. influenzae,¹ ² ²³ ⁴⁴ ⁷⁰ ⁷² ¹⁰³ M. catarrhalis,² ⁴⁴ ⁷⁰ ⁷² ¹⁰³ ¹³⁷ ¹⁶⁶ Escherichia coli, H. parahaemolyticus, or H. parainfluenzae.² ³ ⁴⁴ ⁶⁴ ⁷⁵

Treatment of mild to moderate sinusitis† caused by S. pneumoniae,² ²³ ⁴⁴ ⁷⁰ ⁷² ¹⁰³ H. influenzae,¹ ² ²³ ⁴⁴ ⁷⁰ ⁷² ¹⁰³ M. catarrhalis,² ⁴⁴ ⁷⁰ ⁷² ¹⁰³ ¹³⁷ ¹⁶⁶ E. coli, H. parahaemolyticus, or H. parainfluenzae.² ³ ⁴⁴ ⁷⁵ Because of variable activity against S. pneumoniae and H. influenzae, IDSA no longer recommends second or third generation oral cephalosporins for empiric monotherapy of acute bacterial sinusitis.¹⁹² Oral amoxicillin or amoxicillin and clavulanate usually recommended for empiric treatment.¹⁹² ¹⁹³ If an oral cephalosporin used as an alternative in children (e.g., in penicillin-allergic individuals), combination regimen that includes a third generation cephalosporin (cefixime or cefpodoxime) and clindamycin (or linezolid) recommended.¹⁹² ¹⁹³

Urinary Tract Infections (UTIs)

Treatment of uncomplicated UTIs¹ ² ⁵ ⁴⁰ ⁵¹ ⁶⁴ ⁷⁴ ⁷⁵ ¹⁸² caused by susceptible E. coli¹ ² ⁴⁰ ⁵¹ ⁶⁴ ⁷⁴ ⁷⁵ ¹⁸² or Proteus mirabilis;¹ ² ⁴⁰ ⁵¹ ⁷⁴ ⁷⁵ ¹⁸² also has been used for treatment of uncomplicated UTIs caused by susceptible Citrobacter spp.†,² ⁵¹ ⁶⁴ ⁷⁴ C. diversus†,² ⁷⁴ C. freundii†,² ⁷⁴ Enterobacter spp.†,² ⁴⁰ ⁵¹ E. aerogenes†,² ⁴⁰ ⁷⁴ E. agglomerans†,² ⁶⁴ Klebsiella spp.†,² ⁴⁰ ⁵¹ ¹⁸² K. pneumoniae†,² ⁶⁴ ⁷⁴ Morganella morganii†,² Proteus spp.†,² ⁵¹ ⁶⁴ or Serratia†.² ⁵¹ ⁷⁴

Has been used for treatment of uncomplicated UTIs¹ ² ⁵ ⁴⁰ ⁵¹ ⁶⁴ ⁷⁴ ⁷⁵ ¹⁸² caused by susceptible gram-positive bacteria, including Staphylococcus epidermidis†,² Staphylococcus spp.†,² ⁵¹ Streptococcus agalactiae†,² ⁴⁰ nonhemolytic streptococci†,² ⁴⁰ ⁵¹ or Enterococcus faecalis†.² ⁴⁰ Consider that treatment failures have been reported and gram-positive bacteria (e.g., staphylococci, S. agalactiae, enterococci) have been isolated in urine during or after cefixime treatment and usually are resistant to cefixime.² ⁵¹ ⁷⁴

Treatment of pyelonephritis† and other complicated UTIs†² ²³ ⁴⁰ ⁷⁵ caused by susceptible Enterobacteriaceae, including E. coli.² ²³

Gonorrhea and Associated Infections

Treatment of uncomplicated urethral, endocervical, or rectal infections† caused by susceptible Neisseria gonorrhoeae.¹ ² ²³ ⁴⁸ ⁷¹ ¹⁰⁶ ¹⁰⁸ ¹⁰⁹ ¹¹⁰ ¹¹¹ ¹³⁰ ¹⁹⁷

Because of concerns related to recent reports of N. gonorrhoeae with reduced susceptibility to cephalosporins, CDC states that oral cephalosporins no longer recommended as first-line treatment for uncomplicated gonorrhea.¹⁹⁷ For treatment of uncomplicated urogenital, anorectal, or pharyngeal gonorrhea, CDC recommends a combination regimen that includes a single dose of IM ceftriaxone and either a single dose of oral azithromycin or 7-day regimen of oral doxycycline.¹⁹⁷

Cefixime recommended by CDC as an alternative in patients with urogenital or rectal† gonorrhea when ceftriaxone cannot be used or not available;¹⁹⁷ used in conjunction with single dose of oral azithromycin or 7-day regimen of oral doxycycline.¹⁹⁷

Consider that N. gonorrhoeae with reduced susceptibility to cefixime, including some treatment failures, reported in US and other countries.¹⁹⁴ ¹⁹⁵ ¹⁹⁶ ¹⁹⁷ ¹⁹⁸ Perform test-of-cure follow-up (culture or nucleic acid amplification test [NAAT]) 1 week after cefixime treatment.¹⁹⁷

If infection persists (treatment failure), culture relevant clinical specimens and perform in vitro susceptibility tests.¹⁹⁷ Also consult infectious disease specialist, STD/HIV Prevention Training Center (), or CDC (404-639-8659) for treatment advice and report the case to CDC through local or state health departments within 24 hours of diagnosis.¹⁹⁷

For all gonorrhea patients, ensure that their sex partners from preceding 60 days are evaluated promptly with culture and treated with a recommended regimen if indicated.¹⁹⁷

Lyme Disease

Has been used for treatment of disseminated Lyme disease†.¹⁸¹ Other cephalosporins (cefotaxime, ceftriaxone, cefuroxime axetil) usually recommended by IDSA and others when a cephalosporin is used in the treatment of Lyme disease.¹⁰⁴ ¹⁸⁵

Salmonella and Shigella Infections

Has been used for treatment of typhoid fever (enteric fever) or septicemia caused by multidrug-resistant Salmonella typhi†.¹⁴¹ ¹⁴² ¹⁸⁹ ¹⁹⁰ ¹⁹¹

Has been used for treatment of shigellosis† caused by susceptible Shigella.¹³⁹ ¹⁴⁸

Cefixime Dosage and Administration

Administration

Oral Administration

Administer orally as capsules, conventional tablets, chewable tablets, or oral suspension.¹

Capsules and conventional tablets: Administer without regard to meals.¹ (See Food under Pharmacokinetics.)

Chewable tablets: Must be chewed or crushed before swallowing.¹

Reconstitution

Reconstitute oral suspension at the time of dispensing by adding amount of water specified on the container in 2 equal portions; shake after each addition.¹ The reconstituted suspension contains 100, 200, or 500 mg/5 mL.¹

Shake oral suspension well just prior to administration of each dose.¹

Dosage

Available as cefixime trihydrate; dosage expressed in terms of cefixime.¹

Capsules containing 400 mg of cefixime are bioequivalent to conventional 400-mg tablets when administered under fasting conditions.¹

Chewable tablets are bioequivalent to oral suspension.¹

Conventional tablets and oral suspension are not bioequivalent¹ (see Absorption under Pharmacokinetics).

Pediatric Patients

General Pediatric Dosage

Oral

Children beyond neonatal period: AAP recommends 8 mg/kg daily in 1 or 2 equally divided doses for treatment of mild or moderate infections.⁸² AAP states the drug is inappropriate for treatment of severe infections.⁸²

Children weighing 5–7.5 kg: Oral suspension containing 100 mg/5 mL is preferred preparation.¹

Children weighing 7.6–10 kg: Oral suspension containing 100 or 200 mg/5 mL is preferred preparation.¹

Children weighing <10 kg: Chewable tablets not recommended.¹

Acute Otitis Media (AOM)

Oral

Children 6 months to 12 years of age: 8 mg/kg once daily or 4 mg/kg every 12 hours¹ for 10–14 days.²³ ⁵⁶ ⁶² ⁶³

Children >12 years of age or weighing >45 kg: 400 mg daily¹ for 10–14 days.⁴⁴ ⁶⁴ ⁷²

Do not use capsules or conventional tablets for treatment of AOM.¹

Pharyngitis and Tonsillitis

Oral

Children 6 months to 12 years of age: 8 mg/kg once daily or 4 mg/kg every 12 hours for ≥10 days.¹

Children >12 years of age or weighing >45 kg: 400 mg once daily or 200 mg every 12 hours¹ for ≥10 days.⁴⁴ ⁶⁴ ⁷²

Respiratory Tract Infections

Acute Exacerbations of Chronic Bronchitis

Oral

Children 6 months to 12 years of age: 8 mg/kg once daily or 4 mg/kg every 12 hours¹ for 10–14 days.⁴⁴ ⁶⁴ ⁷²

Children >12 years of age or weighing >45 kg: 400 mg once daily or 200 mg every 12 hours¹ for 10–14 days.⁴⁴ ⁶⁴ ⁷²

Empiric Treatment of Acute Bacterial Sinusitis†

Oral

8 mg/kg daily in 2 equally divided doses for 10–14 days.¹⁹²

Urinary Tract Infections (UTIs)

Uncomplicated UTIs

Oral

Children 6 months to 12 years of age: 8 mg/kg once daily or 4 mg/kg every 12 hours¹ for 5–10 days.² ⁴⁰ ⁵¹ ⁷⁴

Children >12 years of age or weighing >45 kg: 400 mg once daily or 200 mg every 12 hours¹ for 5–10 days.² ⁴⁰ ⁵¹ ⁷⁴

Gonorrhea and Associated Infections

Uncomplicated Urethral, Endocervical, or Rectal† Gonorrhea

Oral

Prepubertal children weighing <45 kg: 8 mg/kg (up to 400 mg) as a single dose.⁸²

Children ≥8 years of age or weighing ≥45 kg: 400 mg as a single dose.⁸²

Use in conjunction with single dose of oral azithromycin or 7-day regimen of oral doxycycline.⁸² ¹⁹⁷ Not recommended by CDC as first-line treatment.¹⁹⁷ (See Gonorrhea and Associated Infections under Uses.)

Salmonella and Shigella Infections†

Typhoid Fever†

Oral

Children 6 months to 16 years of age: 5–10 mg/kg twice daily.¹⁴¹ ¹⁴² ¹⁸⁹ ¹⁹⁰ ¹⁹¹ Usually given for 14 days;¹⁴¹ ¹⁴² ¹⁸⁹ high rate of treatment failure occurred when given for only 7 days.¹⁹⁰

Shigellosis†

Oral

8 mg/kg daily for 5 days.¹³⁹ ¹⁴⁸

Adults

Acute Otitis Media (AOM)

Oral

400 mg once daily or 200 mg every 12 hours¹ for 10–14 days.²³ ⁵⁶ ⁶² ⁶³

Do not use capsules or conventional tablets for treatment of AOM.¹

Pharyngitis and Tonsillitis

Oral

400 mg once daily or 200 mg every 12 hours for ≥10 days.¹

Respiratory Tract Infections

Acute Exacerbations of Chronic Bronchitis

Oral

400 mg once daily or 200 mg every 12 hours¹ for 10–14 days.⁴⁴ ⁶⁴ ⁷²

Urinary Tract Infections (UTIs)

Uncomplicated UTIs

Oral

400 mg once daily or 200 mg every 12 hours¹ for 5–10 days.⁴⁰ ⁵¹ ⁷⁴

Gonorrhea and Associated Infections

Uncomplicated Urethral, Endocervical, or Rectal† Gonorrhea

Oral

400 mg as a single dose.¹ ¹⁰⁶ ¹⁰⁸ ¹³⁰ ¹⁹⁷ Single 800-mg dose also has been used.² ²³ ⁴⁸ ¹⁰⁶ ¹⁰⁹ ¹⁹⁴

Use in conjunction with oral azithromycin (single 1-g dose) or oral doxycycline (100 mg twice daily for 7 days).¹⁹⁷ Not recommended by CDC as first-line treatment.¹⁹⁷ (See Gonorrhea and Associated Infections under Uses.)

Lyme Disease†

Oral

200 mg daily for 100 days (administered with oral probenecid).¹⁸¹

Special Populations

Renal Impairment

Dosage adjustments necessary in patients with Cl_cr <60 mL/minute.¹ ² Adults with Cl_cr 21–59 mL/minute: 260 mg daily as oral suspension, preferably as oral suspension containing 200 or 500 mg/5 mL; conventional tablets and chewable tablets not recommended.¹

Adults with Cl_cr ≤20 mL/minute: 200 mg daily as conventional tablets or chewable tablets, 172 mg daily as oral suspension containing 100 mg/5 mL, 176 mg daily as oral suspension containing 200 mg/5 mL, or 180 mg daily as oral suspension containing 500 mg/5 mL.¹

Adults undergoing hemodialysis: 260 mg daily as oral suspension, preferably as oral suspension containing 200 or 500 mg/5 mL; conventional tablets and chewable tablets not recommended.¹

Adults undergoing continuous peritoneal dialysis: 200 mg daily as conventional tablets or chewable tablets, 172 mg daily as oral suspension containing 100 mg/5 mL, 176 mg daily as oral suspension containing 200 mg/5 mL, or 180 mg daily as oral suspension containing 500 mg/5 mL.¹

Geriatric Patients

No dosage adjustments except those related to renal impairment.² ³⁵ ³⁷ (See Renal Impairment under Dosage and Administration.)

Cautions for Cefixime

Contraindications

Known hypersensitivity to cefixime or other cephalosporins.¹

Warnings/Precautions

Warnings

Superinfection/Clostridium difficile-associated Diarrhea and Colitis

Possible emergence and overgrowth of nonsusceptible bacteria or fungi, especially Enterobacter, Pseudomonas, enterococci, staphylococci, or Candida.¹ ⁵ Careful observation of the patient is essential.¹ Institute appropriate therapy if superinfection occurs.¹

Treatment with anti-infectives alters normal colon flora and may permit overgrowth of Clostridium difficile.¹ ⁴² ¹⁷⁷ ¹⁷⁸ C. difficile infection (CDI) and C. difficile-associated diarrhea and colitis (CDAD; also known as antibiotic-associated diarrhea and colitis or pseudomembranous colitis) reported with nearly all anti-infectives, including cefixime, and may range in severity from mild diarrhea to fatal colitis.¹ ⁴² ¹⁷⁷ ¹⁷⁸ C. difficile produces toxins A and B which contribute to development of CDAD;¹ ⁴⁰ ⁴² hypertoxin-producing strains of C. difficile are associated with increased morbidity and mortality since they may be refractory to anti-infectives and colectomy may be required.¹

Consider CDAD if diarrhea develops during or after therapy and manage accordingly.¹ ⁴² ¹⁷⁷ ¹⁷⁸ Obtain careful medical history since CDAD may occur as late as 2 months or longer after anti-infective therapy is discontinued.⁴²

If CDAD is suspected or confirmed, discontinue anti-infectives not directed against C. difficile whenever possible.⁴² ¹⁷⁷ ¹⁷⁸ Initiate appropriate supportive therapy (e.g., fluid and electrolyte management, protein supplementation), anti-infective therapy directed against C. difficile (e.g., metronidazole, vancomycin), and surgical evaluation as clinically indicated.¹ ⁴² ¹⁷⁷ ¹⁷⁸

Sensitivity Reactions

Hypersensitivity Reactions

Hypersensitivity reactions such as anaphylaxis (including shock and fatalities), angioedema, serum sickness-like reactions, Stevens-Johnson syndrome, and toxic epidermal necrolysis have been reported.¹ ⁵ ⁴⁰ ⁴¹ ⁴³ ⁵⁶ ⁶⁴ ⁷⁵

If an allergic reaction occurs, discontinue cefixime and institute appropriate therapy as indicated (e.g., epinephrine, corticosteroids, and maintenance of an adequate airway and oxygen).¹

Cross-hypersensitivity

Partial cross-allergenicity among cephalosporins and other β-lactam antibiotics, including penicillins and cephamycins.¹ ¹⁷² ¹⁷³ Use caution.¹

Prior to initiation of therapy, make careful inquiry concerning previous hypersensitivity reactions to cephalosporins, penicillins, or other drugs.¹ Cefixime is contraindicated in individuals hypersensitive to cephalosporins.¹ Avoid use in those who have had an immediate-type (anaphylactic) hypersensitivity reaction and administer with caution in those who have had a delayed-type (e.g., rash, fever, eosinophilia) reaction.¹⁷³

General Precautions

Selection and Use of Anti-infectives

To reduce development of drug-resistant bacteria and maintain effectiveness of cefixime and other antibacterials, use only for treatment or prevention of infections proven or strongly suspected to be caused by susceptible bacteria.¹

When selecting or modifying anti-infective therapy, use results of culture and in vitro susceptibility testing.¹ In the absence of such data, consider local epidemiology and susceptibility patterns when selecting anti-infectives for empiric therapy.¹

Phenylketonuria

Chewable tablets containing 100, 150, and 200 mg of cefixime contain aspartame (NutraSweet), which is metabolized in the GI tract to provide 3.3, 5, and 6.7 mg of phenylalanine, respectively.¹

Coombs’ Test Results

Positive direct Coombs’ test results reported with cephalosporins.¹ ^b This may interfere with certain hematologic studies or transfusion cross-matching procedures.^b

Decreased Prothrombin Activity

Prolonged PT¹ ² and prolonged partial thromboplastin time² ³³ ⁴¹ reported rarely.¹ ² ⁴¹

Patients with renal or hepatic impairment, poor nutritional status, prolonged anti-infective therapy, and previous anticoagulant therapy (stabilized) appear to be at risk.¹ Monitor PT in such patients and administer exogenous vitamin K as indicated.¹

Specific Populations

Pregnancy

Category B.¹

Lactation

Distributed into milk in rats;³⁶ not known whether distributed into milk in humans.¹ Discontinue nursing or the drug.¹

Pediatric Use

Safety and efficacy not established in children <6 months of age.¹ Frequency of adverse GI effects (e.g., diarrhea, loose stools) similar to that in adults.¹

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults.¹

Possible increased oral bioavailability;¹ ³⁵ ³⁷ not considered clinically important.³⁵ ³⁷

Consider age-related decreases in renal function when selecting dosage and adjust dosage if necessary.² ³⁵ ³⁷ (See Renal Impairment under Dosage and Administration.)

Renal Impairment

Increased serum half-life.¹ ² ²³ ³³ ³⁷ ⁷⁵ Dosage adjustments necessary if Cl_cr <60 mL/minute.¹ ² ³³ ³⁵ ³⁷ (See Renal Impairment under Dosage and Administration.)

Common Adverse Effects

GI effects (diarrhea,¹ ² ³³ ⁴⁰ ⁴¹ ⁴³ ⁴⁴ ⁵¹ ⁵⁶ ⁶³ ⁶⁴ ⁶⁷ ⁷⁵ ¹⁰³ loose or frequent stools,¹ abdominal pain,¹ ² ²³ ⁴⁰ ⁴¹ ⁴⁴ ⁵¹ ⁵⁶ ⁶⁴ ⁶⁷ ⁷⁵ nausea,¹ ² ²³ ⁴⁰ ⁴¹ ⁴⁴ ⁵¹ ⁶³ ⁶⁴ ⁷⁴ ⁷⁵ dyspepsia,¹ ² ²³ ⁴⁰ ⁴¹ ⁴⁴ ⁵¹ ⁷⁵ flatulence).¹ ² ⁴⁰ ⁴¹ ⁷⁵

Interactions for Cefixime

Specific Drugs and Laboratory Tests

Drug or Test	Interaction	Comments
Antacids (aluminum- or magnesium-containing)	No clinically important effect on cefixime pharmacokinetics ³²
Anticoagulants, oral (warfarin)	Possible increased PT (with or without bleeding)¹
Carbamazepine	Increased carbamazepine concentrations¹	Monitor carbamazepine concentrations¹
Nifedipine	Possible increased plasma concentrations and AUC of cefixime¹⁴³
Probenecid	Increased cefixime plasma concentrations and AUC²
Salicylates	Possible decreased plasma concentrations and AUC of cefixime² ²⁵	Clinical importance unclear² ¹⁰²
Tests for glucose	Possible false-positive reactions in urine glucose tests using Clinitest, Benedict’s solution, or Fehling’s solution¹	Use glucose tests based on enzymatic glucose oxidase reactions (e.g., Clinistix, Tes-Tape)¹
Tests for ketones	Possible false-positive reaction for ketones in urine if nitroprusside tests used; not reported with tests using nitroferricyanide¹

Cefixime Pharmacokinetics

Absorption

Bioavailability

30–50% of a single oral dose absorbed;¹ ² ⁵ ⁷⁵ ¹⁰⁰ peak serum concentrations attained within 2–6 hours.¹ ² ²⁶ ³⁰ ³¹ ³⁵ ³⁷ ¹⁰⁰

Capsules containing 400 mg of cefixime are bioequivalent to conventional tablets containing 400 mg of the drug when administered under fasting conditions.¹

Chewable tablets are bioequivalent to the oral suspension.¹

Conventional tablets and oral suspension are not bioequivalent;¹ studies in adults indicate oral suspension results in peak serum concentrations 25–50% higher than concentrations attained with tablets.¹

Food

Conventional tablets and oral suspension: Food decreases rate¹ but not extent of absorption.¹ ² ³ ²⁶

Capsules: Food decreases absorption by about 15% (based on AUC) or 25% (based on peak serum concentrations).¹

Distribution

Extent

Distributed into bile,¹ ² ⁵ sputum,² ²³ tonsils,²³ maxillary sinus mucosa,²³ middle ear discharge,²³ blister fluid,² ⁷⁵ and prostatic fluid.²

Distribution into CSF unknown.¹

Crosses the placenta.² ²³ Not detected in human milk following a single 100-mg oral dose.²

Plasma Protein Binding

65–70%.¹ ² ²³ ²⁷ ³³ ³⁷ ⁷⁵

Elimination

Metabolism

Does not appear to be metabolized; no biologically active metabolites detected in serum or urine.¹ ² ⁵ ²³ ³⁰

Elimination Route

Eliminated by renal and nonrenal mechanisms.¹ ² ²³ ²⁴ ²⁶ ²⁷ ²⁹ ³⁰ ³¹ ³⁷ ⁵² ⁷⁵

7–50% of a dose excreted unchanged in urine within 24 hours.¹ ² ²³ ²⁴ ²⁶ ²⁷ ²⁹ ³¹ ³⁷ ⁷⁵ ¹⁰⁰ In animal studies, >10% of a dose may be excreted unchanged in bile.¹ ² ⁵²

Not substantially removed by hemodialysis or peritoneal dialysis.¹ ² ³³ ³⁷ ⁷⁵

Half-life

Adults with normal renal function: 2.4–4 hours.¹ ² ⁵ ²³ ²⁴ ²⁶ ²⁷ ²⁹ ³¹ ³³ ³⁷ ⁷⁵ ¹⁰⁰

Special Populations

Adults with moderate renal impairment (Cl_cr 20–40 mL/minute): Serum half-life averages 6.4 hours.¹

Adults with severe renal impairment (Cl_cr 5–20 mL/minute): Serum half-life averages 11.5 hours.¹

Stability

Storage

Oral

Capsules, Conventional Tablets, Chewable Tablets

20–25°C.¹

For Suspension

20–25°C.¹ After reconstitution, store suspension in tight container at room temperature or in the refrigerator; discard after 14 days.¹

Actions and Spectrum

Based on spectrum of activity, classified as a third generation cephalosporin.³ ¹³ ¹⁵ ⁵⁰ ⁶⁹ ⁷⁵ Expanded spectrum of activity against gram-negative bacteria compared with first and second generation cephalosporins;² ³ ⁵ ¹⁴ ²³ ⁵⁹ ⁶⁰ ⁷⁵ less active against Enterobacteriaceae than some other third-generation cephalosporins.¹⁵ ⁷⁵ ¹⁰¹
Usually bactericidal.¹ ² ¹⁴ ³⁴ ⁶⁵ ⁶⁹ ⁷⁸
Like other β-lactam antibiotics, antibacterial activity results from inhibition of bacterial cell wall synthesis.¹ ² ⁷⁵
Spectrum of activity includes many gram-positive and gram-negative aerobic bacteria;¹ inactive against most anaerobic bacteria.² ¹⁴ ²³ ⁵⁹ ⁶⁰ ⁷⁵ Inactive against chlamydia, fungi, and viruses.¹ ² ^b
Gram-positive aerobes: Active in vitro against Streptococcus pneumoniae¹ and Streptococcus pyogenes (group A β-hemolytic streptococci).¹ ² ³ ¹³ ¹⁴ ²⁰ ²³ ⁵⁰ ⁵⁹ ⁶⁰ ⁶⁶ ⁷⁷ ⁷⁸ ⁷⁹ Also active in vitro against S. agalactiae (group B streptococci)¹ ² ¹³ ¹⁵ ¹⁸ ²³ ⁵⁰ ⁵⁹ ⁶⁰ ⁶⁶ ⁷⁵ and groups C, F, and G streptococci.¹³ ²³ ⁵⁹ ⁶⁰ ⁶⁶ Most staphylococci, enterococci, and Listeria monocytogenes are resistant.¹ ² ³ ¹³ ¹⁴ ¹⁸ ²⁰ ²³ ⁵⁹ ⁶⁰ ⁶⁶ ⁶⁹ ⁷⁵ ⁷⁸ ¹⁰¹
Strains of staphylococci resistant to penicillinase-resistant penicillins (methicillin-resistant [oxacillin-resistant] staphylococci) should be considered resistant to cefixime, although results of in vitro susceptibility tests may indicate susceptibility.¹³²
Gram-negative aerobes: Active in vitro against Neisseria gonorrhoeae,¹ ² ³ ⁵ ¹¹ ¹⁴ ²³ ⁵⁹ ⁶⁰ ⁷⁵ Haemophilus influenzae (including β-lactamase-producing strains),¹ ² ³ ⁵ ⁸ ¹⁰ ¹³ ¹⁴ ¹⁸ ²⁰ ²³ ⁵⁰ ⁵⁹ ⁶⁵ ⁶⁶ ⁶⁸ ⁷⁵ ⁷⁶ ⁷⁷ ⁷⁸ Moraxella catarrhalis (including β-lactamase-producing strains),¹ ² ³ ⁵ ¹³ ²⁰ ²³ ⁵⁸ ⁵⁹ ⁶⁶ ⁷⁵ ⁷⁷ ⁷⁸ Escherichia coli,¹ and Proteus mirabilis.¹ ¹⁵ ²¹ ²³ ⁵⁹ ⁶⁰ ⁷⁵ Also active in vitro against H. parainfluenzae,¹ ² ⁸ ¹³ Klebsiella,¹ Pasteurella multocida,¹ P. vulgaris,¹ Providencia,¹ Salmonella,¹ Shigella,¹ and Serratia.¹ Most Enterobacter⁵ ⁶⁰ ⁷⁵ and Pseudomonas are resistant.² ⁵ ¹³ ¹⁴ ¹⁵ ²⁰ ²³ ⁵⁹ ⁶⁰ ⁶⁶ ⁷⁵ ¹⁰¹

Advice to Patients

Advise patients that antibacterials (including cefixime) should only be used to treat bacterial infections and not used to treat viral infections (e.g., the common cold).¹
Importance of completing full course of therapy, even if feeling better after a few days.¹
Advise patients that skipping doses or not completing the full course of therapy may decrease effectiveness and increase the likelihood that bacteria will develop resistance and will not be treatable with cefixime or other antibacterials in the future.¹
Advise patients that diarrhea is a common problem caused by anti-infectives and usually ends when the drug is discontinued.¹ Importance of contacting a clinician if watery and bloody stools (with or without stomach cramps and fever) occur during or as late as 2 months or longer after the last dose.¹
Importance of discontinuing cefixime and informing clinician if an allergic reaction occurs.¹
Importance of women informing clinician if they are or plan to become pregnant or plan to breast-feed.¹
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.¹
Importance of informing patients of other important precautionary information.¹ (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Cefixime (Trihydrate)
Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Capsules	400 mg (of cefixime)	Suprax	Lupin
	For suspension	100 mg (of cefixime) per 5 mL	Suprax	Lupin
		200 mg (of cefixime) per 5 mL	Suprax	Lupin
		500 mg (of cefixime) per 5 mL	Suprax	Lupin
	Tablets, chewable	100 mg (of cefixime)	Suprax	Lupin
		150 mg (of cefixime)	Suprax	Lupin
		200 mg (of cefixime)	Suprax	Lupin
	Tablets, film-coated	400 mg (of cefixime)	Suprax (scored)	Lupin

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

1. Lupin Pharma. Suprax (cefixime) tablets, capsules, chewable tablets, and powder for oral suspension prescribing information. Baltimore, MD; 2013 Mar.

2. Lederle. Suprax (cefixime) product monograph. Pearl River, NY; 1989 Jun.

3. Smith GH. Oral cephalosporins in perspective. DICP. 1990; 24:45-51. [PubMed 2405586]

4. Inamoto Y, Chiba T, Kamimura T et al. FK 482, a new orally active cephalosporin: synthesis and biological properties. J Antibiot. 1988; 41:828-30. [PubMed 3255303]

5. Cooper RJ, Hoffman JR, Bartlett JG et al. Principles of appropriate antibiotic use for acute pharyngitis in adults: background. Ann Intern Med. 2001; 134:509-17. [PubMed 11255530]

6. Knoller J, Schonfeld W, Bremm KD et al. In vitro stability of cefixime (FK-027) in serum, urine and buffer. J Chromatogr. 1987; 389:312-6. [PubMed 3571358]

7. Namiki Y, Tanabe T, Kobayashi T et al. Degradation kinetics and mechanisms of a new cephalosporin, cefixime, in aqueous solution. J Pharm Sci. 1987; 76:208-14. [PubMed 3585736]

8. Kumar A. In vitro activity of cefixime (CL284635) and other antimicrobial agents against Haemophilus isolates from pediatric patients. Chemotherapy. 1988; 34:30-5. [PubMed 3258232]

9. Smith SM. Activity of cefixime (FK 027) for resistant gram-negative bacilli. Chemotherapy. 1988; 34:455-61. [PubMed 3243091]

10. Powell M. In vitro susceptibility of Haemophilus influenzae to cefixime. Antimicrob Agents Chemother. 1987; 31:1841-2. [PubMed 3501703]

11. Bowie WR, Shaw CE, Chan DGW et al. In vitro activity of difloxacin hydrochloride (A-56619), A-56620, and cefixime (CL 284,635; FK 027) against selected genital pathogens. Antimicrob Agents Chemother. 1986; 30:590-3. [PubMed 3098163]

12. Noel GJ. In vitro activities of selected new and long-lasting cephalosporins against Pasteurella multocida. Antimicrob Agents Chemother. 1986; 29:344-5. [PubMed 3087279]

13. Neu HC, Chin NX. Comparative in vitro activity and β-lactamase stability of FR 17027, a new orally active cephalosporin. Antimicrob Agents Chemother. 1984; 26:174-80. [PubMed 6333207]

14. Kamimura T, Kojo H, Matsumoto Y et al. In vitro and in vivo antibacterial properties of FK 027, a new orally active cephem antibiotic. Antimicrob Agents Chemother. 1984; 25:98-104. [PubMed 6561017]

15. Fuchs PC, Jones RN, Barry AL et al. In vitro evaluation of cefixime (FK027, FR17027, CL284635): spectrum against recent clinical isolates, comparative antimicrobial activity, β-lactamase stability, and preliminary susceptibility testing criteria. Diagn Microbiol Infect Dis. 1986; 5:151-62. [PubMed 3522088]

16. Fuchs PC, Barry AL. Cefixime disk susceptibility test criteria. J Clin Microbiol. 1986; 24:647-9. [PubMed 3771755]

17. Jorgensen JH, Doern GV, Thornsberry C et al. Susceptibility of multiply resistant Haemophilus influenzae to newer antimicrob agents. Diagn Microbiol Infect Dis. 1988; 9:27-32. [PubMed 3259490]

18. Cullmann W, Dick W, Stieglitz M et al. Comparative evaluation of orally active beta-lactam compounds in ampicillin-resistant gram-positive and gram-negative rods: role of beta lactamases on resistance. Chemotherapy. 1988; 34:202-15. [PubMed 3262045]

19. Counts GW, Baugher LK, Ulness BK et al. Comparative in vitro activity of the new oral cephalosporin cefixime. Eur J Clin Microbiol Infect Dis. 1988; 7:428-31. [PubMed 3137053]

20. Knapp CC, Sierra-Madero J. Antibacterial activities of cefpodoxime, cefixime, and ceftriaxone. Antimicrob Agents Chemother. 1988; 32:1896-8. [PubMed 3245701]

21. Sanders CC. β-lactamase stability and in vitro activity of oral cephalosporins against strains possessing well-characterized mechanisms of resistance. Antimicrob Agents Chemother. 1989; 33:1313-7. [PubMed 2802558]

22. Garcia-Rodriguez JA, Garcia Sanchez JE, Garcia Garcia MI et al. In vitro activities of new oral β-lactams and macrolides against Campylobacter pylori. Antimicrob Agents Chemother.1989; 33:1650-1.

23. Brogden RN. Cefixime: a review of its antibacterial activity, pharmacokinetic properties and therapeutic potential. Drugs. 1989; 38:524-50. [PubMed 2684593]

24. Faulkner RD, Sia LL, Barone JS et al. Bioequivalency of oral suspension formulations of cefixime. Biopharm Drug Dispos. 1989; 10: 205-11. [PubMed 2706319]

25. Bialer M, Wu WH, Faulkner RD et al. In vitro protein binding interaction studies involving cefixime. Biopharm Drug Dispos. 1988; 9:315-20. [PubMed 3395672]

26. Faulkner RD, Bohaychuk W, Haynes JD et al. The pharmacokinetics of cefixime in the fasted and fed state. Eur J Clin Pharmacol. 1988; 34: 5225-8. [PubMed 3203716]

27. Faulkner RD, Fernandez P, Lawrence G et al. Absolute bioavailability of cefixime in man. J Clin Pharmacol. 1988; 28:700-6. [PubMed 3216036]

28. McAteer JA, Hiltke MF, Silber BM et al. Liquid-chromatographic determination of five orally active cephalosporins—cefixime, cefaclor, cefadroxil, cephalexin, and cephradine—in human serum. Clin Chem. 1987; 33:1788-90. [PubMed 3665031]

29. Faulkner RD, Bohaychuk W, Desjardins RE et al. Pharmacokinetics of cefixime after once-a-day and twice-a-day dosing to steady state. J Clin Pharmacol. 1987; 27:807-12. [PubMed 3429686]

30. Nakashima M, Uematsu T, Takiguchi Y et al. Phase I study of cefixime, a new oral cephalosporin. J Clin Pharmacol. 1987; 27:425-31. [PubMed 3693588]

31. Brittain DC, Scully BE, Hirose T et al. The pharmacokinetic and bactericidal characteristics of oral cefixime. Clin Pharmacol Ther. 1985; 38:590-4. [PubMed 4053491]

32. Healy DP, Sahai JV, Sterling LP et al. Influence of an antacid containing aluminum and magnesium on the pharmacokinetics of cefixime. Antimicrob Agents Chemother. 1989; 33: 1994-7. [PubMed 2610509]

33. Guay DRP, Meatherall RC, Harding GK et al. Pharmacokinetics of cefixime (CL 284,635; FK 027) in healthy subjects and patients with renal insufficiency. Antimicrob Agents Chemother. 1986; 30:485-90. [PubMed 3777912]

34. Bergeron MG. Penetration of cefixime into fibrin clots and in vivo efficacy against Escherichia coli, Klebsiella pneumoniae, and Staphylococcus aureus. Antimicrob Agents Chemother. 1986; 30:913-6. [PubMed 3545070]

35. Faulkner RD, Bohaychuk W, Lanc RA et al. Pharmacokinetics of cefixime in the young and elderly. J Antimicrob Chemother. 1988; 21:787-94. [PubMed 3410802]

36. Halperin-Walega E, Batra VK, Tonelli AP et al. Disposition of cefixime in the pregnant and lactating rat: transfer to the fetus and nursing pup. Drug Metab Dispos. 1988; 16:130-4. [PubMed 2894941]

37. Faulkner RD, Yacobi A, Barone JS et al. Pharmacokinetic profile of cefixime in man. Pediatr Infect Dis. 1987; 6:963-70.

38. Daikos GL, Kathpalia SB, Sharifi R et al. Comparison of ciprofloxacin and beta-lactam antibiotics in the treatment of urinary tract infections and alteration of fecal flora. Am J Med. 1987; 82(Suppl 4A):290-4. [PubMed 3555050]

39. Finegold SM, Ingram-Drake L, Gee R et al. Bowel flora changes in humans receiving cefixime (CL 284,635) or cefaclor. Antimicrob Agents Chemother. 1987; 31:443-6. [PubMed 3579262]

40. Iravani A, Richard GA, Johnson D et al. A double-blind, multicenter, comparative study of the safety and efficacy of cefixime versus amoxicillin in the treatment of acute urinary tract infections in adult patients. Am J Med. 1988; 85(Suppl 3A):17-23. [PubMed 3048090]

41. Tally FP, Desjardins RE, McCarthy EF et al. Safety profile of cefixime. Pediatr Infect Dis. 1987; 6:976-80.

42. Cohen SH, Gerding DN, Johnson S et al. Clinical practice guidelines for Clostridium difficile infection in adults: 2010 update by the Society for Healthcare Epidemiology of America (SHEA) and the Infectious Diseases Society of America (IDSA). Infect Control Hosp Epidemiol. 2010; 31:431-55. [PubMed 20307191]

43. Leigh AP, Robinson D. A general practice comparative study of a new third-generation oral cephalosporin, cefixime, with amoxycillin in the treatment of acute paediatric otitis media. Br J Clin Pract. 1989; 43:140-3. [PubMed 2686744]

44. Kiani R, Johnson D. Comparative multicenter studies of cefixime and amoxicillin in the treatment of respiratory tract infections. Am J Med. 1988; 85(Suppl 3A):6-13. [PubMed 3048092]

45. Ellner JJ. Management of acute and chronic respiratory tract infections. Am J Med. 1988; 85(Suppl 3A):2-5. [PubMed 3048091]

46. Childs SJ. Management of urinary tract infections. Am J Med. 1988; 85(Suppl 3A): 14-6. [PubMed 3048089]

48. Megran DW, Lefebvre K, Willetts V et al. Single-dose oral cefixime versus amoxicillin plus probenecid for the treatment of uncomplicated gonorrhea in men. Antimicrob Agents Chemother. 1990; 34:355-7. [PubMed 2183719]

50. Krepel CJ, Schopf LR, Gordon RC et al. Comparative in vitro activity of cefixime with eight other antimicrobials against Enterobacteriaceae, streptococci, and Haemophilus influenzae. Curr Ther Res. 1988; 43:296-302.

51. Levenstein J, Summerfield PJF, Fourie S et al. Comparison of cefixime and co-trimoxazole in acute uncomplicated urinary tract infection: a double-blind general practice study. S Afr Med J. 1986; 70:455-60. [PubMed 3535127]

52. Yamanaka H, Chiba T, Kawabata K et al. Studies on β-lactam antibiotics: IX. Synthesis and biological activity of a new orally active cephalosporin, cefixime (FK027). J Antibiot. 1985; 38:1738-51. [PubMed 4093334]

53. Rossi R, Castellani P, Younes G et al. Activity of FCE 22891 compared with cefuroxime axetil and cefixime in pulmonary and subcutaneous infections in mice. J Antimicrob Chemother. 1989; 23(Suppl C):149-55. [PubMed 2732136]

54. Dance DAB, Wuthiekanun V, Chaowagul W et al. The antimicrobial susceptibility of Pseudomonas pseudomallei: emergence of resistance in vitro and during treatment. J Antimicrob Chemother. 1989; 24:295-309. [PubMed 2681116]

56. Scott HV, Pannowitz D. Cefixime: clinical trial against otitis media and tonsillitis. N Z Med J. 1990; 103:25-6. [PubMed 2406651]

57. Neu HC. β-Lactam antibiotics: structural relationships affecting in vitro activity and pharmacologic properties. Clin Infect Dis. 1986; 8(Suppl 3):S237-60.

58. Saito A, Yamaguchi K, Shigeno Y et al. Clinical and bacteriological evaluation of Branhamella catarrhalis in respiratory infections. Drugs. 1986; 31(Suppl 3):87-92. [PubMed 3488201]

59. Barry AL. Cefixime: spectrum of antibacterial activity against 16016 clinical isolates. Pediatr Infect Dis. 1987; 6: 954-7.

60. Neu HC. In vitro activity of a new broad spectrum, beta-lactamase-stable oral cephalosporin, cefixime. Pediatr Infect Dis. 1987; 6:958-62.

61. Howie VM. Bacteriologic and clinical efficacy of cefixime compared with amoxicillin in acute otitis media. Pediatr Infect Dis. 1987; 6:989-91.

62. Kenna MA, Bluestone CD, Fall P et al. Cefixime vs. cefaclor in the treatment of acute otitis media in infants and children. Pediatr Infect Dis. 1987; 6:992-6.

63. McLinn SE. Randomized, open label, multicenter trial of cefixime compared with amoxicillin for treatment of acute otitis media with effusion. Pediatr Infect Dis. 1987; 6:997-1001.

64. Risser WL, Barone JS, Clark PA et al. Noncomparative, open label, multicenter trial of cefixime for treatment of bacterial pharyngitis, cystitis and pneumonia in pediatric patients. Pediatr Infect Dis. 1987; 6:1002-6.

65. Mendelman PM, Henritzy LL, Chaffin DO et al. In vitro activities and targets of three cephem antibiotics against Haemophilus influenzae. Antimicrob Agents Chemother. 1989; 33:1878-82. [PubMed 2610499]

66. Neu HC, Saha G. Comparative in vitro activity and β-lactamase stability of FK482, a new oral cephalosporin. Antimicrob Agents Chemother. 1989; 33:1795-800. [PubMed 2589845]

67. Nord CE, Movin G. Impact of cefixime on the normal intestinal microflora. Scand J Infect Dis. 1988; 20:547-52. [PubMed 3222669]

68. Machka K, Balg H, Braveny I. In vitro activity of new antibiotics against Haemophilus influenzae. Eur J Clin Microbiol Infect Dis. 1988; 7:812-4. [PubMed 3145871]

69. Nies BA. Comparative activity of cefixime and cefaclor in an in vitro model simulating human pharmacokinetics. Eur J Clin Microbiol. 1989; 8:558-61.

70. Beumer HM. Cefixime versus amoxicillin/clavulanic acid in lower respiratory tract infections. Int J Clin Pharmacol Ther. 1989; 27:30-3.

71. Kuhlwein A. Efficacy and safety of a single 400 mg oral dose of cefixime in the treatment of uncomplicated gonorrhea. Eur J Clin Microbiol Infect Dis. 1989; 8:261-2. [PubMed 2496996]

72. Dorow P. Safety and efficacy of cefixime versus cefaclor in respiratory tract infections. J Chemother. 1989; 1:257-60. [PubMed 2809693]

73. Faulkner RD, Sia LL, Look ZM et al. Bioequivalency of solid oral dosage forms of cefixime. Int J Pharm. 1988; 43:53-8.

74. Cox CE. Cefixime versus trimethoprim/sulfamethoxazole in treatment of patients with acute, uncomplicated lower urinary tract infections. Urology. 1989; 43:322-6.

75. Leggett NJ, Caravaggio C. Cefixime. DICP. 1990; 24:489-95. [PubMed 2188437]

76. Mortensen JE. Comparative in vitro activity of cefixime against Haemophilus influenzae isolates, including ampicillin-resistant, non-β-lactamase-producing isolates, from pediatric patients. Antimicrob Agents Chemother. 1990; 34:1456-8. [PubMed 2386375]

77. Liebowitz LD, Saunders J. In vitro susceptibility of upper respiratory tract pathogens to 13 oral antimicrobial agents. S Afr Med J. 1987; 72:385-8. [PubMed 3660122]

78. Matsui H, Hiraoka M, Inoue M et al. Antimicrobial activity and stability to β-lactmase of BMY-28271, a new oral cephalosporin ester. Antimicrob Agents Chemother. 1990; 34:555-61. [PubMed 2344162]

79. Jacoby GA. Activities of β-lactam antibiotics against Escherichia coli strains producing extended-spectrum β-lactamases. Antimicrob Agents Chemother. 1990; 34:858-62. [PubMed 2193623]

80. Agger WA, Callister SM. In vitro susceptibility of Borrelia burgdorferi to five oral cephalosporins and ceftriaxone. Antimicrob Agents Chemother. 1992; 36:1788-90. [PubMed 1416868]

81. Hoppe JE. In vitro susceptibilities of Bordetella pertussis and Bordetella parapertussis to six new oral cephalosporins. Antimicrob Agents Chemother. 1990; 34:1442-3. [PubMed 2386374]

82. American Academy of Pediatrics. Red Book: 2012 Report of the Committee on Infectious Diseases. 29th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2012.

83. Food and Drug Administration. Antibiotic drugs; cefixime trihydrate; cefixime trihydrate tablets and cefixime trihydrate powder for oral suspension. (Docket No. 88N-0121). Fed Regist. 1988; 53:24256-9.

84. Dajani AS, Bisno AL, Chung KJ et al. Prevention of rheumatic fever: a statement for health professionals by the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease of the Council on Cardiovascular Disease in the Young, of the American Heart Association. Circulation. 1988; 78: 1082-6.

85. Food and Drug Administration. Specific requirements on content and format of labeling for human prescription drugs; proposed addition of “geriatric use” subsection in the labeling (Docket No. 89N-0474). Fed Regist. 1990; 55:46134-7.

86. Gerber MA, Baltimore RS, Eaton CB et al. Prevention of rheumatic fever and diagnosis and treatment of acute Streptococcal pharyngitis: a scientific statement from the American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee of the Council on Cardiovascular Disease in the Young, the Interdisciplinary Council on Functional Genomics and Translational Biology, and the Interdisciplinary Council on Quality of Care and Outcomes Research: endorsed by the American Academy of Pediatrics. Circulation. 2009; 119:1541-51. [PubMed 19246689]

97. Norrby SR. Adverse reactions and interactions with newer cephalosporin and cephamycin antibiotics. Medical Toxicol. 1986; 1:32-46.

98. Saxon A, Beall GN, Rohr AS et al. Immediate hypersensitivity reactions to beta-lactam antibiotics. Ann Intern Med. 1987; 107: 204-15. [PubMed 3300459]

99. Lederle, Pearl River, NY: Personal communication.

100. Kees F, Naber KG, Sigl G et al. Relative bioavailability of three cefixime formulations. Arzneimittelforschung. 1990; 40:293-7. [PubMed 2346538]

101. Anon. Choice of cephalosporins. Med Lett Drugs Ther. 1990; 32:107-10. [PubMed 2243553]

102. Reviewers’ comments (personal observations).

103. Verghese A, Roberson B, Kalbfleisch JH et al. Randomized comparative study of cefixime versus cephalexin in acute bacterial exacerbation of chronic bronchitis. Antimicrob Agents Chemother. 1990; 34:1041-4. [PubMed 2118322]

104. Anon. Drugs for bacterial infections. Med Lett Treat Guid. 2010; 8:43-52.

106. Handsfield HH, McCormack WM, Hook EW et al. A comparison of single-dose cefixime with ceftriaxone as treatment for uncomplicated gonorrhea. N Engl J Med. 1991; 325:1337-41. [PubMed 1922235]

107. Markowitz M, Gerber MA. Treatment of streptococcal pharyngotonsillitis: reports of penicillin’s demise are premature. J Pediatr. 1993; 123:679-85. [PubMed 8229474]

108. Plourde PJ, Tyndall M, Agoki E et al. Single-dose cefixime versus single-dose ceftriaxone in the treatment of antimicrobial-resistant Neisseria gonorrhoeae infection. J Infect Dis. 1992; 166:919-22. [PubMed 1527431]

109. Anon. Interim guidelines for the treatment of uncomplicated gonococcal infection. CMAJ. 1992; 146:1587-8. [PubMed 1571870]

110. Cates W Jr. Sexually transmitted diseases in the 1990’s. N Engl J Med. 1991; 325:368-9.

111. Cates W Jr. Commentary on “Cefixime or ceftriaxone for gonorrhea?” ACP J Club. 1992; March-April:52. (Ann Intern Med. vol 116, suppl 2). Comment on Handsfield HH, McCormack WM, Hook EW III, et al. A comparison of single-dose cefixime with ceftriaxone as treatment for uncomplicated gonorrhea. N Engl J Med. 1991; 325:1337-41. [PubMed 1922235]

114. Tatsuta M, Ishikawa H, Iishi H et al. Reduction of gastric ulcer recurrence after suppression of Helicobacter pylori by cefixime. Gut. 1990; 31:973-6. [PubMed 2210464]

115. Westblom TU, Gudipati S. In vitro susceptibility of Helicobacter pylori to the new oral cephalosporins cefpodoxime, ceftibuten and cefixime. Eur J Clin Microbiol Infect Dis. 1990; 9:691-3. [PubMed 2226500]

117. Harrison CJ, Chartrand SA, Rodriguez W et al. Middle ear effuxion concentrations of cefixime during acute otitis media with effusion and otitis media with effusion. Pediatr Infect Dis J. 1997; 16:816-7. [PubMed 9271047]

118. Portilla I, Lutz B, Montalvo M et al. Oral cefixime versus intramuscular ceftriaxone in patients with uncomplicated gonococcal infections. Sex Transm Dis. 1992; 19:94-8. [PubMed 1534422]

119. Dunnett DM. Cefixime in the treatment of uncomplicated gonorrhea. Sex Transm Dis. 1992; 19:92-3. [PubMed 1595018]

120. Asbach HW. Single dose oral administration of cefixime 400 mg in the treatment of acute uncomplicated cystitis and gonorrhoea. Drugs. 1991; 42(Suppl 4):10-3. [PubMed 1725148]

121. Loo VG, Sherman P. Helicobacter pylori infection in a pediatric population: in vitro susceptibilities to omeprazole and eight antimicrobial agents. Antimicrob Agents Chemother. 1992; 36:1133-5. [PubMed 1510406]

122. Ateshkadi A, Lam NP. Helicobacter pylori and peptic ulcer disease. Clin Pharm. 1993; 12:34-48. [PubMed 8428432]

123. Millar MR. Bactericidal activity of antimicrobial agents against slowly growing H. pylori. Antimicrob Agents Chemother. 1992; 36:185-7. [PubMed 1590687]

124. Blaser MJ. Helicobacter pylori: its role in disease. Clin Infect Dis. 1992; 15:386-91. [PubMed 1520782]

125. Murray DM, DuPont HL, Cooperstock M et al. Evaluation of new anti-infective drugs for the treatment of gastritis and peptic ulcer disease associated with infection by Helicobacter pylori. Clin Infect Dis. 1992; 15(Suppl 1):S268-73.

126. Peterson WL. Helicobacter pylori and peptic ulcer disease. N Engl J Med. 1991; 324:1043-8. [PubMed 2005942]

127. Graham DY. Evaluation of new anti-infective drugs for Helicobacter pylori infection: revisited and updated. Clin Infect Dis. 1993; 17:293-4. [PubMed 8399892]

128. Murray DM, DuPont HL. Reply. (Evaluation of new anti-infective drugs for Helicobacter pylori infection: revisited and updated.) Clin Infect Dis. 1993; 17:294-5.

129. Marshall BJ. Campylobacter pylori: its link to gastritis and peptic ulcer disease. Clin Infect Dis. 1990; 12(Suppl 1):S87-93.

130. Workowski KA, Berman S, Centers for Disease Control and Prevention (CDC). Sexually transmitted diseases treatment guidelines, 2010. MMWR Recomm Rep. 2010; 59(RR-12):1-110.

132. Clinical and Laboratory Standards Institute. Performance standards for antimicrobial susceptibility testing: Twenty-first informational supplement. CLSI document M100-S21. Wayne, PA; 2011.

133. Bartlett JG. Antibiotic-associated diarrhea. Clin Infect Dis. 1992; 573-81.

134. Kelly CP, Pothoulakis C. Clostridium difficile colitis. N Engl J Med. 1994; 330:257-62. [PubMed 8043060]

135. Centers for Disease Control and Prevention. Decreased susceptibility of Neisseria gonorrhoeae to fluoroquinolone—Ohio and Hawaii, 1992–1994. MMWR Morb Mortal Wkly Rep. 1994; 43:325-7. [PubMed 8164636]

137. Markham A. Cefixime: a review of its therapeutic efficacy in lower respiratory tract infections. Drugs. 1995; 49:1007-22. [PubMed 7641600]

138. Gooch WM, Philips A, Rhoades R et al. Comparison of the efficacy and safety and acceptability of cefixime and amoxicillin/clavulanate in acute otitis media. Pediatr Infect Dis J. 1997; 16:S21-4. [PubMed 9041624]

139. Ashkenazi S, Amir J, Waisman Y et al. A randomized, double-blind study comparing cefixime and trimethoprim-sulfamethoxazole in the treatment of childhood shigellosis. J Pediatr. 1993; 123:817-21. [PubMed 8229498]

140. Salam MA, Seas C, Khan WA et al. Treatment of shigellosis: cefixime is ineffective in shigellosis in adults. Ann Intern Med. 1995; 123:505-8. [PubMed 7661494]

141. Bhutta ZA, Khan IA. Therapy of multidrug-resistant typhoid fever with oral cefixime vs. intravenous ceftriaxone. Pediatr Infect Dis J. 1994; 13:990-4. [PubMed 7845753]

142. Girgis NI, Sultan Y, Hammad O et al. Comparison of the efficacy, safety and cost of cefixime, ceftriaxone and aztreonam in the treatment of multidrug-resistant Salmonella typhi septicemia in children. Pediatr Infect Dis J. 1995; 14:603-5. [PubMed 7567290]

143. Duverne C, Bouten A, Deslandes A et al. Modification of cefixime bioavailability by nefedipine in humans: involvement of the dipeptide carrier system. Antimicrob Agents Chemother. 1992; 36:2462-7. [PubMed 1489189]

144. Gremse DA, Dean PC, Farquhar DS et al. Cefixime and antibiotic-associated colitis. Pediatr Infect Dis J. 1994; 13:331-3. [PubMed 8036057]

145. Gales MA. Recognition of severe cefixime-induced diarrhea. Clin Pharm. 1993; 12:881. [PubMed 8137604]

146. Soe GB. Treatment of typhoid fever and other systemic salmonelloses with cefotaxime, ceftriaxone, cefoperazone, and other newer cephalosporins. Rev Infect Dis. 1987; 9:719-36. [PubMed 3125577]

147. Mermin JH, Townes JM, Gerber M et al. Typhoid fever in the United States, 1985-1994: changing risks of international travel and increasing antimicrobial resistance. Arch Intern Med. 1998; 158:633-8. [PubMed 9521228]

148. Helvaci M, Bektaslar D, Ozkaya B et al. Comparative efficacy of cefixime and ampicillin-sulbactam in shigellosis in children. Acta Paediatr Jpn. 1998; 40:131-4. [PubMed 9581302]

149. Asmar BI, Dajani AS, Del Beccaro MA et al. Comparison of cefpodoxime proxetil and cefixime in the treatment of acute otitis media in infants and children. Pediatrics. 1994; 94:847-52. [PubMed 7971000]

150. Rodriguez WJ, Khan W, Sait T et al. Cefixime vs. cefaclor in the treatment of acute otitis media in children: a randomized, comparative study. Pediatr Infect Dis J. 1993; 12:70-4. [PubMed 8417429]

152. Shulman ST, Bisno AL, Clegg HW et al. Clinical practice guideline for the diagnosis and management of group A streptococcal pharyngitis: 2012 update by the Infectious Diseases Society of America. Clin Infect Dis. 2012; 55:1279-82. [PubMed 23091044]

154. Pichichero ME. Shortened course of antibiotic therapy for acute otitis media, sinusitis and tonsillopharyngitis. Pediatr Infect Dis J. 1997; 16:680-95. [PubMed 9239773]

155. Tack KJ, Henry DC, Gooch WM et al. Five-day cefdinir treatment for streptococcal pharyngitis. Antimicrob Agents Chemother. 1998; 42:1073-5. [PubMed 9593129]

156. Pichichero ME. Cephalosporins are superior to penicillin for treatment of streptococcal tonsillopharyngitis: is the difference worth it? Pediatr Infect Dis. 1993; 12:268-74.

157. Dajani AS, Kessler SL, Mendelson R et al. Cefpodoxime proxetil vs. penicillin V in pediatric streptococcal pharyngitis/tonsillitis. Pediatr Infect Dis J. 1993; 12:275-9. [PubMed 8483620]

158. Aujard Y, Boucot I, Brahimi N et al. Comparative efficacy and safety of four-day cefuroxime axetil and ten-day penicillin treatment of group A beta-hemolytic streptococcal pharyngitis in children. Pediatr Infect Dis J. 1995; 14:295-300. [PubMed 7603811]

159. Mehra S, Van Moerkerke M, Welck J et al. Short course therapy with cefuroxime axetil for group A streptococcal tonsillopharyngitis in children. Pediatr Infect Dis J. 1998; 17:452-7. [PubMed 9655533]

160. Milatovic D. Evaluation of cefadroxil, penicillin and erythromycin in the treatment of streptococcal tonsillopharyngitis. Pediatr Infect Dis J. 1991; 10:S61-3. [PubMed 1945599]

161. Block SL, Hedrick JA. Comparative study of the effectiveness of cefixime and penicillin V for the treatment of streptococcal pharyngitis in children and adolescents. Pediatr Infect Dis J. 1992; 11:919-25. [PubMed 1454432]

162. Friedland IR. Cefixime therapy for otitis media. Pediatr Infect Dis J. 1993; 12:544-5. [PubMed 8345993]

163. Nataro JP. Treatment of bacterial enteritis. Pediatr Infect Dis J. 1998; 17:420-22. [PubMed 9613658]

164. Bluestone CD. Review of cefixime in the treatment of otitis media in infants and children. Pediatr Infect Dis J. 1993; 12:75-82. [PubMed 8417430]

165. Owen MJ, Anwar R, Nguyen HK et al. Efficacy of cefixime in the treatment of acute otitis media in children. Am J Dis Child. 1993; 147:81-6. [PubMed 8418608]

166. Ramirez JA, Srinath L, Ahkee S et al. Early switch from intravenous to oral cephalosporins in the treatment of hospitalized patients with community-acquired pneumonia. Arch Intern Med. 1995; 155:1273-6. [PubMed 7778957]

167. Spangler SK, Jacobs MR. In vitro susceptibilities of 185 penicillin-susceptible and - resistant pneumococci to WY-49605 (SUN/SY 555%), a new oral penem, compared with those to penicillin G, amoxicillin, amoxicillin-clavulanate, cefixime, cefaclor, cefpodoxime, cefuroxime, and cefdinir. Antimicrob Agents Chemother. 1994; 38:2902-4. [PubMed 7695280]

168. Thorburn CE, Knott SJ. In vitro activities of oral β-lactams at concentrations achieved in humans against penicillin-susceptible and -resistant pneumococci and potential to select resistance. Antimicrob Agents Chemother. 1998; 42:1973-9. [PubMed 9687392]

169. Davies HD, Low DE, Schwartz B et al. Evaluation of short-course therapy with cefixime or rifampin for eradication of pharyngeally carried group A streptococci. Clin Infect Dis. 1995; 21:1294-6. [PubMed 8589159]

170. Ottolini M, Ascher D, Cieslak T et al. Pneumococcal bacteremia during oral treatment with cefixime for otitis media. Pediatr Infect Dis J. 1991; 10:467-8. [PubMed 1852543]

171. Adam D, Hostalek U. 5-day cefixime therapy for bacterial pharyngitis and/or tonsillitis: comparison with 10-day penicillin V therapy. Cefixime Study Group. Infection. 1995; 23(Suppl 2):S83-6. [PubMed 8537138]

172. Kishiyam JL. The cross-reactivity and immunology of β-lactam antibiotics. Drug Saf. 1994; 10:318-27. [PubMed 8018304]

173. Thompson JW. Adverse effects of newer cephalosporins: an update. Drug Saf. 1993; 9:132-42. [PubMed 8397890]

174. Zenilman JM. Typhoid fever. JAMA. 1997; 278:847-8. [PubMed 9293994]

177. Fekety R for the American College of Gastroenterology Practice Parameters Committee. Guidelines for the diagnosis and management of Clostridium difficile-associated diarrhea and colitis. Am J Gastroenterol. 1997; 92:739-50. [PubMed 9149180]

178. American Society of Health. ASHP therapeutic position statement on the preferential use of metronidazole for the treatment of Clostridium difficile-associated disease. Am J Health-Syst Pharm. 1998; 55:1407-11. [PubMed 9659970]

180. Lorenz J. Comparison of 5-day and 10-day cefixime in the treatment of acute exacerbation of chronic bronchitis. Chemotherapy. 1998; 44(Suppl):15-8. [PubMed 9797418]

181. Oksi J, Nikoskelainen J. Comparison of oral cefixime and intravenous ceftriaxone followed by oral amoxicillin in disseminated lyme borreliosis. Eur J Clin Microbiol Infect Dis. 1998; 17:715-9. [PubMed 9865985]

182. Hoberman A, Wald ER, Hickey RW et al. Oral versus initial intravenous therapy for urinary tract infections in young febrile children. Pediatrics. 1999; 104:79-86. [PubMed 10390264]

183. Aracil B, Gomez-Garces JL. A study of susceptibility of 100 clinical isolates belonging to the Streptococcus milleri group to 16 cephalosporins. J Antimicrob Chemother. 1999; 43:399-402. [PubMed 10223596]

184. Lieberthal AS, Carroll AE, Chonmaitree T et al. The diagnosis and management of acute otitis media. Pediatrics. 2013; 131:e964-99. [PubMed 23439909]

185. Wormser GP, Dattwyler RJ, Shapiro ED et al. The clinical assessment, treatment, and prevention of lyme disease, human granulocytic anaplasmosis, and babesiosis: clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis. 2006; 43:1089-134. [PubMed 17029130]

189. Memon IA, Billoo AG, Memon HI. Cefixime: an oral option for the treatment of multidrug-resistant enteric fever in children. South Med J. 1997; 90:1204-7. [PubMed 9404906]

190. Cao XT, Kneen R, Nguyen TA et al. A comparative study of ofloxacin and cefixime for treatment of typhoid fever in children. The Dong Nai Pediatric Center Typhoid Study Group. Pediatr Infect Dis J. 1999; 18:245-8. [PubMed 10093945]

191. Girgis NI, Kilpatrick ME, Farid Z et al. Cefixime in the treatment of enteric fever in children. Drugs Exp Clin Res. 1993; 19:47-9. [PubMed 8223140]

192. Chow AW, Benninger MS, Brook I et al. IDSA clinical practice guideline for acute bacterial rhinosinusitis in children and adults. Clin Infect Dis. 2012; 54:e72-e112. [PubMed 22438350]

193. Wald ER, Applegate KE, Bordley C et al. Clinical Practice Guideline for the Diagnosis and Management of Acute Bacterial Sinusitis in Children Aged 1 to 18 Years. Pediatrics. 2013; :. [PubMed 23796742]

194. Allen VG, Mitterni L, Seah C et al. Neisseria gonorrhoeae treatment failure and susceptibility to cefixime in Toronto, Canada. JAMA. 2013; 309:163-70. [PubMed 23299608]

195. Kirkcaldy RD, Bolan GA, Wasserheit JN. Cephalosporin-resistant gonorrhea in North America. JAMA. 2013; 309:185-7. [PubMed 23299612]

196. Centers for Disease Control and Prevention (CDC). Cephalosporin susceptibility among Neisseria gonorrhoeae isolates--United States, 2000-2010. MMWR Morb Mortal Wkly Rep. 2011; 60:873-7. [PubMed 21734634]

197. Centers for Disease Control and Prevention (CDC). Update to CDC's Sexually transmitted diseases treatment guidelines, 2010: oral cephalosporins no longer a recommended treatment for gonococcal infections. MMWR Morb Mortal Wkly Rep. 2012; 61:590-4. [PubMed 22874837]

198. Kirkcaldy RD, Zaidi A, Hook EW et al. Neisseria gonorrhoeae antimicrobial resistance among men who have sex with men and men who have sex exclusively with women: the Gonococcal Isolate Surveillance Project, 2005-2010. Ann Intern Med. 2013; 158:321-8. [PubMed 23460055]

b. AHFS Drug Information 2003. McEvoy GK, ed. Cephalosporins General Statement. American Society of Health-System Pharmacists; 2003:125-39.