Cefpodoxime
Oral third generation cephalosporin for respiratory and urinary tract infections
Cefpodoxime is an oral third generation cephalosporin formulated as the prodrug cefpodoxime proxetil. After absorption in the small intestine, intestinal and plasma esterases cleave the proxetil ester and release the active substance. In Germany it is available under brand names such as Orelox and Podomexef, and as numerous generics. It is one of the preferred oral cephalosporins for outpatient therapy because it combines a broad gram negative spectrum with good stability against many β lactamases.
Its spectrum covers respiratory and urinary tract infections as well as uncomplicated skin and soft tissue infections. Compared with cefuroxime, the classic second generation cephalosporin, the gram negative spectrum is broader while activity against gram positive organisms (staphylococci) is somewhat weaker. Current S3 guidelines of the German Society of General Practice and the Paul Ehrlich Society classify cefpodoxime as a reserve option, so that oral cephalosporin efficacy is preserved for patients with penicillin intolerance or multi resistant organisms.
Mechanism of Action
As with all β lactam antibiotics, cefpodoxime inhibits cell wall synthesis in gram negative and gram positive bacteria. The molecule binds to penicillin binding proteins (PBPs), transpeptidases of the bacterial cell wall. This binding interrupts cross linking of peptidoglycan chains, the cell wall loses its stability, and osmotic pressure shifts lyse the bacteria.
Cefpodoxime is stable against a number of β lactamases that inactivate classic penicillins and some second generation cephalosporins. However, it is not sufficiently effective against extended spectrum β lactamases (ESBL) or AmpC β lactamases. When ESBL producing organisms are suspected, often in recurrent urinary tract infections after hospital stays, targeted microbiological susceptibility testing is required.
The spectrum covers Streptococcus pneumoniae, Streptococcus pyogenes, Moraxella catarrhalis, Haemophilus influenzae, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis and Neisseria gonorrhoeae. Enterococci, Pseudomonas aeruginosa, MRSA and anaerobes such as Bacteroides fragilis are inherently resistant.
Indications
- Acute uncomplicated sinusitis after treatment failure on amoxicillin or in penicillin intolerance
- Acute otitis media in children and adults, usually as second line therapy
- Acute exacerbation of chronic bronchitis of bacterial origin
- Mild community acquired pneumonia, not as first line in the current S3 guideline
- Acute pyelonephritis and complicated urinary tract infections in adults, and in pregnancy under strict indication
- Tonsillitis and pharyngitis caused by group A streptococci in penicillin intolerant patients
- Skin and soft tissue infections by susceptible streptococci and staphylococci
- Uncomplicated gonorrhoea as an alternative; used cautiously today because of the resistance situation
Dosage and Administration
Adults: usually 200 mg twice daily, for pyelonephritis 400 mg twice daily. Children from 15 kg body weight: 4 to 5 mg per kg twice daily, using age appropriate ready to use suspensions. Treatment duration is typically 5 to 10 days, and 10 to 14 days in pyelonephritis.
Absorption is strongly dependent on simultaneous food intake. Taking the drug with or right after a meal significantly increases bioavailability and is the standard recommendation. Tablets should be swallowed with plenty of fluid.
Renal impairment: dose adjustment when creatinine clearance is below 40 ml/min. Typically the dosing interval is prolonged (200 mg once daily or once every 48 hours). In haemodialysis, administer after the dialysis session. Hepatic impairment: no formal adjustment required, cefpodoxime is eliminated predominantly renally.
Side Effects
Common (1 to 10 percent): diarrhoea, nausea, vomiting, abdominal pain, headache, rash, vaginal candidiasis, elevated liver enzymes.
Uncommon (0.1 to 1 percent): allergic reactions (urticaria, pruritus), pseudomembranous colitis caused by Clostridioides difficile, superinfection with non susceptible pathogens, interstitial nephritis, blood count changes (eosinophilia, thrombocytosis).
Rare: anaphylaxis, Stevens Johnson syndrome, toxic epidermal necrolysis, haemolytic anaemia, acute kidney injury, seizures particularly in renal impairment and with high doses.
Important: bloody mucous diarrhoea during therapy or up to two months after the end of treatment should raise the suspicion of Clostridioides difficile associated colitis. Stop the antibiotic immediately and obtain diagnostic workup.
Interactions
- Proton pump inhibitors, H2 receptor antagonists, antacids: reduce absorption, keep a gap of at least two hours
- Oral anticoagulants (warfarin, phenprocoumon): enhanced anticoagulant effect possible, monitor INR closely
- Probenecid: inhibits renal excretion, cefpodoxime plasma levels rise
- Oral contraceptives: theoretical reduction in efficacy through changes in intestinal flora, usually not clinically relevant, consider additional barrier methods in high risk situations
- Aminoglycosides, loop diuretics: additive nephrotoxicity risk when given concomitantly
Special Notes
Penicillin allergy: in patients with severe immediate type penicillin reactions there is cross reactivity with cephalosporins in about 1 to 10 percent of cases. A detailed allergy history is mandatory. Where a type I reaction is suspected, allergological evaluation before use is advisable.
Pregnancy: cefpodoxime is not teratogenic. Under strict indication (pyelonephritis in pregnancy) use is possible, European guidelines list cephalosporins as an acceptable option. Breastfeeding: passage into breast milk is low, breastfeeding during therapy is possible; infants may develop diarrhoea or candidiasis.
Antibiotic stewardship: cefpodoxime is not a top tier reserve antibiotic, but it should not be prescribed casually as first line therapy in uncomplicated infections. First line recommendations remain amoxicillin, and for urinary tract infections nitrofurantoin or fosfomycin trometamol.
Monitoring: during prolonged therapy monitor liver and renal retention values and blood count; in at risk patients also monitor coagulation. Patients should be informed about signs of Clostridioides difficile infection and about the importance of completing the course.
You might also be interested in
- Amoxicillin, standard antibiotic for respiratory tract infections
- Cefaclor, oral second generation cephalosporin
- Clarithromycin, macrolide in penicillin allergy
- Doxycycline, broad spectrum tetracycline
- Ampicillin, classic aminopenicillin in the inpatient setting
Frequently Asked Questions
Why must I take cefpodoxime with food?
Cefpodoxime is a prodrug with poor solubility in pure gastric acid. Food increases absorption by about 50 percent. Taken on an empty stomach, the drug may not reach adequate tissue concentrations, which can make treatment fail. Take it with a main meal whenever possible.
Can cefpodoxime reduce the effectiveness of the pill?
The theoretical interaction lies in effects on intestinal flora and oestrogen absorption. Modern clinical data show no clinically relevant loss of hormonal contraceptive efficacy under most antibiotics except rifampicin. If diarrhoea or vomiting occur during antibiotic therapy, contraceptive efficacy may decline, and an additional barrier method is then advisable.
Can I take cefpodoxime if I have a penicillin allergy?
With a history of a mild rash, use is generally possible. With documented anaphylaxis or a severe immediate reaction to penicillin, cefpodoxime is contraindicated because cross reactions cannot be excluded. In case of doubt, allergological evaluation should precede therapy.
When do I need to see a doctor?
Seek immediate medical attention if you develop bloody or mucous diarrhoea, a severe rash, shortness of breath, facial swelling or high fever during therapy. The same applies if the original complaints do not improve within three days. The diagnosis or the therapy must then be reviewed.
Sources
- EMA, European Medicines Agency
- AWMF, S3 Guidelines on Respiratory and Urinary Tract Infections
- Paul Ehrlich Society for Chemotherapy
- Gelbe Liste, Cefpodoxime active substance profile
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