By Tiffany Wong, PharmD, BCPS

Clinical Pharmacist, Stanford Health Care

Dr. Wong reports no financial relationships relevant to this field of study.

INTRODUCTION1,2

Cefpodoxime is an oral third-generation cephalosporin antibiotic that was FDA-approved in 1998 for the treatment of various mild to moderate susceptible infections. There is now growing interest in the use of cefpodoxime, given the emphasis on early IV to oral conversion in patients hospitalized for community-acquired pneumonia (CAP) as well as the increasing resistance of antibiotics used for urinary tract infections (UTIs). This review focuses specifically on the use of cefpodoxime for community-acquired pneumonia caused by Streptococcus pneumoniae and Haemophilus influenzae (including beta-lactamase-producing strains) and uncomplicated urinary tract infections caused by Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, or Staphylococcus saprophyticus.

GUIDELINES3,4

The Infectious Diseases Society of America (IDSA)/American Thoracic Society Consensus Guidelines on the Management of Community-Acquired Pneumonia in Adults mention cefpodoxime as an alternative to high-dose amoxicillin or amoxicillin/clavulanate, although oral cephalosporins were found to be less effective in vitro.

The International Clinical Practice Guidelines for the Treatment of Acute Uncomplicated Cystitis and Pyelonephritis in Women suggest that cefpodoxime, as well as otherββ-lactam agents, are appropriate when other recommended UTI antimicrobials cannot be used. Caution is advised given the inferior efficacy and adverse effects of the β-lactam agents.

CLINICAL TRIALS5-11

Pneumonia

Combined Phase II and Phase III prospective, comparative, randomized studies in adult patients with lower and upper respiratory tract infections included 1,477 cefpodoxime-treated patients from July 1988 to December 1989. For lower respiratory tract infections, cefpodoxime was found to be as effective as amoxicillin, ceftriaxone in community-acquired bronchopneumonias, and amoxicillin/clavulanate in acute exacerbations of bronchitis.

A 1994 randomized, double-blind, double-dummy multicenter trial compared cefpodoxime and cefaclor for the outpatient treatment of culture-proven acute CAP. Of the 198 isolates recovered, S. pneumoniae and H. influenzae were the most common organisms. Of 178 isolates, 94% were susceptible to cefpodoxime compared to 82% of 181 isolates that were susceptible to cefaclor (P = 0.001). At the end-of-therapy visit, 100% of pathogens were eradicated in the cefpodoxime group and 92% of pathogens were eradicated in the cefaclor group (P = 0.06). For patients with culture-proven pneumonia, both groups had similar clinical cure rates, with 77% of cefpodoxime patients and 71% of cefaclor patients cured.

A more recent study in 2002 compared linezolid with a standard ceftriaxone step-down to cefpodoxime regimen for the treatment of hospitalized patients with CAP. This randomized, comparator-controlled, multicenter, open-label trial compared linezolid IV switch to oral therapy compared to ceftriaxone 1 g IV every 12 hours switch to cefopdoxime oral therapy. Bacterial pathogens were isolated in 33.6% (128/381) of the linezolid group and 34.4% (126/366) of the ceftriaxone/cefpodoxime group, with S. pneumoniae as the most common organism identified in both groups. In the patients who had confirmed S. pneumoniae pneumonia and received ≥ 80% of study drug, there was no difference in clinical cure between cefpodoxime (62/69; 89.9%) and linezolid groups (63/71; 88.7%) (P = 0.830).

Urinary Tract Infection (UTI)

In the early studies, cefpodoxime was evaluated in two prospective, randomized, parallel, double-blind trials that included about 570 patients in each trial. The studies showed that cefpodoxime did not differ in clinical and bacteriological efficacy to that of amoxicillin and cefaclor for uncomplicated UTIs.

A 2002 study compared a three-day regimen of cefopdoxime to an established short-course three-day regimen of oral trimethoprim-sulfamethoxazole (TMP-SMX) for the treatment of women with acute uncomplicated cystitis. E. coli was the most common pathogen isolated in both groups. The results showed no statistically significant difference in clinical or bacteriological cure rates between both groups. All patients in both treatment groups who failed bacteriologically had histories of ≥ 3 episodes of UTI per year (P < 0.001).

A more recent study in 2012 compared a three-day course of cefpodoxime to a standard three-day course of ciprofloxacin for the treatment of acute uncomplicated cystitis. Both groups had similar baseline characteristics except more women had a previous UTI, especially within the past year, in the cefpodoxime group. Of the uropathogens isolated, 75% were E. coli. Overall clinical cure at 30 days was 93% (139/150) for the ciprofloxacin group and 82% (123/150) for the cefpodoxime group (11%; 95% confidence interval [CI], 3%-18%). Cefpodoxime failed to demonstrate clinical non-inferiority to ciprofloxacin given the 11% difference in 95% confidence interval was greater than the pre-specified non-inferiority margin of 10%.

DOSAGE AND ADMINISTRATION1

See Table 1 for dosing regimen.

Cefpodoxime Film-coated Tablets

  • Tablets should be administered orally with food to enhance absorption.

Cefpodoxime Oral Suspension

  • Oral solution may be given without regard to food.

Renal Dose Adjustment

  • Creatinine clearance < 30 mL/min: Reduce dosing interval to every 24 hours.
  • Hemodialysis: Reduce dosing frequency to three times per week after hemodialysis.

Table 1. Dosing Regimen for Adults/Adolescents (≥ 12 years old)

Indication

Dose/Frequency

Duration

Acute CAP

200 mg every 12 hours

14 days

Uncomplicated UTI

100 mg every 12 hours

7 days

PHARMACOLOGY1

Cefpodoxime proxetil is a prodrug that is converted to cefpodoxime. Cefpodoxime is an extended-spectrum, semi-synthetic bactericidal cephalosporin antibiotic that inhibits bacterial cell wall synthesis. Cefpodoxime has activity against some beta-lactamases, both penicillinases, and cephalosporinases.

Pharmacokinetics1

Absorption

• Peak concentration ~ 2-3 hours

Tmax prolonged for 200 mg suspension

taken with food

• Absolute bioavailability 50%

200 mg tablet: AUC 21-33% higher with

food

200 mg suspension: AUC unchanged with

food

Distribution

• Protein binding ~ 21-29%

• Penetrates lung, skin, and tonsil tissue. Data on CSF levels not available.

Metabolism

• De-esterified to active metabolite,
cefpodoxime

• Minimal metabolism of cefpodoxime in vivo

Elimination

• Half-life ~ 2-3 hours

• 29-33% excreted unchanged in urine in 12 hours

MICROBIOLOGY1

Cefpodoxime has been shown to be active against most isolates of the following bacteria in vivo and in clinical infections.

Gram-positive bacteria

Gram-negative bacteria

Staphylococcus aureus (methicillin-susceptible strains, including those producing penicillinases)

Staphylococcus saprophyticus

Streptococcus pneumoniae (excluding penicillin-resistant isolates)

Streptococcus pyogenes

Escherichia coli

Klebsiella pneumoniae

Proteus mirabilis

Haemophilus influenzae (including beta-lactamase producing isolates)

Moraxella catarrhalis

Neisseria gonorrhoeae (including penicillinase-producing isolates)

Cefpodoxime resistance occurs primarily through hydrolysis by beta-lactamase, alteration of penicillin-binding proteins, and decreased permeability.

ADVERSE EFFECTS1

Cefpodoxime Film-coated Tablets

  • No deaths or permanent disabilities related to drug toxicity.
  • Twenty-nine (2.7%) patients discontinued medication due to adverse events possibly related to drug toxicity. Significantly more patients discontinued medication at a total daily dose of 800 mg than 400 mg and 200 mg.
  • Adverse events possibly or probably related to multiple doses of cefpodoxime in clinical trials (N = 4,696 cefpodoxime-treated patients)

Adverse Effect > 1%

Incidence

Diarrhea

7.0%

Nausea

3.3%

Vulvovaginal infections

1.3%

Abdominal pain

1.2%

Vaginal fungal infections

1.0%

Headache

1.0%

Cefpodoxime Oral Suspension

  • No deaths or permanent disabilities related to drug toxicity.
  • Twenty-four (1.1%) patients discontinued medication due to adverse events possibly related to drug toxicity.
  • Adverse events possibly, probably, or of unknown relationship to multiple doses of cefpodoxime oral solution in clinical trials (N = 2,128 cefpodoxime-treated patients)

Adverse Effect > 1%

Incidence

Diarrhea

6.0%

Vomiting

2.3%

Diaper rash/fungal skin rash

2.0%

Other skin rashes

1.8%

CONCLUSION1,2

Cefpodoxime is an oral third-generation cephalosporin antibiotic that received FDA approval many years ago. It has activity against certain Gram-positive pathogens, including S. aureus (methicillin-susceptible strains), S. saprophyticus, S. pneumoniae (excluding penicillin-resistant strains), and S. pyogenes, as well as Gram-negative pathogens, including E. coli, K. pneumoniae, P. mirabilis, H. influenzae, M. catarrhalis, and N. gonorrhoeae. As healthcare costs and resistance rates rise, cefpodoxime may have a more significant role as an oral treatment option for CAP and UTI compared to established therapies. Cefpodoxime is fairly well-tolerated, with diarrhea as the most common adverse event reported for both the tablet and oral suspension formulations.

REFERENCES

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  10. Kavatha D, Giamerellou H, Alexiou Z, et al. Cefpodoxime-proxetil versus trimethoprim-sulfamethoxazole for short-term therapy of uncomplicated acute cystitis in women. Antimicrob Agents Chemother 2003;47:897-900.
  11. Hooton TM, Roberts PL, Stapleton AE. Cefpodoxime vs ciprofloxacin for short-course treatment of acute uncomplicated cystitis: A randomized trial. JAMA 2012;307:583-589.