Cefixime

Cefixime is a third-generation cephalosporin which is administered orally for the treatment of bacterial infections.

Chemistry of Drug

Cefixime has a LogP of -0.4 which means it has a higher affinity of aqueous phase and is more hydrophilic. Cefixime has a water solubility of 55.11mg/L and ethanol solubility of 5000mg/L. This shows that cefuroxime is slightly soluble in water and soluble in ethanol.

It is also very soluble in other organic solvents like dimethyl formamide (DMF).

Its chemical structure is shown below

Mechanism of Action

Cefixime crosses cell wall and enters the periplasmic space where it will bind to penicillin binding protein (PBP) on the cell membrane of bacteria. Particularly, cefixime has a higher affinity for PBP 3, la & lb.

The PBP are responsible for mitosis and cell structure integrity. Inhibition of PBP results in prevention of cell division, resulting in filament formation which cause leakages of bacteria cell content. Cefixime, just like other 3rd cephalosporins, is more stable when there is presence of certain beta lactamases enzymes

Antimicrobial Activity

Gram negative aerobic bacteria

Susceptible species include Neisseria gonorrhoeae, Haemophilus influenza, Escherichia coli, Klebsiella spp, and Salmonella spp

Resistant spp. includes Enterobacter spp

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Gram positive aerobic bacteria

Cefixime has a poor activity against gram positive aerobic bacteria as summarized below.

Susceptible spp include: Penicillin-susceptible Streptococcus pneumonia

?Resistant spp include: Penicillin-resistant Streptococcus pneumonia, Staphylococcus aureus, enterococci spp, Listeria monocytogenes

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Gram positive anaerobes

Cefixime has poor activity and species such as Peptostreptococcus and Clostridium spp. are resistant

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Gram negative anaerobes

Bacteroides fragilis spp. is resistant to cefixime

Indications

Gonorrhea

A dose of 200mg twice a day for 3-7days or a single 400mg dose is used to treat uncomplicated gonorrhea together with other antibiotics. However, due to emergence of resistance and treatment failure, Ceftriaxone is preferred cephalosporin drug choice according to latest Essential Drug List of Zimbabwe (EDLIZ)

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Urinary Tract Infection (UTI)

Cefixime can be used in treatment of uncomplicated and complicated UTIs. However, in the treatment of complicated UTIs, it is less effective and other antibiotics such as ciprofloxacin/norfloxacin are preferred

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Acute Exacerbation of Chronic Obstructive Pulmonary Disease

Cefixime has similar efficacy to that of cefaclor in treatment of bacterial exacerbation of COPD. However other agents such as amoxicillin-clavulanate or cefuroxime axetil, which are more effective are preferred

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Pharyngitis and tonsillitis

Cefixime can be used in cases caused by susceptible Streptococcus pyogenes

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Otitis Media

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Community acquired Pneumonia

Indicated in treatment of pneumonia caused by H.influanzae and S.pneumoniae. However, it is not effective in treatment of pneumonia caused by P.aeruginosa

Pharmacokinetics

Absorption

Following oral administration, peak plasma concentration is reached in 3-4hours. Absolute bioavailability of 400mg cefixime is 40% and for 200mg is 48%.

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Distribution

70% of Cefixime is protein bound and has a volume of distribution of 6.7L.

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Metabolism and Excretion

No metabolites of cefixime have been identified in blood or urine and is mainly excreted renally unchanged. It has a half-life of 3-4hrs and is prolonged in individuals with renal impairment.

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Important interactions

Co-administration with nifedipine increases absorption of cefixime from a baseline of 31% to 53% with nifedipine.

Cefixime is contraindicated in patients who received/receiving typhoid, cholera or BCG vaccine

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Toxicity

Common side effect is diarrhea

Less common are headaches, flatulence, and change in stool color

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Also Read

Brogden, R.N., Campoli-Richards, D.M. Cefixime. Drugs 38, 524–550 (1989). https://doi.org/10.2165/00003495-198938040-00004

Lindsay Grayson, M. (2010). Kucers' The Use Of Antibiotics; A Clinical Review of Antibacterial, Antifungal, Antiparasitic and Antiviral Drugs. 6th Edition. Taylor & Francis Group