Cephalexin

Overview

Cephalexin (Rilexine®, Keflex®) is a first-generation cephalosporin antibiotic widely used in veterinary medicine, particularly in dogs and cats. It is administered orally and is commonly prescribed for treatment of bacterial skin infections caused by susceptible organisms.

Cephalexin is considered a first-line antimicrobial for many uncomplicated bacterial skin infections in dogs, especially superficial bacterial pyoderma caused by Staphylococcus pseudintermedius. It may also be used extra-label in cats for susceptible infections. The drug is generally well tolerated, and gastrointestinal upset is the most commonly reported adverse effect.

Mechanism of Action (MOA): Cephalexin is a time-dependent bactericidal antibiotic that inhibits bacterial cell wall synthesis. It binds to penicillin-binding proteins (PBPs) involved in the final stages of peptidoglycan formation, disrupting the integrity of the bacterial cell wall. This results in formation of a defective cell wall and osmotic instability, leading to bacterial cell lysis and death. Cephalexin has strong activity against many gram-positive organisms such as Staphylococcus and Streptococcus species, while gram-negative activity is more limited.

Indications

Cephalexin is commonly used in dogs and cats for treatment of bacterial infections caused by organisms susceptible to first-generation cephalosporins. It is particularly valuable for skin infections caused by staphylococcal species and is considered a first-tier antimicrobial for many uncomplicated dermatologic infections.

• Superficial bacterial pyoderma (dogs): FDA-approved for treatment of secondary superficial bacterial pyoderma associated with Staphylococcus pseudintermedius.
• Deep pyoderma: Frequently used extra-label for treatment of deeper bacterial skin infections when susceptible organisms are present.
• Other bacterial skin infections: May be used for wound infections, abscesses, and other dermatologic infections caused by susceptible bacteria.
• Urinary tract infections: Extra-label use in dogs and cats for lower UTIs caused by susceptible organisms due to the high drug concentrations achieved in urine.

Dosage (Reference)

Dog

In dogs, cephalexin is commonly administered orally for treatment of bacterial skin infections and urinary tract infections caused by susceptible organisms. It is well absorbed after oral administration and is typically given twice daily in clinical practice.

Cat

In cats, cephalexin is used extra-label for treatment of susceptible bacterial infections, particularly skin infections, wounds, abscesses, and urinary tract infections.

Warnings & Precautions

Cephalexin is generally well tolerated in dogs and cats, but appropriate patient selection and monitoring are important to reduce the risk of adverse reactions or therapeutic failure.

• Hypersensitivity to cephalosporins: Cephalexin is contraindicated in animals with known hypersensitivity to cephalosporins. Allergic reactions may occur independently of dose and can range from mild dermatologic reactions to severe anaphylaxis.
• Cross-reactivity with beta-lactam antibiotics: Animals with a history of hypersensitivity to other beta-lactam antibiotics (e.g., penicillins, carbapenems, cephamycins) may also react to cephalexin. Use cautiously in these patients.
• Severely ill patients: Oral antibiotics may not be appropriate in patients with septicemia, shock, or other serious systemic illness because gastrointestinal absorption may be delayed or reduced. Parenteral antimicrobial therapy is preferred in these situations.
• Renal impairment: Cephalexin is primarily eliminated by the kidneys. Dose reduction or prolonged dosing intervals may be considered in animals with significant renal dysfunction.
• Antimicrobial resistance: Treatment failure may occur in infections caused by resistant organisms such as methicillin-resistant staphylococci or multidrug-resistant bacteria. Culture and susceptibility testing is recommended in recurrent or non-responsive infections.
• Drug name confusion: Cephalexin can be confused with other cephalosporins due to similar drug names. Careful prescribing and dispensing practices are recommended to avoid medication errors.

Drug Interactions

Several drug interactions with cephalexin have been reported or are considered theoretically possible. Most involve altered renal elimination, reduced gastrointestinal absorption, or additive nephrotoxic effects when combined with other medications. Appropriate monitoring should be considered when cephalexin is administered with the following drugs.

• Aminoglycosides and other nephrotoxic drugs (e.g., amphotericin B, furosemide): Concurrent use with cephalosporins may increase the risk of additive nephrotoxicity. However, aminoglycosides and cephalosporins may demonstrate synergistic antibacterial activity against certain bacteria.
• Cholestyramine: May reduce gastrointestinal absorption of cephalexin and decrease therapeutic drug concentrations.
• Estrogens (e.g., estriol): Alteration of gastrointestinal flora by cephalexin may interfere with enterohepatic recirculation of estrogens and potentially reduce their effectiveness.
• Metformin: Cephalexin may increase serum concentrations of metformin due to competition for renal tubular secretion.
• Metoclopramide: When administered intravenously before oral cephalexin, metoclopramide may increase peak drug concentrations and overall systemic exposure.
• Omeprazole: May decrease peak cephalexin concentrations and delay oral absorption, although total time above MIC may not be significantly affected.
• Probenecid: Competitively inhibits renal tubular secretion of cephalosporins, which may increase serum concentrations and prolong the half-life of cephalexin.
• Warfarin: Cephalosporins may enhance the anticoagulant effects of warfarin, potentially increasing the risk of bleeding.
• Zinc (oral): May decrease gastrointestinal absorption of cephalexin when administered concurrently.

Side Effects & Overdose

Side Effects

Adverse reactions associated with cephalexin are generally uncommon and usually mild. Most reported side effects involve the gastrointestinal tract, although hypersensitivity and other systemic reactions may occur in sensitive animals.

• Gastrointestinal effects: Salivation, vomiting, diarrhea, and decreased appetite are the most commonly reported adverse effects following oral administration.
• Hypersensitivity reactions: Allergic reactions may occur independently of dosage and may present as rash, fever, pruritus, eosinophilia, lymphadenopathy, or rarely anaphylaxis.
• Behavioral and systemic effects: Lethargy, excitability, tachypnea, or excessive salivation have been reported in dogs, while vomiting and fever have been observed in cats.
• Dermatologic reactions (rare): Serious immune-mediated skin disorders such as erythema multiforme, toxic epidermal necrolysis, cutaneous vasculitis, or pemphigus foliaceus have been reported in small animals.
• Renal effects (rare): Nephrotoxicity may occur in rare cases, particularly in animals with pre-existing renal disease or those receiving other nephrotoxic medications.
• Hematologic abnormalities: Prolonged or high-dose therapy may be associated with neutropenia, agranulocytosis, thrombocytopenia, or prolonged prothrombin times.

Overdose

Cephalexin has a relatively wide safety margin. Acute overdoses are unlikely to cause severe toxicity, but gastrointestinal disturbances are the most commonly expected clinical signs.

• Gastrointestinal distress: Excessive dosing may result in hypersalivation, vomiting, or diarrhea.
• Biochemical changes: High repeated doses have been associated with mild increases in liver enzymes and decreases in total protein, although these changes may not always be clinically significant.
• Severe toxicity: Extremely high doses or prolonged therapy may contribute to neurologic or renal complications in susceptible patients.
• Management: Treatment is primarily supportive, including discontinuation of the drug and symptomatic management of clinical signs.
• Drug removal: Cephalexin may be removed from circulation by dialysis in severe overdose situations.

Key Notes

Practical clinical points that may assist veterinarians when using cephalexin in dogs and cats:

• First-line dermatologic antibiotic: Cephalexin is widely considered a first-tier systemic antibiotic for treatment of uncomplicated bacterial skin infections in dogs.
• Excellent gram-positive coverage: Particularly effective against staphylococcal and streptococcal organisms commonly involved in canine and feline skin infections.
• High urinary concentrations: The drug is primarily eliminated by the kidneys, producing high concentrations in urine that support its use in lower urinary tract infections.
• Time-dependent antimicrobial: Therapeutic success depends on maintaining drug concentrations above the bacterial MIC for an adequate portion of the dosing interval.
• Resistance considerations: Reduced efficacy may occur with methicillin-resistant staphylococci or ESBL-producing bacteria, making culture and susceptibility testing important in recurrent infections.
• Oral administration advantage: Cephalexin has high oral bioavailability in dogs and moderate absorption in cats, allowing effective outpatient therapy.