Keflex, known generically as cephalexin, is a first-generation cephalosporin antibiotic widely used for the treatment of various bacterial infections. First approved by the U.S. Food and Drug Administration (FDA) in 1971, it has remained a staple in outpatient and inpatient settings due to its efficacy, favorable safety profile, and oral bioavailability. This report provides a brief yet comprehensive overview of Keflex, covering its pharmacology, clinical indications, dosing, adverse effects, resistance patterns, and practical considerations.

Pharmacology and Mechanism of Action

Cephalexin belongs to the beta-lactam class of antibiotics, which inhibit bacterial cell wall synthesis. Specifically, it binds to penicillin-binding proteins (PBPs) located on the inner membrane of the bacterial cell wall. This binding interferes with the final transpeptidation step of peptidoglycan cross-linking, leading to a defective cell wall and ultimately bacterial lysis. Like other beta-lactams, cephalexin exhibits bactericidal activity against susceptible organisms.

As a first-generation cephalosporin, cephalexin is most active against gram-positive cocci, including methicillin-susceptible Staphylococcus aureus (MSSA) and Streptococcus pyogenes (group A streptococci). It also has modest activity against some gram-negative bacteria such as Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis, but it is ineffective against Pseudomonas aeruginosa, Enterobacter species, and methicillin-resistant S. aureus (MRSA). Its spectrum is narrower than later generations, which is advantageous for targeted therapy against common skin, respiratory, and urinary pathogens.

Pharmacokinetics

Cephalexin is well absorbed after oral administration, with a bioavailability of approximately 90%. Peak serum concentrations are achieved within one hour after a dose. The drug is widely distributed in body tissues and fluids, including bile, pleural fluid, synovial fluid, and bone. However, it penetrates the central nervous system poorly unless meninges are inflamed.

Cephalexin is excreted largely unchanged by the kidneys via glomerular filtration and tubular secretion. Its elimination half-life is about 0.5–1.2 hours in patients with normal renal function. Dose adjustment is required in individuals with severe renal impairment (creatinine clearance <30 mL/min). Food does not significantly reduce absorption, but taking it with food can minimize gastrointestinal upset.

Clinical Indications

Keflex is indicated for a variety of mild-to-moderate bacterial infections. Common approved uses include:

• Respiratory tract infections: Pharyngitis, tonsillitis, otitis media, sinusitis, and community-acquired pneumonia caused by susceptible streptococci or staphylococci.
  
• Skin and soft tissue infections: Cellulitis, abscesses, wound infections, and impetigo, particularly due to MSSA and group A streptococci.
  
• Bone and joint infections: Osteomyelitis and Modafresh (https://liporedux.fr) septic arthritis (often used as oral step-down therapy after parenteral treatment).
  
• Genitourinary tract infections: Uncomplicated cystitis, pyelonephritis, and prostatitis caused by susceptible gram-negative bacilli.
  
• Dental infections: As a prophylactic agent for certain dental procedures in patients with specific cardiac conditions (e.g., infective endocarditis prophylaxis).
  
  

Cephalexin is also sometimes used off-label for conditions such as acne vulgaris or as prophylaxis in recurrent urinary tract infections, though guidelines vary.

Dosing and Administration

Cephalexin is available in oral dosage forms: capsules (250 mg, 500 mg), tablets (250 mg, 500 mg, 1 g), and oral suspensions (125 mg/5 mL, 250 mg/5 mL). Dosing depends on the infection site, severity, and patient age/weight.

• Adults: Typical dose is 250–500 mg every 6 hours for most infections. For severe infections (e.g., pelvic inflammatory disease), up to 1 g every 6 hours may be used. Maximum recommended dose is 4 g per day.
  
• Children: 25–100 mg/kg/day divided into 2–4 doses. For otitis media, a common regimen is 75–100 mg/kg/day in four divided doses.
  
• Renal impairment: For CrCl 10–30 mL/min, the interval is extended to every 8–12 hours; for CrCl <10 mL/min, every 12–24 hours.
  
• Duration: Typically 7–14 days, but shorter courses (5–7 days) may be used for uncomplicated infections.
  
  

Adverse Effects

Keflex is generally well tolerated. The most common side effects are gastrointestinal: diarrhea (occurs in ~10% of patients), nausea, vomiting, dyspepsia, and abdominal pain. Less common effects include rash, urticaria, and eosinophilia. Hypersensitivity reactions, including anaphylaxis, are rare but possible, especially in patients with a history of penicillin allergy (cross-reactivity occurs in ~1–10%). Other rare adverse effects include Clostridioides difficile colitis, hepatic enzyme elevation, acute interstitial nephritis, and neurologic symptoms (e.g., dizziness, confusion) at high doses.

Cephalexin can potentiate the effect of warfarin, increasing the international normalized ratio (INR). Concomitant use with probenecid decreases renal excretion and may raise cephalexin levels.

Resistance and Stewardship

Bacterial resistance to cephalexin has increased over decades, primarily via production of beta-lactamases (e.g., TEM-1) by gram-negative organisms and altered PBPs (e.g., PBP2a in MRSA). Many E. coli and Klebsiella strains are now resistant. Cephalexin remains effective against MSSA (>90% susceptibility in many regions), but MRSA rates have shifted empiric therapy in skin infections toward alternatives.

To combat resistance, proper antibiotic stewardship is essential—cultures should be taken when possible, and cephalexin should be prescribed only for documented or strongly suspected bacterial infections for which it is the optimal agent.

Cost and Availability

Cephalexin is inexpensive and widely available generically. A typical course costs under $10–$20 USD, making it accessible in resource-limited settings. It is available in various forms internationally, often under trade names like Keflex, Keftab, and Ceporex.

Conclusion

Keflex (cephalexin) remains a valuable first-line oral antibiotic for the treatment of common gram-positive infections and select gram-negative infections, particularly in the setting of uncomplicated skin and urinary tract infections. Its safety, tolerability, and low cost contribute to its continued use despite evolving resistance. Clinicians should be aware of local susceptibility patterns, appropriate dosing in renal impairment, and potential cross-allergenicity with penicillins. As with all antibiotics, judicious use is key to preserving its effectiveness for future generations.