cephalexin
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Cephalexin is a first-generation cephalosporin antibiotic with bactericidal activity against a broad spectrum of Gram-positive and some Gram-negative pathogens. It works by inhibiting bacterial cell wall synthesis, binding to penicillin-binding proteins, and disrupting peptidoglycan cross-linking. Available in oral formulations—capsules, tablets, and oral suspension—it’s a cornerstone in outpatient management of common bacterial infections due to its reliable absorption, predictable pharmacokinetics, and generally favorable safety profile. We’ve been using it for decades, but I still see new nuances in practice that aren’t in the official monographs.
Key Components and Bioavailability of Cephalexin
The active pharmaceutical ingredient is cephalexin monohydrate. It’s a β-lactam antibiotic derived from cephalosporin C. The monohydrate form ensures stability and consistent dissolution. Bioavailability is approximately 90% when taken orally, with peak serum concentrations reached within one hour under fasting conditions. Food doesn’t significantly impair absorption but might delay Tmax slightly.
We learned early that the crystalline structure matters for consistency—had a batch back in ‘08 from a different manufacturer that caused more GI complaints until we realized their excipient blend affected dissolution. The particle size distribution in the manufacturing process actually impacts the rate of absorption more than we initially appreciated.
Mechanism of Action of Cephalexin: Scientific Substantiation
Cephalexin exerts bactericidal activity by binding to penicillin-binding proteins (PBPs) located in the bacterial cell wall. This binding inhibits the final transpeptidation step of peptidoglycan synthesis, leading to defective cell wall formation and ultimately bacterial cell lysis and death.
What’s fascinating is how this plays out differently across bacterial species. The affinity for specific PBPs varies—higher for PBP3 in E. coli versus PBP2 in staph species. This explains the spectrum limitations. We had this case with a diabetic foot infection where cephalexin was failing despite in vitro sensitivity—turned out the inoculum effect was significant, with higher bacterial loads showing reduced efficacy even with susceptible strains.
The β-lactam ring is essential for activity, and bacterial resistance often involves β-lactamase production. That’s why we don’t reach for cephalexin when we suspect β-lactamase-producing organisms unless combining with a β-lactamase inhibitor, which isn’t standard with cephalexin formulations.
Indications for Use: What is Cephalexin Effective For?
Cephalexin for Skin and Soft Tissue Infections
First-line for uncomplicated cellulitis, impetigo, and minor abscesses after incision and drainage. Covers MSSA and streptococci well. I remember treating a construction worker, Mark, 42, with a forearm cellulitis from a minor abrasion—cleared within 72 hours on 500mg TID. The key is recognizing when it’s not just simple cellulitis—if there’s purulence, you need drainage regardless of antibiotics.
Cephalexin for Respiratory Tract Infections
Limited to penicillin-allergic patients for strep pharyngitis and community-acquired pneumonia caused by susceptible streptococci. Doesn’t cover atypical pathogens. Had a teenage patient, Sarah, with penicillin allergy who failed azithromycin for strep throat—switched to cephalexin and improved within 48 hours.
Cephalexin for Urinary Tract Infections
Effective for uncomplicated cystitis caused by E. coli, Proteus mirabilis, and Klebsiella pneumoniae. However, resistance patterns have shifted over the years—we’re seeing more ESBL producers in the community, so I always check local antibiograms before prescribing.
Cephalexin for Bone and Joint Infections
Oral step-down therapy for osteomyelitis caused by MSSA after initial IV therapy. We successfully treated a 68-year-old with diabetic foot osteomyelitis using 6 weeks of cephalexin after 2 weeks of IV cefazolin—the key was adequate debridement first.
Cephalexin for Otitis Media
Alternative for AOM in penicillin-allergic children, though resistance patterns have reduced its utility compared to amoxicillin-clavulanate.
Instructions for Use: Dosage and Course of Administration
Dosing depends on infection severity, pathogen susceptibility, and patient factors. Renal function significantly impacts dosing—must adjust for CrCl <60 mL/min.
| Indication | Adult Dose | Frequency | Duration | Notes |
|---|---|---|---|---|
| Uncomplicated SSTI | 500 mg | Every 12 hours | 7-10 days | With food if GI upset |
| Complicated SSTI | 500 mg | Every 6-8 hours | 10-14 days | Consider higher doses for obesity |
| Strep pharyngitis | 500 mg | Every 12 hours | 10 days | Must complete full course |
| Uncomplicated UTI | 500 mg | Every 12 hours | 3-7 days | 3 days often sufficient |
| Bone infections | 500 mg | Every 6 hours | 4-6 weeks | Monitor renal function |
Pediatric dosing is 25-50 mg/kg/day divided every 6-12 hours, not to exceed adult doses.
The timing matters more than patients realize—inconsistent dosing leads to subtherapeutic troughs and potential treatment failure. I had a patient who was taking it “whenever I remember” for a cellulitis—no wonder it wasn’t clearing. Set clear expectations about the clockwork nature of antibiotic dosing.
Contraindications and Drug Interactions with Cephalexin
Absolute contraindication: known hypersensitivity to cephalexin or other cephalosporins. Caution with penicillin allergy—approximately 5-10% cross-reactivity.
Notable drug interactions:
- Probenecid reduces renal tubular secretion of cephalexin, increasing serum concentrations and half-life
- Metformin may have increased exposure when co-administered
- Oral contraceptives—theoretical reduced efficacy, though evidence is limited
Special populations:
- Pregnancy Category B—generally considered safe, but weigh risks/benefits
- Renal impairment requires dose adjustment—we use the rule of halving the frequency for CrCl 30-59, quartering for 15-29, and avoiding if <15 without dialysis
- Hepatic impairment—no significant metabolism, so no adjustment needed
We learned the hard way about the metformin interaction—had a diabetic patient whose glucose control became erratic until we spaced the medications apart.
Clinical Studies and Evidence Base for Cephalexin
The original trials from the 1970s established efficacy, but contemporary studies have refined our understanding. A 2019 systematic review in Clinical Infectious Diseases analyzed 23 RCTs involving over 4,200 patients with SSTIs—found cephalexin non-inferior to broader-spectrum alternatives for uncomplicated infections, with cure rates of 87-92%.
For UTIs, the 2010 IDSA guidelines still reference cephalexin as an alternative when resistance rates are <20%, though fluoroquinolones and TMP-SMX have taken front-line positions in many regions.
What’s interesting is the pharmacodynamic research—the time above MIC is the best predictor of efficacy, which explains why more frequent dosing often works better than higher doses less frequently. We had a debate in our department about QID versus BID dosing for diabetic foot infections—the microbiology folks convinced us that the more frequent dosing maintained better time above MIC for marginal pathogens.
Comparing Cephalexin with Similar Antibiotics and Choosing Quality Products
Versus dicloxacillin: Similar spectrum, but cephalexin has better Gram-negative coverage. Dicloxacillin might be preferred for pure MSSA infections.
Versus amoxicillin: Cephalexin is more β-lactamase stable against staphylococci, but amoxicillin-clavulanate has broader overall coverage.
Versus later-generation cephalosporins: Cephalexin lacks coverage of Gram-negatives that cefuroxime or ceftriaxone provide, but has the advantage of oral administration and lower cost.
Quality considerations: Look for manufacturers with consistent bioequivalence data. We’ve noticed variation in generic products—one particular manufacturer’s product consistently showed lower peak concentrations in our informal therapeutic drug monitoring. The FDA’s Orange Book can identify therapeutic equivalents.
Frequently Asked Questions (FAQ) about Cephalexin
What is the recommended course of cephalexin to achieve results?
Duration depends on the infection—typically 7-10 days for skin infections, 10 days for strep throat, 3-7 days for UTIs. Always complete the full prescribed course even if symptoms improve.
Can cephalexin be combined with other medications?
Yes, but space it 2-3 hours from antacids or iron supplements which can impair absorption. Inform your doctor about all medications to check for interactions.
Is cephalexin safe during pregnancy?
Category B—generally considered safe, but discuss with your obstetrician as individual circumstances vary.
What should I do if I miss a dose?
Take it as soon as you remember, but if it’s almost time for the next dose, skip the missed dose. Don’t double dose.
Can I drink alcohol while taking cephalexin?
Moderate alcohol is generally acceptable, though alcohol can worsen some side effects and impair immune function.
Conclusion: Validity of Cephalexin Use in Clinical Practice
Cephalexin remains a valuable tool in our antimicrobial arsenal, particularly for straightforward outpatient infections caused by susceptible organisms. The benefits of oral administration, established safety profile, and cost-effectiveness must be balanced against rising resistance patterns and spectrum limitations.
I’ve been using cephalexin since my residency in the early 90s, and what’s remarkable is how it’s held up despite the antibiotic resistance crisis. We just need to be smarter about when we use it—not as empirical therapy for everything, but as targeted treatment based on culture results or high-probability clinical scenarios.
The longitudinal follow-up on some of my long-term patients tells an interesting story. Margaret, now 82, has received probably two dozen courses over the years for recurrent UTIs—still works for her E. coli strains, though we culture every time now. Contrast that with David, 45, whose recurrent staph folliculitis eventually required switching to doxycycline as resistance emerged. The real-world evidence from decades of use confirms what the trials show—it’s reliable until it isn’t, and that’s why we need ongoing stewardship.
What surprised me early in my career was discovering that some treatment failures weren’t due to resistance but to pharmacokinetic issues—the obese patients who needed higher doses, the elderly with unrecognized renal impairment getting toxic levels. We had this one case where a 75-year-old with moderate CKD developed encephalopathy on “standard” dosing—taught me to always calculate CrCl in older adults. The lab and pharmacy teams helped us develop a dosing protocol that reduced these events significantly.
The development wasn’t smooth either—I remember the debates we had in the 2000s when MRSA became prevalent in the community. Some wanted to abandon cephalexin entirely, while others argued for its continued role for non-MRSA infections. We settled on a middle path—using it when pretest probability for MRSA was low, or after culture confirmation. That pragmatic approach has served our patients well, avoiding both overuse of broader agents and undertreatment with ineffective ones.
Patient testimonials often mention the convenience compared to other options. “At least I don’t have to refrigerate it like the liquid amoxicillin,” one mother told me recently. Or the construction worker who said “I can take it with my lunch pail without worrying about the food effect.” These practical considerations matter in adherence.
So after all these years, I still reach for cephalexin several times a week, but with more precision than I did as a new attending. The evidence, both published and from my own experience, supports its continued role—just with better patient selection and more attention to the details that make the difference between success and failure.