Cephalexin

Cephalexin is a beta-lactam antibiotic and one of the first-generation cephalosporins, a group closely related to the penicillins ^[1][2]. Its molecular formula is C16H17N3O4S, giving a molar mass of about 347 grams per mole ^[1]. The drug is taken orally and is valued for being absorbed thoroughly from the gut, which makes it a convenient oral treatment for infections that do not require injectable antibiotics ^[2].

Cephalexin is most active against gram-positive bacteria, including streptococci and methicillin-susceptible staphylococci, and it also covers some gram-negative organisms ^[1][2]. It has no useful activity against methicillin-resistant Staphylococcus aureus, most enterococci, or Pseudomonas species ^[1]. In practice it is used for skin and soft-tissue infections, streptococcal pharyngitis, middle-ear infections, bone infections, respiratory infections, and urinary tract infections, and it can serve as prophylaxis against recurrent urinary infections or, in some situations, bacterial endocarditis ^[1][2]. For urinary tract infections it is generally regarded as a second-line oral option, useful when first-choice agents are unsuitable ^[4].

After an oral dose cephalexin is absorbed rapidly and almost completely, chiefly from the upper small intestine rather than the stomach, reaching peak blood levels in about an hour ^[2]. It binds only weakly to plasma proteins, is not appreciably broken down in the body, and is cleared quickly by the kidneys, with the great majority of a dose recovered unchanged in the urine within several hours ^[2]. Because of this rapid renal clearance the drug has a short half-life, and doses are spaced through the day; people with significantly reduced kidney function need smaller or less frequent doses ^[2].

Cephalexin was developed in the late 1960s and first went on sale in 1969 as Keflex, from Eli Lilly ^[1]. It has long since become a low-cost generic and is one of the more frequently prescribed antibiotics ^[1]. The World Health Organization includes it on its Model List of Essential Medicines ^[1]. It is supplied in oral forms such as capsules, tablets, and powder for suspension, and it is generally considered acceptable for use during pregnancy ^[1][3].

Cephalexin is prescription only. Most people tolerate it well; the usual complaints are stomach upset, diarrhea, and the occasional rash. Because it carries the beta-lactam ring found in penicillin, anyone with a serious penicillin allergy should be careful, since cross-reactivity is possible though uncommon. Rare but serious problems include Clostridioides difficile colitis, severe skin reactions, and anaphylaxis. It can throw off some urine and blood tests, and probenecid raises cephalexin levels by slowing its exit through the kidneys. The dose should be lowered when kidney function is significantly reduced.

Probenecid significantly increases cephalexin blood levels and area under the curve by inhibiting renal tubular secretion via organic anion transporters, particularly OAT1 and OAT3 ^[6]. This is a pharmacokinetic interaction; probenecid changes how the kidney handles cephalexin, not the drug's metabolism or absorption. In rats, probenecid increases cephalexin AUC by approximately 75 percent (from 68.1 to 117 microg.h/mL), and this effect is reproducible across cephalosporins including cefadroxil and cefdinir ^{[7] [8]}. The clinical consequence is prolonged antibiotic exposure and potentially increased risk of adverse effects; however, this interaction is also sometimes exploited to extend the dosing interval of cephalosporins.

Cephalexin does not inhibit CYP enzymes or induce metabolism of other drugs; the transport interaction is one-directional (probenecid changes cephalexin clearance, not vice versa). What remains unstudied: the interaction with other uricosuric agents that affect OAT transporters, with NSAIDs (which may compete for the same transporters), the clinical significance of the AUC increase in patients with normal renal function, and whether this interaction matters in modern dosing regimens where higher cephalexin doses are standard.

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Cephalexin, also spelled cefalexin, is a semisynthetic first-generation cephalosporin developed by Eli Lilly and Company and first marketed around 1969 and 1970 under the brand name Keflex. It was among the earliest orally active cephalosporins, arriving at a time when the class was largely confined to injectable use, and its good absorption from the gut made it a convenient treatment for common community infections.

The molecule descends chemically from the cephalosporin nucleus originally derived from the fungus Acremonium, work that grew out of Giuseppe Brotzu's mid-twentieth-century discovery of naturally antibacterial compounds. Over more than half a century it has become inexpensive, ubiquitous as a generic, and a familiar first choice for skin infections, streptococcal pharyngitis, ear infections, and urinary tract infections. It is listed on the World Health Organization Model List of Essential Medicines and remains one of the most frequently prescribed oral antibiotics.

Cephalexin is regarded as a reliable, affordable, and well-tolerated workhorse antibiotic, especially trusted for gram-positive infections of the skin and soft tissue. Its long track record, predictable safety profile, and low cost keep it a first-line agent decades after its introduction, and digestive upset is generally the most common complaint. Prescribers appreciate that much of the drug is excreted unchanged into the urine, which supports its use in uncomplicated urinary tract infections.

Modern reappraisal through pharmacokinetic and pharmacodynamic analysis, along with updated susceptibility testing, has in some cases reclassified organisms from resistant to susceptible, reaffirming its usefulness as a fluoroquinolone-sparing option in an era of growing resistance. Its recognized limits, such as inactivity against methicillin-resistant staphylococci and Pseudomonas, are well understood and shape its appropriate use.