In 2010, skin and soft tissue infections (SSTIs) accounted for approximately 4.2 million emergency department visits (1). With such a bread-and-butter emergency medicine encounter, one might not give a second thought as to whether the standard dosing is less than ideal. However, the nuance of appropriate pharmacokinetic dosing that drug references omit may be the more ideal approach. The most appropriate dosing regimen, based on pharmacokinetic parameters, may not be highlighted by tertiary drug resources (2).With a condition seen every day, we should be nailing the treatment. If we see it every day, we should be excellent at treating it, right?
Let’s start with the organisms likely to cause these infections. Generally, gram (+) streptococcal and staphylococcal species are our biggest offenders. For streptococcus, we can utilize first-generation cephalosporins or penicillins. Between 20-50% of SSTIs are secondary to community-acquired methicillin-resistant staphylococcus aureus (MRSA) (3). The Infectious Diseases Society of America guidelines offer insight for purulent and nonpurulent SSTIs, but does not specifically address the scenario of a purulent infection with cellulitis (4). For these patients we often prescribe two antibiotics, adding MRSA coverage with trimethoprim-sulfamethoxazole (Bactrim, TMP/SMX) or doxycycline based on local susceptibilities. In addition, recent literature comparing TMP/SMX to placebo for uncomplicated skin abscesses after drainage found significantly higher cure rates for those who received TMP/SMX (5). If there is concern for streptococcus, TMP/SMX has poor streptococcal coverage and an additional antimicrobial agent should be added, which is often cephalexin.
When prescribing cephalexin, we need to dose it appropriately. So, how do you dose cephalexin in an adult with normal renal function? If you went to a tertiary reference you might see something like the screenshots below.
All of these doses seem reasonable. To maximize adherence you might reach for the 500 mg every 12 hours, because who wants to take an antibiotic four times a day? Especially if also sending the patient home with TMP/SMX, the pill burden grows quickly to 6-8 daily depending on your TMP/SMX dose (see TMP/SMX dosing strategy on ALiEM).
Let’s review the pharmacokinetics and pharmacodynamics of cephalexin. As with all cephalosporins, cephalexin is a time-dependent antibiotic. In other words, this antibiotic needs to be dosed multiple times per day to ensure that the concentration does not fall below the minimum inhibitory concentration, or you risk resistance and insufficient antimicrobial killing (6).
“UpToDate said every 12 hours was okay so…”
To choose the appropriate frequency, we must look to the half-life. The half-life of cephalexin is between 0.5 and 1.5 hours for patients with normal renal function (6,7). In about 5 half-lives, or roughly 5 hours, this drug is almost entirely removed from the body. Therefore, every 12 hours dosing should never be an option for patients with normal renal function. Prescription costs can often be an issue and sending a patient out with two antibiotics may be less than ideal. This is often the burden patients face when providers prescribe cephalexin and TMP/SMX for SSTI outpatient therapy.
Trick of the Trade
For uncomplicated, adult cellulitis, administer a one-time intramuscular injection of Bicillin L-A (benzathine penicillin [PCN] G) at a dose of 1.2 million units in lieu of oral cephalexin every 6 hours to provide streptococcal coverage. Benzathine PCN G has an exceptionally long duration of action, more than sufficient to cover 7-10 days of treatment (8).
Anyone who has received an IM injection of benzathine PCN G will tell you the major drawback is pain, which can last several days. For some providers, this has been a deterrent for prescribing the drug unless it is absolutely indicated. Shared decision-making with the patient may be useful when discussing the advantages and disadvantages of an IM injection of benzathine PCN G.
Can we give this to every patient with some form of cellulitis? Of course not. Allergies must be thoroughly investigated and past medical history reviewed. Patients with diabetes, psoriasis, obesity (BMI > 32), elderly age, or lower extremity cellulitis with impaired venous drainage (varicose veins, deep-venous thrombosis, stasis dermatitis) are at risk for treatment failure with benzathine PCN G (9,10).
The IDSA guidelines recommend IM benzathine PCN G as an option for recurrent cellulitis prophylaxis and oral therapy for treatment of a mild cellulitis (3,8). One may consider use of benzathine PCN G for these mild cellulitis cases as a means to ensure 100% medication compliance.
For a patient that would have been prescribed cephalexin and TMP/SMX for their SSTI, consider simplifying their regimen with a one-time benzathine PCN G IM injection and a single prescription for TMP/SMX.
Note: Bicillin L-A is currently on backorder due to manufacturing delays and expected to resolve by July 2016 as of 5/11/2016 (FDA Drug Shortages).
Grace Benanti, PharmD (@gracebenanti)
Pharmacy Practice Resident (PGY1)
Banner – University Medical Center Phoenix
Mark Culver, PharmD, BCPS (@EMdruggist)
Emergency Medicine Pharmacist
Banner – University Medical Center Phoenix
1. Prusakowski MK, Kuehl DR. Trends in emergency department management of skin abscesses. Am J Infect Control. 2015;43(4):336-40.
2. Randhawa AS, Babalola O, Henney Z, et al. A Collaborative Assessment Among 11 Pharmaceutical Companies of Misinformation in Commonly Used Online Drug Information Compendia. Ann Pharmacother. 2016;50(5):352-9.
3.Wackett A, Nazdryn A, Spitzer E, Singer AJ. MRSA rates and antibiotic susceptibilities from skin and soft tissue cultures in a suburban ED. J Emerg Med. 2012;43(4):754-7.
4. Stevens DL, Bisno AL, Chambers HF, et al: Practice guidelines for the diagnosis and management of skin and soft tissue infections: 2014 update by the infectious diseases society of america. Clin Infect Dis 2014; 59(2):e10-e52.
5. Talan DA, Mower WR, Krishnadasan A, et al. Trimethoprim-Sulfamethoxazole versus placebo for uncomplicated skin abscess. N Engl J Med. 2016;374(9):823-32.
6. Keflex (cephalexin) capsules [prescribing information]. Florham Park, NJ: Shionogi; October 2015.
7. Bergan T. Pharmacokinetic properties of cephalosporins. Drugs 1987; 34 (Suppl 2):89-104.
8. Bicillin L-A suspension for IM injection (penicillin G benzathine injectable suspension) [prescribing information]. Bristol, TN: King Pharmaceuticals; 2006.
9. Wang JH, Liu YC, Cheng DL, et al. Role of benzathine penicillin G in prophylaxis for recurrent streptococcal cellulitis of the lower legs. Clin Infect Dis. 1997;25(3):685-9.
10. Karppelin M, Siljander T, Huhtala H, et al. Recurrent cellulitis with benzathine penicillin prophylaxis is associated with diabetes and psoriasis. Eur J Clin Microbiol Infect Dis. 2013;32(3):369-72.