Las Vegas — Oral doxycycline has been shown to be effective in treating community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA), according to clinical studies and experience, an expert says.

A new enteric-coated form of doxycycline causes fewer gastrointestinal side effects than non-enteric-coated doxycycline and should improve patient compliance, an important factor when treating skin infections, says James Q. Del Rosso, D.O., dermatology residency director, Valley Hospital Medical Center, Las Vegas.

A 15-year study performed in the San Diego area has shown a dramatic increase in CA-MRSA infections since 2002 (Crum NF, Lee RU, Thornton MS et al. Am J Med. 2006;119:943-951.)

"This study, furthermore, revealed that an increasing proportion of cases demonstrated intra-familial spread," Dr. Del Rosso tells Dermatology Times.

As one might expect, CA-MRSA often spreads between individuals in close environmental contact, such as athletes and prison inmates, who may share items such as towels.

However, Dr. Del Rosso says, "Sporadic and unexplained cases often occur as well."

Perhaps more importantly, he says CA-MRSA differs from other staphylococcal infections because colonization is not a necessary precursor, and hosts possess no consistently identifiable comorbidities that might predispose them to infection.

Experts commonly suggest nasal carriage provides a common source of infection, Dr. Del Rosso says, "but in recent community surveillance studies, the prevalence of nares colonization has been reported to be less than one percent (Graham PL, Lin SX, Larson EL. Ann Intern Med. 2006;144:318-325.) "

Carriage and other high inoculum colonization sites such as the perineum and axilla could nevertheless serve as transmission factors, he says.

"Researchers have proposed another explanation for the low rate of colonization observed in CA-MRSA infections. The ’hit-and-run’ theory claims that transmission can occur at the time of direct contact with an affected skin lesion," resulting in infection without colonization, Dr. Del Rosso says.

Fortunately, he says that most CA-MRSA infections are uncomplicated, and physicians can manage them with basic infection control practices (such as handwashing), incision and drainage of abscesses, if present, and administration of properly selected oral antibiotics.

For recurrent infection, Dr. Del Rosso says it's important to consider staphylococcal carriage. To break the cycle of carriage in the nares or other cutaneous locations, he recommends performing cultures to confirm carriage, followed by appropriate topical therapy, in an attempt to eradicate the CA-MRSA strain involved.

In particular, although few reports of CA-MRSA resistance to trimethoprim-sulfamethoxazole exist, this drug has been associated with uncommon, but serious, adverse cutaneous reactions such as toxic epidermal necrolysis.

Similarly, he says that although clindamycin offers high susceptibility rates in treating CA-MRSA, "Many erythromycin-resistant isolates may develop clindamycin resistance within days after starting treatment."

Additionally, Dr. Del Rosso emphasizes that the efficacy of oral clindamycin for treating CA-MRSA varies in different communities, depending on the local prevalence of inducible resistance.

CA-MRSA has proven to be fairly susceptible to treatment with rifampin, he says, although resistance to this drug can develop quickly if it is used as monotherapy.

Additionally, he says, "Rifampin is associated with many clinically significant drug interactions."

And while quinolone antibiotics also demonstrate activity against CA-MRSAin vitro, rapid resistance frequently develops in clinical practice. Thus, quinolones are not commonly recommended.

Conversely, he says, "Tetracycline antibiotics are good first-line choices for treating skin and soft-tissue infections caused by CA-MRSA," in part because they are effective against many strains of CA-MRSA.

Based on analysis of minimum inhibitory concentrations, doxycycline has been shown to be highly active against CA-MRSA, and it offers a favorable safety profile.

As such, he says it's a good choice for use while awaiting results of bacterial sensitivity testing.

In one retrospective cohort study that evaluated 276 patients who presented with 282 episodes of cutaneous CA-MRSA infections, these infections’ rate of susceptibility to extended-spectrum tetracyclines (doxycycline and minocycline) remained stable at 95 percent throughout the study (Ruhe JJ, Menon A. Antimicrob Agents Chemother. 2007 Sep;51(9):3298-3303.)

Extended-spectrum tetracyclines (including doxycycline), moreover, resolved cutaneous infections in 96 percent of patients in whom they were used, while the corresponding figure for patients given B-lactam monotherapy was 88 percent.

In a similar study involving adult patients with MRSA, doxycycline achieved a 92 percent response rate, versus a response rate of 73 percent among minocycline-treated patients (Ruhe JJ, Monson T., Bradsher RW, Menon A. Clin Infect Dis. 2005 May 15;40(10):1429-1434.)

Doxycycline's high success rates in the above studies notwithstanding, Dr. Del Rosso says that when treating individual patients, "It's important to obtain bacterial cultures with sensitivity testing, and to keep track of potential changes in antibiotic sensitivities over time in one's community and practice."

Additionally, he says that no matter how appropriately selected, antibiotic therapy will fail if patients don't adhere to their treatment regimen.

In this area, he says a doxycycline formulation that uses enteric-coated pellets (Doryx, Warner Chilcott) produces far fewer gastrointestinal side effects than do traditional doxycycline formulations, including both the hyclate and monohydrate salts.

In one randomized, double-blind study involving 98 patients, mean gastrointestinal symptoms scores among patients taking enteric-coated doxycycline hyclate (ECDH/Doryx) pellets were about half as high as scores for patients taking non-enteric-coated doxycycline hyclate for symptoms including nausea, vomiting, abdominal discomfort and decreased appetite (Berger RS. J Clin Pharmacol. 1988;28:367-370.)

Similarly, a 120-patient study found that patients taking ECDH reported adverse events on half as many days as did patients taking uncoated doxycycline monohydrate (Jarvinen A et al. Clin Drug Invest. 1995;10(6):323-327.)

Dr. Del Rosso says that, as with other tetracycline antibiotics, physicians must avoid doxycycline use in pregnant patients and children less than 8 years of age.

The typical recommended dose for treating cutaneous CA-MRSA infection with doxycycline is 200 mg per day, he says. DT

Disclosure: Dr. Del Rosso is a researcher, consultant and/or speaker for Allergan, Coria, Galderma, Graceway, Intendis, Medicis, Onset Therapeutics, OrthoNeutrogena, Pharmaderm, Quinnova, Ranbaxy, SkinMedica, Stiefel, Unilever and Warner Chilcott.