Alternatives in the face of antibiotic resistance

In the United States, an estimated 95 million people are nasal carriers of S aureus ; of these, 2.6% or 2.5 million people carry the methicillin-resistant organism. A study in 2004 found the incidence of community-acquired MRSA to be between 15% and 75% in 11 university-associated emergency departments. Although not all acquisitions of MRSA are associated with the development of disease, it is imperative that when physicians encounter a skin and soft tissue infection, (SSTI) they should be aware of the rates of MRSA in their communities in addition to the risk factors present in each patient so that appropriate therapy may be initiated promptly. Risk factors for community-acquired MRSA include close physical contact, poor hygiene, shared sanitary facilities, and living in crowded conditions (eg, military recruits and prisons).

Currently, oral agents used to treat MRSA-associated infections include clindamycin, trimethoprim-sulfamethoxazole, tetracyclines, and, less commonly, linezolid; topical mupirocin has also shown efficacy. Of these, a linezolid-resistant strain of MRSA has already been documented in a hospital setting in Spain. As such, the search for effective and well-tolerated agents is ongoing; one commonly overlooked agent is gentian violet (GV). GV has a varied and lengthy history as a medicinal agent. Both bacteriostatic and bacteriocidal, GV’s utility in antisepsis and thrush and as an antitreponemal agent are well documented ; its first mention in the literature dates back to 1912. Hinton administered GV intravenously to patients with severe sepsis and showed notable efficacy. Once quite commonplace, GV has since fallen out of favor in recent decades due in part to its cosmetic appearance as well as the concurrent increase of antibiotic use; it is of no coincidence that the last major human intervention trial with GV was in 1950, approximately 5 years after the development of mass production techniques for penicillin. Nevertheless, the utility of GV in a variety of infectious settings is well known to generations of physicians and mothers.

More pressingly, GV is active against MRSA in vitro ; its clinical utility was first demonstrated in a series of 14 patients with decubitus ulcers. Saji and colleagues applied a 0.1% ointment of GV to the affected areas after patients had bathed in 0.1% solutions of GV. The average time to eradication of MRSA was 10.8 days (±2.7), while no patients experienced any appreciable side effects. Recently, Okano and colleagues demonstrated the efficacy of GV in a broad range of MRSA SSTI and clearance of nasal carriage. In the 8 cases of impetigo, the mean time to eradication was 6.8 days (±3.7, range 4–15) and the in vitro minimum inhibitory concentration) of GV was 0.0225 μg/mL. The agent was well tolerated in all 37 patients, with no significant side effects being reported.

In the setting of secondary skin infections, the authors’ group has recently reported a case in a patient with impetiginized eczema unresponsive to conventional therapy who showed dramatic clinical and symptomatic improvement with a combination of oral doxycycline and daily applications of GV. This result builds on the work of Brockow and colleagues who previously demonstrated the efficacy of GV alone in clearing S aureus from colonized lesions of atopic eczema. A 0.3% solution of GV was applied twice daily to lesional and nonlesional skin for 4 days and, compared with topical steroids and tar preparations, was the only agent to immediately reduce bacterial density at both sites ( P <.001). GV not only helped clearing bacterial presence but also significantly reduced eczema severity.

Several hypotheses have been proposed to explain the bacteriostatic and bacteriocidal properties of GV, but the exact mechanisms remain unknown. Nonetheless, given its low cost (US $0.08 per mL of a 2% solution), ease of application, and clinical efficacy, GV must be considered as a legitimate treatment option in SSTI, particularly in the face of continued and emerging bacterial resistance.