To the Editor: Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) is usually susceptible to a wider range of antibiotics than nosocomial or multiresistant MRSA, but evidence is lacking to guide antibiotic choices.

Rifampicin plus fusidic acid is commonly used in multiresistant MRSA infection, and familiarity makes this combination attractive for CA-MRSA. We report two cases of CA-MRSA infection in which rifampicin resistance developed during treatment. Non-compliance may have been a significant factor, but high bacterial load and persistent foci of infection were also likely contributors. We caution against using regimens containing rifampicin in such cases.

Patient 1: A previously well 16-year-old girl presented with a 4-day history of left knee pain. She had fever and a moderate joint effusion. Plain x-rays were unremarkable, and blood cultures showed no growth. An aspirate of the knee joint had a white blood cell count of 1100 × 106 cells/L, but showed no growth on culture. Non-multiresistant MRSA (sensitive to all non-β-lactams) was subsequently grown from a synovial biopsy specimen. She was treated with 7 weeks of intravenous vancomycin, followed by 6 months of oral rifampicin (450 mg daily) plus fusidic acid (500 mg twice daily). Her compliance was uncertain, and she did not return for follow-up appointments.

The patient presented again 12 months later with increasing pain in the left knee and thigh. X-ray and magnetic resonance imaging revealed extensive osteomyelitis of the distal femur. Culture of purulent material removed at sequestrectomy grew MRSA with the same sensitivity profile as previously, but now resistant to rifampicin. She was treated with clindamycin, but required further sequestrectomy. She continues to take clindamycin long term.

Patient 2: A 74-year-old man developed severe cellulitis and an abscess of his left hand after a golfing injury. He had bacteraemia with non-multiresistant MRSA (sensitive to all non-β-lactams). He also had significant pain in his left prosthetic hip. After 7 weeks of intravenous vancomycin and oral moxifloxacin, levels of inflammatory markers remained high. He was treated with oral rifampicin (600 mg daily) plus fusidic acid (500 mg twice daily) for several weeks until lost to follow-up.

Four months later, the patient still had pain in the hip, and rifampicin plus fusidic acid treatment was begun again. After 3 months with no improvement, he underwent surgical exploration, and the loose femoral prosthesis was replaced. Culture of debrided material showed MRSA with the same sensitivity pattern as previously, but now resistant to rifampicin. He was treated with intravenous vancomycin for 6 weeks, followed by trimethoprim–sulfamethoxazole, which was later changed to clindamycin because of intolerance. He remains taking indefinite clindamycin suppression therapy.

Traditional oral therapy for MRSA infection is rifampicin plus fusidic acid, but alternative oral agents for non-multiresistant CA-MRSA include clindamycin,1 tetracyclines2 and trimethoprim–sulfamethoxazole.3 There is wider experience with clindamycin, which penetrates well into skin and soft tissues, has good oral bioavailability, and has been used successfully.1 However, a concern is erythromycin-inducible clindamycin resistance, which may lead to clindamycin failure, particularly in severe infections.4 Its prevalence varies.

Studies in vitro have shown that rifampicin resistance develops as readily in CA-MRSA as in nosocomial MRSA,5 through a single-step mutation. Resistance did not develop in vitro to clindamycin,5 suggesting it may be a more reliable alternative in situations where compliance is uncertain, the bacterial load is high, or the source (eg, an infected prosthesis) cannot be removed. Further in-vitro and in-vivo investigations are urgently required to determine the optimal drug therapy for CA-MRSA infections.