IMP-1 metallo-β-lactamase-producing Pseudomonas aeruginosa in a university hospital in the People's Republic of China

Sir, We have noted with interest the points made by Frippiat et al. and make the following comments. We have not stated that the newer quinolones should not be considered for treatment of Gram-positive bone and joint infections. We agree that this group of antibiotics offers an attractive alternative to standard parenteral therapy because of their potency against Gram-positive pathogens and good bioavailability, but caution that the safety of the newer quinolones in long-term use is not yet established. There is a lack of clinical experience and data regarding long-term outcome with these agents treating chronic infections in man, compared with older fluoroquinolones. Quinolone resistance is increasing; the development of resistance to the new fluoroquinolones in Gram-positive organisms has been reported in a pharmacodynamic study, and Frippiat et al. also refer to a clinical case where resistance developed in one of seven of their patients treated for Grampositive prosthetic joint infection. In agreement with Frippiat et al., our advice to clinicians is that until there are more clinical data available, the addition of a second antibiotic (often rifampicin) should be considered when using a quinolone to treat deep infection, over a prolonged duration. The optimum dose of rifampicin for use as a second agent in treatment of orthopaedic infection has not been identified, although bone penetration studies have suggested that 600 mg twice daily will give optimal bone concentrations when compared with 300 mg twice daily or 600 mg daily. We usually recommend a dose between 300–600 mg twice daily, depending on the size of the patient and the causal pathogen. This dose is comparable to the dose of 10–20 mg/kg/day suggested by Frippiat et al. Finally, we agree that whereas linezolid is an attractive option for oral treatment of MRSA and other multi-resistant Gram-positive infection, it is not recommended for use in chronic infection, such as osteomyelitis, due to the lack of safety data when used for >28 days. We have not yet encountered optic neuropathy in association with prolonged linezolid treatment, but have observed thrombocytopenia in some patients, a recognized side effect, and advise clinicians to monitor full blood count weekly when prescribing linezolid for both inpatients and outpatients. References