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Re: Fosfomycin for osteomyelitis?

Dear Editor

We were interested to read the recent article by Corti et al. examining the use of fosfomycin for infective osteomyelitis.[1]

Whilst fosfomycin has good gram-positive including anti- staphylococcal and gram-negative coverage it is only available in the intravenous preparation. Concern regarding the emergence of resistance means that in our hospital it is reserved for resistant / relapsing infections and always given in combination.

British readers should realise that fosfomycin is not routinely available in the UK and has to be specially imported. It was originally marketed in the UK as a once a day therapy for urinary tract infections but proved too expensive.

We feel that the title of the article and the conclusion are misleading as they imply that fosfomycin should be used as an alternative first line therapy in osteomyelitis. This is in comparison to the last paragraph of the discussion where it is stated that following this study their hospital policy for osteomyelitis therapy is intravenous flucloxacillin followed by oral clindamycin. We agree that flucloxacillin is a good choice as initial intravenous therapy but feel that it is also a good option for when intravenous is changed to oral therapy.

Which antibiotics are chosen depends on susceptibility of organisms, antibiotic penetration and ease of administration. The causative organisms and their relative frequencies are similar in this study to those we found in Newcastle between 1991 and 1999; Pathogens were identified in 26/63 (41%) children with osteomyelitis; Staphylococcus aureus 85%, Streptococcus pneumoniae 7.5% and Salmonella sp. 7.5%. It is because of this and other similar data that we would add an intravenous beta-lactam antibiotic into the initial empiric regime e.g. amoxycillin or cefuroxime. The relatively long intravenous courses used in this study (2.5 weeks in fosfomycin group) are disparate to our experience and that of a number of European centres in that short intravenous followed by relatively long oral antibiotics courses has many advantages and do not result in increased relapse rates.[2,3]

The final point is that this study is significantly underpowered to detect any difference between fosfomycin and the others therapies (failure rate of 2/103 (2%)). Using the higher relapse rate from adult studies of approximately 15% [4,5] then to detect an arbitrary 10% improvement or worsening in outcomes / relapse rates with 80% certainty if two therapies are compared approximately 280 or 500 patients would need to be enrolled.[6] In conclusion whilst fosfomycin has good anti-microbial coverage we feel that in the UK its limited supply and the unavailability of an oral preparation mean that conventional beta-lactam antibiotics should remain the main stay of osteomyelitis therapy. We acknowledge that comprehensive evidence based guidelines for acute osteomyelitis therapies are lacking. We are at present developing best evidence guidelines for the British Paediatric Allergy Infection and Immunology Group (BPAIIG).

References

(1) Corti N, Sennhauser FH, Stauffer UG, Nadal D. Fosfomycin for the initial treatment of acute haematogenous osteomyelitis. Arch Dis Child 2003;88(6):512-6.

(2) Peltola H, Unkila-Kallio L, Kallio MJ. Simplified treatment of acute staphylococcal osteomyelitis of childhood. The Finnish Study Group. Pediatrics 1997;99(6):846-50.

(3) Davies EG, Elliman DAC, Hart CA, Nicoll A, Rudd PT. The Child with Bone or Joint Infection. Manual of Childhood Infections, 2nd Edition. London: WB Saunders, 2001:69-71.

(4) Pechere JC, Delisle R. Open study of ceftazidime in serious infections due to multiply- resistant bacteria. J Antimicrob Chemother 1983;12 Suppl A:181-8.

(5) Weinberg WG. Safety and efficacy of teicoplanin for bone and joint infections: results of a community-based trial. South Med J 1993;86(8):891-7.

(6) Altman DG. Clinical trials; Sample size. Practical Statistics for Medical Research. Chapman & Hall, 1991: 455-460.