There is little high quality evidence on which to base the management of bone and joint infections in children. This pragmatic practice note aims to provide a consensus framework of best current practice prior to the availability of data from large national randomised controlled trials. For straightforward infection in previously normal children, recent trends suggest that shorter length of intravenous therapy with switch to oral treatment is acceptable, although this is not the case for the management of complex infections including those with multifocal disease, significant bone destruction, resistant or unusual pathogens, sepsis or in immunosuppressed children. Flowsheets for management based on the evidence reviewed are presented.

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Penciclovir (PCV) and acyclovir are acyclic guanine analogs which inhibit herpes simplex virus (HSV) DNA polymerase. Their 50% infective doses were 0.5 to 0.8 ,ug/ml for clinical isolates of HSV-1 and 1.3 to 2.2 ,ug/ml for HSV-2. Furthermore, HSV-infected cultures receiving 2-h pulses of PCV had 2-to 50-fold less HSV than acyclovir-treated cultures, consistent with the prolonged intracellular half-life of PCV triphosphate.Penciclovir [PCV; 9-(4-hydroxy-3-hydroxymethylbut-1-yl) guanine] is an acyclic guanine derivative with potent activity against herpes simplex viruses type 1 (HSV-1) and 2 (HSV-2), varicella-zoster virus, and Epstein-Barr virus (3). PCV is similar to acyclovir (ACV) in structure, metabolism, and antiviral spectrum. PCV, like ACV, is phosphorylated by a virus-specific thymidine kinase. PCV monophosphate is then phosphorylated by host enzymes to PCV triphosphate, which is a selective inhibitor of viral DNA synthesis. PCV triphosphate has an intracellular half-life of 10 h, which is 14 times longer than that of ACV triphosphate (5), resulting in antiviral activity persisting after the extracellular concentrations drop to low levels. In contrast, intracellular ACV triphosphate is rapidly metabolized to the acyclonucleoside which diffuses out of the cell. PCV triphosphate also achieves higher intracellular concentrations than ACV. The consequences of this difference were demonstrated by experiments showing that PCV reduced HSV yield with shorter periods of in vitro treatment than were required with ACV for the same effect (2). In addition, after removal of PCV from the medium, HSV replication remained inhibited for several days, whereas HSV replication resumed shortly after removing ACV. The persistence of PCV antiviral activity was confirmed by effectively treating HSV-infected mice with single daily doses of PCV (1).We compared PCV with ACV for in vitro activity against additional clinical isolates of HSV-1 and HSV-2 and following intermittent or continuous exposure at concentrations close to their 50% in vitro inhibitory concentrations (ID50s) for HSV.Sensitivity of HSV clinical isolates to ACV and PCV. Twenty clinical isolates each of HSV-1 and HSV-2 from our clinical laboratory were grown and assayed by plaque titration in human embryonic lung fibroblast (HEL) tissue culture. ID50s of the clinical isolates were determined by both plaque reduction assay (PRA) and enzyme-linked immunoassay (EIA) as previously described (4). The mean + standard deviation ID50 values of ACV for HSV-1 isolates * Corresponding author.were 0.5 ± 0.4 ,ug/ml by PRA and 0.7 ± 0.5 ,Lg/ml by EIA (Fig. 1). This was very similar to the sensitivity determined for PCV: 0.6 ± 0.4 ,ug/ml and 0.8 ± 0.3 ,ug/ml, by PRA and EIA, respectively. One HSV-1 isolate had intermediate sensitivity to ACV (ID50 of 2.2 ,ug/ml) and was sensitive to PCV (0.9 ,ug/ml). All others were sensitive to both drugs.

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