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by PID teams. This is becoming increasingly available and is patients’ preference: staying under hospital IV care but being at home. Nevertheless, one should keep in mind that prolonged IV therapy may be associated with catheter-associated © ESPID 2017 – Practice Guideline – Bone and Joint Infections page 18 complications. Moreover, oral therapy does not seem to be associated with a higher risk of treatment failure compared to prolonged intravenous therapy in children with BJI (90,123). 7.3 Antibiotic therapy 7.3.1 Empirical IV therapy Any empirical therapy should include coverage of S. aureus. When CA-MRSA prevalence is 10-15% or higher, this pathogen should be included in the choice of empiric antibiotic therapy. Local, up-to-date resistance patterns are required to decide the best initial empirical therapy (see Chapter 3 and Table 14). The clinical condition of the patient at presentation is also important: the level of severity may lower the threshold to initiate anti-MRSA therapy or other adjuvant measures. Table 9 – Empirical therapy preferences in different Europeans countries Country Author reported empirical therapy preferences Finland Clindamycin or 1st generation cephalosporin for 2-4 days IV, then the same doses orally. France 2 nd G cephasporins or amoxicillin-clavulanate. Cloxacilin in children over 5 years old. 3 rd G cephalosporins (cefotaxime) + gentamicin in children under 3 months of age. Greece Ceftriaxone or cefotaxime plus clindamycin (due to high risk of CA-MRSA BJI). In the very sick child with multifocal disease and/or lung involvement: ceftriaxone or cefotaxime plus vancomycin Netherlands No use of first generation cephalosporins (restricted to surgical prophylaxis). First choice is flucloxacillin; when risk factors present: 2 nd or 3rd generation cephalosporins. Spain 1 st and 2nd G cephalosporins (<= 2 years old). Cloxacillin in >= 5 years old. Few cases of CAMRSA to influence antibiotic resistance in the community. Well tolerated and given in 3 doses PO. United Kingdom Cefuroxime most commonly used <=5 years old Flucloxacillin high dose first line in children >= 6 years old. Ceftriaxone has been used successfully in some centres against S. aureus in BJI Other considerations regarding empirical therapy are: · Beta-lactams, such as 1st generation cephalosporins and cloxacillin or other antistaphylococcal penicillins, are the drugs of choice for good experience and tolerance (30,36,81,91,92). Clindamycin is also a suitable treatment, especially in settings with high rate of CA-MRSA (93). · Amoxicillin-clavulanate may be an option although no published data is available and has a higher reported rate of adverse events (91,92). · Antimicrobials with activity against Kingella should be considered in children < 5 years of age, especially in areas with high rates. 7.3.2 Treatment of MRSA or MSSA PVL-positive S. aureus Clindamycin can be used if CA-MRSA is a possible cause (93–96). Although some authors recommend caution in the case of bacteraemic patients (95), others have good experience with clindamycon in this situation (97). Endocarditis and deep venous thrombosis (DVT), as well as inducible macrolide-lincosamide-streptogramin (MLS) resistance, may be ruled out before treating children with CA-MRSA BJI with clindamycin (94). Some experts may consider if MRSA is sensitive to clindamycin treat with clindamycin ± rifampin. Clindamycin may be combined with a beta-lactam to cover MSSA until antibacterial sensitivity is available. © ESPID 2017 – Practice Guideline – Bone and Joint Infections page 19 In case of severe infection where CA-MRSA or clindamycin-resistance strains are a concern, vancomycin is recommended by the US guidelines (IDSA)(94) at high dose: 60 mg/kg/day qid – (no good data for trough levels in children and, in general, clinical outcome should be the most important outcome) (98). Nevertheless, there is not much evidence of the efficacy of vancomycin in BJI (99–101) and other antibiotic may be used (daptomaycin or linezolid), especially if no initial response or minimum inhibitory concentration (MIC) to vancomycin ³ 2 mcg/ml (94,101–104). Rifampin may be added to all three (101) but with little evidence. Other options may be quinolones or cotrimoxazole (little experience in children) (105) ± rifampin. In severe cases or special circumstances, adding a toxin inhibitor antibiotic such as clindamycin, rifampin (100), or linezolid (106), may be considered (107). Although data are sparse (101,108), this strategy is considered for adults in IDSA guidelines (94), and in children and adults with PVL S. aureus in British guidelines (109). In case of MSSA PVL+ infections, treatment with first generation cephalosporins or anti-staphylococcal penicillins (ASP) plus clindamycin might be suitable. Nevertheless, in most situations the clinicians do not have the PVL results to guide the therapy of BJI and it may need to be a test that is specifically requested There are some reports and in vitro studies of the use of IVIG on severe PVL + S. aureus BJI infections but there is not enough evidence to support its general use (110,111). It may be considered in severe infections suspected to be caused by MRSA or PVL + S. aureus. Table 10 – Initial empirical therapy and rate of methicillin-resistant S. aureus (MRSA) (beyond 3 months of age) Regional rate of MRSA - low/high at 10-15% Recommended initial empirical therapy* Low rate of MRSA
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