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or culture-negative infections · First or second generation cephalosporins · Alternatives: anti-staphylococcal penicillins or 3rd G cephalosporins$ High rate of MRSA · Clindamycin ± rifampin# ± anti-staphylococcal beta-lactam High rate of MRSA plus Severe infection without preliminary results or high-rate clindamycin resistance or in case of failure to respond to initial therapy · Vancomycin or teicoplanin ± rifampin# ± clindamycin · Alternative: daptomycin (112) or linezolid (MRSA-IDSA guidelines) (94) · Always consider adding a beta-lactam until MRSA is confirmed · IVIG may be added where toxin-mediated systemic symptoms (i.e., toxic shock syndrome) is suspected. Notes - * = Consider covering other agents such as Kingella, especially in children < 5 years of age. - $ = Much less experience with 3rd G cephalosporins in children and less in vitro activity than the other options, although some studies in adults showed appropriate clinical outcome (113). # = There is no evidence of rifampin benefit in otherwise healthy children with BJI. Table 11 – Empirical therapy by age Age Empirical IV antibiotic treatment* Up to 3 months old Cefazolin (or ASP) + gentamicin; (ASP + cefotaxime may be an alternative) (30,71) 3 months to 5 yrs old &Cefazolin or $ cefuroxime Clindamycin in regions of non-Kingella; Alternatives: # Amoxicillin-clavulanate or ampicillin-sulbactam (114) or $ ceftriaxone or % ASP 5 yrs and older IV ASP or cefazolin or clindamycin (high MRSA prevalence) When risk factors present (e.g., SCD): other options may be considered such as ceftriaxone (± ASP or clindamycin) © ESPID 2017 – Practice Guideline – Bone and Joint Infections page 20 Notes – * = High rate of MRSA, cover this by adding clindamycin (< 2 years of age) or clindamycin alone (above 2 years of age) – see specific section. – & = Under 2-5 years of age there may be risk of S. pneumoniae or H. influenzae type b BJI in unvaccinated children, thus 1st G cephalosporins may be suboptimal. – $ = Both cefuroxime and ceftriaxone have better coverage for S. pneumoniae and H. influenzae, but may be inferior to 1st G cephalosporins or ASP in S. aureus infections (115). There is experience with cefuroxime (Saavedra J, personal communication)(8) and ceftriaxone (some UK and Greece sites) – # = The amoxicillin-clavulanate PK/PD profile may be suitable for BJI (116). Furthermore, there is a broad experience in BJI in children and has an appropriate activity for MSSA. – % = Narrow spectrum ASP are not appropriate for treatment of K. kingae BJI (117). – ASP = anti-staphylococcal penicillins. SCD=sickle cell disease. MRSA = Methicillin-resistant S. aureus. 7.3.3 Targeted therapy Table 12 – Pathogens and antibiotic treatment (according to local resistance patterns) Pathogen Antibiotic considerations Staphylococcus aureus · ASP, 1st generation (G) cephalosporins (30,36) · Clindamycin – if sensitive MRSA isolated (it may also be used for MSSA) · Trimethoprim-sulfamethoxazole% – in clindamycin resistant cases; 99% of the MRSA strains are susceptible (105) Streptococcus pyogenes · Penicillin, ampicillin, or amoxicillin Streptococcus pneumoniae · Ampicillin, amoxicillin or 2 nd -3 rd G cephalosporins · In the very unusual situation of high beta-lactam resistance may use vancomycin, linezolid or levofloxacin Haemophilus influenza type b · 2 nd G cephasporins or amoxicillin-clavulanate (or ampicillin-sulbactam). · Some strains may be resistant to 2nd G cephalosporins and/or amoxicillinclavulanate: 3rd G cephalosporins may be used Kingella kingae · Sensitive to cephalosporins and penicillins (58) · Resistant to clindamycin, vancomycin, linezolid, daptomycin; ASP not optimum · Rarely produces beta-lactamases (118) Salmonella species · Ceftriaxone or cefotaxime · PO: amoxicillin or quinolones (119), according to sensitivity Escherichia coli and other enterobacteria · According to sensitivity – amoxicillin-clavulanate or 2 nd/ 3 rd G cephalosporins or others Pseudomonas aeruginosa · According to sensitivity – ciprofloxacin PO Neisseria gonorrhoeae · Ceftriaxone or cefotaxime (or PO third generation cephalosporins) Notes - Based on: Pääkkönen M, Peltola H. Bone and joint infections (27) - Resources, policies, and resistance patterns are different across countries and regions; consequently, scenarios may not be ‘pan-European’. Always sensitivity of the strain should be performed - Where p-OPAT is implemented, once/daily regimens such as ceftriaxone (high dose, >80 mg/kg/qd IV) have been found to be useful and effective. - % = There is experience with but little published information on TMP/SMX efficacy in the treatment of S. aureus OM/SA in children, especially as initial therapy (105); It may be combined with rifampin (108,120). - ASP = anti-staphylococcal penicillins. 7.3.4 Allergy In case of allergy to beta-lactams the options are: clindamycin, glycopeptides, quinolones, linezolid and cotrimoxazole. The best alternatives to cover the possibility of Kingella infection are cotrimoxazole and quinolones (levofloxacin may be superior to ciprofloxacin). Cotrimoxazole and quinolones may be suboptimal for S. pyogenes, although recent studies have indicated a better in vitro susceptibility to the former antibiotic (121,122). © ESPID 2017 – Practice Guideline –
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