antibiotic change IV Oral IV IV Oral IV IV IVOST 24 hours IV IVOST 24 hours 72 hours 72 hours IVOST IVOST IV IV Oral IVOST 72 hours NA NA 72 hours

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1 Online Resource 4: Study interventions and definitions Location(s) Randomised Controlled Trials Brack et al, 2012 [1] Cagol et al, 2009[2] Gupta et al, 2009[3] Mullen et al, 1999[4] Orme et al, 2014[5] Paganini et al, 2003 [6] Paganini et al, 2001 [7] Paganini et al, 2000 [8] Petrilli et al, 2000 [9] Santolaya et al, 2004 [10] Shenep et al, 2001 [11] Varan et al, 2005[12] Timing of discharge 9-24 hours 3-16hours 3-16 hours 4 hours 48 hours 48 hours Route(s) OST OST OST OST OST OST OST OST OST Timing of antibiotic change 24 hours 24 hours Antibiotics Risk Tool Fever definition ciprofloxacin + amoxicillin not given ciprofloxacin, co-amoxiclav +oral/ placebos cefipime + oral placebo ofloxacin-clavulanate ceftriaxone ceftazidime ceftriaxone cefipime cefipime ceftriaxone + amikacin, then ciprofloxacin ceftriaxone + amikacin ceftriaxone+ amikacin, then ciprofloxacin ceftriaxone + amikacin, then cefixime ceftriaxone + amikacin, then cefixime ceftriaxone + amikacin ceftriaxone ciprofloxacin ceftrixone + teicoplanin, then cefuroxime ceftrixone +teicoplanin, then cefuroxime 48 hours vancomycin + tobramycin/ticarcillin or ceftazidime, then cefixime vancomycin + tobramycin/ticarcillin or ceftazidime 48 hours 48 hours cefepime then cefixime cefepime then ciprofloxacin + co-amoxiclav Less Less Neutropenia definition Low-grade Compound <1.0 x10 9 /L or Compound Compound <0.5 x10 9 /L or <0.5 x10 9 /L or or Low-grade <0.5 x10 9 /L or Compound Not given Not given Not given

2 Prospective Observational cohorts Abbas et al, 2003 [13] Less Compound < ceftriaxone +amikacin x10 9 /L Aquino et al, 2000[14] ciprofloxacin Bash et al, 1994 then Group A [15] 48 hours stop 48 hours ceftazidime, then oral abx if indicated Bash et al, 1994 then Group B[15] 48 hours stop 48 hours ceftazidime, then oral abx if indicated Dommett et al, 2009 piperacillin/tazobactam + gentamycin, then Compound <1.0 x10 9 /L Group A [16] 48 hours OST 48 hours co-amoxiclav Dommett et al, 2009 piperacillin/tazobactam + gentamycin, then Compound <1.0 x10 9 /L Group B [16] 48 hours OST 48 hours co-amoxiclav Doyle et al, 1996 [17] regime not given, then cefixime and >38 C Not given 24 hours OST 24 hours flucloxacillin Fernandez et al, 2012 [18] Not given Not given 48 hours OST 48 hours Not given Kaplinsky et al, 1994 [19] Less ceftriaxone Karthaus et al, 2000 [20] Less 38.5 C <0.5 x10 9 /L or ceftriaxone Klaassen et al, 2000 piperacillin + gentamycin then cloxacillin + Group A [21] 48 hours OST 48 hours cefixime Klaassen et al, 2000 then Group B [21] 48 hours stop 48 hours piperacillin + gentamycin, then placebo Lau et al, 1994 [22] 12 inpatient, 11 ticarcillin + gentamycin, then cefixime + Not given? Not given outpatient OST cloxacillin Malik, 1997[23] Less or ofloxacin Miedema et al, 2012 [24] Less? Not given 12 hours Nil Mustafa et al, 1996 [25] Less? <0.5 x10 9 /L ceftriaxone Paganini et al, 2001[26] >38 C <0.5 x10 9 /L OST ceftriaxone + amikacin, then cefixime Paganini, 2000 [27] >38 C <0.5 x10 9 /L OST 24 hours ceftriaxone then ciprofloxacin Paganini, 2003 [28] 24 hours OST 24 hours ceftriaxone + amikacin, then cefixime or >38 C <0.5 x10 9 /L

3 ciprofloxacin Park et al, 2003 [29] 48 hours OST 48 hours ceftazidime then ciprofloxacin +amoxicillin Petrilli et al, 2007 [30] gatifloxacin Phillips et al, 2006 [31] piperacillin/tazobactam + tobramycin, then 48 hours OST 48 hours ciprofloxacin Preis et al, 1993 [32] ceftriaxone Quezada et al, 2007 [33] 24 hours OST 24 hours cefepime then ciprofloxacin + azithromycin Sari et al, 2007 [34] cefepime or cefaperazone/sulbactam then Mostly inpatient OST 48 hours co-amoxiclav + ciprofloxacin Shrestha et al, 2009 [35] ofloxacin/amoxy-clav Tordecilla et al, 1998 [36] 96 hours OST 96 hours cloxacillin, amikacin, cefoperazone Wiernikowski et al, 1991 [37] 48 hours multiple Key: - Intravenous, OST Intravenous to Switch of Therapy, not applicable,? - definition unclear or not given, Compound <0.2 x10 9 /L Low-grade <0.5 x10 9 /L or Compound Not given Compound <1.0 x10 9 /L >38.5 C <1.0 x10 9 /L or Not given Not given Not given Compound < x10 9 /L? Not given

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