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Table 2 Table summarizing the evidence on the efficacy of antimicrobial treatment in invasive non-typhoidal Salmonella infections

From: Invasive non-typhoidal Salmonella infections in sub-Saharan Africa: a systematic review on antimicrobial resistance and treatment

Study (first author, year of publication, study site, study period, study design) Population (age category, sample size, infection site, comorbidities) Therapy (antibiotic agent, dose, administration route, duration, control/comparison group) Outcome (in-hospital and post-discharge case fatality, fever clearance, microbiological clearance, recurrence, sequelae)
Chloramphenicol
 Aubry, 1992 [74], 1991, Burundi, retrospective cohort study Adults, n = 69, all BSI, HIV positivity in 86/103 (83%) Chloramphenicol Fever clearance in 72 h: 59/69 (85%)
 Molyneux, 2000 [43], Malawi, 1996–1999, prospective cohort study Children, n = 57, all meningitis, clinical suspicion of AIDS in 16% Chloramphenicol IV until defervescence and able to swallow, then PO and stop after 2–3 weeks oral treatment In-hospital case fatality: 28/57 (49%)
Post-discharge case fatality: 5/29 (17%)
Recurrences: 2/29 (7%)
 Graham, 2000 [81], Malawi, 1996–1998, retrospective cohort study Children, n = 248, all BSI, clinical suspicion of AIDS in 16% Chloramphenicol IV at least 5 days In-hospital case fatality: 59/248 (23.8%)
 Gordon, 2003 [76], Malawi, period not specified, prospective cohort study Adults, n = 100, all BSI, all HIV patients Chloramphenicol 2 g/day in 4 doses/day for 14 days In-hospital case fatality: 47/100 (47%)
Post-discharge case fatality: 5/19 (26%)
Recurrence: 19/44 (43%)
Cephalosporins
 De Carvalho, 1982 [82], setting and period not specified, prospective cohort study Children and adults, n = 11, all BSI Cefamandole IV/IM 60–240 mg/kg/day for 12 days (longer if persistent bacteremia) Persistent bacteremia after 12 days: 4/11 (36%)
 Soe, 1987 [83], the USA, period not specified, retrospective cohort study Children and adults, n = 12, 9 BSI, 2 meningitis, 1 focal infection, sickle cell disease in 1/12, AIDS in 1/12, leukemia in 1/12 Cefotaxime IV in 9/12 for 5–28 days
 Adults: 2–3 g/day in 3–6 doses/day
 Children: 100–200 mg/kg/day in 4 doses/day
Ceftizoxime IV in 1/12 for 19 days
Cefotaxime IV 2 days + change to ceftazidime IV 14 days in 1/12
Cefotaxime IV 2 days + change to cotrimoxazole PO 3 days in 1/12
In-hospital case fatality: 0/12 (0%)
Fever clearance: median 3 days (range 1–17 days)
Recurrences: 1/12 (8%)
 Lepage, 1990 [32], Rwanda, 1982–1987, retrospective cohort study Children, n = 246, 220 BSI, 12 meningitis, 13 focal infections, severe acute malnutrition in 23%, malaria in 11%, severe anemia in 10% Cefotaxime IV 100 mg/kg/day (200 mg/kg/day if meningitis) for 8 days to 6 weeks (depending on the infection site and severity)
Control group (n = 87/246): no cefotaxime because no cefotaxime available/death before blood culture results
In-hospital case fatality: 16/152 (11%)
Recurrence: 4% of NTS BSI
Fever clearance: mean 2.3 days (range 0.5–7.5 days)*
Control group: in-hospital case fatality 64/87 (74%)
 Wang, 1996 [84], Taiwan, 1990–1994, case series Adults (> 65 years), n = 12, all mycotic aneurysms Ceftriaxone (+ surgical intervention in 11/12 patients) for 23–40 days in survivors In-hospital case fatality: 6/12 (50%)
Recurrence: 0/6 (0%)
 Chiu, 2006 [85], Taiwan, 1999–2003, retrospective cohort study Children, n = 27, all BSI Ceftriaxone IV in 25/27; cefixime PO in 2/27 In-hospital case fatality: 1/27 (4%): a leukemic patient with spondylitis and splenic abscess treated with ceftriaxone
Fluoroquinolones
 Cheesbrough, 1991 [78], DR Congo, period not specified, prospective cohort study Children, n = 31, 29 BSI, 4 arthritis (including 2 with BSI) Ciprofloxacin PO 20 mg/kg/day in 2 doses/day In-hospital case fatality: 1/31 (3%)
Post-discharge case fatality: 0/30 (0%)
Microbiological clearance after 48–72 h: 0/30 (0%)
Recurrence: 0/30 (0%)
 Forrest, 2009 [86], USA, 2002–2006, retrospective cohort study Adults, n = 16, all BSI, all HIV patients Quinolones in 15/16 patients for 10–300 days (median 28 days) In-hospital case fatality: 1/15 (7%)
Recurrences: 4/15 (27%)
 Gordon, 2010 [79], Malawi, period not specified, prospective cohort study Adults, n = 70, all BSI, all HIV patients Ciprofloxacin PO 1 g/day, in 2 doses/day 10 days (started after NTS isolation from blood culture) Total case fatality after 1 month: 10/70 (14%)
Recurrence: 63/70 (90%)
Epidemiological comparison between regimens
 Molyneux, 2009 [80], Malawi, 1997–2006, retrospective cohort study Children, n = 105, all meningitis HIV positivity in 49/105 (47%) 1997–2001:
 Chloramphenicol IV 100 mg/kg/day in 4 doses/day for 14 days in 21/29
 Ceftriaxone IV 100 mg/kg/day in 2 doses/day for 10 days in 8/29
2002–2006:
 Ceftriaxone IV 100 mg/kg/day in 2 doses/day for 10 days (76/76) + ciprofloxacin PO 20 mg/kg/day in 2 doses/day for 14 days (76/76)
In-hospital case fatality:
 1997–2001: 14/29 (48.2%)
 2002–2006: 41/76 (53.9%)
Post-discharge case fatality:
 1997–2001: 3/29 (10.3%)
 2002–2006: 4/76 (5.3%)
Recurrences:
 1997–2001: 9/15 (60%), from which 7 HIV+
 2002–2006: 3/35 (8.6%), from which 1 HIV+
Sequelae:
 1997–2001: 11/12 (91.7%)
 2002–2006: 13/31 (41.9%)
Antimicrobial treatment duration
 Tsai, 2007 [87], Taiwan, 1996–2003, retrospective cohort study Children, n = 184, all BSI Group < 7 days:
 Median 5 days antimicrobial treatment
 Ceftriaxone/cefotaxime in 31/49, ampicillin in 16/49, other in 2/49
Group ≥ 7 days:
 Median 9.5 days antimicrobial treatment
 Ceftriaxone/cefotaxime in 121/135, ampicillin in 14/135
In-hospital case fatality: 0/184 (0%)
Post-discharge case fatality: 0/184 (0%)
Recurrences: 0/184 (0%)
Persistent bacteremia:
 Group < 7 days: 1/21 (5%)
 Group ≥ 7 days: 1/43 (2%)
Hess, 2019 [88], USA, 2007–2016, retrospective cohort study Children, n = 51, all BSI Initial treatment:
 Ceftriaxone/cefotaxime IV in 48/51, others in 3/51
Group < 7 days IV treatment:
 Median 4 days IV treatment
 Switch to amoxicillin, cotrimoxazole, third-generation cephalosporins or ciprofloxacin after < 7 days
Group ≥ 7 days IV treatment:
 Median 9 days IV treatment
 Switch to amoxicillin, cotrimoxazole, third-generation cephalosporins or ciprofloxacin after ≥ 7 days or 10 days ceftriaxone/cefotaxime IV
Recurrences: 30-day readmission / emergency visit:
 Group < 7 days IV treatment: 0/32 (0%)
 Group ≥ 7 days IV treatment: 1/19 (5%)
Persistent bacteremia:
 Group < 7 days IV treatment: 7/32 (53%)
 Group ≥ 7 days IV treatment: 9/19 (47%)
  1. BSI bloodstream infection, PO per os, IV intravenous, h hours
  2. *One study was a study on a subgroup [77] from another included study [32]. As data on fever clearance were only reported in the subgroup study [77], the fever clearance data were taken into account and the other data from the subgroup study were disregarded