Table 2.
Table summarizing the evidence on the efficacy of antimicrobial treatment in invasive non-typhoidal Salmonella infections
| 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%) |
BSI bloodstream infection, PO per os, IV intravenous, h hours
*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