Table 3.
Adverse associated with oral use of fosfomycin in individual trials
| References | Trial type | FOM N |
Indication Study population |
FOM dosing regimen Duration of follow-up after the start of therapy |
FOM total dose | COMP N Regimen |
FOM AE No of events (%) |
COMP AE n (%) |
|---|---|---|---|---|---|---|---|---|
| Stein et al. [59] | Prospective randomized controlleda | N = 375 |
Uncomplicated UTI F ≥12 years |
PO 3 g once Follow-up 4-6 weeks |
3 g |
N = 374 Nitrofurantoin × 7 days |
20 (5.3%) GI disorders 12 (3%)b Vaginitis 7 (1.8%) |
21 (5.6%) GI disorders 9 (2%) Vaginitis 6 (1.6%) Dizziness 3 (0.8%) |
| Lista et al. [57] | Prospective randomized controlled | N = 359 | Prophylaxis in transrectal prostate biopsy |
PO 3 g twice 48 h apart Follow-up 3 months |
6 g |
N = 312 Ciprofloxacin × 5 days |
GI disorders 10 (2.8%) |
GI disorders 9 (2.9%) Anaphylaxis 1 (0.3%) |
| Periti et al. [58] | Prospective randomized controlled | N = 256 | Prophylaxis in transurethral prostatic surgery |
PO 3 g twice 27 h apart (before and after surgery) Follow-up 2 weeks |
6 g |
N = 419 Amoxicillin n = 207 3 g × 2 q 24 h CTX n = 212 1.92 g × 2 q 24 h |
12/256 (5%) GI disorders 8 (3%) Allergy 4 (1.5%) |
33 (8%) Amoxicillin 17/207 (8%) GI disorders—15 (7%) Allergy—2 (2%) CTX 16/212/(7.5%) all GI disorders |
| Naber et al. [35] | Prospective randomized controlled | N = 250 |
Uncomplicated UTI F 18–75 years |
PO 3 g once Follow-up 4 weeks |
3 g |
N = 246 Ofloxacin n = 119 CTX n = 127 |
17 (6.8%) GI disorders—16 (6.4%) Rash—1 (0.4%) |
17 (6.9%) Ofloxacin 7 (5.9%), all GI disorders CTX 10 (7.9%); GI disorders—8 (6%) Headache—1 Exanthema—1 |
| Rudenko and Dorofeyev [33] | Prospective randomized controlled | N = 166 |
Prophylaxis of recurrent uncomplicated UTI F 25–63 years |
PO 3 g every 10 days × 6 months Follow-up 360 days |
54 g |
N = 151 Placebo |
2 (1%) Dyspnea—1 (0.6%) Rash—1 (0.6%) |
4 (2.6%) Rash—1 (0.7%) GI disorders—1 (0.7%) Cough—1 (0.7%) Joint pain—1(0.7%) |
| Van Pienbroek et al. [47] | Prospective randomized controlled | N = 113 |
Uncomplicated UTI F >18 years |
PO 3 g once Follow-up 6 weeks |
3 g |
N = 114 Nitrofurantoin × 7 days |
65 (58%) GI disorders—47 (42%) CNS—8 (7%) Urogenital—4 (3%) Skin—2 (2%) Other—4 (3%) |
37 (32%) GI disorders—24 (21%) CNS—7 (6%) Skin—1 (1%) Other—5 (4)% |
| Neu [71] | Prospective randomized controlled | N = 80 |
Uncomplicated UTI F 18–65 years |
PO 3 g once Follow-up 16–32 days |
3 g |
N = 78 Amoxicillin 3 g once |
GI disorders 7 (9%) |
9 (11.5%) GI disorders—8 (10%) Rash—1 (1%) |
| Boerema and Willems [37] | Prospective randomized controlled | N = 79 |
Uncomplicated UTI F 16–50 years of age |
PO 3 g once Follow-up 6 weeks |
3 g |
N = 79 Norfloxacin × 7 days |
16 (20%) GI disorders—14 (18%) Fatigue—1 (1.3%) Dizziness -1 (1.3%) |
2 (2.5%) GI disorders—2 (2.5%) |
| Ceran et al. [53] | Prospective randomized controlled | N = 77 |
Uncomplicated UTI F 18–65 years |
PO 3 g once Follow-up 60 days |
3 g |
N = 65 Ciprofloxacin × 5 days |
GI disorders—3 (3.9%) | GI disorders—2 (3.1%) |
| Costantini et al. [34] | Prospective randomized controlled | N = 76 |
Prophylaxis of recurrent UTI F 58 ± 16.7 years (age ± SD) |
PO 3 g weekly × 12 weeks Follow-up 12 months |
36 g |
N = 71 Prulifloxacin one tablet weekly × 12 weeks |
8 (10%) GI disorders—7 (9%) Vaginitis—1 (1.3%) |
5 (7%) GI disorders—2 (3%) Vaginitis—3(4%) |
| Cooper et al. [38] | Prospective randomized controlled | N = 72 |
Dysuria M and F 17–75 years |
PO 3 g once Follow-up 1 month |
3 g |
N = 69 Amoxicillin clavulanate × 5 days |
6 (8%) GI disorders—5 (7%) Rash—1 (1.4%) |
7 (10%) GI disorders—3 (4%) Vaginitis—3 (4%) Rash—1 (1.5%) |
| Elhanan et al. [48] | Prospective randomized controlled | N = 58 |
Uncomplicated UTI F >16 years |
PO 3 g once Follow-up 1 month |
3 g |
N = 54 Cephalexin × 5 days |
0 (0%) |
3 (5.5%) Vaginitis—3 |
| Selvaggi [39] | Prospective randomized controlled | N = 45 |
Uncomplicated UTI F 16–70 years |
PO 3 g once Follow-up 3 weeks |
3 g |
N = 44 Norfloxacin once |
0 (%) | 0 (%) |
| Crocchiolo [40] | Prospective randomized controlled | N = 38 |
Uncomplicated UTI F 16-70 years |
PO 3 g once Follow-up 30 days |
3 g |
N = 35 CTX × 3 days |
GI disorders—3 (8%) |
2 (6%) Rash—1 Asthenia—1 |
| De Jong et al. [46] | Prospective randomized controlled | N = 33 |
Uncomplicated UTI F >16 years |
PO 3 g once Follow-up 30 days |
3 g |
N = 30 Norfloxacin × 5 days |
9 (27%) GI disorders—8 (24%) Dizziness—1 (3%) |
8 (27%) GI disorders 5 (17%) Dizziness—1 (3%) Headache—1(3%) Hepatic function abnormal—1(3%) |
| Baert et al. [41] | Prospective randomized controlled | N = 31 |
Prevention of infection after prostate resection Males 48–83 years |
PO 3 g daily before and after procedure for a total of 2 doses Follow-up 1 month |
6 g |
N = 30 Placebo |
0 (%) | 0 (%) |
| Ferraro et al. [43] | Prospective randomized controlled | N = 30 |
Uncomplicated UTI F and M >50 years |
PO 3 g once Follow-up 35 days |
3 g |
N = 30 Norfloxacin 400 mg BID × 7 days |
GI disorders—1 (3%) | GI disorders—2 (7%) |
| Caramalli et al. [45] | Prospective randomized controlled | N = 20 |
Complicated and uncomplicated UTI M and F >60 years |
PO 3 g once Follow-up up to 18 months |
N = 76 Netilmicin 5 mg/kg IM once (n = 53) Amikacin 15 mg/kg IM once (n = 23) |
0 (%) | 0 (%) | |
| Reynaert et al. [42] | Prospective randomized controlled | N = 16 |
Uncomplicated UTI F 16–75 years |
PO 3 g once Follow-up 5 weeks |
3 g |
N = 16 Norfloxacin × 3 days |
GI disorders—1 (6%) | GI disorders—1 (6%) |
| Jardin [55] | Prospective comparative | N = 144 |
Uncomplicated UTI F 16–75 years |
PO 3 g once Follow-up 28 days |
3 g |
N = 144 Pipemidic acid |
37 (27%) Diarrhea—11 (8%) Other AE described as medium and slight and were not specified |
27 (19%) Nausea—16 (11%) Other AE described as medium and slight and were not specified |
| Children | ||||||||
| Principi et al. [44] | Prospective randomized controlled | N = 71 |
UTI F and M 1 month–16 years |
PO 2 g once (1 g in children <1 year) Follow-up 30 days |
2 g |
N = 64 Netilmicin 5 mg/kg IM once |
4 (6%) GI disorders—3 (4%) Rash—1 (1.5%) |
0(%) |
| Varese [50] | Prospective randomized controlled | N = 39 |
Uncomplicated UTI F and M 6 months–14 years |
PO 2 g once Follow-up 30 days |
2 g |
N = 35 Netilmicin 5 mg/kg IM once |
0 (0%) | 0 (0%) |
| Careddu et al. [49] | Prospective randomized controlled | N = 24 |
Recurrent UTI M (n = 2) and F (n = 22) 1–14 years |
PO 2 g once Follow-up for 1 month |
2 g |
N = 27 Pipemidic acid 400 or 800 mg (for children > 25 kg) daily × 7 days |
0 (0%) | 0 (0%) |
| Pregnancy | ||||||||
| Zinner [36] | Prospective randomized controlled | N = 153 |
Bacteriuria in pregnancy F 28 ± 5 years |
PO 3 g once Follow-up 30 days |
3 g |
N = 138 Pipemidic acid × 7 days |
14 (9%) Mainly GI disorders No fetal AEs |
20 (15%) Mainly GI disorders |
| Estebanez et al. [52] | Prospective randomized controlled | N = 53 | Asymptomatic bacteriuria in pregnancy |
PO 3 g once Follow-up 10–14 days, then until the end of pregnancy |
3 g |
N = 56 AC 500/125 mg × 7 days |
GI disorders—1 (2%) | GI disorders—11 (20%) |
| Bayrak et al. [51] | Prospective randomized controlled | N = 44 | Asymptomatic bacteriuria in the second trimester of pregnancy |
PO 3 g once Follow-up 1 week |
3 g |
N = 40 Cefuroxime axetyl 250 mg PO twice daily × 5 days |
Rash—1 (2%) | Vaginal candidiasis—2 (5%) |
| Usta et al. [54] | Prospective randomized controlled | N = 28 |
Uncomplicated UTI Pregnant F with a mean age of 26 years |
PO 3 g once Follow-up 2 weeks |
3 g |
N = 56 AC = 27 CA = 29 Both drugs × 5 days |
7 (25%) GI disorders—6 (24%) Vaginitis—1 (4%) |
20 (36%) GI disorders—14 (25%) Vaginitis—6 (11%) |
| Thoumsin et al. [56] | Prospective randomized controlled | N = 13 | Asymptomatic bacteriuria in pregnancy |
PO 3 g once Follow-up until birth |
3 g |
N = 10 Nitrofurantoin × 7 days |
0 (0%) | GI disorders—2 (20%) |
AC amoxicillin clavulanate, AE adverse events, ALP alkaline phosphatase, ALT alanine aminotransferase, BSI bloodstream infection, CA Cefuroxime axetil, CTX cotrimoxazole, cIAI complicated intra-abdominal infection, CNS central nervous system, COMP comparator, F female, FOM fosfomycin, F-up follow-up, GI gastrointestinal, GTP γ- guanosine triphosphate, IM intramuscularly, IV intravenously, LDH lactate dehydrogenase, M male, NA not applicable, PO orally, SD standard deviation, SSI surgical site soft tissue infection, TID three times daily, TMP trimethoprim, UTI urinary tract infection, VAP ventilator-associated pneumonia
aIncluding blinded and open label trials
bThe most common AE reported