Table 2.
References | Trial design | FOM N |
Patients’ gender and age Indication |
FOM dosing regimen | FOM total dose | COMP N Regimen |
FOM AE No of events (%) |
COMP AE n (%) |
---|---|---|---|---|---|---|---|---|
Andaker et al. [15] | Prospective randomized controlleda | N = 259 |
F and M; mean age 67 years Prophylaxis of infection after colorectal surgery |
FOM IV 8 g + metronidazole 1 g once and FOM 8 g 8 h later | 16 g |
N = 258 Doxycycline + metronidazole once |
5% (12/259) Death 2% (5/259) Urticaria/purpura 1% (3/259) Nausea 1% (3/259) Thrombophlebitis 0.5% (1/259) |
4% (11/258) Death 2% (5/259) Urticaria 1% (2/258) Nausea 0.5% (1/258) Leucopenia 0.5% (1/258) Vaginitis 0.5% (1/258) Pulmonary edema 0.5% (1/258) |
Ishizaka et al. [13] | Prospective randomized controlled | N = 101 |
F and M >20 years Prevention of infection after urological surgery |
FOM IV 2 g once + 2 g twice daily × 3 days Follow-up 14 days |
14 g |
N = 101 Cefotiam × 4 days |
3 (3%) Eosinophilia—2 (2%) Elevated LDH—1 (1%) |
6 (6%) Eosinophilia—2 (2%) Elevated LDH—1 (1%) Elevated GTP—1 (1%) GI disorders—2 (2%) |
Nohr et al. [10] | Prospective randomized controlled | N = 84 |
F and M 24–90 years Prophylaxis of infection after colorectal surgery |
FOM IV 8 g + metronidazole 1 g once | 8 g |
N = 88 Bacitracin + neomycin × 2 days + metronidazole and ampicillin once |
2 (2%) Rash—1 (1%) GI disorders—1 (1%) |
7 (8%) Rash—1 (1%) GI disorders—6 (7%) |
Chareancholvanich [14] | Prospective randomized controlled | N = 56 |
F and M 57–86 years Prevention of surgical infection after elective total knee arthroplasty |
FOM IV 2 g 12 h apart Follow-up 6 months |
4 g |
N = 56 Cefuroxime, 3 g total divided in 3 doses q 8 h |
0% (0/56) | 0% (0/56) |
Sirijatuphat and Thamlikitkul [17] | Prospective randomized controlled | N = 47 |
F and M 31–96 years Treatment of carbapenem-resistant Acinetobacter baumannii infection including pneumonia (79%), primary bacteremia, UTI, cIAI, SSI |
FOM IV 4 g every 12 h plus colistin at 5 mg of colistin base activity/kg × median duration 12 days (range 3–14) | 56–168 g |
N = 47 Colistin at 5 mg of colistin base activity/kg × median duration 12 days (range 3–56) |
28-days all cause mortality 46.8% AKI- 53.4% Abnormal liver tests 12.8% |
28-days all cause mortality 57.4% AKI—59.6% Abnormal liver tests 12.8% |
Lindhagen et al. [16] | Prospective randomized controlled | N = 30 | Prophylaxis of infection after elective colorectal surgery | FOM 2 g + metronidazole 0.5 g Q6 h × 3 days for the total dose of FOM of 32 g and metronidazole of 8 g | 32 g |
N = 28 Cephalotin + metronidazole × 3 days for the total dose of cephalotin of 32 g and metronidazole of 8 g |
0% (0/30) | 0% (0/28) |
Nissen et al. [12] | Prospective randomized controlled | N = 17 |
F and M ≥ 18 years of age Mean age 57 years Pneumonia requiring mechanical ventilation in 22 out 32 patients |
FOM IV 4 g every 8 h + AMP 1 g q 6 h Mean treatment duration 5.5 days |
About 180 g |
N = 15 Gentamicin 80 mg every 8 h + AMP 1 g q 6 h |
Peripheral phlebitis—2 (12%) “mild transient” AST elevation—1 (6%) |
0 |
Pontiki et al. [31] | Prospective non-comparative | N = 66 |
F and M 56.7 ± 17.2 years (age ± SD) Infections due to resistant pathogens including primary bacteremia (n = 18), VAP (n = 14), CR-BSI (n = 7), cIAI, UTI, meningitis. |
FOM IV + colisitin (n = 32), tigecycline (n = 19), gentamicin (n = 15), meropenem (n = 12), and piperacillin-tazobactam (n = 4) for median duration of 14 days (IQR 8–17 days) at a median dose 24 g/day (IQR 16–24 g/day) | About 336 g | NA |
Hypokalemia 10 (15.2%) Renal toxicity 3 (4.5%) Thrombocytopenia 4 (6%) Diarrhea 2 (3%) Rash 1 (1.5%) Neutropenia 1 (1.5%) |
NA |
Meissner et al. [20] | Prospective non-comparative | N = 60 |
F and M 17–78 years Chronic post-traumatic osteomyelitis |
FOM IV 10 g once, then 5 g 3 times daily Mean duration 13.9 days (5–28) |
50–420 g | NA |
Peripheral phlebitis—7 (12%) GI disorders—4 (7%) Exanthema—2 (3%) |
NA |
Stengel et al. [21] | Prospective non-comparative | N = 52 |
F and M ≥18 years; mean age 63 years DFI with high risk of major amputation |
FOM IV 8-24 g × 14 days (range 3–40) in combination with carbapenems and other β-lactams, quinolones, clindamycin | Varied | NA | Nausea and rash—4 (8%) | NA |
Rio et al. [32] | Prospective non-comparative | N = 16 | Rescue therapy for MRSA bacteremia or infective endocarditis (n = 12) |
FOM IV 2 g every 6 h plus imipenem 1 g every 6 h Median duration 28 days (range 4–75) |
48–900 g | NA |
Deaths—5 (31%); 1 death due to sodium overload, hypernatremia and acute renal failure was considered FOM related Leucopenia—1 Sodium overload—3 |
NA |
Portier et al. [18] | Prospective non-comparative | N = 16 |
8 days–73 years (five children aged 8 days 14 years) Meningitis (3); bone and joint infections (6); persistent bacteremia (7) |
IV 50 mg/kg 3–4 times daily for 11–21 days in combination with cefotaxime 25 mg/kg 3–4 times daily | About 115–295 g | NA |
Neutropenia—3 (19%) (not specified) AST increase—1 (6%) (not specified) |
NA |
Mirakhur et al. [19] | Prospective non-comparative | N = 15 |
F and M mean age 23 years (18–37) Pulmonary exacerbations of Pseudomonas aeruginosa infection in patient with cystic fibrosis |
FOM IV 5 g three times daily Mean course length 16.6 days (7–36); mean 2 courses per patient (range 1–3), FOM given in combination with 1–2 other intravenous antibacterial drugs |
Varied | NA | Nausea—1 (7%) | NA |
Michalopoulos et al. [22] | Prospective non-comparative | N = 11 |
Adults Carbapenem-resistant Klebsiella pneumoniae infections: VAP, BSI, UTI, and wound infection |
FOM IV 2–4 g every 6 h × 14 ± 5.6 days in combination with colistin, gentamicin, or piperacillin/tazobactam | 72–320 g | NA | 0 (0%) | NA |
Hernandez Casado [26] | Retrospective non-comparative | N = 99 |
M and F 7–74 years (No. of children is not reported) At risk of bone fracture infection or established osteomyelitis |
N = 39 IV 8–16 g × 4 days, then IM 2–8 g × 2–6 days, then PO 2–4 g × 2–6 days N = 60 IM or PO, doses are not specified |
Varied | NA | Rash—1 (1%) | NA |
Florent et al. [23] | Retrospective non-comparative | N = 72 |
M and F 55 ± 19 years Infections of bone and joint (n = 33); CNS (n = 11); ear and sinus (n = 9); UTI (n = 9); bacteremia (n = 5); SSTI (n = 4); pneumonia (n = 1) |
FOM IV 12 g a day in 86% of cases with a median duration of 11 days; co-administered with another antibacterial in all cases | About 132 g | NA |
27 (38%) Hypokalemia—19 (26%) Injection site pain—3 (4%) Heart failure—2 (3%) Hypertension—2 (3%) ALT elevated—1 (1.4%) |
NA |
Gallardo et al. [28] | Retrospective non-comparative | N = 33 |
M and F 10–79 years cIAI (n = 29) SSI (n = 4e) |
IM/IV 4–6 daily × 5 days in the cIAI (n = 29) group and IM 3–6 daily (n = 4) in the SSI group |
IM/IV 18–30 g |
Historical control; but no safety data are reported for the control | Petechial rash—1 (3%) | Not reported |
Ruiz Garcia et al. [30] | Retrospective non-comparative | N = 31 |
Females 16–39 years Endometritis |
FOM IM 4 g/day (N = 29) FOM IV 8–12 g/day (N = 2) for 7 days |
28–84 g | NA | 0 | NA |
Hutzler et al. [24] | Retrospective non-comparative | N = 30 |
M and F 4–77 years UTI (n = 13), pneumonia (n = 14), osteomyelitis (n = 2), septicemia (n = 1) |
IM or PO 2–8 g daily (100–230 mg/kg/day) divided in 4 doses given every 6 h × 5–58 days |
20–200 g | NA |
Pain at the injection site 1 (3%) Transaminase elevation—2 (7%) Eosinophilia—1 (3%) |
NA |
Menendez et al. [27] | Retrospective non-comparative | N = 27 |
M and F 11–80 years Pneumonia and bronchitis |
Parenterally N = 19 PO N = 8 (calcum salt) 4–12 g daily for 1–2 weeks; |
28–168 g | NA |
Rash—1 (4%) Diarrhea—1 (4%) |
NA |
Children | ||||||||
Corti et al. [11] | Retrospective comparative |
N = 70 FOM (23) FOM+(47)b |
Children <16 years of age acute hematogenous osteomyelitis |
IV 200 mg/kg daily Mean duration 2.5–3 weeks |
Varied |
N = 33 Flucloxacillin, amoxicillin, amoxicillin/clavulanic acid, clindamycin |
FOM Exanthema—0 Diarrhea—1 (4%) Leucopenia —0c FOM+ Exanthema—10 (21%) Diarrhea—1 (2%) Leucopenia—1 (2%) |
Exanthema—14 (42%) Diarrhea—7 (21%) Leucopenia—3 (9%)c |
Baquero et al. [29] | Retrospective non-comparative | N = 26 (number of treatments in 24 patients) |
F and M Serratia marcescens bacteremia Children; 22 out of 24 were <1 year including 11 <1 month |
IV 75 mg/kg every 6 h for 2–4 weeks, FOM alone (n = 6), in combination with gentamicin (n = 18) and carbenicillin (2)f | Varied | NA | 0—“no significant side effects” | NA |
Llorens et al. [25] | Retrospective non-comparative | N = 24 |
Children of 11 months to 12 years Pneumonia, empyema, bronchitis |
200 mg/kg/day given in 4 injections every 6 h; IV—10, IM—14; co-administered with ampicillin in 1 case Duration 4–23 days |
Varied | NA |
Transient “slight” transaminase elevation—6 (25%)—resolved without stopping FOM Nicolau syndrome—1 (4%)d |
NA |
AC amoxicillin clavulanate, AE adverse events, AKI acute kidney injury, ALP alkaline phosphatase, ALT alanine aminotransferase, AMP ampicillin, AST aspartate aminotransferase, BSI bloodstream infection, CA cefuroxime axetil, cIAI complicated intra-abdominal infection, CNS central nervous system, COMP comparator, CR-BSI catheter-related bloodstream infection, CTX cotrimoxazole, DFI diabetic foot infection, F female, FOM fosfomycin, F-up follow-up, GI gastrointestinal, GTP γ-guanosine triphosphate, IM intramuscularly, IQR interquartile range, IV intravenously, LDH lactate dehydrogenase, M male, MRSA methicillin-resistant Staphylococcus aureus, NA not applicable, PO orally, SSTI skin and soft tissue infection, TID three times daily, TMP trimethoprim, UTI urinary tract infection, VAP ventilator-associated pneumonia
aIncluding blinded and open label trials
bFOM+ fosfomycin was combined with flucloxacillin (38), amoxicillin (2), amoxicillin/clavulanic acid (4), clindamycin (2), and with gentamicin (1)
cLeucopenia was defined as a leukocyte count <1G/l
dNicolau syndrome—necrosis of the skin and underlying tissues at the site on intramuscular injection
eAdditional 21 patients received FOM orally
fPatients could receive more than one course of treatment