Introduction
Aerobic gram-positive cocci | Aerobic GNB (Enterobacterales) | Aerobic GNB—selected non-fermentative |
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Enterococcus spp. (also VRE) | E. coli (+ ESBL and KPC* producers) | P. aeruginosa* |
S. aureus (also MRSA) | Klebsiella spp. (+ ESBL and KPC* producers) | |
Staphylococcus spp. coagulase-negative | Citrobacter spp. | |
S. lugdunensis | Enterobacter spp. | |
S. saprophyticus* | P. vulgarisa | |
Serratia spp. |
Materials and methods
Results
Author, country and year | Type of paper | Methods | Bacteria (number) | Combination or comparison with | FOS dosing regimens | Comments |
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Guggenbichler et al. 1992 [18] | Original article | Catheter infection model; catheter sepsis (5) | S. aureus (1), S. epidermidis (1) | - | 24-, 48- or 96-hr CI at a concentration of 100 μg/mL (flow rate 20 mL/hr) | Combination of FOS CI and imipenem/cilastatin resulted in microbiological and clinical success in 5 out of 5 episodes (S. epidermidis). |
Chavanet et al. 1995 [19] | Original article | Fibrin clots infection model | S. pneumoniae (1) | Cefotaxime | FOS monotherapy 6-hr CI including a 25 mg/kg LD followed by 75 mg/kg FOS + CTX FOS 6-hr CI including a 25 mg/kg LD followed by 75 mg/kg + CTX 25 mg/kg LD followed by 75 mg/kg | The authors also evaluated single-dose FOS and CTX, alone and in combination, and this resulted in a higher AUC compared with CI. |
Xiong et al. 1995 [20] | Original article | Rabbit endocarditis model | P. aeruginosa (2) | Ciprofloxacin, pefloxacin | FOS + CIP FOS 300 mg/kg 24-hr CI + CIP 64 mg/kg 24-hr CI FOS + PEF FOS 300 mg/kg 24-hr CI + PEF 64 mg/kg 24-hr CI | Additive and synergistic effect was observed for the combinations FOS + CIP and FOS + PEF, respectively. FOS + CIP lead to a greater reduction in the number of CFU per gram of vegetations. |
Bugnon et al. 1997 [21] | Original article | Rabbit endocarditis model | P. aeruginosa (2) | - | 300 mg/kg/day CI | Compared with pefloxacin, FOS had a greater and more constant bactericidal effect. |
Docobo-Pérez et al. 2015 [22] | Original article | Hollow fibre infection model | ESBL-producing E. coli (3) | Meropenem | FOS MIC ≤ 1 mg/L FOS monotherapy 12 g CI FOS + MEM Not evaluated as continuous infusion. FOS 4 g q8hr + MEM 1 g q8hr | For one isolate even higher dosages of FOS monotherapy (24g q24hr; 36 g q24hr) were ineffective due to selection of resistant mutants. |
Asuphon et al. 2016 [23] | Original article | Monte Carlo simulation | P. aeruginosa (120) | Carbapenems | Non-MDR isolates FOS monotherapy 4 g q8hr PI (above 90% PTA) FOS + carbapenems FOS 16 g CI + MEM 1–2 g q8hr PI (80% PTA) FOS 16 g CI + DOM 1 g q8hr PI (80% PTA) MDR isolates FOS monotherapy 4 g q4hr PI (above 90% PTA) FOS + carbapenems All combinations could not achieve the PK/PD targets against MDR PA. FOS 8 g q8hr PI + DOM 1 g q8hr PI achieved the target against CRPA. | Prolonged and continuous infusions improved PK/PD exposure compared with dosage regimens using traditional 30-min infusions. |
Albiero et al. 2016 [24] | Original article | Monte Carlo simulation | KPC-producing K. pneumoniae (18) | Meropenem | FOS monotherapy - FOS + MEM FOS 6 g q6hr PI + MEM 1.5 g q6hr PI (80–90% PTA) FOS 8 g q8hr PI + MEM 1.5 g q6hr PI (80–90% PTA) | Data were simulated for patients with normal renal function. For patients with renal impairment, percentages of PTA are higher (FOS monotherapy 6 g q6hr PI or 8 g q8hr PI above 90%). In case of MEM MICs ≥ 32 mg/L, none of the dosing regimens of MEM reached 90% PTA. |
Bhavnani et al. 2017 [25] | Abstract | PK model simulation | Enterobacterales (considered for their representative MICs) | - | FOS MIC ≤ 64 mg/L, ClCr ≥ 50 mL/min/1.73m2 6 g q8hr PI (> 90% PTA) | - |
Louie et al. 2018 [4] | Original article | Hollow fibre infection model | P. aeruginosa (1) | - | 12 g CI or 18 g CI (see Comments). | All FOS regimens rapidly selected for resistant isolates, irrespective of the dose or fractionation schedule. With CI (12 g CI or 18 g CI) regimens, resistance emerged later (6 hr vs. 4 hr). |
Diep et al. 2018 [26] | Original article | Hollow fibre infection model | K. pneumoniae KPC-producing (2) | Polymyxin B | FOS monotherapy 6 g q6hr PI (1-hr or 3-hr infusion) Rapid bactericidal effect, followed by regrowth after 24 hr FOS + PMB FOS 6 g q6hr PI (1-hr or 3-hr infusion) + PMB 2.5-mg/kg LD (2-hr infusion) followed by 1.5 mg/kg q12hr (1-hr infusion) | The combination of FOS and PMB had a synergistic effect with sustained bactericidal effect. |
Rodrìguez-Gascón et al. 2019 [27] | Review | Revision of literature | Comparison with MICs for Enterobacterales, P. aeruginosa and Staphylococcus spp. | - | FOS MIC ≤ 64 mg/L 6 g q 6hr PI (30 min) 8 g q 8hr PI (30 min or 6 hr) | FOS monotherapy was not able to achieve PK/PD targets for strains of MIC ≥ 128 mg/L. |
Leelawattanachai et al. 2020 [28] | Original article | Monte Carlo simulation | Carbapenem-resistant Enterobacterales: 116 K. pneumoniae, 12 E. coli, 1 E. cloacae | - | FOS MIC ≤ 128 mg/L, weight 50 kg, ClCr ≥ 80 mL/min/1.73m2 8 g q8hr PI (90% PTA) 8 g q12hr PI (90% PTA) 4 g q6hr PI (90% PTA) | - |
Author, country and year | Type of paper | Methods | Bacteria (number) | Combination or comparison with | FOS dosing regimens | Comments |
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Merino-Bohórquez et al. 2018 [29] | Original article (clinical trial) | Bacteraemic UTI; Monte Carlo simulation | MDR E. coli (16) | - | 4 g q6hr PI (non-superior: 8 g q8hr PI) | Decrease 1-log bacterial burden in 89–96% (EUCAST breakpoints) and 33–54% (CLSI breakpoints) of patients. |
Matzneller et al. 2019 [30] | Abstract | Clinical (healthy volunteers) | P. aeruginosa* | - | 1 g/hr CI preceded by a LD of 8 g over 30 min | CI resulted in 100% PTA for MICs up to 128 mg/L. Intermittent intravenous infusion resulted in markedly lower % PTA. |
Eckburg et al. 2017 [31] Kaye et al. 2019 [32] | Original article (clinical trial) | 184 hospitalized patients with complicated UTI or acute pyelonephritis (+ 231 treated with piperacillin-tazobactam) | Enterobacterales, P. aeruginosa, A. baumannii-calcoaceticus complex, E. faecalis, S. aureus, S. saprophyticus | - | ClCr ≥ 20 mL/min/1.73 m2 6 g q8hr PI | FOS resulted as non-inferior to piperacillin-tazobactam. FOS resulted in overall success rate of 64.7% (119/184 patients). PIP/TAZ resulted in overall success rate of 54.5% (97/178 patients). |
Al Jalali et al. 2020 [33] | Original article (clinical trial) | Randomized crossover study in 8 healthy volunteers | - (PK/PD study) | - | 8 g over 30 min LD + 1 g/hr CI | Comparison with intermittent infusion 8 g over 30 min every 8 hr showed better PK/PD parameters in volunteers who received CI. |