Table 2.
Demographics/clinical features and CRRT settings collected from the included studies
| Novel agent (study reference) | Study design | No. of patients | Age, years/sex | Weight (kg) |
Dose | Site of infection | Pathogen/MIC | CRRT modality | Filter | Pre/post-dilution | Effluent flow rate (mL/h) | Blood flow rate (mL/h) |
Net removal (mL/h)—residual diuresis |
Clinical outcome |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Ceftolozane–tazobactam (Sime et al. [24]) |
PK population study | 6 |
55.8 ± 16.5 5M, 1F |
79.7 ± 17.9 |
1.5 g q8h (1-h infusion) |
4 BSI 3 HAP/VAP |
2 Pseudomonas aeruginosa 2 Stenotrophomonas maltophilia 2 Serratia marcescens 1 Klebsiella pneumoniae |
CVVHDF |
ST100/ST150 (surface area 0.9 m2/1.5 m2) |
NA |
Qd: 1250 ± 273.9 mL/ha Quf: 1277.8 ± 743.2 mL/ha |
150 ± 44.7 |
170 ± 173 NA |
NA |
|
Ceftolozane–tazobactam (Kuti et al. [28]) |
Case report | 1 | 75/M | 66 |
3 g q8h (1-h infusion) |
VAP |
Pseudomonas aeruginosa MIC: 0.75/4 mg/L |
CVVHDF | AN-69 high-flux M100 | NA |
Qd: 1000 Quf: 200 |
150 |
NA 76 mL/day |
Clinical cure |
|
Ceftolozane–tazobactam (Bremmer et al. [32]) |
Case report | 1 | 47/M | 82 |
3 g q8h (1-h infusion) |
Bacteraemic VAP and osteomyelitis |
Pseudomonas aeruginosa MIC: 2 mg/L |
CVVHDF | AN-69 high-flux M100 |
50% pre-filter 50% post-filter |
Qd: 1000 Quf: 750 |
200 |
NA 50 mL/day |
Clinical cure (death occurred for non-infective complications) |
|
Ceftolozane–tazobactam (Oliver et al. [27]) |
Case report | 1 | 61/M | 78.8 |
1.5 g q8h (EI 4 h) |
Osteomyelitis |
Pseudomonas aeruginosa MIC: 1.5 mg/L |
CVVH |
AN-69 high-flux M150 (surface area 1.5 m2) |
NA | 2000 | 250 | NA | Clinical cure |
|
Ceftolozane–tazobactam (Aguilar et al. [30]) |
Case report | 1 | 68/NA | NA |
3 g q8h (1-h infusion) |
cIAI | NA | CVVHD | Polysulphone membrane | NA |
Qd: 2000 Quf: 1000 |
100 |
NA Anuric |
Clinical cure |
|
Ceftolozane–tazobactam (Carbonell et al. [29]) |
Case report | 1 | 37/F | NA |
3 g q8h (3-h infusion) |
CR-BSI | Pseudomonas aeruginosa |
CVVHDF + MARS |
AN-69 high-flux M150 (surface area 1.5 m2) |
NA |
Qd: 1600 Quf: 500 |
180 | NA | Clinical failure |
|
Ceftolozane–tazobactam (Butragueño-Laiseca et al. [33]) |
Case report | 1 | 9 months | 5.8 | 30 mg/kg q8h | BSI |
Pseudomonas aeruginosa Escherichia coli ESBL MIC: 4 mg/L |
CVVHDF | NA | NA |
Qd: 250 Quf: 220 |
30 mL/min |
NA Anuric |
NA |
|
Ceftolozane–tazobactam (Mahmoud et al. [31]) |
Case report | 1 | 35/M | 187 | 3 g q8h CI | VAP |
Pseudomonas aeruginosa MIC: 2/4 mg/L |
CVVHDF | HF1400 polyarylethersulfone haemofilter | 100% post-filter |
Qd: 2000 Quf: 2000 |
250 |
25 Anuric |
NA |
|
Ceftazidime–avibactam (Wenzler et al. [35]) |
Case report | 1 | 53/F | NA |
1.25 g q8h (2-h infusion) |
Bacteraemic VAP |
Pseudomonas aeruginosa MIC: 6/4 mg/L |
CVVH |
Polyethersulfone membrane filter (surface area 1.6 m2) |
100% pre-filter | 2000 | 200 | NA | NA |
|
Ceftazidime–avibactam (Soukup et al. [34]) |
Case report | 1 | 50/M | 94 |
2.5 g q8h (2-h infusion) |
VAP |
Pseudomonas aeruginosa MIC 8 mg/L |
CVVHDF | M100 filter |
80% pre-filter 20% post-filter |
Qd: 1500 Quf: 1250 |
250 |
30–73 Anuria |
Clinical cure |
|
Meropenem–vaborbactam (Kufel et al. [36]) |
Case report | 1 | 60/M | 76 |
1 g/1 g q8h (3-h infusion) |
Joint infection |
Carbapenem- resistant Klebsiella pneumoniae MIC 0.094/8 mg/L |
CVVHD |
Polyethersulfone membrane filter (surface area 1.6 m2) |
NA | 3000 | 250 |
NA No residual diuresis |
Clinical failure |
|
Fosfomycin (Gattringer et al. [26]) |
PK study | 12 |
68 ± 8 10M, 2F |
78.7 ± 13.4 | 8 g q12h |
4 pneumonia 2 septic shock 2 endocarditis 2 cardiac failure 1 cIAI 1 aortic aneurysm |
2 Staphylococcus aureus 1 Streptococcus mitis 1 Pseudomonas aeruginosa |
CVVH |
Polyethylene membrane filter (surface area 1.2 m2) |
NA | 1966.7 ± 336 | 180 | NA | NA |
|
Ceftaroline (Kalaria et al. [25]) |
PK study | 4 |
52.3 ± 18.3 1M, 3F |
89.1 ± 19.8 |
300-600 mg q12h (1-h infusion) |
2 BSI 1 Endocarditis 1 HAP |
3 MRSA (MIC not provided) |
2 CVVHD 2 CVVDHF |
AN-69 high-flux M150 (surface area 1.5 m2) |
100% pre-filter | 3190 ± 510.3 |
250 (3 cases) 300 (1 case) |
125 ± 86.6 NA |
Clinical cure rate: 100% |
|
Ceftobiprole (Cojutti et al. [37]) |
Case report | 1 | 48/M | 92 |
250 mg q12h (2-h infusion) |
HCAP |
Empirical (MRSA EUCAST breakpoint 2 mg/L) |
CVVHDF | HF1400 polyarylethersulfone haemofilter |
75% pre-filter 25% post-filter |
Qd: 1500 Quf: 2000 |
150 | NA |
Clinical cure (death occurred for non-infective complications) |
|
Dalbavancin (Corona et al. [38]) |
Case report | 1 | 58/M |
BMI: 31.1 kg/m2 |
1500 mg single dose | NSTI |
Staphylococcus epidermidis MIC: 0.05 mg/L |
NA | NA | NA | NA | NA | NA | Clinical cure |
BMI body mass index, BSI bloodstream infection, cIAI complicated intra-abdominal infection, CI continuous infusion, CR-BSI catheter-related bloodstream infection, CVVH continuous venovenous haemofiltration, CVVHD continuous venovenous haemodialysis, CVVHDF continuous venovenous haemodiafiltration, CRRT continuous renal replacement therapy, EI extended infusion, ESBL extended spectrum β-lactamases, EUCAST European Committee on Antimicrobial Susceptibility Testing, F female, HCAP healthcare-associated pneumonia, HAP hospital-acquired pneumonia, M male, MARS methicillin-resistant Staphylococcus aureus, MIC minimum inhibitory concentration, MRSA methicillin-resistant Staphylococcus aureus, NA not available, NSTI necrotizing soft tissue infection, PK pharmacokinetic, Quf ultrafiltrate rate, Qd dialysate rate, q8h every 8 VAP ventilator-associated pneumonia
aData are expressed as mean ± standard deviation