Table 2.
Summaries of main characteristics of these new antibiotic drugs and their efficacy on KPCp UTIs.
| Antibiotics and Classes | Action Spectre, PK/PD Data | Posology | AEs | Notes |
|---|---|---|---|---|
| CEFIDEROCOL (FETCROJA®), a siderophore cephalosporin | -Amber Class A, B, C and D enterobacteriales. Not active against gram-positive aerobic bacteria and anaerobic bacteria -The urinary excretion is ranged from 61.5% to 68.4% unchanged antibiotic product regardless of the dosage |
2 g administered every 8 h with an eGFR superior to 90 mL/min/1.73 m2 between five to ten days | Diarrhea (19%), fever (14%) and vomiting (13%) | it is the only molecule that has activity on all carbapenemases. It brings a benefit in terms of mechanism of action and diversity of sites of action. To use exclusively as a last resort for reasons of preservation. |
| MEROPENEM/ VABORBACTAM (VABOREM®), a Carbapenem + non-β-lactam, serine beta-lactamase inhibitor |
Aerobic and anaerobic Gram-positive and negative, ESBL and AmpC producing enterobacteriae, Amber Class-A enterobacterial -Urinary excretion of Meropenem and Vaborbactam ranged from 40 to 60% and 75 to 95%respectively. No specific data are available for prostatic diffusion |
Meropenem 2 g and vaborbactam 2 g administered every 8 h with an eGFR superior to 50 mmL/min/1.73 m2, between five to ten days | Headache (3.8–21.6%), infusion site phlebitis (42–62.2%), nausea (19.5%), and diarrhea (14.6%) | M/V shows a better safety profile compared to BAT and presents fewer adverse events |
| CEFTAZIDIME-AVIBACTAM (Zavicefta®), a third generation cephalosporine + non–β-lactam β-lactamase inhibitor | -Ambler class A, C and some of D enterobacteriales -Urinary excretion is excellent and joins a targeted MIC of 8 mg/L in 94.9% to 99.6% even in case of adjusted dosage for renal impairment. |
2 g/0.5 g in 2 h infusions, administered every 8 h with an eGFR superior to 50 mL/min/1.73 m2, between 5 to 10 days. | Nausea 3%, vomiting 3%, diarrhea 2%, Pyrexia 3%, abdominal pain 2% | Reduces all-cause hospital mortality rate Delay in starting CAZ-AVI may not impact the survival and is a good option for salvage. Latest discoveries indicate that widespread use of CAZ-AVI produced a transformation in epidemiology of carbapenemases from KPCp to metallo-b-lactamases. |
| IMIPENEM-CILASTATIN-RELEBACTAM (RECARBRIO®), a Carbapenem + dehydropeptidase inhibitors + non–β-lactam β-lactamase inhibitor | -Amber class A carbapenemases and class C cephalosporinases -Urinary excretion of Relebactam is excellent and ranged from 94.7% to 100% over a 24-h period following single-dose administration. Renal clearance is similar when relebactam is administered with and without imipenem-cilastatin |
2500 mg/500 mg/250 mg (imipenem/cilastatin/relebactam) in 30 min infusions, administered every 6 h with an eGFR superior to 90 mL/min/1.73 m2 | Less nephrotoxicity, headache (7.1%), diarrhea (5.1%), nausea (4.0%) and hypertension (3%) |
IMI/REL have not been studied in case of severe urosepsis or suspected prostatitis Nevertheless, expert opinion recommends IMI/REL in cUTI when the therapeutic arsenal is restricted |