Table 1.

Emerging pharmacotherapies and related clinical trials against MDR Acinetobacter baumannii.

Name of the Drug	Mechanism of Action	Clinical Trials
Sulbactam/durlobactam (SD, Xacduro®)	β-lactamase inhibitor combined with a non-beta-lactam beta-lactamase inhibitor.	1. A randomized, active-controlled study to evaluate the efficacy and safety of intravenous sulbactam/etx2514 in the treatment of patients with infections caused by Acinetobacter baumannii-calcoaceticus complex (ATTACK) (NCT03894046).   2. A double-blind, randomized, placebo-controlled study to evaluate the safety and efficacy of intravenous sulbactam/etx2514 in the treatment of hospitalized adults with complicated urinary tract infections, including acute pyelonephritis (NCT03445195).
Cefepime/zidebactam (FEP-ZID; WCK5222)	Fourth-generation cephalosporin that disrupts the synthesis of the peptidoglycan layer combined with a non-β-lactam β-lactamase inhibitor.	1. A randomized, double-blind, placebo-controlled study to evaluate the safety, tolerability, and pharmacokinetics of multiple escalating doses of intravenous WCK 5222 (zidebactam and cefepime) in healthy adult human subjects (NCT02707107).   2. A phase 1, open-label, single-dose study to investigate the pharmacokinetics of intravenous WCK 5222 (FEP-ZID) in patients with renal impairment (NCT02942810).   3. A phase 1, multiple-dose, open-label study to determine and compare plasma and intrapulmonary concentrations of WCK 5222 (cefepime and zidebactam) in healthy adult human subjects (NCT03630094).   4. A randomized, double-blind, double-dummy, placebo- and positive-controlled, crossover study to evaluate the effect of WCK 5222 on the QT/QTc interval in healthy volunteers (NCT03554304).   5. A phase 3, randomized, double-blind, multicenter, comparative study to determine the efficacy and safety of cefepime/zidebactam vs. meropenem in the treatment of complicated urinary tract infection or acute pyelonephritis in adults (NCT04979806).
Imipenem/cilastatin/funobactam	Broad-spectrum carbapenem, combined with a dehydropeptidase I inhibitor and a novel diazabicyclooctane.	1. Four phase 1 studies evaluated pk properties, safety, and tolerability of funobactam, alone and in combination with imipenem/cilastatin (NCT04801043, NCT04802863, NCT04787562, and NCT04482569).   2. An ongoing multicenter, randomized, double-blind, double-dummy, comparative, phase 3 study evaluating the efficacy and safety of imipenem/cilastatin/funobactam vs. meropenem in hospitalized adults with complicated urinary tract infections, including acute pyelonephritis (NCT05204368).   3. A multicenter, randomized, double-blind, comparative, phase 3 study assessing the efficacy and safety of iv imipenem/cilastatin/funobactam vs. imipenem/cilastatin/relebactam in adults with hospital-acquired bacterial pneumonia or ventilator-associated bacterial pneumonia (NCT05204563).
Xeruborbactam (XER, QPX7728)	Ultra-broad-spectrum cyclic boronate inhibitor of serine and MBL.	1. A phase 1, randomized, double-blind, placebo-controlled, ascending single and multiple-dose study of the safety, tolerability, and pharmacokinetics of intravenous (IV) QPX7728 alone and in combination with QPX2014 in healthy adult subjects (NCT04380207).   2. A phase 1, randomized, double-blind, placebo-controlled, ascending single- and multiple-dose study of the safety, tolerability, and pharmacokinetics of oral QPX7831 in healthy adult subjects (NCT04578873).   3. A phase 1, randomized, double-blind, single-dose, drug–drug interaction study to determine the impact of co-administration of QPX7728 on the pharmacokinetics of QPX2014 in healthy adult subjects (NCT05072444).   4. A phase 1, open-label, drug–drug interaction, and randomized, double-blind, controlled, multiple-dose pharmacokinetics and safety study of xeruborbactam oral prodrug (QPX7831) in combination with ceftibuten in healthy adult participants (NCT06079775).   5. A phase 1, open-label, single-dose study to determine the safety and pharmacokinetics of oravance (ceftibuten/xeruborbactam oral prodrug [QPX7831]) in participants with renal impairment (NCT06157242).
Zosurabalpin (RG6006)	Macrocyclic peptides that inhibit LPS transportation.	1. Phase 1, multicenter, single-dose, uncontrolled, open-label (NCT05614895).   2. Phase 1, randomized, sponsor-open, adaptive, single- and multiple-ascending dose, placebo-controlled study (NCT04605718).
Apramycin (EBL-1003)	Amynoglicoside derivate.	A phase 1, open-label study to evaluate the plasma PK profile of apramycin and lung penetration of apramycin in epithelial lining fluid and alveolar macrophages after a single IV apramycin dose in healthy subjects, a secondary objective is to assess safety and tolerability (NCT05590728).
Zifanocycline (KBP-7072)	Third-generation tetracycline.	Four phase 1 studies assessing safety and tolerability (NCT02454361, NCT05507463, NCT04532957, NCT02654626).
MRX-8 QPX9003 SPR206	Polymixins.	Phase 1 studies to assess safety and tolerability (NCT04649541, NCT04808414, and NCT04868292).