Sulbactam–durlobactam for infections caused by Acinetobacter baumannii–calcoaceticus complex

Giuliano, Simone; Sbrana, Francesco; Tascini, Carlo

doi:10.1016/s1473-3099(23)00422-x

Cited by 6 publications

(4 citation statements)

References 5 publications

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“…Co-administration of imipenem/cilastatin to provide coverage for eventual polymicrobial infections has raised questions about a possible synergic action of imipenem with sulbactam/durlobactam on CRAB, casting doubts on the real efficacy of the new β-lactam agent as monotherapy [18]. In-vitro data on CRAB isolates of ATTACK trial, seems to indicate that imipenem does not provide a meaningful contribution to sulbactam-durlobactam activity against sulbactamdurlobactam-susceptible isolates [19], however a study conducted on 109 CRAB isolates in Greece showed that the addition of imipenem further lowered the MIC90 of sulbactam/durlobactam by one two-fold dilution [20].…”

Section: Sulbactam/durlobactammentioning

confidence: 99%

Antibiotic Treatment of Carbapenem-Resistant <em>Acinetobacter baumannii </em>Infections in View of the Newly Developed β-Lactams: A Narrative Review of the Existing Evidence

Serapide,

Guastalegname,

Gullì

et al. 2024

Preprint

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Carbapenem-resistant Acinetobacter baumannii (CRAB) infections represent the fourth-leading cause of death attributable to antimicrobial resistance globally, but a standardized therapy is still lacking. In this narrative review we focused the antibiotic treatment of CRAB infections in view of newly β-lactam agents (NBLs) like sulbactam/durlobactam and cefiderocol, discussing the main hot points such as the superiority of combination treatment over monotherapy and the best antibiotic partner to use in combination. Sulbactam/durlobactam seems to be the best candi-date to replace current back-bone agents. Cefiderocol, could play a crucial role in combina-tion-regimen. Due to toxicity and the PK/PD limitations, colistin (or polymyxin B) should be used as an alternative agent (when no other options are available). Tigecycline (or minocycline) and fosfomycin could represent suitable partners for both NBLs. Randomized clinical trials (RCTs) are needed to better evaluate the role of NBLs in CRAB infection treatment and to compare the ef-ficacy of tigecycline and fosfomycin as partner antibiotics. Synergism should be tested between NBLs and “old” drugs (rifampicin and trimethoprim/sulfamethoxazole). Huge efforts should be made to accelerate pre-clinical and clinical studies on safer polymyxin candidates with lung im-proved activity, as well as on the i.v. rifabutin formulation.

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Section: Sulbactam/durlobactammentioning

confidence: 99%

Antibiotic Treatment of Carbapenem-Resistant <em>Acinetobacter baumannii </em>Infections in View of the Newly Developed β-Lactams: A Narrative Review of the Existing Evidence

Serapide,

Guastalegname,

Gullì

et al. 2024

Preprint

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“…Co-administration of imipenem/cilastatin to provide coverage for eventual polymicrobial infections has raised questions about a possible synergic action of imipenem with sulbactam/durlobactam on CRAB, casting doubts on the real efficacy of the new β-lactam agent as monotherapy [ 18 ]. In vitro data on CRAB isolates of the ATTACK trial seem to indicate that imipenem does not provide a meaningful contribution to sulbactam–durlobactam activity against sulbactam–durlobactam-susceptible isolates [ 19 ]; however, a study conducted on 109 CRAB isolates in Greece showed that the addition of imipenem further lowered the MIC90 of sulbactam/durlobactam by one two-fold dilution [ 20 ].…”

Section: Considerations and Available Data About New β-Lactam Agentsmentioning

confidence: 99%

Antibiotic Treatment of Carbapenem-Resistant Acinetobacter baumannii Infections in View of the Newly Developed β-Lactams: A Narrative Review of the Existing Evidence

Serapide,

Guastalegname,

Gullì

et al. 2024

Antibiotics

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It is estimated that antimicrobial resistance (AMR) is responsible for nearly 5 million human deaths worldwide each year and will reach 10 million by 2050. Carbapenem-resistant Acinetobacter baumannii (CRAB) infections represent the fourth-leading cause of death attributable to antimicrobial resistance globally, but a standardized therapy is still lacking. Among the antibiotics under consideration, Sulbactam/durlobactam seems to be the best candidate to replace current back-bone agents. Cefiderocol could play a pivotal role within combination therapy regimens. Due to toxicity and the pharmacokinetics/pharmacodynamics (PK/PD) limitations, colistin (or polymyxin B) should be used as an alternative agent (when no other options are available). Tigecycline (or minocycline) and fosfomycin could represent suitable partners for both NBLs. Randomized clinical trials (RCTs) are needed to better evaluate the role of NBLs in CRAB infection treatment and to compare the efficacy of tigecycline and fosfomycin as partner antibiotics. Synergism should be tested between NBLs and “old” drugs (rifampicin and trimethoprim/sulfamethoxazole). Huge efforts should be made to accelerate pre-clinical and clinical studies on safer polymyxin candidates with improved lung activity, as well as on the iv rifabutin formulation. In this narrative review, we focused the antibiotic treatment of CRAB infections in view of newly developed β-lactam agents (NBLs).

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“…25 However, some have questioned the impact of concurrent imipenem-cilastatin as background therapy across both groups, which was used to treat potential gram-negative coinfections, and whether this substantially contributed to the trial’s findings. 25,27 Although clinical guidelines have noted that combination therapy including carbapenems has not been shown to be efficacious for treatment of CRAB infections, in vitro data have shown that carbapenems may achieve synergistic bactericidal activity when combined with other agents used to treat CRAB. 28 Looking at investigations combining imipenem with BLIs differing mechanistically from durlobactam, imipenem has demonstrated bactericidal synergy for certain CRAB isolates, making it difficult to completely exclude the effect of imipenem on the rates of clinical outcome in the aforementioned trials.…”

Section: Relevance To Patient Care and Clinical Practice In Compariso...mentioning

confidence: 99%

“…Further studies are needed to elucidate the role of SUL-DUR alone or in combination with other active antimicrobials for the treatment of multidrug-resistant CRAB infections. 25,27…”

Section: Relevance To Patient Care and Clinical Practice In Compariso...mentioning

confidence: 99%

Sulbactam-Durlobactam in the Treatment of Carbapenem-Resistant Acinetobacter baumannii Infections

August,

Matlob,

Kale-Pradhan

2023

Ann Pharmacother

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Objective: To review the pharmacology, efficacy, and safety of intravenous sulbactam-durlobactam (SUL-DUR) in the treatment of carbapenem-resistant Acinetobacter baumannii (CRAB) infections. Data Sources: PubMed databases and ClinicalTrials.gov were searched using the following terms: Sulbactam Durlobactam, ETX2514, Xacduro, Sulbactam-ETX2514, ETX2514SUL. Study Selection and Data Extraction: Articles published in English between January 1985 and September 13, 2023, related to pharmacology, safety, efficacy, and clinical trials were reviewed. Data Synthesis: A phase II trial compared SUL-DUR with placebo with imipenem and cilastatin in both groups. Overall treatment success in the microbiological intention-to-treat analysis was reported in 76.6% of patients in the SUL-DUR group compared with 81% patients in the placebo group. A phase III trial compared SUL-DUR with colistin in adults with confirmed CRAB infections. Patients received either SUL-DUR or colistin and background therapy with imipenem-cilastatin. SUL-DUR was noninferior to colistin for 28-day all-cause mortality (19% vs 32.3%, treatment difference −13.2%; 95% CI [−30.0 to 3.5]). Relevance to Patient Care and Clinical Practice in Comparison to Existing Drugs: Clinicians have limited options to treat CRAB infections. SUL-DUR has demonstrated efficacy against CRAB in patients with pneumonia and may be considered a viable treatment option. Nonetheless, potential impact of concomitant imipenem-cilastatin as background therapy on clinical trial findings is unclear. Further studies are needed to elucidate the role of SUL-DUR alone or in combination with other active antimicrobials for the treatment of CRAB infections. Conclusions: SUL-DUR has shown to be predominantly noninferior to alternative antibiotics in the treatment of pneumonias caused by CRAB, making it a viable treatment option. Further postmarketing data is needed to ascertain its role in other infections.

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Sulbactam–durlobactam for infections caused by Acinetobacter baumannii–calcoaceticus complex

Cited by 6 publications

References 5 publications

Antibiotic Treatment of Carbapenem-Resistant <em>Acinetobacter baumannii </em>Infections in View of the Newly Developed β-Lactams: A Narrative Review of the Existing Evidence

Antibiotic Treatment of Carbapenem-Resistant <em>Acinetobacter baumannii </em>Infections in View of the Newly Developed β-Lactams: A Narrative Review of the Existing Evidence

Antibiotic Treatment of Carbapenem-Resistant Acinetobacter baumannii Infections in View of the Newly Developed β-Lactams: A Narrative Review of the Existing Evidence

Sulbactam-Durlobactam in the Treatment of Carbapenem-Resistant Acinetobacter baumannii Infections

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