New molecules and adjuvants in the treatment of infections by Acinetobacter baumannii

ABSTRACT

Introduction: The current problems of the treatment of infections by Acinetobacter baumannii are linked with the increase of multidrug- and extensive-drug resistance and the lack of development of new antimicrobial drugs for Gram-negative bacilli. For these reasons, new alternatives for the treatment and control of severe infections by A. baumannii are necessary. Several studies have reported the effect of adjuvants to restore the efficacy of existing antimicrobial agents.

Areas covered: In the present review, the authors describe the main results in the development of adjuvant drugs as well as new data on antimicrobial peptides, in monotherapy or in combination therapy with existing antimicrobial agents, which have shown promising preclinical results in vitro and in vivo.

Expert opinion: The preclinical evaluation of adjuvants and antimicrobial peptides, in monotherapy or in combination therapy, for A. baumannii infections has shown promising results. However, caution is needed and further extensive in vivo studies and clinical trials have to be performed to confirm the potential use of these adjuvants as true therapeutic alternatives.

KEYWORDS:

• Acinetobacter baumannii
• antimicrobial resistance
• adjuvant antibiotics

Article highlights

• Acinetobacter baumannii is a paradigm of multi- and extensively-drug antimicrobial resistance (MDR/XDR), including carbapenem-resistance (CRAb).

• The principal antibiotic resistance mechanisms in A. baumannii are β-lactamases hydrolysis, penicillin-binding protein modification, porins expression loss, efflux pump overexpression, aminoglycoside modifying enzymes activity, mutations in genes codifying DNA gyrase and topoisomerase IV, and in the lpx and pmrAB genes.

• The preclinical evaluation of different adjuvant antibiotics, in vitro and in vivo, alone or in combination therapy, for CRAb causing severe infections has shown promising preliminary results.

• Lysophosphatidylcholine has shown promising in vivo results in experimental murine models by A. baumannii, both as pre-emptive therapy or in combination with colistin, tigecycline, and imipenem.

• In preclinical animal models, the combination of disodium edetate, as adjuvant with ceftriaxone plus sulbactam, has activity against Gram-negative bacilli clinical isolates, including against ESBL and MBL producing MDR A. baumannii strains. Moreover, it has been efficacious in a randomized clinical trial in skin/skin structure and bone/joint infections.

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Declaration of interest

María Eugenia Pachón-Ibáñez is supported by Plan Nacional de I+D+i and Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Economía y Competitividad, Spanish Network for Research in Infectious Diseases (REIPI RD12/0015/0001) - co-financed by European Development Regional Fund ‘A way to achieve Europe’ ERDF.

Younes Smani is supported by Plan Nacional de I+D+i and Instituto de Salud Carlos III, Subdirección General de Evaluación y Fomento de la Investigación, Program ‘Miguel Servet’, Ministerio de Economía y Competitividad, - co-financed by European Development Regional Fund ‘A way to achieve Europe’ ERDF.

Jerónimo Pachón is Full Professor of Medicine at the University of Seville, Spain, and Head of the Infectious Diseases Service, University Hospital Virgen del Rocío, Seville, Spain. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.