Alternative drugs against multiresistant Gram-negative bacteria

Lauro Vieira Perdigão Neto; Maura Salaroli Oliveira; Tatiana D'Annibale Orsi; Gladys Villas Boas do Prado; Roberta Cristina Ruedas Martins; Gleice Cristina Leite; Ana Paula Marchi; Esther Sant'Ana de Lira; Marina Farrel Côrtes; Evelyn Patricia Sanchez Espinoza; Cláudia Maria Dantas de Maio Carrilho; Ícaro Boszczowski; Thais Guimarães; Silvia Figueiredo Costa; Anna S Levin

doi:10.1016/j.jgar.2020.07.025

Alternative drugs against multiresistant Gram-negative bacteria

J Glob Antimicrob Resist. 2020 Dec:23:33-37. doi: 10.1016/j.jgar.2020.07.025. Epub 2020 Aug 18.

Authors

Lauro Vieira Perdigão Neto¹, Maura Salaroli Oliveira², Tatiana D'Annibale Orsi³, Gladys Villas Boas do Prado³, Roberta Cristina Ruedas Martins³, Gleice Cristina Leite³, Ana Paula Marchi³, Esther Sant'Ana de Lira³, Marina Farrel Côrtes², Evelyn Patricia Sanchez Espinoza², Cláudia Maria Dantas de Maio Carrilho⁴, Ícaro Boszczowski², Thais Guimarães², Silvia Figueiredo Costa³, Anna S Levin⁵

Affiliations

¹ Department of Infection Control of Hospital das Clínicas, Faculdade de Medicina, Universidade de Sao Paulo, Rua Dr Ovídio Pires de Campos 225, Sala 629, São Paulo, SP 05403-010, Brazil; Department of Infectious Diseases and LIM-49, Universidade de Sao Paulo, Av. Dr Enéas de Carvalho Aguiar 470, São Paulo, SP 05403-000, Brazil. Electronic address: lauro_perdigao@hotmail.com.
² Department of Infection Control of Hospital das Clínicas, Faculdade de Medicina, Universidade de Sao Paulo, Rua Dr Ovídio Pires de Campos 225, Sala 629, São Paulo, SP 05403-010, Brazil.
³ Department of Infectious Diseases and LIM-49, Universidade de Sao Paulo, Av. Dr Enéas de Carvalho Aguiar 470, São Paulo, SP 05403-000, Brazil.
⁴ Hospital Universitário, Londrina State University, Av. Robert Koch 60, Londrina, PR 86038-440, Brazil.
⁵ Department of Infection Control of Hospital das Clínicas, Faculdade de Medicina, Universidade de Sao Paulo, Rua Dr Ovídio Pires de Campos 225, Sala 629, São Paulo, SP 05403-010, Brazil; Department of Infectious Diseases and LIM-49, Universidade de Sao Paulo, Av. Dr Enéas de Carvalho Aguiar 470, São Paulo, SP 05403-000, Brazil.

PMID: 32822906
DOI: 10.1016/j.jgar.2020.07.025

Abstract

Objectives: Enterobacterales and other non-fermenting Gram-negative bacteria have become a threat worldwide owing to the frequency of multidrug resistance in these pathogens. On the other hand, efficacious therapeutic options are quickly diminishing. The aims of this study were to describe the susceptibility of 50 multiresistant Gram-negative bacteria, mostly pan-resistant, against old and less-used antimicrobial drugs and to investigate the presence of antimicrobial resistance genes.

Methods: A total of 50 genetically distinct isolates were included in this study, including 14 Acinetobacter baumannii (belonging to ST79, ST317, ST835 and ST836), 1 Pseudomonas aeruginosa (ST245), 8 Serratia marcescens and 27 Klebsiella pneumoniae (belonging to ST11, ST340, ST258, ST16, ST23, ST25, ST101, ST234, ST437 and ST442). The isolates were submitted to antimicrobial susceptibility testing and whole-genome sequencing to evaluate lineages and resistance genes.

Results: Our results showed that some strains harboured carbapenemase genes, e.g. bla_KPC-2 (28/50; 56%) and bla_OXA-23 (11/50; 22%), and other resistance genes encoding aminoglycoside-modifying enzymes (49/50; 98%). Susceptibility rates to tigecycline (96%) in all species (except P. aeruginosa), to minocycline (100%) and doxycycline (93%) in A. baumannii, to ceftazidime/avibactam in S. marcescens (100%) and K. pneumoniae (96%), and to fosfomycin in S. marcescens (88%) were high. Chloramphenicol and quinolones (6% susceptibility each) did not perform well, making their use in an empirical scenario unlikely.

Conclusions: This study involving genetically distinct bacteria showed promising results for tigecycline for all Gram-negative bacteria (except P. aeruginosa), and there was good activity of minocycline against A. baumannii, ceftazidime/avibactam against Enterobacterales, and fosfomycin against S. marcescens.

Keywords: Alternative antimicrobials; Carbapenem resistance; Gram-negative; Multiresistance; Polymyxin resistance; Whole-genome sequencing.

MeSH terms

Anti-Bacterial Agents* / pharmacology
Gram-Negative Bacteria* / genetics
Microbial Sensitivity Tests
Minocycline
Tigecycline

Substances

Anti-Bacterial Agents
Tigecycline
Minocycline