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1.
Acta Pharmaceutica Sinica B ; (6): 3678-3693, 2023.
Artigo em Inglês | WPRIM | ID: wpr-1011137

RESUMO

Polymyxin B and polymyxin E (colistin) are presently considered the last line of defense against human infections caused by multidrug-resistant Gram-negative organisms such as carbapenemase-producer Enterobacterales, Acinetobacter baumannii, and Klebsiella pneumoniae. Yet resistance to this last-line drugs is a major public health threat and is rapidly increasing. Polymyxin S2 (S2) is a polymyxin B analogue previously synthesized in our institute with obviously high antibacterial activity and lower toxicity than polymyxin B and colistin. To predict the possible resistant mechanism of S2 for wide clinical application, we experimentally induced bacterial resistant mutants and studied the preliminary resistance mechanisms. Mut-S, a resistant mutant of K. pneumoniae ATCC BAA-2146 (Kpn2146) induced by S2, was analyzed by whole genome sequencing, transcriptomics, mass spectrometry and complementation experiment. Surprisingly, large-scale genomic inversion (LSGI) of approximately 1.1 Mbp in the chromosome caused by IS26 mediated intramolecular transposition was found in Mut-S, which led to mgrB truncation, lipid A modification and hence S2 resistance. The resistance can be complemented by plasmid carrying intact mgrB. The same mechanism was also found in polymyxin B and colistin induced drug-resistant mutants of Kpn2146 (Mut-B and Mut-E, respectively). This is the first report of polymyxin resistance caused by IS26 intramolecular transposition mediated mgrB truncation in chromosome in K. pneumoniae. The findings broaden our scope of knowledge for polymyxin resistance and enriched our understanding of how bacteria can manage to survive in the presence of antibiotics.

2.
Rev. Soc. Bras. Med. Trop ; 55: e0349, 2022. graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1360814

RESUMO

ABSTRACT Polymyxin antibiotics are disfavored owing to their potential clinical toxicity, especially nephrotoxicity. However, the dry antibiotic development pipeline, together with the increasing global prevalence of infections caused by multidrug-resistant (MDR) gram-negative bacteria, have renewed clinical interest in these polypeptide antibiotics. This review highlights the current information regarding the mechanisms of resistance to polymyxins and their molecular epidemiology. Knowledge of the resistance mechanisms and epidemiology of these pathogens is critical for the development of novel antibacterial agents and rapid treatment choices.

3.
Shanghai Journal of Preventive Medicine ; (12): 283-287, 2022.
Artigo em Chinês | WPRIM | ID: wpr-923977

RESUMO

Drug-resistant bacteria have become a serious threat to human health. Polymyxin has shown strong bactericidal activity to some Gram-negative and Gram-positive bacteria that are resistant to antibiotics, and has become a last-resort treatment option against a variety of multi-drug resistant bacteria. However, due to the abuse of polymyxin in animal breeding, the drug resistance rate of polymyxin in human population has significantly increased. In order to further understand the mechanism of polymyxin resistance, and to take measures to reduce the incidence of polymyxin resistance in the population, this paper reviewed the progress in research of the antibacterial mechanism of polymyxin, the prevalence of polymyxin resistance in the population, the mechanism of polymyxin resistance, and its transmission mode.

4.
Shanghai Journal of Preventive Medicine ; (12): 283-287, 2022.
Artigo em Chinês | WPRIM | ID: wpr-923955

RESUMO

Drug-resistant bacteria have become a serious threat to human health. Polymyxin has shown strong bactericidal activity to some Gram-negative and Gram-positive bacteria that are resistant to antibiotics, and has become a last-resort treatment option against a variety of multi-drug resistant bacteria. However, due to the abuse of polymyxin in animal breeding, the drug resistance rate of polymyxin in human population has significantly increased. In order to further understand the mechanism of polymyxin resistance, and to take measures to reduce the incidence of polymyxin resistance in the population, this paper reviewed the progress in research of the antibacterial mechanism of polymyxin, the prevalence of polymyxin resistance in the population, the mechanism of polymyxin resistance, and its transmission mode.

5.
Rev. Soc. Bras. Med. Trop ; 53: e20200032, 2020. tab, graf
Artigo em Inglês | SES-SP, ColecionaSUS, LILACS | ID: biblio-1136877

RESUMO

Abstract INTRODUCTION: Essential oils can serve as novel sources of antibiotics for multidrug-resistant bacteria. METHODS: The multidrug-resistance profile of a Klebsiella aerogenes strain was assessed by PCR and sequencing. The antibacterial activity of Cinnamomum cassia essential oil (CCeo) against K. aerogenes was assessed by broth microdilution and time-kill methods. RESULTS: K. aerogenes showed high antibiotic resistance. The genes bla KPC-2, ampC, bla CTX-M-15, bla OXA-1, and bla TEM were present. CCeo exhibited an inhibitory effect with a minimum inhibitory concentration of 17.57 μg/mL. CONCLUSIONS: The antibacterial activity of CCeo makes it a potential candidate for treating carbapenem- and polymyxin-resistant K. aerogenes strains.


Assuntos
Humanos , Infecções por Klebsiella/tratamento farmacológico , Enterobacter aerogenes , Cinnamomum aromaticum , Antibacterianos/uso terapêutico , beta-Lactamases , Óleos Voláteis , Carbapenêmicos , Polimixinas , Klebsiella pneumoniae
6.
Mem. Inst. Oswaldo Cruz ; 114: e190020, 2019. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1012670

RESUMO

BACKGROUND The multidrug resistance (MDR) phenotype is frequently observed in Acinetobacter baumannii, the most clinically relevant pathogenic species of its genus; recently, other species belonging to the A. calcoaceticus-A. baumannii complex have emerged as important MDR nosocomial pathogens. OBJECTIVES The present study aimed to verify the occurrence of metallo-β-lactamase genes among distinct Acinetobacter species in a hospital located in the Brazilian Amazon Region. METHODS Antimicrobial susceptibility profiles were determined by broth microdilution. The genetic relationships among these isolates were assessed by pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). Pyrosequencing reads of plasmids carrying the bla NDM-1 gene were generated using the Ion Torrent™ platform sequencing. FINDINGS A total of six isolates carried bla NDM-1: A. baumannii (n = 2), A. nosocomialis (n = 3), and A. pittii (n = 1); three carried bla IMP-1: A. baumannii, A. nosocomialis, and A. bereziniae. Resistance to colistin was observed for an NDM-1-producing A. nosocomialis isolate. Diverse PFGE patterns and sequence types were found among A. nosocomialis and A. baumannii isolates. The bla NDM-1 sequence was inserted in a Tn125 transposon, while the bla IMP-1 was found as a gene cassette of the class 1 integron In86. MAIN CONCLUSIONS To the best of our knowledge, this is the first report describing the dissemination of bla NDM-1 among distinct Acinetobacter species recovered from the same hospital in South America.


Assuntos
Humanos , Compostos Organometálicos , Acinetobacter/isolamento & purificação , Acinetobacter/genética , beta-Lactamases , Resistência Microbiana a Medicamentos/efeitos dos fármacos , Infecção Hospitalar/transmissão , Unidades de Terapia Intensiva
7.
Clinics ; 72(10): 642-644, Oct. 2017.
Artigo em Inglês | LILACS | ID: biblio-1039534

RESUMO

OBJECTIVE: We describe an IncX4 pHC891/16mcr plasmid carrying mcr-1 in a colistin-resistant and carbapenem-susceptible E. coli isolate (HC891/16), ST156, which caused a blood infection in a Brazilian patient with gallbladder adenocarcinoma. METHODS: Strain HC891/16 was subjected to whole genome sequencing using the MiSeq Platform (Illumina, Inc., USA). Assembly was performed using Mira and ABACAS. RESULTS: The isolates showed resistance only to ciprofloxacin, ampicillin and cefoxitin, and whole-genome sequencing revealed the presence of aac(6')Ib-cr and blaTEM1. CONCLUSION: Our findings warn of the possible silent dissemination of colistin resistance by carbapenem-susceptible mcr-1 producers, as colistin susceptibility is commonly tested only among carbapenem-resistant isolates.


Assuntos
Humanos , Feminino , Idoso , Carbapenêmicos/farmacologia , Bacteriemia/tratamento farmacológico , Colistina/farmacologia , Proteínas de Escherichia coli/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Antibacterianos/farmacologia , Plasmídeos/efeitos dos fármacos , Brasil , Testes de Sensibilidade Microbiana , Proteínas de Escherichia coli/isolamento & purificação , Proteínas de Escherichia coli/genética , Farmacorresistência Bacteriana Múltipla , Escherichia coli/isolamento & purificação , Escherichia coli/genética , Infecções por Escherichia coli/tratamento farmacológico
8.
Mem. Inst. Oswaldo Cruz ; 108(1): 113-115, Feb. 2013. graf
Artigo em Inglês | LILACS | ID: lil-666054

RESUMO

This study describes a carbapenem-resistant Klebsiella pneumoniae (CRKP) outbreak that occurred from October 2008-December 2010. Polymerase chain reaction assays were performed to detect the blaKPC gene and molecular typing was performed using pulsed-field gel electrophoresis (PFGE). There were 33 CRKP infections; PFGE revealed five genotypes: genotype A in five (15%), B in 18 (55%), C in eight (24%) and two unique profiles. Genotype B was disseminated in all hospital units and belonged to the same clone identified in 11 different hospitals in the state of São Paulo. Sixteen (48%) patients died. Seven isolates (21%) were resistant to polymyxin B and 45% were resistant to tigecycline and amikacin.


Assuntos
Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Antibacterianos/farmacologia , Resistência beta-Lactâmica , Carbapenêmicos/farmacologia , Infecção Hospitalar/epidemiologia , Surtos de Doenças , Infecções por Klebsiella/epidemiologia , Klebsiella pneumoniae/efeitos dos fármacos , Infecção Hospitalar/microbiologia , DNA Bacteriano/genética , Eletroforese em Gel de Campo Pulsado , Genótipo , Infecções por Klebsiella/microbiologia , Klebsiella pneumoniae/genética , Testes de Sensibilidade Microbiana , Reação em Cadeia da Polimerase , Centros de Atenção Terciária , beta-Lactamases/metabolismo
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