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1.
Emerg Microbes Infect ; 9(1): 639-650, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32192413

RESUMO

Acinetobacter baumannii, a Gram-negative opportunistic pathogen, is a leading cause of hospital- and community-acquired infections. Acinetobacter baumannii can rapidly acquire diverse resistance mechanisms and undergo genetic modifications that confer resistance and persistence to all currently used clinical antibiotics. In this study, we found exogenous L-lysine sensitizes Acinetobacter baumannii, other Gram-negative bacteria (Escherichia coli and Klebsiella pneumoniae) and a Gram-positive bacterium (Mycobacterium smegmatis) to aminoglycosides. Importantly, the combination of L-lysine with aminoglycosides killed clinically isolated multidrug-resistant Acinetobacter baumannii and persister cells. The exogenous L-lysine can increase proton motive force via transmembrane chemical gradient, resulting in aminoglycoside acumination that further accounts for reactive oxygen species production. The combination of L-lysine and antibiotics highlights a promising strategy against bacterial infection.


Assuntos
Acinetobacter baumannii/efeitos dos fármacos , Aminoglicosídeos/farmacologia , Antibacterianos/farmacologia , Lisina/farmacologia , Acinetobacter baumannii/metabolismo , Ciclo do Ácido Cítrico , Farmacorresistência Bacteriana Múltipla , Sinergismo Farmacológico , Escherichia coli/efeitos dos fármacos , Concentração de Íons de Hidrogênio , Klebsiella pneumoniae/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Mycobacterium smegmatis/efeitos dos fármacos , Força Próton-Motriz/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo
2.
Medicine (Baltimore) ; 99(10): e19466, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32150105

RESUMO

Multidrug-resistant bacterial (MDRB) infections have been difficult to treat clinically. Tigecycline (TIG) has several advantages, especially in the treatment of severe infections. Many clinicians have considered increasing the TIG dose to improve the efficacy of this molecule. The safety and efficacy of high-dose TIG in elderly patients with MDRB infections were investigated in this study.We conducted a retrospective analysis of the elderly patients with MDRB infections who were treated at the First Affiliated Hospital. A total of 106 patients received a conventional dose (CD-TIG group: 50 mg every 12 hours) of TIG and 51 received a high dose (HD-TIG group: 100 mg every 12 hours). The data from all patients were collected for examining the clinical features and performing the microbiological analysis. The safety profile and efficacy of the HD regimen were investigated.The clinical efficacy and microbiological eradication in the patients with MDRB infection were higher in the HD-TIG group than the CD-TIG group. The independent predictors of clinical cure were the use of TIG at HD (odd ratio [OR], 5.129; 95% confidence interval [CI] [1.890, 13.921]; P = .001) and microbiological eradication (OR, 3.049; 95% CI, [1.251, 7.430]; P = .014). In the ventilator-associated pneumonia (VAP) and bloodstream infection (BSI) subgroups, the sole independent predictor of clinical cure was the HD of TIG, and no significant adverse events were observed. The occurrence of multidrug-resistant Acinetobacter baumannii infection and an MIC value of 1 to 2 g/mL for TIG were independently associated with clinical failure in the VAP subgroup.HDs of TIG was found to associate with better clinical efficacy and microbiological eradication than its CDs in the elderly patients with MDRB infections. In the VAP and BSIs subgroups, administration of HDs of TIG was associated with better outcomes.


Assuntos
Infecções por Acinetobacter/tratamento farmacológico , Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana Múltipla , Pneumonia Associada à Ventilação Mecânica/tratamento farmacológico , Tigeciclina/uso terapêutico , APACHE , Acinetobacter baumannii/efeitos dos fármacos , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/administração & dosagem , Antibacterianos/farmacologia , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Testes de Sensibilidade Microbiana , Estudos Retrospectivos , Tigeciclina/administração & dosagem , Tigeciclina/farmacologia , Resultado do Tratamento
3.
J Photochem Photobiol B ; 204: 111782, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32062389

RESUMO

BACKGROUND: Ultraviolet (UV) fluorescent lamp (FL) was applied in mainstream riboflavin photochemical method (RPM) to inactivate pathogens in blood components. Low UV irradiance emitted by UV-FL resulted in more time to achieve effective inactivation. MATERIALS AND METHODS: A novel light emitting diode (LED) UV illumination with adjustable irradiance was developed by us. Two strains of drug-resistant bacteria (DRB), pan-drug resistant Acinetobacter baumannii (PDRAB) and methicillin-resistant Staphylococcus aureus (MRSA) were cultured and used for evaluating the inactivation effectiveness of RPM using UV-LED or UV-FL against DRB in plasma or platelets. Three plasma factors and four platelet parameters were measured after treatments. RESULTS: There was a linear relationship between UV-LED irradiance and electric current, the minimum UV irradiance was 24 mW/cm2, and the maximum was 258 mW/cm2. At the same UV dose of 15 J/cm2, inactivation effectiveness of UV-LED with 258 mW/cm2 against PDRAB in plasma or platelets were comparable to that of UV-FL with 16 mW/cm2, both above 98%. UV-FL treatment required 10-15 min, but UV-LED only required 1-2 min. However, MRSA showed a resistance to UV-LED (inactivation effectiveness was around 40%) compared with UV-FL (inactivation effectiveness was above 98%). The retention of fibrinogen, factor V, factor VII in plasma and platelet counts in platelets with UV-LED treatment were significantly higher than UV-FL at the same UV dose. CONCLUSION: The treatment of RPM using UV-LED with high UV irradiance was able to dramatically shorten inactivation time against PDRAB in plasma or platelets and improve retention of blood components compared with UV-FL.


Assuntos
Proteínas Sanguíneas/metabolismo , Riboflavina/química , Raios Ultravioleta , Acinetobacter baumannii/efeitos dos fármacos , Acinetobacter baumannii/efeitos da radiação , Plaquetas/citologia , Plaquetas/efeitos dos fármacos , Plaquetas/efeitos da radiação , Farmacorresistência Bacteriana/efeitos dos fármacos , Fator V/metabolismo , Fibrinogênio/metabolismo , Humanos , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/efeitos da radiação , Contagem de Plaquetas , Riboflavina/farmacologia
4.
Mikrobiyol Bul ; 54(1): 40-49, 2020 01.
Artigo em Turco | MEDLINE | ID: mdl-32050877

RESUMO

Acinetobacter baumannii is a multi-drug resistant (MDR) gram-negative pathogen leading to nosocomial infections. Hospital-acquired infections due to A.baumannii occur especially in patients hospitalized in intensive care units. Important infections related to this bacterium are pneumonia, bacteremia, endocarditis, skin and soft tissue, urinary tract infections and meningitis. Human transmission is usually through the hospital environment or through medical personnel. A.baumannii isolates increases their virulence not only being multiple resistance to antibiotics but as well as the ability to form biofilm. The biofilm formation of A.baumannii isolates were mostly related with genes encoding curli fiber (csgA), the chaperone-usher fimbria (csuE) and the outer membrane (ompA). The aim of this study was to demonstrate biofilm production and virulence genes in MDR invasive A.baumannii isolates. MDR and similarity status previously known invasive A.baumannii (n= 156) isolates were included in the study. Biofilm production was determined by quantitative microplate biofilm method. Virulence genes csgA, csuE, fimH, ompA and blaPER-1 were investigated by polymerase chain reaction (PCR). It was determined that 60.3% (94/156) of all the isolates formed biofilm. Of these 94 isolates, 17 were weak, 33 were medium and 44 were strong. The mean biomass forming capacity of the isolates was found to be 2.23 ± 0.0033. Among the isolates included in the study (n= 156) the frequency of csgA, csuE, ompA, fimH and blaPER-1 genes were 71.2%, 32.1%, 21.8%, 7.1% and 3.2% respectively. The frequency of csgA, ompA, bap, csuE, fimH virulence genes were found to be 41.5%, 24.5%, 20.2% and 5.3% among biofilm positive isolates respectively. Biofilm-forming isolates were most commonly found in pulsotype II 19.1% (18/94), pulsotype IX 17.0% (16/94) and pulsotype VI 12.8% (12/94). In this study, when the distribution of virulence genes were compAred with the isolates that have weak, medium and strong biofilm, all of the studied genes were found to be more abundant in isolates with strong and medium positive biofilm production. This has shown that excluding fimH gene, csgA, csuE and ompA genes have contributed to the biofilm formation in invasive A.baumannii isolates, respectively.


Assuntos
Infecções por Acinetobacter , Acinetobacter baumannii , Biofilmes , Farmacorresistência Bacteriana Múltipla , Virulência , Infecções por Acinetobacter/microbiologia , Acinetobacter baumannii/efeitos dos fármacos , Acinetobacter baumannii/genética , Antibacterianos/farmacologia , Farmacorresistência Bacteriana Múltipla/genética , Humanos , Virulência/genética
5.
Mikrobiyol Bul ; 54(1): 154-162, 2020 Jan.
Artigo em Turco | MEDLINE | ID: mdl-32050886

RESUMO

Acinetobacter species lead to nosocomial infections in immunocompromised patients hospitalized in intensive care units or services. Acinetobacter baumannii is a bacterium that is difficult to treat because it is intrinsically resistant to many antibiotics and can develop resistance afterwards. This situation limits the use of existing antibiotics and directs the clinician to new agents, different treatment options and the use of various antibiotic combinations. The aim of this study was to determine the sensitivities of doripenem (DOR), tigecycline (TGC), minocycline (MIN), amikacin (AK) and a newly developed agent ceftolozane-tazobactam (CT) in multidrug resistant A.baumannii strains which were isolated from inpatients in intensive care units and to investigate the in vitro interactions of CT/DOR, CT/TGC, CT/MIN and CT/AK combinations by using antibiotic gradient test method. Thirty-five A.baumannii strains isolated from various clinical specimens (blood, urine, sputum, tracheal aspirate, wound, abscess and catheter) between January 2017 and July 2017 were included in the study. Strains isolated from inpatients in intensive care units and resistant to at least three antibiotic classes were selected. The identification of A.baumannii isolates and the determination of routine antibiotic susceptibility profile were performed according to EUCAST 2017 criteria by the use of BD Phoenix 100 (Becton Dickinson, USA) automated system. Minimum inhibitor concentration values of CT, DOR, TGC, MIN, AK and combinations of CT with four other antibiotics (CT/DOR, CT/TGC, CT/MIN and CT/AK) were determined by antibiotic gradient test method. Fractional inhibitor concentration index (FICI) was used to determine the interactions of the combinations in vitro. According to the data obtained; the FICI was evaluated as synergy if FICI ≤ 0.5, additive if 0.5 > FICI ≤ 1, indifferent (unidentified interaction) if 1

Assuntos
Infecções por Acinetobacter , Acinetobacter baumannii , Cefalosporinas , Tazobactam , Infecções por Acinetobacter/microbiologia , Acinetobacter baumannii/efeitos dos fármacos , Antibacterianos/farmacologia , Cefalosporinas/farmacologia , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Sinergismo Farmacológico , Humanos , Técnicas In Vitro , Testes de Sensibilidade Microbiana , Tazobactam/farmacologia
6.
J Med Microbiol ; 69(1): 35-40, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31647404

RESUMO

Introduction. To identify risk factors for the first episode of Acinetobacter baumannii resistant to colistin (ABCR) infection in critically ill patients.Aim. Prospective observational study.Methodology. ICU patients who required mechanical ventilation for >48 h during a 36 month period. Clinical and microbiological data were studied; characteristics of patients infected with ABCR were compared with those of critically ill patients who presented infection due to A. baumannii sensitive to colistin (ABCS).Results. Twenty patients presented with ABCR infection, and 57 patients ABCS infection. Compared to patients with ABCS infection, patients suffering from ABCR infection had received more frequent and/or for longer duration dosing of several antibiotics active against Gram-negative bacteria (P<.05). Moreover, the duration of mechanical ventilation, and the presence of invasive procedures and tracheostomy prior to infection were associated with ABCR infections. The duration of carbapenem administration was an independent risk factor for ABCR infection [odds ratio (OR), 1.21; 95 % confidence interval (95 %, CI), 1.00 to 1.45; P=.049]. Mortality rate for patients with ABCR infection was higher (85 vs 39 % for the ABCS group). Sequential organ failure assessment score on admission, Charlson score and ABCR infection were independent risk factors for mortality.Conclusion. ABCR infection is a life-threatening infection, which might be more common in patients with previous use of antibiotics, especially carbapenems.


Assuntos
Infecções por Acinetobacter/epidemiologia , Infecções por Acinetobacter/microbiologia , Acinetobacter baumannii/efeitos dos fármacos , Antibacterianos/farmacologia , Colistina/farmacologia , Estado Terminal , Farmacorresistência Bacteriana , Acinetobacter baumannii/isolamento & purificação , Antibacterianos/uso terapêutico , Uso de Medicamentos , Humanos , Estudos Prospectivos , Respiração Artificial/efeitos adversos , Fatores de Risco , Resultado do Tratamento
7.
J Appl Microbiol ; 128(1): 15-27, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31102552

RESUMO

Acinetobacter baumannii causes several nosocomial infections and poses major threat when it is multidrug resistant. Even pan drug-resistant strains have been reported in some countries. The intensive care unit (ICU) mortality rate ranged from 45.6% to 60.9% and it is as high as 84.3% when ventilator-associated pneumonia was caused by XDR (extensively drug resistant) A. baumannii. Acinetobacter baumannii constituted 9.4% of all Gram-negative organisms throughout the hospital and 22.6% in the ICUs according to a study carried out in an Indian hospital. One of the major factors contributing to drug resistance in A. baumannii infections is biofilm development. Quorum sensing (QS) facilitates biofilm formation and therefore the search for 'quorum quenchers' has increased recently. Such compounds are expected to inhibit biofilm formation and hence reduce/prevent development of drug resistance in the bacteria. Some of these compounds also target synthesis of some virulence factors (VF). Several candidate drugs have been identified and are at various stages of drug development. Since quorum quenching, inhibition of biofilm formation and inhibition of VF synthesis do not pose any threat to the DNA replication and cell division of the bacteria, chances of resistance development to such compounds is presumably rare. Thus, these compounds ideally qualify as adjunct therapeutics and could be administered along with an antibiotic to reduce chances of resistance development and also to increase the effectiveness of antimicrobial therapy. This review describes the state-of-art in QS process in Gram-negative bacteria in general and in A. baumannii in particular. This article elaborates the nature of QS mediators, their characteristics, and the methods for their detection and quantification. Various potential sites in the QS pathway have been highlighted as drug targets and the candidate quorum quenchers which inhibit the mediator's synthesis or function are enlisted.


Assuntos
Infecções por Acinetobacter/microbiologia , Acinetobacter baumannii/fisiologia , Percepção de Quorum , Infecções por Acinetobacter/tratamento farmacológico , Acinetobacter baumannii/efeitos dos fármacos , Acinetobacter baumannii/patogenicidade , Acil-Butirolactonas/metabolismo , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Proteínas de Bactérias/metabolismo , Biofilmes/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Desenvolvimento de Medicamentos , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Farmacorresistência Bacteriana Múltipla/genética , Percepção de Quorum/efeitos dos fármacos , Fatores de Virulência/metabolismo
8.
Ann Lab Med ; 40(1): 21-26, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31432635

RESUMO

BACKGROUND: The existing modified carbapenem inactivation methods (mCIMs) recommended by the CLSI for detecting carbapenemase production have not been applicable for Acinetobacter baumannii. We evaluated the influence of matrices used in mCIMs and CIMTris on the stability of the disks for detecting carbapenemase producers and suggested optimal mCIM conditions for detecting carbapenemase-producing A. baumannii. METHODS: Seventy-three A. baumannii isolates characterized for antimicrobial susceptibility and carbapenemase encoding genes were tested for carbapenemase production using mCIM and CIMTris. The influence of the matrices (Tryptic soy broth [TSB] and Tris-HCl) used in these methods on the stability of the meropenem (MEM) disk was also evaluated. The mCIM conditions were adjusted to enhance screening sensitivity and specificity for detecting carbapenemase-producing A. baumannii. RESULTS: The matrices had an impact on the stability of the MEM disk after the incubation period (two or four hrs). TSB nutrient broth is an appropriate matrix for mCIM compared with Tris-HCl pH 7.6, which leads to the loss of MEM activity in CIMTris. The sensitivity and the specificity of the optimal mCIM were both 100%. CONCLUSIONS: We established optimal mCIM conditions for simple, accurate, and reproducible detection of carbapenemase-producing A. baumannii.


Assuntos
Acinetobacter baumannii/metabolismo , Antibacterianos/metabolismo , Proteínas de Bactérias/metabolismo , Testes de Sensibilidade a Antimicrobianos por Disco-Difusão/métodos , Meropeném/metabolismo , beta-Lactamases/metabolismo , Acinetobacter baumannii/efeitos dos fármacos , Acinetobacter baumannii/isolamento & purificação , Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Farmacorresistência Bacteriana/efeitos dos fármacos , Meropeném/farmacologia , beta-Lactamases/genética
9.
Ann Lab Med ; 40(1): 27-32, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31432636

RESUMO

BACKGROUND: Mutations in the quinolone resistance-determining regions (QRDRs) of Acinetobacter baumannii DNA gyrase (gyrA) and topoisomerase IV (parC) are linked to fluoroquinolone (FQ) resistance. We developed a mismatched PCR-restriction fragment length polymorphism (RFLP) assay to detect mutations in the gyrA and parC QRDRs associated with FQ resistance in A. baumannii. METHODS: Based on the conserved sequences of A. baumannii gyrA and parC, two primer sets were designed for mismatched PCR-RFLP to detect mutations in gyrA (codons 83 and 87) and parC (codons 80 and 84) by introducing an artificial restriction enzyme cleavage site into the PCR products. This assay was evaluated using 58 A. baumannii strains and 37 other Acinetobacter strains that have been identified by RNA polymerase ß-subunit gene sequence analysis. RESULTS: PCR amplification of gyrA and parC was successful for all A. baumannii strains. In 11 FQ -susceptible strains, the gyrA and parC PCR products were digested by the selected restriction enzymes at the site containing gyrA (codons 83 and 87) and parC (codons 80 and 84). PCR products from 47 FQ-resistant strains containing mutations in gyrA and parC were not digested by the restriction enzymes at the site containing the mutation. As for the non-baumannii Acinetobacter strains, although amplification products for gyrA were obtained for 28 strains, no parC amplification product was obtained for any strain. CONCLUSIONS: This assay specifically amplified gyrA and parC from A. baumannii and detected A. baumannii gyrA and parC mutations with FQ resistance.


Assuntos
Acinetobacter baumannii/genética , DNA Girase/genética , DNA Topoisomerase IV/genética , Farmacorresistência Bacteriana/genética , Reação em Cadeia da Polimerase/métodos , Acinetobacter baumannii/efeitos dos fármacos , Antibacterianos/farmacologia , Pareamento Incorreto de Bases , DNA Bacteriano/química , DNA Bacteriano/metabolismo , Fluoroquinolonas/farmacologia , Testes de Sensibilidade Microbiana , Mutação , Polimorfismo de Fragmento de Restrição , Análise de Sequência de DNA
10.
S Afr Med J ; 109(12): 934-940, 2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31865955

RESUMO

BACKGROUND: In South Africa (SA), the National Department of Health has developed an Antimicrobial Resistance National Strategy Framework document to manage antimicrobial resistance (AMR). One of the strategic objectives is to optimise surveillance and early detection of AMR. At the National Institute for Communicable Diseases (NICD), an analysis of selected organisms and antimicrobial agents from both the public and the private sectors was conducted. OBJECTIVES: The relevance of surveillance for AMR is increasingly recognised in the light of global action plans to combat resistance. In this report, we present an overview of ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter spp.) organisms and Escherichia coli reported from public and private sector laboratories in SA for the period 2016 - 2017. METHODS: Antimicrobial susceptibility testing (AST) profiles on selected ESKAPE organisms and E. coli isolated from blood cultures from the public and private sectors in 2016 and 2017 were analysed. AST data were extracted from a web-based electronic platform created by the NICD. Drug-bug combinations following the World Health Organization's Global Antimicrobial Surveillance System guidelines were included in the analysis. RESULTS: A total of 28 920 ESKAPE organisms and E. coli were reported in 2016 and 32 293 in 2017 across the two health sectors. Proportions of some organisms differed between the two health sectors, such as E. coli (19% in the public sector and 36% in the private sector), A. baumannii (14% public and 4% private), P. aeruginosa (7% public and 11% private) and S. aureus (27% public and 17% private). Susceptibility data indicated changing patterns in both sectors towards an increase in non-susceptibility to carbapenems in K. pneumoniae (p<0.01). However, we demonstrated an increase in susceptibility to cloxacillin in S. aureus (p<0.01) in both sectors. CONCLUSIONS: The key clinically important finding is the rapidly decreasing carbapenem susceptibility among Enterobacteriaceae reported in SA, irrespective of sector. In addition, the analysis provides information that could be used to monitor the effectiveness of interventions implemented at a national level under the guidance and direction of the national AMR framework.


Assuntos
Antibacterianos/farmacologia , Bacteriemia/microbiologia , Farmacorresistência Bacteriana , Vigilância da População , Setor Privado/estatística & dados numéricos , Setor Público/estatística & dados numéricos , Acinetobacter baumannii/efeitos dos fármacos , Hemocultura , Enterobacter/efeitos dos fármacos , Enterococcus faecium/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Humanos , Klebsiella pneumoniae/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Pseudomonas aeruginosa/efeitos dos fármacos , África do Sul , Staphylococcus aureus/efeitos dos fármacos
11.
Rev Soc Bras Med Trop ; 53: e20190044, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31859941

RESUMO

INTRODUCTION: Acinetobacter baumannii are opportunistic bacteria, highly capable of acquiring antimicrobial resistance through the production of carbapenemases and aminoglycoside modifying enzymes (AMEs). METHODS: Carbapenemase and AME genes were investigated in A. baumannii recovered from inpatients of a Brazilian hospital. RESULTS: The key genes found were bla OXA-51-like, the association ISAba1- bla OXA-23-like, and the AME genes aph(3´)-VI, aac(6´)-Ib, aac(3)-Ia, and aph(3´)-Ia. Different clusters spread through the institution wards. CONCLUSIONS: The dissemination of bla OXA-23-like and AME-carrying A. baumannii through the hospital highlights the need for improved preventive measures to reduce the spread of infection.


Assuntos
Infecções por Acinetobacter/microbiologia , Acinetobacter baumannii/enzimologia , Aminoglicosídeos/genética , Antibacterianos/farmacologia , Proteínas de Bactérias/genética , beta-Lactamases/genética , Acinetobacter baumannii/efeitos dos fármacos , Acinetobacter baumannii/isolamento & purificação , Brasil , Farmacorresistência Bacteriana Múltipla , Humanos , Unidades de Terapia Intensiva , Testes de Sensibilidade Microbiana , Centros de Atenção Terciária
12.
Mem Inst Oswaldo Cruz ; 114: e190232, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31778426

RESUMO

BACKGROUND: Acinetobacter baumannii is a leading cause of nosocomial infections. This species is characterised by the presence of pandemic lineages (International Clones) that present a broad antimicrobial resistance profile. OBJECTIVE: To perform the molecular epidemiology of carbapenem-resistant A. baumannii from a clinical setting in the Amazon Basin, and to characterise their antimicrobial resistance determinants. METHODS: The genetic relationship of carbapenem-resistant A. baumannii were assessed by pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). Class A, B and D ß-lactamase genes were screened by polymerase chain reaction (PCR) and sequencing. The antimicrobial susceptibility profile was obtained by Disc-diffusion method and minimum inhibitory concentration (MIC) determination. FINDINGS: All carbapenem-resistant A. baumannii strains belonged to three international clones, IC-1, IC-5 and IC-6, the latter recently reported by the first time in Brazil. The major determinant of carbapenem resistance in IC-1 and IC-5 strains was bla OXA-23, associated with ISAba1 and ISAba3, respectively, while IC-6 harboured the bla OXA-72. CONCLUSIONS: The A. baumannii epidemiology in Brazilian Amazon Region was unknown. It was demonstrated that A. baumannii XDR international clones were responsible for nosocomial infections in Boa Vista during 2016-2018, revealing that the epidemiological scenario of A. baumannii infections in Amazon Region resembles those from the cosmopolitan regions worldwide.


Assuntos
Infecções por Acinetobacter/virologia , Acinetobacter baumannii/genética , Antibacterianos/farmacologia , Farmacorresistência Bacteriana/genética , beta-Lactamases/genética , Acinetobacter baumannii/classificação , Acinetobacter baumannii/efeitos dos fármacos , Brasil , Testes de Sensibilidade a Antimicrobianos por Disco-Difusão , Eletroforese em Gel de Campo Pulsado , Genótipo , Humanos , Tipagem de Sequências Multilocus , Fenótipo
13.
Medicine (Baltimore) ; 98(38): e17034, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31567940

RESUMO

BACKGROUND: Pericardial infection caused by Acinetobacter baumannii is rare, particularly that of carbapenem-resistant A baumannii (CRAB). CASE PRESENTATION: We describe a rare case of purulent pericarditis due to CRAB in a 76-year-old man with acute myocardial infarction and acute kidney injury. The man was admitted to the intensive care unit for a catheter-related bloodstream infection. Pericardial effusion was detected via the bedside X-ray and ultrasound, and pericardiocentesis was performed. Cultures of the pericardial fluid, catheter tip, and blood independently revealed the presence of CRAB. These findings confirmed a diagnosis of purulent pericarditis. CONCLUSIONS: Clinicians should be reminded that CRAB infection can lead to purulent pericarditis, particularly in patients with congestive heart failure or renal insufficiency.


Assuntos
Infecções por Acinetobacter/diagnóstico , Acinetobacter baumannii/isolamento & purificação , Lesão Renal Aguda/diagnóstico , Infarto do Miocárdio sem Supradesnível do Segmento ST/diagnóstico , Pericardite/diagnóstico , Infecções por Acinetobacter/complicações , Acinetobacter baumannii/efeitos dos fármacos , Lesão Renal Aguda/complicações , Idoso , Carbapenêmicos/farmacologia , Diagnóstico Diferencial , Farmacorresistência Bacteriana , Evolução Fatal , Humanos , Masculino , Infarto do Miocárdio sem Supradesnível do Segmento ST/complicações , Pericardiocentese , Pericardite/complicações , Pericardite/diagnóstico por imagem , Tomografia Computadorizada por Raios X
14.
BMC Infect Dis ; 19(1): 853, 2019 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-31619192

RESUMO

BACKGROUND: Between January 2015 and July 2017, we investigated the frequency of carbapenem resistant Acinetobacter baumannii (CRAB) and carbapenem resistant Pseudomonas aeruginosa (CRPA) at the Mulago Hospital intensive care unit (ICU) in Kampala, Uganda. Carbapenemase production and carbapenemase gene carriage among CRAB and CRPA were determined; mobility potential of carbapenemase genes via horizontal gene transfer processes was also studied. METHODS: Clinical specimens from 9269 patients were processed for isolation of CRAB and CRPA. Drug susceptibility testing was performed with the disk diffusion method. Carriage of carbapenemase genes and class 1 integrons was determined by PCR. Conjugation experiments that involved blaVIM positive CRAB/CRPA (donors) and sodium azide resistant Escherichia coli J53 (recipient) were performed. RESULTS: The 9269 specimens processed yielded 1077 and 488 isolates of Acinetobacter baumannii and Pseudomonas aeruginosa, respectively. Of these, 2.7% (29/1077) and 7.4% (36/488) were confirmed to be CRAB and CRPA respectively, but 46 were available for analysis (21 CRAB and 25 CRPA). Majority of specimens yielding CRAB and CRPA were from the ICU (78%) while 20 and 2% were from the ENT (Ear Nose & Throat) Department and the Burns Unit, respectively. Carbapenemase assays performed with the MHT assay showed that 40 and 33% of CRPA and CRAB isolates respectively, were carbapenemase producers. Also, 72 and 48% of CRPA and CRAB isolates respectively, were metallo-beta-lactamase producers. All the carbapenemase producing isolates were multidrug resistant but susceptible to colistin. blaVIM was the most prevalent carbapenemase gene, and it was detected in all CRAB and CRPA isolates while blaOXA-23 and blaOXA-24 were detected in 29 and 24% of CRAB isolates, respectively. Co-carriage of blaOXA-23 and blaOXA-24 occurred in 14% of CRAB isolates. Moreover, 63% of the study isolates carried class 1 integrons; of these 31% successfully transferred blaVIM to E. coli J53. CONCLUSIONS: CRAB and CRPA prevalence at the Mulago Hospital ICU is relatively low but carbapenemase genes especially blaVIM and blaOXA-23 are prevalent among them. This requires strengthening of infection control practices to curb selection and transmission of these strains in the hospital.


Assuntos
Infecções por Acinetobacter/microbiologia , Acinetobacter baumannii , Infecção Hospitalar/microbiologia , Infecções por Pseudomonas/microbiologia , Pseudomonas aeruginosa , Resistência beta-Lactâmica , Acinetobacter baumannii/efeitos dos fármacos , Acinetobacter baumannii/enzimologia , Humanos , Unidades de Terapia Intensiva , Testes de Sensibilidade Microbiana , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/enzimologia , Uganda , beta-Lactamases
15.
Nat Commun ; 10(1): 4569, 2019 10 08.
Artigo em Inglês | MEDLINE | ID: mdl-31594927

RESUMO

Bacterial pathogens that infect patients also contaminate hospital surfaces. These contaminants impact hospital infection control and epidemiology, prompting quantitative examination of their transmission dynamics. Here we investigate spatiotemporal and phylogenetic relationships of multidrug resistant (MDR) bacteria on intensive care unit surfaces from two hospitals in the United States (US) and Pakistan collected over one year. MDR bacteria isolated from 3.3% and 86.7% of US and Pakistani surfaces, respectively, include common nosocomial pathogens, rare opportunistic pathogens, and novel taxa. Common nosocomial isolates are dominated by single lineages of different clones, are phenotypically MDR, and have high resistance gene burdens. Many resistance genes (e.g., blaNDM, blaOXA carbapenamases), are shared by multiple species and flanked by mobilization elements. We identify Acinetobacter baumannii and Enterococcus faecium co-association on multiple surfaces, and demonstrate these species establish synergistic biofilms in vitro. Our results highlight substantial MDR pathogen burdens in hospital built-environments, provide evidence for spatiotemporal-dependent transmission, and demonstrate potential mechanisms for multi-species surface persistence.


Assuntos
Antibacterianos/farmacologia , Infecção Hospitalar/transmissão , Farmacorresistência Bacteriana Múltipla/genética , Contaminação de Equipamentos , Unidades de Terapia Intensiva , Acinetobacter baumannii/efeitos dos fármacos , Acinetobacter baumannii/isolamento & purificação , Acinetobacter baumannii/fisiologia , Antibacterianos/uso terapêutico , Biofilmes/efeitos dos fármacos , Infecção Hospitalar/tratamento farmacológico , Infecção Hospitalar/microbiologia , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Enterococcus faecium/efeitos dos fármacos , Enterococcus faecium/isolamento & purificação , Enterococcus faecium/fisiologia , Humanos , Testes de Sensibilidade Microbiana , Paquistão , Análise Espaço-Temporal , Estados Unidos
16.
Rev Soc Bras Med Trop ; 52: e20190237, 2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31508785

RESUMO

INTRODUCTION: The increased use of colistin against infections caused by Acinetobacter baumannii and Pseudomonas aeruginosa has resulted in colistin resistance. The purpose of this study was to detect plasmid-mediated mcr-1 gene in colistin-resistant A. baumannii and P. aeruginosa isolates. METHODS: A total of 146 clinical isolates of A. baumannii (n = 62) and P. aeruginosa (n = 84) were collected from the four largest tertiary care hospitals in Peshawar, Pakistan. All bacterial isolates were phenotypically screened for multidrug resistance using the Kirby-Baur disc diffusion method. The minimum inhibitory concentration (MIC) of colistin in all isolates was phenotypically performed using dilution methods. mcr-1 gene was detected through polymerase chain reaction and the nucleotide sequence of amplicon was determined using Sanger sequencing. RESULTS: Approximately 96.7% A. baumannii and 83.3% P. aeruginosa isolates were resistant to multiple antibiotics. Colistin resistance was found in 9.6% (6/62) of A. baumannii and 11.9% (10/84) of P. aeruginosa isolates. Among 16 colistin resistant isolates, the mcr-1 gene was detected in one A. baumannii (1.61% of total isolates; 16.6% of colistin resistant isolates) and one P. aeruginosa strain (1.19% of total isolates; 10% of colistin resistant isolates). Nucleotide BLAST showed 98-99% sequence similarity to sequences of the mcr-1 gene in GenBank. CONCLUSIONS: Our study reports, for the first time, the emergence of plasmid-mediated mcr-1-encoded colistin resistance in multidrug resistant strains of A. baumannii and P. aeruginosa. Further large scales studies are recommended to investigate the prevalence of this mode of resistance in these highly pathogenic bacteria.


Assuntos
Infecções por Acinetobacter/microbiologia , Acinetobacter baumannii/genética , Proteínas de Bactérias/genética , Infecções por Pseudomonas/microbiologia , Pseudomonas aeruginosa/genética , Acinetobacter baumannii/efeitos dos fármacos , Farmacorresistência Bacteriana , Humanos , Testes de Sensibilidade Microbiana , Paquistão , Plasmídeos/genética , Pseudomonas aeruginosa/efeitos dos fármacos
17.
J Med Microbiol ; 68(11): 1607-1613, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31535963

RESUMO

Introduction. Colistin is a last-resort antibiotic used against carbapenem-resistant Acinetobacter baumannii (AB); however, colistin resistance has been reported recently. Methylene blue (MB) is used in microbiology for staining, and in medicine as an antidote drug.Aim. We aimed to investigate the antimicrobial effects of MB and eosin methylene blue (EMB) agar against colistin-resistant AB strains.Methodology. Firstly, a standard strain and AB clinical isolate were included in the study. After determining MICs, two strains were transformed into colistin-resistant forms, using Li's method. At each step, new MICs were determined and subcultures were inoculated onto EMB and sheep blood agar (SBA). Colistin MICs of the subcultures were also determined using Mueller-Hinton agar (MHA) containing MB. Secondly, colistin-resistant clones from 31 multidrug-resistant AB clinical isolates were screened to investigate their susceptibilities to EMB agar.Results. In the first round, MICs of both strains had risen to 64 µg ml-1. Subpopulations with high colistin resistance were inhibited by MB and EMB agar, but could grow well on SBA. In MHA plates containing MB, the MICs decreased to 0.5 µg ml-1 for colistin-susceptible or moderately resistant clones. Additionally, clones with high colistin resistance showed atypical colony morphology on SBA. In the second round, 35 % of the clinical isolates, which had gained resistance to colistin, were inhibited by EMB agar.Conclusion. MB may have inhibitory effects against colistin-resistant AB. Secondly, using only EMB agar for subculturing may cause missing of colistin-resistant strains.


Assuntos
Acinetobacter baumannii/efeitos dos fármacos , Antibacterianos/farmacologia , Colistina/farmacologia , Amarelo de Eosina-(YS)/farmacologia , Azul de Metileno/farmacologia , Acinetobacter baumannii/crescimento & desenvolvimento , Farmacorresistência Bacteriana , Testes de Sensibilidade Microbiana
19.
Molecules ; 24(17)2019 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-31470632

RESUMO

Antimicrobial resistance in bacteria is frightening, especially resistance in Gram-negative Bacteria (GNB). In 2017, the World Health Organization (WHO) published a list of 12 bacteria that represent a threat to human health, and among these, a majority of GNB. Antibiotic resistance is a complex and relatively old phenomenon that is the consequence of several factors. The first factor is the vertiginous drop in research and development of new antibacterials. In fact, many companies simply stop this R&D activity. The finding is simple: there are enough antibiotics to treat the different types of infection that clinicians face. The second factor is the appearance and spread of resistant or even multidrug-resistant bacteria. For a long time, this situation remained rather confidential, almost anecdotal. It was not until the end of the 1980s that awareness emerged. It was the time of Vancomycin-Resistance Enterococci (VRE), and the threat of Vancomycin-Resistant MRSA (Methicillin-Resistant Staphylococcus aureus). After this, there has been renewed interest but only in anti-Gram positive antibacterials. Today, the threat is GNB, and we have no new molecules with innovative mechanism of action to fight effectively against these bugs. However, the war against antimicrobial resistance is not lost. We must continue the fight, which requires a better knowledge of the mechanisms of action of anti-infectious agents and concomitantly the mechanisms of resistance of infectious agents.


Assuntos
Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana Múltipla , Drogas em Investigação/uso terapêutico , Enterobacteriaceae/efeitos dos fármacos , Saúde Global/tendências , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Acinetobacter baumannii/efeitos dos fármacos , Acinetobacter baumannii/patogenicidade , Acinetobacter baumannii/fisiologia , Aminoglicosídeos/síntese química , Aminoglicosídeos/economia , Aminoglicosídeos/uso terapêutico , Antibacterianos/síntese química , Antibacterianos/economia , Aprovação de Drogas/organização & administração , Drogas em Investigação/síntese química , Drogas em Investigação/economia , Enterobacteriaceae/patogenicidade , Enterobacteriaceae/fisiologia , Fluoroquinolonas/síntese química , Fluoroquinolonas/economia , Fluoroquinolonas/uso terapêutico , Saúde Global/economia , Glicopeptídeos/síntese química , Glicopeptídeos/economia , Glicopeptídeos/uso terapêutico , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Negativas/patogenicidade , Bactérias Gram-Negativas/fisiologia , Infecções por Bactérias Gram-Negativas/microbiologia , Infecções por Bactérias Gram-Negativas/patologia , Humanos , Macrolídeos/síntese química , Macrolídeos/economia , Macrolídeos/uso terapêutico , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/patogenicidade , Pseudomonas aeruginosa/fisiologia , beta-Lactamas/síntese química , beta-Lactamas/economia , beta-Lactamas/uso terapêutico
20.
J Appl Microbiol ; 127(5): 1421-1429, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31400237

RESUMO

AIMS: The present study was conducted to investigate the mechanism of carbapenem resistance and the molecular epidemiology of carbapenem-resistant Acinetobacter baumannii (CRAB) isolates collected from two nearby hospitals in Tehran, Iran. METHODS AND RESULTS: A total of 180 CRAB isolates were studied. Antimicrobial susceptibility testing was performed using disk diffusion and Epsilometer tests. The detection of OXA-23, -24 and -58 was implemented for all isolates using polymerase chain reaction. Subsequently, isolates harbouring OXA-24 and -58 were investigated for the presence of resistance determinants of Ambler class A, metallo-ß-lactamases (MBLs), and carbapenem-hydrolysing class D ß-lactamases, ISAba1, and the genetic relatedness between them was analysed using pulsed-field gel electrophoresis (PFGE). All isolates were found to be resistant to imipenem with a MIC of ≥8 µg ml-1 and were susceptible to colistin with a MIC of ≤1·5 µg ml-1 . Sixty percent of the isolates had OXA-23. OXA-24 and -58 were detected in 31 of 180 CRAB isolates. These chosen isolates were devoid of MBLs and blaSHV , blaC TX-M , blaVEB ESBL genes. The PER determinant was detected in 38% of isolates as the most common extended spectrum ß-lactamases (ESBLs). Of these isolates, 51·6% had OXA-23, and ISAba1 was found to be upstream of OXA-23 and OXA-51 in 16 and 8 isolates, respectively. The band patterns produced by PFGE showed nine clonal pulsotypes distributed between the two hospitals. CONCLUSION: The findings showed that the refractory CRAB isolates were transmitted intra- and inter-hospital, particularly in the ICU due to shortcomings in infection control surveillance. SIGNIFICANCE AND IMPACT OF THE STUDY: Carbapenem resistance is a substantial threat in the treatment of infections caused by A. baumannii due to limitations in the therapeutic options.


Assuntos
Infecções por Acinetobacter/microbiologia , Acinetobacter baumannii/efeitos dos fármacos , Antibacterianos/farmacologia , Proteínas de Bactérias/metabolismo , Carbapenêmicos/farmacologia , beta-Lactamases/metabolismo , Infecções por Acinetobacter/epidemiologia , Acinetobacter baumannii/classificação , Acinetobacter baumannii/enzimologia , Acinetobacter baumannii/genética , Proteínas de Bactérias/genética , Colistina/farmacologia , Farmacorresistência Bacteriana , Humanos , Imipenem/farmacologia , Irã (Geográfico)/epidemiologia , Testes de Sensibilidade Microbiana , beta-Lactamases/genética
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