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1.
Braz. J. Pharm. Sci. (Online) ; 57: e19048, 2021. tab, graf
Article in English | LILACS | ID: biblio-1345460

ABSTRACT

Drug-resistant Acinetobacter baumannii is a frightening reality. The aim of this study is to examine the expression profiles of blaOXA-51 gene in carbapenemases producing A. baumannii treated with imipenem/sulbactam combination. Carbapenemases producing A. baumannii was identified among clinical isolates of A. baumannii obtained from patients at Shahid Rajaee hospital, Gachsaran, Iran, from January to June 2018. Synergism testing of imipenem/sulbactam on carbapenemases producing A. baumannii was carried out by broth microdilution method. Eventually, the expression of blaOXA-51 gene was carried out to investigate the inhibitory properties of imipenem/sulbactam combination against carbapenemases producing A. baumannii using quantitative real time RT-PCR. Among A. baumannii isolates, 24% were carbapenemases producing A. baumannii. Imipenem/sulbactam combination revealed synergistic and partial synergistic effect for all tested isolates (FIC= 0.313-0.75). Finally, imipenem/sulbactam combination displayed significant down-regulation of blaOXA-51 gene in carbapenemases producing A. baumannii. Imipenem synergizes with sulbactam against carbapenemases producing A. baumannii by targeting of the blaOXA-51 gene.


Subject(s)
Sulbactam/agonists , Imipenem/agonists , Acinetobacter baumannii/drug effects , Patients/classification , In Vitro Techniques/instrumentation , Pharmaceutical Preparations/analysis , Hospitals/classification , Methods
2.
Rev. chil. infectol ; 37(1): 87-88, feb. 2020.
Article in Spanish | LILACS | ID: biblio-1092727

ABSTRACT

Resumen Utilizando cepas clínicas de bacilos gramnegativos multi-resistentes (MDR), comparamos las CIM obtenidas de la microdilución en caldo, el método de referencia y el método de elución de sensidiscos. Encontramos que, con la excepción de A. baumannii, los resultados fueron muy similares. El método de elución de sensidiscos podría ser una buena alternativa y confiable para la determinación de la resistencia a colistín.


Abstract Using clinical strains of multidrug resistant (MDR) Gram negative bacilli, we compared MICs obtained from both broth microdilution, the reference method, and sensi-disk elution method. We found that, with A. baumannii exception, results were very similar. Sensi-disk elution method could be a good and reliable alternative for colistin resistance determination.


Subject(s)
Microbial Sensitivity Tests/methods , Microbial Sensitivity Tests/standards , Colistin/pharmacology , Gram-Negative Bacteria/drug effects , Anti-Bacterial Agents/pharmacology , Drug Resistance, Multiple, Bacterial , Acinetobacter baumannii/drug effects
3.
Mem. Inst. Oswaldo Cruz ; 115: e200371, 2020. tab, graf
Article in English | SES-SP, LILACS, SES-SP | ID: biblio-1135238

ABSTRACT

BACKGROUND Acinetobacter baumannii outbreaks have been associated with pandemic International Clones (ICs), but the virulence factors involved with their pathogenicity are sparsely understood. Pigment production has been linked with bacterial pathogenicity, however, this phenotype is rarely observed in A. baumannii. OBJECTIVES This study aimed to characterise the reddish-brown pigment produced by A. baumannii strains, and to determine its biosynthetic pathway by genomic approaches. METHODS Pigment characterisation and antimicrobial susceptibility were conducted by phenotypic tests. The clonal relationship was obtained by pulsed field gel electrophoresis (PFGE) and multi-locus sequence typing (MLST). The genome of an A. baumannii was obtained for characterisation of genes involved with pigment production. FINDINGS The pyomelanin was the pigment produced by A. baumannii. Strains were extensively drug resistant and belonged to the IC-5/ST79. The pyomelanin biosynthetic pathway was determined and presented a particular architecture concerning the peripheral (tyrB, phhB and hpd) and central (hmgB, hmgC and hmgR) metabolic pathway genes. The identification of a distant HmgA homologue, probably without dioxygenase activity, could explain pyomelanin production. Virulence determinants involved with adherence (csuA/BABCDE and a T5bSS-carrying genomic island), and iron uptake (basABCDEFGHIJ, bauABCDEF and barAB) were characterised. MAIN CONCLUSION There is a biosynthetic pathway compatible with the pyomelanin production observed in persistent A. baumannii IC-5 strains.


Subject(s)
Humans , Acinetobacter Infections/microbiology , Acinetobacter baumannii/drug effects , Acinetobacter baumannii/genetics , Biosynthetic Pathways/genetics , Melanins , beta-Lactamases , Microbial Sensitivity Tests , Electrophoresis, Gel, Pulsed-Field , Acinetobacter baumannii/isolation & purification , Multilocus Sequence Typing , Pandemics , Anti-Bacterial Agents/pharmacology
4.
Rev. Soc. Bras. Med. Trop ; 53: e20190044, 2020. tab
Article in English | LILACS | ID: biblio-1057279

ABSTRACT

Abstract 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.


Subject(s)
Humans , Bacterial Proteins/genetics , beta-Lactamases/genetics , Acinetobacter Infections/microbiology , Acinetobacter baumannii/enzymology , Aminoglycosides/genetics , Brazil , Microbial Sensitivity Tests , Drug Resistance, Multiple, Bacterial , Acinetobacter baumannii/isolation & purification , Acinetobacter baumannii/drug effects , Tertiary Care Centers , Intensive Care Units , Anti-Bacterial Agents/pharmacology
5.
Rev. epidemiol. controle infecç ; 9(4): 281-286, out.-dez. 2019. ilus
Article in Portuguese | LILACS | ID: biblio-1152242

ABSTRACT

Justificativa e objetivos: Infecções Relacionadas à Assistência à Saúde (IRAS) causadas por bacilos Gram negativos multirresistentes (BGN-MDR) são consideradas um problema de saúde pública e um impacto nas taxas de mortalidade nas Unidades de Terapia Intensiva (UTI). O objetivo deste estudo foi verificar o perfil fenotípico de resistência à colistina e à tigeciclina, consideradas como último recurso terapêutico aos BGN-MDR. Métodos: Os dados foram coletados nas fichas de busca ativa do serviço de controle de infecções e prontuários médicos de pacientes internados em duas UTIs de um hospital público de Joinville, entre janeiro de 2016 e junho de 2017. Resultados: Ocorreram 256 IRAS por BGN, acometendo principalmente o gênero masculino (62%), com mediana de idade de 65 anos. Entre os BGN, 37% expressaram MDR; sendo as espécies mais frequentes: Klebsiella pneumoniae e (47%), Acinetobacter baumannii (23%) e Stenotrophomonas maltophilia (11%). A resistência de BGN-MDR à colistina e tigeciclina foi de 5% e de 12%, respectivamente; 5% dos isolados foram resistentes aos dois antibióticos. A taxa de óbito entre os pacientes com IRAS por BGN-MDR resistentes à colistina foi mais alta (60%) que aquelas à tigeciclina (45%). Conclusão: K. pneumoniae e A. baumannii produtores de carbapenemases, resistentes a colistina e tigeciclina prevaleceram entre os BGN-MDR, e estiveram associadas a maioria dos óbitos. Essas observações, junto com o alto uso de carbapenêmicos na terapia empírica, mostra a necessidade do uso racional de antimicrobianos.(AU)


Background and objectives: Healthcare-associated Infections (HAIs) caused by multidrug-resistant Gram-negative bacilli (GNB-MDR) are considered a public health problem and have an impact on mortality rates in Intensive Care Units (ICU). The aim of this study was to verify the phenotypic profile of resistance to colistin and tigecycline, considered as the last antimicrobial choice to treat BGNMDR infections. Methods: Data were collected on the active search records of the infection control service and medical records of patients admitted to two ICUs at a public hospital in Joinville between January 2016 and June 2017. Results: There were 256 HAIs caused by GNB, mainly affecting males (62%), with a median age of 65 years. Among GNBs, 37% expressed MDR; the most frequent species were: Klebsiella pneumoniae (47%), Acinetobacter baumannii (23%) and Stenotrophomonas maltophilia (11%). The resistance of GNB-MDR to colistin and tigecycline was 5% and 12%, respectively; 5% of the isolates were resistant to both antibiotics. The death rate among patients with HAIs caused by colistin-resistant GNB-MDR was higher (60%) than those to tigecycline (45%). Conclusion: Carbapenemase-producing K. pneumoniae and A. baumannii, resistant to colistin and tigecycline, prevailed among GNB-MDRs, and were associated with most deaths. These observations, coupled with the high use of carbapenems in empirical therapy, show the need for rational use of antimicrobials.(AU)


Justificación y objetivos: Las Infección nosocomial (IHs) causadas por bacilos Gram negativos multirresistentes (BGN-MDR) se consideran un problema de salud pública y un impacto en las tasas de mortalidad en las Unidades de Terapia Intensiva (UTI). El objetivo de este estudio fue verificar el perfil fenotípico de resistencia a la colistina ya la tigeciclina, consideradas como último recurso terapéutico a los BGN-MDR. Métodos: Los datos fueron recolectados en las fichas de búsqueda activa del servicio de control de infecciones y prontuarios médicos de pacientes internados en dos UTIs de un hospital público de Joinville, entre enero de 2016 y junio de 2017. Resultados: Ocurrieron 256 IHs por BGN, que afectan principalmente al género masculino (62%), con mediana de edad de 65 años. Entre los BGN, el 37% expresó MDR; siendo las especies más frecuentes: Klebsiella pneumoniae (47%), Acinetobacter baumannii (23%) y Stenotrophomonas maltophilia (11%). La resistencia de BGN-MDR a la colistina y tigeciclina fue del 5% y del 12%, respectivamente; 5% de los aislados fueron resistentes a los dos antibióticos. La tasa de muerte entre los pacientes con IH causadas por los BGN-MDR resistentes la colistina fue más alta (60%) que aquellas a tigeciclina (45%). Conclusión: K. pneumoniae y A. baumannii productoras de carbapenemases, resistentes la colistina y la tigeciclina, fueron más frecuentes entre los BGN-MDR y su asociación estuvo presente en la mayoría de las muertes. Estas observaciones, junto con el alto uso de carbapenems en la terapia empírica, muestran la necesidad de un uso racional de los antimicrobianos.(AU)


Subject(s)
Humans , Male , Female , Adolescent , Adult , Middle Aged , Aged , Young Adult , Colistin/pharmacology , Drug Resistance, Multiple, Bacterial , Tigecycline/pharmacology , Gram-Negative Bacteria/drug effects , Anti-Bacterial Agents/pharmacology , Phenotype , Cross Infection/drug therapy , Gram-Negative Bacterial Infections/drug therapy , Colistin/therapeutic use , Stenotrophomonas maltophilia/drug effects , Stenotrophomonas maltophilia/genetics , Acinetobacter baumannii/drug effects , Acinetobacter baumannii/genetics , Tigecycline/therapeutic use , Gram-Negative Bacteria/genetics , Hospitalization , Klebsiella pneumoniae/drug effects , Klebsiella pneumoniae/genetics , Anti-Bacterial Agents/therapeutic use
6.
Rev. Soc. Bras. Med. Trop ; 52: e20180502, 2019. tab, graf
Article in English | LILACS | ID: biblio-1041563

ABSTRACT

Abstract INTRODUCTION: Plant products are sources for drug development against multidrug resistant bacteria. METHODS The antimicrobial activity of Origanum vulgare L. essential oil (OVeo) against carbapenem-resistant strains was assessed by disk-diffusion, microdilution (REMA-Resazurin Microtiter Assay), and time kill assays. RESULTS Carbapenemase production was confirmed for all strains. OVeo exhibited a minimum inhibitory concentration of 0.059% v/v for Klebsiella pneumoniae and Serratia marcescens, and of 0.015 % v/v for Acinetobacter baumannii. A decrease in cell count was observed after a 4 h treatment. CONCLUSIONS OVeo antimicrobial effect was rapid and consistent, making it a candidate for developing alternative therapeutic options against carbapenem-resistant strains.


Subject(s)
Humans , Serratia marcescens/drug effects , Oils, Volatile/pharmacology , Acinetobacter baumannii/drug effects , Origanum/chemistry , Gram-Negative Bacteria/drug effects , Klebsiella pneumoniae/drug effects , Anti-Bacterial Agents/pharmacology , Serratia marcescens/growth & development , Bacterial Proteins , beta-Lactamases , Microbial Sensitivity Tests , Carbapenems/pharmacology , Drug Resistance, Multiple, Bacterial , Acinetobacter baumannii/growth & development , Gram-Negative Bacteria/growth & development , Klebsiella pneumoniae/growth & development , Anti-Bacterial Agents/classification
7.
Rev. Soc. Bras. Med. Trop ; 52: e20190237, 2019. tab, graf
Article in English | LILACS | ID: biblio-1020446

ABSTRACT

Abstract 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.


Subject(s)
Humans , Pseudomonas aeruginosa/genetics , Pseudomonas Infections/microbiology , Bacterial Proteins/genetics , Acinetobacter Infections/microbiology , Acinetobacter baumannii/genetics , Pakistan , Plasmids/genetics , Pseudomonas aeruginosa , Microbial Sensitivity Tests , Drug Resistance, Bacterial , Acinetobacter baumannii/drug effects
9.
Braz. j. infect. dis ; 22(5): 438-441, Sept.-Oct. 2018. tab, graf
Article in English | LILACS | ID: biblio-1039218

ABSTRACT

ABSTRACT Acinetobacter baumannii is one of the most frequent Gram-negative opportunistic pathogens associated with hospital-acquired infection worldwide. We briefly describe A. baumannii isolates that were recovered from surrounding ICU bed surfaces, exhibiting multidrug resistance phenotype and belonging to some widely spread clonal complexes of clinical A. baumannii isolates.


Subject(s)
Beds/microbiology , Drug Resistance, Multiple, Bacterial/genetics , Acinetobacter baumannii/isolation & purification , Intensive Care Units , Bacteria/isolation & purification , Bacteria/drug effects , Brazil , Microbial Sensitivity Tests , Cross Infection/microbiology , Acinetobacter baumannii/drug effects , Acinetobacter baumannii/genetics , Tertiary Care Centers , Genes, Bacterial
10.
Rev. chil. infectol ; 34(4): 413-414, ago. 2017.
Article in Spanish | LILACS | ID: biblio-1042639

ABSTRACT

Currently, there is a controversy in how to determine the minimal inhibitory concentration (MIC) of colistin against Acinetobacter baumannii. We compared three methods, concluding that the addition of Tween-80 (0.002%) to Müller-Hinton broth in the microdilution method could improve MIC determination and it could reduce false resistance.


Subject(s)
Humans , Microbial Sensitivity Tests/methods , Colistin/pharmacology , Acinetobacter baumannii/drug effects , Anti-Bacterial Agents/pharmacology
11.
Rev. Soc. Bras. Med. Trop ; 50(2): 167-172, Mar.-Apr. 2017. tab
Article in English | LILACS | ID: biblio-842841

ABSTRACT

Abstract INTRODUCTION: Acinetobacter baumannii is a major pathogen causing infections in intensive care units (ICUs). In this study, we aimed to evaluate the presence of A. baumannii in an ICU environment and gloves from ICU workers and to characterize the antimicrobial resistance of the isolates in comparison with those isolated from ICU patients at the same hospital. METHODS: ICU samples were collected from March to November 2010. Isolates biochemically characterized as Acinetobacter calcoaceticus-Acinetobacter baumannii complex were evaluated by PCR targeting the 16S rDNA and bla OXA-51 genes. Antimicrobial susceptibility was determined using the disk diffusion method, and carbapenem-resistant isolates were also evaluated for the minimum inhibitory concentration of imipenem using broth microdilution. The presence of the bla OXA-23 gene was evaluated in isolates with reduced susceptibility to carbapenems. RESULTS: A. baumannii was detected in 9.5% (84) of the 886 samples collected from the ICU environment, including from furniture, medical devices, and gloves, with bed rails being the most contaminated location (23.8%; 20/84). Multidrug-resistant (MDR) A. baumannii was found in 98.8% (83/84) of non-clinical and 97.8% (45/46) of clinical isolates. Reduced susceptibility to carbapenems was detected in 83.3% (70/84) of non-clinical and 80.4% (37/46) of clinical isolates. All isolates resistant to carbapenems harbored bla OXA-23. CONCLUSIONS: We found a strong similarity between the antimicrobial susceptibility profiles of non-clinical and clinical A. baumannii isolates. Such data highlight the ICU environment as a potential origin for the persistence of MDR A. baumannii, and hence the ICU may be a source of hospital-acquired infections caused by this microorganism.


Subject(s)
Humans , Carbapenems/pharmacology , Polymerase Chain Reaction , Gloves, Protective/microbiology , Acinetobacter baumannii/drug effects , Environmental Microbiology , Equipment and Supplies, Hospital/microbiology , Anti-Bacterial Agents/pharmacology , Drug Resistance, Bacterial , Acinetobacter baumannii/isolation & purification , Acinetobacter baumannii/enzymology , Disk Diffusion Antimicrobial Tests
12.
Braz. j. microbiol ; 47(4): 785-792, Oct.-Dec. 2016. tab
Article in English | LILACS | ID: biblio-828193

ABSTRACT

Abstract Acinetobacter baumannii is widely recognized as an important pathogen associated with nosocomial infections. The treatment of these infections is often difficult due to the acquisition of resistance genes. A. baumannii presents a high genetic plasticity which allows the accumulation of these resistance determinants leading to multidrug resistance. It is highlighted the importance of the horizontal transfer of resistance genes, through mobile genetic elements and its relationship with increased incidence of multidrug resistant A. baumannii in hospitals. Considering that resistance to carbapenems is very important from the clinical and epidemiological point of view, the aim of this article is to present an overview of the current knowledge about genetic elements related to carbapenem resistance in A. baumannii such as integrons, transposons, resistance islands and insertion sequences.


Subject(s)
DNA, Bacterial , DNA Transposable Elements , Carbapenems/pharmacology , beta-Lactam Resistance , Acinetobacter baumannii/drug effects , Acinetobacter baumannii/genetics , Anti-Bacterial Agents/pharmacology , Mutagenesis, Insertional , Integrons , Genomic Islands
13.
Braz. j. infect. dis ; 20(6): 556-563, Nov.-Dec. 2016. tab
Article in English | LILACS | ID: biblio-828166

ABSTRACT

ABSTRACT Background: Carbapenem-resistant Acinetobacter baumannii (CRAb) is an important cause of nosocomial infections especially in intensive care units. This study aimed to assess clinical aspects and the genetic background of CRAb among ICU patients at a Brazilian teaching hospital. Methods: 56 critically ill patients colonized or infected by CRAb, during ICU stay, were prospectively assessed. Based on imipenem MIC ≥ 4 µg/mL, 28 CRAB strains were screened for the presence of genes encoding metallo-β-lactamases and OXA-type β-lactamases. The blaOXA-type genes were characterized by PCR using primers targeting ISAba-1 or -3. Genetic diversity of blaOXA-positive strains was determined by ERIC-PCR analysis. Results: Patient's mean age (±SD) was 61 (±15.1), and 58.9% were male. Eighty-percent of the patients presented risk factors for CRAb colonization, mainly invasive devices (87.5%) and previous antibiotic therapy (77.6%). Thirty-three patients died during hospital stay (59.0%). Resistance to carbapenems was associated with a high prevalence of blaOXA-23 (51.2%) and/or blaOXA-143 (18.6%) genes. ERIC-PCR genotyping identified 10 clusters among OXA-producing CRAb. Three CRAb strains exhibited additional resistance to polymyxin B (MIC ≥ 4 µg/mL), whereas 10 CRAb strains showed tigecycline MICs > 2 µg/mL. Conclusions: In this study, clonally unrelated OXA-123- and OXA-143-producing A. baumannii strains in ICU patients were strongly correlated to colonization with infected patients being associated with a poor outcome.


Subject(s)
Humans , Male , Female , Middle Aged , beta-Lactamases/biosynthesis , Acinetobacter Infections/microbiology , Cross Infection/microbiology , Acinetobacter baumannii/enzymology , Anti-Bacterial Agents/pharmacology , beta-Lactamases/genetics , Brazil , Microbial Sensitivity Tests , Prospective Studies , Acinetobacter baumannii/drug effects , Acinetobacter baumannii/genetics , Multiplex Polymerase Chain Reaction , Genotype , Hospitals, Teaching , Intensive Care Units
14.
Rev. Soc. Bras. Med. Trop ; 49(4): 433-440, July-Aug. 2016. tab, graf
Article in English | LILACS | ID: lil-792800

ABSTRACT

Abstract: INTRODUCTION: Members of the Acinetobacter genus are key pathogens that cause healthcare-associated infections, and they tend to spread and develop new antibiotic resistance mechanisms. Oxacillinases are primarily responsible for resistance to carbapenem antibiotics. Higher rates of carbapenem hydrolysis might be ascribed to insertion sequences, such as the ISAba1 sequence, near bla OXA genes. The present study examined the occurrence of the genetic elements bla OXA and ISAba1 and their relationship with susceptibility to carbapenems in clinical isolates of the Acinetobacter calcoaceticus-Acinetobacter baumannii complex. METHODS: Isolates identified over 6 consecutive years in a general hospital in Joinville, Southern Brazil, were evaluated. The investigation of 5 families of genes encoding oxacillinases and the ISAba1 sequence location relative to bla OXA genes was conducted using polymerase chain reaction. RESULTS: All isolates presented the bla OXA-51-like gene (n = 78), and 91% tested positive for the bla OXA-23-like gene (n = 71). The presence of ISAba1 was exclusively detected in isolates carrying the bla OXA-23-like gene. All isolates in which ISAba1 was found upstream of the bla OXA-23-like gene (n = 69) showed resistance to carbapenems, whereas the only isolate in which ISAba1 was not located near the bla OXA-23-like gene was susceptible to carbapenems. The ISAba1 sequence position of another bla OXA-23-like-positive isolate was inconclusive. The isolates exclusively carrying the bla OXA-51-like gene (n = 7) showed susceptibility to carbapenems. CONCLUSIONS: The presence of the ISAba1 sequence upstream of the bla OXA-23-like gene was strongly associated with carbapenem resistance in isolates of the A. calcoaceticus-A. baumannii complex in the hospital center studied.


Subject(s)
Humans , Bacterial Proteins/genetics , DNA, Bacterial/genetics , Carbapenems/pharmacology , Acinetobacter calcoaceticus/drug effects , beta-Lactam Resistance/genetics , Acinetobacter baumannii/drug effects , Anti-Bacterial Agents/pharmacology , Phenotype , Bacterial Proteins/metabolism , Brazil , Acinetobacter Infections/microbiology , Polymerase Chain Reaction , Electrophoresis, Gel, Pulsed-Field , Acinetobacter calcoaceticus/isolation & purification , Acinetobacter calcoaceticus/genetics , Acinetobacter baumannii/isolation & purification , Acinetobacter baumannii/genetics , Genotype
15.
Rev. Soc. Bras. Med. Trop ; 49(2): 165-171, Mar.-Apr. 2016. tab, graf
Article in English | LILACS | ID: lil-782103

ABSTRACT

Abstract: INTRODUCTION: Due to the wide use of tigecycline in the treatment of severe infections caused by multidrug-resistant (MDR) bacteria, clinical resistance to tigecycline has increased in recent years. Here, we investigated the relationship between tigecycline resistance and the expression of efflux pumps. METHODS: Clinical isolates of Acinetobacter baumannii and Klebsiella pneumoniae were consecutively collected from hospitalized patients in three hospitals. The minimum inhibitory concentration (MIC) of tigecycline was determined using the broth microdilution method. Expression levels of efflux pump genes and regulators were examined by quantitative real-time reverse transcription polymerase chain reaction. The correlations between tigecycline MICs and gene expression levels were analyzed. RESULTS: Overall, 1,026 A. baumannii and 725 K. pneumoniae strains were collected. Most strains were isolated from sputum. The tigecycline resistance rate was 13.4% in A. baumannii isolates and 6.5% in K. pneumoniae isolates. Overexpression of AdeABC and AcrAB-TolC efflux systems was observed found in clinical tigecycline-resistant isolates. The tigecycline MIC had a linear relationship with the adeB expression level in A. baumannii isolates, but not with the acrB expression level in K. pneumoniae isolates. There were significant linear trends in the overexpression of ramA as the tigecycline MIC increased in K. pneumoniae isolates. CONCLUSIONS: Tigecycline resistance in A. baumannii and K. pneumoniae was strongly associated with the overexpression of efflux systems. More studies are needed to elucidate whether there are other regulators that affect the expression of adeB in A. baumannii and how ramA affects the expression of acrB in K. pneumoniae.


Subject(s)
Humans , Drug Resistance, Bacterial/genetics , Acinetobacter baumannii/drug effects , Klebsiella pneumoniae/drug effects , Minocycline/analogs & derivatives , Anti-Bacterial Agents/pharmacology , Microbial Sensitivity Tests , Gene Expression Regulation, Bacterial , Acinetobacter baumannii/genetics , Multilocus Sequence Typing , Real-Time Polymerase Chain Reaction , Tigecycline , Minocycline/pharmacokinetics
16.
Article in English | WPRIM | ID: wpr-109561

ABSTRACT

BACKGROUND/AIMS: Nosocomial infections caused by multidrug-resistant (MDR) Acinetobacter baumannii have become public-health problem. However, few studies have evaluated the control of endemic MDR A. baumannii in Intensive Care Units (ICUs). Therefore, we investigated the effectiveness of antimicrobial stewardship and comprehensive intensified infection control measures for controlling endemic MDR A. baumannii in ICUs at a tertiary care center. METHODS: Carbapenem use was strictly restricted through antimicrobial stewardship. Environmental cleaning and disinfection was performed at least 3 times per day in addition to basic infection control measures. Isolation using plastic curtains and contact precautions were applied to patients who were colonized or infected with MDR A. baumannii. The outcome was measured as the incidence density rate of hospital-onset MDR A. baumannii among patients in the ICUs. RESULTS: The incidence density rate of hospital-onset MDR A. baumannii decreased from 22.82 cases per 1,000 patient-days to 2.68 cases per 1,000 patient-days after the interventions were implemented (odds ratio, 0.12; 95% confidence interval, 0.03 to 0.4; p < 0.001). The mean monthly use of carbapenems also decreased from 134.99 +/- 82.26 defined daily doses per 1,000 patient-days to 94.85 +/- 50.98 defined daily doses per 1,000 patient-days (p = 0.016). CONCLUSIONS: Concomitant implementation of strict antimicrobial stewardship and comprehensive infection control measures effectively controlled endemic MDR A. baumannii in our ICUs within 1 year.


Subject(s)
Acinetobacter Infections/epidemiology , Acinetobacter baumannii/drug effects , Anti-Bacterial Agents/adverse effects , Carbapenems/adverse effects , Chi-Square Distribution , Cross Infection/epidemiology , Disinfection , Drug Resistance, Multiple, Bacterial , Endemic Diseases , Hand Disinfection , Humans , Incidence , Infection Control/methods , Microbial Sensitivity Tests , Odds Ratio , Patient Isolation , Program Evaluation , Republic of Korea/epidemiology , Risk Factors , Tertiary Care Centers , Time Factors , Treatment Outcome
17.
Article in English | WPRIM | ID: wpr-48339

ABSTRACT

BACKGROUND: We investigated the whole genome sequence (WGS) of a carbapenem-resistant Acinetobacter baumannii isolate belonging to the global clone 2 (GC2) and predicted resistance islands using a software tool. METHODS: A. baumannii strain YU-R612 was isolated from the sputum of a 61-yr-old man with sepsis. The WGS of the YU-R612 strain was obtained by using the PacBio RS II Sequencing System (Pacific Biosciences Inc., USA). Antimicrobial resistance genes and resistance islands were analyzed by using ResFinder and Genomic Island Prediction software (GIPSy), respectively. RESULTS: The YU-R612 genome consisted of a circular chromosome (ca. 4,075 kb) and two plasmids (ca. 74 kb and 5 kb). Its sequence type (ST) under the Oxford scheme was ST191, consistent with assignment to GC2. ResFinder analysis showed that YU-R612 possessed the following resistance genes: four β-lactamase genes bla(ADC-30), bla(OXA-66), bla(OXA-23), and bla(TEM-1); armA, aadA1, and aacA4 as aminoglycoside resistance-encoding genes; aac(6')Ib-cr for fluoroquinolone resistance; msr(E) for macrolide, lincosamide, and streptogramin B resistance; catB8 for phenicol resistance; and sul1 for sulfonamide resistance. By GIPSy analysis, six putative resistant islands (PRIs) were determined on the YU-R612 chromosome. Among them, PRI1 possessed two copies of Tn2009 carrying bla(OXA-23), and PRI5 carried two copies of a class I integron carrying sul1 and armA genes. CONCLUSIONS: By prediction of resistance islands in the carbapenem-resistant A. baumannii YU-R612 GC2 strain isolated in Korea, PRIs were detected on the chromosome that possessed Tn2009 and class I integrons. The prediction of resistance islands using software tools was useful for analysis of the WGS.


Subject(s)
Acinetobacter Infections/drug therapy , Acinetobacter baumannii/drug effects , Anti-Bacterial Agents/pharmacology , Bacterial Proteins/genetics , Carbapenems/therapeutic use , DNA, Bacterial/chemistry , Drug Resistance, Bacterial , Genomic Islands/genetics , Humans , Microbial Sensitivity Tests , Multilocus Sequence Typing , Plasmids/genetics , Polymerase Chain Reaction , Sequence Analysis, DNA
18.
Article in English | WPRIM | ID: wpr-34959

ABSTRACT

BACKGROUND: Acinetobacter baumannii infections are difficult to treat owing to the emergence of various antibiotic resistant isolates. Because treatment options are limited for multidrug-resistant (MDR) A. baumannii infection, the discovery of new therapies, including combination therapy, is required. We evaluated the synergistic activity of colistin, doripenem, and tigecycline combinations against extensively drug-resistant (XDR) A. baumannii and MDR A. baumannii. METHODS: Time-kill assays were performed for 41 XDR and 28 MDR clinical isolates of A. baumannii by using colistin, doripenem, and tigecycline combinations. Concentrations representative of clinically achievable levels (colistin 2 microg/mL, doripenem 8 microg/mL) and achievable tissue levels (tigecycline 2 microg/mL) for each antibiotic were used in this study. RESULTS: The colistin-doripenem combination displayed the highest rate of synergy (53.6%) and bactericidal activity (75.4%) in 69 clinical isolates of A. baumannii. Among them, thedoripenem-tigecycline combination showed the lowest rate of synergy (14.5%) and bacteri-cidal activity (24.6%). The doripenem-tigecycline combination showed a higher antagonistic interaction (5.8%) compared with the colistin-tigecycline (1.4%) combination. No antagonism was observed for the colistin-doripenem combination. CONCLUSIONS: The colistin-doripenem combination is supported in vitro by the high rate of synergy and bactericidal activity and lack of antagonistic reaction in XDR and MDR A. baumannii. It seems to be necessary to perform synergy tests to determine the appropri-ate combination therapy considering the antagonistic reaction found in several isolates against the doripenem-tigecycline and colistin-tigecycline combinations. These findings should be further examined in clinical studies.


Subject(s)
Acinetobacter Infections/drug therapy , Acinetobacter baumannii/drug effects , Anti-Bacterial Agents/pharmacology , Bacterial Proteins/genetics , Carbapenems/pharmacology , Colistin/pharmacology , Drug Resistance, Multiple, Bacterial/drug effects , Drug Synergism , Drug Therapy, Combination , Humans , Microbial Sensitivity Tests , Minocycline/analogs & derivatives , Multilocus Sequence Typing , beta-Lactamases/genetics
19.
Article in English | WPRIM | ID: wpr-34957

ABSTRACT

BACKGROUND: Extensively drug-resistant (XDR) Pseudomonas aeruginosa and Acinetobacter baumannii are a threat to hospitalized patients. We evaluated the effects of antimicrobial combinations on XDR P. aeruginosa and A. baumannii isolates. METHODS: P. aeruginosa and A. baumannii isolates, which were resistant to all antibiotics except colistin (CL), were collected from eight hospitals in Korea. Genes encoding metallo-beta-lactamases (MBLs) and OXA carbapenemases were detected by PCR in eight P. aeruginosa and 30 A. baumannii isolates. In vitro synergy of antimicrobial combinations was tested by using the checkerboard method. RESULTS: Minimum inhibitory concentrations of beta-lactams, aminoglycosides, and fluoroquinolones were very high, while that of CL was low for majority of XDR P. aeruginosa and A. baumannii isolates. Antimicrobial combinations including Imipenem (IPM)-CL, ceftazidime (CAZ)-CL, and rifampin (RIF)-CL exerted only additive/indifferent effects on majority of XDR P. aeruginosa isolates. Proportions of XDR A. baumannii isolates that showed synergistic and additive/indifferent inhibition after treatment with antimicrobial combinations used are as follows: IPM-ampicillin-sulbactam (AMS), 17% and 80% isolates, respectively; IPM-rifampin (RIF), 13% and 81% isolates, respectively; IPM-CL, 13% and 87% isolates, respectively; and RIF-COL, 20% and 73% isolates, respectively. Significant proportion (19%) of XDR P. aeruginosa isolates produced MBLs, and majority (82%) of A. baumannii isolates produced either MBLs or OXA-23. CONCLUSIONS: Our results suggest that combinations of IPM-AMS, IPM-RIF, IPM-CL, and RIF-CL are more useful than individual drugs for treating 13-20% of XDR A. baumannii infections.


Subject(s)
Acinetobacter baumannii/drug effects , Aminoglycosides/pharmacology , Anti-Infective Agents/pharmacology , Bacterial Proteins/genetics , Drug Resistance, Multiple, Bacterial/drug effects , Drug Synergism , Fluoroquinolones/pharmacology , Imipenem/pharmacology , Microbial Sensitivity Tests , Polymerase Chain Reaction , Pseudomonas aeruginosa/drug effects , beta-Lactamases/genetics
20.
Braz. j. microbiol ; 46(4): 1119-1124, Oct.-Dec. 2015. tab
Article in English | LILACS | ID: lil-769658

ABSTRACT

Abstract Acinetobacter baumannii is a frequently isolated etiologic agent of nosocomial infections, especially in intensive care units. With the increase in multi-drug resistance of A. baumannii isolates, finding appropriate treatment alternatives for infections caused by these bacteria has become more difficult, and available alternate treatments include the use of older antibiotics such as colistin or a combination of antibiotics. The current study aimed to evaluate the in vitro efficacy of various antibiotic combinations against multi-drug resistant A. baumannii strains. Thirty multi-drug and carbapenem resistant A. baumannii strains isolated at the Ankara Training and Research Hospital between June 2011 and June 2012 were used in the study. Antibiotic susceptibility tests and species-level identification were performed using conventional methods and the VITEK 2 system. The effects of meropenem, ciprofloxacin, amikacin, tigecycline, and colistin alone and in combination with sulbactam against the isolates were studied using Etest (bioMérieux) in Mueller-Hinton agar medium. Fractional inhibitory concentration index (FIC) was used to determine the efficacy of the various combinations. While all combinations showed a predominant indifferent effect, a synergistic effect was also observed in 4 of the 5 combinations. Synergy was demonstrated in 43% of the isolates with the meropenem-sulbactam combination, in 27% of the isolates with tigecycline-sulbactam, and in 17% of the isolates with colistin-sulbactam and amikacin-sulbactam. No synergy was detected with the sulbactam-ciprofloxacin combination and antagonism was detected only in the sulbactam-colistin combination (6.66% of the isolates). Antibiotic combinations can be used as an alternative treatment approach in multi-drug resistant A. baumannii infections.


Subject(s)
Acinetobacter Infections/drug effects , Acinetobacter Infections/growth & development , Acinetobacter Infections/microbiology , Acinetobacter Infections/pharmacology , Acinetobacter baumannii/drug effects , Acinetobacter baumannii/growth & development , Acinetobacter baumannii/microbiology , Acinetobacter baumannii/pharmacology , Anti-Bacterial Agents/drug effects , Anti-Bacterial Agents/growth & development , Anti-Bacterial Agents/microbiology , Anti-Bacterial Agents/pharmacology , Drug Resistance, Multiple, Bacterial/drug effects , Drug Resistance, Multiple, Bacterial/growth & development , Drug Resistance, Multiple, Bacterial/microbiology , Drug Resistance, Multiple, Bacterial/pharmacology , Drug Synergism/drug effects , Drug Synergism/growth & development , Drug Synergism/microbiology , Drug Synergism/pharmacology , Humans/drug effects , Humans/growth & development , Humans/microbiology , Humans/pharmacology , Microbial Sensitivity Tests/drug effects , Microbial Sensitivity Tests/growth & development , Microbial Sensitivity Tests/microbiology , Microbial Sensitivity Tests/pharmacology , Sulbactam/drug effects , Sulbactam/growth & development , Sulbactam/microbiology , Sulbactam/pharmacology
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