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1.
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
2.
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
4.
São Paulo; s.n; s.n; 2019. 142 p. tab, graf.
Thesis in Portuguese | LILACS | ID: biblio-1361765

ABSTRACT

Linhagens de Escherichia coli produtoras de ß-lactamase de espectro estendido (ESßL) do tipo CTX-M são endêmicas no Brasil, sendo prevalentes em casos de infecções hospitalares e ambulatoriais. Atualmente, cepas produtoras de CTX-M têm sido recuperadas de ambientes urbanos, animais de companhia ou de produção e de alimentos de origem animal, inclusive afetando o agronegócio, o que aponta uma possível rota de disseminação em diferentes ecossistemas. Recentemente, nesta espécie, foi descoberto um novo gene, chamado de mcr-1, que confere resistência transferível à colistina, um dos últimos antibióticos eficazes para o tratamento de infecções causadas por bactérias produtoras de ESBL e carbapenemases. Deste modo, o presente estudo tem como objetivo elucidar os aspectos sobre a caracterização e a relação de plasmídeos que carregam genes do tipo blaCTX-M-8 e mcr- 1 em cepas de E. coli isoladas de seres humanos, animais, ambiente aquático e alimentos, no Brasil. Neste estudo são apresentados os resultados da análise plasmidial de 25 cepas de E. coli, das quais nove apresentaram o genótipo blaCTX-M-8/IncI1, 11 apresentaram o genótipo mcr-1/IncX4 e cinco apresentaram ambos os genótipos blaCTX-M-8/IncI1 e mcr-1/IncX4. Dos resultados, podemos observar que plasmídeos IncI1 (blaCTX-M-8) e IncX4 (mcr-1) estão circulando no Brasil desde o ano de 2009 entre diferentes clones (STs) de E. coli e em diferentes ambientes e hospedeiros. Os plasmídeos IncI1 foram conjugativos e pertencentes ao ST113, exceto o plasmídeo recuperado de um isolado humano, que foi pertencente ao ST131. Os plasmídeos IncI1 apresentaram sua arquitetura conservada, com a presença de genes de replicação, transferência e estabilidade. A partir do alinhamento, os plasmídeos IncI1 apresentaram 94-99% de similaridade genética entre eles. Dentre os plasmídeos IncX4, independente da fonte de isolamento, todos permaneceram com sua arquitetura altamente conservada. Entretanto, apenas dois plasmídeos (um encontrado em uma cepa de animal e outro encontrado em uma cepa de ambiente aquático) apresentaram uma IS1294, truncando o gene de mobilização. Na análise comparativa, todos os plasmídeos IncX4 apresentaram similaridade genética de 95-99,9% entre eles. No alinhamento de plasmídeos IncX4 brasileiros contra plasmídeos de outras regiões geográficas, foi observada similaridade genética > 99,9%, o que confirma a estabilidade e conservação desses plasmídeos. Neste estudo foram reportados dados inéditos da primeira identificação do gene mcr-1 em diferentes ecossistemas no Brasil, assim como a nova variante mcr-5.3. A análise filogenética dos plasmídeos IncI1 e IncX4, destacam que ambos compartilham uma arquitetura conservada, e a evolução é atribuída à aquisição de genes de resistência. Adicionalmente, um novo vetor de disseminação do gene mcr-1 no Brasil foi identificado - o plasmídeo IncHI2. Os resultados desse estudo demonstram o grave problema da resistência bacteriana dentro do conceito One-health e que, com o avanço de ferramentas moleculares, a identificação e a resolução desse problema poderá estar cada vez mais próxima de ser elucidada


CTX-M-type extended-spectrum-ß-lactamase (ESßL)-producing-Escherichia coli are endemic in Brazil and are prevalent in cases of nosocomial and ambulatory infections. Currently, CTXM-producing strains have been recovered from urban environments, companion/production animals and animal source foods, which indicates a possible route of dissemination in different ecosystems. Recently, in this species, a new gene, called mcr-1, has been discovered, conferring transferable resistance to colistin, one of the last effective antibiotics for the treatment of infections caused by ESBL- and carbapenemases -producing bacteria. Thus, the present study aims to elucidate unknown aspects of the pan-resistome and ancestral relationship of plasmids carrying blaCTX-M-8 and mcr-1 genes in strains of E. coli isolated from humans, animals, aquatic environment and food, in Brazil. In this study, we present results from the plasmidial analysis of 25 E. coli strains, from which nine presented the blaCTX-M-8/IncI1 genotype, 11 presented the mcr-1/IncX4, and five presented both blaCTX-M-8/IncI1 and mcr-1/IncX4 genotypes. Among these results, we can observe that IncI1 (blaCTX-M-8) and IncX4 (mcr-1) plasmids are circulating in Brazil since 2009, between different E. coli clones (STs) and different hosts and environments. IncI1 plasmids were conjugative and assigned to ST113, with exception of a plasmid recovered from a human isolate, which was assigned to ST131. IncI1 plasmids presented conserved architecture, with the presence of genes of replication, transference, and stability. From the alignment analysis, IncI1 plasmids presented 94-99% genetic similarity among them. Among the IncX4 plasmids, regardless the isolation source, their architecture remained highly conserved. However, only two plasmids (one detected in an animal's strain and another detected in an aquatic environment's strain) presented an IS1294, truncating the mobilization gene. In the comparative analysis, all IncX4 plasmids presented 95-99,9% genetic similarity among them. In the alignment of Brazilian IncX4 plasmids against plasmids from other geographic regions, >99.9% genetic similarity was observed, confirming the stability and conservation of these plasmids. In this study, unprecedented data from the first identification of the mcr-1 gene in different ecosystems in Brazil, as well as the new variant, mcr-5.3. Additionally, it was identified a new dissemination vector of the mcr-1 gene in Brazil - the IncHI2 plasmid. Phylogenetic analysis of IncI1and IncX4 plasmids highlight that both share a conserved backbone, and evolution is attributed to the acquisition of clinically relevant antimicrobial resistance genes. The results from this study demonstrate the serious problem of the bacterial resistance within the "One-Health" concept and that, with the advance of molecular tools, identification and resolution of this problem may be increasingly closer to being elucidate


Subject(s)
Plasmids/analysis , Escherichia coli/genetics , Colistin/pharmacology , Aquatic Environment , Environment , Food/adverse effects , Anti-Bacterial Agents/administration & dosage
5.
Rev. Soc. Bras. Med. Trop ; 51(5): 674-675, Sept.-Oct. 2018.
Article in English | LILACS | ID: biblio-1041482

ABSTRACT

Abstract INTRODUCTION: Enterobacter cloacae is a clinically important bacterium from the Enterobacteriaceae family. This study evaluated resistance of E. cloacae strains from fish (n=14) and shrimp (n=9) to colistin. METHODS: Biochemical identification and antimicrobial susceptibility tests were carried out in an automated Vitek®2 instrument. RESULTS: Colistin resistance was observed in 21.4% and 66.7% of the strains from fish and shrimp, respectively. We observed minimum inhibitory concentrations of ≥16 mg/L and ≤5 mg/L in 8 and 15 of all strains, respectively. CONCLUSIONS: Fish and shrimp can carry drug-resistant enterobacteria, which can be of clinical interest.


Subject(s)
Animals , Shellfish/microbiology , Enterobacter cloacae/drug effects , Seafood/microbiology , Colistin/pharmacology , Penaeidae/microbiology , Anti-Bacterial Agents/pharmacology , Microbial Sensitivity Tests , Drug Resistance, Bacterial
6.
Rev. chil. infectol ; 35(4): 453-454, ago. 2018.
Article in Spanish | LILACS | ID: biblio-1042649

ABSTRACT

Recently it was described the plasmidial gene mcr-1 associated with colistin resistance. We screened by PCR and sequencing for gene mcr-1 in thirteen clinical isolates resistant to colistin. We observed amplification in one E. coli. To our knowledge, this is the first report of the presence of mcr-1 gene in Chile.


Subject(s)
Colistin/pharmacology , Escherichia coli Proteins/isolation & purification , Drug Resistance, Bacterial/genetics , Escherichia coli/isolation & purification , Escherichia coli/genetics , Anti-Bacterial Agents/pharmacology , Microbial Sensitivity Tests , Escherichia coli/drug effects , Escherichia coli Infections/microbiology
7.
Braz. j. infect. dis ; 22(3): 235-238, May-June 2018. graf
Article in English | LILACS, SES-SP, SESSP-IDPCPROD, SES-SP | ID: biblio-974217

ABSTRACT

ABSTRACT Herein we report a fatal case of donor-derived transmission of XDR-resistant carbapenemase-producing Klebsiella pneumoniae (KPC-Kp) in cardiac transplantation. A 59-year-old male patient with non-obstructive hypertrophic cardiomyopathy underwent heart transplantation. On day 5 post-operation, blood cultures from the donor were positive for colistin-resistant carbapenemase-producing K. pneumoniae (ColR KPC-Kp) susceptible only to amikacin. Recipient blood cultures were also positive for ColR KPC-Kp with the same sensitivity profile as the donor isolate with an identical PFGE pattern. The patient was treated with double-carbapenems and amikacin. The patient evolved to pericarditis, osteomyelitis, and pulmonary necrosis, all fragment cultures positive for the same agent. The patient developed septic shock, multiple organ failure and died on day 50 post-transplantation. Based on current microbiological scenario worldwide the possibility of transmitting multidrug resistant (MDR) organisms should be considered.


Subject(s)
Humans , Male , Middle Aged , Tissue Donors , Klebsiella Infections/transmission , Heart Transplantation/adverse effects , Transplant Recipients , Carbapenem-Resistant Enterobacteriaceae/isolation & purification , Klebsiella pneumoniae/isolation & purification , Klebsiella Infections/drug therapy , Risk Factors , Colistin/pharmacology , Fatal Outcome , Drug Resistance, Multiple, Bacterial , Anti-Bacterial Agents/pharmacology
8.
Clinics ; 72(10): 642-644, Oct. 2017.
Article in English | LILACS | ID: biblio-1039534

ABSTRACT

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.


Subject(s)
Humans , Female , Aged , Carbapenems/pharmacology , Bacteremia/drug therapy , Colistin/pharmacology , Escherichia coli Proteins/drug effects , Escherichia coli/drug effects , Anti-Bacterial Agents/pharmacology , Plasmids/drug effects , Brazil , Microbial Sensitivity Tests , Escherichia coli Proteins/isolation & purification , Escherichia coli Proteins/genetics , Drug Resistance, Multiple, Bacterial , Escherichia coli/isolation & purification , Escherichia coli/genetics , Escherichia coli Infections/drug therapy
9.
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
10.
Braz. j. infect. dis ; 21(1): 98-101, Jan.-Feb. 2017. tab
Article in English | LILACS | ID: biblio-1039180

ABSTRACT

Abstract Colistin resistance involving Gram-negative bacilli infections is a challenge for health institutions around of the world. Carbapenem-resistance among these isolates makes colistin the last therapeutic option for this treatment. Colistin resistance among Enterobacteriaceae, Acinetobacter spp., and Pseudomonas spp. was evaluated between 2010 and 2014 years, at Hospital das Clínicas, São Paulo, Brazil. Over five years 1346 (4.0%) colistin resistant Gram-negative bacilli were evaluated. Enterobacteriaceae was the most frequent (86.1%) pathogen isolated, followed by Acinetobacter spp. (7.6%), and Pseudomonas spp. (6.3%). By temporal analysis there was a trend for an increase of colistin resistance among Enterobacteriaceae, but not among non-fermentative isolates. Among 1346 colistin resistant isolates, carbapenem susceptibility was observed in 21.5%. Colistin resistance in our hospital has been alarmingly increased among Klebsiella pneumoniae isolates in both KPC positive and negative, thus becoming a therapeutic problem.


Subject(s)
Humans , Pseudomonas/drug effects , Acinetobacter/drug effects , Colistin/pharmacology , Drug Resistance, Bacterial/drug effects , Enterobacteriaceae/drug effects , Anti-Bacterial Agents/pharmacology , Pseudomonas/isolation & purification , Time Factors , Acinetobacter/isolation & purification , Brazil , Microbial Sensitivity Tests , Retrospective Studies , Enterobacteriaceae/isolation & purification , Hospitals, University
14.
Braz. j. microbiol ; 47(2): 381-388, Apr.-June 2016. tab, graf
Article in English | LILACS | ID: lil-780828

ABSTRACT

Abstract Pan-drug resistant Gram-negative bacteria, being resistant to most available antibiotics, represent a huge threat to the medical community. Colistin is considered the last therapeutic option for patients in hospital settings. Thus, we were concerned in this study to demonstrate the membrane permeabilizing activity of colistin focusing on investigating its efficiency toward those pan-drug resistant isolates which represent a critical situation. We determined the killing dynamics of colistin against pan-drug resistant isolates. The permeability alteration was confirmed by different techniques as: leakage, electron microscopy and construction of an artificial membrane model; liposomes. Moreover, selectivity of colistin against microbial cells was also elucidated. Colistin was proved to be rapid bactericidal against pan-drug resistant isolates. It interacts with the outer bacterial membrane leading to deformation of its outline, pore formation, leakage of internal contents, cell lysis and finally death. Furthermore, variations in membrane composition of eukaryotic and microbial cells provide a key for colistin selectivity toward bacterial cells. Colistin selectively alters membrane permeability of pan-drug resistant isolates which leads to cell lysis. Colistin was proved to be an efficient last line treatment for pan-drug resistant infections which are hard to treat.


Subject(s)
Humans , Cell Membrane/metabolism , Gram-Negative Bacterial Infections/microbiology , Colistin/metabolism , Drug Resistance, Multiple, Bacterial , Gram-Negative Bacteria/metabolism , Anti-Bacterial Agents/metabolism , Microbial Sensitivity Tests , Cell Membrane/drug effects , Cell Membrane Permeability , Gram-Negative Bacterial Infections/drug therapy , Colistin/pharmacology , Gram-Negative Bacteria/isolation & purification , Gram-Negative Bacteria/drug effects , Gram-Negative Bacteria/ultrastructure , Anti-Bacterial Agents/pharmacology
15.
Rev. chil. infectol ; 33(2): 166-176, abr. 2016. ilus, tab
Article in Spanish | LILACS | ID: lil-784867

ABSTRACT

One of the most important features of the post-antibiotic era in the late 20th century is the resurgence of colistin for the treatment of extensively drug resistant gram-negative bacteria (XDR). Colistin is a narrow spectrum anti-biotic, active against microorganisms with clinical significance such as Acinetobacter baumannii, Pseudomonas aeruginosa and Klebsiella pneumoniae. Nowadays its toxicity is lower, partly explained by better pharmaceuticals and management of the critically ill patients. However, there has been much confusion regarding the dosage of the drug, its name and labeling, therefore, experts have recommended using a common language about this polymyxin. The lack of PK/PD studies for colistin is perhaps the main weakness of this area of knowledge, even though the before mentioned approach has contributed with new ways to manage and calculate the dose of this antimicrobial. Indeed, the efficiency of colistin in association with a second agent in reducing mortality has not been demonstrated.


El resurgimiento de colistín para el tratamiento de bacilos gramnegativos extensamente resistentes a antimicrobianos a fines del siglo pasado es una de las características más importantes de la era post-antimicrobiana. Su espectro es reducido y cubre microorganismos con importancia clínica como Acinetobacter baumannii, Pseudomonas aeruginosa y Klebsiella pneumoniae. En contraste a lo que se vio en el pasado, la toxicidad descrita en la actualidad es menor, en parte explicado por las mejores preparaciones farmacéuticas y la optimización del manejo del paciente crítico. Mucha confusión se ha generado respecto a la dosificación del fármaco, debido a la distinta denominación, etiquetado y sugerencias de los laboratorios, a pesar de que el compuesto es el mismo. Por lo anterior, el llamado de los expertos es a utilizar un lenguaje común para referirnos a esta polimixina. Los estudios modernos de PK/PD han contribuido con nuevas formas de administrar y calcular las dosis de este antimicrobiano; no obstante, falta mucho por desarrollar en esta área que se posiciona como su gran debilidad. A pesar que la terapia combinada se sustenta sobre una base teórica lógica, no se ha demostrado que la asociación de colistín con un segundo agente logre disminuir la mortalidad.


Subject(s)
Colistin/pharmacology , Anti-Bacterial Agents/pharmacology , Structure-Activity Relationship , Gram-Negative Bacterial Infections/drug therapy , Drug Resistance, Bacterial , Gram-Negative Bacteria/drug effects
16.
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
17.
Yonsei Medical Journal ; : 928-934, 2015.
Article in English | WPRIM | ID: wpr-40872

ABSTRACT

PURPOSE: Colistin resistance in Acinetobacter baumannii (A. baumannii) is mediated by a complete loss of lipopolysaccharide production via mutations in lpxA, lpxC, and lpxD gene or lipid A modifications via mutations in the pmrA and pmrB genes. However, the exact mechanism of therapy-induced colistin resistance in A. baumannii is not well understood. MATERIALS AND METHODS: We investigated the genotypic and phenotypic changes that underlie pan-drug resistance mechanisms by determining differences between the alterations in extensively drug-resistant (XDR) A. baumannii (AB001 and AB002) isolates and a pan-drug resistant (PDR) counterpart (AB003) recovered from one patient before and after antibiotic treatment, respectively. RESULTS: All three clinical isolates shared an identical sequence type (ST138), belonging to the global epidemic clone, clonal complex 92, and all produced OXA-23 carbapenemase. The PDR AB003 showed two genetic differences, acquisition of armA gene and an amino acid substitution (Glu229Asp) in pmrB gene, relative to XDR isolates. No mutations were detected in the pmrA, pmrC, lpxA, lpxC, or lpxD genes in all three isolates. In matrix-assisted laser desorption ionization-time of flight analysis, the three isolates commonly showed two major peaks at 1728 m/z and 1912 m/z, but peaks at 2034 m/z, 2157 m/z, 2261 m/z, and 2384 m/z were detected only in the PDR A. baumannii AB003 isolate. CONCLUSION: Our results show that changes in lipid A structure via a mutation in the pmrB gene and acquisition of armA gene might confer resistance to colistin and aminoglycosides to XDR A. baumannii strains, resulting in appearance of a PDR A. baumannii strain of ST138.


Subject(s)
Acinetobacter Infections/drug therapy , Acinetobacter baumannii/drug effects , Aged , Anti-Bacterial Agents/pharmacology , Bacterial Proteins/genetics , Colistin/pharmacology , Drug Resistance, Bacterial , Electrophoresis, Gel, Pulsed-Field , Genotype , Humans , Male , Microbial Sensitivity Tests , Molecular Typing , Mutation , Polymerase Chain Reaction , Transcription Factors , beta-Lactamases
18.
Rev. Soc. Bras. Med. Trop ; 47(4): 451-456, Jul-Aug/2014. tab, graf
Article in English | LILACS | ID: lil-722304

ABSTRACT

Introduction Acinetobacter baumannii has attained an alarming level of resistance to antibacterial drugs. Clinicians are now considering the use of older agents or unorthodox combinations of licensed drugs against multidrug-resistant strains to bridge the current treatment gap. We investigated the in vitro activities of combination treatments that included colistin with vancomycin, norvancomycin or linezolid against multidrug-resistant Acinetobacter baumannii. Methods The fractional inhibitory concentration index and time-kill assays were used to explore the combined effects of colistin with vancomycin, norvancomycin or linezolid against 40 clinical isolates of multidrug-resistant Acinetobacter baumannii. Transmission electron microscopy was performed to evaluate the interactions in response to the combination of colistin and vancomycin. Results The minimum inhibitory concentrations (MICs) of vancomycin and norvancomycin for half of the isolates decreased below the susceptibility break point, and the MIC of linezolid for one isolate was decreased to the blood and epithelial lining fluid concentration using the current dosing regimen. When vancomycin or norvancomycin was combined with subinhibitory doses of colistin, the multidrug-resistant Acinetobacter baumannii test samples were eradicated. Transmission electron microscopy revealed that subinhibitory doses of colistin were able to disrupt the outer membrane, facilitating a disruption of the cell wall and leading to cell lysis. Conclusions Subinhibitory doses of colistin significantly enhanced the antibacterial activity of vancomycin, norvancomycin, and linezolid against multidrug-resistant Acinetobacter baumannii. .


Subject(s)
Acinetobacter baumannii/drug effects , Anti-Bacterial Agents/pharmacology , Acetamides/pharmacology , Acinetobacter Infections/microbiology , Acinetobacter baumannii/ultrastructure , Colistin/pharmacology , Microbial Sensitivity Tests , Microscopy, Electron, Transmission , Oxazolidinones/pharmacology , Time Factors , Vancomycin/analogs & derivatives , Vancomycin/pharmacology
19.
Rev. argent. microbiol ; 45(3): 185-90, set. 2013.
Article in Spanish | LILACS, BINACIS | ID: biblio-1171786

ABSTRACT

Sixty-four colistin-resistant Klebsiella pneumoniae isolates recovered from clinical specimens from 57 patients admitted to Hospital de Clinicas Jose de San Martin during the period 2010-2012 were studied to describe the microbiological and epidemiological characteristics and factors associated with the emergence of colistin-resistance. Fifty-four colistin-susceptible K. pneumoniae isolates from the same period were also included in the study. The genetic relatedness among the isolates was studied by a PCR assay. Fifty percent of the resistant isolates were KPC-2 producers, 45.3


were ESBL producers and 4.7


only showed resistance to aminopenicilins. All KPC-producers (resistant and susceptible to colistin) were genotipically indistinguishable except for one, whereas the presence of 7 clonal types, which were different from the ones identified in the colistin-susceptible isolates, were detected among ESBL producers. The previous use of colistin was the main factor associated with the acquisition of resistance, and in the case of non-KPC producers the stay in ICU was another significant factor observed. Colistin resistance emerged in our hospital in the year 2010, reaching 3


in nosocomial isolates and maintaining this rate in successive years, due to the selection of resistant subpopulations in the epidemic clonal type in KPC-producers and due to the dispersion of colistin-resistant clonal types in non-KPC producing-isolates.


Subject(s)
Colistin/pharmacology , Klebsiella pneumoniae/drug effects , Klebsiella pneumoniae/enzymology , Bacterial Proteins/biosynthesis , beta-Lactamases/biosynthesis , Drug Resistance, Bacterial , Female , Humans , Klebsiella Infections/epidemiology , Male , Bacterial Proteins/classification , beta-Lactamases/classification
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