RESUMO
The emergence of metallo-ß-lactamase (MBL)-producing Enterobacterales, mainly New Delhi metallo-ß-lactamase (NDM), represents a clinical threat due to the limited therapeutic alternatives. Aztreonam (AZT) is stable to MBLs, but most MBL-producing Enterobacterales isolates usually co-harbour other ß-lactamases that confer resistance to AZT and, consequently, its use is restricted in these isolates. We compared the ability of sulbactam (SUL), tazobactam (TAZ), clavulanic acid (CLA) and avibactam (AVI) to restore the AZT activity in MBL-producing AZT-resistant Enterobacterales isolates. A collection of 64 NDM-producing AZT-resistant Enterobacterales from five hospitals in Buenos Aires city, Argentina, were studied during the period July-December 2020. MICs were determined using the agar dilution method with Mueller-Hinton agar according to Clinical and Laboratory Standards Institute (CLSI) recommendations. AVI, SUL and TAZ were used at a fixed concentration of 4 mg l-1, whereas CLA was used at a fixed concentration of 2 mg l-1. A screening method based on disc diffusion to evaluate this synergy was also conducted. Detection of bla KPC, bla OXA, bla NDM, bla VIM, bla CTXM-1, bla PER-2 and bla CIT was performed by PCR. The AZT-AVI combination restored the AZT activity in 98.4â% of AZT-resistant strains, whereas CLA, TAZ and SUL did so in 70.3, 15.6 and 12.5â%, respectively, in isolates co-harbouring extended-spectrum ß-lactamases, but were inactive in isolates harbouring AmpC-type enzymes and/or KPC. The synergy screening test showed an excellent negative predictive value to confirm the absence of synergy, but positive results should be confirmed by a quantitative method. The excellent in vitro performance of the AZT-CLA combination represents a much more economical alternative to AZT-AVI, which could be of use in the treatment of MBL-producing, AZT-resistant Enterobacterales.
Assuntos
Aztreonam/farmacologia , Farmacorresistência Bacteriana , Enterobacteriaceae/efeitos dos fármacos , Inibidores de beta-Lactamases/farmacologia , beta-Lactamases/metabolismo , Aztreonam/administração & dosagem , Sinergismo Farmacológico , Enterobacteriaceae/enzimologia , Testes de Sensibilidade Microbiana , Inibidores de beta-Lactamases/administração & dosagem , beta-Lactamases/química , beta-Lactamases/genéticaRESUMO
Therapeutic options for the treatment of infections by multidrug-resistant Acinetobacter baumannii strains are often limited. Minocycline (MIN) is an old antibiotic, with excellent activity against A. baumannii isolates, which can be administered orally. Currently, there is no single criterion regarding the breakpoints for MIN and A. baumannii. The activity of MIN was examined against a collection of A. baumannii isolates recovered from 15 hospitals of 6 countries of South America. A review of the literature was also performed. In our series and most of the studies, the percentages of MIN susceptible isolates exceeded 50%, regardless of the breakpoints utilized (4-2 or 1 µg/mL). However, a greater number of isolates not harboring Tet B were considered resistant with the breakpoints of 1 or 2 µg/mL, whereas isolates with tet(B) genes were still detected with minimum inhibitory concentration below all breakpoints considered. Tetracycline susceptibility may be used as a screening to discriminate the populations with and without acquired resistance mechanisms to MIN. In this study, MIN-resistant subpopulations were found in isolates harboring Tet B, with MIC ≤1 µg/mL, and their frequency increased after incubation with MIN. These subpopulations were not detected in isolates not harboring Tet B. The clinical correlation of these subpopulations should be evaluated in future studies.
Assuntos
Acinetobacter baumannii/efeitos dos fármacos , Antibacterianos/farmacologia , Minociclina/farmacologia , Acinetobacter baumannii/genética , Testes de Sensibilidade MicrobianaRESUMO
A rapid colorimetric method, the Andrade screening antimicrobial test, was compared with the E-test method to detect ceftazidime/avibactam (CZA) resistance in carbapenem resistant Enterobacterales clinical isolates. A 106 non-duplicated isolates (86 susceptible and 20 resistant to CZA) were chosen for validation. The sensitivity and specificity were 100%. This method investigates CZA resistance regardless of the resistance mechanism involved. It represents an economical and easy technique that can be applied to routine microbiology laboratories. It allows the detection of CZA resistance at 3 hours of incubation and consequently, the early implementation of accurate therapeutic interventions.
Assuntos
Antibacterianos/farmacologia , Compostos Azabicíclicos/farmacologia , Carbapenêmicos/farmacologia , Ceftazidima/farmacologia , Farmacorresistência Bacteriana/efeitos dos fármacos , Enterobacteriaceae/efeitos dos fármacos , Colorimetria/métodos , Combinação de Medicamentos , Humanos , Testes de Sensibilidade MicrobianaRESUMO
Introduction. The therapeutic options to treat Acinetobacter baumannii infections are very limited.Aim. Our aim was to evaluate the activity of sulbactam combined directly with avibactam or the ampicillin-sulbactam/ceftazidime-avibactam combination against extensively drug-resistant A. baumannii isolates.Methodology. Extensively drug-resistant A. baumannii isolates (n=127) collected at several South American hospitals were studied. Synergy with the sulbactam/avibactam combination was assessed in all isolates using the agar dilution method. Avibactam was used at a fixed concentration of 4 mg l-1. A disc diffusion synergy test was also performed. Synergy by a time-kill experiment was performed in a selected isolate.Results. Synergy with sulbactam/avibactam was demonstrated in 124 isolates and it showed MIC values ≤4 mg l-1. This synergy was not detected in the three New Delhi metallo-ß-lactamase-harbouring isolates. Similar results were observed with the disc diffusion synergy test of ampicillin-sulbactam/ceftazidime-avibactam. In the time-kill experiments, sulbactam/avibactam showed a rapid synergistic and bactericidal activity in ampicillin-sulbactam-resistant isolates.Conclusions. This study demonstrated that the sulbactam/avibactam combination displayed synergistic activity against A. baumannii isolates. This synergy was observed when both inhibitors were also used as part of the commercially available combinations: ampicillin-sulbactam and ceftazidime-avibactam.
Assuntos
Infecções por Acinetobacter/terapia , Compostos Azabicíclicos/metabolismo , Sulbactam/farmacologia , Infecções por Acinetobacter/metabolismo , Acinetobacter baumannii/metabolismo , Ampicilina/farmacologia , Antibacterianos/farmacologia , Compostos Azabicíclicos/farmacologia , Ceftazidima/farmacologia , Combinação de Medicamentos , Farmacorresistência Bacteriana/efeitos dos fármacos , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Quimioterapia Combinada/métodos , Humanos , Testes de Sensibilidade Microbiana , Tienamicinas/farmacologiaRESUMO
A rapid colorimetric method, the Andrade Screening Antimicrobial Test (ASAT) was evaluated to detect colistin resistance in Enterobacteriales clinical isolates. The sensitivity and specificity were 90.7% and 100%, respectively. In 10/26 E. coli isolates the automatized method failed to detect the resistance, whereas the ASAT detected it accurately. Most of these isolates showed COL MIC values in the range 4-8 µg mL-1 and carried mcr-1. As regards K. pneumoniae COL- resistant isolates, discrepancies between the Phoenix system and the ASAT were observed only in 3/44 isolates, most of them carried the blaKPC gene and showed COL MIC values >16 µg mL-1.
Assuntos
Colistina/farmacologia , Colorimetria/métodos , Infecções por Escherichia coli/microbiologia , Escherichia coli/isolamento & purificação , Infecções por Klebsiella/microbiologia , Klebsiella pneumoniae/isolamento & purificação , Antibacterianos/farmacologia , Proteínas de Bactérias/metabolismo , Farmacorresistência Bacteriana , Escherichia coli/metabolismo , Humanos , Klebsiella pneumoniae/metabolismo , Testes de Sensibilidade Microbiana/métodos , Sensibilidade e EspecificidadeRESUMO
INTRODUCTION: Corynebacterium coyleae is a Gram-stain-positive non-lipophilic coryneform rod first described in blood samples and pleural fluid. There is scarce information about the clinical relevance of C. coyleae and none on complicated urinary tract infections has been described so far. CASE PRESENTATION: A 36-year-old woman with a history of chronic kidney failure, under thrice-weekly haemodialysis since 2014 due to polycystic kidney disease, presented with hypogastric pain, lower left quadrant pain and nausea. Since 1997, the patient had developed several episodes of urinary tract infection. On admission, the patient presented tenderness in the lower abdomen and fist positive lumbar percussion. Urine culture showed significant bacterial growth (>105 c.f.u. ml-1). Slightly glistening colonies of 1 mm in diameter were observed after a 24 h incubation. Gram staining showed coryneform Gram-stain-positive rods. The patient was diagnosed as having a complicated urinary tract infection. A bilateral nephrectomy was performed on the fourth day of hospitalization. Two samples of kidney tissue were sent for culture. Direct examination of the material revealed the presence of abundant inflammatory reaction and Gram-positive diphtheroid rods. The organism was identified using MALDI-TOF and conventional biochemical tests; in both isolates further identification was performed by PCR amplification and sequence analysis of the rpoB gene as Corynebacterium coyleae. CONCLUSIONS: C. coyleae is an infrequent species among the genus Corynebacterium that should be considered as an emerging pathogen that can be involved in nosocomial infections and complicated urinary tract infections.
RESUMO
Carbapenem resistance in gram-negative bacteria by production of carbapenemases is one of the most challenging issues regarding healthcare worldwide. We review the epidemiology and prevalence of carbapenemases in carbapenem-resistant Acinetobacter baumannii isolates from Latin American countries. High resistance rates to antimicrobial agents, particularly to carbapenems, are observed in this region. OXA-23 is the most widely disseminated class D-carbapenemase; it is present in all the countries of the region and is frequently associated to endemic clones CC113/CC79, CC104/CC15, CC110/ST25 and CC109/CC1. The emergence of OXA-72 and NDM-1 represents a novel finding which is observed simultaneously and without clonal relatedness in different countries, some of which are distant from one another, whereas OXA-143 is only present in Brazil. Further collaborative intraregional studies would provide a better understanding of these issues in most of the countries and thus, policies to control the spread of these isolates could be implemented.
En bacilos gram negativos, la resistencia a carbapenemes por producción de carbapenemasas es uno de los mayores problemas en la atención de la salud a nivel mundial. Reseñamos en este artículo la epidemiologia y la prevalencia de las carbapenemasas descritas en aislamientos de Acinetobacter baumannii recuperados en América Latina. En esta región se ha observado un alto porcentaje de resistencia a los antimicrobianos, particularmente a los carbapenemes. La carbapenemasa más frecuentemente descrita es OXA-23, que ha sido recuperada en todos los países de la región y fue asociada a los clones endémicos CC113/CC79, CC104/CC15, CC110/ST25 y CC109/CC1. La emergencia de OXA-72 y NDM-1 representa un nuevo hallazgo en varios países, algunos de los cuales se encuentran muy distantes entre sí. Por el momento, OXA-143 solo se recuperó de aislamientos obtenidos en Brasil. Serían necesarios estudios colaborativos dentro de la región para lograr una mejor comprensión de la resistencia a carbapenemes en Acinetobacter baumannii, a fin de poder instaurar medidas de control que eviten una mayor diseminación de esta bacteria.
Assuntos
Humanos , Proteínas de Bactérias , beta-Lactamases , Infecções por Acinetobacter , Acinetobacter baumannii , Proteínas de Bactérias/metabolismo , beta-Lactamases/metabolismo , Brasil , Testes de Sensibilidade Microbiana , Resistência beta-Lactâmica , Acinetobacter baumannii/enzimologia , Acinetobacter baumannii/genética , América Latina , AntibacterianosRESUMO
OBJECTIVES: Although Corynebacterium spp. are part of the microbiota of the skin and mucous membranes, human infections caused by Corynebacterium spp. have been reported and the multidrug resistance pattern of the recovered isolates was emphasised. Due to the usefulness of disk diffusion in daily practice, the purpose of this study was to compare disk diffusion with agar dilution to determine disk diffusion breakpoints and to review the antimicrobial susceptibility of the most frequent Corynebacterium spp. isolated in clinical samples. METHODS: Susceptibility to 20 antimicrobial agents of 143 Corynebacterium spp. isolates recovered from relevant clinical samples was determined. Comparison between the disk diffusion and agar dilution methods for eight antimicrobial agents was performed to establish new breakpoints using simple linear regression analysis. RESULTS: All of the isolates tested were susceptible to vancomycin, minocycline and linezolid. A typical susceptibility profile to ß-lactam antibiotics among the different species included was not observed. Almost all isolates showed resistance to macrolides and lincosamides. Using a simple linear regression method, it was possible to establish breakpoints for penicillin, erythromycin, clindamycin, gentamicin and ciprofloxacin. However, the low correlation coefficient obtained for vancomycin, minocycline and trimethoprim/sulfamethoxazole did not allow establishment of breakpoints for the disk diffusion method. CONCLUSION: The disk diffusion method could only be used to evaluate susceptibility to penicillin, erythromycin, clindamycin, gentamicin and ciprofloxacin. These data show that the presence of a Corynebacterium spp. isolate in a clinical sample demands the performance of antimicrobial susceptibility testing since the susceptibility profile is not predictable.
Assuntos
Anti-Infecciosos/farmacologia , Infecções por Corynebacterium/microbiologia , Corynebacterium/efeitos dos fármacos , Argentina , Contagem de Colônia Microbiana , Corynebacterium/isolamento & purificação , Infecções por Corynebacterium/tratamento farmacológico , Testes de Sensibilidade a Antimicrobianos por Disco-Difusão , Farmacorresistência Bacteriana Múltipla , Humanos , Modelos LinearesRESUMO
Carbapenem resistance in gram-negative bacteria by production of carbapenemases is one of the most challenging issues regarding healthcare worldwide. We review the epidemiology and prevalence of carbapenemases in carbapenem-resistant Acinetobacter baumannii isolates from Latin American countries. High resistance rates to antimicrobial agents, particularly to carbapenems, are observed in this region. OXA-23 is the most widely disseminated class D-carbapenemase; it is present in all the countries of the region and is frequently associated to endemic clones CC113/CC79, CC104/CC15, CC110/ST25 and CC109/CC1. The emergence of OXA-72 and NDM-1 represents a novel finding which is observed simultaneously and without clonal relatedness in different countries, some of which are distant from one another, whereas OXA-143 is only present in Brazil. Further collaborative intraregional studies would provide a better understanding of these issues in most of the countries and thus, policies to control the spread of these isolates could be implemented.
Assuntos
Infecções por Acinetobacter , Acinetobacter baumannii , Proteínas de Bactérias , beta-Lactamases , Acinetobacter baumannii/enzimologia , Acinetobacter baumannii/genética , Antibacterianos , Proteínas de Bactérias/metabolismo , Brasil , Humanos , América Latina , Testes de Sensibilidade Microbiana , Resistência beta-Lactâmica , beta-Lactamases/metabolismoRESUMO
The increase in carbapenem-resistant gram-negative bacteria is a matter of concern due to the limited therapeutic options available. In severe infections caused by these isolates, the rapid detection of the mechanisms of resistance is vital. We described a slightly modified version of the Blue-Carba test, rapid Blue-Carba test, which allows the detection of carbapenemases at 4 h of incubation from a haze of bacterial growth obtained from a positive blood culture. It was able to detect carbapenemase-producing isolates (Enterobacteriaceae, Pseudomonas aeruginosa and Acinetobacter baumannii) with a sensitivity and specificity of 98.1 and 100%, respectively. It is a rapid, easy-to-perform and an inexpensive technique that can be applied to routine laboratories, together with the simultaneous identification by mass spectrometry which would help to screen non-enzymatic carbapenem resistance; this method allows the detection of clinically relevant multidrug-resistant bacteria and the early implementation of accurate therapeutic interventions.