Antimicrobial activity of plant extracts against carbapenem-producing Klebsiella pneumoniae and in vivo toxicological assessment.

The global spread of multidrug-resistant strains has prompted the scientific community to explore novel sources of chemicals with antimicrobial activity. The aim of the study was to examine the antimicrobial activity in vitro of 28 extracts against carbapenem-producing Klebsiella pneumoniae, individually and in combination with antibiotics and in vivo toxicological assessment of the most active product. The multi-resistant K. pneumoniae strain was submitted for phenotypic and molecular characterization. The antibacterial activity of 28 plant extracts was evaluated alone and in combination with antibiotics against this strain through the agar disk diffusion. Of these, 16 extracts showed synergism against carbapenem-producing K. pneumoniae, being that B. crassifolia extract exhibited synergism with three antibiotics. Based on this assessment, B. crassifolia-extract-induced toxicity on Swiss male mice was evaluated by administering this extract and subsequently determining apoptosis and splenic phagocytosis using the comet and micronucleus assays. The results of this study showed that B. crassifolia extract had synergistic activity promising and groups treated with B. crassifolia exhibited no genotoxic or mutagenic activity, indicating that B. crassifolia extract exerted beneficial effects and appeared safe to use at the studied concentrations.

Genetic Diversity of Virulent Polymyxin-Resistant Klebsiella aerogenes Isolated from Intensive Care Units.

This study evaluated the scope and genetic basis of polymyxin-resistant Klebsiella aerogenes in Brazil. Eight polymyxin-resistant and carbapenemase-producing K. aerogenes strains were isolated from patients admitted to the ICU of a tertiary hospital. Bacterial species were identified by automated systems and antimicrobial susceptibility profile was confirmed using broth microdilution. The strains displayed a multidrug resistant profile and were subjected to whole-genome sequencing. Bioinformatic analysis revealed a variety of antimicrobial resistance genes, including the blaKPC-2. No plasmid-mediated colistin resistance gene was identified. Nonetheless, nonsynonymous mutations in mgrB, pmrA, pmrB, and eptA were detected, justifying the colistin resistance phenotype. Virulence genes encoding yersiniabactin, colibactin, and aerobactin were also found, associated with ICEKp4 and ICEKp10, and might be related to the high mortality observed among the patients. In fact, this is the first time ICEKp is identified in K. aerogenes in Brazil. Phylogenetic analysis grouped the strains into two clonal groups, belonging to ST93 and ST16. In summary, the co-existence of antimicrobial resistance and virulence factors is deeply worrying, as it could lead to the emergence of untreatable invasive infections. All these factors reinforce the need for surveillance programs to monitor the evolution and dissemination of multidrug resistant and virulent strains among critically ill patients.

Antibacterial activity of Cinnamomum cassia L. essential oil in a carbapenem- and polymyxin-resistant Klebsiella aerogenes strain.

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

Synergistic effects of Cinnamomum cassia L. essential oil in combination with polymyxin B against carbapenemase-producing Klebsiella pneumoniae and Serratia marcescens.

Multidrug resistance prompts the search for new sources of antibiotics with new targets at bacteria cell. To investigate the antibacterial activity of Cinnamomum cassia L. essential oil (CCeo) alone and in combination with antibiotics against carbapenemase-producing Klebsiella pneumoniae and Serratia marcescens. The antimicrobial susceptibility of the strains was determined by Vitek® 2 and confirmed by MALDI-TOF/TOF. The antibacterial activity of CCeo and its synergism with antibiotics was determined using agar disk diffusion, broth microdilution, time-kill, and checkboard methods. The integrity of the bacterial cell membrane in S. marcescens was monitored by protein leakage assay. CCeo exhibited inhibitory effects with MIC = 281.25 µg.mL-1. The association between CCeo and polymyxin B showed a decrease in terms of viable cell counts on survival curves over time after a 4 hour-treatment with a FIC index value of 0.006. Protein leakage was observed with increasing concentrations for CCeo and CCeo + polymyxin B treatments. CCeo showed antibacterial activity against the studied strains. When associated with polymyxin B, a synergistic effect was able to inhibit bacterial growth rapidly and consistently, making it a potential candidate for the development of an alternative treatment and drug delivery system for carbapenemase-producing strains.

Origanum vulgare L. essential oil inhibits the growth of carbapenem-resistant gram-negative bacteria.

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.

High mortality rate associated with KPC-producing Enterobacter cloacae in a Brazilian hospital.

We describe a clonal dissemination of KPC-producing Enterobacter cloacae in a Brazilian hospital. Patients diagnosed with theses isolates showed high mortality rate (41.8%) and were associated with previous use of antibiotics and urinary catheterization. Therefore, infection control measures and use of stricter antibiotic policies are required to control the spread of these organisms.

A high mortality rate associated with multidrug-resistant Acinetobacter baumannii ST79 and ST25 carrying OXA-23 in a Brazilian intensive care unit.

The global spread of carbapenem-resistant Acinetobacter baumannii (A. baumannii) strains has restricted the therapeutic options available to treat infections due to this pathogen. Understanding the prevalence of such infections and the underlying genetic mechanisms of resistance may help in the implementation of adequate measures to control and prevent acquisition of nosocomial infections, especially in an intensive care unit setting. This study describes the molecular characteristics and risk factors associated with OXA-23-producing A. baumannii infections. A case-control study was undertaken from September/2013 to April/2015. Acquisition of OXA-23-producing A. baumannii was found to be associated with the use of nasogastric tubes, haemodialysis, and the use of cephalosporins. These isolates were only susceptible to amikacin, gentamicin, tigecycline, and colistin, and contained the ISAba1 insertion sequence upstream ofblaOXA-23 and blaOXA-51 genes. Twenty-six OXA-23-producing A. baumannii strains belonged to the ST79 (CC79) clonal group,and patients infected or colonised by these isolates had a higher mortality rate (34.6%). In conclusion, this study showed a dissemination of OXA-23-producing A. baumannii strains that was associated with several healthcare-related risk factors and high mortality rates among intensive care unit patients.

Antibacterial activity of Cinnamomum cassia L. essential oil in a carbapenem- and polymyxin-resistant Klebsiella aerogenes strain

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

Origanum vulgare L. essential oil inhibits the growth of carbapenem-resistant gram-negative bacteria

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.

Fatores relacionados à injúria crônica do enxerto / Factors related to chronic allograft injury

A injúria crônica do enxerto (ICE) é também conhecida como nefropatia crônica do enxerto ou rejeição crônica e possui vários fatores em sua gênese. Os fatores relacionados a esta condição podem ser divididos em imunológicos e não-imunológicos, podendo surgir a qualquer momento após o transplante. Considerando que ainda não houve melhorias significativas nas taxas de sobrevida de enxertos renais a longo-prazo, e que muitos dos transplantados acometidos pela ICE não têm ciência de seus fatores desencadeantes, é importante que se tenha maior conhecimento do processo como um todo. Deste modo, o objetivo deste trabalho foi verificar, por meio de levantamento bibliográfico, os fatores relacionados à injúria crônica do enxerto, suas incidências em transplantados renais e suas possíveis procedências. A pesquisa realizada levou em consideração todos os fatores associados à injúria crônica do enxerto que haviam sido analisados em outros estudos e que possuíam, portanto, alguma relação com esta patologia. Dentre os fatores de risco relacionados com o surgimento da injúria crônica e, consequentemente, com a redução da sobrevida do enxerto, destacam-se episódios de rejeição aguda, baixa compatibilidade HLA entre o doador e receptor, toxicidade dos imunossupressores, lesão de isquemia/reperfusão, hipertensão, entre outros. Diante do exposto, foi possível observar algumas interações nos mecanismos patológicos dos fatores de risco da ICE, onde existe uma espécie de reação em cadeia que leva ao acúmulo de diversas lesões renais e, finalmente, ao desenvolvimento da injúria crônica do enxerto.

The chronic allograft injury (CAI) is also known as chronic graft nephropathy (CAN) or chronic rejection and has several factors in its genesis. Factors associated with this condition can be divided into immunological and non-immunological and may arise at any time after the transplant. Since there have been no significant improvements in long-term survival rates of kidney graft and many renal transplant patients affected by the CAI are unaware of its causative factors, is important to have greater knowledge of the process as a whole. Thus, the aim of this study was to verify through a literature review the factors related to chronic allograft injury, its incidences on renal transplant patients and its possible origins. The research investigated all factors associated with chronic allograft injury discussed in other studies. Among the risk factors associated with the onset of chronic kidney injury and consequently with reduced graft survival, stand out episodes of acute rejection, low HLA compatibility between donor and receptor, toxicity of immunosuppressive agents, ischemia/reperfusion, hypertension, and others. This review article showed interactions in the pathological mechanisms of risk factors, which present a chain reaction that may lead to the accumulation of several kidney injuries and eventually to the development of chronic allograft injury.