High Levels of Resistance to Cephalosporins Associated with the Presence of Extended-Spectrum and AmpC ß-Lactamases in Escherichia coli from Broilers in Southern Brazil.

The clinical importance of extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli has increased steadily over the years. The presence of the blaTEM, blaSHV, and blaCTX-M genes in the environment has been recently recognized as an important issue in the dissemination of resistance to cephalosporins. Food animals are considered important vectors for transfer of ESBL genes from the environment to humans. The objective of this study was to characterize the ESBL genes (blaTEM, blaSHV, and blaCTX-M types) that were most prevalent among 343 ceftazidime-resistant E. coli isolates (17 batches from 12 different farms) obtained from cloacal swabs of broiler chicken in southern Brazil. The blaSHV, blaCTX-M, blaTEM, blaIMP-type, blaVIM-type, blaNDM-1, blaKPC-type, blaGES-type, blaOXA-48, and mcr-1 genes were evaluated by polymerase chain reaction. A total of 27 (7.9%) E. coli isolates were positive for ESBL genes as follows: 24 for blaCTX-M (23 blaCTX-M-2 Group and 1 blaCTX-M-8) and 3 for blaSHV (2 blaSHV-2a and 1 blaSHV-18). A random sample of 32 ceftazidime/cefotaxime-resistant isolates that were negative for ESBL genes were evaluated for the presence of blaCMY-2 and 24 (75%) tested positive. We detected the blaCMY-2 gene in isolates from all farms. All isolates positive for ESBL or blaCMY-2 are considered multidrug resistant (resistant to at least three antibiotic classes). Our results suggest that broiler chickens are an important reservoir of blaCMY-2 and ESBL genes, including blaSHV-2a, described for the first time in animals originating from Brazil in this study, and blaSHV-18, which has never been described in Brazil before. This fact highlights the importance of controlling the use of antibiotics in animal production to reduce environmental sources of resistance genes.

Synergy of polymyxin B, tigecycline and meropenem against carbapenem-resistant Enterobacter cloacae complex isolates.

Here, we evaluated the combinations of antibiotics polymyxin B (PMB), tigecycline (TGC) and meropenem (MEM) by time-kill curves (TKC) against carbapenem-resistant Enterobacter cloacae isolates. Combination of PMB/TGC and PMB/MEM showed promising results in sub-inhibitory concentration of PMB indicating the possibility of reducing the dose of PMB used in the treatment.

Rapid tools to gain insights into the interaction dynamics of new 8-hydroxyquinolines with few fungal lines.

The combination of tools such as time-kill assay with subsequent application of mathematical modeling can clarify the potential of new antimicrobial compounds, since minimal inhibitory concentration (MIC) value does not provide a very detailed characterization of antimicrobial activity. Recently, our group has reported that the 8-hydroxy-5-quinolinesulfonic acid presents relevant antifungal activity. However, its intrinsic acidity could lead to an ionization process, decreasing fungal cell permeability. To overcome this potential problem and enhance activity, the purpose of this study was to synthesize and evaluate a novel series of hybrids between the 8-hydroxyquinoline core and sulfonamide and to prove their potential using broth microdilution method, obtaining the pharmacodynamic parameters of the most active derivatives combining time-kill studies and mathematical modeling and evaluating their toxicity. Compound 5a was the most potent, being active against all the fungal species tested, with low toxicity in normal cells. 5a and 5b have presented important antibacterial activity against Staphylococcus aureus strain. The EC50 values obtained by combination of time-kill studies with mathematical model were similar to those of MIC, which confirms the potential of compounds. In addition, these derivatives are non-irritant molecules with the absence of topical toxicity. Finally, 5a and 5b are promising candidates for treatment of dermatomycosis and candidiasis.