A short synthetic peptide, based on LyeTx I from Lycosa erythrognatha venom, shows potential to treat pneumonia caused by carbapenem-resistant Acinetobacter baumannii without detectable resistance.

The emergence of antibiotic-resistant bacteria, especially carbapenem-resistant Acinetobacter baumannii (CRAB), together with relative stagnation in the development of effective antibiotics, has led to enormous health and economic problems. In this study, we aimed to describe the antibacterial spectrum of LyeTx I mnΔK, a short synthetic peptide based on LyeTx I from Lycosa erythrognatha venom, against CRAB. LyeTx I mnΔK showed considerable antibacterial activity against extensively resistant A. baumannii, with minimum inhibitory and bactericidal concentrations ranging from 1 to 16 µM and 2 to 32 µM, respectively. This peptide significantly increased the release of 260 nm-absorbing intracellular material from CRAB, suggesting bacteriolysis. LyeTx I mnΔK was shown to act synergistically with meropenem and colistin against CRAB. The cytotoxic concentration of LyeTx I mnΔK against Vero cells (CC50 = 55.31 ± 5.00 µM) and its hemolytic activity (HC50 = 77.07 ± 4.00 µM) were considerably low; however, its antibacterial activity was significantly reduced in the presence of human and animal serum and trypsin. Nevertheless, the inhalation of this peptide was effective in reducing pulmonary bacterial load in a mouse model of CRAB infection. Altogether, these results demonstrate that the peptide LyeTx I mnΔK is a potential prototype for the development of new effective and safe antibacterial agents against CRAB.

Exploring antibiotic resistance in environmental integron-cassettes through intI-attC amplicons deep sequencing.

INTRODUCTION: Freshwater ecosystems provide propitious conditions for the acquisition and spread of antibiotic resistance genes (ARGs), and integrons play an important role in this process. MATERIAL AND METHODS: In the present study, the diversity of putative environmental integron-cassettes, as well as their potential bacterial hosts in the Velhas River (Brazil), was explored through intI-attC and 16S rRNA amplicons deep sequencing. RESULTS AND DISCUSSION: ORFs related to different biological processes were observed, from DNA integration to oxidation-reduction. ARGs-cassettes were mainly associated with class 1 mobile integrons carried by pathogenic Gammaproteobacteria, and possibly sedentary chromosomal integrons hosted by Proteobacteria and Actinobacteria. Two putative novel ARG-cassettes homologs to fosB3 and novA were detected. Regarding 16SrRNA gene analysis, taxonomic and functional profiles unveiled Proteobacteria, Bacteroidetes, Firmicutes, and Actinobacteria as dominant phyla. Betaproteobacteria, Alphaproteobacteria, and Actinobacteria classes were the main contributors for KEGG orthologs associated with resistance. CONCLUSIONS: Overall, these results provide new information about environmental integrons as a source of resistance determinants outside clinical settings and the bacterial community in the Velhas River.

Rate of polymyxin resistance among Acinetobacter baumannii recovered from hospitalized patients: a systematic review and meta-analysis.

We conducted a systematic review and meta-analysis to determine the rate of polymyxin resistance among Acinetobacter baumannii isolates causing infection in hospitalized patients around the world during the period of 2010-2019. The systematic review was performed on September 1, 2019, using PubMed/MEDLINE, Scopus, and Web of Science; studies published after January 1, 2010, were selected. The data were summarized in tables, critically analyzed, and treated statistically using the RStudio® Software with Meta package and Metaprop Command. After applying exclusion factors, 41 relevant studies were selected from 969 articles identified on literature search. The overall rate of polymyxin-resistant A. baumannii (PRAB) related to hospitalized patients was estimated to be 13% (95% CI, 0.06-0.27), where a higher rate was observed in America (29%; 95% CI, 0.12-0.55), followed by Europe (13%; 95% CI, 0.02-0.52), and Asia (10%; 95% CI, 0.02-0.32). The extensive use of polymyxins on veterinary to control bacterial infection and growth promotion, as well as the resurgence in prescription and use of polymyxins in the clinics against carbapenem-resistant gram-negative bacteria, may have contributed to the increased incidence of PRAB. The findings of this meta-analysis revealed that the rate of PRAB recovered from hospitalized patients is distinctively high. Thus, action needs to be taken to develop strategies to combat the clinical incidence of PRAB-induced hospital infections.

Plasmid-mediated quinolone resistance (PMQR) among Enterobacteriales in Latin America: a systematic review.

The plasmid-mediated quinolone resistance (PMQR) genes have changed the resistance pattern to quinolones, especially among Enterobacteriales. The dissemination of these genes in Latin American countries, where the prescription of fluoroquinolones is high, has been described in several studies; however, no review of the impact of PMQR in this continent has been conducted. This review summarized current knowledge about the circulation of PMQR among Enterobacteriales in Latin American. After the search and selection, 61 articles were included in the study. Most of studies reported PMQR genes among Enterobacteriales from human (47/61, 77%) and animal (18/61, 29.5%) samples, recovered mainly in Brazil (23/61, 37.7%), Mexico (11/61, 18%), and Uruguay (7/61, 11.5%). Nine different PMQR genes (qnrA, qnrB, qnrS, qnrD, qnrE, aac-(6')-Ib-cr, oqxA, oqxB, and qepA) were found in Latin America, with aac (6')-Ib-cr (37/61, 60.6%) and qnrB (26/61, 42.6%) being the most frequently reported. Escherichia coli (40/61, 65.6%) was the species most frequently reported to carry a PMQR gene, followed by Klebsiella pneumoniae (24/61, 39.3%), Enterobacter cloacae (15/61, 24.6%), and Salmonella spp. (14/61, 22.9%). Thus, this review provides important information which might help in designing measures to control the spread of quinolone resistance determinants on this continent.

Carbapenem-resistant Acinetobacter baumannii in patients with burn injury: A systematic review and meta-analysis.

PURPOSE: In this study, we aimed reviewed the data about the patterns of antimicrobial susceptibility and resistance determinants among carbapenem-resistant Acinetobacter baumannii (CRAB) from patients with burn injury. METHODS: A systematic review was conducted using the PRISMA statement in PUBMED/MEDLINE, Scopus, Scientific Electronic Library Online (SciELO), Biblioteca Virtual de Saúde (BVS) and Cochrane Library. The data referring to enzymatic resistance mechanisms were evaluated by meta-analyses according to random effect. RESULTS: 17 articles that evaluated 1226 CRAB recovered from patients with burn injury were included in study. The majority of studies are from Iran (12/17; 70.6%), published in 2016 (6/17; 35.3%) and showed prospective design (15/17; 88.2%). The samples were obtained mainly from burn wounds (14/17; 82.3%) and more than half of the studies did not identify if the isolates originated from infected or colonized patients (10/17; 58.8%). Second the meta-analyses, OXA-type carbapenemase was the main mechanism involved in low susceptibility to carbapenems (53.2%; 95% CI = 60, 80.0%, I2 = 86.0%), followed by metallo-ß-lactamases (MBL) (30.2%; 95% CI = 11, 42.0%, I2 = 93.0%), and Klebsiella pneumoniae carbapenemase (KPC) (16.6%; 95% CI = 5, 63.0%, I2 = 88.0%). The majority of strains harbored blaOXA-23-like (12/17; 70.6%) or blaOXA-24/40-like (12/17; 35.3%) genes. The studies included showed that minocycline (69.5%) and colistin (99.9%) susceptibility remains high and is not impacted by carbapenem resistance in these isolates. CONCLUSIONS: The results summarized in this review indicate the importance of a high-quality surveillance program to design suitable and effective interventions to control CRAB infection in burn units worldwide.