Co-carriage of Plasmid NDM and Chromosomal KPC in Klebsiella pneumoniae ST255 Human Wound Isolate in Brazil.

Multidrug-resistant K. pneumoniae is one of the main causes of hospital-acquired infections worldwide and frequently carries antimicrobial resistance genes in moving elements. In this study, we described a K. pneumoniae clinical isolate carrying simultaneous chromosomal blaKPC, and plasmid-mediated blaNDM and blaOXA-9. The isolate is multidrug-resistant and belongs to ST 225. While blaKPC were identified in the chromosome, the blaNDM was mediated by IncFII(K) plasmid and the blaOXA-9, in a IncFIB(K) plasmid. The blaKPC context was composed by Tn4401 transposon and two insertion sequences ISKpn6 and ISKpn7. The co-production of diverse ß-lactamases brings an alert about a new adaptive profile of K. pneumoniae strains and their dissemination in the hospital-acquired infectious.

Evaluation of XGEN Multi Sepsis Flow Chip Molecular Assay for Early Diagnosis of Bloodstream Infection.

Among healthcare-associated infections that can affect a critically ill patient, bloodstream infections are one of the most frequent causes of mortality, especially in hospitalized patients. The objective of this work is to evaluate the performance of the XGEN Multi Sepsis Flow Chip for the rapid diagnosis of bloodstream infections compared with conventional tests. In total, 101 positive blood culture samples were included, and the results obtained by the phenotypic conventional method (culture with susceptibility profile) were compared with results obtained by the XGEN Multi Sepsis Flow Chip. This molecular assay allows the simultaneous detection of the main bloodstream infection pathogens, and their most common antibiotic resistance markers in a short period of time. It was possible to observe substantial agreement between the methods for identifying the genus of pathogens. Considering species, the agreement was excellent. In relation to susceptibility, excellent agreement was noted between the detected resistance genes and susceptibility profile obtained through conventional antibiograms. The evaluated assay presented very early and satisfactory results for identification and detection of resistance genes of the main pathogens involved in bloodstream infections.

Genomic analyses of ciprofloxacin-resistant Neisseria gonorrhoeae isolates recovered from the largest South American metropolitan area.

We sequenced 13 Neisseria gonorrhoeae isolates exhibiting distinct susceptibility profiles and which were recovered over 12 years in the metropolitan region of São Paulo, Brazil. Whole Genome Sequencing (WGS) was performed on an Illumina MiSeq™ 2 × 300 bp paired-end reads. Bioinformatics analyses were carried out using CGE, PATRIC, and BLAST databases for manual curation of obtained genomes. Multilocus sequence typing (MLST) analysis identified seven STs, namely ST1580, ST1590, ST1901, ST1902, ST8161, ST9363, and ST15640. Moreover, a diversity of mutations was observed in MtrR/G45D-A39T, PIB/G120K-A121S, and PBP1/L421P. Mutations associated with sulfonamides (DHPS/R228S) and rifampicin (RNAP/H552N) were also detected, as well as tetracycline resistance determinants, namely rpsJ/V57M and tet(M). The results presented herein can contribute to the knowledge of N. gonorrhoeae strains circulating in Sao Paulo, Brazil.

New species records of Gasteruptiidae (Hymenoptera, Evanioidea) from Eastern Uruguay.

In this study, the Gasteruptiidae (Hymenoptera, Evanioidea) collected in three environments at the Department of Rocha, in Eastern Uruguay, were documented based on a survey carried out with Malaise traps between December 2014 and December 2016. During the samplings, four species of Gasteruption Latreille, 1796 were captured, being 14 females and three males of Gasteruption brachychaetun Schrottky, 1906; eight females and five males of Gasteruption brasiliense (Blanchard, 1840); one female of Gasteruption helenae Macedo, 2011 and one female of Gasteruption brandaoi Macedo, 2011. Gasteruption brachychaetun, G. helenae and G. brandaoi are recorded by the first time from Uruguay.

In vitro synergy of ceftolozane/tazobactam in combination with fosfomycin or aztreonam against MDR Pseudomonas aeruginosa.

OBJECTIVES: Carbapenem-resistant Pseudomonas aeruginosa (CR-PSA) imposes great limitations on empirical therapeutic choices, which are further complicated by metallo-ß-lactamase production. This study evaluated in vitro antimicrobial synergy of ceftolozane/tazobactam in combination with aztreonam and fosfomycin against MDR PSA. METHODS: MICs were determined by broth microdilution and gradient strips. The effect of ceftolozane/tazobactam+aztreonam and ceftolozane/tazobactam+fosfomycin combinations were tested against 27 MDR PSA isolates carrying blaSPM-1 (n = 13), blaIMP (n = 4), blaVIM (n = 3), blaGES-1 (n = 2) and blaCTX-M-like (n = 2), and 3 isolates with no acquired ß-lactamase production detected by gradient diffusion strip crossing (GDSC). Six genetically unrelated SPM-1-producing isolates were also evaluated by time-kill analysis (TKA). RESULTS: All CR-PSA isolates harbouring blaSPM-1, blaGES-1 and blaIMP-1 were categorized as resistant to ceftolozane/tazobactam, meropenem and fosfomycin, with 70% being susceptible to aztreonam. Synergism for ceftolozane/tazobactam+fosfomycin and ceftolozane/tazobactam+aztreonam combinations was observed for 88.9% (24/27) and 18.5% (5/27) of the isolates by GDSC, respectively. A 3- to 9-fold reduction in ceftolozane/tazobactam MICs was observed, depending on the combination. Ceftolozane/tazobactam+fosfomycin was synergistic by TKA against one of six SPM-1-producing isolates, with additional non-synergistic bacterial density reduction for another isolate. Aztreonam peak concentrations alone demonstrated a ≥3 log10 cfu/mL reduction against all six isolates, but all strains were within the susceptible range for the drug. No antagonism was observed. CONCLUSIONS: In the context of increasing CR-PSA and the genetic diversity of resistance mechanisms, new combinations and stewardship strategies may need to be explored in the face of increasingly difficult to treat pathogens.

Gasteruptiidae (Hymenoptera, Evanioidea) of three savannah phytophysiognomies of the Estação Ecológica do Jataí, in southeastern Brazil, under three sampling methods and a new record for Gasteruption helenae Macedo, 2011.

In this study, the Gasteruptiidae species found at the Estação Ecológica de Jataí (EEJ), in Luiz Antonio, São Paulo, Brazil, were documented, based on a survey carried out with Malaise, Moericke and light traps that lasted for three years, between January 2007 and December 2009. During the samplings at EEJ, 13 female specimens of Gasteruption Latreille, 1796 were captured: six of G. bispinosum Kieffer, 1904, six of G. brasiliense (Blanchard, 1840) and a single specimen of G. helenae Macedo, 2011 that is the first record for São Paulo state.

Gut Microbiota Differences in Children From Distinct Socioeconomic Levels Living in the Same Urban Area in Brazil.

OBJECTIVE: To compare gut microbiota in impoverished children versus children of high socioeconomic status living in the same urban area in Brazil. METHODS: A cross-sectional study was conducted to evaluate 100 children living in a slum and 30 children from a private school, ages between 5 and 11 years old, in Sao Paulo State, Brazil. To characterize the groups, data based on socioeconomic status, sanitation, and housing conditions were collected. Anthropometric measurements and neonatal data were obtained from both groups. Gut microbiota were quantified in fecal samples by real-time polymerase chain reaction. RESULTS: The children in the private school group had higher rates of cesarean delivery and premature birth than the children in the slum group. Staphylococcus aureus (90% vs 48.0%) and Clostridium difficile (100% vs 43.0%) were more commonly found in the children from the private school than in the impoverished children (P < 0.0001). C perfringens was most frequently identified in the group of children from the slum (92.0% vs 80%; P = 0.064). Higher counts of total eubacteria, Firmicutes and Bacteroidetes phyla organisms, Escherichia coli, Lactobacillus spp., and Methanobrevibacter smithii were found in the children living in poverty, whereas higher counts of Salmonella spp., C difficile, and C perfringens were observed in the children living in satisfactory housing conditions (P < 0.05). CONCLUSIONS: Important differences were observed between the gut microbiota of children living under distinct socioeconomic and environmental conditions within the same city. Our findings suggest that children of high socioeconomic status have less favorable gut microbiota than do children who live in poverty.

Characterization of ocular methicillin-resistant Staphylococcus epidermidis isolates belonging predominantly to clonal complex 2 subcluster II.

Staphylococcus epidermidis is an abundant member of the microbiota of the human skin and wet mucosa, which is commonly associated with sight-threatening infections in eyes with predisposing factors. Ocular S. epidermidis has become notorious because of its capability to form biofilms on different ocular devices and due to the evolving rates of antimicrobial resistance. In this study, the molecular epidemiology of 30 ocular methicillin-resistant S. epidermidis (MRSE) isolates was assessed using multilocus sequence typing (MLST). Antimicrobial resistance, accessory gene-regulator and staphylococcal cassette chromosome mec (SCCmec) types, biofilm formation, and the occurrence of biofilm-associated genes were correlated with MLST clonal complexes. Sequence types (STs) frequently found in the hospital setting were rarely found in our collection. Overall, 12 different STs were detected with a predominance of ST59 (30%), ST5 and ST6 (13.3% each). Most of the isolates (93.3%) belonged to the clonal complex 2 (CC2) and grouped mainly within subcluster CC2-II (92.9%). Isolates grouped within this subcluster were frequently biofilm producers (92.3%) with a higher occurrence of the aap (84.5%) and bhp (46.1%) genes compared to icaA (19.2%). SCCmec type IV (53.8%) was predominant within CC2-II strains, while 38.4% were nontypeable. In addition, CC2-II strains were frequently multidrug resistant (80.7%) and demonstrated to be particularly resistant to ciprofloxacin (80.8%), ofloxacin (77%), azithromycin (61.5%), and gentamicin (57.7%). Our findings demonstrate the predominance of a particular MRSE cluster causing ocular infections, which was associated with high rates of antimicrobial resistance and particularly the carriage of biofilm-related genes coding for proteinaceous factors implicated in biofilm accumulation.

Preparation of stable and long-lived source samples for the stand-alone beam program at the Facility for Rare Isotope Beams.

At the Facility for Rare Isotope Beams (FRIB), an oven-ion source combination was used to create rare isotope beams in support of the stand-alone user beam program of the ReAccelerator (ReA) facility. This ion source, called Batch-Mode Ion Source (BMIS), was loaded with enriched stable nuclides (30Si, 50Cr, and 58Fe) and long-lived radionuclides (26Al, 32Si). The introduced samples, herein designated as source samples, were thermally volatilized in the BMIS oven, and then ionization was used to generate the required beams. Owing to the different chemical behavior of the used samples, it was important to tailor the sample loading process for each desired beam species. An important parameter here is the volatility of the introduced species, which influences the adequate release of the isotope of interest. Additionally, any co-present, volatile components will affect the ion yields of the desired isotope, while isobaric contaminants will decrease the beam purity. To manufacture isotope source samples that meet these characteristics, various chemical methodologies were developed. All prepared samples were successfully used in BMIS to deliver beams for various user beam experiments. The here-established sample preparation techniques will greatly aid future efforts in developing offline rare-isotope beams.

Rapid detection of carbapenemase genes by multiplex real-time PCR.

OBJECTIVES: To develop a single multiplex real-time PCR assay to detect six different genetic types of carbapenemases already identified in Enterobacteriaceae (KPC, GES, NDM, IMP, VIM and OXA-48). METHODS: A total of 58 bacterial isolates were tested. Thirty were previously characterized as resistant to carbapenems and documented by PCR and sequencing analysis to carry the following genes: bla(KPC) type, bla(GES) type, bla(IMP) type, bla(VIM) type, bla(OXA-48) and bla(NDM-1). These positive strains included 21 Enterobacteriaceae, 1 Acinetobacter baumannii and 8 Pseudomonas aeruginosa isolates. The remaining 28 isolates previously tested susceptible to carbapenems and were negative for these genes. Bacterial DNA was extracted using the easyMag extractor (bioMérieux, France). The real-time PCR was performed using the Rotor-Gene 6000 instrument (Corbett Life Science, Australia) and specific primers for each carbapenemase target were designed using the DNAStar software (Madison, WI, USA). RESULTS: Each one of the six carbapenemase genes tested presented a different melting curve after PCR amplification. The melting temperature (T(m)) analysis of the amplicons identified was as follows: bla(IMP) type (T(m) 80.1°C), bla(OXA-48) (T(m) 81.6°C), bla(NDM-1) (T(m) 84°C), bla(GES) type (T(m) 88.6°C), bla(VIM) type (T(m) 90.3°C) and bla(KPC) type (T(m) 91.6°C). No amplification was detected among the negative samples. The results showed 100% concordance with the genotypes previously identified. CONCLUSIONS: The new assay was able to detect the presence of six different carbapenemase gene types in a single 3 h PCR.

Acyclovir susceptibility of herpes simplex virus isolates from transplanted and nontransplanted patients in Rio de Janeiro, Brazil.

Herpes simplex virus (HSV) is prevalent worldwide and known as a notorious opportunistic pathogen ofimmunocompromised patients. During the course of HSV treatment, acyclovir (ACV)-resistant HSV strains may emerge, causing many clinical complications. Because few studies in this area showing the presence and/or frequency ofACV-resistant HSV are available, the authors evaluated the sensitivity of HSV isolated from 3 hematopoietic stem cell transplant recipients and 24 normal patients observed in a University Hospital in Rio de Janeiro, Brazil. Twenty-seven HSV isolated in VERO cells and typed by the direct immunofluorescence assay were tested for their susceptibility to various concentrations ofACV by the dye-uptake method. The susceptibility of the HSV strains was expressed as ED50 (the concentration of drug reducing viral cytophatic effect by 50%). The sensitivity to ACV by the dye-uptake assay revealed that 25 samples (92.6%) were sensitive to ACV concentrations < 1.5 microg/mL. One sample (3.7%) showed intermediate susceptibility (1.56 microg/mL) and one other sample (3.7%) showed resistance to ACV concentrations above the cut-off (2 microg/mL). The presence of resistance in immunocompetent patients could be the result of the frequent use of ACV for the treatment of recurrence. The routine use of HSV susceptibility testing is fundamental in the clinical suspicion of resistance not only for the knowledge of the incidence of HSV resistance in Brazil, but also to understand the mechanism of HSV resistance.

Broad-spectrum antimicrobial consumption trends and correlation with bacterial infections and antimicrobial resistance over 5 years.

OBJECTIVES: Consumption trends of four broad-spectrum antimicrobials and their correlation with antimicrobial resistance in Gram-negative bacilli (GNB) from 2013-2017 within intensive care units (ICUs) were explored. METHODS: Consumption of meropenem (MEM), polymyxin B (PMB), piperacillin/tazobactam (TZP) and cefepime (FEP) in defined daily doses per 1000 patient-days (DDD/1000PD) was measured. Infection-related GNB isolates were grouped according to specific resistance profiles. Time series of antimicrobial consumption and their parametric correlation with each grouped resistant GNB were explored. RESULTS: A total of 1423 GNB were evaluated. A significant linear decline in consumption was observed for MEM [slope -3.88, 95% confidence interval (CI) -4.96 to -2.81; P < 0.0001] and PMB (slope -3.51, 95% CI -5.528 to -1.495; P = 0.0009). A significant decline in MEM-non-susceptible Acinetobacter spp. (R2 = 0.476; P = 0.006) and an increase in FEP-non-susceptible Escherichia coli (R2 = 0.124; P = 0.006) was observed. A significant correlation between MEM consumption and MEM-non-susceptible Acinetobacter spp. (r = 0.43; P = 0.001) was observed. MEM consumption and MEM-non-susceptible Acinetobacter spp. showed a positive correlation. CONCLUSION: Reduction in the consumption of broad-spectrum antimicrobials may alter the frequency of infection-related isolates and their antimicrobial resistance profiles.

Unravelling complex transposable elements surrounding blaGES-16 in a Pseudomonas aeruginosa ExoU strain.

OBJECTIVES: We characterised the complex surrounding regions of blaGES-16 in a Pseudomonas aeruginosa exoU+ strain (P-10.226) in Brazil. METHODS: Species identification was performed by MALDI-TOF MS, and the antimicrobial susceptibility profile was determined by broth microdilution based on European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints. The whole genome sequencing (WGS) of P-10.226 strain was performed using both short-read paired-end sequencing on the Illumina MiSeq platform as well as the long-read Oxford Nanopore MinION. RESULTS: WGS analysis showed that P-10.226 carried blaGES-16, which was found as a gene cassette inserted into a novel class I integron, In1992 (aadB-blaOXA-56-blaGES-16-aadB-aadA6c), whose 3'-CS was truncated by a nested transposable element, IS5564::ISPa157. The structure was even more complex since IS6100-ΔIS6100 structure and a TnAs2-like harbouring the operon merRTPADE was found downstream In1992. Fragments of TnAs3 harbouring 25-bp imperfect inverted repeats were identified bordering the intl1 of In1992 and also flanking IS6100-ΔIS6100, which might be genetic marks of its previous presence in the genome. Interestingly, In1992 also shows a distinct cassette array from In581 (blaGES-16-dfrA22-aacA27-aadA1), which was previously reported in Serratia marcescens strains recovered in Brazil. Finally, exoU gene, which encodes a potent cytotoxin of type III secretion systems (T3SS) effector proteins from P. aeruginosa and is associated to severe infections, was also detected. CONCLUSION: We described the novel In1992 carrying blaGES-16 surrounded by complex transposition events in a XDR P. aeruginosa strain. The identification of many sets of direct repeats adjacent to TnAs3 fragments indicates a major past of transposition events that shaped the current genetic environment of In1992.

A spatial approach for the epidemiology of antibiotic use and resistance in community-based studies: the emergence of urban clusters of Escherichia coli quinolone resistance in Sao Paulo, Brasil.

BACKGROUND: Population antimicrobial use may influence resistance emergence. Resistance is an ecological phenomenon due to potential transmissibility. We investigated spatial and temporal patterns of ciprofloxacin (CIP) population consumption related to E. coli resistance emergence and dissemination in a major Brazilian city. A total of 4,372 urinary tract infection E. coli cases, with 723 CIP resistant, were identified in 2002 from two outpatient centres. Cases were address geocoded in a digital map. Raw CIP consumption data was transformed into usage density in DDDs by CIP selling points influence zones determination. A stochastic model coupled with a Geographical Information System was applied for relating resistance and usage density and for detecting city areas of high/low resistance risk. RESULTS: E. coli CIP resistant cluster emergence was detected and significantly related to usage density at a level of 5 to 9 CIP DDDs. There were clustered hot-spots and a significant global spatial variation in the residual resistance risk after allowing for usage density. CONCLUSIONS: There were clustered hot-spots and a significant global spatial variation in the residual resistance risk after allowing for usage density. The usage density of 5-9 CIP DDDs per 1,000 inhabitants within the same influence zone was the resistance triggering level. This level led to E. coli resistance clustering, proving that individual resistance emergence and dissemination was affected by antimicrobial population consumption.

Use of right ventricular remodeling surgery with a porcine pulmonary prosthesis for congenital heart disease.

BACKGROUND: The reconstruction of the right ventricular outflow tract (RVOT) in congenital heart disease has attracted the interest of cardiac surgeons determined to alleviate the anatomic obstruction and restore RV function. METHODS: From June 1991 to September 2008, 203 consecutive patients (mean, 3.0 years; range, 2 months to 35 years) underwent operations. These patients were classified into 5 groups: group 1, tetralogy of Fallot with pulmonary hypoplasia (144 cases, 70.9%); group 2, pulmonary atresia (PA) with ventricular septal defect (VSD) (32 cases, 15.7%); group 3, truncus arteriosus (12 cases, 5.9%); group 4, transposition of the great arteries with left ventricular outflow tract obstructions (8 cases, 3.9%); and group 5, PA with intact ventricular septum (7 cases, 3.4%). Remodeling surgery of the RV consisted of patch closure of the VSD (n = 176), tricuspid valvoplasty repair (n = 25), infundibulum muscle resection, and reconstruction of the RVOT (all patients). The Lecompte procedure was performed in 8 patients in group 4, and the one and a half ventricle technique was performed in 7 patients in group 5. RESULTS: There were 21 hospital deaths (10.3%); 180 patients (88.6%) survived. Patients were followed up from 4 to 206 months (mean, 98.0 months). Sixteen patients (8.8%) underwent reoperation for prosthesis dysfunction, with 2 in-hospital deaths (12.5%). The rest of the patients (164, 80.7%) remain free of reoperation. CONCLUSION: Earlier reconstruction of the pulmonary valve and the RVOT may preserve ventricular performance for a long period. Nevertheless, the porcine pulmonary prosthesis has shown satisfactory results when it has been used for the reconstruction of different types of RV obstructions.

Role of the left coronary artery geometry configuration in atherosusceptibility: CFD simulations considering sPTT model for blood.

The achievement of clinically viable methodologies to simulate the hemodynamics in patient-specific coronary arteries is still a major challenge. Therefore, the novelty of this work is attained by the introduction of the viscoelastic property of blood in the numerical simulations, to study the role of the left coronary artery (LCA) geometry configuration in the atherosusceptibility. Apparently healthy patients were used and four different methodologies were tested. The methodology giving the most accurate results at the same time of having the lowest computational time is the one considering the viscoelastic property of blood and computational fluid dynamics. A Pearson correlation analysis was used to highlight relationships between geometric configuration and hemodynamic descriptors based on the simulated wall shear stress (WSS). The left main stem (LMS) has the greatest atherosusceptibility followed by the left anterior descending artery (LAD) since the relative residence time (RRT) average values are 3.81 and 3.70 Pa-1, respectively. The geometric parameters with relevant contribution to directional flow change are the cross-sectional areas, especially the one of LMS segment (ALMS), and the curvature of LMS segment. For LMS and LAD segments, when ALMS increases, blood flow disturbance (r = 0.81 in LMS and r = 0.74 in LAD) and atherosusceptibility (r = 0.84 in LMS and r = 0.85 in LAD) increases. When the LMS curvature decreases, the WSS magnitude (r = 0.80 in LMS and r = 0.83 in LAD) decreases, and disturbance (r=-0.80 in LMS and r=-0.91 in LAD) and atherosusceptibility (r=-0.74 in LMS and r=-0.74 in LAD) increases.

In vitro synergy of ticarcillin/clavulanate in combination with aztreonam and ceftolozane/tazobactam against SPM-1-producing Pseudomonas aeruginosa strains.

Minimal inhibitory concentrations (MICs) of ticarcillin/clavulanic acid (TLc), ceftolozane/tazobactam (C/T), and aztreonam (AT) were determined for 6 SPM-1-producing Pseudomonas aeruginosa (PSA) using Etest® strips and the synergistic effect of such antimicrobials against was evaluated by gradient diffusion strip crossing (GDSC) test. The fraction inhibitory concentration indexes (FICI) were calculated and showed a synergistic (n = 3) and additive (n = 2) effects of TLc + AT against SPM-1 producers, while TLc + C/T combination caused no effect. Average MIC reduction of TLc and AT by GDSC was 3-fold and 2-fold dilutions, respectively. Thus, TLc + AT might be a candidate as a combination therapy to treat SPM-1-producing PSA infections.

Dynamic of High-Risk Acinetobacter baumannii Major Clones in a Brazilian Tertiary Hospital During a Short Time Period.

We characterized by whole-genome sequencing (WGS) six carbapenem-resistant Acinetobacter baumannii strains isolated from a Brazilian tertiary hospital during a 14-day period. The ISAba1-blaOXA-23 structure was found in the chromosome of five isolates, whereas blaOXA-72 was inserted in a 16.6-kb plasmid in two isolates. The presence of ISAba1-blaADC-like justified the high broad-spectrum cephalosporins minimal inhibitory concentrations (MICs) (MIC50, > 512 mg/L) verified in all isolates. Only minocycline (MIC50, ≤ 0.5 µg/mL), polymyxin B (MIC50, 0.5 µg/mL), and tigecycline (MIC50, 0.5 µg/mL) were in vitro active against such isolates. A diversity of other antimicrobial resistance determinants (aph(3')-VIa, aadA1, aac(3')-IIa, strA, strB, sul2, drfA1, mph(E), msr(E), tetB, and floR) was also observed, which may confer resistance to at last six distinct antimicrobial classes. Four distinct pulsed-field gel electrophoresis (PFGE) profiles were observed during the study period, which belonged to ST79/ST258 (n = 2; IC5), ST25/ST229 (n = 2; IC7), ST1 (n = 1; IC1), and ST162/ST235 (n = 1; IC4). Although the ST1 isolate that carried blaOXA-23 and blaOXA-72 was introduced in this hospital setting by a transferred patient, two clonally related ST79/ST258 isolates carrying either one of these carbapenemase encoding genes were recovered from two patients who were hospitalized within the same period of time in the same hospital unit. Finally, a good correlation between PFGE/MLST, blaOXA-51 variant, and single nucleotide polymorphisms was also observed. Here we demonstrated that distinct extensively drug-resistant A. baumannii clones can circulate in the same hospital setting during a short time period, illustrating a very complex epidemiological scenario for this priority pathogen.

Synthesis, antichagasic in vitro evaluation, cytotoxicity assays, molecular modeling and SAR/QSAR studies of a 2-phenyl-3-(1-phenyl-1H-pyrazol-4-yl)-acrylic acid benzylidene-carbohydrazide series.

Chagas disease (American trypanosomiasis) is one of the most important parasitic diseases with serious social and economic impacts mainly on Latin America. This work reports the synthesis, in vitro trypanocidal evaluation, cytotoxicity assays, and molecular modeling and SAR/QSAR studies of a new series of N-phenylpyrazole benzylidene-carbohydrazides. The results pointed 6k (X=H, Y=p-NO2, pIC(50)=4.55 M) and 6l (X=F, Y=p-CN, pIC(50)=4.27 M) as the most potent derivatives compared to crystal violet (pIC(50)=3.77 M). The halogen-benzylidene-carbohydrazide presented the lowest potency whereas 6l showed the most promising profile with low toxicity (0% of cell death). The best equation from the 4D-QSAR analysis (Model 1) was able to explain 85% of the activity variability. The QSAR graphical representation revealed that bulky X-substituents decreased the potency whereas hydrophobic and hydrogen bond acceptor Y-substituents increased it.

Surveillance programs for detection and characterization of emergent pathogens and antimicrobial resistance: results from the Division of Infectious Diseases, UNIFESP.

Several epidemiological changes have occurred in the pattern of nosocomial and community acquired infectious diseases during the past 25 years. Social and demographic changes possibly related to this phenomenon include a rapid population growth, the increase in urban migration and movement across international borders by tourists and immigrants, alterations in the habitats of animals and arthropods that transmit disease, as well as the raise of patients with impaired host defense abilities. Continuous surveillance programs of emergent pathogens and antimicrobial resistance are warranted for detecting in real time new pathogens, as well as to characterize molecular mechanisms of resistance. In order to become more effective, surveillance programs of emergent pathogens should be organized as a multicenter laboratory network connected to the main public and private infection control centers. Microbiological data should be integrated to guide therapy, adapting therapy to local ecology and resistance patterns. This paper presents an overview of data generated by the Division of Infectious Diseases, Federal University of São Paulo, along with its participation in different surveillance programs of nosocomial and community acquired infectious diseases.