Autonomic neuropathic symptoms in patients with diabetes: practical tools for screening in daily routine.

BACKGROUND: Diabetic autonomic neuropathy (DAN) is a frequent complication in people with diabetes whose screening is often neglected. This study aimed to evaluate DAN through practical tools in people with diabetes in a referral center for diabetes treatment. METHODS: DAN symptoms and severity were assessed using the Survey of Autonomic Symptoms (SAS) via digital application (app) in patients attended from June 1, 2021, to November 12, 2021. SAS scoring for DAN was performed using established validated cutoffs. The adhesive with cobalt salt color indicator (Neuropad™) was used as a measure of sudomotor dysfunction. Demographical and clinical data were also collected. RESULTS: Data from 109 participants, 66.9% T2DM, 73.4% female, with a median age of 54.00 (± 20.00) years, were analyzed. Symptomatic DAN was present in 69.7% of participants and was associated with older age (p = 0.002), higher HbA1c (p = 0.043), higher abdominal circumference (p = 0.019), higher BMI (p = 0.013), more likely to have metabolic syndrome (MS) with a 10-fold increased risk, and more frequent association with diabetic peripheral neuropathy (p = 0.005). Sudomotor dysfunction was found in 65 participants with positive Neuropad™ detected in 63.1% of them. CONCLUSION: The use of SAS through an app proved to be a practical and easy-to-use instrument to document symptoms of DAN in busy clinical practice. The high frequency of symptoms draws attention to the importance of screening this underdiagnosed diabetes complication. The risk factors and comorbidities associated with symptomatic DAN highlight the patients' phenotypes linked to MS that should be targeted for DAN evaluations in larger samples in the community.

In vitro activity of imipenem/relebactam against Pseudomonas aeruginosa isolates recovered from ICU patients in Spain and Portugal (SUPERIOR and STEP studies).

OBJECTIVES: To study the in vitro activity of imipenem/relebactam and comparators and the imipenem/relebactam resistance mechanisms in a Pseudomonas aeruginosa collection from Portugal (STEP, 2017-18) and Spain (SUPERIOR, 2016-17) surveillance studies. METHODS: P. aeruginosa isolates (n = 474) were prospectively recovered from complicated urinary tract (cUTI), complicated intra-abdominal (cIAI) and lower respiratory tract (LRTI) infections in 11 Portuguese and 8 Spanish ICUs. MICs were determined (ISO broth microdilution). All imipenem/relebactam-resistant P. aeruginosa isolates (n = 30) and a subset of imipenem/relebactam-susceptible strains (n = 32) were characterized by WGS. RESULTS: Imipenem/relebactam (93.7% susceptible), ceftazidime/avibactam (93.5% susceptible) and ceftolozane/tazobactam (93.2% susceptible) displayed comparable activity. The imipenem/relebactam resistance rate was 6.3% (Portugal 5.8%; Spain 8.9%). Relebactam restored imipenem susceptibility to 76.9% (103/134) of imipenem-resistant isolates, including MDR (82.1%; 32/39), XDR (68.8%; 53/77) and difficult-to-treat (DTR) isolates (67.2%; 45/67). Among sequenced strains, differences in population structure were detected depending on the country: clonal complex (CC)175 and CC309 in Spain and CC235, CC244, CC348 and CC253 in Portugal. Different carbapenemase gene distributions were also found: VIM-20 (n = 3), VIM-1 (n = 2), VIM-2 (n = 1) and VIM-36 (n = 1) in Spain and GES-13 (n = 13), VIM-2 (n = 3) and KPC-3 (n = 2) in Portugal. GES-13-CC235 (n = 13) and VIM type-CC175 (n = 5) associations were predominant in Portugal and Spain, respectively. Imipenem/relebactam showed activity against KPC-3 strains (2/2), but was inactive against all GES-13 producers and most of the VIM producers (8/10). Mutations in genes affecting porin inactivation, efflux pump overexpression and LPS modification might also be involved in imipenem/relebactam resistance. CONCLUSIONS: Microbiological results reinforce imipenem/relebactam as a potential option to treat cUTI, cIAI and LRTI caused by MDR/XDR P. aeruginosa isolates, except for GES-13 and VIM producers.

Imipenem-Relebactam Susceptibility in Enterobacterales Isolates Recovered from ICU Patients from Spain and Portugal (SUPERIOR and STEP Studies).

Imipenem-relebactam is a novel ß-lactam-ß-lactamase inhibitor combination. We evaluated the in vitro activity of imipenem-relebactam and comparators against Enterobacterales clinical isolates recovered in 8 Spanish and 11 Portuguese intensive care units (ICUs) (SUPERIOR, 2016-2017; STEP, 2017-2018). Overall, 747 Enterobacterales isolates (378 Escherichia coli, 252 Klebsiella spp., 64 Enterobacter spp., and 53 other species) were prospectively collected from ICU patients with complicated intraabdominal (cIAI), complicated urinary tract (cUTI), and lower respiratory tract (LRTI) infections. MICs were determined (ISO-broth microdilution), and whole-genome sequencing (WGS) was performed in a subset of isolates displaying susceptible and resistant imipenem-relebactam MICs. Imipenem-relebactam (98.7% susceptible) showed similar activity to ceftazidime-avibactam (99.5% susceptible) and higher than ceftolozane-tazobactam (86.9% susceptible). Imipenem-relebactam was inactive against 1.3% (10/747) isolates, all of them due to carbapenemase production (9 K. pneumoniae and 1 E. cloacae). Imipenem-relebactam was active against 100% of extended-spectrum ß-lactamase (ESBL)-E. coli and ESBL-Klebsiella spp. isolates and 80.4% of carbapenemase-Klebsiella spp. producers. Carbapenemase genes were confirmed by WGS in 41 Klebsiella spp.: OXA-48 (20/41), KPC-3 (14/41), OXA-181 (4/41), NDM-1 (1/41), OXA-48 + VIM-2 (1/41), and KPC-3 + VIM-2 (1/41). In Klebsiella spp. isolates, relebactam restored imipenem susceptibility in all KPC-3 producers, and resistant isolates (7/41) were mostly OXA-48 + CTX-M-15-K. pneumoniae high-risk clones (7/9). Intercountry differences were detected as follows: OXA-48 (17/21) was dominant in Spain, unlike KPC-3 (14/15) in Portugal. Imipenem-relebactam was 100% active against CTX-M-15-ST131-H30Rx-E. coli high-risk clone, predominant in both countries. Our results depict the potential role of imipenem-relebactam in ICU patients with cIAIs, cUTIs, and LRTIs due to wild-type ESBL- and carbapenemase-producing Enterobacterales, particularly KPC producers. IMPORTANCE We comparatively evaluate the in vitro activity of a drug combination consisting of a carbapenem (imipenem) and a novel inhibitor of beta-lactamases (relebactam), a mechanism that destroys beta-lactam antibiotics. We assess the activity against a collection of Enterobacterales clinical isolates recovered from difficult-to-treat infections in patients admitted to different intensive care units in Portugal and Spain. Imipenem-relebactam shows excellent activity in avoiding common resistance mechanisms in this setting, such as extended-spectrum beta-lactamases and carbapenemases widely distributed, including KPCs. We show few resistant isolates (<2%). Molecular characterization by whole-genome sequencing shows that most of the resistant isolates produced specific carbapenemase, such as OXA-48 or metalo-betalactamases. Our study updates the activity of imipenem-relebactam in light of current epidemiology in a hospital setting in which the use of this combination is needed due to the presence of infections due to multidrug-resistant isolates.

Distinct epidemiology and resistance mechanisms affecting ceftolozane/tazobactam in Pseudomonas aeruginosa isolates recovered from ICU patients in Spain and Portugal depicted by WGS.

OBJECTIVES: To analyse the epidemiology, the resistome and the virulome of ceftolozane/tazobactam-susceptible or -resistant Pseudomonas aeruginosa clinical isolates recovered from surveillance studies in Portugal (STEP, 2017-18) and Spain (SUPERIOR, 2016-17). METHODS: P. aeruginosa isolates were recovered from intra-abdominal, urinary tract and lower respiratory tract infections in ICU patients admitted to 11 Portuguese and 8 Spanish hospitals. MICs were determined (ISO-standard broth microdilution, EUCAST 2020 breakpoints). A subset of 28 ceftolozane/tazobactam-resistant P. aeruginosa isolates were analysed and compared with 28 ceftolozane/tazobactam-susceptible P. aeruginosa strains by WGS. RESULTS: Clonal complex (CC) 235 (27%) and CC175 (18%) were the most frequent, followed by CC244 (13%), CC348 (9%), CC253 (5%) and CC309 (5%). Inter-hospital clonal dissemination was observed, limited to a geographical region (CC235, CC244, CC348 and CC253 in Portugal and CC175 and CC309 in Spain). Carbapenemases were detected in 25 isolates (45%): GES-13 (13/25); VIM type (10/25) [VIM-2 (4/10), VIM-20 (3/10), VIM-1 (2/10) and VIM-36 (1/10)]; and KPC-3 (2/25). GES-13-CC235 (13/15) and VIM type-CC175 (5/10) associations were observed. Interestingly, KPC-3 and VIM-36 producers showed ceftolozane/tazobactam-susceptible phenotypes. However, ceftolozane/tazobactam resistance was significantly associated with GES-13 and VIM-type carbapenemase production. Six non-carbapenemase producers also displayed ceftolozane/tazobactam resistance, three of them showing known ceftolozane/tazobactam resistance-associated mutations in the PBP3 gene, ftsI (R504C and F533L). Overall, an extensive virulome was identified in all P. aeruginosa isolates, particularly in carbapenemase-producing strains. CONCLUSIONS: GES-13-CC235 and VIM type-CC175 were the most frequent MDR/XDR P. aeruginosa clones causing infections in Portuguese and Spanish ICU patients, respectively. Ceftolozane/tazobactam resistance was mainly due to carbapenemase production, although mutations in PBP-encoding genes may additionally be involved.

In vitro activity of ceftolozane-tazobactam against Enterobacterales and Pseudomonas aeruginosa causing urinary, intra-abdominal and lower respiratory tract infections in intensive care units in Portugal: The STEP multicenter study.

The STEP surveillance study was designed to increase knowledge about distribution of multidrug-resistant (MDR) Enterobacterales and Pseudomonas aeruginosa in Portugal, focusing on the intensive care unit (ICU). Antimicrobial susceptibility of common agents was also evaluated and compared with that of one of the latest therapeutic introductions, ceftolozane-tazobactam (C/T). Clinical isolates of Enterobacterales (n=426) and P. aeruginosa (n=396) from patients admitted in Portuguese ICUs were included. Activity of C/T and comparators was investigated using standard broth microdilution. Isolates were recovered from urinary tract (UTI, 36.9%), intra-abdominal (IAI, 24.2%) and lower respiratory tract (LRTI, 38.9%) infections. In P. aeruginosa, overall distribution of MDR/extremely-drug resistant (XDR)/pan-drug resistant (PDR) isolates accounted for 21.2%, 23.2% and 0.8%, respectively. C/T was the most potent agent tested against P. aeruginosa and MDR/XDR/PDR phenotypes. In Escherichia coli, extended-spectrum beta-lactamases (ESBL) and carbapenemase (CP) phenotypes accounted for 16.6% and 1.7%, respectively, whereas in Klebsiella spp., ESBL and CP-phenotypes represented 28.5% and 17.9%, respectively. Overall, susceptibility of C/T against Enterobacterales was 86.9%. C/T was the least affected agent in E. coli (99.4% susceptibility), whereas its activity was moderate in Klebsiella spp. (71.5%) and Enterobacter spp. (70.4%), due in part to a high rate of ESBL and CP-phenotypes. In Enterobacterales, blaKPC was the most prevalent CP gene (63.0%), followed by blaOXA-48 (33.3%) and blaVIM (3.7%). These microbiological results reinforce C/T as a therapeutic option in ICU patients with UTI, IAI or LRTI due to P. aeruginosa or Enterobacterales isolates, but not for CP producers.

Ecological aspects of mosquitoes (Diptera: Culicidae) in the gallery forest of Brasília National Park, Brazil, with an emphasis on potential vectors of yellow fever.

INTRODUCTION: We analyzed the vertical and monthly distributions of culicid species in the gallery forest of Brasília National Park, with an emphasis on the potential vectors of yellow fever (YF). METHODS: Between September 2010 and August 2011, mosquitoes were captured on the ground and in the canopy of the forest for five consecutive days per month, from nine to 15 hours. The mosquitoes were examined to verify natural infection with flaviviruses by isolation in Aedes albopictus Skuse, 1864 cells followed by indirect immunofluorescence. RESULTS: We identified 2,677 culicids distributed in 29 species. Most of the mosquitoes were captured at ground level (69%) during the rainy season (86%). The most abundant species were Sabethes (Sabethes) albiprivus Theobald, 1903; Limatus durhamii Theobald, 1901; Haemagogus (Conopostegus) leucocelaenus Dyar & Shannon, 1924; Haemagogus (Haemagogus) janthinomys Dyar, 1921; Aedes (Ochlerotatus) scapularis Rondani, 1848; Psorophora (Janthinosoma) ferox Von Humboldt, 1819; and Aedes (Ochlerotatus) serratus Theobald, 1901. Limatus durhamii, Limatus durhamii, Psorophora ferox, Aedes scapularis and Aedes serratus showed significant differences (p<0.05) in their habitat use. Limatus durhamii was found more often in the canopy, unlike the other species. During the rainy season, the most abundant species were Sa. albiprivus, Haemagogus leucocelaenus and Limatus durhamii. During the dry season, the potential YF vectors exhibited a very low frequency and abundance, except Aedes scapularis and Aedes serratus. No flavivirus was detected in the 2,677 examined mosquitoes. CONCLUSIONS: We recommend continued and systematic entomological monitoring in areas vulnerable to the transmission of YF in the Federal District of Brazil.

Ecological aspects of mosquitoes (Diptera: Culicidae) in the gallery forest of Brasilia National Park, Brazil, with an emphasis on potential vectors of yellow fever

Introduction We analyzed the vertical and monthly distributions of culicid species in the gallery forest of Brasília National Park, with an emphasis on the potential vectors of yellow fever (YF). Methods Between September 2010 and August 2011, mosquitoes were captured on the ground and in the canopy of the forest for five consecutive days per month, from nine to 15 hours. The mosquitoes were examined to verify natural infection with flaviviruses by isolation in Aedes albopictus Skuse, 1864 cells followed by indirect immunofluorescence. Results We identified 2,677 culicids distributed in 29 species. Most of the mosquitoes were captured at ground level (69%) during the rainy season (86%). The most abundant species were Sabethes (Sabethes) albiprivus Theobald, 1903; Limatus durhamii Theobald, 1901; Haemagogus (Conopostegus) leucocelaenus Dyar & Shannon, 1924; Haemagogus (Haemagogus) janthinomys Dyar, 1921; Aedes (Ochlerotatus) scapularis Rondani, 1848; Psorophora (Janthinosoma) ferox Von Humboldt, 1819; and Aedes (Ochlerotatus) serratus Theobald, 1901. Limatus durhamii, Limatus durhamii, Psorophora ferox, Aedes scapularis and Aedes serratus showed significant differences (p<0.05) in their habitat use. Limatus durhamii was found more often in the canopy, unlike the other species. During the rainy season, the most abundant species were Sa. albiprivus, Haemagogus leucocelaenus and Limatus durhamii. During the dry season, the potential YF vectors exhibited a very low frequency and abundance, except Aedes scapularis and Aedes serratus. No flavivirus was detected in the 2,677 examined mosquitoes. Conclusions We recommend continued and systematic entomological monitoring in areas vulnerable to the transmission of YF in the Federal District of Brazil. .

Estado nutricional na primeira infância e cárie dentária na dentição decídua: uma revisão de literatura / Nutritional status in the early childhood and dental caries in deciduous teeth: a literature review

Objetivo: O objetivo do estudo foi realizar uma revisão da literatura acerca da relação entre o estado nutricional das crianças durante a primeira infância e a ocorrência e a gravidade da cárie dentária na dentição decídua. Método: Realizou-se uma busca nas bases de dados eletrônicas BBO (Biblioteca Brasileira de Odontologia), Lilacs (Literatura Latino Americana e do Caribe em Saúde), Scielo e Medline, do início da disponibilidade dessas bases até julho de 2007. Foram incluídos somente estudos epidemiológicos realizados em seres humanos, escritos em espanhol, inglês e português. Características metodológicas, como tamanho de amostra, medidas de exposição e desfecho, e os principais resultados, foram analisadas. Resultado: A busca eletrônica inicial resultou em 60 artigos científcos, sendo que apenas cinco preencheram os critérios de inclusão. Outros cinco importantes artigos foram encontrados na lista de referências dos estudos selecionados e foram considerados na análise, totalizando dez artigos. Apenas um estudo utilizou o desenho longitudinal, sendo todos os demais transversais. Em oito estudos, encontrou-se associação entre algum grau de má nutrição e prevalência ou incremento de cárie dentária na dentição decídua. Não foram identificados estudos que adotaram estratégias para controlar potenciais variáveis de confusão. Conclusão: Embora a maioria dos estudos analisados aponte associação entre estado nutricional desfavorável e experiência ou maior gravidade de cárie dentária, estes estudos apresentam importantes limitações metodológicas. Consequentemente, a força de evidência científica entre estado nutricional e cárie dentária na dentição decídua pode ser considerada fraca.

Objective: The aim of this study was to undertake a literature review assessing the relationship between children's nutritional status during the early childhood and dental caries in deciduous teeth. Method: The BBO (Dental Brazilian Library), Lilacs (Latin American and Caribbean Health Literature), Scielo and Medline electronics databases were searched with retrospective no time limitation until July 2007. Only epidemiological studies published in Spanish, English and Portuguese were selected. Methodological characteristics such as sample size, exposure and outcome measures and main results were analyzed. Result: Of the total of 60 articles found in the initial electronic search only fve fulflled the inclusion criteria. Other fve important studies were found in the lists of references of the selected studies and were considered in the analysis totalizing 10 papers. Only one study adopted a longitudinal design; the others were cross-sectional studies. In eight studies were identifed association between some level of malnutrition and prevalence or incidence of dental caries in the deciduous teeth. It was not identify any study which adopted strategies to control potential confounding variables. Conclusion: Although the vast majority of the analyzed studies reported association between malnutrition status and experience or severity of dental caries, important methodological limitations were observed. Consequently, there is a lack of good scientifc evidence about the relationship between malnutrition and dental caries in deciduous teeth.