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1.
PLoS One ; 15(1): e0228079, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31999747

RESUMO

We report on the genomic characterization of 47 multi-drug resistant, carbapenem resistant and ESBL-producing K. pneumoniae isolates from the influent (I) and effluent (E) of three wastewater treatment plants (WWTPs) and from Romanian hospital units which are discharging the wastewater in the sampled WWTPs. The K. pneumoniae whole genome sequences were analyzed for antibiotic resistance genes (ARGs), virulence genes and sequence types (STs) in order to compare their distribution in C, I and E samples. Both clinical and environmental samples harbored prevalent and widely distributed ESBL genes, i.e. blaSHV, blaOXA, blaTEM and blaCTX M. The most prevalent carbapenemase genes were blaNDM-1, blaOXA-48 and blaKPC-2. They were found in all types of isolates, while blaOXA-162, a rare blaOXA-48 variant, was found exclusively in water samples. A higher diversity of carbapenemases genes was seen in wastewater isolates. The aminoglycoside modifying enzymes (AME) genes found in all types of samples were aac(6'), ant(2'')Ia, aph(3'), aaD, aac(3) and aph(6). Quinolone resistance gene qnrS1 and the multi-drug resistance oqxA/B pump gene were found in all samples, while qnrD and qnrB were associated to aquatic isolates. The antiseptics resistance gene qacEdelta1 was found in all samples, while qacE was detected exclusively in the clinical ones. Trimethroprim-sulfamethoxazole (dfrA, sul1 and sul2), tetracyclines (tetA and tetD) and fosfomycin (fosA6, known to be located on a transpozon) resistance genes were found in all samples, while for choramphenicol and macrolides some ARGs were detected in all samples (catA1 and catB3 / mphA), while other (catA2, cmIA5 and aac(6')Ib / mphE and msrE) only in wastewater samples. The rifampin resistance genes arr2 and 3 (both carried by class I integrons) were detected only in water samples. The highly prevalent ARGs preferentially associating with aquatic versus clinical samples could ascribe potential markers for the aquatic (blaSHV-145, qacEdelta1, sul1, aadA1, aadA2) and clinical (blaOXA-1, blaSHV-106,blaTEM-150, aac(3)Iia, dfrA14, oqxA10; oqxB17,catB3, tetD) reservoirs of AR. Moreover, some ARGs (oqxA10; blaSHV-145; blaSHV-100, aac(6')Il, aph(3')VI, armA, arr2, cmlA5, blaCMY-4, mphE, msrE, oqxB13, blaOXA-10) showing decreased prevalence in influent versus effluent wastewater samples could be used as markers for the efficiency of the WWTPs in eliminating AR bacteria and ARGs. The highest number of virulence genes (75) was recorded for the I samples, while for E and C samples it was reduced to half. The most prevalent belong to three functional groups: adherence (fim genes), iron acquisition (ent, fep, fyu, irp and ybt genes) and the secretion system (omp genes). However, none of the genes associated with hypervirulent K. pneumoniae have been found. A total of 14 STs were identified. The most prevalent clones were ST101, ST219 in clinical samples and ST258, ST395 in aquatic isolates. These STs were also the most frequently associated with integrons. ST45 and ST485 were exclusively associated with I samples, ST11, ST35, ST364 with E and ST1564 with C samples. The less frequent ST17 and ST307 aquatic isolates harbored blaOXA-162, which was co-expressed in our strains with blaCTX-M-15 and blaOXA-1.

2.
Clin Gastroenterol Hepatol ; 18(2): 457-467.e21, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31306800

RESUMO

BACKGROUND & AIMS: Treatment of chronic hepatitis B virus (HBV) infection with entecavir suppresses virus replication and reduces disease progression, but could require life-long therapy. To investigate clinical outcome events and safety associated with long-term treatment with entecavir, we followed up patients treated with entecavir or another standard-of-care HBV nucleos(t)ide analogue for up to 10 years. We assessed long-term outcomes and relationships with virologic response. METHODS: Patients with chronic HBV infection at 299 centers in Asia, Europe, and North and South America were assigned randomly to groups that received entecavir (n = 6216) or an investigator-selected nonentecavir HBV nucleos(t)ide analogue (n = 6162). Study participants were followed up for up to 10 years in hospital-based or community clinics. Key end points were time to adjudicated clinical outcome events and serious adverse events. In a substudy, we examined relationships between these events and virologic response. RESULTS: There were no significant differences between groups in time to event assessments for primary end points including malignant neoplasms, liver-related HBV disease progression, and death. There were no differences between groups in the secondary end points of nonhepatocellular carcinoma malignant neoplasms and hepatocellular carcinoma. In a substudy of 5305 patients in China, virologic response, regardless of treatment group, was associated with a reduced risk of liver-related HBV disease progression (hazard ratio, 0.09; 95% CI, 0.038-0.221) and hepatocellular carcinoma (hazard ratio, 0.03; 95% CI, 0.009-0.113). Twelve patients given entecavir (0.2%) and 50 patients given nonentecavir drugs (0.8%) reported treatment-related serious adverse events. CONCLUSIONS: In a randomized controlled trial of patients with chronic HBV infection, we associated entecavir therapy with a low rate of adverse events over 10 years of follow-up evaluation. Patients receiving entecavir vs another nucleos(t)ide analogue had comparable rates of liver- and non-liver-related clinical outcome events. Participants in a China cohort who maintained a virologic response, regardless of treatment group, had a reduced risk of HBV-related outcome events including hepatocellular carcinoma. ClinicalTrials.gov identifier no: NCT00388674.

3.
BMC Infect Dis ; 19(1): 967, 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31718578

RESUMO

BACKGROUND: Seasonal influenza causes a considerable burden to healthcare services every year. To better measure the impact of severe influenza cases in Romania, we analyzed active surveillance data collected during the 2017-2018 season from patients admitted for influenza-like illness (ILI) at a tertiary care hospital in Bucharest. METHODS: Patients admitted for acute ILI were included if they were resident in the Bucharest-Ilfov region, had been hospitalized for at least 24 h, and had onset of symptoms within 7 days before admission. Patient demographics, healthcare use, vaccination status, and outcome data were collected by questionnaire or by searching clinical records. Respiratory swabs were also obtained from each patient to confirm influenza A (A/H1 and A/H3 subtypes) or influenza B (Yamagata and Victoria lineages) infection by real-time reverse-transcription polymerase chain reaction assay. RESULTS: The study included 502 patients, many (45.2%) of whom were aged < 5 years. Overall, 108 patients (21.5%) had one or more comorbidities. Seventeen adults aged 18-64 years (3.4%) had been vaccinated against influenza. Patients were hospitalized for a median of 5 days and most (90.4%) were prescribed antiviral treatment. More than one-half of the patients (n = 259, 51.6%) were positive for influenza. Most influenza cases were caused by B viruses (172/259, 66.4%), which were mostly of the B/Yamagata lineage (85 of 94 characterized, 90.4%). Most of the subtyped A viruses were A/H1 (59/74, 79.7%). A/H1 viruses were frequently detected in influenza-positive admissions throughout the 2017-2018 season, whereas the predominant B/Yamagata viruses were detected around the middle of the season, with a peak in cases at week 7 of 2018. Eleven patients were admitted to an intensive care unit; of these, one patient with confirmed B/Yamagata infection died. CONCLUSIONS: These results show that seasonal influenza results in considerable hospitalization in Bucharest-Ilfov, Romania and suggest vaccine coverage should be extended, especially to the youngest age groups. The data from this study should help inform and optimize national influenza healthcare policies.


Assuntos
Hospitalização/estatística & dados numéricos , Influenza Humana/diagnóstico , Adolescente , Adulto , Idoso , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/diagnóstico , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Vírus da Influenza B/genética , Vírus da Influenza B/isolamento & purificação , Vacinas contra Influenza/imunologia , Influenza Humana/complicações , Influenza Humana/epidemiologia , Influenzavirus A/genética , Influenzavirus A/isolamento & purificação , Masculino , Pessoa de Meia-Idade , Romênia/epidemiologia , Estações do Ano , Adulto Jovem
4.
Germs ; 9(3): 142-147, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31646144

RESUMO

Introduction: Patients with diabetes may be at a higher risk of developing complicated influenza. We report the characteristics of influenza in hospitalized elderly patients with and without diabetes, in three consecutive influenza seasons. Methods: The study included patients admitted for severe acute respiratory infection (SARI) in the National Institute for Infectious Diseases "Prof. Dr. Matei Balș", Bucharest, during a three-year active epidemiological surveillance study (2015/16, 2016/17, 2017/18), in the I-MOVE+ hospital network. Results: A total of 349 patients were tested by PCR over the duration of the study. The percentage of patients with diabetes was comparable throughout the seasons: 34.7%, 28.3% and 30.4% (p=0.587). Influenza A was the main viral type circulating in 2015/16 and 2016/17 (100% and 97.6%) in our study population, while in 2017/18, B viruses predominated (90.0%). Diabetics presented a higher median number of comorbidities (3 vs. 2) p<0.001, and two-fold higher odds of also associating obesity (OR=2.1, 95%CI:1.3-3.4, p=0.003), compared to those without diabetes. Diabetics also tested positive for influenza more often (p=0.296). Only 6 patients with diabetes (5.4%) from our study had been vaccinated against influenza, and most (n=4) of those who had been vaccinated tested negative for influenza. Conclusions: Our study is the first to describe the circulation of influenza viral types in elderly diabetic patients hospitalized for SARI. The results reinforce the national and international recommendation to vaccinate against influenza all patients with diabetes.

7.
J Viral Hepat ; 26(1): 109-117, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30187612

RESUMO

Addition of peginterferon alpha (PEG-IFN add-on) to entecavir (ETV) treatment after a short lead-in phase results in more response than ETV monotherapy in HBeAg-positive chronic hepatitis B infection (CHB). This study is the first to assess long-term efficacy of this treatment strategy. Patients who received ETV ± 24 weeks of PEG-IFN add-on in a global trial (ARES study) and completed follow-up were eligible to participate in this observational LTFU study if they had at least one combined HBeAg and HBV DNA measurement beyond week 96 of the ARES study. The primary endpoint was combined response (HBeAg loss and HBV DNA <200 IU/mL) at LTFU. In total, 48 patients treated with PEG-IFN add-on and 48 patients treated with ETV monotherapy were included. The median follow-up duration was 226 (IQR 51) weeks, and 86/96 (90%) patients were initial non-responders. At LTFU, combined response was present in 13 (27%) vs 11 (23%) patients (P = 0.81), and 1 log10  HBsAg decline in 59% vs 28% (P = 0.02) for PEG-IFN add-on and ETV monotherapy, respectively. In 41 initial non-responders who continued ETV therapy, combined response at LTFU was present in 9 patients (PEG-IFN add-on: 5/22 [23%]; ETV monotherapy: 4/19 [21%]). Beyond week 96 of follow-up, rates of serological response became comparable between PEG-IFN add-on and ETV monotherapy. Although in this LTFU study initial non-responders were overrepresented in the add-on arm, PEG-IFN add-on possibly leads rather to accelerated HBeAg loss than to increased long-term HBeAg loss rates.

8.
J Infect Public Health ; 12(2): 182-189, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30344102

RESUMO

BACKGROUND: Malignancies have become a leading cause of morbidity and mortality in people living with HIV (PLHIV). The primary endpoint of our study was to describe the epidemiology of acquired immunodeficiency syndrome (AIDS)-defining cancers (ADCs) and non-AIDS-defining cancers (NADCs). Epidemiological disparities, mortality predictors and survival analysis within the two groups of patients were key secondary endpoints. METHODS: We retrospectively evaluated all adult PLHIV with histopathologically proven cancers registered from 2010 to 2016 in the "Matei Balș" National Institute for Infectious Diseases, Bucharest, Romania. RESULTS: 110 eligible patients have been included in the study. The incidence of ADCs decreased from 1.6% in 2010 to 0.3% in 2016, unlike NADCs which remained fairly stable over time (0.3%). The higher CD4 count and lower HIV-RNA level at the cancer diagnosis were associated with prolonged survival in ADCs group, but not in NADCs group. The mean CD4 count was 449/mm3 to survivors and 92/mm3 to non-survivors (p=0.017). The mean level of HIV-RNA was 64,671 copies/mL to survivors and 1,760,345 copies/mL to non-survivors (p=0.002). CONCLUSIONS: A good therapeutic control of HIV infection at the diagnosis of ADCs was associated with better survival, emphasizing the key role of the effective cART in the management of HIV-associated cancers.


Assuntos
Infecções por HIV/complicações , Neoplasias/epidemiologia , Adulto , Antirretrovirais/uso terapêutico , Contagem de Linfócito CD4 , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/patologia , Infecções por HIV/virologia , Humanos , Incidência , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Neoplasias/mortalidade , Estudos Retrospectivos , Romênia/epidemiologia , Análise de Sobrevida , Centros de Atenção Terciária , Carga Viral
9.
Balkan Med J ; 36(3): 155-161, 2019 05 10.
Artigo em Inglês | MEDLINE | ID: mdl-30457109

RESUMO

Background: Young, non-obese adults are considered at low risk for cardiometabolic diseases, although markers of an unhealthy metabolic state are not uncommon findings in this population. Adipose tissue dysfunction, evaluated by the adipokine profile, significantly influences lipid and glucose metabolism and low-grade systemic inflammation. Aims: To determine the relation between adipose tissue dysfunction and the already confirmed cardiometabolic risk indicators, including the atherogenic index of plasma, lipid accumulation product, homeostatic model assessment of insulin resistance, and the low-grade inflammation markers, namely, interleukin 6 and high-sensitivity C-reactive protein. Study Design: Cross-sectional study. Methods: We recruited 93 non-obese, healthy young adults. Anthropometric, lipid profile, inflammatory markers, and adipokines were measured. An abnormal adipokine profile (high leptin-to-adiponectin ratio) was considered as a marker of a dysfunctional adipose tissue. The correlation between the leptin-to-adiponectin ratio and the anthropometric measurements, atherogenic index of plasma, lipid accumulation product, homeostatic model assessment of insulin resistance, interleukin 6, and high-sensitivity C-reactive protein was determined. Results: We found a direct correlation between the abnormal adipokine profile and the cardiometabolic risk indicators mentioned above, except for the low-grade inflammatory markers. In the regression model derived from our data, the leptin-to-adiponectin ratio was best correlated with the unfavorable plasma lipid profile, as estimated by the atherogenic index of plasma (r=0.097, confidence interval=0.015-0.180, p=0.021). A significantly higher leptin-to-adiponectin ratio was found in the insulin-resistant group (p=0.012) and in the highest lipid accumulation product quartile (p=0.032). Conclusion: In a non-obese young population, the high rate of leptin-adiponectin may be a good predictor of cardiovascular and metabolic risk assessment.


Assuntos
Adipocinas/análise , Doenças Cardiovasculares/classificação , Doenças Metabólicas/classificação , Medição de Risco/métodos , Adipocinas/sangue , Análise de Variância , Biomarcadores/análise , Biomarcadores/sangue , Índice de Massa Corporal , Proteína C-Reativa/análise , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/fisiopatologia , Estudos Transversais , Feminino , Voluntários Saudáveis/estatística & dados numéricos , Humanos , Resistência à Insulina , Interleucina-6/análise , Interleucina-6/sangue , Masculino , Doenças Metabólicas/sangue , Doenças Metabólicas/fisiopatologia , Medição de Risco/normas , Adulto Jovem
10.
Braz J Infect Dis ; 22(5): 377-386, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30391275

RESUMO

BACKGROUND: Influenza continues to drive seasonal morbidity, particularly in settings with low vaccine coverage. OBJECTIVES: To describe the influenza cases and viral circulation among hospitalized patients. METHODS: A prospective study based on active surveillance of inpatients with influenza-like illness from a tertiary hospital in Bucharest, Romania, in the season 2016/17. RESULTS: A total of 446 patients were tested, with a balanced gender distribution. Overall, 192 (43%) patients tested positive for influenza, with the highest positivity rate in the age groups 3-13 years and >65 years. Peak activity occurred between weeks 1 and 16/2017, with biphasic distribution: A viruses were replaced by B viruses from week 9/2017; B viruses predominated (66.1%). Among the 133 (69.3%) subtyped samples, all influenza A were subtype H3 (n=57) and all influenza B were B/Victoria (n=76). Patients who tested positive for influenza presented fewer comorbidities (p=0.012), except for the elderly, in whom influenza was more common in patients with comorbidities (p=0.050). Disease evolution was generally favorable under antiviral treatment. The length of hospital stay was slightly longer in patients with influenza-like illness who tested patients negative for influenza (p=0.031). CONCLUSIONS: Distinctive co-circulation of A/H3 and B/Victoria in Bucharest, Romania in the 2016/17 influenza season was found. While the A/H3 subtype was predominant throughout Europe that season, B/Victoria appears to have circulated specifically in Romania and the Eastern European region, predominantly affecting preschoolers and school children.


Assuntos
Monitoramento Epidemiológico , Influenza Humana/epidemiologia , Estações do Ano , Síndrome Respiratória Aguda Grave/epidemiologia , Adolescente , Adulto , Distribuição por Idade , Idoso , Criança , Pré-Escolar , Comorbidade , Feminino , Humanos , Lactente , Vírus da Influenza A/isolamento & purificação , Vírus da Influenza B/isolamento & purificação , Influenza Humana/patologia , Influenza Humana/virologia , Masculino , Vacinação em Massa/estatística & dados numéricos , Pessoa de Meia-Idade , Vigilância da População , Estudos Prospectivos , Romênia/epidemiologia , Síndrome Respiratória Aguda Grave/patologia , Síndrome Respiratória Aguda Grave/virologia , Centros de Atenção Terciária/estatística & dados numéricos , Fatores de Tempo , Adulto Jovem
11.
PLoS One ; 13(10): e0204974, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30325939

RESUMO

BACKGROUND: The nucleotide analog AL-335 is a pangenotypic hepatitis C virus (HCV) nonstructural protein (NS)5B inhibitor being evaluated as treatment for chronic HCV infection. METHODS: This three-part randomized, double-blind study evaluated the safety and pharmacokinetics of single and multiple ascending oral doses of AL-335. Healthy volunteers (HVs) received single doses of AL-335 (100-1,200 mg) or placebo in a fasted or fed (400 mg) state. Non-cirrhotic subjects (HCV genotype [GT]1-4) and GT1-infected subjects with Child Pugh A cirrhosis received multiple doses of AL-335 (400, 800, 1,200 mg) or placebo once daily (QD) for 7 days. RESULTS: Forty-eight HVs and 64 subjects with HCV GT1-4 were randomized and received treatment. AL-335 was well tolerated in HVs and HCV-infected subjects with/without cirrhosis. AL-335 was rapidly absorbed and converted to the metabolites ALS-022399 and ALS-022227. ALS-022227 exposure increased less than dose-proportionally and was unaffected by food, while AL-335 and ALS-022399 exposure increased with food by 85% and 50%, respectively, in HVs. Rapid and dose-dependent reductions in HCV-RNA were observed in GT1-infected subjects. In non-cirrhotic, GT1-4-infected subjects receiving AL-335 800 mg QD, potent antiviral activity was observed, regardless of genotype (mean maximum reductions in HCV-RNA of 4.0-4.8 log10 IU/mL). The same dose in GT1-infected cirrhotic subjects resulted in a 3.5 log10 IU/mL mean maximum reduction in HCV-RNA. CONCLUSIONS: AL-335 was well tolerated when administered as single and multiple doses, with an acceptable pharmacokinetic profile. The drug also demonstrated potent antiviral activity in HCV GT1-4-infected subjects, including GT1-infected subjects with cirrhosis.


Assuntos
Alanina/análogos & derivados , Antivirais/uso terapêutico , Hepatite C/tratamento farmacológico , Uridina/análogos & derivados , Adulto , Alanina/efeitos adversos , Alanina/farmacocinética , Alanina/uso terapêutico , Antivirais/efeitos adversos , Antivirais/farmacocinética , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Genótipo , Meia-Vida , Hepacivirus/genética , Hepatite C/complicações , Humanos , Cirrose Hepática/complicações , Masculino , Pessoa de Meia-Idade , Efeito Placebo , RNA Viral/sangue , Uridina/efeitos adversos , Uridina/farmacocinética , Uridina/uso terapêutico
12.
Braz. j. infect. dis ; 22(5): 377-386, Sept.-Oct. 2018. tab, graf
Artigo em Inglês | LILACS-Express | ID: biblio-974239

RESUMO

ABSTRACT Background: Influenza continues to drive seasonal morbidity, particularly in settings with low vaccine coverage. Objectives: To describe the influenza cases and viral circulation among hospitalized patients. Methods: A prospective study based on active surveillance of inpatients with influenza-like illness from a tertiary hospital in Bucharest, Romania, in the season 2016/17. Results: A total of 446 patients were tested, with a balanced gender distribution. Overall, 192 (43%) patients tested positive for influenza, with the highest positivity rate in the age groups 3-13 years and >65 years. Peak activity occurred between weeks 1 and 16/2017, with biphasic distribution: A viruses were replaced by B viruses from week 9/2017; B viruses predominated (66.1%). Among the 133 (69.3%) subtyped samples, all influenza A were subtype H3 (n = 57) and all influenza B were B/Victoria (n = 76). Patients who tested positive for influenza presented fewer comorbidities (p = 0.012), except for the elderly, in whom influenza was more common in patients with comorbidities (p = 0.050). Disease evolution was generally favorable under antiviral treatment. The length of hospital stay was slightly longer in patients with influenza-like illness who tested patients negative for influenza (p = 0.031). Conclusions: Distinctive co-circulation of A/H3 and B/Victoria in Bucharest, Romania in the 2016/17 influenza season was found. While the A/H3 subtype was predominant throughout Europe that season, B/Victoria appears to have circulated specifically in Romania and the Eastern European region, predominantly affecting preschoolers and school children.

13.
Anal Bioanal Chem ; 410(29): 7723-7737, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30255322

RESUMO

Two stochastic sensors based on the modification of graphite paste with the complexes formed by phthalocyanine (PhCN) with Ni and Cu were designed and used for molecular recognition of IL-8, IL-10, IL-12, and IL-15. The four interleukins were recognized according to their signatures-called toff (qualitative parameter) from the diagrams obtained after measurements. The limit of determination for IL-8 was 1 × 10-4µg mL-1 when both stochastic sensors were used; for IL-10, the determination limit was 4.5 × 10-4µg mL-1 for the Ni complex-based sensor, and 4.5 × 10-7µg mL-1 for the Cu complex-based sensor, respectively; for IL-12, the determination limit was 5 × 10-4µg mL-1 for the Ni complex-based sensor, and 5 × 10-7µg mL-1 for the Cu complex-based sensor, respectively; while for IL-15, the determination limit was 5 × 10-5µg/mL for the Ni complex-based sensor, and 5 × 10-5µg/mL for the Cu complex-based sensor, respectively. The stochastic method used was validated using the following biological fluids: nasal lavage, saliva, serum, and whole blood. Graphical abstract ᅟ.


Assuntos
Indóis/química , Interleucina-10/química , Interleucina-15/química , Interleucina-8/química , Técnicas Biossensoriais/métodos , Humanos , Interleucina-10/sangue , Interleucina-12 , Interleucina-15/sangue , Interleucina-8/sangue , Lavagem Nasal , Saliva/química
14.
AIDS Rev ; 20(1): 43-57, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29628514

RESUMO

This article is the second of a two-part review aiming to identify gaps in the knowledge and management of human immunodeficiency virus type 1 drug resistance (HIVDR) from global and regional perspectives. Here, we examine the policy and programmatic gaps in HIVDR surveillance, the affected populations and settings, and implications for clinical practice. The expert authorship of this review convened to identify gaps in HIVDR surveillance, with a particular focus on specific regional variations within and between Europe and Asia, to highlight directions for research and implementation. Further, evidence was gathered from a review of published studies, guidelines, and current practices. This review found that despite recent progress in the development, harmonization, and implementation of guidelines on HIVDR reporting and surveillance, programmatic, and policy gaps reflect the regional variability in HIV epidemics, clinical practice, and resources. The need for representative surveillance was identified as a key gap that has the potential to inform management policies. Monitoring must keep up with the evolution of transmission routes to adapt appropriately, and this will be further impacted by migration from areas with increasing levels of resistance. Analysis of the latest clinical data, regional practice, policy, and guidelines has identified a number of gaps in HIVDR population monitoring and surveillance. More efforts are needed to align surveillance platforms with harm reduction and patient education, particularly in vulnerable subgroups. Addressing these gaps will facilitate research into and progress in the management of HIV across a wide range of health-care settings.


Assuntos
Antirretrovirais/uso terapêutico , Infecções por HIV/tratamento farmacológico , Farmacorresistência Viral/genética , Feminino , HIV-1/efeitos dos fármacos , HIV-1/patogenicidade , Humanos , Masculino
15.
AIDS Rev ; 20(1): 27-42, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29628515

RESUMO

Resistance to antiretroviral therapy (ART) threatens the efficacy of human immunodeficiency virus type 1 (HIV-1) treatment. We present a review of knowledge gaps in the science and technologies of acquired HIV-1 drug resistance (HIVDR) in an effort to facilitate research, scientific exchange, and progress in clinical management. The expert authorship of this review convened to identify data gaps that exist in the field of HIVDR and discuss their clinical implications. A subsequent literature review of trials and current practices was carried out to provide supporting evidence. Several gaps were identified across HIVDR science and technology. A summary of the major gaps is presented, with an expert discussion of their implications within the context of the wider field. Crucial to optimizing the use of ART will be improved understanding of protease inhibitors and, in particular, integrase strand transfer inhibitors (INSTI) in the context of HIVDR. Limited experience with INSTI represents an important knowledge gap in HIV resistance science. Utilizing such knowledge in a clinical setting relies on accurate testing and analysis of resistance-associated mutations. As next-generation sequencing becomes more widely available, a gap in the interpretation of data is the lack of a defined, clinically relevant threshold of minority variants. Further research will provide evidence on where such thresholds lie and how they can be most effectively applied. Expert discussion identified a series of gaps in our knowledge of HIVDR. Addressing prefsuch gaps through further research and characterization will facilitate the optimal use of ART therapies and technologies.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , Farmacorresistência Viral/genética , Infecções por HIV/genética , HIV-1/efeitos dos fármacos , HIV-1/patogenicidade , Humanos , Mutação/genética
16.
Microb Pathog ; 102: 45-53, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27856272

RESUMO

Despite their commensal status, staphylococci can become problematic pathogens expressing multiple and redundant virulence factors. This study aimed to evaluate aggressiveness markers comparatively in staphylococcal strains isolated from severe infections versus asymptomatic carriage in order to identify clinically relevant bacterial traits that could easily be detected in clinical practice and could be suggestive for particular host-pathogen interactions such as cyto-adhesion or biofilm formation, ultimately orienting the clinical decision-making process. We have used in vitro phenotypic methods to assess adhesion to and invasion of eukaryotic cells, biofilm development, and expression of soluble virulence factors in 92 Staphylococcus spp. strains. The adhesion index, invasion capacity, biofilm formation and expression of soluble factors did not differ significantly between clinical and commensal strains. The major bacterial traits we found to be significantly more prevalent in clinical staphylococci were the aggregative adhesion pattern (P = 0.012), cluster adhesion (P = 0.001) and tetrad morphology (P = 0.018). The aggregative adhesion pattern was correlated with higher cyto-adhesion (P < 0.001), higher invasion capacity (P = 0.003) and lower Carmeli scores (P = 0.002). Three major bacterial traits, namely tetrad morphology, aggregative adhesion pattern, and resistance to methicillin (acronym: TAM), can be used to compute an aggressiveness score (SAS) predictive of the staphylococcal strain's virulence and capacity to initiate and develop a biofilm-driven chronic infectious process versus a fulminant acute infection, in a susceptible host.


Assuntos
Portador Sadio , Nasofaringe/microbiologia , Infecções Estafilocócicas/diagnóstico , Infecções Estafilocócicas/microbiologia , Staphylococcus/fisiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/farmacologia , Aderência Bacteriana , Biofilmes , Linhagem Celular , Criança , Pré-Escolar , Comorbidade , Feminino , Variação Genética , Humanos , Lactente , Recém-Nascido , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Característica Quantitativa Herdável , Índice de Gravidade de Doença , Staphylococcus/classificação , Staphylococcus/efeitos dos fármacos , Staphylococcus/patogenicidade , Virulência , Fatores de Virulência , Adulto Jovem
17.
FEMS Microbiol Lett ; 363(18)2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27521261

RESUMO

The increasing burden of invasive biofilm-related staphylococcal infections has led to a dire need for new agents to prevent biofilm formation. Bacteriophages may hypothetically alter a biofilm through several mechanisms, including induction of depolymerizing enzymes and lysis of persistent bacteria. We have assessed the influence of commercially available bacteriophage cocktails on Staphylococcus spp. clinical strains viability and biofilm formation. We analyzed 83 staphylococcal strains from patients consecutively admitted to a Romanian infection reference center from October 2014 through May 2015; the strains were characterized by phenotypic and genetic tools for their resistance and virulence features and for their phyliation. Experiments were performed in triplicate. Methicillin-susceptible strains were significantly more susceptible to all tested phages: 1.7-fold higher susceptibility for PYO, 1.4-fold for INTESTI, 2.9-fold for PHAGYO, 2.7-fold for PHAGESTI and 3.9-fold for STAPHYLOCOCCAL; t030 strains were significantly more susceptible to PYO and INTESTI compared with t127 strains. We identified a significant decrease in biofilm formation in the presence of both low and high PYO and INTESTI concentrations (P < 0.001). In conclusion, Staphylococcus strains from Romania displayed fairly good susceptibility to commercially available bacteriophages. We have also ascertained there is phage-driven in vitro inhibition of biofilm formation, the results potentially impacting prevention of prosthetic infections.

18.
BMC Infect Dis ; 16 Suppl 1: 93, 2016 03 08.
Artigo em Inglês | MEDLINE | ID: mdl-27169468

RESUMO

BACKGROUND: The Romanian HIV cohort has certain particularities that render it unique in Europe. We have performed a study to evaluate the prevalence of bone and kidney impairment in this particular group of HIV-infected patients. METHODS: We performed dual-energy X-ray absorptiometry (DXA) evaluation of the lumbar vertebrae and the femur, as well as laboratory tests including standard serum panels, bone-related markers and urinalysis in patients from the Romanian HIV cohort. RESULTS: The study included 72 patients, of which 46 (58.3 %) were males. The median (IQR) age was 38 (18) years and the median (IQR) time from HIV infection diagnosis was 9 (13) years. Most patients (55.6 %) were non-smokers, but a relatively high proportion (37.5 %) was currently smoking. Only a small percentage of patients (20.8 %) did not present any comorbidities, while 40.3 % had one comorbidity, the most frequent being dyslipidemia (present in 25 patients, 38.5 %). Only 6 patients had a medical history suggestive for renal disease and 3 for bone-related abnormalities. The median (IQR) glomerular filtration rate was 97.5 (33.0) mL/min/1.73sqm. We diagnosed 21 patients (29.6 %) with stage 2 chronic kidney disease and one patient (1.4 %) with stage 3 chronic kidney disease. Proteinuria was present in 9 (12.7 %) patients. The estimated glomerular filtration rate was significantly lower in patients with cardiac comorbidities (p = 0.013). Vitamin D was significantly lower in smokers compared with non-smokers, with a mean value of 15 vs. 21 ng/mL and a moderate effect size (Cohen's d = -0.5) (p = 0.046). Lumbar osteopenia and osteoporosis were diagnosed in 33.3 and 13.7 % of patients, while femoral osteopenia and osteoporosis were diagnosed in 37.3 and 7.8 %, respectively. Lower nadir CD4 cell counts were found in patients with bone-related comorbidities (p = 0.000). CONCLUSIONS: We identified a relatively high prevalence of chronic kidney disease in the Romanian HIV cohort, and a fairly low prevalence of osteopenia and osteoporosis, compared with other European countries. In this category of patients smoking should be avoided altogether, as it may be an indirect risk factor for kidney disease (associating cardiac comorbidities) and it may impair bone metabolism by altering serum levels of hydroxy-vitamin D.


Assuntos
Infecções por HIV , Vértebras Lombares , Osteoporose/epidemiologia , Insuficiência Renal Crônica/epidemiologia , Absorciometria de Fóton , Adulto , Contagem de Linfócito CD4 , Estudos de Coortes , Comorbidade , Estudos Transversais , Feminino , Taxa de Filtração Glomerular , Humanos , Masculino , Osteoporose/sangue , Osteoporose/complicações , Prevalência , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/urina , Fatores de Risco , Romênia/epidemiologia
19.
Germs ; 6(1): 14-20, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27019828

RESUMO

BACKGROUND: Healthcare workers constitute a population at high risk for HBV infection. Efficient vaccination options are available; however, the individual response to HBV vaccination may vary widely between subjects, potentially due to cytokine profiles and genetic variations. In the present study, we investigated the relationship between IL-17 and IL-22 gene polymorphisms versus non- and low-responsiveness to HBV vaccination in healthcare workers. METHODS: We selected the following IL-17 and IL-22 polymorphisms: rs4711998 (A/G) from IL-17 and rs2227501 (A/T), rs2227503 (A/G), rs1026786 (A/G) from IL-22 sequences genes. These were determined by polymerase chain reaction restriction fragment length polymorphisms. RESULTS: The IL-17 rs4711998 GG genotype had a significantly lower frequency in non-responders compared to low-responders (p=0.025). However, we did not identify a relationship between IL-22 rs1026780, rs2227501 and rs2227503 genotypes and the anti-HBs response following HBV vaccination. CONCLUSION: These data suggest that genetic variation in rs4711998 polymorphisms in the IL-17 cytokine may influence vaccine-induced immune responses to HBV vaccine in healthcare workers.

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