RESUMO
INTRODUCTION: Guillain-Barré syndrome associated with Coronavirus-2-related severe acute respiratory syndrome (COV-GBS) occurs as para- or post-infectious forms, depending on the timing of disease onset. In these two forms, we aimed to compare the cerebrospinal fluid (CSF) and serum proinflammatory cytokine profiles to evaluate differences that could possibly have co-pathogenic relevance. MATERIALS AND METHODS: We studied a retrospective cohort of 26 patients with either post-COV-GBS (n = 15), with disease onset occurring > 7 days after SARS-CoV-2 infection, or para-COV-GBS (n = 11), with disease onset 7 days or less. TNF-α, IL-6, and IL-8 were measured in the serum with SimplePlex™ Ella™ immunoassay. In addition to the para-/post-COV-GBS patients, serum levels of these cytokines were determined in those with non-COVID-associated-GBS (NC-GBS; n = 43), paucisymptomatic SARS-CoV-2 infection without GBS (COVID, n = 20), and in healthy volunteers (HV; n = 12). CSF cytokine levels were measured in patients with para-/post-COV-GBS, in those with NC-GBS (n = 29), or with Alzheimer's disease (AD; n = 24). RESULTS: Serum/CSF cytokine levels did not differ in para- vs post-COV-GBS. We found that SARS-CoV-2 infection raises the serum levels of TNF-α, IL-6, and IL-8, as well as an increase of IL-6 (in serum and CSF) and IL-8 (in CSF) in either NC-GBS or COV-GBS than controls. CSF and serum cytokine levels resulted independent one with another. CONCLUSIONS: The change of cytokines linked to SARS-CoV-2 in COV-GBS appears to be driven by viral infection, although it has unique characteristics in GBS as such and does not account for cases with para- or post-infectious onset.
Assuntos
COVID-19 , Síndrome de Guillain-Barré , Humanos , COVID-19/complicações , SARS-CoV-2 , Síndrome de Guillain-Barré/complicações , Citocinas , Interleucina-6/líquido cefalorraquidiano , Fator de Necrose Tumoral alfa , Estudos Retrospectivos , Interleucina-8RESUMO
Guillain-Barré syndrome (GBS) is a peripheral nervous system disease caused by an immune-mediated inflammatory mechanism, usually triggered by a previous infectious process or vaccine; its typical presentation is a rapid and progressive bilateral limb hyposthenia, associated with sensory deficits and reduction or absence of osteotendinous reflexes. However, also autonomic nervous system can be involved with heart rate fluctuations, blood pressure instability, pupillary dysfunction, and urinary retention. Since the beginning of COVID-19 pandemic, GBS has been reported among neurological complications of SARS-CoV-2 infection, although etiopathological mechanisms still have to be clearly defined. We report the case of a 79-year-old man with multiple comorbidities, including diabetes, who was affected by SARS-CoV-2 interstitial pneumonia and developed dysautonomic symptoms after 10 days of hospitalization. A neurological evaluation was performed, and GBS was considered as a possible cause of the clinical manifestations. This hypothesis was confirmed by electrophysiological study and further supported, ex-juvantibus, by the satisfactory response to immunoglobulin treatment. In our opinion, this case of pure dysautonomic presentation of GBS in a SARS-CoV-2 positive patient is relevant because it suggests to consider GBS upon SARS-CoV-2 infection even if the symptoms have uncommon characteristics (e.g., pure vegetative manifestations) and if there are confounding factors which could lead to a misdiagnosis (e.g., old age, SARS-CoV-2 infection consequences and diabetes).
Assuntos
COVID-19/complicações , Síndrome de Guillain-Barré/diagnóstico , Síndrome de Guillain-Barré/virologia , Disautonomias Primárias/virologia , Idoso , Síndrome de Guillain-Barré/complicações , Humanos , Masculino , Disautonomias Primárias/etiologia , SARS-CoV-2RESUMO
OBJECTIVE: To describe bacterial resistance and antimicrobial consumption ratio at the subnational level in Argentina during 2018, considering beta-lactams group as a case-study. METHODS: Antimicrobial consumption was expressed as defined daily doses (DDD)/1000 inhabitants. Resistance of Escherichia coli, Streptococcus pneumoniae, Pseudomonas aeruginosa, Klebsiella pneumoniae and Staphylococcus aureus to beta-lactams was recorded. Resistance/consumption ratio was estimated calculating "R" for each region of Argentina, and this data was compared with other countries. RESULTS: The most widely consumed beta-lactams in Argentina were amoxicillin (3.64) for the penicillin sub-group, cephalexin (0.786) for first generation cephalosporins, cefuroxime (0.022) for second generation; cefixime (0.043) for third generation and cefepime (0.0001) for the fourth generation group. Comparison between beta-lactams consumption and bacterial resistance demonstrated great disparities between the six regions of the country. CONCLUSIONS: The case-study of Argentina shows that antimicrobial consumption and resistance of the most common pathogens differed among regions, reflecting different realities within the same country. Because this situation might also be occurring in other countries, this data should be taken into account to target local efforts towards better antimicrobial use, to improve antimicrobial stewardship programs and to propose more suitable sales strategies in order to prevent and control antimicrobial resistance.
RESUMO
Control of HIV replication in elite controller (EC) and long-term nonprogressor (LTNP) patients has been associated with efficient CD8(+)cytotoxic T-lymphocyte function. However, innate immunity may play a role in HIV control. We studied the expression of natural cytotoxicity receptors (NKp46, NKp30, and NKp44) and their induction over a short time frame (2-4 d) on activation of natural killer (NK) cells in 31 HIV controller patients (15 ECs, 16 LTNPs). In EC/LTNP, induction of NKp46 expression was normal but short (2 d), and NKp30 was induced to lower levels vs. healthy donors. Notably, in antiretroviral-treated aviremic progressor patients (TAPPs), no induction of NKp46 or NKp30 expression occurred. More importantly, EC/LTNP failed to induce expression of NKp44, a receptor efficiently induced in activated NK cells in TAPPs. The specific lack of NKp44 expression resulted in sharply decreased capability of killing target cells by NKp44, whereas TAPPs had conserved NKp44-mediated lysis. Importantly, conserved NK cell responses, accompanied by a selective defect in the NKp44-activating pathway, may result in lack of killing of uninfected CD4(+)NKp44Ligand(+) cells when induced by HIVgp41 peptide-S3, representing a relevant mechanism of CD4(+) depletion. In addition, peripheral NK cells from EC/LTNP had increased NKG2D expression, significant HLA-DR up-regulation, and a mature (NKG2A-CD57(+)killer cell Ig-like receptor(+)CD85j(+)) phenotype, with cytolytic function also against immature dendritic cells. Thus, NK cells in EC/LTNP can maintain substantially unchanged functional capabilities, whereas the lack of NKp44 induction may be related to CD4 maintenance, representing a hallmark of these patients.
Assuntos
Infecções por HIV/imunologia , Sobreviventes de Longo Prazo ao HIV , Imunidade Inata/imunologia , Interleucina-2/imunologia , Células Matadoras Naturais/imunologia , Receptor 2 Desencadeador da Citotoxicidade Natural/metabolismo , Anticorpos Monoclonais/imunologia , Citometria de Fluxo , Imunofluorescência , Humanos , Imunofenotipagem , Interleucina-2/metabolismo , Células Matadoras Naturais/citologia , Subfamília K de Receptores Semelhantes a Lectina de Células NK/metabolismo , Estatísticas não ParamétricasRESUMO
GOALS: To characterize the clinical and treatment pattern in a large population of hepatitis B virus (HBV) patients managed at tertiary referral centers in clinical practice. BACKGROUND: Successful treatment, either with interferon (IFN) or nucleos(t)ide analogs (NUCs), of chronic HBV infection is associated with improved long-term patient outcome. However, in clinical practice, the actual management of these patients is not well characterized, and data regarding treatment pattern in this setting are lacking. METHODS: In this cross-sectional study, we evaluated 505 patients chronically infected with HBV alone and who had at least 1-year follow-up. We assessed indication to, rate of, and type of treatment as well as the characteristics of treated patients. RESULTS: Overall prevalence of positivity for HBe antigen was 19.3%, and the majority of patients had chronic hepatitis (47.5%). Non-Italian patients represented approximately one third of the population (27.1%). Among patients with indication to antiviral therapy (n=318), treatment was actually carried out in 264 patients (83.0%), prevalently with NUCs (65.9%). IFN-treated patients were younger (P<0.001), more frequently male (P=0.025) and HBeAg positive (P=0.003), and less frequently cirrhotics (P<0.001) as compared with patients treated with NUCs. CONCLUSIONS: In a geographical area with a low positivity for HBe antigen, antiviral therapy is actually carried out in the majority of patients who have indication to treatment, prevalently with NUCs, whereas IFN treatment is more frequently carried out in young, HBe antigen-positive patients who do not have advanced liver disease.
Assuntos
Antivirais/uso terapêutico , Vírus da Hepatite B/efeitos dos fármacos , Hepatite B Crônica/tratamento farmacológico , Interferons/uso terapêutico , Padrões de Prática Médica/tendências , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Estudos Transversais , Progressão da Doença , Feminino , Pesquisas sobre Atenção à Saúde , Antígenos E da Hepatite B/sangue , Vírus da Hepatite B/imunologia , Hepatite B Crônica/sangue , Hepatite B Crônica/diagnóstico , Hepatite B Crônica/epidemiologia , Humanos , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Soroepidemiológicos , Centros de Atenção Terciária , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND AND AIMS: Ceftobiprole is a recent 5th generation parenteral cephalosporin with antibacterial activity against a large range Gram+ and Gram- bacteria. Therapeutic drug monitoring (TDM) is an essential tool for maintaining plasma concentrations of antibiotics above the MIC by the end of the dosing interval, thus preventing the resistant strain diffusion. TDM is already recommended for other cephalosporins, and it is a reasonable tool contributing to the safety and efficacy of these drugs. During the treatment of patients in real-life, a number of pharmacokinetic (PK) changes not normally seen in healthy volunteers can occur which can impair the pharmacokinetic/pharmacodynamic target attainment. We aimed to develop simple and rapid HPLC-UV method for determination of ceftobiprole in human serum to implement TDM in clinical practice and support PKs and pharmacokinetic/pharmacodynamic (PK/PD) studies. MATERIALS AND METHODS: Samples preparation of calibration standards, QC, and anonymous patients serum samples was performed by protein precipitation by adding 0.01 ml of sulphosalicylic acid at 30 % to 0.1 ml of each sample. Then samples were vortexed and the centrifuged at 12,000 rpm for 10 min at 4 °C. Fifty microlitres of clear supernatant were diluted 1:1 with mobile phase and transferred into HPLC autosampler held at 8 °C. Chromatographic separation was carried out in a gradient mode at 35 °C on an ultra-Biphenyl column using a Thermo Scientific chromatographic system with a Diode array. Data management was performed with Chromeleon 7.4 software. RESULTS: The HPLC-UV method proved to be linear over wide concentration ranges (0.5-50.0 mg/L) and was accurate and reproducible in the absence of matrix effects, allowing for robust, specific, and rapid quantification of ceftobiprole from a low amount of serum (0.1 mL). The mean steady state Ctrough and Cend values measured in the anonymous patients' samples were 6.26 ± 3.81 mg/L and 22.56 ± 15.69 mg/L, respectively. CONCLUSIONS: We report a broadened simple and fast HPLC with UV detection method for quantification of ceftobiprole in human serum to implement ceftobiprole TDM as clinical routine, and support future (PK/PD) studies in special patients' population.
Assuntos
Cefalosporinas , Monitoramento de Medicamentos , Humanos , Cromatografia Líquida de Alta Pressão/métodos , Monitoramento de Medicamentos/métodos , Cefalosporinas/sangue , Cefalosporinas/farmacocinética , Espectrofotometria Ultravioleta , Antibacterianos/sangue , Antibacterianos/farmacocinética , CalibragemRESUMO
In several settings, the COVID-19 pandemic determined a negative impact on the occurrence of healthcare-associated infection, particularly for on central lines associated bloodstream infections (CLABSI). In our setting, we observed a significant increase in CLABSI in our intensive care unit (ICU) during 2020 and 2021 vs. 2018 to 2019. A refresher training activity on central venous catheter (CVC) management bundles was carried out in September-October 2021 for the ICU health staff. We assessed the impact of bundle implementation by means of standardized indicators, such as the Device Utilization Ratio (DUR), in this case, the Central Line Utilization Ratio, the Standardized Utilization Ratio (SUR), and the device Standardized Infection Ratio (dSIR). Standardized ratios for device use and infection ratio were computed using data from 2018 and 2019 as expectation data. After bundle implementation, we observed a significant reduction of dSIR (p < 0.001), which dropped from 3.23 and 2.99 in the 2020-2021 biennium to 1.11 in 2022 (CLABSI in the first quarter only); no more CLABSI were observed afterwards. Standardized ratios proved helpful in identify increasing trends of CLABSI in the ICU and monitoring the impact of a simple effective tool, i.e., training on and implementation of a bundle for CVC management.
RESUMO
INTRODUCTION: Knowing the characteristics of the pharmaceutical market allows obtaining sensitive information to understand the supply, demand and access of the population to medicines. In order to provide primary data regarding the marketing of drugs in Argentina, the following research was performed. METHOD: This is a cross-sectional quantitative-qualitative descriptive study of the Argentine pharmaceutical market, taking into account 30 years of official information provided by the National Regulatory Agency (ANMAT). RESULTS: Two hundred and sixteen laboratories (182 national) drug producers / importers, 53 distributors and 479 drugstores (wholesale drug distribution establishments) were identified. A high concentration of marketing was detected, grouping 90% in only 5 intermediaries. There are currently 6670 products/certificates in the country, an amount that fluctuated over the last 30 years. Six laboratories are owners of between 116 and 208 certificates; 84% of these products come from national laboratories, 5002 are mono-drugs, while 83% are marketed under a fancy name. The three main indications for which the registration of drugs in Argentina is intended are diseases of digestive system, nervous system and infectious diseases; 58% of the marketed products consist of oral formulations. DISCUSSION: Based on data provided by this study, it is possible to assert that the Argentinian pharmaceutical market has a majority share of national capital, with a great concentration in a few pharmaceutical companies and distributors. The products are mostly available as non-combined drugs, in their oral form, and available by their brand names.
Introducción: Conocer las características del mercado farmacéutico permite obtener información sensible para entender la oferta, la demanda y el acceso de la población a los medicamentos. Con el objetivo de aportar datos primarios respecto a la comercialización de fármacos en Argentina, se desarrolló la siguiente investigación. Métodos: Se trata de un estudio descriptivo cuantitativo-cualitativo transversal del mercado farmacéutico argentino, tomando en cuenta 30 años de información oficial aportada por la Agencia Reguladora Nacional (ANMAT). Resultados: Se identificaron 216 laboratorios (182 nacionales) productores/importadores de medicamentos, 53 distribuidores y 479 droguerías (establecimientos de distribución de medicamentos al por mayor). Se detectó una alta concentración de la comercialización, agrupándose el 90% de la misma, en solo 5 intermediarios. En el país existen actualmente 6670 productos/certificados, cantidad que fluctuó a lo largo de los últimos 30 años. Seis laboratorios son dueños de entre 116 y 208 certificados. El 84% de estos productos provienen de laboratorios nacionales, 5002 son monofármacos, mientras que el 83% se comercializa bajo un nombre de fantasía. Las tres principales indicaciones a las que se destina el registro de medicamentos en la Argentina son enfermedades del aparato digestivo, sistema nervioso, e infecciosas; el 58% es comercializado como formulaciones orales. Discusión: el presente trabajo muestra que el mercado farmacéutico argentino tiene una participación mayoritaria de capitales nacionales, existiendo gran concentración en pocas empresas productoras y distribuidoras. Los productos son mayormente monodrogas comercializadas en forma oral y ofrecidas por su nombre de fantasía.
Assuntos
Estudos Transversais , Humanos , Argentina , Preparações FarmacêuticasRESUMO
Background: In a preliminary study during the first COVID-19 pandemic wave, we reported a high rate of success with continuous positive airway pressure (CPAP) in preventing death and invasive mechanical ventilation (IMV). That study, however, was too small to identify risk factors for mortality, barotrauma and impact on subsequent IMV. Thus, we re-evaluated the efficacy of the same CPAP protocol in a larger series of patients during second and third pandemic waves. Methods: 281 COVID-19 patients with moderate-to-severe acute hypoxaemic respiratory failure (158 full-code and 123 do-not-intubate (DNI)), were managed with high-flow CPAP early in their hospitalisation. IMV was considered after 4â days of unsuccessful CPAP. Results: The overall recovery rate from respiratory failure was 50% in the DNI and 89% in the full-code group. Among the latter, 71% recovered with CPAP-only, 3% died under CPAP and 26% were intubated after a median CPAP time of 7â days (IQR: 5-12â days). Of the patients who were intubated, 68% recovered and were discharged from the hospital within 28 days. Barotrauma occurred during CPAP in <4% of patients. Age (OR 1.128; p <0.001) and tomographic severity score (OR 1.139; p=0.006) were the only independent predictors of mortality. Conclusions: Early treatment with CPAP is a safe option for patients with acute hypoxaemic respiratory failure due to COVID-19.
RESUMO
Candida auris has become a major concern in critical care medicine due to the increasing number of immunocompromised patients and candidiasis is the most frequent cause of fungal infections. C. auris and other fungal pathogens are responsible for at least 13 million infections and 1.5 million deaths globally per year. In immunocompromised patients, infections can quickly become severe, causing wound infections, otitis and candidemia, resulting in high morbidity and mortality. The clinical presentation of C. auris is often non-specific and similar to other types of systemic infections; in addition, it is harder to identify from cultures than other, more common types of Candida spp. Some infections are particularly difficult to treat due to multi-resistance to several antifungal agents, including fluconazole (and other azoles), amphotericin B and echinocandins. This entails treatment with more drugs and at higher doses. Even after treatment for invasive infections, patients generally remain colonized for long periods, so all infection control measures must be followed during and after treatment of the C. auris infection. Screening patients for C. auris colonization enables facilities to identify individuals with C. auris colonization and to implement infection prevention and control measures. This pathogenic fungus shows an innate resilience, enabling survival and persistence in healthcare environment and the ability to rapidly colonize the patient's skin and be easily transmitted within the healthcare setting, thus leading to a serious and prolonged outbreak.
RESUMO
The SARS-CoV-2 pandemic caused an increase in intensive care unit (ICU) hospitalizations with a rise in morbidity and mortality; nevertheless, there is still little evidence on the impact of the pandemic on antibiotic resistance in ICUs. This is a retrospective, monocentric epidemiological study. The aim of the study was to describe and analyze the impact of the SARS-CoV-2 pandemic on ICU bacterial resistance patterns. All bacteria isolated from all patients admitted to the E.O. Galliera ICU from January 2018 to December 2022 were included. Antibiotic resistance (AR) profiles were evaluated. A total of 1021 microorganisms were identified, of which 221 (12.47%) had a resistance pattern (resistant organisms; ROs). In this time, there were 1679 patients with a total of 12,030 hospitalization days. The majority of microorganisms were Gram-negative (79.66% in 2018, 77.29% in 2019, 61.83% in 2020, 62.56% in 2021, and 60.75% in 2022), but an increase in Gram-positive microorganisms was observed (20.34 to 39.25% between 2018 and 2022). The prevalence of AR was 19.44% in 2018, 11.54% in 2019, 38.04% in 2020, 34.15% in 2021, and 39.29% in 2022 for Gram-positive microorganisms and 19.86% in 2018, 13.56% in 2019, 18.12% in 2020, 12.41% in 2021, and 12.31% in 2012 for Gram-negative microorganisms. The incidence of ROs showed a COVID-19-related increase in 2020-2021, followed by a lowering trend since 2021, and a new increase in 2022. Possible explanations are antibiotic overtreatment and a decrease in containment measures. An interesting finding was the cumulative lowering trend of carbapenem-resistant K. pneumoniae and P. aeruginosa, probably due to different patient features.
RESUMO
BACKGROUND: Irrational use of antimicrobials (ATMs) triggers microbial resistance (AMR) which has severe consequences for human health. ATM consumption varies among countries and within each territory. These data should be known, in order to perform local policies towards AMR reduction. This work aimed to expose the association of the level of consumption of carbapenems and fluoroquinolones with their resistance rates in Pseudomonas aeruginosa in Argentina. METHOD: Consumption of antimicrobials was expressed by defined daily dose (DDD)/1000 inhabitants for each ATM during one year period, discriminating by each country region. Resistance of P. aeruginosa to carbapenems/fluoroquinolones groups was recorded. Consumption/resistance ratio "R" was calculated for each region of the country, comparing results with other countries. RESULTS: P. aeruginosa resistance rate to fluoroquinolone (F) was 26.4% in blood samples and 29.7% in urine samples, whereas resistance rates to carbapenems (C) were 19.9 and 17.7% in blood and urine, respectively. Correlation between consumption and resistance was demonstrated for both antimicrobials (C : R = 0.58; p=0.003 and F : R = 0.77; p=0.0001). Great fluctuations of resistance levels were seen among regions within the country, always correlating resistance with areas in which a higher level of ATM consumption was detected. CONCLUSION: P. aeruginosa resistance to fluoroquinolone/carbapenems in Argentina directly correlated with antimicrobial consumption levels. A great heterogeneity in resistance profile was observed among areas where ATMs were widely used. Global data at the national level might mask local realities that require specific health policies in order to control the irrational use of ATMs.
RESUMO
Ceftobiprole (CFB), especially in combination, could be a promising alternative treatment for infective endocarditis. A main determinant of clinical response to antibiotic treatment is drug concentration at the infected site. Data on CFB and Daptomycin (DPT) heart valve penetration are lacking.Here we report a clinical case of CFB and DPT treatment combination for endocarditis. Then, we measured CFB and DPT concentrations in a native infected valve to verify their pharmacokinetic penetration and relationship with pharmacodynamic microbiological markers.The isolated microorganism was a MRSA with CFB and DPT MIC < 2 mg/L and <1 mg/L, respectively. The CFB and DPT plasma concentrations were 36.2 and 14.1 mg/L, respectively and the extrapolated concentration, based on each half-life, at the operatory time were 16.4 and 19.1 mg/L for CFB and DPT, respectively; the corresponding median CFB and DPT valve concentrations were 2.26 (IQR 2.14-2.69) and 12.9 µg/g (IQR 5.69-20.9), respectively; the estimated tissue/plasma ratios for CFB and DTP were 0.14 and 0.67, respectively.The association of CFB and DPT showed a good efficacy in this single endocarditis clinical case, confirmed by plasma and tissue PK/PD data.This report shows the first data on CFB valve tissue penetration, and it needs to be confirmed in other patient valve tissues. Moreover, relative studies of correlation with clinical efficacy are needed.
Assuntos
Cefalosporinas , Daptomicina , Endocardite Bacteriana , Endocardite , Infecções Estafilocócicas , Antibacterianos/farmacocinética , Cefalosporinas/farmacocinética , Daptomicina/farmacocinética , Endocardite/tratamento farmacológico , Endocardite Bacteriana/tratamento farmacológico , Endocardite Bacteriana/microbiologia , Humanos , Testes de Sensibilidade Microbiana , Infecções Estafilocócicas/tratamento farmacológicoRESUMO
BACKGROUND: Irrational antimicrobial consumption (AMC) became one of the main global health problems in recent decades. OBJECTIVE: In order to understand AMC in Latin-American Region, we performed the present research in 6 countries. METHODS: Antimicrobial consumption (J01, A07A, P01AB groups) was registered in Argentina, Chile, Colombia, Costa Rica, Paraguay, and Peru. Source of information, AMC type, DDD (Defined Daily Doses), DID (DDD/1000 inhabitants/day), population were variables explored. Data was analyzed using the Global Antimicrobial Resistance and Use Surveillance System (GLASS) tool. RESULTS: Source of information included data from global, public, and private sectors. Total AMC was highly variable (range 1.91-36.26 DID). Penicillin was the most consumed group in all countries except in Paraguay, while macrolides and lincosamides were ranked second. In terms of type of AMC according to the WHO-AWaRe classification, it was found that for certain groups like "Reserve," there are similarities among all countries. CONCLUSION AND RELEVANCE: This paper shows the progress that 6 Latin-American countries made toward AMC surveillance. The study provides a standardized approach for building a national surveillance system for AMC data analysis. These steps will contribute to the inclusion of Latin-America among the regions of the world that have periodic, regular, and quality data of AMC.
Assuntos
Antibacterianos , Antibacterianos/uso terapêutico , Argentina , Chile , Colômbia , Humanos , América Latina/epidemiologiaRESUMO
BACKGROUND: Italy was the first western country to face an uncontrolled outbreak of SARS-CoV-2 infection. The epidemic began in March 2020 within a context characterised by a general lack of knowledge about the disease. The first scientific evidence emerged months later, leading to treatment changes. The aim of our study was to evaluate the effects of these changes. METHODS: Data from a hospital in Genoa, Italy, were analysed. Patients deceased from SARS-CoV-2 infection were selected. Data were compared by dividing patients into two cohorts: "phase A" (March-May 2020) and "phase B" (October-December 2020). RESULTS: A total of 5142 patients were admitted. There were 274 SARS-CoV-2-related deaths (162 phase A and 112 phase B). No differences were observed in terms of demographics, presentation, or comorbidities. A significant increase was recorded in corticosteroid use. Mortality was 33.36% during phase A, falling to 21.71% during phase B. When subdividing the trend during the two phases by age, we found a difference in people aged 65-74 years. CONCLUSIONS: There is scarce evidence regarding treatment for SARS-CoV-2 (especially for severe infection). However, treatment changes improved the prognosis for people under the age of 75. The prognosis for older people remains poor, despite the improvements achieved.
RESUMO
BACKGROUND: Experience in real clinical practice with ceftazidime-avibactam for the treatment of serious infections due to gram-negative bacteria (GNB) other than carbapenem-resistant Enterobacterales (CRE) is very limited. METHODS: We carried out a retrospective multicenter study of patients hospitalized in 13 Italian hospitals who received ≤72 h of ceftazidime-avibactam for GNB other than CRE to assess the rates of clinical success, resistance development, and occurrence of adverse events. RESULTS: Ceftazidime-avibactam was used to treat 41 patients with GNB infections other than CRE. Median age was 62 years and 68% of them were male. The main causative agents were P.aeruginosa (33/41; 80.5%) and extended spectrum beta lactamase (ESBL)-producing Enterobacterales (4/41, 9.8%). Four patients had polymicrobial infections. All strains were susceptible to ceftazidime-avibactam. The most common primary infection was nosocomial pneumonia (n = 20; 48.8%), primary bacteremia (n = 7; 17.1%), intra-abdominal infection (n = 4; 9.8%), and bone infection (n = 4; 9.8%). Ceftazidime-avibactam was mainly administered as a combination treatment (n = 33; 80.5%) and the median length of therapy was 13 days. Clinical success at the end of the follow-up period was 90.5%, and the only risk factor for treatment failure at multivariate analysis was receiving continuous renal replacement therapy during ceftazidime-avibactam. There was no association between clinical failures and type of primary infection, microbiological isolates, and monotherapy with ceftazidime-avibactam. Only one patient experienced recurrent infection 5 days after the end of treatment. Development of resistance to ceftazidime-avibactam was not detected in any case during the whole follow-up period. No adverse events related to ceftazidime-avibactam were observed in the study population. CONCLUSIONS: Ceftazidime-avibactam may be a valuable therapeutic option for serious infections due to GNB other than CRE.
RESUMO
OBJECTIVES: The aim of this study was to assess colistin use in a country endemic for multidrug-resistant Gram-negative bacteria (MDR-GNB). METHODS: Colistin prescription patterns were evaluated in 22 Italian centres. Factors associated with use of colistin in combination with other anti-MDR-GNB agents were also assessed. RESULTS: A total of 221 adults receiving colistin were included in the study. Their median age was 64 years (interquartile range 52-73 years) and 134 (61%) were male. Colistin was mostly administered intravenously (203/221; 92%) and mainly for targeted therapy (168/221; 76%). The most frequent indications for colistin therapy were bloodstream infection and lower respiratory tract infection. Intravenous colistin was administered in combination with at least another anti-MDR-GNB agent in 80% of cases (163/203). A loading dose of 9 MU of colistimethate was administered in 79% of patients receiving i.v. colistin and adequate maintenance doses in 85%. In multivariable analysis, empirical therapy [odds ratio (OR) = 3.25, 95% confidence interval (CI) 1.24-8.53;P = 0.017] and targeted therapy for carbapenem-resistant Enterobacterales infection (OR = 4.76, 95% CI 1.69-13.43; P = 0.003) were associated with use of colistin in combination with other agents, whilst chronic renal failure (OR = 0.39, 95% CI 0.17-0.88; P = 0.024) was associated with use of colistin monotherapy. CONCLUSION: Colistin remains an important option for severe MDR-GNB infections when other treatments are not available. Despite inherent difficulties in optimising its use owing to peculiar pharmacokinetic/pharmacodynamic characteristics, colistin was mostly used appropriately in a country endemic for MDR-GNB.
Assuntos
Antibacterianos/administração & dosagem , Colistina/administração & dosagem , Farmacorresistência Bacteriana Múltipla , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Infecções Respiratórias/tratamento farmacológico , Sepse/tratamento farmacológico , Administração Intravenosa , Idoso , Antibacterianos/uso terapêutico , Colistina/uso terapêutico , Estudos Transversais , Prescrições de Medicamentos/estatística & dados numéricos , Quimioterapia Combinada/estatística & dados numéricos , Doenças Endêmicas , Feminino , Infecções por Bactérias Gram-Negativas/epidemiologia , Humanos , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Infecções Respiratórias/microbiologia , Sepse/microbiologiaRESUMO
The aim of this study was to determine the prevalence of hepatitis B virus (HBV) infection in an Italian region, Liguria (1,572,000 inhabitants), by means of a network of 12 referral centers for liver diseases. All patients with HBV surface antigen followed throughout 2006 were included. Personal data, infectious status with risk factors, other non-infectious risk factors for liver disease, clinical status, and treatment were the questionnaire. Four hundred forty-five patients (71% male) were evaluated. Their median age was 48 years (range 5-84), and 83.4% were of Italian origin. Community-acquired infection was the principal mode of HBV transmission (82.5%), followed by previous intravenous drug use (9.4%), perinatal transmission (6.3%), and transfusion-associated transmission (1.8%). Hepatitis B e-antigen was present in 20.4% of the patients, while co-infections with hepatitis D virus and/or hepatitis C virus and/or human immunodeficiency virus (HIV) were observed in 18.7% of the patients. Chronic active hepatitis was present in 62.5% of the patients, cirrhosis in 13.5%, hepatocellular carcinoma in 2.2%, and 21.8% of the patients were inactive carriers of HBV. In all, 42.5% of the patients were treated with interferon or lamivudine and/or adefovir-dipivoxil. Forty-nine patients were co-infected with HIV (86% on highly active antiviral therapy). Nevertheless, this study identified only 2.2% of the expected patients with HBV. Hence, it has to be reasoned that few potential infectious or treatable patients are referred to liver disease centers. HBV infection is still an underestimated health problem, and few potential infectious or treatable patients are referred to tertiary centers.
Assuntos
Antígenos de Superfície da Hepatite B/sangue , Hepatite B Crônica/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/epidemiologia , Criança , Pré-Escolar , Estudos de Coortes , Comorbidade , Estudos Transversais , Feminino , Infecções por HIV/epidemiologia , Antígenos E da Hepatite B/sangue , Hepatite C/epidemiologia , Hepatite D/epidemiologia , Humanos , Itália/epidemiologia , Cirrose Hepática/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Adulto JovemRESUMO
BACKGROUND: Between 350 and 400 million people worldwide have chronic hepatitis B virus (HBV) infection, and in Italy this figure is 1% to 2% in the general population. In clinical practice, however, it is not known how many patients chronically infected by HBV and eligible for antiviral therapy are not treated. AIM: To characterize the clinical picture of untreated HBV patients, and to assess whether current experts' recommendations for treatment are actually applied. METHODS: We evaluated 362 patients chronically infected by HBV alone who were followed for at least 1 year at tertiary referral centers in Liguria region, Italy. Patients' data were evaluated on the basis of the Panel of Experts algorithm for the management of HBV [ie, HBV DNA levels > or =20,000 IU/mL in hepatitis B e antigen (HBeAg)-positive patients, HBV DNA levels > or =2000 IU/mL in HBeAg-negative patients, and evidence of biochemical and/or histologic activity of disease in both groups]. RESULTS: One-hundred and sixteen viremic chronic hepatitis B disease patients were not on antiviral therapy (33 HBeAg positive, 83 HBeAg negative). Serum HBV DNA was > or =20,000 IU/mL and > or =2000 IU/mL in 32 HBeAg-positive and 54 HBeAg-negative patients, respectively, and disease was present in 59 of these 86 patients. Treatment was not indicated in 10 of 59 patients, and had been planned in 8 (4 HBeAg positive), thus 84% potential treatment candidates (41 of 49 patients) were not treated. CONCLUSIONS: Evaluation of a large series of patients chronically infected by HBV alone identified a significant proportion of patients who are actually untreated despite being potential candidates for antiviral therapy.