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1.
Microb Pathog ; 146: 104241, 2020 Sep.
Article in English | MEDLINE | ID: mdl-32387389

ABSTRACT

The recent epidemic outbreak of a novel human coronavirus called SARS-CoV-2 and causing the respiratory tract disease COVID-19 has reached worldwide resonance and a global effort is being undertaken to characterize the molecular features and evolutionary origins of this virus. Therefore, rapid and accurate identification of pathogenic viruses plays a vital role in selecting appropriate treatments, saving people's lives and preventing epidemics. Additionally, general treatments, coronavirus-specific treatments, and antiviral treatments useful in fighting COVID-19 are addressed. This review sets out to shed light on the SARS-CoV-2 and host receptor recognition, a crucial factor for successful virus infection and taking immune-informatics approaches to identify B- and T-cell epitopes for surface glycoprotein of SARS-CoV-2. A variety of improved or new approaches also have been developed. It is anticipated that this will assist researchers and clinicians in developing better techniques for timely and effective detection of coronavirus infection. Moreover, the genomic sequence of the virus responsible for COVID-19, as well as the experimentally determined three-dimensional structure of the Main protease (Mpro) is available. The reported structure of the target Mpro was described in this review to identify potential drugs for COVID-19 using virtual high throughput screening.


Subject(s)
Betacoronavirus/genetics , Coronavirus Infections/pathology , Peptidyl-Dipeptidase A/metabolism , Pneumonia, Viral/pathology , Receptors, Virus/metabolism , Angiotensin-Converting Enzyme 2 , Antiviral Agents/therapeutic use , Betacoronavirus/drug effects , Betacoronavirus/immunology , COVID-19 , Coronavirus 3C Proteases , Coronavirus Infections/diagnosis , Coronavirus Infections/drug therapy , Coronavirus Nucleocapsid Proteins , Cysteine Endopeptidases/metabolism , Epitopes, T-Lymphocyte/immunology , Humans , Nucleocapsid Proteins/metabolism , Pandemics , Phosphoproteins , Pneumonia, Viral/diagnosis , Pneumonia, Viral/drug therapy , Protein Conformation , SARS-CoV-2 , Viral Nonstructural Proteins/metabolism
2.
Infez Med ; 28(2): 153-165, 2020.
Article in English | MEDLINE | ID: mdl-32275257

ABSTRACT

The novel coronavirus SARS-CoV-2 (Covid-19), spreading from Wuhan, China, is one of the causes of respiratory infections that can spread to other people through respiratory particles, and can cause symptoms such as fever, dry cough, shortness of breath, anorexia, fatigue and sore throat in infected patients. This review summarizes current strategies on the diagnosis. Additionally, treatments, infection prevention and control of the SARS-CoV-2 are addressed. In addition to the respiratory system, this virus can infect the digestive system, the urinary system and the haematological system, which causes to observe the virus in the stool, urine and blood samples in addition to throat sample. The SARS-CoV-2 causes changes in blood cells and factors and makes lung abnormalities in patients, which can be detected by serological, molecular, and radiological techniques by detecting these changes and injuries. Radiological and serological methods are the most preferred among the other methods and the radiological method is the most preferred one which can diagnose the infection quickly and accurately with fewer false-negatives, that can be effective in protecting the patient's life by initiating treatment and preventing the transmission of infection to other people.


Subject(s)
Betacoronavirus/isolation & purification , Coronavirus Infections/diagnosis , Coronavirus Infections/therapy , Pandemics , Pneumonia, Viral/diagnosis , Pneumonia, Viral/therapy , Animals , Betacoronavirus/genetics , Betacoronavirus/pathogenicity , COVID-19 , Coronavirus Infections/epidemiology , Coronavirus Infections/physiopathology , Disease Outbreaks , Humans , Pneumonia, Viral/epidemiology , Pneumonia, Viral/physiopathology , SARS-CoV-2
3.
Virus Res ; 277: 197840, 2020 02.
Article in English | MEDLINE | ID: mdl-31846615

ABSTRACT

AIM: To assess the association of viral and host genetic variability with the outcome of acute infection with hepatitis B virus subgenotype F1b (HBV/F1b). METHODS: The cohort consisted of 26 patients with acute HBV/F1b infection who exhibit different outcomes: spontaneous resolution (n = 10), progression to chronic hepatitis (n = 10) and acute liver failure (n = 6). HLA SNPs (rs3077, rs9277542, rs2856718 and rs7453920) were determined. The S gene and core promoter/precore/core region were direct sequenced, and this latter region was also ultra-deep sequenced. Mean number of mutations, mutation rate, Shannon entropy, positive selection sites and mutational patterns of quasispecies were compared between groups. RESULTS: HLA SNPs were associated with spontaneous resolution or progression to chronic hepatitis, but not with the development of acute liver failure. The mean number of mutations in the S gene was similar among the three groups. Patients with spontaneous resolution had the lowest number of mutations, mutation rates and Shannon entropy values in the precore/core compared to the other two groups. Ten positive selection sites mapped on HLA-restricted epitopes were related to progression to chronic hepatitis and acute liver failure. Mutations T1753C, A1762T, G1764A, C1766T, T1768A G1896A, G2092T and T2107C were associated with acute liver failure and progression to chronic hepatitis. CONCLUSION: Highly heterogeneous and complex HBV precore/core carrying specific point mutations, combined with the host HLA background, were associated with a worse clinical outcome of acute HBV/F1b infection.


Subject(s)
Genetic Variation , HLA Antigens/genetics , Hepatitis B virus/genetics , Hepatitis B/genetics , Hepatitis B/virology , Point Mutation , Acute Disease , Aged , Female , Genotype , Hepatitis B Core Antigens/blood , Humans , Male , Middle Aged , Mutation Rate , Polymorphism, Single Nucleotide , Prospective Studies , Quasispecies/genetics
4.
Viruses ; 11(1)2018 12 21.
Article in English | MEDLINE | ID: mdl-30577623

ABSTRACT

This study aimed to assess the prevalence of natural resistance-associated substitutions (RASs) to NS3, NS5A and NS5B inhibitors in 86 genotype 1 Hepatitis C Virus (HCV)-infected patients from Buenos Aires, Argentina, and to determine their effect on therapy outcome. Additionally, virological, clinical and host genetic factors were explored as predictors of the presence of baseline RASs. NS3 RASs (39.2%) were more prevalent than NS5A RASs (25%) and NS5B RASs (8.9%). In the three regions, the frequencies of RASs were significantly higher in HCV-1b than in HCV-1a. The prevalence of Y93H, L159F and Q80K were 1.3%, 6.3% and 2.5%, respectively. IFNL3 CC genotype was identified as an independent predictor of the presence of baseline RASs in NS5A and NS3 genes (p = 0.0005 and p = 0.01, respectively). Sustained virologic response was achieved by 93.3% of the patients after receiving direct-acting antivirals (DAAs), although 48.7% of them showed baseline RASs related to the DAA-regimen. Notably, the prevalence of clinically relevant RASs in the three genes was lower than that observed around the world. The baseline presence of RASs in both subtypes did not appear to affect therapy outcome. These results support the need to evaluate resistance patterns in each particular country since RASs´ prevalence significantly vary worldwide.


Subject(s)
Antiviral Agents/therapeutic use , Drug Resistance, Viral , Hepatitis C, Chronic/drug therapy , Viral Nonstructural Proteins/genetics , Adult , Aged , Amino Acid Substitution , Argentina , Female , Genotype , Hepacivirus/drug effects , Hepacivirus/genetics , Humans , Male , Middle Aged , Prevalence , Quasispecies , Sustained Virologic Response , Viral Nonstructural Proteins/antagonists & inhibitors
5.
Expert Opin Drug Metab Toxicol ; 14(6): 649-657, 2018 Jun.
Article in English | MEDLINE | ID: mdl-29855221

ABSTRACT

INTRODUCTION: Many reports have evaluated the clinical efficacy and safety of the fixed-dose all-oral combination of daclatasvir, asunaprevir, and beclabuvir (DCV-TRIO), which was approved in Japan in December 2016 for the treatment of hepatitis C genotype (GT)-1 infection. Areas covered: This article reviews the pharmacodynamic and pharmacokinetic properties of the DCV-TRIO combination. The topics covered include data regarding the drug's absorption, distribution, metabolism, excretion, and antiviral activity strategies. Its therapeutic efficacy and safety in GT-1 infection from phase 2/3 clinical trials are also discussed. Expert opinion: The ideal regimen for the treatment of Hepatitis C virus infection should be potent, pangenotypic, Ribavirin-free, safe, co-formulated, and affordable. Considering these characteristics, DCV-TRIO is neither pangenotypic nor potent enough against GT-1a, regardless of the presence or absence of cirrhosis. Other potential limitations of this regimen are its dosification (twice-daily), and the fact that since it includes a protease inhibitor, it is contraindicated in decompensated cirrhosis. For these reasons, it has only been approved in Japan, where more than 70% of the patients are infected with GT-1b. However, this co-formulation might still have a place in the treatment of non-cirrhotic patients infected with GT-1b provided that massive access to treatment is facilitated.


Subject(s)
Antiviral Agents/administration & dosage , Hepacivirus/genetics , Hepatitis C/drug therapy , Administration, Oral , Antiviral Agents/pharmacokinetics , Antiviral Agents/pharmacology , Benzazepines/administration & dosage , Benzazepines/pharmacokinetics , Benzazepines/pharmacology , Carbamates , Drug Combinations , Genotype , Hepacivirus/isolation & purification , Hepatitis C/virology , Humans , Imidazoles/administration & dosage , Imidazoles/pharmacokinetics , Imidazoles/pharmacology , Indoles/administration & dosage , Indoles/pharmacokinetics , Indoles/pharmacology , Isoquinolines/administration & dosage , Isoquinolines/pharmacokinetics , Isoquinolines/pharmacology , Japan , Pyrrolidines , Sulfonamides/administration & dosage , Sulfonamides/pharmacokinetics , Sulfonamides/pharmacology , Valine/analogs & derivatives
6.
J Med Internet Res ; 20(6): e10197, 2018 06 14.
Article in English | MEDLINE | ID: mdl-29903701

ABSTRACT

BACKGROUND: Electronic health records (EHRs) have been widely proposed as a mechanism for improving health care quality. However, rigorous research on the impact of EHR systems on behavioral health service delivery is scant, especially for children and adolescents. OBJECTIVE: The current study evaluated the usability of an EHR developed to support the implementation of the Wraparound care coordination model for children and youth with complex behavioral health needs, and impact of the EHR on service processes, fidelity, and proximal outcomes. METHODS: Thirty-four Wraparound facilitators working in two programs in two states were randomized to either use the new EHR (19/34, 56%) or to continue to implement Wraparound services as usual (SAU) using paper-based documentation (15/34, 44%). Key functions of the EHR included standard fields such as youth and family information, diagnoses, assessment data, and progress notes. In addition, there was the maintenance of a coordinated plan of care, progress measurement on strategies and services, communication among team members, and reporting on services, expenditures, and outcomes. All children and youth referred to services for eight months (N=211) were eligible for the study. After excluding those who were ineligible (69/211, 33%) and who declined to participate (59/211, 28%), a total of 83/211 (39%) children and youth were enrolled in the study with 49/211 (23%) in the EHR condition and 34/211 (16%) in the SAU condition. Facilitators serving these youth and families and their supervisors completed measures of EHR usability and appropriateness, supervision processes and activities, work satisfaction, and use of and attitudes toward standardized assessments. Data from facilitators were collected by web survey and, where necessary, by phone interviews. Parents and caregivers completed measures via phone interviews. Related to fidelity and quality of behavioral health care, including Wraparound team climate, working alliance with providers, fidelity to the Wraparound model, and satisfaction with services. RESULTS: EHR-assigned facilitators from both sites demonstrated the robust use of the system. Facilitators in the EHR group reported spending significantly more time reviewing client progress (P=.03) in supervision, and less time overall sending reminders to youth/families (P=.04). A trend toward less time on administrative tasks (P=.098) in supervision was also found. Facilitators in both groups reported significantly increased use of measurement-based care strategies overall, which may reflect cross-group contamination (given that randomization of staff to the EHR occurred within agencies and supervisors supervised both types of staff). Although not significant at P<.05, there was a trend (P=.10) toward caregivers in the EHR group reporting poorer shared agreement on tasks on the measure of working alliance with providers. No other significant between-group differences were found. CONCLUSIONS: Results support the proposal that use of EHR systems can promote the use of client progress data and promote efficiency; however, there was little evidence of any impact (positive or negative) on overall service quality, fidelity, or client satisfaction. The field of children's behavioral health services would benefit from additional research on EHR systems using designs that include larger sample sizes and longer follow-up periods. TRIAL REGISTRATION: ClinicalTrials.gov NCT02421874; https://clinicaltrials.gov/ct2/show/NCT02421874 (Archived by WebCite at http://www.webcitation.org/6yyGPJ3NA).


Subject(s)
Child Health Services/trends , Electronic Health Records/trends , Adolescent , Child , Humans , Internet , Surveys and Questionnaires
7.
Antivir Ther ; 22(7): 571-575, 2017.
Article in English | MEDLINE | ID: mdl-28198349

ABSTRACT

BACKGROUND: Single nucleotide polymorphisms (SNPs) at the ITPA gene are associated with haemolytic anaemia in chronic hepatitis C patients treated with pegylated interferon-ribavirin (RBV). Information in patients treated with interferon-free, direct-acting antivirals (DAA) is scarce. METHODS: Median haemoglobin (Hb) levels were compared at baseline and at week 4, when ribavirin concentration achieves steady state, in all consecutive chronic hepatitis C patients treated with oral DAA plus RBV at our clinic. RESULTS: Median Hb drop in 55 patients was greater in rs1127354-CC than -CA/AA (1.8 versus 0.7 g/dl; P=0.029), and in rs6051702-AA than -AC/CC carriers (2.2 versus 1.1 g/dl; P=0.016). Eleven (20%) patients experienced severe anaemia, defined as Hb drop >3 g/dl or to <10 g/dl. All of them were rs6051702-AA. CONCLUSIONS: Baseline testing of rs6051702 may identify the subset of patients at greatest risk for RBV-induced anaemia using interferon-free hepatitis C therapies.


Subject(s)
Anemia, Hemolytic/etiology , Antiviral Agents/adverse effects , Disease Susceptibility , Hepatitis C, Chronic/complications , Polymorphism, Single Nucleotide , Pyrophosphatases/genetics , Ribavirin/adverse effects , Adult , Aged , Alleles , Antiviral Agents/therapeutic use , Female , Genotype , Hepatitis C, Chronic/drug therapy , Humans , Male , Middle Aged , Retrospective Studies , Ribavirin/therapeutic use
8.
Expert Opin Drug Metab Toxicol ; 12(10): 1197-209, 2016 Oct.
Article in English | MEDLINE | ID: mdl-27384079

ABSTRACT

INTRODUCTION: The treatment of hepatitis C virus (HCV) infection has dramatically improved in recent years with the widespread use of interferon-free combination regimens. Despite the high sustained virological response (SVR) rates (over 90%) obtained with direct-acting antivirals (DAAs), drug resistance has emerged as a potential challenge. The high replication rate of HCV and the low fidelity of its RNA polymerase result in a high degree of genetic variability in the HCV population, which ultimately explains the rapid selection of drug resistance associated variants (RAVs). AREAS COVERED: Results from clinical trials and real-world experience have both provided important information on the rate and clinical significance of RAVs. They can be present in treatment-naive patients as natural polymorphisms although more frequently they are selected upon treatment failure. In patients engaged in high-risk behaviors, RAVs can be transmitted. EXPERT OPINION: Although DAA failures generally occur in less than 10% of treated chronic hepatitis C patients, selection of drug resistance is the rule in most cases. HCV re-treatment options are available, but first-line therapeutic strategies should be optimized to efficiently prevent DAA failure due to baseline HCV resistance. Considerable progress is being made and next-generation DAAs are coming with pangenotypic activity and higher resistance barrier.


Subject(s)
Antiviral Agents/pharmacology , Hepacivirus/drug effects , Hepatitis C/drug therapy , Drug Resistance, Viral , Hepacivirus/genetics , Hepacivirus/isolation & purification , Hepatitis C/virology , Hepatitis C, Chronic/drug therapy , Humans , Treatment Failure , Virus Replication
9.
Expert Opin Pharmacother ; 17(2): 217-29, 2016.
Article in English | MEDLINE | ID: mdl-26595348

ABSTRACT

INTRODUCTION: Chronic hepatitis C virus (HCV) infection has become a curable disease. More than 90% sustained virologic response rates have been obtained with 8-24 weeks of treatment with distinct combinations of direct-acting antivirals (DAA) in most registration trials. However, outcomes in real-world patients tend to be lower and treatment of special patient populations is often challenging. AREAS COVERED: We address the treatment of chronic hepatitis C with DAA in major special patient populations, such as HIV-positive persons, transplant recipients, patients with advanced cirrhosis, renal insufficiency, hepatitis B or D coinfection, injection drug users (IDUs) and prior DAA failures. EXPERT OPINION: Drug interactions between DAA and medications given to persons with HIV infection or transplant recipients can result in treatment failure and adverse events. Severe organ dysfunction as in kidney insufficiency or decompensated cirrhosis may lead to DAA overexposure and toxicities. Dysfunctional social circumstances and behavior are associated to poor drug adherence and increased risk for HCV re-infection in active IDUs. Finally, DAA response might be impaired by viral interference in patients with hepatitis B or D coinfection or drug resistance in HCV either at baseline or after prior DAA failures.


Subject(s)
Antiviral Agents/therapeutic use , Hepatitis C/drug therapy , Coinfection , Drug Interactions , Female , HIV Infections/complications , HIV Infections/drug therapy , Hepacivirus , Hepatitis B/complications , Hepatitis C/complications , Hepatitis C/transmission , Hepatitis C, Chronic/complications , Hepatitis C, Chronic/drug therapy , Humans , Liver Cirrhosis/complications , Liver Cirrhosis/drug therapy , Liver Transplantation , Pregnancy , Pregnancy Complications, Infectious/drug therapy , Renal Insufficiency/complications , Substance Abuse, Intravenous/complications
10.
Antivir Ther ; 21(1): 1-8, 2016.
Article in English | MEDLINE | ID: mdl-26110692

ABSTRACT

Liver disease is the major complication of chronic HCV infection. However, extrahepatic complications are common (50-75%), including mixed cryoglobulinaemia and B-cell lymphomas. Given that chronic hepatitis C has become curable using expensive oral direct-acting antivirals (DAAs), it seems worth revisiting the whole spectrum and burden of disease in HCV carriers.Herein, we update the most clinically significant medical complications associated with chronic hepatitis C and the evidence of benefits that would derive from a wide use of curative DAA therapies.Chronic HCV infection is associated with a broad spectrum of clinical conditions, including distinct rheumatic disorders (polyarthritis, sicca syndrome), lymphoproliferative conditions (mixed cryoglobulinaemia, monoclonal gammapathies and B-cell lymphomas) and damage at other organs due to persistent systemic inflammation, leading to renal, bone, neurological and/or cardiovascular disease. Eradication of HCV with DAAs is associated with amelioration and/or resolution of most liver-related and extrahepatic complications. Ultimately, gains in quality of life and survival favour treating everyone with hepatitis C regardless of liver fibrosis stage.


Subject(s)
Antiviral Agents/therapeutic use , Hepacivirus , Hepatitis C/drug therapy , Hepatitis C/virology , Antiviral Agents/pharmacology , Cause of Death , Hepatitis C/complications , Hepatitis C/epidemiology , Hepatitis C, Chronic/complications , Hepatitis C, Chronic/drug therapy , Hepatitis C, Chronic/virology , Humans , Immune System Diseases/diagnosis , Immune System Diseases/etiology , Liver/drug effects , Liver/pathology , Liver/virology , Lymphoproliferative Disorders/diagnosis , Lymphoproliferative Disorders/etiology , Mental Disorders/diagnosis , Mental Disorders/etiology , Mortality , Treatment Outcome
11.
Expert Opin Drug Saf ; 14(9): 1421-34, 2015.
Article in English | MEDLINE | ID: mdl-26212044

ABSTRACT

INTRODUCTION: Roughly 20% of HIV-positive persons worldwide are coinfected with hepatitis C virus (HCV). The recent advent of direct-acting antivirals (DAA) that cure most hepatitis C patients has attracted much attention. Knowledge on drug interactions between DAA and antiretrovirals (ARV) may allow maximizing antiviral efficacy while minimizing drug-related toxicities. AREAS COVERED: We review the most frequent side effects and clinically significant drug interactions between DAA and ARV. We further discuss how they can be prevented and managed in HIV/HCV-coinfected patients. EXPERT OPINION: The safety profile of current DAA and the most recently approved ARV is quite favorable. Interactions between DAA and ARV could be frequent in clinical practice. The most common drug interactions affect drug metabolism by inducing or inhibiting the cytochrome P450 system, leading to abnormal drug exposures. Throughout this mechanism HCV and HIV protease inhibitors interact, especially when co-formulated with ritonavir as a pharmacoenhancer, and non-nucleoside HCV and HIV polymerase inhibitors. In contrast, HIV and HCV nucleos(t)ide polymerase inhibitors, and most HCV NS5A inhibitors (i.e., ledipasvir) and HIV integrase inhibitors (i.e., dolutegravir), do not or only marginally affect CYP450, and therefore are free of significant drug interactions. Exposure to HIV and HCV nucleos(t)ide analogues (i.e., tenofovir and sofosbuvir, respectively) is subject to induction/inhibition of drug transporters (i.e., P-glycoprotein).


Subject(s)
Antiviral Agents/therapeutic use , HIV Infections/drug therapy , Hepatitis C/drug therapy , Anti-HIV Agents/administration & dosage , Anti-HIV Agents/adverse effects , Anti-HIV Agents/therapeutic use , Antiviral Agents/administration & dosage , Antiviral Agents/adverse effects , Coinfection , Drug Interactions , HIV Infections/virology , Hepatitis C/virology , Humans
12.
Curr HIV/AIDS Rep ; 12(3): 344-52, 2015 Sep.
Article in English | MEDLINE | ID: mdl-26156570

ABSTRACT

Roughly 10 % of HIV-positive individuals worldwide have concomitant chronic hepatitis B virus (HBV) infection, with large differences between geographical regions and/or risk groups. Hepatitis B is a preventable infection with vaccines. However, it cannot be eradicated once acquired, resembling HIV and in contrast with HCV. In developed countries, hepatitis B exhibits particular features in the HIV population. First, HBV infection is less frequently misdiagnosed than in the general population. Second, nucleos(t)ide analogs active against HBV are widely used as part of antiretroviral combinations and are taken by most HIV patients. Lastly, as the HIV population ages given the success of antiretroviral therapy, non-AIDS co-morbidities are becoming a major cause of disease, for which specific drugs are required, increasing the risk of interactions and hepatotoxicity. Furthermore, concern on HBV reactivation is rising as immunosuppressive drug therapies are increasingly been used for cancers and other non-malignant conditions. In this scenario, new challenges are emerging in the management of hepatitis B in HIV-positive individuals. Among them, major interest is focused on failures to suppress HBV replication, HBV breakthroughs and reactivations, the meaning of isolated anti-HBc, screening for liver cancer, and the complexity arising when hepatitis viruses C and/or D are additionally present. This review will focus on these challenges and the major advances in HBV coinfection in HIV.


Subject(s)
Antiviral Agents/therapeutic use , HIV Infections/complications , Hepatitis B/complications , Coinfection/therapy , Disease Management , HIV Infections/therapy , Hepatitis B/therapy , Humans , Immunosuppression Therapy/adverse effects , Virus Activation/drug effects
13.
AIDS Rev ; 17(2): 121-2, 2015.
Article in English | MEDLINE | ID: mdl-26035170

ABSTRACT

The hepatitis C field is living a revolution following the introduction of all-oral therapies that can cure most patients with short courses of direct-acting antiviral (DAA) combinations. Given that chronic hepatitis C affects globally around 20% of HIV persons, major attention has been focused on the HIV/HCV-coinfected population. Current evidence suggests that these patients depict cure rates of over 90%, similar to HCV-monoinfected individuals. Accordingly, current guidelines for hepatitis C therapy no longer separate mono- and coinfected subjects.


Subject(s)
Antiviral Agents/adverse effects , Antiviral Agents/therapeutic use , Hepatitis C, Chronic/drug therapy , Protease Inhibitors/adverse effects , Protease Inhibitors/therapeutic use , Drug-Related Side Effects and Adverse Reactions/epidemiology , Humans
14.
Expert Opin Drug Metab Toxicol ; 11(3): 333-41, 2015 Mar.
Article in English | MEDLINE | ID: mdl-25553890

ABSTRACT

INTRODUCTION: Chronic hepatitis C virus (HCV) infection has recently become a curable disease with antiviral therapy. The knowledge of drug interactions using direct-acting antivirals (DAA) may permit maximizing antiviral efficacy and avoiding drug-related toxicities. Ageing in the chronic hepatitis C population, along with added co-morbidities that require other medications, has increased the attention on drug interactions using DAA. AREAS COVERED: This review provides an update of the most clinically significant pharmacokinetic and pharmacodynamic drug interactions occurring between currently available DAA and other medications. The review also revisits how drug interactions with DAA can be prevented and managed. EXPERT OPINION: Interactions between DAA and other drugs are frequent in clinical practice. The most frequent drug interactions modify drug metabolism by inducing or inhibiting the cytochrome P450, leading to abnormal drug exposures. Through this mechanism HCV protease inhibitors, especially when co-formulated with ritonavir as pharmacoenhancer, and non-nucleoside HCV polymerase inhibitors interact with other medications. In contrast, NS5B nucleos(t)ide analog inhibitors (i.e., sofosbuvir) and some HCV NS5A inhibitors (i.e., ledipasvir), which do not or only marginally affect CYP450, are relatively free of significant pharmacokinetic interactions. However, exposure to HCV nucleos(t)ide analogs may be influenced by induction/inhibition of drug transporters (i.e., P-glycoprotein) as well as by pharmacodynamic interference with other nucleos(t)ide analogs used as antivirals or cancer drugs. Drug interactions for some NS5A inhibitors (i.e., daclatasvir) are generally moderate and can be managed with dose adjustments.


Subject(s)
Antiviral Agents/therapeutic use , Drug Interactions , Hepatitis C, Chronic/drug therapy , Administration, Oral , Antiviral Agents/pharmacokinetics , Antiviral Agents/pharmacology , Cytochrome P-450 Enzyme System/drug effects , Cytochrome P-450 Enzyme System/metabolism , Humans , Risk Factors
15.
J Chemother ; 27(3): 163-6, 2015 Jun.
Article in English | MEDLINE | ID: mdl-24625286

ABSTRACT

We focused our attention on susceptibility profile of Acinetobacter spp., Pseudomonas spp., and Klebsiella spp. isolated from biological specimens at the University Hospital of Salerno between June 2011 and October 2012. Acinetobacter, with a prevalence of Acinetobacter baumannii (97%) presented a high range of resistance to the antimicrobials considered, excluding colistin (COL). Klebsiella spp. isolates, with a prevalence of Klebsiella pneumoniae (90%), presented a variable pattern of resistance [from 9·8% for COL to 50% for levofloxacin (LEV)]. Extended-spectrum beta-lactamases production was detected in 15% of isolates. Most Pseudomonas isolates were P. aeruginosa with a high rate of resistance (95% to amoxicillin/clavulanate and trimethoprim/sulfamethoxazole, and <50% to the other antibiotics). Colistin remained the most effective drug tested. This study provided useful information of the local bacterial epidemiology hopefully permitting to establish a more effective empirical therapy, preventing the inappropriate use of antibacterial agents and possibly limiting the diffusion of antibacterial resistance.


Subject(s)
Acinetobacter Infections/epidemiology , Acinetobacter baumannii/drug effects , Anti-Bacterial Agents/pharmacology , Drug Resistance, Multiple, Bacterial , Klebsiella Infections/epidemiology , Klebsiella pneumoniae/drug effects , Pseudomonas Infections/epidemiology , Pseudomonas aeruginosa/drug effects , Acinetobacter Infections/microbiology , Acinetobacter baumannii/isolation & purification , Cross Infection/epidemiology , Cross Infection/microbiology , Hospitals, Teaching , Humans , Italy/epidemiology , Klebsiella Infections/microbiology , Klebsiella pneumoniae/isolation & purification , Microbial Sensitivity Tests , Pseudomonas Infections/microbiology , Pseudomonas aeruginosa/isolation & purification , beta-Lactamases/analysis
16.
Antiviral Res ; 102: 35-43, 2014 Feb.
Article in English | MEDLINE | ID: mdl-24316030

ABSTRACT

Interleukin (IL)28-B polymorphism has been related to interferon response in the treatment of hepatitis C, but its role in chronic hepatitis B (CHB) therapy is still poorly understood. We aimed to investigate the effect of IL28-B polymorphisms in the treatment with pegylated-interferon (PEG-IFN) of patients with CHB. We retrospectively analyzed 190 patients with chronic hepatitis B e antigen (HBeAg) negative, genotype A (22%), B (12%), C (10%), D (33%), E (20%), treated with PEG-IFN alfa-2a for 48weeks; genotype analysis was performed for IL28-B polymorphisms rs12979860, rs8099917 and rs12980275 according to virological, serological and biochemical response. During 2years of follow-up 12 patients (6.3%) cleared hepatitis B surface antigen (HBsAg) with seroconversion, 40 (21%) obtained a negative viral load and 104 (54.7%) gained a biochemical response. We found a difference of distribution of rs12979860 CC genotype among different ethnicity (p=0.013). Rs12979860 CC genotype was significantly associated with serological and virological response (p<0.001); rs8099917 TT and rs12980275 AA genotypes were mostly related with virological response (p<0.001). In multivariate logistic analysis rs12979860 CC was predictive of virological response (OR=4.290; CI=1.589-11.580, p=0.004) and serological response (OR=10.129; CI=2.440-42.044; p<0.001). Rs8099917 TT was predictive only of virological response (OR=3.746, CI=1.235-11.355; p=0.020). The E genotype was a negative predictive factor of virological response (OR=0.057; CI=0.014-0.238; p<0.001). IL28-B polymorphisms are related to different response in the treatment of CHB HBeAg-negative with PEG-IFN, and the E genotype is a novel negative predictive factor.


Subject(s)
Antiviral Agents/therapeutic use , Hepatitis B e Antigens/blood , Hepatitis B, Chronic/drug therapy , Interferon-alpha/therapeutic use , Interleukins/genetics , Polyethylene Glycols/therapeutic use , Polymorphism, Genetic , Adult , Genotype , Hepatitis B virus/classification , Hepatitis B virus/genetics , Hepatitis B, Chronic/virology , Humans , Interferons , Male , Middle Aged , Recombinant Proteins/therapeutic use , Treatment Outcome
17.
New Microbiol ; 36(4): 423-6, 2013 Oct.
Article in English | MEDLINE | ID: mdl-24177306

ABSTRACT

Sphingomonas paucimobilis occurs widely both in natural and nosocomial environments, including hospital water systems, respiratory therapy equipment, and laboratory instruments. It is an opportunistic pathogen that rarely causes infections in humans. Among S. paucimobilis nosocomial infections, osteomyelitis is particularly rare. Almost all infections occur in patients with comorbidities such as malignancy, immunosuppressant therapy, diabetes mellitus and acquired immunodeficiency syndrome. We present the first case of Sphingomonas paucimobilis osteomyelitis in an immunocompetent patient and include updated literature concerning infections by this microorganism.


Subject(s)
Gram-Negative Bacterial Infections/microbiology , Osteomyelitis/microbiology , Sphingomonas/isolation & purification , Adult , Anti-Bacterial Agents/therapeutic use , Cross Infection/drug therapy , Gram-Negative Bacterial Infections/diagnosis , Gram-Negative Bacterial Infections/drug therapy , Humans , Immunocompromised Host , Male , Osteomyelitis/diagnosis , Osteomyelitis/drug therapy , Sphingomonas/genetics
18.
Infez Med ; 20 Suppl 1: 14-9, 2012.
Article in Italian | MEDLINE | ID: mdl-22982693

ABSTRACT

The diabetic foot lesions are the result of a complex set of factors including peripheral neuropathy, trauma, joint deformities and perfusion abnormalities. The foot becomes vulnerable and insensitive to minor injuries caused by excessive pressure, mechanically or minimum thermal insults that can determine the primum movens of a foot ulcer. Due to the trauma, the subcutaneous tissues are exposed to bacterial colonization. Therefore, the wound can develop an infection. So, the first step in the treatment of the lesion is the evaluation of tissue damage, in order to guide therapy and prognosis. Wagner's classification, used by over 25 years, is still one of the best known systems of lesion classification; however, it is giving way to the most recent Texas's classification. However, in both systems infection have a minority role. Therefore, the Infectious Diseases Society of America has developed a classification system that divides infections in mild, moderate and severe. The purpose of this classification is to recognize the severe patients because they require immediate hospitalization, parenteral antibiotic therapy and specific instrumental examinations.


Subject(s)
Bacterial Infections/etiology , Diabetic Foot/complications , Foot Diseases/etiology , Abscess/etiology , Arthritis, Infectious/etiology , Bacterial Infections/classification , Diabetic Foot/physiopathology , Fasciitis, Necrotizing/etiology , Foot Injuries/complications , Gangrene , Humans , Immunocompromised Host , Microcirculation , Mycoses/etiology , Osteomyelitis/etiology , Skin Diseases, Infectious/etiology , Tendinopathy/etiology , Wound Infection/etiology
19.
Infez Med ; 20 Suppl 1: 20-7, 2012.
Article in Italian | MEDLINE | ID: mdl-22982694

ABSTRACT

The diagnosis of wound infection is based on clinical signs and local and/or systemic inflammation. Therefore, the examination has a major role in the diagnosis of infected lesions of the foot. Once the clinical diagnosis of infection is made, the next step is to determine the etiology with the aim to undertake a rational and appropriate treatment. The most reliable method for assessing microbiological etiology is the specimen of material from infected lesion to perform a bacterioscopic examination and culture. The microorganisms involved in the etiology of diabetic foot depends on the type of injury and on specific patient features (antibiotic therapy, previous hospitalization). The most frequently detected pathogen is Staphylococcus aureus. Mild infections are mostly caused by Gram positive cocci, with a prevalence of S. aureus. Moderate infections are mostly supported by pyogenic Gram positive cocci, but also Gram-negative bacteria can be involved. In severe infections the etiology is polymicrobial. As regards the involvement of fungi in diabetic foot infections data are few and mostly conflicting.


Subject(s)
Bacterial Infections/microbiology , Dermatomycoses/microbiology , Diabetic Foot/complications , Foot Diseases/microbiology , Anti-Bacterial Agents/therapeutic use , Antifungal Agents/therapeutic use , Bacterial Infections/diagnosis , Bacterial Infections/drug therapy , Bacterial Infections/epidemiology , Cellulitis/etiology , Dermatomycoses/diagnosis , Dermatomycoses/drug therapy , Dermatomycoses/etiology , Diabetic Foot/epidemiology , Diabetic Foot/microbiology , Foot Diseases/diagnosis , Foot Diseases/drug therapy , Foot Diseases/etiology , Foot Injuries/complications , Foot Injuries/microbiology , Gangrene , Gram-Negative Bacterial Infections/diagnosis , Gram-Negative Bacterial Infections/drug therapy , Gram-Negative Bacterial Infections/etiology , Gram-Negative Bacterial Infections/microbiology , Gram-Positive Bacterial Infections/diagnosis , Gram-Positive Bacterial Infections/drug therapy , Gram-Positive Bacterial Infections/etiology , Gram-Positive Bacterial Infections/microbiology , Humans , Practice Guidelines as Topic , Wound Infection/diagnosis , Wound Infection/drug therapy , Wound Infection/microbiology
20.
J Antimicrob Chemother ; 67(11): 2570-5, 2012 Nov.
Article in English | MEDLINE | ID: mdl-22833640

ABSTRACT

Despite the large number of suggestions available in the literature, the optimal duration of antibiotic treatment remains an individual decision mainly based on clinical criteria. Shorter but equally effective regimens would reduce the side effect rates, including both antibiotic resistance and drug expenses. Although several prospective, randomized trials and meta-analyses with the aim of comparing a standard duration with a shorter one for most bacterial infections have been published, to date most current recommendations carry little weight, as they are based on expert opinions or practical experience. This review will briefly touch upon the clinical evidence of short-course versus long-course antibiotic therapy for the most common community- and hospital-acquired bacterial infections.


Subject(s)
Anti-Bacterial Agents/administration & dosage , Bacterial Infections/drug therapy , Community-Acquired Infections/drug therapy , Cross Infection/drug therapy , Drug Resistance, Bacterial , Humans , Time Factors
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