1,720,994 research outputs found
Carbapenem-sparing strategy: carbapenemase, treatment, and stewardship
describing the current role of carbapenems and carbapenem-sparing strategies in the setting of antimicrobial stewardship programs
Daclatasvir Plasma Levels in a Cohort of Patients with Hepatitis C Virus Infection Taking Methadone: A Prospective Analysis
Backround: The effect of methadone (MET) during therapy with novel direct-acting antiviral agents is still not fully understood. Currently, no data are available about the influence of MET on daclatasvir (DCV) plasma levels in patients affected by chronic hepatitis C (CHC). The aim of this study was to assess the DCV plasma concentrations in patients treated with sofosbuvir (SOF) plus DCV, with or without ribavirin (RBV) and with or without MET
Predictors of Mortality in Patients with COVID-19 Infection in Different Health- Care Settings: A Retrospective Analysis from a CORACLE Study Group
BACKGROUND: Despite the large number of hospitalized patients affected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, few data are available about risk factors and mortality in subjects with nosocomially acquired respiratory infection of Coronavirus Disease 2019 (COVID-19). METHODS: We retrospectively evaluated in a multicentric study -during the pre-vaccination era-all patients admitted with confirmed diagnosis of nosocomial COVID-19 (NC). Patients were classified according to provenance: hospital-acquired NC or long-term care (LTC) facilities. RESULTS: Among overall 1047 patients evaluated with COVID-19, 137 had a confirmed diagnosis of NC (13%). 78 (56.9%) patients had hospital-acquired NC and 59 (43%) had LTC NC. Overall mortality was 35.8%, in hospital-acquired NC 24.4%, in LTC NC 50.8% (p<0.001) (Log Rank test: p=0.001). Timing of diagnosis was significantly different between hospital acquired and LTC NC (3.5 vs 10 days, p<0.001). In multivariate analysis age, intensive-care unit admission, LTC provenance and sepsis were significant predictors of mortality in patients with NC infection. CONCLUSION: Patients with NC are at higher risk of mortality (especially for LTC NC) and required preventive strategies, early diagnosis, and treatment to avoid COVID-19 cluster
Elvitegravir/Cobicistat/Tenofovir/Emtricitabine Penetration in the Cerebrospinal Fluid of Three HIV-Positive Patients
Treatment with direct-acting antiviral agents of hepatitis C virus infection in injecting drug users: a prospective study
In this prospective study, we evaluated the effectiveness and tolerability of novel therapies against hepatitis C virus (HCV) in a cohort of PWID enrolled at our centre from April 2015 to July 2016. In this analysis, a total of 174 patients were included: 11 (6.3%) were treated with pegylated-interferon (PEG-IFN) and ribavirin (RBV) containing regimens, 163 (93.7%) with IFN-free treatments. RBV has been used in 70 patients (40.2%); 59 (33.9%) patients were in opioid substitution therapy (OST) with methadone or buprenorphine. Overall, sustained virological response (SVR) has been observed in 162 subject (93.1%), breakthrough (BT) in 3 (1.7%), relapse in 1 (0.6%), drop-out in 8 (4.6%). Treatment was interrupted for clinical conditions in 7 patients: 6 (3.4%) had hepatic decompensation and 1 died for hepatocellular carcinoma (HCC). In multivariate analysis, predictive factors of treatment failure were: albumin level below 3 g/dL (OR=7.190; 95%IC=1.236-41.837; p10 (OR=5.886; 95%IC=1.411-35.994; p20 (OR=1.286; 95%IC=0.556-9.455; p=0.016). In conclusion, treatment with DAAs was effective and well tolerated in PWID; cirrhotic subjects with MELD >10 and albumin low level showed a higher risk of developing serious adverse events and treatment failure. This article is protected by copyright. All rights reserved
Current and emerging pharmacotherapy for the treatment of infections following open-heart surgery
Introduction: Patients undergoing open-heart surgery may suffer from postoperative complications, including severe infections. Antimicrobials to treat infectious complications in this population should be selected thoughtfully, taking into account three different and fundamental issues: (i) the site of infection; (ii) the suspected or proven causative agent and its susceptibility pattern; and (iii) the risk of suboptimal pharmacokinetic characteristics and potential toxicity of the chosen drug/s. Areas covered: The present narrative review summarizes the current and future antimicrobial options for the treatment of infections developing after open-heart surgery. Expert opinion: The pharmacological treatment of infections developing in cardiac surgery patients poses peculiar challenges, including the need for an active empirical therapy for severe events such as bloodstream infections, deep sternal wound infections, or early-onset postoperative prosthetic endocarditis. In addition, the risk for multidrug-resistant pathogens should also be taken into account in endemic areas. A multidisciplinary evaluation on a patient-by-patient basis, deeply involving infectious diseases specialists and cardiothoracic surgeons, remains essential for appropriately balancing both short-term and long-term risks and benefits of any possible surgical reintervention in combination with adequate pharmacotherapy
Role of simeprevir plasma concentrations in HCV treated patients with dermatological symptoms
Up till now the role of simeprevir plasma concentrations has not been described in treated patients affected by chronic hepatitis C and with dermatological side-effects. In this study, we have evaluated a possible relationship between plasma levels and the onset of skin complaints for the first time
Temocillin: Applications in Antimicrobial Stewardship as a Potential Carbapenem-Sparing Antibiotic
Temocillin is an old antibiotic, but given its particular characteristics, it may be a suitable alternative to carbapenems for treating infections due to ESBL-producing Enterobacterales and uncomplicated UTI due to KPC-producers. In this narrative review, the main research question was to summarize current evidence on temocillin and its uses in infectious diseases. A search was run on PubMed using the terms (‘Temocillin’ [Mesh]) AND (‘Infection’ [Mesh]). Current knowledge regarding temocillin in urinary tract infection, blood-stream infections, pneumonia, intra-abdominal infections, central nervous system infections, skin and soft tissues infections, surgical sites infections and osteoarticular Infections were summarized. Temocillin retain a favourable profile on microbiota and risk of Clostridioides difficile infections and could be an option for treating outpatients. Temocillin may be a valuable tool to treat susceptible pathogens and for which a carbapenem could be spared. Other advantages in temocillin use are that it is well-tolerated; it is associated with a low rate of C. difficile infections; it is active against ESBL, AmpC, and KPC-producing Enterobacterales; and it can be used in the OPAT clinical setting
Vitamin D pathway genetic variants are able to influence sofosbuvir and its main metabolite pharmacokinetics in HCV mono-infected patients
Vitamin D levels and genetic variants were associated with drug outcome/toxicity and concentrations. The plasma exposure of GS-331007, the main sofosbuvir metabolite, has been related to SVR. We evaluated the impact of polymorphisms in genes (CYP27B1, CYP24A1, VDBP and VDR) related to vitamin D pathway on sofosbuvir and GS-331007 plasma levels in HCV mono-infected patients at one month of treatment. Polymorphisms were investigated through real-time PCR; drug plasma quantification was performed through a UHPLC-MS/MS method. GS-331007 levels were associated with CYP24A1rs2248359 and VDRCdx2 variants in all the analyzed patients and linear regression analysis showed that sex, body mass index, HCV genotype, baseline estimated glomerular filtration rate, VDRCdx2AG/GG and CYP27B1-1260TT genotypes significantly predict concentrations. We performed sub-analyses considering the HCV genotype and the concomitant drug, identifying polymorphisms associated with GS-331007 concentrations. This is the first study focusing on vitamin D pathway gene variants and DAAs concentrations, but further studies are required
Ten Years of KPC-Kp Bloodstream Infections Experience: Impact of Early Appropriate Empirical Therapy on Mortality
Background. In K. pneumoniae KPC (KPC-Kp) bloodstream infections (BSI), INCREMENT CPE score >7, Charlson Comorbidity Index (CCI) ≥3 and septic shock are recognized predictors of mortality, with a possible beneficial effect of combination therapy in seriously ill patients. Materials and Methods. We conducted a ten-year retrospective study including all KPC-Kp BSI in patients ≥18 years of age with the aim to evaluate the characteristics and impact of appropriate empirical therapy, either monotherapy or combination therapy, and targeted therapy on mortality. Appropriate therapy was defined as at least one active antimicrobial agent with in vitro activity against KPC-kp demonstrated by susceptibility testing, administered within 48 h from blood culture collection. Results. The median age of the 435 analyzed patients was 66.09 years (IQR 54.87–73.98). The median CCI was 4. KPC-Kp colonization was present in 324 patients (74.48%). The probable origin of the KPC-Kp BSI was not identified in 136 patients (31.26%), whereas in 120 (27.59%) patients, it was CVC-related, and in 118 (27.13%), it was respiratory. Source control was achieved in 87 patients (72.5%) with CVC-related KPC-Kp BSI. The twenty-eight-day survival was 70.45% for empirical monotherapy, 63.88% for empirical combination therapy and 57.05% for targeted therapy (p = 0.0399). A probable source of KPC-Kp BSI other than urinary, CVC or abdominal [aHR 1.64 (IC 1.15–2.34) p = 0.006] and deferred targeted therapy [HR 1.67 (IC 1.12–2.51), p= 0.013] emerged as predictors of mortality, whereas source control [HR 0.62 (IC 0.44–0.86), p = 0.005] and ceftazidime/avibactam administration in empirical therapy [aHR 0.37 (IC 0.20–0.68) p = 0.002] appeared as protective factors. Discussion. These data underline the importance of source control together with timing appropriateness in the early start of empirical therapy over the choice of monotherapy or combination therapy and the use of ceftazidime/avibactam against KPC-Kp BSI
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