An Aminoglycoside-Sparing Regimen with Double Beta-Lactam to Successfully Treat Prosthetic Aortic Valve Endocarditis-Time to Change Paradigm?

(1) Background: is a former nutritionally variant streptococci (NVS). NVS infective endocarditis (IE) is generally characterized by a higher rate of morbidity and mortality, partially due to difficulties in choosing the most adequate microbiological culture method and the most effective treatment strategy, and partially due to higher rates of complications, such as heart failure, peripheral septic embolism, and peri-valvular abscess, as well as a higher rate of valve replacement. Depending on the affected valve (native valve endocarditisNVE, or prosthetic valve endocarditisPVE), the American Heart Association (AHA) 2015 treatment guidelines (GLs) suggest penicillin G, ampicillin, or ceftriaxone gentamicin (2 weeks for NVE and up to 6 weeks for PVE), while vancomycin alone may be a reasonable alternative in patients who are intolerant of β-lactam therapy.

Population Pharmacokinetic and Pharmacodynamic Analysis of Valganciclovir for Optimizing Preemptive Therapy of Cytomegalovirus Infections in Kidney Transplant Recipients.

This study aimed to develop a population pharmacokinetic/pharmacodynamic (PK/PD) model of valganciclovir for preemptive therapy of cytomegalovirus (CMV) infection in kidney transplant patients. A population PK/PD model was developed with Monolix. Ganciclovir concentrations and CMV viral loads were obtained retrospectively from kidney transplant patients receiving routine clinical care.

Linezolid Population Pharmacokinetics to Improve Dosing in Cardiosurgical Patients: Factoring a New Drug-Drug Interaction Pathway.

Background: Linezolid-induced myelosuppression limits optimal therapy in cardiosurgical patients with deep-seated infections at current doses.

Methods: Adult patients who received a cardiac surgery intervention and linezolid for a documented or presumed serious gram-positive infection were evaluated. Therapeutic monitoring data, dosing, concomitant medications, and other pertinent laboratory data were collected retrospectively.

Approach to patients with COVID-19 disease: the procedure in Udine.

Coronavirus disease 2019 poses a serious threat to public health. The protocol developed at the Azienda Sanitaria Universitaria Friuli Centrale (Italy) is based on clinical data, laboratory tests, chest echography and HRCT. Several therapeutic options are considered, since patients vary in disease severity, evolution and co-morbidities and because so far there are no clear indications about therapeutic strategy based on randomized clinical trial.

Clinical presentation and immunological features of Post-Malaria Neurologic Syndrome: a case report and review of literature.

Background: Malaria still represents a major health threat, in terms of both morbidity and mortality. Complications of malaria present a diversified clinical spectrum, with neurological involvement leading to the most serious related-conditions. The authors recently encountered a case of a 60-year old Italian man presenting with confusion, language disturbances and Parkinson-like syndrome 3 weeks after complete remission from severe Plasmodium falciparum cerebral malaria.

Ceftobiprole and pneumonia in adults admitted to the emergency department is it time to assess a new therapeutic algorithm?

Objective: Ceftobiprole is an advance generation cephalosporin which has broad-spectrum bacterial activity (both against Gram-positive and negative pathogens) and was approved for the treatment of community-acquired pneumonia (CAP) and non-ventilated hospital-acquired pneumonia (HAP) in most European countries. We aimed to evaluate the efficacy and safety of ceftobiprole in the treatment of pneumonia in a cohort of severely ill patients admitted to the emergency department (ED).

Methods: 1-year observational retrospective mono-centric study.

Comparative Population Pharmacokinetics of Darunavir in SARS-CoV-2 Patients vs. HIV Patients: The Role of Interleukin-6.

Background: Darunavir is an anti-HIV protease inhibitor repurposed for SARS-CoV-2 treatment.

Objective: The aim of this study was to assess the population pharmacokinetics of darunavir in SARS-CoV-2 patients compared with HIV patients.

Methods: Two separate models were created by means of a nonlinear mixed-effect approach.

Higher fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) uptake in tuberculous compared to bacterial spondylodiscitis.

Background: Tuberculous spondylodiscitis can be difficult to diagnose because of its nonspecific symptoms and the similarities with non-tubercular forms of spinal infection. Fluorine-18-fluorodeoxyglucose positron emission tomography combined with computed tomography (FDG PET-CT) is increasingly used for the diagnosis and monitoring of tubercular diseases.

Methods: Retrospective, case-control study comparing tuberculous spondylodiscitis with biopsy-confirmed pyogenic spondylodiscitis in the period 2010-2012.

Might real-time pharmacokinetic/pharmacodynamic optimisation of high-dose continuous-infusion meropenem improve clinical cure in infections caused by KPC-producing Klebsiella pneumoniae?

The effect of real-time pharmacokinetic/pharmacodynamic (PK/PD) optimisation of high-dose continuous-infusion meropenem on the clinical outcome of patients receiving combination antimicrobial therapy for treatment of KPC-producing Klebsiella pneumoniae (KPC-Kp) infections was retrospectively assessed. Data for all patients with KPC-Kp-related infections who received antimicrobial combination therapy containing high-dose continuous-infusion meropenem optimised by means of therapeutic drug monitoring (TDM) were retrieved. Optimal PK/PD exposure was considered a steady-state concentration to minimum inhibitory concentration ratio (C/MIC) of 1-4.

Gitelman syndrome disclosed by calcium pyrophosphate deposition disease: early diagnosis by ultrasonographic study.

Gitelman's syndrome is a rare autosomal-recessive tubular disorder characterized by hypomagnesemia and hypocalciuria associated to hypokalemia. The clinical spectrum is wide and usually characterized by chronic fatigue, cramps, muscle weakness and paresthesiae. We describe a case of a 43 year-old male patient with early onset of knee arthritis and no other symptoms.

Determination of PCT on admission is a useful tool for the assessment of disease severity in travelers with imported Plasmodium falciparum malaria.

Procalcitonin (PCT) and C-reactive protein (CRP) may be useful to predict complicated forms of malaria. A total of 30 consecutive travelers diagnosed with Plasmodium falciparum malaria over a two-year period were included in the study. Patients with complicated Plasmodium falciparum malaria showed higher levels of parasitemia (P = 0.

Risk factors for ventilator associated pneumonia due to carbapenemase-producing Klebsiella pneumoniae in mechanically ventilated patients with tracheal and rectal colonization.

Background: The aim of this study was to identify the risk factors for ventilator associated pneumonia (VAP) due to Klebsiella pneumoniae carbapenemase-producing K (KPC-Kp) development in ICU patients with documented rectal and tracheal colonization.

Methods: We performed a retrospective, matched case-control study in a medical-surgical ICU (January 2011-December 2013) comparing 30 patients who developed KPC-Kp VAP during the ICU stay to 60 colonized patients not developing KPC-Kp VAP. Analysed risk factors included: age, sex, SAPS II and SOFA scores, comorbidities, type and length of antibiotic therapy, previous non KPC-Kp infections, time between admission to rectal and tracheal colonization.

Comparison of clinical characteristics of tuberculosis between two age groups at an Italian Tertiary Hospital.

Differences in clinical characteristics and outcome between elderly (>60 years) and younger (18-59 years) tuberculosis (TB) patients were retrospectively evaluated. Alcohol abuse, radiological evidence of cavitation, and cough at presentation were more frequent among younger patients. Older patients were more likely to have comorbidities, disseminated TB, longer duration of symptoms and higher TB-related mortality (19 vs 0%).

Antiretroviral blood levels in HIV/HCV-coinfected patients with cirrhosis after liver transplant: a report of three cases.

Since the introduction of combined antiretroviral therapy, human immunodeficiency virus (HIV) infection is no longer a contraindication for solid organ transplantation. In HIV/hepatitis C virus (HCV)-coinfected patients undergoing liver transplantation, HCV-related cirrhosis, drug-drug interactions, and calcineurin inhibitors-related toxicity affect clinical outcomes. Therapeutic drug monitoring can be useful to assess antiretroviral over- or underexposure in this cohort.

Delafloxacin for the treatment of respiratory and skin infections.

Introduction: There has been a striking increase in the emergence of multidrug-resistant pathogens in recent times. Delafloxacin is a novel, broad-spectrum fluoroquinolone with antimicrobial activity against resistant Gram-positive, Gram-negative and anaerobic organisms. It has the potential to treat a variety of infections including complicated skin and skin structure infections and respiratory tract infections.

Linezolid-resistant staphylococcal bacteraemia: A multicentre case-case-control study in Italy.

The aim of this multicentre study was to analyse the characteristics of patients with bloodstream infections due to staphylococcal strains resistant to linezolid. This was a retrospective case-case-control study of patients hospitalised in three large teaching hospitals in Italy. A linezolid-resistant (LIN-R) Staphylococcus spp.

Current and future therapies for invasive aspergillosis.

Invasive fungal infections have increase worldwide and represent a threat for immunocompromised patients including HIV-infected, recipients of solid organ and stem cell transplants, and patients receiving immunosuppressive therapies. High mortality rates and difficulties in early diagnosis characterize pulmonary fungal infections. Invasive pulmonary aspergillosis has been reviewed focussing on therapeutic management.

Trans and cis effects of axial fluoroalkyl ligands in vitamin B12 analogues: relationship between alkyl- and fluoroalkyl-cobalamins.

CF2HCbl, CF3Cbl , and CF3CH2Cbl have been synthesized and characterized in solution by (1)H NMR and UV-vis spectroscopy, and their X-ray crystal structures have been determined using synchrotron radiation. The structure of CF3CH2Cbl is reported for the first time, whereas those of CF2HCbl and CF3Cbl are re-examined to obtain more precise structural data. Comparison of the structural data obtained with the alkylcobalamin analogues, MeCbl and EtCbl, indicates that the Co-C and Co-NB3 bond lengths are shorter in the fluoroalkylcobalamins.

Release of toxic Gd3+ ions to tumour cells by vitamin B12 bioconjugates.

Two probes consisting of vitamin B(12) (CNCbl) conjugated to Gd chelates by esterification of the ribose 5'-OH moiety, Gd-DTPA-CNCbl (1; DTPA = diethylenetriamine-N,N,N',N'',N''-pentaacetic acid) and Gd-TTHA-CNCbl (2; TTHA = triethylenetetramine-N,N,N',N'',N''',N'''-hexaacetic acid), have been synthesised and characterised. The crystal structure of a dimeric form of 1, obtained by crystallisation with an excess of GdCl(3), has been determined. The kinetics of binding to and dissociation from transcobalamin II show that 1 and 2 maintain high-affinity binding to the vitamin B(12) transport protein.

Metal coordination by sterically hindered heterocyclic ligands, including 2-vinylpyridine, assessed by investigation of cobaloximes.

Structural and 1H NMR data have been obtained for cobaloximes with the bulkiest substituted pyridines reported so far. We have isolated in noncoordinating solvents the complexes CH3Co(DH)2L (methylcobaloxime, where DH = the monoanion of dimethylglyoxime) with L = sterically hindered N-donor ligands: quinoline, 4-CH3quinoline, 2,4-(CH3)2pyridine, and 2-R-pyridine (R = CH3, OCH3, CH2CH3, CH=CH2). We have found that the Co-N(ax) bond is very long in the structurally characterized complexes.

Synthesis, characterization, and solution behavior of optically active cis beta organocobalt salen complexes with L-amino acids.

The reaction of a cis beta folded organocobalt derivative with a salen-type ligand, 1, isolated as racemic compound of Delta and Lambda enantiomers, with enantiomerically pure alpha-l amino acids is reported. The reaction between racemic 1 and l-tyrosine afforded a mixture of the two diastereoisomers Delta-2 and Lambda-2, which could be separated by fractional crystallization owing to the lower solubility of Delta-2. The absolute configuration of the two diastereomers was unequivocally assigned from the X-ray structure, using the known absolute configuration of the asymmetric carbon of the amino acid as internal reference.