FDA, CDC, and NIH Co-sponsored Public Workshop Summary-Development Considerations of Antimicrobial Drugs for the Treatment of Gonorrhea.

There is an unmet need for developing drugs for the treatment of gonorrhea, due to rapidly evolving resistance of Neisseria gonorrhoeae against antimicrobial drugs used for empiric therapy, an increase in globally reported multidrug resistant cases, and the limited available therapeutic options. Furthermore, few drugs are under development. Development of antimicrobials is hampered by challenges in clinical trial design, limitations of available diagnostics, changes in and varying standards of care, lack of robust animal models, and clinically relevant pharmacodynamic targets.

Risk Analysis Stratification of CIN 2+ Development in a Cohort of Women Living with HIV with Negative Pap Smear and HR-HPV Test during a Long-Term Follow-Up.

Background: Women living with Human Immunodeficiency Virus are at higher risk of cervical cancer and precancer compared to women without HIV infection. The aim of the study is to evaluate the risk factors for the development of CIN2+ in a cohort of WLWH with negative colposcopy and cytology during a long follow-up period.

Methods: We enrolled, in a multicentric retrospective cohort study, WLWH who attended the colposcopic services from 1999 to 2019.

Polarization Control in Integrated Graphene-Silicon Quantum Photonics Waveguides.

We numerically investigated the use of graphene nanoribbons placed on top of silicon-on-insulator (SOI) strip waveguides for light polarization control in silicon photonic-integrated waveguides. We found that two factors mainly affected the polarization control: the graphene chemical potential and the geometrical parameters of the waveguide, such as the waveguide and nanoribbon widths and distance. We show that the graphene chemical potential influences both TE and TM polarizations almost in the same way, while the waveguide width tapering enables both TE-pass and TM-pass polarizing functionalities.

Pharmacokinetic-Pharmacodynamic Target Attainment Analyses as Support for Meropenem-Vaborbactam Dosing Regimens and Susceptibility Breakpoints.

Meropenem-vaborbactam is a fixed-dose beta-lactam/beta-lactamase inhibitor with potent and activity against Klebsiella pneumoniae carbapenemase (KPC)-producing . Pharmacokinetic-pharmacodynamic (PK-PD) target attainment analyses were undertaken using population pharmacokinetic models, nonclinical PK-PD targets for efficacy, surveillance data, and simulation to provide support for 2 g meropenem-2 g vaborbactam every 8 h (q8h) administered as a 3-h intravenous (i.v.

Systematic Data Monitoring and Analysis of Cardiovascular Off-label Prescriptions in Pediatrics: Focus on Angiotensin-Converting Enzyme Inhibitors (ACE-I) and Beta Blockers.

Introduction: Many efforts have been made to stimulate clinical trials (CTs) in pediatrics but most of the drugs are still authorized only in adults and used off-label in the pediatric population.

Aim: To assess how widespread is the off-label prescription in Italy and to identify areas of unmet medical need by applying a model for the systematic collection and analysis of data.

Methods: A study was performed using 2015 data from the Italian Medicines Utilization Monitoring Centre Health Database (OsMed).

Arthroscopic single anchor repair techniques for upper third subscapularis tears provide sufficient biomechanical stability.

Purpose: Upper third tears of the subscapularis tendon can be repaired successfully with a single anchor according to previous literature. The aim of the present study was to compare three single anchor repair techniques regarding fixation strength, footprint coverage and contact pressure in a biomechanical test set-up on human cadaveric shoulders.

Methods: Eighteen human cadaveric shoulders were randomized in three groups with respect to the repair technique; group 1: knotted lasso-loop mattress, group 2: knotted mattress and group 3: knotless tape repair.

[Social inequalities in the use of medicines for the treatment of the major chronic diseases. Evidence from the AIFA Atlas.].

The Atlas of social inequalities in the use of medicines for the treatment of the major chronic diseases is the first national report published on social inequalities in the context of pharmaceutical care in Italy. The results highlighted how the socioeconomic position was strongly correlated with the use of medicines: for many therapeutic categories, the highest per capita consumption rates were recorded in the areas with a higher socioeconomic deprivation index. On the other hand, no correlations emerged between the level of deprivation and adherence and persistence to pharmacological treatment.

Serotype distribution and antimicrobial susceptibility of isolates from a Phase III community-acquired bacterial pneumonia (CABP) trial.

Objectives: To report serotyping and susceptibility data from a recent clinical trial (ML-3341-306) comparing delafloxacin with moxifloxacin in the treatment of adults with community-acquired bacterial pneumonia (CABP).

Methods: Serotyping and susceptibility testing were conducted on 142 baseline isolates recovered from subjects participating in a CABP clinical trial.

Results: Overall, 113/142 (79.

Analysis of SARS-CoV-2 vertical transmission during pregnancy.

The impact of SARS-CoV-2 infection during gestation remains unclear. Here, we analyse the viral genome on maternal and newborns nasopharyngeal swabs, vaginal swabs, maternal and umbilical cord plasma, placenta and umbilical cord biopsies, amniotic fluids and milk from 31 mothers with SARS-CoV-2 infection. In addition, we also test specific anti-SARS-CoV-2 antibodies and expression of genes involved in inflammatory responses in placentas, and in maternal and umbilical cord plasma.

Efficacy of delafloxacin versus moxifloxacin against atypical bacterial respiratory pathogens in adults with community-acquired bacterial pneumonia (CABP): Data from the Delafloxacin Phase 3 CABP Trial.

Objectives: To report atypical pathogens from clinical trial data comparing delafloxacin to moxifloxacin in the treatment of adults with community-acquired bacterial pneumonia (CABP).

Methods: Multiple diagnostic methods were employed to diagnose atypical infections including culture, serology, and urinary antigen.

Results: The microbiological intent-to-treat (MITT) population included 520 patients; 30% had an atypical bacterial pathogen identified (156/520).

A Phase 3 Study to Compare Delafloxacin With Moxifloxacin for the Treatment of Adults With Community-Acquired Bacterial Pneumonia (DEFINE-CABP).

Background: The clinical and economic burden of community-acquired bacterial pneumonia (CABP) is significant and is anticipated to increase as the population ages and pathogens become more resistant. Delafloxacin is a fluoroquinolone antibiotic approved in the United States for the treatment of adults with acute bacterial skin and skin structure infections. Delafloxacin's shape and charge profile uniquely impact its spectrum of activity and side effect profile.

Efficacy of Delafloxacin versus Moxifloxacin against Bacterial Respiratory Pathogens in Adults with Community-Acquired Bacterial Pneumonia (CABP): Microbiology Results from the Delafloxacin Phase 3 CABP Trial.

Delafloxacin is a novel fluoroquinolone with activity against Gram-positive, Gram-negative, and atypical pathogens, including fluoroquinolone-nonsusceptible methicillin-resistant (MRSA). The microbiological results of a phase 3 clinical trial in adults with community-acquired pneumonia (CAP) comparing delafloxacin (300 mg intravenously [i.v.

Efficacy and Safety of Single-Dose Oral Delafloxacin Compared With Intramuscular Ceftriaxone for Uncomplicated Gonorrhea Treatment: An Open-Label, Noninferiority, Phase 3, Multicenter, Randomized Study.

Background: We evaluated single oral dose of delafloxacin versus single intramuscular ceftriaxone in participants with uncomplicated urogenital gonorrhea (primary objective). Secondary objectives included the efficacy, safety, and tolerability of delafloxacin versus ceftriaxone for uncomplicated urogenital, rectal, and/or pharyngeal gonorrhea.

Methods: In this open-label, multicenter study, 460 participants at 25 study centers were randomized (2:1) to receive a single 900-mg oral dose of delafloxacin or 250-mg intramuscular ceftriaxone.

Analysis of Pooled Phase III Efficacy Data for Delafloxacin in Acute Bacterial Skin and Skin Structure Infections.

Background: Delafloxacin is an oral or intravenous (IV) antibiotic indicated for the treatment of acute bacterial skin and skin structure infections (ABSSSI), including both gram-positive (including methicillin-resistant Staphylococcus aureus [MRSA]) and gram-negative organisms. Chemically distinct from other quinolones, delafloxacin exhibits enhanced potency, particularly against gram-positive pathogens. The integration of efficacy data across the Phase III ABSSSI studies is presented here and allows for additional examination of results across subgroups.

Extragenital chlamydia infection among active-duty women in the United States Navy.

Background: Pharyngeal and anorectal reservoirs of gonorrhea (GC) and chlamydia (CT) are increasingly recognized among heterosexual women. While a number of studies performed at sexually transmitted disease (STD) clinics have found a high prevalence of extragenital GC/CT infection, such screening is typically not offered during routine primary care visits for women. We sought to define the prevalence of and factors associated with extragenital GC/CT among women in the U.

Evidence-Based Study Design for Hospital-Acquired Bacterial Pneumonia and Ventilator-Associated Bacterial Pneumonia.

Background: The US Food and Drug Administration solicited evidence-based recommendations to improve guidance for studies of hospital-acquired bacterial pneumonia (HABP) and ventilator-associated bacterial pneumonia (VABP).

Methods: We analyzed 7 HABP/VABP datasets to explore novel noninferiority study endpoints and designs, focusing on alternatives to all-cause mortality (ACM).

Results: ACM at day 28 differed for ventilated HABP (27.

Safety of Delafloxacin: Focus on Adverse Events of Special Interest.

Background: Fluoroquinolones have been widely used for a variety of Gram-positive and Gram-negative infections, and by 2002 they had become the most commonly prescribed class of antibiotics for adults in the United States. With widespread use, the class has become associated with a range of adverse events. Delafloxacin is a fluoroquinolone approved in the United States for the treatment of adults with acute bacterial skin and skin structure infections (ABSSSIs).

Lack of phototoxicity potential with delafloxacin in healthy male and female subjects: comparison to lomefloxacin.

Aims: Delafloxacin is a fluoroquinolone antibiotic recently approved by the FDA for treatment of acute bacterial skin and skin structure infections (ABSSSI). Delafloxacin was assessed for phototoxicity potential compared with a known phototoxic fluoroquinolone.

Methods: A Phase 1, investigator-blind, placebo/active-controlled, randomized, parallel-group study was conducted in 52 healthy male and female volunteers who received 200 or 400 mg of oral delafloxacin, 400 mg oral lomefloxacin or placebo once daily for 6 days.

Clinical Pharmacokinetics of Sulfobutylether-β-Cyclodextrin in Patients With Varying Degrees of Renal Impairment.

Delafloxacin, a fluoroquinolone, has activity against Gram-positive organisms including methicillin-resistant S aureus and fluoroquinolone-susceptible and -resistant Gram-negative organisms. The intravenous formulation of delafloxacin contains the excipient sulfobutylether-β-cyclodextrin (SBECD), which is eliminated by renal filtration. This study examined the pharmacokinetics and safety of SBECD after single intravenous (IV) infusions in subjects with renal impairment.

Pharmacokinetics of Intravenous Delafloxacin in Patients With End-Stage Renal Disease.

This was an open-label, parallel-group, crossover study that examined the pharmacokinetics and safety of delafloxacin, an anionic fluoroquinolone, after a single intravenous infusion in subjects with end-stage renal disease (ESRD; creatinine clearance <15 mL/min) undergoing hemodialysis compared with healthy subjects. Subjects received 300 mg delafloxacin containing sulfobutylether-β-cyclodextrin in 2 periods separated by ≥14-day washouts. Blood and urine samples were collected, and pharmacokinetic parameters were calculated using noncompartmental methods.

A Comparison of the Efficacy and Safety of Intravenous Followed by Oral Delafloxacin With Vancomycin Plus Aztreonam for the Treatment of Acute Bacterial Skin and Skin Structure Infections: A Phase 3, Multinational, Double-Blind, Randomized Study.

Background: Delafloxacin is an intravenous (IV)/oral anionic fluoroquinolone with activity against gram-positive (including methicillin-resistant Staphylococcus aureus [MRSA]), gram-negative, atypical, and anaerobic organisms. It is approved in the United States for acute bacterial skin and skin structure infections (ABSSSIs) caused by designated susceptible gram-positive and gram-negative organisms, and is in development for the treatment of community-acquired bacterial pneumonia.

Methods: A multicenter, randomized, double-blind trial of 850 adults with ABSSSI compared delafloxacin 300 mg IV every 12 hours for 3 days with a switch to 450 mg oral delafloxacin, to vancomycin 15 mg/kg IV with aztreonam for 5-14 days.