Small-Molecule Neutrophil Modulator ADS051 is Safe and Well-Tolerated in a Phase 1 Single Ascending Dose Study.

Introduction: A need for better treatment options for moderate to severe ulcerative colitis (UC) persists because of the efficacy and safety limitations of current therapies. Neutrophil epithelial transmigration is associated with the characteristic colonic mucosal inflammation in and very likely involved with the pathogenesis and clinical symptoms of UC. ADS051 is a small-molecule inhibiting neutrophil migration and activation, which are potentially important therapeutic targets in UC.

Prevention of COVID-19 Following a Single Intramuscular Administration of Adintrevimab: Results From a Phase 2/3 Randomized, Double-Blind, Placebo-Controlled Trial (EVADE).

Background: The prevention of coronavirus disease 2019 (COVID-19) in vulnerable populations is a global health priority. EVADE was a phase 2/3 multicenter, double-blind, randomized, placebo-controlled trial of adintrevimab, an extended-half-life monoclonal antibody, for postexposure (PEP) and pre-exposure prophylaxis (PrEP) of symptomatic COVID-19.

Methods: Eligible participants (vaccine-naive, aged ≥12 years) were randomized 1:1 to receive a single 300-mg intramuscular injection of adintrevimab or placebo.

Daptomycin for Pediatric Gram-Positive Acute Hematogenous Osteomyelitis.

Background: We prospectively evaluated efficacy and safety of daptomycin versus active comparator in children with acute hematogenous osteomyelitis (AHO).

Methods: Randomized, controlled, double-blind, global, multicenter, phase 3 trial. Patients 1-17 years of age with suspected/confirmed AHO requiring hospitalization and intravenous therapy were randomized 1:1 to intravenous daptomycin (once-daily, age-adjusted doses) or comparator (vancomycin, nafcillin or equivalent) ≥4 days, followed by oral therapy (14-42 days total).

Safety and efficacy of monoclonal antibody VIS410 in adults with uncomplicated influenza A infection: Results from a randomized, double-blind, phase-2, placebo-controlled study.

Background: VIS410, a broadly neutralizing monoclonal antibody that binds the hemagglutinin stem of influenza A viruses, was safe and efficacious in a human H1N1 virus challenge study. This study evaluated the safety and tolerability of VIS410 in non-hospitalized adult patients with uncomplicated influenza A.

Methods: Patients 18 to 65 years of age with symptom onset within 72 h were randomized 1:1:1 to receive a single intravenous infusion of VIS410 4000 mg, 2000 mg, or placebo.

Safety, Tolerability, and Pharmacokinetics of 3 g of Ceftolozane/Tazobactam in Healthy Adults: A Randomized, Placebo-Controlled, Multiple-Dose Study.

Ceftolozane/tazobactam is an antibacterial approved at 1.5 g (1g/0.5 g) every 8 hours (q8h); higher doses may provide additional benefits in difficult-to-treat infections.

Characteristics and Outcomes of Complicated Intra-abdominal Infections Involving Pseudomonas aeruginosa from a Randomized, Double-Blind, Phase 3 Ceftolozane-Tazobactam Study.

Ceftolozane-tazobactam is active against Gram-negative pathogens, including multidrug-resistant Pseudomonas aeruginosa In a subgroup analysis of patients with complicated intra-abdominal infections (cIAIs) involving P. aeruginosa from a phase 3 program, ceftolozane-tazobactam demonstrated potent in vitro activity against P. aeruginosa Clinical cure in the microbiologically evaluable population was 100% (26/26) for ceftolozane-tazobactam plus metronidazole and 93.

Ceftolozane/Tazobactam Plus Metronidazole for Complicated Intra-abdominal Infections in an Era of Multidrug Resistance: Results From a Randomized, Double-Blind, Phase 3 Trial (ASPECT-cIAI).

Background: Increasing antimicrobial resistance among pathogens causing complicated intra-abdominal infections (cIAIs) supports the development of new antimicrobials. Ceftolozane/tazobactam, a novel antimicrobial therapy, is active against multidrug-resistant Pseudomonas aeruginosa and most extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae.

Methods: ASPECT-cIAI (Assessment of the Safety Profile and Efficacy of Ceftolozane/Tazobactam in Complicated Intra-abdominal Infections) was a prospective, randomized, double-blind trial.

Population pharmacokinetics of ceftolozane/tazobactam in healthy volunteers, subjects with varying degrees of renal function and patients with bacterial infections.

Ceftolozane/tazobactam is a novel antipseudomonal cephalosporin and β-lactamase inhibitor in clinical development for treatment of complicated urinary tract (cUTI) and intra-abdominal (cIAI) infections and nosocomial pneumonia. The population pharmacokinetics of ceftolozane/tazobactam were characterized in healthy volunteers, subjects with varying degrees of renal function, and patients with cIAI or cUTI. Serum concentration data from 376 adults who received ceftolozane/tazobactam in doses ranging from 500 to 3000 mg were analyzed to identify factors contributing to the pharmacokinetic variability.

Multicenter, double-blind, randomized, phase II trial to assess the safety and efficacy of ceftolozane-tazobactam plus metronidazole compared with meropenem in adult patients with complicated intra-abdominal infections.

Ceftolozane-tazobactam (TOL-TAZ) is a novel antibacterial with activity against Pseudomonas aeruginosa and other common Gram-negative pathogens, including extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae, that are associated with complicated intra-abdominal infections (cIAIs). This prospective, double-blind, randomized, multicenter, phase II trial assessed patient clinical and microbiological responses to and the safety of TOL-TAZ plus metronidazole compared with those of meropenem. Hospitalized adults with cIAIs that required surgical intervention were randomized (2:1) to receive intravenous (i.

Impact of renal function on the pharmacokinetics and safety of ceftolozane-tazobactam.

Ceftolozane-tazobactam is a novel antipseudomonal cephalosporin with a β-lactamase inhibitor. We investigated the pharmacokinetics (PK) and safety of ceftolozane-tazobactam in subjects with various degrees of renal function. In two phase I, open-label studies, a single dose of ceftolozane-tazobactam was administered as a 1-h intravenous infusion to 24 subjects with normal, mild, or moderate renal impairment (1,000/500 mg) and six subjects with severe renal impairment (500/250 mg).

Pharmacokinetics and safety of intravenous ceftolozane-tazobactam in healthy adult subjects following single and multiple ascending doses.

The pharmacokinetics and safety of ceftolozane, a novel cephalosporin, and tazobactam, a β-lactamase inhibitor, alone and in combination as a 2:1 ratio in single doses of up to 2,000 and 1,000 mg of ceftolozane and tazobactam, respectively, and multiple doses of up to 3,000 and 1,500 mg of ceftolozane and tazobactam, respectively, per day were evaluated in healthy adult subjects. In part 1, groups of six subjects each received single ascending doses of ceftolozane, tazobactam, and ceftolozane-tazobactam in a within-cohort crossover design. In part 2, groups of 5 or 10 subjects each received multiple doses of ceftolozane, tazobactam, or ceftolozane-tazobactam for 10 days.

Safety and clinical outcomes among older adults receiving daptomycin therapy: Insights from a patient registry.

Background: Serious gram-positive bacterial infections are an important cause of morbidity and mortality among older adults and can present significant challenges to clinicians. Data evaluating the safety and effectiveness of newer agents in this population are limited.

Objective: Daptomycin is a lipopeptide with activity against resistant gram-positive organisms.

Safety and clinical outcomes when utilizing high-dose (> or =8 mg/kg) daptomycin therapy.

Background: Daptomycin is approved for the treatment of skin and skin-structure infections (4 mg/kg) and Staphylococcus aureus bacteremia, including right-sided endocarditis (6 mg/kg). In vitro and animal studies have reported increased activity with increased daptomycin doses. There are limited clinical data on use of daptomycin at doses greater than 6 mg/kg.

Quinupristin-dalfopristin resistance in Enterococcus faecium isolates from humans, farm animals, and grocery store meat in the United States.

Three hundred sixty-one quinupristin-dalfopristin (Q-D)-resistant Enterococcus faecium (QDREF) isolates were isolated from humans, turkeys, chickens, swine, dairy and beef cattle from farms, chicken carcasses, and ground pork from grocery stores in the United States from 1995 to 2003. These isolates were evaluated by pulsed-field gel electrophoresis (PFGE) to determine possible commonality between QDREF isolates from human and animal sources. PCR was performed to detect the streptogramin resistance genes vatD, vatE, and vgbA and the macrolide resistance gene ermB to determine the genetic mechanism of resistance in these isolates.

Epidemiology of antimicrobial resistance in enterococci of animal origin.

Objective: We evaluated the epidemiology of antimicrobial resistance in enterococci from animal farms and the potential relation of resistance to antimicrobial use.

Methods: Enterococci from faecal samples from 18 beef cattle, 18 dairy cattle, 18 swine, 13 chicken, and eight turkey farms were prospectively evaluated over a 6 year period from 1998 to 2003.

Results: We evaluated 1256 isolates of Enterococcus faecium and 656 isolates of Enterococcus faecalis.

Molecular and clinical epidemiology of vancomycin-resistant Enterococcus faecalis.

Objectives: With the recent emergence of vancomycin-resistant (VR) Staphylococcus aureus, subsequent to the suggested transfer of the vanA resistance gene from Enterococcus faecalis, we sought to determine risk factors for acquisition of VR E. faecalis and to evaluate the molecular epidemiology of this less-prevalent and less-studied species of VR enterococcus.

Methods: We compared clinical isolates of VR E.

Relationship between fluoroquinolone use and changes in susceptibility to fluoroquinolones of selected pathogens in 10 United States teaching hospitals, 1991-2000.

We retrospectively examined the relationship between fluoroquinolone use and the susceptibilities of 11 bacterial pathogens to fluoroquinolones in 10 US teaching hospitals from 1991 through 2000. Statistical significance was determined by 2-way analysis of variance, with the number of isolates tested each year as a weighting factor. The analysis of baseline-to-end point change in the percentage of susceptibility and the slope of the regression line (trend line) for logit percentage of susceptibility showed that the overall percentage of susceptibility to fluoroquinolones decreased significantly during the study period (P<.

Quinupristin-dalfopristin resistance in gram-positive bacteria: mechanism of resistance and epidemiology.

Antimicrobial resistance in gram-positive bacteria is a continuing problem resulting in significant morbidity, mortality, and cost. Because of this resistance, new antimicrobial agents have been needed. Quinupristin-dalfopristin is a recently approved agent for treatment of these infections.

Antimicrobial resistance in swine and chickens fed virginiamycin for growth promotion.

In a prospective controlled study, we evaluated pigs (5-month period) and chickens (11-week period) fed subtherapeutic levels of virginiamycin. A total of 13 Enterococcus faecium were isolated from 10 pigs and 17 from 8 chickens. There were 8 pulsed-field gel electrophoresis (PFGE) patterns in E.

Antimicrobial resistance among gram-positive organisms in the intensive care unit.

Purpose Of Review: The epidemiology of gram-positive pathogens in the intensive care unit are reviewed, recent trends in antimicrobial resistance among these organisms are discussed, and the significance of these data with respect to treatment are considered.

Recent Findings: Results of surveillance studies published in 2001 and 2002 have demonstrated that gram-positive organisms such as Staphylococcus aureus, coagulase-negative staphylococci, and enterococci are among the most common bacteria infecting patients in intensive care units. Furthermore, these organisms are becoming increasingly resistant to available antimicrobial agents, and 2002 has ushered in worrisome developments such as the appearance of vancomycin-resistant S.

Molecular characterization of gentamicin-resistant Enterococci in the United States: evidence of spread from animals to humans through food.

We evaluated the molecular mechanism for resistance of 360 enterococci for which the gentamicin MICs were >/=128 micro g/ml. The aac(6')-Ie-aph(2")-Ia, aph(2")-Ic, and aph(2")-Id genes were identified by PCR in isolates from animals, food, and humans. The aph(2")-Ib gene was not identified in any of the isolates.

The Role of Fluoroquinolones in the Treatment of Skin and Soft Tissue Infection.

Skin and soft tissue infections vary widely in their nature and severity, and their nomenclature is complex. Most are readily recognized and easily treated, but more severe infections may masquerade in forms similar to those of more innocent infections, causing delay in diagnosis and treatment that may result in loss of limb or life. Antimicrobial therapy is clearly beneficial for both recovery from these infections as well as preventing disease progression.