scholarly journals Pharmacokinetics of EDP-420 after Ascending Single Oral Doses in Healthy Adult Volunteers

2009 ◽  
Vol 53 (5) ◽  
pp. 1786-1792 ◽  
Author(s):  
Li-Juan Jiang ◽  
Michelle Wang ◽  
Yat Sun Or
Keyword(s):  
Tract Infection ◽  
Adverse Events ◽  
Respiratory Tract ◽  
Respiratory Tract Infection ◽  
Half Life ◽  
Respiratory Tract Infections ◽  
Healthy Adult ◽  
Tract Infections

ABSTRACT EDP-420 (EP-013420, S-013420) is a first-in-class bicyclolide (bridged bicyclic macrolide) currently in clinical development for the treatment of respiratory tract infections. It has good preclinical pharmacokinetic properties across multiple species and potent in vitro and in vivo activity against respiratory tract infection pathogens, including Haemophilus influenzae, atypical organisms (e.g., Chlamydia pneumoniae, Mycoplasma pneumoniae, and Legionella pneumophila), and multidrug-resistant streptococci. The safety, tolerability, and pharmacokinetics of an orally administered EDP-420 suspension in 40 healthy adult subjects were assessed in a randomized, double-blind, placebo-controlled, ascending single-dose study. Eligible subjects were sequentially randomized into one of five study groups (i.e., 100-, 200-, 400-, 800-, or 1,200-mg dosing groups) consisting of eight subjects (six active and two placebo) each. EDP-420 was well tolerated. There were no serious adverse events reported, nor were there any dose-limiting clinical or laboratory adverse events reported. EDP-420 was rapidly absorbed after a single oral dose. The mean plasma terminal half-life ranged from 15.6 to 20.1 h with low clearance. At the 400-mg dose, the area under the curve was 14.4 μg·h/ml, which well exceeded the required area under the concentration-time curve to cover common respiratory tract infection pathogens based on preclinical pharmacokinetic/pharmacodynamic modeling. The long half-life and high systemic exposure of EDP-420 support once-daily dosing and may allow for shorter treatment durations compared to other macrolide antibiotics. Based on its human pharmacokinetic profiles, taken together with its in vitro/in vivo activity against common respiratory pathogens, EDP-420 warrants efficacy trials for the treatment of respiratory tract infections.

scholarly journals Whether immunostimulants are effective in susceptible children suffering from recurrent respiratory tract infections: a modeling analysis based on literature aggregate data

2021 ◽  
Author(s):  
Weilong Zhang ◽  
Jihan Huang ◽  
Hongxia Liu ◽  
Xin Wen ◽  
Qingshan Zheng ◽  
...  
Keyword(s):  
Tract Infection ◽  
Adverse Events ◽  
Respiratory Tract ◽  
Respiratory Tract Infection ◽  
Respiratory Tract Infections ◽  
Meta Analysis ◽  
Cumulative Number ◽  
Recurrent Respiratory Tract Infection ◽  
Prevention And Treatment ◽  
Tract Infections

Background: Immunostimulants are gradually being used in the prevention and treatment of recurrent respiratory tract infection (RRTIs) in susceptible children, but its drug effects have not been quantified. The purpose of this paper is to confirm the efficacy of immunostimulants in the prevention and treatment of RRTIs in susceptible children. Methods: Model-based meta-analysis (MBMA) was used to describe the time-course of placebo and immunostimulants in the prevention of RRTIs in children. The cumulative number of acute respiratory tract infections (ARTIs) was used as the indicator of efficacy. The single-arm meta-analysis was used to analyze the incidence of drug related adverse events. Results: A total of 14 articles with 2,400 pediatric subjects were finally included for analysis. The results showed that the cumulative number of ARTIs increased linearly with time, and the incidence of ARTIS in the placebo group was 0.65 (95% CI: 0.55 to 0.75) per month. OM-85 BV and pidotimod significantly reduced the incidence of ARTIs by 0.21 (95% CI: 0.16 to 0.26) and 0.19 (95% CI: 0.17 to 0.21) compared with placebo per month, respectively. The incidence of drug-related adverse events of pidotimod and OM-85 BV was comparable with that of placebo. Conclusions: Pidotimod and OM-85 BV can effectively reduce the incidence of ARTIs in susceptible children, and there is no significant increase in the incidence of drug-related adverse events. This study provides quantitative support for the application of immunostimulants for the prevention of recurrent respiratory tract infection in children.

scholarly journals Multiple Roles for BordetellaLipopolysaccharide Molecules during Respiratory Tract Infection

2000 ◽  
Vol 68 (12) ◽  
pp. 6720-6728 ◽  
Author(s):  
Eric T. Harvill ◽  
Andrew Preston ◽  
Peggy A. Cotter ◽  
Andrew G. Allen ◽  
Duncan J. Maskell ◽  
...  
Keyword(s):  
Tract Infection ◽  
Respiratory Tract ◽  
Respiratory Tract Infection ◽  
Adaptive Immunity ◽  
Lipid A ◽  
Core Oligosaccharide ◽  
O Antigen ◽  
Tract Infections

ABSTRACT Bordetella pertussis, Bordetella parapertussis, and Bordetella bronchiseptica are closely related subspecies that cause respiratory tract infections in humans and other mammals and express many similar virulence factors. Their lipopolysaccharide (LPS) molecules differ, containing either a complex trisaccharide (B. pertussis), a trisaccharide plus an O-antigen-like repeat (B. bronchiseptica), or an altered trisaccharide plus an O-antigen-like repeat (B. parapertussis). Deletion of the wlb locus results in the loss of membrane-distal polysaccharide domains in the three subspecies of bordetellae, leaving LPS molecules consisting of lipid A and core oligosaccharide. We have used wlb deletion (Δwlb) mutants to investigate the roles of distal LPS structures in respiratory tract infection by bordetellae. Each mutant was defective compared to its parent strain in colonization of the respiratory tracts of BALB/c mice, but the location in the respiratory tract and the time point at which defects were observed differed significantly. Although the Δwlb mutants were much more sensitive to complement-mediated killing in vitro, they displayed similar defects in respiratory tract colonization in C5−/− mice compared with wild-type (wt) mice, indicating that increased sensitivity to complement-mediated lysis is not sufficient to explain the in vivo defects. B. pertussis andB. parapertussis Δwlb mutants were also defective compared to wt strains in colonization of SCID-beige mice, indicating that the defects were not limited to interactions with adaptive immunity. Interestingly, the B. bronchiseptica Δwlbstrain was defective, compared to the wt strain, in colonization of the respiratory tracts of BALB/c mice beginning 1 week postinoculation but did not differ from the wt strain in its ability to colonize the respiratory tracts of B-cell- and T-cell-deficient mice, suggesting that wlb-dependent LPS modifications in B. bronchiseptica modulate interactions with adaptive immunity. These data show that biosynthesis of a full-length LPS molecule by these three bordetellae is essential for the expression of full virulence for mice. In addition, the data indicate that the different distal structures modifying the LPS molecules on these three closely related subspecies serve different purposes in respiratory tract infection, highlighting the diversity of functions attributable to LPS of gram-negative bacteria.

scholarly journals Manejo perioperatorio de niños con infección respiratoria superior

2019 ◽  
Vol 67 (2) ◽  
pp. 341-347
Author(s):  
Norma Constanza Corrales-Zúñiga ◽  
Nelly Patricia Martínez-Muñoz ◽  
Sara Isabel Realpe-Cisneros ◽  
Carlos Eberth Pacichana-Agudelo ◽  
Leandro Guillermo Realpe-Cisneros ◽  
...  
Keyword(s):  
Tract Infection ◽  
Respiratory Tract ◽  
Respiratory Tract Infection ◽  
Respiratory Tract Infections ◽  
Upper Respiratory Tract Infection ◽  
Cochrane Library ◽  
Upper Respiratory Tract ◽  
Upper Respiratory ◽  
Tract Infections

Introducción. Es frecuente que muchos niños sometidos a procedimientos con anestesia general tengan historia de infección viral respiratoria superior reciente o activa.Objetivo. Realizar una revisión narrativa acerca de las pautas de manejo anestésico para los niños con infección reciente o activa de la vía aérea superior.Materiales y métodos. Se realizó una búsqueda estructurada de la literatura en las bases de datos ProQuest, EBSCO, ScienceDirect, PubMed, LILACS, Embase, Trip Database, SciELO y Cochrane Library con los términos Anesthesia AND Respiratory Tract Infections AND Complications; Anesthesia AND Upper respiratory tract infection AND Complications; Anesthesia, General AND Respiratory Tract Infections AND Complications; Anesthesia, General AND Upper respiratory tract infection AND Complications; Anesthesia AND Laryngospasm OR Bronchospasm. La búsqueda se hizo en inglés con sus equivalentes en español.Resultados. Se encontraron 56 artículos con información relevante para el desarrollo de la presente revisión.Conclusiones. Una menor manipulación de la vía aérea tiende a disminuir la frecuencia de aparición y severidad de eventos adversos respiratorios perioperatorios. No existe evidencia suficiente para recomendar la optimización medicamentosa en pacientes con infección respiratoria superior.

Effectiveness of Oral Rinse with Chlorhexidine in Preventing Nosocomial Respiratory Tract Infections among Intensive Care Unit Patients

2009 ◽  
Vol 30 (10) ◽  
pp. 952-958 ◽  
Author(s):  
Fernando Bellissimo-Rodrigues ◽  
Wanessa Teixeira Bellissimo-Rodrigues ◽  
Jaciara Machado Viana ◽  
Gil Cezar Alkmim Teixeira ◽  
Edson Nicolini ◽  
...  
Keyword(s):  
Intensive Care Unit ◽  
Intensive Care ◽  
Length Of Stay ◽  
Tract Infection ◽  
Respiratory Tract ◽  
Respiratory Tract Infection ◽  
Respiratory Tract Infections ◽  
Icu Patients ◽  
Oral Application ◽  
Tract Infections

Objective.To evaluate the effectiveness of the oral application of a 0.12% solution of Chlorhexidine for prevention of respiratory tract infections among intensive care unit (ICU) patients.Design.The study design was a double-blind, randomized, placebo-controlled trial.Setting.The study was performed in an ICU in a tertiary care hospital at a public university.Patients.Study participants comprised 194 patients admitted to the ICU with a prospective length of stay greater than 48 hours, randomized into 2 groups: those who received Chlorhexidine (n = 98) and those who received a placebo (n = 96).Intervention.Oral rinses with Chlorhexidine or a placebo were performed 3 times a day throughout the duration of the patient's stay in the ICU. Clinical data were collected prospectively.Results.Both groups displayed similar baseline clinical features. The overall incidence of respiratory tract infections (RR, 1.0 [95% confidence interval [CI], 0.63-1.60]) and the rates of ventilator-associated pneumonia per 1,000 ventilator-days were similar in both experimental and control groups (22.6 vs 22.3; P = .95). Respiratory tract infection-free survival time (7.8 vs 6.9 days; P = .61), duration of mechanical ventilation (11.1 vs 11.0 days; P = .61), and length of stay (9.7 vs 10.4 days; P = .67) did not differ between the Chlorhexidine and placebo groups. However, patients in the Chlorhexidine group exhibited a larger interval between ICU admission and onset of the first respiratory tract infection (11.3 vs 7.6 days; P = .05). The chances of surviving the ICU stay were similar (RR, 1.08 [95% CI, 0.72-1.63]).Conclusion.Oral application of a 0.12% solution of Chlorhexidine does not prevent respiratory tract infections among ICU patients, although it may retard their onset.

scholarly journals Anemia as a Risk Factor for Acute Lower Respiratory Tract Infection in Children Below Five Years of Age

2018 ◽  
Vol 1 (1) ◽  
pp. 5-8
Author(s):  
Henish Shakya ◽  
Saurav Singh ◽  
Ashish Lakhey
Keyword(s):  
Risk Factor ◽  
Tract Infection ◽  
Respiratory Tract ◽  
Respiratory Tract Infection ◽  
Lower Respiratory Tract Infection ◽  
Lower Respiratory Tract ◽  
Respiratory Tract Infections ◽  
P Value ◽  
Lower Respiratory Tract Infections ◽  
Tract Infections

Introduction: Lower respiratory tract infection is a major cause of death in children in a developing country and anemia is found to be one of the commonest associated cofactors. This study was aimed to determine association of anemia in children with lower respiratory tract infections.Materials and Methods: The retrospective study was done over a one-year period for children under 5 years of age, admitted in Pediatric Ward of a tertiary Hospital in Lalitpur. The study included 100 diagnosed cases of lower respiratory tract infections as per WHO criteria and 100 age and sex matched patients who did not have respiratory complaints as controls, excluding prematurity, chronic diseases, malnutrition and severe systemic illness. Appropriate clinical history, examination routine investigations like hemoglobin, peripheral smear, and Chest X-ray were included.Results: The age distribution maximum children were in the age group of 3 months to 23 months with significant association with prevalence of both pneumonia (p value 0.005) and anemia (p value 0.002). Anemia was found to be a significant risk factor for LRTI (p value < 0.001) with odds ratio of 2.68 and 95% CI (1.51 – 4.75).Conclusions: Anemia was significantly found to be associated with lower respiratory tract infections and these children were found to be 2.68 times more susceptible to lower respiratory tract infections. Early diagnosis and prevention of anemia is thus important to reduce the incidence of lower respiratory tract infections in children.Nepalese Medical Journal. vol.1, No. 1, 2018, page: 5-8

scholarly journals Role of Bordetella O Antigen in Respiratory Tract Infection

2003 ◽  
Vol 71 (1) ◽  
pp. 86-94 ◽  
Author(s):  
Valorie C. Burns ◽  
Elizabeth J. Pishko ◽  
Andrew Preston ◽  
Duncan J. Maskell ◽  
Eric T. Harvill
Keyword(s):  
Tract Infection ◽  
Respiratory Tract ◽  
Respiratory Tract Infection ◽  
Human Pathogen ◽  
O Antigen ◽  
Highly Sensitive ◽  
Major Surface

ABSTRACT Lipopolysaccharide (LPS), as the major surface molecule of gram-negative bacteria, interacts with the host in complex ways, both inducing and protecting against aspects of inflammatory and adaptive immunity. The membrane-distal repeated carbohydrate structure of LPS, the O antigen, can prevent antibody functions and may vary as a mechanism of immune evasion. Genes of the wbm locus are required for the assembly of O antigen on the animal pathogen Bordetella bronchiseptica and the human pathogen B. parapertussis. However, the important human pathogen B. pertussis lacks these genes and a number of in vitro and in vivo characteristics associated with O antigen in other organisms. To determine the specific functions of O antigen in these closely related Bordetella subspecies, we compared wbm deletion (Δwbm) mutants of B. bronchiseptica and B. parapertussis in a variety of assays relevant to natural respiratory tract infection. Complement was not activated or depleted by wild-type bordetellae expressing O antigen, but both Δwbm mutants activated complement and were highly sensitive to complement-mediated killing in vitro. Although the O-antigen structures appear to be substantially similar, the two mutants differed strikingly in their defects within the respiratory tract. The B. parapertussis Δwbm mutant was severely defective in colonization of the tracheas and lungs of mice, while the B. bronchiseptica Δwbm mutant showed almost no defect. While in vitro characteristics such as serum resistance may be attributable to O antigen directly, the role of O antigen during infection appears to be more complex, possibly involving factors differing among the closely related bordetellae or different interactions between each one and its host.

scholarly journals In Vitro and Murine Efficacy and Toxicity Studies of Nebulized SCC1, a Methylated Caffeine-Silver(I) Complex, for Treatment of Pulmonary Infections

2009 ◽  
Vol 53 (8) ◽  
pp. 3285-3293 ◽  
Author(s):  
Carolyn L. Cannon ◽  
Lisa A. Hogue ◽  
Ravy K. Vajravelu ◽  
George H. Capps ◽  
Aida Ibricevic ◽  
...  
Keyword(s):  
Respiratory Tract ◽  
Respiratory Tract Infections ◽  
Airway Epithelial Cells ◽  
Clinical Strain ◽  
Resistant Bacteria ◽  
Infection Model ◽  
Airway Epithelial ◽  
Tract Infections

ABSTRACT The expanding clinical challenge of respiratory tract infections due to resistant bacteria necessitates the development of new forms of therapy. The development of a compound composed of silver coupled to a methylated caffeine carrier (silver carbene complex 1 [SCC1]) that demonstrated in vitro efficacy against bacteria, including drug-resistant organisms, isolated from patients with respiratory tract infections was described previously. The findings of current in vitro studies now suggest that bactericidal concentrations of SCC1 are not toxic to airway epithelial cells in primary culture. Thus, it was hypothesized that SCC1 could be administered by the aerosolized route to concentrate delivery to the lung while minimizing systemic toxicity. In vivo, aerosolized SCC1 delivered to mice resulted in mild aversion behavior, but it was otherwise well tolerated and did not cause lung inflammation following administration over a 5-day period. The therapeutic efficacy of SCC1 compared to that of water was shown in a 3-day prophylaxis protocol, in which mice infected with a clinical strain of Pseudomonas aeruginosa had increased survival, decreased amounts of bacteria in the lung, and a lower prevalence of bacteremia. Similarly, by using an airway infection model in which bacteria were impacted in the airways by agarose beads, the administration of SCC1 was significantly superior to water in decreasing the lung bacterial burden and the levels of bacteremia and markers of airway inflammation. These observations indicate that aerosolized SCC1, a novel antimicrobial agent, warrants further study as a potential therapy for bacterial respiratory tract infections.

scholarly journals Recurrent Respiratory Tract Infection in an infant: Early Diagnosis by Clinical and Radiological Pearls

2021 ◽  
Vol 41 (1) ◽  
pp. 111-114
Author(s):  
Shatanik Sarkar ◽  
Chaitali Patra ◽  
Shibani Pal ◽  
Arkapriya Pramanik
Keyword(s):  
Tract Infection ◽  
Early Diagnosis ◽  
Respiratory Tract ◽  
Respiratory Tract Infection ◽  
Clinical Examination ◽  
Respiratory Tract Infections ◽  
Recurrent Respiratory Tract Infection ◽  
Organ Systems ◽  
Tract Infections ◽  
Recurrent Respiratory Tract Infections

Recurrent respiratory tract infections, a cause of concern for both parents and paediatricians, can have various etiologies entitled to different organ systems. Diagnosing the exact cause warrants both clinical acumen and timely investigations. Here, we are reporting an infant with recurrent respiratory tract infections, where adequate clinical examination prompted us to diagnose the extra-respiratory cause with simple investigations.

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