scholarly journals The Evolution of Antimicrobial Resistance in Respiratory Pathogens in Canada: What are the Clinical Consequences?

1998 ◽  
Vol 9 (suppl e) ◽  
pp. 10E-15E
Author(s):  
Donald E Low
Keyword(s):  
Antimicrobial Resistance ◽  
Respiratory Tract ◽  
Antimicrobial Agents ◽  
Public Health Problem ◽  
Antibiotic Use ◽  
Respiratory Pathogens ◽  
Important Public Health Problem ◽  
Tract Infections

The use of antimicrobial agents has led to reductions in illnesses and deaths from a variety of infectious diseases. Antimicrobial resistance has followed the introduction of almost every new antimicrobial agent and is now emerging as an important public health problem, especially in respiratory tract pathogens in the community. During the past decade in Canada, a rapid and relentless increase in antimicrobial resistance inStreptococcus pneumoniaeandHaemophilus inflluenzaehas been witnessed. Adverse implications as a result of the treatment of an infection with an antibiotic to which the offending pathogen is resistant have been recognized in only a few infectious disease syndromes (eg. bacterial meningitis). More often, resistance in vitro does not result in resistance in vivo (eg, respiratory tract infections). Therefore, before recommendations regarding empirical or directed therapy are changed, it is essential that evidence to support those decisions is obtained. More important, the prevention and control of such resistance must be addressed by reducing the burden of antibiotic selective pressure by curtailing inappropriate antibiotic use.

scholarly journals Viral and Bacterial Co-Infections in the Lungs: Dangerous Liaisons

Viruses ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1725
Author(s):  
Justine Oliva ◽  
Olivier Terrier
Keyword(s):  
Respiratory Tract ◽  
Current Knowledge ◽  
Influenza Infection ◽  
Public Health Problem ◽  
Experimental Models ◽  
Influenza Viruses ◽  
Host Cells ◽  
Tract Infections

Respiratory tract infections constitute a significant public health problem, with a therapeutic arsenal that remains relatively limited and that is threatened by the emergence of antiviral and/or antibiotic resistance. Viral–bacterial co-infections are very often associated with the severity of these respiratory infections and have been explored mainly in the context of bacterial superinfections following primary influenza infection. This review summarizes our current knowledge of the mechanisms underlying these co-infections between respiratory viruses (influenza viruses, RSV, and SARS-CoV-2) and bacteria, at both the physiological and immunological levels. This review also explores the importance of the microbiome and the pathological context in the evolution of these respiratory tract co-infections and presents the different in vitro and in vivo experimental models available. A better understanding of the complex functional interactions between viruses/bacteria and host cells will allow the development of new, specific, and more effective diagnostic and therapeutic approaches.

Preliminary Report of In vitro and In vivo Effectiveness of Dornase Alfa on SARS-CoV-2 Infection (Preprint)

2020 ◽  
Author(s):  
Hacer Kuzu Okur ◽  
Koray Yalcin ◽  
Cihan Tastan ◽  
Sevda Demir ◽  
Bulut Yurtsever ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Respiratory Tract ◽  
Mononuclear Cells ◽  
Multiple Organ ◽  
Peripheral Blood Mononuclear ◽  
Dornase Alfa ◽  
Tract Infections ◽  
Adult Peripheral Blood

UNSTRUCTURED Dornase alfa, the recombinant form of the human DNase I enzyme, breaks down neutrophil extracellular traps (NET) that include a vast amount of DNA fragments, histones, microbicidal proteins and oxidant enzymes released from necrotic neutrophils in the highly viscous mucus of cystic fibrosis patients. Dornase alfa has been used for decades in patients with cystic fibrosis to reduce the viscoelasticity of respiratory tract secretions, to decrease the severity of respiratory tract infections, and to improve lung function. Previous studies have linked abnormal NET formations to lung diseases, especially to acute respiratory distress syndrome (ARDS). Coronavirus disease 2019 (COVID-19) pandemic affected more than two million people over the world, resulting in unprecedented health, social and economic crises. The COVID-19, viral pneumonia that progresses to ARDS and even multiple organ failure, is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). High blood neutrophil levels are an early indicator of SARS-CoV-2 infection and predict severe respiratory diseases. A similar mucus structure is detected in COVID-19 patients due to the accumulation of excessive NET in the lungs. Here, we show our preliminary results with dornase alfa that may have an in-vitro anti-viral effect against SARS-CoV-2 infection in a bovine kidney cell line, MDBK without drug toxicity on healthy adult peripheral blood mononuclear cells. In this preliminary study, we also showed that dornase alfa can promote clearance of NET formation in both an in-vitro and three COVID-19 cases who showed clinical improvement in radiological analysis (2-of-3 cases), oxygen saturation (SpO2), respiratory rate, disappearing of dyspnea and coughing.

scholarly journals Pharmacokinetics of EDP-420 after Multiple Oral Doses in Healthy Adult Volunteers and in a Bioequivalence Study

2009 ◽  
Vol 53 (8) ◽  
pp. 3218-3225 ◽  
Author(s):  
Li-Juan Jiang ◽  
Yat Sun Or
Keyword(s):  
Systemic Exposure ◽  
Bioequivalence Study ◽  
Respiratory Pathogens ◽  
Capsule Formulation ◽  
Dose Study ◽  
Effect Of Food ◽  
Tract Infections ◽  
Oral Doses

ABSTRACT EDP-420 (also known as EP-013420, or S-013420) is a first-in-class bridged bicyclolide currently in clinical development for the treatment of respiratory tract infections (RTI) and has previously shown favorable pharmacokinetic (PK) and safety profiles after the administration of single oral doses of a suspension to healthy volunteers. Here we report its PK profile after the administration of multiple oral doses of a suspension to healthy adults. Bioequivalence between suspension and capsule formulations, as well as the effect of food, is also reported. The most important PK features of EDP-420 observed in these clinical studies are its long half-life of 17 to 18 h and its high systemic exposure, which support once-daily dosing and treatment durations potentially shorter than those of most other macrolide antibiotics. EDP-420 is readily absorbed following oral administration in both suspension and capsule formulations. In the multiple-oral-dose study, steady state was achieved on day 1 by using a loading dose of 400 mg/day, followed by 2 days of 200 mg/day. A high-fat meal had no effect on the bioavailability of EDP-420 administered in a capsule formulation. EDP-420 was well tolerated, with no serious or severe adverse events reported, and no subject was discontinued from the study due to an adverse event. Based on its human PK and safety profiles, together with its in vitro/in vivo activities against common respiratory pathogens, EDP-420 warrants further development, including trials for clinical efficacy in the treatment of RTI.

Cephazolin Sodium—An In Vivo and In Vitro Evaluation of 100 Patients with Urinary Tract Infections

1975 ◽  
Vol 20 (5) ◽  
pp. 259-260
Author(s):  
Diana M. D. Rimmer
Keyword(s):  
Urinary Tract Infection ◽  
Urinary Tract ◽  
Tract Infection ◽  
General Hospital ◽  
Urinary Tract Infections ◽  
Antimicrobial Agents ◽  
Random Group ◽  
Tract Infections

A random group of 100 patients in a general hospital were treated with cephazolin sodium for proven urinary tract infections. Sixty-six per cent had conditions predisposing to urinary tract infection. Under these somewhat difficult conditions the original infecting organism remained absent from the urine of 75 per cent of the 70 patients followed in the 3rd to 6th week period. This compares very favourably with response to other antimicrobial agents currently used in urinary tract infections.

scholarly journals Macrolones Are a Novel Class of Macrolide Antibiotics Active against Key Resistant Respiratory PathogensIn VitroandIn Vivo

2016 ◽  
Vol 60 (9) ◽  
pp. 5337-5348 ◽  
Author(s):  
Hana Čipčić Paljetak ◽  
Donatella Verbanac ◽  
Jasna Padovan ◽  
Miroslava Dominis-Kramarić ◽  
Željko Kelnerić ◽  
...  
Keyword(s):  
Murine Model ◽  
Bacterial Resistance ◽  
Volume Of Distribution ◽  
Macrolide Antibiotics ◽  
Respiratory Pathogens ◽  
Protein Synthesis Inhibitors ◽  
Content Type ◽  
Tract Infections

ABSTRACTAs we face an alarming increase in bacterial resistance to current antibacterial chemotherapeutics, expanding the available therapeutic arsenal in the fight against resistant bacterial pathogens causing respiratory tract infections is of high importance. The antibacterial potency of macrolones, a novel class of macrolide antibiotics, against key respiratory pathogens was evaluatedin vitroandin vivo. MIC values againstStreptococcus pneumoniae,Streptococcus pyogenes,Staphylococcus aureus, andHaemophilus influenzaestrains sensitive to macrolide antibiotics and with defined macrolide resistance mechanisms were determined. The propensity of macrolones to induce the expression of inducibleermgenes was tested by the triple-disk method and incubation in the presence of subinhibitory concentrations of compounds.In vivoefficacy was assessed in a murine model ofS. pneumoniae-induced pneumonia, and pharmacokinetic (PK) profiles in mice were determined. Thein vitroantibacterial profiles of macrolones were superior to those of marketed macrolide antibiotics, including the ketolide telithromycin, and the compounds did not induce the expression of inducibleermgenes. They acted as typical protein synthesis inhibitors in anEscherichia colitranscription/translation assay. Macrolones were characterized by low to moderate systemic clearance, a large volume of distribution, a long half-life, and low oral bioavailability. They were highly efficacious in a murine model of pneumonia after intraperitoneal application even against anS. pneumoniaestrain with constitutive resistance to macrolide-lincosamide-streptogramin B antibiotics. Macrolones are the class of macrolide antibiotics with an outstanding antibacterial profile and reasonable PK parameters resulting in goodin vivoefficacy.

scholarly journals National and Regional Assessment of Antimicrobial Resistance among Community-Acquired Respiratory Tract Pathogens Identified in a 2005-2006 U.S. Faropenem Surveillance Study

2007 ◽  
Vol 51 (12) ◽  
pp. 4382-4389 ◽  
Author(s):  
Ian A. Critchley ◽  
Steven D. Brown ◽  
Maria M. Traczewski ◽  
Glenn S. Tillotson ◽  
Nebojsa Janjic
Keyword(s):  
United States ◽  
Respiratory Tract ◽  
Respiratory Infections ◽  
Empirical Therapy ◽  
The United States ◽  
Respiratory Pathogens ◽  
Study Objective ◽  
Tract Infections ◽  
Resistance Rates

ABSTRACT Surveillance studies conducted in the United States over the last decade have revealed increasing resistance among community-acquired respiratory pathogens, especially Streptococcus pneumoniae, that may limit future options for empirical therapy. The objective of this study was to assess the scope and magnitude of the problem at the national and regional levels during the 2005-2006 respiratory season (the season when community-acquired respiratory pathogens are prevalent) in the United States. Also, since faropenem is an oral penem being developed for the treatment of community-acquired respiratory tract infections, another study objective was to provide baseline data to benchmark changes in the susceptibility of U.S. respiratory pathogens to the drug in the future. The in vitro activities of faropenem and other agents were determined against 1,543 S. pneumoniae isolates, 978 Haemophilus influenzae isolates, and 489 Moraxella catarrhalis isolates collected from 104 U.S. laboratories across six geographic regions during the 2005-2006 respiratory season. Among S. pneumoniae isolates, the rates of resistance to penicillin, amoxicillin-clavulanate, and cefdinir were 16, 6.4, and 19.2%, respectively. The least effective agents were trimethoprim-sulfamethoxazole (SXT) and azithromycin, with resistance rates of 23.5 and 34%, respectively. Penicillin resistance rates for S. pneumoniae varied by region (from 8.7 to 22.5%), as did multidrug resistance rates for S. pneumoniae (from 8.8 to 24.9%). Resistance to β-lactams, azithromycin, and SXT was higher among S. pneumoniae isolates from children than those from adults. β-Lactamase production rates among H. influenzae and M. catarrhalis isolates were 27.4 and 91.6%, respectively. Faropenem MICs at which 90% of isolates are inhibited were 0.5 μg/ml for S. pneumoniae, 1 μg/ml for H. influenzae, and 0.5 μg/ml for M. catarrhalis, suggesting that faropenem shows promise as a treatment option for respiratory infections caused by contemporary resistant phenotypes.

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 Antimicrobial Resistance in Bacteria Isolated From Cats and Dogs From the Iberian Peninsula

2021 ◽  
Vol 11 ◽  
Author(s):  
Yanli Li ◽  
Rubén Fernández ◽  
Inma Durán ◽  
Rafael A. Molina-López ◽  
Laila Darwich
Keyword(s):  
Antimicrobial Resistance ◽  
Respiratory Tract ◽  
Iberian Peninsula ◽  
Antimicrobial Susceptibility ◽  
Respiratory Tract Infections ◽  
Antimicrobial Agents ◽  
Close Contact ◽  
Clinical Samples ◽  
Private Laboratory ◽  
Tract Infections

Pet animals are assumed to be potential reservoirs in transferring antimicrobial resistance (AMR) to humans due to the extensively applied broad-spectrum antimicrobial agents and their close contact with humans. In this study, microbiological data and antimicrobial susceptibility results of dog (n = 5,086) and cat (n = 789) clinical samples from a private Laboratory of Diagnosis in Barcelona were analyzed. Samples came from different counties of the Iberian Peninsula during 2016–2018. In dogs, clinical samples were most commonly from otitis, and in cats from wounds, respiratory tract infections and conjunctivitis. In both pet groups, Staphylococcus spp. (31% in dogs vs 30% in cats), Streptococcus spp. (19% vs 17%), Pseudomonas spp. (16% vs 10%), Escherichia coli (8% vs 5.6%), and Enterococcus spp. (5.5% vs 6.8%) were shown as the most predominant bacteria. However, higher frequencies of P. aeruginosa, P. canis, and S. pseudintermedius were found in dogs, while S. aureus and P. multocida were more prevalent in cats. The antimicrobial susceptibility testing demonstrated that Enterococcus spp. and Pseudomonas spp. presented the highest levels of AMR in both dogs and cats. Within the Enterobacteriaceae, E. coli showed low levels of AMR compared to Klebsiella, Proteus, or Enterobacter spp. Respiratory tract infections caused by K. pneumoniae presented higher AMR in cats. By contrast, Pasteurella isolates from the respiratory tract were highly sensitive to all the antimicrobials in cats and dogs. Data from this study could be used to guide empirical antimicrobial selection in companion animal veterinary practices in the Iberian Peninsula.

scholarly journals In Vitro Activity of Lefamulin Against a Global Collection of Bacterial Pathogens Commonly Causing Community-Acquired Bacterial Pneumonia (CABP, SENTRY 2015)

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S373-S373 ◽  
Author(s):  
Susanne Paukner ◽  
Helio S Sader ◽  
Jennifer M Streit ◽  
Robert K Flamm ◽  
Steven P Gelone
Keyword(s):  
Respiratory Tract ◽  
Bacterial Pathogens ◽  
Bloodstream Infections ◽  
Vitro Activity ◽  
Asia Pacific ◽  
Respiratory Pathogens ◽  
In Vitro Activity ◽  
Tract Infections ◽  
Research Grant

Abstract Background CABP is the number one reason for death by infectious diseases worldwide and emerging resistance complicates its treatment. Lefamulin is the first semi-synthetic pleuromutilin antibiotic for IV and oral use in humans. It is currently in Phase 3 trials for the treatment of CABP in adults. Lefamulin effectively and selectively inhibits bacterial translation by binding to the peptidyl transferase center (PTC) via four H-bonds and other interactions at the A- and P-site resulting in an “induced fit.” This study investigated the activity of lefamulin and comparators against a contemporary set of bacterial pathogens associated with community-acquired respiratory infections collected worldwide. Methods Unique patients’ isolates (n = 2817) were collected globally in US (19.7%), Europe (36.9%), Latin America (5.7%) and Asia-Pacific region (37.6%) (30 countries, 116 sites) from adult and pediatric patients with respiratory tract infection (88.0%), bloodstream infections (5.5%) and other infections (2.4%). Lefamulin and comparators were tested by CLSI broth microdilution and susceptibility was determined using the CLSI (2017) breakpoints. Results LEF was the most potent compound tested, with 99.7% of all S. pneumoniae isolates being inhibited at a concentration of ≤0.25 mg/L (MIC50/90 values of 0.06/0.12 mg/L) and its activity was not affected by resistance to other antibiotic classes. S. pneumoniae isolates were largely susceptible to levofloxacin (99.1%) and ceftriaxone (96.5%), while 34.5%, 23.3% and 16.8% of isolates were resistant to macrolides, tetracycline and clindamycin, respectively. Lefamulin also showed potent activity against H. influenzae (MIC50/90 of 0.5/1 mg/L), including 22.0% of ß-lactamase producing strains, and M. catarrhalis (0.06/0.12 mg/L). Conclusion Lefamulin demonstrated potent in vitro activity against this global collection of contemporary respiratory pathogens and its activity was unchanged regardless of resistance phenotype to the other antibiotic classes including macrolides, ß-lactams, tetracyclines or fluoroquinolones. These data support the continued clinical development of lefamulin for the treatment of respiratory tract infections, including CABP. Disclosures S. Paukner, Nabriva Therapeutics: Employee and Shareholder, Salary; H. S. Sader, Nabriva Therapeutics: Research Contractor, Research grant; J. M. Streit, Nabriva Therapeutics: Research Contractor, Research grant; R. K. Flamm, Nabriva Therapeutics: Research Contractor, Research grant; S. P. Gelone, Nabriva Therapeutics: Employee and Shareholder, Salary

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