scholarly journals Expanding clinical phage microbiology: simulating phage inhalation for respiratory tract infections

2021 ◽  
pp. 00367-2021
Author(s):  
Shira Ben Porat ◽  
Daniel Gelman ◽  
Ortal Yerushalmy ◽  
Sivan Alkalay-Oren ◽  
Shunit Coppenhagen-Glazer ◽  
...  
Keyword(s):  
Respiratory Tract ◽  
Respiratory Tract Infections ◽  
Phage Therapy ◽  
Specific Model ◽  
Patient Specific ◽  
Diverse Range ◽  
Jet Nebulizer ◽  
Tract Infections ◽  
Therapy Success

Phage therapy is a promising antibacterial strategy for resistant respiratory tract infections. Phage inhalation may serve this goal; however, it requires a careful assessment of their delivery by this approach. Here we present an in-vitro model to evaluate phage inhalation. Eight phages, most of which target cystic fibrosis (CF)-common pathogens, were aerosolized by jet nebulizer and administered to a real-scale computed tomography (CT)-derived 3D airways model with a breathing simulator. Viable phage loads reaching the output of the nebulizer and the tracheal level of the model were determined and compared to the loaded amount. Phage inhalation resulted in a diverse range of titer reduction, primarily associated with the nebulization process. No correlation was found between phage delivery to the phage physical or genomic dimensions. These findings highlight the need for tailored simulations of phage delivery, ideally by a patient-specific model in addition to proper phage matching, to increase the potential of phage therapy success.

scholarly journals Expanding Clinical Phage Microbiology:‎ Simulating Phage Inhalation for Respiratory Tract Infections ‎

2021 ◽  
Author(s):  
Shira Ben-Porat ◽  
Daniel Gelman ◽  
Ortal Yerushalmy ◽  
Sivan Alkalay-Oren ◽  
Shunit Coppenhagen-Glazer ◽  
...  
Keyword(s):  
Respiratory Tract ◽  
Respiratory Tract Infections ◽  
Phage Therapy ◽  
Specific Model ◽  
Patient Specific ◽  
Diverse Range ◽  
Vitro Model ◽  
Tract Infections ◽  
Therapy Success

Phage therapy is a promising antibacterial strategy for resistant respiratory tract infections. Phage inhalation may serve this goal; however, it requires a careful assessment of their delivery by this approach. Here we present an in-vitro model to evaluate phage inhalation. Eight phages, most of which target CF-common pathogens, were aerosolized and administered to a real-scale CT derived 3D airways model with a breathing simulator. Viable phage loads reaching the output of the nebulizer and the tracheal level of the model were determined and compared to the loaded amount. Phage inhalation resulted in a diverse range of titer reduction, primarily associated with the nebulization process. No correlation was found between phage delivery to the phage physical or genomic dimensions. These findings highlight the need for tailored simulations of phage delivery, ideally by a patient-specific model in addition to proper phage matching, to increase the potential of phage therapy success.

Telithromycin: The First of the Ketolides

2002 ◽  
Vol 36 (3) ◽  
pp. 452-464 ◽  
Author(s):  
Christopher S Shain ◽  
Guy W Amsden
Keyword(s):  
Respiratory Tract ◽  
Clinical Efficacy ◽  
Respiratory Tract Infections ◽  
Safety Issue ◽  
Qtc Interval ◽  
Phagocytic Cells ◽  
Medline Search ◽  
Atypical Pathogens ◽  
Tract Infections

OBJECTIVE: To review the chemistry, spectrum of activity, pharmacology, clinical efficacy, and safety of telithromycin. DATA SOURCES: A MEDLINE search from 1966 to December 2000 was performed via OVID and PubMed using the following search terms: HMR 3647, HMR3647, Ketek, RU 66647, and telithromycin. An extensive review of retrieved literature, abstracts from international scientific conferences, and minutes from regulatory authority meetings was also performed. DATA EXTRACTION: Medicinal chemistry, in vitro, animal, and human trials were reviewed for information on the antimicrobial activity, clinical efficacy, pharmacology, and safety of telithromycin. DATA SYNTHESIS: Several chemical modifications to the macrolide structure have led to the development of telithromycin, the first ketolide antimicrobial that demonstrates improved activity against penicillin- and macrolide/azalide-resistant Streptococcus pneumoniae due to its unique binding to the ribosomal target site. Although telithromycin may be useful in the treatment of community-acquired respiratory tract infections due to its activity against common typical and atypical pathogens, questions concerning its reliable activity against Haemophilus influenzae need to be addressed. Telithromycin's pharmacokinetics permit once-daily dosing for abbreviated periods and good distribution into lung tissue and phagocytic cells. Clinical and bacteriologic cure rates have been similar to those of comparator agents in human efficacy trials; however, the incidence of adverse gastrointestinal events were generally higher with telithromycin patients. Like other macrolides and many newer fluoroquinolones, telithromycin's ability to prolong the QTc interval is a potential safety issue, especially in elderly patients with predisposing conditions or those who are concurrently receiving drugs that are substrates for CYP2D6 and 3A4. Liver function test elevations demonstrated during clinical trials, although not overtly severe, may warrant monitoring in some patients taking multiple hepatically metabolized/cleared agents. CONCLUSIONS: Telithromycin offers potential advantages over traditional macrolides/azalides for community-acquired respiratory tract infections caused by macrolide-resistant pathogens. Further studies are needed to elucidate its clinical efficacy against H. influenzae, potential drug interactions, and safety in various subpopulations.

scholarly journals In Vitro Activities of Peptide Deformylase Inhibitors against Gram-Positive Pathogens

2002 ◽  
Vol 46 (4) ◽  
pp. 1117-1118 ◽  
Author(s):  
R. Wise ◽  
J. M. Andrews ◽  
J. Ashby
Keyword(s):  
Respiratory Tract ◽  
Respiratory Tract Infections ◽  
Active Agent ◽  
Peptide Deformylase ◽  
Gram Positive ◽  
Similar Activity ◽  
Amoxicillin Clavulanate ◽  
Tract Infections

ABSTRACT The activities of six peptide deformylase (PDF) inhibitors against 107 respiratory tract pathogens were studied and compared to those of ciprofloxacin and amoxicillin-clavulanate. Against Streptococcus pneumoniae, BB-83698 and BB-83815 were the most active PDF inhibitors (MIC at which 90% of the organisms tested were inhibited [MIC90], 0.25 μg/ml). Five of the agents showed similar activity against Moraxella catarrhalis (MIC90, 0.12 μg/ml). All PDF inhibitors were less active against Haemophilus influenzae; BB-3497 was the most active agent (MIC90, 2 μg/ml). Five agents were studied against Chlamydia spp. and showed activity similar to that of ciprofloxacin (MIC, 0.5 to 4 μg/ml). This study demonstrates that PDF inhibitors have the potential to be developed for the treatment of respiratory tract infections.

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 Effectiveness of Electronic Guidelines (GERH®) to Improve the Clinical Use of Antibiotics in An Intensive Care Unit

Antibiotics ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 521
Author(s):  
Paola Navarro-Gómez ◽  
Jose Gutierrez-Fernandez ◽  
Manuel Angel Rodriguez-Maresca ◽  
Maria Carmen Olvera-Porcel ◽  
Antonio Sorlozano-Puerto
Keyword(s):  
Urinary Tract ◽  
Respiratory Tract ◽  
Lower Respiratory Tract ◽  
Respiratory Tract Infections ◽  
Bacterial Species ◽  
Lower Respiratory Tract Infections ◽  
Icu Patients ◽  
Study Results ◽  
Tract Infections

The objective of the study was to evaluate the capacity of GERH®-derived local resistance maps (LRMs) to predict antibiotic susceptibility profiles and recommend the appropriate empirical treatment for ICU patients with nosocomial infection. Data gathered between 2007 and 2016 were retrospectively studied to compare susceptibility information from antibiograms of microorganisms isolated in blood cultures, lower respiratory tract samples, and urine samples from all ICU patients meeting clinical criteria for infection with the susceptibility mapped by LRMs for these bacterial species. Susceptibility described by LRMs was concordant with in vitro study results in 73.9% of cases. The LRM-predicted outcome agreed with the antibiogram result in >90% of cases infected with the bacteria for which GERH® offers data on susceptibility to daptomycin, vancomycin, teicoplanin, linezolid, and rifampicin. Full adherence to LRM recommendations would have improved the percentage adequacy of empirical prescriptions by 2.2% for lower respiratory tract infections (p = 0.018), 3.1% for bacteremia (p = 0.07), and 5.3% for urinary tract infections (p = 0.142). LRMs may moderately improve the adequacy of empirical antibiotic therapy, especially for lower respiratory tract infections. LRMs recommend appropriate prescriptions in approximately 50% of cases but are less useful in patients with bacteremia or urinary tract infection.

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