scholarly journals Ambroxol Treatment Suppresses the Proliferation of Chlamydia pneumoniae in Murine Lungs

2021 ◽  
Vol 9 (4) ◽  
pp. 880
Author(s):  
Dávid Kókai ◽  
Dóra Paróczai ◽  
Dezső Peter Virok ◽  
Valéria Endrész ◽  
Renáta Gáspár ◽  
...  
Keyword(s):  
Respiratory Tract Infections ◽  
Chlamydia Pneumoniae ◽  
Respiratory Infections ◽  
Surfactant Protein ◽  
Interleukin 12 ◽  
Immunomodulating Effect ◽  
Expression Levels ◽  
Ifn Γ ◽  
Tract Infections

Ambroxol (Ax) is used as a mucolytics in the treatment of respiratory tract infections. Ax, at a general dose for humans, does not alter Chlamydia pneumoniae growth in mice. Therefore, we aimed to investigate the potential anti-chlamydial effect of Ax at a concentration four timed higher than that used in human medicine. Mice were infected with C. pneumoniae and 5-mg/kg Ax was administered orally. The number of recoverable C. pneumoniae inclusion-forming units (IFUs) in Ax-treated mice was significantly lower than that in untreated mice. mRNA expression levels of several cytokines, including interleukin 12 (IL-12), IL-23, IL-17F, interferon gamma (IFN-γ), and surfactant protein (SP)-A, increased in infected mice treated with Ax. The IFN-γ protein expression levels were also significantly higher in infected and Ax-treated mice. Furthermore, the in vitro results suggested that the ERK 1/2 activity was decreased, which is essential for the C. pneumoniae replication. SP-A and SP-D treatments significantly decreased the number of viable C. pneumoniae IFUs and significantly increased the attachment of C. pneumoniae to macrophage cells. Based on our results, a dose of 5 mg/kg of Ax exhibited an anti-chlamydial effect in mice, probably an immunomodulating effect, and may be used as supporting drug in respiratory infections caused by C. pneumoniae.

scholarly journals Roles of Interleukin-12 and Gamma Interferon in Murine Chlamydia pneumoniae Infection

2000 ◽  
Vol 68 (4) ◽  
pp. 2245-2253 ◽  
Author(s):  
Yuemei Geng ◽  
Klara Berencsi ◽  
Zsofia Gyulai ◽  
Tibor Valyi-Nagy ◽  
Eva Gonczol ◽  
...  
Keyword(s):  
Chlamydia Pneumoniae ◽  
Inflammatory Responses ◽  
Gamma Interferon ◽  
Interleukin 12 ◽  
Chain Gene ◽  
Pathological Changes ◽  
Necrosis Factor Alpha ◽  
Ifn Γ ◽  
And Control

ABSTRACT BALB/c and strain 129 mice infected intranasally withChlamydia pneumoniae displayed a moderate-to-severe inflammation in the lungs and produced interleukin-12 (IL-12), gamma interferon (IFN-γ), tumor necrosis factor alpha (TNF-α), and IL-10, with peak levels on days 1 to 3 postinfection (p.i.), returning to basal levels by day 16 p.i. Anti-IL-12 treatment resulted in less-severe pathological changes but higher bacterial titers on days 3 and 7 p.i. By day 16 p.i., the inflammatory responses of control antibody-treated mice subsided. The bacterial titers of both anti-IL-12- and control antibody-treated mice decreased within 3 weeks to marginally detectable levels. Anti-IL-12 treatment significantly reduced lung IFN-γ production and in vitro spleen cell IFN-γ production in response to either C. pneumoniae or concanavalin A. In γ-irradiated infected mice, cytokine production was delayed, and this delay correlated with high bacterial titers in the lungs. Following C. pneumoniae infection, 129 mice lacking the IFN-γ receptor α chain gene (G129 mice) produced similar IL-12 levels and exhibited similarly severe pathological changes but had higher bacterial titers than 129 mice. However, by day 45 p.i., bacterial titers became undetectable in both wild-type 129 and G129 mice. Thus, during C. pneumoniae lung infection, IL-12, more than IFN-γ, plays a role in pulmonary-cell infiltration. IFN-γ and IL-12, acting mostly through its induction of IFN-γ and Th1 responses, play an important role in controlling acuteC. pneumoniae infection in the lungs, but eventually all mice control the infection to undetectable levels by IL-12- and IFN-γ-independent mechanisms.

scholarly journals Revisiting cefditoren for the treatment of community-acquired infections caused by human-adapted respiratory pathogens in adults

2018 ◽  
Vol 13 ◽  
Author(s):  
María-José Giménez ◽  
Lorenzo Aguilar ◽  
Juan José Granizo
Keyword(s):  
Respiratory Tract Infections ◽  
Respiratory Infections ◽  
Community Acquired Pneumonia ◽  
Intrinsic Activity ◽  
Published Data ◽  
Oral Antibiotic ◽  
Respiratory Pathogens ◽  
Tract Infections

Fifteen years after its licensure, this revision assesses the role of cefditoren facing the current pharmacoepidemiology of resistances in respiratory human-adapted pathogens (Streptococcus pneumoniae, Streptococcus pyogenes, Haemophilus influenzae and Moraxella catarrhalis). In the era of post- pneumococcal conjugate vaccines and in an environment of increasing diffusion of the ftsI gene among H. influenzae isolates, published studies on the cefditoren in vitro microbiological activity, pharmacokinetic/pharmcodynamic (PK/PD) activity and clinical efficacy are reviewed. Based on published data, an overall analysis is performed for PK/PD susceptibility interpretation. Further translation of PK/PD data into clinical/microbiological outcomes obtained in clinical trials carried out in the respiratory indications approved for cefditoren in adults (tonsillitis, sinusitis, acute exacerbation of chronic bronchitis and community-acquired pneumonia) is commented. Finally, the role of cefditoren within the current antibiotic armamentarium for the treatment of community respiratory tract infections in adults is discussed based on the revised information on its intrinsic activity, pharmacodynamic adequacy and clinical/bacteriological efficacy. Cefditoren remains an option to be taken into account when selecting an oral antibiotic for the empirical treatment of respiratory infections in the community caused by human-adapted pathogens, even when considering changes in the pharmacoepidemiology of resistances over the last two decades.

scholarly journals Ability of Microorganisms, Causing Respiratory Infections in Children, to Form Biofilms in vitro

2021 ◽  
Vol 6 (1) ◽  
pp. 177-183
Author(s):  
H. O. Isaieva ◽  
◽  
M. M. Mishyna ◽  
Y. A. Mozgova ◽  
M. O. Gonchar ◽  
...  
Keyword(s):  
Intensive Care Unit ◽  
Respiratory Tract ◽  
Optical Density ◽  
Respiratory Diseases ◽  
Respiratory Tract Infections ◽  
Respiratory Infections ◽  
Gram Positive ◽  
Gram Negative ◽  
Tract Infections

The purpose of the study was to detect ability to form biofilms by microorganisms that cause respiratory tract infections. Materials and methods. The study involved 97 strains of microorganisms. Microorganisms were isolated from children with respiratory tract infections. All strains, isolated from patients, were able to form biofilms. There were 44 strains of S. aureus (from patients with pneumonia – 13 strains, from patients with other respiratory diseases – 31), 34 strains of S. pneumoniae (pneumonia – 27 strains, other respiratory diseases – 7), 13 strains of K. pneumoniae (pneumonia – 6 strains, other respiratory diseases – 7), 6 strains of P. aeruginosa (pneumonia – 5 strains, other respiratory diseases – 1). Children were treated at the pulmonary department and intensive care unit in Kharkiv Regional Children's Clinical Hospital. Results and discussion. The optical density of primary biofilms formed by Gram-positive microorganisms was 1.33±0.24 Units of OD, and their secondary biofilms was 0.32±0.10 Units of OD. In patients with pneumonia optical density of primary biofilms of Gram-positive microorganisms was 1.48±0.21 Units of OD and of secondary biofilms was 0.30±0.08 Units of OD. Optical density of primary biofilms of Gram-positive microorganisms in patients with other respiratory infections was 1.18±0.15 Units of OD, of secondary biofilms was 0.35±0.12 Units of OD. The optical density of primary biofilms formed by Gram-negative microorganisms was 2.01±1.03 Units of OD, optical density of secondary biofilms was 1.06±0.42 Units of OD. In patients with pneumonia optical density of primary biofilms of Gram-negative microorganisms was 2.57±0.87 Units of OD, of secondary biofilms was 1.21±0.50 Units of OD. Optical density of primary biofilms of Gram-negative microorganisms in patients with other respiratory infections was 1.24±0.66 Units of OD, of secondary biofilms was 0.84±0.11 Units of OD. Conclusion. Gram-negative microorganisms in general formed more massive biofilms compared with Gram-positive microorganisms. Among all microorganisms P. aeruginosa formed the thickest primary and secondary biofilms. Strains of P. aeruginosa isolated from patients with pneumonia formed the thickest primary and secondary biofilms. Strains of S. aureus isolated from patients with other respiratory infections formed most massive primary biofilms, strains of K. pneumoniae formed the hardest secondary biofilms in this group

scholarly journals Inhaled Antibiotics for Gram-Negative Respiratory Infections

2016 ◽  
Vol 29 (3) ◽  
pp. 581-632 ◽  
Author(s):  
Eric Wenzler ◽  
Dustin R. Fraidenburg ◽  
Tonya Scardina ◽  
Larry H. Danziger
Keyword(s):  
Respiratory Tract Infections ◽  
Respiratory Infections ◽  
Systemic Exposure ◽  
Lung Parenchyma ◽  
Gram Negative ◽  
Disease States ◽  
Inhaled Antibiotics ◽  
Gram Negative Organisms ◽  
Tract Infections

SUMMARYGram-negative organisms comprise a large portion of the pathogens responsible for lower respiratory tract infections, especially those that are nosocomially acquired, and the rate of antibiotic resistance among these organisms continues to rise. Systemically administered antibiotics used to treat these infections often have poor penetration into the lung parenchyma and narrow therapeutic windows between efficacy and toxicity. The use of inhaled antibiotics allows for maximization of target site concentrations and optimization of pharmacokinetic/pharmacodynamic indices while minimizing systemic exposure and toxicity. This review is a comprehensive discussion of formulation and drug delivery aspects,in vitroand microbiological considerations, pharmacokinetics, and clinical outcomes with inhaled antibiotics as they apply to disease states other than cystic fibrosis. In reviewing the literature surrounding the use of inhaled antibiotics, we also highlight the complexities related to this route of administration and the shortcomings in the available evidence. The lack of novel anti-Gram-negative antibiotics in the developmental pipeline will encourage the innovative use of our existing agents, and the inhaled route is one that deserves to be further studied and adopted in the clinical arena.

scholarly journals Viral etiology and epidemiology of pediatric patients hospitalized for acute respiratory tract infections in Macao: a retrospective study from 2014 to 2017

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Cheng Lei ◽  
Lisong Yang ◽  
Cheong Tat Lou ◽  
Fan Yang ◽  
Kin Ian SiTou ◽  
...  
Keyword(s):  
Respiratory Tract ◽  
Lower Respiratory Tract ◽  
Respiratory Tract Infections ◽  
Pediatric Patients ◽  
Respiratory Infections ◽  
Upper Respiratory Tract ◽  
Viral Etiology ◽  
Upper Respiratory ◽  
Syncytial Virus ◽  
Tract Infections

Abstract Background Acute respiratory infections (ARIs) are among the leading causes of hospitalization in children. Understanding the local dominant viral etiologies is important to inform infection control practices and clinical management. This study aimed to investigate the viral etiology and epidemiology of respiratory infections among pediatric inpatients in Macao. Methods A retrospective study using electronic health records between 2014 and 2017 at Kiang Wu Hospital was performed. Nasopharyngeal swab specimens were obtained from hospitalized children aged 13 years or younger with respiratory tract diseases. xMAP multiplex assays were employed to detect respiratory agents including 10 respiratory viruses. Data were analyzed to describe the frequency and seasonality. Results Of the 4880 children enrolled in the study, 3767 (77.1%) were positive for at least one of the 13 viral pathogens tested, of which 2707 (55.5%) being male and 2635 (70.0%) under 2 years old. Among the positive results, there were 3091 (82.0%) single infections and 676 (18.0%) multiple infections. The predominant viruses included human rhinovirus/enterovirus (HRV/EV 27.4%), adenovirus (ADV, 15.8%), respiratory syncytial virus B (RSVB, 7.8%) and respiratory syncytial virus A (RSVA, 7.8%). The detection of viral infection was the most prevalent in autumn (960/1176, 81.6%), followed by spring (1095/1406, 77.9%), winter (768/992, 77.4%), and summer (944/1306, 72.3%), with HRV/EV and ADV being most commonly detected throughout the 4 years of study period. The detection rate of viral infection was highest among ARI patients presented with croup (123/141, 87.2%), followed by lower respiratory tract infection (1924/2356, 81.7%) and upper respiratory tract infection (1720/2383, 72.2%). FluA, FluB and ADV were positive factors for upper respiratory tract infections. On the other hand, infection with RSVA, RSVB, PIV3, PIV4, HMPV, and EV/RHV were positively associated with lower respiratory tract infections; and PIV1, PIV2, and PIV3 were positively associated with croup. Conclusions This is the first study in Macao to determine the viral etiology and epidemiology of pediatric patients hospitalized for ARIs. The study findings can contribute to the awareness of pathogen, appropriate preventative measure, accurate diagnosis, and proper clinical management of respiratory viral infections among children in Macao.

scholarly journals Interleukin-12 Is the Optimum Cytokine To Expand Human Th17 Cells In Vitro

2009 ◽  
Vol 16 (6) ◽  
pp. 798-805 ◽  
Author(s):  
Soad Nady ◽  
James Ignatz-Hoover ◽  
Mohamed T. Shata
Keyword(s):  
T Cells ◽  
Peripheral Blood ◽  
Th17 Cells ◽  
Interleukin 12 ◽  
Interleukin 17 ◽  
Functional Evaluation ◽  
Optimum Conditions ◽  
T Helper ◽  
Ifn Γ

ABSTRACT Recently, a new lineage of CD4+ T cells in humans and in mice has been reported. This T helper cell secretes interleukin-17 (IL-17) and has been defined as T helper 17 (Th17). Th17 cells express the IL-23 receptor (IL-23R) and play an important pathogenic role in different inflammatory conditions. In this study, our aim was to characterize the optimum conditions for isolation and propagation of human peripheral blood Th17 cells in vitro and the optimum conditions for isolation of Th17 clones. To isolate Th17 cells, two steps were taken. Initially, we negatively isolated CD4+ T cells from peripheral blood mononuclear cells of a normal human blood donor. Then, we isolated the IL-23R+ cells from the CD4+ T cells. Functional studies revealed that CD4+ IL-23R+ cells could be stimulated ex vivo with anti-CD3/CD28 to secrete both IL-17 and gamma interferon (IFN-γ). Furthermore, we expanded the CD4+ IL-23R+ cells for 1 week in the presence of anti-CD3/CD28, irradiated autologous feeder cells, and different cytokines. Our data indicate that cytokine treatment increased the number of propagated cells 14- to 99-fold. Functional evaluation of the expanded number of CD4+ IL-23R+ cells in the presence of different cytokines with anti-CD3/CD28 revealed that all cytokines used (IL-2, IL-7, IL-12, IL-15, and IL-23) increased the amount of IFN-γ secreted by IL-23R+ CD4+ cells at different levels. Our results indicate that IL-7 plus IL-12 was the optimum combination of cytokines for the expansion of IL-23R+ CD4+ cells and the secretion of IFN-γ, while IL-12 preferentially stimulated these cells to secrete predominately IL-17.

Treatment of upper respiratory tract infections: the role of doxycycline

2021 ◽  
pp. 29-36
Author(s):  
A. P. Pereverzev ◽  
A. S. Pereverzeva ◽  
G. P. Kovaleva ◽  
O. D. Ostroumova
Keyword(s):  
Respiratory Tract ◽  
Respiratory Tract Infections ◽  
Chlamydia Pneumoniae ◽  
Upper Respiratory Tract Infections ◽  
Temporal Region ◽  
Upper Respiratory Tract ◽  
Nasal Breathing ◽  
Diagnostic Center ◽  
Upper Respiratory ◽  
Tract Infections

Upper respiratory tract infections (URTI) are a large group of infectious diseases (mainly viral and bacterial), affecting the mucous of the nasal cavity, paranasal sinuses, pharynx and larynx. URTI are very common in inpatient and outpatient clinical practice. In this article, we present a clinical case of Patient N., 20 years old, consulted with upper respiratory tract damage caused by Chlamydia pneumoniae. The patient admitted to clinical diagnostic center on 07.07.2021 with complaints of pain in the left maxillary sinus with irradiation to the left temporal region, difficulty in nasal breathing, pain in the pharynx, aggravated by swallowing, and increased body temperature (37,5 °C). The patient was consulted by an interdisciplinary team (ENT doctor and clinical pharmacologist). After carrying out physical, instrumental and laboratory tests the diagnose Chlamydia pneumoniae - associated URTI was established and, the patient was prescribed doxycycline at a dose of 100 mg 2 two times a day on the 1st day following by 100 once a day for the next 6 days with a positive effect. The doxycycline was choisen because of a more favorable safety and efficacy profile compared to fluoroquinolones and some other antibacterial agents. After 7 days of treatment, the patient recovered completely. Among all doxycycline drugs available on the market of the Russian Federation, Doxycycline Express (JSC Pharmstandard-Leksredstva) stands out due to its high quality, bioequivalence to the original drug and comfortable regime of use due to the dosage form (dispersible tablets), that increases the patient’s compliance and allows it to be used by some special categories of patients (elderly and senile patients, patients with dysphagia, etc.

scholarly journals 2018 recommendations for the management of community acquired pneumonia

2018 ◽  
Vol 44 (5) ◽  
pp. 405-423 ◽  
Author(s):  
Ricardo de Amorim Corrêa ◽  
Andre Nathan Costa ◽  
Fernando Lundgren ◽  
Lessandra Michelin ◽  
Mara Rúbia Figueiredo ◽  
...  
Keyword(s):  
Cause Of Death ◽  
Respiratory Tract Infections ◽  
Respiratory Infections ◽  
Scientific Evidence ◽  
Prognostic Score ◽  
Community Acquired Pneumonia ◽  
Lower Respiratory Tract Infections ◽  
Etiologic Agents ◽  
Tract Infections ◽  
Respiratory Microbiota

ABSTRACT Community-acquired pneumonia (CAP) is the leading cause of death worldwide. Despite the vast diversity of respiratory microbiota, Streptococcus pneumoniae remains the most prevalent pathogen among etiologic agents. Despite the significant decrease in the mortality rates for lower respiratory tract infections in recent decades, CAP ranks third as a cause of death in Brazil. Since the latest Guidelines on CAP from the Sociedade Brasileira de Pneumologia e Tisiologia (SBPT, Brazilian Thoracic Association) were published (2009), there have been major advances in the application of imaging tests, in etiologic investigation, in risk stratification at admission and prognostic score stratification, in the use of biomarkers, and in the recommendations for antibiotic therapy (and its duration) and prevention through vaccination. To review these topics, the SBPT Committee on Respiratory Infections summoned 13 members with recognized experience in CAP in Brazil who identified issues relevant to clinical practice that require updates given the publication of new epidemiological and scientific evidence. Twelve topics concerning diagnostic, prognostic, therapeutic, and preventive issues were developed. The topics were divided among the authors, who conducted a nonsystematic review of the literature, but giving priority to major publications in the specific areas, including original articles, review articles, and systematic reviews. All authors had the opportunity to review and comment on all questions, producing a single final document that was approved by consensus.

scholarly journals Could Chlamydia Pneumoniae Be Considered an Infectious Risk Factor for Inflammatory Diseases Such as Atherosclerosis ?

2005 ◽  
Vol 3 (3) ◽  
pp. 109-112
Author(s):  
R. Sessa ◽  
M. Di Pietro ◽  
G. Schiavoni ◽  
I. Santino ◽  
M. Del Piano
Keyword(s):  
Risk Factor ◽  
Chlamydia Pneumoniae ◽  
Direct Detection ◽  
Inflammatory Diseases ◽  
Cell Types ◽  
Chronic Inflammatory Disease ◽  
Upper Respiratory Tract ◽  
Infectious Risk ◽  
Tract Infections

Chlamydia pneumoniae, a Gram-negative intracellular obligate bacteria, is recognised as a common cause of upper respiratory tract infections, and accounts for ∼10% of community-acquired pneumonia. In recent years, chronic and persistent infection with C. pneumoniae has been implicated in the pathogenesis of atherosclerosis. Atherosclerosis is regarded as a chronic inflammatory disease that results from complex interactions between a variety of cell types such as endothelial cells, vascular smooth muscle cells, monocytes/macrophages and inflammatory mediators. Involvement of C. pneumoniae in the pathogenesis of atherosclerosis has been supported by findings from seroepidemiologic studies, direct detection of chlamydial DNA, experimental animal and in vitro studies, and antibiotic intervention trials. The spectrum of cell biological, animal, and human clinical data suggests that C. pneumoniae may be considered an infectious risk factor for atherosclerosis but further studies are needed to clarify the etiopathogenetic role of C. pneumoniae in atherosclerotic vessel walls.

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.

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