Complications Of Respiratory Infections Research Articles

Oral microbiota autobacteriocins directed against pathogens of bacterial complications of respiratory infections

Recent years have been marked by a wide spread of respiratory viral infections, which are often accompanied by the development of bacterial complications. The greatest danger is posed by nosocomial strains with multidrug resistance. One of the ways to combat antibiotic-resistant strains is the possibility of using bacteriocins produced by certain bacteria that are present in the human body, food, and the environment. The most interesting are the strains of autobacteriocins isolated from the human's own normal microbiota, which does not have immune rejection. The purpose of the study: to investigate the antibacterial effect of autobacteriocins of the oral microbiota against the main pathogens of bacterial complications in respiratory infections. Six reference strains from the ESKAPE group (Enterococcus faecalis, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter spp.) and 18 multi-resistant strains of the same group isolated from the respiratory tract of individuals with bacterial complications of viral infections were examined. The study used bacteriological, molecular biological, and statistical methods, as well as mass spectrometric research method. The autobacteriocins isolated from Enterococcus faecalis, Streptococcus salivarius, and Lactobacillus paracasei bacteria were the most effective against multidrug-resistant strains from the ESKAPE group. Notably, the concentration of bacteriocin-producing bacteria in the medium of co-cultivation was 500 and 1,000 times less than the strains against which they were directed. Suppression of the growth of multidrug-resistant strains by 2-3 times compared with the initial one was observed after 2 hours. Thus, the antibacterial effectiveness of autobacteriocins against resistant strains of bacteria isolated from the same individual suggests the possibility of a personalized approach to obtaining and using autoprobiotic strains of bacteria to combat bacterial complications of the respiratory tract.

Risk Factors for the Development of Post-Infectious Bronchiolitis Obliterans in Children: A Systematic Review and Meta-Analysis.

Post-infectious bronchiolitis obliterans (PIBO), one of the major complications of respiratory tract infection, is commonly underdiagnosed. To identify the risk groups that may develop PIBO and avoid misdiagnoses, we investigated the risk factors associated with the development of PIBO. We searched PubMed, Embase, and MEDLINE databases for studies that included risk factors for the development of PIBO published from inception to 13 June 2022. We limited our search to studies that reported the estimates of odds ratio (OR), hazard ratio (HR), or relative risks for developing PIBO. A fixed-effect and a random-effect model were used. We included seven studies reporting data on the risk factors for PIBO in 344 children with PIBO and 1310 control children. Twenty-two variables, including sex, age, respiratory pathogens, symptoms, laboratory and radiologic findings, and mechanical ventilation, were mentioned in at least one study. The significant risk factors mentioned in two or more studies included elevated lactate dehydrogenase levels, pleural effusion, hypoxemia, sex, and mechanical ventilation. The significance of the duration of hospitalization and fever as risk factors for PIBO differed when the studies were classified according to the statistical method. In addition, the risk factors differed according to respiratory infection pathogens. This meta-analysis identified potential risk factors associated with the development of PIBO. The results of this study highlight the importance of avoiding misdiagnosis and help establish management strategies for patients at a high risk of developing PIBO.

DISSEMINATED INVASIVE ASPERGILLUS MASQUERADING AS AMIODARONE-INDUCED THYROTOXICOSIS

DISSEMINATED INVASIVE ASPERGILLUS MASQUERADING AS AMIODARONE-INDUCED THYROTOXICOSIS

Pediatric Brain Abscesses, Epidural Empyemas, and Subdural Empyemas Associated with Streptococcus Species - United States, January 2016-August 2022.

In May 2022, CDC learned of three children in California hospitalized concurrently for brain abscess, epidural empyema, or subdural empyema caused by Streptococcus intermedius. Discussions with clinicians in multiple states raised concerns about a possible increase in pediatric intracranial infections, particularly those caused by Streptococcus bacteria, during the past year and the possible contributing role of SARS-CoV-2 infection (1). Pediatric bacterial brain abscesses, epidural empyemas, and subdural empyemas, rare complications of respiratory infections and sinusitis, are often caused by Streptococcus species but might also be polymicrobial or caused by other genera, such as Staphylococcus. On June 9, CDC asked clinicians and health departments to report possible cases of these conditions and to submit clinical specimens for laboratory testing. Through collaboration with the Children's Hospital Association (CHA), CDC analyzed nationally representative pediatric hospitalizations for brain abscess and empyema. Hospitalizations declined after the onset of the COVID-19 pandemic in March 2020, increased during summer 2021 to a peak in March 2022, and then declined to baseline levels. After the increase in summer 2021, no evidence of higher levels of intensive care unit (ICU) admission, mortality, genetic relatedness of isolates from different patients, or increased antimicrobial resistance of isolates was observed. The peak in cases in March 2022 was consistent with historical seasonal fluctuations observed since 2016. Based on these findings, initial reports from clinicians (1) are consistent with seasonal fluctuations and a redistribution of cases over time during the COVID-19 pandemic. CDC will continue to work with investigation partners to monitor ongoing trends in pediatric brain abscesses and empyemas.

Staphylococcus aureus and Pseudomonas aeruginosa Isolates from the Same Cystic Fibrosis Respiratory Sample Coexist in Coculture.

ABSTRACTRespiratory infections with bacterial pathogens remain the major cause of morbidity in individuals with the genetic disease cystic fibrosis (CF). Some studies have shown that CF patients that harbor both Staphylococcus aureus and Pseudomonas aeruginosa in their lungs are at even greater risk for more severe and complicated respiratory infections and earlier death. However, the drivers for this worse clinical condition are not well understood. To investigate the interactions between these two microbes that might be responsible for their increased pathogenic potential, we obtained 28 pairs of S. aureus and P. aeruginosa from the same respiratory samples from 18 individuals with CF. We compared the survival of each S. aureus CF isolate cocultured with its corresponding coinfecting CF P. aeruginosa to when it was cocultured with non-CF laboratory strains of P. aeruginosa. We found that the S. aureus survival was significantly higher in the presence of the coinfecting P. aeruginosa compared to laboratory P. aeruginosa strains, regardless of whether the coinfecting isolate was mucoid or nonmucoid. We also tested how a non-CF S. aureus strain, JE2, behaved with each P. aeruginosa CF isolate and found that its interaction was similar to how the CF S. aureus isolate interacted with its coinfecting P. aeruginosa. Altogether, our work suggests that interactions between S. aureus and P. aeruginosa that promote coexistence in the CF lung are isolate-dependent and that this interaction appears to be driven mainly by P. aeruginosa.IMPORTANCE Previous studies have shown that in laboratory settings, Pseudomonas aeruginosa generally kills Staphylococcus aureus. However, these bacteria are often found coinfecting the lungs of cystic fibrosis (CF) patients, which has been associated with worse patient outcomes. To investigate the interactions between these two bacteria, we competed 28 coinfection pairs obtained from the same lung samples of 18 different CF patients. We compared these results to those we previously reported of each CF S. aureus isolate against a non-CF laboratory strain of P. aeruginosa. We found that S. aureus survival against its corresponding coinfection P. aeruginosa was higher than its survival against the laboratory strain of P. aeruginosa. These results suggest that there may be selection for coexistence of these microbes in the CF lung environment. Further understanding of the interactions between P. aeruginosa and S. aureus will provide insights into the drivers of coexistence and their impact on the host.

First-Response ABCDE Management of Status Epilepticus: A Prospective High-Fidelity Simulation Study.

Respiratory infections following status epilepticus (SE) are frequent, and associated with higher mortality, prolonged ICU stay, and higher rates of refractory SE. Lack of airway protection may contribute to respiratory infectious complications. This study investigates the order and frequency of physicians treating a simulated SE following a systematic Airways-Breathing-Circulation-Disability-Exposure (ABCDE) approach, identifies risk factors for non-adherence, and analyzes the compliance of an ABCDE guided approach to SE with current guidelines. We conducted a prospective single-blinded high-fidelity trial at a Swiss academic simulator training center. Physicians of different affiliations were confronted with a simulated SE. Physicians (n = 74) recognized SE and performed a median of four of the five ABCDE checks (interquartile range 3–4). Thereof, 5% performed a complete assessment. Airways were checked within the recommended timeframe in 46%, breathing in 66%, circulation in 92%, and disability in 96%. Head-to-toe (exposure) examination was performed in 15%. Airways were protected in a timely manner in 14%, oxygen supplied in 69%, and antiseizure drugs (ASDs) administered in 99%. Participants’ neurologic affiliation was associated with performance of fewer checks (regression coefficient −0.49; p = 0.015). We conclude that adherence to the ABCDE approach in a simulated SE was infrequent, but, if followed, resulted in adherence to treatment steps and more frequent protection of airways.

Respiratory infections and acute respiratory distress syndrome

Respiratory infections and acute respiratory distress syndrome (ARDS) are closely related. Pneumonia is the most common cause of ARDS, and patients with ARDS usually develop infectious respiratory complications. Sixty percent of the cases of ARDS are due to pneumonia, but only some patients with pneumonia will develop ARDS. Viral pneumonia is a common cause of ARDS, especially in seasonal outbreaks or pandemics. Patients admitted with ARDS could present a secondary infection, and ventilator-associated pneumonia may impair prognosis. Several conditions that predispose patients with ARDS to respiratory infections are present. Decisions regarding antimicrobial treatment should be based on epidemiology, risk factors and current recommendations. Corticosteroids may be used as adjunctive therapy in both pathologies in selective patients.

Aetiology and presentation of childhood pleural infections in the post-pneumococcal conjugate vaccine era in South Africa.

Background Complications of respiratory infections including pleural effusion (PE) are associated with a high morbidity. Differentiating between PE caused by Mycobacterium tuberculosis (Mtb) infection and other bacterial infections in endemic areas is difficult in children, thus, impacting treatment. Objectives To investigate the aetiology of PE and features distinguishing tuberculosis (TB) from bacterial PE in children. Methods We conducted a prospective study in children with PE admitted to a tertiary hospital in Cape Town from December 2017 to December 2019. Clinical information and routine laboratory investigations were compared between children with bacterial, Mtb or unclassified PE, categorised according to study definitions. Results A total of 91 patients were included in the present study and their median age was 31 months (interquartile range (IQR) 11.8 - 102.1). The aetiology was bacterial in 40% (n=37), Mtb in 39% (n=36) and unclassified in 20% (n=18) of patients. Staphylococcus aureus was the most common bacterial isolate, confirmed in 65% (n=24/37) patients, and Streptococcus pneumoniae was confirmed in only 8% of patients. TB was microbiologically confirmed in 33% (n=12/36) of patients. Patients with TB were older (91.6 v. 11.8 months; p<0.001), with more weight loss (28 v. 12 patients; p<0.001), and longer cough duration (10 v. 4 days; p<0.001) than those with other bacterial PE. In contrast, the latter had significantly higher serum C-reactive protein (median 250 v. 122 mg/L; p<0.001), procalcitonin (11 v. 0.5 mg/L; p<0.001), pleural fluid lactate dehydrogenase (7 280 v. 544 U/L; p<0.001), and adenosine deaminase levels (162 v. 48 U/L; p<0.001) and lower glucose levels (1.3 v. 4 mmol/L; p<0.001). Conclusion Post 13-valent pneumococcal conjugate vaccine, S. aureus is the dominant cause of PE in children using traditional culture methods, while Mtb remains a common cause of PE in our setting. Useful clinical and laboratory differences between Mtb and other bacterial PE were identified, but the cause of PE in 20% of children was underdetermined. Molecular testing of pleural fluid for respiratory pathogens may be useful in such children.

Hemodynamic management and surgical site infection: Network meta-analysis of randomized controlled trials

Study objectiveTo investigate which hemodynamic management strategy is most effective in reducing surgical site infection (SSI). DesignNetwork meta-analysis of randomized controlled trials. SettingPerioperative setting. PatientsSurgical patients. InterventionsUsual care vs. optimized hemodynamic management, including goal-directed hemodynamic therapy (GDHT) and liberal/restrictive fluid therapy. MeasurementsThe primary outcome was SSI arising within postoperative 30 days. The secondary outcomes included postoperative respiratory and urinary system infectious complications and sepsis/septic shock. The effect and ranking were assessed using network meta-analysis and the surface under the cumulative ranking curve (SUCRA) scores, respectively. Main resultsWe systematically searched Ovid MEDLINE, Ovid Embase, and Web of Science for eligible randomized controlled trials from inception to October 11, 2019. Fifty-three eligible studies reported SSI and comprised of 56 GDHT groups (patients, n = 4205) and 51 usual care groups (patients, n = 3895). Comparing with usual care, GDHTs aimed at intravascular volume and stroke volume optimization (odds ratio (OR), 0.28 [95% credible interval (CrI), 0.13 to 0.56]; moderate quality), stroke volume and cardiac output optimization (OR, 0.34 [95% CrI, 0.16 to 0.70]; moderate quality), and intravascular volume and cardiac output optimization (OR, 0.51 [95% CrI, 0.24 to 0.99]; low quality) significantly reduced SSI. GDHT strategy aimed at intravascular volume and stroke volume optimization was likely most effective (SUCRA = 80%). Certain GDHTs significantly reduced respiratory infectious complications; however, no GDHT significantly reduced urinary infectious complications and sepsis/septic shock. GDHT strategy aimed at intravascular volume, stroke volume, and cardiac output optimization was likely most effective for reducing respiratory infectious complications (SUCRA = 88%). ConclusionsDifferent hemodynamic managements exert different effectiveness for SSI reduction. GDHTs aimed at intravascular volume, stroke volume, and cardiac output optimization are likely most effective based on the overall evidence.

Myocardial Injury and Myocarditis in SARS-CoV-2 Patients

Abstract Myocarditis is one of the relatively common complications of respiratory infection with SARSCoV-2. As several patients confirmed with the new SARS-CoV-2 are known with cardiovascular disease (CVD) and data from the literature show negative prognosis and a higher risk of complications, this subgroup of subjects represents a particular situation. Therefore, an adequate understanding of the mechanisms involved in myocardial injury and interaction between COVID-19 and CVD is essential for optimal further management. Studies have proved that in COVID-19 patient myocarditis is determined via three pathological mechanisms of cardiomyocyte injury: direct viral cell entry and binding to ACE2, vasculitis-mediated injury, and systemic inflammatory response leading to pro-inflammatory cytokine discharge. Studies show that the incidence of myocarditis in patients with SARS-CoV-2 is relatively low, 4.8%, but myocardial damage occurs in more than 25% of critical cases in the form of acute fulminant myocarditis with severe hemodynamic degradation, or develops when the severity of SARS-CoV-2 infection intensifies. The mortality rate in myocarditis from COVID-19 infection ranges between 50–70%, with poorer prognosis and a higher risk of complications in CVD patients. As in all of these cases increased troponin and natriuretic peptide levels proved to be a negative prognostic factor, for risk stratification and prompt treatment, cardiac biomarkers should be evaluated in all patients with COVID-19.

Active humidification in mechanical ventilation is not associated to an increase in respiratory infectious complications in a quasi-experimental pre–post intervention study

ObjectiveThere is controversy regarding the influence of humidification systems upon the incidence of respiratory infections associated to invasive mechanical ventilation (IMV). An evaluation was made of the differences in the incidence of pneumonia and tracheobronchitis associated to mechanical ventilation (VAP and VAT, respectively) with passive and active humidification. DesignA retrospective pre–post quasi-experimental study was carried out. SettingA polyvalent ICU with 14 beds. PatientsAll patients connected to IMV for >48h during 2014 and 2016 were included. InterventionsDuring 2014, passive humidification with an hygroscopic heat and moisture exchanger (HME) was used, while during 2016 active humidification with a heated humidifier (HH) and an inspiratory heated wire was used. Identical measures for the prevention of VAP were established (Zero Pneumonia Project). Main outcome measuresThe incidence of VAP and VAT was estimated for 1000 days of IMV in both groups, and statistically significant differences were assessed using Poisson regression analysis. ResultsA total of 287 patients were included (116 with HME and 171 with HH). The incidence density of VAP per 1000 days of IMV was 5.68 in the HME group and 5.80 in the HH group (p=ns). The incidence density of VAT was 3.41 and 3.26 cases per 1000 days of VMI with HME and HH respectively (p=ns). The duration of IMV was identified as a risk factor for VAP. ConclusionsIn our population, active humidification in patients ventilated for >48h was not associated to an increase in respiratory infectious complications.

Inducible epithelial resistance promotes survival of viral pneumonia by inactivating virus particles and preventing CD8+ T cell dependent immunopathology

Abstract Respiratory viral infections cause significant morbidity and mortality worldwide, necessitating the development of novel strategies to prevent complications of respiratory infections. Our group has discovered the phenomenon of inducible epithelial resistance where mice treated with combination inhalation of Toll-like receptor (TLR) 2/6 and TLR9 agonists (Pam2-ODN) are protected against respiratory pathogens, including viruses. We investigated the mouse survival benefits of paramyxovirus, Sendai (SeV) infection and found that Pam2-ODN treatment one day prior to SeV challenge enhanced survival of mice. This protection was associated with reduced CD8+ T cell inflammation. Depletion of CD8+T cells prior to infection increased baseline virus susceptibility but did not affect protection afforded by Pam2-ODN. Depletion of CD8+T cells after viral burden waned but before peak mortality enhanced SeV pneumonia survival, even in the absence of Pam2-ODN pretreatment, revealing the profound role of CD8+ T cell mediated immunopathology in virus-induced mortality. We further demonstrated that Pam2-ODN treatment controls viral replication by inactivation of SeV prior to epithelial internalization. Epithelial generation of reactive oxygen species induced by Pam2-ODN treatment is necessary for SeV inactivation and preventing CD8+T cell mediated immunopathology. These findings highlight antiviral mechanisms of inducible epithelial resistance and may provide means to protect vulnerable immunocompromised patients against respiratory diseases.

Molecular Diagnosis of Atypical Pneumonia Infection in Children Presenting with Acute Respiratory Tract Infection Attending Yangon Children’s Hospital

Acute respiratory tract infection (ARI) is a clinical condition which causes high morbidity and mortality, especially in infants and young children. Pneumonia is a common complication of respiratory tract infection. Atypical pneumonia, which is commonly caused by Mycoplasma pneumoniae, Chlamydophila pneumoniae and Legi-onella pneumophila, is difficult to be detected because the causal bacteria cannot be diagnosed by routine culture method and presenting with non-specific clinical symptoms. This study aimed to diagnose the atypical pneumonia infection in children presenting with ARI attending Yangon Children’s Hospital during 2014-15 by using multiplex polymerase chain reaction (M-PCR). The bacterial DNA was extracted from nasopharyngeal swab samples by using Qiagen DNA minikit and detected by M-PCR. Of 245 patients with ARI, 140(57%) were males and 105(43%) were females. Eleven samples (4.4%) were positive for atypical pneumonia infection, among which 4(1.6%) were Mycoplasma pneumoniae,5(2%) were Chlamydophila pneumoniae and 2(0.8%) were Legionella pneumophila. The atypical pneumonia cases were mostly seen among the age of 1 to 5 years and sex distribution was nearly equal. The infected cases were detected from pneumonia (36.4%), severe pneumonia (27.3%), viral-induced wheeze (18.2%), severe bronchiolitis (9.1%) and bronchiolitis (9.1%). This study highlights the role of atypical pneumonia infection in ARI cases among children.

Impact of fluid overload and infection on respiratory adverse event development during induction therapy for childhood acute myeloid leukemia.

Treatment-related morbidity and mortality occur frequently in childhood acute myeloid leukemia (AML) induction. Yet the contributions of respiratory adverse events (AEs) within this population are poorly understood. Furthermore, the roles of fluid overload (FO) and infection in AML pulmonary complications have been inadequately examined. To describe the incidence, categories, and grades of respiratory AEs and to assess the associations of FO and infection on respiratory AE development in childhood AML induction. We retrospectively examined the induction courses of a cohort of de novo pediatric AML patients for any NCI CTCAE grade 2 to 5 respiratory AE, FO, and systemic/pulmonary infection occurrence. Demographic, disease, and treatment-related data were abstracted. Descriptive, univariate, survival, and multivariable analyses were conducted. Among 105 eligible subjects from 2009 to 2016, 49.5% (n=52) experienced 63 discrete respiratory AEs. FO occurred in 28.6% of subjects (n=30), with half occurring within 24hours of hospitalization. Positive FO status<10 days (aHR 5.5, 95% CI 2.3-12.8), ≥ 10 days (aHR 13, 95% CI 4.1-41.8), and positive infection status ≥ 10 days into treatment (aHR 14.9, 5.4-41.6) were each independently associated with AE development. We describe a higher incidence of respiratory AEs during childhood AML induction than previously illustrated. FO occurs frequently and early in this course. Late infections and FO at any time frame were strongly associated with AE development. Interventions focused on the prevention and management of FO and infectious respiratory complications could be instrumental in reducing preventable treatment-related morbidity and mortality.

Clinical, microbiological research of the effectiveness of inhalation use of quaternary ammonium antiseptic in the prevention and treatment of infectious respiratory complications in critically ill patients

Introduction: The aim is to study the microbiological and clinical efficacy of decamethoxinebased quaternary ammonium antiseptic inhalations in the complex management of respiratory infectious complications in critically ill children.&#x0D; Methods: The use of inhalation of antiseptic medicinal decamethoxine (DCM) was studied in patients with ventilator-associated pneumonia (VAP) (n=30), of ages 12-18 years. All patients received standard intensive care according to the guidelines. Inhalations of 5 mL DCM (0.02%) antiseptic per inhalation TID for 7 days in combination with systemic antibiotic therapy were used in the study group (n=15). Clinical microbiological studies and assessment of Toll-like receptor (e.g. TLR-4) serum levels were performed in patients.&#x0D; Results: The use of DCM inhalations along with systemic antibiotic therapy improved parameters of dynamic compliance by 3.4-fold and decreased lung resistance by 2.4-fold in patients after 48-72 hours of mechanical ventilation. The microbial spectrum of patients at the beginning of VAP was represented by gram-positive (S. aureus — 28.6%, S. pyogenes — 10.2%) and gramnegative (P. aeruginosa — 16.3%; A. baumannii — 12.24%; K. pneumoniae — 10.2%) pathogens. The pathogens were isolated in the monoculture (20.4%) and in microbial associations (79.6%). A significant decrease by 3 orders of magnitude (log (2.640.43) CFU/mL) in the microbial count in tracheobronchial secretions was determined after 7 days of additional use of DCM inhalations when compared to the initial levels of microbial colonization (p&lt;0.001). The microbial spectrum of the respiratory tract was predominantly represented by S. aureus (27.78%), A. baumannii (11.11%) and E. cloacae (5.56%) in monoculture (61.11%), whereas the microbial count was 4 orders of magnitude higher in the comparison group, versus that of the study group (p&lt;0.001), and was represented by microbial associations (93.33%). A strong correlation was found between the reduction of the gram-negative pathogen count and the decrease of TLR-4 serum levels (r-Pearson=0.893), that almost reached baseline levels after DCM inhalations, while TLR-4 levels remained 2 times higher than baseline levels after the use of systemic antimicrobial therapy alone (p&lt;0.001).&#x0D; Conclusion: The use of DCM inhalations in combination with systemic antibiotic therapy provides for an effective reduction of pathogen count in the respiratory tract, leading to the early (48-72h) improvement in lung ventilation and TLR-4 serum levels, and subsequent significant improvement of treatment efficacy in severe VAP patients.

Blunt abdomen trauma: a study of 50 cases

Background: Blunt abdominal trauma is a leading cause of morbidity and mortality among all age groups. Identification of serious intra-abdominal pathology is often challenging; many injuries may not manifest during the initial assessment and treatment period.Methods: This study was conducted on 50 patients of blunt abdominal trauma admitted in a Tertiary Care Hospital, Including All patients with blunt abdominal trauma and Patients of all age groups.Results: In present study age group affected was 11 to 20 years and 41 to 50 years (20% each). Next group was 21 to 30 years (18%), male: female ratio was 2.8:1, most common mode of injury was road traffic accidents. Incidence of road traffic accidents was 48%. In study 2 patients out of 3 patients expired due to late presentation, liver injured (34%), followed by spleen (16%). Other injuries were small intestine and mesentery (14%), Urethral injury (12%) and muscular hematoma (8%), clinical presentation was abdominal pain (90). Extremity fractures 14% of cases, postoperative complication of respiratory infections (50%). Wound infection was 25% of patients. 2 patients who died suffered postoperative complications. Mortality rate (40%) in hemodynamically unstable patients than in hemodynamically stable patients (3%), Survival rate 94% while mortality rate 6%.Conclusions: Morbidity and mortality can be prevented by timely initial resuscitation and correct diagnosis as well as management (operative or non-operative) which depend on patient’s hemodynamic stability and findings of imaging studies.

Prevention of influenza virus induced bacterial superinfection by standardized Echinacea purpurea, via regulation of surface receptor expression in human bronchial epithelial cells

Viral infections may predispose the airways to secondary bacterial infections that can lead to unfavorable progression of principally self-limiting illnesses. Such complicated respiratory infections include pneumonia, bronchitis, sinusitis, acute otitis media, and sepsis, which cause high morbidity and lethality. Some of the pathogenic consequences of viral infections, like the expression of bacterial adhesion receptors and the disturbance of physical barrier integrity due to inflammation, may create permissive conditions for co-infections. Influenza virus A (H3N2) is a major pathogen that causes secondary bacterial infections and inflammation that lead to pneumonia. The herbal medicine Echinacea purpurea, on the other hand, has been widely used to prevent and treat viral respiratory infections, and recent clinical data suggest that it may prevent secondary infection complications as well. We investigated the role of standardized E. purpurea (Echinaforce® extract or EF) on H3N2-induced adhesion of live nontypeable Haemophilus influenzae (NTHi) and Staphylococcus aureus, along with the expression of bacterial receptors, intracellular adhesion molecule-1 (ICAM-1), fibronectin, and platelet activating factor receptor (PAFr), by BEAS-2B cells. Inflammatory processes were investigated by determining the cellular expression of IL-6 and IL-8 and the involvement of Toll-like receptor (TLR-4) and NFκB p65. We found that influenza virus A infection increased the adhesion of H. influenzae and S. aureus to bronchial epithelial cells via upregulated expression of the ICAM-1 receptor and, to some extent, of fibronectin and PAFr. Echinaforce (EF) significantly reduced the expression of ICAM-1, fibronectin, and PAFr and consequently the adhesion of both bacterial strains. EF also effectively prevented the super-expression of inflammatory cytokines by suppressing the expression of NFκB and possibly TLR-4. These results indicate that E. purpurea has the potential to reduce the risk of respiratory complications by preventing virus-induced bacterial adhesion and through the inhibition of inflammation super-stimulation (cytokine storms).

CE-C4D method development and validation for the assay of ciprofloxacin

A capillary electrophoresis method with capacitively coupled contactless conductivity detection (CE-C4D) has been developed, optimized and validated for the determination of ciprofloxacin.Ciprofloxacin is a member of the fluoroquinolone antibiotics with a broad spectrum bactericidal activity and recommended for complicated respiratory infections, sexually transmitted diseases, tuberculosis, bacterial diarrhea etc.Method development was conducted with major focus on the quality by design (QbD) approach. During method development, multiple buffers were tried at different ionic strength. However, the optimized method finally involved a very simple background electrolyte, monosodium citrate at a concentration of 10mM without pH adjustment.The optimized CE-C4D method involved an uncoated fused silica capillary (59/39cm, 50μm i.d.) and hydrodynamic sample injection at a pressure of 0.5 p.s.i. for 5s. The actual separation was conducted for 10min at normal polarity with a voltage of 20kV corresponding to 5.9μA current. LiCl (1mg/mL) was used as an internal standard.The optimized method is robust and accurate (recovery >98%) which rendered the ciprofloxacin peak within five minutes with good linearity (R2>0.999) in the concentration range of 0.0126–0.8mg/mL. The repeatability is expressed by percentage relative standard deviation (%RSD) of the relative peak areas (RPA) and it showed good repeatability both intra-day (<3%) and inter-day (3.1%). This method, proven to be free of matrix interference, showed that the estimated percent content of ciprofloxacin (102%) was within the official requirements.Moreover, due to its ease of use and robustness, the method should also be applicable in less well controlled laboratory environments.

Zeolites in Sustainable Chemistry: Synthesis, Characterization and Catalytic Applications (Green Chemistry and Sustainable Technology Series)

A capillary electrophoresis method with capacitively coupled contactless conductivity detection (CE-C4D) has been developed, optimized and validated for the determination of ciprofloxacin.Ciprofloxacin is a member of the fluoroquinolone antibiotics with a broad spectrum bactericidal activity and recommended for complicated respiratory infections, sexually transmitted diseases, tuberculosis, bacterial diarrhea etc.Method development was conducted with major focus on the quality by design (QbD) approach. During method development, multiple buffers were tried at different ionic strength. However, the optimized method finally involved a very simple background electrolyte, monosodium citrate at a concentration of 10 mM without pH adjustment.The optimized CE-C4D method involved an uncoated fused silica capillary (59/39 cm, 50 μm i.d.) and hydrodynamic sample injection at a pressure of 0.5 p.s.i. for 5 s. The actual separation was conducted for 10 min at normal polarity with a voltage of 20 kV corresponding to 5.9 μA current. LiCl (1 mg/mL) was used as an internal standard.The optimized method is robust and accurate (recovery >98%) which rendered the ciprofloxacin peak within five minutes with good linearity (R2 > 0.999) in the concentration range of 0.0126–0.8 mg/mL. The repeatability is expressed by percentage relative standard deviation (%RSD) of the relative peak areas (RPA) and it showed good repeatability both intra-day (<3%) and inter-day (3.1%). This method, proven to be free of matrix interference, showed that the estimated percent content of ciprofloxacin (102%) was within the official requirements.Moreover, due to its ease of use and robustness, the method should also be applicable in less well controlled laboratory environments.

Efficient generation of recombinant influenza A viruses employing a new approach to overcome the genetic instability of HA segments.

Influenza A viruses (IAVs) are the most relevant and continual source of severe infectious respiratory complications in humans and different animal species, especially poultry. Therefore, an efficient vaccination that elicits protective and neutralizing antibodies against the viral hemagglutinin (HA) and neuraminidase (NA) is an important strategy to counter annual epidemics or occasional pandemics. With the help of plasmid-based reverse genetics technology, it is possible that IAV vaccine strains (IVVS) are rapidly generated. However, the genetic instability of some cloned HA-cDNAs after transformation into competent bacteria represents a major obstacle. Herein, we report efficient cloning strategies of different genetically volatile HA segments (H5- and H9-subtypes) employing either a newly constructed vector for reverse genetics (pMKPccdB) or by the use of the Escherichia coli strain HB101. Both approaches represent improved and generalizable strategies to establish functional reverse genetics systems preventing genetic changes to the cloned (HA) segments of IAV facilitating more efficient rescue of recombinant IAV for basic research and vaccine development.