scholarly journals Adenosine A2BReceptor Deficiency Promotes Host Defenses against Gram-Negative Bacterial Pneumonia

2012 ◽  
Vol 186 (10) ◽  
pp. 1044-1050 ◽  
Author(s):  
Kathryn E. Barletta ◽  
R. Elaine Cagnina ◽  
Marie D. Burdick ◽  
Joel Linden ◽  
Borna Mehrad
Keyword(s):  
Bacterial Pneumonia ◽  
Host Defenses ◽  
Gram Negative

scholarly journals mSphere of Influence: Adenosine in Host Defense against Bacterial Pneumonia—Friend or Foe?

mSphere ◽  
2019 ◽  
Vol 4 (4) ◽  
Author(s):  
Elsa N. Bou Ghanem
Keyword(s):  
Host Defense ◽  
Bacterial Pneumonia ◽  
Pneumococcal Pneumonia ◽  
Respir Crit ◽  
Innate Immune ◽  
Immune Senescence ◽  
Host Defenses ◽  
Extracellular Adenosine ◽  
Gram Negative

ABSTRACT Elsa N. Bou Ghanem works in the field of innate immune senescence, inflammation, and host defense. In this mSphere of Influence article, she reflects on how “Adenosine A2B receptor deficiency promotes host defenses against Gram-negative bacterial pneumonia” by Barletta et al. (K. E. Barletta, R. E. Cagnina, M. D. Burdick, J. Linden, and B. Mehrad, Am J Respir Crit Care Med 186:1044–1050, 2012, https://doi.org/10.1164/rccm.201204-0622OC) impacted her own work examining the role of the extracellular adenosine pathway in neutrophil responses and host defense against pneumococcal pneumonia.

scholarly journals TLR4-dependent GM-CSF protects against lung injury in Gram-negative bacterial pneumonia

2012 ◽  
Vol 302 (5) ◽  
pp. L447-L454 ◽  
Author(s):  
Louis R. Standiford ◽  
Theodore J. Standiford ◽  
Michael J. Newstead ◽  
Xianying Zeng ◽  
Megan N. Ballinger ◽  
...  
Keyword(s):  
Lung Injury ◽  
Bacterial Pneumonia ◽  
Lavage Fluid ◽  
Alveolar Epithelial Cells ◽  
Intratracheal Administration ◽  
Bacterial Colony ◽  
Gram Negative ◽  
Gm Csf

Toll-like receptors (TLRs) are required for protective host defense against bacterial pathogens. However, the role of TLRs in regulating lung injury during Gram-negative bacterial pneumonia has not been thoroughly investigated. In this study, experiments were performed to evaluate the role of TLR4 in pulmonary responses against Klebsiella pneumoniae (Kp). Compared with wild-type (WT) (Balb/c) mice, mice with defective TLR4 signaling (TLR4lps-d mice) had substantially higher lung bacterial colony-forming units after intratracheal challenge with Kp, which was associated with considerably greater lung permeability and lung cell death. Reduced expression of granulocyte-macrophage colony-stimulating factor (GM-CSF) mRNA and protein was noted in lungs and bronchoalveolar lavage fluid of TLR4 mutant mice postintratracheal Kp compared with WT mice, and primary alveolar epithelial cells (AEC) harvested from TLR4lps-d mice produced significantly less GM-CSF in vitro in response to heat-killed Kp compared with WT AEC. TLR4lps-d AEC underwent significantly more apoptosis in response to heat-killed Kp in vitro, and treatment with GM-CSF protected these cells from apoptosis in response to Kp. Finally, intratracheal administration of GM-CSF in TLR4lps-d mice significantly decreased albumin leak, lung cell apoptosis, and bacteremia in Kp-infected mice. Based on these observations, we conclude that TLR4 plays a protective role on lung epithelium during Gram-negative bacterial pneumonia, an effect that is partially mediated by GM-CSF.

A Clinical Pharmacy-Oriented Drug Surveillance Network: Results of a Nationwide Antibiotic Utilization Review of Bacterial Pneumonia–1987

DICP ◽  
1989 ◽  
Vol 23 (2) ◽  
pp. 162-170
Author(s):  
Thaddeus H. Grasela ◽  
Jerome J. Schentag ◽  
Steven J. Boekenoogen ◽  
Kenneth D. Crist ◽  
William L. Lowes ◽  
...  
Keyword(s):  
Bacterial Pneumonia ◽  
Prescribing Patterns ◽  
Oral Drug ◽  
Utilization Review ◽  
Antibiotic Prescribing ◽  
Drug Surveillance ◽  
Surveillance Network ◽  
Gram Negative ◽  
Days Of Therapy ◽  
Culture Positive

One hundred eighteen pharmacists enrolled in the Drug Surveillance Network completed a survey of antibiotic prescribing patterns for bacterial infections. A total of 319 hospitalized patients being treated for suspected or documented bacterial pneumonia were monitored, and this paper summarizes the data collected on this specific subpopulation. Two hundred three patients (64 percent) were treated for community-acquired pneumonia and 116 patients (36 percent) were treated for nosocomial pneumonia. Seventy-three percent of the nosocomial pneumonias were culture-positive, with a gram-negative microorganism as the predominant isolate. Forty-eight percent of the community-acquired pneumonias were culture-positive with a mixture of gram-positive and gram-negative organisms. Fifty percent of patients were treated with a single agent, 33 percent with two antibiotics, and the remaining 17 percent with a combination of three or more antibiotics. A satisfactory response was noted for 62 and 76 percent of the patients with nosocomial and community-acquired pneumonias, respectively. Twenty percent of the pneumonia patients were switched to oral drug after an average of five days of therapy and discharged from the hospital. Twenty-five adverse events that were possibly or probably related to the antibiotic regimen were reported in 23 of the 350 patients for an overall incidence of 6.5 percent. The results of this survey provide a cross-sectional view of antibiotic prescribing patterns for the treatment of bacterial pneumonia and the outcome of therapy under actual clinical conditions of use.

TLR4-Mediated GM-CSF Protects Against Lung Injury In Gram-Negative Bacterial Pneumonia

2011 ◽  
Author(s):  
Urvashi Bhan ◽  
Louis Standiford ◽  
Theodore J. Standiford ◽  
Xianying Zeng ◽  
Michael W. Newstead ◽  
...  
Keyword(s):  
Lung Injury ◽  
Bacterial Pneumonia ◽  
Gram Negative ◽  
Gm Csf

scholarly journals A Randomized, Double-blind, Multicenter Trial Comparing Efficacy and Safety of Imipenem/Cilastatin/Relebactam Versus Piperacillin/Tazobactam in Adults With Hospital-acquired or Ventilator-associated Bacterial Pneumonia (RESTORE-IMI 2 Study)

2020 ◽  
Author(s):  
Ivan Titov ◽  
Richard G Wunderink ◽  
Antoine Roquilly ◽  
Daniel Rodríguez Gonzalez ◽  
Aileen David-Wang ◽  
...  
Keyword(s):  
Clinical Response ◽  
Bacterial Pneumonia ◽  
Severe Renal Impairment ◽  
Apache Ii Score ◽  
Efficacy And Safety ◽  
Double Blind ◽  
Gram Negative ◽  
Mitt Population ◽  
All Cause Mortality ◽  
Hospital Acquired

Abstract Background Imipenem combined with the β-lactamase inhibitor relebactam has broad antibacterial activity, including against carbapenem-resistant gram-negative pathogens. We evaluated efficacy and safety of imipenem/cilastatin/relebactam in treating hospital-acquired/ventilator-associated bacterial pneumonia (HABP/VABP). Methods This was a randomized, controlled, double-blind phase 3 trial. Adults with HABP/VABP were randomized 1:1 to imipenem/cilastatin/relebactam 500 mg/500 mg/250 mg or piperacillin/tazobactam 4 g/500 mg, intravenously every 6 hours for 7–14 days. The primary endpoint was day 28 all-cause mortality in the modified intent-to-treat (MITT) population (patients who received study therapy, excluding those with only gram-positive cocci at baseline). The key secondary endpoint was clinical response 7–14 days after completing therapy in the MITT population. Results Of 537 randomized patients (from 113 hospitals in 27 countries), the MITT population comprised 264 imipenem/cilastatin/relebactam and 267 piperacillin/tazobactam patients; 48.6% had ventilated HABP/VABP, 47.5% APACHE II score ≥15, 24.7% moderate/severe renal impairment, 42.9% were ≥65 years old, and 66.1% were in the intensive care unit. The most common baseline pathogens were Klebsiella pneumoniae (25.6%) and Pseudomonas aeruginosa (18.9%). Imipenem/cilastatin/relebactam was noninferior (P < .001) to piperacillin/tazobactam for both endpoints: day 28 all-cause mortality was 15.9% with imipenem/cilastatin/relebactam and 21.3% with piperacillin/tazobactam (difference, −5.3% [95% confidence interval {CI}, −11.9% to 1.2%]), and favorable clinical response at early follow-up was 61.0% and 55.8%, respectively (difference, 5.0% [95% CI, −3.2% to 13.2%]). Serious adverse events (AEs) occurred in 26.7% of imipenem/cilastatin/relebactam and 32.0% of piperacillin/tazobactam patients; AEs leading to treatment discontinuation in 5.6% and 8.2%, respectively; and drug-related AEs (none fatal) in 11.7% and 9.7%, respectively. Conclusions Imipenem/cilastatin/relebactam is an appropriate treatment option for gram-negative HABP/VABP, including in critically ill, high-risk patients. Clinical Trials Registration NCT02493764.

Effect of ciprofloxacin on levels of lipopolysaccharide and cytokines in experimentally induced Gram-negative bacterial pneumonia in mice

2006 ◽  
Vol 12 (3) ◽  
pp. 119-123 ◽  
Author(s):  
Shin Kawai ◽  
Tomoyuki Nakagawa ◽  
Susumu Sakayori ◽  
Osamu Kobayashi ◽  
Shigeru Kamiya
Keyword(s):  
Bacterial Pneumonia ◽  
Gram Negative ◽  
Experimentally Induced

scholarly journals Systematic Literature Review of Real-World Evidence of C Eftolozane/Tazobactam for the Treatment of Respiratory Infections

2021 ◽  
Author(s):  
Laura Puzniak ◽  
Ryan Dillon ◽  
Thomas Palmer ◽  
Hannah Collings ◽  
Ashley Enstone
Keyword(s):  
Clinical Trials ◽  
Literature Review ◽  
Systematic Literature Review ◽  
Real World ◽  
Bacterial Pneumonia ◽  
Respiratory Infections ◽  
Clinical Success ◽  
Multidrug Resistant ◽  
Success Rates ◽  
Gram Negative

Abstract Background: Gram-negative nosocomial pneumonia (NP), including hospital-acquired bacterial pneumonia (HABP), ventilated HABP (vHABP), and ventilator-associated bacterial pneumonia (VABP), is a significant cause of morbidity and mortality. Common pathogens, including Enterobacterales and Pseudomonas aeruginosa are highly prevalent in healthcare settings and have few effective treatment options due to high rates of antibacterial resistance. Resistant pathogens are associated with significantly worse outcomes and higher costs, relative to patients with susceptible infections. Ceftolozane/tazobactam (C/T) has established efficacy in clinical trials of patients with NP. This review aimed to collate data on C/T use for HABP/vHABP/VABP infections in real-world clinical practice. Methods: This systematic literature review searched online biomedical databases for real-world studies of C/T for gram-negative respiratory tract infections (RTIs) up to June 2020. Relevant study, patient, and treatment characteristics, microbiology, and efficacy outcomes were captured.Results: Thirty-three studies comprising 658 patients were identified. Pneumonia was the most common infection C/T was used to treat (85%), with a smaller number of unspecified RTIs (9%) and tracheobronchitis (5%) reported. Data on severity of illness and comorbidity were inconsistently reported. The majority of patients had respiratory infections caused by P. aeruginosa (92.8%), of which 88.1% were multidrug-resistant (including extensively drug-resistant or pandrug-resistant). Examination of these studies demonstrated an increase in the percentage of patients receiving the recommended dose of C/T for respiratory infections (3 g q8h or renal impairment-adjusted) over time (36.8% of patients in 2017 to 71.5% in 2020). Clinical success rates ranged from 51.4–100%, with 10 studies (55.6% of studies reporting clinical success) reporting clinical success rates of >70%; microbiological success rates ranged from 57.0–100.0%, with three studies (60.0% of studies reporting microbiological success) reporting microbiological success rates of >70%. Thirty-day mortality ranged from 0.0–33.0%, with nine studies (90% of studies reporting mortality) reporting 30-day mortality of <30%. Conclusions: The studies identified in this review demonstrate that C/T shows similar outcomes as those seen in clinical trials, despite the higher frequency of multidrug-resistant pathogens, and comorbidities/conditions that may have been excluded from the trials.

scholarly journals Clinical management of cUTI, cIAI, and HABP/VABP attributable to carbapenem-resistant Gram-negative infections in Spain

2021 ◽  
Author(s):  
Ricard Ferrer ◽  
María Carmen Fariñas ◽  
Emilio Maseda ◽  
Miguel Salavert ◽  
German Bou ◽  
...  
Keyword(s):  
Clinical Management ◽  
Bacterial Pneumonia ◽  
Chart Review ◽  
Complicated Urinary Tract Infection ◽  
Public Health Problem ◽  
Major Public Health Problem ◽  
Post Discharge ◽  
Gram Negative ◽  
Carbapenem Resistant ◽  
Healthcare Associated

Introduction. Carbapenem-resistant Gram-negative (CRGN) infections are a major public health problem in Spain, often implicated in complicated, healthcare-associated infections that require the use of potentially toxic antibacterial agents of last resort. The objective of this study was to assess the clinical management of complicated infections caused by CRGN bacteria in Spanish hospitals. Methods. The study included: 1) a survey assessing the GN infection and antibacterial susceptibility profile in five participating Spanish hospitals and 2) a non-interventional, retrospective single cohort chart review of 100 patients with complicated urinary tract infection (cUTI), complicated intra-abdominal infection (cIAI), or hospital-acquired bacterial pneumonia/ventilator-associated bacterial pneumonia (HABP/VABP) attributable to CRGN pathogens. Results. In the participating hospitals CRGN prevalence was 9.3% amongst complicated infections. In the retrospective cohort, 92% of infections were healthcare-associated, and Klebsiella pneumoniae and Pseudomonas aeruginosa were the most common pathogens. OXA was the most frequently detected carbapenemase type (71.4%). We found that carbapenems were frequently used to treat cUTI, cIAI, HABP/VABP caused by CRGN pathogens. Carbapenem use, particularly in combination with other agents, persisted after confirmation of carbapenem resistance. Clinical cure was 66.0%, mortality during hospitalization 35.0%, mortality at the time of chart review 62.0%, and 6-months-post-discharge readmission 47.7%. Conclusion. Our results reflect the high burden and unmet needs associated with the management of complicated infections attributable to CRGN pathogens in Spain and highlight the urgent need for enhanced clinical management of these difficult-to-treat infections.

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