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 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 1609. Epidemiology and Susceptibility to Imipenem/Relebactam of Gram-Negative Pathogens from Patients with Lower Respiratory Tract Infections – SMART United States 2017-2018

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S799-S799
Author(s):  
Sibylle Lob ◽  
Meredith Hackel ◽  
Katherine Young ◽  
Mary Motyl ◽  
Daniel F Sahm
Keyword(s):  
Respiratory Tract ◽  
Lower Respiratory Tract ◽  
Respiratory Tract Infections ◽  
Surveillance Program ◽  
Lower Respiratory Tract Infections ◽  
Independent Contractor ◽  
Gram Negative ◽  
The Us ◽  
Tract Infections

Abstract Background Relebactam (REL) inhibits class A and C β-lactamases and was approved in the US combined with imipenem (IMI) and cilastatin for complicated urinary tract and intraabdominal infections. Using isolates collected as part of the global SMART surveillance program in the US, we evaluated the activity of IMI/REL against gram-negative pathogens (GNP) from patients with lower respiratory tract infections (LRTI), including a comparison of isolates from ICU and non-ICU wards. Methods In 2017-2018, 27 US hospitals each collected up to 100 consecutive aerobic or facultative GNP from LRTI patients per year. MICs were determined using CLSI broth microdilution and breakpoints. Results Among 3878 GNP isolates from LRTI, the most common species collected were P. aeruginosa (Psa, 33.3%), K. pneumoniae (10.9%), E. coli (10.4%), and S. marcescens (6.9%). Susceptibility of GNP is shown in the table. IMI/REL inhibited 93% of Psa and Enterobacterales, which included 174 isolates of Morganellaceae that are not expected to be susceptible to IMI or IMI/REL. S. marcescens also showed low susceptibility to IMI, with improved but still reduced activity upon addition of REL. IMI/REL inhibited 83% of all GNP combined, 7-18 percentage points higher than the comparator β-lactams. Of the tested comparators, only amikacin exceeded the activity of IMI/REL. Only Psa showed substantial differences in susceptibility between isolates from ICU (n=486) and non-ICU wards (n=611), with 63.4% and 70.2%, respectively, susceptible to IMI, 71.6/78.7% to cefepime, and 64.2/73.3% to piperacillin/tazobactam (P/T). Susceptibility to IMI/REL was high in both settings (91.4/93.6%). Among Enterobacterales, susceptibility was generally similar in ICU and non-ICU wards (IMI/REL, 92.5% in both settings; IMI, 86.3 and 87.1%, respectively; cefepime, 89.9/89.0%; P/T, 88.7/87.4%). Table Conclusion Although resistance rates have frequently been reported to be higher in ICU than non-ICU wards, this pattern was seen in the current study only among Psa isolates. IMI/REL showed activity >90% against both Enterobacterales and Psa from both ward types. These in vitro data suggest that IMI/REL could provide an important treatment option for patients with LRTI in the US, including those in ICUs. Disclosures Sibylle Lob, PhD, IHMA (Employee)Pfizer, Inc. (Consultant) Katherine Young, MS, Merck & Co., Inc. (Employee, Shareholder)Merck & Co., Inc. (Employee, Shareholder) Mary Motyl, PhD, Merck & Co, Inc (Employee, Shareholder) Daniel F. Sahm, PhD, IHMA (Employee)Pfizer, Inc. (Consultant)Shionogi & Co., Ltd. (Independent Contractor)

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 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.

Cefuroxime Axetil

1988 ◽  
Vol 22 (9) ◽  
pp. 651-658 ◽  
Author(s):  
Michael A. Marx ◽  
William K. Fant
Keyword(s):  
Respiratory Infections ◽  
Acute Otitis Media ◽  
Cefuroxime Axetil ◽  
Moderate Activity ◽  
Beta Lactamase ◽  
Amoxicillin Clavulanic Acid ◽  
Gram Negative Organisms ◽  
Tract Infections ◽  
Branhamella Catarrhalis

Cefuroxime axetil is a orally active prodrug formulation of cefuroxime, which upon absorption undergoes immediate deesterification to free cefuroxime. Cefuroxime axetil offers an in vitro antibacterial spectrum against many gram-positive and some gram-negative organisms. Its beta-lactamase stability makes it useful in treating a variety of infections caused by beta-lactamase-producing strains of Haemophilus influenzae, Branhamella catarrhalis, and Staphylococcus aureus. Cefuroxime axetil has good activity against the Enterobacteriaceae and moderate activity against non-Bacteroides fragilis anaerobes. Clinical studies suggest it is at least as effective as ampicillin, amoxicillin, amoxicillin/clavulanic acid, penicillin V, or cefaclor in the treatment of uncomplicated urinary tract infections, acute otitis media, upper respiratory infections, skin and soft tissue infections, and uncomplicated gonorrhea.

scholarly journals In vitro Activity of Ceftaroline Against Pathogens Collected Globally from the AWARE Surveillance Program, 2016

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S379-S379
Author(s):  
Meredith Hackel ◽  
Joseph Iaconis ◽  
Dan Sahm
Keyword(s):  
Respiratory Tract Infections ◽  
Blood Stream ◽  
Vitro Activity ◽  
Surveillance Program ◽  
In Vitro Activity ◽  
Ceftaroline Fosamil ◽  
Gram Negative ◽  
Complicated Skin ◽  
Tract Infections

Abstract Background Ceftaroline, the active metabolite of ceftaroline fosamil, is a cephalosporin developed for treating infections caused by Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA), Streptococcus pneumoniae, β-hemolytic streptococci, and some Gram-negative pathogens. This study reports the in vitro activity of ceftaroline against clinically relevant isolates collected in 2016 from the AWARE Surveillance Program. Methods 22,752 non-duplicate methicillin-sensitive S. aureus (MSSA), MRSA, S. pneumoniae, β-hemolytic streptococci (S. pyogenes, S. agalactiae, S. dysgalactiae) Haemophilus influenzae, and extended spectrum β-lactamase (ESBL)-negative Enterobacteriaceae were collected from (n/%) Asia/South Pacific (4,215/18.5%), Europe (12,962/57.0%), Latin America (3,384/14.9%), and Middle East/Africa (2,191/9.6%) during 2016. Isolates were from (n/%) complicated intraabdominal (2,149/9.5%), complicated urinary tract (3,029/13.3%), complicated skin and skin structure (8,271/36.4%), blood stream (2,422/10.6%) and lower respiratory tract infections (6,881/30.2%). MIC values were determined by broth microdilution and interpreted using CLSI breakpoints. Results Ceftaroline activity, based on % susceptibility (%S) and MIC90, is shown in the table. Ceftaroline was active in vitro against both Gram-positive (100% of MSSA, 93.6% of MRSA and 99.7% of S. pneumoniae) and Gram-negative (99.7% of H. influenzae and 91.7% of ESBL-negative Enterobacteriaceae) isolates. Conclusion Based on these data generated with isolates collected in 2016, ceftaroline exhibited potent in vitro activity against clinically relevant isolates, with >91% of all isolates susceptible at their CLSI breakpoints. Funding: This study was sponsored by AstraZeneca. The AstraZeneca product ceftaroline fosamil was acquired by Pfizer in December 2016. Disclosures J. Iaconis, AstraZeneca: Employee and Shareholder, Salary and Shareholder in AstraZeneca

Sign in / Sign up

Export Citation Format

Share Document