scholarly journals Inhaled ciprofloxacin-loaded poly(2-ethyl-2-oxazoline) nanoparticles from dry powder inhaler formulation for the potential treatment of lower respiratory tract infections

PLoS ONE ◽  
2021 ◽  
Vol 16 (12) ◽  
pp. e0261720
Author(s):  
Mohammad Zaidur Rahman Sabuj ◽  
Tim R. Dargaville ◽  
Lisa Nissen ◽  
Nazrul Islam
Keyword(s):  
Respiratory Tract ◽  
Lower Respiratory Tract ◽  
Respiratory Tract Infections ◽  
Drug Loading ◽  
Dry Powder Inhaler ◽  
Pulmonary Delivery ◽  
Lower Respiratory Tract Infections ◽  
Dry Powder ◽  
Tract Infections

Lower respiratory tract infections (LRTIs) are one of the fatal diseases of the lungs that have severe impacts on public health and the global economy. The currently available antibiotics administered orally for the treatment of LRTIs need high doses with frequent administration and cause dose-related adverse effects. To overcome this problem, we investigated the development of ciprofloxacin (CIP) loaded poly(2-ethyl-2-oxazoline) (PEtOx) nanoparticles (NPs) for potential pulmonary delivery from dry powder inhaler (DPI) formulations against LRTIs. NPs were prepared using a straightforward co-assembly reaction carried out by the intermolecular hydrogen bonding among PEtOx, tannic acid (TA), and CIP. The prepared NPs were characterized by scanning electron microscopy (SEM), dynamic light scattering (DLS), Fourier transform infrared spectroscopy (FTIR), powder X-ray diffraction analysis (PXRD), differential scanning calorimetry (DSC), and thermogravimetric analysis (TGA). The CIP was determined by validated HPLC and UV spectrophotometry methods. The CIP loading into the PEtOx was between 21–67% and increased loading was observed with the increasing concentration of CIP. The NP sizes of PEtOx with or without drug loading were between 196–350 nm and increased with increasing drug loading. The in vitro CIP release showed the maximum cumulative release of about 78% in 168 h with a burst release of 50% in the first 12 h. The kinetics of CIP release from NPs followed non-Fickian or anomalous transport thus suggesting the drug release was regulated by both diffusion and polymer degradation. The in vitro aerosolization study carried out using a Twin Stage Impinger (TSI) at 60 L/min air flow showed the fine particle fraction (FPF) between 34.4% and 40.8%. The FPF was increased with increased drug loading. The outcome of this study revealed the potential of the polymer PEtOx as a carrier for developing CIP-loaded PEtOx NPs as DPI formulation for pulmonary delivery against LRTIs.

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.

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 1231. In Vitro Activity of Aztreonam-Avibactam and Comparator Agents Against Enterobacterales from Patients with Lower Respiratory Tract Infections Collected During the ATLAS Global Surveillance Program, 2017-2019

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S705-S705
Author(s):  
Sibylle Lob ◽  
Krystyna Kazmierczak ◽  
Francis Arhin ◽  
Daniel F Sahm
Keyword(s):  
Respiratory Tract ◽  
Lower Respiratory Tract ◽  
Respiratory Tract Infections ◽  
Vitro Activity ◽  
Drug Resistant ◽  
In Vitro Activity ◽  
Lower Respiratory Tract Infections ◽  
Independent Contractor ◽  
Tract Infections

Abstract Background β-lactamase-producing Enterobacterales (Ebact) frequently co-carry resistance to antimicrobials from other classes, limiting treatment options. Avibactam (AVI) inhibits class A, class C, and some class D serine β-lactamases, while aztreonam (ATM) is refractory to hydrolysis by class B metallo-β-lactamases (MBLs). ATM-AVI is being developed for use against drug-resistant isolates of Ebact, especially those co-producing MBLs and serine β-lactamases. This study evaluated the in vitro activity of ATM-AVI and comparators against Ebact collected in 2017-2019 from patients with lower respiratory tract infections (LRTI) as part of the Antimicrobial Testing Leadership and Surveillance (ATLAS) program. Methods Non-duplicate clinical isolates were collected in 52 countries in Europe, Latin America, Asia/Pacific (excluding mainland China and India), and Middle East/Africa. Susceptibility testing was performed by CLSI broth microdilution and interpreted using CLSI 2021 and FDA (tigecycline) breakpoints. ATM-AVI was tested at a fixed concentration of 4 µg/mL AVI. MDR was defined as resistant (R) to ≥3 of 7 sentinel drugs: amikacin, aztreonam, cefepime, colistin, levofloxacin, meropenem, and piperacillin-tazobactam. PCR and sequencing were used to determine the β-lactamase genes present in all isolates with meropenem MIC >1 µg/mL, and Escherichia coli, Klebsiella spp. and Proteus mirabilis with ATM or ceftazidime MIC >1 µg/mL. Results ATM-AVI was active in vitro against Ebact isolates from LRTI (MIC90, 0.25 µg/mL), with 99.97% of isolates inhibited by ≤8 µg/mL of ATM-AVI, including 100% of isolates that produced MBLs. ATM-AVI tested with MIC90 values of 0.5 µg/mL against subsets of cefepime-nonsusceptible (NS), meropenem-NS, amikacin-NS, colistin-resistant, and MBL-positive Ebact (Table). The tested β-lactam comparators showed susceptibility of < 78% against these subsets of resistant isolates. Results Table Conclusion Based on MIC90 values, ATM-AVI was the most potent agent tested against drug-resistant and MBL-positive subsets of Ebact collected from LRTI. The promising in vitro activity of ATM-AVI warrants further development of this combination for treatment of LRTI caused by drug-resistant Ebact. Disclosures Sibylle Lob, PhD, IHMA (Employee)Pfizer, Inc. (Independent Contractor) Krystyna Kazmierczak, PhD, IHMA (Employee)Pfizer, Inc. (Independent Contractor) Francis Arhin, PhD, Pfizer, Inc. (Employee) Daniel F. Sahm, PhD, IHMA (Employee)Pfizer, Inc. (Independent Contractor)

Sign in / Sign up

Export Citation Format

Share Document