Dataset Information

Sodium Hyaluronate Nanocomposite Respirable Microparticles to Tackle Antibiotic Resistance with Potential Application in Treatment of Mycobacterial Pulmonary Infections.

ABSTRACT: Tuberculosis resistant cases have been estimated to grow every year. Besides Mycobacterium tuberculosis, other mycobacterial species are responsible for an increasing number of difficult-to-treat infections. To increase efficacy of pulmonary treatment of mycobacterial infections an inhalable antibiotic powder targeting infected alveolar macrophages (AMs) and including an efflux pump inhibitor was developed. Low molecular weight sodium hyaluronate sub-micron particles were efficiently loaded with rifampicin, isoniazid and verapamil, and transformed in highly respirable microparticles (mean volume diameter: 1 ?m) by spray drying. These particles were able to regenerate their original size upon contact with aqueous environment with mechanical stirring or sonication. The in vitro drugs release profile from the powder was characterized by a slow release rate, favorable to maintain a high drug level inside AMs. In vitro antimicrobial activity and ex vivo macrophage infection assays employing susceptible and drug resistant strains were carried out. No significant differences were observed when the powder, which did not compromise the AMs viability after a five-day exposure, was compared to the same formulation without verapamil. However, both preparations achieved more than 80% reduction in bacterial viability irrespective of the drug resistance profile. This approach can be considered appropriate to treat mycobacterial respiratory infections, regardless the level of drug resistance.

SUBMITTER: Rossi I

PROVIDER: S-EPMC6571635 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Sodium Hyaluronate Nanocomposite Respirable Microparticles to Tackle Antibiotic Resistance with Potential Application in Treatment of Mycobacterial Pulmonary Infections.

Rossi Irene I Buttini Francesca F Sonvico Fabio F Affaticati Filippo F Martinelli Francesco F Annunziato Giannamaria G Machado Diana D Viveiros Miguel M Pieroni Marco M Bettini Ruggero R

Pharmaceutics 20190501 5

Tuberculosis resistant cases have been estimated to grow every year. Besides <i>Mycobacterium tuberculosis</i>, other mycobacterial species are responsible for an increasing number of difficult-to-treat infections. To increase efficacy of pulmonary treatment of mycobacterial infections an inhalable antibiotic powder targeting infected alveolar macrophages (AMs) and including an efflux pump inhibitor was developed. Low molecular weight sodium hyaluronate sub-micron particles were efficiently load ...[more]

PMID: 31052403

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Project description:Background:Recent artificial tear preparations have provided 0.2% concentration of sodium hyaluronate. However, no published data exist on their potential superiority against 0.1% in alleviating dry-eye-disease symptoms in cataract extraction surgery. Methods:A total of 180 patients that underwent cataract extraction surgery were randomly divided into 2 groups according to their postoperative regime: Study group (SG) received fixed combination of tobramycin and dexamethasone (FCTD) quid for 3?weeks, and additionally 0.2% sodium hyaluronate provided in the COMOD® device quid for 6?weeks. Control group (CG) received fixed combination of tobramycin and dexamethasone (FCTD) quid for 3?weeks, and additionally 0.1% sodium hyaluronate provided in the COMOD® device quid for 6?weeks. The following indexes were evaluated at 3 postoperative checkpoints: 1) Surface discomfort index (SDI) which was derived by four direct 10-scale Likert-type questions that were addressed to the patient and pertained to: a) foreign body sensation (FBS), b) blinking discomfort (BD), c) stinging sensation (SS), d) tearing sensation (TS), 2) Tear break-up time (TBUT), 3) Schirmer's test, 4) Central corneal thickness (CCT), and 4) Central Corneal Sensitivity (CCS). Results:Both groups showed reduced CCS values at all postoperative examination points; however, SG participants had significantly better CCS (all p <?0.05). SG had better TBUT than CG at the 3rd (p =?0.03) and 6th examination points (p =?0.04). Moreover, SG had better SDI scores at the 3rd (SDI?=?9.26?±?0.55) and 6th weeks (SDI?=?9.47?±?0.48) vs. CG participants (p =?0.03 and p <?0.01, respectively). Conclusion:The increased 0.2% sodium hyaluronate concentration in the artificial tears provided in the COMOD® device seems to address dry-eye-disease symptoms better in patients who underwent phacoemulsification surgery than the 0.1% concentration. Trial registration:ClinicalTrials.gov Identifier: NCT03705949 Oct 15, 2018, retrospectively registered.

Project description:Background: Considering the global burden of pulmonary infections, there is an urgent need for optimal empirical antimicrobial therapy strategies for pulmonary infections, which should rely on reliable evidence. Therefore, we aim to investigate the optimal treatment options for pulmonary infections in adults and assess the strength of that evidence. Methods: We searched PubMed, Embase, the Cochrane Library, and China Biology Medicine disc to identify systematic reviews and meta-analyses of randomized controlled trials (RCTs) focusing on antimicrobial treatments for pulmonary infections. The outcomes of the included meta-analyses should include all-cause mortality or clinical treatment success. For each meta-analysis, we estimated relative risk (RR) with 95% CI. We also created an evidence map to show the efficacy of each antimicrobial treatment strategy and the certainty of the evidence. Results: Twenty-six meta-analyses and two new RCTs were included that contained 31 types of antimicrobial therapy strategies. We found that carbapenems were related to lower mortality than other β-lactams or fluoroquinolones alone or in combination with aminoglycosides for HAP patients (RR 0.76, 95% CI: 0.58–0.99). There was no statistical difference in all-cause mortality between the other antimicrobial therapy strategies. As for clinical cure, treatment with fluoroquinolones was associated with better success versus macrolides or β-lactams alone for CAP patients in both the intention-to-treat (ITT) population (RR 1.22, 95% CI: 1.02–1.47) and clinically evaluable (CE) population (RR 1.37, 95% CI: 1.11–1.68). Treatment with carbapenems showed a better clinical cure over non-carbapenems for VAP patients (RR 1.21, 95% CI: 1.05–1.4). Adjunctive inhaled antibiotics compared with intravenous antibiotics alone showed a benefit for VAP (RR 1.2, 95% CI: 1.05–1.35). In addition, adjunctive nebulized aminoglycoside for nosocomial pneumonia was associated with a higher cure rate versus intravenous antibiotics alone in the ITT population (RR 1.28, 95% CI: 1.04–1.57), while no statistical difference in clinical cure was observed between other intervention groups. Conclusions: We cannot evaluate which antibiotic is the best choice for the treatment of pulmonary infection. Carbapenems or adjunctive inhaled antibiotics showed a reasonable choice for HAP or VAP. However, we do not find a statistical difference between most antimicrobial therapy strategies for CAP patients.

Dataset Information

Sodium Hyaluronate Nanocomposite Respirable Microparticles to Tackle Antibiotic Resistance with Potential Application in Treatment of Mycobacterial Pulmonary Infections.

Publications

Sodium Hyaluronate Nanocomposite Respirable Microparticles to Tackle Antibiotic Resistance with Potential Application in Treatment of Mycobacterial Pulmonary Infections.

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