METHODS: In this retrospective multicenter study conducted from 2016-2019, enrolled patients were divided into 2 treatment groups. Group 1 patients were started on Antiviral drug (oseltamivir) alone therapy. Group 2 patients were initiated on Antiviral drug (oseltamivir) in combination with Antibiotic therapy. Using acute respiratory illness scoring, symptom severity score was assessed daily for 8 symptoms namely, fever, fatigue, headache, cough, sore throat, wheezing, muscle ache and nasal congestion. For each symptom the severity was scored from scale 0-3. Results: Overall mean ARI severity score was statistically significantly lower (p less than 0.05) on day 2 (14.65-vs-13.68), day 3 (12.95-vs-11.67) and day 4 (10.31-vs-9.12 ) for influenza-A (non-H1N1) while day 3 (12.52-vs-11.87) and day 4 (11.21-vs-10.18) for influenza-B patients for patients who were initiated on oseltamivir-antibiotic combination therapy. Fever, cough and nasal congestion showed statistically significant improvement within 4 days of initiation of combination treatment. Fatigue, sore throat and muscle ache improvement pattern was same for both treatment protocols.
CONCLUSION: Oseltamivir-antibiotic combination treatment showed early resolution of some symptoms with cumulatively reduced mean symptom severity score in severe influenza infection hospitalized patients.
METHODS: Herein, we have engineered antibiotic-loaded (doxycycline or vancomycin) LPHNPs with cationic and zwitterionic lipids and examined the effects on their physicochemical characteristics (size and charge), antibiotic entrapment efficiency, and the in vitro intracellular bacterial killing efficiency against Mycobacterium smegmatis or Staphylococcus aureus infected macrophages.
RESULTS: The incorporation of cationic or zwitterionic lipids in the LPHNP formulation resulted in a size reduction in LPHNPs formulations and shifted the surface charge of bare NPs towards positive or neutral values. Also observed were influences on the drug incorporation efficiency and modulation of the drug release from the biodegradable polymeric core. The therapeutic efficacy of LPHNPs loaded with vancomycin was improved as its minimum inhibitory concentration (MIC) (2 µg/mL) versus free vancomycin (4 µg/mL). Importantly, our results show a direct relationship between the cationic surface nature of LPHNPs and its intracellular bacterial killing efficiency as the cationic doxycycline or vancomycin loaded LPHNPs reduced 4 or 3 log CFU respectively versus the untreated controls.
CONCLUSION: In our study, modulation of surface charge in the nanomaterial formulation increased macrophage uptake and intracellular bacterial killing efficiency of LPHNPs loaded with antibiotics, suggesting alternate way for optimizing their use in biomedical applications.