METHODS: A 1085-bp fragment of 23S rRNA domain V from samples of 62 treatment-naïve patients with H. pylori infection was amplified by PCR with newly designed primers, followed by sequencing.
RESULTS: Of the 62 cases, 42 patients were treated with clarithromycin-based triple therapy and 20 patients were treated with amoxicillin and proton pump inhibitor only; both therapies showed successful eradication rates of 70-73.8%. Sequencing analysis detected 37 point mutations (6 known and 31 novel) with prevalences ranging from 1.6% (1/62) to 72.6% (45/62). A2147G (aka A2143G) appears to be associated with a low eradication rate [40% (2/5) failure rate and 13.3% (6/45) treatment success rate], supporting its role as a clinically significant point mutation. T2186C (aka T2182C) was found in 71.1% (32/45) and 80% (4/5) of treatment success and failure cases, respectively, suggesting that the mutation is clinically insignificant. The eradication success rate in patients with the novel T2929C mutation was decreased three-fold (6.7%; 3/45) compared with the failure rate (20%; 1/5), suggesting that it may play an important role in clarithromycin resistance, thus warranting further study.
CONCLUSION: This study identified multiple known and novel mutations in 23S rRNA domain V through direct sequencing. Molecular detection of clarithromycin resistance directly on biopsies offers an alternative to conventional susceptibility testing.
RECENT FINDINGS: Optimal antibiotic treatment is challenging in critically ill patients with nosocomial pneumonia; most dosing guidelines do not consider the altered physiology and illness severity associated with severe lung infections. Antibiotic dosing can be guided by plasma drug concentrations, which do not reflect the concentrations at the site of infection. The application of aggressive dosing regimens, in accordance to the antibiotic's pharmacokinetic/pharmacodynamic characteristics, may be required to ensure rapid and effective drug exposure in infected lung tissues.
SUMMARY: Conventional antibiotic dosing increases the likelihood of therapeutic failure in critically ill patients with nosocomial pneumonia. Alternative dosing strategies, which exploit the pharmacokinetic/pharmacodynamic properties of an antibiotic, should be strongly considered to ensure optimal antibiotic exposure and better therapeutic outcomes in these patients.
METHODS USED TO CONDUCT THE REVIEW: This review was conducted in accordance with the Meta-analysis of Observational Studies in Epidemiology (MOOSE) recommendation. Electronic databases including MEDLINE, CINAHL, PubMed, Embase, Cochrane Databases and Cochrane Central Register of Controlled Trials were searched up to March 2017 for relevant trials. The methodological quality of included trials was assessed by using a modified version of the Newcastle-Ottawa Quality Assessment Scale for Case-Control and Cohort Studies. A meta-analysis was conducted using the random-effect model to combine the rate of mortality and length of stay outcomes.
FINDINGS OF THE REVIEW: Nine observational trials involving 2128 patients were considered eligible for inclusion. Although based on low quality evidence, there was a statistically significant difference in favour of the impact of de-escalation on hospital stay but not mortality (MD -5.96 days; 95% CI -8.39 to -3.52).
INTERPRETATIONS AND IMPLICATIONS OF THE FINDINGS: This review highlights the need for more rigorous studies to be carried out before a firm conclusion on the benefit of de-escalation therapy is supported.
Purpose of study: The study aimed to mask and evaluate the unpleasant bitter taste of azithro-mycin (AZ) in the dry suspension dosage form by physisorption technique.
Materials and methods: AZ was selected as an adsorbent and titanium dioxide nanoparticles as adsorbate. The AZ nanohybrids (AZN) were prepared by treating fixed amount of adsorbent with a varied amount of adsorbate, prepared separately by dispersing it in an aqueous medium. The mixture was sonicated, stirred followed by filtration and drying. The AZN produced were characterized by various techniques including scanning electron microscopy (SEM), energy dispersive X-rays (EDX), powder X-ray diffraction (PXRD), HPLC and Fourier-transformed infrared (FTIR). The optimized nanohybrid was blended with other excipients to get stable and taste masked dry suspension dosage form.
Results: The results confirmed the adsorption of titanium dioxide nanoparticles on the surface of AZ. The fabricated optimized formulation was subjected for taste masking by panel testing and accelerated stability studies. The results showed a remarkable improvement in bitter taste masking, inhibiting throat bite without affecting the dissolution rate. The product showed an excellent stability both in dry and reconstituted suspension. The optimized formulation of AZN and was found stable when subjected to physical and chemical stability studies, this is because of short and single step process which interns limits the exposure of the product to various environmental factors that could potentially affect the stability of the product. The dissolution rate of the optimized formulation of AZN was compared with its marketed counterpart, showing the same dissolution rate compared to its marketed formulation.
Conclusion: The current study concludes that, by fabricating AZ-titanium nanohybrids using physisorption can effectively mask the bitter taste of the drug. The palatability and stability of azithromycin formulation was potentially enhanced without affecting its dissolution rate.
METHODS: This was a prospective cohort study conducted in the neonatal intensive care units of two public hospitals in Malaysia. Neonates with a gestational age greater than 34 weeks who were started on empiric antibiotics within 72 h of life were screened. The data were then stratified according to de-escalation and non-de-escalation practices, where de-escalation practice was defined as narrowing down or discontinuation of empiric antibiotic within 72 h of treatment.
RESULTS: A total of 1045 neonates were screened, and 429 were included. The neonates were then divided based on de-escalation (n = 207) and non-de-escalation (n = 222) practices. Neonates under non-de-escalation practices showed significantly longer durations of antibiotic use compared to those under de-escalation practices (p