Increased antimicrobial resistance against azithromycin during COVID: role of irrational utilization.

Objectives: To assess the use of azithromycin during coronavirus disease-2019 pandemic and its impact on antimicrobial resistance in an urban setting. METHODS: The retrospective, cross-sectional study was conducted on two different data sets. The first data set was of inpatients (N = 300) during the first wave of COVID 19 i.e. January to December, 2020. Data was collected from tertiary care hospitals in Karachi between October 2021 and November 2022 after approval from the ethics review committee of Ziauddin University, Karachi. Drug utilisation evaluation was done using a structured and validated tool. The treatment protocols were evaluated by comparing against the coronavirus disease-2019 treatment protocol 2020 and the guidelines issued by the Medical Microbiology and Infectious Diseases Society of Pakistan. Second data set comprised of the consumption data (obtained from pharmacies for both inpatients and outpatients) as well as the antimicrobial resistance, (obtained from antibiogram collected from the microbiology departments of the participating hospitals). This data was taken for the period of three years i.e. 2019 (Pre-COVID) to 2021 (Post-first wave of COVID) to establish trends of both consumption and antibiotic resistance. Data was analysed using SPSS 20. RESULTS: Of the 300 patients, 207(69%) were males and 93(31%) were females. There were 162(54%) adults with mean age 40.06±10.48 years, followed by 120(40%) geriatrics with mean age 70.37±6.94 years, 18(6%) paediatrics with mean age 13.5±3.60 years. All patients were given Azithromycin empirically followed by culture sensitivity test in 21% cases only. Comparison with COVID treatment protocols revealed the non-compliance of just 3%. However, in case of Community Acquired Pneumonia (CAP), sinusitis, typhoid and urethritis, comparison with MMIDSP guidelines revealed non-compliance of 95%, 22%, 75% and 100% respectively. Moreover, in 11% of patients, it was administered for conditions not recommended by guidelines. Furthermore, the Antibiogram exhibited percent increase in resistance against azithromycin. CONCLUSIONS: Enhanced consumption and irrational use of azithromycin during the coronavirus disease-2019 pandemic most likely contributed to increase in antimicrobial resistance.

Light transmission properties of pharmaceutical liquid bottles and evaluation of their photoprotective efficacy.

The light sensitive pharmaceutical dosage forms are well protected from light by packing in light protective bottles especially the colored glass and plastic bottles. In the present study the transmission characteristics of transparent glass bottle, amber glass bottle, polyvinyl chloride amber plastic bottle (PVC) and low density polyethylene semi-opaque plastic bottles (LDPE) (empty and drug filled) have been evaluated and the data compared for compliance with Pharmacopoeial limits of percentage transmission. The variations in thickness affect the amount of light transmitted through the bottles. For an average thickness, the transmission of bottles was not uniform indicated the effect of manufacturing variables on the transmission of light. The drug filled bottles showed an increase in light transmission probably as a result of interaction between drug and bottle components. The leaching of any coloring agents from glass bottles or the pigments from plastic bottles into the solution during storage appeared to increase the transmission of light which could be detrimental to photosensitive drugs in a formulation. The light protective efficacy of bottles was in the order: Semi-opaque plastic (LDPE) > amber plastic (PVC) > amber glass. The photoprotection of aqueous solution of riboflavin as a model compound in these bottles has been studied and its shelf-lives and stability ratio were determined.

Effect of solvent polarity on the extraction of components of pharmaceutical plastic containers.

A study of the extraction of polymeric material and dyes from the pharmaceutical plastic containers using various organic solvents was conducted to evaluate the effect of polarity on the extraction process. The plastic containers used included semi-opaque, opaque, transparent and amber colored and the solvent used were acetonitrile, methanol, ethanol, acetone, dichloroethane, chloroform and water. The determination of extractable material was carried out by gravimetric and spectrometric methods. The yield of extractable materials from containers in 60 h was 0.10-1.29% (w/w) and the first-order rate constant (kobs) for the extraction of polymeric material ranged from 0.52-1.50 × 10-3 min-1 and for the dyes 6.43- 6.74 x10-3min-1. The values of (kobs) were found to be an inverse function of solvent dielectric constant and decreased linearly with the solvent acceptor number. The extractable polymeric materials exhibited absorption in the 200-400 nm region and the dyes in the 300-500nm region. The rates of extraction of polymeric material and dyes from plastic containers were dependent on the solvent dielectric constant. The solvents of low polarity were more effective in the extraction of material indicating that the extracted material were of low polarity or have non-polar character. The dyes were soluble in acetone and chloroform. No plastic material was found to be extracted from the containers in aqueous solution.

Formulation and stabilization of norfloxacin in liposomal preparations.

A number of liposomal preparations of norfloxacin (NF) containing variable concentrations of phosphatidylcholine (PC) (10.8-16.2mM) have been formulated and an entrapment of NF to the extent of 41.7-56.2% was achieved. The values of apparent first-order rate constants (kobs) for the photodegradation of NF in liposomes (pH7.4) lie in the range of 1.05-2.40×10(-3)min(-1) compared to a value of 8.13×10(-3)min(-1) for the photodegradation of NF in aqueous solution (pH7.4). The values of kobs are a linear function of PC concentration indicating an interaction of PC and NF during the reaction. The second-order rate constant for the photochemical interaction of PC and NF has been determined as 8.92×10(-2)M(-1)min(-1). Fluorescence measurements on NF in liposomes indicate a decrease in fluorescence with an increase in PC concentration as a result of formation of NF(-) species which exhibits poor fluorescence. Dynamic light scattering has shown an increase in the size of NF encapsulated liposomes with an increase in PC concentration. The stabilization of NF in liposomes is achieved by the formation of a charge-transfer complex between NF and PC.

Resistance pattern of clinical isolates involved in surgical site infections.

Wound infections due to the incursion of microbes need to be averted or to heal the wounds by antibiotics. Antibiotics are not only aid in cure of infections but also help to prevent the flourishing and production of one or more species of microorganism, resultant in purulent discharge. This current study was carried out to evaluate the resistance pattern of clinical isolates from surgical site infections by the Kirby Bauer disc diffusion method. A total of 257 clinical isolates were collected from different hospitals in Karachi and evaluated by using fifteen antibiotics belonging to different groups. Staphylococcus aureus (n=87), Escherichia coli (n=76), Pseudomonas aeruginosa (n=56), Proteus (n=21) and Klebsiella (n=17) species are the most common clinical isolates of surgical site infections. Among the semi-synthetic penicillins, ampicillin was found to be resistant to nearly all clinical isolates but amoxicillin was moderately sensitive to S. aureus. Combinations of semi-synthetic penicillins are more sensitive than the penicillin alone. Co-amoxiclave exhibits superior sensitivity to all the surgical infection isolates except Pseudomonas aeruginosa which showed 68.75% resistance. Pseudomonas aeruginosa was highly resistant to cephalosporin except ceftraixone which showed 21.88% resistance. S. aureus was slightly responsive to cefazolin, cephradine, cefaclor, ceftizoxime, cefuroxime and ceftriaxone. E. coli, Gram-negative clinical isolate was showed 25% and 31.25% resistance to ceftriaxone and cefuroxime. In the Klebsiella species, 71.42% and 64.29% resistance to cefazolin and cefuroxime respectively, was observed. Aminoglycosides such as gentamycin and tobramycin were found to be more susceptible to all the clinical isolates. Quinolones like ofloxacin and enoxacin were showed good sensitivity to nearly all the clinical isolates.On the basis of the present study, it is recommended to adopt a rational use of antibiotics in prophylaxis and the utilization of a coordinated scheme of surgical wound inspections.