Using Culture Sensitivity Reports to Optimize Antimicrobial Therapy: Findings and Implications of Antimicrobial Stewardship Activity in a Hospital in Pakistan.

Background: There are concerns with inappropriate prescribing of antibiotics in hospitals especially broad spectrum in Pakistan and the subsequent impact on antimicrobial resistance rates. One recognized way to reduce inappropriate prescribing is for empiric therapy to be adjusted according to the result of culture sensitivity reports. Objective: Using culture sensitivity reports to optimize antibiotic prescribing in a teaching hospital in Pakistan. Methods: A retrospective observational study was undertaken in Ghurki Trust Teaching Hospital. A total of 465 positive cultures were taken from patients during the study period (May 2018 and December 2018). The results of pathogen identification and susceptibility testing from patient-infected sites were assessed. Additional data was collected from the patient's medical file. This included demographic data, sample type, causative microbe, antimicrobial treatment, and whether empiric or definitive treatment as well as medicine costs. Antimicrobial data was assessed using World Health Organization's Defined Daily Dose methodology. Results: A total of 497 isolates were detected from the 465 patient samples as 32 patients had polymicrobes, which included 309 g-negative rods and 188 g-positive cocci. Out of 497 isolates, the most common Gram-positive pathogen isolated was Staphylococcus aureus (Methicillin-sensitive Staphylococcus aureus) (125) (25.1%) and the most common Gram-negative pathogen was Escherichia coli (140) (28.1%). Most of the gram-negative isolates were found to be resistant to ampicillin and co-amoxiclav. Most of the Acinetobacter baumannii isolates were resistant to carbapenems. Gram-positive bacteria showed the maximum sensitivity to linezolid and vancomycin. The most widely used antibiotics for empiric therapy were cefoperazone plus sulbactam, ceftriaxone, amikacin, vancomycin, and metronidazole whereas high use of linezolid, clindamycin, meropenem, and piperacillin + tazobactam was seen in definitive treatment. Empiric therapy was adjusted in 220 (71.1%) cases of Gram-negative infections and 134 (71.2%) cases of Gram-positive infections. Compared with empiric therapy, there was a 13.8% reduction in the number of antibiotics in definitive treatment. The average cost of antibiotics in definitive treatment was less than seen with empiric treatment (8.2%) and the length of hospitalization also decreased. Conclusions: Culture sensitivity reports helped reduced antibiotic utilization and costs as well as helped select the most appropriate treatment. We also found an urgent need for implementing antimicrobial stewardship programs in hospitals and the development of hospital antibiotic guidelines to reduce unnecessary prescribing of broad-spectrum antibiotics.

Impact of an educational program on community pharmacist's preparedness to conduct pharmacist-led diabetes clinic in Saudi Arabia.

BACKGROUND: Demand for diabetes care and prevention has increased due to Saudi Arabia's high prevalence of diabetes mellitus and its insufficient treatment. This raised awareness of the significance of community pharmacists in Saudi Arabia, who may significantly improve diabetes treatment by setting up pharmacist-led diabetic clinics. Thus, to assess community pharmacists' readiness to lead diabetes clinics in Saudi Arabia, this study evaluated the usefulness of an educational session on diabetes care. METHOD: The preparation of community pharmacists for diabetes treatment and management was assessed using a validated diabetes-specific questionnaire. An engaging and thorough diabetes education class was presented by two licensed diabetes educators. One-way ANOVA, chi-square, and the Mann-Whitney U-test were used to statistically assess the pre- and post-knowledge and attitude scores of community pharmacists. RESULTS: Following a learning session, the community pharmacists had a significant increase in understanding oral hypoglycemic medicines, monitoring the disease's course, and dosing of insulin for diabetics (p = 0.01). Additionally, the community pharmacist's perspective and attitude score on managing diabetes increased from 49.74 to 52.74 (p = 0.01). CONCLUSION: The study's findings demonstrated a marked improvement in community pharmacist's knowledge of and attitude toward running pharmacist-led diabetic clinics following a session on diabetes education in collaboration with the Pharmacy College. The study's findings also emphasized the significance of developing a structured programme for diabetes education in Saudi Arabia to address the demands of community pharmacists in terms of professional development.

Pharmacists' Understanding and Attitudes Toward Pharmaceutical Care in Saudi Arabia.

Background It has been proposed that pharmacy practice moves from product-focused to patient-focused. The major goals of pharmaceutical care are to improve the patient's quality of life, approve the safety of drug therapy, and seek to enhance the quality of life related to the patient's health within reasonable financial constraints. One of the biggest issues facing Saudi Arabia's healthcare system is including a pharmacist in the healthcare team who uses the most up-to-date pharmaceutical services and cares for the patient with medical and nursing care. This study aims to assess the opinions and knowledge concerning pharmaceutical care of hospital pharmacists working in three major governmental hospitals in the Al-Qassim region. Methodology A descriptive cross-sectional survey using an anonymous, structured, validated, and pilot-tested questionnaire of hospital pharmacists was utilized to address the study's objectives. The data were collected in four weeks between November and December 2021 from three major governmental hospitals in the Al-Qassim region. Data were analyzed using the SPSS software version 24 (IBM Corp., Armonk, NY, USA), and the associations between variables were evaluated. Results The survey was completed by 130 of the 160 pharmacists during the four-week study period (the overall response rate was 81%). The majority of those who responded were Saudi males, and only 19 (14.6%) participants had more than 15 years of practice. The majority of pharmacists had favorable opinions on providing pharmaceutical care. Overall, 122 (93.9%) respondents knew what pharmaceutical care meant. Most pharmacists (120, 92.3%) agreed to always counsel the patient on how to use their medications. Nearly half of the pharmacists (58, 45.0%) lacked knowledge about the clinical disease states, and 108 (83.0%) pharmacists knew how to obtain information. Conclusions Pharmacists reported a positive attitude regarding pharmaceutical treatment. Awareness and attitudes concerning pharmaceutical treatment were associated with a variety of demographic parameters, including gender, years of experience, and place of employment, to name a few. They reported that they were willing but concerned about their clinical expertise and ability to communicate effectively. Therefore, pharmacists should be permitted to enroll in programs that teach them how to provide pharmacological care.

Resveratrol Inhibited ADAM10 Mediated CXCL16-Cleavage and T-Cells Recruitment to Pancreatic ß-Cells in Type 1 Diabetes Mellitus in Mice.

Background: CXCL16 attracts T-cells to the site of inflammation after cleaving by A Disintegrin and Metalloproteinase (ADAM10). Aim: The current study explored the role of ADAM10/CXCL16/T-cell/NF-κB in the initiation of type 1 diabetes (T1D) with special reference to the potential protecting role of resveratrol (RES). Methods: Four sets of Balb/c mice were created: a diabetes mellitus (DM) group (streptozotocin (STZ) 55 mg/kg, i.p.], a control group administered buffer, a RES group [RES, 50 mg/kg, i.p.), and a DM + RES group (RES (50 mg/kg, i.p.) and STZ (55 mg/kg, i.p.) administered daily for 12 days commencing from the fourth day of STZ injection). Histopathological changes, fasting blood insulin (FBI), glucose (FBG), serum and pancreatic ADAM10, CXCL16, NF-κB, T-cells pancreatic expression, inflammatory, and apoptotic markers were analyzed. Results: FBG, inflammatory and apoptotic markers, serum TNF-α, cellular CXCL16 and ADAM10 protein expression, pancreatic T-cell migration and NF-κB were significantly increased in diabetic mice compared to normal mice. RES significantly improved the biochemical and inflammatory parameters distorted in STZ-treated mice. Conclusions: ADAM10 promotes the cleaved form of CXCL16 driving T-cells into the islets of the pancreatic in T1D. RES successfully prevented the deleterious effect caused by STZ. ADAM10 and CXCL16 may serve as novel therapeutic targets for T1D.

Simvastatin mitigates streptozotocin-induced type 1 diabetes in mice through downregulation of ADAM10 and ADAM17.

BACKGROUND: T cell mediates immune response in type 1 diabetes mellitus (T1DM) through its trafficking into pancreatic islets. The role of A Disintigrin And Metalloproteinase 10 (ADAM10) and 17 (ADAM17) in pancreatic T-cells recruitment into the pancreatic islets during T1DM is not known. AIM: Explore the role of ADAM10 and ADAM17 in the processing of CXCL16 in T1DM and possible protective effect of simvastatin (SIM) in streptozotocin (STZ)-induced T1DM. MAIN METHODS: Balb/c mice were classified into 4 groups, 10 each. Control group received buffer while SIM group received 50 mg/kg, i.p daily for 12 days starting from day 4 of the experiment. Diabetic group; received STZ (55 mg/kg, i.p.) for 5 consecutive days starting from day 1 of the experiment. SIM + STZ group; received SIM (50 mg/kg, i.p.) daily for 12 days and STZ (55 mg/kg, i.p.) for 5 consecutive days. Biochemical, inflammatory and apoptotic markers as well as expression of CXCL16, ADAM10, NF-κB and pancreatic T-cells expression were analyzed. KEY FINDINGS: Significant increase in biochemical, inflammatory, apoptotic parameters, expression of ADAM10, ADAM17, CXCL16, NF-κB, and infiltrated T-cells to the pancreatic islets were found in STZ group. SIM treatment in the presence of STZ improved biochemical and inflammatory parameters as well as it reduced the expression of CXCL16, ADAM10, ADAM17, NF-κΒ, T-cells migration and apoptosis in the pancreatic islets. SIGNIFICANCE: SIM mitigated pancreatic ß-cell death induced by STZ through down regulation of ADAM10, ADAM17and CXCL16. Therefore, ADAM10/ADAM17 and CXCL16 may serve as novel therapeutic targets for T1DM.

Loss of RAR-α and RXR-α and enhanced caspase-3-dependent apoptosis in N-acetyl-p-aminophenol-induced liver injury in mice is tissue factor dependent.

Tissue factor (TF) activates the coagulation system and has an important role in the pathogenesis of various diseases. Our previous study stated that retinoid receptors (RAR-α and RXR-α) are released as a lipid droplet in monocrotaline/ lipopolysaccharide-induced idiosyncratic liver toxicity in mice. Herein, the interdependence between the release of retinoid receptors RAR-α and RXR-α and TF in Nacetyl-p-aminophenol (APAP)-induced mice liver toxicity, is investigated. Serum alanine transaminase (ALT) level, platelet and white blood cells (WBCs) counts, protein expression of fibrin, TF, cyclin D1 and cleaved caspase-3 in liver tissues are analyzed. In addition, histopathological evaluation and survival study are also performed. The results indicate that using of TF-antisense (TF-AS) deoxyoligonucleotide (ODN) injection (6 mg/kg), to block TF protein synthesis, significantly restores the elevated level of ALT and WBCs and corrects thrombocytopenia in mice injected with APAP. TF-AS prevents the peri-central overexpression of liver TF, fibrin, cyclin D1 and cleaved caspase- 3. The release of RXR-α and RAR-α droplets, in APAP treated sections, is inhibited upon treatment with TF-AS. In conclusion, the above findings designate that the released RXR-α and RAR-α in APAP liver toxicity is TF dependent. Additionally, the enhancement of cyclin D1 to caspase-3-dependent apoptosis can be prevented by blocking of TF protein synthesis.

Effect of inhaled anaesthetics gases on cytokines and oxidative stress alterations for the staff health status in hospitals.

OBJECTIVES: The present study aimed to evaluate the effects of waste anaesthetic gases on cytokines and oxidative stress of hospital health team members following exposure to waste anaesthetic gases (WAGs). SUBJECTS AND METHODS: In total, 180 participants took part in this study; 60 of these were healthy male controls and the 120 participants in the intervention group were staff who work in the operating room. This latter group comprises six occupational subgroups (1) surgeons, (2) surgical assistants, (3) anaesthesiologists (4) anaesthesiology assistants, (5) nurses and (6) janitors. The following parameters were assessed: catalase (CAT), glutathione peroxidase (GSHpx) and superoxide dismutase (SOD) activities, plasma fluoride, serum interferon gamma (IFN-γ), serum interleukin 2 (IL2), serum interleukin 4 (IL4) and plasma thiobarbituric acid reactive substances (TBARS). RESULTS: Anaesthesiologists and their assistants exhibited the highest levels of plasma fluoride, serum IFN-γ and IL 2, exceeding the levels in detected in all the other occupational subgroups. Furthermore, the serum levels of IL4 were significantly raised in anaesthesiologists and the difference between this group and other groups was statistically significant. However, compared with the other subgroups, surgeons exhibited elevated plasma TBARS and reduced CAT, GSHpx and SOD; these variances were also statistically significant. CONCLUSION AND RECOMMENDATIONS: The findings of this study indicate that operating room staff exposed to WAGs are vulnerable to experiencing immunotoxicity as the WAGs are considered to initiate oxidative stress and increase the levels of cytokines in serum. Thus, an education programme is warranted to inform staff working in environments where they may be subjected to WAGs on the effects that the gases can have upon their health and how to minimise their exposure to WAGs. An ongoing effort is also needed to ensure anaesthesia safety standards are maintained at all times. The findings of this study may provide a springboard for future research into occupational exposure to WAGs and their wider effect upon health.

Silver Citrate Nanoparticles Inhibit PMA-Induced TNFα Expression via Deactivation of NF-κB Activity in Human Cancer Cell-Lines, MCF-7.

BACKGROUND: The nuclear factor kappa-B (NF-κB) is a major transcription factor responsible for the production of numerous inflammatory mediators, including the tumor necrosis factor (TNFα), which has a lethal association with cancer's onset. The silver nanoparticles (AgNPs) are widely used in cancer treatment and several other biomedical applications. OBJECTIVE: The study aimed to determine the effects of silver citrate nanoparticles (AgNPs-CIT) on NF-κB activation together with TNFα mRNA/protein expressions in the phorbol myristate acetate (PMA)-stimulated MCF-7 human breast cancer cell-lines. METHODS: The AgNPs-CIT were synthesized by the reduction method, and the prepared AgNPs-CIT were characterized for their shape, absorption in UV-VIS electromagnetic radiations, size distribution, ζ-potential, and antioxidant activity. The MCF-7 cell-lines were pretreated with AgNPs-CIT and stimulated with PMA. The TNFα mRNA expressions were determined by real-time PCR, whereas the protein production was determined by the ELISA. The NF-κB activity was distinctly observed by highly-specific DNA-based ELISA, and by NF-κB-specific inhibitor, Bay 11-7082. RESULTS: The prepared AgNPs-CIT were spherical and have an absorption wavelength range of 381-452 nm wherein the particles size ranged between 19.2±0.1 to 220.77±0.12 nm with the charge range -9.99±0.8 to -34.63±0.1 mV. The prepared AgNPs-CIT showed comparative antioxidant activity at >40% inhibitions level of the DPPH radicals. The AgNPs-CIT were found to be non-toxic to MCF-7 cell-lines and inhibited PMA-induced activation of the NF-κBp65, and also the mRNA/protein expression of TNFα. CONCLUSION: This is the first report that showed AgNPs-CIT inhibited TNFα expression via deactivation of the NF-κB signaling event in stimulated breast cancer cells. The results have important implications for the development of novel therapeutic strategies for the prevention/treatment of cancers and/or inflammatory disorders.

Adherence to Statin Therapy and Attainment of LDL Cholesterol Goal Among Patients with Type 2 Diabetes and Dyslipidemia.

BACKGROUND: Statins are widely utilized antidyslipidemics with a proven track record of safety and efficacy. However, the efficacy of these therapeutic agents hinges on patients' adherence to their prescribed statins. OBJECTIVE: The primary objectives of this study were to examine the relationship between adherence to prescribed statins and its impact on the low-density lipoprotein (LDL) level, and to explore the factors that influence patient adherence to statins among patients with diabetes and dyslipidemia. METHODS: This was a retrospective, cross-sectional study using the electronic health records data of adults (≥18 years) with type 2 diabetes and dyslipidemia visiting outpatient clinics at a university-affiliated tertiary care center. Adherence to statin therapy was estimated using the proportion of days covered (PDC). Patients with diabetes were considered adherent to statins if they had a PDC of ≥80%. Treatment success was considered if the LDL level of < 2.6 mmol/L. RESULTS: Out of 10,226 of patients with diabetes, 1532 met the inclusion criteria and were included in the study. Seventy-nine percent of the patients with diabetes were on atorvastatin and 21% were on simvastatin. The vast majority of the patients with diabetes (77%) were considered adherent and about 42% achieved LDL-cholesterol goal < 2.6 mmol/L. No association between adherence to statin therapy and LDL goal attainment was observed. Women had lower odds of being adherent to statin therapy (AOR=0.66, 95% CI: 0.49-0.87) compared to men. Further, young adults (18-44 years) had lower odds of being adherent to statin therapy (AOR=0.58, 95% CI: 0.32-0.97) compared to older adults (age>65 years). CONCLUSION: The findings of this study highlight the need to examine the impact of adherence to statins on healthcare services utilization due to different complications of uncontrolled dyslipidemia.