Antibiotic Susceptibility Surveillance in the Punjab Province of Pakistan: Findings and Implications.

Background and Objectives: The increase in antimicrobial resistance (AMR) across countries has seriously impacted the effective management of infectious diseases, with subsequent impact on morbidity, mortality and costs. This includes Pakistan. Antimicrobial surveillance activities should be mandatory to continually assess the extent of multidrug-resistant bacteria and the implications for future empiric prescribing. The objective of this retrospective observational study was to monitor the susceptibility pattern of microbes in Pakistan. Materials and Methods: Clinical samples from seven laboratories in Punjab, Pakistan were collected between January 2018 and April 2019, with Punjab being the most populous province in Pakistan. The isolates were identified and their antimicrobial susceptibility was tested using the Kirby-Bauer disc diffusion assay and micro broth dilution methods. The antibiotics assessed were those typically prescribed in Pakistan. Results: In total, 2523 bacterial cultural reports were studied. The most frequently isolated pathogens were Staphylococcus aureus (866, 34.3%), followed by Escherichia coli (814, 32.2%), Pseudomonas aeruginosa (454, 18.0%) and Klebsiella pneumoniae (269, 10.7%). Most pathogens were isolated from pus (1464, 58.0%), followed by urine (718, 28.5%), blood (164, 6.5%) and sputum (81, 3.2%). Conclusions: The findings suggest that current antimicrobial options are severally restricted in Pakistan due to the emergence of multidrug-resistant pathogens. This calls for urgent actions including initiating antimicrobial stewardship programs to enhance prudent prescribing of antibiotics. This includes agreeing on appropriate empiric therapy as part of agreed guidelines, in line with the WHO EML and AWaRe book, whilst awaiting culture reports. This is alongside other measures to reduce inappropriate antimicrobial prescribing and reverse the threat of rising AMR.

Ongoing Strategies to Improve Antimicrobial Utilization in Hospitals across the Middle East and North Africa (MENA): Findings and Implications.

Antimicrobial resistance (AMR) is an increasing global concern, increasing costs, morbidity, and mortality. National action plans (NAPs) to minimize AMR are one of several global and national initiatives to slow down rising AMR rates. NAPs are also helping key stakeholders understand current antimicrobial utilization patterns and resistance rates. The Middle East is no exception, with high AMR rates. Antibiotic point prevalence surveys (PPS) provide a better understanding of existing antimicrobial consumption trends in hospitals and assist with the subsequent implementation of antimicrobial stewardship programs (ASPs). These are important NAP activities. We examined current hospital consumption trends across the Middle East along with documented ASPs. A narrative assessment of 24 PPS studies in the region found that, on average, more than 50% of in-patients received antibiotics, with Jordan having the highest rate of 98.1%. Published studies ranged in size from a single to 18 hospitals. The most prescribed antibiotics were ceftriaxone, metronidazole, and penicillin. In addition, significant postoperative antibiotic prescribing lasting up to five days or longer was common to avoid surgical site infections. These findings have resulted in a variety of suggested short-, medium-, and long-term actions among key stakeholders, including governments and healthcare workers, to improve and sustain future antibiotic prescribing in order to decrease AMR throughout the Middle East.

Antibiotic Utilization Patterns for Different Wound Types among Surgical Patients: Findings and Implications.

Antimicrobial prophylaxis is effective in reducing the rate of surgical site infections (SSIs) post-operatively. However, there are concerns with the extent of prophylaxis post-operatively, especially in low- and middle-income countries (LMICs). This increases antimicrobial resistance (AMR), which is a key issue in Pakistan. Consequently, we conducted an observational cross-sectional study on 583 patients undergoing surgery at a leading teaching hospital in Pakistan with respect to the choice, time and duration of antimicrobials to prevent SSIs. The identified variables included post-operative prophylactic antimicrobials given to all patients for all surgical procedures. In addition, cephalosporins were frequently used for all surgical procedures, and among these, the use of third-generation cephalosporins was common. The duration of post-operative prophylaxis was 3-4 days, appreciably longer than the suggestions of the guidelines, with most patients prescribed antimicrobials until discharge. The inappropriate choice of antimicrobials combined with prolonged post-operative antibiotic administration need to be addressed. This includes appropriate interventions, such as antimicrobial stewardship programs, which have been successful in other LMICs to improve antibiotic utilization associated with SSIs and to reduce AMR.

Beneficial Effects of Black Cardamom (Amomum subulatum) on Hemodynamic Parameters in Normotensive and Spontaneously Hypertensive Rats.

<b>Background and Objectives:</b> <i>Amomum subulatum</i> (AS) is used to improve cardiac health in traditional medicine practice. The present study evaluates the pharmacological effect of AS aqueous extract on blood pressure in Normotensive (NR) and Spontaneously Hypertensive Rats (SHR). <b>Materials and Methods:</b> Blood pressure, Heart Rate (HR) and Heart Rate Variability (HRV), was recorded in catheterized Sprague-Dawley rats before and after AS intravenous administration by using Mikro-Tip Pressure-Volume System (MPVS), PowerLab. The receptor activity was assessed by using the drugs Acetylcholine (ACh) and Atropine (Atr). <b>Results:</b> Preliminary phytochemistry of AS suggests that it contains tannins, flavonoids and saponins. Mean Arterial Pressure (MAP) was found to decrease significantly in NR and SHR as compared with the control. The lowest dose (1 mg kg¹) produced the least (16%) while 30 mg kg¹ caused the maximum reduction (40%) in MAP. Electrocardiograph analysis revealed a significant increase in RR interval (decreased heart rate), time-domain Standard Deviation of Interbeat Interval (SDNN) and the Root Mean Square of the Successive Differences (RMSSD) and High-frequency Domain (HF%) parameters and a decrease in the Low-Frequency (LF) range, suggesting the activation and involvement of the parasympathetic limb. It was also observed that the cardiovascular effects of AS were comparable to Acetylcholine (ACh) and both were completely blocked by Atropine (1 µg kg¹). <b>Conclusion:</b> The obtained results suggest that AS has a hypotensive effect, with an impact on the HRV of NR and SHR. <i>Amomum subulatum</i> might cause an augmented effect on the cholinergic limb of the Autonomic Nervous System (ANS) and decrease the blood pressure and heart rate significantly.

Comparative effect of coffee robusta and coffee arabica (Qahwa) on memory and attention.

The comparative effects of coffee robusta and coffee arabica (Qahwa) on different attention and memory related assignments were measured in a double-blind study of 300 healthy young adult women who were randomly assigned to one of three different drinks: Group I (coffee robusta sachet dissolved in 100 ml of hot water): Group II (coffee arabica): and group III (100 ml water only). Cognitive function was assessed by standardized tests. Several monitoring cognitive tests and tasks were specifically chosen and performed to investigate the comparative effects of coffee robusta (CR) and coffee arabica (Qahwa; AC) on sleepiness (sleep and clear headed scale), attention (trail A & B, symbol digit, letter cancellation), general cognitive ability (stroop test) and memory (card test). Data was interpreted by analysis of variance (ANOVA). The present study revealed that coffee robusta has beneficial effects on attention, general cognitive ability and memory. Higher though non-significant cognitive scores were associated with coffee robusta consumption. Although, consumption of coffee arabica (Qahwa) has significant effects (P < 0.05) on sleepiness, attention, general cognitive ability and memory and it significantly improve reaction time and correct responses. Since different tasks were related to the sustained attention and working memory processes, results would suggest that coffee arabica (qahwa) could increase the memory and efficiency of the attentional system might be due to the presence of chlorogenic acids (CGA) which are found in less quantity in coffee robusta. However, more studies using larger samples and different tasks are necessary to better understand the effects of coffee robusta and arabica (Qahwa) on attention and memory.

Decreased brain serotonin turnover rate following administration of Sharbat-e-Ahmed Shah produces antidepressant and anxiolytic effect in rats.

Sharbat-e-Ahmed Shah (SAS) has usually been used in Traditional Unani Medicine (TUM) for depression and insomnia but still not evaluated for its anti-depressant and Neuropharmacological activity. In the present study, a Human dose of SAS (0.6 ml/kg/d) was administered orally to the rats for 15 consecutive days. Antidepressant and anxiolytic were screened scientifically in rats by using Forced swim test and light and dark box test. At the end of study high-performance liquid chromatographic (HPLC) method with electrochemical (EC) detector was used for the measurement of blood and brain tryptophan and brain serotonin levels. The present reported results are according to what is known in TUM, where is prescribed as an antidepressant agent. After the administration, SAS (at a human dose for 15 days) reduced the immobility time in rats analogous to Imipramine (positive control) indicating the antidepressant effect of SAS. In the present study, Diazepam or SAS (0.6 ml/kg/day) treated rats stayed in the illuminated side of the light-dark box, as compare to control rats (Veh, 134.62 ± 4.430 s; SAS 0.6 ml/kg, 192.2 ± 8.11 s; DZP 1.0 mg/kg, 205.21.20 ± 10.26 s, p < 0.05). It was also observed that SAS increased the availability of tryptophan in blood and brain and hence increases 5-hydroxytryptamine (Serotonin: 5HT) in the brain. At the end, it was concluded that SAS contains some active principles which increase the availability of neurochemical (tryptophan and 5HT) and decrease the 5HT turnover rate thus causes antidepressant and anxiolytic effects in experimental animals.

Acute hypotensive and diuretic activities of Berberis vulgaris root bark aqueous extract in normal rats

The aim of this study is to investigate the effectiveness of intravenous administration of Berberis vulgaris root bark aqueous extract (BRBD) on the cardiovascular and renal functions of healthy normotensive rats. The different doses of BRBD 1, 10 and 20 mg/kg were administered intravenously (i.v) in normal rats. Blood pressure, diuretic activity and serum renal profile were analyzed. Intravenous injection of BRBD at the different doses of 1, 10 and 20 mg/kg showed a dose-dependent reduction in mean arterial blood pressure (P<0.001). At different doses of 1, 10 and 20 mg/kg, the hypotensive effect remained for more than one hour. Single dose administration of BRBD at doses of 10 and 20 mg/kg caused a significant increase in urine output (P<0.001) as compared to the control rats. Serum renal profile test (albumin, Urea, Uric Acid, creatinine and BUN) did not show any significant alteration. The authors conclude that the BRBD is a potent hypotensive and possesses diuretic potential

Pharmacological evidence of neuro-pharmacological activity of Acacia tortilis leaves in mice.

Acacia tortilis is abundantly present in Saudi Arabia but its neuro-pharmacological activity has not yet been evaluated. In this study, the antidepressant by Forced swim test, Anxiolytic (Light and Dark box) and sedative effects (by using Open Field) of Acacia leaves extract were evaluated in mice. Aqueous extracts of the Acacia tortilis leaves were prepared. Two different doses (400 and 800 mg/kg) of the extracts were administered to the mice orally (p.o.). In exploratory behavior, Acacia leave extract (800 mg/kg) produced a significant reduction (Veh, 91.00 ± 5.26; Acacia 800 mg/kg, 46.33 ± 3.24 p < 0.05) similar to the effect observed with chlorpromazine (CPZ) (Veh, 91.00 ± 5.26; CPZ 1.0 mg/kg, 24.20 ± 3.40 p < 0.05). A dose-dependent significant decrease in immobility time was also observed in mice and this effect was comparable to its positive control (Imipramine). However, In light-dark box test, mice treated with high dose (800 mg/kg/day) spent significant (p < 0.05) time on the light side of the light-dark box similar to positive control DZP. (Veh, 114.40 ± 6.30 s; Acacia 800 mg/kg, 162.2 ± 14.9; DZP 1.0 mg/kg, 184.20 ± 9.24 p < 0.05). The present research propounded that Acacia tortilis leave extract contains some active ingredients with potential anxiolytic activity at low doses and antidepressant and sedative activity at high doses.

Anticonvulsant and neuroprotective effects of the Acacia tortilis growing in KSA.

In different region of Saudi Arabia Acacia tortilis (Fabaceae) is present but still the medicinal properties of Acacia tortilis have not been studied. However, in Zimbabwe different species of Acacia are already used for the treatment of convulsions and dizziness. In the present study, the anticonvulsant and neuroprotective effects of the Acacia tortilis, were evaluated by using different paradigms. For extraction, the leaves of acacia were blended with distilled water at 40°C and filtered. Two different doses of the extracts (400 and 800mg/kg) were administered in the mice once orally (p.o.) and after 30 min occurrence of seizures (strychnine at the dose of 1mg/kg, i.m.) were monitored. In the present work, acute toxicity and neurotoxicity of the extracts were also assessed by inducing hypoxic stress. The Acacia tortilis leaves AAq (400 and 800 mg/kg) produced a dose dependent increase in time of onset of seizures (197.8±32.4 and 338.2±40.6 respectively) when compared with its respective control (184.0±13.8sec). The anticonvulsant effect after administration of AAq (800mg/kg: 338.2±40.6 sec) was more pronounced than diazepam (290.6±1.38 sec). The high dose (800mg/kg) of AAq administered orally prolonged the onset of convulsion and latencies for death following hypoxic stress. The present study suggested that Acacia have anticonvulsant property and may probably be affecting the inhibitory mechanism of glycine. It is also concluded that chemical constituent of acacia might act on BZD or 5-HT(1A) receptor and decrease the oxidative brain membrane damage process induced by psychological/hypoxic stress. Further experiments will be required to identify the active molecules (s) and their mechanism (s) of action.

Hypotensive activity, toxicology and histopathology of opuntioside-I and methanolic extract of Opuntia dillenii.

Methanolic extract of Opuntia dillenii cladodes and its pure compound alpha-pyrone glycoside, opuntioside-I showed potent hypotensive activity in normotensive rats. Both the extract and opuntioside-I showed comparable effect of 44-54% fall in Mean Arterial Blood Pressure (MABP) at the dose of 10 mg/kg. No mortality was observed in rats even at the doses of 1000 mg/kg/d and 900 mg/kg/d per oral of extract and opuntioside-I respectively. However, histopathology revealed adverse effects of high doses on liver and spleen of the experimental animals.