Correlation between a Change of Drug Resistance of <i>Klebsiella pneumonia</i>and Defined Daily Doses of Antimicrobial Agents from 2014 to 2018

Introduction: The prevalence of Klebsiella pneumoniae has rapidly increased in recent years and the distribution differed greatly by region, We aimed to study the relationship between antibiotic resistance and K. pneumoniae, especially carbapenem-resistant Klebsiella pneumoniae (CRKP) in our tertiary hospitals from 2014 to 2018. Methodology: The antibiotic consumption data of K. pneumoniae were expressed as the defined daily dose (DDD) per 100 inpatient days (DDDs). K. pneumoniae which isolated from clinical samples in hospital between January 2014 and December 2018 were retrospectively analyzed, and the correlation between antibiotic resistance rate and antibiotic frequency was analyzed. Results: From 2014 to 2018, a total of 2295 strains of K. pneumoniae were isolated, with the detection rates of 8.2%, 9.2%, 11.9%, 13.4% and 14.0%. There were 423 strains of CRKP, with the detection rates of 7.5%, 5.8%, 17.8% 24.2% and 25.2% respectively. K. pneumoniae showed different degrees of resistance to antibiotics and showed an increasing trend year by year to carbapenems. The resistance rate of imipenem was 2.5%, 2.8%, 9.9%, 12.3%, 13.4%, and the resistance rate of meropenem was 2.0%, 3.0%, 8.8%, 12.6%, 12.7%, respectively. The resistance rate of most other drugs decreased. The DDDs values of cefoperazone/sulbactam, piperacillin-tazobactam and gentamicin showed a strong positive correlation with K. pneumoniae drug resistance rate (r > 0.8, P < 0.05). Conclusions: The detection rate of K. pneumoniae and CRKP increased year by year, which was closely related to the dose of antibiotics. Strengthening the management of antimicrobial drugs and standardising the use of antimicrobial prescriptions were of great significance for delaying the emergence of drug-resistant bacteria.

Basal or bolus dose, which is the key factor in CSII?

Objective: To observe the value of HbA1c level evaluating the total daily basal insulin dose by continuous subcuta- neous insulin infusion (CSII) in 268 patients with type 2 diabetes mellitus. Methods: 5-point capillary blood glucose was moni- tored in pre- and post-CSII and the insulin dose which could stabilize blood glucose was defined as the total daily dose of insulin, including basal and bolus total dose. Correlation between HbA1c level and total daily dose of insulin in patients with type 2 dia- betes mellitus was analyzed. Correlation between HbA1c level and 5-point capillary blood glucose was also analyzed. Results: Obvious correlation was observed between HbA1c level and the basal total daily dose of insulin if HbA1c was more than 9.3% (r=0.635, P<0.05). The average of 5-point capillary blood glucose was best correlated with HbA1c and fasting blood glucose next best. Conclusion: HbA1c level can forecast basal total daily dose of insulin in CSII.

Clinical pharmacists’ involvement in carbapenem antibiotics management at Wenzhou Integrated Hospital

BACKGROUND Carbapenem antibiotics are a pivotal solution for severe infections,particularly in hospital settings.The emergence of carbapenem-resistant bacteria owing to the irrational and extensive use of carbapenems underscores the need for meticulous management and rational use.Clinical pharmacists,with their specialized training and extensive knowledge,play a substantial role in ensuring the judicious use of carbapenem.This study aimed to elucidate the patterns of carbapenem use and shed light on the integral role played by clinical pharmacists in managing and promoting the rational use of carbapenem antibiotics at Wenzhou Integrated Traditional Chinese and Western Medicine Hospital.AIM To analyze carbapenem use patterns in our hospital and role of clinical pharmacists in managing and promoting their rational use.METHODS We performed a retrospective analysis of carbapenem use at our hospital between January 2019 and December 2021.Several key indicators,including the drug utilization index,defined daily doses(DDDs),proportion of antimicrobial drug costs to total hospitalization expenses,antibiotic utilization density,and utilization rates in different clinical departments were comprehensively analyzed.RESULTS Between 2019 and 2021,there was a consistent decline in the consumption and sales of imipenem-cilastatin sodium,meropenem(0.3 g),and meropenem(0.5 g).Conversely,the DDDs of imipenem-cilastatin sodium for injection increased in 2020 and 2021 vs 2019,with a B/A value of 0.67,indicating a relatively higher drug cost.The DDDs of meropenem for injection(0.3 g)exhibited an overall upward trend,indicating an increasing clinical preference.However,the B/A values for 2020 and 2021 were both>1,suggesting a relatively lower drug cost.The DDDs of meropenem for injection(0.5 g)demonstrated a progressive increase annually and consistently ranked first,indicating a high clinical preference with a B/A value of 1,signifying good alignment between economic and social benefits.CONCLUSION Carbapenem use in our hospital was generally reasonable with a downward trend in consumption and sales over time.Clinical pharmacists play a pivotal role in promoting appropriate use of carbapenems.

Ground level utility of Access, Watch, Reserve classification: Insights from a tertiary care center in North India

BACKGROUND The overuse and misuse of antimicrobials contribute significantly to antimicrobial resistance(AMR),which is a global public health concern.India has particularly high rates of AMR,posing a threat to effective treatment.The World Health Or-ganization(WHO)Access,Watch,Reserve(AWaRe)classification system was introduced to address this issue and guide appropriate antibiotic prescribing.However,there is a lack of studies examining the prescribing patterns of antimi-crobials using the AWaRe classification,especially in North India.Therefore,this study aimed to assess the prescribing patterns of antimicrobials using the WHO AWaRe classification in a tertiary care centre in North India.Ophthalmology,Obstetrics and Gynecology).Metronidazole and ceftriaxone were the most prescribed antibiotics.According to the AWaRe classification,57.61%of antibiotics fell under the Access category,38.27%in Watch,and 4.11%in Reserve.Most Access antibiotics were prescribed within the Medicine department,and the same department also exhibited a higher frequency of Watch antibiotics prescriptions.The questionnaire survey showed that only a third of participants were aware of the AWaRe classification,and there was a lack of knowledge regarding AMR and the potential impact of AWaRe usage.RESULTS The research was carried out in accordance with the methodology presented in Figure 1.A total of n=123 patients were enrolled in this study,with each of them receiving antibiotic prescriptions.The majority of these prescriptions were issued to inpatients(75.4%),and both the Medicine and Surgical departments were equally represented,accounting for 49.6%and 50.4%,respectively.Among the healthcare providers responsible for prescribing antibiotics,72%were Junior Residents,18.7%were Senior Residents,and 9.3%were Consultants.These findings have been summarized in Table 1.The prescriptions included 27 different antibiotics,with metronidazole being the most prescribed(19%)followed by ceftriaxone(17%).The mean number of antibiotics used per patient was 1.84±0.83.The mean duration of antibiotics prescribed was 6.63±3.83 days.The maximum number of antibiotics prescribed per patient was five.According to the AWaRe classification,57.61%of antibiotics fell under the Access,38.27%in Watch,and 4.11%in Reserve categories,suggesting appropriate antibiotic selection according to these criteria.The distribution of antibiotics prescribed according to the WHO AWaRe categories is presented in Figure 2.The difference in prescribing frequencies amongst departments can be noted.Most of the antibiotics prescribed in the Access category were from the Medicine department(75.4%),followed by Surgery(24.6%).For Watch antibiotics,Medicine had a higher proportion(63.4%)compared to Surgery(36.6%).In terms of seniority,Junior Residents prescribed the highest number of antibiotics for both Access and Watch categories in Medicine and Surgery departments.Senior residents and Consultants prescribed a lower number of antibiotics in all categories and departments.Only a few antibiotics were prescribed in the Reserve category,with most prescriptions being from the Medicine department.The study also evaluated the Knowledge and Awareness of Healthcare professionals towards the WHO AWaRe classi-fication through a questionnaire survey.A total of 93 participants responded to the survey.Among them,most parti-cipants were Junior Residents(69.9%),followed by Senior Residents(25.8%)and Faculty(4.3%).When enquired if they knew about the WHO AWaRe classification only 33.3%of the participants responded positively.Of those who were aware of the AWaRe classification,the most common source of information was the internet(31.2%),followed by the antimicrobial policy of their institution(15.1%)as seen in Table 2.The survey results on the knowledge and awareness of AMR among healthcare professionals are also presented in Tables 3 and 4.Out of the 93 participants,68(73.1%)agreed that the emergence of AMR is inevitable,while only 13(14.0%)disagreed that AWaRe usage will result in the inability to treat serious infections.Additionally,58(62.4%)agreed that it will lead to lengthier hospital stays,43(46.2%)agreed that the success of chemotherapy and major surgery will be hampered,and the majority also agreed that its use will lead to increased cost of treatment and increased mortality rates.Regarding the utilization of AWaRe in the hospital summarized in Tables 4 and 5,35.5%of the participants agreed that it should be used,while only 2.2%disagreed.Additionally,34.4%agreed that AWaRe reduces adverse effects of inappro-priate prescription.However,37.6%of the participants considered that AWaRe threatens a clinician's autonomy and 30.1%thought that its use can delay treatment.Additionally,the DDD of each drug was also evaluated.The usage of various antimicrobial drugs in a hospital setting,along with their daily doses and DDD according to the WHO's Anatomical Therapeutic Chemical classification system was calculated.Some of the important findings include high usage rates of ceftriaxone and metronidazole,and relatively low usage rates of drugs like colistin and clindamycin.Additionally,some drugs had wider ranges than others.Comparison of WHO defined DDD with Daily Drug dose(Mean)in the studied prescriptions is represented in the Clustered Bar chart in Figure 3.Finally,the Mean Daily Drug Dose for prescribed drugs was compared with WHO defined DDD for each drug using a Student’s T test.The mean daily drug dose of amoxy/clav was significantly higher than the WHO DDD(1.8 vs 1.50,P=0.014),while the mean daily drug dose of metronidazole and doxycycline were significantly lower than the WHO DDD(P<0.001 and P=0.008,respectively).The mean daily drug dose of piperacillin/tazobactam,amikacin,clindamycin,and levofloxacin did not show significant differences compared to the WHO DDD(P>0.05).CONCLUSION This research indicates an appropriate proportion of prescriptions falling under the Access category(57.61%),suggesting appropriate antibiotic selection,a significant proportion also belongs to the Watch category(38.27%),emphasizing the need for greater caution to prevent the escalation of AMR.There is a moderate level of awareness among healthcare professionals about AMR and the steps being taken to tackle it,highlighting the gap in implementation of policies and need for more steps to be taken in spreading the knowledge about the subject.However,there is a significant difference between the WHO DDD and the prescribed daily dose in the analysed prescriptions suggesting overuse and underuse of antibiotics.

Poor awareness of preventing aspirin-induced gastrointestinal injury with combined protective medications

AIM:To investigate prescribing pattern in low-dose aspirin users and physician awareness of preventing aspirin-induced gastrointestinal(GI) injury with combined protective medications.METHODS:A retrospective drug utilization study was conducted in the 2nd Affiliated Hospital,School of Medicine,Zhejiang University.The hospital has 2300 beds and 2.5 million outpatient visits annually.Data mining was performed on all aspirin prescriptions for outpatients and emergency patients admitted in 2011.Concomitant use of proton-pump inhibitors(PPIs),histamine 2-receptor antagonists(H2RA) and mucoprotective drugs(MPs) were analyzed.A defined daily dose(DDD) methodology was applied to each MP.A further investigation was performed in aspirin users on combination use of GI injurious medicines [non-steoid anti-inflammatory drugs(NSAIDs),corticosteroids and clopidogrel and warfarin] or intestinal protective drugs(misoprostol,rebamipide,teprenone and gefarnate).Data of major bleeding episodes were derived from medical records and adverse drug reaction monitoring records.The annual incidence of major GI bleeding due to low-dose aspirin was estimated for outpatients.RESULTS:Prescriptions for aspirin users receiving PPIs,H2RA and MPs(n = 1039) accounted for only 3.46% of total aspirin prescriptions(n = 30 015).The ratios of coadministration of aspirin/PPI,aspirin/H2RA,aspirin/MP and aspirin/PPI/MP to the total aspirin prescriptions were 2.82%,0.12%,0.40% and 0.12%,respectively.No statistically significant difference was observed in age between patients not receiving any GI protective medications and patients receiving PPIs,H2RA or MPs.The combined medication of aspirin and PPI was used more frequently than that of aspirin and MPs(2.82% vs 0.40%,P < 0.05) and aspirin/H2RA(2.82% vs 0.12%,P < 0.05).The values of DDDs of MPs in descending order were as follows:gefarnate,hydrotalcite > teprenone > sucralfate oral suspension > L-glutamine and sodium gualenate granules > rebamipide > sucralfate chewable tablets.The ratio of MP plus aspirin prescriptions to the total MP prescriptions was as follows:rebamipide(0.47%),teprenone(0.91%),L-glutamine and sodium gualenate granules(0.92%),gefarnate(0.31%),hydrotalcite(1.00%) and sucralfate oral suspension(0.13%).Percentages of prescriptions containing aspirin and intestinal protective drugs among the total aspirin prescriptions were:rebamipide(0.010%),PPI/rebamipide(0.027%),teprenone(0.11%),PPI/teprenone(0.037%),gefarnate(0.017%),and PPI/gefarnate(0.013%).No prescriptions were found containing coadministration of aspirin and other NSAIDs.Among the 3196 prescriptions containing aspirin/clopidogrel,3088(96.6%) prescriptions did not contain any GI protective medicines.Of the 389 prescriptions containing aspirin/corticosteroids,236(60.7%) contained no GI protective medicines.None of the prescriptions using aspirin/warfarin(n = 22) contained GI protective medicines.Thirty-five patients were admitted to this hospital in 2011 because of acute hemorrhage of upper digestive tract induced by low-dose aspirin.The annual incidence rates of major GI bleeding were estimated at 0.25% for outpatients taking aspirin and 0.5% for outpatients taking aspirin/warfarin,respectively.CONCLUSION:The prescribing pattern of low-dose aspirin revealed a poor awareness of preventing GI injury with combined protective medications.Actions should be taken to address this issue.

Assessment of Erythemal UV Level in Nepal Based on Solar UV Estimates from Total Ozone Mapping Spectrometer

Nepal lies on the southern slope of Himalaya in Asia. In a width ranging between 150 and 250 km, the altitude varies greatly from about 100 m at its southern border to a maximum of 8848 min the northern part. Like the variation in altitude, climatic condition varies quite a lot. Long-term monthly mean erythemal UV daily dose values for Nepal are evaluated using Total Ozone Mapping Spectrometer （TOMS） estimation from the time of its overpass between 1996 and 2003. The results are presented as summer and winter maps of mean UV levels in each satellite grid. The mean winter erythemal UV daily dose ranges between 2.1 and 3.6 kJ m-2 whereas summer values are found to lie between 4.6 and 9.7 kJ m-2. The altitude variation increases the UV levels by about 0.2 kJ km-1 in winter months, and 0.9 kJ km-1 in summer. A multiyear monthly average erythemal daily dose in most of the areas shows that the summer value is about three times higher than that in winter. Although year-to-year variation is not pronounced in high- and mid-elevation regions, UV levels seemed to decrease from 1997 to 2002 in the southern part of the country in the low elevation region by about 5.35%. Due to the combined effects of the altitude, low ozone concentration in the troposphere, and thin air, surface UV radiation at higher altitudes is found to be higher than in the surrounding regions.

Treatment of genotype 2 and 3 chronic hepatitis C virus-infected patients

AIM： Before pegylated interferon alpha （IFN） was introduced for the therapy of chronic hepatitis C virus （HCV）-induced hepatitis, conventional thrice weekly IFN therapy was supplemented by ribavirin. Also, at that time, higher and more frequent doses of IFN were expected to be more effective than the standard regimen of 3 MU thrice weekly. As ribavirin significantly increases side effects and negatively influences the quality of life particularly in young patients, we started a prospective non-randomized study with a daily IFN-2a monotherapy as an initial treatment for chronic hepatitis C. METHODS： Forty-six consecutive chronic HCV-infected patients received 3 MU IFN-2a per day as an initial treatment. Patients with genotype 2 or 3 （n = 12） were treated for 24 wk, and patients with genotypes other than 2 or 3 （n = 34） for 48 wk. Treatment outcome was followed up for 48 wk after the end of treatment （EOT）. Virological response was defined as the absence of detectable serum HCV-RNA. Patients without virological response at 12 wk after the start of treatment received low-dose ribavirin （10 mg（kg·d）） additionally. RESULTS： During treatment, three genotype 3 patients were excluded from the study due to incompliance. The remaining patients （n = 9） infected with genotype 2 or 3 showed an initial virological response rate of 100%. Six patients （66.7%） were still found to be virus-free at the end of follow-up period. In these patients, initial virological response was evident already after 2 wk of treatment. In contrast, initial virological response occurred first after 4 wk of treatment in the three patients who relapsed （33.3%）. In comparison, patients infected with genotypes other than 2 or 3 （n = 34） showed an initial virological response rate of only 23.5% （n = 8）, and even in combination with ribavirin a sustained virological response （SVR） rate of only 11.8% （n = 4） could be achieved. CONCLUSION： In chronic HCV-infected patients with genotype 2 or 3, a SVR can be expected after 24 wk of daily dose IFN-2a treatment without ribavirin, if initial virological response develops early. This finding is worth to be confirmed in a prospective randomized study with pegylated IFN.

Vitamin D in Food Supplements:Labeling Survey

An adequate vitamin D(vitD)intake(Recommended Daily Allowance,RDA=5μg)is crucial for health maintenance and its deficiency is associated with several health problems.The increase in hypovitaminosis D cases and the proliferation of food supplements(FS)that are easily accessible by the population,have led to an unrestrained chronic consumption of FS.VitD may accumulate in the body and originate toxicity(Tolerable Upper Limit,UL=100μg).The aim of this study was to evaluate if daily vitD doses mentioned in FS labels are in conformity with RDA.210 solid and liquid FS(for pediatrics and adults)sold in Portuguese pharmacies,supermarkets,health shops and on the internet were examined for indicated daily intake of vitD and compared to RDA and UL values.51.43%of FS have values higher than RDA,8.57%higher than UL.The average vitD daily dose in FS is 24.48μg,with a high variability between samples(0.25-250μg).Majority of FS labels recommend vitD daily doses above RDA and some even above UL,regardless of being for adults or children.Therefore,it is crucial that vitD dose in FS is reviewed to ensure the safety of these products.

Short-term intravenous interferon therapy for chronic hepatitis B

AIM:To investigate the therapeutic efficacy of short- term, multiple daily dosing of intravenous interferon (IFN) in patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B. METHODS:IFN-β was intravenously administered at a total dose of 102 million international units (MIU) over a period of 28 d in 26 patients positive for HBeAg and HBV-DNA. IFN-beta was administered at doses of 2 MIU and 1 MIU on d 1, 3 MIU twice daily from d 2 to d 7, and 1 MIU thrice daily from d 8 to d 28. Patients were followed up for 24 wk after the end of treatment. RESULTS:Six months after the end of the treatment, loss of HBV-DNA occurred in 13 (50.0%) of the 26 patients, loss of HBeAg in 9 (34.6%), development of anti-HBe in 10 (38.5%), HBeAg seroconversion in 8 (30.8%), and normalization of alanine aminotransferase (ALT) levels in 11 (42.0%). CONCLUSION:This 4-wk long IFN-β therapy, which was much shorter than conventional therapy lasting 12 wk or even more than 1 year, produced therapeutic effects similar to those achieved by IFN-α or pegylated- IFN-α (peg-IFN). Fewer adverse effects, greater efficacy, and a shorter treatment period led to an improvement in patients’ quality of life. IFN-β is administered intravenously, whereas IFN-α is administered intramuscularly or subcutaneously. Because both interferons are known to bind to an identical receptor and exert antiviral effects through intracellular signal transduction, the excellent results of IFN-β found in this study may be attributed to the multiple doses allowed by the intravenous route.

Environmental contamination and health hazard of lead and cadmium around Chatian mercury mining deposit in western Hunan Province,China

A field survey concerning lead and cadmium pollution in environment mediums and hair samples around the Chatian mercury mining deposit in western Hunan Province,China,was conducted to preliminarily evaluate their health hazard to local inhabitants.The results show that mining wastes,especially tailing,contain high cadmium level with the maximum of 79.92μg/g. High levels of lead and cadmium are accumulated in surface water and paddy soil,respectively,and both metals pollution occurs in brown rice.The average daily intake dose(ADD)of lead for local adults via three routes reaches up to 7.7μg/(kg·d),exceeding the provision tolerable daily intake by JECFA of 3.5μg/(kg·d),and drinking water exposure route contributes the highest daily intake.As an indicator for heavy metal exposure,the hair of local population contains Pb(5.06±3.02)μg/g.The average daily intake dose of cadmium for adults is 0.119μg/(kg·d).More attention must be paid on health risk from lead pollution compared with cadmium.

Sources and Deficiency Diseases of Mineral Nutrients in Human Health and Nutrition:A Review

Mineral nutrients are fundamentally metals and other inorganic compounds. The life cycle of these mineral nutrients begins in soil, their primary source. Soil provides minerals to plants and through the plants the minerals go to animals and humans; animal products are also the source of mineral nutrients for humans. Plant foods contain almost all of the mineral nutrients established as essential for human nutrition. They provide much of our skeletal structure, e.g., bones and teeth. They are critical to countless body processes by serving as essential co-factors for a number of enzymes. Humans can not utilize most foods without critical minerals and enzymes responsible for digestion and absorption. Though mineral nutrients are essential nutrients, the body requires them in small, precise amounts. We require them in the form found in crops and they can be classified into three different categories： major, secondary, and micro or trace minerals. This classification is based upon their requirement rather than on their relative importance. Major minerals such as potassium （K） and phosphorus （P） are required in amounts of up to 10 g d-1. The daily requirement of secondary and micro minerals ranges from 400 to 1 500 mg d-1 and 45 ~tg d-1 to 11 mg d-1, respectively. To protect humans from mineral nutrient deficiencies, the key is to consume a variety of foods in modest quantities, such as different whole grains, low fat dairy, and different meats, vegetables and fruits. For insurance purposes, a supplement containing various mineral nutrients can be taken daily.

Occurrence and impact of polychlorinated dibenzo-p-dioxins/dibenzofurans in the air and soil around a municipal solid waste incinerator

To assess the influence of polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans（PCDD/Fs） on the environment in the vicinity of municipal solid waste incinerators（MSWIs）, we determined the levels of PCDD/Fs in air and soil samples collected around a MSWI, which is the largest in China. The International Toxicity Equivalency Quantity（I-TEQ） concentrations of PCDD/Fs in air samples were from 0.0300 to 1.03 pg I-TEQ/m^3（0.445–13.6 pg/m^3）, with an average of 0.237 pg I-TEQ/m^3, while in soil samples they ranged from 0.520 to 3.40 pg I-TEQ/g（2.41–88.7 pg/g） with an average of1.49 pg I-TEQ/g. The concentrations of PCDD/Fs in air and soil samples were comparable to other areas, and Pe CDFs were the dominant contributors, which was different from stack gas homologue patterns. Multivariate statistical analysis showed that PCDD/Fs emission from the MSWI did not directly affect the profiles of PCDD/Fs in air and soils, so that vehicles and unidentified emission sources should be considered. The daily inhalation levels of PCDD/Fs for children（0.0110 to 0.392 pg I-TEQ/（kg·day） and adults（0.00600 to 0.221 pg I-TEQ/（kg·day） near the MSWI were lower than the tolerable daily intake of 1.00 to 4.00 pg WHO-TEQ/（kg·day）, but in winter the values were higher than in summer. These results can be used as basic data for assessing the risk of PCDD/Fs exposure in residents living around this MSWI, and more monitoring programs and studies should be carried out around MSWIs.