prospective study to assess vancomycin serum concentrations in pediatric patients with current dosing guidelines

Concerns about increasing bacterial resistance to vancomycin, have caused the adult treatment guidelines to recommend higher trough concentrations based on the type and location of infectious disease. Although these recommendations are not specific to children, the values can be extrapolated. This prospective study was designed to evaluate efficacy of current vancomycin dosing recommendations to achieve therapeutic trough serum concentration in pediatric patients. Laboratory data, vancomycin dosing and subsequent serum concentrations of children in a community teaching pediatrics hospital were collected and analyzed. Trough serum levels were determined at steady state and compared with Infectious Disease Society of America [IDSA] 2011 guidelines for the treatment of Methicillin-Resistant Staphylococcus Aureus [MRSA] infections. In a prospective observational, cross-sectional study in a university medical center in Tehran, Iran, 50 patients, who received vancomycin for more than 4 doses, were recruited and their trough vancomycin level was determined. The mean age and creatinine clearance of patients were 5.47 +/- 4.24 and 87.5 +/- 31.25, respectively. Eleven [22%] patients received vancomycin at 40 mg/kg/day [low dose] and 39 [78%] at 60 mg/kg/day [high dose]. Considering trough goals of 10-14 and 15-20mg/L in low and high dose groups, serum levels in 91% [73% sub-therapeutics] and 85% [69% sub-therapeutics] of patients were not in recommended therapeutic range, respectively. This study has shown that current recommended vancomycin dosing regimens in pediatric patients [40-60 mg/kg/day], resulted in sub-therapeutic serum concentrations in our study population

randomized placebo-controlled trial of clonidine impact on sedation of mechanically ventilated ICU patients

Clonidine has sedative and analgesic properties. Randomized studies examining these properties in mechanically ventilated ICU patients are scarce. This study was designed to assess the impact of clonidine on sedative agent use in mechanically ventilated patients. In a prospective, randomized, double blind, placebo-controlled study in a general ICU of a university medical center in Tehran, Iran, 40 patients, over 18 years on mechanical ventilation for 3 days or more randomized into 2 equal groups of clonidine and placebo. Clonidine arm received usual sedation and enteral clonidine 0.1 mg TID and escalated to 0.2 mg TID on the second day if hemodynamics remained stable. Ramsay Sedation Score was used to assess sedation. Opioids and midazolam were used in all patients. 10 patients in clonidine and 3 in placebo arms had history of drug abuse [P = 0.018]. The mean of sedatives used in the clonidine/placebo arms [mg/day] were; MED [Morphine Equivalent Dose] 91.4 +/- 97.9/112.1 +/- 98.8 P=0.39, midazolam 7.1 +/- 7.9/8.3 +/- 9.2 P=0.66 and propofol 535.8 +/- 866.7/139.1 +/- 359.9 P=0.125. After adjusting for addiction and propofol, clonidine reduced MED use by 79.6 mg/day [P=0.005] and midazolam by 5.41 mg/day [P = 0.05]. Opioids and midazolam need reduced by clonidine co-administration regardless of history of drug abuse. Acceptable side effect profile and the lower cost of clonidine could make it an attractive adjunct to sedative agents in ICU

efficacy of gabapentin in patients with central post-stroke pain

Thalamic pain syndrome, a type of central post-stroke pain [CPSP], may develops after a hemorrhagic or ischemic stroke and results in impairment of the thalamus. There is limited experience about gabapentin in treatment of central pains like CPSP. In a prospective observational study, the intensity of pain was recorded using the Numeric Rating Scale [NRS] at the entrance to the study. Patients eligible for treating with gabapentin, received gabapentin 300 mg twice-daily. The pain intensity was measured at entrance to the study and after one month using NRS. Decrease of 3 points from the initial NRS considered being clinically significant. From a total of 180 primarily screened patients, 84 [44 men and 40 women] were recruited. There was a significant difference between pre-treatment and post-treatment NRS [5.9 +/- 2.51 vs. 4.7 +/- 3.01; 95% CI: 0.442-1.962, p = 0.002]. Fisher›s exact test showed no statistically significant effect of clinical and demographic characteristics of patients on their therapeutic response to gabapentin. Given the safety, efficacy, well tolerability and lack of interaction with other drugs we suggest gabapentin to be more considered as a first line therapy or as add-on therapy for reducing the pain severity in patients with thalamic syndrome

Study of the neuroprotective effects of memantine in patients with mild to moderate ischemic stroke

Ischemic stroke is amongst the top four causes of mortality and the leading cause of disability in the world. The aim of this study was to evaluate the efficacy of a high dose memantine on neurological function of patients with ischemic stroke. In a randomized. 2 armed, open-label study, patients with mild to moderate cerebral thromboembolic event [CTEE] who admitted to Imam Hossein Hospital. Tehran. Iran, during preceding 24 hours, entered the study. Patients allocated in two study groups of memantine [as add-on therapy] and control. All patients were managed based on the American Heart Association and American Stroke Association [AHA/ASA] guidelines. Patients in memantine group received conventional treatment plus memantine 20 mg TID. The National Institute of Health Stroke Scale [NIHSS] was determined and recorded daily. The primary objective was comparison of the changes in NIHSS in the study groups at day 1 and day 5 of intervention. Significance level of p<0.05 was considered for statistical analysis. Patients were randomly allocated in control [15 women and 14 men, age 70.78 +/- 10.92 years] and memantine [16 women and 8 men, age 73.33 +/- 9.35 years] groups. There were no significant differences in age and sex distribution of two study groups as well as in comorbidities and concurrent drugs. NIHSS changes were significantly different between control [1.24 +/- 0.96] and memantine group [2.96 +/- 0.1], [p < 0.0001]. Our results reveal that memantine added to standard treatment of CTEE could result in a remarkable decrease in the NIHSS confirming improvement of the neurological function of the patients

Magnesium sulfate in exacerbations of COPD in patients admitted to internal medicine ward

The purpose of this study was to examine the effect of intravenous magnesium sulfate on patients with COPD exacerbation requiring hospitalization. In this randomized clinical trial 30 patients with COPD exacerbation were studied. Patients were randomly assigned to group A [case] who concurrent with standard therapy received 2 g magnesium sulfate in normal saline infused in 20 minutes on days one to three and group B [control] who received standard medications and placebo. PEFR and FEV1 were measured by before, 45 minutes and third day of entering the study. Vital signs HR, BP, RR, temperature and SpO2 were monitored during hospitalization. 21 males and 9 females patients with mean age of 68 +/- 9 years, case 67 +/- 10 and control 70 +/- 8 were studied [15 patients in each arm of study]. The mean pretreatment FEV1 was 26% +/- 12, and 35% +/- 18 in case and control groups respectively [P=0.137]. FEV1 after 45 minutes in case group was 27% +/- 9 and control group 36% +/- 20 [p=0.122]. FEV1 after 3 days of study was 32% +/- 17 in case and 41% +/- 22 in control groups [P=0.205]. The mean pretreatment PEFR was 126 +/- 76 l/min in case and 142 +/- 62 l/min in control groups [P=0.46]. Changes in PEFR were not significant 45 min [p=0.540] and 3 days [p=0.733] of the administration of intravenous magnesium sulfate. Duration of hospital stay between the two groups did not show any significant difference. This study showed that administration of intravenous magnesium sulfate in hospitalized patients with COPD exacerbation neither revealed any significant bronchodilating effect nor reduced duration of hospital stay

Comparative study of intravenous paracetamol and fentanyl for pain management in ICU

Pain in ICU patients should be managed effectively and safely. Fentanyl and Paracetamol are used frequently in ICU. However experience using IV Paracetamol in the setting of critically ill patients is limited. We evaluated the analgesic effect and adverse reactions of intravenous Paracetamol compared to Fentanyl in ICU patients with mild to moderate pain. Forty patients in a general ICU were randomized into two groups of IV Paracetamol and IV Fentanyl in a single blinded fashion. Pain was assessed by Visual Analogue Scale [VAS] before drug administration and six hourly for 48 h of 1 g IV Paracetamol every 6 h for 48 h in the first group and 25 [micro]g Fentanyl intravenously every three hours for 48 h in the second group. Patients were monitored for significant adverse reactions particularly of CNS and hepatic nature. Results showed the age, sex and pain score before analgesia was matched in both groups. Pain scores were similar in both groups at 24 h 2.60 [+/- 1.2] and 2.40 [+/- 1.5] and at 48 h 2.25 [+/- 0.96] and 2.05 [+/- 1.1] in Paracetamol and Fentanyl groups respectively. Clinical and laboratory adverse reactions were also similar in both groups. The analgesic properties of Paracetamol and Fentanyl were similar in this study. We did not observe any significant adverse effects in the two groups. Clinical and laboratory findings including liver functions remained without any statistically significant difference in two groups. This study demonstrates intravenous Paracetamol may be as safe and effective as Fentanyl in ICU patients with mild to moderate pain

Potential drug-drug interactions in post-CCU of a teaching hospital

Drug-drug interactions [DDIs] can lead to increased toxicity or reduction in therapeutic efficacy. This study was designed to assess the incidence of potential drug interactions [PDI] and rank their clinical value in post coronary care unit [Post-CCU] of a teaching hospital in Tehran, Iran

In this prospective study, three pharmacists with supervision of a clinical pharmacist actively gathered necessary information for detection of DDIs. Data were tabulated according to the combinations of drugs in treatment chart. Verification of potential drug interactions was carried out using the online Lexi-Interact[TM] 2011

A total of 203 patients [113 males and 90 females] were enrolled in the study. The mean age of patients was 61 +/- 12.55 years [range = 26-93]. A total of 90 drugs were prescribed to 203 patients and most prescribed drugs were atorvastatin, clopidogrel and metoprolol. Mean of drugs was 11.22 per patient. A total of 3166 potential drug interactions have been identified by Lexi- Interact[TM], 149 [4.71%] and 55 [1.73%] of which were categorized as D and X, respectively. The most serious interactions were clopidogrel+omeprazole and metoprolol+salbutamol

Drug interactions leading to serious adverse effects are to be cautiously watched for when multiple drugs are used simultaneously. In settings with multiple drug use attendance of a pharmacist or clinical pharmacist, taking the responsibility for monitoring drug interactions and notifying the physician about potential problems could decrease the harm in patient and increase the patient safety

Resistance to clopidogrel among Iranian patients undergoing angioplasty intervention

To study the resistance to standard dosage of clopidogrel among Iranian patients following percutaneous coronary intervention measured by platelet aggregation test

Patients undergoing percutaneous coronary intervention in Imam Hussein Medical center, Tehran, Iran, who were under treatment with aspirin, but had no history of clopidogrel usage, entered the study. Patients received standard dosage of clopidogrel [Plavix®, Sanofi, France, 600 mg loading dose and 75 mg/day afterward]. Platelet aggregation was measured using light transmission aggregometer. The response to the drug was categorized as complete resistance [platelet aggregation decreased less than 10%], intermediate resistance [platelet aggregation decreased between 10 to 30%] and complete response [platelet aggregation decreased to 30% or more]. All patients were evaluated for major adverse cardio vascular events one month after the angioplasty based on MACE criteria by phone contact

Thirty-one patients with a mean age of 59 +/- 13 entered the study. Sixty-five percent of patients showed complete response to clopidogrel [95% CI: 45% to 81%], 22% showed intermediate resistance [95% CI: 10-41%] and 13% showed complete resistance [95% CI: 4-30%]. One month after the angioplasty, no major adverse cardiovascular event was recorded

Based on our findings, it seems that there is no major difference between Iranian population and other studies regarding the resistance to clopidogrel. Due to the limited number of participants in our study, further investigations with higher number of patients are recommended to more precisely calculate the percentage of resistance among Iranian patients

Carbapenem restriction and its effect on bacterial resistance in an intensive care unit of a teaching hospital

Development of antibiotic resistance in Intensive Care Units [ICUs] is a worldwide problem. The purpose of this study was to evaluate the effect of an antibiotic stewardship program [ASP] by carbapenems restriction on gram-negative antimicrobial resistance in ICU. The study was designed in a 21 bedded general ICU of a teaching hospital with two wings [one and two] in Tehran, Iran. Carbapenem prescription in ICU1 was restricted to only the culture proven multi-drug-resistant bacteria with the absence of sensitivity to other antimicrobial agents. Carbapenem had to be prescribed by a trained ICU physician with close consultation with infectious disease specialist and the clinical pharmacist posted in ICU. Post-prescription reviews and de-escalations were carried out by the same team on regular basis. Restriction policy was commenced in January 2011 in ICU1. All documented infections and resistance patterns of isolated pathogens were recorded in both ICUs during two periods of 6 months before and 9 months after restriction policy implementation. During this study bacterial growth was detected in 51.5% of 1601 samples. Carbapenem administration was decreased from 6.86 to 2.75 DDD/100 patients day [60% decreases] pre-restriction and post-restriction respectively. Significant increase in sensitivity of pseudomonas to imipenem was observed in ICU1 comparing with pre-restriction period six months post restriction [p = 0.000]. Sensitivity of Klebsiella and Acinetobacter to imipenem did not change significantly during the study period. Our study demonstrated that restriction of carbapenems can increase sensitivity of P. aeroginosa to imipenem

Methacoline challenge test as an evaluator of response to statins in bronchial hyperresponsiveness

3-hydroxy-3-methylglutaryl-CoA reductase inhibitors [statins], are effective serum cholesterol-lowering agents which also have anti-inflammatory properties. The objective of this study was to evaluate the effect of atorvastatin on bronchial hyperresponsiveness. Adult patients [age 14 to 65 years] with bronchial hyperresponsiveness [BHR] diagnosis based on the spirometry with methacholine challenge test were entered into the study. The study was conducted in the National Research Institute of Tuberculosis and Lung Disease. Patients were randomized to receive either atorvastatin 20 mg/day or placebo for 4 weeks. Spirometric parameters were determined at baseline and at completion of the study. Twenty two patients with the age of 32.95 +/- 10.30 years completed the trial. Changes in airway responsiveness categories [moderate to severe, mild, borderline, normal] after the intervention were not significant in atorvastatin group as in placebo group [p-value= 0.131 for atorvastatin group and p-value = 0.305 for placebo group]. Also, changes in methacholine solution number [different concentrations of methacholine] which caused at least 20% decrease in FEV1 were not significant between groups [p-value = 0.089]. Although we could not find a significant difference, the patients' fall in FEV1 in atorvastatin group was observed in higher concentrations of methacholine. Median before treatment versus after treatment in atorvastatin group was 1 versus 4 mg/mL, while those were 2 versus 1 mg/mL in placebo group. This study showed a better but not significant hyperresponsiveness control in the treatment group. The result might be presented more pronounced, if we could increase the sample size