Intra-operative drug level monitoring of pre-operative antibiotic for surgical prophylaxis in the patients of elective spinal surgery.

OBJECTIVES: Single dose prophylaxis is good enough for general surgery with low risk patients. However, the evidence for the effectiveness of single dose anti-microbial prophylaxis (AMP) is not conclusive in high risk patients and spinal surgeries requiring instrumentation or the use of implants in particular. No studies have explored the various concentration of ceftriaxone in plasma and tissue as well during an ongoing spinal surgery. Therefore, the objective of study was to correlate the serum and tissue concentrations of ceftriaxone with the SSI and identify patients with increased risk of SSI. METHODS: It was an open label prospective study in 50 consecutive patients who underwent elective spine surgery under prophylactic cover of ceftriaxone. Serum and tissue concentration were estimated by high pressure liquid chromatography during the ongoing surgery. RESULTS: Subjects were observed for any post-operative complications including SSI. Serum (p=0.002) and tissue (p=0.012) concentrations of ceftriaxone at the closure of spinal surgery were associated with SSI. Duration of the surgery (p=0.04) and use of implants (p=0.02) were also important surgery related risk factors. CONCLUSIONS: Serum and tissue concentrations of ceftriaxone at the closure and duration of surgery and instrumentation or use of implants in the spinal surgery are good predictors of SSI.

Variability in the serum and tissue concentrations of pre-incisional ceftriaxone for surgery in paediatric population and outcome of surgical-site infections; An open labelled, prospective, non-randomized, analytical study.

Studies have determined the serum concentration of ceftriaxone in the adult population, but there are only a few studies that measured the tissue concentrations. However, no studies have concurrently evaluated the serum and tissue concentrations of ceftrixaone in elective pediatric surgery patients. Therefore, our study was planned to evaluate the serum and tissue concentrations of single dose intravenous prophylactic ceftriaxone intra-operatively during an ongoing pediatric surgery and the outcome of surgical-site infections (SSIs). We did a correlation analysis to determine the relationship of various concentrations and surgery related risk factors with the outcome of SSIs. It was an open label prospective study in 50 patients who underwent elective pediatric surgery under prophylactic cover of ceftriaxone. Serum and tissue concentration were estimated by High Pressure Liquid Chromatography (HPLC). Subjects were observed for post operative complications including SSI. Serum and tissue concentrations of ceftriaxone were significant at test value of 4 â€‹mg/L. Tissue concentrations of ceftriaxone at incision (p â€‹= â€‹0.02) and closure (p â€‹= â€‹0.04) were significantly correlated with SSI but there was no significant association. The measured serum ceftriaxone concentrations were more than 20 times the susceptible minimum inhibitory concentration (MIC) at any given point of the surgery. On the other hand, this target level was achieved at the tissue levels in the majority of the patient. The factors associated with SSI were duration of surgery, wound category of contaminated clean type, the use of urinary catheter and implants in the surgery. An intra-operative re-dose, extension of dose or addition of another antibiotic may be considered for such patients.

Steady-state pharmacokinetic and pharmacodynamic profiling of colistin in critically ill patients with multi-drug-resistant gram-negative bacterial infections, along with differences in clinical, microbiological and safety outcome.

Limited data are present regarding the steady-state pharmacokinetics and pharmacodynamics of colistin in critically ill patients suffering from multi-drug-resistant gram-negative bacterial (MDR-GNB) infections. We aimed to profile the steady-state pharmacokinetics and pharmacodynamics of colistin in critically ill patients with MDR-GNB infections, along with determining the predictors that could influence the clinical, microbiological and safety outcome. We recruited 30 critically ill patients suffering from MDR-GNB infections in our prospective open-label study. Intravenous colistimethate sodium (CMS) 2 million IU was administered concurrently with inhalational CMS 1 million IU every 8 hours. Steady-state plasma colistin levels were measured. Logistic regression analysis was used to identify various predictors of clinical, microbiological and safety outcome. A large variability was observed in the steady-state colistin pharmacokinetic/pharmacodynamic parameters, along with the factors that influenced the clinical, microbiological and safety outcome. In conclusion, steady-state colistin pharmacokinetic and pharmacodynamic parameters observed in our study were largely consistent with those reported in previous studies. High acute physiology and chronic health evaluation II scores were associated with poor clinical outcome. Log-transformed colistin maximum concentration, area under the plasma concentration curve for 8 hours, apparent total body clearance and apparent volume of distribution were significantly associated with the safety outcome.

Predictive Validity of Some Common Animal Models of Bipolar Disorder Using Lithium and Lamotrigine Therapy: An Attempt towards a Battery-Based Approach for the Evaluation of Mood Stabilizers.

OBJECTIVE: To determine the predictive validity of some of the commonly employed models of mania and depression using standard drugs i.e. lithium (70 mg/kg) and lamotrigine (5 mg/kg) in male Wistar rats. METHODS: The depression facet of bipolar disorder was evaluated using forced swim test, tail suspension test, and chronic mild stress test. The models used to evaluate the mania facet of bipolar disorder were isolation-induced aggression test, saccharine preference test, and morphine-sensitized hyperlocomotion test. RESULTS: The immobility time was significantly (p<0.05) reduced by lamotrigine in the tail suspension test and the forced swim test, while lithium caused significant (p<0.05) reduction only in the tail suspension test. Rats exposed to chronic mild stress showed the maximal increment of 1% sucrose consumption at the 3rd week of treatment in both the lithium (p<0.001) and lamotrigine (p<0.01) groups. In the isolation-induced aggression test, the aggressive behaviour of rats was significantly reduced by both lithium [approach (p<0.001), attack (p<0.01), and bite (p<0.01)] and lamotrigine [approach (p<0.001), and attack (p<0.05)]. Neither of the drugs were effective in the saccharine preference test. Only lithium was able to significantly (p<0.05) reduce the crossing parameter in morphine-sensitized rats. CONCLUSION: Our study identifies the chronic mild stress test and isolation-induced aggression test of having the highest predictive validity in the depression and mania facets of bipolar disorder, respectively, and should be a part of a battery of tests used to evaluate novel mood stabilizers.

Drug combinations in diabetic neuropathic pain: an experimental validation.

BACKGROUND: Diabetic neuropathy is the most common complication of diabetes mellitus, and the different drug combinations available do not provide effective pain relief. The present study was performed to observe the effect of amitripyline, duloxetine, sitagliptin, and pregabalin, and their combinations on streptozotocin (STZ)-induced diabetic neuropathy. METHODS: Diabetic neuropathy was induced by STZ, and the tail-flick test was used to assess thermal hyperalgesia before and after (at 30, 60, and 120 min) drug administration. One week after STZ administration, the blood glucose level was observed to be in the diabetic range. RESULTS: Administration of all the drugs except sitagliptin increased the tail-flick latency significantly as compared to control. Further, the drugs amitriptyline, duloxetine, and pregabalin showed significant pain-relieving effect, when either two of them were administered in combination, although the different combinations had varied degree of pain relief. However, sitagliptin was observed to have no effect when administered alone or in combination with the other three drugs. CONCLUSIONS: Therefore, the study provides new insights concerning combined therapy of pain, which further needs clinical exploration.

Variability in plasma concentration of cefotaxime in critically ill patients in an Intensive Care Unit of India and its pharmacodynamic outcome: A nonrandomized, prospective, open-label, analytical study.

BACKGROUND: Cefotaxime is a widely utilized cephalosporin in most intensive care units of India. However, no data are available about its pharmacokinetic/pharmacodynamic variability in critically ill patients of the Indian population. AIM: To investigate the variability in the plasma concentration and pharmacodynamic profile of intermittent dosing of cefotaxime in critically ill patients, according to their locus of infection and causative organism. MATERIALS AND METHODS: Cefotaxime levels were determined using high-performance liquid chromatography by grouping patients according to their locus of infection as hepatobiliary, renal, pulmonary, and others. Patients with cefotaxime concentration below the minimum inhibitory concentration (MIC) and 5 times below the MIC for the isolated organism were determined. RESULTS: The difference in the plasma cefotaxime concentration between the hepatobiliary and the nonhepatobiliary groups was significant at 1 h (P = 0.02) following drug dosing, while the difference was significant between the renal and nonrenal group at 1 h (P = 0.001), 4 h (P = 0.009), and 8 h (P = 0.02) after drug dosing. The pulmonary group showed significantly (P < 0.05) lower plasma cefotaxime levels than the nonpulmonary group at all-time points. The cefotaxime levels were below the MIC and below 5 times the MIC for the isolated organism in 16.67% and 43.33% of the patients, respectively. CONCLUSION: The concentration of cefotaxime differs according to the locus of an infection in critically ill patients. Use of another class of antibiotic or shifting to continuous dosing of cefotaxime, for organisms having MIC values above 1 mg/L, is advisable due to the fear of resistance.

Pharmacokinetic/pharmacodynamic profiling of imipenem in patients admitted to an intensive care unit in India: A nonrandomized, cross-sectional, analytical, open-labeled study.

BACKGROUND AND AIM: Widespread use of imipenem in intensive care units (ICUs) in India has led to the development of numerous carbapenemase-producing strains of pathogens. The altered pathophysiological state in critically ill patients could lead to subtherapeutic antibiotic levels. Hence, the aim of this study was to investigate the variability in the pharmacokinetic and pharmacodynamic profile of imipenem in critically ill patients admitted to an ICU in India. MATERIALS AND METHODS: Plasma concentration of imipenem was determined in critically ill patients using high performance liquid chromatography, at different time points, by grouping them according to their locus of infection. The elimination half-life (t΍) and volume of distribution (Vd) values were also computed. The patients with imipenem trough concentration values below the minimum inhibitory concentration (MIC) and 5 times the MIC for the isolated pathogen were determined. RESULTS: The difference in the plasma imipenem concentration between the gastrointestinal and the nongastrointestinal groups was significant at 2 h (P = 0.015) following drug dosing; while the difference was significant between the skin/cellulitis and nonskin/cellulitus groups at 2 h (P = 0.008), after drug dosing. The imipenem levels were above the MIC and 5 times the MIC for the isolated organism in 96.67% and 50% of the patients, respectively. CONCLUSIONS: The pharmacokinetic profile of imipenem does not vary according to the locus of an infection in critically ill patients. Imipenem, 3 g/day intermittent dosing, maintains a plasma concentration which is adequate to treat most infections encountered in patients admitted to an ICU. However, a change in the dosing regimen is suggested for patients infected with organisms having MIC values above 4 mg/L.

Comparison of the species-sensitive effects of different dosages of calcium and verapamil on gentamicin-induced nephrotoxicity in rats and rabbits.

AIM: To compare the effects of different dosages of calcium and verapamil on gentamicin-induced nephrotoxicity in rats and rabbits. MATERIALS AND METHODS: Rabbits and rats of either sex in weight range of 1.5-2.5 kg and 175-225 g, respectively were used in study. Gentamicin 80 mg/kg i.m., calcium carbonate 0.5 g/kg/day oral, calcium carbonate 1.0 g/kg/day oral, and verapamil 7 mg/kg/day i.m. were administered for 6 days in either species containing 7 groups. Blood urea nitrogen (BUN), serum creatinine and, urine protein levels were assessed on day 0 and day 7 for kidney function. The animals were sacrificed on day 7 for histopathplogical examination and kidney superoxide dismutase levels (SOD) were measured. Statistical analysis was done using student's unpaired t-test, analysis of variance (ANOVA) and Wilcoxon Rank Sum test. P-value less than 0.05 was considered significant. RESULTS: The results showed that calcium was able to reverse significantly increased BUN, serum creatinine, urine protein, and reduced kidney SOD levels in gentamicin-treated nephrotoxic rats or rabbits in a dose-dependent manner while verapamil had no protective or nephrotoxic effect. CONCLUSION: Calcium 0.5 g/kg/day and 1.0 g/kg/day were able to reverse tubular necrosis and mesangial proliferation in gentamicin-treated nephrotoxic animals. There was no species-sensitive variation in reversal of nephrotoxicity by calcium in rats and rabbits.

Evaluation of antiobesity and cardioprotective effect of Gymnema sylvestre extract in murine model.

OBJECTIVE: Obesity plays a central role in the insulin resistance syndrome, which is associated with hyperinsulinemia, hypertension, hyperlipidemia, type 2 diabetes mellitus, and an increased risk of atherosclerotic cardiovascular disease. The present study was done to assess the effect of Gymnema sylvestre extract (GSE) in the high fat diet (HFD)-induced cellular obesity and cardiac damage in Wistar rats. MATERIALS AND METHODS: Adult male Wistar rats (150-200 g body weight) were used in this study. HFD was used to induce obesity. Body mass index, hemodynamic parameters, serum leptin, insulin, glucose, lipids, apolipoprotein levels, myocardial apoptosis, and antioxidant enzymes were assessed. Organ and visceral fat pad weights and histopathological studies were also carried out. RESULTS: Oral feeding of HFD (20 g/day) for a period of 28 days resulted in a significant increase in body mass index, organ weights, visceral fat pad weight, cardiac caspase-3, cardiac DNA laddering (indicating apoptotic inter-nucleosomal DNA fragment), and lipid peroxide levels of cardiac tissues of rats. Further, mean arterial blood pressure, heart rate, serum leptin, insulin, LDH, LDL-C, total cholesterol, triglycerides, and apolipoprotein-B levels were enhanced significantly, whereas serum HDL-C, apoliporotein-A1 levels, and cardiac Na(+) K(+) ATPase, antioxidant enzymes levels were significantly decreased. Furthermore, treatment with standardized ethanolic GSE (200 m/kg/p.o.) for a period of 28 days resulted in significant reversal of above mentioned changes in the obese Wistar rats. CONCLUSION: The present study has demonstrated the significant antiobesity potential of GSE in murine model of obesity.