Investigating the need for therapeutic drug monitoring of imipenem in critically ill patients: Are we getting it right?

Background. The drug levels and clearances of imipenem in critically ill patients are not comprehensively described in current literature, yet it is vital that adequate levels be achieved for therapeutic success. Objectives. To determine the proportion of critically ill patients treated with imipenem/cilastatin with sub-therapeutic imipenem plasma levels, and to compare the clinical outcomes of those patients with therapeutic levels with those who had sub-therapeutic levels. Methods. Trough imipenem plasma levels of 68 critically ill patients from a surgical intensive care unit were measured using a validated high-performance liquid chromatography method. Imipenem trough levels were compared with the minimum inhibitory concentration (MIC) of the causative bacterial agents, based on a target value of 100% time above MIC (ƒT >MIC). Results. The proportion of participants with sub-therapeutic imipenem levels was 22% (95% confidence interval (CI) 13% - 34%). The 14- and 28-day mortality rates in the sub-therapeutic group were 33% and 40%, respectively, compared with 19% (p=0.293) and 26% (p=0.346), respectively, in the therapeutic group. Sub-therapeutic imipenem plasma levels are associated with adjusted hazard ratio of 1.47 (95% CI 0.55 - 3.91). Conclusions. The lower proportion of critically ill patients with sub-therapeutic imipenem plasma levels in this study compared with previous studies may be attributed to the practice of higher dosages and the administration method of extended infusions of imipenem/ cilastatin in our setting. The results demonstrate a trend of higher mortality in patients with sub-therapeutic imipenem levels, although the results were not statistically significant at this sample size

Investigating the need for therapeutic drug monitoring of imipenem in critically ill patients: Are we getting it right?

Background. The drug levels and clearances of imipenem in critically ill patients are not comprehensively described in current literature, yet it is vital that adequate levels be achieved for therapeutic success.Objectives. To determine the proportion of critically ill patients treated with imipenem/cilastatin with sub-therapeutic imipenem plasma levels, and to compare the clinical outcomes of those patients with therapeutic levels with those who had sub-therapeutic levels.Methods. Trough imipenem plasma levels of 68 critically ill patients from a surgical intensive care unit were measured using a validated high-performance liquid chromatography method. Imipenem trough levels were compared with the minimum inhibitory concentration (MIC) of the causative bacterial agents, based on a target value of 100% time above MIC (¦T >MIC).Results. The proportion of participants with sub-therapeutic imipenem levels was 22% (95% confidence interval (CI) 13% - 34%). The 14- and 28-day mortality rates in the sub-therapeutic group were 33% and 40%, respectively, compared with 19% (p=0.293) and 26% (p=0.346), respectively, in the therapeutic group. Sub-therapeutic imipenem plasma levels are associated with adjusted hazard ratio of 1.47 (95% CI 0.55 - 3.91).Conclusions. The lower proportion of critically ill patients with sub-therapeutic imipenem plasma levels in this study compared with previous studies may be attributed to the practice of higher dosages and the administration method of extended infusions of imipenem/cilastatin in our setting. The results demonstrate a trend of higher mortality in patients with sub-therapeutic imipenem levels, although the results were not statistically significant at this sample size.

Improved understanding of the pathophysiology of sepsis: Setting the scene for potential novel adjunctive therapies

The occurrence of sepsis in the critically ill population is a dreaded phenomenon when taking into consideration the devastating complications associated with the disease. Despite its high incidence and unacceptably high mortality, this complex syndrome remains poorly understood in terms of defining the disease, detecting the presence or absence of an infection, and therapeutic strategies to optimise immediate and long-term outcomes. Global efforts to address these issues coupled with significant advances in medical technologies and our improved understanding of the pathophysiology of the disease have led to some exciting developments in the domain of adjunctive therapies for sepsis. In particular, interest has focused around immunomodulation strategies and metabolic resuscitation. Some of these therapies sound particularly promising in terms of the early available evidence. The concept of personalised or individualised medicine takes centre stage when considering such therapies, as it is becoming increasingly evident that in order to achieve benefits, we need to introduce appropriate therapies at the right time, the right dose and for an appropriate duration. This review encapsulates a selection of these new adjunctive therapies

Starvation ketoacidosis in pregnancy presenting as euglycaemic, high anion gap metabolic acidosis: A case report highlighting the significance of early recognition and prompt intervention

Starvation ketoacidosis (SKA) constitutes an important consideration in the pregnant patient who presents with profound metabolic acidosis. Pregnancy-related changes predispose the patient to develop SKA following relatively short periods (12 - 14 hours) of ‘starvation’. Patients also typically look clinically well in relation to the significant metabolic derangements that accompany the condition. Prompt recognition and early institution of appropriate therapy is therefore extremely important in terms of optimising maternal and fetal outcome. We describe a pregnant patient with SKA who presented with profound euglycaemic ketoacidosis that resolved rapidly following the early initiation of appropriate therapy. Furthermore, appropriate therapy resulted in our patient avoiding the need for an emergency caesarean section, which is often reported in this scenario. The ensuing discussion addresses SKA in pregnancy, the unique features of our patient, and management considerations from a maternal and fetal perspective. We also discuss the various causes of ketoacidosis such as diabetic ketoacidosis (DKA), euglycaemic DKA, alcohol-induced euglycaemic ketoacidosis and SKA in pregnant patients

Evaluating the usefulness of the estimated glomerular filtration rate for determination of imipenem dosage in critically ill patients

BACKGROUND. Antibiotic dosing in critically ill patients is complicated by variations in the pharmacokinetics of antibiotics in this group. The dosing of imipenem/cilastatin is usually determined by severity of illness and renal function. OBJECTIVES. To determine the correlation between estimated glomerular filtration rates (eGFRs) calculated with the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation and imipenem trough levels in critically ill patients. METHODS. This prospective observational study was done in the surgical intensive care unit (ICU) at Steve Biko Academic Hospital, Pretoria, South Africa. Imipenem trough levels were measured by high-performance liquid chromatography and compared with eGFRs calculated with the CKD-EPI equation. Correlation was evaluated by the Pearson product-moment correlation coefficient. RESULTS. The study population consisted of 68 critically ill patients aged between 18 and 81 years; 43 (63%) were male, and the mean weight was 78 kg (range 40 - 140). On admission, 30 patients (44%) had sepsis, 16 (24%) were admitted for trauma, and 22 (32%) were admitted for miscellaneous surgical conditions. Acute Physiology and Chronic Health Evaluation II (APACHE II) scores ranged from 4 to 39 (mean 18). The 28-day mortality rate was 29%. The mean albumin level was 16 g/L (range 7 - 25), the mean creatinine level 142 μmol/L (range 33 - 840), and the mean eGFR 91 mL/min/1.73 m2 (range 6 - 180). Imipenem trough levels ranged between 3.6 and 92.2 mg/L (mean 11.5). The unadjusted Pearson product-moment correlation coefficient between eGFR and imipenem trough level was –0.04 (p=0.761). CONCLUSION. Considering the high mortality rate of sepsis in ICUs and the rapid global increase in antimicrobial resistance, it is crucial to dose antibiotics appropriately. Owing to the variability of antibiotic pharmacokinetics in critically ill patients, this task becomes almost impossible when relying on conventional dosing guidelines. This study found that eGFRs do not correlate with imipenem blood levels in critically ill patients and should not be used to determine the dose of imipenem/cilastatin. Instead, the dose should be individualised for patients through routine therapeutic drug monitoring.A Federation of Infectious Diseases Societies of South Africa-GlaxoSmithKline Research Fellowship.http://www.samj.org.zadm2022Critical CareMedical Microbiolog

Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease

BACKGROUND: Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization. RESULTS: During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events. CONCLUSIONS: Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo. (Funded by Merck and others; Current Controlled Trials number, ISRCTN48678192 ; ClinicalTrials.gov number, NCT01252953 ; and EudraCT number, 2010-023467-18 .)

La téléxérographie du crâne : étude clinique et radiologique

Les auteurs démontrent, sur 70 clichés comparatifs, la supériorité de la téléxérographie pour la céphalométrie orthodontique ou chirurgicale. Le squelette et les tissus mous sont toujours également lisibles sur le même cliché dont la réalisation technique est simple. L'irradiation nécessaire a été mesurée. Elle est actuellement un peu plus élevée en xérographie, mais devrait être inférieure à l'avenir

Seasonal variation of water-soluble inorganic components in aerosol size-segregated at the puy de Dôme station (1,465 ma.s.l.), France

The size-segregated chemical composition of aerosol particles was investigated during 1 year at the puy de Dôme (1,465 ma.s.l.), France. These measurements aimed to a better understanding of the influence of the air mass origin on the size-segregated chemical composition of the aerosol at an altitude site. Mountain site measurements are important because they are representative of long range transport and useful for model validation. PM1 mass concentration exhibits a seasonal variability with a summer maximum. The composition of PM1 did not change significantly in terms of relative contribution of water soluble inorganic ions but is rather variable in term of total mass concentrations. For the PM10-1, a different seasonal behaviour was found with maxima concentrations in autumn-winter. Aerosols were classified into four different categories according to their air mass origin: marine, marine modified, continental and Mediterranean. The PM10 aerosol mass at 50 % relative humidity was close to 2.5 μg m−3 in the marine, 4.3 μg m−3 in the marine modified, 10.3 μg m−3 in the continental and 7.7 μg m−3 in the Mediterranean sectors. We noted that the influence of the air mass origin (on the chemical properties) could be seen especially on the PM10-1. A significant PM10-1 mode was found in marine, modified marine, and Mediterranean air masses, and PM1 dominated in the continental air masses samples. As a result, the aerosol chemical composition variability at the puy de Dôme is a function of both the season and air mass type and we provide a chemical composition of the aerosol as a function of each of these environmental factors.JRC.D.3-Knowledge Transfer and Standards for Securit