A population pharmacokinetic model of polymyxin B based on prospective clinical data to inform dosing in hospitalized patients.

Objectives: To develop a population pharmacokinetic (PK) model with data from the largest polymyxin B-treated patient population studied to date to optimize its dosing in hospitalized patients.

Methods: Hospitalized patients receiving intravenous polymyxin B for ≥48 hours were enrolled. Blood samples were collected at steady state and drug concentrations were analysed by liquid chromotography tandem mass spectrometry (LC-MS/MS).

Assessing the predictive performance of population pharmacokinetic models for intravenous polymyxin B in critically ill patients.

Polymyxin B (PMB) has reemerged as a last-line therapy for infections caused by multidrug-resistant gram-negative pathogens, but dosing is challenging because of its narrow therapeutic window and pharmacokinetic (PK) variability. Population PK (POPPK) models based on suitably powered clinical studies with appropriate sampling strategies that take variability into consideration can inform PMB dosing to maximize efficacy and minimize toxicity and resistance. Here we reviewed published PMB POPPK models and evaluated them using an external validation data set (EVD) of patients who are critically ill and enrolled in an ongoing clinical study to assess their utility.

Population pharmacokinetics of intravenous polymyxin B in critically ill patients: implications for selection of dosage regimens.

Background: Polymyxin B is a last-line therapy for multidrug-resistant gram-negative bacteria. There is a dearth of pharmacokinetic data to guide dosing in critically ill patients.

Methods: Twenty-four critically ill patients were enrolled and blood/urine samples were collected over a dosing interval at steady state.

Pharmacokinetics of polymyxin B in patients on continuous venovenous haemodialysis.

Objectives: To evaluate the pharmacokinetics of polymyxin B in patients on continuous venovenous haemodialysis (CVVHD) after intravenous administration of unadjusted dosage regimens.

Patients And Methods: Two critically ill patients had eight blood samples collected during a 12 h interval on days 8 and 10 of polymyxin B therapy. Dialysate was collected every hour during the 12 h dosing interval.

Outbreak of carbapenem-resistant Providencia stuartii in an intensive care unit.

Outbreaks by carbapenem-resistant Providencia stuartii (CRPS) are rarely described. Clinical characteristics of patients with CRPS in an intensive care unit and resistance mechanisms were investigated. Carbapenemase production and/or outer membrane alterations were not detected; only CTX-M-2 and AmpC hyperproduction were noted.

Treatment of hepatitis C-mediated glomerular disease.

Chronic kidney disease (CKD) is becoming a major public health issue worldwide, mainly due to the increasing prevalence of hypertension, diabetes and aging population. Chronic hepatitis C virus (HCV) infection commonly involves the kidneys, can be a cause of CKD, and significantly impacts morbidity and mortality in these patients. Prompt recognition and knowledge of how to best manage these patients are essential in order to have a successful renal outcome.

Treatment of hepatitis B virus-associated nephropathy.

Epidemiological studies have shown a relationship between hepatitis B virus (HBV) infection and development of proteinuria in some patients (most commonly children), with a predominance for male gender and histological findings of membranous nephropathy on renal biopsy. The presence of immune complexes in the kidney suggests an immune complex basis for the disease, but a direct relation between HBV and membranous nephropathy (or other types of glomerular diseases) remains to be proven. Clearance of HBV antigens, either spontaneous or following antiviral treatments results in improvement in proteinuria.

Treatment of HIV-associated nephropathies.

In patients with HIV, the use of highly active antiretroviral therapy has improved life expectancy. At the same time, this increase in life expectancy has been associated with a higher frequency of chronic kidney disease due to factors other than HIV infection. Besides HIV-associated nephropathy, a number of different types of immune complex and non-immune complex-mediated processes have been identified on kidney biopsies, including vascular disease (nephrosclerosis), diabetes, and drug-related renal injury.

Reduction in incidence of nosocomial methicillin-resistant Staphylococcus aureus (MRSA) infection in an intensive care unit: role of treatment with mupirocin ointment and chlorhexidine baths for nasal carriers of MRSA.

After the introduction of routine treatment for every nasal carrier of methicillin-resistant Staphylococcus aureus, active follow-up surveillance for nosocomial methicillin-resistant S. aureus infection was conducted for 5 years in an intensive care unit of a tertiary-care teaching hospital. There was a significant decrease in the incidence of nosocomial methicillin-resistant S.