Antibiotic Dosing

We aimed to characterize real-world dosing of weight-based intravenous (IV) antibiotic therapy in patients hospitalized for methicillin-resistant Staphylococcus aureus (MRSA) complicated skin and soft-tissue infections (cSSTIs). This was a subgroup analysis of a retrospective chart review that captured data from 12 European countries. The study included patients ≥18 years old, hospitalized with an MRSA cSSTI between 1 July 2010 and 30 June 2011 and discharged alive by 31 July 2011. Patients treated with IV vancomycin, teicoplanin or daptomycin at any stage during hospitalization were included in this analysis...

Meropenem dosing in critically ill patients with septic shock and continuous renal replacement therapy (CRRT) is complex, with the recommended maintenance doses being 500 mg to 1,000 mg every 8 h (q8h) to every 12 h. This multicenter study aimed to describe the pharmacokinetics (PKs) of meropenem in this population to identify the sources of PK variability and to evaluate different dosing regimens to develop recommendations based on clinical parameters. Thirty patients with septic shock and CRRT receiving meropenem were enrolled (153 plasma samples were tested)...

End-stage renal disease (ESRD) patients receiving hemodialysis (HD) are at heightened risk for influenza, but the optimal oseltamivir dosage regimen for treating or preventing influenza in this high-risk population is still uncertain. Pharmacokinetic data for 24 adults with ESRD were pooled from a single-dose and a multiple-dose study to develop a population pharmacokinetic model using nonlinear mixed-effects modeling. The final model comprised five compartments, two each to describe the systemic pharmacokinetics of oseltamivir phosphate and its metabolite, oseltamivir carboxylate (OC), and a delay compartment to describe oseltamivir metabolism...

Antibiotic dosing in septic shock patients poses a challenge for clinicians due to the pharmacokinetic (PK) variability seen in this patient population. Piperacillin-tazobactam is often used for empirical treatment, and initial appropriate dosing is crucial for reducing mortality. Accordingly, we determined the pharmacokinetic profile of piperacillin (4 g) every 8 h, during the third consecutive dosing interval, in 15 patients treated empirically for septic shock. We developed a population pharmacokinetic model to assess empirical dosing and to simulate alternative dosing regimens and modes of administration...

No abstract text is available yet for this article.

Treatment of infectious diseases is becoming increasingly challenging with the emergence of less-susceptible organisms that are poorly responsive to existing antibiotic therapies, and the unpredictable pharmacokinetic alterations arising from complex pathophysiologic changes in some patient populations. In view of this fact, there has been a progressive work on novel dose optimization strategies to renew the utility of forgotten old antibiotics and to improve the efficacy of those currently in use. This review summarizes the different approaches of optimization of antibiotic dosing regimens and the special patient populations which may benefit most from these approaches...

OBJECTIVES: The objectives of this study were to describe piperacillin exposure in febrile neutropenia patients and determine whether therapeutic drug monitoring (TDM) can be used to increase the achievement of pharmacokinetic (PK)/pharmacodynamic (PD) targets. METHODS: In a prospective randomized controlled study (Australian New Zealand Registry, ACTRN12615000086561), patients were subjected to TDM for 3 consecutive days. Dose was adjusted in the intervention group to achieve a free drug concentration above the MIC for 100% of the dose interval (100% fT>MIC), which was also the primary outcome measure...

No abstract text is available yet for this article.

Administration of inhaled antimicrobials affords the ability to achieve targeted drug delivery into the respiratory tract, rapid entry into the systemic circulation, high bioavailability and minimal metabolism. These unique pharmacokinetic characteristics make inhaled antimicrobial delivery attractive for the treatment of many pulmonary diseases. This review examines recent pharmacokinetic trials with inhaled antibacterials, antivirals and antifungals, with an emphasis on the clinical implications of these studies...

BACKGROUND: Meropenem is an anti-Gram-negative antimicrobial, the time-dependent activity of which may be maximized through administration by continuous infusion. OBJECTIVES: The objectives of this study were to characterize the pharmacokinetics of continuous infusion meropenem in relation to body size and Cockcroft-Gault estimated creatinine clearance (CLCR) in overweight and obese patients with stable and unstable kidney function with the intent of creating a nomogram for optimal dosing...

BACKGROUND AND OBJECTIVES: Therapeutic drug monitoring (TDM) of voriconazole is increasingly being implemented in clinical practice. However, as blood sampling can be difficult in paediatric and ambulatory patients, a non-invasive technique for TDM is desirable. The aim of this study was to compare the pharmacokinetics of voriconazole in saliva with the pharmacokinetics of unbound and total voriconazole in plasma in order to clinically validate saliva as an alternative to plasma in voriconazole TDM...

No abstract text is available yet for this article.

Neither guidelines nor best practices for the treatment of external ventricular drain (EVD) and ventriculoperitoneal shunt infections exist. An antimicrobial regimen with a broad spectrum of activity and adequate cerebrospinal fluid (CSF) penetration is vital in the management of both EVD and ventriculoperitoneal infections. In this case report, we describe the pharmacokinetics of continuous-infusion meropenem for a 2-year-old girl with Serratia marcescens ventriculitis. A right frontal EVD was placed for the management of a posterior fossa mass with hydrocephalus and intraventricular hemorrhage...

BACKGROUND: Current medical center practice allows for the automatic conversion of all piperacillin/tazobactam orders from intermittent to extended infusion (EI). OBJECTIVE: To compare the clinical and cost impact of empirical extended-infusion piperacillin/tazobactam. METHODS: All consecutive patients treated with piperacillin/tazobactam for >48 hours were reviewed for inclusion. Patients were stratified into 2 groups: (1) traditional infusion (TI), preprotocol implementation, and (2) EI, postprotocol implementation...

OBJECTIVE: In patients with cerebrospinal fluid (CSF) shunt infection, removal of the shunt and antibiotic administration is the current standard of care. In 1986, we developed a protocol for the conservative management of patients with infected but functioning shunts. Treatment was based on the administration of a combination of intraventricular and systemic antibiotics. Intraventricular antibiotics were instilled via a separate access device. The purpose of this report is to describe our experience with this therapeutic intervention...

Use of high ultrafiltrate flow rates with continuous venovenous hemofiltration (CVVHF) in critically ill patients is an emerging setting, for which there are few data to guide drug dosing. The objectives of this study were, firstly, to investigate the pharmacokinetics of meropenem in critically ill patients with severe sepsis who are receiving high-volume CVVHF with high-volume exchanges (> or = 4 liters/h); secondly, to determine whether standard dosing regimens (1,000 mg intravenously [i.v.] every 8 h) are sufficient for treatment of less susceptible organisms such as Burkholderia pseudomallei (MIC, 4 mg/liter); and, finally, to compare the clearances observed in this study with data from previous studies using lower-volume exchanges (1 to 2 liters/h)...

OBJECTIVE: To discuss administering vancomycin directly into the cerebrospinal fluid (CSF) to treat serious central nervous system (CNS) infections. DATA SOURCES: References were obtained through an online search of MEDLINE, limited to material published in English. In addition, information was extracted from clinical trials, review articles, abstracts, and textbooks. STUDY SELECTION: Systematic evaluation of this topic in humans has not been done in a prospective manner...

The CLSI reduced the cefepime Enterobacteriaceae susceptibility breakpoint and introduced the susceptible-dose-dependent (S-DD) category. In this study, MICs were determined for a Gram-negative collection to assess the impact of this change. For Enterobacteriaceae, this resulted in <2% reduction in susceptibility, with 1% being S-DD. If applied to Pseudomonas aeruginosa, the % susceptibility (%S) dropped from 77% to 43%, with 34% being S-DD. The new breakpoints did little to the Enterobacteriaceae %S, but for P...

OBJECTIVES: Colistin, administered intravenously as its inactive prodrug colistin methanesulphonate (CMS), is being increasingly used. However, there is very limited information available on the impact of haemodialysis (HD) on the pharmacokinetics of CMS and formed colistin. PATIENTS AND METHODS: A single 30 min intravenous dose of CMS (150 mg of colistin base activity) was administered to 10 patients undergoing HD. HD was performed from 1.5 to 5.5 h after the start of the CMS infusion...

We report safety, tolerability, and 12-week sustained virologic response with half-standard dose sofosbuvir and standard-dose simeprevir combination therapy in a hepatitis C virus genotype 1a-infected liver transplant recipient on hemodialysis - uncharted territory for sofosbuvir-based therapy. The patient was a non-responder to prior treatment with pegylated interferon plus ribavirin. Sofosbuvir efficacy was maintained despite pill-splitting and administration of half-standard dose, 200 mg per day. No drug-drug interactions were noted with tacrolimus-based immunosuppression...