Relationship between vancomycin exposure and outcomes among patients with MRSA bloodstream infections with vancomycin Etest® MIC values of 1.5mg/L: A pilot study.

Data suggest that vancomycin is less effective for methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infection (BSI) with vancomycin Etest® MIC (MICEtest) ≥1.5 mg/L. No published studies have evaluated the relationship between vancomycin exposure and outcomes among patients with MRSA BSIs vancomycin MICEtest ≥1.5 mg/L. This study was a retrospective cohort of 71 hospitalized, adult, non-dialysis patients with MRSA BSIs treated with vancomycin. All but three patients had a vancomycin MICEtest of 1.5 mg/L. Achievement of CART-derived AUC24-48h of at least 550 mg*h/L (AUC24-48h/MIC of 366 mg*h/L) was associated with a lower incidence of treatment failure. In multivariate analyses, the risk ratio was 0.45 for the CART-derived AUC24-48h threshold, indicating that achievement of the CART-derived AUC24-48h threshold of 550 was associated with a 2-fold decrease in treatment failure. These findings suggest a potential association between vancomycin exposure and outcomes in patients with MRSA BSIs with MICEtest ≥1.5 mg/L. As this study was retrospective, these findings provide the basis for a future large-scale, multi-center prospective study.

Performance of Redox Active and Chelatable Iron Assays to Determine Labile Iron Release From Intravenous Iron Formulations.

Emerging data from global markets outside the United States, where many generic iron sucrose formulations are available, have revealed that non-US generic intravenous (i.v.) iron formulations may have iron release profiles that differ from the reference listed drug (RLD). The first generic i.v. iron approved in the United States was sodium ferric gluconate complex in 2011. We evaluated chelatable and redox labile iron assay methods to measure the amount of labile iron released from i.v. iron formulations in biorelevant matrices in vitro. The majority of published labile iron assays evaluated were not suitable for use in vitro due to overwhelming interference by the presence of the i.v. iron products. However, an optimized high-performance liquid chromatography (HPLC)-based method performed well for use in vitro labile iron detection in a biorelevant matrix. Application of this method may enhance bioequivalence evaluation of generic i.v. iron formulations in the future.

Epoetin in the 'untransfusable' anaemic patient: a retrospective case series and systematic analysis of literature case reports.

BACKGROUND: Erythropoiesis stimulating agents [erythropoietin (EPO)] have been recommended to treat anaemic patients who cannot receive or refuse blood tranfusion ('untransfusable' patients). OBJECTIVE: The objective of the study was to quantify the association of EPO use with haemoglobin (Hgb) recovery in anaemic untransfusable hospitalised patients. METHODS/MATERIALS: EPO treated anaemic untransfusable patients were identified through the combination of a retrospective case review and a systematic review of the medical literature. Literature reports of untransfusable patients not treated with any EPO were used as a comparator group. Hgb concentrations before and following EPO use were abstracted and used to determine the rate of Hgb recovery for each case. Multilevel mixed effects modelling was used to determine the association of Hgb recovery with EPO use. RESULTS: A total of 76 EPO treated cases (19 cases from the retrospective hospital case review and 57 from the literature), and 33 non-EPO treated comparator patients from the literature were included in the study. Hgb increased similarly over time in all groups at an overall mean standard error (SE) rate of 0·13 (0·01) g dL(-1) day(-1) . The Hgb recovery rate was higher in patients with lower baseline Hgb, regardless of EPO use. No association was found between the rate of Hgb recovery and EPO use, dose or therapy duration. CONCLUSIONS: In anaemic, 'untransfusable' hospitalised patients, EPO use was not associated with increased Hgb recovery at anytime within 28 days.

Antimicrobial-coated/bonded and -impregnated intravascular catheters.

OBJECTIVE: To review the literature regarding the prevention of catheter colonization and catheter-related bloodstream infections (CRBIs) with the use of antimicrobial-coated/bonded and -impregnated intravascular catheters. DATA SOURCES: Primary and review English-language literature were identified using MEDLINE (1966-September 2000) pertaining to the key terms antibiotic, antimicrobial, antiseptic, silver, and bonded, coated, Impregnated catheters. In addition, textbooks and relevant reference lists were reviewed. DATA EXTRACTION: All articles identified through the data sources were evaluated. Information deemed relevant to the objectives of the review was included. DATA SYNTHESIS: Significant morbidity and mortality are associated with the development of CRBIs. Preventative measures such as modification of these catheters with antimicrobial coating/bonding have produced varying results. Trials evaluating cefazolin, teicoplanin, vancomycin, silver, and chlorhexidine-silver sulfadiazine (C-SS) used for coated/bonded intravascular catheters have not demonstrated a consistent decrease in the incidence of CRBIs. However, a meta-analysis of trials evaluating C-SS intravascular catheters demonstrated a statistically significant reduction in CRBIs. A larger reduction in CRBIs has been reported with minocycline-rifampin (M-R) versus C-SS intravascular catheters. Use of the M-R and C-SS catheters may result in a cost savings of $100 million and reduce as many as 12,000 CRBI-related deaths annually when used short term (<7 d). CONCLUSIONS: When used for short-term catheterization, M-R catheters appear to be superior to the currently available C-SS catheters at preventing CRBIs. Significant cost savings and reduction in mortality can be anticipated with the use of M-R catheters.

Plasma Pharmacokinetics and Tissue Penetration of Alatrofloxacin in Morbidly Obese Individuals.

OBJECTIVES: To characterise the peritoneal and subcutaneous adipose penetration of alatrofloxacin. If the extent of penetration of this lipophilic fluoroquinolone is adequate in patients with extensive adipose layers, it may provide better antimicrobial coverage than more commonly used antibiotics that are less lipophilic. STUDY PARTICIPANTS AND METHODS: Six morbidly obese individuals undergoing a Roux-Y gastric bypass procedure received single 1-hour infusions of alatrofloxacin equivalent to 300mg of its active metabolite, trovafloxacin. Blood samples were obtained over a 24-hour period and adipose tissue from subcutaneous and deep tissue sites were obtained approximately 3 hours post-infusion of alatrofloxacin. Plasma and adipose tissue concentrations of trovafloxacin were determined by high pressure liquid chromatography with fluorescence detection. RESULTS: The mean maximum plasma concentration, area under the concentration-time curve, and elimination half-life of trovafloxacin were 3.6 mg/L, 37.4 mg/L·h, and 12.1h, respectively. The mean tissue concentrations at the subcutaneous and deep adipose sites were 0.43 and 0.41 µ/g, respectively. CONCLUSIONS: These results indicated that the pharmacokinetics of trovafloxacin in morbidly obese individuals are similar to those in healthy control individuals. In addition, the concentrations of trovafloxacin achieved in the adipose tissue were above the minimum inhibitory concentration of most pathogens responsible for surgical and decubitus ulcer infections.

The origin of the "ideal" body weight equations.

OBJECTIVE: To provide a historical perspective on the origin and similarity of the "ideal" body weight (IBW) equations, and clarify the terms ideal and lean body weight (LBW). DATA SOURCES: Primary and review literature were identified using MEDLINE (1966-November 1999) and International Pharmaceutical Abstracts (1970-November 1999) pertaining to ideal and lean weight, height-weight tables, and obesity. In addition, textbooks and relevant reference lists were reviewed. DATA EXTRACTION: All articles identified through the data sources were evaluated. Information deemed to be relevant to the objectives of the review were included. DATA SYNTHESIS: Height-weight tables were generated to provide a means of comparing a population with respect to their relative weight. The weight data were found to correlate with mortality and resulted in the use of the terms desirable or ideal to describe these weights. Over the years, IBW was interpreted to represent a "fat-free" weight and thus was used as a surrogate for LBW. In addition, the pharmacokinetics of certain drugs were found to correlate with IBW and resulted in the use of IBW equations published by Devine. These equations were consistent with an old rule that was developed from height-weight tables to estimate IBW. Efforts to improve the IBW equations through regression analyses of height-weight data resulted in equations similar to those published by Devine. CONCLUSIONS: The similarity between the IBW equations was a result of the general agreement among the various height-weight tables from which they were derived. Therefore, any one of these equations may be used to estimate IBW.

Waste generation of drug product samples versus prescriptions obtained through pharmacy dispensing.

Drug samples are often packaged differently from bulk packaging and thus they may contain a disproportionate amount of waste material. Fifteen drug samples were obtained from seven pharmaceutical companies and the packaging materials were weighed after the samples were removed. The waste produced by the samples was determined for a standard amount of drug and compared with the weight of the waste produced when the same quantity of drug was dispensed through a pharmacy. The average weight of the sample package for a standard course of therapy was significantly greater (p< or =0.05) than that of the pharmacy-dispensed prescription waste weight. The former was 5+/-4.5-fold heavier than the latter. The waste generated by drug samples in the United States was determined to be 5740 metric tons/year.

Macrolide drug interactions: an update.

OBJECTIVE: To describe the current drug interaction profiles for the commonly used macrolides in the US and Europe, and to comment on the clinical impact of these interactions. DATA SOURCES: A MEDLINE search (1975-1998) was performed to identify all pertinent studies, review articles, and case reports. When appropriate information was not available in the literature, data were obtained from the product manufacturers. STUDY SELECTION: All available data were reviewed to provide an unbiased account of possible drug interactions. DATA EXTRACTION: Data for some of the interactions were not available from the literature, but were available from abstracts or company-supplied materials. Although the data were not always explicit, the best attempt was made to deliver pertinent information that clinical practitioners would need to formulate practice opinions. When more in-depth information was supplied in the form of a review or study report, a thorough explanation of pertinent methodology was supplied. DATA SYNTHESIS: Several clinically significant drug interactions have been identified since the approval of erythromycin. These interactions usually were related to the inhibition of the cytochrome P450 enzyme systems, which are responsible for the metabolism of many drugs. The decreased metabolism by the macrolides has in some instances resulted in potentially severe adverse events. The development and marketing of newer macrolides are hoped to improve the drug interaction profile associated with this class. However, this has produced variable success. Some of the newer macrolides demonstrated an interaction profile similar to that of erythromycin; others have improved profiles. The most success in avoiding drug interactions related to the inhibition of cytochrome P450 has been through the development of the azalide subclass, of which azithromycin is the first and only to be marketed. Azithromycin has not been demonstrated to inhibit the cytochrome P450 system in studies using a human liver microsome model, and to date has produced none of the classic drug interactions characteristic of the macrolides. CONCLUSIONS: Most of the available data regarding macrolide drug interactions are from studies in healthy volunteers and case reports. These data suggest that clarithromycin appears to have an interaction profile similar to that of erythromycin. Given this similarity, it is important to consider the interaction profile of clarithromycin when using erythromycin. This is especially necessary as funds for further studies of a medication available in generic form (e.g., erythromycin) are limited. Azithromycin has produced few clinically significant interactions with any agent cleared through the cytochrome P450 enzyme system. Although the available data are promising, the final test should come from studies conducted in patients who are taking potentially interacting compounds on a chronic basis.