Evaluating the impact of a pharmacist's absence from an antimicrobial stewardship team.

PURPOSE: Results of a study to determine the impact of a clinical pharmacist's temporary absence from a hospital's antimicrobial stewardship team are presented. METHODS: A retrospective chart review was conducted to compare the appropriateness of the use of selected antimicrobial medications with and without regular pharmacist involvement on the hospital's antimicrobial stewardship team. The charts of two samples of patients were evaluated: (1) 119 patients who had received prolonged (≥72 hours) imipenem-cilastatin, linezolid, or micafungin therapy over a three-month period during which a clinical pharmacist routinely provided interventions to help ensure the drugs were used according to institutional guidelines and (2) 111 patients treated with one of the three drugs during a three-month period when the clinical pharmacist did not serve on the stewardship team. RESULTS: Relative to the period of active pharmacist involvement in antimicrobial stewardship, rates of inappropriate use of imipenem-cilastatin, linezolid, and micafungin during the pharmacist's absence were deemed to have increased by 27, 39, and 35 percentage points, respectively, with corresponding increases in the average duration of therapy of 0.7, 4.0, and 3.2 days; in addition, the number of cases of Clostridium difficile infection increased more than threefold (from 8 to 25) during the pharmacist's absence. CONCLUSION: The temporary absence of a pharmacist from the antimicrobial stewardship team was associated with increased rates of inappropriate use of restricted antimicrobial agents and consequent increases in average durations of therapy.

Development and validation of a stability-indicative agar diffusion assay to determine the potency of linezolid in tablets in the presence of photodegradation products.

Linezolid (LNZ) is one of the first commercially available (and most widely used) oxazolidinone antibiotics. This study describes the development and validation of a microbiological assay, applying the cylinder-plate method, for the determination of the antibiotic linezolid, as well as the evaluation of the ability of the method in determining the stability of linezolid in tablets. The validation method yielded good results and included linearity, precision, accuracy, robustness and selectivity. The assay is based on the inhibitory effect of LNZ upon the strain of Bacillus subtilis ATCC 9372 used as the test microorganism. The results of the assay were treated statistically by analysis of variance (ANOVA) and were found to be linear (r(2)=0.9998) in the range of 20-80 microg mL(-1), precise (inter-assay: R.S.D.=0.61) and accurate (R.S.D.=1.7). The method developed and validated proved to be indicative of stability and capable of determining the decay of linezolid in the presence of photodegradation products. Comparison of bioassay and liquid chromatography by ANOVA showed no significant difference between methodologies. The results demonstrated the validity of the proposed bioassay, which is a simple and useful alternative methodology for LNZ determination in routine quality control.

Determination of linezolid and its achiral impurities using sweeping preconcentration by micellar capillary electrophoresis.

Linezolid is the first compound of a truly new class of antibiotics--the oxazolidinones. The elaborated method of capillary electrophoresis (CE) of linezolid separation from its achiral impurities was successfully performed using sweeping preconcentration, followed by UV absorption detection at 254nm. The best results were obtained with 125mM Tris buffer, pH 2.0, with addition of 20% (v/v) methanol as background electrolyte. Sodium dodecyl sulfate (150mM) was added to the electrolyte in the inlet vial as the sweeping agent. The separation was carried out at negative polarity. Then, the optimized method was validated in terms of linearity, accuracy and precision. Sweeping preconcentration of linezolid provides detection limit at 0.05microg/ml level. The evaluated CE method was applied in the analysis of medicinal product containing linezolid-linezolid solution for infusion.

Efficacy and safety of linezolid in multidrug resistant tuberculosis (MDR-TB)--a report of ten cases.

OBJECTIVES: Multidrug resistant tuberculosis (MDR-TB) is an increasing problem in many parts of the world and in Norway the increase has been substantial since 1998. New therapies for MDR-TB have not been introduced since the fluoroquinolones in the 1970s. The cure rate of this disease has been reported to be lower than for non-drug resistant TB, and the use of new experimental drugs in combination therapy is warranted. METHODS: Ten consecutive patients with culture proven MDR-TB were treated with the novel antibiotic drug linezolid in combination regimens for 6-40 (median 17) weeks and followed up 11-50 (median 24) months after end of treatment. All strains were sensitive to linezolid with MIC<4 mg/l. Treatment was given as direct observed therapy (DOT) and sputum cultures, blood chemistry and neurologic examination were undertaken on a regular basis. RESULTS: Nine patients were cured, one patient with poor adherence to treatment and advanced AIDS died. Seven of 10 patients experienced serious adverse events, which led to withdrawal of linezolid in all seven. Six patients developed peripheral neuropathy and five patients bone marrow depression, blood transfusions were given to three patients and in all five patients bone marrow function normalized after cessation of linezolid. Peripheral neuropathy was not fully reversed in all patients. CONCLUSION: Linezolid seems highly active in combination treatment of MDR-TB. Cultures became negative 10-37 days after the introduction of the drug. However, peripheral neuropathy and bone marrow depression led to linezolid withdrawal in seven patients, and neuropathy may not be fully reversible in all patients.