ABSTRACT
Traditionally, reduced daily doses of colistin methanesulphonate (CMS) in critically ill patients receiving continuous venovenous haemodiafiltration (CVVHDF) have resulted in suboptimal colistin concentrations. The necessity of a loading dose (LD) at treatment initiation has been proposed. A LD of 9 million IU (MU) [ca. 270 mg of colistin base activity (CBA)] was administrated with a maintenance dose of 4.5 MU (ca. 140 mg CBA) every 12 h (q12h) to eight critically ill patients receiving renal replacement therapy. Blood samples were collected immediately before and at different time intervals after the LD and the fourth dose, whilst pre-filter and post-filter blood samples were also collected. CMS and colistin concentrations were determined using an LC-MS/MS assay. Median maximum observed concentrations after the LD were 22.1 mg/L for CMS and 1.55 mg/L for colistin, whereas during maintenance dosing the corresponding values were 12.6 mg/L and 1.72 mg/L, respectively. CVVHDF clearance was determined as 2.98 L/h for colistin, equivalent to 62% of total apparent colistin clearance in CVVHDF patients. Both CMS and colistin were cleared by CVVHDF. Application of a LD of 9 MU CMS resulted in more rapid achievement of the target colistin concentration. Following implementation of a predicted pharmacokinetic model on plasma CMS/colistin concentrations, a LD of 12 MU CMS appears more appropriate, whilst a CMS maintenance dosage of at least 6.5-7.5 MU q12h is suggested in patients undergoing CVVHDF. However, further clinical studies are warranted to assess the safety of a LD of 12 MU CMS in patients receiving CVVHDF.
Subject(s)
Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/pharmacokinetics , Colistin/administration & dosage , Colistin/pharmacokinetics , Hemodiafiltration , Adult , Aged , Chromatography, Liquid , Critical Illness , Female , Humans , Male , Middle Aged , Models, Statistical , Plasma/chemistry , Tandem Mass SpectrometryABSTRACT
Treatment results of six post-neurosurgical ventriculitis and meningitis cases caused by extensively drug-resistant Acinetobacter baumannii after application of an intraventricular loading dose of 500000 IU (40 mg) of colistin followed by a dose of 125000-250000 IU (10-20 mg) every 24-48 h plus parenteral colistin are reported. Simultaneous bacteraemia with an identical Acinetobacter strain was observed in three patients. The mean duration of treatment was 17.2 days (range 15-21 days) and the median time of sterilisation of cerebrospinal fluid was 2.5 days (range 1-5 days). All patients were cured, however one patient presented with chemical meningitis and one with chemical ventriculitis, conditions that clinically and biochemically resemble bacterial meningitis.
Subject(s)
Acinetobacter Infections/drug therapy , Acinetobacter baumannii/drug effects , Anti-Bacterial Agents/administration & dosage , Cerebral Ventriculitis/drug therapy , Colistin/administration & dosage , Drug Resistance, Multiple, Bacterial , Meningitis/drug therapy , Acinetobacter baumannii/isolation & purification , Adult , Cerebral Ventriculitis/complications , Cerebrospinal Fluid/microbiology , Female , Humans , Infusions, Intraventricular , Male , Meningitis/complications , Middle Aged , Surgical Wound Infection/drug therapy , Time Factors , Treatment OutcomeABSTRACT
OBJECTIVE: To prospectively evaluate the diagnostic accuracy of spiral computed tomography (CT) versus ventilation/perfusion (V/Q) scanning in the examination of patients clinically suspected of having pulmonary embolism (PE). PATIENTS AND METHODS: Sixty-three patients, presenting to the emergency department and departments of radiology and nuclear medicine of a large hospital, highly suspected of having PE, underwent sequential imaging testing with V/Q scanning and contrast-enhanced spiral CT, in addition to other clinical and laboratory tests. RESULTS: PE was diagnosed in 42 (66.7%) of the 63 patients. Thirty-nine of these 42 patients had positive findings in their CT scans, while 18 of the remaining 21 patients without PE had negative findings in their spiral CT [sensitivity, 92.9%, specificity, 85.7% Positive Predictive Value (PPV), 92.9%, Negative Predictive Value (NPV), 85.7%]. V/Q scans showed high-probability of PE in 24 of the 42 patients with PE and were negative in 9 of the remaining 21 patients without PE (sensitivity, 571%, specificity, 42.9%, PPV, 66.7%, NPV, 33.3%). There were statistically significant differences in specificity and sensitivity favoring spiral CT among men and women patients or patients > 50 years old. Fifty-four patients (85.7%) rated their satisfaction towards spiral CT as 'good' or 'very good', whereas the respective rate for V/Q scanning was only 14.3%. CONCLUSION: Spiral CT has an excellent sensitivity, specificity, PPV and NPV for the diagnosis of PE and it could be used as the first-line imaging modality in patients suspected of PE.
