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3.  Meropenem Dosing in Critically Ill Patients with Sepsis Receiving High-Volume Continuous Venovenous Hemofiltration ▿  
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 (≥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). We recruited 10 eligible patients and collected serial pre- and postfilter blood samples and ultrafiltrate and urine samples. A noncompartmental method was used to determine meropenem pharmacokinetics. The cohort had a median age of 56.6 years, a median weight of 70 kg, and a median APACHE II (acute physiology and chronic health evaluation) score of 25. The median (interquartile range) values for meropenem were as follows: terminal elimination half-life, 4.3 h (2.9 to 6.0); terminal volume of distribution, 0.2 liters/kg (0.2 to 0.3); trough concentration, 7.7 mg/liter (6.2 to 12.9); total clearance, 6.0 liters/h (5.2 to 6.2); hemofiltration clearance, 3.5 liters/h (3.4 to 3.9). In comparing the meropenem clearance here with those in previous studies, ultrafiltration flow rate was found to be the parameter that accounted for the differences in clearance of meropenem (R2 = 0.89). In conclusion, high-volume CVVHF causes significant clearance of meropenem, necessitating steady-state doses of 1,000 mg every 8 h to maintain sufficient concentrations to treat less susceptible organisms such as B. pseudomallei.
PMCID: PMC2897321  PMID: 20479205
5.  Augmented renal clearance in traumatic brain injury 
Critical Care  2010;14(Suppl 1):P521.
PMCID: PMC2934362
9.  Low Plasma Cefepime Levels in Critically Ill Septic Patients: Pharmacokinetic Modeling Indicates Improved Troughs with Revised Dosing 
Antimicrobial Agents and Chemotherapy  1999;43(10):2559-2561.
The pharmacokinetics of a 2-g bolus of cefepime were measured in critically ill patients with normal renal function. Variable and low trough plasma drug concentrations were found, and 8 of 10 patients had levels below the MIC at which 50% of the isolates are inhibited for Pseudomonas aeruginosa. Computer simulations predicted that continuous infusion and shorter dosing intervals would increase trough levels.
PMCID: PMC89521  PMID: 10508045
10.  Pharmacokinetic Profiles of High-Dose Intravenous Ciprofloxacin in Severe Sepsis 
The pharmacokinetics of 400 mg of ciprofloxacin given intravenously (i.v.) every 8 h (q8h) in severely septic adults was documented in a multidisciplinary, tertiary referral intensive care unit (ICU). Sixteen evaluable patients (three pharmacokinetic profiles) without renal dysfunction and with severe sepsis were studied. Ciprofloxacin at a dosage of 400 mg given i.v. q8h was administered over 1 h. Plasma samples for assay (high-pressure liquid chromatography) were taken at timed intervals (preinfusion, at the end of infusion, and at 1, 2, 3, 5, and 7 h postinfusion) for first-dose kinetics (day 0 [D0]), D2, and between D6 and D8. All pharmacokinetic variables were calculated by noncompartmental methods. Standard intensive care was provided. Peak ciprofloxacin concentrations were as follows: D0, 6.01 ± 1.93 mg/liter; D2, 6.68 ± 2.01 mg/liter; and D6 to D8 6.45 ± 1.54 mg/liter. Trough levels were as follows: D0, 0.6 ± 0.5 mg/liter; D2, 0.7 ± 0.4 mg/liter; and D6 to D8 0.6 ± 0.4 mg/liter. The areas under the concentration curves (8 h) were as follows: D0, 13.3 ± 3.8 mg · h/liter; D2, 16.8 ± 5.4 mg · h/liter; and D6 to D8, 15.5 ± 4.7 mg · h/liter. No drug-related serious adverse events occurred. For 17 of 18 patients enrolled in the study, the causative organisms were susceptible to ciprofloxacin. One patient developed renal failure (non-drug related) after the administration of three doses of ciprofloxacin. One patient was infected with ciprofloxacin-resistant organisms on enrollment. Nine of 16 evaluable patients had clinical cures, and 8 had bacteriological cures. One patient developed a ciprofloxacin-resistant superinfection. In two patients the clinical course was indeterminate. Two bacteriological failures occurred. We conclude that in critically ill adults ciprofloxacin at a dosage of 400 mg given i.v. q8h is safe. Its pharmacokinetic profile provides bactericidal activity against most organisms encountered in an ICU. Except for some initial accumulation on D2, no further accumulation occurred in patients without renal failure. Ciprofloxacin should be administered i.v. at a dosage of 400 mg q8h for severe sepsis.
PMCID: PMC105792  PMID: 9736541
11.  Haemodynamic and oxygen transport response during exchange transfusion for severe falciparum malaria. 
Postgraduate Medical Journal  1994;70(829):801-804.
We describe the haemodynamic and oxygen transport response in a patient undergoing exchange transfusion for severe falciparum malaria. We found that exchange transfusion produced a significant increase in left ventricular stroke work index, systemic oxygen delivery and oxygen consumption. This potentially beneficial effect of exchange transfusion has not been reported previously.
PMCID: PMC2397837  PMID: 7824413
12.  Fungal infections in critically ill patients. 
BMJ : British Medical Journal  1997;315(7103):266-267.
PMCID: PMC2127195  PMID: 9274541
13.  Malignant astrocytoma of the cervico-medullary junction masquerading as Guillain-Barré syndrome. 
Postgraduate Medical Journal  1994;70(825):499-502.
Brainstem gliomas are rare primary brain tumours which most commonly occur in the midbrain and pons. Malignant gliomas and tumours at the cervico-medullary junction are particularly unusual. The diagnosis of tumours at this site is particularly difficult using computed tomographic (CT) scanning owing to artifacts around the base of the skull. Intrinsic tumours of the cervico-medullary junction may lead to a dissociated motor deficit and the onset of symptoms can be rapid. We describe a patient in whom an isolated ascending motor deficit in association with a raised cerebrospinal fluid protein and a normal CT scan led to an erroneous diagnosis of Guillain-Barré syndrome. The patient was treated on the intensive care unit for an 8-week period before further investigation demonstrated a malignant glioma of the cervico-medullary junction. We recommend confirmation of the diagnosis of polyradiculopathy by nerve conduction studies wherever possible.
PMCID: PMC2397676  PMID: 7937428
14.  Multiple organ failure after trauma. 
BMJ : British Medical Journal  1996;313(7057):573-574.
PMCID: PMC2352070  PMID: 8806242
15.  Shoulder magnetic resonance imaging. 
Western Journal of Medicine  1992;156(3):299.
PMCID: PMC1003245  PMID: 1595254
16.  Fatal infection caused by a multiply resistant type 3 pneumococcus. 
Journal of Clinical Microbiology  1988;26(8):1590-1591.
The most virulent pneumococcal serotype (type 3) has not to date been associated with multiple antimicrobial resistance. We report an unusual gastrointestinal presentation of fatal septicemia caused by a multiply resistant type 3 pneumococcus in a setting of increasing prevalence of multiple resistance, including resistance to erythromycin, clindamycin, and tetracycline.
PMCID: PMC266669  PMID: 3170717

Results 1-16 (16)