Intrapatient variation in tobramycin kinetics in low birth weight infants during first postnatal week

Summary Nineteen newborn infants receiving tobramycin, 2.5 mg/kg every 12 h were studied on two occasions at steady-state during the first week of postnatal age. The two studies were separated by two to four days. Total body clearance of tobramycin averaged 1.15 and 1.14 ml/min/kg (p>0.05), apparent volume of distribution averaged 0.82 and 0.68 l/kg (p>0.05), and elimination half-life averaged 8.6 and 7.1 h (p>0.05), during the first and second study, respectively. When the data were further analyzed based on the birth weight, tobramycin kinetics changed during the second study compared to the first study in very low birth weight infants. In eight infants 1.5 kg birth weight, although total clearance of tobramycin was similar, the average apparent volume of distribution decreased from 1.04 l/kg during the first study to 0.73 l/kg during the second study (p<0.05) and elimination half-life from 11.1 h during the first study to 8.7 h during the second study (p<0.05). These data indicate that these infants may require a change in dosing interval with continued tobramycin therapy during the first week of postnatal age. Intrapatient variation in tobramycin kinetics should be considered, in addition to the interpatient variation reported previously, when monitoring the serum concentration to individualize tobramycin therapy in newborn infants 1.5 kg birth weight.supported by Lilly Research Laboratories, Indianapolis, USA     

Duplex-guided balloon angioplasty and subintimal dissection of infrapopliteal arteries: early results with a new approach to avoid radiation exposure and contrast material

OBJECTIVE: Balloon angioplasties of stenotic or occluded infrapopliteal arteries may be helpful in selected high-risk patients threatened with limb loss. Thus far, these procedures have demanded fluoroscopy and the injection of potentially nephrotoxic contrast material. Herein, we proposed a new alternative to avoid the harmful effects of radiation exposure and the risk of acute renal failure. METHODS: Over the last 16 months, 30 patients (57% male) aged 74 +/- 9 years (mean +/- SD) had a total of 52 attempted balloon angioplasties of the infrapopliteal arteries in 32 limbs under duplex guidance. Indications for the procedure were critical ischemia in 20 limbs (63%), including rest pain, ischemic ulcers, and gangrene in 4 (13%), 10 (31%), and 6 (19%) limbs, respectively. Severe disabling claudication was an indication in the remaining 12 limbs (37%). All patients had concomitantly performed balloon angioplasties of the superficial femoral and popliteal arteries (28 cases) or the popliteal artery alone (4 cases). Balloon angioplasty of the infrapopliteal arteries was performed as an adjunct to improve runoff. Hypertension, diabetes, renal insufficiency, smoking, and coronary artery disease were present in 77%, 73%, 50%, 47%, and 37% of cases, respectively. There were 42 cases (81%) with infrapopliteal arterial stenoses (25 tibioperoneal trunks, 9 peroneal arteries, 4 anterior tibial arteries, and 4 posterior tibial arteries) in 26 limbs. The remaining 10 cases (19%) had infrapopliteal arterial occlusions (4 tibioperoneal trunks, 5 peroneal arteries, and 1 anterior tibial artery) in 6 limbs. All these cases were combined with more proximal endovascular procedures (21 femoropopliteal stenoses and 11 femoropopliteal occlusions). All patients had preprocedure duplex arterial mapping and ankle/brachial index (ABI) measurement. Local anesthesia with light sedation was used in all cases. The common femoral artery was cannulated under direct duplex visualization. Still under duplex guidance, a guidewire was directed into the proximal superficial femoral artery and distally, beyond the infrapopliteal diseased segment. The diseased segment was then balloon-dilated. Balloon diameter and length were chosen according to the arterial measurements obtained by duplex guidance. Completion duplex examinations were performed and postprocedure ABIs were obtained in all cases. RESULTS: Although the overall technical success was 94% (49/52 cases), it was 95% for those with stenoses (40/42 cases) and 90% for those with occlusions (9/10 cases; P < .5). Intraoperative thrombosis occurred in three infrapopliteal cases (two tibioperoneal trunks and one peroneal artery) and in one popliteal artery. All four cases were successfully managed with intra-arterial infusion of thrombolytic agents under duplex guidance. Overall, the preprocedure and postprocedure ABIs ranged from 0.4 to 0.8 (mean +/- SD, 0.58 +/- 0.15) and 0.7 to 1.1 (mean +/- SD, 0.9 +/- 0.16), respectively (P < .0001). Twenty-two (88%) of 25 patients experienced a significant (> 0.15) postoperative ABI increase. Overall 30-day survival and limb salvage rates were 100%. CONCLUSIONS: The proposed technique eliminates the need for radiation exposure and the use of contrast material, and it seems to be an effective alternative approach for the treatment of infrapopliteal occlusive disease. Additional advantages include accurate selection of the proper size of balloon and confirmation of the adequacy of the technique by hemodynamic and imaging parameters.     

New Indices in Scholarship Assessment

Faculty members'' contributions to research and scholarship are measured by a variety of indices. Assessment also has become an integral part of the Accreditation Council for Pharmacy Education''s accreditation process for professional programs. This review describes some of the newer indices available for faculty scholarship assessment. Recently described metrics include the h-index, m-quotient, g-index, h(2) index, a-index, m-index, r-index, ar index, and the creativity index. Of the newer scholarship metrics available, the h-index and m-quotient will likely have the most widespread application in the near future. However, there is no substitute for thoughtful peer review by experienced academicians as the primary method of research and scholarship assessment.     

Pharmacotherapy of acute sinusitis in children.

The pharmacotherapeutic options for acute sinusitis in children are reviewed. Acute sinusitis occurs more frequently in children than in adults. The diagnosis is based primarily on clinical signs and symptoms. Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis are the organisms most frequently implicated. A variety of antimicrobials have FDA-approved labeling for use in the treatment of sinusitis. In randomized, controlled clinical trials identified in a MEDLINE search for the period from 1966 to 1999, amoxicillin had efficacy similar to that of amoxicillin-clavulanate, azithromycin, cefuroxime, and clarithromycin in treating acute sinusitis in children. Azithromycin was effective as a three-day course of treatment. Amoxicillin and cefuroxime are better tolerated than most antibiotics; azithromycin and clarithromycin are also well tolerated. Amoxicillin-clavulanate tends to cause more gastrointestinal symptoms than amoxicillin and is more expensive. Azithromycin is more expensive than amoxicillin but less expensive than other broad-spectrum antimicrobials. Amoxicillin remains the drug of first choice for treating acute sinusitis in children. It has been found to be as effective as other broad-spectrum agents, better tolerated, and less expensive.     

Pharmacokinetics of amphotericin B in children.

Amphotericin B is the most effective agent for the majority of systemic fungal infections but often causes toxicity, and specific dosage guidelines for amphotericin B in pediatric patients are lacking. The purpose of this study was to characterize the pharmacokinetics of amphotericin B in children. Twelve patients (mean age, 6.6 years; range, 4 months to 14 years) receiving amphotericin B, 0.68 +/- 0.34 mg/kg per day (mean plus or minus standard deviation), were studied. Four to eight blood samples were collected during a 24-h period and analyzed by high-pressure liquid chromatography. The peak concentration of amphotericin B in serum was 2.9 +/- 2.8 micrograms/ml. The mean total clearance, apparent volume of distribution, and elimination half-life were 0.46 +/- 0.20 ml/min per kg, 0.76 +/- 0.52 liters/kg, and 18.1 +/- 6.6 h, respectively. Total clearance decreased with age (p less than 0.01). In children aged 8 months to 9 years, the mean total clearance was 0.57 +/- 0.15 ml/min per kg, and in children older than 9 years, it was 0.24 +/- 0.02 ml/min per kg. Interpatient variation in the clearance and volume of distribution of amphotericin B was greater than threefold and greater than eightfold, respectively. However, pharmacokinetic parameters did not change in two stable patients who were studied again. Because clearance decreased substantially with age, older children may require lower doses of amphotericin B per kilogram to decrease the potential for toxicity.