Linezolid for the treatment of community-acquired pneumonia in hospitalized children. Linezolid Pediatric Pneumonia Study Group.

OBJECTIVE: To determine the safety, tolerance, pharmacokinetics and efficacy of linezolid, a new oxazolidinone antibiotic in the treatment of community-acquired pneumonia in hospitalized children. DESIGN: A Phase II, open label multicenter study of intravenous linezolid followed by oral linezolid suspension, both at a dose of 10 mg/kg every 12 h. Efficacy was assessed at 7 to 14 days after the last dose of linezolid. PATIENTS: Children 12 months to 17 years old with community-acquired pneumonia admitted to the hospital of 14 participating centers. RESULTS: From July 21, 1998, through May 14, 1999, 79 children were enrolled and 78 received linezolid. Sixty-six children completed treatment and follow-up and were evaluable for clinical outcome. The median age of the evaluable patients was 3 years (range, 1 to 12 years); 47 were 2 to 6 years old. Pathogens were isolated from blood or pleural fluid cultures in 8 children: Streptococcus pneumoniae, 6 (2 penicillin-resistant); Group A Streptococcus, 1; methicillin-resistant Staphylococcus aureus, 1. Chest tubes were placed in 9 patients. The mean total duration of intravenous and oral administration was 12.2 +/- 6.2 days (range, 6 to 41 days). The mean peak and trough plasma concentrations of linezolid were 9.5 +/- 4.8 and 0.8 +/- 1.2 microg/ml, respectively. At the follow-up visit 7 to 14 days after the last dose of linezolid, 61 patients (92.4%) were considered cured including all the patients with proven pneumococcal pneumonia, one failed (methicillin-resistant Staphylococcus aureus) and 4 were considered indeterminate. The most common adverse effects in the intent to treat group were diarrhea (10.3%), neutropenia (6.4%) and elevation in alanine aminotransferase (6.4%). CONCLUSIONS: Linezolid was well-tolerated and could be considered an alternative to vancomycin for treating serious infections caused by antibiotic-resistant Gram-positive cocci in children pending results of additional studies.

Multidisciplinary committee on the abuse of prescription medications.

A program for (1) coordinating the care of patients suspected of abusing prescription medications and (2) providing data on the long-term outcomes of these interventions is described. A substance abuse committee composed of physicians, psychologists, pharmacists, and administrators was established to review individual cases of suspected misuse or abuse of medications at a large Department of Veterans Affairs medical center. After reviewing each case, the committee recommended specific actions, such as requesting that the identified medication be restricted from the patient or that the patient receive counseling or treatment for substance abuse. To evaluate the program's effectiveness, the records of the 161 cases referred to the committee between 1981 and 1992 were reviewed. The patient's outcome one year after committee intervention could be determined in 105 cases. Of those, 70 revealed either no evidence of continuing prescription drug abuse or reduced use of the targeted medication in the medical center. Eighteen other patients were no longer receiving care at the institution. A multidisciplinary substance abuse committee helped identify and treat patients suspected of abusing prescription drugs.

[Behavior of the joint surface of the distal radio-ulnar joint in malposition of the distal radius]. / Gelenkflächenverhalten der Articulatio radioulnaris distalis bei fehlgestelltem distalem Radius.

Pathological changes of wrist bones and ligaments after radial fracture loco typico induce permanent functional restriction and pain. In this paper the effects of malunion on the distal radioulnar joint are investigated and osteotomic therapy of Kienböck's disease gets a new evaluation. By simulating radial malunions on anatomic forearm specimen the effects of these malunions on the contact area during supination, neutral position and pronation are measured. Isolated posttraumatic radial shortening as well as epiphyseal inclination and torsion cause a reduction of radioulnar contact. During supination and pronation the loss of radioulnar contact increases. Most significant reduction of contact takes place at a lower graduation of radial malunion. Pronatory torsion of distal radius compensates for a radioulnar contact reduction from combining dorsal inclination with radial shortening. One conclusion of this paper is an exact restitution of anatomical relations between ulnar head and radial notch after fracture of the distal radius.

Clinical outcome and adverse effect profile associated with concurrent administration of alprazolam and imipramine.

Clinical outcome and adverse effects associated with concurrent alprazolam and imipramine administration were studied in 29 patients with major depressive disorder who completed a 6-week trial in which they served as their own controls. Alprazolam was added on Day 8 in gradually escalating, then gradually tapering dosages while imipramine dosages remained unchanged. Significant decreases were observed in scores on the Hamilton Rating Scales for Depression and Anxiety at all later evaluation days with Day 8 as baseline. The mean total Symptom and Side Effects score decreased significantly from Day 8 to Day 22 when alprazolam doses were 1 mg q.i.d. For most side effects, total number of reports remained constant or decreased from Day 1 to later evaluation days. Standing diastolic blood pressures were significantly lower on Day 22 than on Day 1. No significant relationship was found between any rating scale score and plasma concentration data.

Haloperidol decanoate: a depot antipsychotic.

This article reviews the role of a new depot antipsychotic dosage form, haloperidol decanoate (HD), in relationship to other comparable pharmacotherapies (oral and injectable). The chemistry, indications, contraindications, and pharmacokinetics of HD are discussed. The available clinical research in humans is presented and evaluated with respect to efficacy, adverse effects, and dosing. HD is clearly an effective antipsychotic dosage form. Certainly, HD can improve compliance and possibly outcome for selected patients. HD should be reserved for chronic relapsing schizophrenic patients who have responded to oral haloperidol. Considering the pharmacokinetics, potential risks, and cost of HD, the clinician needs to be prepared with recommendations to effect optimal use of HD (guidelines are presented).

A review of lithium dosing methods.

Lithium's narrow therapeutic range, concentration-effect relationship, and large differences in interindividual disposition make it an attractive candidate for predictive dosing methods. Lithium disposition is influenced by a number of factors, including patient characteristics, renal function, and concomitant drug therapies. These factors are accounted for, in varied degrees, in the different dosing methods available. One a priori method takes many of these factors into account and appears to have better reliability than others that ignore nonrenal influences on lithium disposition. The lack of data on pharmacokinetic values in different populations limits the usefulness of many of the single-point methods. Better data on the disposition of lithium in differing populations would greatly enhance the utility of both the a priori and single-point methods. Several multipoint methods, which estimate an individual's pharmacokinetic values, have also been described. These appear to be the most reliable, although they are time consuming and may delay the initiation of therapy. A well-designed Bayesian approach to the dosing of lithium, although not currently available, would be the most useful.