Tobramycin pharmacokinetics in very low birth weight infants.

Tobramycin is commonly used at a dose of 2.5 mg kg-1 12h-1, but this regimen often results in trough serum concentrations exceeding 2 mg l-1. Because of limited data in infants weighing less than 1,000 g at birth, we studied eight newborn infants (gestational age 24-30 weeks; postnatal age 3 X 4 days; birth weight 0.60-0.97 kg) at a modified dosing regimen of 2.5 mg kg-1 18 h-1 or 3.0 mg kg-1 24 h-1. Tobramycin peak and trough serum concentrations ranged from 6.0-10.8 (7.8 +/- 1.5) mg l-1 and 1.2-2.4 (1.7 +/- 0.4) mg l-1, respectively. Serum concentration exceeded 2 mg l-1 in seven of eight patients at 12 h and two of eight at 18 h; none had a trough serum concentration above 2 mg l-1 at 24 h. Total body clearance ranged from 0.55 to 0.82 (0.69 +/- 0.10) ml min-1 kg-1; apparent volume of distribution ranged from 0.44 to 0.71 (0.59 +/- 0.10) 1 kg-1; and elimination half-life ranged from 7.7 to 12.6 (9.9 +/- 1.5) h. These data indicate that the modified dosage regimen of 2.5 mg kg-1 18 h-1 or 3.0 mg kg-1 24 h-1 appears to be more acceptable than the current regimen in achieving effective and safe peak and trough serum concentration of tobramycin in newborn infants weighing less than 1 kg at birth.     

Clinical use of antiviral drugs

Remarkable progress has been made in antiviral chemotherapy. Six approved antiviral drugs are now available for the treatment of various viral infections. Trifluridine, idoxuridine and vidarabine are all effective in patients with herpes keratitis; trifluridine is preferred due to its low toxicity. Acyclovir is the drug of choice in patients with infections due to herpes simplex viruses, including genital herpes, herpes encephalitis, and neonatal herpes, and infections due to varicella-zoster virus. Amantadine is the only drug currently available for prophylaxis and treatment of influenza A, but an investigational drug, rimantadine, appears to be equally effective and less toxic than amantadine. Ribavirin is the most recently approved antiviral agent for the treatment of respiratory syncytial virus infections. Numerous antiviral drugs are being studied in patients with acquired immunodeficiency syndrome. Although currently available drugs have improved our ability to manage a variety of viral illnesses, much needs to be learned about specific dosage guidelines based on the studies of pharmacokinetics, pharmacodynamics, potential adverse effects and viral resistance, and the role of combination therapy to optimize therapy.     

Pharmacologic treatment of chronic pediatric hypertension

Improved recognition of the relationship between childhood and adult blood pressures and identification of end-organ damage in children, adolescents, and young adults with hypertension has led to increased focus by pediatricians and general practitioners on the detection, evaluation, and treatment of hypertension. Notably, detection, evaluation, and treatment of pediatric hypertension has increased significantly since the first Task Force Report on High Blood Pressure in Children and Adolescents in 1977 with advances in both nonpharmacologic and pharmacologic treatments.Angiotensin-converting enzyme inhibitors (e.g. captopril, enalapril, lisinopril, ramipril) and calcium channel antagonists (e.g. nifedipine, amlodipine, felodipine, isradipine) are the most commonly prescribed antihypertensive medications in children due to their low adverse-effect profiles. Diuretics (e.g. thiazide diuretics, loop diuretics, and potassium-sparing diuretics) are usually reserved as adjunct therapy. Newer agents, such as angiotensin receptor antagonists (e.g. irbesartan), are currently being studied in children and adolescents. These agents may be an option in children with chronic cough secondary to angiotensin-converting enzyme inhibitors. beta-Adrenoreceptor antagonists (e.g. propranolol, atenolol, metoprolol, and labetalol), alpha-adrenoreceptor antagonists, alpha-adrenoreceptor agonists, direct vasodilators, peripheral adrenoreceptor neuron agonists, and combination products are less commonly used in pediatric patients because of adverse events but may be an option in children unresponsive to calcium channel blockers, angiotensin converting-enzyme inhibitors, or angiotensin receptor blockers.     

Abnormal left ventricular mass and aortic distensibility in pediatric dialysis patients

There is ample evidence that the same pathophysiological processes that affect cardiovascular function in adults with end-stage renal disease (ESRD) also operate in children with ESRD. In adults undergoing hemodialysis (HD), a good correlation has been established between left ventricular mass (LVM) and aortic distensibility (AD) as markers of cardiovascular disease progression; however, this correlation has not been established in children. Therefore, in this retrospective study we investigated some aspects of cardiovascular damage (i.e., LVM, LVMI, and AD) in children with ESRD undergoing HD ( n =9) or peritoneal dialysis (PD, n =9), and analyzed the relationship between AD, LVM, LVMI, pre-dialysis, post-dialysis blood pressure (BP), and demographic factors in children and adolescents with ESRD. Both LVM and AD were significantly greater in the dialysis population than in a control population derived from our institutional files ( P =0.015, P =0.001). LVM and LVMI in children undergoing HD (92.9±83.7 g, 80.1±31.1 g/cm) were not statistically different from the values in children on PD (130.0±89.2 g, 89.6±35.9 g/cm), ( P =0.3, P =0.5). AD in children on HD (2.2±0.55 cm² * dynes^–1*10–6) was significantly lower than in children on PD (2.7±0.54 cm² * dynes^–1*10–6), ( P =0.01). The findings in this study confirm earlier studies that demonstrated that LVMI is greater in children on dialysis. This study also demonstrates that abnormal vascular stiffness, as defined by AD, is present in these children. The degree of vascular stiffness in children receiving HD is greater than in children receiving PD. However, further study is needed to address how control of BP, uremia, and other factors may affect these abnormalities in children with ESRD.     

Periorbital cellulitis secondary to Conidiobolus incongruus

A previously healthy, 18-month-old girl developed edema and erythema around her left eye 1 week after getting sand in that eye. The patient did not respond to oral or intravenous antibiotics. A mass developed around the eye, and biopsy revealed Conidiobolus incongruus. The patient failed to respond to amphotericin B 1 mg/kg, and susceptibility tests indicated multiantifungal resistance. A combination of antifungal therapy, hyperbaric oxygen, and surgery was required for successful treatment. Three months after treatment the child was disease free. There is no definitive therapy for Conidiobolus incongruus infections, although various drugs have been administered with some success. When susceptibility tests determine multidrug resistance, radical resection with antifungal chemotherapy and hyperbaric oxygen may be necessary as well as lifesaving.     

Advancing patient care through innovative practice: the Clinical Partners Program.

PURPOSE: The development, implementation, and outcomes assessment of an innovative pharmacist-managed ambulatory care and community pharmacy practice clinic are described. SUMMARY: The Clinical Partners Program at The Ohio State University (OSU) provides an active learning environment for students and residents, offers a patient-focused practice model based on pharmaceutical care principles, and serves as an arena for applied research in pharmacy practice. The program offers multiple services, including anticoagulation management, diabetes self-management, cholesterol management, hepatitis C education, herbal product and dietary supplement consultations, medication management, smoking cessation, and wellness. The practice is currently staffed by two faculty members from the college of pharmacy, with a 0.8 full-time-equivalent (FTE) pharmacist and a 0.65 FTE community pharmacy resident. It has served as a training site for 17 pharmacy residents, 28 bachelor of science (B.S.) in pharmacy students, 30 post-B.S. doctor of pharmacy (Pharm.D.) students, and 132 entry-level Pharm.D. students at various levels of training. The most successful methods of reimbursement for programs have been contracted services with OSU Managed Health Care Systems, Inc., which serves OSU faculty and staff and fee-for-service billing, charged directly to non-OSU patients. Numerous studies have shown that Clinical Partners has consistently demonstrated improved therapeutic outcomes over those achieved in traditional practice. Faculty are exploring outreach services, including the development of advanced practice community sites for the college, establishing patient care services within physician offices, and providing disease management services for self-insured employers. CONCLUSION: The Clinical Partners Program has improved patient care and provided education and training opportunities for pharmacy students and residents.     

Pharmacokinetics of fluconazole in young infants.

Intravenous fluconazole is used in the treatment of fungal infections in infants. Little is known, however, about the pharmacokinetics of fluconazole after oral administration in premature infants. Oral fluconazole was administered at a dose of 6 mg/kg. The peak serum concentration (Cmax), area under the serum concentration-time curve (AUC), and apparent clearance ranged from 6.0-13.5 micrograms/ml, 340-636 micrograms.h/ml, and 0.16-0.29 ml/min/kg, respectively. The Cmax and AUC were comparable after oral and intravenous doses of fluconazole. Oral fluconazole was well absorbed and tolerated. The use of oral fluconazole may offer an important alternative to the intravenous therapy; it may improve patient convenience, reduce the need for venous access and decrease complications and the cost of health care.