Delivery of tobramycin by three infusion systems

The delivery of tobramycin was studied at the flow rates of 2, 4 and 6 ml/h after injection into the various sites of IVAC, IMED and Auto Syringe infusion systems. The actual times were markedly longer than the predicted times of delivery, especially for all sites of IVAC system and Buretrol site of IMED system. About 20% of tobramycin was never delivered by the Buretrol sites of IVAC and IMED during a 12-hour period at the flow rate of 2 ml/h. If tobramycin delivery is to be assured within 30 min after the start of infusion, at 2-6 ml/h, proximal y-site of IMED or Auto Syringe systems must be utilized. These data suggest the need for considering the method of tobramycin infusion when monitoring and interpreting its serum concentrations.     

Clinical use of systemic antifungal agents

The chemistry, pharmacology, pharmacokinetics, clinical uses, adverse effects, and drug interactions of amphotericin B, flucytosine, ketoconazole, and miconazole are reviewed. Amphotericin B, a heptaene compound with poor water solubility, disrupts the fungal cell wall by binding to ergosterol. Ketoconazole and miconazole, imidazole derivatives, are poorly water soluble and inhibit the synthesis of ergosterol. Flucytosine is a readily water-soluble, fluorinated pyrimidine agent that may be metabolized to fluorouracil. The pharmacokinetics of amphotericin B is unique and has not yet been clearly defined. After oral administration, absorption of flucytosine from the gastrointestinal tract is rapid and nearly complete. In adults, oral administration of ketoconazole produces peak concentrations of drug one to two hours after the dose. Miconazole is administered only intravenously and distributes well into most tissues. Amphotericin B remains the drug of choice for most systemic mycoses. Dosing of amphotericin B is often empiric and patient specific. Flucytosine is rarely used alone; the combination of flucytosine and amphotericin B exerts synergistic killing of many fungi. Ketoconazole is effective for treating many chronic fungal infections. Miconazole is seldom used because of the availability of agents that are equally effective, less toxic, or both. Nephrotoxicity can occur with amphotericin B therapy, while flucytosine is associated with gastrointestinal and hematologic toxicities. Ketoconazole is much less toxic than any of the other agents, while miconazole has a high incidence of adverse effects. In addition to the need for more effective and less toxic agents, research is needed to clearly define the pharmacokinetics and pharmacodynamics of currently available antifungal drugs.     

SERUM CONCENTRATIONS OF GENTAMICIN IN PATIENTS WITH MYELOMENINGOCELE

Gentamicin serum concentrations were studied in 18 paediatric and adult patients. The doses of gentamicin had to be adjusted for 6 of 18 patients to keep peak and trough serum concentrations below 8 and 2 micrograms/ml, respectively. Thus, serum concentrations monitoring of gentamicin may be useful to individualize doses in patients with myelomeningocele. Additional studies are needed to define specific dosage guidelines in patients of varying ages and disease severity for optimal therapy.     

Abstracts of papers and posters advanced activities in pharmaceutical care 24th European Symposium on Clinical Pharmacy

Supported by JNICT - Programa Ciência. Portugal     

Variability in clinical pharmacology of drugs in children.

Numerous factors can lead to variability in pharmacokinetics, pharmacodynamics, efficacy, and toxicity of drugs in infants and children. These may include age, race or genetic status, organ function, underlying disease(s), drug formulation, concomitant drugs, and compliance with therapy. Further research is needed to clarify the mechanisms for variability in drug response to achieve optimal use of drugs in paediatric patients.     

Treatment and prevention of infections of cerebrospinal fluid shunts

The etiology, pathogenesis, clinical manifestations, diagnosis, and treatment of cerebrospinal fluid (CSF) shunt infections are reviewed. Infection is a frequent complication of neurosurgical procedures performed for the treatment of hydrocephalus. Shunt infections generally occur within the first two months after surgery. Staphylococcus epidermidis is the most common cause of infections of both ventriculoatrial and ventriculoperitoneal shunts. The preferred treatment of CSF shunt infections involves intravenous antimicrobial therapy, surgical removal of the infected shunt, installation of an extraventricular drainage device, and placement of a new shunt once the CSF is sterile. However, many aspects of therapy are controversial because few controlled, comparative studies have been reported. Intravenous vancomycin is the drug of choice for empiric treatment of shunt infections. Nafcillin is recommended for infections caused by methicillin-sensitive strains of staphylococci. Vancomycin should be used for infections caused by methicillin-resistant strains of staphylococci or in patients who are allergic to penicillin. The addition of rifampin has eradicated infections that failed to respond to monotherapy with vancomycin or nafcillin. Intraventricular antimicrobial therapy is indicated if the risks associated with surgery are high or if ventriculitis is persistent and refractory to systemic antimicrobial therapy. The role of prophylactic antimicrobial therapy is controversial. Infection continues to be an important complication of CSF shunt placement; many aspects of treatment are controversial.     

Effectiveness of pretreatment in decreasing adverse events associated with pamidronate in children and adolescents

STUDY OBJECTIVES: To assess the effectiveness of pretreatment with ibuprofen or acetaminophen compared with no pretreatment in decreasing adverse events in children and adolescents receiving the first and second series of pamidronate therapy; and to compare the effectiveness of ibuprofen versus acetaminophen for prevention of adverse events associated with pamidronate infusion. DESIGN: Retrospective case review. SETTING: Children's hospital. PATIENTS: Twenty-seven children and adolescents aged 3-21 years receiving pamidronate therapy. MEASUREMENTS AND MAIN RESULTS: Data for patient demographics, medical history, genetic history of disease, pamidronate infusion dosage, and concurrent drug therapy were collected. Adverse drug events secondary to pamidronate infusion and subsequent drug therapies received were documented. Data were categorized by presence or absence of pretreatment and analyzed by cross-tabulation to determine whether the presence of adverse events differed between groups (no pretreatment, acetaminophen pretreatment, and ibuprofen pretreatment). Fewer adverse events were reported in patients receiving ibuprofen (17% of patients) versus acetaminophen (83%). Differences in presence of fever (chi2 = 10.5, p = 0.005) and bone pain (chi2 = 7.3, p = 0.027) among the three pretreatment groups were also statistically significant. CONCLUSION: Pretreatment with ibuprofen or acetaminophen appears to decrease the occurrence of adverse events from pamidronate therapy. However, adverse events seem less likely to occur with ibuprofen. Further study is necessary to determine the relationship between occurrence of adverse events, other possible treatment strategies, and patient adherence with pamidronate therapy.     

The safety and antiviral effect of protease inhibitors in children

STUDY OBJECTIVE: To determine the safety and antiviral effect of protease inhibitors (PIs) over 36 months in pediatric patients infected with the human immunodeficiency virus (HIV). DESIGN: Observational study SETTING: Pediatric immunodeficiency clinic. PATIENTS: Twenty-one children. INTERVENTION: Demographics, dosage regimens, genotype data, viral RNA and CD4+ lymphocyte counts, adverse drug events (ADEs), laboratory tests, and compliance were evaluated over 3 years. Data were analyzed by chi2, repeated measures analysis of variance, and paired t tests. MEASUREMENTS AND MAIN RESULTS: Twenty-one pediatric patients (aged 3 mo-15 yrs) received PIs over the study period. Average daily doses were ritonavir 26 mg/kg in 12 patients, nelfinavir 94 mg/kg in 16, indinavir 49 mg/kg in 5, and saquinavir 43 mg/kg in 4. Five patients developed resistance to an existing PI. Overall compliance was 70%. Baseline HIV-1 RNA plasma concentrations were significantly higher than average follow-up concentrations during 3-36 months in patients taking ritonavir (p<0.001) and nelfinavir (p<0.001). Sample size was insufficient for indinavir or saquinavir. Sixty ADEs occurred, diarrhea being most common. Of patients with ADEs, 55% required increased monitoring and 43% treatment. Ritonavir was associated with the most ADEs (28), followed by nelfinavir (16), indinavir (11), and saquinavir (5). Significant increases between baseline and follow-up cholesterol levels were found with ritonavir (p=0.02) and nelfinavir (p=0.001), and for serum creatinine (p=0.02) and triglycerides (p=0.02) with ritonavir. Follow-up triglycerides were significantly higher than baseline for indinavir (p=0.003). CONCLUSION: Nelfinavir and ritonavir were effective in decreasing HIV-1 viral loads and improving CD4+ lymphocyte counts. Ritonavir was associated with more ADEs than other PIs. Changes in cholesterol, serum creatinine, and triglycerides were noted with some PIs.