Interaction between ciprofloxacin and rifampin.

OBJECTIVE: To discuss the necessity of dose adjustment for ciprofloxacin or rifampin during their concurrent use. DATA SOURCES: A MEDLINE search (1966-December 1998) was completed using key terms rifampin and fluoroquinolone. English-language journals were considered. DATA SYNTHESIS: Studies in elderly patients after 14 days of therapy with oral ciprofloxacin and rifampin did not demonstrate significant differences in the pharmacokinetics of ciprofloxacin as compared with those in patients receiving ciprofloxacin alone. Similar results were found in intravenous drug abusers. In comparison to the pharmacokinetics of both ciprofloxacin and rifampin when given alone, the serum bactericidal activity of rifampin, when given with ciprofloxacin in healthy elderly volunteers, was reduced but still evident. Ciprofloxacin pharmacodynamics were not significantly altered. Serum bacterial titers of ciprofloxacin and pefloxacin increased twofold when given with rifampin, although their clinical significance is unknown. RECOMMENDATION: No strong evidence of a significant interaction exists to support dose adjustment for ciprofloxacin or rifampin during their concurrent use.     

Pharmacokinetics and tissue concentrations of cefazolin in pediatric patients undergoing gastrointestinal surgery

Limited information is available on the pharmacokinetics and tissue penetration of cefazolin in pediatric patients. Nine children (age 0.8-10 years) undergoing gastrointestinal operations were studied. A single dose of cefazolin, 15-26 mg/kg was given i.v. over 2-3 min at the time of induction of anaesthesia. Multiple (5-8) blood samples were collected during the operative procedure and in the recovery room. Tissue samples from the rectus abdominis muscle were obtained at the time of incision, during surgery, and at closure. The concentration of cefazolin was measured by a high performance liquid chromatographic method. Peak serum concentrations of cefazolin ranged from 85.8-269.4 mcg/ml. Serum and tissue concentrations at incision were 50.5-169.9 mcg/ml and 1.8-29.7 mcg/g; at closure the serum and tissue concentrations ranged from 17.3-60.9 mcg/ml and 1.19-29.70 mcg/g, respectively. Total clearance, apparent distribution volume, and elimination half-life of cefazolin were 1.43 +/- 0.54 ml/min/kg, 0.08 +/- 0.03 l/kg, and 1.68 +/- 0.55 h respectively. Tissue concentrations of cefazolin were maintained above its minimum inhibitory concentrations against common susceptible pathogens. Hence, the current dosing regimen of cefazolin is adequate to protect against infection in pediatric patients undergoing gastrointestinal surgery.     

Pharmacokinetics of cefotaxime and its active metabolite in children with renal dysfunction.

We studied cefotaxime (CTX) and desacetylcefotaxime (dCTX) pharmacokinetics in 19 children (ages, 7 to 16 years) with various degrees of renal function. The patients were stratified into three groups according to 24-h urinary creatinine clearance (CLCR) values: group I, CLCR greater than 80 ml/min/1.73 m2 (n = 7); group II, CLCR from 30 to 80 ml/min/1.73 m2 (n = 6); and group III, CLCR less than 30 ml/min/1.73 m2 (n = 6). A single 50-mg/kg dose of CTX was given intravenously to each patient after which blood and urine samples were collected and analyzed for CTX and dCTX by high-performance liquid chromatography. Safety was assessed by pre- and poststudy blood chemistries and urinalysis. The mean values for total body clearance of CTX for groups I, II, and III were 158.1 +/- 38.8, 118.3 +/- 50.8, and 84.8 +/- 11.7 ml/min/1.73 m2, respectively (P less than 0.01). Renal clearance also decreased across groups, I, II, and III, with values of 77.5 +/- 20.2, 41.3 +/- 18.5, and 11.4 +/- 7.7 ml/min/1.73 m2 respectively (P less than 0.0001). Both the CTX fraction nonrenally cleared and elimination half-life increased with decreasing renal function. The CTX volume of distribution at steady state was not affected by renal disease. The renal clearance values of dCTX were 146.4 +/- 71.4, 64.5 +/- 32.1, and 14.4 +/- 8.7 ml/min/1.73 m2 for groups I, II, and III, respectively (P less than 0.0004). Elimination half-life values were 2.04 +/- 0.39, 3.87 +/- 1.93, and 6.19 +/- 3.22 h for the respective groups (P less than 0.006). Both the maximum concentration of dCTX in plasma and time to reach the maximum concentration of dCTX in plasma were increased with decreased CLCR. The results of this study indicate that dosage adjustment may be necessary for CTX in children with renal dysfunction. On the basis of the pharmacokinetics and antimicrobial activities of the parent drug and its metabolite, dosage reductions of 25 to 50% in children with moderate renal impairment (CLCR from 30 to 80 ml/min/1.73 m2) and 50 to 75% in children with severe renal impairment (CLCR < 30 ml/min/1.73 m2) are recommended.     

Pharmacokinetics and cerebrospinal fluid concentration of nafcillin in pediatric patients undergoing cerebrospinal fluid shunt placement

Postoperative infection is among the most common complications in patients with cerebrospinal fluid shunt placement. Nafcillin is often used for prophylaxis but not pharmacokinetic data are available perioperatively in pediatric patients. The objectives of this study were to characterize the pharmacokinetics and determine the cerebrospinal concentrations of nafcillin. Ten patients (mean age 8.0 +/- 5.6 years) received three doses of intravenous nafcillin, 50 mg/kg every 6 h; the first dose was administered 1 h prior to surgery. Multiple blood samples were collected during and after surgery and the cerebrospinal fluid sample was obtained at the time of shunt insertion. Urine samples were collected for 24 h after initiation of nafcillin. Nafcillin was analyzed with an HLPC method. The peak serum concentrations ranged from 22 to 107 micrograms/ml; cerebrospinal fluid concentrations ranged from 0.02 to 0.30 (mean 0.16 +/- 0.11) micrograms/ml. The mean total clearance, renal clearance, apparent volume of distribution, and elimination half-life were 0.90 +/- 0.55 l/kg/h, 0.12 +/- 0.04 l/kg/h, 0.70 +/- 0.52 l/kg, and 0.5 +/- 0.1 h, respectively. 16% of total nafcillin dose was excreted in the urine. A 4-fold variability in total clearance and a 10-fold variation in cerebrospinal fluid concentrations of nafcillin was observed in these patients. Further, the concentrations of nafcillin attained in the cerebrospinal do not appear to be adequate, based on its minimum inhibitory concentration of 0.5 micrograms/ml against very susceptible staphylococci. These data, in addition to the fact that an increasing number of staphylococci are becoming resistant to nafcillin, question the usefulness of prophylactic nafcillin in pediatric patients undergoing shunt procedures.     

Development of a Pediatric Fertility Preservation Program: A Report From the Pediatric Initiative Network of the Oncofertility Consortium

Infertility is known to decrease quality of life among adults. In some cases, infertility is caused by medical conditions and/or treatments prescribed in childhood, and using methods to protect or preserve fertility may expand future reproductive possibilities. Structured programs to offer counseling about infertility risk and fertility preservation options are essential in the care of pediatric patients facing fertility-threatening conditions or treatments, yet multiple barriers to program development exist. This report was developed from the institutional experiences of members of the Pediatric Initiative Network of the Oncofertility Consortium, with the intent of providing guidance for health care providers aiming to establish programs at institutions lacking pediatric fertility preservation services. The mechanics of building a fertility preservation program are discussed, including essential team members, target populations, fertility preservation options (both established and experimental), survivorship issues, research opportunities, and ethical considerations. Common barriers to program development and utilization, including low referral rates and financial concerns, are also discussed, and recommendations made for overcoming such barriers.     

Advances in paediatric pharmacotherapy.

Marked differences in body composition and organ function development have been demonstrated among neonates, infants, and children versus adults. Specific dosage guidelines for the paediatric population, however, are still not available for the majority of marketed drugs. Much needs to be learned about the pharmacokinetics, pharmacodynamics, comparative efficacy and safety of drugs in infants and children. Recent developments in paediatric therapeutics include the availability of several new antibiotics for the treatment of infections including, streptococcal pharyngitis, otitis media, bacterial meningitis, herpes encephalitis, neonatal herpes, and AIDS. Corticosteroids and intravenous immunoglobulin have become important adjunctive treatments for certain infections. A variety of drugs are available to treat asthma but the mortality due to this disease is still increasing. The identification of a gene defect in patients with cystic fibrosis could lead to more effective treatment in the future. Ondansetron, marketed for use in adults only, shows promise as a more effective and safer antiemetic in children receiving cancer chemotherapy. Numerous drugs are not available in suitable dosage forms for paediatric use and extemporaneous formulations are required. Documentation on the stability of the reformulated drugs is therefore needed. Studies have shown that the methods used for intravenous delivery can influence the serum concentrations of drugs in infants and children. Large numbers of children could be saved worldwide solely with improved vaccination and control of diarrhoea. Despite this, it is encouraging to witness the continued advances being made in paediatric pharmacotherapy.     

Pharmacokinetics of azithromycin in pediatric patients after oral administration of multiple doses of suspension.

Azithromycin is an azalide antibiotic. On the basis of data in adults, azithromycin appears to have a greater distribution into tissues, a longer elimination half-life, and a lower incidence of adverse effects than the macrolide antibiotic erythromycin. However, little about the pharmacokinetics of azithromycin in children is known. The objective of our study was to characterize the pharmacokinetics of azithromycin after oral administration of multiple doses of suspension to children with streptococcal pharyngitis. Fourteen children (6 to 15 years of age) received a single oral dose of 10 mg of azithromycin per kg of body weight on day 1 followed by single daily doses of 5 mg/kg on days 2 to 5. Each child fasted overnight before receiving the final dose on day 5. Blood samples were collected at 0, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, and 72 h after this last dose. Concentrations of azithromycin in serum were measured by a specific high-performance liquid chromatography-mass spectrometry method. The mean +/- standard deviation for maximum concentration of drug in serum, time to maximum concentration of drug in serum, and area under the curve (0 to 24 h) were 383 +/- 142 ng/ml, 2.4 +/- 1.1 h, and 3,109 +/- 1,033 ng.h/ml, respectively. Concentrations in serum at 0 h (predose) and at 24, 48, and 72 h after the final dose were 67 +/- 31, 64 +/- 24, 41 +/- 17, and 29 +/- 14 ng/ml, respectively. Thus, once-daily administration of azithromycin resulted in sustained systemic exposure to the drug.     

Impact of a novel family-centered values clarification tool on adolescent sperm banking attempts at the time of a new cancer diagnosis

Purpose

Over half of males experience fertility impairment after childhood cancer therapy, which often causes psychosocial distress. Yet, fertility preservation (FP) remains underutilized. The goals of this study were to determine the feasibility and impact of implementing a family-centered FP values clarification tool on sperm banking attempts among adolescent males newly diagnosed with cancer, and identify key determinants of banking attempts.

Methods

A prospective pilot study was conducted among families of males (12–25 years old), prior to cancer therapy. Thirty-nine of 41 families agreed to participate (95%); 98 participants (32 adolescents, 37 mothers, 29 fathers) completed the Family-centered Adolescent Sperm banking values clarification Tool (FAST). Analyses assessed the impact of the FAST on banking attempts and examined associations between demographic/medical characteristics, FAST subscales (perceived threat, benefits, barriers), and banking attempts.

Results

Twenty-three (59%) adolescents attempted to bank, compared to 8 adolescents (33%) during baseline assessment (p=.04). Significant associations were identified between banking attempts and adolescents’ report of perceived threat (r_pb=.45, p=.01) and benefits (r_pb=.57, p=.01). Only mothers’ proxy reports of adolescent perceived threat (r_pb=.42, p=.01) and benefits (r_pb=.47, p=.003) were associated with banking attempts, while fathers’ self-reported perceived benefits (r_pb=.43, p=.03), self-reported barriers (r_pb=.49, p=.01), and proxy reports of adolescent perceived threat (r_pb=.38, p=.04) and benefits (r_pb=.59, p=.02) were associated with banking attempts.

Conclusion

Adolescent sperm banking attempt rates significantly increased after implementation of a family-centered FP values clarification tool prior to cancer treatment. Findings underscore the importance of targeting both adolescents and their parents, particularly fathers, in FP efforts.