Cystic Fibrosis (CF) is a genetic disease, leading to changes of membrane secretions causing obstruction of smaller airways. CF patients often develop pulmonary infections and require antibiotic treatment. Meropenem is a broad spectrum beta lactam that acts by lysing microbes through interfering with bacterial cell wall synthesis. Although a safe and effective treatment, data on pediatric patients is limited

Cushing, Marissa

Draime, Juanita A.

Gryka, Rebecca J.

Ho, Bao-Ngoc

Nicholls, Jordan

Sibbitt, Bethany

Simpson, Denise S.

Widder, Rebecca

English

Cystic fibrosis (CF), a genetic disease affecting the lungs and Gl tract, is the second most common disease leading to shortened life spans in children. As a result of disease pathology, patients experience frequent lung infections along with nausea, loss of appetite, and poor absorption of nutrients. Current treatment for these infections involves continuous or intermittent IV meropenem therapy. One frequent side effect of meropenem in cystic fibrosis patients is nausea, vomiting, and diarrhea, leading to further weight loss in these patients. It is hypothesized that increased serum concentrations of meropenem lead to increased incidences of the Gl side effects, and that continuous IV administration of meropenem will reduce nausea when compared to intermittent administration. This collaborative project with Dayton Children\u27s Hospital, to be completed in the spring of 2015, proposes to improve the quality of life and care for pediatric CF patients by assessing reported nausea and its relationship to serum concentration of meropenem as well as testing established clinical protocols for meropenem administration in pediatric CF patients admitted to Dayton Children\u27s. A crossover design will be used, with patients randomly divided into two treatment groups. One group will receive four days of a 120 mg/kg/day continuous IV dose of meropenem followed by an intermittent 40 mg/kg/dose infused over 30 minutes every eight hours for another four days. The other group will receive the intermittent dose followed by the continuous infusion. Serum concentrations will be quantified utilizing a High Pressure Liquid Chromatography instrument and incidence of nausea will be measured through the average doses of kytril, an antiemetic, ordered for each patient in addition to the number of episodes of emesis. This study will be carried out with around 10 participants in order to provide a framework for further multi-site studies of the same nature

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A Comparison of the Effect of Intermittent and Continuous Infusion of Meropenem on the Prevalence of Nausea in Pediatric Cystic Fibrosis Patients

Cedarville UniversityDigitalCommons@CedarvillePharmacy and Nursing Student Research and Evidence-Based Medicine Poster Session11-2012A Comparison of the Effect of Intermittent andContinuous Infusion of Meropenem on thePrevalence of Nausea in Pediatric Cystic FibrosisPatientsMarissa CushingCedarville University, mcushing@cedarville.eduJuanita A. DraimeCedarville University, juanitaadraime@cedarville.eduBao-Ngoc HoCedarville University, blho@cedarville.eduJordan NichollsCedarville University, jnicholls@cedarville.eduBethany SibbittCedarville University, bgsibbitt@cedarville.eduSee next page for additional authorsFollow this and additional works at: http://digitalcommons.cedarville.edu/pharmacy_nursing_poster_sessionPart of the Chemicals and Drugs Commons, and the Medicinal and Pharmaceutical ChemistryCommonsThis Poster Session is brought to you for free and open access byDigitalCommons@Cedarville, a service of the Centennial Library. It hasbeen accepted for inclusion in Pharmacy and Nursing Student Researchand Evidence-Based Medicine Poster Session by an authorizedadministrator of DigitalCommons@Cedarville. For more information,please contact digitalcommons@cedarville.edu.Recommended CitationCushing, Marissa; Draime, Juanita A.; Ho, Bao-Ngoc; Nicholls, Jordan; Sibbitt, Bethany; Widder, Rebecca; Gryka, Rebecca J.; andSimpson, Denise S., "A Comparison of the Effect of Intermittent and Continuous Infusion of Meropenem on the Prevalence of Nauseain Pediatric Cystic Fibrosis Patients" (2012). Pharmacy and Nursing Student Research and Evidence-Based Medicine Poster Session. 6.http://digitalcommons.cedarville.edu/pharmacy_nursing_poster_session/6AuthorsMarissa Cushing, Juanita A. Draime, Bao-Ngoc Ho, Jordan Nicholls, Bethany Sibbitt, Rebecca Widder,Rebecca J. Gryka, and Denise S. SimpsonThis poster session is available at DigitalCommons@Cedarville: http://digitalcommons.cedarville.edu/pharmacy_nursing_poster_session/6• Background • Cystic Fibrosis and Treatment • Cystic Fibrosis (CF) is a genetic disease, leading to changes of membrane secretions causing obstruction of smaller airways • CF patients often develop pulmonary infections and require antibiotic treatment • Loss of lung function increases the risk of death in CF patients  • Standard treatment involves beta-lactam antibiotics ex. meropenem • Pharmacokinetics and Pharmacodynamics of Meropenem • Meropenem is a broad spectrum beta lactam that acts by lysing microbes through interfering with bacterial cell wall synthesis.  • Safe and effective treatment, however data on pediatric patients is limited • Effectiveness of meropenem determined by time sensitive dosing and is effective only when the minimum inhibitory concentration (MIC) is reached • Meropenem can be administered as a continuous infusion or intermittent bolus • Significance of the Problem • There is a lack of information regarding the use of meropenem in pediatric CF patients • There is a lack of supporting information for the use of one treatment regimen over the other • Quality of Life – CF patients struggle with malnutrition and treatment with meropenem compounds the problem due to significant nausea  • Would a different dosing regimen reduce side effects of meropenem treatment?      A comparison of the effect of intermittent and continuous infusion of meropenem on the prevalence of nausea in pediatric cystic fibrosis patients  Marissa Cushing, Juanita Draime, Bao-Ngoc Ho, Jordan Nicholls, Bethany Sibbitt, Rebecca Widder Drs. Rebecca Gryka and Denise Simpson Dayton Children’s Hospital STATEMENT OF THE PROBLEM To test establish clinical protocols for meropenem administration in pediatric CF patients admitted to Dayton Children’s with the goal of reducing nausea as a side effect.  To assess reported nausea and its relationship to serum concentration of meropenem in pediatric CF patients after administration of meropenem in either a continuous or intermittent IV infusion.  OBJECTIVES PROPOSED METHODS Study Design Crossover study designed to compare blood levels of meropenem and effect on nausea in pediatric cystic fibrosis patients Sample This pilot study will comprise approximately 10 subjects from ages seven to twenty-one Data Collection and Measurement Cross over study • Patients randomly divided into two treatment groups • One initially receives intermittent dosing of meropenem  • One receives continuous infusion of meropenem • Then groups will switch after four days • Continuous dose 120 mg/kg/day  • Intermittent dose 40 mg/kg/dose infused over 30 minutes every 8 hours Serum Meropenem • Determined through blood draw  • Intermittent dose: After the third dose • Continuous dose: After day three  Nausea Scale • Levels of nausea will be determined by recording frequency of Kytril doses requested PICC line • Sub-study to be conducted to determine reliability of serum levels taken from PICC line • Serum levels of meropenem in both groups compared between PICC line blood draws and peripheral blood draws. HPLC Assay • Meropenem concentrations will be measured utilizing a High Pressure Liquid Chromatography (HPLC) instrument       HYPOTHESES Null Hypotheses:  •Continuous IV administration of meropenem will have no effect on the side effects of nausea when compared to intermittent administration.  •The differences in serum concentrations between intermittent and continuous IV administration of meropenem do not change the number of dosages of anti-nausea medications ordered in pediatric CF patients   • Small sample size will limit the generalizability of the results. • Additional medication regimens may contribute to nausea. LIMITATIONS The goal of this study is to provide a framework for further multi-site studies of the same nature.  FUTURE DIRECTION Alternative hypotheses: •Continuous IV administration of meropenem will reduce the side effects of nausea when compared to intermittent administration  •The differences in serum concentration between intermittent and continuous IV administration of meropenem do change the number of dosages of anti-nausea medications ordered in pediatric CF patients   REFERENCES  •Newborn screening for cystic fibrosis evaluation of benefits and risks and recommendations for state newborn screening programs. Retrieved 25 Sept 2012.   <http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5313a1.htm>. •Flume, P. A., & Van Devanter, D. R. State of progress in treating cystic fibrosis respiratory disease BMC Medicine, 2012, 10(1), 88.  •“Cystic fibrosis.” A.D.A.M. Medical Encyclopedia. Retrieved 16 May 2012. <http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001167/>. •Christensson BA, Ljungberg B, Eriksson L, Nilsson-Ehle I. Pharmacokinetics of meropenem in patients with cystic fibrosis. Eur J Clin Microbiol Infect Dis. 1998, 17, 873–876. •Goss CH, Burns JL. Exacerbations in cystic fibrosis: Epidemiology and pathogenesis. Thorax. 2007, 62, 360–367. •Prescott, William, Allison Gentile, Jerod Nagel, and Rebecca Pettit. Continuous-Infusion Antipseudomonal Beta-Lactam Therapy in Patients with Cystic Fibrosis. Pharmacy and Therapeutics. 2011, 36(11), 723-763 •Gildon, K. Norrby, S. Safety profile of meropenem: A review of nearly 5,000 patients treated with meropenem. Scandinavian Journal of Infectious Diseases,1999, 31, 3. •Nicolau, David. Pharmacokinetics and Pharmacodynamic Properties of Meropenem. Clinical Infectious Diseases. 2008, 47, 32-40. •Byl B, Jacobs F, Roucloux I, de Franquen P, Cappello M, Thys J-P. Penetration of meropenem in lung, bronchial mucosa, and pleural tissues. Antimicrob Agents Chemother 1999, 43, 681–2. •Lodise TP, Lomaestro BM, Drusano GL, Society of Infectious Diseases Pharmacists. Application of antimicrobial pharmacodynamic concepts into clinical practice: focus on b-lactam antibiotics; insights from the Society of Infectious Diseases Pharmacists. Pharmacotherapy 2006, 26,1320–32. •Condon RE, Walker AP, Hanna CB, Greenberg RN, Broom A, Pitkin D. Penetration of meropenem in plasma and abdominal tissues from patients undergoing intraabdominal surgery. Clin Infect Dis. 1997, 24(Suppl 2), S181–3. •Blumer JL, Reed MD, Kearns GL, et al. Sequential, single-dose pharmacokinetic evaluation of meropenem in hospitalized infants and children. Antimicrob Agents Chemother. 1995, 39, 1721–5. •Du, Xiaoli, Li, Chonghua, Kuti, Joseph L., Nightingale, Charles H., and David P. Nicolau.Population Pharmacokinetics and Pharmacodynamics of Meropenem in Pediatric •Patients. Journal of Clinical Pharmacology. 2006, 46, 69-75. •Ellis JM, Kuti JL, Nicolau DP. Pharmacodynamic evaluation of meropenem and cefotaxime for pediatric meningitis: a report from the OPTAMA Program. Pediatric Drugs. 2006, 8,131–8. •ClinicalTrials.gov. clinicaltrials.gov. Retrieved 28 Sept, 2012. http://www.clinicaltrials.gov •Legrand, T., Chhun, S., Rey, E., Blanchet, B., et al. (2008). Simultaneous determination of three carbapenem antibiotics in plasma by HPLC with ultraviolet detection Journal of Chromatography B, 875(2; v875i0002), 551-556. •McWhinney, B. C., Wallis, S. C., Hillister, T., Roberts, J. A., Lipman, J., & Ungerer, J. P. (2010). Analysis of 12 beta-lactam antibiotics in human plasma by HPLC with ultraviolet detection Journal of Chromatography.B, Analytical Technologies in the Biomedical and Life Sciences, 878, 2039-2043. doi:10.1016/j.jchromb.2010.05.027 •FDA Bioanalytical Method Validation, 2001   We would like to thank Drs. Chen, Gryka and Simpson for their input and expertise on this project as well as acknowledging the ongoing collaboration with Dayton Children’s Hospital. Nausea levels: average the doses of Kytril requested by each patient, number of episodes of emesis Two tailed t test (α =0.05, and β = 0.2) Comparison of the means of two treatment arms. Concentration of meropenem in blood Arithmetic mean will be calculated for each sample (95% confidence interval) Comparison of Treatment Arms Two-tailed t-test will be used to compare means of the two treatment arms Two-tailed t-test will be used to compare the two types of blood draw methods PROPOSED ANALAYSES ACKNOWLEDGEMENTS TIMELINE • September 2013: Obtain IRB approval • September 2013-2014: Enrollment and sample collection • September 2013-March 2015: Sample and Data analysis 

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A Comparison of the Effect of Intermittent and Continuous Infusion of Meropenem on the Prevalence of Nausea in Pediatric Cystic Fibrosis Patients

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