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Showing content with the highest reputation on 06/30/2017 in all areas

  1. 1 point
    Dose & administration 10-15 mg/kg/dose given intravenously per the following interval recommendations, and directed/adjusted by serum concentration measurements: Postmenstrual age (PMA) ≤29 weeks PMA: 0-14 days postnatal age, dosing interval = 18 hours; >14 days postnatal age, dosing interval = 12 hours 30 to 36 weeks PMA: 0-14 days postnatal age, dosing interval = 12 hours; >14 days postnatal age, dosing interval = 8 hours 37 to 44 weeks PMA: 0-7 days postnatal age, dosing interval = 12 hours; >7 days, dosing interval = 8 hours ≥45 weeks PMA: all postnatal ages, dosing interval = 6 hours Indications Beta-lactam resistant coagulase negative staphylococci Whenever Methicillin-Resistant Staphylococcus aureus (MRSA) coverage is needed in suspected neonatal bacterial infections Serious infections due to staphylococci or streptococci in a patient with a severe B-lactam allergy Contraindications and special considerations (incl incompatibilities) Contraindications: hypersensitivity to vancomycin or any component of the formulation Special considerations: Prolongation of the dosing interval should be considered in neonates also receiving ibuprofen or indomethacin. Additionally, because infusion reactions such as red man syndrome are commonly associated with administration, the recommended infusion time is 60-120 minutes with a maximum of 10 mg/minute Incompatibilities, terminal site: Cefazolin, cefepime, cefotaxime, cefoxitin, ceftazidime, ceftriaxone, chloramphenicol, dexamethasone, heparin (concentrations greater than 1 unit/mL), nafcillin, pentobarbital, phenobarbital, piperacillin/tazobactam, and ticarcillin/clavulanate Adverse effects Nephrotoxicity, ototoxicity, red man syndrome (rash and hypotension), neutropenia, phlebitis Pharmacological aspects Mechanism of action: Vancomycin exhibits time-dependent killing and is bacteriocidal for most gram positive organisms, except for enterococci, for which it is bacteriostatic. Sensitive MICs are generally regarded as those ≤1 milligram/liter. Vancomycin disrupts bacterial cell wall synthesis, RNA synthesis, and plasma membrane function. Half-Life: highly dependent on renal function; Newborns: 6 – 10 hours; Infants and children 3 months – 4 years: 4 hours Excretion: Primarily excreted unchanged in the urine by glomerular filtration Monitoring: Goal trough level is between 15-20 milligram/liter. Although there are recommendations for dosing in the neonatal population, individual needs and renal function vary greatly. Adjust dosing to optimize antibiotic therapy and minimize toxicity. It is generally recommended to draw a trough level before the fourth dose as the drug is approaching steady-state and will give the clinician a more accurate pharmacokinetic picture and dosing can be adjusted accordingly. However, a level can be obtained earlier if renal function declines during treatment. If long-term therapy is indicated, a level may be checked every 5 days once the patient is stabilized within therapeutic range. References (incl URLs to PubMed) Liu C, Bayer A, Cosgrove SE et al: Clinical practice guidelines by the infectious diseases society of America for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children. Clin Infect Dis. Feb1, 2011; 52(3): e18-e55. PMID: 21208910. Elyasi S, Khalili H. Vancomycin dosing nomograms targeting high serum trough levels in different populations: pros and cons. Eur J Clin Pharmacol. 2016 Jul;72(7):777-88. PMID: 27117446. Pharmacokinetic comparison of nomogram-based and individualized vancomycin regimens in neonates. Am J Health Syst Pharm. 2009 Jan 15;66(2):149-53. PMID: 19139479. Trissel LA, Gilbert DL, Martinez JF: Concentration dependency of vancomycin hydrochloride compatibility with beta-lactam antibiotics during simulated y-site administration. Hosp Pharm 1998;33:1515-1520. PMID: 24421422 Reiter PD, Doron MW: Vancomycin cerebrospinal fluid concentrations after intravenous administration in premature infants. J Perinatol 1996;16:331-335. PMID: 8915929 Levy M, Koren G, Dupuis L, Read SE. Vancomycin-induced red man syndrome. Pediatrics. 199086(4):572-80. PMID: 2216623 Document version history Created 2016/09/02 / Laurie Rollins
  2. 1 point
    Dose & administration Acyclovir is dosed 20mg/kg/dose IV at intervals depending on gestational age. Specifically, Sampson et al (PMID: 24346595) recommend dosing intervals to be 12 hours (q12h) in infants < 30 weeks PMA; 8 hours (q8h) in infants 30 to <36 weeks PMA; and 6 hours (q6h) in infants 36-41 weeks PMA. Administer over one hour in order to prevent adverse effects. For congenital HSV infections, treatment course depends on type of infection. SEM disease is treated for 14 days. Disseminated and CNS infections require a minimum of 21 days of therapy. Asymptomatic infants born to mothers with active genital lesions may require 10 days of treatment. Oral acyclovir may be used for suppressive therapy following completion of full IV course. This dose is 300mg/m2 PO three times daily. Indications Acyclovir is most commonly used in the neonatal population as treatment for congenital herpes simplex infections. It may also be used for chronic suppression of HSV or for treatment of herpes zoster infection. Contraindications and special considerations (incl incompatibilities) The risk of nephrotoxicity is increased when acyclovir is administered in conjunction with other nephrotoxic drugs. Acyclovir’s incompatibilities include: dopamine, dobutamine, epinephrine, fat emulsions, aztreonam, caffeine, caspofungin, cefepime, meropenem, piperacillin/tazobactam, and parenteral nutrition solutions. Adverse effects The most common adverse effects are neutropenia and renal dysfunction secondary to crystalluria. Ensuring adequate hydration during therapy can prevent crystalluria and subsequent renal dysfunction. Frequent monitoring of CBCs can detect neutropenia. With a pH of 10, acyclovir can cause phlebitis and may be very damaging to tissue if extravasation occurs. One might consider using a dedicated PICC-line for acyclovir administration. Pharmacological aspects Acyclovir works by inhibiting viral DNA synthesis. Its primary route of elimination is renal. Postmenstrual age has been determined to be the variable with the most significant influence on clearance of acyclovir. References Oral acyclovir suppression and neurodevelopment after neonatal herpes. NEJM. 2011;365:1284-92. PMID 21991950. Population pharmacokinetics of intravenous acyclovir in preterm and term infants. Pediatr Infect Dis J. 2014;33:42-9. PMID 24346595. Guidance on management of asymptomatic neonates born to women with active genital herpes lesions. Pediatrics. 2013;131:e635-e646. PMID 23359576. The use of antiviral drugs during the neonatal period. Clin Perinatol. 2012;39:69-81. PMID 22341538. Document version history Created 2016/6/26 / Amy Holmes
  3. 1 point
    Dose & administration There are different schools of thought regarding gentamicin dosing in neonates and tertiary dosing references vary in their dosing recommendations. Commonly accepted dosing regimens include both a gestational age based dosing approach as well as birth-weight based dosing approach. Doses range from 4-5mg/kg per dose administered every 24 to 48 hours with lower gestational ages requiring the higher weight based dosing and longer dosing interval than older gestational age infants. The NICE guidelines (UK) recommend 5 mg/kg every 36 hours as the starting dose. The dose and interval should be guided by measurements of blood gentamicin concentrations, typically immediately before the second dose and before later doses if the serum concentration is high. The recommended concentration is < 2 mg/L. Indications Widely used in the NICU in combination with a beta lactam or other antibiotic as empiric therapy in both early onset and late onset sepsis. Contraindications and special considerations (including incompatibilities) Caution should be used in infants with decreased renal function or history that might suggest poor renal perfusion such as asphyxiation, indomethacin exposure, PDA, etc. May interact with neuromuscular blockers. Additional monitoring of gentamicin levels may be required during ECMO and/or therapeutic hypothermia as either may affect gentamicin pharmacokinetics. Target peaks of 8-12 mcg/mL; target troughs < 1 to minimize toxicity. Due to incompatibility, gentamicin should not be administered in the same line with ampicillin, indomethacin, amphotericin B, and furosemide. Adverse effects Nephrotoxicity Ototoxicity May enhance neuromuscular blockade when administered concomitantly with neuromuscular blockers Pharmacological aspects Gentamicin, like other aminoglycosides, exhibits its action by inhibiting protein synthesis by irreversibly binding to ribosomal RNA of the microorganism. Gentamicin is active against Gram-negative bacteria including Pseudomonas aeruginosa. It may be used with other agents for synergy against Gram-positive organisms, but should not be used alone to treat these infections. Aminoglycosides are concentration dependent antibiotics. They work best when the serum concentration of the drug reaches very high concentrations. Conversely, they also possess a unique property known as post-antibiotic effect where bacterial killing continues to occur when the drug is no longer present in appreciable amounts in the bloodstream. References Neonatal infection: antibiotics for prevention and treatment. NICE guidelines [CG149]. 2012. https://www.nice.org.uk/guidance/CG149/ Effect of hypothermia and extracorporeal life support on drug disposition in neonates. Seminars in Fetal & Neonatal Medicine. 2013; 18(1): 23-27. PMID 23158109. Dose optimisation of antibiotics in children: application of pharmacokinetics/ pharmacodynamics in paediatrics. Int J Antimicrob Agents. 2014 Mar;43(3):223-30. PMID: 24389079. Developmental pharmacokinetics of gentamicin in preterm and term neonates: population modelling of a prospective study. Clin Pharmacokinet. 2009 Jan;48(4):253-63. PMID: 19492870. Document version history Created 2016/06/22 / Amy Holmes
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