Presentation on theme: "Anti-Infective Prophylaxis in the Solid-Organ Transplant Population W. Scott Waggoner, PharmD Solid-Organ Transplant Pharmacist Children’s Hospital of."— Presentation transcript:
Anti-Infective Prophylaxis in the Solid-Organ Transplant Population W. Scott Waggoner, PharmD Solid-Organ Transplant Pharmacist Children’s Hospital of Wisconsin
296 bed hospital Largest pediatric solid-organ transplant center in Wisconsin 2012 Solid-Organ Transplant Statistics – 18 Heart – 1 Heart-Liver – 6 Kidney – 1 Liver
Objectives Identify prophylactic anti-infective agents in the solid-organ transplant population. – Pneumocystis – Fungus – Virus Describe consensus guidelines for anti- infective prophylaxis in the solid-organ transplant population. Not become the next treatment for insomnia
Pneumocystis prophylaxis Trimethoprim-Sulfamethoxazole (TMP/SMX) – 5mgTMP/kg/day on 3 days a week (max 160mg TMP) – Stendahl et al. – 88% of pediatric heart centers surveyed Pentamidine 300mg inhaled every 30 days – Children < 4 yoa: 150mg inhaled every 30 days Dapsone 2mg/kg once daily (max. 100mg) or 4mg/kg weekly (max 200mg) – Hemolytic anemia (G6PD def.), aplastic anemia, nephrotic syndrome, albuminuria, cholestatic jaundice syndrome, elevated liver transaminases, toxic hepatitis Atovaquone 30mg/kg once daily (max. 1500mg)
Pneumocystis prophylaxis cont. Duration varies greatly by organ transplanted and transplant center – None-lifetime Lung and Small-Bowel – Lifetime Children’s Hospital of Wisconsin – Heart – 6 months – Kidney – lifetime – Liver – 12 months
Pneumocystis prophylaxis cont. Kidney – recent data points that lifelong prophylaxis not necessary – Anand et al. – 4/1352 (0.3%) PCP infections over 7 years 2 patients < 12 months post-kidney transplant – Both had CMV infection 2 & 4 months prior to PCP 3 patients received 1 month of PCP prophylaxis – Inhaled pentamidine – 2 TMP-SMX 1 patient received 1 year of TMP-SMX prophylaxis
Pneumocystis prophylaxis survey! First-line agent other than TMP/SMX? Second line agent – Dapsone – Atovaquone – Inhaled Pentamidine – IV Pentamidine Duration of prophylaxis – < 3months – 3-6 months – 6-12 months – > 12 months
Fungal Infection Incidence varies greatly by organ 5-42% overall – Liver 7-42% – Heart 5-21% – Lung 15-35% – Pancreas 18-38% Candida and Aspergillus spp. are most common – Blastomycosis, Histoplasmosis, Coccidiodomycosis less common Mortality rates for invasive infection – Candida spp. 70% – Aspergillus spp. 100%
Pappas PG, Silveira FP, et al. Candida in solid organ transplant recipients. American Journal of Transplantation 2009; 9 (Suppl 4): S173- S179.
Singh N, Husain S, et al. Invasive Aspergillosis in solid organ transplant recipients. American Journal of Transplantation 2009; 9 (Suppl 4): S180-S191.
Anti-fungal prophylaxis Always watch for Drug-Drug Interactions! – Fluconazole 6mg/kg once daily (max. 400mg) – Nystatin 1-5mL swish & swallow TID-QID Stendahl et al. – 94% of pediatric heart centers surveyed Select Populations – Voriconazole 6-8mg/kg IV/PO Q12h (max. 400mg) Follow Kinetics – some need Q8h dosing – Amphotericin B lipid formulations 1-5mg/kg IV Q24h Amphotericin B aerosolized – limited data in lung transplant – Micafungin 4-12mg/kg IV q24h – Caspofungin 70mg/m² x 1, then 50mg/m² IV Q24h
Anti-fungal prophylaxis survey! Nothing Fluconazole Nystatin Amphotericin B Echinocandin Other
Cytomegalovirus (CMV) Herpes-virus family 60-90% of adults are seropositive – Less in children CMV infection – Evidence of CMV replication CMV disease – CMV infection with attributable symptoms
Incidence of CMV OrganCMV Infection (%)CMV Disease (%) Kidney8-328 Liver22-2929 Heart9-3525 Lung or Heart-Lung39-4139 Pancreas or Kidney-Pancreas50 McDevitt LM. Etiology and impact of cytomegalovirus disease on solid organ transplant recipients. Am J Health-Sys Pharm 2006; 63(Suppl 5): S3-S9.
CMV Disease Risk Factors Donor CMV-seropositivity and recipient CMV- seronegativity (D+/R-) Certain types of organ transplants – Liver – Lung – Pancreas Use of highly immunosuppressive drug therapies High degree of HLA mismatch Young patient age
CMV Prevention Prophylaxis – All patients or at-risk patients receive medication – Stendahl et al. – 91% of pediatric heart centers surveyed use routine prophylaxis Preemptive therapy – Regular, frequent CMV monitoring – Initiate treatment therapy at certain viral replication threshold – Little evidence in some populations Combination of both
CMV Prophylaxis Valganciclovir – 15-18mg/kg orally daily (max. 900mg) – Adverse effects: anemia, neutropenia, GI effects – Manufacturer’s dosing (mg) = 7 x body surface area x creatinine clearance (CrCl Schwartz) 25kg, 128cm, CrCl 120ml/min: Dose = 800mg/day – Some evidence of 450mg orally daily Lower drug cost, less neutropenia Not recommended in “International Consensus Guidelines on Management of CMV in Solid-Organ Transplant Patients” – sponsored by Roche
CMV Prophylaxis cont. Ganciclovir – 5mg/kg IV every 24h – Adjust in renal dysfunction Valacyclovir – limited data available – 15-30mg/kg/dose 3 times daily (max. dose 2000mg) Resistant CMV – no data for best practice – Foscarnet has most evidence – Cidofovir has little evidence
Duration of CMV Prophylaxis D+/R- patients – Should be between 3-6 months (longer for high risk groups) – Humar et al. (IMPACT) trial 200 vs. 100 days of prophylaxis in kidney transplants 21.3% vs 38.7% incidence of CMV disease at 2 years No difference in acute rejection or graft survival D+/R+ & D-/R+ patients: at least 3 months D-/R- patients: consider acyclovir or valacyclovir
References 1.Fishman, JA. Infection in solid-organ transplant recipients. NEJM 2007; 357: 2601-14. 2.Anand S, Samaniego M, et al. Pneumocystis jiroveci pneumonia is rare in renal tranplant recipients receiving only one month of prophylaxis. Transpl Infect Dis 2011; 13: 570-4. 3.Goto N & Oka S. Pneumocystis jiroveci pneumonia in kidney transplantation. Transpl Infect Dis 2011; 13: 551-8. 4.de Boer MGJ, Kroon FP, et al. Risk factors for Pneumocystis jiroveci pneumonia in kidney transplant recipients and appraisal of strategies for selective use of chemoprophylaxis. Transpl Infect Dis 2011; 13: 559-69. 5.Wang EHZ, Partovi N, et al. Pneumocystis pneumonia in solid organ transplant recipients: not yet an infection of the past. Transpl Infect Dis 2012; 14: 519-25. 6.Martin SI, Fishman JA, et al. Pneumocystis pneumonia in solid organ transplant recipients. American Journal of Transplantation 2009; 9 (Suppl 4): S227-S233. 7.Playford EG, Webster AC, et al. Antifungal agents for preventing fungal infections in solid-organ transplant recipients. The Cochrane Database of Systematic Reviews 2004, Issue 3. 8.Singh N, Husain S, et al. Invasive Aspergillosis in solid organ transplant recipients. American Journal of Transplantation 2009; 9 (Suppl 4): S180-S191. 9.Pappas PG, Silveira FP, et al. Candida in solid organ transplant recipients. American Journal of Transplantation 2009; 9 (Suppl 4): S173-S179. 10.Proia L, Miller R, et al. Endemic fungal infections in solid organ trasplant recipients. American Journal of Transplantation 2009; 9 (Suppl 4): S199-S207.
References 11.Kotton CN, Kumar D, et al. International consensus guidelines on the management of Cytomegalovirus in solid organ transplantation. Transplantation 2010; 89: 779-95. 12.Luan FL, Kommareddi M, et al. Impact of Cytomegalovirus Disease in D+/R- kidney transplant patients receiving 6 months low-dose valganciclovir prophylaxis. American Journal of Transplantation 2011; 11: 1936-42. 13.Humar A, Lebranchu Y, et al. The efficacy and safety of 200 days valganciclovir Cytomegalovirus prophylaxis in high-risk kidney transplant recipients. American Journal of Transplantation 2010; 10: 1228-37. 14.Kalil AC, Sun J, et al. IMPACT trial results should not change current standard of 100 days for cytomegalovirus prophylaxis. American Journal of Transplantation 2011; 11(1): 18-21. 15.Snydman DR. Putting the IMPACT study into perspective: should CMV prophylaxis be extended 6 months for high risk transplants? American Journal of Transplantation 2011; 11: 6-7. 16.McDevitt LM. Etiology and impact of cytomegalovirus disease on solid organ transplant recipients. Am J Health- Sys Pharm 2006; 63(Suppl 5): S3-S9. 17.Subramanian AK. Antimicrobial prophylaxis regimens following transplantation. Curr Opin Infect Dis 2011; 24: 344-9. 18.Snydman DR, Limaye AP, et al. Update and review: state of the art management of Cytomegalovirus infection and disease following thoracic organ transplantation. Transplantation Proceedings 2011; 43: S1-S17. 19.Demmler-Harrison GJ. Cytomegalovirus infection and disease in newborns, infants, children and adolescents. In: UpToDate, Edwards, MS (Ed), UpToDate, Waltham, MA, 2012. 20.Lexi-Comp Online TM, Pediatric & Neonatal Lexi-Drugs Online TM, Hudson, Ohio: Lexi-Comp, Inc.; October 5, 2012. 21.Stendahl G, Bobay K, et al. Organizational structure and processes in pediatric heart transplantation: A survey of practices. Pediatric Transplantation 2012; 16(3):257-64.