2011 Martin E Weisse Resident Research Competition . WV AAP chapter meeting. Charleston, WV

1. 2011 Martin E Weisse Resident Research Competition. WV AAP chapter meeting. Charleston, WV Successful treatment of persistent methicillin-resistant Staphylococcus aureus (MRSA) bacteremia in a preterm neonate using Daptomycin – A case report Rohit Aswani, MD and Maria G. Lopez-Marti, MD

2. Birth History • Baby born at 31 weeks gestation, via c-section due to Placenta Previa • APGAR 9,9. Birth weight=1.87kg • Mother was a 25 year, G4P3 woman • Prenatal labs: Rubella immune, HepBsAg (-), RPR (-), GC/Chlamydia (-), GBS unknown • On admission to CHH, initial work-up for early-onset sepsis was negative • Baby stable on C-PAP, “feeding and growing”

3. DOL5-6: Onset of Sepsis ●Abdominal distention and bilious gastric residuals were noted. KUB was done ●Respiratory distress ●Labs: -CRP=8.6 mg/dl -WBC = 4.300. Diff: 28% segs/ 38% bands -Platelets: 21,000 ●Cultures sent ●LP done with normal results ●Vancomycin and gentamycin were started ●Clinical deterioration requiring mechanical ventilation and dopamine

4. Clinical worsening ●After 12 hs, initial Blood Culture (DOL6) + for Methicillin resistant S. aureus ( MRSA) ●DOL 7=Multiple erythematouspustular lesions over trunk and extremities. Wound Culture turned positive for MRSA ● Endotracheal aspirate culture positive for MRSA ● 2nd Blood culture Positive for MRSA (DOL 8) -Rifampin was added to vancomycin + gentamicin -Umbilical arterial line pulled

5. DOL 9 to DOL 12 • Worsening of chest x-ray – Progression to Pneumothorax requiring chest tube • Blood cultures on DOL 10 and 11 also + for MRSA • Persistent leukocytosisand thrombocytopenia • A 2D ECHO revealed structurally normal heart with no vegetations or effusion

6. Persistent Bacteremia ●5 Blood cultures (+ ) Vancomycin MIC=1 Vancomycin therapeutic( trough 15-20) ●Day 7 of Vancomycin and Gentamicin;4 of Rifampin ●No clinical or Laboratory response Persistent bacteremia for 8 days

7. DOL 14 • Decision to add Daptomycin • Dose = 12mg/kg/dose IV Q24 hrs • Based on preliminary neonatal PK data (Duke) • Side-effect profile →CK level once a week

8. Subsequent course • Signs of Clinical Improvement in Cardio- respiratory status seen • Improvement in WBC and platelet count • DOL 16: • On vancomycin, gentamicin, rifampin and daptomycin • Blood Culture drawn after 48 hrs of starting Daptomycin: NEGATIVE

9. WBC count (trend) Improvement in WBC count after starting of Daptomycin Vancomycin start Daptomycin start

10. Immature neutrophil count (trend) decrease in bands (immature neutrophils) on Daptomycin therapy Daptomycin start Vancomycin start

11. Platelet count (trend) Improvement in thrombocytopenia after starting daptomycin Vancomycin start Daptomycin start

12. Discussion: Daptomycin • Cyclic lipopeptide- Bactericidal activity against resistant Gram-positive bacteria • Currently approved by FDA only for Adults • Bacteremia and complicated skin and soft tissue infections • Adverse reactions: eosinophilic pneumonia, CK elevation • Dose in adults = 6mg/kg IV Q24 hr

13. Discussion • Very limited data of use of Daptomycin in children (off-label) • Different PK in children • Higher renal clearance • Case reports of use in NICU • 6 mg/kg/dose IV q 12 hs ( 2 cases) • 10 mg/kg/dose IV q 24 hs (1 case) • Higher dose used in our case = 12mg/kg IV q24 hs • Preliminary data showing less elevation of CK with once daily dosing (Duke University) • Safety profile similar to adults • CK elevation possible

14. Effect on CK in this neonate Total CK was monitored for 3 weeks showing to be within acceptable range

15. Update on the clinical course • DOL 16 : swelling and erythema of Right hip joint→septic arthritis with secondary osteomyelitis, confirmed by radiography • Debridement in OR→ Culture negative • 6 weeks IV antibiotic therapy was completed from 1st negative blood culture (for endovascular disease and osteomyelitis) • 3 weeks of combination Daptomycin+ Vancomycin • 3 weeks of Vancomycin • Baby was discharged home after 2 months of admission and is now doing well, followed by Orthopedics

16. Conclusion • MRSA infections are difficult to treat • Daptomycin is a bactericidal drug, useful to treat MRSA infections • This report highlights the potential advantage of daptomycin use in neonates with severe infections due to MRSA • Clear need of more clinical and pharmacological studies for FDA approval of daptomycin for use in pediatric patients

17. References : • Abdel-Rahman SM, Chandorkar G, Akins RL et al. Single-dose pharmacokinetics and tolerability of daptomycin 8 to 10 mg/kg in children ages 2 to 6 years with suspected or proved gram-positive infections. Pediatr Infect Dis J. 2011 Feb 10 • Cohen-Wolkowiez M, Smith PB, Benjamin DK Jr et al. Daptomycin use in infants: report of two cases with peak and trough drug concentrations. J Perinatol. 2008 Mar;28(3):233-4 • Daptomycin prescribing information (www.cubicin.com) • Enoch DA, Bygott JM, Daly ML et al. Daptomycin. J Infect. 2007 Sep;55(3):205-13 • Hussain A, Kairamkonda V, Jenkins DR. Successful treatment of meticillin-resistant Staphylococcus aureusbacteraemia in a neonate using daptomycin. J Med Microbiol. 2011 Mar;60(Pt 3):381-3 • Sarafidis K, Iosifidis E, Gikas E et al. Daptomycin use in a neonate: serum level monitoring and outcome. Am J Perinatol. 2010 May;27(5):421-4