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Successful treatment of persistent methicillin-resistant Staphylococcus aureus (MRSA) bacteremia in a preterm neonate using Daptomycin – A case report
2011 Martin E Weisse Resident Research Competition. WV AAP chapter meeting. Charleston, WV
Rohit Aswani, MD and Maria G. Lopez-Marti, MD
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”
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
Clinical worsening
● After 12 hs, initial Blood Culture (DOL6) + for Methicillin resistant S. aureus ( MRSA)
● DOL 7=Multiple erythematous pustular 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
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 leukocytosis and thrombocytopenia
A 2D ECHO revealed structurally normal heart with no vegetations or effusion
Persistent Bacteremia
●5 Blood cultures (+ ) Vancomycin MIC=1Vancomycin therapeutic( trough 15-20)
●Day 7 of Vancomycin and Gentamicin;4 of Rifampin
●No clinical or Laboratoryresponse Persistent bacteremia for 8 days
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
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
WBC count (trend)
Improvement in WBC count after starting of Daptomycin
Daptomycin start
Vancomycin start
Immature neutrophil count (trend)
decrease in bands (immature neutrophils) on Daptomycin therapy
Daptomycin start
Vancomycin start
Platelet count (trend)
Improvement in thrombocytopenia after starting daptomycin
Daptomycin start
Vancomycin start
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
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
Effect on CK in this neonate
Total CK was monitored for 3 weeks showing to be within acceptable range
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
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
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 aureus bacteraemia 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
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