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 HistoryBaby 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