Methicillin-Resistant Staphylococcus aureus Endovascular Infection in a Neonate: Prolonged, Safe, and Effective Use of Daptomycin and Enoxaparin

Abstract

We report on a former 28-week gestation neonate with persistent methicillin-resistant Staphylococcus aureus (MRSA) endocarditis, with a heterozygous Factor V Leiden mutation. The neonate became clinically ill after 1 week of life, with positive blood cultures for MRSA. Echocardiography revealed large thrombi in the inferior vena cava and right atrium. Bacteremia persisted despite removal of umbilical arterial and venous catheters and empiric administration of therapeutic doses of vancomycin (minimum inhibitory concentration [MIC] 2 mg/L) and ceftazidime. To narrow therapy, ceftazidime was discontinued, while gentamicin and rifampin were added. Cultures remained positive and, therefore, linezolid was added, and subsequent blood cultures became negative. Since prolonged linezolid use of 2 weeks or longer carries potential adverse effects, antibiotics were changed to daptomycin, which is bactericidal and recommended for treatment of invasive MRSA infections when vancomycin MICs are ≥2 mg/L to minimize vancomycin treatment failure. Enoxaparin was initiated, with anti-Xa assay monitoring. A workup for thrombophilia revealed heterozygous Factor V Leiden mutation. Serial echocardiograms demonstrated decreasing size of the thrombi, which were no longer visualized at 2 months of age. Creatinine kinase remained normal. The infant had no seizures on daptomycin. The management of persistent MRSA bacteremia in neonates associated with a large thrombus poses a unique challenge due to the long duration of treatment. To our knowledge, this is the first case of prolonged and safe daptomycin and enoxaparin use in a preterm neonate. Daptomycin may be considered in cases of clinical failure with vancomycin when a lengthy treatment course is contemplated.

Daptomycin Use for Persistent Coagulase-Negative Staphylococcal Bacteremia in a Neonatal Intensive Care Unit

“…There were similar findings from a case report describing an ex-28 weeker with infective endocarditis due to methicillin-resistant staphylococcus aureus , which was successfully treated with daptomycin. The dose used was 6 mg/kg, and the course lasted for 40 days [ 16 ].…”

“…Linezolid can be used as a second-line treatment for persistent CoNS bacteremias. Linezolid has excellent CSF penetration and ubiquitous tissue distribution [ 16 ]. However, in neonates, it should be used with caution, under specific circumstances, due to its bacteriostatic effect and the risk of myelosuppression in prolonged courses [ 17 ].…”

“…Since daptomycin’s action is dose-dependent, the specific neonatal dose that minimizes the risk of adverse side effects has yet to be confirmed. Recent studies have shown that a neonatal dose of 6 mg/kg twice daily (versus 10 mg/kg once daily—adult dose) is efficient to treat associated infections (across different causative organisms) [ 16 , 17 ]; however, there are no pharmacokinetic data available in the neonatal population. It is possible that higher doses would be needed in neonates compared to adults and children because of the relatively larger neonatal volume of distribution and faster renal clearance of the drug.…”

Clinical characteristics and antibiotic resistance profile of invasive MRSA infections in newborn inpatients: a retrospective multicenter study from China

“…Daptomycin is not routinely used in neonates because of a scarcity of literature on its efficacy and safety in infants. but numerous cases have shown the benefits and relative safety of daptomycin use in neonates [ 31 , 32 ]. Daptomycin may be considered in cases of clinical failure with vancomycin.…”

cydA, spdC, and mroQ are novel genes involved in the plasma coagulation of Staphylococcus aureus

“…Staphylococcus aureus is an important bacterial pathogen that causes both local and severe systemic infections, such as skin and soft tissue infection, endocarditis, osteomyelitis, and sepsis. 1 , 2 Many virulence factors produced by S. aureus , such as coagulase, surface adhesive protein, and leukocidin assist in mediating the pathogenicity of S. aureus infections, 3 and these are associated with different pathogenic mechanisms. For example, coagulase acts as a mechanical barrier to antagonize leukocyte phagocytosis by promoting plasma hemagglutination.…”