Use of intravenous rifampin in neonates with persistent staphylococcal bacteremia

Abstract

Ten neonates with persistent staphylococcal bacteremia (positive blood cultures for 25 days despite appropriate antibiotic therapy) received intravenous (i.v.) rifampin in combination with vancomycin with or without aminoglycoside. Their mean birth weight and length of gestation were 900 g and 27 weeks, respectively.Their ages at the time of infection ranged from 6 to 64 days (mean, 26 days). The staphylococcal isolates were methicillin-resistant Staphylococcus aureus (five isolates), methicillin-susceptible S. aureus (two isolates), and coagulase-negative staphylococci (three isolates). The mean number of bacteremia days prior to administration of i.v. rifampin was 8.3 (range, 5 to 15 days), despite a mean peak vancomycin concentration of 33 ,ug/ml. The dosing of rifampin varied from 2.5 to 10 mg/kg of body weight every 12 h. The mean duration of the rifampin course was 9.7 days (range, 3 to 16 days). Of the 10 neonates, 8 (80%) had sterile blood cultures within 24 h, 1 (10%N) had a sterile blood culture within 48 h, and 1 (10%S) had a sterile blood culture within 5 days of being placed on i.v. rifampin. No adverse effects were noted in this small group of infants. Seven of the 10 neonates survived; three died from unrelated complications. The MIC ranges of amikacin, vancomycin, and rifampin for the isolates were 2.0 to 16, 0.5 to 2.0, and 0.0013 to 0.04 ,Ig/ml, respectively. We also studied eight infants, with a mean age of 23 days, who were receiving i.v. or oral rifampin at a dose of 10 mg/kg/day. For i.v. administration, the peak serum concentration of rifampin (mean standard deviation) was 4.02 1.22 ,Lg/ml.The mean trough level at 12 h postinfusion was 1.11 + 0.48 ;ig/ml. For oral administration, the concentrations of rifampin in serum ranged from 0.59 to 2.86 p.g/ml (mean, 1.86 0.96 pLg/ml) at 2 h postingestion, increasing to a peak concentration of 2.8 ,a.g/ml at 8 h postingestion. The mean 12-h postingestion level was 0.77 0.03 pg/ml. From the study of this limited series of neonates, rifampin appears to be a safe and effective addition to therapy when staphylococcal bacteremia is persistent despite vancomycin treatment.

Clinical Characteristics, Outcomes, and Microbiologic Features Associated with Methicillin-Resistant Staphylococcus aureus Bacteremia in Pediatric Patients Treated with Vancomycin

“…Only one isolate had the hVISA phenotype; the remainder of the isolates were considered susceptible to vancomycin. Addition of rifampin to patients who were failing vancomycin appeared to be beneficial, as has been reported previously for pediatric patients (33).…”

Nosocomial Spread of a Staphylococcus capitis Strain with Heteroresistance to Vancomycin in a Neonatal Intensive Care Unit

“…Persistent staphylococcal bacteremia in premature neonates that does not respond to vancomycin therapy, despite the susceptibility of the bacteria to vancomycin, has been described in a series of 10 neonates by Tan et al (34). The isolates in that study were methicillin-resistant S. aureus (n ϭ 5), methicillinsensitive S. aureus (n ϭ 2), and CoNS (n ϭ 3; the isolates were not further identified).…”

Clinical Microbiology of Bacterial and Fungal Sepsis in Very-Low-Birth-Weight Infants

“…Most S. aureus strains causing colonization and infection in NICUs have remained sensitive to extended-spectrum penicillins, and treatment with oxacillin or nafcillin usually eradicates infection. Persistent or deep-seated infections may require the addition of an aminoglycoside or rifampin for effective clearance (465). Methicillin resistance among S. aureus strains in NICUs has been reported and is commonly associated with episodic outbreaks from a single clone (486).…”