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VANCOMYCIN-RESISTANT ENTEROCOCCUS FAECIUM MENINGITIS SUCCESSFULLY TREATED WITH CHLORAMPHENICOL

1999; Lippincott Williams & Wilkins; Volume: 18; Issue: 5 Linguagem: Inglês

10.1097/00006454-199905000-00023

1532-0987

Sayonara Pérez Mato, Sandra Robinson, Rodolfo E. Bégué,

Antimicrobial Resistance in Staphylococcus

Vancomycin-resistant Enterococcus faecium (VREF) isolates have emerged as significant nosocomial pathogens.1, 2 Of the infections caused by VREF, meningitis has rarely been documented and represents a therapeutic challenge for reasons that include limited treatment options because of the frequent multidrug resistance of VREF and difficulty reaching therapeutic drug concentrations in the cerebrospinal fluid (CSF). We describe a case of meningitis caused by VREF in an infant successfully treated with chloramphenicol. Case report. The patient, a female African American infant born at 32 weeks gestation, developed hydrocephalus and required placement of a ventriculoperitoneal (VP) shunt at 3 months of age. Two weeks after shunt placement she was hospitalized with erythema and purulent discharge at the distal shunt tubing site. A wound culture grew methicillin-and vancomycin-susceptible Staphylococcus aureus. CSF from an aspirate of the shunt reservoir showed 290 white blood cells/mm3 with 32% neutrophils and a sterile culture (Fig. 1, Day 2). The distal shunt tubing was externalized and the patient received vancomycin therapy with clinical resolution of the abdominal wound infection.Fig. 1: Antibiotics administered and CSF profile.On Day 8 of vancomycin therapy, the infant developed fever and changes in his mental status accompanied by CSF abnormalities characteristic of acute bacterial meningitis (Day 12). Culture of the ventricular CSF grew E. faecium resistant to multiple antibiotics including vancomycin, ampicillin and gentamicin by Kirby-Bauer disk diffusion testing. Two blood cultures were sterile. The VP shunt was then removed and replaced with a ventriculostomy catheter, and the infant was treated with ampicillin/sulbactam (250 mg/kg/day divided into four doses) plus gentamicin (10 mg/kg/day divided into two doses). This regimen produced partial clinical improvement but the CSF was persistently abnormal and positive for VREF (day 17). The MICs as determined by the broth dilution method were vancomycin >16 μg/ml, gentamicin >6 μg/ml and ampicillin >8 μg/ml. High level gentamicin resistance was confirmed (MIC > 500 μg/ml). Further testing of the isolate showed susceptibility to chloramphenicol and quinupristin/dalfopristin (Synercid) by Kirby-Bauer disk diffusion test. The MICs were chloramphenicol ≤4 μg/ml and quinupristin/dalfopristin 2 μg/ml. In view of these findings intravenous chloramphenicol (100 mg/kg/day divided into four doses) was administered as single therapy. Clinical improvement was noted within 48 h and a CSF specimen obtained 72 h after initiation of chloramphenicol therapy was sterile (Day 21). The CSF remained sterile when last tested 2 weeks after completion of the 21 days of chloramphenicol therapy (Day 60). Serum chloramphenicol concentrations were monitored, attaining a peak value of 19.5 mg/l and a trough value of 5.3 mg/l. No signs of bone marrow suppression were seen during or after therapy. A new VP shunt was inserted at the end of therapy, and the infant has remained asymptomatic 4 months after completion of therapy. Discussion. Vancomycin-resistant E. faecium isolates are associated with considerable morbidity, most frequently urinary tract infections, central catheter-related bacteremias, abdominal and pelvic wound infections and abscesses and endocarditis.3 In spite of its increasing importance as a human pathogen, VREF is clearly an unusual etiologic agent of bacterial meningitis in pediatric patients.4 In the cases of E. faecium meningitis described, the neonates and children often had underlying central nervous system pathology, such as neural tube defects and hydrocephalus,2 and most patients had received vancomycin or broad spectrum antibiotics before VREF isolation.5 Our patient fit this profile. His CSF on presentation was sterile and yielded a cell count and chemistry which can be seen in children with uninfected VP shunts.6 Also VREF was first isolated from the CSF near completion of a course of intravenous vancomycin, a known independent risk factor for infection with VREF.1 Treatment is a major challenge because these organisms are usually resistant to multiple antibiotics. In fact some serious infections with VREF strains have no proven antimicrobial therapy. Therapeutic options that can be considered include penicillin, ampicillin, ampicillin/sulbactam plus an aminoglycoside, chloramphenicol, quinupristin/dalfopristin and investigational agents with in vitro activity against VREF, such as oxazolidinones.1 Perhaps because of its current infrequent use, chloramphenicol remains one of the few agents that retains its in vitro activity against many VREF strains, with reported clinical efficacy of 53% for the treatment of serious VREF infections.1, 7 The efficacy of chloramphenicol may be a result of: (1) the relatively low plasma concentration needed to inhibit susceptible organisms8, 9; (2) its excellent diffusion into the CSF as indicated by the average ratio of CSF:serum chloramphenicol concentration of 0.67 (range, 0.45 to 0.99), unaffected by the presence of pyogenic meningitis.8 These two factors allow adequate CSF drug concentrations, sufficient to treat susceptible organisms. The use of chloramphenicol, however, is hampered by its hematologic toxicity related to high plasma concentrations (which can be in part prevented by careful monitoring of serum drug concentrations) and by its mostly bacteriostatic effect. It is accepted that optimal treatment of bacterial meningitis requires bactericidal antibiotic activity to compensate for the relatively inefficient leukocytic phagocytosis in the subarachnoid space. Although chloramphenicol is regarded as bacteriostatic against enterococci,9 it was effective in our patient. The role of timely management of the infected VP shunt with early removal, ventricular drainage and placement of a new shunt followed by a course of antimicrobial therapy active against VREF cannot be over-emphasized given that antimicrobial therapy alone might not be sufficient for effective treatment of these infections.10 New antimicrobials against VREF are under development and not readily available. Quinupristin/dalfopristin is licensed for the treatment of serious VREF infections, but it has bacteriostatic activity against strains of this species and its efficacy is expected to be ∼50%.11 Meanwhile containment of the VREF epidemic by infection control measures is crucial, along with restricted use of broad spectrum antibiotics and rational use of vancomycin.1, 3 In summary we report a case of an infant with VREF meningitis, successfully treated with removal of the VP shunt and a 21-day course of intravenous chloramphenicol therapy. Until other antimicrobial drugs become available that are effective against serious VREF infections, especially in the central nervous system, resorting to older agents such as chloramphenicol can be beneficial in selected patients. Sayonara Pérez Mato, M.D. Sandra Robinson, M.D. Rodolfo E. Bégué, M.D. Department of Pediatrics; Division of Infectious Diseases; Louisiana State University School of Medicine (SPM, REB) Children's Hospital (SPM, SR, REB) New Orleans, LA