A New Twist on an Old Problem

To the Editors: The introduction of heptavalent pneumococcal conjugate vaccine (PCV7; Prevnar, Wyeth) has resulted in a sustained decrease in the incidence of invasive pneumococcal disease (IPD) across North America.1 However, serotype replacement by vaccine-related and nonvaccine serotypes has begun to emerge.2 A significant increase in Streptococcus pneumoniae serotype 19A (SP19A) as a cause of IPD has been observed.1,3,4 A more recent trend is that SP19A is becoming increasingly penicillin-, ceftriaxone-, and multidrug- (≥3 drugs) resistant.1,3,4 We describe a clinical case of a child with meningitis caused by a multidrug-resistant SP19A. A previously well 14-month-old infant initially presented to a community hospital with a fever and a short focal seizure involving the left hand and foot. There was no otitis media, evidence of pneumonia, or neurologic abnormality. Hematologic, biochemical, and coagulation studies were normal. A head CT scan revealed left ethmoid sinus opacification and small bilateral cerebral and white matter hypodensities. The child was treated with intravenous cefuroxime. Twenty-four hours later, there was deterioration in neurologic status. A lumbar puncture at that time was consistent with bacterial meningitis [WBC 63 × 109/L (25% neutrophils), glucose 0.1 mM/L, protein 3.6 g/L]. Gram-positive cocci in pairs and chains were identified. Intravenous vancomycin and cefotaxime were started and transfer to the ICU of a tertiary care pediatric hospital arranged. Now in septic shock, the patient had a fever, Glascow Coma Scale of 6, bulging anterior fontanelle, and multiorgan dysfunction. A brain MRI was consistent with meningoencephalitis. Blood and cerebral spinal fluid (CSF) cultures grew S pneumoniae. The organism was susceptible only to vancomycin, levofloxacin, rifampin, and telithromycin, and serotyped as 19A. Multilocus sequence typing (MLST) revealed this to be sequence type 320. Levofloxacin was started 3 days after initial presentation (10 mg/kg q12 hours for day 1; then 10 mg/kg daily), and vancomycin was continued. Ceftriaxone was discontinued, and rifampin was avoided due to hepatic dysfunction. The child had received 3 doses of PCV7. No ill contacts or travel outside the province were identified, and the child did not attend daycare. Within 48 hours of starting levofloxacin, the raised intracranial pressure and sepsis resolved, and repeat blood cultures had cleared. Neurologic recovery was slow, but 6 months after hospital discharge the child was verbal and interactive and regaining all age-appropriate milestones. The shifting resistance pattern of IPD in general, and our case specifically, reenforces the need for vancomycin as part of empiric therapy for meningitis. For S. pneumoniae meningitis caused by a fully cephalosporin-resistant strain vancomycin and ceftriaxone (or cefotaxime) +/− rifampin are recommended.5,6 Fluoroquinolones are also considered as alternative agents in the IDSA guidelines. Levofloxacin was added in our case. Rifampin was avoided given our patient's severe liver and renal dysfunction. Levofloxacin's lipophilic nature should permit a rapid attainment of a CSF drug concentration that is bactericidal for penicillin susceptible and nonsusceptible S. pneumoniae.7 Experimental animal models have shown good CSF levofloxacin concentrations and corresponding bactericidal activity.8 Although there is limited clinical experience to support the use of levofloxacin to treat meningitis, and the safety of fluoroquinolones in children is debatable, the potential benefits in this case outweighed theoretical risks. Evidence has emerged that the most rapidly expanding penicillin resistant SP19A MLST clonal complex in the United States since the introduction of PCV7 is CC320, which is the clonal complex in which our isolate lies.4 It has been postulated that multidrug-resistant SP19A CC320 in the United States emerged because of serotype switching through genetic recombination between non-CC320 SP19A and the internationally disseminated multidrug-resistant CC320 Taiwan19F-14 which is covered by PCV7.4 As serotype 19A increases in prevalence as a cause of childhood IPD, the development of an effective vaccine that provides protection against this serotype becomes increasingly important. Laboratory-based surveillance including serotype determination and MLST of IPD isolates is critical to be able to determine which new vaccine would offer the best protection now and in the future. William A. Ciccotelli, MD Department of Infectious Diseases and Medical Microbiology M.G. DeGroote Institute for Infectious Disease Research McMaster University Hamilton, ON, Canada Susan M. Poutanen, MD, MPH University Health Network and Mount Sinai Hospital Department of Microbiology University of Toronto Departments of Laboratory Medicine and Pathobiology and Medicine Toronto, ON, Canada Manaf Alqahtani, MD Division of Infectious Diseases, Dept of Medicine Toronto General Hospital University of Toronto Toronto, ON, Canada Shaun K. Morris, MD, MPH Division of Infectious Diseases Department of Paediatrics Hospital for Sick Children Toronto, ON, Canada Peter Cox, MBChB, DCH Department of Critical Care Medicine Hospital for Sick Children University of Toronto Toronto, ON, Canada Donald E. Low, MD Dylan R. Pillai, MD, PhD Ontario Ministry of Health and Long Term Care University of Toronto Mount Sinai Hospital University Health Network Toronto, ON, Canada Mary Anne Opavsky, MD, PhD Division of Infectious Diseases Department of Paediatrics Hospital for Sick Children Toronto, ON, Canada

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