Sepsis and Meningitis Caused by Pasteurella Multocida and Echovirus 9 in a Neonate

To The Editors: We present a 22-day-old previously healthy female who came to the hospital with fever (maximum 38.6°C) of 24 hours evolution without any other symptoms. She was born at term by vaginal delivery. A vaginal smear for Streptococcus group B was negative at 35 weeks of gestation. On admission to the emergency room the patient had rectal temperature of 39.4°C with a normal heart rate and blood pressure. The physical examination was normal and she was in good condition. The blood count gave a 8310 leukocytes/mm3, with no left shift, a C-reactive protein value of 41 mg/L (maximum 161 mg/L) and procalcitonin of 2.4 ng/mL (maximum 14 ng/mL). Blood biochemistry and urinalysis were normal. Cerebrospinal fluid (CSF) analysis, sampled after 2 doses of antibiotics, showed a leukocyte count of 5.920 cells/mm3, 95% neutrophils, proteins at 161 mg/dL and glucose of 40 mg/dL (110 mg/dL in blood). Empiric antibiotic therapy was initiated with ampicillin and cefotaxime. A Gram-negative coccobacillus, susceptible to cefotaxime, was isolated in blood culture 48 hours after admission. Ampicillin was discontinued and cefotaxime (200 mg/kg/d) maintained for 14 days. The urine and CSF cultures were negative for bacterial studies. A pediatric bottle of blood culture was incubated in the Bact/Alert 3D system (BioMérieux SA, Marcy-l´Etoile, France) and after 48 hours incubation Gram-negative coccobacilli were observed by Gram stain. The API NE strips (BioMérieux) identified the isolate as Pasteurella multocida with a probability rate of 96% and the strain was sent to the Reference Laboratory for further characterization. Isolates were sensitive to penicillin and ceftriaxone. Definitive characterization of the isolate was performed in the Taxonomy Laboratory (National Microbiology Reference Centre), with the commercial BIOLOG GN2 panel (BIOLOG Inc, Hayward, CA, with 95 carbon sources). A similarity of 100% (T = 0.920) with P. multocida was found. The result was confirmed by sequencing of a 16sRNA fragment of 1429 bp.1 For virological investigation, 200 microl of CSF specimen was sent to the National Microbiology Reference Centre (Enterovirus Laboratory). A real-time polymerase chain reaction for simultaneous detection of human enterovirus (EVs) and parechoviruses (HPeVs) was performed. The sample was EV positive. The type of the EV strain was determined by amplification of the partial 3′-VP1 region, sequencing and BLAST analysis,2 and found to be echovirus 9. The patient made a good recovery, remaining afebrile from the fourth day of admission. She is now 7 months old and psychomotor development and auditory evoked potentials are normal. P. multocida is a Gram-negative cocobacillus that colonizes the respiratory and digestive tract of domestic animals such as dogs and cats. The infection of the skin and soft tissues as a result of bites and scratches is frequent, but systemic involvement by hematogenous spread is less common. There are reports of neonatal sepsis and meningitis caused by P. multocida by vertical transmission, animal contact through bites and scratches, nontraumatic animal contact and horizontal transmission between humans.3 Mortality rate is around 20% and the absence of risk factors and early initiation of treatment could contribute to good outcomes. The treatment of choice is penicillin, although aminoglycosides and third-generation cephalosporins have also been used. Human enteroviruses are the most frequent cause of aseptic meningitis in infants. The clinical course is usually benign although fatal cases have been described especially in newborns.4 Mixed infections of the central nervous system with EVs and bacteria are rare. To our knowledge, only 1 study describing presumed bacterial meningitis and a coinfection with different EVs in 4 children has been reported.5 These mixed infections were infrequent (4% of the 142 tested patients) and the authors concluded that detection of a picornavirus did not affect the clinical picture and outcome of bacterial meningitis. One case of mixed meningitis with isolation of echovirus 9 and Haempophilus influenzae type b, was also described some years ago.6 Our patient had a dog at home, but the parents reported no injury or direct contact between them took place. We did not find any other case described in the literature of simultaneous infection by P. multocida and an EV. Isabel Aguado, MD Cristina Calvo, MD, PhD Servicio de Pediatría Isabel Wilhelmi, MD, PhD María E. Pablo-Hernando, MD Servicio de Microbiología, Hospital Universitario Severo Ochoa, Leganés Maria J. Medina, MD Juan A. Sáez-Nieto, PhD Servicio de Bacteriología, Centro Nacional de Microbiología, Instituto de Salud Carlos III María Cabrerizo, PhD Unidad de Enterovirus, Área de Virología, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Madrid, Spain