Letter to the Editor Safety of Empiric Outpatient Treatment of Suspected Tick-Borne Infection in the Pediatric Emergency Department To The Editors: ocky Mountain spotted fever and human ehrlichiosis are common tick-borne infections in the United States and many patients may be treated as outpatients with doxycycline.1–3 However, bacterial meningitis presents with similar symptoms.4 We evaluated whether empiric outpatient treatment for possible tick-borne illness resulted in cases of inadequately treated bacterial meningitis. We performed a review of all patients seen in our tertiary children’s hospital emergency department (PED) from May to August of 2004–2013 who had a diagnosis consistent with possible tick-borne infection. Clinical and laboratory characteristics of all patients who returned to the PED within 2 weeks were collected from the electronic medical record. During the study period, 718 children were seen in the PED during the months of May to August and discharged with an ICD-9 code concerning for possible tick-borne infection. Of this group, 43 (6.0%) returned to the PED within 2 weeks of initial evaluation. Demographic information from both groups is included in Table (Supplemental Digital Content 1, http://links.lww.com/INF/ B930). The average return visit to the PED occurred 3.4 days after initial visit, and 14 (33%) returned the next day. Thirty-seven (86%) presented initially with at least 2 of the 3 classic findings of tick-borne illness (fever, headache and rash), and 27 (63%) were discharged with a prescription for doxycycline, including all patients who were diagnosed with a tick-borne illness by the PED physician. Titers for Ehrlichia and Rocky Mountain spotted fever were collected at the initial visit in 8 (19%) and 7 (16%) patients, respectively, and all titers were ultimately negative. A majority of children had a complete blood count and basic metabolic profile performed at the initial and return visit. Eleven (26%)


The authors have no funding or conflicts of interest to disclose. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (www.pidj.com). Copyright © 2014 by Lippincott Williams & Wilkins ISSN: 0891-3668/14/3312-1308 DOI: 10.1097/INF.0000000000000426

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had lumbar puncture performed at the initial visit but only 3 patients, all of whom had neck pain, had a lumbar puncture at the return visit and all 3 were subsequently diagnosed with viral meningitis. There were no deaths and no cases of bacterial meningitis among our cohort of children. Sixteen children (37%) were admitted after their return PED visit, although 10 of these children (63%) were discharged the following day. One child was admitted for 16 days and subsequently was found to have anaplastic large cell lymphoma. Excluding this patient, the average length of stay was 1.8 days. Empiric outpatient treatment of children with possible tick-borne illness did not result in any missed diagnoses of meningitis among our patient cohort. These results suggest that empiric outpatient treatment of suspected tick-borne illness in the summer is a viable strategy and support PED providers’ ability to effectively distinguish between serious infection such as bacterial meningitis and those which can be treated on an outpatient basis (viral syndrome, viral meningitis, mild tick-borne illness). Our study results also suggest that there is a tendency for unnecessary testing in this cohort of patients who were initially discharged from the PED and prospective studies are needed to determine whether certain signs or symptoms may be used to identify children with suspected tick-borne illness who may be discharged from the PED without extensive laboratory testing.

Ian D. Kane, MD Donald H. Arnold, MD

Department of Pediatric Emergency Medicine Vanderbilt Children’s Hospital Nashville, TN REFERENCES 1. Woods CR. Rocky Mountain spotted fever in children. Pediatr Clin North Am. 2013;60:455– 470. 2. Marshall GS, Jacobs RF, Schutze GE, et al.; Tick-Borne Infections in Children Study Group. Ehrlichia chaffeensis seroprevalence among children in the southeast and south-central regions of the United States. Arch Pediatr Adolesc Med. 2002;156:166–170. 3. Chapman AS, Bakken JS, Folk SM, et al.; Tickborne Rickettsial Diseases Working Group; CDC. Diagnosis and management of tickborne rickettsial diseases: Rocky Mountain spotted fever, ehrlichioses, and anaplasmosis–United States: a practical guide for physicians and other health-care and public health professionals. MMWR Recomm Rep. 2006;55(RR-4):1–27. 4. Curtis S, Stobart K, Vandermeer B, et al. Clinical features suggestive of meningitis in children: a systematic review of prospective data. Pedia­ trics. 2010;126:952–960.

Sepsis and Meningitis Caused by Pasteurella Multocida and Echovirus 9 in a Neonate To The Editors:


e 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 Pas­ teurella 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

The authors declare no conflict of interest. Copyright © 2014 by Lippincott Williams & Wilkins ISSN: 0891-3668/14/3312-1308 DOI: 10.1097/INF.0000000000000504

The Pediatric Infectious Disease Journal  •  Volume 33, Number 12, December 2014

The Pediatric Infectious Disease Journal  •  Volume 33, Number 12, December 2014


Maria J. Medina, MD Juan A. Sáez-Nieto, PhD

published yet demonstrating the relationship between DTR and RTI in childhood. In an attempt to test our hypothesis, we retrospectively collected the daily emergency-room visits of children 5 years old and younger for RTI between January 1, 2011, and December 31, 2013, at the Guangzhou childhood medical center, and simultaneous meteorologic data from the Guangzhou Meteorological Bureau. RTI was described in our analysis as a diagnosis of common cold, pharyngitis, laryngitis, croup, viral otitis, sinusitis, acute bronchitis, viral exacerbations in chronic bronchitis, bronchiolitis and/or community-acquired pneumonia. A negative binomial regression model was used to assess the relationship between DTR and RTI. On examination of the lag effects of DTR on RTI, we developed 2 different lag structures: single-day lag from days 0 to 5 and multiday average starting from lag 0 (up to 5). For example, lag 02 stands for the 3-day moving average of current and previous day values. To quantify the effects of DTR, we computed the influences (eβ − 1) × 100, that correspond to percent increase. A sensitivity analysis was conducted to validate the DTR effects, including possible confounding factor in studying association between DTR and adverse health outcomes, daily air pollution data (PM10, SO2 and NO2), in the model using data from 2011 and 2013. During the study period, the annual mean temperature ranged from 18°C to 25°C. A total of 209,747 emergency-room visits of children younger than 5 years for RTI were recorded in Guangzhou childhood medical center. On average, there were approximately 194 visits for RTI per day. Table 1 shows results from the single-day lag (L0–L5) and the cumulative exposure models (L02 and L05) for the percentage increase in emergency-room visits for RTI per 1°C increase in DTR after adjusting mean temperature, day of the week and seasonal and long-term trends. The effects of DTR on RTI are statistically significant for single-day lag (L1 and L2) and multiday lag (L02 and L05). For instance, a 1°C increase in 1-day lagged (L1) and 2-day lagged (L2) DTR corresponded to 2.55% [95% confidence interval (CI): 1.97–4.01%] and 1.61% (95% CI: 1.30–2.54%) increase in the number of daily emergency-room visits of children ≤5 years of age for RTI, respectively. Likewise, a 1°C increase in 3-day moving average (L02) and 6-day moving average (L05) corresponded to an increase in the number of visits by 2.47% (95% CI: 2.01–3.37%) and 0.97% (95% CI: 0.79–1.54%), respectively. We conducted a sensitivity analysis to compare the DTR effects with or without PM10, SO2 and NO2 in the model from 2010 to 2012. There were

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 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 REFERENCES 1. Drancourt M, Bollet C, Carlioz A, et al. 16s ribosomal DNA sequence analysis of a large collection of environmental and clinical unidentified bacterial isolates. J Clin Microbiol 2000;38:2623–2630. 2. Cabrerizo M, Echevarria JE, González I, et al. Molecular epidemiological study of HEV-B enteroviruses involved in the increase in meningitis cases occurred in Spain during 2006. J Med Virol. 2008;80:1018–1024. 3. Nakwan N, Kakwan N, Atta T, et al. Neonatal pasteurellosis: a review of reported cases. Arch Dis Child Fetal Neonatal Ed. 2009;94:F373–F376. 4. Khetsuriani N, Lamonte A, Oberste MS, et al. Neonatal enterovirus infections reported to the national enterovirus surveillance system in the United States, 1983-2003. Pediatr Infect Dis J. 2006;25:889–893. 5. Pelkonen T, Roine I, Anjos E, et al. Picornaviruses in cerebrospinal fluid of children with meningitis in Luanda, Angola. J Med Virol. 2012;84:1080–1083. 6. Wright HT Jr, McAllister RM, Ward R. “Mixed” meningitis. Report of a case with isolation of Haemophilus influenzae type B and ECHO virus type 9 from the cerebrospinal fluid. N Engl J Med. 1962;267:142–144.

Diurnal Temperature Range Related to Respiratory Tract Infection in Childhood To the Editors: espiratory tract infection (RTI), including upper and lower respiratory infections, is the leading cause of acute illness worldwide and is the most frequent cause of infant and young childhood mortality. In our medical practice, a number of parents complained to us that when the temperature varies dramatically, their children are more likely to have cough or fever. Previous researches have revealed that diurnal temperature range (DTR) was a risk factor for coronary heart disease1 and stroke.2 No surveys have been


Servicio de Pediatría

Isabel Wilhelmi, MD, PhD María E. Pablo-Hernando, MD

Servicio de Microbiología, Hospital Universitario Severo Ochoa, Leganés © 2014 Lippincott Williams & Wilkins

The authors have no relevant conflicts of interest to disclose. Copyright © 2014 by Lippincott Williams & Wilkins ISSN: 0891-3668/14/3312-1309 DOI: 10.1097/INF.0000000000000461

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Sepsis and meningitis caused by Pasteurella multocida and echovirus 9 in a neonate.

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