Acta Pdiatrica ISSN 08035253

REGULAR ARTICLE

Bacteremia in feverish children presenting to the emergency department: a retrospective study and literature review
Silvia Bressan (silvia.bressan.1@unipd.it)1, Paola Berlese1, Teresa Mion1, Susanna Masiero1, Antonietta Cavallaro2, Liviana Da Dalt1
1.Department of Pediatrics, University of Padova, Padova, Italy 2.Department of Microbiology and Virology, Padova Hospital, Padova, Italy

Keywords Bacteremia, Children, Emergency department, Fever, Streptococcus pneumoniae Correspondence Silvia Bressan, M.D., Dipartimento di Pediatria` di Padova, Via Giustiniani 3, 35128 Universita Padova, Italy. Tel: +39 049 821 3501 | Fax: +39 049 821 3502 | Email: silvia.bressan. 1@unipd.it Received 19 June 2011; revised 21 September 2011; accepted 22 September 2011. DOI:10.1111/j.1651-2227.2011.02478.x

ABSTRACT Aim: To evaluate the incidence of bacteremia, and the isolated pathogens, in wellappearing children with fever without source (FWS) presenting to the pediatric emergency department (PED), after pneumococcal conjucate vaccine - 7 valent (PCV-7) widespread introduction in the Veneto region of north-eastern Italy, and to review the main literature contributions on the subject. Methods: Blood cultures performed at the PED of Padova from 1 June 2006 to 31 January 2009 in febrile children aged 136 months were retrospectively retrieved. Medical records of previously healthy well-appearing children with FWS were identied and reviewed. Results: The study nally included 392 patients. Bacteremia rate was 0.34% (95% CI 01) in the age group 336 months and 2% (95% CI 04.7) in infants 13 months. No Streptococcus pneumoniae was isolated. The literature review identied 10 relevant studies carried out in the USA and Spain showing an overall bacteremia rate <1% for feverish children aged 336 months, with values <0.5% in settings with high PCV-7 coverage. Conclusion: Overall bacteremia rate is currently <0.5% in well-appearing children aged 336 months with FWS attending the PED in areas with PCV-7 widespread vaccination and is sufciently low to preclude laboratory testing in favour of close followup. Further research is needed to evaluate a more conservative approach in infants 23 months of age.

INTRODUCTION In the prevaccine era, approximately 310% of well-appearing children younger than 3 years with fever without source (FWS) were found to have an occult bacteremia (OB). Because of the concern of bacteremia becoming an invasive illness, many practitioners recommended routine blood tests, including blood culture (BC), and antibiotic therapy based on white blood cell count (WBC) results, as part of the management strategy for these children (14). After the introduction of Haemophilus inuenza type B (HiB) vaccination since the late 1980s, and the consequent virtual elimination of HiB bacteremia, the rate of OB in

children with FWS decreased to <5% and Streptococcus pneumoniae (SP) became then the most important pathogen responsible for OB in this category of patients (4,5). The introduction of the conjugate pneumococcal vaccine (PCV7), licensed for use by the FDA on February 2000, has been associated with a prompt and dramatic decline in

Key notes
Our study found a bacteremia rate <0.5% in well-appearing children aged 336 months with fever without source attending the Pediatric Emergency Department, after widespread diffusion of PCV-7 in the Veneto region, Italy. These results, along with the provided summary of the main literature contributions on the subject, support managing these children with a close follow-up without laboratory testing. Further research is needed to evaluate a more conservative approach in infants aged 23 months.

Abbreviations
ANC, Absolute neutrophil count; BC, Blood culture; CI, Condence interval; CRP, C-reactive protein; FWS, Fever without source; HiB, Haemophylus inuenzae type B; OB, Occult bacteremia; PCV-7, Pneumococcal conjucate vaccine 7 valent; PED, Pediatric emergency department; SP, Streptococcus pneumoniae; UTI, Urinary tract infection; WBC, White blood cell count.

2011 The Author(s)/Acta Pdiatrica 2011 Foundation Acta Pdiatrica 2012 101, pp. 271277

271

Bacteremia in feverish children in the emergency department

Bressan et al.

bacteremia in children, reaching rates of <1%, as broadly reported in studies mainly conducted in United States (6 12) and Spain (1316). A previous Italian multicenter study carried out in hospitalized children younger than 5 years of age with fever, with or without focalized infection, prior to the introduction of PCV-7 in Italy, found a SP bacteremia rate of 1.2% (17). However, no Italian study has so far evaluated the current rate and causative agents of bacteremia in the PCV-7 universal vaccination era, especially in well-appearing children with FWS presenting to the Pediatric Emergency Department (PED). In the Veneto region, in north-eastern Italy, PCV-7 was offered since 2003 as a free of charge 2 + 1 dose schedule vaccination (given at 3, 5 and 1112 months) for specic atrisk groups of children and children attending day care, and following payment of a regional fee for other children. A universal actively recommended free-of-charge immunization was implemented in 2006, gaining a 92% coverage for children born since 2007 (18). The aims of the present study were (1) to evaluate the rate of bacteremia in the PCV-7 universal vaccination era in well-appearing children 136 months of age evaluated for FWS in the PED, (2) to describe the isolated pathogens and the clinical characteristics of patients with bacteremia, (3) to review the main literature contributions assessing the rate and features of bacteremia in children with fever presenting to the emergency department in the PCV-7 era.

cell count (WBC) 15 000 mm3 and or absolute neutrophil count (ANC) 10 000 mm3, and or C-reactive protein (CRP) 20 mg L. Blood for BC was routinely obtained by PED nurses according to internal protocols and inoculated into BACTEC Peds Plus F culture vials (enriched soybean-casein digest broth with CO2) for the qualitative culture and recovery of aerobic micro-organisms (mainly bacteria and yeast) from blood specimens <3 mL in volume. Blood cultures were continuously monitored using the BacTec 920 machine (Becton Dickinson, Franklin Lakes, NJ, USA). Positive culture bottles were identied and further subcultured. More than one culture could be included per patient in the study period if they were performed at separate visits. Denitions Fever without source: axillary temperature 37.5C or rectal temperature 38C at home or in the PED with no apparent source of infection after a thorough physical examination, as reported in the medical chart by the physician in charge of the patient (i.e. absence of respiratory distress or diarrhoeal process, no signs of acute otitis media, osteoarticular or soft tissues infection and normal pulmonary auscultation; the presence of isolated mild nasal congestion was not considered as a sign of localization of fever). Well-appearing children: a priori dened in the presence of normal mental status, respiratory and circulatory items, as reected in the patients chart, and absence of any of the following terminology found on clinical documentation: ill appearing, unwell, lethargic, less responsive, irritable (persistent), hyporeactive, or toxic. True bacterial pathogens on BC: organisms that have been reported to consistently cause disease in children and mainly including Streptococcus pneumoniae, Haemophilus inuenzae, Neisseria meningitidis, Enterococcus, Escherichia coli, Klebsiella pneumoniae, Staphylococcus aureus, group A and B Streptococcus, Salmonella sp. or Pseudomonas aeruginosa. Contaminants on BC: organisms considered as contaminants were coagulase-negative staphylococci, nonhaemolytic streptococci, alpha-haemolytic streptococci, diptheroids, Propionibacterium sp., Aerococcus sp., Bacillus sp., Micrococcus, Corynebacterium or any culture growing multiple organisms in previously healthy immunocompetent children. Data collection Using the clinical electronic PED database, all children 1 36 months of age who had a BC performed in the PED because of fever were identied. Charts were then carefully reviewed to select patients with FWS according to the inclusion and exclusion criteria. Data on demographic characteristics, vital signs, body temperature, maximum degree and duration of fever, presenting symptoms, past medical history, physical ndings, laboratory tests values, blood culture results, as well as

PATIENTS AND METHODS Study design, setting and period This retrospective study was conducted in the tertiary care PED of the Childrens Hospital of the University of Padova (Italy) between 1 June 2006 and 31 January 2009. Our Childrens Hospital provides primary and secondary care for a metropolitan area of 350 000 people (45 000 below 15 years of age) and tertiary care for a regional and extraregional population, with approximately 25 000 PED visits per year. Patient characteristics and inclusion criteria The study included all previously healthy well-appearing children aged 136 months who had a BC performed as part of their evaluation for FWS. Children with a history of antibiotic use within the 72 h before admission to the PED, known immunodecits, underlying diseases resulting in immunodepression, longterm vascular catheter or ventriculoperitoneal shunt were excluded. According to the standard of care in use in our PED at the time of the study for the management of well-appearing children younger than 3 years with FWS, a blood culture was recommended in infants younger than 3 months of age with rectal temperature >38C or axillary temperature >37.5C and in children aged 336 months with rectal temperature >39.5C or axillary temperature >39C if displaying the following results on blood screening tests: a white blood

272

2011 The Author(s)/Acta Pdiatrica 2011 Foundation Acta Pdiatrica 2012 101, pp. 271277

Bressan et al.

Bacteremia in feverish children in the emergency department

results of any other microbiological or imaging test, evolution and nal diagnosis, were extracted in a standardized data collection form. The electronic database was also checked to determine whether there had been any new, unscheduled visit within 1 week from the initial discharge. Data abstractors (BP and MT) received formal training in medical records review, but were not blinded to the study objectives. Periodic meetings with the study coordinators (SB and LDD) were held to discuss conicting, ambiguous or missing data as well as review of inclusion and exclusion criteria. A coinvestigator (SB) nally reviewed separately 20% of randomly selected records of patients with fever, who did not meet the exclusion criteria, to determine interrater agreement with respect to the variables FWS and well appearance. PCV-7 immunization status data were obtained by searching the local health service database for patients living in the metropolitan area and from other local provincial health authorities for patients residing outside the metropolitan area. Literature review The PubMed database was searched for relevant articles using the following research strategy: (bacteremia OR blood culture) AND (fever OR febrile) AND emergency department AND (pneumococcal OR streptococcus pneumoniae) limited to English language, All Child: 018 years and Publication Date from 2001 to 2011 (last searched April 2011). Statistical analysis Categorical variables were expressed as percentages. Condence intervals (CI) were reported for main results. Quantitative variables were expressed as median and interquartile range, as a result of nonnormal data distribution. Comparison of categorical variables was performed by means of v2 test. The j -statistic was used to determine inter-rater agreement. Parameters displaying P 0.05 were considered statistically signicant. Statistical analyses were conducted using the statistical program MedCalc 11.1. The study was approved by the hospital Ethics Committee. As data were retrospectively collected and information registered as anonymous, no informed consent was requested.

Table 1 Clinical characteristics of study population Variable Age (months) Age >3 months Sex Male Female Median fever duration (h) Fever duration 12 h >12 24 h >24 48 h >48 h Not known Max body temperature (C) PCV* 1 dose 2 doses PCV = pneumococcal conjucate vaccine. *Data for the age group >3 months. Result 8.4 (316) 291 (74.2%) 219 (56%) 173 (44%) 24 (1060) 137 (35%) 79 (20%) 60 (15.3%) 102 (26%) 14 (3.7%) 39.2 (38.539.8) 205 (70.5%) 174 (59.8%)

RESULTS Study results During the study period, 666 children aged 136 months had a BC obtained in the PED because of a febrile illness. Of these, 259 were excluded because of antibiotic therapy in the prior 72 h (144 patients), underlying diseases resulting in immunodepression, presence of long-term vascular catheter or ventriculoperitoneal shunt (74 patients) and diagnosis of focal infection (41 patients). Of the remaining 407 patients identied as presenting FWS, 15 were excluded because they did not meet the denition of well appearing. A nal number of 392 children were included in the study.

The j value for classication of FWS was 0.97 (95% CI, 0.921.00). The j value for well-appearance classication was 0.92 (95% CI, 0.761.0). Demographic characteristics and clinical data of study subjects are reported in Table 1. Sixteen children (4.1%) presented to the PED for an unscheduled visit within one week from initial evaluation for reasons related to the same febrile episode (nine for persistence of fever and eight for reported worsening of clinical conditions or new symptoms). None of them was nally diagnosed with bacteremia, sepsis or meningitis (14 16 had not received antibiotics after the initial evaluation). During the study period, the percentage of enrolled children older than 3 months of age, who had received 1 dose of PCV-7, increased from 42.5% (second semester of 2006) to 87% (second semester of 2008). Sixty per cent of the enrolled children older than 3 months received two or more vaccine doses. A true pathogen was identied in three BC (0.77%, 95% CI, 0.01.64), none of which grew SP. A contaminant was isolated in 15 patients (3.83%, 95% CI, 1.935.73). The clinical features of patients with bacteremia are reported in Table 2. A lower bacteremia rate of 0.34% (95% CI, 0-1) was found in the age group 336 months compared with children 13 months of age (2%, 95% CI, 04.7), but the difference was not statistically signicant. No bacteremia was reported in the group 23 months of age, while bacteremia was associated with Urinary tract infection in one of two children in the age group 12 months (Table 2). Literature review results Of the 35 articles retrieved, a careful reading of abstracts or full-text articles nally identied 10 relevant papers responding to the purpose of this study (6,816). Their characteristics are summarized in Table 3. Five studies included only well-appearing children aged 336 months with FWS

2011 The Author(s)/Acta Pdiatrica 2011 Foundation Acta Pdiatrica 2012 101, pp. 271277

273

Bacteremia in feverish children in the emergency department

Bressan et al.

Table 2 Data of children with bacteremia Age (months) 1.8 1.1 11.2 Sex M F F No of PCV-7 doses 0 0 2 Max temp (C) 39.4 38.7 39.5 Fever duration (h) 4 16 12 WBC ( mm3) 3740 12 700 10 200 ANC ( mm3) 2320 7970 8670 CRP (mg L) 3.3 113 250 Pathogen on BC Streptococcus agalactiae Klebsiella ornithinolytica Streptococcus pyogenes Final diagnosis Occult bacteremia UTI + bacteremia Osteomyelithis

UTI = urinary tract infection; ANC = absolute neutrophil count; CRP = C-reactive protein; PCV-7 = pneumococcal conjucate vaccine 7 valent.

(10,1215), one study specically addressed children younger than 3 months of age with FWS independently of general appearance (16) and four studies included feverish children with no distinction between fever with or without source and or general appearance (6,8,9,11). In wellappearing children 336 months of age with FWS, overall OB rates <0.5% were found in studies with general population PCV-7 coverage of approximately 80% (10,12), while rates between 0.7% and 0.9% were found in the studies carried out in the Basque Country in Spain (1315), where PCV-7 coverage in the general population was lower (50 70%) and patients included in the study were mostly unvaccinated (study subjects who received at least 1 PCV-7 dose represented 27% and 11%, respectively, in two of these studies) (14,15). In the Spanish PED, PCV-7 introduction was associated with an important reduction in blood tests performance for vaccinated children (19). The study including only infants younger than 3 months of age showed an overall bacteremia rate of 2.2% with no SP cases; bacteremia was found more frequently in patients considered not well appearing and in those with leukocyturia and or nitrituria (16).

DISCUSSION The present study, evaluating the rate of bacteremia in wellappearing children 136 months of age with FWS presenting to the PED in the era of universal PCV-7 vaccination in Italy, found an overall bacteremia rate of 0.77% and of 0.34% for the age group 336 months. Our results are in accordance with those of previous similar studies (10,12 15). Despite the differences in inclusion criteria and PCV-7 coverage among the studies retrieved through our literature search, their results concordantly highlight a marked decrease in SP bacteremia and a relative increase in the rate of contaminants, between 1.2% and 4.9%, (6,812), as found in the present work. A previous study carried out in our PED before the widespread implementation of PCV-7 showed an occult SP bacteremia in 1% of the children <36 months of age with FWS (20), while no SP bacteremia was detected in the present work, thus reecting the effectiveness of widespread PCV-7 vaccination in our area. The vaccination coverage (of at least two doses) in the Veneto region increased from <50% in the years 20032005, to 80% in 2006, 92% in 2007 and 93.5% in 2008 (18). In the PCV-7 era, the distribution of pathogens responsible of OB in well-appearing children

aged 336 months with FWS has markedly changed. S. pyogenes, Enterococcus spp., N. meningitidis, nontype B H. inuenzae, E. coli, M. catharralis, Salmonella spp., and S. aureus were the most commonly isolated in the analysed studies, with a slight prevalence of S. pyogenes (10,1215). Of notice, no study has so far evaluated the occurrence of OB with the sensitive RT-PCR method, and therefore, the present and previous results probably underestimate the true bacteremia rates. RT-PCR takes only 2 h and does not require viable bacteria as BC does, and by detecting bacterial DNA, can identify bacteremia despite antibiotic treatment during the preceding 4 days (21). The decrease in SP bacteremia rate, as well as the epidemiological change of the responsible pathogens, questions the current usefulness of traditionally recommended screening tests for OB in well-appearing children 336 months of age with FWS (22,23). Previous studies have demonstrated that the yield of WBC value >15 000 mm3 and ANC >10 000 mm3, mainly targeted at identifying SP bacteremia, has decreased in the PCV-7 era (7,11,15,16). In 2001, the study by Lee et al. (24) showed that for bacteremia rate <0.5%, in children 336 months of age with FWS, management strategies that involve routine testing and empirical administration of antibiotics is no longer cost effective. Costs and risks (because of the invasive procedure, excessive use of antibiotics and antibiotic resistance, as well as return visit and management for BC contaminations) outweigh benets in these circumstances (4,25). According to the NICE guidelines for feverish children issued in the UK in May 2007 (26), routine blood tests on well-appearing children with fever are not justied. A review article on FWS published by Baraff (27) recommended no routine blood tests in well-appearing infants 336 months of age who received HiB and PCV-7 vaccinations. More recently, Trainor and Stamos (28) stated that well-appearing children (older than 3 months of age) with FWS should no longer be routinely subject to laboratory investigations to detect OB. However, despite the growing data on this topic, the policy issued by the American College of Emergency Physicians in 2003 (23) has not yet been updated readdressing the utility of blood tests and blood culture after the widespread implementation of PCV-7, and Italian guidelines have not been issued yet. In Italy, however, large differences in PCV-7 coverage among regions should be taken into account. While the recommended management for children younger than 3 months of age has not changed because of the

274

2011 The Author(s)/Acta Pdiatrica 2011 Foundation Acta Pdiatrica 2012 101, pp. 271277

Bressan et al.

Table 3 Summary of studies identied trhough the literature search

Study
20012003 19972000 20012005 136 NR 1.3% 0.43% 1% 0.2% 2.2% 3.1% ED 911 2060 No ED UCC 329 236 No NR 0.91% 0.91% 1.20% Non-toxic appearing All children None

Country

Design

Timing to PCV-7 introduction Study period Setting No of BC FWS General appearance Overall bacteremia rate SP bacteremia rate Contam. rate

Patients Age (months)

PCV-7 average coverage*

Pathogens other than SP

Stoll, 2004 (8)

USA

Post

Sard, 2006 (10)

USA

Pre post

USA 20002001 20022003 20042005 20042007 336 Yes Well-appearing NR 0.25% PED 8408 PED 1171 1117 1575** 336 Yes Well-appearing NR 1.8% 0.7%0.76% 1.6% 0.6% 0.7%

Pre-post

20002002

ED

1383 036 No All children 64% 2.4% 0.2% 2.4% 0%

5% 1.8% NR

4 GBS 1 E. coli 1 M. catharralis 1 E. fecalis 1 S. aureus 2 Enterococcus

Carstairs, 2007 (11) Fernandez, 2007 (15)

Spain

Pre transition post

Wilkinson, 2008 (14)

USA

Post

0.17%

1.89%

Rudinsky, 2009 (13) 024 No All children 79% 19971999 20012004 PED 148 275 336 Yes Non-toxic appearing NR

USA

Post

20022003

ED

690

0.7%

0.14%

4.90%

2011 The Author(s)/Acta Pdiatrica 2011 Foundation Acta Pdiatrica 2012 101, pp. 271277

Waddle, 2009 (12)

USA

Pre post

6.7% 0.4%

4% 0%

4.7% 4.7%

Mintegi 2009 (17) 336 Yes

Spain

Post

20042006

PED

1586

Well-appearing

27%

0.90%

0.60%

NR

Spain 336 <3 20032008 PED 1018

Post

20062009

PED

3088

Yes Yes

Well appearing All children

11% NA

0.70% 2.20%

0.60% 0.40%

NR NR

Fernandez 2010 (16) Gomez 2010 (18)

Spain

Post

2 S. enteritidis 1 H. inuenzae 1 S. pyogenes 1 N. meningitidis 3 H. inuenzae (not Type B) 3 E. coli 2 S. pyogenes 1 M. catarrhalis 1 S. aureus 1 Salmonella sp. 2 Enterococcus 1 E. coli 1 GBS 2 M. catharralis 1 S. aureus 1 S. pyogenes 1 Enterococcus 2 N. meningitidis 1 S. pyogenes 1 Enterococcus 1 Salmonella sp. 2 S. pyogenes 2 N. meningitidis 9 E coli 2 GBS 3 N. meningitis 3 Enterococcus 1 K. penumoniae 1 S. aureus

Bacteremia in feverish children in the emergency department

R = retrospective; NR = not reported; NA = not applicable; GBS = group B streptococcus; UCC = urgent care centers; FWS = fever without source; PED = pediatric emergency department. *Refers to oneor more doses of pneumococcal conjucate vaccine - 7 valent (PCV-7) received in the study population at the time of evaluation for fever. Total number of children with FWS attended during the study period not known. Six hundred and fty six of patients, in the whole study population, were well appearing with FWS > 39C. In this subgroup of patients 5 (0.7%) had true positive BC results (all SP)- of these only one belonged to the post PCV-7 era- Not reported how many patients with FWS presented before and after PCV-7 introduction. Immunized vs non immunized children. corresponding to 39% of children younger than 36 months attended for fever in the study period. **Corresponding to 15% of all children 336 months attended for FWS in the study period. Corresponding to 70% of 985 children younger than 24 months attended for fever in the study period. Included only patients with normal urine dipstick. Corresponding to 17.5% of all children 336 months admitted for FWS in the study period. Corresponding to 91.5% of all infants <3 months admitted for FWS in the study period; 8 23 (35%) of the patients with true positive BC had E. coli bacteremia associated with Urinary tract infection; bacteremia rate in well-appearing infants with normal urine dipstick was 1%.

275

Bacteremia in feverish children in the emergency department

Bressan et al.

particular predisposing factors to severe bacterial infections in this age group, as well as age schedule of PCV-7, studies assessing bacteremia rate in these infants suggested that the practice of routinely obtaining complete blood cell count may no longer be necessary or cost effective even in the management of previously healthy, well-appearing febrile children 23 months of age who have been immunized with at least one dose of PCV-7 (6), and whose urinalysis is normal (16). Our results show no OB in the age group 2 3 months, but this nding may be likely related to our small sample size. Even though laboratory markers have shown to be inaccurate predictors of OB in the PCV-7 era, their determination in well-appearing children with FWS may help in detecting occult severe bacterial infections (such as occult pneumonia or early-stage meningitis) especially in younger children, for whom clinical assessment is more challenging. However, their role in the identication of such occult infections in these children has not been specically investigated in the PCV-7 era. Our study presents several limitations mainly related to its retrospective design. First of all is the possibility of a selection bias. As selection of patients for the study was based on performance of blood culture for a febrile illness and following identication of children with FWS, the number of patients who presented to the PED with FWS during the study period and did not have a BC drawn is not known. The real denominator is the number of well-appearing children with FWS regardless of whether a BC was performed. According to the protocol in use in our PED for infants and children with FWS at the time of the study, children who had a BC performed were mainly those at higher risk of bacteremia and the inclusion of children with FWS who had no testing would merely increase the denominator and further decrease the incidence of bacteremia in our study population. However, the lack of follow-up did not allow us to ascertain whether patients with FWS who did not have a BC obtained in the PED could have had bacteremia at their rst PED visit and might subsequently have developed a severe pneumococcal disease. A separate record review of children 136 months of age hospitalized in our department did not identify any pneumococcal bacteremia, sepsis or meningitis in children who were previously evaluated and discharged from the PED for FWS. Nevertheless, the small possibility that discharged children were subsequently examined at other hospitals or outpatient medical ofces, despite recommendations to return to our centre in case of worsening clinical course or persistence of symptoms, cannot be excluded. Second, the retrospective design may lead to errors associated with data review and related to the inherent difculty of abstracting reliable data on complex variables, like FWS and well appearance, without prospective data collection. However, a priori denitions, measure of interobserver agreement, as well as other recommended strategies for retrospective data abstraction (29) were used to limit this possibility. Third, the small sample size of our study with respect to the age group 13 months does not allow to draw denitive conclusions on bacteremia rate in these children. Finally, our literature search did not follow

the methodological criteria of a systematic review, as our aim was rather to give an overview of the main studies assessing bacteremia rate in febrile children presenting to the emergency department in the postPCV-7 era, facilitating comparison of their results with the ones of our study.

CONCLUSIONS SP is a rare cause of bacteremia in the postPCV-7 era. Overall OB rate is currently <0.5% in well-appearing children 3 36 months of age with FWS attending the PED in areas with high PCV-7 coverage and is sufciently low to preclude laboratory testing in favour of close follow-up in these settings. Bacteremia in well-appearing infants with FWS <3 months of age is rarely caused by SP and often presents in association with urinary tract infection. Further research is required to evaluate a more conservative approach for wellappearing children aged 23 months, with FWS and negative urinalysis.

References
1. Lee GM, Harper MB. Risk of bacteremia for febrile young children in the post-Haemophilus inuenzae type b era. Arch Pediatr Adolesc Med 1998; 152: 6248. 2. Baraff LJ. Management of fever without source in infants and children. Ann Emerg Med 2000; 36: 60214. 3. Baraff LJ, Bass JW, Fleisher GR, Klein JO, McCracken GH Jr, Powell KR, et al. Practice guideline for the management of infants and children 0 to 36 months of age with fever without source. Agency for Health Care Policy and Research. Ann Emerg Med 1993; 22: 1198210. 4. Joffe MD, Alpern ER. Occult pneumococcal bacteremia: a review. Pediatr Emerg Care 2010; 26: 44854. 5. Alpern ER, Alessandrini EA, Bell LM, Shaw KN, McGowan KL. Occult bacteremia from a pediatric emergency department: current prevalence, time to detection, and outcome. Pediatrics 2000; 106: 50511. 6. Stoll ML, Rubin LG. Incidence of occult bacteremia among highly febrile young children in the era of the pneumococcal conjugate vaccine: a study from a Childrens Hospital Emergency Department and Urgent Care Center. Arch Pediatr Adolesc Med 2004; 158: 6715. 7. Herz AM, Greenhow TL, Alcantara J, Hansen J, Baxter RP, Black SB, et al. Changing epidemiology of outpatient bacteremia in 3- to 36-month-old children after the introduction of the heptavalent-conjugated pneumococcal vaccine. Pediatr Infect Dis J 2006; 25: 293300. 8. Sard B, Bailey MC, Vinci R. An analysis of pediatric blood cultures in the postpneumococcal conjugate vaccine era in a community hospital emergency department. Pediatr Emerg Care 2006; 22: 295300. 9. Carstairs KL, Tanen DA, Johnson AS, Kailes SB, Riffenburgh RH. Pneumococcal bacteremia in febrile infants presenting to the emergency department before and after the introduction of the heptavalent pneumococcal vaccine. Ann Emerg Med 2007; 49: 7727. 10. Waddle E, Jhaveri R. Outcomes of febrile children without localising signs after pneumococcal conjugate vaccine. Arch Dis Child 2009; 94: 1447. 11. Rudinsky SL, Carstairs KL, Reardon JM, Simon LV, Riffenburgh RH, Tanen DA. Serious bacterial infections in febrile

276

2011 The Author(s)/Acta Pdiatrica 2011 Foundation Acta Pdiatrica 2012 101, pp. 271277

Bressan et al.

Bacteremia in feverish children in the emergency department

12.

13.

14.

15.

16.

17.

18.

19.

infants in the post-pneumococcal conjugate vaccine era. Acad Emerg Med 2009; 16: 58590. Wilkinson M, Bulloch B, Smith M. Prevalence of occult bacteremia in children aged 3 to 36 months presenting to the emergency department with fever in the postpneumococcal conjugate vaccine era. Acad Emerg Med 2009; 16: 2205. ndez J, Raso SM, Pocheville-Gurutzeta I, Sa nBenito-Ferna ez B, Capape -Zache S. chez-Etxaniz J, Azcunaga-Santiban Pneumococcal bacteremia among infants with fever without known source before and after introduction of pneumococcal conjugate vaccine in the Basque Country of Spain. Pediatr Infect Dis J 2007; 26: 66771. ndez J, Mintegi S, Pocheville-Gurutzeta I, Sa nBenito-Ferna mez Corte s B, Herna ndez Almaraz JL. Pneuchez Etxaniz J, Go mococcal bacteremia in febrile infants presenting to the emergency department 8 years after the introduction of pneumococcal conjugate vaccine in the Basque Country of Spain. Pediatr Infect Dis J 2010; 29: 11424. Mintegi S, Benito J, Sanchez J, Azkunaga B, Iturralde I, Garcia S. Predictors of occult bacteremia in young febrile children in the era of heptavalent pneumococcal conjugated vaccine. Eur J Emerg Med 2009; 16: 199205. mez B, Mintegi S, Benito J, Egireun A, Garcia D, Astobiza E. Go Blood culture and bacteremia predictors in infants less than three months of age with fever without source. Pediatr Infect Dis J 2010; 29: 437. Tarallo L, Tancredi F, Schito G, Marchese A, Bella A. Italian ` Italiana Pediatria and Associazione Pneumonet Group (Societa Italiana Studio Antimicrobici e Resistenze). Active surveillance of Streptococcus pneumoniae bacteremia in Italian children. Vaccine 2006; 24: 693843. Veneto Region website: http://www.regione.veneto.it/Servizi+alla+Persona/Sanita/Prevenzione/Malattie+Infettive/ Malattie+prevenibili+con+vaccinazione/ (accessed on July 31, 2011). lez M, Astobiza E, Sanchez J, SantiMintegi S, Benito J, Gonza ago M. Impact of the pneumococcal conjugate vaccine in the management of highly febrile children aged 6 to 24 months in an emergency department. Pediatr Emerg Care 2006; 22: 5669.

20. Andreola B, Bressan S, Callegaro S, Liverani A, Plebani M, Da Dalt L. Procalcitonin and C-reactive protein as diagnostic markers of severe bacterial infections in febrile infants and children in the emergency department. Pediatr Infect Dis J 2007; 26: 6727. 21. Azzari C, Moriondo M, Indol G, Massai C, Becciolini L, de Martino M, et al. Molecular detection methods and serotyping performed directly on clinical samples improve diagnostic sensitivity and reveal increased incidence of invasive disease by Streptococcus pneumoniae in Italian children. J Med Microbiol 2008; 57: 120512. 22. Baraff LJ. Management of infants and children 3 to 36 months of age with fever without source. Pediatr Ann 1993; 22: 4978. 5014. 23. American College of Emergency Physicians Clinical Policies Committee; American College of Emergency Physicians Clinical Policies Subcommittee on Pediatric Fever. Clinical policy for children younger than three years presenting to the emergency department with fever. Ann Emerg Med 2003; 42: 530 45. 24. Lee GM, Fleisher GR, Harper MB. Management of febrile children in the age of the conjugate pneumococcal vaccine: a costeffectiveness analysis. Pediatrics 2001; 108: 83544. 25. Avner JR, Baker MD. Occult bacteremia in the post-pneumococcal conjugate vaccine era: does the blood culture stop here? Acad Emerg Med 2009; 16: 25860. 26. NICE. Feverish illness in children: assessment and initial management in children younger than 5 years. CG47. London: National Institute for Health and Clinical Excellence, 2007. Available from http://www.nice.org.uk/CG47 (accessed on May 31, 2011). 27. Baraff LJ. Management of infants and young children with fever without source. Pediatr Ann 2008; 37: 6739. 28. Trainor JL, Stamos JK. Fever without a localizing source. Pediatr Ann 2011; 40: 215. 29. Gilbert EH, Lowenstein SR, Koziol-McLain J, Barta DC, Steiner J. Chart reviews in emergency medicine research: where are the methods? Ann Emerg Med 1996; 27: 3058.

2011 The Author(s)/Acta Pdiatrica 2011 Foundation Acta Pdiatrica 2012 101, pp. 271277

277