Bacteremia in Children-JTP

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356 Journal of Tropical Pediatrics Vol. 47 December 2001 Oxford University Press 2001

IntroductionBacteremia has been increasingly reported inchildren under 5 years of age. There are no reliabledata on the incidence or prevalence of invasivebacterial infections involving children in Jordan.Bacteremia in certain infections is considered the bestpractical way to identify the causative organism. Theisolation of bacteria from blood cultures is usuallyindicative of a serious invasive infection that requiresimmediate antibiotic treatments. 1 Septicemia is apathological condition with a high mortality rate thatvaries between 30 and 70 per cent and depends onseveral factors including virulence of the pathogenand host factors. 21,22 The majority of the bacteremiacases are caused by a number of pathogens includingStaphylococcus spp., Streptococcus spp., Enterobacter spp., Escherichia coli, Klebsiella pneumoniae, andPseudomonas spp. 20

In such a potentially life-threatening condition,isolation of the causative pathogen in blood culture iscrucial for proper antimicrobial treatment. Differentorganisms have different antimicrobial susceptibili-

ties and successful treatment is dependent on theprompt administration of the correct drug. 10,15 Thismay improve the prognosis of the patients withsepticemia. The delay, however, may mean unneces-sary treatment or the use of ineffective therapy given

to antibiotic resistant organisms.There is a wide variation in the incidence andclinical characteristics of invasive infections causedby different species of bacteria. Identifying thecausative species and characterizing the clinicalsignicance in a particular age group in a communityis essential for the prevention and treatment of theseinfections.

We carried out a prospective study in childrenunder 10 years old who had a temperature of 39C,regardless of the presumed clinical source of fever, toidentify the most frequently encountered causativeagents, their susceptibilities to the commonly used

antibiotics, and factors contributing to these infec-tions in this age group.

Methods

SubjectsA total of 210 children under 10 years old presentingto a pediatrician with a temperature of 39C duringthe 2-year period between 1998 and 1999 wereeligible for this study. These included cases of gastroenteritis, respiratory tract infection, meningitis,

Bacteremia in Children: Etiologic Agents, Focal Sites, andRisk Factors

by L. F. Nimri, a M. Rawashdeh, b and M. M. Meqdam aaDepartment of Applied Biology, and bDepartment of Pediatrics, Jordan University of Science and Technology, Irbid, Jordan

SummaryA prospective study was carried out on 210 cases of children under 10 years of age with fever. Casesof gastroenteritis, respiratory tract infections, and suspected sepsis in children seen or admitted tothe pediatric hospital were studied. Clinical and microbiological data were recorded in a question-naire or obtained from patient medical records.Most of the children with septicemia (71.3 per cent)were less than 1 year old. Focal source of bacteremia was gastroenteritis (40.4 per cent),pneumoniaor bronchopneumonia (20 per cent), meningitis (7.4 per cent), and urinary tract infections (7.4 percent). The predominant pathogens isolated from blood or stool specimens were Gram-positivebacteria (53.3 per cent), mainly Streptococcus pneumoniae and coagulase-negative Staphylococcusspp. The Gram-negative bacteria (45.6 per cent) were mainly Escherichia coli , Klebsiella pneu-moniae, Haemophilus inuenzae, Neisseria meningitidis , and Yersinia spp . One case of Candida

albicans (1.1 per cent) was reported. Pasteurella pneumotropica was reported in two cases for therst time. The mortality rate was 4 per cent, mostly from septicemia cases. Long duration of hospi-talization (> 10 days) and parenteral feeding were identied as risk factors. Resistance of theisolated pathogens to several commonly used antibiotics was observed. Empirical treatment withantibiotics is recommended only in life-threatening cases.

AcknowledgementsThis study was supported by a grant (no. 25/97) from the Deanshipof Research at Jordan University of Science and Technology.

Correspondence: Dr Laila Nimri, Department of Applied Biology,JUST, P.O. Box 3030, Irbid 22110, Jordan. Tel 9622 709-5111; Fax9622 709-5014. E-mail .


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urinary tract infections (UTI), or suspected sepsisthat were admitted to Prince Rahma Hospital inIrbid, Jordan. It is the largest community pediatrichospital afliated with Jordan University of Scienceand Technology that receives patients from thenorthern region in the country. Clinical, microbiolog-ical data and other information such as temperature,immunodeciencies, and antibiotic therapy were

recorded from the patients medical record. A ques-tionnaire concerning demographic data, age, sex,chief complaint, duration of symptoms, and hospitalstay was completed for each patient.

MicrobiologyA blood specimen was collected from each patientand inoculated in a biphasic blood culture bottle(BioMerieux, France). Bottles were incubated at37C and continuously monitored for evidence of bacterial growth. An aliquot of the positive bloodculture was aseptically taken by a syringe for Gramstain and subcultured on enriched and selective

media for a wide variety of pathogens. Stool sampleswere also collected from the same patients andcultured on selective media. The organisms grown onagar plates from both blood and stool specimenswere identied by standard laboratory methodsincluding biotyping and API 20E (BioMerieux,France).

Susceptibility testsThe antibiotic sensitivity of the isolates was tested for11 antibiotics on MullerHinton agar using discdiffusion assay. 14 Susceptibility testing to at least sixout of 10 antibiotics was performed on each isolate.

Antibiotics tested were amoxicillin, ampicillin,augmentin, doxicillin, gentamicin, novecin, tetracy-cline, tobramycin, rifampicin, erythromycin andvancomycin (for the Gram-positive isolates). Non-susceptible refers to resistant and intermediatelyresistant.

Data analysisUnivariate analyses were performed using Epi-Infoversion 6.0 (Centers for Disease Control and Preven-tion, Atlanta, USA). Means and proportions werecompared by standard tests (chi-squared and t -tests)A p value of 0.05 was considered signicant.

Results

Positive culturesPathogens were isolated from a total of 94 out of the210 patients (44.8 per cent). The mean age of thepatients was 16.6 months 14.8 (range: 1120months), 61.3 per cent of these patients were males(Table 1). Results of stool cultures and the isolatedspecies are shown in Table 2.

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Journal of Tropical Pediatrics Vol. 47 December 2001 357

TABLE 2Bacterial species isolated from 94 blood and stool

cultures

Species isolated No. of isolates (%)

Blood cultures

Coagulase negative Staphylococcus spp. 19 (20.1)Staphylococcus aureus 5 (5.3)Streptococcus spp. 21 (22.3)Enterococcus spp. 3 (3.2)Escherichia coli 9 (9.6)Enterobacter taylorae 2 (2.1)Salmonella typhi 4 (4.3)Shigella sonnei 1 (1.1)Klebsiella pneumoniae 8 (8.5)Neisseria meningitidis 4 (4.3)Haemophilus inuenzae 6 (6.4)Pseudomonas aeruginosa 1 (1.1)Pasteurella pneumotropica 2 (2.1)Yersinia enterocolitica 2 (2.1)

Yersinia pseudotuberculosis 2 (2.1)Candida albicans 1 (1.1)Unidentied 4 (4.3)

Stool culturesEscherichia coli 19 (50.0)Candida albicans 5 (13.2)Salmonella typhi 4 (10.5)Shigella spp. 2 (5.3)Yersinia enterocolitica 4 (10.5)Yersinia pseudotuberculosis 2 (5.3)

Aeromonas salmonicida 2 (5.3)

TABLE 1Characteristics of 94 patients with bacteremia

Characteristics No. of patients (%)

Age group (months)112 67 (71.3)

1324 10 (10.6)2536 8 (8.5)

> 36 9 (9.6)Sex

Males 57 (60.6)Females 37 (39.4)

Primary infectionGastroenteritis 38 (40.4)Pneumonia or 19 (20.2)bronchopneumoniaMeningitis 7 (7.4)Sepsis 7 (7.4)Urinary tract infections 7 (7.4)Septic arthritis 2 (2.1)Undetermined 14 (14.9)


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Focal sites and causative speciesClinically, focal source of bacteremia was determinedin 80 out of the 94 positive cases (85.1 per cent) (Table2). A focal site of infection could not be identied in14 (14.9 per cent) of the patients. Most of thebacteremia cases (71.3 per cent) were documented inpatients less than 1 year old, of whom 51.1 per centwere less than 6 months old. Only 9.5 per cent of the

cases were documented in children aged between 3and 10 years. From the diagnosis made by the pedia-trician, the focal infections of bacteremia in thesepatients were gastroenteritis (40.4 per cent), pneu-monia or bronchopneumonia (20 per cent), meningi-tis (7.4 per cent), sepsis (7.4 per cent), UTI (7.4 percent), and septic arthritis (2.1 per cent). None of thepatients were documented to have immunode-ciency. Gram-positive bacteria were predominant(53.3 per cent), while Gram-negative accounted for45.6 per cent, and Candida albicans accounted for 1.1per cent. The most common cause of bacteremia inthese patients was coagulase negative Staphylococcus

spp. (CoNS) (20.1 per cent), mainly Staphylococcusepidermidis, Streptococcus spp. (22.3 per cent),mainly group A beta-hemolytic streptococci, Neisse-ria meningitidis (4.3 per cent), Klebsiella pneumoniae(8.5 per cent), Haemophilus inuenzae (6.4 per cent),Salmonella typhi (4.5 per cent), Yersinia enterocolitica(2.1 per cent), Yersinia pseudotuberculosis (2.1 percent), Pasteurella pneumotropica (2.1 per cent), andShigella sonnei (1.1 per cent). (Table 2).

The majority of CoNS spp. (70 per cent) wereisolated from children less than 18 months old; 30 percent were isolated from the age group 1836 months.Ten per cent of the bacteremia in the hospitalized

cases were suspected to be nosocomial in origin andone case was polymicrobial. Risk factors identiedwere: age of 1 year or less (95 per cent CI = 1.162.55,

p < 0.001); length of stay in hospital (10 12.2 days, p = 0.008); and parenteral feeding ( p < 0.001).Symptoms recorded beside fever depending on theprimary site of infection were vomiting (90.9 percent), diarrhea in 85.5 per cent of the gastroenteritiscases, cough (95 per cent) in respiratory tract infec-tions, and febrile convulsions were reported in eightpatients (8.5 per cent).

Mortality rate

The overall mortality rate in these cases was 4 percent due to infections with Neisseria meningitides(two cases), Streptococcus pneumoniae (one case),and Candida albicans (one case).

Treatment Oral treatment was given to the majority of thesecases, i.e. 92 (97.8 per cent) on the date of the initialblood culture. Of these treated patients, 35 (38 percent) received parenteral antibiotics either as singleor as combination antibiotics. The combination of claforan/ampicillin was the most prescribed.

Electrolytes and intravenous uids were given tocases with diarrhea and dehydration. Patientssuspected of having meningitis or sepsis receivedempiric parenteral antibiotics and were reported tohave improved conditions at follow-up.

Susceptibility testingNon-susceptibility of the isolates was observed for at

least two of the antibiotics tested. The highest wasrecorded for ampicillin (72.2 per cent), augmentin(50 per cent), amoxicillin (46.2 per cent), anderythromycin (45.4 per cent of the Gram-positiveisolates).

Other laboratory testsAdditional laboratory tests were performed on allpatients, such as the white blood cell counts whichwere 20000 cells/mm 3. Other tests were performeddepending on the primary diagnosis of the pedia-trician. These tests included serological tests (e.g.latex test for Brucella and Widal test for Salmonella ),

tests and cultures of CSF obtained from eightpatients suspected to have meningitis, detection of parasites in stool for patients with gastroenteritis,and urine analysis and cultures in the case of patientswith suspected UTI.

DiscussionBacterial infections are major causes of morbidityand mortality in children. The detection, identi-cation, and susceptibility testing of a causativespecies of bacteremia is essential for the proper treat-ment, and better prognosis of the patient.

In this study, bacteremia was conrmed in 94 (44.8per cent) patients out of 210 children with variousdiseases. The most common primary infection wasidentied in 80 (85.1 per cent): gastroenteritis (40.4per cent) and pneumonia (20.4 per cent). Thecausative species were also identied in 90 (95.7 percent) of the cases in blood and stool cultures.

The most common pathogens were Streptococcusspp. (22.3 per cent) especially S. pneumoniae mainlyisolated from cases with pneumonia. Streptococcus

pneumoniae was also reported as the most commonpathogen in children with bacteremia aged 336months. 8 Pneumonia counted for 7 per cent of these

children while other respiratory tract infectionscounted for 24 per cent, gastroenteritis (9 per cent),and UTI (5 per cent). In another study, the source of bacteremia cases of pneumococcal infections, werepneumonia (37 per cent), otitis media (30 per cent),meningitis (11.5 per cent), and no focal source (33per cent). 19 Group A streptococci (e.g. S. pyogenes )although an uncommon cause of meningitis, wasreported in few cases as a result of bacteremia orsurgery. 13

Coagulase negative staphylococci (CoNS)accounted for 20.1 per cent of the blood culture

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358 Journal of Tropical Pediatrics Vol. 47 December 2001


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isolates obtained from clinically dened infections.The highest incidence of sepsis caused by Staphylo-coccus epidermidis was observed in children less than12 months old. Our results are in agreement withother studies that reported CoNS as the mostcommon bacteria isolated from infants with sepsis. 17The frequent nding of CoNS and S. pneumoniaewere also reported by a study that used molecular

diagnosis by PCR.1

Staphylococcus epidermidis and other CoNS wasreported to have emerged as a major cause of noso-comial infections. 6 They are part of the normal skinand mucosal micro ora, and their presence in bloodcultures might indicate catheter and medical device-related sepsis or a contaminant of blood cultures. 9The interpretation of their presence is a majorconcern for clinicians and clinical microbiologylaboratories. The decision for therapy relies mostlyon the observation of sepsis symptoms and thenumber of positive blood cultures. However, thecriteria of multiple blood cultures could not be

applied in pediatric patients who cannot undergomultiple venous puncture. Escherichia coli wasisolated from 9.6 per cent of the cases; it was reportedto be the most frequent Gram-negative bacterialspecies recovered from blood cultures. 1

Bacteremia caused by Klebsiella pneumoniaeaccounted for 7.4 per cent of the cases. In a study of neonatal sepsis in Ethiopia, Klebsiella was reportedas the leading etiologic agent (38 per cent). 7 Yersiniaenterocolitica (two cases) and Yersinia pseudotuber-culosis (two cases) were isolated from blood andstool cultures of gastroenteritis cases; these isolateswere non-susceptible to ampicillin. Pasteurella pneu-

motropica was isolated from blood cultures of twopatients and were identied by the API system but,the source of infection, which is usually from animals,was not established. Shigella sonnei was isolatedfrom blood and stool cultures of a 10-month-oldchild who had severe diarrhea. Isolation of Shigellaspp. from blood is considered as an unusual medicalevent and is not frequently reported. 3

Candida albicans was isolated from the bloodculture of a 10-month-old male. This was a fatal casebecause antifungal treatment was not given. TheCanadian Infectious Disease Society reported 11.6per cent infection rate in children and an overall

mortality rate of 27 per cent that varies with thespecies of Candida .23Enterococcus taylorae was isolated from blood

cultures of three children (3.2 per cent) who had beenhospitalized for 10 days. Intravascular device wasused during their stay, which might be a risk factor fora nosocomial infection with these species. They werereported as a nosocomial infection due to use of intravascular device in 44 per cent of the bacteremiacases in 66 per cent of children 1 year old or less. 5

Haemophilus inuenzae was isolated from six (6.4per cent) blood cultures mostly from children


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L. F. NIMRI ET AL .

360 Journal of Tropical Pediatrics Vol. 47 December 2001

4. Chumpa A, Bachura RG, Harper MB. Bacteremia-associatedpneumococcal pneumonia and the benet of initial parenteralantimicrobial therapy. Pediatr Infect Dis J 1999; 18: 108185.

5. Das I, Gray J. Enterococcal bacteremia in children: a review of seventy-ve episodes in a pediatric hospital. Pediatr Infect Dis J1998; 17: 115458.

6. Frebourg NB, Lefebvre S, Baert S, Lemeland JF. PCR-basedassay for discrimination between invasive and contaminatingStaphylococcus epidermidis strains. J Clin Microbiol 2000; 38:

87780.7. Ghiorghis B. Neonatal sepsis in Addis Ababa, Ethiopia: a

review of 151 bacteremic neonates. Ethiop Med J 1997; 35:16976.

8. Haddon RA, Barnett PL, Grinwood K, Hogg G. Bacteremia infebrile children presenting to a pediatric emergency depart-ment. Med J Aust 1999; 170: 47578.

9. Kloos WE, Bannerman TL. Update on clinical signicance of coagulase-negative staphylococci. Clin Microbiol Rev 1994; 7:11740.

10. Lebovici LS, Shraga I, Drucker M, Konigsberger H, Samara Z,Pitlik SD. The benet of appropriate empirical antibiotic treat-ment in patients with blood stream infection. J Intern Med 1998;244: 37986.

11. Lee HJ. Epidemiology of systemic Haemophilus inuenzaedisease in Korean children. Pediatr Infect Dis J 1998; 17(Suppl9): S18589.

12. Lee WS, Puthucheary SD, Boey CC. Non-typhoid Salmonellagastroenteritis. J Paediat Child Health 1998; 34: 38790.

13. Moses AE, Beeri M, Engelhard D. Group A streptococcalmeningitis: report of two cases. J Infect 1998; 36: 11618.

14. National Committee for Clinical Laboratory Standards.

Performance standards for antimicrobial disk and dilutionsusceptibility tests for bacteria isolated from animals. Approvedstandard M31-A. National Committee for Clinical LaboratoryStandards, Wayne, PA, 1999.

15. Pedersen G, Schonheyder HC, Sorensen HT. Antibiotic therapyand outcome of antimicrobial Gram-negative bacteremia: a 3-year population-based study. Scand J Infect Dis 1997; 29:60106.

16. Pichichero ME. Group A beta-hemolytic streptococcal infec-

tions. Pediatr Rev 1998; 19: 291302.17. Sabui T, Tudehope DI, Tilse M. Clinical signicance of quanti-

tative blood cultures in newborn infants. J Paediatr ChildHealth 1999; 35: 57881.

18. Silverstein M, Bachura R, Harper MB. Clinical implications of penicillin and cetriaxone resistance among children withpneumococcal bacteremia. Pediatr Infect Dis J 1999; 18: 3541.

19. Totapally BR, Walsh WT. Pneumococcal bacteremia in child-hood: a 6-year experience in a community hospital. Chest 1999;115: 120714.

20. Weinstein MP, Merrett S, Reimer LG, et al . Controlled evalu-ation of BacT/Alert standard aerobic and FAN aerobic bloodculture bottles for detection of bacteremia and fungemia. J ClinMicrobiol 1995; 33: 97881.

21. Wenzel RP, Pinsky MR, Ulevitch RJ, Young L. Current under-standing of sepsis. Clin Infect Dis 1996; 22: 40712.

22. Wheeler AP, Bernard GR. Treating patients with severe sepsis.N Engl J Med 1999; 340: 20714.

23. Yamamura DL, Rotstein C, Nicolle LE, Ioannou S. Candidemiaat selected Canadian sites: results from the Fungal DiseaseRegistry, 19921994. Fungal Disease Registry of the CanadianInfectious Disease Society. CMAJ 1999; 160: 49399.

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Bacteremia in Children-JTP