Bacteremia in Children-JTP

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  356Journal of Tropical PediatricsVol. 47 December 2001  © Oxford University Press 2001 Introduction Bacteremia 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 including Staphylococcus spp., Streptococcus spp., Enterobacter  spp., Escherichia coli, Klebsiella pneumoniae, and Pseudomonas 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 givento 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 clinicalsignificance 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 ≥ 39ºC,regardless of the presumed clinical source of fever, toidentify the most frequently encountered causativeagents, their susceptibilities to the commonly usedantibiotics, and factors contributing to these infec-tions in this age group. Methods Subjects A total of 210 children under 10 years old presentingto a pediatrician with a temperature of ≥ 39ºC 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 aa Department of Applied Biology,and b Department 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  Staphylococcus spp.The Gram-negative bacteria (45.6 per cent) were mainly  Escherichia coli  ,  Klebsiella pneu-moniae, Haemophilus influenzae, Neisseria meningitidis ,and Yersinia spp  . One case of Candidaalbicans (1.1 per cent) was reported.  Pasteurella pneumotropica was reported in two cases for thefirst time.The mortality rate was 4 per cent,mostly from septicemia cases.Long duration of hospi-talization (> 10 days) and parenteral feeding were identified as risk factors.Resistance of theisolated pathogens to several commonly used antibiotics was observed.Empirical treatment withantibiotics is recommended only in life-threatening cases.Acknowledgements This 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 <>.  urinary tract infections (UTI), or suspected sepsisthat were admitted to Prince Rahma Hospital inIrbid, Jordan. It is the largest community pediatrichospital affiliated 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,immunodeficiencies, and antibiotic therapy wererecorded from the patient’s medical record. A ques-tionnaire concerning demographic data, age, sex,chief complaint, duration of symptoms, and hospitalstay was completed for each patient. Microbiology A blood specimen was collected from each patientand inoculated in a biphasic blood culture bottle(BioMerieux, France). Bottles were incubated at37ºC 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 selectivemedia 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 identified by standard laboratory methodsincluding biotyping and API 20E (BioMerieux,France). Susceptibility tests The antibiotic sensitivity of the isolates was tested for11 antibiotics on Muller–Hinton 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 analysis Univariate 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 significant. Results Positive cultures Pathogens 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: 1–120months), 61.3 per cent of these patients were males(Table 1). Results of stool cultures and the isolatedspecies are shown in Table 2. L. F. NIMRI ET AL . Journal of Tropical PediatricsVol. 47 December 2001357 T ABLE 2 Bacterial species isolated from 94 blood and stool cultures Species isolatedNo. of isolates (%)Blood culturesCoagulase 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 influenzae 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)Unidentified4 (4.3)Stool cultures Escherichia 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) T ABLE 1 Characteristics of 94 patients with bacteremia CharacteristicsNo. of patients (%)Age group (months)1–1267 (71.3)13–2410 (10.6)25–368 (8.5)> 369 (9.6)SexMales57 (60.6)Females37 (39.4)Primary infectionGastroenteritis38 (40.4)Pneumonia or19 (20.2)bronchopneumoniaMeningitis7 (7.4)Sepsis7 (7.4)Urinary tract infections7 (7.4)Septic arthritis2 (2.1)Undetermined14 (14.9)  Focal sites and causative species Clinically, 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 identified 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 thecases 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 immunodefi-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 influenzae (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), and Shigella 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 18–36 months.Ten per cent of the bacteremia in the hospitalizedcases were suspected to be nosocomial in srcin andone case was polymicrobial. Risk factors identifiedwere: age of 1 year or less (95 per cent CI = 1.16–2.55,  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 fluids 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 testing Non-susceptibility of the isolates was observed for atleast 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 tests Additional 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. Discussion Bacterial infections are major causes of morbidityand mortality in children. The detection, identifi-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 confirmed in 94 (44.8per cent) patients out of 210 children with variousdiseases. The most common primary infection wasidentified in 80 (85.1 per cent): gastroenteritis (40.4per cent) and pneumonia (20.4 per cent). Thecausative species were also identified in 90 (95.7 percent) of the cases in blood and stool cultures.The most common pathogens were Streptococcus spp. (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 3–36months. 8 Pneumonia counted for 7 per cent of thesechildren 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 L. F. NIMRI ET AL . 358Journal of Tropical PediatricsVol. 47 December 2001  isolates obtained from clinically defined 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. 17 The frequent finding of CoNS and S. pneumoniae were also reported by a study that used moleculardiagnosis 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 flora, and their presence in bloodcultures might indicate catheter and medical device-related sepsis or a contaminant of blood cultures. 9 The 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 beapplied 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 pneumoniae accounted 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 identified 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 Shigella spp. 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 overallmortality rate of 27 per cent that varies with thespecies of Candida . 23 Enterococcus taylorae was isolated from bloodcultures 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 influenzae was isolated from six (6.4per cent) blood cultures mostly from children <5years old. A study on the epidemiology of systemic Haemophilus influenzae disease in Korean childrenreported infections in 92 per cent of children <5 yearsold. 11 Pseudomonas aeruginosa was isolated from oneblood culture of a 12-month-old male in our study. Itwas reported with the predominant pathogens in astudy of cases of children undergoing transplant-ation. 20 Polymicrobial bacteremia was reported in a 6-month-old male diagnosed with sepsis; the speciesisolated from the blood culture were Pasteurella pneumotropica and Enterococcus taylorae . He wasdischarged with no complications after a parenteralantibiotics treatment, a combination of claforan andampicillin.There was no attempt to isolate anaerobic bacteriain this study although it might have been the cause of bacteremia in some of the cases where no aerobicbacteria were detected in blood cultures. Anaerobicbacteria were reported to constitute 18 per cent of the total number of isolates from blood. 2 Of particu-lar concern is the increased number of non-susceptible isolates to more than one antimicrobialagent commonly used for treatment. Multiple drugnon-susceptibility was observed in 62 per cent of theisolates especially in species isolated from patientswho had a long duration of stay (> 10 days).Multiple-drug resistance of isolates frombacteremic children is also reported by others. 18,19 This is of particular concern to clinicians since theyhave to treat patients with invasive disease morecautiously.The use of parenteral antibiotics at the initial visitresulted in improved conditions at follow-up thanthose cases who were treated with oral antibiotics.This was reported in cases of pneumococcal infec-tions. 4 Early treatment also prevented compli-cations, such as rheumatic fever, that might resultfrom infections with group A  -hemolytic strepto-cocci. 16 Empirical treatment with antibiotics forfebrile infants until the blood culture results wereavailable was used and was recommended in anotherstudy. 12 This kind of treatment for febrile infants whodo not appear toxic, may promote further develop-ment of drug-resistant bacteria and is not recom-mended for those children who look well and arewithout any obvious focus of infection. References 1.Anthony RM, Brown TJ, French GL. Rapid diagnosis of bacteremia by universal amplification of 23S ribosomal DNAfollowed by hybridization to an oligonucleotide array: J ClinMicrobiol 2000; 38: 781–88.2.Anuradha DE, Saraswath K, Gogate A. Anaerobic bacteremia:a review of 17 cases. J Postgrad Med 1998; 44: 63–66.3.Ben Sales C, Cruz Robania JC, Monte Boada RJ, Bravo FarinasL. Septicemia due to Shigella . A case report and review of theliterature. Rev Cuban Med Trop 1995; 117: 131–34. L. F. NIMRI ET AL . Journal of Tropical PediatricsVol. 47 December 2001359

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