Bacteremia in Children: Etiologic Agents, Focal Sites, and Risk Factors

Transcription

1 Bacteremia in Children: Etiologic Agents, Focal Sites, and Risk Factors by L. F. Nimri, a M. Rawashdeh, b and M. M. Meqdam a a Department of Applied Biology, and b Department of Pediatrics, Jordan University of Science and Technology, Irbid, Jordan Summary A prospective study was carried out on 210 cases of children under 10 years of age with fever. Cases of gastroenteritis, respiratory tract infections, and suspected sepsis in children seen or admitted to the pediatric hospital were studied. Clinical and microbiological data were recorded in a questionnaire 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), pneumonia or bronchopneumonia (20 per cent), meningitis (7.4 per cent), and urinary tract infections (7.4 per cent). The predominant pathogens isolated from blood or stool specimens were Gram-positive bacteria (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 pneumoniae, Haemophilus influenzae, Neisseria meningitidis, and Yersinia spp. One case of Candida albicans (1.1 per cent) was reported. Pasteurella pneumotropica was reported in two cases for the first time. The mortality rate was 4 per cent, mostly from septicemia cases. Long duration of hospitalization (> 10 days) and parenteral feeding were identified as risk factors. Resistance of the isolated pathogens to several commonly used antibiotics was observed. Empirical treatment with antibiotics is recommended only in life-threatening cases. Acknowledgements This study was supported by a grant (no. 25/97) from the Deanship of 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 ; Fax <nimri@just.edu.jo>. Introduction Bacteremia has been increasingly reported in children under 5 years of age. There are no reliable data on the incidence or prevalence of invasive bacterial infections involving children in Jordan. Bacteremia in certain infections is considered the best practical way to identify the causative organism. The isolation of bacteria from blood cultures is usually indicative of a serious invasive infection that requires immediate antibiotic treatments. 1 Septicemia is a pathological condition with a high mortality rate that varies between 30 and 70 per cent and depends on several factors including virulence of the pathogen and host factors. 21,22 The majority of the bacteremia cases 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 is crucial for proper antimicrobial treatment. Different organisms have different antimicrobial susceptibilities and successful treatment is dependent on the prompt administration of the correct drug. 10,15 This may improve the prognosis of the patients with septicemia. The delay, however, may mean unnecessary treatment or the use of ineffective therapy given to antibiotic resistant organisms. There is a wide variation in the incidence and clinical characteristics of invasive infections caused by different species of bacteria. Identifying the causative species and characterizing the clinical significance in a particular age group in a community is essential for the prevention and treatment of these infections. We carried out a prospective study in children under 10 years old who had a temperature of 39ºC, regardless of the presumed clinical source of fever, to identify the most frequently encountered causative agents, their susceptibilities to the commonly used antibiotics, and factors contributing to these infections in this age group. Methods Subjects A total of 210 children under 10 years old presenting to a pediatrician with a temperature of 39ºC during the 2-year period between 1998 and 1999 were eligible for this study. These included cases of gastroenteritis, respiratory tract infection, meningitis, 356 Journal of Tropical Pediatrics Vol. 47 December 2001 Oxford University Press 2001

2 urinary tract infections (UTI), or suspected sepsis that were admitted to Prince Rahma Hospital in Irbid, Jordan. It is the largest community pediatric hospital affiliated with Jordan University of Science and Technology that receives patients from the northern region in the country. Clinical, microbiological data and other information such as temperature, immunodeficiencies, and antibiotic therapy were recorded from the patient s medical record. A questionnaire concerning demographic data, age, sex, chief complaint, duration of symptoms, and hospital stay was completed for each patient. Microbiology A blood specimen was collected from each patient and inoculated in a biphasic blood culture bottle (BioMerieux, France). Bottles were incubated at 37ºC and continuously monitored for evidence of bacterial growth. An aliquot of the positive blood culture was aseptically taken by a syringe for Gram stain and subcultured on enriched and selective media for a wide variety of pathogens. Stool samples were also collected from the same patients and cultured on selective media. The organisms grown on agar plates from both blood and stool specimens were identified by standard laboratory methods including biotyping and API 20E (BioMerieux, France). Susceptibility tests The antibiotic sensitivity of the isolates was tested for 11 antibiotics on Muller Hinton agar using disc diffusion assay. 14 Susceptibility testing to at least six out of 10 antibiotics was performed on each isolate. Antibiotics tested were amoxicillin, ampicillin, augmentin, doxicillin, gentamicin, novecin, tetracycline, tobramycin, rifampicin, erythromycin and vancomycin (for the Gram-positive isolates). Nonsusceptible refers to resistant and intermediately resistant. Data analysis Univariate analyses were performed using Epi-Info version 6.0 (Centers for Disease Control and Prevention, Atlanta, USA). Means and proportions were compared 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 the 210 patients (44.8 per cent). The mean age of the patients was 16.6 months ± 14.8 (range: months), 61.3 per cent of these patients were males (Table 1). Results of stool cultures and the isolated species are shown in Table 2. TABLE 1 Characteristics of 94 patients with bacteremia Characteristics No. of patients (%) Age group (months) (71.3) (10.6) (8.5) > 36 9 (9.6) Sex Males 57 (60.6) Females 37 (39.4) Primary infection Gastroenteritis 38 (40.4) Pneumonia or 19 (20.2) bronchopneumonia Meningitis 7 (7.4) Sepsis 7 (7.4) Urinary tract infections 7 (7.4) Septic arthritis 2 (2.1) Undetermined 14 (14.9) TABLE 2 Bacterial 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 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) Unidentified 4 (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) Journal of Tropical Pediatrics Vol. 47 December

3 Focal sites and causative species Clinically, focal source of bacteremia was determined in 80 out of the 94 positive cases (85.1 per cent) (Table 2). A focal site of infection could not be identified in 14 (14.9 per cent) of the patients. Most of the bacteremia cases (71.3 per cent) were documented in patients less than 1 year old, of whom 51.1 per cent were less than 6 months old. Only 9.5 per cent of the cases were documented in children aged between 3 and 10 years. From the diagnosis made by the pediatrician, the focal infections of bacteremia in these patients were gastroenteritis (40.4 per cent), pneumonia or bronchopneumonia (20 per cent), meningitis (7.4 per cent), sepsis (7.4 per cent), UTI (7.4 per cent), and septic arthritis (2.1 per cent). None of the patients were documented to have immunodeficiency. Gram-positive bacteria were predominant (53.3 per cent), while Gram-negative accounted for 45.6 per cent, and Candida albicans accounted for 1.1 per cent. The most common cause of bacteremia in these patients was coagulase negative Staphylococcus spp. (CoNS) (20.1 per cent), mainly Staphylococcus epidermidis, Streptococcus spp. (22.3 per cent), mainly group A beta-hemolytic streptococci, Neisseria 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 per cent), Pasteurella pneumotropica (2.1 per cent), and Shigella sonnei (1.1 per cent). (Table 2). The majority of CoNS spp. (70 per cent) were isolated from children less than 18 months old; 30 per cent were isolated from the age group months. Ten per cent of the bacteremia in the hospitalized cases were suspected to be nosocomial in origin and one case was polymicrobial. Risk factors identified were: age of 1 year or less (95 per cent CI = , 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 the primary site of infection were vomiting (90.9 per cent), diarrhea in 85.5 per cent of the gastroenteritis cases, cough (95 per cent) in respiratory tract infections, and febrile convulsions were reported in eight patients (8.5 per cent). Mortality rate The overall mortality rate in these cases was 4 per cent 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 these cases, i.e. 92 (97.8 per cent) on the date of the initial blood culture. Of these treated patients, 35 (38 per cent) received parenteral antibiotics either as single or as combination antibiotics. The combination of claforan/ampicillin was the most prescribed. Electrolytes and intravenous fluids were given to cases with diarrhea and dehydration. Patients suspected of having meningitis or sepsis received empiric parenteral antibiotics and were reported to have improved conditions at follow-up. Susceptibility testing Non-susceptibility of the isolates was observed for at least two of the antibiotics tested. The highest was recorded for ampicillin (72.2 per cent), augmentin (50 per cent), amoxicillin (46.2 per cent), and erythromycin (45.4 per cent of the Gram-positive isolates). Other laboratory tests Additional laboratory tests were performed on all patients, such as the white blood cell counts which were cells/mm 3. Other tests were performed depending on the primary diagnosis of the pediatrician. These tests included serological tests (e.g. latex test for Brucella and Widal test for Salmonella), tests and cultures of CSF obtained from eight patients suspected to have meningitis, detection of parasites in stool for patients with gastroenteritis, and urine analysis and cultures in the case of patients with suspected UTI. Discussion Bacterial infections are major causes of morbidity and mortality in children. The detection, identification, and susceptibility testing of a causative species of bacteremia is essential for the proper treatment, and better prognosis of the patient. In this study, bacteremia was confirmed in 94 (44.8 per cent) patients out of 210 children with various diseases. The most common primary infection was identified in 80 (85.1 per cent): gastroenteritis (40.4 per cent) and pneumonia (20.4 per cent). The causative species were also identified in 90 (95.7 per cent) of the cases in blood and stool cultures. The most common pathogens were Streptococcus spp. (22.3 per cent) especially S. pneumoniae mainly isolated from cases with pneumonia. Streptococcus pneumoniae was also reported as the most common pathogen in children with bacteremia aged 3 36 months. 8 Pneumonia counted for 7 per cent of these children while other respiratory tract infections counted for 24 per cent, gastroenteritis (9 per cent), and UTI (5 per cent). In another study, the source of bacteremia cases of pneumococcal infections, were pneumonia (37 per cent), otitis media (30 per cent), meningitis (11.5 per cent), and no focal source (33 per cent). 19 Group A streptococci (e.g. S. pyogenes) although an uncommon cause of meningitis, was reported in few cases as a result of bacteremia or surgery. 13 Coagulase negative staphylococci (CoNS) accounted for 20.1 per cent of the blood culture 358 Journal of Tropical Pediatrics Vol. 47 December 2001

4 isolates obtained from clinically defined infections. The highest incidence of sepsis caused by Staphylococcus epidermidis was observed in children less than 12 months old. Our results are in agreement with other studies that reported CoNS as the most common bacteria isolated from infants with sepsis. 17 The frequent finding of CoNS and S. pneumoniae were also reported by a study that used molecular diagnosis by PCR. 1 Staphylococcus epidermidis and other CoNS was reported to have emerged as a major cause of nosocomial infections. 6 They are part of the normal skin and mucosal micro flora, and their presence in blood cultures might indicate catheter and medical devicerelated sepsis or a contaminant of blood cultures. 9 The interpretation of their presence is a major concern for clinicians and clinical microbiology laboratories. The decision for therapy relies mostly on the observation of sepsis symptoms and the number of positive blood cultures. However, the criteria of multiple blood cultures could not be applied in pediatric patients who cannot undergo multiple venous puncture. Escherichia coli was isolated from 9.6 per cent of the cases; it was reported to be the most frequent Gram-negative bacterial species 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 reported as the leading etiologic agent (38 per cent). 7 Yersinia enterocolitica (two cases) and Yersinia pseudotuberculosis (two cases) were isolated from blood and stool cultures of gastroenteritis cases; these isolates were non-susceptible to ampicillin. Pasteurella pneumotropica was isolated from blood cultures of two patients and were identified by the API system but, the source of infection, which is usually from animals, was not established. Shigella sonnei was isolated from blood and stool cultures of a 10-month-old child who had severe diarrhea. Isolation of Shigella spp. from blood is considered as an unusual medical event and is not frequently reported. 3 Candida albicans was isolated from the blood culture of a 10-month-old male. This was a fatal case because antifungal treatment was not given. The Canadian Infectious Disease Society reported 11.6 per cent infection rate in children and an overall mortality rate of 27 per cent that varies with the species of Candida. 23 Enterococcus taylorae was isolated from blood cultures of three children (3.2 per cent) who had been hospitalized for 10 days. Intravascular device was used during their stay, which might be a risk factor for a nosocomial infection with these species. They were reported as a nosocomial infection due to use of intravascular device in 44 per cent of the bacteremia cases in 66 per cent of children 1 year old or less. 5 Haemophilus influenzae was isolated from six (6.4 per cent) blood cultures mostly from children <5 years old. A study on the epidemiology of systemic Haemophilus influenzae disease in Korean children reported infections in 92 per cent of children <5 years old. 11 Pseudomonas aeruginosa was isolated from one blood culture of a 12-month-old male in our study. It was reported with the predominant pathogens in a study of cases of children undergoing transplantation. 20 Polymicrobial bacteremia was reported in a 6- month-old male diagnosed with sepsis; the species isolated from the blood culture were Pasteurella pneumotropica and Enterococcus taylorae. He was discharged with no complications after a parenteral antibiotics treatment, a combination of claforan and ampicillin. There was no attempt to isolate anaerobic bacteria in this study although it might have been the cause of bacteremia in some of the cases where no aerobic bacteria were detected in blood cultures. Anaerobic bacteria were reported to constitute 18 per cent of the total number of isolates from blood. 2 Of particular concern is the increased number of nonsusceptible isolates to more than one antimicrobial agent commonly used for treatment. Multiple drug non-susceptibility was observed in 62 per cent of the isolates especially in species isolated from patients who had a long duration of stay (> 10 days). Multiple-drug resistance of isolates from bacteremic children is also reported by others. 18,19 This is of particular concern to clinicians since they have to treat patients with invasive disease more cautiously. The use of parenteral antibiotics at the initial visit resulted in improved conditions at follow-up than those cases who were treated with oral antibiotics. This was reported in cases of pneumococcal infections. 4 Early treatment also prevented complications, such as rheumatic fever, that might result from infections with group A -hemolytic streptococci. 16 Empirical treatment with antibiotics for febrile infants until the blood culture results were available was used and was recommended in another study. 12 This kind of treatment for febrile infants who do not appear toxic, may promote further development of drug-resistant bacteria and is not recommended for those children who look well and are without any obvious focus of infection. References 1. Anthony RM, Brown TJ, French GL. Rapid diagnosis of bacteremia by universal amplification of 23S ribosomal DNA followed by hybridization to an oligonucleotide array: J Clin Microbiol 2000; 38: Anuradha DE, Saraswath K, Gogate A. Anaerobic bacteremia: a review of 17 cases. J Postgrad Med 1998; 44: Ben Sales C, Cruz Robania JC, Monte Boada RJ, Bravo Farinas L. Septicemia due to Shigella. 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