Pneumococcal Bacteremia In Children Research Articles

Evaluation of the Clinical Utility of a Real-time PCR Assay for the Diagnosis of Streptococcus pneumoniae Bacteremia in Children: A Retrospective Diagnostic Accuracy Study.

The widespread uptake of pneumococcal vaccines has substantially reduced the incidence of invasive pneumococcal disease, such that pneumococcal bacteremia in children is now considered a relatively rare event. The objective of this study was to ascertain the clinical utility of a Streptococcus pneumoniae real-time polymerase chain reaction (PCR) assay compared with standard blood culture for the diagnosis of pneumococcal bacteremia in children in the post-vaccine era. A systematic retrospective review of laboratory and patient records from Children's University Hospital, Temple Street, during a 6-year period was performed. Paired blood PCR and blood culture specimens from children younger than 16 years of age were investigated. Statistical analysis was performed to measure the diagnostic accuracy of PCR versus routine bacterial culture techniques. More than 1900 PCR test requests were examined from 2010 to 2015, of which 1561 paired PCR and blood culture specimens met criteria for inclusion in the statistical analysis. The PCR assay demonstrated high specificity (99%, confidence interval 95%: 98.81%-99.69%); however, the sensitivity was low compared with that of blood culture (47%, confidence interval 95%: 21.27%-73.41%). Investigation of 10 PCR-positive/culture-negative cases revealed that these cases ranged from definite, probable, and possible significance, indicating a low false positivity rate associated with the assay. This study demonstrates the limited utility of blood PCR testing for S. pneumoniae in pediatric patients without radiographic evidence pneumonia or empyema. Moreover, we report that PCR may be a useful diagnostic tool when blood cultures are negative because of antimicrobial therapy before sampling. Given that the incidence of pneumococcal disease has decreased considerably in recent years, justification of S. pneumoniae PCR requisition is necessary. Hence, new guidelines for pediatric pneumococcal blood PCR testing have been introduced at the Irish Meningitis and Sepsis Reference Laboratory.

Emergency Department Epidemiology of Pneumococcal Bacteremia in Children Since the Institution of Widespread PCV7 Vaccination

BackgroundThe heptavalent pneumococcal conjugate vaccine (PCV7) has produced a shift in the epidemiology of invasive infections from Streptoccoccus pneumoniae. ObjectiveOur aim was to determine the temporal changes in pneumococcal bacteremia (Streptococcus pneumoniae bacteremia [SPB]) in the emergency department (ED) since the introduction of PCV7. MethodsThis was a retrospective cohort study of children 0−18 years with SPB evaluated from 1998−2009 in a tertiary-care pediatric ED. The primary outcome was annual proportion of children with SPB from PCV7 serotypes (ie, 4, 6B, 9V, 14, 18C, 19F, and 23F) and nonvaccine serotypes (NVT). Rates of SPB (per 10,000 ED visits) were calculated. SPB was analyzed by time period: before October 2000 was considered “pre-PCV7,” November 2000 to October 2003 was considered “peri-PCV7,” and after November 2003 was “post-PCV7.” Febrile young children (FYC) were defined as children age <36 months and fever without source. ResultsA total of 201 episodes of SPB occurred during the study, with a median age of 20.3 months (interquartile range 10.7−49.5 months; range 1.6−215.4 months); 56.7% were male and 69.7% were African American. SPB from PCV7 serotypes decreased more than fourfold, from 82.2% pre-PCV7 to 19.5% peri- and post-PCV7. Most SPB was from NVT serotype 19A (31.3%) peri- and post-PCV7. Annual rates of SPB were 4.01/10,000 ED visits pre-PCV7, decreasing to 2.10 peri-PCV7, and 1.75 post-PCV7. Among the 56 (27.8%) FYC with SPB, NVT were responsible for 11.5% of SPB pre-PCV7, and increased to 80.0% peri- and post-PCV7 (p < 0.001). ConclusionsRates of SPB have decreased since the introduction of PCV7, yet SPB still occurs among children in the ED. NVT are increasing in prevalence, and SPB from PCV7-serotypes have decreased.

Prevalence of Pneumococcal Bacteremia in Children with Sickle Cell Disease

We performed a retrospective chart review of children with sickle cell disease hospitalized for fever at our local institution. We reviewed 456 hospitalizations in 133 patients between January 2006 and June 2012. The prevalence of true bacteremia was 4%. The mean C-reactive protein values and temperatures were nonsignificantly higher in patients with positive blood cultures. The mean time to detection was 22.5 hours in bacteremia compared to 32.6 hours in blood cultures that grew contaminants (p = .034). Only two (0.4%) cases of pneumococcal bacteremia were reported and both occurred before May 2010, which marks the introduction of 13-valent pneumococcal vaccine (PCV13). Both patients with pneumococcal bacteremia had discontinued penicillin prophylaxis after the age of 5 years. The first patient was immunized but contracted a nonvaccine serotype (23B). The second patient was partially vaccinated and acquired a vaccine-preventable serotype (23F). Both serotypes were sensitive to ceftriaxone and vancomycin; one was resistant to penicillin. This is the first study reporting the prevalence of pneumococcal bacteremia since the introduction of PCV13.

Prevalence of Pneumococcal Bacteremia in Children with Sickle Cell Disease Hospitalized for Management of a Febrile Illness

AbstractAbstract ▪3214▪This icon denotes a clinically relevant abstract Introduction:Children with sickle cell disease are at a high risk of death from pneumococcal bacteremia due to functional asplenia. The common practice for management of any fever in a child with sickle cell disease is in-patient antibiotic therapy for presumed bacteremia, until the blood cultures have remained negative for 48 hours. We hypothesize that interventions such as penicillin prophylaxis, use of polyvalent pneumococcal vaccine at 2 years of age in addition to the primary immunization series with pneumococcal conjugate vaccine 13 have decreased the prevalence of pneumococcal bacteremia in children with sickle cell disease. Outpatient management of an uncomplicated febrile illness may be a safe alternative. Methods:We conducted a retrospective chart review of children with sickle cell disease hospitalized with a fever at Children's and Women's Hospital between January 2006 and June 2012. We collected demographical parameters, temperature, white blood cell count and C-reactive protein level at the time of presentation as possible predictors of true bacteremia. The continuous variables were compared between the two groups (positive and negative blood cultures) using independent t-test. We also recorded the time to positivity of blood cultures, pathogens identified in positive blood cultures, serotypes and sensitivities of pneumococcal bacteria. Results:A total of 133 patients, aged 2 months to 18 years, met the inclusion criteria with 456 hospital admissions. The prevalence of culture proven bacteremia was 3.7% with only two (0.44%) cases of pneumococcal bacteremia. We have not had any patient with pneumococcal bacteremia reported since the start of pneumococcal conjugate vaccine 13, in May 2010. Both the patients with pneumococcal bacteremia were older than five years and had discontinued taking penicillin prophylaxis. The first patient was fully vaccinated with pneumococcal conjugate vaccine 7 but had not received polyvalent vaccine. She contracted a non-vaccine serotype (23B) that was susceptible to penicillin, ceftriaxone, and vancomycin. The second patient was partially vaccinated and acquired a serotype (23F) that is included in pneumococcal conjugate vaccine 7. The bacterium was resistant to penicillin but sensitive to ceftriaxone and vancomycin. In the analysis of predictors of bacteremia, the average C-reactive protein level was found to be 6.3mg/dL in patients with positive blood cultures and 4.5mg/dL in patients with negative blood cultures (p=0.02). The mean age of patients with positive blood cultures was 11 years compared to 7.4 years in patients with negative blood cultures (p=0.03). The differences in body temperature and white blood cell count between the two groups were not statistically significant. The average time to positivity measured from the time of collection was 25.4 hours. Discussion:Penicillin prophylaxis and complete immunization, in accordance with the centers for disease control and prevention guidelines are important for patients with sickle cell disease. Patients with an uncomplicated febrile illness may not necessarily need to be hospitalized to continue antibiotics. We support an outpatient care model proposed by Williams et al, comprising of a single 24-hour dose of ceftriaxone followed by oral cefixime for 5 days and follow-up telephone calls by a nurse. Good patient education may help ensure compliance with outpatient care. Outpatient management of an uncomplicated febrile illness will be more cost-effective and beneficial to the patients and families. With this approach, however, patients may not be fully protected against ceftriaxone resistant pneumococccal infections. Bacterial resistance patterns in the community should be brought under consideration when implementing such a model. Conclusion:The prevalence of pneumococcal bacteremia in children with sickle cell disease has decreased in the past few years. In our analyses, we found older age and an elevated C-reactive protein level to be statistically significant predictors of a positive blood culture. Disclosures:No relevant conflicts of interest to declare.

Blood culture sampling rates at a German pediatric university hospital and incidence of invasive pneumococcal disease.

Recent pediatric surveillance studies suggest the incidence of pneumococcal bacteremia, but not meningitis, is lower in Germany than in most developed countries. Suboptimal case assessment in routine clinical practice has been suspected of contributing to this apparent discrepancy. We aimed to assess the blood culture sampling rate at a German pediatric university hospital and the disease burden associated with pneumococcal bacteremia in children under 5 years of age. The study design was retrospective, based on data-linkage and chart review. Blood cultures were frequently obtained in sepsis (96%; CI 78-99%) and meningitis (95%; CI 77-99%), but less commonly in pneumonia (49%; CI 43-54%) and fever without focus (48%; CI 38-59%). Pneumococci were the most common source of clinically significant bacteremia in previously healthy children. These blood culture sampling rates may be insufficient for the sensitive detection of pneumococcal bacteremia. Epidemiological surveillance based on poorly standardized diagnostic practices is prone to under-assessment.

Increased incidence of pneumococcal bloodstream infections

Pneumococcal bloodstream infections in pediatric patients rose from 3.6 to 14.8 episodes per 100,000 from 1986 to the year 2000 (P < 0.001) in a population of approximately 650,000 inhabitants (16% <16 years of age). Incidence in the group <24 months of age increased from 7.4 to 78.6 episodes per 100,000 per year (P < 0.001). Overall 75% of the serogroups are included in the new heptavalent vaccine.

Rapid antigen assay for the diagnosis of pneumococcal bacteremia in children: A preliminary study

Study objective: We determine the sensitivity of a new Streptococcus pneumoniae antigen assay in children with S pneumoniae bacteremia and also determine the specificity of the assay in afebrile children without apparent pneumococcal infection. Methods: We enrolled 2 groups of children, 3 months to 5 years of age, presenting to an urban pediatric emergency department or hospital-based clinic between January 1, 2000, and January 1, 2001. The study group included patients with S pneumoniae bacteremia. The control group included patients without fever or identified focal bacterial infection (other than a urinary tract infection). We excluded from the control group patients with a recent diagnosis (prior 4 weeks) of bacteremia, pneumonia, meningitis, acute otitis media, or other suspected S pneumoniae infection. Results: Ninety-six patients were enrolled: 24 children with S pneumoniae bacteremia and 72 afebrile control patients. The assay produced a positive result in 23 of 24 patients with pneumococcal bacteremia, yielding a sensitivity of 95.8% (95% confidence interval [CI] 78.9% to 99.9%). The test result was negative in 67 of 72 afebrile patients without apparent pneumococcal infection, yielding a specificity in this population of 93.0% (95% CI 83.4% to 97.5%). Conclusion: This S pneumoniae assay demonstrated high sensitivity for the defined bacteremic population, as well as high specificity among afebrile children without apparent pneumococcal infection. Further study in febrile children at risk of pneumococcal bacteremia is needed before the value of the test in children at risk for invasive pneumococcal disease can be determined. [Ann Emerg Med. 2002;40:399-404.]

Rapid antigen assay for the diagnosis of pneumococcal bacteremia in children: A preliminary study

Study objective: We determine the sensitivity of a new Streptococcus pneumoniae antigen assay in children with S pneumoniae bacteremia and also determine the specificity of the assay in afebrile children without apparent pneumococcal infection. Methods: We enrolled 2 groups of children, 3 months to 5 years of age, presenting to an urban pediatric emergency department or hospital-based clinic between January 1, 2000, and January 1, 2001. The study group included patients with S pneumoniae bacteremia. The control group included patients without fever or identified focal bacterial infection (other than a urinary tract infection). We excluded from the control group patients with a recent diagnosis (prior 4 weeks) of bacteremia, pneumonia, meningitis, acute otitis media, or other suspected S pneumoniae infection. Results: Ninety-six patients were enrolled: 24 children with S pneumoniae bacteremia and 72 afebrile control patients. The assay produced a positive result in 23 of 24 patients with pneumococcal bacteremia, yielding a sensitivity of 95.8% (95% confidence interval [CI] 78.9% to 99.9%). The test result was negative in 67 of 72 afebrile patients without apparent pneumococcal infection, yielding a specificity in this population of 93.0% (95% CI 83.4% to 97.5%). Conclusion: This S pneumoniae assay demonstrated high sensitivity for the defined bacteremic population, as well as high specificity among afebrile children without apparent pneumococcal infection. Further study in febrile children at risk of pneumococcal bacteremia is needed before the value of the test in children at risk for invasive pneumococcal disease can be determined. [Ann Emerg Med. 2002;40:399-404.]

Pneumococcal bacteremia during a decade in children in Soweto, South Africa.

To monitor for a decade the incidence and the clinical and microbiologic characteristics of pneumococcal bacteremia in children in Soweto and to assess the influence of HIV infection on any changes. Case records of children with pneumococcal bacteremia at Chris Hani Baragwanath Hospital from July, 1986, to June, 1987 (1986/ 1987), and from July, 1996, to June, 1997 (1996/ 1997), were retrospectively reviewed. There were 194 episodes, 62 in 19861 1987 and 132 in 1996/1997. The minimum annual incidence for children younger than 5 years of age increased from 61 per 100000 (179 per 100000 for those <12 months old) in 1986/1987 to 130 per 100000 (349 per 100000 for those <12 months old) in 1996/1997. Sixty-seven (60%) of 111 patients tested in 1996/1997 were HIV-seropositive; none were tested in 1986/1987. The HIV-infected compared with HIV-noninfected were more likely to be malnourished (61% vs. 36%, P = 0.02), less likely to have other underlying disease (12% vs. 50%, P = 0.00001) and more frequently used antibiotics recently (69% vs. 43%, P = 0.008). Penicillin-nonsusceptible isolates were found in 22 (35%) patients in 1986/1987 and 52 (39%) in 1996/1997. There was no significant change in antimicrobial susceptibility during the decade or by HIV serostatus. Children in Soweto had a high incidence of pneumococcal bacteremia which doubled during the decade mainly as a result of the impact of the HIV epidemic. There has been no significant change in antimicrobial susceptibility for the decade.

Streptococcus pneumoniae bacteremia in children infected with HIV: presentation, course, and outcome.

To examine the presentation, course, and outcome of pneumococcal bacteremia in children infected with human immunodeficiency virus (HIV). A retrospective series of HIV-infected children less than 18 years of age with Streptococcus pneumoniae bacteremia from four urban, tertiary care hospitals was evaluated. The main outcome measures included persistent bacteremia, the development of a focal infection, and death. Seventy-two episodes of pneumococcal bacteremia were identified in 59 patients. Fifty-four first episodes were included; 26/54 were occult. Mean temperature was 39.8 degrees C. In patients with bacteremia, white blood cells (WBCs) > or = 15,000 and > or = 10,000 had sensitivities of 40% and 75%, respectively. At the time of bacteremia, age >3 years old was associated with a lower mean WBC count compared with episodes occurring in patients <3 years old (11.2 vs 16.1, P < 0.05). Patients with occult bacteremia who were discharged with antibiotics (12 i.m., 7 p.o.) were less likely than patients without antibiotic treatment to have persistent bacteremia at a return visit within 72 hours (0/19 vs 2/5, P < 0.05). No patient with occult bacteremia died, progressed to clinical meningitis, or had other sequelae. Two of fifty-four patients died as a result of their first episode of invasive pneumococcal disease. Both patients who died had meningitis and appeared ill on initial presentation. Neither a WBC count > or = 15,000 nor > or = 10,000 is a sensitive indicator of pneumococcal bacteremia in HIV-infected children. Empiric antibiotics are useful to decrease the risk of persistent bacteremia. Children infected with HIV who have occult pneumococcal bacteremia appear to do well with appropriate antibiotics. Patients who are afebrile and well appearing on reevaluation may be safely treated as outpatients.

Occult pneumococcal bacteremia

There is little information on the outcome of occult pneumococcal bacteremia in children who appear well at the time of first reevaluation. To determine the outcome of such children we reviewed the medical records of 364 children with blood cultures positive for Streptococcus pneumoniae managed at 2 hospitals in New Haven from 1973 to 1987. One hundred eighty of the 364 children were initially managed as outpatients; 111 of the 180 (62%) were afebrile and appeared well at the first reevaluation. Twenty-two of these 111 children (20%) were hospitalized and treated with intravenously administered antimicrobials at the first reevaluation visit; 2 of these 22 were still bacteremic, although no focal infection was found. Seventy-eight children (70%) were sent home after the first reevaluation visit with orally administered antimicrobials; 1 of these 78 children was still bacteremic and another subsequently was found to have meningitis that had been present at the first visit (culture of the cerebrospinal fluid obtained at the first visit subsequently grew S. pneumoniae). Eleven children (10%) were sent home from the reevaluation visit without antimicrobial treatment and none had persistent or recurrent pneumococcal infection. We conclude that the child who is afebrile and appears well at reevaluation for a blood culture positive for S. pneumoniae is unlikely to develop serious sequelae. Outpatient management with careful follow-up is essential for such children.

Bacteremia in sickle hemoglobinopathies

We analyzed 178 episodes of bacteremia that occurred during 13,771 patient-years of follow-up of 3451 patients with sickle hemoglobinopathies. Age-specific incidence rates of bacteremia were calculated for patients with sickle cell anemia (SS) and sickle cell-hemoglobin C (SC) disease. The incidence rate was highest among children with SS and SC younger than age 2 years. Children with SC showed an abrupt decrease after age 2 years, whereas children with SS had a gradual decline in rate from 2 to 6 years of age. The predominant pathogen in patients younger than 6 years was Streptococcus pneumoniae (66%); gram-negative organisms were responsible for 50% of bacteremias in patients 6 years and older. Urinary tract infection was present during 73% of Escherichia coli bacteremias, and 77% of Salmonella bacteremias were associated with osteomyelitis. In contrast, no focus of infection was present in 52% of pneumococcal bacteremias. The incidence of pneumococcal bacteremia in children with SS younger than age 3 years was 6.1 events/100 patient-years; the case fatality rate for pneumococcal sepsis in this age group was 24%. No hematologic or demographic variables were associated with occurrence of pneumococcal bacteremia in young children. Retrospective analysis of pneumococcal bacteremia suggests that the prophylactic use of penicillin may decrease the incidence in children younger than 3 years of age.

Antibiotic-resistant pneumococcal disease in children at Baragwanath Hospital, Johannesburg.

Seventeen of 60 cases of pneumococcal bacteremia in children at Baragwanath Hospital in 1983 were caused by strains not fully susceptible to penicillin G. Eight strains had minimal inhibitory concentrations of greater than 1 microgram/ml and five were resistant to four or more antimicrobial agents. Only three isolates were resistant to chloramphenicol. Antibiotic-resistant strains occurred in younger children with a mean age of 13.1 months compared with a mean age of 31.6 months in children with susceptible strains (P less than 0.01). Underlying conditions, including nutritional status, did not correlate with antibiotic resistance of isolates from blood. Some of the resistant strains were apparently community-acquired. Of 3379 nasopharyngeal swabs taken from hospitalized children 829 yielded pneumococci and 408 of these carrier strains were either relatively or fully resistant to penicillin while 241 were resistant to four or more antibiotics. Multiply resistant strains from patients and carriers belonged to serovars 6A, 6B and 19A.

Complications of occult pneumococcal bacteremia in children

Children with occult pneumococcal bacteremia have not been considered to be at significant risk of developing complications. However, three of seven children, without an apparent source of pneumococcal bactermia, developed meningitis after a period of well-being, and two others developed an identifiable respiratory focus of infection. Meningitis occurred in spite of oral or low-dose intravenous penicillin therapy. We conclude that the identification of occult pneumococcal bacteremia places the child at significant risk to develop serious sequelae and that initiation of high-dose parenteral penicillin therapy, as in the treatment of pneumococcal meningitis, is indicated.

PNEUMOCOCCAL INFECTIONS IN SICKLE CELL ANEMIA-Reply

To the Editor .—In response to Dr. Austrian's comments, I admit to being by nature a pessimist but not a defeatist. Studies are already in progress along the lines that he suggests. Our series now consists of 17 episodes of pneumococcal bacteremia in children with sickle cell anemia. The serotypes are as follows: type 1, one; type 3, one; type 4, one; type 6, five; type 12, one; type 14, four; type 18, one; type 23, two; and type 24, one. Thus, it appears that certain serotypes are definitely appearing to be more common. We are examining the specific antibody response of the children with sickle cell anemia and documented pneumococcal infections to see if the response is comparable to that of normal children. Secondly, we are doing a cross-sectional survey of a large number of our children to determine specific pneumococcal antibody profiles. These data will then provide the