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

OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.     

Non-typhi Salmonella bacteremia in children

BACKGROUND: Non-typhi Salmonella (NTS) infections are a frequent cause of self-limited diarrheal illness in healthy children. Bacteremia is a known complication of NTS infection, but the management of children with bacteremia has been based on limited data. OBJECTIVE: To study the outcomes of pediatric patients with NTS bacteremia. METHODS: Retrospective review of patients with NTS bacteremia covering a 16-year period at an urban pediatric hospital. Clinical data from the initial visits and any follow-up visits or hospitalizations were abstracted from the medical record. RESULTS: We studied 144 patients. Median age was 10.5 months. Fifty-four patients were hospitalized at the initial visit including all the patients with immunodeficiency (n = 12). Of the 90 patients initially managed as outpatients, 79 were subsequently admitted; only 1 of these patients developed a focal complication. Persistent bacteremia was found in 51 (41%) patients. Among nonimmunocompromised patients, persistent bacteremia was noted in 34% [95% confidence interval (CI), 20 to 52%] of those initially treated with oral antibiotics, 52% (CI 30 to 74%) of those initially treated with a parenteral dose of antibiotics and in 31% (CI 22 to 43%) of those who were not initially given antibiotics. No laboratory or clinical factors predicted persistent bacteremia. Twelve patients developed focal infections: 3 of 119 previously healthy children (2.5%, CI 0.5 to 7%); and 9 of 25 children with underlying medical conditions (36%, CI 19 to 57%). Focal infections included meningitis (3), osteomyelitis (4), septic arthritis (2), pneumonia (2) and cholangitis (1). CONCLUSIONS: NTS bacteremia occurs in otherwise healthy children, although the risk of focal infections is small. Patients with NTS bacteremia frequently have persistent bacteremia at follow-up regardless of initial antibiotic treatment.     

Clinical profile of serologically diagnosed pneumococcal pneumonia.

OBJECTIVE: To describe the characteristics of serologically diagnosed pneumococcal pneumonia and compare them with those of respiratory syncytial virus (RSV) pneumonia and bacteremic pneumococcal pneumonia. METHODS: IgG antibodies to pneumococcal pneumolysin and C-polysaccharide as well as immune complexes containing IgG antibodies to pneumolysin and C-polysaccharide were measured from acute and convalescent sera of 254 children with community-acquired pneumonia. Evidence of pneumococcal infection was found in 93 children. Clinical and laboratory data were retrospectively collected from the records of 38 children with sole (all tests for 16 other microbes negative) pneumococcal pneumonia and compared with 26 sole RSV-induced pneumonia from the present series and with the data of our 85 bacteremic pneumococcal pneumonia cases reported earlier. RESULTS: Serologically diagnosed sole pneumococcal pneumonia clinically overlapped with RSV pneumonia, but RSV pneumonia was more often associated with tachypnea (45% vs. 17%, P < 0.05) and low white blood cell counts (means, 12.0 x 109/l vs. 20.8 x 109/l; P < 0.001) as well as low serum C-reactive protein levels (means, 28 mg/l vs. 137 mg/l; P < 0.001). Alveolar infiltrates were found in 15% of chest radiographs of children with RSV pneumonia compared with 76% of those in children with sole pneumococcal pneumonia (P < 0.001). Patients with bacteremic pneumonia more often appeared ill (79% vs. 50%, P < 0.001) and more often had typical pneumococcal pneumonia with high fever, leukocytosis and lobar infiltrates in their chest radiographs (70% vs. 34%, P < 0.05) than those with serologically diagnosed pneumococcal pneumonia. CONCLUSIONS: Serologically detected pneumococcal pneumonia differs significantly from RSV pneumonia in laboratory and chest radiography findings, but the clinical signs and symptoms overlap considerably. Bacteremic pneumococcal pneumonia is a more severe illness than the serologically diagnosed one.     

Impact of human immunodeficiency virus type 1 on the disease spectrum of Streptococcus pneumoniae in South African children

BACKGROUND: HIV-infected children are at increased risk of developing invasive Streptococcus pneumoniae disease. OBJECTIVE: To determine the impact of the HIV epidemic on the epidemiology of invasive pneumococcal disease in hospitalized African children. METHODS: Children <12 years of age with invasive pneumococcal disease were enrolled between March, 1997, and February, 1999. RESULTS: The seroprevalence of HIV was 64.9% (146 of 225). In children with pneumococcal isolates from serogroups 6, 9, 14, 19 or 23 (pediatric serogroups), pneumonia and pneumonia with concurrent meningitis was more common in HIV-infected children (P = 0.03 and P = 0.003, respectively), whereas septic shock occurred more often in HIV-uninfected children (P = 0.0003). The overall burden of severe invasive pneumococcal disease was 41.7 (95% confidence interval, 26.5 to 65.6) fold increased in HIV-infected compared with HIV-uninfected children. Reduced susceptibility to penicillin (45.91% vs. 27.9%, P = 0.009), trimethoprim-sulfamethoxazole (44.5% vs. 19.0%, P = 0.0002) and multiple drug resistance was more common in HIV-infected than in HIV-uninfected children (24.0% vs. 6.4%, P = 0.01), respectively. The increased burden of disease and reduced antibiotic susceptibility of pneumococcal isolates in HIV-infected children was because of a heightened susceptibility to disease caused by pediatric serogroups in these children than in HIV-uninfected children (P = 0.01). Although the case fatality rates did not differ between HIV-infected and -uninfected children, mortality in HIV-infected children with advanced AIDS (Stage C, 22 of 61; 36.1%) was greater than that in children with moderate AIDS (Stage B, 12 of 85; 14.1%, P = 0.002). CONCLUSIONS: In children with invasive pneumococcal disease caused by the pediatric serogroups, HIV-infected children have more antibiotic-resistant isolates and have a different clinical presentation than do HIV-uninfected children.     

Evolution of the epidemiology of pneumococcal disease among Utah children through the vaccine era

From 1996 to 2009, we analyzed changes in pneumococcal disease (PD) in Utah children aged <18 years using International Classification of Diseases, ninth revision coded hospital discharges. We observed a sustained decrease in the incidence of PD among children <5 years in 2001-2004 (-36%) and 2005-2009 (-34%) compared with 1996-2000 (pre-7-valent pneumococcal conjugate vaccine). Decreases were primarily in bacteremia, uncomplicated pneumonia, and meningitis. In contrast, significant increases in complicated pneumonia/empyema were noted in children <5 years (+95% and +85%) and 5 to 17 years (+2% and +70%). Despite decreases in PD among Utah children, complicated pneumonia/empyema has increased during the 7-valent pneumococcal conjugate vaccine era.     

Pneumococcal meningitis in children: relationship of antibiotic resistance to clinical characteristics and outcomes.

BACKGROUND: The relationship of antibiotic susceptibility to clinical outcome in children with pneumococcal meningitis is uncertain. Previous studies have been limited by inclusion of relatively few patients infected with nonsusceptible pneumococci and inconsistent use of empiric vancomycin. METHODS: Medical records of 86 children with culture-confirmed pneumococcal meningitis at a single institution from October, 1991, to October, 1999, were retrospectively reviewed, and differences in presentation and outcome based on antibiotic susceptibility of pneumococcal isolates were assessed. RESULTS: Of 86 isolates 34 were nonsusceptible to penicillin (12 resistant). Of 60 isolates for which cefotaxime susceptibility data were available, 17 were nonsusceptible (12 resistant). Antibiotic susceptibility was not significantly associated with death, intensive care unit admission, mechanical ventilation, focal neurologic deficits, seizures, secondary fever, abnormal neuroimaging studies or hospital days. Children with penicillin-resistant isolates had significantly higher median blood leukocyte counts (24,100/microliter vs. 15,700/microliter, P = 0.03) and lower median CSF protein concentrations (85 mg/dl vs. 219 mg/dl, P = 0.04), were more likely to have a CSF glucose concentration of > or = 50 mg/dl (7 of 11 vs. 15 of 68, P = 0.009) and had lower rates of sensorineural hearing loss (1 of 8 vs. 25 of 40, P = 0.02) than children with isolates that were not resistant to penicillin. Children with cefotaxime-nonsusceptible isolates had an increased median duration of primary fever compared with those with nonsusceptible strains (6 days vs. 3.5 days, P = 0.02). CONCLUSIONS: In children with pneumococcal meningitis, penicillin resistance was associated with a reduced risk of hearing loss, while cefotaxime resistance was associated with a longer duration of fever. Other outcome measures were not significantly influenced by the antibiotic susceptibility of pneumococcal isolates.     

Risk of bacteremia in young children with pneumonia treated as outpatients

BACKGROUND: Blood cultures are often obtained as part of the evaluation of children with pneumonia. There are few data regarding the risk of bacteremia with pneumonia in children since introduction of the Haemophilus influenzae type b vaccine. OBJECTIVE: To evaluate the risk of bacteremia in young children with pneumonia who were treated as outpatients. METHODS: A retrospective cohort study of 580 children aged 2 to 24 months who were evaluated by blood culture in a tertiary care children's hospital emergency department between February 1, 1993, and May 31, 1996, and discharged with the diagnosis of pneumonia. RESULTS: The mean patient age was 14.1 months; 339 patients (58.4%) were boys. Thirty-eight patients (6.6%) reported the use of oral antibiotics before initial emergency department evaluation. The prevalence of bacteremia was 1.6% (95% confidence interval, 0.7%-2.9%). Streptococcus pneumoniae was the causative organism in all 9 cases. The serotype was available for 8 of 9 cases. Six (75%) of 8 cases of S pneumoniae bacteremia were caused by serotypes included in the current heptavalent pneumococcal conjugate vaccine, which was not available at the time of this study. The contamination rate was 1.9% (95% confidence interval, 1.0%-3.4%). The mean +/- SD time to blood culture positive for organisms in a continuously monitored system was significantly shorter for pathogens (13.9 +/- 1.3 hours) than for contaminants (21.2 +/- 6.1 hours; P =.01). CONCLUSIONS: Children aged 2 to 24 months with pneumonia who are treated as outpatients are at low risk of bacteremia. Widespread use of the pneumococcal conjugate vaccine may further decrease the incidence of bacteremia in this population.     

Haemophilus influenzae type b unsuspected bacteremia

To further define the clinical features and natural history of unsuspected Haemophilus influenzae type b (Hib) bacteremia, we retrospectively reviewed the records of 322 Hib infections observed during a 45-month period at Children's Hospital, Boston. We identified 31 patients with unsuspected Hib bacteremia and 19 with unsuspected Hib antigenemia and sterile blood cultures. Bacteremic patients were typically under two years of age (81%), had high fevers (mean = 39.5 degrees C), and frequently had otitis media (65%) diagnosed as their only focus of infection at presentation. Nineteen of 31 were empirically treated with oral antibiotics. Ten of 31 (32%) developed focal infectious complications consisting of meningitis (n = 7), cellulitis (n = 2), and pneumonia (n = 1). Children with focal infectious complications differed from those without infectious complications in having a significantly higher mean fever of 40.3 degrees C compared to 39.7 degrees C (P less than 0.05). Five of 19 (26%) empirically treated patients developed focal complications (all meningitis) compared to five of 12 (42%) untreated patients. Blood cultures at follow-up visit were positive in three of 19 (9%) treated patients and seven of 12 (42%) untreated patients (P less than 0.05). Of the 19 children with antigenemia and sterile blood cultures, 16 (84%) were empirically treated with antibiotics, and none had positive blood cultures or focal infections on follow-up evaluation. Children with occult Hib bacteremia are at high risk for developing serious focal infections, particularly meningitis, despite empiric antibiotic therapy. Once Hib bacteremia is suspected, strong consideration should be given to parenteral in hospital antibiotic therapy. The utility of rapid antigen detection for identifying high-risk patients requires further evaluation.     

High pneumococcal DNA loads are associated with mortality in Malawian children with invasive pneumococcal disease

BACKGROUND: In bacteremia owing to Streptococcus pneumoniae, high bacterial counts at presentation have been shown to be predictive of the development of serious invasive disease. Using real-time PCR, we aimed to determine pneumococcal DNA loads in blood and CSF, and their relationship to cytokine concentrations, clinical presentation and outcome. METHODS: Children with confirmed meningitis (n = 82) or pneumonia (n = 13) were prospectively recruited, and blood and CSF samples taken for pneumococcal bacterial DNA loads and cytokine determination. RESULTS: At the time of admission, the median bacterial load in blood was 1.6 x 10 DNA copies/mL (range 0.00-1.54 x 10) and in CSF it was 5.77 x 10 DNA copies/mL (range 4.42 x 10 to 6.15 x 10). Median blood and CSF bacterial loads (log DNA copies/mL) were significantly higher in nonsurvivors than in survivors; blood (3.80 vs. 2.97, P = 0.003), CSF (8.17 vs. 7.50, P = 0.03). In HIV-infected children (n = 59), blood and CSF loads and plasma tumor necrosis factor-alpha, interleukin-1beta (IL-1beta), IL-6 and IL-10 were all significantly higher in nonsurvivors than in survivors, but in HIV-uninfected children (n = 36) this difference was not significant. Blood bacterial loads and plasma cytokine concentrations were significantly associated, and were all significantly higher in children with meningitis than in those with pneumonia. In children with meningitis, median CSF cytokine concentrations were significantly higher than median plasma cytokine concentrations (P < 0.001) and CSF bacterial loads were significantly associated with CSF IL-1beta (P = 0.002) and IL-10 (P = 0.001) concentrations. CONCLUSIONS: Pneumococcal DNA loads are associated with plasma cytokine concentrations, and are higher in meningitis than in pneumonia. High blood and CSF pneumococcal DNA loads are associated with a fatal outcome.     

Outcome of invasive infections outside the central nervous system caused by Streptococcus pneumoniae isolates nonsusceptible to ceftriazone in children treated with beta-lactam antibiotics

OBJECTIVE: To determine the outcome of children treated primarily with beta-lactam antibiotics for a systemic infection outside the central nervous system (CNS) caused by isolates of Streptococcus pneumoniae nonsusceptible to ceftriaxone (MIC > or = 1.0 microg/ml). DESIGN: Retrospective review of the medical records of children identified prospectively with invasive infections outside of the CNS caused by isolates of S. pneumoniae that were not susceptible to ceftriaxone between September, 1993, and August, 1999. A subset of this group treated primarily with beta-lactam antibiotics was analyzed for outcome. PATIENTS: Infants and children with pneumococcal infections cared for at eight children's hospitals. RESULTS: Among 2,100 patients with invasive infections outside the CNS caused by S. pneumoniae, 166 had isolates not susceptible to ceftriaxone. One hundred patients treated primarily with beta-lactam antibiotics were identified. From this group 71 and 14 children had bacteremia alone or with pneumonia, respectively, caused by strains with an MIC of 1.0 microg/ml. Bacteremia or pneumonia caused by isolates with a ceftriaxone MIC > or = 2.0 microg/ml occurred in 6 and 5 children, respectively. Three children with septic arthritis and 1 with cellulitis had infections caused by strains with an MIC to ceftriaxone of 1.0 microg/ml. Most were treated with parenteral ceftriaxone, cefotaxime or cefuroxime for one or more doses followed by an oral antibiotic. All but one child were successfully treated. The failure occurred in a child with severe combined immune deficiency and bacteremia (MIC = 1.0 microg/ml) who remained febrile after a single dose of ceftriaxone followed by 12 days of cefprozil. CONCLUSION: Ceftriaxone, cefotaxime or cefuroxime are adequate to treat invasive infections outside the CNS caused by pneumococcal isolates with MICs up to 2.0 microg/ml, a concentration currently considered resistant for these antibiotics by National Committee for Clinical Laboratory Standards breakpoints.     

Colonization by Streptococcus penumoniae in human immunodeficiency virus-infected children

OBJECTIVE: Children with HIV infection are particularly susceptible to invasive pneumococcal disease, yet the effect of HIV infection and its medical management on colonization and resistance to antibiotics are poorly described. To provide a basis for medical practice, we determined the prevalence of nasopharyngeal colonization and antibiotic resistance of Streptococcus pneumoniae in children with HIV infection. METHODS: Cross-sectional prevalence sample of children attending the pediatric HIV and pulmonary clinics to examine nasopharyngeal colonization with S. pneumoniae and antibiotic resistance to beta-lactams and trimethoprim-sulfamethoxazole (T/S). Subjects were matched by age and date of clinic visit. RESULTS: The colonization rate with S. pneumoniae of HIV-infected and -indeterminate children was equal to that of controls (20% vs. 19%). HIV infection, CDC staging or receipt of oral antibiotic therapy did not affect colonization. Isolates from HIV-infected and -indeterminate children were less likely to be penicillin-resistant than those from controls (18% vs. 50%). There was no difference in pneumococcal resistance to T/S among isolates from subjects and controls, despite 72% T/S use in the HIV clinic. CONCLUSION: Colonization with S. pneumoniae in HIV disease is no different from that of comparable children. The high incidence of pneumococcal disease and prophylaxis with T/S are not related to nasopharyngeal colonization. Antibiotic prophylaxis of HIV-infected children does not necessarily lead to increased resistance of S. pneumoniae.     

Six year multicenter surveillance of invasive pneumococcal infections in children

OBJECTIVE: Monitor clinical and microbiologic features including antimicrobial susceptibility of invasive pneumococcal infections among children. DESIGN: A 6-year (September, 1993, through August, 1999) prospective surveillance study of all invasive pneumococcal infections in children. PATIENTS: Infants and children cared for at eight children's hospitals in the United States with culture-proved invasive pneumococcal infection. RESULTS: During the 6-year period 2581 episodes of invasive pneumococcal infection occurred in 2498 children. Underlying conditions were present in 29% of the children. Of children without an underlying condition, 15% of the total infections occurred in those 25 to 60 months old. As the ages of the children advanced the proportion of cases classified as bacteremia declined, whereas the proportion classified as pneumonia increased. Also, as the ages of the children increased the proportion of isolates in serotypes/serogroups 1, 3 and 23 increased. whereas the proportion for serotype 14 diminished. During the 6 years of the study, there was a significant increase in the percentage of isolates intermediate or resistant to penicillin (P < 0.000001) or intermediate to ceftriaxone (P < 0.002). By the sixth year of the study, 37 and 11% of the isolates were nonsusceptible to penicillin or ceftriaxone, respectively. Antibiotic use in the 30 days before diagnosis of systemic pneumococcal infection occurred in 30 to 35% of the children for each of the 6 years. The overall case-fatality rate for children with systemic pneumococcal infection was 1.56%. Mortality was greatest in children >60 months old and in those with underlying conditions; mortality was not related to antibiotic susceptibility. CONCLUSIONS: The percentage of pneumococcal isolates recovered from children with systemic infection which were intermediate for penicillin or ceftriaxone or resistant to penicillin increased steadily during the 6-year period. There was also a trend toward increasing rates of resistance to ceftriaxone. The age and serogroup/serotype distributions of our patients support the recommendations to consider administration of the seven valent pneumococcal conjugate vaccine for all children 24 to 59 months old, with special consideration for selected groups.     

Diagnosis of pneumonia by counterimmunoelectrophoresis of respiratory secretions.

Several recent studies in adults have indicated that counterimmunoelectrophoresis (CIE) of sputum can distinguish persons with pneumococcal pneumonia vs those in whom merely colonization of pneumococcus occurs--CIE being positive in the former and negative in the latter. Counterimmunoelectrophoretic determinations were done on nasopharyngeal (NP) secretions in 20 children with bacterial pneumonia as evidenced by physical and radiological findings, leukocytosis, response to a penicillin, and in some cases, evidence of bloodstream invasion. Thirty-five children with other types of respiratory illness served as controls. Ten of 16 children from the pneumonia group had pneumococcal antigen in their NP secretions. Four of the six patients without pneumonia had evidence of disease associated with type 14 pneumococcus, which is not generally detected by CIE. The four additional patients with pneumonia had Haemophilus influenzae type b, and H influenzae type b antigen was present in the NP secretions. In the control group, one patient had pneumococcal antigen, and one patient had H influenzae type b antigen in the NP secretions, although 17/35 were positive for pneumococcus by culture. Counterimmunoelectrophoretic determinations of NP secretins are reliable in distinguishing patients with pneumococcal pneumonia vs those who are merely carriers (P less than .001).     

Correlates of high grade and low grade Haemophilus influenzae bacteremia

Routine use of the Isolator 1.5 Microbial Tube lysis direct plating blood culture system at our institution since November, 1983, provided a unique opportunity to study bacteremia in children from a quantitative perspective. In a 3-year period, 90 episodes of Haemophilus influenzae bacteremia occurred in immunocompetent outpatients; 83 of these met the criteria for study. Patients with high grade bacteremia (greater than 100 colony-forming units/ml) were more likely to have meningitis than those with low grade bacteremia (less than or equal to 100 colony-forming units/ml); conversely low grade bacteremia patients were more likely to have cellulitis or arthritis. Of 38 meningitis patients those with high grade bacteremia (n = 25) had a significantly shorter duration of illness before presentation than those with low grade bacteremia (median, 1 vs. 3 days; P less than or equal to 0.006). In addition high grade bacteremia patients had significantly lower white blood cell counts (median, 11.4 vs. 17.3 X 10(3)/mm3; P less than or equal to 0.007) and absolute neutrophil counts (5.5 vs. 11.1 X 10(3)/mm3; P less than or equal to 0.01). Only 1 of 8 meningitis patients who were pretreated with appropriate antibiotics had high colony counts compared to 7 of 8 matched controls (P = 0.04).     

Population-based surveillance for hospitalized and ambulatory pediatric invasive pneumococcal disease in Santiago,Chile

BACKGROUND: Nine- and 11-valent pneumococcal conjugate vaccines under development may control pediatric pneumococcal disease in nonindustrialized countries. Because these vaccines are expensive, population-based surveillance of pneumococcal disease in children <36 months of age was undertaken in Santiago, Chile to provide health authorities with reliable data on the burden of invasive pneumococcal disease and causative serotypes, including those in outpatients with high fever. METHODS: Automated blood culture machines were introduced into 9 hospitals that admit 85% of all hospitalized children in Santiago. Acutely ill pediatric febrile ambulatory patients are attended at 8 emergency rooms (ERs) and 36 urgent primary care services. After a 12-month pilot study in 3 ERs, health authorities collected blood cultures from children <36 months of age with high fever seen in the ER as standard practice. isolates were serotyped. RESULTS: Blood cultures of 18 (1.2%) of 1,503 outpatients 6 to 35 months of age with high fever in the pilot study yielded S. In the ensuing 24 months 236 children <36 months old were hospitalized with invasive pneumococcal disease (incidence, 33.9 cases/10(5) children), and 188 bacteremias were detected among ambulatory ER patients with high fever (incidence, 27.0 cases/10(5) children). Although serotypes were similar among hospitalized and ambulatory cases (except 18C, which was more common in the latter), case fatality was 9.5% in hospitalized (21 of 236) 0% in ambulatory cases (0 of 188) (P = <0.0001). High level resistance to penicillin (25.8% vs 10.1%) and cefotaxime (19.5% vs 6.2%) was observed more often among pneumococcal isolates from hospitalized than among ambulatory cases (P < 0.001). CONCLUSIONS: ER surveillance detected approximately one case of pneumococcal bacteremia among febrile ambulatory patients for each hospitalized invasive case. Because 71% of cases were caused by vaccine serotypes (and 87% by vaccine serogroups), 9- and 11-valent pneumococcal conjugate vaccines could prevent most invasive pediatric pneumococcal disease in Chile.     

Pneumococcal and Haemophilus influenzae type b antigen detection in children at risk for occult bacteremia

We prospectively evaluated pneumococcal and Haemophilus influenzae type b antigen detection in serum and urine of young (3 to 30 months of age) febrile (temperature greater than or equal to 39 degrees C) children at risk for occult bacteremia. Patients with septic shock, meningitis, or epiglottitis were excluded. Of 576 patients, 16 had pneumococcal bacteremia (final diagnoses: primary bacteremia, nine; otitis media, four; pneumonia, two; unknown, one), and five had H influenzae b bacteremia (final diagnoses: primary bacteremia, two; cellulitis, two; arthritis, one). Latex agglutination was positive in all five patients with H influenzae b bacteremia (positive in three of three urine specimens, three of four sera tested) but only one of 16 patients with pneumococcal bacteremia (positive in one of seven urine samples, zero of 13 sera tested). Both assays had specificities of greater than 95%. Nonspecific agglutination occurred in 7% of specimens tested. Enzyme immunoassay for pneumococcal antigen, although more sensitive than latex agglutination, failed to detect antigen in ten sera and three urine specimens from patients with pneumococcal bacteremia. Thus, neither latex agglutination nor enzyme immunoassay was sufficiently sensitive for detection of occult pneumococcal bacteremia. Latex agglutination for H influenzae b holds promise as a sensitive and specific test for rapid diagnosis of occult bacteremia due to H influenzae b.     

Linezolid versus vancomycin for treatment of resistant Gram-positive infections in children

BACKGROUND: Pediatric infections caused by resistant Gram-positive infections are an increasing concern with limited treatment options. Linezolid, a new oxazolidinone, is active against staphylococci, streptococci and enterococci. OBJECTIVE: To assess clinical efficacy and safety of linezolid vs.vancomycin in antibiotic-resistant Gram-positive infections in children.DESIGN Hospitalized children (birth to 12 years of age) with nosocomial pneumonia, complicated skin/skin structure infections, catheter-related bacteremia, bacteremia of unknown source or other infections caused by Gram-positive bacteria were randomized 2:1 to receive linezolid intravenously followed by oral linezolid or vancomycin and then by an appropriate oral agent. Treatment duration was 10 to 28 days. RESULTS: There were 321 patients enrolled (linezolid 219, vancomycin 102). Clinical cure rates were 79% vs.74% (P = 0.36) and 89% vs.85% (P = 0.31) for linezolid and vancomycin in intent-to-treat and clinically evaluable patients, respectively. Cure rates were similar by age and infection diagnosis. Pathogen eradication rates in microbiologically evaluable patients were high for linezolid and vancomycin, respectively, for methicillin-susceptible S. aureus (95% vs.94%; P = 0.82), methicillin-resistant S. aureus (88% vs.90%; P = 0.89) and methicillin-resistant coagulase-negative staphylococci (85% vs.83%, P = 0.87). In clinically evaluable patients, linezolid-treated patients required significantly fewer days of intravenous therapy compared with vancomycin-treated patients (8.0 +/- 4.8; 10.9 +/- 5.8 days, respectively; P < 0.001). In addition significantly fewer linezolid-treated patients had drug-related adverse events than did vancomycin-treated patients (19% vs.34%, respectively; P = 0.003). Hematologic events were uncommon and similar between treatment groups. CONCLUSIONS: Linezolid was well-tolerated and as effective as vancomycin in treating serious Gram-positive infections in children.     

Pseudomonas aeruginosa bacteremia in children: analysis of trends in prevalence, antibiotic resistance and prognostic factors

OBJECTIVE: To determine the factors predisposing to Pseudomonas aeruginosa bacteremia as well as the prevalence, source of infection, outcome and prognostic factors in pediatric patients. METHODS: Retrospective review of pediatric patients with P. aeruginosa bacteremia, at a large tertiary care hospital during a 6.5-year period. RESULTS: Seventy patients with P. aeruginosa bacteremia were identified. The annual rate of P. aeruginosa bacteremia remained unchanged during the study period. Antibiotic susceptibility remained unchanged except for two patients with extensive burns who developed resistant strains. Underlying diseases were malignancy (50%), prematurity (6%), burns (7%) and others (37%). The overall mortality associated with P. aeruginosa bacteremia was 20%. The fatality rate was higher among the young infants (compared with older children) and those who received previous antibiotic therapy (P = 0.02). Mortality rate was higher in nosocomial than in community-acquired infections (25% compared with 11.5%). The mortality rate of low birth weight and burns patients was significantly higher when compared with oncology patients or other patients, 75 and 40% compared with 11 and 19%, P = 0.01. Multiple regression analysis revealed a correlation only between the underlying disease and mortality (P = 0.02). In the oncology patients the only significant risk factor for mortality was absolute neutrophil count < or =0.1 x 10(9)/l (P = 0.06). CONCLUSION: P. aeruginosa bacteremia, although apparently not increasing in incidence and antibiotic resistance, is still a common serious complication in immunocompromised children with a high mortality rate. We conclude that the underlying disease is the main determinant of the clinical outcome.     

Characteristics of coagulase-negative staphylococci from infants with bacteremia

Twenty-nine infants were identified as having coagulase-negative staphylococcal (C-S) bacteremia. Fourteen infants had pneumonia and 10 had central line-associated bacteremia. Twenty-four of 29 (83%) had invasion of the mucocutaneous barrier at the time the positive blood culture was drawn. Clinical signs and symptoms were nonspecific. Apnea/bradycardia was the most prevalent clinical feature, occurring in 20 (69%) infants. Staphylococcus epidermidis was the most frequent blood culture isolate, occurring in 21 (72%) cases. Slime production by C-S blood culture isolates occurred in 23 (79%) cases. There was no prevalent antibiotic resistance pattern, phage type or plasmid profile among blood culture isolates from infants with bacteremia. Mucocutaneous isolates of C-S from infants with bacteremia were compared with those from infants without invasive disease. Infants with bacteremia had a significantly higher percentage of slime-producing organisms (75% vs. 58%, P = 0.027) and a significantly higher percentage of S. epidermidis species (79% vs. 53%, P = 0.001) than isolates from infants without bacteremia. Our data support the relationship of slime production and the S. epidermidis species of C-S as virulence factors in infants with foreign bodies. Testing C-S for slime production is a relatively simple laboratory procedure which may be an additional aid in the evaluation of their clinical significance.