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PubMed1996

Monovalent latex agglutination reagents for the diagnosis of nonmeningitic pneumococcal infection.

The pneumococcus is a leading cause of serious bacterial infection worldwide. Given the difficulties with available assays for the diagnosis of invasive nonmeningitic pneumococcal infection, we evaluated monovalent slide latex agglutination reagents among patients with blood culture-confirmed pneumococcal infection and control patients in Baltimore, Maryland, USA; São Paulo, Brazil; and Cairo, Egypt. Among 50 patients with invasive nonmeningitic pneumococcal infection, 23 had a positive urine test for a sensitivity of 46% (95% confidence intervals of 32% and 61%). Among 39 healthy children, 36 had a negative assay, for a specificity of 92% (95% confidence intervals of 78% and 98%). Among 80 children with pneumonia without a positive blood culture for Streptococcus pneumoniae, the specificity was 88% (95% confidence intervals of 78% and 94%). Although the assay was fairly specific, the positive predictive value using optimistic assumptions was only 73%-83%. This study suggests that this assay has a sensitivity and positive predictive value that may limit its value in some settings.

Child, Preschool↗

PubMed2005

Poor antibody response to pneumococcal polysaccharide vaccination suggests increased susceptibility to pneumococcal infection in splenectomized patients with hematological diseases.

Patients with hematological diseases undergoing diagnostic or therapeutic splenectomy are at increased risk of pneumococcal infections. Vaccination is a straightforward option in preventing these infections. A well-defined cohort of splenectomized patients with hematological disorders was followed according to response to 23-valent pneumococcal capsular polysaccharide (Pneumovax N) vaccination. A total of 76 splenectomized patients (Hodgkin lymphoma, HL 26, non-Hodgkin lymphoma, NHL 19, immune-mediated cytopenias 28, and others 3) with a median age of 52 years (range 18-82 years) were included. Pneumococcal polysaccharide (PS) antibodies were determined using an enzyme-linked immunosorbent assay before vaccination, at peak, and follow-up. A poor response to vaccination was observed in 21 (28%) patients and a good response in 55 (72%), respectively. During the follow-up period of 7.5 years (range 3.5-10.5 years) after vaccination, and despite repeated revaccination in many cases, a total of five episodes (in three patients) of pneumococcal infections were reported, all confined to the poor responder group. Revaccination did not improve antibody levels in this group. The median age at vaccination was significantly higher in the group of poor responders (p=0.0006). None of the following factors could predict a poor antibody response: gender, disease activity or aggressiveness in hematological malignancies, previous radiotherapy and/or chemotherapy, time between splenectomy and pneumococcal vaccination, time between chemotherapy/radiotherapy and study pneumococcal vaccination (1 year), or the presence of hypogammaglobulinemia. In conclusion, a substantial proportion of splenectomized patients with hematological diseases mounted a poor PS antibody response and remained at risk for pneumococcal infections despite vaccination. In the absence of apt indirect clinical predictors of antibody response, with the exception of age, measurement of antibody levels seems to be a feasible method for early identification of this patient subgroup. Poor responders do not benefit from revaccination, and should be offered other prophylactic measures.

Adolescent↗

PubMed1984

Recurrent pneumococcal infections in a patient with lack of specific IgG and IgM pneumococcal antibodies and deficiency of serum IgA, IgG2 and IgG4.

Disseminated pneumococcal infections in a young woman are described. Serum from the patient showed reduced opsonic capacity for pneumococci and absence of pneumococcal anticapsular IgG and IgM antibodies even after pneumococcal immunization. Total serum IgG level was normal, but IgG2, IgG4, and IgA were deficient. The possible location of pneumococcal IgG antibodies in the IgG2 subclass is discussed as well as the existence of serious antibody deficiencies in patients with normal total IgG levels.

Adult↗

PubMed1997

Risk factors for penicillin-resistant systemic pneumococcal infections in children.

The purpose of this study was to identify risk factors that may differentiate children who develop systemic infections with resistant strains of Streptococcus pneumoniae from those who develop penicillin-susceptible pneumococcal infections. A retrospective case-controlled study was performed of all patients with positive blood and/or cerebrospinal fluid isolates for S. pneumoniae over a 13 1/2-month period. Patients with penicillin-susceptible strains of S. pneumoniae were compared with those with penicillin-resistant infections in terms of age, race, gender, diagnosis, underlying conditions, antibiotic therapy within 1 month prior to systemic infection, treatment, and outcome. Sixty-nine patients with systemic pneumococcal infections were identified over the study period. Nine (13%) of these patients had infection with a penicillin-resistant isolate. Six of these patients were infected with a relatively resistant strain (MIC 0.1-1.0 microgram/mL) while three were infected with a fully resistant strain (MIC > or = 2.0 micrograms/mL). There was no difference between the two groups in terms of age, race, gender, underlying diagnosis, treatment, or outcome. Sixty-seven percent of the patients who developed a penicillin-resistant pneumococcal infection had received antibiotics in the month prior to systemic illness versus 4% of those infected with a penicillin-susceptible strain (P < 0.0000097). In conclusion, when compared with children who develop systemic infection with a penicillin-susceptible strain of S. pneumoniae, children who develop infection with a penicillin-resistant strain are significantly more likely to have received antibiotics within 1 month prior to their illness.

Adolescent↗

PubMed2006

Assessment of a rapid urinary antigen detection by an immunochromatographic test for diagnosis of pneumococcal infection in children.

The aim of the study was to evaluate the Binax Now rapid immunochromatographic test (ICT) for the detection of Streptococcus pneumoniae urinary antigen in children suffering from potentially pneumococcal infections. A total of 287 patients, with a median age of 34.9 months and divided into 3 groups, were studied; the first group of patients with a suspected pneumococcal infection (n = 112), the second group with infectious symptoms nonsuggestive of a pneumococcal infection (n = 54), and the third group was composed of asymptomatic children (n = 121). In group 1, sensitivity of ICT was 100% and specificity was 55.9% (95% confidence interval, 44.1- 67.7). Forty-six (85.1%) patients from the second group were true negatives. Twenty-five (20.7%) patients from the third study group were nasopharyngeal pneumococcal carriers, and the ICT was positive in 13 carriers (10.7%). The high sensitivity level of ICT in our study indicates that a negative test could rule out a pneumococcal infection, contrasted with a poor specificity.

Antigens, Bacterial↗

PubMed1990

Immunoglobulin G subclass deficiency and pneumococcal infection after allogeneic bone marrow transplantation.

Serum immunoglobulin (Ig) G subclass levels were measured in a radial immunodiffusion assay in 25 leukemic patients before and after allogenic bone marrow transplantation. All patients received a conditioning regimen of busulfan and cyclophosphamide followed by infusion of marrow from an HLA-identical sibling. Intravenous infusions of a commercial Ig preparation were administered every 2 weeks until day 120 posttransplant. Nine patients developed pneumococcal infections at 6 months or greater posttransplant. Infection was associated with low levels or the absence of detectable serum IgG2 and IgG4. At the time of infection, 4 of 7 patients evaluated had undetectable IgG2, while 5 of 7 had undetectable levels of IgG4. After infection, none of the 8 patients evaluated had detectable levels of IgG2, and only 2 of 8 had detectable levels of IgG4. In contrast, all 16 patients without pneumococcal infection had IgG2 levels of 102 mg/dL or greater, and IgG4 levels of 20 mg/dL or greater. It appears that IgG2 and IgG4 subclass deficiencies after allogenic bone marrow transplantation contribute to susceptibility to pneumococcal infection. After pneumococcal infection, IgG2 and IgG4 levels remain low for a prolonged period and patients remain susceptible to infection by encapsulated organisms.

Adult↗

PubMed2002

Occurrence and clinical presentation of systemic pneumococcal infections in an unselected population in Oslo, Norway, between 1993 and 1997.

In order to describe the clinical and microbiological manifestations of systemic pneumococcal infection in an unselected urban population, 147 cases that occurred in the period 1993-1997 were retrospectively reviewed. An unexpected finding was that gastrointestinal symptoms were remarkably common. All pneumococcal isolates were fully susceptible to penicillin. The 7-valent conjugated vaccine covered 71% of those under 2 years of age, but only 21% of those 15-65 years of age were covered. Although the case fatality rate was 17%, the rate of early fatality due to systemic pneumococcal infection was unchanged compared with data published in the era before antibiotics. This study emphasizes the importance of continuing efforts to prevent systemic pneumococcal infections.

Adolescent↗

PubMed1998

Three-year multicenter surveillance of systemic pneumococcal infections in children.

OBJECTIVE: To track antibiotic susceptibility of Streptococcus pneumoniae isolates obtained from children with systemic infections and determine outcome of treatment. DESIGN: A 3-year (September 1993 through August 1996) 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-proven systemic pneumococcal infection. RESULTS: One thousand two hundred ninety-one episodes of systemic pneumococcal infection were identified in 1255 children. An underlying illness was present in the children for 27% of the episodes. The proportion of isolates that were nonsusceptible to penicillin or ceftriaxone increased annually and nearly doubled throughout the 3-year period; for the last year the percentages of isolates nonsusceptible to penicillin and ceftriaxone were 21% and 9.3%, respectively. There was no difference in mortality between patients with penicillin-susceptible or nonsusceptible isolates. Only 1 of 742 patients with bacteremia had a repeat blood culture that was positive > 1 day after therapy was started. All 24 normal children with bacteremia attributable to isolates resistant to penicillin had resolution of their infection; the most common treatment regimen was a single dose of ceftriaxone followed by an oral antibiotic. CONCLUSIONS: The percentage of pneumococcal isolates nonsusceptible to penicillin and ceftriaxone increased yearly among strains recovered from children with systemic infection. Because empiric antibiotic therapy already has changed for suspected pneumococcal infections, antibiotic resistance has not been associated with increased mortality. Careful monitoring of antibiotic susceptibility and outcome of therapy is necessary to continually reassess current recommendations for treatment.

Adolescent↗

PubMed1995

Epidemiology and clinical spectrum of pneumococcal infections: an Israeli viewpoint.

We performed a prospective study of consecutive pneumococcal infections documented during a six-month period in our clinical microbiology laboratory. A total of 59 cultures obtained from clinically significant specimens of 58 patients were positive for Streptococcus pneumoniae. Relative penicillin resistance occurred in 14 strains (24%) and only one (1.7%) was highly resistant to penicillin (minimum inhibitory concentration = 2.0 micrograms ml-1). Resistance to common alternative drugs was not found. Serotypes were of a wide variety, however types 1, 7 and 14 predominated (60% of all blood culture isolates). Twenty-three patients with community-acquired infection required hospitalization. Nosocomial pneumonia developed in three additional cases (14%). Invasive disease was diagnosed in 24 patients with pneumonia representing the most common infection (22 patients). Pneumonia was characterized by a high incidence of serious underlying diseases (82%) and associated bacteraemia (68%). Compared with controls, patients with penicillin-resistant pneumococcal pneumonia had a significantly higher incidence of previous hospitalizations and use of antibiotics (57 vs. 7%, P = 0.02). The overall case fatality rate was high (36%) and did not differ significantly between patients with pneumonia due to resistant and susceptible strains. The epidemiology and clinical spectrum of serious pneumococcal infections in Israel is similar to those described in many parts of the world, but high level resistance to penicillin and to other alternative drugs is still rare.

Aged↗

PubMed2002

Will the 7-valent pneumococcal vaccine have a similar impact on all invasive pneumococcal infections in children in Germany as in the Kaiser Permanente Trial?

UNLABELLED: A 7-valent pneumococcal conjugate (7-vPc) vaccine was shown to be highly effective in California preventing 89.1% of all invasive pneumococcal infections (IPI) regardless of serotype. There is concern whether a similar effectiveness will be attained in Germany where 52% of all IPI in children <16 years were caused by the serotypes in the vaccine. The study was based on prospective, active surveillance of IPI in German children aged <16 years during 1997 to 2000. Coverage by the 7-vPc vaccine (with and without 6A) in unvaccinated children in the Kaiser Permanente Trial (KPT) was compared to the coverage in German children in the same age period as in the KPT. The proportion of potentially preventable cases was estimated both for unvaccinated children in the KPT and for Germany by multiplication of the coverage rates with the vaccine efficacy estimate from the KPT (intention to treat analysis). Successful serotyping could be attained for 38.3% of the 1,743 German IPI cases. In the age period from 7 to 43 months concerned in the KPT, the proportion of cases with serotypes covered by the 7-vPc vaccine (+6A) was 91% (95% CI 80%-97%) in the unvaccinated children in the KPT compared to 76% (95% CI 71%-80%) in Germany. The respective estimates for the number of potentially preventable IPI cases were 85% (95% CI 75%-91%) in the KPT compared to 71% (95% CI 67%-75%) in Germany. CONCLUSION: Age specific serotype coverage rates have to be considered for extrapolation of the Kaiser Permanente Trial to the German situation. Although 14% lower than in the Kaiser Permanente Trial, 71% of potentially preventable cases of invasive pneumococcal infection still predict an excellent effectiveness for the 7-valent pneumococcal conjugate vaccine in Germany.

Adolescent↗

PubMed2002

Population-based epidemiology of invasive pneumococcal infection in children in nine urban centers in Canada, 1994 through 1998.

PURPOSE: To describe the epidemiology of invasive pneumococcal infections in Canadian children 0 to 12 years old. METHODS: At each of nine urban centers, active surveillance was conducted to identify all cases of invasive pneumococcal infection in children during 1994 to 1998. Postal codes were used to distinguish cases resident in defined urban areas from referral cases. Census data were obtained for each defined area to calculate age-specific incidence rates. Features of population-based cases were described. RESULTS: From an average defined population of approximately 1 million children, 937 eligible cases arose. Those 6 to 17 months old had the highest average incidence rate of 98.6/100 000/year. The average cumulative risk of infection was 1 in 460 between birth and 59 months, by which age 92% of cases had occurred. Among cases younger than 2 years of age, simple bacteremia accounted for 66%, pneumonia with bacteremia accounted for 14.7% and meningitis accounted for 11% (average incidence rate, 9.0/100 000/year). An underlying illness was present in 16% of all cases. The mortality rate was 1.8%. CONCLUSIONS: Invasive pneumococcal infections are relatively common in early childhood, based on 5 years of data from nearly 20% of the Canadian population ages 0 to 12 years. These data will be valuable for calculating the economic case for universal infant vaccination with newly available vaccines.

Age Distribution↗

PubMed1997

Antibiotic management of pneumococcal infections in an era of increased resistance.

Pneumococci are a leading cause of bacterial meningitis and bacteraemia, as well as pneumonia, otitis media and sinusitis in childhood. These organisms recently have shown a dramatic increase in antibiotic resistance. Penicillin-resistant pneumococci are of special concern as they are often resistant to other unrelated antibiotics. This is of particular significance to Aboriginal children who have among the highest rates of pneumococcal infection in the world. Laboratories should now test all invasive pneumococcal isolates for penicillin and third generation cephalosporin resistance. Local treatment guidelines are required for pneumococcal infections, especially for meningitis, taking into account the prevalence of resistant strains within the community. At present, penicillin and amoxycillin remain the drugs of choice for pneumococcal infections, with the exception of meningitis where initial empirical therapy must be with a third generation cephalosporin. Judicious antibiotic use, which avoids over-prescribing and unnecessary use of broad-spectrum agents, improved living standards in underprivileged communities and introduction of an effective conjugate vaccine, able to reduce the rates of pneumococcal infection and hopefully colonization, may limit the spread of resistant strains.

Anti-Bacterial Agents↗

PubMed1999

Pneumolysin PCR-based diagnosis of invasive pneumococcal infection in children.

Blood-based pneumolysin PCR was compared to blood culture and detection of pneumolysin immune complexes, as well as to detection of antibodies to pneumolysin and to C polysaccharide, in the diagnosis of pneumococcal infection in 75 febrile children. Invasive pneumococcal infection was suspected on clinical grounds in 67 of the febrile children, and viral infection was suspected on clinical grounds in 8 of the febrile children. In addition, 15 healthy persons were examined to test the specificity of the PCR assay. Plasma, serum, and leukocyte fractions were analyzed by PCR. The combination of all test results led to the diagnosis of pneumococcal infection in 25 patients. Pneumolysin PCR was positive in 44% of these children, an increase occurred in the pneumolysin antibodies in 39% and in the C polysaccharide antibodies in 30% of the patients; pneumolysin immune complexes were found in convalescent serum in 30%, pneumolysin immune complexes occurred in acute-phase serum samples in 16%, and a positive blood culture was found in 20% of the patients. None of the healthy controls had positive results by PCR. The results suggest that the diagnosis of Streptococcus pneumoniae infection from blood samples necessitates the use of several different assays. Pneumolysin PCR was the most sensitive assay, but its clinical value is reduced by the fact that three blood fractions are needed.

Antibodies, Bacterial↗

PubMed2006

Impaired anti-pneumococcal polysaccharide antibody production and invasive pneumococcal infection following heart transplantation.

An increased risk of invasive pneumococcal infection has been described among adult heart transplant (HT) recipients. Vaccination has been recommended before HT but the appropriate time for revaccination is not known. In a preliminary analysis of a prospective study involving a cohort of 32 HT recipients receiving daclizumab and triple immunosuppresion therapy, a progressive decline in pneumococcal polysaccharide antibody (anti-PPS) levels was observed during the first year after HT. One of the patients who was found to have a decrease in the levels of anti-PPS developed severe pneumococcal meningitis 20 months after HT. Before HT he had received non-conjugated 23-valent pneumococcal vaccine and showed a normal post-immunization anti-PPS production. The data suggest that long-term immunologic monitoring might be useful to recognize impairment of antibody responses under immunosuppressive therapy in HT.

Antibody Formation↗

PubMed2002

Prophylactic antibiotics for preventing pneumococcal infection in children with sickle cell disease.

BACKGROUND: People with sickle cell disease are particularly susceptible to infection. Infants and very young children are especially vulnerable, and the Cooperative Study of Sickle Cell Disease observed an incidence rate of 10 per 100 patient years of pneumococcal septicaemia in children under the age of three. Vaccines, including customary pneumococcal vaccines, may be of limited use in this age group. Therefore, prophylactic penicillin regimes may be advisable for this population. OBJECTIVES: To assess the effects of prophylactic antibiotic regimes for preventing pneumococcal infection in children with sickle cell disease. SEARCH STRATEGY: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group specialist trials register which comprises references identified from comprehensive electronic database searches, hand searching relevant journals and hand searching abstract books of conference proceedings. Date of the most recent search: December 2001. SELECTION CRITERIA: All randomised or quasi-randomised controlled trials comparing prophylactic antibiotics to prevent pneumococcal infection in children with sickle cell disease with placebo, no treatment or a comparator drug. DATA COLLECTION AND ANALYSIS: Both reviewers independently extracted data and assessed trial quality. MAIN RESULTS: Five trials were identified by the initial search, of which three trials met the inclusion criteria. All of the included trials showed a reduced risk of infection in children with sickle cell disease (SS or Sb0Thal) receiving prophylactic penicillin. For initiation of treatment the odds ratio was 0.37 (95% CI 0.16, 0.86), and for withdrawal OR= 0.49 (95% CI 0.09, 2.71). Adverse drug effects were rare and minor. Rates of pneumococcal infection were found to be relatively low in children over the age of five. REVIEWER'S CONCLUSIONS: Prophylactic penicillin significantly reduces risk of pneumococcal infection in children with homozygous sickle cell disease, and is associated with minimal adverse reactions. Further research may help to determine the ideal age to safely withdraw penicillin.

Adolescent↗

PubMed2003

Rapid diagnosis of bacteremic pneumococcal infections in adults by using the Binax NOW Streptococcus pneumoniae urinary antigen test: a prospective, controlled clinical evaluation.

The diagnosis of severe pneumococcal infections is inadequate, relying heavily on culture of Streptococcus pneumoniae from blood or other normally sterile fluids, and is severely limited by prior administration of antibiotics. We evaluated prospectively the Binax NOW S. pneumoniae urinary antigen test, a rapid immunochromatographic assay, for the diagnosis of bacteremic pneumococcal infections in hospitalized adult patients. Antigen was detected in 88 of 107 cases overall, resulting in a test sensitivity of 82% (95% confidence interval [95% CI], 74 to 89%). Antigen detection was greater in those with pneumonia (67 of 77 [87%]) than in those without pneumonia (21 of 30 [70%]) (P = 0.04). Urinary antigen was also detected in 3 of 106 adult patients with community-acquired septicemic infections caused by other organisms, giving a test specificity of 97% (95% CI, 92 to 99%). For 45 pneumococcal bacteremia patients with a positive test on treatment day 1, urinary antigen excretion was monitored for the first week of antibiotic treatment. Antigen was still detectable in 83% (29 of 35 tested; 95% CI, 66 to 93%) on treatment day 3. Detection of urinary antigen is a valuable, sensitive, and rapid test for the early diagnosis of bacteremic pneumococcal infections in adult patients, even after antibiotic treatment has commenced.

Adolescent↗

PubMed1979

[Contribution of the counter-immunoelectrophoresis for the diagnosis of pneumococcal infections (author's transl)].

Using counter-immunoelectrophoresis (CIE), the authors have looked for pneumococcal antigens in biological fluids in 141 pneumococcal infections cases (70 meningitis, 25 empyema, 40 pneumonia, 5 peritonitis, 1 pericarditis). The best results (superior to bacteriological results) were obtained with CSF and pleural fluid. Testing sputum by CIE seems to have a real interest in pneumonia. CIE associated with bacteriology, gives more than 20% increase in aetiological diagnosis in pneumococcal infections and permits to set accurate aetiological diagnosis in less than two hours.

Cerebrospinal Fluid↗

PubMed2001

Invasive pneumococcal infections in Southwestern Sweden: a second follow-up period of 15 years.

In a retrospective study, the incidence, clinical manifestations, concomitant conditions and case fatality rate were studied in patients with invasive pneumococcal infections in the Göteborg area of Sweden during 1981-95, when the pneumococcal polysaccharide vaccine was available but little used. Patients were identified from the records of the Departments of Clinical Bacteriology and from the computer-based hospital discharge registers of the relevant departments. Individual case records were found for 876 patients with invasive pneumococcal infections verified by cultures from blood, cerebrospinal fluid or other sterile body fluids. A study from the same area with the same design covering the years 1964-80 has previously been published. There was an increase in total incidence from 5.3 to 10.3 cases/100,000/y from the previous to the present study. This increase was due to an increase in patients with non-meningitic infections aged > or = 60 y. The incidence of meningitis was virtually unchanged (1.4/100,000/y), as was the incidence of non-meningitic infections in individuals < 60 y. There were no other important changes between the 2 studies, which confirm that invasive pneumococcal infections have the highest incidence rates in children < 2 y and in the elderly, that a wide variety of underlying conditions are seen in the patients and that the case fatality rate, 15% in the present study, is still high.

Adolescent↗