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Proportion of invasive pneumococcal infections in German children preventable by pneumococcal conjugate vaccines.

The incidence and serotype distribution of Streptococcus pneumoniae as a cause of invasive diseases are unknown with regard to most European countries. From January 1997 through December 1998, population-based nationwide prospective surveillance was undertaken for invasive pneumococcal disease (IPD) in children in Germany, based on monthly independent reports from all pediatric hospitals and from clinical microbiology laboratories. On the basis of 896 reported IPD cases (including 404 with meningitis), the incidences per 10(5) children in different age groups were as follows: children aged <1 year, 18.9 (9.7 for meningitis); children aged <2 years, 16. 0 (7.2 for meningitis); for children aged <5 years, 8.9 (3.9 for meningitis); and for children aged <16 years, 3.2 (1.4 for meningitis). The proportions of cases involving strains (304 serotyped) included in conjugate vaccines were as follows: for the 7-valent vaccine, 52%; for the 9-valent, 62%; and for the 11-valent, 71%. None of the isolates were resistant to penicillin or cefotaxime. Although the rate for meningitis is similar, other manifestations of IPD are less commonly diagnosed in Germany than in other countries. The serotype distribution only partially matched that used in the recent development of pneumococcal conjugate vaccines.

Adolescent↗

Risk factors for acquiring pneumococcal infections.

To identify risk factors for developing pneumococcal infections, we carried out a case-controlled study on a retrospectively constituted cohort of 3074 clinic patients in a presumed high-risk population. Culture-proved pneumococcal infections were identified in 63 men over a period of 5.5 years, yielding an estimated incidence of 6.3 cases per 1000 person-years. By comparing these patients with 130 uninfected control patients, the relative risk of pneumococcal infections related to various exposures was calculated by logistic regression analysis. Statistically significant independent risk factors (and their relative risks) were as follows: dementia (5.82), seizure disorders (4.38), current cigarette smoking (4.00), congestive heart failure (3.83), cerebrovascular disease (3.82), institutionalization (3.13), and chronic obstructive pulmonary disease (2.38). Risk was increased with age and previous hospitalizations, and, to a nonsignificant degree, by hotel residence (3.93), lung cancer (2.24), previous smoking (2.14), corticosteroid use (1.81), and alcoholism (1.35); but not by diabetes mellitus (0.99), nonlung malignancies (0.93), nonwhite race (0.89), or ischemic heart disease (0.58).

Aged↗

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.

Age Factors↗

Effect of splenectomy and hemisplenectomy on pneumococcal infection and bacteria clearance in the rat.

Median survival times 1 month after intraperitoneal inoculation of Streptococcus pneumoniae Felton UC 41 show that the difference between hemisplenectomized and control rats is not at all significant (chi 2 = 0.04). On the other hand, comparing splenectomized rats with hemisplenectomized and control rats taken together, there is a significant difference: 10% level (chi 2 = 2.84; 1 degree of freedom; p less than 0.10). The blood concentrations of pneumococci at different time intervals after inoculation do not differ between control and hemisplenectomized rats (F = 0.02; 1 and 135 degrees of freedom), but they differ very significantly when the splenectomized rats are compared with the hemisplenectomized rats and controls taken together (F = 10.00; 1 and 135 degrees of freedom; p less than 0.01).

Animals↗

Pneumococcal infections during childhood: serotyping of pneumococcal strains from forty-six children.

The results of serotyping of forty-six strains of pneumococci isolated from children aged 3/12 to 14 9/12 years and diagnosed as having pneumonia, meningitis, primary peritonitis, otitis media, lymphadenitis, osteomyelitis, bacteraemia and conjunctivitis are presented. The results of serotyping and the frequency distribution of the detected serotypes were compared to the particular diagnoses established and the age at which the subjects involved had become ill. Questions of epidemiology and possibilities of immunoprophylaxis are discussed. Finally, the occurrence of pneumococci that are resistant to antibiotic agents are discussed since an isolated strain was found to show reduced susceptibility to penicillin G.

Adolescent↗

The role of age in susceptibility to pneumococcal infections.

Whether or not age by itself increases susceptibility to pneumococcal infections separate from the effects of chronic disease is controversial. To address this issue, data collected for a retrospective cohort study of pneumococcal infections among 63 middle-aged and older veterans and 126 uninfected controls were reanalysed. Univariate analysis suggested a linear increase in risk with increasing age for patients 50 years old and older (p = 0.03). Subjects over age 80 years seemed to be at particularly high risk when compared with patients under 50 (odds ratio = 4.3, p less than 0.03). The odds of pneumococcal infection increased by an estimated factor of 1.33 (95% confidence interval = 1.03, 1.71) for each 10-year increase in age. Controlling for other risk factors did not appreciably change the point estimate of the age effect, but statistical significance was lost. This result however suggests that age has an independent association with the risk of pneumococcal infections. The potential impact of this finding on public policy urges that the association of age with the risk of pneumococcal disease be re-examined in a study of sufficient sample size to resolve the issue.

Age Factors↗

Investigational new drugs for the treatment of resistant pneumococcal infections.

Antibiotic resistance in Streptococcus pneumoniae is not only increasing with penicillin but also with other antimicrobial classes including the macrolides, tetracyclines and sulfonamides. This trend with antibiotic resistance has highlighted the need for the further development of new anti-infectives for the treatment of pneumococcal infections, particularly against multi-drug resistant pneumococci. Several new drugs with anti-pneumococcal activity are at various stages of development and will be discussed in this review. Two new cephalosporins with activity against S. pneumoniae include ceftobiprole and RWJ-54428. Faropenem is in a new class of beta-lactam antibiotics called the penems. Structurally, the penems are a hybrid between the penicillins and cephalosporins. Sitafloxacin and garenoxacin are two new quinolones that are likely to have a role in treating pneumococcal infections. Oritavancin and dalbavancin are glycopeptides with activity against methicillin-resistant S. aureus and vancomycin-resistant Enterococcus spp. as well as multi-drug resistant pneumococci. Tigecycline is the first drug in a new class of anti-infectives called the glycycyclines that has activity against penicillin-resistant pneumococci.

Animals↗

Combating drug-resistant pneumococcal infections.

Penicillin-resistant pneumococcal strains continue to spread. Some strains are also resistant to other antibiotics, including the cephalosporins. Better utilization of the 23-valent pneumococcal vaccine, which covers the serotypes responsible for 90% of pneumococcal infections, is an important step in combating resistance.

Aged↗

Risk of pneumococcal infections in renal transplant patients.

Because of the recent licensing of pneumococcal vaccine, the risk of pneumococcal infections on a renal transplant service was determined. The overall risk of infection was 7% (14 of 197 patients) over a six-year period, or 1% per year. In patients with functioning allografts, this represented a risk of 28 infections per 1,000 patient-years of follow-up. Clinically, the major presentations of pneumococcal infection were pneumonia in the patient who was rejecting his kidney and pneumococcemia of sudden onset that was often fatal. Five of the pneumococci isolated from bacteremic patients were typed; three of the isolates were types that are in the vaccine. The frequency and seriousness of pneumococcal infections in renal transplant patients suggest that pneumococcal vaccine should be given to these patients, probably before transplantation.

Bacterial Vaccines↗

Invasive pneumococcal infection in Baltimore, Md: implications for immunization policy.

BACKGROUND: Streptococcus pneumoniae is a leading cause of infectious morbidity and mortality. Although blacks are known to have a higher incidence of invasive pneumococcal infection than whites, detailed analyses of these differences and their implications for vaccine prevention have not been reported. OBJECTIVE: To describe the epidemiological characteristics of invasive pneumococcal infection in Baltimore, Md, and its implications for immunization policy. METHODS: Analysis of active, laboratory-based surveillance during 1995 and 1996 among residents of the Baltimore metropolitan area. RESULTS: Of 1412 cases, 615 patients (43.6%) were classified as white and 766 (54.2%) as black. The annual incidence of invasive pneumococcal infection among white and black residents of the Baltimore metropolitan area was 17.8 and 59.2 per 100000 population, respectively (P<.01). Among patients aged 18 years and older, the median age of blacks with invasive pneumococcal infections was 27 years younger than that of whites (P<.01). Among males 40 to 49 years old, blacks had a 12-fold higher average incidence than whites (average incidence, 114.5 and 9.3, respectively; P<.01). By the age of 65 years, 83.8% of cases had occurred in black adults, as compared with 43.8% in white adults (P<.01). In a regression model, age, black race, male sex, low median family income, and county prevalence of acquired immunodeficiency syndrome were each independently associated with a higher incidence of pneumococcal infection. CONCLUSIONS: Young urban black adults in the Baltimore metropolitan area have a dramatically higher incidence of invasive pneumococcal infection than whites. The vast majority of cases of invasive pneumococcal infection in blacks occur before age 65 years. Current immunization efforts have not addressed the high incidence of pneumococcal infection in this population.

Adult↗

Pneumonia and pneumococcal infections, with special reference to pneumococcal pneumonia. The 1979 J. Burns Amberson lecture.

An etiologic classification of acute pneumonia was presented and the relative importance of some of the causative agents was briefly reviewed. The early developments of the therapy of pneumococcal pneumonia with type-specific antisera, sulfonamide drugs, and antimicrobial drugs were reviewed, mostly from the experiences of the author at Boston City Hospital. Changes in the occurrence and relative importance of the pneumococcus as a cause of infections associated with bacteremia, empyema, and meningitis were demonstrated, based on cases observed at Boston City Hospital during 12 selected years between 1935 and 1972. These findings, among others, indicate that the pneumococcus is still one of the most important causes of serious bacterial infections and of mortality from such infections, particularly in the elderly. Some possible indications for polyvalent pneumococcal capsular polysaccharide vaccine were discussed, and the need for further extensive clinical and field trials to demonstrate its range of effectiveness was stressed.

Age Factors↗

Epidemiology and prevention of pneumococcal infections.

There are comparatively few data on the incidence and morbidity from pneumococcal disease, which is greatly underestimated by case ascertainment from sterile site isolates alone. New diagnostic methods, such as serology and polymerase chain reaction, to detect components of the pneumococcal cell wall promise to significantly enhance detection of pneumococci causing childhood pneumonia. There is increasing evidence that excessive antibiotic use in children is a major factor promoting antibiotic resistance in pneumococci. Resistance is a problem worldwide and has focused attention on vaccine prevention. Fortunately, antibiotic-resistant pneumococci appear to belong to a limited range of serotypes, those commonly colonizing children, in all areas so far studied. If conjugate pneumococcal vaccines prove to eradicate carriage, immunization may be the major weapon against the spread of antibiotic-resistant pneumococcal infection. Conjugate pneumococcal vaccines are now being studied in large-scale efficacy trials with outcomes of bacteremia and otitis media, the results of which are eagerly awaited.

Bacterial Vaccines↗

Pneumococcal infection and vaccination in the elderly.

The burden of pneumococcal disease among elderly people is not widely known. In most countries, the annual incidence of invasive pneumococcal disease in elderly people is most probably >50 cases/100000 persons. Over the past 20 years, only the United States has used pneumococcal vaccine to any appreciable extent, yet among all vaccine-preventable diseases, pneumococcal infections account for the largest proportion of still unprevented illness in Western Europe. Retrospective studies show that vaccination prevents invasive pneumococcal disease. Pneumococcal vaccination appears to be more cost-effective than any other medical intervention commonly used in the elderly. As new data confirm the benefits of vaccination of the elderly against pneumococcal infections, vaccine use has increased in recent years associated with a decline in invasive disease.

Aged↗

The burden of severe pneumococcal infection in Ireland: potential effectiveness and indirect benefits of the 7-valent pneumococcal conjugate vaccine.

This study attempts to overcome the problem of under-reporting of serious pneumococcal infection in the Republic of Ireland by adding a proportion of 'unspecified' disease to pneumococcal disease reports. ICD-9 data for all age groups was collected on meningitis (from the National Disease Surveillance Centre), and septicaemia and pneumonia (from the Hospital In-Patient Enquiry system) for the year 1999. A 7-valent pneumococcal conjugate vaccine (PCV) has been shown to have significant effectiveness in the target paediatric age group and also indirect herd effects on the US adult population. The implications of these direct and indirect effects were applied to the epidemiology of serious pneumococcal infection in Ireland. The annual reported incidence rates for laboratory confirmed severe pneumococcal disease in Ireland in 1999 may underestimate both the morbidity and mortality of disease by 21% and 28% respectively. In all age groups 1,183 cases and 132 deaths may be prevented annually by the introduction of the vaccine. In addition, the vaccine provides an effective new tool for reducing disease caused by antibiotic resistant pneumococci thus assisting in the control of anti-microbial resistance in humans.

Age Distribution↗