Pulmonary infections: what to do when it's a bug that you do not know.
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Anti-Bacterial Agents↗
Biomedical subjects
A Ortqvist
Publications and source records attributed to A Ortqvist.
Treatment of community-acquired lower respiratory tract infections in adults.
Community-acquired lower respiratory tract infection (LRTI) is a common cause of acute illness in adults. The spectrum of disease ranges from a mild mucosal colonisation or infection, acute bronchitis or acute exacerbation of chronic bronchitis/chronic obstructive pulmonary disease (AE-CB/COPD), to an overwhelming parenchymal infection with the patient presenting with severe community-acquired pneumonia (CAP). Although the great majority of LRTIs are self-limiting viral infections, CAP is most often a bacterial disease with a substantial mortality. Thus, antibiotic treatment is rarely indicated for acute bronchitis and is only indicated for the more severe cases of AE-CB/COPD, but it is nearly always indicated for CAP, for which a delay in treatment may increase the risk of a fatal outcome. It may be difficult to differentiate between a viral and a bacterial LRTI, or between bronchitis/AE-CB/COPD and CAP. This may be one reason why antibiotics are prescribed to more than two-thirds of patients with LRTIs in Europe and the USA. Considering the worldwide development of antibiotic resistance, this is not an acceptable situation. Since an empirical approach is nearly always necessary in the management of LRTI, greater emphasis must be placed on the decision of whether or not to prescribe an antibiotic at all. This decision should be based on an assessment of the severity of the disease, including underlying risk factors, and on markers for bacterial/parenchymal/ invasive LRTI. The choice of empirical therapy must be based on the same data together with epidemiological information. The choice of antibiotic must always cover Streptococcus pneumoniae, which remains the main pathogen of morbidity and mortality in CAP. In hospital, attempts should be made to obtain an aetiological diagnosis in order to be able to switch to a specific treatment or to evaluate a failure of empirical therapy. Several guidelines for the management of community-acquired pneumonia have been published during the last 10 yrs. Some reports indicate that the implementation of such guidelines has resulted in lowered costs, length of stay in hospital and mortality. However, the results from these studies are not consistent and the evidence is still weak.
Adult↗
Negligible adjuvant effect for antibody responses and frequent adverse events associated with IL-12 treatment in humans vaccinated with pneumococcal polysaccharide.
To assess whether co-administration of recombinant human IL-12 (rhIL-12) and 23-valent pneumococcal polysaccharide vaccine (PPV) enhances the antibody response to this T cell-independent antigen, healthy immunocompetent volunteers (n=34, 55-65 years old) were vaccinated intramusculary with PPV and concurrently-treated subcutaneously with either rhIL-12 (1 or 4 microg) or placebo. The increases of total anti-pneumococcal IgG antibodies were numerically higher among the rhIL-12 recipients compared with placebo recipients, but the difference was not significant. The rhIL-12 recipients had a high incidence of local and systemic side effects. Given the lack of convincing evidence that rhIL-12 enhances the antibody response to PPV, the frequency and severity of the side effects was unacceptable.
Adjuvants, Immunologic↗
Dynamics of penicillin-susceptible clones in invasive pneumococcal disease.
In a 10-year period, 1987-1997, there was a >4-fold increase in the rate of pneumococcal bacteremia in Sweden. Invasive pneumococcal isolates (n=1136), which were obtained from 18 Swedish clinical microbiology laboratories from 1987 through 1997, and other national and international isolates were serotyped, and their clonal relationships were determined by molecular typing. The increase in invasive pneumococcal disease in Sweden during this period was associated particularly with an increase in isolates of serotypes 1 and 14. A 3-fold increase of type 14 was seen from 1987 through 1992, and a 10-fold increase of type 1 occurred from 1992 through 1997. One dominating penicillin-susceptible clone of type 14 was responsible for the increase of type 14 during the first 5 years. This clone also was found in Canada and the United States and was shown by multilocus sequence typing to correspond to a previously identified hyper-virulent clone. A novel penicillin-susceptible clone of type 1, which was not found among invasive isolates from 1987 or 1992, was responsible for the increase of serotype 1 during the last 5 years. These results illustrate the ability of virulent penicillin-susceptible pneumococcal clones to emerge and spread rapidly within a country.
Alleles↗
Effects of a large-scale intervention with influenza and 23-valent pneumococcal vaccines in adults aged 65 years or older: a prospective study.
BACKGROUND: The effectiveness of influenza and pneumococcal vaccination in the prevention of hospital admissions and death has not been assessed prospectively. We have therefore examined the effects of influenza and pneumococcal vaccination in individuals aged 65 years and older in a 3-year prospective study, between Dec 1, 1998 and May 31, 1999. METHODS: All individuals in Stockholm County aged 65 years or older (259,627) were invited to take part in a vaccination campaign against influenza and pneumococcal infection. We recorded for all vaccine recipients (100,242) name, and date of birth, and whether they had been given both or one of the vaccines. All individuals (> or = 65 years) admitted to hospital in Stockholm County with influenza and pneumonia related diagnoses were identified between Dec 1, 1998, and May 31, 1999. FINDINGS: The incidence (per 100,000 inhabitants per year) of hospital treatment was lower in the vaccinated than in the unvaccinated cohort for all diagnoses: 263 versus 484 (-46% [95% CI 34-56]) for influenza; 2199 versus 3097 (-29% [24-34)) for pneumonia; 64 versus 100 (-36% [3-58]) for pneumococcal pneumonia; and 20 versus 40 (-52% [1-77]) for invasive pneumococcal disease. The total mortality was 57% (55-60) lower in vaccinated than in unvaccinated individuals (15.1 vs 34.7 deaths per 1000 inhabitants). INTERPRETATION: These findings show that general vaccination leads to substantial health benefits and to a reduction of mortality from all causes in this age group.
Aged↗
Clinical isolates of Streptococcus pneumoniae that exhibit tolerance of vancomycin.
The ability of Streptococcus pneumoniae to escape lysis and killing by vancomycin, a property termed "tolerance," has recently been noted in a laboratory strain of the species. Vancomycin tolerance in clinical isolates represents a potential new health risk. We determined the prevalence of vancomycin and penicillin tolerance among 116 clinical isolates of pneumococci by monitoring lysis and viability after exposure to the respective antibiotic for 4 hours. Eight percent of the strains were tolerant to penicillin and 3% were tolerant to vancomycin. The 3 vancomycin-tolerant isolates also had a high ratio of minimum bactericidal concentration to minimum inhibitory concentration, in contrast to nontolerant strains. They were of serotype 9V and had reduced susceptibility to penicillin. Only 1 was also tolerant to penicillin. Growth rate and ability to divide were not affected in the 3 vancomycin-tolerant strains, and they all lysed with deoxycholate, which indicates autolysin production. Vancomycin tolerance among clinical isolates of pneumococci will necessitate tracking to determine the magnitude of the evolving health risk, since tolerance may contribute to treatment failure (in particular, cases of meningitis, in which bactericidal activity is critical for eradication) and since it may also be a favored background for acquisition of resistance of vancomycin.
Amino Acid Sequence↗
Changes in serotype distribution may hamper efficacy of pneumococcal conjugate vaccines in children.
During the last 10 y we have observed an increased incidence of pneumococcal bacteremia in Sweden. In order to study the serotype distribution over time we collected 1136 invasive pneumococcal isolates from 1987, 1992 and 1997 from Swedish microbiological laboratories. Currently, new pneumococcal conjugate vaccines are being considered for introduction in the general childhood vaccination program in several countries, including Sweden. We studied the potential vaccine coverage rate for the new conjugate vaccines among our Swedish invasive isolates. We found that the serotype distribution fluctuated with time and observed a surprisingly low potential coverage rate for the 7-valent vaccine in Sweden, in contrast to other countries. Therefore we argue that pneumococcal conjugate vaccines have to be tailored to suit current, local serotype patterns and most likely will need to be changed over time.
Adolescent↗
Pneumococcal vaccination: current and future issues.
Infection with Streptococcus pneumoniae remains a major global health burden meaning the development of effective vaccines is urgently needed. The current 23-valent polysaccharide vaccine has been shown to prevent pneumococcal pneumonia in immunocompetent young adults, but not in elderly persons. However, in prevention of invasive pneumococcal disease, the vaccine is efficacious in the elderly and may also be effective in some groups of immunocompromised patients. The polysaccharide vaccine is, therefore, recommended in all older (> or = 55-65 yrs of age) adults and in young children (>2 yrs of age) who have a high risk for pneumococcal disease. Revaccination can be safely performed and is recommended 5 yrs after the first dose. In children <2 yrs of age, the new polysaccharide-protein conjugate vaccines, including 7-11 serotypes, seem to be effective in the prevention of invasive disease, severe pneumonia and serotype-specific (and vaccine-related types) otitis media. The low serotype coverage, need for repeated doses, and high price, may decrease the usefulness of the new conjugates. However, the included serotypes correspond to those most often associated with penicillin resistance and vaccination is, therefore, a possible tool in limiting the spread of antibiotic-resistant pneumococci.
Adolescent↗
[Vaccination of the elderly against pneumococcal disease is cost-efficient. Mass vaccination of all aged 65 and over is recommended].
The pneumococcal vaccine has been shown to be about 70 percent efficacious in preventing invasive pneumococcal disease in elderly persons. In a European multicenter study, pneumococcal vaccination was moderately cost-effective in preventing hospital admission due to invasive pneumococcal disease in persons 65 years of age or above. In Sweden the cost was approximately 300,000 SEK per quality adjusted life years (QALY) gained, but only about 60,000 SEK per QALY in a two-way sensitivity analysis making reasonable assumptions regarding the incidence and mortality of invasive pneumococcal disease in this age group. On the basis of these findings, pneumococcal vaccination should be recommended for all persons 65 years of age or older.
Aged↗
Cost-effectiveness of pneumococcal vaccination of older people: a study in 5 western European countries.
Pneumococcal vaccination of older persons is thought to be cost-effective in preventing pneumococcal pneumonia, but evidence of clinical protection is uncertain. Because there is better evidence of vaccination effectiveness against invasive pneumococcal disease, we determined the cost-effectiveness of pneumococcal vaccination of persons aged > or =65 years in preventing hospital admission for both invasive pneumococcal disease and pneumococcal pneumonia in 5 western European countries. In the base case analyses, the cost-effectiveness ratios for preventing invasive disease varied from approximately 11,000 to approximately 33,000 European currency units (ecu) per quality-adjusted life year (QALY). Assuming a common incidence (50 cases per 100,000) and mortality rate (20%-40%) for invasive disease, the cost-effectiveness ratios were <12,000 ecu per QALY in all 5 countries. For preventing pneumococcal pneumonia, vaccinating all elderly persons would be highly cost-effective to cost saving. Public health authorities should consider policies for encouraging pneumococcal vaccination for all persons aged > or =65 years.
Aged↗
Prospective study of prognostic factors in community-acquired bacteremic pneumococcal disease in 5 countries.
To define the influence of prognostic factors in patients with community-acquired pneumococcal bacteremia, a 2-year prospective study was performed in 5 centers in Canada, the United States, the United Kingdom, Spain, and Sweden. By multivariate analysis, the independent predictors of death among the 460 patients were age >65 years (odds ratio [OR], 2.2), living in a nursing home (OR, 2.8), presence of chronic pulmonary disease (OR, 2.5), high acute physiology score (OR for scores 9-14, 7.6; for scores 15-17, 22; and for scores >17, 41), and need for mechanical ventilation (OR, 4.4). Of patients with meningitis, 26% died. Of patients with pneumonia without meningitis, 19% of those with >/=2 lobes and 7% of those with only 1 lobe involved (P=.0016) died. The case-fatality rate differed significantly among the centers: 20% in the United States and Spain, 13% in the United Kingdom, 8% in Sweden, and 6% in Canada. Differences of disease severity and of frequencies and impact of underlying chronic conditions were factors of probable importance for different outcomes.
Aged↗
Molecular epidemiology of Streptococcus pneumoniae causing invasive disease in 5 countries.
A multicenter study was done during 1993-1995 to investigate prospectively the influence of several prognostic factors for predicting the risk of death among patients with pneumococcal bacteremia. Five centers located in Canada, the United Kingdom, Spain, Sweden, and the United States participated. Clinical parameters were correlated to antibiotic susceptibility and serotyping of the 354 invasive pneumococcal isolates collected and to molecular typing of 173 isolates belonging to the 5 most common serotypes (14, 9V, 23F, 3, and 7F). Serotype 14 was the most common among all isolates, but serotype 3 dominated in fatal cases and in isolates from Spain and the United States, the countries with the highest case-fatality rates. Fewer different patterns were found among the type 3 isolates, which suggests a closer clonal relationship than that among isolates belonging to other serotypes. Of type 3 isolates from fatal cases, 1 clone predominated. Other penicillin-susceptible invasive clones were also shown to spread in and between countries.
Adult↗
Recurrence of pneumonia in relation to the antibody response after pneumococcal vaccination in middle-aged and elderly adults.
We have recently studied the efficacy of pneumococcal vaccine in preventing pneumonia recurrences after hospital treatment for community-acquired pneumonia in non-immunocompromised patients aged 50-85 y. Among these patients, we have now compared the antibody response to the pneumococcal vaccine between patients who developed pneumonia (n = 50) and patients without pneumonia recurrences (n = 100), during a mean follow-up period of 32 months after vaccination. The antibody levels of 5 pneumococcal serotypes were measured before, and 4 weeks, 1 y and 3 y after vaccination. A lower risk of pneumonia recurrences was seen in patients with antibody fold increases (FIs) > 4 from pre-vaccination to post-vaccination compared with patients with lower FIs (p = 0.02). The results suggest that in this patient category, the antibody response to pneumococcal vaccination is of importance for the risk of pneumonia recurrence.
Aged↗
Pneumococcal disease in Sweden: experiences and current situation.
During the last decade, the incidence of invasive pneumococcal disease in Sweden has risen, seemingly due chiefly to an increasing incidence of pneumococcal bacteremia among the elderly. On the other hand, mortality due to invasive disease in Sweden is low, approximately 10% for bacteremic pneumococcal pneumonia. Beta-lactam resistance in Streptococcus pneumoniae is still a relatively minor problem in Sweden, with only 3%-4% of strains demonstrating decreased susceptibility to penicillin. However, local outbreaks of pneumococcal disease with up to 10% resistance have occurred among children, especially in southern Sweden.
Adolescent↗
[The elderly should be vaccinated against pneumococci].
Invasive pneumococcal diseases are associated with substantial mortality in the elderly. The incidence of such diseases, particularly that of bacteraemic pneumococcal pneumonia, has increased in Sweden during the past decade. At the same time, there is a growing problem with beta-lactam-resistant and multiresistant pneumococci in many nearlying countries. Although pneumococcal vaccine probably provides only limited protection against pneumococcal pneumonia in the elderly, it yields approximately 70 per cent protection against invasive pneumococcal disease. Pneumococcal vaccination should therefore be recommended to all those 65 years old and above, and a nationwide strategy developed to implement good coverage in the age group.
Aged↗
In-hospital management of adults who have community-acquired pneumonia.
The initial in-hospital management of adult patients with community-acquired pneumonia can be divided into five major steps: an early recognition of the patient with presumptive pneumonia, assessment of the severity of illness, establishment of an etiologic diagnosis, supportive therapy, and decision regarding initiation of empirical therapy. In most European recommendations, the empirical antibiotic treatment is directed against "the most likely pathogen," based on epidemiological, clinical, and laboratory data, and on the severity of illness. In contrast, newer North American guidelines have focused on the severity of illness of community-acquired pneumonia. As a consequence, the use of a broader initial antibiotic coverage, including extended-spectrum cephalosporins and combinations, seems to be more common in North America than in Europe.
Adult↗
Randomised trial of 23-valent pneumococcal capsular polysaccharide vaccine in prevention of pneumonia in middle-aged and elderly people. Swedish Pneumococcal Vaccination Study Group.
BACKGROUND: We assessed the effectiveness of a 23-valent pneumococcal vaccine in the prevention of pneumococcal pneumonia and of pneumonia overall in non-immunocompromised middle-aged and elderly people. METHODS: The prospective, multicentre, double-blind, randomised, placebo-controlled trial was carried out across departments of infectious diseases at six tertiary-care or university hospitals in Sweden. 691 non-immunocompromised patients aged 50-85 years who had been treated as inpatients for community-acquired pneumonia (CAP) were randomly assigned either 23-valent pneumococcal capsular polysaccharide vaccine or placebo (sodium chloride). We used Cox regression models to estimate the relative risks of pneumonia overall and pneumococcal pneumonia for the placebo group compared with the vaccine group. FINDINGS: 63 (19%) of 339 patients in the vaccine group and 57 (16%) of 352 patients in the placebo group developed a new pneumonia, corresponding to a relative risk over time for the placebo group compared with the vaccine group of 0.83 (95% CI 0.58-1.12, p=0.31). Pneumococcal pneumonia was diagnosed in 16 (4.5%) patients in the placebo group and in 19 (5.6%) in the vaccine group, corresponding to a relative risk for the placebo group of 0.78 (95% CI 0.40-1.51, p=0.45). We found no difference in the death rate between the two study groups. INTERPRETATION: The 23-valent pneumococcal polysaccharide vaccine did not prevent pneumonia overall or pneumococcal pneumonia in middle-aged and elderly individuals.
Aged↗
[X-ray check up after pneumonia. "A healthy approach" helps in new diagnosis].
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Follow-Up Studies↗