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Altered expression of immune surface markers in children with recurrent infections of respiratory tract.

Infections of the respiratory tract are very common in young children. They may affect the quality of life and have a great economic impact. On the other hand, respiratory tract infections through MALT system play a positive role in the maturation and development of the immune system. The aim of the study was to examine quantitative and qualitative changes of T and B cells and granulocytes surface molecules in 24 children with recurrent (more than 8 episodes per year) infections of the respiratory tract and in 18 healthy children. The expression of CD2, CD3, CD4, CD8 on T cells; HLA-DR, CD19, CD5/CD20 on B cells, and CD11a/CD18, CD11b/CD18, CD62L, CD16 on granulocytes from peripheral blood was evaluated by a flow cytometry method. We observed a significant increase in the CD5+/CD20+ positive cells on B cells. We also observed a decreased expression of CD11c+/CD18+ cells, CD11a, and CD62L on granulocytes. The expression of other structures on lymphocytes and the CD11b/CD18+ on granulocytes remained unchanged. CD5+/CD20+ cells constitute a filogenetically old population responsible for the production of IgM of low specificity and affinity for specific antigens. The prevalence of this fetal phenotype population may be explained as a delayed maturation of the humoral immune system leading to increased susceptibility to infections. A lower percentage of CD11a may be related to the blockade of that molecule by rhinoviruses.

Antibody Formation↗

Management of respiratory syncytial virus with lower respiratory tract infection in infants and children.

Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infection in infants and children requiring pediatric hospitalizations. Infants with chronic lung, cardiac, or neuromuscular conditions are at increased risk for RSV infection. Early RSV is associated with subsequent diagnosis of reactive airway disease. The management of RSV with lower respiratory track infection in infants and children remains controversial. Bronchodilators may have some short-term benefit, but are not recommended as standard practice for infants and children. Antiviral therapy may be used for high-risk and severely ill patients. Corticosteroids may be effective in cases of moderate to severe RSV with lower respiratory track infection. Monoclonal antibodies have shown some promise in achieving passive immunity for those at greatest risk, including preterm infants younger than 1 year or infants younger than 2 years with chronic lung disease. Emergency management remains primarily supportive, with vigilant monitoring of oxygenation and hydration status. Interventions include supplemental oxygen therapy, ventilation, and fluid and nutrition therapy. Respiratory syncytial virus prophylaxis for high-risk patients includes intramuscular injections of palivizumab (Synagis) each month during RSV season, from November through April. Prevention strategies include washing hands, cleaning environment surfaces, and isolating infants and children with RSV in the emergency care area.

Adrenal Cortex Hormones↗

Respiratory syncytial virus infection in children hospitalised with acute lower respiratory tract infection.

BACKGROUND: Data are lacking on respiratory syncytial virus. (RSV) respiratory tract infections in children from developing countries. OBJECTIVE: To determine the importance of RSV as a cause of acute lower respiratory tract infection (ALRTI) in Cape Town children. METHODS: Children younger than 2 years of age admitted to hospital with ALRTI over a 15-month period from 1 June 1995 to 31 August 1996 were studied prospectively. Sociodemographic data, risk factors for severe RSV disease, clinical signs, diagnosis and hospital course were documented. A nasopharyngeal aspirate (NPA) for detection of RSV by enzyme immunoassay (EIA) was obtained in all cases. The NPA of every fifth child was sent for viral culture. RESULTS: A total of 1,288 patients (60% male, 40% female) with a median age (25th-75th percentile) of 6 months (2-11 months) was enrolled; 32.4 had one or more risk factors for severe RSV infection. Pneumonia was diagnosed in 62.2%, bronchiolitis in 20.6%, laryngotracheobronchitis (LTB) in 8% and other respiratory illnesses in 9.2%. Mild disease, requiring admission to an overnight ward, was documented in 38.1%, while 48.9% and 13% respectively had moderate and severe disease requiring admission to a general ward and intensive care unit (ICU). Supplemental oxygen and mechanical ventilation were required by 68.9% and 8.5% of patients, respectively. The median duration of hospital stay was 5 days (range 1-10 days). RSV EIA was positive in 16.4% of cases, and there was no difference in detection rates according to diagnosis. Viral culture performed in 162 of the 1,288 study patients (12.6%) grew RSV in 11.7% of cases, adenovirus in 3.7%, para-influenza virus type 3 in 2.5% and influenza B virus in 0.6%. Patients who tested RSV EIA-positive did not significantly differ from those who tested negative with regard to demographic variables, clinical diagnoses, risk factors for RSV or length of hospitalisation. The only significant difference noted was the presence of hyperinflation, which occurred in 70.1% of EIA-positive patients compared with 57.1% of those testing negative (P = 0.0005). The mortality rate (2%) was similar for both groups. CONCLUSION: This study indicates that RSV is an important cause of hospitalisation in infants and young children with ALRTI. Distinguishing RSV from other ALRTIs is difficult because of similarity in clinical presentation among children.

Data Interpretation, Statistical↗

Antibiotic prophylaxis for surgery for proximal femoral and other closed long bone fractures.

BACKGROUND: Antibiotic prophylaxis has been established policy for major surgical operations for many years. In fracture fixation, the effectiveness, and the duration of administration, have been a matter of debate. OBJECTIVES: To assess the effects of the prophylactic administration of antibiotics in patients undergoing surgical management of hip or other long bone fractures. SEARCH STRATEGY: We searched MEDLINE, EMBASE, Current Contents, Dissertation Abstracts, and Index to UK Theses, and bibliographies of identified articles. Trials were also obtained from the Cochrane Musculoskeletal Injuries Group trials register. Date of the most recent search: end of 1997. SELECTION CRITERIA PARTICIPANTS: Any patients with a hip or other closed long bone fracture undergoing surgery for internal fixation or replacement arthroplasty. INTERVENTIONS: Any regimen of systemic antibiotic prophylaxis administered at the time of surgery. OUTCOME MEASURES: Wound infection (deep and superficial), urinary tract infection, respiratory tract infection, adverse effects of prophylaxis, economic evaluations. DATA COLLECTION AND ANALYSIS: Both reviewers independently selected trials for inclusion, and assessed methodological quality and extracted data. Where possible, data were pooled and Peto odds ratios and absolute risk reductions, each with 95% confidence intervals, calculated. MAIN RESULTS: Twenty one randomised trials of only poor or moderate quality were included. The comparisons tested fell within six comparison groups, principally multiple dose or a single dose of antibiotic versus a placebo or no treatment. Antibiotic prophylaxis reduces wound, urinary and respiratory tract infections in patients undergoing surgery for closed fracture fixation. Economic modelling has indicated that this is a cost-effective intervention. There are limited data for the incidence of adverse effects, but as expected they appear to be more common in those receiving antibiotics. REVIEWER'S CONCLUSIONS: Antibiotic prophylaxis should be offered to those undergoing surgery for closed fracture fixation. On ethical grounds, further placebo controlled randomised trials of the effectiveness of antibiotic prophylaxis in closed fracture surgery are unlikely to be justified. Trials addressing the cost-effectiveness of different effective antibiotic regimens would need to be very large and may not be feasible.

Antibiotic Prophylaxis↗

Improving care for patients with respiratory tract infections.

The common respiratory tract infections of acute bacterial sinusitis, acute exacerbation of chronic bronchitis, and community-acquired pneumonia are responsible for millions of physician office visits every year. Despite advances in diagnostic testing and the development of new antimicrobial agents, these infections continue to contribute significantly to patient morbidity and mortality worldwide. Physicians are faced with multiple challenges in the management of patients with these diseases. These challenges include the selection of appropriate empiric therapy, the increasing emergence of resistant pathogens, patient noncompliance with therapeutic regimens, and the pressure to use cost-effective agents. Patients expect their antibiotics to work rapidly so that they can feel better quickly and return swiftly to their normal activities. Moxifloxacin has been developed to address many of these problems. Its efficacy has been demonstrated in an extensive clinical trial program the results of which are summarized below. The excellent pharmacokinetics and pharmacodynamics of moxifloxacin are covered elsewhere in this supplement, as is moxifloxacin's impressive safety and tolerability profile. Accordingly, this paper focuses on the clinical trial data currently available.

Anti-Infective Agents↗

Lower respiratory tract infections.

Although lower respiratory tract infections are frequently diagnosed in a primary care setting, they are still associated with a significant morbidity and mortality, which warrants a careful approach to treatment. Knowledge of the most common cause based on the age of the patient, location where the infection was acquired, and clinical presentation helps to direct empiric treatment. A few basic laboratory studies, especially a sputum Gram stain, can allow for more specific treatment. Identification of patients at increased risk for virulent organisms should make the primary care physician consider inpatient treatment along with an aggressive diagnostic workup and broad-spectrum antimicrobial treatment. Prevention should always be considered.

Acute Disease↗

Prevalence of Chlamydia pneumoniae in healthy children and in children with respiratory tract infections.

BACKGROUND: Chlamydia pneumoniae causes respiratory tract infections in adults, but little is known about its significance for acute or persistent respiratory tract infections in children. METHODS: We studied the prevalence of C. pneumoniae by polymerase chain reaction in children younger than the age of 11: 85 consecutive children with respiratory tract infections; and 93 children presumed to be healthy. Throat swabs for PCR analysis were taken from all children, and serology was done for 54 of the 85 sick children and from all but one of the presumed healthy children positive for C. pneumoniae by PCR. RESULTS: PCR was positive in 38 (45%) of the sick children and in 5 (5.7%) of the healthy children. All but 2 of 19 sick children with serologic findings suggesting recent or ongoing infection with C. pneumoniae were positive by PCR. Most children positive for C. pneumoniae by PCR had upper respiratory tract infections. Four children had recurrent respiratory tract infections and otitis media with effusion treated by tubal insertion. CONCLUSION: The findings suggest that C. pneumoniae is common among children with respiratory tract infections.

Age Factors↗

[Identification of strains on recurrent Haemophilus influenzae infections in patients with chronic respiratory tract infections].

Nontypable Haemophilus influenzae is one of the most important pathogenic bacteria in respiratory tract infections. H. influenzae is most frequently associated with recurrent infections in chronic respiratory tract infections (CRTIs). It is known that H. influenzae often reemerges after the antibiotic treatment has been stopped. We analyzed serotype, biotype, and the OMP patterns of H. influenzae isolates from sputum of CRTIs patients to determine whether an exacerbation is caused by an identical H. influenzae strain, or by a new H. influenzae strain. One hundred eighty nine strains of H. influenzae were obtained from 124 exacerbation from 24 patients. The first and second isolates were identical in 23 out of 33 exacerbations (< or = 15-days interval between each exacerbation) and also in 22 out of 34 exacerbations (15 < days but < or = 30-days interval between each exacerbation). This is called early recurrence. In contrast, the first and second isolates were different in 28 out of 34 exacerbations (> 30-days interval between each exacerbation). This is called late recurrence. These results suggest that early recurrence and late recurrence of recurrent H. influenzae infections occur in a different mechanism.

Adult↗

Immunology of viral respiratory tract infection in infancy.

Respiratory viruses such as respiratory syncytial virus (RSV), parainfluenza viruses (PIV) and the influenza viruses cause severe lower respiratory tract disease in infants and children throughout the world. We discuss the recent discovery of the epidemiologic importance of the human metapneumoviruses, first reported in 2001. Experimental live-attenuated vaccines for each of these viruses are being developed for intranasal administration in the first weeks or months of life. The immunology of these infections in humans is poorly defined but many studies are ongoing. A significant obstacle to successful immunisation of infants against respiratory-virus-associated disease early in life may be the relatively poor immune response of very young infants to primary virus infection. This paper reviews the immune correlates of protection against disease caused by these viruses, immune responses of infants to naturally acquired infection or experimental infection with candidate vaccine viruses and the genetics of susceptibility to severe disease.

Animals↗

Current issues on resistance, treatment guidelines, and the appropriate use of fluoroquinolones for respiratory tract infections.

BACKGROUND: Community-acquired respiratory tract infections comprise a large percentage of diseases treated by primary care physicians, and rates of antimicrobial use for respiratory tract infections are increasing. The fluoroquinolones comprise a drug class with broad-spectrum activity against many of the key pathogens associated with community-acquired respiratory tract infections, including Streptococcus pneumoniae, and other significant pathogens, such as Staphylococcus aureus and Pseudomonas aeruginosa. While fluoroquinolones have gained popularity, the settings for their appropriate use in treating respiratory tract infections remain unclear. OBJECTIVE: In this article, the mechanisms of fluoroquinolone resistance in S. pneumoniae, treatment guidelines, and the mode of spread of resistance are reviewed. METHODS: The authors conducted a MEDLINE search for articles published from 1990 to the present. Search terms included Streptococcus pneumoniae, fluoroquinolones, and resistance. Articles were selected for inclusion based on their relevance to the objective of this review. RESULTS: Although 3 sets of treatment guidelines for community-acquired pneumonia (CAP) currently exist in the United States, a consensus for the role of fluoroquinolones in the outpatient management of CAP has not been achieved. Factors mitigating for restraint in the outpatient use of fluoroquinolones include concern for the spread of resistance to "innocent-bystander" organisms, such as S. aureus and P. aeruginosa, as well as possible inappropriate "trickle-down" use for other, less severe respiratory syndromes, such as bronchitis. CONCLUSION: Although the fluoroquinolones are potent agents against respiratory pathogens and have a clearly defined role in the treatment of hospitalized patients with CAP, their optimal role in the outpatient management of respiratory tract infections remains controversial.

Anti-Infective Agents↗

A comparative study of the etiology of adult upper and lower respiratory tract infections in the community.

Lower respiratory tract infection and upper respiratory tract infection (URTI) are very common, but the etiology is not diagnosed in routine practice. The objective of this study was to determine and compare the frequency distribution of the various infectious etiologies for these diseases. One hundred seventy five adults in the community with febrile LRTI and 75 with febrile URTI were included in a purely serologically based prospective study. Paired sera were obtained for each of the patients and were tested by EIA or immunofluorescence methods to identify 14 different pathogens. Only a significant change in antibody titers between the paired sera was considered diagnostic. At least one infectious etiology was identified in 167 patients (67%). In the LRTI group, infection with at least one of 7 respiratory viruses was found in 88 patients (50%). One of the atypical pathogens was found in 40 patients (23%), of these Legionella spp. in 19 (11%) and Mycoplasma pneumoniae in 18 (10%). A bacterial etiology was found in 19 patients (11%), of these Streptococcus pneumoniae in 8 (5%) and beta-hemolytic streptococci group A in 5 (3%). The frequency distribution of etiologies in the URTI group was not significantly different from the LRTI group, except for M. pneumoniae that was identified in only one patient with URTI (p = 0.015). More than one etiologic agent was found in 42 (17%) of the patients. LRTI is caused by a broad spectrum of etiologies, with respiratory viruses predominating and a moderate, but significant, prevalence of atypical pathogens. The frequency distribution of etiologies for URTI is similar to LRTI. In a significant proportion of patients with URTI and LRTI there is serologic evidence of infection with more than one pathogen. The justification and benefit of distinguishing between URTI and LRTI in routine clinical work is doubtful. When a decision is reached to treat RTI patients with an antibiotic, it is logical to use a macrolide or tetracycline.

Adult↗

Do radiographic features of acute infection influence management of lower respiratory tract infections in the community?

Community-acquired lower respiratory tract infection (LRTI) is a common clinical problem, and a chest radiograph is the most common investigation. This study investigated why general practitioners (GPs) request radiographs and whether radiographic features of LRTI affect management. The 12 month study included GP-requested chest radiographs performed at the Manchester Royal Infirmary. The GPs of patients with radiographic evidence of LRTI were sent a questionnaire. Radiographs (n=2,538) were performed in patients aged >15 yrs. One hundred and eleven (4.4%) chest radiographs showed evidence of LRTI, and 97 (87%) were included in the analysis. Fifty-six (62%) had their radiograph requested at the second or third visit. Forty-five (58%) radiographs were performed to confirm infection. In 47 (48%) of cases the GP felt the radiograph had affected treatment. An effect on treatment was significantly more common in patients not receiving antibiotics prior to the radiograph. Twenty-nine (32%) of GPs felt a normal radiograph would have affected management, most often with respect to antibiotic prescriptions (17 (58%)). Where the radiologist's report suggested a repeat radiograph or hospital referral, this was significantly more likely to have occurred. The commonest reason for a radiograph in patients with suspected lower respiratory tract infection is to confirm the infection. In the opinion of the general practitioner the results of the radiograph do affect patient treatment. The wording of the radiologists report is associated with patient management.

Acute Disease↗

Pediatric Investigators Collaborative Network on Infections in Canada (PICNIC) study of admission and management variation in patients hospitalized with respiratory syncytial viral lower respiratory tract infection.

OBJECTIVE: To describe differences in patients hospitalized with respiratory syncytial virus (RSV) lower respiratory tract infection (LRI) at nine Canadian tertiary care hospitals. In addition, this study describes the variation in use of drug and other interventions. METHODS: Data on patients hospitalized with RSV LRI and their outcomes were prospectively collected. Demographic data were obtained on enrollment by center study nurses. Data recorded daily included clinical assessment, oxygen saturation determination, and interventions (bronchodilators, steroids, ribavirin, antibiotics, intensive care, and mechanical ventilation) received during the day. Patients were divided into those with underlying diseases including congenital heart disease, chronic lung disease, immunodeficiency, or multiple congenital anomalies and those who were previously healthy. Mean RSV-associated length of stay and the proportion of patients receiving each intervention in each group were determined by hospital. RESULTS: A total of 1516 patients were enrolled at nine hospitals during January 1 to June 30, 1993, and January 1 to April 30, 1994. Significant differences were observed among hospitals in the proportion of patients with underlying disease, postnatal age less than 6 weeks, hypoxia, and pulmonary infiltrate on chest radiograph. The mean length of stay varied among hospitals from 8.6 to 11.8 days and 4.6 to 6.7 days in compromised and previously healthy patients, respectively. Except for receipt of bronchodilators, compromised patients were significantly more likely to receive interventions than previously healthy patients. There was variation among hospitals in receipt of most interventions in compromised and previously healthy patients. This variation was statistically significant for previously healthy patients but not statistically significant in those with underlying disease, because the numbers of patients in the latter group were much smaller. The magnitude of the variation for each intervention, however, was not different between those with underlying disease compared with previously healthy patients. CONCLUSION: Differences exist among tertiary pediatric hospitals in the nature of the patients admitted with RSV LRI. Variation occurred in the use of five interventions among the hospitals, regardless of whether the patient had underlying illness or was previously healthy. Given their current widespread use, high cost, and potential side effects, randomized clinical trials are needed to determine the efficacy of different drug treatments used to treat infants hospitalized with RSV.

Adrenal Cortex Hormones↗