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A total of 2081 adult patients with community-acquired lower respiratory tract infections participated in Phase III clinical trials of sparfloxacin. A total of 1040 patients were randomised to sparfloxacin and 1041 patients received a comparator regimen. Sparfloxacin was administered as a 400 mg loading dose on day 1 followed by 200 mg once daily to patients with community-acquired pneumonia and as a 200 mg loading dose on day 1 followed by 100 mg daily to patients with acute exacerbations of chronic obstructive pulmonary disease. Comparator regimens were amoxycillin/clavulanic acid 500/125 mg tid, amoxycillin 1000 mg tid, a combination of amoxycillin 1000 mg tid plus ofloxacin 200 mg bid or erythromycin 1000 mg bid. The incidence of adverse events, the incidence and severity of antibacterial-related adverse events and the incidence of antibacterial discontinuation due to adverse events were no different among patients treated with sparfloxacin compared with those who received a comparator antibacterial agent. Sparfloxacin appears to be as well tolerated as other oral antibacterial regimens commonly used to treat lower respiratory tract infections.
BACKGROUND: There is growing interest in the role of infections in the aetiology of acute myocardial infarction (AMI). We undertook a large, population-based study to explore the association between risk of AMI and recent acute respiratory-tract infection. METHODS: We used data from general practices in the UK (General Practice Research Database). Potential cases were people aged 75 years or younger, with no history of clinical risk factors, who had a first-time diagnosis of AMI between Jan 1, 1994, and Oct 31, 1996. Four controls were matched to each case on age, sex, and the practice attended. The date of the AMI in the case was defined as the index date. For both cases and controls the date of the last respiratory-tract infection before the index date was identified. We also did a case-crossover analysis of cases who had an acute respiratory-tract infection either before the index date or before an arbitrarily chosen date (1 year before AMI). FINDINGS: In the case-control analysis of 1922 cases and 7649 matched controls, significantly more cases than controls had an acute respiratory-tract infection in the 10 days before the index date (54 [2.8%] vs 72 [0.9%]). The odds ratios, adjusted for smoking and body-mass index, for first-time AMI in association with an acute respiratory-tract infection 1-5, 6-10, 11-15, or 16-30 days before the index date (compared with participants who had no such infection during the preceding year) were 3.6 (95% CI 2.2-5.7), 2.3 (1.3-4.2), 1.8 (1.0-3.3), and 1.0 (0.7-1.6); (test for trend p<0.01). The case-crossover analysis showed a relative risk of 2.7 (1.6-4.7) for AMI in relation to an acute respiratory-tract infection in the 10 days before the index date. INTERPRETATION: Our findings suggest that in people without a history of clinical risk factors for AMI, acute respiratory-tract infections are associated with an increased risk of AMI for a period of about 2 weeks. We cannot, however, completely exclude the possibility of misdiagnosis bias, if prodromal symptoms of AMI were mistaken for respiratory-tract infection.
The aim of this study was to compare the clinical course of severe lower respiratory tract infections associated with human parainfluenza virus types 1-3 (HPIV 1-3) in hospitalised children infected with the human immunodeficiency virus type 1 (HIV-1) versus that in hospitalised children not infected with HIV-1. Children were enrolled prospectively as part of a broader study that evaluated the aetiology of lower respiratory tract infections in HIV-1-infected and -noninfected children from March 1997 through March 1999. HPIV types 1-3 were isolated from nasopharyngeal aspirate samples that were analysed using immunofluorescein monoclonal antibody assays. Thirty percent (24 of 80) of the children from whom HPIV was isolated were infected with HIV-1. Sixty-six percent (47 of 62) and 22% (14 of 62) of the HPIV isolates that were typed were subtypes 3 and 1, respectively. The clinical presentation of severe lower respiratory tract infection was similar in both HIV-1-infected and -noninfected children, except that the former were less likely to have wheezing (4.2% vs. 28.6%, P=0.01). Furthermore, the duration of hospitalisation was longer in HIV-1-infected children than in HIV-1-noninfected children (median 11.5 days [range 1-15 days] vs. median 7.5 days [range 1-22 days]; P=0.02), and mortality was higher (5 of 24 [20.8%] infected children vs. 0 of 56 noninfected children; P=0.001). Importantly, four of five (80%) of the HIV-1-infected children who died had other concurrent illnesses or predisposing factors for severe HPIV-associated disease. HPIV-associated lower respiratory tract infection causes greater morbidity and mortality in HIV-1-infected children than in HIV-1-noninfected children; however, this may be due to other concurrent illnesses in HIV-1-infected children.
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PURPOSE OF REVIEW: Most studies on the natural history of viral upper respiratory tract infections and their complications rely for ascertainment on self-assessed cold/flu illness or the identification of presumed complications. The criteria for cold/flu definition, however, are variable within and between individuals and illness is not prerequisite for a viral upper respiratory tract infection. These factors bias estimates of the incidence and prevalence of viral upper respiratory tract infections and their complications. Here we review new methodologies that can be adapted for use in future studies to refine those estimates. RECENT FINDINGS: We present a theoretical basis for standardized assignment of cold/flu episodes using a minimal algorithm template that operates on a structured set of symptoms/signs. We emphasize the greater accuracy of information derived from longitudinal studies that incorporate identification algorithms and assay of nasal secretions for causal virus by polymerase chain reaction and for proinflammatory chemicals to confirm nasal inflammation. SUMMARY: The methodologies and sampling strategies that we describe hold promise for better characterizing the incidence of complications for symptomatic and asymptomatic expressions of a viral upper respiratory tract infection caused by specific viruses. These data can then be used to estimate the efficacy and efficiency in a specified target population of prophylactic or intercurrent treatments to prevent the complications.
Children infected with Chlamydia pneumoniae sometimes experience lower respiratory tract infections such as pneumonia and bronchitis. Although numerous anti-microbial compounds have been reported to be active against the organism, most of them have not been in a clinical trial in infants and children with C. pneumoniae infection. Clarithromycin has been shown to express anti-chlamydial effects in vitro. In this study, we evaluated the clinical anti-C. pneumoniae properties of clarithromycin in children with mainly lower respiratory tract infection. We administered clarithromycin orally to 21 infants and children at a dose of 10-15 mg/kg/day divided into two or three doses for 4-21 days. Clinical symptoms, roentgenographic and laboratory abnormal findings improved. The overall clinical efficacy rate was 85.7% (18 of 21 cases). Administration of clarithromycin was considered to be a suitable treatment for improving lower respiratory infections in infants and children caused by C. pneumoniae.
The efficacy rate, minimal inhibitory concentrations (MICs), and resistance of fluoroquinolone agents against causative organisms in respiratory tract infections from January to March, 1988 were investigated. Of 333 pathogenic strains 85% consisted of 5 major causative organisms of respiratory tract infection (Haemophilus influenzae, Pseudomonas aeruginosa, Streptococcus pneumoniae, Branhamella catarrhalis, and Staphylococcus aureus). In 61 (59 cases) of these 333 strains, including 3 cases of acute pharyngitis, 5 of acute bronchitis, 3 of pneumonia, and 48 of chronic lower respiratory tract infection fluoroquinolone agents were administered. The efficacy rate was 76.3% in all cases, and 75% in cases with chronic lower respiratory tract infection. The fluoroquinolone agents were 100% effective in H. influenzae and B. catarrhalis, though the efficacy rate was 67% in S. aureus and 40% in P. aeruginosa. The susceptibility of all strains to fluoroquinolone agents were investigated. There was no resistant strain in H. influenzae and B. catarrhalis, though resistant strains to fluoroquinolone agents have increased in S. aureus and P. aeruginosa. The efficacy rate was investigated using the MIC of administered fluoroquinolone agent against causative organisms. It is surmised that the efficacy of that agent has an MIC of 1.56-3.13 micrograms/ml.
The effectiveness and outcomes of an educational program to decrease ribavirin and antimicrobial prescribing rates and associated costs for patients with respiratory syncytial virus (RSV) lower-respiratory-tract infection are described. An educational program on the appropriate treatment for RSV infections was conducted for attending physicians and medical residents with multiple methods and forums during the 1994-95 RSV season. A retrospective chart review of 2396 patients admitted to a pediatric teaching hospital from July 1, 1991, through June 30, 1998, was conducted to measure the frequencies of ribavirin and antimicrobial prescribing in infants and young children hospitalized with RSV lower-respiratory-tract infection. The results before and after the educational program were compared. Ribavirin was prescribed for 37.9% of patients before the program, and only 9.0% received it afterward (p < 0.001). Before the program, 24.8% of patients with no risk factors received ribavirin compared with 1.6% of patients after the program (p < 0.001). However, more patients with three or more risk factors for morbidity and mortality received ribavirin before the program than afterward (97.8% versus 39.2%, respectively). A broad-spectrum i.v. antimicrobial was prescribed for 85.6% of patients before the program while 60.6% received one afterward (p < 0.001). The cost savings for ribavirin and antimicrobials during the three-year period after the program were $1,235,484 and $34,839, respectively. Hospital length of stay decreased from 5.6 to 5.1 days (p < 0.001). No readmissions occurred during the study period. A multifaceted educational intervention program may have been somewhat effective in modifying physician's prescribing habits for the treatment of RSV lower-respiratory-tract infection.
Streptococcus pneumoniae is still the most important pathogen of community-acquired respiratory tract infections. During the last decades in many countries an increase in the spread of antibiotic resistant strains (e. g. against beta-lactams, macrolides, tetracyclin) was observed. Resistance against penicillin is often associated with resistance against macrolides and other antibiotic classes. In Germany surveillance studies including isolates from patients with community-acquired respiratory tract infections have shown that about 14 % of strains show a reduced susceptibility against penicillin (MIC-values 0.12 - 1 mg/L) and up to 4 % are highly resistant against penicillin (MIC >/= 2 mg/L). Resistance against tetracycline or macrolides was detected in up to 12 and 15 % of strains, respectively. According to the treatment guidelines of the Paul-Ehrlich-Gesellschaft für Chemotherapie and the Deutschen Atemwegsliga penicillins and cephalosporins are recommended as first line antibiotics for the treatment of community-acquired respiratory tract infections. As pneumococcal strains with reduced susceptibility against penicillin show often also a reduced susceptibility against cephalosporins the questions arises which beta-lactam antibiotics should still be used in empirical treatment of such strains. beta-Lactam-antibiotics highly differ in their in-vitro-activity against S. pneumoniae and their pharmacokinetic properties. In different models is has been demonstrated for beta-lactams that an adequate clinical and bacteriological efficacy is achievable when the serum levels of the free, i. e. not protein bound fraction of drug exceeds the MIC of the pathogen for at least 40 to 50 % of the dosing interval (T > MIC). In a clinical situation where pneumococci with reduced susceptibility against penicillin cannot be ruled out, only beta-lactam antibiotics with favourable pharmacological properties (good in-vitro activity, high and long lasting serum levels) should be used for treatment.
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OBJECTIVE: To review the literature on mannose-binding lectin (MBL) polymorphisms and susceptibility for upper respiratory tract infection (URI) in children and adolescents. DATA SOURCES: We searched PubMed from 1966 and EMBASE from 1974 to July 2005, using the terms respiratory tract infection, respiratory infection, upper respiratory infection, MBL, and mannose-binding lectin. STUDY SELECTION: Initially, 110 studies were identified. Two reviewers independently screened identified titles and abstracts. Potentially relevant studies were obtained and the full text examined. Inclusion criteria were human subjects, 18 years or younger, URI, and MBL polymorphisms. Seven of the initially identified studies met the inclusion criteria. DATA EXTRACTION: Information was gathered for each study on study design, population, possible confounders, and outcomes measured. DATA SYNTHESIS: Because there was significant heterogeneity between the identified studies, we had to describe the identified studies separately. The largest case-control studies (n = 3) as well as the cohort study (n = 1) suggest an association between MBL polymorphisms and URI, especially in young children. Results of the smaller studies (n = 3) are inconsistent. CONCLUSIONS: The association between MBL polymorphisms and URI in children remains controversial. Large prospective cohort studies with regular documentation of URI and possible confounders such as atopy and environmental factors are required to establish the role of MBL polymorphisms in susceptibility for URI.
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This study investigated histamine concentration in nasal secretions from children who had viral respiratory tract infection. It demonstrated that (1) there may be appreciable histamine in nasal secretions during viral respiratory tract infection; (2) concentration of histamine in serum may be elevated at the same time; and (3) children with past medical or family history of atopy had more histamine in nasal secretions during viral infections than did nonatopic children.
Forty patients with chronic respiratory infections were randomly assigned to 2 groups to compare the effect of once daily administration of 300 mg each and 3 times daily administration of 600 mg each of ofloxacin (OFLX). Twenty patients were administered with 300 mg OFLX a day and 18 cases received 600 mg. The number of underlying diseases in the 300 mg group was greater than that in the 600 mg group. The ratios of general amelioration of clinical symptoms were 80.0% in the 300 mg group and 88.9% in the 600 mg group. For bacteriological effects, the eradication rate was 80.0% in the 300 mg group and it was 84.6% in the 600 mg. The incidence of side effects in the 300 mg group was 0% and that of the 600 mg group was 5.6% (1 patient) but the symptom was mild. The incidence of abnormal laboratory test results was 15.0% in the 300 mg group and it was 11.2% in the 600 mg group, but all of these abnormalities were slight and transient. The safety rates in the 300 mg and the 600 mg groups were 95.0% and 94.4%, respectively. Efficacy rates in the 300 mg and the 600 mg groups were 80.0% and 88.9%, respectively. There was no statistically significant difference in all the results between the 2 treatment groups, and the both treatments were highly effective. From the above results, we consider that once daily administration of 300 mg is a useful therapy in respiratory tract infections.