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[Managing lower respiratory tract infections in immunocompetent patients. Definitions, epidemiology, and diagnostic features].

Particular attention is given to lower respiratory tract infections because of their frequency and potential severity. These infections represent a major cause of death worldwide and pneumonia remains the first cause of death from infectious origin in France. Three nosological entities are usually described according to the anatomic localization of the infectious process: acute bronchitis, pneumonia, and bronchopneumonia (if the infection involves the bronchial tree and the lung parenchyma). If bronchial infection occurs within the context of a chronic respiratory tract disease, it is called acute decompensation of chronic lung disease (usually chronic obstructive pulmonary disease). The major diagnostic difficulties are to be able to confirm alveolar implication in the infectious process and to determine the pathogenic agent(s) responsible for the clinical pattern. This information is essential for subsequent care depends. Apart from clinical examination, essential in this context, only chest-X-rays can be of any help to confirm alveolar involvement in the disease process. On the contrary, the interest of systematic microbiological confirmation and its value according to various techniques and swab conditions may be questioned for the clinical diagnosis. Microbiological confirmation does not seem essential in every case. The feasibility and relevance of microbiological techniques must be determined before any decision is taken on documentation. The microbiological documentation value depends on its yield and sensitivity profile in identifying the pathogen.

France↗

Do delayed prescriptions reduce antibiotic use in respiratory tract infections? A systematic review.

BACKGROUND: There is concern about the increasing resistance of antibiotics to common bacteria. Delayed prescribing for respiratory tract infections is a strategy that may reduce the use of antibiotics. AIM: To systematically review controlled trials of delayed prescriptions to establish their capacity to reduce antibiotic intake. DESIGN OF STUDY: A systematic review of the literature. SETTING: Four studies were conducted in the United Kingdom and one in New Zealand. METHODS: We searched MEDLINE from 1966 to April 2003, EMBASE, and the Cochrane Controlled Trials Register using the following terms: 'delayed', 'antibiotics', 'prescriptions', and 'back-up' (as in back-up prescription). We included controlled trials of studies in which the intervention was a delayed prescription compared to an immediate prescription for patients with upper respiratory tract infections. The studies were selected independently and the results compared. Disagreements were resolved by discussion. The data and quality of the studies were extracted and assessed independently by two of the authors. RESULTS: Four randomised controlled trials and one before-after controlled trial contributed to the review. The relative risk in the randomised trials for lower antibiotic usage when a delayed prescription was given ranged from 0.54 for the common cold to 0.25 for otitis media. CONCLUSION: The consistent reduction in antibiotic usage in the five controlled trials included in this review suggests that delayed prescription is an effective means of reducing antibiotic usage for acute respiratory infections. The duration of delay for prescriptions ranged widely, from 1 to 7 days.

Anti-Bacterial Agents↗

Asymptomatic respiratory tract infection with Chlamydia pneumoniae TWAR.

Chlamydia pneumoniae is a newly recognized organism associated with respiratory tract infections. Asymptomatic infection with C. pneumoniae, although it has been suggested to occur, has not been previously documented. We describe two asymptomatic individuals infected with this organism; these infections demonstrate that C. pneumoniae is able to establish a subclinical infection.

Antibodies, Bacterial↗

[Clinical study of cefoxitin in chronic respiratory tract infections: evaluation in poorly responding cases to other antibiotics (author's transl)].

The therapeutic efficacy of cefoxitin (CFX) in chronic respiratory tract infection was evaluated in patients who poorly responded to other antibiotics. To 20 patients, CFX was administered 2 g b.i.d. intravenously by drip infusion. Clinical efficacy was judged based on the criteria by score. 1. Bacterial elimination rate with CFX was 73.7%. 2. A clinical cure rate was 80.0% was obtained by doctors in charge. 3. According to the score assessment, the overall clinical effectiveness rate was 60.0%, clinical symptom cure rate was 85.0% and improvement rate of X-ray findings was 55.0%. 4. Usefulness rate which was assessed by clinical effect and side effect was 70.0%. 5. No side effects and abnormal laboratory findings were observed in this study. We used the new antibiotic CFX in patients with chronic respiratory tract infections who responded poorly to other antibiotics and obtained satisfactory results. Especially CFX indicated more effective possibility in cases from whom Gram-negative bacilli was isolated.

Adult↗

Molecular epidemiology of pneumococcal carriage among children with upper respiratory tract infections in Hanoi, Vietnam.

To investigate the molecular epidemiology of pneumococcal nasopharyngeal carriage in Hanoi, Vietnam, we studied 84 pneumococcal strains retrieved from children with upper respiratory tract infections. Serotypes 23F (32%), 19F (21%), 6B (13%), and 14 (10%) were found most often. A significant number of strains were antibiotic resistant. Fifty-two percent of the strains were (intermediate) resistant to penicillin, 87% were (intermediate) resistant to co-trimoxazole, 76% were resistant to tetracycline, 73% were resistant to erythromycin, and 39% were (intermediate) resistant to cefotaxime. Seventy-five percent were resistant to three or more classes of antibiotics. A high degree of genetic heterogeneity among the penicillin resistance genes was observed. In addition, the tetracycline resistance gene tet(M) and the erythromycin resistance gene erm(B) were predominantly observed among the isolates. Molecular analysis of the 84 isolates by restriction fragment end labeling (RFEL) revealed 35 distinct genotypes. Twelve of these genotypes represented a total of eight genetic clusters with 61 isolates (73%). The two largest clusters contained 24 and 12 isolates, and the isolates in those clusters were identical to the two internationally spreading multidrug-resistant clones Spain 23F-1 and Taiwan 19F-14, respectively. The remaining RFEL types were Vietnam specific, as they did not match the types in our reference collection of 193 distinct RFEL types from 16 countries. Furthermore, 57 of the 61 horizontally spreading isolates (93%) in the eight genetic clusters were covered by the seven-valent conjugate vaccine, whereas this vaccine covered only 43% of the isolates with unique genotypes. According to the serotype distribution of the nasopharyngeal pneumococcal isolates, this study suggests a high potential benefit of the seven-valent pneumococcal conjugate vaccine for children in Hanoi.

Carrier State↗

Serological study of responses to selected pathogens causing respiratory tract infection in the institutionalized elderly.

In a prospective 2-year study, serological responses to selected pathogens were analyzed in 224 episodes of fever attributable to respiratory tract infection (51.8%) or of unknown source (48.2%) in 131 residents of two long-term-care facilities. A serological response was identified in 45 episodes (20.1%): Chlamydia pneumoniae (14 episodes), Haemophilus influenzae type b (1), influenza virus type A (14), respiratory syncytial virus (RSV;2), parainfluenza virus type 3 (7), C. pneumoniae and H. influenzae (3), C. pneumoniae and influenza virus type A (2), C. pneumoniae and RSV (1), and C. pneumoniae and parainfluenza virus type 3 (1). No serological responses to Chlamydia psittaci, Chlamydia trachomatis, parainfluenza virus types 1 and 2, influenza virus type B, or Mycoplasma pneumoniae were seen. Vaccination did not affect the duration of fever in those residents with serologically confirmed influenza A. Serologically confirmed C. pneumoniae infection was detected in 9.4% of all febrile episodes. Serological responses to a second agent were detected in 33% of the patients with C. pneumoniae infections, and these dual infections were associated with an underlying malignancy (P = .02). C. pneumoniae should be recognized as a potential pathogen when choosing empirical antimicrobial therapy for respiratory tract infection in residents of long-term-care facilities.

Aged↗

Telithromycin: a new ketolide antimicrobial for treatment of respiratory tract infections.

Telithromycin is a new ketolide antimicrobial, specifically developed for the treatment of community-acquired respiratory tract infections. It has a wide spectrum of antibacterial activity against common respiratory pathogens including Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis and Streptococcus pyogenes. It also has activity against atypical pathogens, such as Chlamydia pneumoniae, Legionella pneumophila and Mycoplasma pneumoniae. Telithromycin maintains activity against beta-lactam and macrolide-resistant respiratory tract pathogens and does not appear to induce cross-resistance to other members of the macrolide-lincosamide-streptogramin (MLS) group of antimicrobials. It demonstrates bactericidal activity against S. pneumoniae and H. influenzae and has a prolonged concentration-dependent post-antibiotic effect (PAE) in vitro. The drug has favourable pharmacokinetics following oral administration. It is well absorbed, achieves good plasma levels and is highly concentrated in pulmonary tissues and white blood cells. In clinical trials, telithromycin given orally at a dose of 800 mg once daily for 5 - 10 days was as effective as comparator antimicrobials for the treatment of adults with community-acquired pneumonia, acute exacerbations of chronic bronchitis, acute maxillary sinusitis and group A-beta-haemolytic streptococcal pharyngitis or tonsillitis. The adverse events and safety profile were similar to comparator antimicrobials. The most common adverse events were diarrhoea, nausea, headache and dizziness. Telithromycin should provide an effective, convenient and well-tolerated once-daily oral therapy for treatment of respiratory infections.

Anti-Bacterial Agents↗

Comparative clinical evaluation of ceftriaxone in treating lower respiratory tract infections.

To evaluate the clinical and microbiological efficacy and safety of ceftriaxone in comparison with cefotaxime in treating acute lower respiratory tract infections two open randomized trials were performed. Sixty-two adult hospital in-patients were entered and 58 completed the study. The patients suffered from either acute (broncho-)pneumonia (19pts) or severe exacerbation of chronic bronchopneumonia (39 pts). Forty-one of the patients had severe underlying or concurrent diseases. Diagnoses were in all cases confirmed by isolation of the causative pathogen(s) from bronchial brushing or washing under fiberoptic bronchoscopy. Twenty-eight patients were administered at random with either a single 2g daily dose of ceftriaxone or 2g twice daily dose of cefotaxime (1st trial). Successively (2nd trial) ceftriaxone was administered at a dose of 1g once daily either i.v. or i.m. The duration of treatment ranged from 7 to 12 days. A satisfactory response was observed in all patients suffering from acute pneumonia or bronchopneumonia; the eradication rate of the causative pathogen was 73% and 62% for ceftriaxone and cefotaxime, respectively. Concerning the exacerbation of chronic bronchopneumonia (39 patients) an overall satisfactory response to both treatments was registered in about 80% of cases. No significant differences between the 1g and 2g single daily dosing regimens of ceftriaxone appeared. Both ceftriaxone and cefotaxime were well tolerated: no or minimal changes in laboratory values were noticed. It is concluded that a 1g or 2g single daily dose of ceftriaxone were at least as effective as a 2g twice daily dose of cefotaxime in treating acute lower respiratory tract infections due to susceptible pathogens.

Adult↗

Gatifloxacin in community-acquired respiratory tract infection.

Gatifloxacin (Tequin, Kyorin Pharmaceutical Co. Ltd) is a new fluoroquinolone with a broad spectrum of activity for pathogens implicated in community-acquired respiratory tract infections, including Gram-positive, -negative and atypical bacteria. Excellent oral bioavailability, a half-life allowing once-daily administration and excellent penetration into respiratory tissues are desirable pharmacokinetic characteristics of gatifloxacin. Monte Carlo simulation of gatifloxacin in Streptococcus pneumoniae infection demonstrates that adequate levels of pharmacokinetic/pharmacodynamic parameters are obtained with gatifloxacin in almost all instances. In randomised, controlled trials and a large open-label, community-based study, gatifloxacin has shown excellent clinical and bacteriological efficacy in acute bacterial sinusitis, acute exacerbations of chronic bronchitis and community-acquired pneumonia. Current guidelines recommend the initial empiric use of gatifloxacin (along with the other new fluoroquinolones) for community-acquired respiratory tract infection in patients who have increased likelihood of infection with resistant pathogens. Another group of patients where this agent is recommended for initial antimicrobial therapy are those who, because of underlying disease and/or comorbid conditions, need an antibiotic with high antimicrobial efficacy to achieve optimal outcomes.

Anti-Bacterial Agents↗

Toll-like receptor 4 is not involved in host defense against respiratory tract infection with Sendai virus.

Toll-like receptors (TLR) induce innate immune responses upon stimulation by a wide variety of pathogens. TLR4 has been implicated in innate immunity against respiratory syncytial virus (RSV) by an interaction with the viral envelope fusion (F) protein. Sendai virus (mouse parainfluenza type 1) shares many features with RSV, including a structurally and functionally similar F protein. To determine the role of TLR4 in host defense against Sendai virus respiratory tract infection, TLR4 mutant and wildtype mice were intranasally infected with Sendai virus. Sendai infection resulted in an increase in viral RNA copies in lung homogenates peaking on day 4. Pulmonary viral loads, histopathology, cytokine levels and leukocyte influx were similar in TLR4 mutant and wildtype mice. In spite of the structural similarities shared by the F proteins of Sendai virus and RSV, TLR4 is not involved in host defense against respiratory tract infection with Sendai virus.

Animals↗

Doxycycline in respiratory tract infections. Report of a retrospective study in Spain during the winter 1972-1973.

In the winter of 1972-1973 a multicentre trial of the treatment of upper and lower respiratory tract infections was carried out in Spain using doxycycline. 85 physicians participated in the study and treated 1,653 patients. The infections included acute bronchitis, acute exacerbation of chronic bronchitis, pneumonia, bronchopneumonia, tonsillitis, pharyngitis, trachetis, sinusitis, and otitis media. The majority of the patients were adult out-patients although some children and adolescents were included: 1,011 of the patients were male and 642 female. A number of the signs of respiratory infection such as temperature, cough, pain and inflammatory symptoms were examined. A rapid reduction in intensity and severity was noted in all of these parameters. Tolerance to the antibiotic was excellent. Only minor side-effects were reported and these were mild and mainly limited to the gastro-intestinal tract - in no case was treatment discontinued. The total number of side-effects was 37; they occurred in 31 out of the 1,653 patients. The overall evaluation of results showed a very good or good response in 85% of the patients. It appears from this multicentre study that the efficacy of doxycycline has in no way decreased over the 7 years of its extensive use in Spain. It remains a fast acting and effective antibiotic in upper and lower respiratory tract infections irrespective of age, sex or diagnosis.

Acute Disease↗

Respiratory tract infections in general practice: considerable differences in prescribing habits between general practitioners in Denmark and Spain.

OBJECTIVE: The prevalence of antibiotic resistance in a country reflects the local consumption of antibiotics. The majority of antibiotics are prescribed in general practice and most prescriptions are attributable to treatment of respiratory tract infections (RTIs). The aim of this study was to compare general practitioners' (GPs') prescribing of antibiotics for respiratory tract infections in a country with a high prevalence of antibiotic resistance (Spain) with a country with a low prevalence of antibiotic resistance (Denmark). METHODS: A group of GPs in Copenhagen and Barcelona registered all contacts ( n=2833) with patients with RTIs during a 3-week period between 1 November 2001 and 31 January 2002. RESULTS: Overall, Spanish GPs treated a higher proportion of patients than Danish GPs. After adjusting for unequal distribution of age and sex, we found that Spanish GPs prescribed significantly more antibiotics to patients with focus of infection in tonsils and bronchi/lungs. Narrow-spectrum penicillin was the most used antibiotic in Denmark, representing 58% of all prescriptions issued, followed by macrolide and broad-spectrum penicillin. In Spain, prescriptions were distributed among a great number of compounds, with broad-spectrum penicillins and combinations of amoxicillin plus beta-lactamase inhibitors most frequently used. CONCLUSION: The substantial difference in the way GPs manage respiratory tract infections in Denmark and Spain cannot be explained by different patterns of RTIs in general practice. The discrepancies indicate variations in national recommendations, different treatment traditions or different impact of pharmaceutical marketing.

Adolescent↗

[Relation between erythrocyte sedimentation and C-reactive protein in serum of adults with lower respiratory tract infections. Significance of microbiological agents].

Correlation between erythrocyte sedimentation rate and C-reactive protein was determined in 239 adult patients in general practice who were suspected of having an infection of the lower respiratory tract. A correlation coefficient of 0.62 (95% CI 0.54-0.69) was found, but there was no association between the results of the two tests when the illness had lasted less than four days. With such a short duration of illness a test for C-reactive protein is to be preferred before erythrocyte sedimentation rate when evaluating lower respiratory tract infections.

Adult↗

Respiratory tract infections caused by beta-lactamase producing organisms treated with augmentin.

Twenty-three patients were treated with Augmentin for severe respiratory tract infections caused by beta-lactamase producing organisms. The success rate, clinically and bacteriologically, was 19 out of 23. One non beta-lactamase producing H. influenzae, and three mixed organisms including Staph aureus accounted for the four failures. The elimination of the organisms, sensitive to Augmentin were quick and clinical improvement was seen in 72 hours. The only side effects noted were nausea in three patients, which abated on taking the tablets with meals. Augmentin is a useful drug in the treatment of respiratory tract infection particularly in acute exacerbation of chronic bronchitis.

Amoxicillin↗

Evaluation of the efficacy of sequential intravenous-oral administration of pefloxacin in community-acquired lower respiratory tract infections in patients with underlying conditions.

We studied the efficacy of sequential intravenous-oral pefloxacin therapy in community-acquired lower respiratory tract infection in 24 patients with one or more underlying conditions. Twenty-eight patients were enrolled into the study but only 24 patients were evaluated. There were 16 males and 8 females with a mean age of 66.9 +/- 11.2 years (mean +/- SD, range 46 to 87 years). The underlying conditions present were bronchiectasis, chronic obstructive lung disease and diabetes mellitus. Patients who were older than 70 years but without any underlying condition were also enrolled. All received 4 days of intravenous pefloxacin 400 mg twice a day followed by oral pefloxacin 400 mg twice a day for another 10 days. Assessment of success was based on clinical, microbiological and radiological improvement. Pefloxacin produced 79.2% clinical cure rate. Another 8.3% showed improvement. Pefloxacin was well tolerated. There were few adverse effects and none of the patients required a change of antibiotic. Pefloxacin was an effective and well tolerated treatment for respiratory tract infection and had the advantage of broad in-vitro antibacterial activity, twice daily dosing and sequential availability in an intravenous and oral formulation.

Administration, Oral↗

A diagnostic rule for the aetiology of lower respiratory tract infections as guidance for antimicrobial treatment.

BACKGROUND: The majority of patients with lower respiratory tract infections (LRTIs) are treated with antibiotics; some of them are unnecessary because of a viral cause. Information on prediction of the aetiology, especially in a general practice setting, is missing. AIM: To differentiate between viral and bacterial LRTI on simple clinical criteria, easily obtained at the bedside. DESIGN OF STUDY: Prospective observational study. SETTING: General practices in the Leiden region of The Netherlands. METHOD: Adult patients with LRTI were included. Standard medical history and physical examination were performed. Sputum, blood and throat swabs were collected for diagnostic tests. According to microbiological findings, patients were classified as bacterial, viral, dual infection and unknown cause. In a logistic regression model independent predictors were determined. Scoring systems were developed. The accuracies of the diagnostic rules were tested by using receiver operating characteristic (ROC) curves. RESULTS: One-hundred and forty-five patients were classified as having bacterial (n = 35), viral (n = 49), or dual infection (n = 8), or infection of unknown cause (n = 53), respectively. Independent predictors for bacterial infection were fever (odds ratio [OR] = 8.0; 95% confidence interval [CI] = 0.9 to 71.0), headache (OR = 4.3; 95% CI = 1.0 to 19.1) cervical painful lymph nodes (OR = 8.7; 95% CI = 1.1 to 68.0), diarrhoea (OR = 0.3; 95% CI = 0.1 to 1.0) and rhinitis (OR = 0.3; 95% CI = 0.1 to 0.9). As an additional independent predictor, an infiltrate on chest X-ray (OR = 5.0; 95% CI = 1.2 to 20.5) was found. The diagnostic rules developed from these variables classified the aetiology of LRTI with a ROC curve area of 0.79 (clinical score), 0.77 (simplified score) and 0.83 (extended score). CONCLUSIONS: A diagnostic rule was developed, based on information that is easy to obtain at the bedside, to predict a bacterial infection. This diagnostic rule may be a tool for general practitioners in their management of patients with LRTI.

Anti-Bacterial Agents↗

Roxithromycin versus amoxicillin-clavulanic acid in the treatment of respiratory tract infections.

A multicenter, double-blind, double-dummy trial was conducted in 96 general practice patients with upper and lower respiratory tract infection to compare the efficacy and tolerance of roxithromycin (150 mg b.i.d.) and amoxicillin-clavulanic acid (500 mg/125 mg t.i.d.). Good clinical response was obtained in 96% and 95% of cases, respectively, but only 4% of patients receiving roxithromycin volunteered adverse events possibly or probably related to their test treatment, as opposed to 17% of those receiving amoxicillin-clavulanic acid. The results indicate that both drugs are equally effective in the treatment of respiratory tract infection, but that roxithromycin is better tolerated.

Adult↗

Daily tympanometry in children during the cold season: association of otitis media with upper respiratory tract infections.

The causal association between otitis media and viral upper respiratory tract infections (URI) suggests that early intervention during the course of a viral URI could prevent many episodes of otitis media. However, the feasibility of this approach can not be assessed at present since many aspects of the epidemiology and natural history of URI-associated otitis media are undefined. To address this deficiency, daily monitoring of middle ear status (tympanometry) and cold symptoms and weekly pneumatic otoscopy were done on a pilot cohort of 20 children. These children, between the ages of 2 and 6, were followed from November 1996 to April 1997. Compliance with symptom diaries was 85%, with tympanograms was 90%, and with weekly physician visits was 70%. During the study period, there were 53 'colds' (average 2.65 per child) and 28 new episodes of middle ear effusion (10 unilateral and 9 bilateral). Overall, 47.3% of the tympanograms were Type A, 17.2% Type C1, 9.4% Type C2, and 21.8% Type B. Children who developed MEE during the study spent more time with abnormal MEP (either MEP < -150 or flat) during both cold and healthy days than children who did not develop MEE. Temporally, during colds, high negative pressures preceded the development of Type B tympanograms in children who developed middle ear effusions. Children who did not develop effusions still had high negative pressures during colds, but recovered to a normal pressure within days. These observations document the feasibility of this investigational format for study of the sequential changes in middle ear status before, during and after a URI.

Acoustic Impedance Tests↗