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Lower respiratory tract infections: prevention using vaccines.

In summary, vaccines are available to prevent two of the most common and most deadly causes of lower respiratory tract infections: pneumococcal disease and influenza. Pneumococcal polysaccharide vaccine prevents pneumococcal bacteremia; influenza vaccines prevent influenza as well as several complications of influenza. Despite all that is known about how well these vaccines work, influenza and pneumococcal vaccines are underused markedly, especially among some minority groups that are affected dis-proportionately by disease. Coverage also remains low among health care workers, although providing influenza vaccine to health care workers saves lives among patients. Tools such as standing orders can help clinicians increase vaccine coverage in their patient populations. While research for new and improved vaccines to prevent lower respiratory tract infections continues,focusing on simple measures for increasing vaccine use can help prevent morbidity and mortality now.

Adult↗

An open non-comparative pilot study of the safety and efficacy of oral sultamicillin in the treatment of mild to moderate upper respiratory tract infections in children.

A total of 49 children (20 females, 29 males; age range, 6 months-12 years) with upper respiratory tract infections (otitis media, sinusitis, pharyngitis and/or tonsillitis) were treated orally with 25 mg/kg.day sultamicillin suspension in two equal doses for an average of 9.2 days. There was bacteriological evidence of sultamicillin-sensitive pathogens in 44 patients prior to treatment. On completion of treatment, 42 (85.7%) patients were rated as clinically cured and there was improvement in the remaining seven (14.2%) patients. Pathogens were totally eradicated in 32/44 (73.7%) cases but were still present in two (4.5%) and in 10 cases follow-up bacteriological evaluation was not possible. Tolerability of sultamicillin was good and only three possible or probable treatment-related adverse events were recorded.

Administration, Oral↗

The state of leukocyte adhesiveness/aggregation in the peripheral blood of patients with respiratory tract infections.

The state of leukocyte adhesiveness/aggregation (LAA) in the peripheral blood has been employed as a marker of inflammation. In the present study we examined patients with varying intensities of inflammation caused by respiratory tract infections to further investigate the reliability of the state of LAA for the detection and assessment of the severity of disease activity. The study includes 140 controls, 46 patients with upper respiratory tract infection, 30 with bronchitis, 27 with suspicion of pulmonary infiltrate, and 39 with small and 18 with large pulmonary infiltrate. Assessment was based on assuming an increasing severity of inflammation from the 1st to the 6th diagnostic category and by making use of discriminant analysis. It was found that the state of LAA proved to be the best variable to classify the patients into their diagnostic category (F to enter 27), followed by erythrocyte sedimentation rate at the 1st h (F to enter 20.8) and total white blood cell count (F to enter 8.3). These studies were followed by animal experimentation. A highly significant correlation (p = 0.005) was found between the state of LAA in the peripheral blood and the degree of pulmonary leukostasis in a model of endotoxemia in rabbits. These results suggest that the state of LAA is not an epiphenomenon and represents the tendency of the white blood cells to stick to the endothelium which facilitates their migration into the tissues.

Adolescent↗

Steady-state pharmacokinetics of rufloxacin in elderly patients with lower respiratory tract infections.

The pharmacokinetics of rufloxacin, after repeated doses, was evaluated in 12 elderly patients with lower respiratory tract infections. Patients were given a single loading dose of 400 mg on the first day of treatment and single daily maintenance doses of 200 mg for the next 6-9 days. Serum concentrations of the drug were determined by high-performance liquid chromatography (HPLC) at regular intervals during treatment and fitted to a one-compartment open model for repeated doses. The maximum serum concentration after the first dose was 6.46 +/- 1.06 (mean +/- SEM) micrograms/ml and was reached in 4.3 +/- 0.8 h after the first administration. The elimination half-life was 28.7 +/- 4.1 h. The area under the serum levels-time curve from 0 to 24 h was 103 +/- 14 micrograms/h/ml after the first dose. On the last day of observation it increased to 155 +/- 28 micrograms/h/ml, with a mean extent of accumulation of 2.3 +/- 0.3 times. The elimination half-life was comparable to those in other studies in healthy young subjects, while plasma levels were about 80% higher. These results suggest that in elderly patients elevated drug concentrations may be reached in the serum. Although no untoward reactions related either to the drug concentration in serum or the dose have been noted with rufloxacin, this patient population should nevertheless be monitored carefully for adverse effects.

Aged↗

Clinical trials on pediatric lower-respiratory-tract infection: results and comments with cefetamet pivoxil.

A total of 30 pediatric patients suffering from lower-respiratory-tract infections were admitted to a three-arm, open, randomized study comparing two different doses of cefetamet pivoxil (either 10 or 20 mg/kg b.i.d.; groups A and B, respectively) with the standard cefaclor treatment (10 mg/kg t.i.d.; group C) for 7-12 days. The 30 cases were randomly assigned to the three treatment arms which were comparable with regard to demographics as well as to diagnosis on admission and concomitant medication. The children ranged from 1.08 to 12 years in age, and comprised 18 males and 12 females, with a weight range of 11-42 kg. As is to be expected in these patients, bacteriology was mostly not assessable. The overall clinical outcome was cure in 9, 8 and 9 cases, respectively, and improvement in 1, 2 and 0 cases, respectively. In the cefaclor group 1 patient failed to respond. Signs and symptoms of disease improved significantly in the three treatment groups; there were no intergroup differences. Vital signs (morning and evening temperature and pulse rate) improved in parallel. Radiological results had improved by the end of treatment in 9/10 patients in group A, in 10/10 patients in group B, and in 9/10 evaluable patients in group C. Mild to moderate nausea or vomiting were each reported in 1 patient in group A. Platelet increase was reported as a mild adverse event in 2 patients in each of the cefetamet pivoxil groups and in 4 patients given cefaclor.(ABSTRACT TRUNCATED AT 250 WORDS)

Bacterial Infections↗

Lack of effect of codeine in the treatment of cough associated with acute upper respiratory tract infection.

Codeine is often used as a standard antitussive against which new antitussives are compared. However there is little information available about the effects of codeine on cough associated with upper respiratory tract infection. The present study investigated the effects of codeine syrup B.P. (30 mg/10 ml, q.d.s.) or syrup vehicle on cough frequency and the subjective severity of cough during a 3-h laboratory phase and a 4-day home phase of treatment. Cough frequency and subjective scores of cough severity were significantly decreased during the 3-h laboratory phase but at no time point was there a significant difference between the codeine- and placebo-treated groups. The results of the 4-day home phase diary were similar to those of the laboratory phase as at no time point was there a significant difference between the mean scores for the codeine- and placebo-treated groups. The results indicate that codeine, either as a single 30-mg dose or in a total daily dose of 120 mg, is no more effective than the syrup vehicle in controlling cough associated with acute upper respiratory tract infection.

Acute Disease↗

Comparison of aztreonam and tobramycin in the treatment of lower respiratory tract infections caused by gram-negative bacilli.

A comparison of aztreonam and tobramycin was carried out in 49 hospitalized patients with lower respiratory tract infections caused by gram-negative bacilli. Patients were randomly assigned to the treatment drug. Clindamycin was given concomitantly until the pathogen was identified and the presence of a gram-positive microorganism was ruled out. Samples of sputum were obtained for culture from the lung parenchyma by deep expectoration or transtracheal aspiration. A pathogen was defined as an organism that showed heavy growth and predominated in the culture. Pseudomonas aeruginosa was the most frequently isolated pathogen, followed by Haemophilus influenzae and Proteus mirabilis. A variety of less common pathogens were represented. Thirty-five patients were treated with intravenous aztreonam (1-2 g every 8 hr) and 14 with intravenous tobramycin (3-5 mg/kg per day) until they were afebrile and sputum cultures had been free of the pathogen for 48 hr. The minimum duration of treatment was five days. In the aztreonam group, only two (5%) of the 37 gram-negative pathogens--one P. aeruginosa and one Escherichia coli--persisted. In the tobramycin group, seven (50%) of the 14 pathogens persisted. Clinical response paralleled microbiologic response. Adverse effects in both treatment groups were minor and transient. In this trial aztreonam was effective and safe for treatment of lower respiratory tract infections caused by P. aeruginosa and a variety of other gram-negative bacilli.

Aztreonam↗

The use of acoustic reflectometry in the study of middle ear effusion in children suffering from acute otits media, upper respiratory tract infection and in healthy children.

UNLABELLED: This report focuses on the occurrence of middle ear effusion in children with acute otitis media (n = 62), upper respiratory tract infection (n = 81) as well as in healthy control children (n = 152). Data are reported in age categories 0-4 and 5-13 years. Middle ear effusion was found in 86% of children with acute otitis media, 49% of children with upper respiratory infection and 13% of healthy children. The younger the child, the more likely the presence of middle ear effusion in all groups. Acute otitis media and upper respiratory tract infection were clinically indistinguishable in infants. CONCLUSION: Middle ear effusion is not generally a particularly significant clinical problem in children.

Acoustic Impedance Tests↗

[A clinical study of respiratory tract infection due to Staphylococcus aureus detected by transtracheal aspiration].

A clinical study of 24 patients with respiratory tract infection due to S. aureus detected by transtracheal aspiration (TTA) was conducted, and the following results were obtained. 1) The detection frequency of S. aureus was relatively low (4.6%). 2) Pneumonia was the principal clinical manifestation. 3) Approximately one half of the patients had previously received antimicrobials. 4) Multiple organisms were frequently detected, particularly in cases of hospital-acquired infection. H. influenzae was the most frequently simultaneously detected organism. 5) On sputum examination, approximately 20 ml of purulent sputum was found in most cases, and S. aureus was detected in sputum specimens from 20 of the patients. 6) The largest number of cases was found in 1987. Onset was most common from autumn to spring. 7) Undernutrition was the most frequently associated host factor. As indicated by the above findings, the clinical expression of S. aureus infection is variable, and it is important that it be diagnosed accurately.

Adult↗

Incidence of lower respiratory tract infections caused by Mycoplasma, Chlamydia and Legionella: an Italian Multicenter Survey.

A collaborative retrospective study based on serologic diagnosis was conducted to assess the etiological role sustained by privileged pathogens in Italy. The results obtained indicate the Mycoplasma, Chlamydia and Legionella are important etiologic agents of lower respiratory tract infections in Italy since they account for about 31% of the cases taken into consideration in this survey. We found a high incidence of M. pneumoniae (12.3%), C. pneumoniae (10.5%) and L. pneumophila (8.3%). These results are in line with similar figures reported in the recent literature. While the data gathered in our survey do not allow us to clarify the nature of the agents involved in the etiology of the majority (70%) of the respiratory infections occurring in Italy, it seems safe to assume that after Streptococcus pneumoniae and Haemophilus influenzae, the privileged pathogens represent the most common cause of lower respiratory tract infections.

Chlamydia Infections↗

Grade I Reye's syndrome. A frequent cause of vomiting and liver dysfunction after varicella and upper-respiratory-tract infection.

In a one-year prospective study we assessed the incidence of Reye's syndrome in children presenting with the acute onset of vomiting after a prodromal upper-respiratory-tract infection or varicella, and with serum alanine or aspartate aminotransferase levels at least three times higher than normal, and a paucity of neurologic findings. Of 25 patients meeting the above criteria, 19 had liver biopsies yielding adequate tissue for diagnostic purposes. Biopsy specimens from 14 of these 19 patients (74 per cent) were diagnostic of Reye's syndrome, according to rigorous light-microscopical, histochemical, and ultrastructural criteria. None of the biopsy specimens contained evidence of other acute pathologic processes, including hepatitis. A wide spectrum of mitochondrial alterations existed at the ultrastructural level, ranging from mild to severe lesions that were indistinguishable from those seen in comatose patients with Reye's syndrome. Our findings suggest that the clinical complex of vomiting, hepatic dysfunction, and minimal neurologic impairment after varicella or an upper-respiratory-tract infection usually represents Reye's syndrome. This syndrome occurs more frequently than previously recognized.

Adolescent↗

Respiratory tract infection: epidemiology and surveillance.

Streptococcus pneumoniae and Haemophilus influenzae are the key pathogens implicated in bacterial infections of the upper and lower respiratory tract. Choice of empiric oral antimicrobial chemotherapy is guided by the clinical presentation, severity of the infection and epidemiological knowledge. beta-Lactams and the macrolides are the two major groups of antibiotics used to treat respiratory tract infections. The prevalence of penicillin-resistant strains of S. pneumoniae is increasing world-wide (up to 30% in the USA), as is the prevalence of beta-lactamase-producing strains of H. influenzae. Macrolide resistance in S. pneumoniae is increasing and is absolute, and some of the macrolides have only limited activity against H. influenzae. Knowledge of local and global antibiotic resistance patterns should be used as the key to directing empiric choice of antibiotic treatment.

Anti-Bacterial Agents↗

Activity of erythromycin against Haemophilus influenzae from respiratory tract infections.

Ampicillin and amoxycillin are very frequently used for treating respiratory infections due to Haemophilis influenzae, but the emergence of beta-lactamase producing strains of this organism may limit their use. Erythromycin would be a suitable alternative but to date variable absorptions and reported minimal inhibitory concentrations (MICs) outside the range of achievable blood levels of erythromycin have prevented its use. The purpose of this study was to determine the MICs of erythromycin for strains of H. influenzae isolated from patients with lower respiratory tract infection and the frequency of beta-lactamase production in these strains. Eighty-five of 100 strains were sensitive to erythromycin (MIC much less than 2.00 mg/L). Eleven strains were resistant to ampicillin and 10 of these produced beta-lactamase. Nine beta-lactamase producing strains had MICs to erythromycin of 2.0 mg/L or less. With the blood levels of erythromycin obtainable with new formulations, this antibiotic should prove of use in the treatment of respiratory infections due to H. influenzae.

Adolescent↗

Acute lower respiratory tract infections in children: possible criteria for selection of patients for antibiotic therapy and hospital admission.

Acute lower respiratory tract infections are a common cause of morbidity and mortality in children in the less developed countries. Considering the urgent need for rational protocols for the management of these infections in children and how little is known about the clinical signs that might predict the need for antibiotic therapy in a primary health care setting, a prospective study of the clinical signs in 200 paediatric outpatients presenting with a cough, 100 age-matched controls without cough, and 50 children admitted to hospital with pneumonia was carried out.In children with cough, a respiratory rate greater than 40 or 50 per minute (or a qualitative impression of tachypnoea) is probably the best indicator of the need for starting antibiotic treatment by primary health workers. The presence of fever appeared to be a poor guide to the need for antibiotic therapy. The presence of chest indrawing is, however, a reliable indication that a child with cough should be admitted to a health centre or a hospital. Further prospective studies are needed to determine the ability of these clinical signs to predict the course of these infections.

Acute Disease↗

Doxycycline in the treatment of respiratory tract infections. Results of a pan-European multi-centre trial.

In the winter of 1973-4, general practitioners from seven European countries took part in a multi-centre trial of doxycycline in the treatment of infections of the respiratory tract. The carefully designed protocol was observed by all participants. A total of 1,747 patients were admitted to the trial; their ages ranged from 6 years to over 80. The commonest diagnoses (50%) were acute bronchitis and acute exacerbations of chronic bronchitis. On the recommended dosage of 200 mg doxycycline on the first day, followed by 100 mg daily thereafter (though 200 mg could be continued daily in severe cases), 87% of patients achieved good or very good results. Both subjective (pain) and objective (sputum volume and viscosity, temperature, cough) measures showed rapid improvement, usually by the third to fifth days. Side-effects were minimal and mainly gastrointestinal and caused only 4 patients to discontinue treatment. Overall, doxycycline proved its effectiveness and rapidity of action.

Acute Disease↗

Open clinical trial of roxithromycin amongst patients of Jos University Teaching Hospital with lower and upper respiratory tract infections.

An open non-comparative clinical study to determine the efficacy and tolerance of Roxithromycin 150 mg twice daily was carried out amongst Nigerian patients with acute upper and lower respiratory tract infections. Twenty-four (24) patients (mean age 21.6 years, male 13; females 11 who completed the study presented with acute tonsillitis (33.3%, acute bronchitis (12.5%), lober pneumonia (12.5%), Otitis media (8%), acute pharyngitis (4%) and acute sinusitis (4%). Most of the patients had normal bacterial flora isolated (50.3%). Pathogens isolated included streptococcus pyogenes (21%), moraxella catarhalis (8.3%), streptococcus pneumonia (8.3%) and Klebsiella pneumonia (4%). The quick clinical response, lack of major adverse drug reactions and susceptibility of the bacterial isolates to Roxithromycin were very significant attributes of the drug. In addition, there was complete recovery in 95.8% of the patients. Roxithromycin is therefore a well tolerated and effective drug for the treatment of acute respiratory tract infections in Nigerian patients.

Acute Disease↗

[Investigation of Streptococcus pneumoniae and Haemophilus influenzae isolated from pediatric outpatients nationwide with a respiratory tract infection at the first consultation (2002-2003)--proportion of resistant strains and sensitivity to oral antibacterial agents].

The propotions of resistant strains and sensitivity to oral antibacterial agents were determined for 468 strains of Streptococcus pneumoniae and 557 strains of Haemophilus influenzae isolated from pediatric outpatients with a respiratory tract infection at the first consultation at 20 medical institutions nationwide in the predefined 4-week period during November 2002 and June 2003. PRSP of the S. pneumoniae strains, accounted for 27%, and BLNAR accounted for 35% of the H. influenzae strains. Against the S. pneumoniae strains, faropenem showed the best MIC90 value, 0.5 microg/mL, of the beta-lactam antibacterial agents, followed by cefditoren-pivoxil, and among the macrolide and ketolide antibacterial agents, telithromycin showed the best MIC90 value, 0.12 microg/mL. Against the H. influenzae strains, cefditoren-pivoxil showed the best MIC90 value, 0.25 microg/mL, among the beta-lactam antibacterial agents, and among the macrolide and ketolide antibacterial agents, azithromycin showed the best activity, followed by telithromycin. It seems necessary to take these results into consideration when choosing drugs for treatment. It will be necessary to survey the trends in resistant strains and the clinical efficacy of various oral antibacterial agents in the future.

Administration, Oral↗

Role of sultamicillin and ampicillin/sulbactam in the treatment of upper and lower bacterial respiratory tract infections.

The emergence of beta-lactamase-mediated resistance to beta-lactam antibiotics among key respiratory tract pathogens has threatened the usefulness of the beta-lactam agents familiar to physicians as being clinically effective and well tolerated. This article reassesses the clinical usefulness of ampicillin when administered in combination with the beta-lactamase inhibitor sulbactam, either intravenously or orally (as the mutual prodrug sultamicillin), in the treatment of upper and lower respiratory tract infections. Numerous clinical studies and several meta-analyses indicate that ampicillin/sulbactam and sultamicillin are clinically effective and well tolerated in both adults and children, in agreement with published North American and European guidelines.

Administration, Oral↗