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PubMed2005

Role of atypical bacteria and azithromycin therapy for children with recurrent respiratory tract infections.

BACKGROUND: The aim of this study of 352 patients, 1-14 years of age, with acute respiratory infections and a history of recurrent respiratory tract infections (RRTIs), and 208 healthy subjects was to evaluate whether Mycoplasma pneumoniae and Chlamydia pneumoniae played a role in causing acute respiratory episodes among children with RRTIs and whether specific antibiotic treatment for these bacteria could improve the acute episodes and reduce recurrences. METHODS: The patients were blindly randomized to receive azithromycin (10 mg/kg/d for 3 days weekly, for 3 weeks) together with symptom-specific agents or symptom-specific agents alone. Acute M. pneumoniae and/or C. pneumoniae infection was diagnosed if the child had a significant antibody response in paired sera and/or if the DNA of the bacteria was detected in nasopharyngeal aspirates. RESULTS: Atypical bacterial infections were identified for 190 patients (54.0%) and 8 healthy control subjects (3.8%; P < 0.0001). Short term (1-month) clinical success was significantly more frequent among the patients who had received azithromycin together with symptom-specific agents than among those who had received symptom-specific agents alone, but the difference was significant only for the group of patients with atypical bacteria. In contrast, long term (6-month) clinical success was significantly more frequent among the patients who had received azithromycin in addition to symptom-specific agents, regardless of whether they experienced infections with atypical bacteria or other pathogens, although positive outcomes were significantly more frequent among those with atypical bacteria. CONCLUSIONS: Atypical bacteria seem to play a role among children with RRTIs, and prolonged azithromycin therapy can significantly improve the acute episodes and reduce the risk of recurrences.

Adolescent↗
PubMed1999

Upper airway reactivity and upper respiratory tract infection: effect of nebulized lidocaine.

Patients presenting for elective anaesthesia and surgery may be suffering with, or recovering from, a recent upper respiratory tract infection. Airway reflexes are heightened and these individuals may be more likely to suffer airway complications on administration of general anaesthesia. We have examined the effect of nebulized lidocaine on upper airway reflexes in such subjects. Using dilute ammonia as a chemical stimulus to the upper airway, we measured upper airway reactivity in 15 volunteers (aged 22-43 yr) with symptoms of an upper respiratory tract infection for 4 days or less. The threshold concentration of ammonia producing a brief reduction in inspiratory flow was determined. Measurements were made before and after administration of a nebulized solution of 4% lidocaine 4 ml or saline. After a 2-h interval the procedure was repeated with the alternative solution. The order of administration was randomized. The observer was blind to the solution given. Ammonia threshold was found to increase in subjects after nebulized lidocaine, from a median value of 327 (range 76-878) ppm to 878 (251-1620) ppm (P = 0.0007, Wilcoxon); there was no significant change after nebulized saline. After a convalescence period of at least 4 weeks, with no return of symptoms in the preceding 2 weeks, ammonia threshold was reassessed. It was found to be increased in all 15 subjects. Comparison of the five different times of measurement showed a highly significant difference (P < 0.001, Friedman). Subsequent analysis showed significant differences (P < 0.05, Wilcoxon) between convalescent ammonia threshold and both baseline and post-saline nebulizer values. There was no significant difference between convalescent and post-lidocaine ammonia threshold. We conclude that in adult subjects, nebulized lidocaine attenuated the heightened airway reflex sensitivity associated with symptoms and signs of upper respiratory tract infection.

Adult↗
PubMed1995

Increased nitric oxide in exhaled air of normal human subjects with upper respiratory tract infections.

Viral infection may induce the expression of nitric oxide (NO) synthase, resulting in increased NO formation that has an antiviral effect. NO may be produced by various cells of the upper and lower respiratory tract, and may be detected in the exhaled air. We have studied the levels of exhaled NO in 18 normal subjects during symptomatic upper respiratory tract infections and during recovery 3 weeks later. Exhaled NO was measured using a modified chemiluminescence analyser. At the time of symptoms of upper respiratory tract infection, the peak exhaled NO values were 315 +/- 57 ppb (mean +/- SEM) and decreased to 87 +/- 9 ppb during recovery. Recovery values of exhaled NO were similar to those reported in age-matched normal control subjects (88 +/- 3 ppb, n = 72). These findings suggest that symptomatic upper respiratory tract infections markedly increase the concentration of NO in exhaled air. This may reflect the induction of nitric oxide synthase (NOS) in upper and lower respiratory tract, and may be relevant to viral exacerbations of asthma.

Adult↗
PubMed2004

Antibacterial resistance among children with community-acquired respiratory tract infections (PROTEKT 1999-2000).

OBJECTIVE: To determine the susceptibility of bacterial respiratory tract pathogens, isolated from children (0-12 years) as part of the global PROTEKT surveillance study (1999-2000), to a range of antibacterials, including the ketolide telithromycin. METHODS: Minimum inhibitory concentrations of the antibacterials studied were determined at a central laboratory using the NCCLS microdilution broth method. Macrolide resistance mechanisms were detected by PCR. RESULTS: Of 779 Streptococcus pneumoniae isolates worldwide, 43% were non-susceptible to penicillin (18% intermediate; 25% resistant) and 37% were resistant to erythromycin, with considerable intercountry variation. Eighteen per cent of 653 Haemophilus influenzae and >90% of 316 Moraxella catarrhalis isolates produced beta-lactamase. Of 640 Streptococcus pyogenes isolates, 10% were resistant to erythromycin, with considerable intercountry variation. All S. pneumoniae and 99.8% of H. influenzae isolates were susceptible to telithromycin using breakpoints proposed to the NCCLS (<or=1 and <or=4 mg/L, respectively). All M. catarrhalis and 97% of S. pyogenes and isolates were susceptible to <or=1 mg/L telithromycin. CONCLUSIONS: Antibacterial resistance complicates the empirical treatment of respiratory tract infections in children and requires continued monitoring. Telithromycin may be a useful therapeutic alternative as it is highly active against strains exhibiting various resistance phenotypes.

Anti-Bacterial Agents↗
PubMed1995

Upper respiratory tract infections and exercise.

The epidemiological data suggest that endurance athletes are at increased risk for upper respiratory tract infections during periods of heavy training and the 1-2 week period following a marathon or similar event. At present there is no clear indication that chronic alterations in immune function explain this increased risk. Following acute bouts of prolonged heavy endurance exercise, several components of the immune system are suppressed for several hours. This has led to the concept of the "open window" theory described as the 1-9 hour period following prolonged endurance exercise when host defense is decreased and the risk of upper respiratory tract infection is increased.

Adult↗
PubMed1994

Evaluation of OPC-17116 against important pathogens that cause respiratory tract infections.

The antibacterial activity of OPC-17116, a new fluoroquinolone antibacterial agent, against important pathogens that cause respiratory tract infections was evaluated in vitro and in vivo and compared with those of ciprofloxacin, ofloxacin, and norfloxacin. The pharmacokinetic profiles of OPC-17116 were studied in both mice and rats given the drug orally at doses of 50 and 40 mg/kg of body weight, respectively. OPC-17116 showed a high degree of distribution in the lung tissues of both species, with maximum concentrations of 29.6 and 32.0 micrograms/g, respectively. Furthermore, the drug concentrations in lung tissue were about 10 to 15 times greater than the concentrations in plasma. OPC-17116 showed potent antibacterial activity against such pathogens as Staphylococcus aureus, Streptococcus pneumoniae, Klebsiella pneumoniae, Pseudomonas aeruginosa, Haemophilus influenzae, and Moraxella catarrhalis. The MICs of this compound for 90% of these organisms except methicillin-resistant S. aureus and P. aeruginosa ranged from < or = 0.006 to 0.78 microgram/ml. The in vitro antibacterial activity of OPC-17116 was reflected by the efficacy of a single oral dose against systemic bacterial infections in mice. OPC-17116 showed a superior effect against gram-positive bacteria, H. influenzae, and M. catarrhalis. In comparison with the other reference compounds, the efficacy of OPC-17116 was less than that of ciprofloxacin against K. pneumoniae and P. aeruginosa. OPC-17116 showed a greater therapeutic effect than the other drugs against experimental acute pneumonia caused by these organisms in mice or rats. This excellent therapeutic effect against respiratory tract infections may be a result of its high level of distribution in lung tissue.

Animals↗
PubMed1987

Role of anaerobic beta-lactamase-producing bacteria in upper respiratory tract infections.

Bacteroides sp. (Bacteroides melaninogenicus, Bacteroides oralis and Bacteroides fragilis), peptostreptococci and Fusobacterium sp. are important pathogens in upper respiratory tract infections. A recent increase in numbers of beta-lactamase-producing strains of anaerobic Gram-negative bacteria in upper respiratory tract infections has been associated with increased failure rates of penicillins in eradication of these infections. These infections include chronic otitis media, chronic sinusitis and mastoiditis, chronic recurrent tonsillitis and lung abscesses. The indirect pathogenicity of these organisms is apparent through their ability not only to survive penicillin therapy but also to protect penicillin-susceptible pathogens from the drug. These direct and indirect virulence characteristics of anaerobic bacteria require the administration of appropriate antimicrobial therapy directed against all pathogens in mixed infections.

Bacteroides↗
PubMedDate not supplied

An international clinical trial on the efficacy and safety of roxithromycin in 40,000 patients with acute community-acquired respiratory tract infections.

An ongoing eight-country study is being conducted in an unprecedented number of general practice patients with acute upper and lower respiratory tract infections to compare the efficacy and tolerance of roxithromycin 150 mg b.i.d. for 7-14 days with the data acquired in the prelaunch studies of these same parameters. The target population is 40,000 (to be achieved by the end of 1991) and we report the interim results from 32,405 patients, 18,020 with upper and 14,385 with lower respiratory tract infections. In acute pharyngitis/tonsillitis sinusitis, and otitis, clinical resolution or improvement has been achieved in 97%, 96%, and 96% of cases, respectively. The figures for bronchitis, exacerbation of chronic bronchitis, and pneumonia are 97%, 94%, and 95%. Side effects have been reported in only 4% of patients to date, 75% consisting of moderate gastrointestinal upsets. Of the patients, 1% withdrew from treatment because of side effects. These interim figures confirm the data from the prelaunch, controlled comparative trials and show roxithromycin to be an appropriate choice of first-line antibiotic therapy in the management of respiratory tract infections in general practice.

Acute Disease↗
PubMed1988

Management of acute and chronic respiratory tract infections.

Pharyngitis, bronchitis, and pneumonia represent the most common respiratory tract infections. With a view to establishing effective management strategies, the origins of these illnesses and the diagnostic techniques that have been developed to discover them are reviewed. Therapeutic regimens with documented efficacy are outlined with emphasis on specific rather than empiric treatment. Although many respiratory tract pathogens remain exquisitely sensitive to penicillin, the emergence of resistant strains underscores the need for safe and effective alternative therapies.

Acute Disease↗
PubMed1997

Long term follow-up of children hospitalized with respiratory syncytial virus lower respiratory tract infection and randomly treated with ribavirin or placebo.

PURPOSE: To determine the long term effects of ribavirin therapy in children hospitalized for respiratory syncytial virus (RSV) lower respiratory tract infection. METHODS: Fifty-four of 60 children in randomized trials of ribavirin therapy were enrolled in a prospective follow-up study. Subjects were examined annually and had age-appropriate pulmonary function tests; interim histories were obtained from families and personal physicians. RESULTS: Recurrent lower respiratory tract illness was reported at least once for 79% of the ribavirin and 73% of placebo group. In the first 5 years after RSV, 54% of the ribavirin group and 50% of the placebo group reported wheezing. There were no significant differences between the groups in annual rates, timing, or severity of recurrent lower respiratory tract illness. No significant differences in pulmonary function were detected by tests of oxygen saturation, peak expiratory flow and spirometry. CONCLUSIONS: Children in the ribavirin treatment group did not have exacerbated respiratory symptoms compared with those in the control group, and their pulmonary function measurements were equal to those of the placebo-treated group, suggesting no long term adverse effect or benefit of ribavirin therapy.

Antiviral Agents↗
PubMed1997

[The evaluation of interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-alpha) level in peripheral blood of patients with chronic lower respiratory tract infection].

In the present study, we assessed the serum level of IL-6 and TNF-alpha by ELISA in patients with chronic lower respiratory tract infection. The serum levels of IL-6 and TNF-alpha of patients in acute exacerbation phase are higher than that of in stable phase. We also classified patients in acute exacerbation phase into two groups according to the microorganism of persistent infection. The serum level of IL-6 and TNF-alpha in the patients with persistent infection with Pseudomonas aeruginosa were higher than that with Haemophilus influenzae. Moreover, the serum level of IL-6 and TNF-alpha were found to be related with malnutrition which assessed by clinical indices such as the serum level of albumin and cholinesterase. The present result suggests that IL-6 and TNF-alpha may have relationship with not only inflammation in airway but also indices of nutrition in patients with chronic lower respiratory tract infection.

Acute-Phase Reaction↗
PubMed1991

Antibiotic prophylaxis of respiratory tract infection in mechanically ventilated patients. A prospective, blinded, randomized trial of the effect of a novel regimen.

The objective of this study was to assess the effect of a novel regimen of antibiotic prophylaxis on the incidence of lower respiratory tract infection in patients requiring prolonged (at least five days) mechanical ventilation. The design was a controlled, prospective, randomized trial, with blinded comparison of the groups regarding the incidence of respiratory tract infection in an intensive care unit of a university hospital. After determination of the APACHE II score for severity of disease, 88 patients were randomly divided in three groups. Twenty-four of these patients did not complete five days of mechanical ventilation, and eight were withdrawn for other reasons. Fifty-six patients (18 in group 1, 21 in group 2, 17 in group 3) completed the study. Patients in both control groups 1 and 2 did not receive antibiotic prophylaxis, but the two groups differed in the antibiotic policy in case of infection. Patients in group 3 received antibiotic prophylaxis consisting of norfloxacin, polymyxin E, and amphotericin B, applied topically in oropharynx and stomach from time of ICU admission until extubation, and intravenous cefotaxime 500 mg three times a day during the first five days of admission. In both control groups, about 90 percent of the patients acquired microbial colonization of oropharynx or stomach. In group 3, only 12 percent and 24 percent of the patients acquired colonization of oropharynx and stomach, respectively (p less than 0.001). This resulted in a reduction of the incidence of lower respiratory tract infection (78 percent in group 1, 62 percent in group 2, 6 percent in group 3 [p = 0.0001]). The regimen of antibiotic prophylaxis studied prevented respiratory tract infection in mechanically ventilated patients. Antibiotic prophylaxis should be considered in all patients expected to require prolonged mechanical ventilation.

Administration, Topical↗
PubMed1985

Defective interferon-alpha production in children with recurrent respiratory tract infections. A primary or secondary deficiency?

Interferon-alpha and -gamma production was assayed in 44 children with recurrent respiratory tract infections, in 9 patients with recurrent stomatitis and in 32 control subjects. A partial, transitory deficiency in interferon-alpha production was found in 2 children with recurrent respiratory tract infections. The deficiency may be either cause or effect of the recurrent infections. Many data support the latter hypothesis.

Adolescent↗
PubMed1991

A randomized study of ciprofloxacin versus ceftriaxone in the treatment of nursing home-acquired lower respiratory tract infections.

OBJECTIVE: To compare the efficacy and safety of ciprofloxacin and ceftriaxone in patients with nursing home-acquired lower respiratory tract infections requiring initial hospitalization. DESIGN: Prospective, randomized trial. SETTING: Extended care nursing homes affiliated with a teaching hospital. PATIENTS: Fifty patients aged 60 years or older with normal or mildly impaired renal function admitted to the hospital for treatment of lower respiratory tract infections. INTERVENTIONS: Twenty-four patients received initial therapy with intravenous ciprofloxacin, 200 mg every 12 hours (19 patients) or 400 mg every 12 hours (5 patients) during the acute phase followed by 750 mg orally every 12 hours during the convalescence phase. Twenty-six patients received initial therapy with intravenous ceftriaxone, 2 g every 24 hours during the acute phase followed by 1 g administered intramuscularly every 24 hours during the convalescent phase. The total duration of therapy was 14 days. MAIN OUTCOME MEASUREMENTS: Successful outcome was defined as resolution or marked improvement in clinical signs and symptoms of lower respiratory tract infection upon completion of the treatment course. RESULTS: Twelve (50%) of the ciprofloxacin-treated and 14 (54%) of ceftriaxone-treated patients had successful outcomes. Recurrent oropharyngeal aspiration was the reason for treatment failure in most patients refractory to either antibiotic. Mortality during therapy was 8% in each group. From 21 satisfactory sputum specimens collected, S. pneumoniae was the most common isolate, followed by H. influenzae and other Gram-negative bacteria. Ciprofloxacin therapy was well tolerated; ceftriaxone therapy was discontinued in two patients (8%) due to adverse reactions (intramuscular pain and drug fever). CONCLUSIONS: Sequential intravenous/oral ciprofloxacin appears to be as safe and effective as sequential intravenous/intramuscular ceftriaxone. The optimal dosage of intravenous ciprofloxacin in this patient population appears to be 400 mg every 12 hours; however, additional clinical and pharmacokinetic studies with this regimen are warranted.

Administration, Oral↗
PubMedDate not supplied

Hypoxaemia in infants with respiratory tract infections.

Nineteen infants who were graduates from special care baby units underwent two overnight tape recordings of oxygen saturation (SaO2) and breathing movements; one during an upper (n = 12) or lower (n = 7) respiratory tract infection and the other when free of infection. Baseline SaO2 was lower during infection (median 99.6 vs 100%, p less than 0.01), with four patients having values (84.3-95.5%) below the normal lower limit for full-term infants (97%). The median number of apnoeic pauses was also lower during respiratory tract infection (4.7 vs 15.7/h, p less than 0.02). The median number of episodic desaturations (SaO2 less than or equal to 80%) did not change significantly (1.3 vs 1.9/h, p greater than 0.05), with the exception of one patient who had extremely increased values during infection for both apnoeic pauses (63/h) and desaturations (112/h). No infant, however, was considered clinically hypoxaemic. Clinically unsuspected hypoxaemia may thus occur during respiratory tract infection in a proportion of infants graduating from special care baby units. Such hypoxaemia may have potentially deleterious effects.

Apnea↗
PubMed2005

Impact of rapid detection of viral and atypical bacterial pathogens by real-time polymerase chain reaction for patients with lower respiratory tract infection.

BACKGROUND: Rapid diagnostic tests with a high sensitivity for lower respiratory tract infection (LRTI) could lead to improved patient care and reduce unnecessary antibiotic use and associated costs. Diagnostic yields, feasibility, and costs of real-time polymerase chain reaction (PCR) of nasopharyngeal and oropharyngeal swab specimens in the routine diagnostic work-up for LRTI were determined. METHODS: In a randomized controlled trial, nasopharyngeal and oropharyngeal swab specimens from patients admitted for antibiotic treatment of LRTI were evaluated by means of real-time PCR for respiratory viruses and atypical pathogens, as well as by conventional diagnostic procedures. Real-time PCR results for patients in the intervention group were reported to the treating physician; results for patients in the control group were not made available. RESULTS: A total of 107 patients (mean age [+/- standard deviation], 63.6+/-16.3 years) were included, of whom 55 were allocated to the intervention group. The pathogens detected most frequently were influenza virus (14 patients), Streptococcus pneumoniae (8), coronavirus (6), Staphylococcus aureus (5), and rhinoviruses (5). Real-time PCR increased the diagnostic yield from 23 cases (21% of patients) to 47 cases (43% of patients), compared with conventional diagnostic tests. The detection of viral pathogens by PCR was associated with the winter season, less infiltrates on chest radiographs, lower C-reactive protein levels, and shorter duration of symptoms. Use of real-time PCR results resulted in partial or total cessation of antibiotic treatment for 6 patients (11%; 95% confidence interval, 2-19), but overall antibiotic use was comparable in the intervention group and the control group (median duration of treatment, 10.0 vs. 9.0 days; P=not significant). Use of real-time PCR increased treatment and diagnostic costs with 318.17 per patient. CONCLUSIONS: Implementation of real-time PCR for the etiological diagnosis of LRTI increased the diagnostic yield considerably, but it did not reduce antibiotic use or costs.

Adult↗
PubMed2001

Pathogenesis of RSV lower respiratory tract infection: implications for vaccine development.

Respiratory syncytial virus (RSV) infection is the most prevalent cause of severe respiratory disease in infants. It also causes considerable morbidity in older children and adults with underlying risk factors. RSV vaccine development has been complicated by the need to administer the vaccine at a very young age and by enhanced disease observed after vaccination with formalin inactivated RSV. For infants live attenuated vaccines, which may not be expected to predispose for vaccine induced enhanced pathology, hold the greatest promise. However, the balance between attenuation and immunogenicity appears to be delicate. For older risk groups, results with subunit vaccines are most promising.

Antibodies, Viral↗