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Significance of human beta-defensins in the epithelial lining fluid of patients with chronic lower respiratory tract infections.

Human beta-defensins (hBDs) are the most abundant antimicrobial peptides in epithelial cells, and function in the host immune system. Respiratory epithelial cells express hBDs to inhibit bacterial proliferation during respiratory tract infections. The aim of this study was to investigate the release of hBDs into the respiratory tract and their benefit as a host defence system in chronic Pseudomonas aeruginosa infections. The levels of four hBD peptides (hBD-1-hBD-4) were measured in the bronchial epithelial lining fluid (ELF) of nine patients with chronic lower respiratory tract infection caused by P. aeruginosa. Eight patients with idiopathic pulmonary fibrosis and eight volunteers free of pulmonary disease were recruited as controls. ELF was obtained by bronchoscopic microsampling and hBD levels were measured by radioimmunoassays. The antimicrobial effects of hBDs were studied individually and in combination using an in-vitro colony count assay for P. aeruginosa. Concentrations of hBD-1 and hBD-3 tended to be higher in patients with chronic lower respiratory tract infection than in the controls. hBD-2 and hBD-4 were detected in ELF from five and four of nine patients, respectively, but the hBD levels in controls were all below the limits of detection. All patients with infection caused by mucoid P. aeruginosa had detectable hBD-2 and hBD-4 levels in ELF. In-vitro colony count assays showed a potential synergism between hBD-2 and hBD-4 in inhibiting bacterial proliferation. The findings indicate that hBDs, especially hBD-2 and hBD-4, are pathophysiologically important in infections caused by mucoid strains of P. aeruginosa.

Aged↗

Self-reported prescribing of antibiotics for children with undifferentiated acute respiratory tract infections with cough.

BACKGROUND: Physicians are often called on to manage children with acute respiratory tract infections with cough when the clinical presentation may not allow a differentiation between viral and bacterial etiology. To develop guidelines for appropriate antibiotic use, it is necessary to understand the present prescribing patterns of physicians who manage children presenting with such an undifferentiated acute respiratory tract infection with cough (UARTIC). OBJECTIVES: To determine the variability of self-reported prescribing habits for antibiotics for children with UARTIC. METHODS: In this cross-sectional survey by a modified Dillman's Total Design Method, a mail-out questionnaire was administered to a random sample of 181 primary care family physicians and pediatricians (Toronto, Ontario, Canada) to assess perceptions of their own antibiotic-prescribing habit. RESULTS: Completed questionnaires were received from 136 (75%) eligible physicians; 32% reported that > 10% of their office visits were for UARTIC. For a 3-day history of UARTIC 24% reported prescribing antibiotics or antibiotics in reserve (i.e. a prescription to be filled if the patient's condition does not improve) always or most times. This increased to 45% when UARTIC had worsened in the 24 h before the office visit (P < 0.001). CONCLUSION: When a pediatric patient presented with UARTIC, antibiotics or antibiotics in reserve were prescribed in the absence of clear indicators of bacterial infection. Research- and evidence-based guidelines are needed to support rational antibiotic use for UARTIC.

Acute Disease↗

Optimizing the management of community-acquired respiratory tract infections in the age of antimicrobial resistance.

Community-acquired respiratory tract infections (CARTIs) are the most common reason for prescribing antibiotics in the primary care setting. However, over the last decade, the management of CARTIs has become increasingly complicated by the steady increase in prevalence of drug-resistant pathogens responsible for these infections. As a result, significant attention has been directed at understanding the mechanisms of pathogen acquisition of resistance, drivers of resistance and methods for preventing the development of resistance. Data from recent surveillance studies suggest a slowing or decline in resistance rates to agents, such as beta-lactams, macrolides, tetracyclines and folic acid metabolism inhibitors. However, resistance to one antimicrobial family--the fluoroquinolones--while still low, appears to be on the increase. This is of significant concern given the rapid increase in resistance noted with older antibiotics in recent history. While the clinical implications of antibacterial resistance are poorly understood, the overall rates of antimicrobial resistance, as reported in recent surveillance studies, do not correspond to current rates of failure in patients with CARTIs. This disconnection between laboratory-determined resistance and clinical outcome has been termed the in vitro-in vivo paradox and several explanations have been offered to explain this phenomenon. Solving the problem of antimicrobial resistance will be multifactorial. Important factors in this effort include the education of healthcare providers, patients and the general healthcare community regarding the hazards of inappropriate antibiotic use, prevention of infections through vaccination, development of accurate, inexpensive and timely point-of-care diagnostic tests to aid in patient assessment, institution of objective treatment guidelines and use of more potent agents, especially those with a focused spectrum of activity, earlier in the treatment of CARTIs as opposed to reserving them as second-line treatment options. Ultimately, the single-most important factor will be the judicious use of antibiotics, as fewer antibiotic prescriptions lead to fewer antimicrobial-resistant bacteria.

Anti-Bacterial Agents↗

[Hypersensitivity to house dust mites and incidence of acute respiratory tract infections in children with bronchial asthma].

The aim of the study was to evaluate the relationship between h.d.m. allergy and incidence of respiratory tract infections in children with episodic, mild and moderate asthma. 32 children with bronchial asthma being followed up at the I. Department of Children Diseases P.A.I.P. CMUJ in Cracow were included into the study. The positive skin prick test (SPT) with H.D.M. allergens was confirmed in 18 children. The negative SPT allergens were observed in 14 patients. All patients were examinated by the retrospective inquiry which included the degree of asthma, severity of therapy schedule and incidence of acute respiratory tract infections during the last 6 months. The anthropometric measurement (length, weight, body mass index, thorax circumference) and spirometric parameters with physical examination challenge were introduced. The mean number of infections in group of patients sensitive to H.D.M. was 6.8; in non sensitive group-4.6. There was no significant difference in incidence of acute respiratory tract infections between both groups. It seems likely that small number of patients may influence the statistics. To verify the results, prospective observation of wider group of patients is planned in forthcoming winter.

Animals↗

Comparative evaluation of cefpodoxime versus cefixime in children with lower respiratory tract infections.

OBJECTIVE: The emergence of penicillin and macrolide resistant strains, responsible for Acute Lower Respiratory Tract Infections in children has offered third generation cephalosporins the platform to perform. The aim of the present study was to evaluate two third generation oral cephalosporins for their empirical use in community acquired lower respiratory tract infections in pediatric patients. An assessment of the clinical cure and bacteriological eradication rates and an overall tolerability was made. METHODS: It was a prospective, open, comparative, multicentric study. 776 children (Mean age 10 years) with LRTIs were included and randomly allotted to two groups respectively. A total of 396 children were given cefpodoxime susp 5 mg/kg b.i.d. and 380 patients on cefixime 4 mg/kg b.i.d. for 10-14 days. RESULTS: At the end of therapy, the clinical success with cefpodoxime was 97% as against 86.8% with cefixime. Bacterial eradication was 93.4% with cefpodoxime and 82.9% with cefixime. CONCLUSION: Cefpodoxime has been found to be a well-tolerated and superior alternative to cefixime synergistically documenting the extended spectrum of activity.

Acute Disease↗

Single-dose azithromycin for respiratory tract infections.

OBJECTIVE: To describe the pharmacology, efficacy, and safety data of the use of single-dose azithromycin for respiratory tract infections in children and adults. DATA SOURCES: A MEDLINE search (1990-September 2003) was performed to identify all pertinent studies and review articles. When appropriate information was not available in the literature, data were obtained from the product manufacturers or abstracts from international conferences. STUDY SELECTION AND DATA EXTRACTION: All available studies were reviewed to provide pharmacokinetic, pharmacodynamic, efficacy, and safety data on use of single-dose azithromycin for respiratory tract infections. DATA SYNTHESIS: Several studies have demonstrated that shorter regimens of azithromycin (1500 mg over 3 day vs 5 day or single dose vs 3 day) provide higher serum exposures compared with the longer regimens. This makes it possible to give the same dose over a shorter period of time and achieve the same efficacy with the potential for enhanced adherence. Single-dose azithromycin 30 mg/kg was approved in 2003 for treatment of acute otitis media (AOM) in children. Studies have demonstrated that, when administering azithromycin as a single dose, its efficacy and safety are comparable to that of other standard regimens for AOM. Single-dose regimens for treatment of respiratory tract infections in adults have not been studied widely, with only 2 studies being conducted for treatment of community-acquired pneumonia and one study for treatment of tonsillitis; all demonstrated at least equal efficacy with the single-dose regimen compared with comparators given for longer periods of time. CONCLUSIONS: Available data regarding single-dose azithromycin are promising. Although use of this regimen in children is warranted based on studies to date, additional large-scale trials are needed prior to mainstream use of the regimen in adults.

Adult↗

Two pharmacodynamic models for assessing the efficacy of amoxicillin-clavulanate against experimental respiratory tract infections caused by strains of Streptococcus pneumoniae.

Two models of respiratory tract infection were used to investigate the pharmacodynamics of amoxicillin-clavulanate against Streptococcus pneumoniae. Eight strains of S. pneumoniae were used in a mouse model in which the animals were infected intranasally and were then treated with a range of doses and dose intervals. The time that the plasma amoxicillin concentration remained above the MIC (T>MIC) correlated well with bacterial killing, such that if T>MIC was below 20% there was no effect on bacterial numbers in the lungs. As T>MIC increased, the response, in terms of decreased bacterial load, improved and at T>MICs of greater than 35 to 40% of the dosing interval, bacteriological cure was maximal. On the basis of equivalent T>MICs, these data would suggest that in humans a dosage of 500 mg three times daily (t.i.d.) should have efficacy equal to that of a dosage of 875 mg twice daily (b.i.d.). This hypothesis was evaluated in a rat model in which amoxicillin-clavulanate was given by computer-controlled intravenous infusion to achieve concentrations that approximate the concentrations achieved in the plasma of humans following oral administration of 500/125 mg t.i.d. or 875/125 mg b.i.d. Infusions continued for 3 days and bacterial numbers in the lungs 2 h after the cessation of the infusion were significantly reduced (P < 0.01) by both treatments in strains of S. pneumoniae for which amoxicillin MICs were below 2 microg/ml. When tested against a strain of S. pneumoniae for which the amoxicillin MIC was 4 microg/ml, the simulated 500/125-mg dose was ineffective but the 875/125-mg dose demonstrated a small but significant (P < 0. 01) reduction in bacterial numbers. These data confirm the findings in the mouse and indicate that amoxicillin-clavulanate administered at 875/125 mg b.i.d. would be as effective clinically as amoxicillin-clavulanate administered at 500/125 mg t.i.d.

Amoxicillin-Potassium Clavulanate Combination↗

Pefloxacin in the treatment of lower respiratory tract infections in geriatrics.

Pefloxacin was administered to 24 geriatric patients as treatment for lower respiratory tract infections contracted in hospital. Efficacy was evaluated by clinical, bacteriological and radiological parameters. Two-thirds of the patients responded well to therapy. Only two of 30 pathogens were not eradicated, but seven patients had superinfection or colonization by another organism. Tolerance was excellent, with only slight gastro-intestinal disorders. Pefloxacin was shown to be an effective and safe therapy for lower respiratory tract infections contracted in hospital in elderly patients.

Aged↗

[Bacteria isolated from chronic upper and lower respiratory tract infections and the associated therapeutic strategies--in paranasal sinusitis].

Nasal sinusitis, tonsillitis, and pharyngolaryngitis typify upper respiratory tract infections, while bronchitis and pneumonia typify lower respiratory tract infections. Cases of paranasal sinusitis with severe suppuration are reportedly becoming less frequent, while those of chronic catarrhal paranasal sinusitis and edematous allergic paranasal sinusitis are becoming more so, The primary factor in paranasal sinusitis, a typical infectious disease encountered in otolaryngology, is bacterial infection. The main causative bacteria are Streptococcus pneumoniae, reported in 13.4% of cases, Haemophilus influenzae in 12.8% Moraxella catarrhalis in 5.5%, Staphylococcus aureus in 26.5%, Pseudomonas aeruginosa in 5.2%, and anaerobes. The incidence of strains resistant to antimicrobial agents has grown for S. pneumoniae, H. influenzae, and M. catarrhalis and decreased for S. aureus and P. aeruginosa. Acute exacerbation or severe suppuration in chronic paranasal sinusitis requires the administration of antimicrobial agents, with the same agent administered 2 weeks for maximal effect. First-line agents are AMPC/CVA, SBTPC, CDTR-PI, CFPN-PI, and GFLX for adults, with ASPC, SBPC, ACPC, CTRX, CMZ, FMOX, PAPM/BP, and MEPM injected in severe cases. Attention must be paid to strains that resist cephems and macrolides, such as PISP, PRSP, and BLNAR. In refractory chronic paranasal sinusitis, attention must also be paid to biofilms produced by S. aureus and P. aeruginosa. Suitable antimicrobial agents should be determined for treating of chronic paranasal sinusitis, in addition to the best procedure to ensure early recovery from inflammation, such as puncturing or irrigating the maxillary sinus, injecting a suitable agent, nebulization, and/or surgically widening the middle meatus.

Anti-Infective Agents↗

[Four cases of respiratory tract infections caused by Corynebacterium pseudodiphtheriticum].

Four cases of respiratory tract infections caused by Corynebacterium pseudodiphtheriticum were reported. The first two patients developed pneumonia with Corynebacterium pseudodiphtheriticum during steroid therapy used against their underlying diseases. The other two patients had acute exacerbation of chronic pulmonary diseases caused by C. pseudodiphtheriticum. These four patients improved by antibiotic therapy. Though nondiphtheria corynebacteria are regarded as "normal flora" when they are isolated from sputum, they should be recognized as potential pathogens.

Aged↗

Echinacea root extracts for the prevention of upper respiratory tract infections: a double-blind, placebo-controlled randomized trial.

OBJECTIVE: To investigate the safety and efficacy of 2 extracts of echinacea for preventing upper respiratory tract infections. DESIGN: Three-armed, randomized, double-blind, placebo-controlled trial. SETTING: Four military institutions and 1 industrial plant. PARTICIPANTS: Three hundred two volunteers without acute illness at time of enrollment. INTERVENTIONS: Ethanolic extract from Echinacea purpurea roots, Echinacea angustifolia roots, or placebo, given orally for 12 weeks. MAIN OUTCOME MEASURE: Time until the first upper respiratory tract infection (time to event). Secondary outcome measures were the number of participants with at least 1 infection, global assessment, and adverse effects. RESULTS: The time until occurrence of the first upper respiratory tract infection was 66 days (95% confidence interval [CI], 61-72 days) in the E angustifolia group, 69 days (95% CI, 64-74 days) in the E purpurea group, and 65 days (95% CI, 59-70 days) in the placebo group (P = .49). In the placebo group, 36.7% had an infection. In the treatment groups, 32.0% in the E angustifolia group (relative risk compared with placebo, 0.87; 95% CI, 0.59-1.30) and 29.3% in the E purpurea group (relative risk compared with placebo, 0.80; 95% CI, 0.53-1.31) had an infection. Participants in the treatment groups believed that they had more benefit from the medication than those in the placebo group (P = .04). Adverse effects were reported by 18 subjects in the E angustifolia group, 10 in the E purpurea group, and 11 in the placebo group. CONCLUSION: In this study a prophylactic effect of the investigated echinacea extracts could not be shown. However, based on the results of this and 2 other studies, one could speculate that there might be an effect of echinacea products in the order of magnitude of 10% to 20% relative risk reduction. Future studies with much larger sample sizes would be needed to prove this effect.

Adult↗

Treatment of respiratory tract infections with a combination of amoxycillin and clavulanic acid.

Forty-four patients with respiratory tract infections were treated using a new formulation of amoxycillin and clavulanic acid. Clinical diagnosis was classified as follows: 19 cases of acute exacerbations of chronic bronchitis, 10 cases of bronchiectasis, and 15 cases of diffuse or localized pneumonia. Amoxycillin/clavulanic acid combination (amoxycillin 250 mg + clavulanic acid 125 mg per tablet) was administered as 2 tablets three times per day for 7-14 days. The efficacy was as follows: chronic bronchitis 94.7%, bronchiectasis 80.0% and pneumonia 93.3%. No severe adverse reactions occurred in treated patients and no renal, hepatic or hematological toxicity was observed. Amoxycillin/clavulanic acid combination was a safe and effective antimicrobial agent for the treatment of respiratory tract infections.

Adult↗

Respiratory tract infection due to Arcanobacterium haemolyticum--a case report.

A case of respiratory tract infection due to Arcanobacterium haemolyticum is reported. A female of 26 years presented with cough with expectoration and fever off and on for a duration of six weeks. Mycobacterium tuberculosis and Arcanobacterium haemolyticum were isolated. Arcanobacterium haemolyticum was isolated on three separate occasions.

Actinomycetaceae↗

[Viruses and bacteria in the etiology of acute respiratory tract infections in young children].

Respiratory infections in small children are among the major problems in paediatrics. They are caused most frequently by viruses or bacteria. The role played by certain types of respiratory viruses in these infections is discussed, considering selected subgroups of children and the seasonal incidence of infections. The usefulness of certain virological investigations in clinical diagnosis is analysed. In the description of bacterial respiratory infections in small children attention is called also to certain bacteria belonging to opportunistic commensals and the importance of anaerobes. The main stress is laid on infections of newborns and infants which may be connected with the transfer of pathogens from mothers. Attention is called to the necessity of close monitoring of the aetiological factors of acute respiratory infections in the youngest children which could increase the accuracy of therapeutic management and prophylactic measures which should be regarded as a very important factor in the control of these infections.

Acute Disease↗

A case-control study of acute respiratory tract infection in general practice patients in The Netherlands.

BACKGROUND: Acute respiratory tract infections (ARTIs) are responsible for considerable morbidity in the community, but little is known about the presence of respiratory pathogens in asymptomatic individuals. We hypothesized that asymptomatic persons could have a subclinical infection and thus act as a source of transmission. METHODS: During the period of 2000-2003, all patients with ARTI who visited their sentinel general practitioner had their data reported to estimate the incidence of ARTI in Dutch general practices. A random selection of these patients (case patients) and an equal number of asymptomatic persons visiting for other complaints (control subjects) were included in a case-control study. Nose and throat swabs of participants were tested for a broad range of pathogens. RESULTS: The overall incidence of ARTI was 545 cases per 10,000 person-years, suggesting that, in the Dutch population, an estimated 900,000 persons annually consult their general practitioner for respiratory complaints. Rhinovirus was most common in case patients (24%), followed by influenza virus type A (11%) and coronavirus (7%). Viruses were detected in 58% of the case patients, beta -hemolytic streptococci group A were detected in 11%, and mixed infections were detected in 3%. Pathogens were detected in approximately 30% of control subjects, particularly in the youngest age groups. CONCLUSION: This study confirms that most ARTIs are viral and supports the reserved policy of prescribing antibiotics. In both case and control subjects, rhinovirus was the most common pathogen. Of bacterial infections, only group A beta-hemolytic streptococci were more common in case patients than in control subjects. Furthermore, we demonstrated that asymptomatic persons might be a neglected source of transmission.

Acute Disease↗

Antitussive efficacy of dextromethorphan in cough associated with acute upper respiratory tract infection.

Dextromethorphan is one of the most widely used antitussives for the treatment of cough associated with acute upper respiratory tract infection. However, there is very little data to support the efficacy of dextromethorphan in this disease state. This aim of this study was to obtain more information about the efficacy of a single dose of 30 mg dextromethorphan in the treatment of cough associated with acute upper respiratory tract infection. The study was a double-blind, stratified, randomized and parallel group design. Both objective and subjective measurements of cough were recorded over 10-min recording periods in a quiet room before (baseline) and at 90, 135 and 180 min after treatment. Forty-three patients (30 females and 13 males), mean age 22.9 years (range 18-46 years), with acute dry or slightly productive cough and otherwise healthy were included in the study. Patients were randomized to placebo treatment (n = 22) and dextromethorphan treatment (n=21). The results showed similar trends in both treatment groups with statistically significant reductions (P < 0.05) in cough sound pressure level (CSPL), cough frequency (CF) and subjective scores for cough severity within treatment groups but little difference between the treatment groups during the study period. The only statistically significant difference between treatment groups was for the mean CSPL changes from baseline to 90 min (P=0.019). There was a significant positive correlation between CSPL and CF (r = 0.752, P= 0.000) for changes in cough measurements from baseline to 90 min after treatment and this indicates that CSPL may be a useful measure of cough severity. This study provides very little if any support for clinically significant antitussive activity of a single 30 mg dose of dextromethorphan in patients with cough associated with acute upper respiratory tract infection.

Adolescent↗

Efficacy of ceftizoxime administered twice daily in hospitalized patients with respiratory tract infections.

The efficacy and safety of ceftizoxime administered twice daily were evaluated in 215 hospitalized patients with documented lower respiratory tract infections. The majority of patients received 1 to 2 gm of ceftizoxime intramuscularly or intravenously every 12 hours; the mean dosage was 2 gm/day, and the mean duration of therapy was 8.9 days. Clinical cure was achieved in 204 (95%) of the 215 patients with lower respiratory tract infection. One hundred and thirty-eight patients were both clinically and bacteriologically evaluable. The clinical response rates, by organism, were: Streptococcus pneumoniae, 100% (50/50); Haemophilus influenzae, 96% (25/26); gram-negative bacilli (Escherichia coli, Proteus mirabilis, Enterobacter sp, Serratia sp, Pseudomonas sp, Klebsiella sp, Citrobacter sp, and Morganella morganii), 86% (32/37); and Staphylococcus aureus, 92% (12/13). In the other 77 patients with clinical symptoms, no pathogen was isolated or insufficient follow-up data were collected to assess bacteriologic response. Adverse reactions, which were infrequent, were similar to those reported in other US trials of the drug. The findings indicate that ceftizoxime, 1 to 2 gm BID, is effective and safe in the treatment of lower respiratory tract infections in hospitalized patients. This low-dose regimen can significantly reduce the cost of cephalosporin therapy.

Adolescent↗