High levels of inherent variability in microbiological assessment of bronchoalveolar lavage samples from children with persistent bacterial bronchitis and healthy controls.

Bronchoalveolar lavage (BAL) is widely regarded as providing "gold standard" samples for infective lower respiratory tract disease. Current approaches have been adopted empirically without robust assessment and hence carry many assumptions that have not been tested. Many of these uncertainties were highlighted in the ATS pediatric bronchoscopy guidelines. This study was designed to explore some of these issues. BAL was undertaken via an endotracheal tube in 13 subjects aged less than 6 years with persistent bacterial bronchitis and five healthy controls. Aliquots of the same pooled BAL sample were sent to two accredited laboratories. one producing semiquantitative results and the other quantitative results. For five patients potentially pathogenic bacteria were grown by one laboratory but not the other, while in three more there were discrepancies in the organisms reported. Despite being symptomatic and off antibiotics, only 3 of 13 patients were reported to have a pathogen at a density of more than 1 × 104 colony forming unit. There was at best a poor correlation between semiquantitative and quantitative data. Potential pathogens were cultured in two of five control samples. The results suggest that the results from conventional microbiological assessment of BAL samples can be highly variable and that the proposal that a discrete cut-off is of value in patients with chronic endobronchial infection is probably invalid.

Valuing the Economic Costs of Allergic Rhinitis, Acute Bronchitis, and Asthma from Exposure to Indoor Dampness and Mold in the US.

Two foundational methods for estimating the total economic burden of disease are cost of illness (COI) and willingness to pay (WTP). WTP measures the full cost to society, but WTP estimates are difficult to compute and rarely available. COI methods are more often used but less likely to reflect full costs. This paper attempts to estimate the full economic cost (2014$) of illnesses resulting from exposure to dampness and mold using COI methods and WTP where the data is available. A limited sensitivity analysis of alternative methods and assumptions demonstrates a wide potential range of estimates. In the final estimates, the total annual cost to society attributable to dampness and mold is estimated to be $3.7 (2.3-4.7) billion for allergic rhinitis, $1.9 (1.1-2.3) billion for acute bronchitis, $15.1 (9.4-20.6) billion for asthma morbidity, and $1.7 (0.4-4.5) billion for asthma mortality. The corresponding costs from all causes, not limited to dampness and mold, using the same approach would be $24.8 billion for allergic rhinitis, $13.5 billion for acute bronchitis, $94.5 billion for asthma morbidity, and $10.8 billion for asthma mortality.

Prospective assessment of protracted bacterial bronchitis: airway inflammation and innate immune activation.

Protracted bacterial bronchitis (PBB) is a common cause of paediatric chronic moist cough. PBB is defined as the presence of isolated chronic moist cough which resolves with antibiotic therapy within 2 weeks and an absence of pointers suggesting alternative diagnoses. Our aim was to describe the clinical profile and examine the airway cellularity and likely promoters of neutrophilic inflammation in the bronchoalveolar lavage (BAL) of children with PBB compared with chronic cough due to other causes and controls. We explored the innate immune signaling receptors, toll-like receptors (TLR)-2 and TLR-4, as well as relevant effector molecules. A cross-sectional comparison was made of 100 children median age 2.58 years (with either PBB, coughing due to another cause or no cough controls) who underwent flexible bronchoscopy with lavage. BAL was evaluated for airway cytology, microbiology, inflammatory mediators interleukin 8 (IL-8) and active matrix metalloproteinase 9 (MMP-9) and TLR-2 and TLR-4 messenger RNA (mRNA) expression. Children with PBB had marked airway neutrophilia and increased median cytokine levels when compared to those with cough that resolved naturally and no cough controls: IL-8 0.67 versus 0.07 and 0.06 ng/ml (P < 0.005) and active MMP-9 7.25 versus 1.35 and 0.38 ng/ml (P < 0.005). The values for TLR-2 and TLR-4 mRNA expression were significantly elevated in children with PBB when compared to the control group. PBB is a paediatric condition which presents with chronic moist cough and its airway profile is characterized by intense neutrophilic airway inflammation with marked inflammatory mediator response and evidence of innate immune activation.

Optimizing economic outcomes in antibiotic therapy of patients with acute bacterial exacerbations of chronic bronchitis.

The social, medical and economic effects of acute bacterial exacerbations of chronic bronchitis on individual patients and the resource implications of this disease for the healthcare sector are considerable. Optimizing the selection of patients who should receive antibiotics according to stringent clinical criteria is the first step in promoting good clinical practice and cost-effectiveness. Antibiotic efficacy is then the major driver of cost, especially when it reduces the need for hospitalization. Resistance to first-line antibiotics can be expected to increase the risk of treatment failure. Other drivers of cost include non-compliance, which predisposes to therapeutic failure, and the selection of resistant strains. Treatment regimens of short duration, once-daily dosing and good tolerability are determinants of good compliance and cost savings. The expenses of first-line antibiotics typically account for only a small proportion of the overall costs of healthcare and the cheapest antibiotics are not necessarily the most cost-effective. The clinical success rate of first-line therapy is the primary determinant of the overall expenditure on healthcare because of the high costs associated with treatment failure, especially if it leads to hospitalization. Factors such as poor patient compliance and high antibiotic resistance rates, which undermine the clinical efficacies of first-line therapy, will increase the overall costs of treatment.

A randomised, multicentre study of ceftriaxone versus standard therapy in the treatment of lower respiratory tract infections.

In this study the efficacy and cost-effectiveness of i.v. ceftriaxone 1 g once daily (CTX) was compared with standard i.v. antibiotic treatment (STD) for lower respiratory tract infections (LRTI). STD was given according to the guidelines of the American Thoracic Society and consisted of either cefuroxime 1500 mg three times daily (q8h), amoxicillin/clavulanic acid 1200 mg q8h or ceftriaxone 2 g once daily; each with or without a macrolide. After a minimum of 5 days i.v. therapy, patients could be switched to oral therapy. One hundred patients were enrolled in the study; 52 patients received CTX and 48 STD. Groups were comparable with respect to demographic and baseline characteristics. Seventy patients had a confirmed diagnosis of pneumonia. Twenty-nine patients had a severe type I exacerbation of chronic bronchitis. In one patient the diagnosis of LRTI could not be confirmed. In approximately 50% of the patients a microbiological diagnosis could be made. The most important isolated pathogens from sputum and blood were (positive blood cultures in brackets): Streptococcus pneumoniae 14 (9) and Haemophilus influenzae 16. Mean duration of i.v. therapy was 7.4 days in both groups. Average duration of hospitalisation was 15.0 days for CTX patients and 15.9 days for STD patients. Overall cure and improvement rate at the end of treatment was 47 (90%) for patients receiving ceftriaxone 1 g compared to 37 (77%) for patients receiving standard therapy. Pathogens were eradicated or presumed to be eradicated in 84% of the CTX patients and in 76% of the STD patients. Mean total costs per treatment were lower for CTX than for STD treatment: NLG 169 versus 458. These results show, that i.v. ceftriaxone 1 g once daily is as effective as standard therapy in the treatment of LRTI and that its use reduces treatment costs, in view of the multiple daily dosing regimens of most standard therapies.

Comparative study of dirithromycin and azithromycin in the treatment of acute bacterial exacerbations of chronic bronchitis.

We compared the clinical and microbiological efficacy of dirithromycin with that of azithromycin in outpatients with acute bacterial exacerbations of chronic bronchitis who could be graded into stage III according to Ball's system of stratification. A total of 80 patients was studied. Of these, 40 were treated with dirithromycin as a once-daily dose of 500 mg for 5 days, and 40 with azithromycin as a once-daily dose of 500 mg for 3 days. At post-therapy, treatment success (cure or improvement) was achieved in 36 out of 40 (90%) patients receiving dirithromycin compared with 37 out of 40 (92.5%) in the azithromycin group. At the late post-therapy visit, 34 out of 36 (94.4%) dirithromycin-treated patients were cured as were 33 of 37 (89.2%) azithromycin-treated patients. A small proportion of patients treated with dirithromycin (10%) or with azithromycin (12.5%) suffered mild side effects. Gastrointestinal disorders, including abdominal cramps, nausea, or diarrhea, were common adverse effects. The main pathogens isolated before treatment were Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. Eradication rates at the end of treatment were 90% (36 out of 40) for the dirithromycin group and 92.5% (37 out of 40) for the azithromycin group. Persistence of H. influenzae isolates was found in 3 out of 11 (27.3%) patients treated with dirithromycin and in 2 out of 9 (22.2%) who had received azithromycin. At the late post-therapy visit, eradication occurred in 34 out of 36 (94.4%) strains in the dirithromycin group and in 33 out of 37 (89.2%) in the azithromycin group. We conclude that dirithromycin and azithromycin appear to be equally effective in the treatment of acute bacterial exacerbations of chronic bronchitis.

How do we achieve cost-effective options in lower respiratory tract infection therapy?

Acute bronchitis and acute exacerbations of chronic bronchitis, common illnesses encountered by general and family physicians, account for approximately 14 million physician visits per year. The pattern of antibiotic prescribing for these infections varies from country to country, but there is no clear rationale for these antimicrobial choices. A recent meta-analysis of all randomized, placebo-controlled trials of patients treated with antibiotics for acute exacerbations of chronic bronchitis concluded that a small but statistically significant improvement could be expected in antibiotic-treated patients. Haemophilus influenzae is the most commonly isolated organism from sputum in patients with acute exacerbations of chronic obstructive lung disease but other Haemophilus species, Streptococcus pneumoniae, and Moraxella catarrhalis may also be found. High-risk patients can be defined as being elderly, with significant impairment of lung function, having poor performance status with other comorbid conditions, having frequent exacerbations, and often requiring oral corticosteroid medication. Well-defined clinical trials measure efficacy of a drug but not the effectiveness in a real world situation. Future studies of new antimicrobials should examine their efficacy in patients with an increased risk of true bacterial infection.

Antibiotics: neither cost effective nor 'cough' effective.

BACKGROUND: Clinicians often prescribe antibiotics to treat acute bronchitis despite scant evidence that this approach is effective at speeding symptom resolution. Because patients infected with bacteria but not treated with antibiotics may need to return in the future for therapy, however, this approach may be cost effective. METHODS: To evaluate the cost of various treatment strategies to treat acute bronchitis, this study examined three different strategies including: (1) withholding antibiotics and treating only patients with persistent cough; (2) screening patients for Mycoplasma pneumoniae or Chlamydia pneumoniae and treating all patients with positive results with antibiotics; and (3) treating all patients with antibiotics. The cost analysis was approached from the patient's perspective. The main outcome measured was the cost per person in whom acute bronchitis was diagnosed. RESULTS: Withholding antibiotics and treating only patients with a persistent cough was the most cost-effective strategy given the baseline assumptions. If the cost per patient visit was over $110, the cost of an initial course of antibiotics less than $2.72, or the prevalence of bacterial infection greater than 25%, then treatment of all patients was more cost effective. Assuming a screening test of 90% sensitivity and specificity, the screening strategy was only cost effective if the cost of the screening test was less than $2.35, or less than $3.80 if the test had no false-positive or false-negative results. CONCLUSIONS: Under most circumstances, the most cost-effective strategy for treating acute bronchitis is to withhold antibiotics and treat only patients whose cough does not resolve.

[Treatment of lower respiratory tract infections in the elderly]. / Lecheniie infektsil nizhnikh dykhatel'nykh putel u lits pozhilogo vozrasta.

Sixty outpatients at the age of 65 to 75 years with exacerbated chronic bronchitis were treated with antibiotics: amoxycillin/clavulanic acid (20 patients), cefaclor (20 patients) and ciprofloxacin (20 patients). The treatment course in all the cases was 5 days. Bacteriological tests of the sputum specimens and estimation of the isolate antibiotic susceptibility by the disk diffusion method were applied to all the patients before and after the treatment. 73 per cent of the patients had mixed infection. The microflora mainly included various species of streptococci highly susceptible to the drugs (54 per cent) as well as highly susceptible strains of pneumococci and hemophilic bacilli (33 and 17 per cent respectively). Atypical microflora was detected in 10 per cent of the cases. Pseudomonas aeruginosa strains were isolated in 2 cases. Acinetobacter sp. slightly susceptible only to ciprofloxacin was isolated in 1 case. Citrobacter sp. slightly susceptible to cefaclor and moderately susceptible to ciprofloxacin was detected in 1 case. Enterobacter sp. moderately susceptible only to ciprofloxacin was isolated in 1 case. A positive factor was moderate susceptibility of Proteus mirabilis to all the three drugs. In 24 patients (the average age of 54.7 years) the pharmacokinetics of ofloxacin administered under 2 different regimens was studied. The drug was used in a single dose of 400 mg once a day (group 1) or in a dose of 200 mg twice a day (group II) followed by estimation of the drug concentration in the blood and sputum. The pathogen eradication was stated in 61.5 and 72.7 per cent of the patients in groups I and II, respectively. By the results of the treatment with the use of the above mentioned antibiotics in the elderly patients fluoroquinolones should be considered preferable from the clinical and pharmacoeconomic viewpoints.

Acute exacerbations of chronic bronchitis. Preventing treatment failures and early reinfection.

Although antimicrobial agents from a number of classes have been used with a good degree of clinical success for acute bacterial exacerbations of chronic bronchitis, the incidence of resistance by beta-lactamase-producing strains to certain penicillins and cephalosporins continues to increase and represents a growing clinical problem. There also have been reports of significant resistance by Streptococcus pneumoniae to tetracyclines and of treatment failures caused by this organism among patients receiving fluoroquinolones. The emergence of penicillin-resistant pneumococci in North America also is of concern. Although first-generation cephalosporins are no longer regarded as first-line therapy or optimal alternatives for acute exacerbations of chronic bronchitis, more recently developed agents of this class have better activity against the primary pathogens, and their efficacy and safety have been demonstrated in a number of clinical trials. Newer macrolide agents probably should be reserved for infections caused by atypical organisms.

Con: antibiotic use in exacerbations of chronic bronchitis.

An acute exacerbation of chronic bronchitis represents one of the most common illnesses treated by physicians. In spite of this, the role of infection in general, and bacterial infection in particular, is difficult to establish. Clinical signs and symptoms in patients with bacterially associated disease are not separable from those in patients without bacterial infection. Studies evaluating the efficacy of antibiotics in this setting, though suggesting that antibiotics are useful, do not provide sufficient benefit to justify routine antibiotic use. Further, these studies have not defined a subpopulation for whom antibiotics are necessary. Routine antibiotic use may delay diagnosis of other serious disease and is unequivocally very expensive, primarily because of the use of the newer and higher-cost drugs. In some situations, such as severe infection or associated with surgery, routine antibiotic use may be justified, but the use of sputum culture to guide antibiotic choice is recommended. A well designed study to finally settle the issue of antibiotic need in acute exacerbations of chronic bronchitis is badly needed.