Indicators of bacterial infection in patients with acute exacerbation of chronic bronchitis for application in clinical trials of antibacterial drugs.

OBJECTIVES: This study examined the accuracy of: (a) patient symptoms; (b) microscopic examination of sputum purulence (>25 WBCs and <10 epithelial cells) and (c) microscopic examination of morphological bacterial cell types, in identifying bacterial infection in patients with an acute exacerbation of chronic bronchitis (AECB) for entry to clinical trials. METHODS: Subjects had a worsening of at least two symptoms from: dyspnoea, sputum volume, and sputum purulence (Anthonisen Type 1 or 2 exacerbation). Sputum samples were collected from all subjects. RESULTS: A total of 97 sputum samples were evaluated. Overall, 58 (60%) subjects were culture-positive; 22 of 29 (76%) subjects with Type 2 exacerbation had a bacterial pathogen isolated compared with 36 of 68 (53%) Type 1 subjects. This difference was not statistically significant. Microscopically purulent samples were found to be significantly more likely to be culture-positive than non-purulent samples. However, the sensitivity (60%) and specificity (67%); and the positive predictive value (73%) and negative predictive value (53%) observed, means that this is not an ideal predictive test for clinical trials. A semi-quantitative approach to Gram staining was identified as a potential indicator of bacterial infection. Sputum specimens with one bacterial cell type present at >10 cells per field, or more than one cell type present with at least one type at a concentration of >25 cells per field, had a high proportion (91%) of culture-positive specimens. CONCLUSIONS: Symptoms alone are a poor indicator of bacterial infection. A semi-quantitative examination of a Gram-stained sputum preparation was the best indicator of bacterial infection. This finding may have relevance in the design of clinical trials of antibacterial drugs in AECB.

Antimicrobial selection for community-acquired lower respiratory tract infections in the 21st century: a review of gemifloxacin.

Community-acquired lower respiratory tract infections (LRTIs) are more prevalent in the elderly than in children and younger adults and form a significant proportion of all consultations and hospital admissions in this older age group. Furthermore, in a world of increasing life expectancy the trend seems unlikely to be reversed. Antimicrobial treatment of community-acquired pneumonia (CAP) must cover Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis, and in many circumstances should also cover the intracellular (atypical) pathogens. In contrast, acute exacerbations of chronic bronchitis (AECB) are mainly associated with H. influenzae and S. pneumoniae and not with atypical bacteria: in severe cases, other Gram-negative bacteria may be involved. Frequently in LRTIs, the aetiology of the infection cannot be identified from the laboratory specimens and treatment has to be empirical. In such situations it is important to not only to use an antibiotic that covers all likely organisms, but also one that has good activity against these organisms given the local resistance patterns. Gemifloxacin is a new quinolone antibiotic that targets pneumococcal DNA gyrase and topoisomerase IV and is highly active against S. pneumoniae including penicillin-, macrolide- and many ciprofloxacin-resistant strains, as well as H. influenzae and the atypical pathogens. In clinical trials in CAP and AECB, gemifloxacin has been shown to be as effective a range of comparators and demonstrated an adverse event profile that was in line with the comparator agents. In one long-term study in AECB significantly more patients receiving gemifloxacin than clarithromycin remained free of recurrence after 26 weeks. The improved potency, broad spectrum of activity and proven clinical and bacteriological efficacy and safety profile should make it a useful agent in the 21st century battle against community-acquired LRTIs.

Randomized, double-blind study comparing 5- and 7-day regimens of oral levofloxacin in patients with acute exacerbation of chronic bronchitis.

A randomized, double-blind, multicentre study was conducted in adult patients with acute exacerbation of chronic bronchitis (AECB), to compare the efficacy of a 5-day course of levofloxacin 500 mg once daily, with the standard 7-day regimen at the same dose. Five hundred and thirty-two patients from 48 centres in 10 countries were randomized to receive levofloxacin: 268 and 264 received the 5- and 7-day courses, respectively. The primary efficacy analysis was the clinical response at 7-10 days post-treatment in the per-protocol (PP) population. Clinical success rates in the primary PP analysis of 482 patients were 82.8% (197/238) for the 5-day group and 84.8% (207/244) for the 7-day group. The difference in success rates was -2.1% with a 95% CI of (-9.1 to 4.9%). The bacteriological response showed eradication rates of 82.1% (92/112) and 83.2% (84/101) in the 5- and 7-day groups, respectively. Both treatments were well tolerated. These results show that for patients with AECB levofloxacin 500 mg once daily for 5 days provides equivalent clinical and bacteriological success to the same dose given for 7 days irrespective of the patient's age, the frequency of exacerbations or the presence of co-existing cardiopulmonary or chronic obstructive airways disease.