Clinical and bacteriological efficacy and tolerability of FCE 22891 in patients with exacerbations of chronic obstructive pulmonary disease

Abstract

A 1-lactamase-stable antibiotic, the oral penem FCE 22891 (ritipenem acoxil), was investigated for use in exacerbations of chronic obstructive pulmonary disease (COPD). Thirteen Exacerbations of chronic obstructive pulmonary disease (COPD) are often caused by viral and bacterial infections, which are the most common causes of death in patients with this disease (5). The three major pathogens isolated from sputum specimens from COPD patients during an exacerbation are Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. In the past decade an increasing resistance to ampicillin due to production of P-lactamase has been recorded for H. influenzae (15 to 30%) (10, 11, 13) andM.catarrhalis (up to 85%) (8,10,22). When the choice of treatment is empiric, especially in seriously ill patients, the agent should be directed against these P-lactamase-producing bacteria (17).The penem FCE 22891 (ritipenem acoxil) can be orally administered and is hydrolized in the intestine into its active moiety, FCE 22101 (7). FCE 22101 is active against staphylococci (including some methicillin-resistant Staphylococcus aureus strains), streptococci, anaerobes (including Bacteroides species), and gram-negative aerobic bacteria, particularly the 3-lactamase-producing strains (17,18,24) antibiotics during the week preceding admission to the hospital, sputum culture yielding Pseudomonas species, allergy or hypersensitivity to 1-lactam antibiotics, severe renal or liver disease, and pregnancy or breast-feeding.All patients were treated according to standardized therapy. Prednisolone (60 mg/24 h, tapering dosage) and theophylline (500 to 800 mg/24 h) was administered intravenously, salbutamol (2,500 ,ug) and ipratropium bromide (500 ,ug) were administered via a nebulizer four times a day, and FCE 22891 (2 tablets of 500 mg three times a day) was given orally with a meal for 10 days. This was the maximum dosage which was tolerated well when given to healthy individuals in multiple administrations. Moreover, pharmacokinetic studies showed an acceptable bioavailability after a single oral administration of 1 g of FCE 22891 (20).Symptoms were assessed before, during (days 4 and 8), and after (day 11) treatment and during follow-up (day 18) by the same investigator (S.P.). The severity of symptoms (dyspnea, cough, rales, signs of bronchial obstruction, and sputum production) was scaled from 0 to 2 (absent, mild, and severe). Sputum samples were examined and given a score of 0 (absent), 1 (mucous), 2 (mucopurulent), or 3 (purulent) (max-

Chemical and Microbiologic Aspects of Penems, a Distinct Class of β‐Lactams: Focus on Faropenem

“…37 It also was tested in exacerbations of chronic obstructive pulmonary disease, where significant improvements in symptoms and lung function were seen, although it was not effective against H. influenzae and was associated with gastrointestinal disturbances. 38 In other studies, ritipenem was compared with cefotiam against lower respiratory tract infections and bacterial pneumonia. 39,40 In these studies, ritipenem had a similar efficacy to that of cefotiam (with excellent or good efficacy in 85% and 91.8%, respectively) and did not present any safety issues.…”