Clinical and Laboratory Evaluation of Cefamandole in the Therapy of Haemophilus spp. Bronchopulmonary Infections

Abstract

A prospective, randomized, single-blind comparison of parenteral cefamandole and ampicillin was conducted in 27 hospitalized adult patients with pneumonia or purulent tracheobronchitis due to Haemophilus spp. Patients received either parenteral cefamandole or ampicillin in a dose of 1 g every 6 h. Cefamandole was as effective and safe as ampicillin. Of the 14 patients treated with cefamandole, 13 were considered cured, as were 12 of the 13 treated with ampicillin. One patient in each treatment group improved clinically but did not clear his sputum of Haemophilus spp. One patient treated with cefamandole had a recurrence of Haemophilus spp. bronchitis 9 days after cure. Adverse effects were more common in the cefamandole-treated group (50% versus 15%), but were mild and did not require discontinuation of therapy in any patient. The in vitro susceptibilities of 64 clinical isolates of Haemophilus spp. to 10 antibiotics were determined.Cefamandole was the most active of the cephalosporin-cephamycin antibiotics tested, inhibiting 98% of 61 non-beta-lactamase-producing isolates at 2 ,ug/ml and 100% at 4 ,g/ml. Cefamandole inhibited the three ampicillin-resistant isolates at 2 ug/ml or less. Cephapirin, cefoxitin, and cephalothin were the next most active, whereas cefazolin and cephradine were the least active.Ampicillin has generally been regarded as the antimicrobial agent of choice for Haemophilus influenzae bronchopulmonary infections (13). However, there have been recent reports of ampicillin-resistant H. influenzae strains, particularly type B (10,12,20,23). Recently, there have also been sporadic reports of resistance to chloramphenicol and tetracycline (14,23), the usual alternative drugs. Cefamandole, a new cephalosporin with a broad spectrum of activity, has been shown to be effective against various infectious disorders caused by H. influenzae (2,18

Ampicillin versus cefamandole as initial therapy for community-acquired pneumonia

“…Several other antibiotic trials of patients hospitalized with communityacquired respiratory infections have reported mortality rates ranging from 4 to 11% and have noted that most deaths resulted from the patients' underlying disorders (10,20,22,25,26,31,53,58). The mortality rate for our patients is lower than the 8 to 24% reported for patients hospitalized with community-acquired pneumonia but not specifically entered in a therapeutic trial (14,15,21,40,46,61,66).…”

“…Side effects and superinfections were infrequent, and their incidence did not differ between the ampicillin and cefamandole groups. Previous antibiotic trials have demonstrated that cefamandole is as efficacious as penicillin for pneumococcal pneumonia (54,55) and as efficacious as ampicillin for lower respiratory infection due to H. influenzae (10). Further, broad-spectrum cephalosporins have not been shown to be more efficacious than cefamandole for communityacquired pneumonia (6,16,20,24,25,31,35,39,58,65).…”

Ceforanide and cefazolin therapy of pneumonia: comparative clinical trial

“…Pretreatment sputum samples grew H. influenzae usually contained "many" organisms on culture and were all positive on gram stain, whereas samples on therapy were gram stain-negative in the small number of patients in which this test was performned, and contained only "few" or "moderate" numbers of organisms on culture. Newer secondand third-generation cephalosporins may have better in vitro potency than ceforanide against H. influenzae (3,15). It remains to be established whether this enhanced potency will lead to superior bacteriological responses.…”

“…or intravenous (i.v.) injection is approximately 3.0 h (9). In normal adults, peak serum levels of ceforanide are in excess of 30 ,g/ml after a 0.5-g dose and exceed 60 ,ig/ml after a 1.0-g dose.…”

Pharmacology, Safety, and efficacy of cefamandole in childhood infections

“…The drug was tolerated well. Cefamandole appears to be a reasonable alternative in the initial treatment of skeletal infections in children, but needs to be administered every 4 h to maintain suprainhibitory serum levels between doses.…”