R J Wallace

Comparative trial of cefonicid and cefamandole in the therapy of community-acquired pneumonia.

Cefonicid (Smith Kline & French Laboratories; D-75073) is a new parenteral cephalosporin with a markedly long half-life, high serum levels, and good in vitro activity against Haemophilus influenzae. Patients with community-acquired pneumonia were randomized 2:1 to receive cefonicid, 1 g daily (21 cases) or cefamandole, 1 g every 6 h (12 cases). The two groups were similar, except that the cefonicid patients were older (mean 42 versus 31 years). Peak serum levels of cefonicid averaged 133 microgram/ml after intravenous and 83 microgram/ml after intramuscular administration compared with 55 microgram/ml with intravenous cefamandole. All 9 patients on intramuscular cefonicid and 8 or 12 patients on intravenous cefonicid had trough serum levels of greater than 2.0 microgram/ml at 24 h. Sputum levels of cefonicid were usually between 2.0 and 4.0 microgram/ml and did not correlate with serum levels. Cefonicid was well tolerated, and all cefonicid patients responded clinically. Sputum cultures for H. influenzae or Streptococcus pneumoniae became negative in 6 of 7 cefamandole patients and 13 or 15 cefonicid patients. In in vitro studies, cefonicid inhibited 90% of beta-lactamase-negative h. influenzae at 0.5 microgram/ml and beta-lactamase-positive strains at 2.0 microgram/ml. Cefonicid inhibited 50% of S. pneumoniae at 1.6 microgram/ml, but required 6.4 microgram/ml to inhibit 90%. Cefonicid once a day appears to be as safe and as effective as cefamandole four times a day for therapy of community-acquired pneumonia.

Susceptibility of Mycobacterium marinum to tetracyclines and aminoglycosides.

Current agar dilution methods for susceptibility testing of Mycobacterium marinum versus the tetracyclines have failed to show in vitro susceptibility despite good in vivo results. We found that the tetracyclines were unstable in agar and resulted in a fine haze of growth for several concentrations before complete inhibition of growth was seen. In contrast, the aminoglycosides resulted in sharp minimal inhibitory concentration endpoints, which were generally independent of the length of incubation. The problems with the tetracyclines can be lessened by shortening the incubation time to 5 days and redefining the minimal inhibitory concentration as the lowest concentration resulting in no growth or a slight haze of growth. By this methodology, 19 clinical isolates of M. marinum were tested for susceptibility to the tetracyclines and aminoglycosides. Minocycline inhibited greater than 50% of isolates at 2.0 microgram/ml, whereas both minocycline and doxycycline inhibited greater than 90% of isolates at 4.0 microgram/ml. These studies support the usage of the tetracyclines in the treatment of clinical diseases due to M. marinum and suggest a susceptibility method which is more predictive of clinical results.

Comparison of the activity of cefixime and activities of other oral antibiotics against adult clinical isolates of Moraxella (Branhamella) catarrhalis containing BRO-1 and BRO-2 and Haemophilus influenzae.

MICs of 10 oral antibiotics were determined for 105 Moraxella catarrhalis and 96 Haemophilus influenzae isolates from adults. A two- to fourfold increase in MICs of oral cephalosporins was seen in the presence of BRO-1 but not with TEM-1 or BRO-2. The MICs of cefixime for 90% of strains of H. influenzae (0.125 microgram/ml) and M. catarrhalis (0.25 microgram/ml) were 8- to 64-fold lower than those of other oral cephalosporins.

Susceptibilities of Mycobacterium fortuitum biovariant fortuitum and the unnamed third biovariant complex to heavy-metal salts.

Fifty-three clinical isolates of Mycobacterium fortuitum were tested for susceptibility to heavy-metal salts and antimicrobial agents. The isolates exhibited a bimodal distribution for several heavy metals including mercury, whose resistance is often plasmid mediated. There was a biovariant difference in the incidence of resistance, and resistance to several metal ions was often observed together. There was no apparent relationship between resistance to heavy-metal salts and resistance to antimicrobial agents such as tetracycline.

Inhibition of Chlamydia trachomatis growth in McCoy, HeLa, and human prostate cells by zinc.

Zinc salts (10(-4) and 10(-5) M) inhibited the number of Chlamydia trachomatis inclusions in McCoy, HeLa, and primary human prostate epithelial cell cultures. Addition of zinc salts 1 h before or 24 h after inoculation with C. trachomatis was found to inhibit growth. Both C. trachomatis serotype D and a lymphogranuloma venereum strain were inhibited by the zinc salts. Although the mechanism of inhibition is not known, the continued presence of the zinc appeared necessary for maximal effect. At the concentrations tested, zinc was not directly toxic to the McCoy cells. These results suggest that the levels of zinc in prostatic secretions may be sufficient to preclude the recovery of chlamydia in the diagnostic laboratory or to inhibit chlamydia from infecting the prostate in vivo.

Ceforanide and cefazolin therapy of pneumonia: comparative clinical trial.

Ceforanide is a new (parenteral) long-acting cephalosporin with antimicrobial activity comparable to those of other second-generation cephalosporins. In a randomized prospective study, patients with community-acquired bacterial pneumonia were treated with ceforanide at 0.5 g every 12 h (28 cases) or with cefazolin at 1.0 g every 8 h (26 cases). The study groups were comparable in clinical and laboratory findings, including etiological diagnosis. Streptococcus pneumoniae was isolated from the sputum of 38 patients, of whom 8 (21%) were bacteremic. Mean peak and trough serum levels of ceforanide drawn 1 and 11.5 h after the 0.5-g intravenous dose were 39.6 and 2.5 microgram/ml, respectively. Of the 50 patients evaluable for efficacy, all responded clinically with no serious adverse reactions. In spite of clinical improvement and in vitro susceptibility, Haemophilus influenzae persisted in the sputum of five of the eight cefazolin-treated patients and four of the five patients treated with ceforanide. Ceforanide appears to be as safe and effective as cefazolin for the therapy of pneumonia caused by S. pneumoniae or H. influenzae, but neither drug was effective in clearing H. influenzae from the sputum.

Ceforanide (BL-S 786) in the treatment of community-acquired bacterial pneumonia

SummaryCeforanide (BL-S 786) is a new long-acting parenteral cephalosporin which has the major pharmacologic advantage of requiring only twice a day dosage. We treated 28 adult patients with community-acquired bacterial pneumonia using doses of 500 or 1000 mg every 12 hours. Twenty-four of 28 infections were due toStreptococcus pneumoniae and/orHemophilus influenzae, and all pathogens were susceptible in vitro to both cephalothin and ceforanide. Patients were treated for a mean of 7.5 days, and all showed a good clinical and radiographic response with no mortality. Of the 13 patients withH. influenzae, the organism could still be recovered during therapy in 9/12 and post therapy in 3/8. One clinical superinfection (sepsis due toPseudomonas aeruginosa) occurred during therapy. Side effects with therapy included thrombocytosis (15), asymptomatic eosinophilia (5), and mild elevation of the serum transaminases (3). These studies suggest that ceforanide is a safe and effective agent for the treatment of adult patients with bacterial pneumonia due toS. pneumoniae; further experience in therapy ofH. influenzae is needed because of frequent failure of ceforanide to eradicate this organism from the sputum.ZusammenfassungCeforanid (BL-S 786) ist ein neues, lang wirkendes parenterales Cefalosporin, das den wesentlichen pharmakologischen Vorteil hat, daß es nur zweimal am Tag verabreicht werden muß. Wir behandelten 28 erwachsene Patienten mit nicht im Krankenhaus erworbener bakterieller Pneumonie, dabei wurden Dosen von 500 mg oder 1000 mg alle 12 Stunden gegeben. Vierundzwanzig der 28 Infektionen waren durchStreptococcus pneumoniae und/oderHaemophilus influenzae verursacht, und alle pathogenen Erreger waren in vitro empfindlich gegenüber Cefalothin und Ceforanid. Die Kranken wurden im Durchschnitt 7,5 Tage lang behandelt, alle zeigten einen guten klinischen und röntgenologischen Therapieerfolg, keiner verstarb. Von den 13 Patienten mitHaemophilus influenzae konnte der Organismus während der Therapie noch bei 9/12 und nach Abschluß der Therapie noch bei 3/8 gefunden werden. Unter der Behandlung kam es in einem Fall zu einer klinischen Superinfektion (Sepsis durchPseudomonas aeruginosa). Nebenwirkungen der Therapie umfaßten Thrombozytose (15), asymptomatische Eosinophilie (5) und leichte Erhöhung der Serum-Transaminasen (3). Die vorgelegten Untersuchungen lassen annehmen, daß Ceforanid ein sicheres und wirksames Mittel für die Behandlung erwachsener Patienten mit bakterieller Pneumonie durchS. pneumoniae ist; in der Behandlung vonH. influenzae bedarf es noch weiterer Erfahrung, da es unter Ceforanid häufig nicht gelungen ist, diesen Erreger aus dem Sputum zu beseitigen.