cefamandole and Haemophilus-Infections

Topics: Bacterial Infections; Bacteroides Infections; Cefamandole; Cefazolin; Cefonicid; Cefoxitin; Cefuroxime; Cephalosporins; Gonorrhea; Haemophilus Infections; Humans; Respiratory Tract Infections; Structure-Activity Relationship

In a patient with pneumonia, sputum culture revealed ampicillin-resistant Haemophilus influenzae, type b. Although nontypable H influenzae is a normal inhabitant of the upper respiratory tract and should be considered normal flora, typable H influenzae is found in less than 5% of healthy persons. Although only 1.8% of sputum cultures reveal typable H influenzae, these strains account for 98.3% of isolates from blood cultures of patients with pneumonia due to H influenzae. Serotyping of sputum isolates is recommended in patients with pneumonia to separate pathogenic typable strains from nonpathogenic nontypable strains.

Topics: Cefamandole; Child; Haemophilus Infections; Haemophilus influenzae; Humans; Male; Penicillin Resistance; Pneumonia; Serotyping; Sputum

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.

Topics: Adult; Cefamandole; Cefonicid; Cephalosporins; Clinical Trials as Topic; Female; Haemophilus Infections; Haemophilus influenzae; Humans; Male; Middle Aged; Pneumococcal Infections; Pneumonia; Random Allocation

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.

Topics: Adult; Cefamandole; Cefazolin; Cephalosporins; Clinical Trials as Topic; Female; Haemophilus Infections; Haemophilus influenzae; Humans; Male; Pneumonia; Pneumonia, Staphylococcal; Pneumonia, Viral; Sputum; Staphylococcus

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 mug/ml and 100% at 4 mug/ml. Cefamandole inhibited the three ampicillin-resistant isolates at 2 mug/ml or less. Cephapirin, cefoxitin, and cephalothin were the next most active, whereas cefazolin and cephradine were the least active.

Topics: Adult; Aged; Ampicillin; Blood Bactericidal Activity; Bronchitis; Cefamandole; Cephalosporins; Clinical Trials as Topic; Female; Haemophilus Infections; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Pneumonia

The efficacy and safety of cefamandole nafate and penicillin G procaine suspension were compared in the treatment of pneumococcal pneumonia in hospitalized adults. One hundred thirteen patients with clinical and radiographic evidence of pneumococcal pneumonia were randomly assigned to receive 600,000 units of procaine penicillin intramuscularly every 12 hr or 500 mg of cefamandole intramuscularly every 6 hr. The two groups were comparable with regard to patient type and extent and severity of pneumonia. Alcohol abuse was a host factor in 31% of all patients in the trial. All strains of Streptococcus pneumoniae isolated were inhibited by less than or equal to 1.6 microgram of cefamandole/ml. Of 58 patients treated with cefamandole, 50 had a satisfactory response, as did 46 of the 55 patients treated with penicillin. Results of tests of liver function were abnormal (primarily, elevated levels of transaminase or alkaline phosphatase) in 38% of the entire group of patients and occurred with equal frequency in patients receiving cefamandole or penicillin. Side effects during therapy, including superinfection, occurred equally with either drug. In a random trial, cefamandole was as effective and safe as penicillin in the treatment of pneumococcal pneumonia in adults.

Topics: Adult; Aged; Cefamandole; Cephalosporins; Clinical Trials as Topic; Drug Evaluation; Female; Haemophilus Infections; Haemophilus influenzae; Humans; Male; Middle Aged; Penicillin G Procaine; Pneumonia, Pneumococcal; Streptococcal Infections; Streptococcus pyogenes

Topics: Aged; Aged, 80 and over; Cefamandole; Cefonicid; Endocarditis, Bacterial; Female; Haemophilus Infections; Humans; Microbial Sensitivity Tests

The prevalence of antimicrobial resistance was assessed among a total of 3,356 clinical isolates of Haemophilus influenzae obtained from 22 medical centers distributed throughout the United States during the period July, 1983 through June, 1984. All strains were examined for beta-lactamase production with a rapid acidometric assay and for resistance to ampicillin, chloramphenicol, cephalothin, cefamandole, cefaclor, tetracycline, and erythromycin with a standardized disk diffusion procedure. The overall rate of beta-lactamase production was 15.2%, although results of disk diffusion tests suggested that the overall rate of ampicillin resistance was 19.5%. Twenty-one percent of encapsulated type b strains produced beta-lactamase; 12.1% of non-type b strains were beta-lactamase positive. Specific rates of beta-lactamase production obtained at individual study centers varied widely with no evidence of geographic clustering. The highest rates of beta-lactamase production were observed with isolates of H. influenzae recovered from infants and young children, and from blood and cerebrospinal fluid specimens. The overall rate of chloramphenicol resistance was 0.6%. The prevalence of cephalothin, cefamandole, cefaclor, tetracycline, and erythromycin resistance was 9.9%, 2.4%, 2.8%, 6.4%, and 64.2%, respectively. beta-Lactamase positive isolates of H. influenzae had higher rates of resistance to all of the cephalosporins than did strains that lacked beta-lactamase.

Topics: Adolescent; Adult; Age Factors; Aged; Ampicillin; Anti-Bacterial Agents; beta-Lactamases; Cefaclor; Cefamandole; Cephalothin; Child; Child, Preschool; Chloramphenicol; Erythromycin; Haemophilus Infections; Haemophilus influenzae; Humans; Infant; Microbial Sensitivity Tests; Middle Aged; Penicillin Resistance; Tetracycline; United States

A model of pneumonia due to Haemophilus influenzae type b was developed in mice and used for exploration of the pathophysiology of the infection and evaluation of the efficacy of five antimicrobial agents. Adult C57BL/6 mice were challenged with 3 X 10(9) cfu of H influenzae by intratracheal inoculation. Mice given placebo or no treatment experienced a uniformly bacteremic and fatal infection. Animals given ampicillin, cefamandole, chloramphenicol, erythromycin plus sulfisoxazole, or fludalanine plus pentizidone (MK 0641/MK 0642, an investigational combination drug) survived at a higher rate than did controls (P less than .001 at 72 hr for each antibiotic). However, survival rates for the various antibiotic-treated groups were similar. Viable organisms were eradicated from the lungs of antibiotic-treated mice more quickly than from the lungs of controls (P less than .001 at 24 hr for each drug). Studies of pulmonary clearance revealed significant differences among regimens; the order of efficacy (from most to least) was ampicillin, chloramphenicol, erythromycin/sulfisoxazole, cefamandole, and fludalanine / pentizidone . This model represents an appropriate system for evaluation of invasive pulmonary infection caused by H influenzae type b. Of the antibiotics assessed, ampicillin was most active in vivo.

Topics: Alanine; Ampicillin; Animals; Anti-Bacterial Agents; Cefamandole; Chloramphenicol; Drug Combinations; Drug Evaluation, Preclinical; Erythromycin; Female; Haemophilus Infections; Haemophilus influenzae; Isoxazoles; Lung; Mice; Mice, Inbred C57BL; Pneumonia; Sulfisoxazole

The bactericidal effects of chloramphenicol and three beta-lactams (ampicillin, cefamandole, and penicillin G) were measured for 27 strains of Haemophilus influenzae type b isolated from the blood or cerebrospinal fluid of infected infants. Of the ampicillin-susceptible strains, 75% were killed by less than 2.0 micrograms of each antibiotic per ml; however, the concentration of the beta-lactam agents required for bactericidal activity was higher than that required for inhibitory activity. Chloramphenicol was the only agent which had no marked discrepancy between inhibitory and bactericidal concentrations regardless of beta-lactamase production. Importantly, chloramphenicol was more rapidly bactericidal than either ampicillin or cefamandole. The bactericidal requirement of ampicillin was increased by the presence of chloramphenicol for about one-third of the isolates examined. Neither the inhibitory nor the bactericidal activity of chloramphenicol was influenced by ampicillin. Synergy occurred for only two beta-lactamase-positive isolates. The more rapid bactericidal action of chloramphenicol persisted even in the presence of ampicillin. The rapid bactericidal action of chloramphenicol with or without ampicillin supports the use of chloramphenicol alone or with ampicillin for H. influenzae infections.

Topics: Ampicillin; Cefamandole; Cephalosporins; Chloramphenicol; Drug Interactions; Drug Synergism; Haemophilus Infections; Haemophilus influenzae; Humans; Microbial Sensitivity Tests

Topics: Ampicillin; Cefamandole; Cephalosporins; Female; Haemophilus Infections; Haemophilus influenzae; Humans; Infant; Penicillin Resistance; Sepsis

Topics: Ampicillin; Anti-Bacterial Agents; Cefamandole; Chloramphenicol; Haemophilus Infections; Humans; Penicillin Resistance

A woman with rheumatoid arthritis and ampicillin-resistant Haemophilus influenzae type b (Hib) pneumonia complicated by bacteremia and empyema is reported. Initial therapy with cefamandole failed to eliminate bacteria from the pleural space and did not substantially affect the clinical course. However, cultures became negative and fever resolved when therapy was changed to chloramphenicol. Ampicillin-resistant Hib pneumonia in adults is an increasing problem and may be a difficult diagnosis to establish initially. Counterimmunoelectrophoresis may be useful in adults with pneumonia. If Hib antigen is detected, or if H influenzae is suspected on the basis of Gram stains and cultures, chloramphenicol should be given until the isolate is shown to be sensitive to ampicillin.

Topics: Ampicillin; Cefamandole; Cephalosporins; Chloramphenicol; Female; Haemophilus Infections; Haemophilus influenzae; Humans; Middle Aged; Penicillin Resistance; Pneumonia

We examined the minimal inhibitory concentrations and minimal bactericidal concentrations of chloramphenicol, ampicillin, ticarcillin, cefamandole, cefazolin, cefoxitin, cefotaxime, ceforanide, and moxalactam for 100 isolates of Haemophilus influenzae, 25 of which produced beta-lactamase. Susceptibility was not influenced by the capsular characteristic of the organism. The mean minimal inhibitory concentrations of cefamandole, ticarcillin, and ampicillin for beta-lactamase-producing strains were 3-, 120-, and 400-fold higher than their respective mean minimal inhibitory concentrations for beta-lactamase-negative strains. No such difference was noted for the other antibiotics. We performed time-kill curve studies, using chloramphenicol, ampicillin, cefamandole, cefotaxime, and moxalactam with two concentrations of the antimicrobial agents (4 or 20 times the minimal inhibitory concentrations) and two inoculum sizes (10(4) or 10(6) colony-forming units per ml). The inoculum size had no appreciable effect on the rate of killing of beta-lactamase-negative strains. The rates at which beta-lactamase-producing strains were killed by chloramphenicol, cefotaxime, and moxalactam was not influenced by the inoculum size. Whereas cefamandole in high concentrations was able to kill at 10(6) colony-forming units/ml of inoculum, it had only a temporary inhibiting effect at low drug concentrations. Methicillin and the beta-lactamase inhibitor CP-45,899 were able to neutralize the inactivation of cefamandole by a large inoculum of beta-lactamase-producing H. influenzae.

Topics: beta-Lactamase Inhibitors; Cefamandole; Cephalosporins; Chloramphenicol; Haemophilus Infections; Haemophilus influenzae; Humans; Microbial Sensitivity Tests; Penicillins

Topics: Cefamandole; Cephalosporins; Haemophilus Infections; Humans; Meningitis, Haemophilus

In an eight year period 16 cases of serious extrapulmonary Hemophilus influenzae infection in adults were identified, including cases of meningitis, pericarditis, epiglottitis, empyema, cellulitis, osteomyelitis, endometritis, urinary tract infection, orbital cellulitis, primary peritonitis, mesenteric lymphadenitis and aortic graft infection. An 18 month prospective study of H. influenzae infection in hospitalized adults identified 10 cases of bronchitis, 25 of pneumonia and 65 of respiratory tract colonization, but there were no extrapulmonary infections. In 29 percent of the respiratory tract infections, H. influenzae appeared to be a nosocomial pathogen; in 71 percent, the infection was mixed. Finally, 110 clinical isolates of H. influenzae were studied for antimicrobial susceptibility. Eight percent were ampicillin resistant, two strains were resistant to tetracycline and one to chloramphenicol, but all were susceptible to trimethoprim-sulfamethoxazole and cefamandole.

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Cefamandole; Cross Infection; Drug Resistance, Microbial; Female; Haemophilus Infections; Haemophilus influenzae; Hospitalization; Humans; Male; Middle Aged; Prospective Studies; Respiratory Tract Infections; Sulfamethoxazole; Trimethoprim

Ceforanide (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 to Streptococcus pneumoniae and/or Hemophilus 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 with H. influenzae, the organism could still be recovered during therapy in 9/12 and post therapy in 3/8. One clinical superinfection (sepsis due to Pseudomonas 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 to S. pneumoniae; further experience in therapy of H. influenzae is needed because of frequent failure of ceforanide to eradicate this organism from the sputum.

Topics: Adult; Cefamandole; Cephalosporins; Female; Haemophilus Infections; Haemophilus influenzae; Humans; Injections, Intramuscular; Injections, Intravenous; Male; Pneumonia; Pneumonia, Pneumococcal

When Haemophilus influenzae infections are treated by an antibiotic acting on the bacterial wall, the adequacy of antimicrobial therapy can be assessed by Schlichter's test. This test may be carried out using Mueller Hinton broth (or Mueller Hinton broth with 50% pooled serum and a supplement of Ca++ and Mg++) supplemented with Fildes' enrichment and an inoculum adjusted to the 0.5 McFarland turbidity standard diluted 200x. However, correct reading of end points can be obtained only by phase contrast microscopic examination, which allows the establishment of good correlation between the in vitro and in vivo findings. In patients with lung infections successfully treated with cefamandole, the presence of spheroplasts in samples derived from Schlichter's tests correlates well with clinical improvement and eradication of the pathogenic organism checked by transtracheal aspiration.

Topics: Blood Bactericidal Activity; Cefamandole; Cephalosporins; Haemophilus Infections; Haemophilus influenzae; Humans; Microbial Sensitivity Tests

Fifty-three infants and children, aged three months to 15 years, were treated with an average daily dose of 100 mg of cefamandole/kg intravenously. Of these patients, 47 had soft tissue cellulitis and six had pneumonia. Primary pathogens, including Staphylococcus aureus, Streptococcus pyogenes, Streptococcus pneumoniae, and Haemophilus influenzae, were isolated from 43 of the 53 patients. Bacteremia was documented in six of the 53 patients. A satisfactory clinical and bacteriologic response to cefamandole was achieved in all cases except on (98%). The only treatment failure occurred in an infant with both periorbital cellulitis and bacteremia due to H. influenzae who developed meningitis while receiving cefamandole; no extravasation of the drug across the blood-brain barrier could be detected in spite of inflamed meninges. In general, the only aberrant effects of cefamandole were the appearance of eosinophilia in 28% of patients and a positive indirect Cooms' test without hemolysis in one patient. Cefamandole showed excellent in vitro activity against 87 ampicillin-resistant strains of H. influenzae. Because it has greater activity than any of the other cephalosporins against this important pediatric pathogen, cefamandole may have particular pertinence in the treatment of infections in infants and young children.

Topics: Adolescent; Bacterial Infections; Cefamandole; Cellulitis; Cephalosporins; Child; Haemophilus Infections; Haemophilus influenzae; Humans; Infant; Pneumonia; Pneumonia, Pneumococcal; Staphylococcal Infections; Streptococcal Infections

Cefamandole nafate was effective in the treatment of a variety of infections caused by Staphylococcus aureus, Streptococcus pyogenes group A, Streptococcus pneumoniae, and Haemophilus influenzae in infants and children. The infections included periorbital cellulitis and ethmoiditis, bacteremia, cellulitis, pneumonia, and lymphadenitis. In vitro, cefamandole was effective in inhibiting the growth of H. influenzae isolated from blood or cerebrospinal fluid of patients with meningitis or sepsis. In two patients rash developed and cefamandole was discontinued. Other significant adverse effects were not noted.

Topics: Adolescent; Bacterial Infections; Cefamandole; Cellulitis; Cephalosporins; Child; Child, Preschool; Ethmoid Sinus; Female; Haemophilus Infections; Haemophilus influenzae; Humans; Infant; Male; Microbial Sensitivity Tests; Pneumonia, Pneumococcal; Sinusitis; Staphylococcal Infections; Streptococcal Infections; Streptococcus pyogenes

Organisms of the Haemophilus group isolated from nonrespiratory and respiratory sources were studied taxonomically. All biotypes of Haemophilus influenzae and Haemophilus parainfluenzae were encountered. However, nearly all H. influenzae from cerebrospinal fluids belonged to biotype I, while nearly all of those from conjunctivae belonged to biotype II. Only two of the 78 biotypable strains of H. influenzae produced beta-lactamase, but there was no other substantial difference in antimicrobial susceptibilities among biotypes of H. influenzae. Biotypes of H. parainfluenzae were less susceptible to penicillins and cephalosporins than those of H. influenzae.

Topics: Ampicillin; Anti-Bacterial Agents; Bacteriological Techniques; Cefamandole; Cephalothin; Chloramphenicol; Gentamicins; Haemophilus; Haemophilus Infections; Haemophilus influenzae; Humans; Microbial Sensitivity Tests; Penicillin Resistance; Penicillins; Sulfamethoxazole; Trimethoprim

Forty-four patients with serious bacterial infections were treated with cefamandole in a dose 1--2 g every four to six hours. Thirty-two patients were cured and six were markedly improved. Three of six failures were due to superinfection with cephalothin-resistant microorganisms. The over-all bacteriologic response was 80%. In 12 of 13 patients with bacteremia the blood was sterilized. Ten of 14 patients with gram-negative bacillary infections responded to treatment. Six of these were due to cephalothin-resistant microorganisms, three of which responded. Fifteen patients who were treated had a history of penicillin allergy. There were no serious reactions although skin rash did develop. Phlebitis was uncommon.

Topics: Adolescent; Adult; Aged; Bacterial Infections; Cefamandole; Cephalosporins; Enterobacteriaceae Infections; Escherichia coli Infections; Female; Haemophilus Infections; Haemophilus influenzae; Humans; Male; Middle Aged; Sepsis; Staphylococcal Infections; Streptococcal Infections

Topics: Adult; Bacterial Infections; Cefamandole; Cellulitis; Cephalosporins; Enterobacteriaceae Infections; Enterococcus faecalis; Haemophilus Infections; Humans; Pneumococcal Infections; Respiratory Tract Infections; Skin Diseases, Infectious; Staphylococcal Infections; Streptococcal Infections; Streptococcus pyogenes