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PubMed1994

Activity of aztreonam in pneumology, Part 2: Influence on phagocytosis and intracellular killing of human alveolar macrophages.

The study aim was to evaluate the activity of aztreonam on phagocytosis and intracellular killing of Staphylococcus aureus ATCC6538 by human alveolar macrophages. Drug concentrations of 1, 10, 25, 100 micrograms/ml were assayed in culture medium. Aztreonam induces dose-dependent phagocytosis up to 25 micrograms/ml concentrations; with a phagocytosis index (PIa) of 1.18 +/- 0.2 at 1 microgram/ml; of 1.27 +/- 0.2 at 10 micrograms/ml; of 1.42 +/- 0.3 at 25 micrograms/ml. No phagocytosis increase or inhibition, with unchanged cell viability compared to controls, is shown at 100 micrograms/ml aztreonam (PI 1.03 +/- 0.3). Intracellular killing acts in a similar way: the killing index (KIa) is 1.27 +/- 0.3 at 1 microgram/ml concentrations; 1.38 +/- 0.3 at 10 micrograms/ml; 1.61 +/- 0.4 at 25 micrograms/ml whereas at 100 micrograms/ml the KIa is 1.03 +/- 0.3. This study shows aztreonam's ability to stimulate macrophages' functional activity against a microorganism (S. aureus) which is not susceptible to its antibacterial activity.

Adjuvants, Immunologic↗

PubMedDate not supplied

Aztreonam in the treatment of gram-negative bacterial meningitis.

Aztreonam was administered to 122 patients with presumptive or confirmed gram-negative bacillary meningitis in an open, multinational study. The antibiotic was administered at a dosage of 1-2 g to adults, 50 mg/kg to children greater than 2 years old, and 30 mg/kg to infants three or four times daily. Seventy-seven patients had microbiologically confirmed gram-negative meningitis due to an aztreonam-susceptible organism and received aztreonam for at least 48 hours. Haemophilus influenzae was the most frequently recovered pathogen (40 patients), followed by Enterobacteriaceae (16 patients), Neisseria meningitidis (15 patients), and Pseudomonas species (six patients). All but four patients were microbiologically cured. Microbiologic failure was associated with either a persistent intracerebral abscess (one patient) or a foreshortened course of therapy before microbiologic reevaluation and death (at 48 hours, 48 hours, and 72 hours after initiation of treatment, respectively). These data suggest that aztreonam is effective in the treatment of gram-negative bacillary meningitis caused by susceptible organisms.

Adult↗

PubMedDate not supplied

Aztreonam versus gentamicin for short-term prophylaxis in biliary and gastric surgery.

Short-term antibiotic prophylaxis was studied in 80 patients undergoing biliary or gastric surgery. The patients were randomized to receive 1 g of aztreonam or 80 mg of gentamicin intravenously 30 minutes before surgery and 8 and 16 hours after surgery. Of samples taken from the abdominal cavity for bacteriologic study, 53% were culture positive. Wound infections developed in two (4.5%) of 44 patients receiving aztreonam and in seven (19.4%) of 36 patients treated with gentamicin. Staphylococcus epidermidis and Enterobacter species were isolated from sites of wound infection in the aztreonam group; Escherichia coli (two isolates), Pseudomonas aeruginosa (two isolates), Enterobacter species, Klebsiella species, Enterococcus faecalis, and Aeromonas hydrophila were isolated from the gentamicin group. Our data indicate that aztreonam is safe and effective for the prevention of infections following biliary and gastric surgery.

Adult↗

PubMedDate not supplied

Aztreonam monotherapy as prophylaxis in transurethral resection of the prostate: a multicenter study.

The efficacy and safety of aztreonam in the prophylaxis of urinary tract infection following transurethral resection of the prostate (TURP) in patients with preoperatively sterile urine were studied in a multicenter trial including 300 patients at six Italian urology centers. The present report describes the first 192 patients enrolled in the protocol. Aztreonam or placebo was administered to each patient in three doses, which were given at the induction of anesthesia and 8 and 16 hours later. The development of bacteriuria was monitored by cultures of urine obtained before surgery, 3 days later, at removal of the bladder catheter, at discharge from the hospital, and at a follow-up visit 39-46 days after surgery. A febrile peak was observed for 6% of aztreonam-treated patients and for 20.9% of the placebo group (P less than .005), while bacteriuria was reported in 17.9% and 59.3% of these groups, respectively (P less than .001). From our data, TURP appears to be a clean-contaminated procedure requiring antibiotic prophylaxis, and aztreonam appears to reduce significantly the incidence of postoperative bacteriuria after this surgical procedure.

Adult↗

PubMedDate not supplied

Aztreonam: antibacterial activity, beta-lactamase stability, and interpretive standards and quality control guidelines for disk-diffusion susceptibility tests.

In vitro activity of aztreonam was compared with that of ceftazidime, cefotaxime, cefoperazone, piperacillin, and ticarcillin against 656 representative bacterial pathogens. Aztreonam was not active against gram-positive cocci but was as active as the third-generation cephalosporins against the Enterobacteriaceae, Haemophilus influenzae, and Neisseria gonorrhoeae. Additional data for 5,262 gram-negative bacilli isolated in four separate medical centers documented the low incidence of resistance to aztreonam; 97.2% of 4,312 isolates of Enterobacteriaceae and 79% of 854 isolates of Pseudomonas aeruginosa were inhibited by less than or equal to 8.0 micrograms of aztreonam/ml. Additional studies confirmed the stability of aztreonam in the presence of seven different beta-lactamases. For disk-diffusion susceptibility tests, 30-micrograms disks are recommended, with interpretive breakpoints of less than or equal to 15 mm for resistance (MIC greater than or equal to 32 micrograms/ml), 16-21 mm for intermediate susceptibility (MIC, 16 micrograms/ml), and greater than or equal to 22 mm for susceptibility (MIC less than 8.0 micrograms/ml). For quality control of tests with 30-micrograms disks, zone-size limits for Escherichia coli (ATCC 25922) should be 28-36 mm and those for P. aeruginosa (ATCC 27853) should be 23-29 mm.

Aztreonam↗

PubMedDate not supplied

Comparison of aztreonam and tobramycin in the treatment of lower respiratory tract infections caused by gram-negative bacilli.

A comparison of aztreonam and tobramycin was carried out in 49 hospitalized patients with lower respiratory tract infections caused by gram-negative bacilli. Patients were randomly assigned to the treatment drug. Clindamycin was given concomitantly until the pathogen was identified and the presence of a gram-positive microorganism was ruled out. Samples of sputum were obtained for culture from the lung parenchyma by deep expectoration or transtracheal aspiration. A pathogen was defined as an organism that showed heavy growth and predominated in the culture. Pseudomonas aeruginosa was the most frequently isolated pathogen, followed by Haemophilus influenzae and Proteus mirabilis. A variety of less common pathogens were represented. Thirty-five patients were treated with intravenous aztreonam (1-2 g every 8 hr) and 14 with intravenous tobramycin (3-5 mg/kg per day) until they were afebrile and sputum cultures had been free of the pathogen for 48 hr. The minimum duration of treatment was five days. In the aztreonam group, only two (5%) of the 37 gram-negative pathogens--one P. aeruginosa and one Escherichia coli--persisted. In the tobramycin group, seven (50%) of the 14 pathogens persisted. Clinical response paralleled microbiologic response. Adverse effects in both treatment groups were minor and transient. In this trial aztreonam was effective and safe for treatment of lower respiratory tract infections caused by P. aeruginosa and a variety of other gram-negative bacilli.

Aztreonam↗

PubMedDate not supplied

Summary of worldwide clinical trials of aztreonam in patients with lower respiratory tract infections.

Aztreonam was administered to 226 patients with lower respiratory tract infections--primarily pneumonia (181 patients)--due to gram-negative bacilli. The clinical response rate was 93%, and the microbiologic cure rate was 78%. Most patients received 1-g or 2-g intravenous doses of aztreonam three times daily for at least five days. Ninety-eight of the 226 patients were involved in a randomized comparison of aztreonam with tobramycin; the latter drug was administered to a group of 34 patients. The overall microbiologic cure rates for the two drugs were 86% and 71%, respectively. Aztreonam is effective for the treatment of lower respiratory tract infections due to susceptible gram-negative bacilli.

Aztreonam↗

PubMedDate not supplied

Aztreonam plus vancomycin (plus amikacin) vs. moxalactam plus ticarcillin for the empiric treatment of febrile episodes in neutropenic cancer patients.

Aztreonam plus vancomycin (AV), aztreonam plus vancomycin and amikacin (AVA), and moxalactam plus ticarcillin (MT) were compared in an ongoing, randomized, prospective trial of the treatment of febrile episodes in neutropenic patients with cancer. Vancomycin was combined with aztreonam to provide coverage against gram-positive bacteria. Patients with gram-negative bacterial infections who were given AV in effect received single-agent therapy with aztreonam. Overall, AVA was more effective than MT and somewhat more effective than AV in the treatment of 170 documented infections. AV and AVA were each more effective than MT in the treatment of 29 gram-positive infections (response rates of 90%, 80%, and 43%, respectively). The three regimens were equally effective in the treatment of 39 aerobic gram-negative infections (response rates of 88%, 100%, and 100% for AV, AVA, and MT, respectively). Thus far, the addition of amikacin to the AV regimen appears to offer no advantage in the treatment of documented gram-negative infections.

Adolescent↗

PubMedDate not supplied

Clinical experience with aztreonam in Germany and Austria.

Of 146 hospitalized patients treated with aztreonam for infections, primarily of the urinary and lower respiratory tracts, 142 had a satisfactory clinical response. An initial microbiologic cure was found in 106 (84%) of 126 patients. Relapse, reinfection, or superinfection occurred in 28 patients. Thirty-nine of 43 patients treated with a control drug (gentamicin, cefotaxime, cefamandole, or tobramycin) had a satisfactory clinical response, 25 of 34 such patients showed microbiologic cure, and 12 experienced relapse, reinfection, or superinfection. Short-term perioperative treatment with aztreonam in male patients whose urine was positive for gram-negative organisms was successful for 10 of 11 patients. Pharmacokinetic studies demonstrated that dosage adjustment of aztreonam in geriatric patients should be based on creatinine clearance. No nephrotoxicity was demonstrated in 10 healthy male volunteers. Satisfactory concentrations of aztreonam were found in sputum, vagina, cervix, perimetrium, myometrium, endometrium, parametrium, fallopian tube, fat, muscle, and kidney tissues.

Adult↗

PubMedDate not supplied

Clinical experience with aztreonam in four Mediterranean countries.

Aztreonam is a new, synthetic, monobactam beta-lactam antibiotic with activity directed specifically against aerobic gram-negative bacteria. At doses of 1-8 g per day, aztreonam was administered parenterally to patients with serious gram-negative infections of the urinary tract or other sites. A total of 462 organisms were isolated from sites of urinary tract infection; 93% of the isolates obtained within 48 hr before the initiation of aztreonam therapy were eradicated. Forty-three (86%) of 50 strains of Pseudomonas aeruginosa from urinary sites were eradicated. Eighty-six percent of gram-negative organisms isolated before treatment from other sites of infection were eradicated. Whatever the site of infection, the percentage of patients with a complete resolution of signs and symptoms was similar. Aztreonam was well tolerated both locally and systemically.

Adolescent↗

PubMed1983

Effectiveness of aztreonam, a new monobactam antibiotic, against penicillin-resistant gonococci.

Since the recognition of penicillinase-producing strains of N gonorrhoeae (PPNG) in 1976, these organisms have attained a worldwide distribution. The treatment of choice for infection due to PPNG has generally been spectinomycin administered im. In 1981, however, an infection from California was reported to be due to a strain of PPNG that was also resistant to spectinomycin (MIC, greater than 2,048 micrograms/ml) [1]. Throughout 1982, seven such isolates were reported worldwide [2], and in January 1983 an epidemiologically linked series of 27 cases of infection due to spectinomycin-resistant PPNG occurred in Korea. Because of the apparent declining utility of spectinomycin, we studied the efficacy and safety of aztreonam, a synthetic monobactam antibiotic from the Squibb Institute for Medical Research (Princeton, NJ) [3], in the treatment of acute uncomplicated gonococcal urethritis in men. Men with gonococcal urethritis were randomly treated with either 1 g of aztreonam or 2 g of spectinomycin im. Of the 112 men so treated, 93 could ultimately be evaluated: 51 who received aztreonam and 42 who received spectinomycin. Both drugs were 100% effective in the treatment of urethritis produced by both penicillin-sensitive and penicillin-resistant strains of gonococci. Furthermore, there were no reported side effects in either group and no laboratory abnormalities attributable to the aztreonam, with the exception of one patient with a minimally elevated level of serum glutamic oxaloacetic transaminase (serum glutamic pyruvic transaminase and alkaline phosphatase levels were normal).(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-Bacterial Agents↗

PubMed1984

Selective decontamination of the digestive tract with aztreonam: a study of 10 healthy volunteers.

Aztreonam, a minimally absorbable monobactam antibiotic that is active primarily against gram-negative bacilli, was given orally to 10 healthy volunteers in three regimens: 60 mg, 300 mg, and 1,500 mg daily for five days. The regimens were administered at least two weeks apart so that the flora could return to normal. Aztreonam had no effect on oropharyngeal flora cultured every other day. Fecal cultures from volunteers receiving the 300-mg regimen yielded no gram-negative bacilli after an average of 4.4 days of treatment. Administration of the highest dose gave similar results, albeit after a shorter interval (3.0 days). None of the regimens appreciably influenced total microscopic (anaerobic) bacterial counts in the feces. However, during administration of the 1,500-mg regimen, fecal counts of enterococci increased from an average of approximately 10(4)/g to greater than 10(7)/g, and fecal counts of yeasts tended to increase by the end of the five-day treatment period. Fecal concentrations of aztreonam increased as the dose increased in eight volunteers. No aztreonam was recovered from the feces of two volunteers, perhaps because of drug inactivation.

Adult↗

PubMed1985

Aztreonam in patients with acute purulent exacerbations of chronic bronchitis: failure to prevent emergence of pneumococcal infections.

A group of 36 patients, all requiring hospital admission because of acute purulent exacerbations of chronic bronchitis, were treated with 1 or 2 g intramuscular injections of aztreonam for ten days. Patients with Streptococcus pneumoniae infections were excluded from the study. Sputum cultures before treatment revealed the other usual respiratory pathogens but repeat cultures on days 3, 10 and 17 sometimes yielded Str. pneumoniae, occasionally combined with Haemophilus influenzae or Branhamella catarrhalis. Ten patients had to be given other antimicrobial agents for Str. pneumoniae infections which developed during the study or follow-up periods. Pseudomonas aeruginosa failed to respond well to aztreonam. All the H. influenzae strains were sensitive to aztreonam (MIC 0.25 mg/l, or less) but all strains of Str. pneumoniae were resistant (MIC greater than 32 mg/l). Ps. aeruginosa strains were moderately resistant (MIC generally 4-16 mg/l) and Bran. catarrhalis strains only moderately sensitive (MICs generally 0.5-4 mg/l). Peak serum concentrations averaging approximately 37 mg/l were observed after the 1 g injections (55 mg/l after 2 g) and the corresponding mean peak concentrations in the sputum were 1.3 mg/l and 2.5 mg/l, respectively. The penetration from blood to sputum was thus approximately 3.5% and 4.6% after the 1 g and 2 g doses. No unwanted local or general reactions were observed. The disappointing clinical results (only 23 out of 36 patients with excellent or good clinical results) one week after the end of the treatment were mainly due to the emergence of pneumococcal infections during (and immediately after) therapy. Considering that Str. pneumoniae is still one of the most important organisms associated with acute purulent exacerbations of chronic bronchitis, and that conventional sputum cultures may not always reveal its presence, there is considerable doubt if aztreonam has any place in the treatment, especially as the results in Ps. aeruginosa infections have also been much poorer than expected.

Adolescent↗

PubMed1986

The in-vitro activity of SQ 82,291, a new monobactam, in comparison with aztreonam.

The in-vitro activity of a new monobactam antibiotic, SQ 82,291, was compared with that of aztreonam against 529 strains of aerobic and facultatively anaerobic bacteria. SQ 82,291, which is absorbed orally when administered as an ester, has shown good activity against different bacteria of the family Enterobacteriaceae and Haemophilus influenzae. The susceptibility of SQ 82,291 is lower than that to aztreonam in the species that were sensitive and SQ 82,291 showed no activity at all against staphylococci and strict anaerobes (like aztreonam); unlike aztreonam SQ 82,291 was not effective against Pseudomonas aeruginosa.

Aztreonam↗

PubMed1989

Efficacy and safety of low dose aztreonam in the treatment of moderate to severe gram-negative bacterial infections.

One hundred and fifty-three patients with moderate to severe infections due to Gram-negative bacteria, including septicaemia (60 cases), lower respiratory tract infection (32 cases), intra-abdominal infection (40 cases) and urinary tract infection (21 cases), were treated with aztreonam 1 g every 12 h. This dosage is lower than usual. Criteria for inclusion included documented Gram-negative bacterial infections, and assessment of the severity of the disease by a scoring system for both community and hospital acquired infections. No other antibiotic active against Gram-negative bacteria was allowed. In 71 patients, in whom Gram-positive or anaerobic organisms were detected or suspected, additional agents effective against these organisms were administered. One hundred and forty-one patients (92.2%) were cured with a mean duration of treatment of 10.9 +/- 4.0 days. None of the Gram-negative bacteria initially isolated became resistant to aztreonam. Colonization, generally by a Gram-positive organism, was observed in 27 patients and superinfection in five. Aztreonam was well tolerated. This study suggests that a daily dosage of 2 g of aztreonam should be sufficient in the treatment of moderate to severe Gram-negative bacillary infections due to sensitive organisms.

Adolescent↗

PubMed1989

Inactivation of aztreonam by faecal supernatants of healthy volunteers as determined by HPLC.

The enzymatic inactivation of aztreonam to its biologically inactive open ring form, by faecal enzyme preparations from 12 volunteers, was investigated. The percentage inactivation was determined by a high-performance liquid chromatography assay at months 0, 6 and 24. Faecal enzyme preparations from five volunteers could inactivate aztreonam by more than 50% within 20 h at one or more of these sampling times. Monitoring of aztreonam inactivation over a shorter period of time (14 days) in three of the volunteers showed that aztreonam inactivation cannot be predicted.

Adult↗

PubMed1991

Antimicrobial effect of clindamycin in combination with aztreonam or aminoglycosides against Klebsiella spp.

The antimicrobial effect of clindamycin combined with aztreonam or an aminoglycoside (gentamicin, tobramycin or amikacin) was studied against 84 strains of Klebsiella pneumoniae and 18 strains of K. oxytoca with an agar dilution technique. Clindamycin concentrations of 1-20 mg/l and an inoculum of 10(4) cuf/spot were used. Anaerobic incubation of agar plates was associated with an increase in the MIC of aminoglycosides and no change or a decrease in the MIC of aztreonam. Lower concentrations of clindamycin (1-2 mg/l) were associated with a decrease in the MIC of aztreonam for 18% and an increase in the MIC of aminoglycosides for between 7% and 44% of the strains, depending upon the precise concentration used. However, higher concentrations of clindamycin (10-20 mg/l) were associated with a decrease in the MIC of aztreonam for between 36 and 87% and an increase in the MIC of aminoglycosides for between 13 and 64% of the isolates. These observations could be important when treatment plans for mixed aerobic/anaerobic infections including mixed Klebsiella spp. are considered.

Aminoglycosides↗

PubMed1992

Pharmacokinetics of aztreonam in patients with liver cirrhosis and ascites.

The pharmacokinetics of aztreonam were studied in six healthy male subjects (group I) and 12 male patients with post-hepatitis liver cirrhosis and ascites. Patients were allocated into two groups according to serum creatinine; group II included nine patients with serum creatinine. < or = 15 mg/L while group III included three patients with serum creatinine > 15 mg/L. Aztreonam 1 g was given as iv bolus injection. Aztreonam reached a peak concentration in the ascitic fluid (AF) of 6.2 +/- 2.3 mg/L at 4 h, and of 8.7 +/- 4.4 mg/L at 6 h in groups II and III respectively. The level of the drug in AF 24 h post-dosing was still higher than MIC90 for Enterobacteriaceae in most patients. The half-life of elimination from serum increased significantly (P > 0.001) from 1.82 +/- 0.14 h in group I to 6.6 +/- 2.1 h and to 8.87 +/- 0.2 h in groups II and III, respectively. Both the central and the terminal volumes of distribution were higher in cirrhotic patients than in healthy volunteers. Liver cirrhosis and ascites resulted in a significant increase (P < 0.001) of the total body clearance (Cl) of aztreonam from 84 +/- 8 mL/h/kg in group I to 209 +/- 87 mL/h/kg in group II. However, the concomitant association of mild renal impairment in group III abolished this increase; Cl in group III was 122 +/- 50 mL/h/kg. The AUC0-infinity serum was 137.5 +/- 12.2, 78.5 +/- 24.9 and 151 +/- 42 mg.h/L in groups I, II and II, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗