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Results for “Aztreonam”

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PubMed1994

Clindamycin plus amikacin versus clindamycin plus aztreonam in established intraabdominal infections.

BACKGROUND: A prospective, randomized, single-blind study evaluated the efficacy and safety of clindamycin plus amikacin versus clindamycin plus aztreonam (Cl-Az) in treating intraabdominal infections in adults. METHODS: Patients were treated intravenously for 7 to 10 days, clindamycin 900 mg plus amikacin 5.0 mg/kg three times a day or clindamycin 900 mg plus aztreonam 2.0 gm three times a day. All 67 patients enrolled were evaluated for safety and 31 in each group for clinical and microbiologic response. Both groups were similar in initial diagnosis, perforated appendicitis or intraabdominal abscess. In each group 24 patients (77%) were admitted in serious condition and three (10%) in critical condition. Twenty-five patients (80.6%) in each group had aerobic and anaerobic pathogens; the remainder had either aerobic or anaerobic pathogens. RESULTS: On therapy completion, clinical and bacteriologic responses were as follows: clindamycin plus amikacin group, 26 (84%) cured, 3 (9.7%) improved, and 2 (6.3%) failed; Cl-Az group, 25 (80.7%) cured, 6 (19.3%) improved, and 0 failed. Rapid temperature decrease occurred in Cl-Az group (p = 0.007). Forty-one mild adverse medical events reported were evenly distributed, but no patients were removed as a result. CONCLUSIONS: Both combinations were highly effective in managing intraabdominal sepsis. Clindamycin aztreonam showed a slight advantage because of absence of renal toxicity and shorter time to apyrexia.

Abdomen↗

PubMed1991

Comparison of two schedules of cefoperazone plus aztreonam in the treatment of neutropenic patients with fever.

Cancer patients were randomized to receive an every 4 hour or every 8 hour schedule of cefoperazone plus aztreonam during 617 febrile episodes. The overall response rate for the 478 evaluable episodes was 76% and there was no difference in response rate between the two schedules. The response rate was 79% for cases of pneumonia and 63% for cases of bacteremia. Only 50% of the microbiologically documented infections caused by gram-positive organisms responded whereas 95% of gram-negative infections, including all of those caused by Pseudomonas aeruginosa, responded. Response rates were lower among patients whose neutrophil counts decreased during therapy than among those whose neutrophil counts increased (64% vs. 85%, p = 0.008). Side-effects that were possibly or probably related to antibiotic therapy were observed during 11% of the episodes. The most common side-effects were diarrhea and rashes including one case of Stevens-Johnson syndrome. Three patients developed a coagulopathy during therapy. Cefoperazone plus aztreonam proved to be an effective combination for treatment of gram-negative infections and fever of unknown origin in cancer patients and an every 8-hour schedule of administration was as effective as an every 4-hour schedule. Approximately half of the patients with gram-positive infections required additional antibiotics for successful therapy.

Aztreonam↗

PubMed1985

Aztreonam therapy for gram-negative pneumonia.

Nineteen patients with community- or hospital-acquired gram-negative pneumonia were treated with aztreonam. Other gram-negative antibiotics were withheld. Thirteen patients (68 percent) had clinical cures and 15 (79 percent) had microbiologic cures with aztreonam. No adverse reactions or drug toxicity occurred in this population.

Adult↗

PubMed1985

Aztreonam plus clindamycin as therapy for pelvic infections in women.

Aztreonam, a new monobactam antibiotic with specific gram-negative aerobic activity, was used in combination with clindamycin in the treatment of 40 women with pelvic infection, including post-partum endometritis, pelvic inflammatory disease, and post-hysterectomy pelvic cellulitis. Clinical cure was achieved in 87 percent of patients. Failure was related to the limited gram-positive aerobic spectrum of clindamycin. All aerobic gram-negative enteric organisms were sensitive in vitro to less than 0.125 microgram/ml of aztreonam.

Adult↗

PubMed1985

Aztreonam in the treatment of serious orthopedic infections.

Aztreozam was evaluated in the treatment of a variety of orthopedic infections. Included were 17 patients with osteomyelitis, three with purulent arthropathy with prostheses, and 16 with superficial infections secondary to trauma or surgical procedure. Pathogens were gram-negative bacilli sensitive to aztreonam. Concomitant antibiotics were administered for gram-positive cocci that were present initially or by superinfection. Infecting organisms included Pseudomonas aeruginosa (minimal inhibitory concentration 4 to 16 micrograms/ml), Serratia marcescens, Enterobacter cloacae, Enterobacter sakazakii, Morganella morganii, Citrobacter freundii, Proteus vulgaris, Proteus rettgeri, Acinetobacter calcoaceticus and others (all with minimal inhibitory concentrations less than 1.0 microgram/ml). Dosage of aztreonam was 2 to 8 g per day administered intravenously or intramuscularly for five to 52 days. Clinical and bacteriologic responses were adequate in all instances. Recurrences were observed in two individuals with osteomyelitis and one with purulent arthropathy. Adverse clinical or laboratory observations were infrequent and inconsequential.

Adult↗

PubMed1986

In vitro activity of carumonam (RO 17-2301), BMY-28142, aztreonam, and ceftazidime against 7,620 consecutive clinical bacterial isolates.

For 45-60 days four geographically separate clinical laboratories tested routine clinical bacterial isolates for susceptibility to carumonam, aztreonam, BMY-28142, and ceftazidime by the broth microdilution method. All four drugs were highly active against Enterobacteriaceae, inhibiting greater than 96% of the 4887 strains tested at less than or equal to 8.0 microgram/ml. The minimal inhibitory concentration at which 50% of the isolates were inhibited for each drug was less than or equal to 0.125 micrograms/ml. Ceftazidime was the most active against nonenteric gram-negative bacilli (86% inhibited at less than or equal to 8.0 micrograms/ml), followed by BMY 28142 (82%), carumonam (75%), and aztreonam (68%). The two monobactams exhibited no activity against gram-positive cocci at the concentrations tested, whereas BMY-28142 had excellent activity against nonenterococcal streptococci and good activity against staphylococci.

Anti-Bacterial Agents↗

PubMed1986

Intraphagocytic bactericidal activity of ofloxacin compared with that of aztreonam and ceftriaxone against Serratia marcescens.

Addition of phenylbutazone (2 mg/ml) to 55 vol % of fresh defibrinated human blood permitted leukocytic ingestion of serum-resistant Serratia marcescens bacteria, but blocked phagocytic killing activity. The group A (phage tail) bacteriocin bA+ 16 served to kill extraphagocytic test bacteria. At greater than or equal to 2 X MBC, the DNA gyrase inhibitor ofloxacin revealed potent intraphagocytic bactericidal activity against S. marcescens test bacteria (99% kill; 3 h observation period) which corresponded to that of the control drug rifampin (97% kill). The monobactam aztreonam (11% kill) and the third generation cephalosporin ceftriaxone (14% kill) corresponded to cefotaxime (26% kill) in terms of suboptimal intraphagocytic activity. Ofloxacin and aztreonam yielded additive effects following combination of supra-(2 X MIC) and inhibitory (MIC), but not sub-inhibitory (0.5 X MIC) concentrations with 55 vol % of defibrinated human blood against S. marcescens and Escherichia coli control strain ATCC 25922; sub- and inhibitory concentrations of ceftriaxone yielded indifferent effects.

Aztreonam↗

PubMed2000

Utilization of colorimetric and atomic absorption spectrometric determination of aztreonam through ion pair complex formation.

Three rapid and sensitive, colorimetric and atomic absorption spectrometric methods were developed for the determination of aztreonam. The proposed methods depend upon the reaction of cobaltthiocyanate (I) or reineckate (II) ions with the drug to form stable ion-pair complexes which extractable with chloroform. The greenish blue and pink color complexes are determined either colorimetrically at lambda(max) 625 and 525 nm for I and II reagents, respectively, or by atomic absorption spectrometry, directly using the organic extracted complex, or indirectly, using the supernatant. The three procedures are applied for the determination of aztreonam in pure and in pharmaceutical dosage forms applying the standard additions technique and the results obtained agreed well with those obtained by the official method.

Aztreonam↗

PubMed2001

In vitro activity of mezlocillin, meropenem, aztreonam, vancomycin, teicoplanin, ribostamycin and fusidic acid against Borrelia burgdorferi.

The in vitro susceptibility profile of Borrelia burgdorferi is not yet well defined for several antibiotics. Our study explored the in vitro susceptibility of B. burgdorferi to mezlocillin, meropenem, aztreonam, vancomycin, teicoplanin, ribostamycin and fusidic acid. Minimal inhibitory concentrations (MICs) and minimal borreliacidal concentrations (MBCs) were measured using a standardised colorimetric microdilution method and conventional subculture experiments. MIC values were lowest for mezlocillin (MIC(90), < or =0.06 mg/l) and meropenem (MIC(90), 0.33 mg/l). Vancomycin (MIC(90), 0.83 mg/l) was less effective in vitro. Borreliae proved to be resistant to aztreonam (MIC(90), >32 mg/l), teicoplanin (MIC(90), 6.6 mg/l), ribostamycin (MIC(90), 32 mg/l), and fusidic acid (MIC(90), >4 mg/l). The mean MBCs resulting in 100% killing of the final inoculum after 72 h of incubation were lowest for mezlocillin (MBC, 0.83 mg/l). This study gathered further data on the in vitro susceptibility patterns of the B. burgdorferi complex. The excellent in vitro effectiveness of acylamino-penicillin derivatives and their suitability for the therapy of Lyme disease is emphasised.

Anti-Bacterial Agents↗

PubMed1985

Binding to and antibacterial effect of aztreonam, temocillin, gentamicin and tobramycin on human faeces.

Aztreonam, temocillin, gentamicin and tobramycin were studied for their effect on the human faecal flora in vitro and for their usefulness for selective decontamination (SD) of the gastrointestinal tract. The sensitivities of the obligately anaerobic flora and the Gram-negative facultatively anaerobic bacteria were determined and the ratio was expressed as SD factor. The high SD factor of the flora from most subjects for aztreonam and tobramycin indicates that the drugs are useful for SD in contrast to temocillin and gentamicin. Binding to and subsequent release of tobramycin from faeces are presumed to facilitate the maintenance of adequate concentrations in the intestine despite the discontinuous intake.

Aztreonam↗

PubMed1991

Substitution of lysine at position 104 or 240 of TEM-1pTZ18R beta-lactamase enhances the effect of serine-164 substitution on hydrolysis or affinity for cephalosporins and the monobactam aztreonam.

By site-directed mutagenesis, TEM-1 beta-lactamase was altered to contain single amino acid changes of E104K, R164S, and E240K, in addition to double changes of E104K/R164S or R164S/E240K and the triple change of E104K/R164S/E240K. Hydrolysis rates for cephaloridine and benzylpenicillin were lowered at least 1 order of magnitude for all enzymes containing R164S substitutions. All mutant enzymes exhibited increased kcat values for beta-lactam antibiotics containing an aminothiazole oxime side chain. Hydrolysis of ceftazidime was most affected, with kcat values increased 3-4 orders of magnitude in all enzymes with the substituted R164S moiety. Km values decreased for all substrates except ceftazidime in the enzymes with multiple mutations. Aztreonam was most affected, with Km values lowered 23-56-fold in the enzymes bearing multiple mutations. When the crystal structures of aztreonam and related monobactams were studied and projected into an active-site model of the PC1 beta-lactamase, it became apparent that the two lysine residues might serve equivalent roles by interacting with the carboxylate of the aminothiazole oxime side chain. Hydrogen-bonding interactions involving the oxime and N7 of the lysine, particularly Lys-104, may also be important in some antibiotics. Ser-164 apparently serves an indirect role, since it is somewhat distant from the active-site cleft.

Aztreonam↗

PubMed2006

Assessing the protonation state of drug molecules: the case of aztreonam.

Herein we examine the viability of physicochemical approaches based on standard computational chemistry tools to characterize the structure and energetics of flexible drug molecules with various titratable sites. We focus on the case of the monobactam antibiotic aztreonam, whose structure and physicochemical properties have been ascribed to several tautomeric forms, although it is still unclear which protonation states are responsible for its biological activity. First, we experimentally determined the pKa values for aztreonam over the pH range 0.8-7.0 using both 1H NMR and 13C NMR spectroscopy. Second, we carried out quantum chemical calculations on snapshots extracted from classical molecular dynamics simulations. Various levels of approximation were used in the energy calculations: ONIOM(HF/3-21G*:AMBER) for geometry relaxation, B3LYP/6-31+G** for electronic and electrostatic solvation energies, and molecular mechanics for attractive dispersion energy. The value of the free energy of solvation of a proton was treated as a parameter and chosen to give the best match between calculated and experimental pKa values for small molecules. Overall, this computational scheme can give satisfactory results in the pKa calculations for drug molecules.

Anti-Bacterial Agents↗

PubMed1991

Aztreonam activity in pneumology. Part 1: Clinical activity and pulmonary bioavailability of two different administration regimens.

Twenty-three patients suffering from lower respiratory tract infections caused by Gram-negative germs were treated with aztreonam (AZT) administered according to two different regimens: 17 subjects (Group A) with 2 g i.v. every 12 h and 6 patients (Group B) with 4 g in 100 ml of saline every 24 hours. Group A included 8 cases of superinfected bronchiectasis, 8 purulent bronchitis and 1 gangrene caused by Gram-negative and anaerobic agents. Group B comprised 6 patients with severe bronchiectasis infection. Pseudomonas aeruginosa was isolated from the sputum in 10/23 cases. The treatment was performed for 10 days on the average. The local and systemic tolerability was good. Group B, with higher antibiotic sputum concentrations for at least 12 hours, attained a better response than Group A: with clinical cure in 100% vs 76% cured plus 18% improved patients; therapy lasted 9.5 days for Group B vs 10.8 days for Group A. Moreover, in 14 subjects affected by pulmonary interstitial diseases who underwent diagnostic broncho-alveolar lavage, we dosed AZT in lavage fluids about 1 hour after the injection of a 2 g dose (Group C: 8 cases) or a 4 g dose (Group D: 6 cases). In group D antibiotic concentrations were significantly higher (P less than 0.005) than group C, while all the parameters that usually define the intensity of the alveolar alterations were not significantly different. Therefore, aztreonam administration in a daily monodose seems able to assure higher and longer lasting concentrations at the site of infection.

Adult↗

PubMed1991

Aztreonam biliary excretion in bile duct ligated jaundiced rats.

An experimental study was undertaken to assess aztreonam biliary concentrations in bile duct ligated jaundiced rats. The study proved that aztreonam biliary concentrations are sufficient to inhibit Gram-negative bacteria within the first and the second hour after antibiotic administration. The experimental model suggests that clinical conditions such as lithiasis or neoplasms of the biliary tree should not totally inhibit the antibiotic excretion.

Animals↗

PubMed1992

Clinical use of aztreonam in a psychogeriatric population.

Aztreonam is a safe, well-tolerated antibiotic with a good response in psychogeriatric patients. The combination of aztreonam with flucloxacillin is an acceptable first-choice treatment for severe infections in psychogeriatric patients.

Aged↗

PubMed1991

Aztreonam-flucloxacillin double beta-lactam treatment as empirical therapy of serious infections in very elderly patients.

Aztreonam, the first monocyclic beta-lactam antibiotic with pure anti-Gram-negative activity, combined with flucloxacillin, a penicillinase resistant penicillin, was given as empirical treatment of 53 serious infections in very elderly people. Eighteen of the cases had positive blood cultures and 11 had a clinical picture of sepsis without positive blood cultures: Of 49 evaluable infections, 45 (92%) were cured. In 40% of the infections, antibiotic treatment could be narrowed after 72 hours to one antibiotic. Diarrhoea, mostly transitory, was the only side-effect. Aztreonam-flucloxacillin combination is a safe and effective empirical treatment regimen for serious infections in very elderly patients.

Aged↗

PubMedDate not supplied

Plasmid-mediated beta-lactamase (TEM-7) involved in resistance to ceftazidime and aztreonam.

TEM-7, a novel TEM-type beta-lactamase (pI 5.41) encoded on a plasmid of approximately 85 kilobases, was found in a clinical isolate of Citrobacter freundii. Strains containing this enzyme exhibited decreased susceptibility to ceftazidime (64-fold) and aztreonam (16-fold) but not to other third-generation cephalosporins. Addition of a beta-lactamase inhibitor--clavulanic acid, sulbactam, or YTR 830--restored normal susceptibility to associated compounds such as ampicillin, piperacillin, ceftazidime, and aztreonam. DNA-DNA hybridization of an intragenic probe of TEM-1 occurred with a 19-kilobase EcoRI fragment of the plasmid encoding TEM-7. A TEM-2 derivative, TEM-201, with characteristics similar to those of TEM-7 was selected spontaneously in the presence of ceftazidime in vitro.

Aztreonam↗

PubMedDate not supplied

Retrospective clinical study of hypersensitivity reactions to aztreonam and six other beta-lactam antibiotics in cystic fibrosis patients receiving multiple treatment courses.

A total of 2,793 courses of treatment with seven beta-lactam antibiotics were administered to 121 cystic fibrosis patients chronically infected with Pseudomonas aeruginosa, and the patients were evaluated with respect to clinical hypersensitivity reactions. Seventy-five patients (62%) experienced 125 reactions, for an overall frequency (based on the number of courses) of 4.5%. Immediate reactions occurred in 34 patients (28.1%) during 53 courses (1.9%). The highest rate of reactions involved piperacillin (50.9% of patients), and the lowest rate involved imipenem and aztreonam (4.0% and 6.5% of patients, respectively); intermediate reaction rates were noted for carbenicillin (23.6% of patients), azlocillin (20.8%), cefsulodin (17.1%), and ceftazidime (13.0%). Cross-reactivity did not appear to be a major problem. Reactions to aztreonam seemed to be restricted to a small group of patients with a high propensity for beta-lactam hypersensitivity.

Anti-Bacterial Agents↗