Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q96DG6 (Pseudomonas)
 76,258 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The pharmacodynamics of once-daily amikacin administered as monotherapy and in combination with aztreonam, ceftazidime, and cefepime against Pseudomonas aeruginosa ATCC 27853 and clinical isolate 16690 (moderately susceptible to ceftazidime) were investigated with an in vitro model of infection over a 24-h period. Monotherapy with aztreonam, ceftazidime, and cefepime and combinations of aztreonam with cefepime or ceftazidime were also studied. MICs and MBCs were determined for viable organisms at 24 h to test for the development of resistance. Once-daily amikacin demonstrated killing activity over the initial 8 h superior to those of all other drugs administered as monotherapy against both strains tested (P < 0.01). Regrowth by 24 h was greatest for the amikacin regimen (P < 0.01) but was apparent for all monotherapy regimens against both strains. No changes in susceptibilities were observed. All combination therapies containing once-daily amikacin achieved 99.9% reductions in log10 CFU/ml by 2.0 h against both strains, with no regrowth of organisms at 24 h. Aztreonam-cefepime and -ceftazidime combinations required approximately 5 to 6 h to achieve a 99.9% reduction in log10 CFU/ml. Although there was no difference in time to the 99.9% kill between the aztreonam-cefepime and -ceftazidime regimens against either strain, the killing activity of these combinations was significantly less than those of regimens containing once-daily amikacin (P < 0.01). Minor differences in the initial susceptibilities of beta-lactams and the monobactam aztreonam against P. aeruginosa may not be important for therapeutic outcomes when used in combination with single-daily aminoglycoside therapy.
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PMID:Pharmacodynamics of once-daily amikacin in various combinations with cefepime, aztreonam, and ceftazidime against Pseudomonas aeruginosa in an in vitro infection model. 148 42

The in vivo activity and source of beta-lactamase in sputum samples from 43 patients with cystic fibrosis (CF) during a 2-week antipseudomonal treatment were studied. A colorimetric method, based on the conversion of nitrocefin, was used for quantitation of the sputum beta-lactamase activity. beta-Lactamases in sputum were characterized by isoelectric focusing and inhibition profile and were compared with the beta-lactamases extracted from Pseudomonas aeruginosa isolated from the paired sputum samples. We found that the beta-lactamase activity increased to high levels in sputum from patients with CF during the course of piperacillin, ceftazidime, cefsulodin, or imipenem therapy. Aztreonam therapy lead to opposite results because the beta-lactamase activity decreased and aztreonam was able to mask beta-lactamase activity by acting as an inhibitor. All sputum beta-lactamases displayed characteristics indicative of a class I enzyme, identical to the beta-lactamases extracted from P. aeruginosa. The presence of beta-lactamase at such levels could lead to in vivo inactivation of beta-lactam antibiotics. This study supports the hypothesis that beta-lactamase production is an important in vivo resistance mechanism in P. aeruginosa-infected patients with CF.
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PMID:High-level beta-lactamase activity in sputum samples from cystic fibrosis patients during antipseudomonal treatment. 159 Jul 4

Aztreonam is a synthetic, monobactam antibiotic structurally related to the beta-lactam class of drugs. It has inhibitory activity against many aerobic gram-negative bacteria, although it does not inhibit gram-positive or anaerobic bacteria. Administration of aztreonam occasionally is associated with minimal and transient adverse effects. This case report describes a patient we believe experienced bone marrow suppression approximately ten days after aztreonam was given for treatment of pneumonia caused by Pseudomonas aeruginosa. This untoward effect primarily was manifested as neutropenia, although normochromic, normocytic anemia and thrombocytopenia were noted as well. One week after aztreonam was discontinued, the patient's bone marrow suppression resolved spontaneously. Although the mechanism responsible for myelosuppression is unclear, aztreonam may be implicated as the offending agent based on the temporal relationship between the development of neutropenia and its administration, and the resolution of neutropenia upon its discontinuation.
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PMID:Aztreonam-induced myelosuppression during treatment of Pseudomonas aeruginosa pneumonia. 187 66

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.
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PMID:Aztreonam in the treatment of gram-negative bacterial meningitis. 206 63

Aztreonam was investigated as to its characteristics as a substrate, inhibitor and inducer for the well-defined beta-lactamases of Gram-negative bacteria, and its antibacterial efficacy as to bacterial cells producing eight types of beta-lactamases was also evaluated. Aztreonam was hydrolyzed at measurable rates by class A beta-lactamases, a TEM-2 type penicillinase and the Proteus vulgaris cephalosporinase with a broad substrate range. However, the affinity of aztreonam for the class A enzymes was low, this property being well reflected by its high antibacterial activity toward producers of class A beta-lactamases. Aztreonam was extremely stable as to the typical class C cephalosporinase of Citrobacter freundii, and acted as a competitive and progressive inhibitor for the beta-lactamase. While the MICs of aztreonam in the cases of the constitutive producers of class C beta-lactamases were evidently affected by enzyme production. An experiment involving aztreonam as a inhibitor in combination with a hydrolyzable beta-lactam gave ambiguous results, however, a strong synergistic effect was found in combination with mecillinam. Using Pseudomonas aeruginosa, aztreonam was confirmed to be a poor inducer of beta-lactamases.
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PMID:Characteristics of aztreonam as a substrate, inhibitor and inducer for beta-lactamases. 211 33

Aztreonam, the first monobactam, has been used extensively in the treatment of a variety of infections caused by gram-negative pathogens. It has been shown to be highly effective against susceptible bacteria without causing serious adverse reactions. Its pharmacologic profile can be attributed to its unique chemical properties and mechanisms of action, which differ substantially from those of the bicyclic beta-lactams, such as the penicillins and cephalosporins. Administered parenterally, aztreonam provides peak serum concentrations for most Enterobacteriaceae and Pseudomonas aeruginosa. It is widely distributed throughout the body. Excretion is largely dependent on renal mechanisms, so dosage can be adjusted in the presence of renal impairment. The clinical uses of aztreonam include treatment of urinary tract, lower respiratory tract, and intraabdominal infections, as well as septicemia, endometritis, pelvic cellulitis, and skin and skin structure infections due to aerobic gram-negative organisms. It is concluded that aztreonam can be used with confidence in the single-drug treatment of susceptible aerobic, gram-negative pathogens. In the treatment of mixed infections, or those of unknown etiology, however, combination therapy is recommended to ensure coverage of gram-positive and anaerobic bacteria.
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PMID:Aztreonam activity, pharmacology, and clinical uses. 218 Feb 93

Aztreonam is a structurally and immunologically unique beta-lactam antibiotic with activity exclusively against aerobic gram-negative micro-organisms. Between 1983 and 1988, its antimicrobial spectrum was evaluated against more than 5,800 fresh clinical isolates at a 300-bed community teaching hospital. Only 1.1 percent of Enterobacteriaceae isolates were resistant to aztreonam over the five-year study period, an incidence similar to that observed with aminoglycoside antibiotics. Aztreonam was found to be more active than third-generation cephalosporins and comparable with mezlocillin against Enterobacter spp., Morganella, and Citrobacter freundii. Although aztreonam was somewhat less active against nonfermenting gram-negative bacilli, such as Pseudomonas and Acinetobacter, overall more than 90 percent of Pseudomonas aeruginosa isolates were susceptible. Ceftazidime was the most active beta-lactam tested against nonfermenters. Against aerobic gram-positive cocci, aztreonam possessed no clinically useful activity. No significant change in susceptibility to aztreonam was observed over the five-year study period for Enterobacteriaceae. For third-generation cephalosporins, however, a trend toward increased resistance was noted, particularly for Enterobacter spp. and C. freundii. A 50 percent increase in resistance to aztreonam was observed over the five-year study period for nonfermenters, particularly P. aeruginosa and Acinetobacter anitratus. Similar increases in resistance were seen with other beta-lactams and gentamicin. Based on its potent in vitro activity, aztreonam appears to be a useful agent and a desirable alternative to aminoglycoside antibiotics for the treatment of pure aerobic gram-negative bacillary infections, or as a component in combination therapy against mixed infections.
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PMID:Aztreonam susceptibility testing. A retrospective analysis. 218 Feb 95

Aztreonam is the first monocyclic beta-lactam antibiotic (monobactam) to be tested clinically. Its synthetic structure determines specific areas of activity, including enhanced activity against Pseudomonas species, exceptional activity against gram-negative bacteria, stability to beta-lactamases and lack of activity against gram-positive bacteria--all of which can be directly related to its chemical composition. Aztreonam has a high affinity for the protein-binding protein 3 (PBP-3) of aerobic gram-negative bacteria. Most of these organisms are inhibited and killed at low concentrations of the drug. Aztreonam binds poorly to PBP sites of the aerobic gram-positive and anaerobic bacteria and consequently has relatively poor inhibitory effects against these bacteria. In vitro, minimum inhibition concentration (MIC) values against almost all of the Enterobacteriaceae and against Neisseria and Haemophilus strains are typically below 1 microgram per milliliter. MIC values against Pseudomonas aeruginosa of 8 micrograms per milliliter are comparable with those of other antipseudomonal beta-lactams and the acylureidopenicillins. As combination therapy with amino-glycosides, aztreonam acts in synergy against P. aeruginosa, Acinetobacter and gentamicin-resistant gram-negative rods. Aztreonam is widely distributed in the body tissues and fluids, and the average elimination half-life is 1.7 hours. Intramuscular dosing results in peak serum levels in approximately one hour, while intravenous dosing results in peak levels within five minutes. After a 2 gram dose given intravenously, MIC90 values for most of the Enterobacteriaceae are exceeded for eight hours, and those for P. aeruginosa, for almost six hours. The steady-state volume of distribution is approximately 0.18 liter per kilogram. Concentrations above the MIC90 for most gram-negative bacteria are also present within bone, prostate and cerebrospinal fluid. Between 60 and 70 per cent of the drug is excreted unchanged in the urine, resulting in concentrations approximating 3,000 micrograms per milliliter two hours after a 1 gram dose given intravenously. Serum clearance of aztreonam is directly proportional to creatinine clearance. Dosage adjustment must, therefore, be made in the presence of reduced clearance. Dosing varies between 0.5 and 2.0 grams every six to 12 hours, depending on the severity of the infection. The characteristics of aztreonam suggest that it is a useful nonnephrotoxic drug for treatment of aerobic gram-negative infection.
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PMID:How and why aztreonam works. 224 91

Empiric antibiotic therapy, which accounts for over 90 percent of in-hospital therapeutic antibiotic decisions, may be defined as tentative therapy designed to decrease morbidity and mortality associated with severe infection due to unidentified bacterial pathogens. In the 48- to 72-hour interim between presentation and the availability of reliable culture and sensitivity data that allow for definitive therapy, empiric therapy is extremely important. Aztreonam, the first member of the monobactam class of monocyclic beta-lactam antibiotics, is highly active against most gram-negative aerobic bacteria, including Pseudomonas aeruginosa. Its spectrum of activity is similar to that of the aminoglycosides but without the toxicity associated with those agents. For this reason, aztreonam may play an important role in empiric therapy. Currently, it can be recommended as single-agent empiric therapy only for severe urinary tract infections, but in combination with a variety of other agents, it has proved useful against a wide range of bacterial infections, and in certain subgroups, such as penicillin-allergic patients, it may represent the treatment of choice. It is not yet clear whether aztreonam is superior to other relatively nontoxic agents, such as the third-generation cephalosporins or carbapenems, but there is little doubt that this new agent is a generally safe and effective drug for the treatment of suspected gram-negative sepsis.
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PMID:Empiric antibiotic use--aztreonam as a model. 231 55

The pharmacokinetics of Aztreonam (AZT) administered i.p. in six stable patients undergoing continuous ambulatory peritoneal dialysis (CAPD) for end-stage renal disease (ESRD) were studied. One gram of AZT was added into a 2 L bag of dialysate (Medital-Bieffe) just prior to infusion into the peritoneal cavity. The dwell time was 8 h. The serum maximum concentration of AZT was 42.5 +/- 12.4 mg/L (mean +/- SD), achieved in 4.6 +/- 1.0 h. The elimination half-life was 2.4 +/- 0.8 h, almost equal to that found in normal subjects (1.7-2 h). The pharmacokinetic parameters of elimination, as elimination rate constant and clearance of AZT from peritoneal cavity were found 0.305 +/- 0.101 h-1 and 10.05 +/- 3.7 mL/min, respectively, while the bioavailability via the peritoneal membrane was 90.8 +/- 3.05% of administered dose. It is concluded that AZT is eliminated from dialysate at a high rate after i.p. administration and its dialysate and serum levels exceed the MIC for the majority of sensitive organisms including Pseudomonas species. Aztreonam appears to be a potentially useful antibiotic for CAPD peritonitis.
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PMID:Pharmacokinetics of aztreonam administered i.p. in continuous ambulatory peritoneal dialysis (CAPD) patients. 248 83


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