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PubMed1988

Clinical pharmacokinetics of aztreonam.

Aztreonam (azthreonam) is practically completely absorbed after intramuscular injection. After intravenous injection plasma concentrations follow a 2-compartment open model, with a t1/2 alpha of 0.20 hours. Volume of distribution at steady-state (Vdss) after intravenous or intramuscular injection is about 0.16 L/kg (0.42 L/kg for the free drug). After oral administration less than 1% of the drug is absorbed. Over a large dosage range plasma concentrations increase linearly with dose. No accumulation occurs after multiple dosing. Plasma binding in healthy subjects is about 56% and is not concentration dependent. Diffusion into tissues is generally slow, and the ratio between mean tissue and plasma concentration seems to depend mainly on the composition of the tissue. In inflamed meninges, penetration of aztreonam into CSF is more rapid than with uninflamed meninges. Diffusion through the placenta is poor, as is diffusion into breast milk. The main route of elimination of aztreonam is by the kidney, partly by active tubular excretion, but this can be inhibited by probenecid. Extrarenal clearance is probably due to excretion by the liver. Metabolism occurs to a very limited extent. Total plasma clearance in healthy adults is about 140 ml/min (8.4 L/h) or 2 ml/min/kg (0.12 L/h/kg), and terminal half-life is 1.7 hours. In children clearance is similar to that in adults when expressed as a function of bodyweight, but in neonates, especially in low birthweight infants, it is less [about 1 ml/min/kg (0.06 L/h/kg)]. In various disease states the Vdss of aztreonam is not appreciably different from that found in healthy individuals.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

PubMed1988

A comparative study of aztreonam and procaine penicillin/probenecid in the treatment of uncomplicated gonorrhoea.

236 patients with uncomplicated gonorrhoea were randomly allocated to receive either aztreonam or procaine penicillin plus probenecid. 115 patients (50 men and 65 women) with uncomplicated gonorrhoea were treated with 1 g aztreonam as a single intramuscular injection. The success rate among those who attended at least one follow up examination after treatment was 99%. The antibiotic was well tolerated and there were no side effects. The observed minimum inhibitory concentrations (MICs) of aztreonam in vitro were very much lower than obtainable serum concentrations. The penicillin treated patients who were evaluable showed a failure rate of 12.8%. We conclude that aztreonam is effective against Neisseria gonorrhoeae, including penicillinase-producing strains, both in vivo and in vitro.

Aztreonam↗

PubMed1989

[Aztreonam and aminoglycosides in the therapy of urinary infections associated with renal calculosis].

Renal calculosis associated with urinary tract infections due to urease-positive or -negative microorganisms poses difficult therapeutic problems. The introduction of monobactam antibiotics such as aztreonam offers a valid therapeutic alternative thanks to the action of this drug on the gram-negative organism often at the root of these infections. The above study has been carried out in 10 patients with infections due to organisms sensitive to aztreonam and aminoglucosides. Treatment with aztreonam (1 g i.m. 3 times daily) brought about sterilization lasting from 3 weeks to permanently in 5 cases. In one case sterilization was transitory and in 4 cases treatment was unsuccessful. Creatinine blood level and other biochemical parameters did not vary. Aminoglucosides alone brought about transitory sterility in 2 cases and was unsuccessful in 6. At the end of treatment, creatinine blood level had increased significantly. Given the absence of toxicity the definitely better therapeutic result, and the absence of induced resistance, aztreonam should be considered the drug of choice and should be preferred to aminoglucosides for the management of urinary tract infections due to microorganisms sensitive to both types of drugs in patients with urinary calculosis.

Adolescent↗

PubMed1989

[Aztreonam versus tobramycin in acute pyelonephritis. A comparative study].

We performed a comparative study between the monobactam antibiotic aztreonam and the aminoglycoside tobramycin in patients diagnosed as having acute pyelonephritis. The respective doses were 1 gr. IM daily for 7 days, and 100 mgr. IM q 12 h for the same period of time. Clinically, 100% of uncomplicated acute pyelonephritis and 87.5% of complicated infections cured with aztreonam. Tobramycin achieved an 80% cure rate for both types of infections. Microbiologically aztreonam was effective in all uncomplicated acute pyelonephritis, and in 69.56% of the complicated cases (overall microbiological cure rate = 78.7%). The therapeutic failures were ascribable to infections from S. faecalis, an organism naturally resistant to aztreonam. Thus, the microbiological cure rate was 84.2% in complicated pyelonephritis from organisms sensitive to this antimicrobial. The microbiological cure rate for tobramycin was 70% in acute uncomplicated, and 80% in complicated infections. We observed a good clinical and biological tolerance to both antimicrobials. No side effects were observed. Serum and blood biochemical analyses, and coagulation tests revealed no changes.

Acute Disease↗

PubMed1986

Synergistic activity of amikacin with aztreonam against Pseudomonas aeruginosa and other gram-negative organisms.

The effects of amikacin in combination with aztreonam were tested on 100 strains of gram-negative bacteria by means of the microtiter checkerboard system. Eighty-one strains were Pseudomonas aeruginosa, eight were Enterobacter species, seven were Acinetobacter species, two were Alcaligenes species, one was a Citrobacter organism, and one was Pseudomonas stutzeri. All strains had a minimal inhibitory concentration (MIC) to aztreonam between 4 and 256 micrograms/ml (MIC50 = 16 micrograms/ml) and an MIC to amikacin between 8 and greater than 128 micrograms/ml (MIC50 = 16 micrograms/ml). A synergistic effect (fourfold less MIC when both aztreonam and amikacin were present) was observed for 40 (49%) of 81 P aeruginosa and three (16%) of 19 of the other strains tested. All the remaining test strains showed an additive response; no antagonism was observed. The MICs to aztreonam and to amikacin for 98% of strains that exhibited synergism ranged from 2 to 32 micrograms/ml.

Amikacin↗

PubMed1986

In vitro activity of aztreonam against gram negative bacteria from clinical specimens and its comparison with other commonly used antibiotics.

A total of 755 gram negative bacteria isolated from clinical specimens were tested against aztreonam by the disc agar diffusion test. The strains of bacteria used in this study consisted of Escherichia coli (314), Enterobacter aerogenes (30), E. agglomerans (7), E. cloacae, (39), Citrobacter diversus (9), C. freundii (13), Hafnia alvei (3), Acinetobacter calcoaceticus (10), Klebsiella oxytoca (6), K. ozaenae (5), K. pneumoniae (107), Morganella morganii (3), Moraxella sp. (10), Pasteurella multocida (1), Proteus mirabilis (66), P. vulgaris (4), Providencia rettgeri (12), P. stuartii (5), Pseudomonas aeruginosa (85), P. fluorescens (2), P. maltophila (7), Salmonella sp. (1) and Serratia marcescens (17). In vitro activity against aztreonam was compared with amikacin, ampicillin, carbenicillin, cephalosporin, cefoxitin, chloramphenicol, gentamicin, nitrofurantoin, piperacillin, tetracycline, sulfamethoxazole-trimethoprim and tobramycin. Over 99% of E. coli and Enterobacter species were susceptible to aztreonam. All the 118 strains of Klebsiella, 87 strains of Proteus-Providencia and 17 strains of S. marcescens were also susceptible. Aztreonam also showed good activity against P. aeruginosa, inhibiting 90% of the 85 isolates tested.

Anti-Bacterial Agents↗

PubMed1988

Aztreonam in treatment of intra-abdominal infections.

Aztreonam is a monobactam antibiotic with a broad antimicrobial spectrum against Gram-negative facultative bacteria. It possesses many of the characteristics of antibiotics that are useful for the treatment of intra-abdominal infections. While this drug is effective against the Gram-negative enteric bacilli usually encountered in intra-abdominal infections, it is not practical as a single agent since anaerobic bacteria are not susceptible to aztreonam. The use of aztreonam avoids the nephrotoxicity and ototoxicity associated with aminoglycoside antibiotics. Its pharmacokinetic parameters allow administration 3 or 4 times daily, and it is less expensive than many alternative agents. Studies comparing aztreonam to tobramycin in patients who also received clindamycin for acute appendicitis note similar rates of success in both antibiotic treatment groups.

Abdomen↗

PubMed1987

In vitro activity of aztreonam, cefuroxime and ceftazidime against gram-negative rods isolated from hospital patients with urinary tract infection.

The in vitro activity of aztreonam, cefuroxime and ceftazidime was determined against 2,372 Gram-negative rods (including Pseudomonas spp.) isolated from hospital patients with urinary tract infections during 1985. Minimum inhibitory concentrations (MICs) were determined using an agar incorporation technique in Mueller-Hinton agar. The inoculum used was approximately 10(5) colony forming units (cfu) contained in 10 microliter Mueller-Hinton broth, which was applied to the surface of the agar plates using a multipoint inoculator. Following inoculation plates were incubated aerobically at 37 degrees C for 18 h. The MIC of each antimicrobial for each organism examined was determined as the lowest concentration of the antimicrobial which completely inhibited growth of the inoculum. The minimum concentration required to inhibit the growth of 90% (MIC90) of the bacterial isolates in each genus or species examined was also determined. In general the antibacterial spectrum of aztreonam was comparable to that of ceftazidime and superior to that of cefuroxime. Against Escherichia coli, which accounted for 72% of the isolates examined, aztreonam (MIC90 less than or equal to 0.25 microgram/ml) was slightly more active than ceftazidime (MIC90 0.5 microgram/ml) and considerably more active than cefuroxime (MIC90 8 micrograms/ml). Aztreonam was active against Pseudomonas spp. (MIC90 16 micrograms/ml), although somewhat less so than ceftazidime (MIC90 4 micrograms/ml). Cefuroxime showed low activity against this genus (MIC90 greater than 128 micrograms/ml).

Anti-Bacterial Agents↗

PubMed1986

Empiric antimicrobial therapy with aztreonam or ceftazidime in gram-negative septicemia.

In an open, comparative study, 225 patients with severe underlying diseases and suspected gram-negative bacillary septicemia were randomly assigned to receive aztreonam or ceftazidime empirically, 2 g intravenously three times daily. Twenty-five patients in the aztreonam group and 22 in the ceftazidime group had blood cultures that grew aerobic gram-negative bacilli and were evaluable for response to therapy. All pathogenic strains were sensitive to treatment. In the aztreonam group, 22 (88 percent) patients had cures, three (12 percent) had failures, and seven (28 percent) had development of superinfections (five were caused by gram-positive cocci and two by fungi). In the ceftazidime group, 18 (82 percent) patients had cures, one had improvement, three (14 percent) had failures, and three had superinfections. The median peak serum bactericidal activity was 1:2,048 after aztreonam administration and 1:512 after ceftazidime administration. Failures were not related to resistant strains or to low serum bactericidal activity.

Adult↗

PubMed1986

Interaction of aztreonam with nafcillin in intravenous admixtures.

An interaction between aztreonam and nafcillin sodium in 0.9% sodium chloride injection or 5% dextrose injection stored in glass or plastic containers is reported. During preliminary experiments, admixtures of aztreonam 10 or 20 mg/mL and nafcillin sodium 10 or 20 mg/mL in 0.9% sodium chloride injection or 5% dextrose injection prepared in glass flasks became cloudy and showed evidence of a fine precipitate. Drug concentrations were measured with a stability-indicating high-performance liquid chromatographic (HPLC) assay. Admixtures of aztreonam 20 mg/mL and nafcillin sodium 20 mg/mL in 5% dextrose injection or 0.9% sodium chloride injection were prepared in polyvinyl chloride bags and stored at room temperature (23-25 degrees C) for 48 hours. The admixtures were assayed at 0, 24, and 48 hours with the same HPLC procedure used during the pretesting experiments. The precipitates were isolated, washed, and centrifuged; the supernatant was analyzed by HPLC assay, and the final residue was analyzed by nuclear magnetic resonance (NMR) spectroscopy. The initial recoveries of drug from the pretesting experiments ranged from 99.2 to 102.4%. Analysis of the precipitates indicated that the precipitate was neither a salt nor a complex formed by the physical interaction of aztreonam and nafcillin sodium, but probably a high-molecular-weight polymer formed by the covalent bonding of subunits of the formulation components. Substantial losses of both drugs from the admixtures were evident after 48 hours of storage. The precipitate was observed sooner in the admixtures containing 0.9% sodium chloride injection than in the admixtures prepared in 5% dextrose injection.(ABSTRACT TRUNCATED AT 250 WORDS)

Aztreonam↗

PubMed1985

Comparative in vitro activity of aztreonam and other antimicrobial agents against Salmonella species.

The in vitro activity of aztreonam, the first monobactam antibiotic, was compared with that of 17 other antimicrobial agents against 79 strains of Salmonella species. The microorganisms were isolated from hospitalized patients, surface waters and seafoods during the decade 1975-1984. They included the following species: Salmonella typhi 63, Salmonella typhimurium 5, Salmonella wien 5, Salmonella heidelberg 2, Salmonella arizonae 2, Salmonella paratyphi B 1 and Salmonella enteritidis 1. The minimum inhibitory concentration (MIC) values of the antibiotics were determined using a serial dilution method in agar. A final inoculum size of 10(5) colony-forming units (CFU) X ml-1 of the tested microorganisms was used. Aztreonam exhibited a superior antimicrobial activity to that of the other antibiotics tested. Aztreonam inhibited 90% of the strains by 0.8 micrograms X ml-1 (MIC range was 0.05 to 1.56 micrograms X ml-1). There was no major difference between minimum bactericidal concentration and MIC values of aztreonam and the effect of inoculum size upon MIC values was observed at 10(7) CFU X ml-1.

Anti-Bacterial Agents↗

PubMed1985

Aztreonam versus gentamicin, each with clindamycin, in the treatment of endometritis.

A randomized comparison of aztreonam (2 g intravenously every eight hours) versus gentamicin (1.5 mg/kg intravenously every eight hours), each with clindamycin (600 mg intravenously every six hours), was performed in 119 patients with endometritis after cesarean section. Patients in both groups had similar risk factors. Genital cultures revealed an average of 3.0 isolates per specimen. Eighty-five aerobic gram-negative rods were isolated from 57 (48%) patients. All were susceptible to both aztreonam and gentamicin. Of 133 anaerobic isolates, 131 (98%) were susceptible to clindamycin. The failures in the aztreonam group were associated with a wound abscess and with an enterococcal bacteremia. Of the six failures in the gentamicin group, two were associated with persistent isolation of enteric bacilli. In the other four failures, no explanation was evident. Side effects occurred in four patients, (three diarrhea, one allergic reaction). All were self-limited and appeared to be due to clindamycin. No patient showed nephrotoxicity. When used in combination with clindamycin, aztreonam gave clinical results similar to gentamicin.

Adult↗

PubMed1985

[Comparative in vitro activity of 2 monobactams (RO 172301 (AMA 1080)and aztreonam), ceftazidime and cefotaxime on Gram-negative bacilli].

In vitro activities of two monobactams (RO 172301 and aztreonam), ceftazidime and cefotaxime against 739 bacterial strains belonging to different species of Gram negative aero-anaerobic bacilli were studied comparatively. Strains were studied according to their resistance phenotype to beta-lactams. Minimal inhibitory concentrations (MIC) of the four antibiotics were determined using the agar dilution method. RO 172301 and aztreonam exhibited a similar activity against P. aeruginosa with a MIC around 2 mg/l for 50% of strains and around 4 mg/l for 90% of strains. As compared to the two monobactams, ceftazidime was more active and cefotaxime less active (one halving dilution either way). Activity of antibiotics was not dependent upon the mechanism of resistance to beta-lactams, except for strains producing a constitutive cephalosporinase. Against Enterobacteriaceae, RO 172301 proved slightly more active than aztreonam and cefotaxime; ceftazidime was the least active drug. Only 12 of the 739 strains tested (1.6%) had a MIC for RO 172301 above 32 mg/l. The percentage of resistant strains was 2.4% for aztreonam and ceftazidime and 8.8% for cefotaxime.

Acinetobacter↗

PubMed1985

[Susceptibility of Pseudomonas aeruginosa to aztreonam in comparison to other pseudomonas-active beta-lactam antibiotics and gentamicin].

The in vitro activity of aztreonam, a synthetic monobactam, was evaluated against 245 strains of Pseudomonas aeruginosa, 130 of them being recent clinical isolates from patients and 115 from hospital environment. Minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC) and bactericidal kinetics were determined. The possibility of resistance development in vitro was studied. Gentamicin, cefsulodin, piperacillin and azlocillin were used as comparative agents with known antipseudomonal activity. At a concentration of 8 mg/l 83.3%, at 16 mg/l 92% of the tested strains were susceptible to aztreonam. Thus, the activity of aztreonam against Pseudomonas aeruginosa is equivalent to that of gentamicin and cefsulodin and better than that of piperacillin and azlocillin in terms of resistance. Bactericidal kinetics with fourfold MIC, which is equivalent to MBC, are nearly identical for aztreonam, piperacillin and cefsulodin. In vitro induced resistance additionally causes increased resistance against the other beta-lactam antibiotics.

Anti-Bacterial Agents↗

PubMed1985

In vitro activity of aztreonam--a new monocyclic beta-lactam antibiotic.

The in vitro antibacterial activity of aztreonam (SQ 26776), a new beta-lactam antibiotic, was measured by the agar dilution technique. Aztreonam is known to have a narrow spectrum with activity only against Gram negative bacteria. The strains tested were 223 clinical isolates from blood cultures obtained at Rigshospitalet, Copenhagen, Denmark. Its activity against E. coli, Klebsiella spp., Proteus spp., Enterobacter spp., Citrobacter, Salmonella typhimurium and Serratia marcescens was satisfactory with MIC values normally below 0.5 mg/l. However, six out of 135 strains of E. coli showed surprisingly high MIC values of eight and 16 mg/l. The activity against Pseudomonas spp. and Acinetobacter spp. were limited, but the majority were inhibited by concentrations of aztreonam between 2.0 and 8.0 mg/l. The MIC values for the tested anaeobic bacteria were high, ranging from 8.0 to above 512 mg/l. With its narrow spectrum of activity, aztreonam seems to be a valuable addition to the antibiotic arsenal. Clinical studies will determine its real value.

Anti-Bacterial Agents↗

PubMed1985

[Clinical evaluation of aztreonam for complicated urinary tract infection].

Efficacy and safety of Aztreonam, a monobactam antibiotic developed by E.R. Squibb & Sons, Inc. U.S.A., in complicated urinary tract infections (UTI) were studied. Aztreonam was administered to 15 patients with complicated UTI admitted to our Hospitals between July, 1984 and January, 1985. A two-gram dose of Aztreonam was administered twice a day intravenously or intraductally for 5 days consecutively. There were 11 evaluable cases in accordance with the UTI Drug Efficacy Evaluation Standard (the second issue). Overall clinical effect of these cases were "excellent" in 6 cases, "good" in 2 cases and "poor" in 3 cases. All the effective cases ("excellent" and "good") were of single infections and all the non-effective cases ("poor") were of complicated infections. All of the gram-negative pathogens and 4 of the 8 gram-positive pathogens were eliminated. In no cases were side effects or significantly abnormal laboratory findings reported. Therefore, Aztreonam is very effective and safe for complicated UTI, especially gram-negative infections.

Adult↗

PubMed1984

Aztreonam versus cefamandole in the treatment of urinary tract infections.

The in vivo efficacy and safety of aztreonam compared to that of cefamandole was randomly and prospectively studied in the treatment of 30 patients suffering from recurrent urinary tract infections with a patient ratio of 2 aztreonam to 1 cefamandole. The mean age was 51.6 +/- 15.4 and 59.8 +/- 13 years respectively. Both antibiotics were given at a dose of 1 g, 8 hourly i.m. for 7-13 days. Sixty-seven percent versus 70% of the patients given aztreonam and cefamandole respectively were suffering from upper urinary tract infections. X ray abnormalities predisposing to relapse or reinfections were present in 88% vs 80% of the patients, while all patients had typical symptoms of urinary tract infections, with high fever (greater than or equal to 38.5 degrees C) reported in 70% and 60% of the patients in the two treatment groups respectively. Escherichia coli and Proteus mirabilis were the predominant isolates in urine cultures. During treatment all patients responded favourably both clinically and bacteriologically, while after a 6-week follow-up 20% versus 30% relapsed clinically with 15% vs 30% bacteriologic relapses in the two groups, but only in patients suffering from upper urinary tract infections. No development of bacterial resistance was observed in the relapses, while mainly Enterococcus spp was implicated in reinfections. No appreciable side effects of toxicity were observed. It was concluded that aztreonam is a promising new antibiotic that deserves further clinical trials in systemic infections.

Adolescent↗

PubMedDate not supplied

Comparative study of aztreonam and cefamandole in the treatment of serious urinary tract infections.

In a single blind study we compared the efficacy of aztreonam (Az), a novel monocyclic beta-lactam antibiotic, to that of cefamandole (Cef) in the treatment of serious urinary tract infections (UTIs). Twenty-one patients were studied (6 men and 15 women, 18-75 years old), 12 suffering from an upper and 9 from a lower UTI; 14 of them received Az and 7 Cef (2:1 ratio), according to a prospective randomization schedule. Az or Cef were administered intramuscularly (1 g every 8 hours) for 5 to 10 days. Patients were followed up for 28 to 42 days after end of treatment. The following bacteria were isolated in the urine cultures: E. coli (in 14 cases), Proteus sp. (4), Klebsiella sp. (2) and Pseudomonas sp. (in 1 case). All 21 bacterial isolates were susceptible to Az while 19 of them were susceptible to Cef (the Pseudomonas strain was sensitive to Az but resistant to Cef). During the entire period of observation, we had 13 cures and 1 relapse in Az-group and 5 cures and 2 relapses in the Cef-group. Aztreonam was as equally well tolerated as cefamandole and no major side effects were observed in either group. In 4 Az- and 3 Cef-patients a rise of SGOT and SGPT (up to 2 1/2 times the upper normal limits) was observed, but it subsided a few days after the end of treatment. Our study shows that aztreonam is at least as effective, safe and well tolerated an antimicrobial agent for the treatment of serious urinary tract infections as cefamandole; In the future aztreonam deserves a large scale, systematic trial in all infections caused by gram-negative bacteria.

Adolescent↗