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PubMed1990

[Pharmacokinetics and clinical studies on aztreonam in neonates and premature infants (the first report). Study on effectiveness and safety in mono-therapy with aztreonam. A study of aztreonam in the Perinatal Co-research Group].

Pharmacokinetics and clinical study of aztreonam (AZT) in neonates and premature infants were conducted with the following results: 1. Pharmacokinetics (1) Serum concentrations of AZT at 30 minutes after one-shot intravenous injection of 10 mg/kg and 20 mg/kg to neonates including premature infants were 20.6-26.6 micrograms/ml and 38.5-46.4 micrograms/ml, respectively, and decreased thereafter. A dose response was observed in the serum concentrations with administration of AZT 10 mg/kg and 20 mg/kg. (2) Serum half-lives (T1/2) tended to be shorter in both mature and premature infants as their day-ages increased and T1/2 tended to be prolonged in premature infants compared with mature infants. (3) Changes in serum concentration upon one-hour intravenous drip infusion of AZT 20 mg/kg were very similar to those upon one-shot intravenous injection. (4) Urinary excretions in the first 6 hours after one-shot intravenous injection of AZT 10 mg/kg or 20 mg/kg tended to increase in mature infants as they grew and showed excretion rate of 26.2-54.3% but those in premature infants did not show any specific tendency with rate of 17.5-45.1%. Urinary excretions upon intravenous drip-infusion showed a tendency very similar to those upon intravenous injection. 2. Clinical studies (1) Clinically evaluable cases of AZT treatment were 88 cases (91 diseases), in which pathogenic organisms were identified in 56 cases (Group A), i.e., sepsis 9, purulent meningitis 2, pneumonia 8, urinary tract infection (UTI) 33 and others. Total efficacy rate was 98.2% including "excellent" (39), "good" (16) and "fair" (1). Number of cases in which pathogenic organisms were unknown (Group B) was 11, i.e., suspected sepsis (4), pneumonia (3) and intrauterine infection (4) and the efficacy rate was 100% with "excellent" (4) and "good" (7). Thus, both group A and B showed excellent results. AZT was also given to 24 cases for prophylaxis and all the cases showed prophylactic effect of AZT.4+ Bacteriologically AZT was deemed effective in 53 cases out of 56 (Group A) with identified pathogens "eradicated" and "unchanged" (2), thus the bacterial eradication rate was 96.2%. (3) A minor degree of loose feces was observed in 1 (1.3%) of 80 cases as a side effect. Abnormal laboratory test values found were eosinophilia (3 cases), elevation of GOT and GPT (2), platelet-increase (1), elevation of GOT (1), and thrombocytopenia.elevation of GOT.GPT.LDH (1). Every one of these was of a minor degree and transient. From the above pharmacokinetics and clinical results, standard dosage of AZT to neonates and premature infants should be in a unit dose of 20 mg/kg, twice daily to those with ages between 0 and 3 days, and 2 to 3 times daily to those with ages 4 days and above, by intravenous injection or intravenous drip infusion.

Age Factors↗
PubMed1990

[Pharmacokinetics and clinical studies on aztreonam in neonates and premature infants (the second report). Study on effectiveness and safety in combination therapy using aztreonam and ampicillin. A study of aztreonam in the Perinatal Co-research Group].

Pharmacokinetics and clinical effects were studied in a combination therapy with aztreonam (AZT) and ampicillin (ABPC) in neonates and premature infants. The results obtained are summarized as follows. 1. Pharmacokinetics (1) Average serum concentrations at 30 minutes after one-shot intravenous injection of AZT 20 mg/kg and ABPC 25 mg/kg to a 4-7 days age-group of neonates were 41.3 (AZT) and 30.5 (ABPC) micrograms/ml, respectively. They gradually decreased to 14.7 and 2.7 micrograms/ml at 6 hours after the administration, but the concentration of AZT was always higher than that of ABPC. (2) Serum half-lives (T1/2) in the 4-7 days age-group were 3.61 hours for AZT and 1.42 hours for ABPC, thus T1/2 of AZT was longer. However, T1/2 of AZT was scarcely affected in the concomitant administration of ABPC. (3) Urinary excretion of AZT in the concomitant administration to the 4-7 days age-group was 52.7%, which was the same or a little higher comparing to that in AZT alone administration. 2. Clinical studies (1) AZT and ABPC were concomitantly administered to 160 cases and 133 cases were evaluated for efficacy. Pathogenic organisms were identified in 29 cases (Group A) and the efficacy rate was 86.2% (25/29). The number of cases in which pathogenic organisms were not identified (Group B) was 50 and in this group, the efficacy rate was excellent, 94.0% (47/50). AZT and ABPC were concomitantly administered to 54 cases for prophylaxis and in all the cases the administrations showed prophylactic effect. (2) Bacterial changes were confirmed in 21 of the 29 cases in which pathogenic organisms were identified initially and all of these 21 cases showed bacterial eradication, i.e., the bacterial eradication rate in the treatment was 100%. (3) There were 2 cases in which side-effects were observed among the analyzed 152 cases (1.3%). The side effects found were 1 case each of diarrhea and eruption. Abnormal laboratory values were found in 23 cases (15.9%), i.e., eosinophilia (9 cases), platelet-increase (4), elevation of GOT (4), elevation of GOT and GPT (3) and others (3). From the above pharmacokinetics and clinical results, the combination therapy of AZT and ABPC is considered to be one of the useful empiric antibiotic-therapies when pathogenic organisms are unknown in the infections of neonates and premature infants.

Ampicillin↗
PubMed1985

[Bacteriological, pharmacokinetic and clinical studies on aztreonam in the pediatric field. Pediatric Study Group of Aztreonam].

This report summarizes the results of joint studies in pediatrics on aztreonam, the first monobactam antibiotic for practical use. Pharmacokinetics was studied in 53 cases administered with 10, 20, 40 and 50 mg/kg of aztreonam (AZT) by intravenous injection and 20 cases with 10, 20, 30, and 40 mg/kg by drip infusion. All the cases had normal hepatic and renal functions at the administration. T1/2 was in a relatively fixed range of 1.35-1.56 hours in intravenous injection cases and 1.30-1.55 hours in drip infusion. One hour after commencing administration of standard 20 mg/kg, the serum concentrations were 50.18 +/- 4.24 micrograms/ml in intravenous injection and 116.33 +/- 10.18 micrograms/ml in drip infusion and even 6 hours after the end of the administration, they were 5.80 +/- 1.16 micrograms/ml and 3.38 +/- 0.58 micrograms/ml, respectively. The cerebrospinal fluid penetration was studied on suppurative meningitis (5 cases) and nonbacterial meningitis (3 cases). The penetration was generally good with sufficient concentration for meningitis caused by E. coli and H. influenzae. Amount of the penetration decreased as the cases were improved. Twenty-nine (29) cases were excluded and 262 cases of total 291 were clinically assessed, and the pathogen-isolated 167 cases of 262 were principally analyzed. Efficacy of AZT was "excellent" for all 3 cases of E. coli sepsis and 1 case of N. meningitidis meningitis and "good" for 1 case of H. influenzae meningitis. The effective rate was 94.6% for 37 pneumonia cases, 94.7% for 76 UTI cases and 88.5% on the whole including as many as 98 "excellent" cases. However, the effective rate for 21 enteritis cases was only 52.4%. Similar trend was observed in the pathogen-unknown group and overall effective rate of total 267 cases was 86.8%. The clinical effect by pathogen was 97.7% for 44 E. coli cases and 97.1% for 34 H. influenzae cases, showing excellent results for the GNB group. AZT was also effective for 8 out of 11 P. aeruginosa cases. With regard to microbiological effect by pathogen, AZT showed a high rate of bacterial elimination for GNB, primarily 98.1% for E. coli and 100% for H. influenzae followed by 76.9% for P. aeruginosa. However, it was only 30.0% for Salmonella. Excluding the Salmonella cases, GNB elimination rate was 93.5%. Clinical and microbiological dose response was not clear partly because, same as the previous studies, the effective rate of AZT was high. It was considered, however, standard dose of 20 mg/kg X 3 approximately 4 times a day was recommendable.(ABSTRACT TRUNCATED AT 400 WORDS)

Age Factors↗
PubMed1991

Aztreonam therapy in children with febrile neutropenia: a randomized trial of aztreonam plus flucloxacillin versus piperacillin plus gentamicin.

In a prospective, randomized trial in 100 febrile neutropenic children, aztreonam plus flucloxacillin was compared with piperacillin plus gentamicin. At the 72 h clinical assessment there was no statistically significant difference between the two groups. However, in microbiologically documented infections there was a higher response rate in the piperacillin/gentamicin group (57%) than in the aztreonam/flucoxacillin group (41%). This was contributed to by the poorer Gram-positive cover of the aztreonam/flucloxacillin combination. In clinically documented infections and unexplained fevers the response rate of the two antibiotic regimens was identical. There were two deaths; one early death (in the piperacillin/gentamicin arm) and one late death. At the final assessment a successful outcome was obtained in the remaining patients. In the aztreonam/flucloxacillin group 75% of the episodes required modification compared with 59% in the piperacillin/gentamicin group.

Adolescent↗
PubMed1990

[Pharmacokinetics and clinical evaluations on aztreonam in perinatal infections in obstetrics and gynecology. A study of aztreonam in the perinatal co-research group].

Pharmacokinetics and clinical studies on an injectable monobactam antibiotic aztreonam (AZT), were carried out in perinatal infections in obstetrics and gynecology and the obtained results are summarized as follows. 1. Pharmacokinetic study (1) Upon one-shot intravenous injection of AZT 1 g before delivery, maternal serum concentration of AZT was 89.0 micrograms/ml immediately after the injection and a half-life (T 1/2) of 0.96 hour was observed. Umbilical-cord serum concentration showed a peak value of 16.5 micrograms/ml at 1.26 hours after the injection and gradually decreased with a T 1/2 of 1.91 hours. The transfer into amniotic fluid was observed and the peak value of AZT in amniotic fluid reached 12.9 micrograms/ml at 5.57 hours after the injection and slowly decreased thereafter with a T 1/2 of 4.42 hours. Transfer and disappearance in one-shot 2 g intravenous injection and 1 g intravenous drip infusion (1 hour) of AZT were very similar to the results obtained with the one-shot 1 g intravenous injection. (2) The residual serum concentration in neonates after one-shot 1 g intravenous injection of AZT to the mother was almost below the detectable limit. Transfer of AZT into milk was scarcely recognized. 2. Clinical studies (1) AZT was injected to 47 cases with various perinatal infections and it was more than "effective" in 45 cases with an efficacy rate of 95.7%. Also, all the 12 cases to which AZT was administered for prophylaxis of infections showed prophylactic effect. Bacterial eradication was obtained with 25 strains out of 29 aerobic Gram-negative bacteria, but 1 strain "persisted" and for 3 strains results were "unknown", hence an eradication rate of 96.2% was obtained. However, AZT treatment resulted in a little lower eradication rate against Gram-positive bacteria. (2) One case (1.3%) of minor degree of urticaria was found as a side effect, and one case each of eosinophilia and elevation of GOT, GPT and Al-P was observed as abnormal laboratory value. From the above results of pharmacokinetics and clinical evaluation, it has been concluded that AZT is a useful and highly safe drug in various perinatal infections and prophylaxis.

Adult↗
PubMed1990

[Pharmacokinetic and clinical evaluations of aztreonam monotherapy and aztreonam and ampicillin combination therapy in neonates and premature infants].

One-shot intravenous injection of aztreonam (AZT), a monobactam-class beta-lactam antibiotic, 20 mg/kg was administered to 4 neonates and 2 premature infants, a total of 6 cases, and plasma and urinary concentrations and urinary recovery rates were determined. Also, one-shot intravenous injection averaging 70.9 mg/kg/day of AZT alone was given to 0- to 43-day neonates and premature infants in b.i.d. to q.i.d. for an average of 8 days for the treatment (6 cases) and prophylaxis (11 cases) of infections. Furthermore, a combination therapy of AZT and ampicillin (ABPC) was applied to 0- to 79-day neonates and premature infants for the treatment (28 cases) and prophylaxis (18 cases) of infections. Average daily dosage of AZT 46.6 mg/kg was given by one-shot intravenous injection or by drip infusion in b.i.d. or t.i.d. for an average of 8 days. Average daily dosage of ABPC 78.6 mg/kg was given in the same daily frequency, route and average duration as AZT. Thus, clinical effects, prophylactic effects against infection, bacteriological effects as well as side effects and clinical laboratory test values were studied with the following results. 1. When AZT 20 mg/kg was administered to 1 case each of 6- and 7-day neonates by one-shot intravenous injection, the plasma concentrations were the highest at 5 minutes after the administration in both cases. Specifically, they were 62.9 and 72.7 micrograms/ml with AUCs of 216.6 and 231.6 micrograms.hr/ml and half-lives of 2.80 and 2.97 hours, respectively. When AZT 20 mg/kg was administered to 5- and 6-day premature infants by one-shot intravenous injection, the plasma concentrations were the highest at 15 minutes after administration in the former and 5 minutes in the latter, at values of 59.8 and 67.7 micrograms/ml, respectively. AUCs were 356.6 and 363.2 micrograms.hr/ml, respectively, and larger than AUCs of the above-mentioned neonates. Half-lives were 5.74 and 4.87 hours, respectively and longer than those of the above-mentioned neonates. When AZT 20 mg/kg was administered to 8- and 13-day neonates by one-shot intravenous injection, the plasma concentrations were the highest at 30 minutes after administration in the former and 5 minutes in the latter, at values of 43.4 and 76.9 micrograms/ml, respectively. AUCs were 202.9 and 189.8 micrograms.hr/ml, and 76.9 micrograms/ml, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)

Ampicillin↗
PubMed1985

Investigation into the immunologic cross-reactivity of aztreonam with other beta-lactam antibiotics.

The cross-reactivity between the monobactam antibiotic aztreonam and the commonly used beta-lactam antibiotics, penicillins, and cephalosporins was investigated. Antibodies to aztreonam, penicillin, and cephalothin were raised in rabbits. The ability of the homologous or heterologous drug or drug conjugates to inhibit antibody binding was assessed in a solid-phase radioimmunoassay. Aztreonam demonstrated very little ability to interact with anti-penicillin or anti-cephalothin antibodies as it required 10,000-fold higher concentrations than other beta-lactams to achieve equivalent blocking. Similarly, penicillin and cephalothin conjugates did not cross-react, to any significant degree, with anti-aztreonam rabbit antiserums. Interestingly, free aztreonam was as effective as conjugated aztreonam in reacting with antibodies raised against conjugated aztreonam. This result suggested that, in contrast to the other beta-lactams, antibodies to aztreonam recognize the side chain rather than the nuclear structures. Studies with other beta-lactam analogs confirmed that the IgG rabbit anti-aztreonam binding was indeed side chain-specific. Thirty-six volunteers were given a seven-day course of therapeutic doses of aztreonam and in none did any detectable IgE anti-aztreonam antibodies develop. Four of these subjects had evidence of preexisting IgG antibodies cross-reactive with aztreonam, but the levels rose in only one patient following drug exposure. This human IgG anti-aztreonam was also directed to the side chain and did not cross-react with cephalothin or penicillin. The ability of aztreonam to cross-react with human IgE to various penicillin determinants was also investigated. Aztreonam determinants analogous to the penicillin determinants (penicillin, penicilloyl, and penicilloate) were constructed and the maximal concentration that did not evoke false-positive skin test results was determined to be 6 X 10(-3) mol/liter. None of 41 patients with documented IgE-reactive skin tests to various penicillin determinants concurrently demonstrated reproducible reactivity to any aztreonam reagents. IgE anti-penicilloyl antibodies from three persons were also tested in vitro for their ability to cross-react with conjugated or free aztreonam. Minimal, if any, reactivity was observed between the IgE anti-penicilloyl and any of the aztreonam materials. These results indicate that there is very little cross-reactivity between the monobactam aztreonam and other beta-lactam antibiotics.

Adult↗
PubMed1986

Stability of intravenous admixtures of aztreonam and cefoxitin, gentamicin, metronidazole, or tobramycin.

The stability of aztreonam and cefoxitin, gentamicin, metronidazole, or tobramycin in intravenous admixtures containing aztreonam and one of the other drugs was studied. Admixtures of aztreonam and gentamicin, aztreonam and tobramycin, and aztreonam and cefoxitin were each prepared in four different concentrations in both 0.9% sodium chloride injection and 5% dextrose injection. Admixtures of aztreonam and metronidazole were prepared in two different concentrations using a commercially available solution of metronidazole 5 mg/mL in a phosphate-citrate buffer. One of each of these admixtures was stored at 25 degrees C for 48 hours and at 4 degrees C for seven days. At various storage times, 1-mL samples of the admixtures were tested for pH and assayed using high-performance liquid chromatography or fluorescence polarization immunoassay. The pH of all admixtures except admixtures of aztreonam and cefoxitin decreased only slightly during storage. Concentrations of aztreonam and tobramycin under both storage conditions decreased by less than 10%. Concentrations of cefoxitin and aztreonam decreased by more than 10% at 25 degrees C, and concentrations of gentamicin decreased by more than 10% under both storage conditions. Visual inspection of admixtures of aztreonam and metronidazole revealed an incompatibility between the two drugs, as evidenced by the appearance of a cherry-red color. Admixtures of aztreonam 10 and 20 mg/mL and tobramycin 0.2 and 0.8 mg/mL in 5% dextrose injection or 0.9% sodium chloride injection are stable for 48 hours at 25 degrees C or seven days at 4 degrees C. Admixtures of aztreonam 10 and 20 mg/mL and gentamicin 0.2 and 0.8 mg/mL in 5% dextrose injection or 0.9% sodium chloride injection are stable for eight hours at 25 degrees C and 24 hours at 4 degrees C. Admixtures of aztreonam 10 and 20 mg/mL and cefoxitin 10 and 20 mg/mL in 5% dextrose injection or 0.9% sodium chloride injection are stable for 12 hours at 25 degrees C and seven days at 4 degrees C. Aztreonam and metronidazole should be administered separately.

Aztreonam↗
PubMed1986

Comparative pharmacokinetics of carumonam and aztreonam in mice, rats, rabbits, dogs, and cynomolgus monkeys.

The pharmacokinetic properties of carumonam (AMA-1080, Ro 17-2301) were studied in mice, rats, rabbits, dogs, and cynomolgus monkeys and compared with those of aztreonam. Carumonam administered subcutaneously in mice or intramuscularly in rats, rabbits, dogs, and cynomolgus monkeys at a dose of 20 mg/kg was readily absorbed and distributed at high concentrations in the plasma, kidneys, liver, and lungs, as was aztreonam. The peak level of carumonam in plasma, ranging from 41 micrograms/ml in mice to 68 micrograms/ml in monkeys; the area under the plasma concentration-time curve, ranging from 20 micrograms X h/ml in mice to 80 micrograms X h/ml in monkeys; the plasma half-life, ranging from 0.24 h in mice to 1.10 h in dogs; and the plasma clearance, ranging from 4.5 ml/min per kg in monkeys to 16.7 ml/min per kg in mice, resembled respective values of aztreonam. In rats, carumonam was eliminated faster than aztreonam. The levels of both antibiotics in the kidneys and liver were usually higher than respective levels in plasma. The level of carumonam in the kidney was usually higher than that of aztreonam, whereas the level of aztreonam in the liver was usually higher than that of carumonam. Both antibiotics showed similar distribution in the lung and spleen; the levels in these tissues were less than the levels in plasma. Carumonam was excreted mainly in the urine; the recovery ranged from 52% (from dogs) to 73% (from rabbits). The urinary recovery of carumonam from mice, rats, and monkeys was higher, but the recovery of carumonam from rabbits and dogs was lower than that of aztreonam. The biliary excretion of carumonam, amounting to 4.1% from rats and less than 0.3% from rabbits and dogs, was smaller than that of aztreonam, amounting to 19.1% from rats and around 1% from rabbits and dogs. The extent of protein binding at 20 micrograms of carumonam per ml was lower than that of aztreonam. For all species except dogs, which have very low binding in their serum (11% for carumonam and 20% for aztreonam), the binding of carumonam ranged from 21% (in rabbits) to 36% (in rats), whereas that of aztreonam ranged from 55% (in rabbits) to 85% (in rats). Thus, the plasma pharmacokinetics of carumonam and aztreonam were generally similar for all animals tested except dogs, but the two antibiotics differed slightly in their distribution in tissue, excretion, and protein binding in serum.

Animals↗
PubMed1986

Aztreonam. A review of its antibacterial activity, pharmacokinetic properties and therapeutic use.

Aztreonam (azthreonam; SQ 26,776) is the first member of a new class of beta-lactam antibiotics, the monobactams. Aztreonam is selectively active against Gram-negative aerobic bacteria and inactive against Gram-positive bacteria. Thus, in vitro, aztreonam is inhibitory at low concentrations (MIC90 less than or equal to 1.6 mg/L) against Enterobacteriaceae except Enterobacter species, and is active against Pseudomonas aeruginosa, 90% of pseudomonads being inhibited by 12 to 32 mg/L. Aztreonam is inactive against Gram-positive aerobic bacteria and anaerobes, including Bacteroides fragilis. Therefore, when administered alone, aztreonam has minimal effect on indigenous faecal anaerobes. Aztreonam must be administered intravenously or intramuscularly when used to treat systemic infections, since absolute bioavailability is very low (about 1%) after oral administration. Since elimination half-life is less than 2 hours, 6- or 8-hourly administration is used in the treatment of moderately severe or severe infections, although 12-hourly injection is adequate in less severe systemic and some urinary tract infections. Therapeutic trials have shown aztreonam to be effective in Gram-negative infections including complicated infections of the urinary tract, in lower respiratory tract infections and in gynaecological and obstetric, intra-abdominal, joint and bone, skin and soft tissue infections, uncomplicated gonorrhoea and septicaemia. In comparisons with other antibiotics, aztreonam has been at least as effective or more effective than cefamandole in urinary tract infections and similar in efficacy to tobramycin or gentamicin. Where necessary, aztreonam and the standard drug have both been combined with another antibiotic active against Gram-positive and/or anaerobic bacteria. Aztreonam has been effective in eradicating pseudomonal infections in most patients (except in patients with cystic fibrosis), but the inevitably limited number of pseudomonal infections available for study prevents any conclusions as to the relative efficacy of aztreonam compared with other appropriate regimens against these infections. Thus, with an antibacterial spectrum which differs from that of other antibiotics, aztreonam should be a useful alternative to aminoglycosides or 'third generation' cephalosporins in patients with proven or suspected serious Gram-negative infections.

Anti-Bacterial Agents↗
PubMed1983

Aztreonam, cefoperazone, and gentamicin in the treatment of experimental Enterobacter aerogenes endocarditis in rabbits.

The effectiveness of aztreonam, cefoperazone, and gentamicin alone and in combination was evaluated in Enterobacter aerogenes endocarditis in rabbits. The minimal inhibitory concentration/minimal bactericidal concentration ratios for E. aerogenes were as follows: aztreonam, 0.4/0.4 microgram/ml; cefoperazone, 0.8/0.8 microgram/ml; and gentamicin, 3.1/3.1 micrograms/ml. With an inoculum of 10(9) organisms per ml, aztreonam and cefoperazone were equivalent in reducing titers of E. aerogenes in broth, and both drugs demonstrated an increased rate of reduction when gentamicin was added; gentamicin alone was least effective. E. aerogenes endocarditis in rabbits was treated intramuscularly with aztreonam (60 mg/kg) every 6 h, with cefoperazone (60 mg/kg) every 6 h, with gentamicin (1.7 mg/kg) every 8 h, and with aztreonam plus gentamicin or cefoperazone plus gentamicin for 5 and 10 days, respectively. All of the therapeutic regimens were effective in reducing vegetation titers as compared with untreated controls. Aztreonam plus gentamicin was more effective than either aztreonam or gentamicin alone. Cefoperazone plus gentamicin was more effective than cefoperazone alone but was not more effective than gentamicin alone. Neither aztreonam and cefoperazone nor aztreonam and gentamicin differed significantly, but gentamicin was significantly more effective than cefoperazone. Aztreonam plus gentamicin did not differ significantly in effectiveness from cefoperazone plus gentamicin. Aztreonam gave a peak level of about 135 micrograms/ml and a half-life of 0.7 h. Cefoperazone gave a peak level of about 155 micrograms/ml and a half-life of 1.1 h. Gentamicin gave a peak level of 7.4 micrograms/ml and a half-life of 1.3 h.

Animals↗
PubMedDate not supplied

Cross-allergenicity and immunogenicity of aztreonam.

The immunochemistry of aztreonam, the prototype of the new monobactam class of beta-lactam antibiotics, was studied in a series of experimental and clinical investigations. Rabbit antibodies to aztreonam and naturally occurring human antibodies that recognize aztreonam were found to have negligible cross-reactivity with benzylpenicillin, cephalothin, and cefotaxime. Aztreonam likewise displayed negligible cross-reactivity (less than or equal to 0.001%) with antibodies to penicillin (including human IgE antibodies to major and minor penicillin determinants) and to cephalothin. These studies suggest that aztreonam may be well tolerated by penicillin-allergic individuals, and this possibly is now being evaluated in clinical trials. Seven (6.25%) of 112 healthy persons tested had preexisting IgG antibodies to aztreonam in low titer, presumably as a result of exposure to naturally occurring cross-reacting moieties. Only two of seven patients with preexisting IgG antibodies to aztreonam had a rise in titer following aztreonam treatment. No IgE antibody to aztreonam was detected in serum specimens obtained on day 10 during any of the 112 courses of therapy. These clinical observations suggest but do not prove that aztreonam has only weak potential to elicit a drug-specific immunologic response.

Allergens↗
PubMed1983

Pharmacokinetics of aztreonam in patients with various degrees of renal dysfunction.

We have studied the pharmacokinetics of 1-g intravenous doses of aztreonam in four groups of six volunteers each, distinguished by their creatinine clearances (greater than 80, 30 to 80, 10 to 29, and less than 10 ml/min). Subjects received 1 g of aztreonam intravenously without any complications. Aztreonam serum and urine levels were measured by microbiological methods and by high-pressure liquid chromatography, and unbound serum aztreonam was determined by ultrafiltration. Serum levels were well described by a two-compartment infusion model. From this model we determined steady-state volume of distribution, alpha distribution phase half-life, beta elimination phase half-life, and total clearance of aztreonam. The mean of beta elimination phase half-life ranged from 2 h in normal subjects to 6 h in anephric patients. The total clearance of aztreonam correlated closely with corrected creatinine clearance calculated from serum creatinine, age, and sex (r = 0.97, P less than 0.001) and ranged from a mean value of 107 ml/min in normal subjects to 29 ml/min in functionally anephric patients. Some 75% of aztreonam excretion was renal. Urinary recovery of aztreonam ranged from 58% of the administered dose in normal subjects to 1.4% in uremic patients. Free aztreonam in serum correlated inversely with creatinine clearance (P less than 0.001). A nomogram was developed as a guide for adjustment of aztreonam dosage according to renal function.

Adult↗
PubMedDate not supplied

Comparison of the inhibitory and bactericidal activity of aztreonam and amikacin against gram negative aerobic bacilli.

Aztreonam has been compared both in vitro and in clinical trials to aminoglycosides in its activity against aerobic gram-negative bacteria. The inhibitory and killing abilities of aztreonam and amikacin were examined against five gram-negative bacillary strains. Time kill analysis was carried out at serum-achievable concentrations (25 micrograms per ml amikacin, 100 and 200 micrograms per ml aztreonam) and levels found three to five hours post-infusion (8 micrograms per ml amikacin and 25 micrograms per ml aztreonam). Amikacin killed all five strains faster than aztreonam at all the concentrations tested. Regrowth and the presence of persisters were observed in aztreonam-treated cultures. In the presence of amikacin, there was no detectable increase in cell mass, as measured by optical density. However, following aztreonam treatment, bacterial cell mass increased in the first two to three hours before decreasing. Long, filamentous cells were observed in aztreonam-containing cultures. Though amikacin and aztreonam are bactericidal drugs, prolonged bacterial survival, continued cell growth, regrowth, and persisters were observed only in aztreonam-treated cultures.

Amikacin↗
PubMed1985

Stability of intravenous admixtures of aztreonam and ampicillin.

The stability of aztreonam and ampicillin in intravenous admixtures containing both drugs was studied. Each of the following drugs and combinations of drugs was added to both 5% dextrose injection and 0.9% sodium chloride injection: aztreonam 10 and 20 mg/mL, ampicillin sodium 5 and 20 mg/mL, aztreonam 20 mg/mL and ampicillin sodium 20 mg/mL, aztreonam 20 mg/mL and ampicillin sodium 5 mg/mL, aztreonam 10 mg/mL and ampicillin sodium 20 mg/mL, and aztreonam 10 mg/mL and ampicillin sodium 5 mg/mL. One of each of these admixtures was stored at 25 degrees C for 48 hours and 4 degrees C for seven days. At various storage times the admixtures were inspected for visual changes and 2-mL samples were examined microscopically for crystalline and particulate matter, tested for pH, and assayed by high-performance liquid chromatography. No visual changes were observed. In the two-drug solutions, pH was influenced by concentrations of the two drugs and stability of the drugs was influenced by the solution pH. The pH of single-drug aztreonam admixtures did not change during storage, but the pH of single-drug and two-drug admixtures containing ampicillin decreased. In single-drug admixtures, aztreonam loss under both storage conditions was less than 10% but ampicillin loss was more than 10% in 0.9% sodium chloride injection and more than 50% in 5% dextrose injection. The stability of ampicillin was increased in the presence of aztreonam, and the stability of aztreonam was decreased in the presence of ampicillin.(ABSTRACT TRUNCATED AT 250 WORDS)

Ampicillin↗
PubMed1991

Sensitization to aztreonam and cross-reactivity with other beta-lactam antibiotics in high-risk patients with cystic fibrosis.

The immunogenicity, allergenicity, and cross-reactivity of aztreonam were investigated in 21 patients with cystic fibrosis (CF) (aged 5 to 39 years) with well-documented histories of allergic systemic reactions (SRs) to penicillin and/or cephalosporin antipseudomonal beta-lactam antibiotics (BLAs). Skin tests (STs) with penicilloyl-polylysine (PPL), penicillin minor determinant mixture, and antipseudomonal BLA were positive in 19 patients (90%). The BLA causing the most recent allergic reaction, minor determinant mixture, or PPL, was positive in 89%, 53%, and 32% of ST-positive patients, respectively. Serum PPL-specific IgE antibodies were not detectable, although PPL-specific IgG antibodies were found in 64% of patients tested. STs to aztreonam reagents were performed and were initially negative in 20 patients. One patient was ST positive to the polylysine conjugate of hydrolyzed aztreonam (SQ 27629), despite no prior exposure to aztreonam, and was not treated. Of 20 patients treated with aztreonam, four were demonstrated to be sensitized by exposure (one had an SR during initial treatment course, two had SRs on reexposure, and one patient was asymptomatic after intravenous desensitization) by positive aztreonam reagent skin responses on repeat testing. Aztreonyl-specific IgE and IgG serum antibodies were not detected in any patients, including patients with allergic reactions to aztreonam. Thus, aztreonam is generally well tolerated in high-risk patients with CF allergic to other BLAs and appears to have reduced immunogenicity by serologic testing. However, caution should be exercised with aztreonam in BLA-allergic patients with CF in light of 5% preexisting ST cross-reactivity and 20% sensitization rates found in this study.

Adolescent↗
PubMed1984

Effect of hemodialysis and peritoneal dialysis on aztreonam pharmacokinetics.

Aztreonam, a new monobactam, will be widely used because of its broad aerobic gram-negative bacterial coverage and its apparent low risk of allergic phenomena in penicillin/cephalosporin-sensitive patients. We examined aztreonam kinetics in patients during hemodialysis and in the interdialytic period and in patients on continuous ambulatory peritoneal dialysis (CAPD), and related aztreonam to urea clearance (CL). In hemodialysis patients, aztreonam serum half-life was 7.9 hr between and 2.7 hr during dialysis sessions. CLserum, CLrenal, and CLother were 24.4, 0.5, and 23.9 ml/min, respectively, during the interdialytic period. Four hours of dialysis removed 38.2% (range, 27 to 58%) of antibiotic. CL of aztreonam by hemodialysis was 36.6 to 43.2 ml/min, 50 to 77% greater than interdialytic CL. CL of urea by hemodialysis was 112.4 to 115.6 ml/min; CLaztreonam/CLurea ratio was 0.28 to 0.33 during the hemodialysis sessions. During CAPD, aztreonam serum half-life after intravenous dosing was 7.1 hr; dialysate recovery, 9.7% of the dose; CLserum, CLrenal, CLperitoneal dialysis, and CLother were 23.8, 0.5, 2.1, and 21.3 ml/min, respectively. CLurea by CAPD was 6.5 ml/min. Thus, CLaztreonam during CAPD was 32% of CLurea. Aztreonam was detectable in dialysate at 48 hr (eight exchanges) after peritoneal administration in the first exchange. Hemodialysis and CAPD patients given aztreonam treatment should receive the standard dose of aztreonam as a loading dose, followed by one-fourth the loading dose at standard dose intervals. Hemodialysis patients should receive a supplemental dose equal to half their usual maintenance dose immediately after each dialysis session. For CAPD patients with peritonitis due to susceptible organisms, a 1-g i.v. loading dose followed by a 0.5-g i.p. dose every 6 hr is suggested. In any individual patient undergoing hemodialysis or CAPD, the relationship between CLurea and CLaztreonam should allow appropriate antibiotic dose adjustment.

Adult↗