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[Clinical evaluation on aztreonam in pediatric field and fundamental study on its penetration into cerebrospinal fluid].

The penetration of aztreonam (AZT), a new synthetic monobactam, into cerebrospinal fluid (CSF) and the clinical studies for bacterial infections were carried out. The following results were obtained. The concentrations of AZT in CSF were less than 0.31 microgram/ml and 0.42 microgram/ml, respectively, at 1 hour after intravenous administration of 34 mg/kg and 71 mg/kg in 2 cases of aseptic meningitis at the acute stage. The concentration of AZT in CSF was 6.9 micrograms/ml at 1 hour after intravenous administration of 100 mg/kg in 1 case of purulent meningitis at the acute stage and was 0.62-0.98 micrograms/ml even at the recovering stage. At each stage, its concentration was more than the minimum inhibitory concentration of E. coli (0.10, less than 0.05 microgram/ml; at inoculum size of 10(8), 10(6) cells/ml). Clinical efficacy of AZT was good in 2 cases of purulent meningitis, excellent in 1 case of septicemia, excellent in 5 cases of urinary tract infection, excellent in 1 case and good in 3 cases out of 4 cases of gastroenteritis, excellent in 4 cases and poor in 2 cases out of 6 cases of pneumonia and bronchitis, excellent in 2 cases and good in 1 case out of 3 cases of tonsillitis. No side effects and no abnormal laboratory findings were observed except 1 case of mild diarrhea out of 21 cases.

Adolescent↗

[Clinical study on aztreonam in pediatrics].

Efficacy and safety of aztreonam (AZT) for 31 cases of infections of children were studied with the following results. Clinical efficacy of AZT for 22 respiratory tract infections, 5 urinary tract infections and 2 gastrointestinal infections was "excellent" for 19 cases (65.5%), "good" for 9 cases (31.0%) and "poor" for 1 case (3.4%) with an overall effective rate of 96.6%. Microbiological effect of AZT for 19 isolated strains (15 cases) was 100% in disappearance of the Gram-negative bacteria and 89.5% on the whole. With regard to side effect of AZT in 31 cases, there was a slight elevation of GPT in 1 case and eosinophilia in 2 cases. It was considered from the above results that AZT is a useful and safe antibiotic for infections of children.

Age Factors↗

[Laboratory and clinical studies on aztreonam in the pediatric field].

Laboratory and clinical studies were performed as follows on aztreonam (AZT), a new monobactam antibiotic. Pharmacokinetics Serum concentrations of AZT were measured in 1 patient given 20 mg/kg by intravenous bolus injection. The peak concentration was 100 micrograms/ml at 15 minutes, and T 1/2 was 1.85 hours. Clinical efficacy AZT was administrated intravenously to 10 patients in doses of 59.2-170.7 mg/kg (average 76.1 mg/kg) t.i.d. for 3-8 days (average 5.3 days); 5 with pneumonia, 1 with bronchitis, 1 with lymphadenitis, 1 with sepsis (suspected) and 2 with urinary tract infections. The overall efficacy rate was 80%, i.e., efficacy was excellent in 5, good in 3, fair in 1 and poor in 1. Bacteriological efficacy was excellent, i.e., 4 of 4 Gram-negative strains disappeared. Any clinical side effects and laboratory abnormalities were not observed. The above results suggest that AZT is a useful antibiotic for treating pediatric bacterial infections, especially due to Gram-negative bacteria.

Age Factors↗

[Clinical efficacy of aztreonam in refractory infections in children].

Aztreonam (AZT) is the first monobactam antibiotic that has significant activity in vitro against aerobic Gram-negative bacteria but not against Gram-positive or anaerobic bacteria. The agent was used 120-200 mg/kg in daily dose to treat 10 hospitalized cases of refractory infections in pediatric field. There were 3 cases of 1 pneumonia, 4 cases of urinary tract infections, 2 cases of pyogenic meningitis and 1 case of septicemia. Seven aerobic Gram-negative bacteria were isolated from patients and 4 bacteria were eradicated by treatment. Clinical cure was achieved in 8 out of 10 cases without adverse reaction or drug toxicity.

Adolescent↗

[Penetration of aztreonam and ampicillin to cerebrospinal fluid in the concomitant administration to rabbits with Staphylococcus aureus meningitis].

Aztreonam (AZT) and ampicillin (ABPC) were independently administered to 6 and 7 rabbits respectively, with S. aureus meningitis. Additionally, AZT and ABPC were concomitantly given to 6 rabbits with S. aureus meningitis. Concentrations of AZT and ABPC in cerebrospinal fluid (CSF) and serum were determined by HPLC method, and the results in concomitant treatment were compared with those for single treatment of each agent. Results were as follows: Maximum serum concentrations of AZT in concomitant treatment of AZT and ABPC were higher than those in single treatment of AZT. However, there was no significant difference between the 2 treatment groups with regard to maximum CSF concentration, percentage of AUC of CSF to serum, and T1/2 of the CSF and serum concentrations of AZT. ABPC in the concomitant treatment did not influence the CSF concentration of AZT. There was no significant difference in serum concentration of ABPC between concomitant treatment and the single one. However, the values of maximum CSF concentration, percentage of maximum CSF to serum concentration and percentage of AUC of CSF to serum in the concomitant treatment were lower than those in the single treatment of ABPC. With regard to T1/2 of CSF concentration of ABPC, there was no remarkable difference between the 2 treatment groups. The above results suggest that the distribution of ABPC into CSF is suppressed in the concomitant treatment of AZT and ABPC. AZT has no antimicrobial activity against Gram-positive bacteria. The CSF concentration of ABPC is suppressed in the concomitant treatment. Those facts suggest that AZT should be administered for meningitis cases after the identification of causative pathogens.

Ampicillin↗

[Effect of aztreonam on bacterial flora in human feces].

Aztreonam (AZT), a new injectable monobactam antibiotic, was administered to 7 healthy male volunteers, aged 21-28 years (23 years, on average) and weighing 60.5-87.0 kg, (69.5 kg, on average) by one shot intravenous injection of 1,000 mg twice a day for 5 days. The effect of AZT on the fecal flora was studied 3 days before administration, on the day of the initiation, 3 and 5 days (end of the administration course) after the initiation, and 3, 5 and 10 days after the end of the administration. Fecal concentration of AZT was also studied. Also, fecal concentration and recovery rate of AZT in 4 healthy male volunteers aged 23-31 years (26 years, on average), weighing 59.5-70.5 kg (65.6 kg, on average) were measured by injecting 1,000 mg of AZT by intravenous injection only one time. Susceptibility of the bacteria isolated from the 7 cases receiving consecutive dosage to AZT, cefmetazole (CMZ), latamoxef (LMOX), cefoperazone (CPZ) and ceftazidime (CAZ) as well as side effect and laboratory values were examined with the following results. In the fecal flora, the population of Enterobacteriaceae on average was 10(7) cells/g feces on the day of the initiation and decreased by 2 logarithms to 10(5) cells/g 3 days after the initiation, 10(5) cells/g feces 5 days after the initiation with no bacterial isolation in 2 cases, 10(7) cells/g feces on 3 and 5 days after the end of administration respectively with recovery of the population to the average population on the day of the initiation. However, it increased 10 days after the end of administration with the population of 10(9) cells/g feces due to the isolation of one 10(10) cells/g feces, which was an increase by 2 logarithms as compared with average population before the administration. It was also higher than the average population 3 days before the initiation of administration. Temporal decrease or disappearance of the bacteria were noted by the administration of AZT. As to other cases of Gram-negative bacilli, Pseudomonas sp. was detected from only 2 cases 3 days before the initiation of administration and on the day of the initiation, but there was an increase to 4 and 5 cases 3 and 5 days after the initiation respectively. Number of isolation returned to 2 cases, 3, 5 and 10 days after the end of administration respectively and it was same as the number before the initiation of administration.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

The newer cephalosporins. Aztreonam and imipenem.

Many of the antimicrobial agents described here exhibit great advances over older drugs in terms of antimicrobial spectrum, clinical utility, and, sometimes, safety. The newer cephalosporins are useful for treatment of many common outpatient and inpatient infections. Aztreonam provides excellent coverage against a broad range of aerobic gram-negative bacteria, without the toxicity associated with aminoglycosides. Imipenem exhibits activity against an impressive array of pathogens. These antimicrobials are expensive, however, and some offer no advantages over older agents. Finally, all--including imipenem--are faced with increasing resistance of bacteria.

Aztreonam↗

[The levels of aztreonam in the cord bloods and tissues after administration to pregnant women].

The monobactam antibiotic aztreonam (AZT) was administered by intravenous drip infusion to women with intrauterine infections at 6-hour intervals and its concentrations in the maternal blood, umbilical blood, and umbilical tissue were determined at parturition to evaluate its transport to the umbilicus and fetus, and this accumulation in the tissue. Further, umbilical tissue was cultured to detect bacteria and examined histologically to evaluate the efficacy of AZT its treatment of omphalitis. Neither maternal nor umbilical blood showed any signs of drug accumulation, and there was a correlation between maternal and umbilical blood levels of AZT and time lapsed after most recent administration. Umbilical tissue levels of AZT tended to increase with time for about 12 hours after the start of administration, but showed no tendency to further rise thereafter. The umbilical tissue cultures were negative for causative pathogens 12 hours or more after the initial dosing. Histological examination of umbilical tissue was negative for omphalitis 12 hours or more after the start of administration in all but one patient. After the administration of AZT to pregnant women with intrauterine infections, it was detected in the umbilicus and fetus in high concentrations at parturition without appreciable tissue accumulation, newborn infection or adverse reaction. The overall results suggest that AZT is clinical effective when used in the treatment of omphalitis.

Aztreonam↗

Transduction of resistance to Imipenem, Aztreonam and Ceftazidime in nosocomial strains of Pseudomonas aeruginosa by wild-type phages.

Two wild-type bacteriophages, designated AP-2 (for P. aeruginosa phage) and AP-12, have been isolated and propagated from two multiple drug resistant strains of P. aeruginosa. Both phages were found to transduce Imipenem- (IMI), Aztreonam- (AZA) and Ceftazidime- (CTZ) resistance as well as resistance determinants to other drugs. Genetic analysis showed that resistance determinants to newest anti-pseudomonal antibiotics IMI, AZA and CTZ could be separated by transduction. Thus the resistance to these antibiotics is presumably coded by different genes. In some transductans also the presence of the tra+ has been demonstrated, indicating that they can transfer the resistance to other strains by conjugation.

Anti-Bacterial Agents↗

[Antibacterial activity of aztreonam against clinical isolates].

To evaluate the antibacterial activity of a monobactam antibiotic, aztreonam (AZT), MICs of AZT and other antibiotics against clinical isolates collected at 36 participating institutions after January 1992 were determined using the agar plate dilution method (size of inoculum, 10(6) cfu/ml) according to the Japan Society of Chemotherapy standard. The antibiotics that were tested along with AZT included piperacillin (PIPC), cefoperazone (CPZ), and amikacin (AMK). AZT was found to be more active against Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Proteus vulgaris, Morganella morganii, and Providencia rettgeri than CPZ, PIPC, and AMK. AZT was also more active against Serratia marcescens than the other antibiotics, but about 6% of the strains tested were resistant to AZT with MIC of 12.5 micrograms/ml. Against Enterobacter cloacae and Citrobacter freundii, however, was more active AMK than AZT. AZT showed a normal activity distribution with a single peak at the MIC of 3.13-6.25 micrograms/ml against Pseudomonas aeruginosa, and 35% of inoculum was resistant with high MIC values (MIC > or = 25 micrograms/ml). Activities of AZT against Haemophilus influenzae and Neisseria gonorrhoeae were comparable to those of CPZ.

Aztreonam↗

[Variation in transfer resistance to cefotaxime, ceftazidime and aztreonam in strains of Acinetobacter sp., Enterobacter sp. and Citrobacter sp. isolated from the same university hospitals].

BACKGROUND: In the last decade were in SR documented new problems in resistance to the newer antibiotics that with regard to their structure and antibacterial properties resisted to the known mechanism of bacterial resistance. The emergence of multiple drug resistance to the new betalactams is connected both with frequent application of these drugs in the hospitals and transfer of R plasmids. METHODS AND RESULTS: We studied composition and transferability of resistance to newer betalactam antibiotics in strains of Acinetobacter sp., Enterobacter sp, and Citrobacter sp. isolated during one month in patients from two teaching University Hospitals. All strains studied were resistant to cefotaxime (CTX), ceftazidime (CAZ) and aztreonam (ATM) but Acinetobacter strains, although resistant also to CAZ and ATM transferred the resistance to CTX only. Thus, resistance to CAZ and ATM has a chromosomal origin in these strains. A strain of Citrobacter sp., resistant to CTX, CAZ and ATM, produced a ESBL betalactamase detectable in a double-disk diffusion method (Fig. 1). An Enterobacter cloacae strain transfers directly the resistance to all new betalactams indicated. Their hydrolysis by these strains points to their production of new types of extended-spectrum beta-lactamases ESBL). CONCLUSIONS: We strongly recommend to be strictly rational in the use of new betalactams of CTX, CZA or ATM type because it is suspected that, especially in so-called empirical prophylaxis or treatment, they exert a strong selective pressure toward the prevalence of mutants with transferable ESBL-producing nosocomial bacteria resistant to these drugs.

Acinetobacter↗

[Determination of moxalactam, aztreonam and imipenem by the perchloric hydroxylamine method].

The reaction of perchloric hydroxylamine was adopted for determination of new beta-lactam antibiotics within monobactam, carbapenem and oxazepam groups. Complexes formed in colour reaction are stable over 2 hours in the case of aztreonam and imipenem, and over 1 hour for moxalactam, statistical analysis proved that both hydroxylamine-perchloric and spectrophotometric methods can be used alternatively.

Anti-Bacterial Agents↗

A Double-Blind, Randomized Comparison of Aztreonam Plus Clindamycin with Tobramycin Plus Clindamycin in Abdominal Infections.

Seventy patients with intraabdominal infections were randomly assigned in double-blinded fashion to receive either the combination of tobramycin plus clindamycin (TM/C) or aztreonam plus clindamycin (AZ/C). Thirty-four patients received AZ/C and 36 were given TM/C. Average ages were 62 years (TM/C) and 66 years (AZ/C). In approximately one-half of both groups, the source of infection was perforated colon or perforated appendix. There were no significant differences in demographic factors between these groups, although those given AZ/C had a more serious long-term prognosis due to underlying diseases. The average lengths of treatment were 10 days (TM/C) and 9 days (AZ/C). Clinical response to therapy did not differ, as 84% of the TM/C patients and 78% of the AZ/C patients had satisfactory clinical responses. The two regimens differed in adverse effects, as an elevated PT/PTT was more frequently (p < 0.05) observed in AZ/C. All PT/PTT elevations responded to injections of vitamin K, and no serious bleeding occurred. Choice between these regimens depends on differences in cost and the risk of adverse effects, as both regimens appear equally effective for treatment of abdominal infections in conjunction with appropriate surgical intervention.

Journal Article↗