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PubMed1992

Effect of aztreonam upon human polymorphonuclear leukocyte functions.

Aztreonam (SQ 26,776), a new synthetic monobactam with an excellent antibacterial spectrum was analyzed in vitro. In this paper, the effect of aztreonam on the phagocytic process of human neutrophils isolated from fifteen healthy volunteers was studied. Chemotaxis was not modified with aztreonam at any of the doses used (10, 20, 40, 60, 80 and 100 micrograms/ml). On the other hand, this antibiotic at 100 micrograms/ml significantly increases (P less than 0.05) Candida albicans ingestion as well as their digestion by neutrophils at 10 and 100 micrograms/ml.

Aztreonam↗
PubMed1990

The distribution of aztreonam in serum, bile, skin and subcutaneous tissues in patients undergoing cholecystectomy.

The distribution of aztreonam was measured in patients undergoing elective cholecystectomy. In 14 patients 2 g aztreonam was injected preoperatively and the concentration of the antibiotic was assessed in the bile from the gall bladder and common bile duct, subcutaneous tissues and serum. Samples from bile and any wound discharge were cultured and sensitivities determined. The antibiotic reached bactericidal levels in the common bile duct within 30 min of injection and such levels were maintained in skin and gall bladder for at least 4 h after injection. Aztreonam was highly effective against the Gram-negative organisms that were cultured in bile but was less effective against Enterococcus faecalis.

Aztreonam↗
PubMed2004

Pharmacokinetic interactions of ceftazidime, imipenem and aztreonam with amikacin in healthy volunteers.

The common usage of extended spectrum beta-lactams co-administered with amikacin in everyday clinical practice for infections by multidrug-resistant isolates has created the need to search for pharmacokinetic interaction. Eighteen healthy volunteers were enrolled in the study; six were administered 1g of ceftazidime singly intravenously or combined with 0.5 g of amikacin; six received 0.5 g of imipenem singly or combined with 0.5 g of amikacin and six 1g of aztreonam singly or combined with 0.5 g of amikacin. Blood and urine samples were collected at regular time intervals and apparent serum levels were determined by a microbiological assay. Co-administration of ceftazidime and amikacin resulted in higher C(max) and AUC for amikacin than when administered alone. Co-administration of imipenem and amikacin resulted in higher C(max) for imipenem than when administered alone. The tested interactions did not affect plasma half-life (t(1/2)) and clearance rate of any antimicrobial compared with its single administration. All tested drugs were mainly eliminated by glomerular filtration. It is concluded that co-administration of ceftazidime, imipenem or aztreonam with amikacin in healthy volunteers might affect C(max) and AUC without influencing any other pharmacokinetic parameter. The probable clinical endpoint is that giving ceftazidime, imipenem or aztreonam with amikacin might result in a transient elevation of beta-lactam serum levels without further affecting the complete pharmacokinetic profile of each drug as obtained after administration of the drug alone.

Adult↗
PubMed2000

Modification of acquired immunity in BALB/c mice by aztreonam.

Recent studies have suggested that antibiotics may act as biological response modifiers. In this study we investigated the effect of aztreonam, a monobactam antibiotic, on different parameters of acquired immunity in BALB/c mice. Different dosages of aztreonam injected into mice induced an increase in the lymphoproliferative response to specific mitogens and in the production of interleukin-2 by splenic cells, as well as a decreased response of this immune population to sheep erythrocytes lower total blood cell counts and a lower percentage of monocytes than in untreated mice. These results show a modulatory action of aztreonam on different immune parameters, which is independent of its antimicrobial activity and that could be of interest in human therapy.

Animals↗
PubMed2003

Piperacillin plus aztreonam for treatment of neutropenic fever.

BACKGROUND: A combination of beta-lactam plus an aminoglycoside is the most frequently used regimen for febrile episodes in neutropenic cancer patients. However, aminoglycoside-related toxicity occasionally makes this regimen difficult to use as the first-line drug therapy. In the present study, we chose aztreonam as the alternative to aminoglycoside in combination with piperacillin for neutropenic fever in pediatric patients and we evaluated its effectiveness. METHODS: A total of 31 febrile episodes in 16 patients with malignant neoplasms were evaluted. Piperacillin (200 mg/kg per day) plus aztreonam (150 mg/kg per day) were administered intravenously following a routine fever work-up. RESULTS: The overall response rate was 67%. The response rate when neutrophil count was less than 100/mm3 was 63%. The side effects were mild and rare. In three patients, all of the microbiologically documented infections were caused by alpha-streptococcus, which required a change in the regimen. CONCLUSIONS: A combination of piperacillin and aztreonam provides an effective and non-toxic regimen for first-line therapy in febrile patients with neutropenia. In contrast, the results of the present study suggest the need for caution with regard to alpha-streptococcus infections.

Adolescent↗
PubMedDate not supplied

Efficacy of aztreonam in the treatment of neonatal sepsis.

In Greece the majority of infections that affect the neonatal population are caused by gram-negative bacteria rather than by group B streptococci as in the United States. The present study investigated the efficacy of aztreonam, a beta-lactam antibiotic that is effective against gram-negative organisms, in this population. Fifty-five neonates aged 2 hours to 36 days who had sepsis were enrolled in this open study. Laboratory tests were extensive, and follow-ups were detailed. Aztreonam (90-125 mg/[kg.d]) administered in two or three doses was given in combination with penicillin (100,000 U/[kg.d]) for 6-15 days. Fifty-two infants were cured, one improved, and two did not improve and received other, more effective regimens. Adverse effects were minimal, and tolerance of aztreonam was excellent.

Aztreonam↗
PubMedDate not supplied

Colorectal surgery: short-term prophylaxis with clindamycin plus aztreonam or gentamicin.

A randomized study was conducted to compare the effectiveness of aztreonam plus clindamycin with that of gentamicin plus clindamycin for prophylaxis of infection following colorectal surgery. A total of 138 patients undergoing elective colorectal surgery were randomized to treatment with clindamycin (600 mg) plus either aztreonam (1 g) or gentamicin (80 mg) 30 minutes before and 8 and 16 hours after surgery. The study included 122 patients (88.4%) with colorectal carcinoma. Samples from the abdominal cavity and from the subcutaneous tissues were taken for bacteriologic study. All samples from the abdominal cavity yielded microorganisms; both aerobic and anaerobic bacteria were isolated. Wound infections occurred in eight patients (12.1%) in the aztreonam group and in 12 patients (16.7%) in the gentamicin group. Escherichia coli, Bacteroides species, enterococci, and staphylococci were isolated most frequently from wounds and were often isolated from bacteriologic samples from the abdominal cavity of the same patients. The incidence of septic complications reflected the extent of nutritional and immunologic impairment. No significant differences were found between groups in the rate of urinary tract or lower respiratory tract infections. Aztreonam/clindamycin appears to be a valid alternative to gentamicin/clindamycin for the prophylaxis of infections following colorectal surgery.

Adult↗
PubMedDate not supplied

Multicenter trial of prophylaxis with clindamycin plus aztreonam or cefotaxime in gynecologic surgery.

A prospective, randomized, multicenter study was conducted on the efficacy and safety of two prophylactic antibiotic regimens in both abdominal and vaginal hysterectomy. Patients received three intravenous doses of clindamycin (900 mg) plus either aztreonam (1 g) or cefotaxime (1 g); the doses were given at the induction of anesthesia and 8 and 16 hours later. A total of 170 patients undergoing abdominal hysterectomy and 142 patients undergoing vaginal hysterectomy completed the trial and were evaluated. Following abdominal hysterectomy infections occurred at the operative site in 1.2% of patients given a regimen including aztreonam and in 4.7% of those given a regimen including cefotaxime; the difference between the two groups was not significant. Neither were significant differences observed in the incidence of fever, the incidence of bacteriuria, the need for postoperative antibiotics, or the duration of postoperative hospitalization, although results were slightly better for patients receiving clindamycin plus aztreonam. Following vaginal hysterectomy, slightly but not significantly better results for the same parameters were obtained in the group given clindamycin plus cefotaxime. Diarrhea was the only adverse reaction attributable to antibiotic treatment and occurred more frequently in patients given cefotaxime. It was concluded that the two regimens were similarly effective and safe in preventing infections following hysterectomy.

Adult↗
PubMedDate not supplied

Aztreonam plus clindamycin versus tobramycin plus clindamycin in the treatment of intraabdominal infections.

In a multicenter, randomized clinical trial, aztreonam and tobramycin were compared for efficacy and safety in the treatment of intraabdominal infections. Patients were randomly assigned to one of the drug regimens, and all but two patients were treated concomitantly with clindamycin. Efficacy of treatment could not be evaluated for 107 of the 316 patients enrolled in the study. Among the 209 patients who could be evaluated (104 treated with aztreonam and 105 with tobramycin), microbiologic cure was achieved in 93% and 86%, respectively, and a favorable clinical response was noted in 85% of the patients in both groups. The frequency of adverse drug reactions in the two groups was similar. In this study, the efficacy and safety profiles of aztreonam plus clindamycin were comparable to those of tobramycin plus clindamycin.

Abdomen↗
PubMedDate not supplied

Efficacy and safety of aztreonam in the treatment of patients with renal failure.

The efficacy and safety of aztreonam for treatment of gram-negative bacterial infections in patients with renal failure were evaluated in an open study. Thirty-nine patients (22-82 years old) with renal failure (chronic, 25; acute, 14) were treated for 40 severe gram-negative bacterial infections. All 41 gram-negative pathogens isolated were sensitive to aztreonam; the pathogens included Escherichia coli (12), Pseudomonas aeruginosa (8), Klebsiella species (7), Proteus species (7), Enterobacter species (5), Serratia marcescens (1), and Acinetobacter species (1). Complete cure (clinical and bacteriologic) was achieved in 31 (77.5%) of 40 infections and improvement (clinical improvement with or without bacteriologic cure) in four (10%). Bacterial eradication of 34 (82.9%) of the infecting pathogens was achieved. The only significant adverse effect noted was a slight, transient elevation in the level of serum transaminases in four patients (10%). Renal function of the patients improved with treatment. Levels of serum creatinine decreased from 3.79 +/- 2.84 to 3.30 +/- 2.52 mg/dL after treatment (P less than .002). It was concluded that aztreonam is effective and safe for the treatment of gram-negative bacterial infections in patients with renal failure.

Acinetobacter Infections↗
PubMedDate not supplied

Aztreonam plus clindamycin vs. tobramycin plus clindamycin for the treatment of intraabdominal infections.

Sixty-six patients with acute intraabdominal infections due to gram-negative aerobic organisms were treated with aztreonam plus clindamycin or with tobramycin plus clindamycin in a multicenter, comparative, randomized study. The patients had undergone a variety of surgical procedures; most of them had peritonitis. Thirty-three of the 36 patients in the aztreonam group and 26 of the 30 patients in the tobramycin group had satisfactory clinical responses. Only one gram-negative aerobic pathogen, a strain of Pseudomonas aeruginosa, persisted after treatment; the patient involved was in the tobramycin group. The incidences of adverse reactions, superinfections, and abnormal laboratory values were low in each treatment group. The difference between the efficacies of the two regimens was not statistically significant. This study suggests that aztreonam may be a useful alternative to the aminoglycosides in the treatment of gram-negative intraabdominal infections.

Abdomen↗
PubMedDate not supplied

Overall clinical experience with aztreonam in the treatment of intraabdominal infections.

Response to aztreonam (1-2 g administered intravenously three or four times daily) was evaluated in a multiclinic study of 113 patients with intraabdominal infections due to gram-negative aerobic organisms. Appropriate therapy with an antibiotic (usually clindamycin) active against gram-positive and/or anaerobic organisms was administered concomitantly for mixed-pathogen infections. A favorable clinical response and microbiologic cure occurred in 90% of the patients treated. All of the 13 patients with infections due to Pseudomonas aeruginosa responded clinically, and 11 of the 13 patients experienced microbiologic cure. In a comparative study, 59 patients were treated with aztreonam and 56 were treated with tobramycin (3-5 mg/kg per day); 95% of the patients in the aztreonam group and 81% of those in the tobramycin group experienced microbiologic cure.

Abdomen↗
PubMedDate not supplied

Aztreonam therapy for complicated urinary tract infections caused by multidrug-resistant bacteria.

Aztreonam was administered to 145 consecutive patients with complicated urinary tract infections caused by multidrug-resistant, aztreonam-sensitive bacteria. Multidrug resistance was defined by disk diffusion testing as resistance to aminopenicillins and to first- and second-generation cephalosporins, with or without resistance to aminoglycosides. The first 40 assessable patients received 1 g of aztreonam intravenously three times daily for a median period of eight days; the remaining 95 assessable patients received 0.5 g twice daily for a median period of nine days. Fifty-five patients were infected with Pseudomonas aeruginosa, 24 with Escherichia coli, 18 with Serratia marcescens, 13 with Morganella morganii, 12 with Providencia rettgeri, and 10 with Enterobacter species. Bacteriologic cure rates were 98% for the group given 3 g daily and 96% for that given 1 g daily. Minimal and transient adverse reactions occurred with both dosages.

Adolescent↗
PubMedDate not supplied

Summary of worldwide clinical trials of aztreonam in patients with urinary tract infections.

Aztreonam was administered to a total of 681 patients with urinary tract infections due to susceptible gram-negative bacteria; 56 patients received a single 1-g intramuscular dose for acute uncomplicated cystitis, and 625 patients received multiple parenteral doses (usually a five-day course of 1 g two or three times daily) for a variety of urinary tract infections, including pyelonephritis, cystitis, prostatitis, and epididymitis. Microbiologic cure was achieved in 84% of patients in the single-dose study and in 85% of patients in the multiple-dose studies. In the latter studies the microbiologic cure rates for infections with Escherichia coli, the Klebsiella-Enterobacter-Serratia group, and Pseudomonas aeruginosa were 87%, 90%, and 76%, respectively. In a comparative study of aztreonam and cefamandole, the overall microbiologic cure rates were 89% and 80%, respectively. Of the 625 patients receiving multiple-dose therapy, 149 had urinary tract infections due to multiply drug-resistant bacteria; among these patients the microbiologic cure rate was 93%. Aztreonam constitutes effective therapy for urinary tract infections due to susceptible gram-negative bacilli.

Adult↗
PubMedDate not supplied

Aztreonam therapy for serious gram-negative bacillary infections.

Fifty episodes of gram-negative bacillary infection, including episodes of bacteremia, pneumonia, and skin and soft tissue, complicated urinary tract, and abdominal infections, were treated with aztreonam. Eighty-eight percent of patients were cured of their infection, including all nine patients with bacteremia and 15 of 17 patients with pneumonia. Thirty percent of all infections were caused by Pseudomonas, and all of these responded to treatment with aztreonam. A low incidence of toxicity and a high rate of efficacy make treatment with aztreonam as a single agent feasible. When gram-positive or anaerobic organisms were encountered or their presence in the infection was suspected, additional agents effective against these organisms were necessary for cure.

Aged↗
PubMedDate not supplied

Clinical studies of aztreonam in Japan.

Clinical studies of aztreonam were undertaken by 220 investigators in 86 university and general hospitals in Japan. A total of 1,447 patients were treated by investigators in various fields. Satisfactory clinical responses were achieved in 67% of all patients. Efficacy rates by field of specialty were: internal medicine, 67%; urology, 61%; general surgery, 73%; and surgical patients in other fields (obstetrics-gynecology, otorhinolaryngology, and ophthalmology), 78%. Among 364 patients with complicated urinary tract infections, the efficacy rate was 60%. Seventy-four percent of 1,122 gram-negative aerobic organisms were eradicated after treatment with aztreonam. Adverse reactions occurred in 2.1% of patients; none were serious. Mild elevations of serum aminotransferases were observed in approximately 4% of patients for whom test results were reported. In conclusion, aztreonam demonstrated remarkable effectiveness in the treatment of gram-negative infections in hospitalized patients.

Adolescent↗
PubMedDate not supplied

Clinical experience with aztreonam in Europe: a summary of studies in Belgium, England, Finland, Ireland, the Netherlands, Norway, Portugal, and Sweden.

Therapeutic results are given for 342 patients treated with various doses of aztreonam in 20 studies. One hundred sixty-five patients had urinary tract infections; 40 of these patients were bacteremic. Favorable clinical response was reported for 91.5% of the patients, and only one bacteremic patient failed to respond to treatment. Pneumonia was treated in 99 patients, 11 of whom were bacteremic; 86 responded favorably to treatment. In 22 patients with bacteremia of unknown focus, only one failure was noted. Of 368 bacterial isolates, 323 were eliminated during treatment. Pseudomonas aeruginosa was eradicated in 28 of 41 infections. Adverse reactions were rare and led to discontinuation of aztreonam treatment in only one patient. In 37 patients superinfections with 42 bacterial strains were reported. Four of these patients, all of whom were seriously debilitated by underlying conditions, had staphylococcal septicemia and died. One patient developed bacteroides septicemia but recovered. In seven patients with pneumonia, superinfections with Streptococcus pneumoniae were reported. The use of aztreonam in combination with antibiotics active against gram-positive and/or anaerobic organisms should be considered in treatment of infections other than those of the urinary tract.

Adult↗