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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↗

PubMedDate not supplied

Comparison of empiric aztreonam and aminoglycoside regimens in the treatment of serious gram-negative lower respiratory infections.

An open-label, controlled, randomized study was performed to assess the efficacy and safety of combination regimens using either aztreonam or an aminoglycoside control regimen as empiric therapy for suspected aerobic gram-negative bacillary pneumonia or purulent bronchitis. Eighty-four patients, 42 in each arm of the study, were randomly assigned to one of two treatment regimens. The combination aztreonam regimen included aztreonam, 2 gm every 8 hours (q8h), plus either clindamycin, 600 to 900 mg q8h, or nafcillin, 1.5 gm to 2 gm every 6 hours (q6h). The control regimen was one of the following depending on the combination therapy that was designated standard at each of the three study institutions: amikacin, 5 mg/kg q8h, plus cefazolin, 1 gm q8h; amikacin, 500 mg every 12 hours plus mezlocillin, 4 gm q6h; or kinetically dosed tobramycin plus ticarcillin, 3 gm to 4 gm q4h. The two groups were well matched in terms of demographics and clinical characteristics. Among the 84 patients, organisms from the Enterobacteriaceae family accounted for the largest proportion of isolates (44%) including Escherichia coli (13%), Klebsiella species (14%), and Serratia species (9%). Other commonly identified organisms were Pseudomonas aeruginosa (19%), Haemophilus influenzae (15%), Streptococcus pneumoniae (12%), and Staphylococcus aureus (8%). Results of this trial included clinical response rates of 83% in both groups (P = 0.951) and a microbiologic cure rate of 75% in the aztreonam group and 63% in the control group (P = 0.291). In the 59 patients with documented aerobic gram-negative pneumonia, microbiologic eradication rates were 72% in the aztreonam group versus 57% in the control group (P = 0.359). Duration of treatment tended to be shorter in the aztreonam group than in the control group, with a median 10 days of therapy versus 12 days of therapy (P = 0.095), respectively. In addition, the percentage of patients requiring nonstudy antimicrobial agents tended to be lower in the aztreonam group than the control group, involving 21% of patients in the aztreonam group compared with 36% of patients in the control group (P = 0.086). All regimens were well tolerated, and no patient was withdrawn because of adverse reactions to the study medications. Two patients, both in the control group, required dose reduction, which was necessitated by possible aminoglycoside-induced nephrotoxicity. This trial shows that aztreonam is an effective agent with an excellent safety profile when used in combination regimens for the empiric treatment of pneumonia. A well-controlled trial is needed to verify the trend toward shorter hospital stays and a reduced need for additional antimicrobial agents seen with the aztreonam regimen when compared with those receiving aminoglycoside-combination regimens.

Adolescent↗

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↗

PubMed1986

Comparative clinical evaluation of aztreonam versus aminoglycosides in gram-negative septicaemia.

We have conducted an open randomized comparison of aztreonam versus an aminoglycoside in 100 adult, non-granulocytopenic patients with suspected or proven aerobic Gram-negative septicaemia. Forty-three patients with negative blood cultures, with blood isolates resistant to the antibiotic used, or who died within the first 24 h were excluded. Of the 57 evaluable patients, 31 received aztreonam and 26 aminoglycoside (13 gentamicin and 13 tobramycin). Patients in both groups were comparable with respect to age, sex, underlying diseases, sites of local infection and risk factors. There were 39 blood isolates in the aztreonam group and 28 in the aminoglycoside group. The overall cure rate was 83.8% in aztreonam-treated patients and 76.9% in aminoglycoside-treated patients. There were five failures (2 aztreonam, 3 aminoglycoside) and in six patients only clinical improvement could be achieved (3 aztreonam, 3 aminoglycoside). Both antibiotics were well tolerated. Nephrotoxicity was found in seven patients of the aminoglycoside group (P = 0.004), whereas enterococcal superinfections occurred in six of the aztreonam group (P = 0.0124). The results of our study suggest that aztreonam is at least as effective as gentamicin or tobramycin in patients with septicaemic infections due to susceptible bacteria. Aztreonam-treated patients are free of nephrotoxicity but are at risk of enterococcal superinfections.

Adult↗

PubMed1983

Metabolism and pharmacokinetics of aztreonam in healthy subjects.

The metabolism and pharmacokinetics of aztreonam (SQ 26,776) were studied in four healthy male volunteers, each of whom received single 500-mg intravenous and intramuscular doses of 14C-labeled drug according to a two-way crossover design. Serial samples of serum, urine, and feces were assayed for aztreonam and metabolites. Serum pharmacokinetics of aztreonam administered intravenously were described by an open, linear, two-compartment kinetic model. Kinetics of intramuscular aztreonam followed a one-compartment model with first-order absorption and elimination. Intramuscular bioavailability was 100%. After either intravenous or intramuscular administration, aztreonam was eliminated primarily by urinary excretion of unchanged drug (about 66% of dose), whereas only 1% of the dose was found as unchanged drug in the feces, presumably owing to biliary secretion. The average elimination half-life of aztreonam was 1.6 and 1.7 h, respectively, for intravenous and intramuscular administration. Aztreonam did not undergo extensive metabolism; the most prominent biotransformation product of aztreonam was SQ 26,992, the compound resulting from the hydrolytic opening of the beta-lactam ring. Urinary and fecal SQ 26,992 constituted 7 and 3% of the administered dose, respectively. SQ 26,992 was eliminated at a considerably slower rate than was aztreonam.

Adult↗

PubMed1984

In vitro antimicrobial activity of aztreonam alone and in combination against bacterial isolates from pediatric patients.

We examined 134 pediatric clinical isolates of Enterobacteriaceae, Pseudomonas aeruginosa, and gram-positive cocci for susceptibility to aztreonam alone and in combination with seven other antibiotics. All 98 gram-negative isolates were susceptible to aztreonam with similar inhibitory and bactericidal activity. Combinations of aztreonam with cefoxitin, ampicillin, or clindamycin were generally indifferent or additive. Synergism was occasionally seen against enteric organisms with aztreonam plus cefoxitin or clindamycin. Combinations of tobramycin and aztreonam were synergistic (62%) against P. aeruginosa; aztreonam plus piperacillin or ticarcillin was additive. Aztreonam did not affect the activity of nafcillin against Staphylococcus aureus, or of ampicillin against species of Streptococcus group B or D. Antagonism was seen only with aztreonam plus cefoxitin against Enterobacter species, but not at clinically significant concentrations. Several combinations of antibiotics with aztreonam should be appropriate for initial therapy of infections in children without major risks of antibacterial antagonism.

Anti-Bacterial Agents↗

PubMed2003

In vitro synergy studies using aztreonam and fluoroquinolone combinations against six species of Gram-negative bacilli.

BACKGROUND: Combination antimicrobial therapy is often necessary to eradicate infections caused by gram-negative bacteria. METHODS: To evaluate the potential benefit of aztreonam and fluoroquinolone combination therapy, the activity of aztreonam in combination with ciprofloxacin, gatifloxacin, levofloxacin and moxifloxacin was assessed using checkerboard testing for four clinical isolates of each of Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Enterobacter cloacae, Burkholderia cepacia and Pseudomanas aeruginosa. RESULTS: All aztreonam and fluoroquinolone combinations demonstrated additive activity [fractional inhibitory concentration (FIC) index >0.5-4] or synergy (FIC index <or=0.5) for all 24 isolates tested. Aztreonam plus ciprofloxacin was the most effective combination, demonstrating synergy against 16.7% of isolates (2 P. mirabilis, 1 E. cloacae, 1 B. cepacia). Aztreonam in combination with moxifloxacin was synergistic against 2 isolates (P. mirabilis, E. cloacae), and in combination with gatifloxacin against 1 isolate (E. cloacae). Aztreonam and levofloxacin demonstrated only additive activity. CONCLUSION: Additive activity was observed for the majority of the aztreonam and fluoroquinolone combinations tested against six species of gram-negative bacilli. Synergy involving aztreonam and fluoroquinolone combinations was less common than additive activity and was isolate dependent. Although in vivo clinical successes have been documented using aztreonam in combination with other agents, confirmation by laboratory techniques requires further investigation.

Anti-Bacterial Agents↗

PubMed1992

Epitope analysis of aztreonam by antiaztreonam monoclonal antibodies and possible consequences in beta-lactams hypersensitivity.

Three cell lines producing monoclonal antibodies, Az-1 (IgG1), Az-2 (IgG1) and Az-3 (IgM) against aztreonam were established. The epitopes and the cross-reactions of the antibodies with various beta-lactams, which were conjugated with human serum albumin (HSA), were examined by enzyme-linked immunosorbent assay (ELISA) and ELISA inhibition test. In ELISA, Az-1 and Az-2 reacted only with aztreonam and ceftazidime, which have the same acyl side chain. Furthermore, Az-2 showed a strong cross-reaction with carumonam. In the ELISA inhibition test, Az-1 and Az-2 were inhibited from binding to aztreonam-HSA by aztreonam, ceftazidime, aztreonam hydrolysate, aztreonam-epsilon-amino-n-caproic acid (EACA) and ceftazidime-EACA. Az-2 was also inhibited with carumonam. From the above results, it seems that Az-1 can recognize only the degraded structure of monobactam nucleus, and Az-2 can recognize the degraded nucleus moiety and the acyl side chain. On the other hand, Az-3 displayed broad cross-reaction to various beta-lactams in ELISA. Furthermore, the MAb showed no inhibitory reaction with various beta-lactams except aztreonam- and ceftazidime-EACA conjugates in the ELISA inhibition test, suggesting that Az-3 recognize a new antigenic determinant (NAD), which is formed by the conjugation of beta-lactam and carrier protein. The above results indicate that antibodies can recognize at least three epitopes of the degraded product(s) of aztreonam nucleus, acyl side chain and NAD in aztreonam-protein conjugate.

Animals↗

PubMedDate not supplied

Pharmacokinetics of aztreonam in patients with chronic renal failure.

The elimination kinetics of aztreonam (SQ 26,776), a new, completely synthetic, monocyclic beta-lactam antibiotic, were studied after the administration of a single 1g intravenous dose. Five healthy volunteers and 20 patients with various degrees of renal insufficiency were enrolled in this study. Concentrations of aztreonam in serum and urine were determined by both microbiological and high pressure liquid chromatography (HPLC) assays. The pharmacokinetic parameters for aztreonam were calculated on the basis of a 2-compartment open model. Serum concentrations of aztreonam at 10 minutes after administration were approximately 100 micrograms/ml in all subjects, regardless of renal function (HPLC assay). The mean serum half-life during the alpha-phase showed no important variation with renal function. The mean serum half-life during the beta-phase was 1.8 hours in normal subjects and 8.4 hours in haemodialysis patients (HPLC assay). There was a linear correlation between the serum clearance of aztreonam and creatinine clearance. The mean cumulative urinary recovery of aztreonam in 48 hours was 60 to 70% of the administered dose in normal subjects but this was reduced in the presence of renal insufficiency. SQ 26,992, the microbiologically inactive metabolite of aztreonam resulting from hydrolytic opening of the beta-lactam ring, was undetectable in the serum of normal subjects but was found in low levels in uraemic patients. Half of a 1g intravenous dose of aztreonam was eliminated during 4 hours of haemodialysis. Guidelines for administration of aztreonam in the presence of renal failure are given.

Adult↗

PubMedDate not supplied

[Aztreonam: monocenter microbiological study with prevention experience in surgery].

Aztreonam is a monobactam antibiotic active against aerobic gram-negative bacteria. The susceptibility of 127 urinary tract isolates to aztreonam, cefotaxime, cefonicid and ceftazidime was determined. Aztreonam showed good antibacterial activity even against Pseudomonas spp. Only 7 bacterial strains were resistant to aztreonam. The clinical efficacy and pharmacokinetics of aztreonam were assessed in two patients treated for urinary tract infections. The concentrations of aztreonam in serum and urine are reported. Aztreonam safety was evaluated on 20 patients given aztreonam immediately prior to an elective abdominal, urinary or gynecological operation. The results provide support for the use of aztreonam for prophylaxis.

Aztreonam↗

PubMedDate not supplied

Aztreonam, a new monobactam antimicrobial.

The chemistry, in vitro activity, pharmacokinetics, adverse reactions, and clinical use of the monobactam antimicrobial aztreonam are reviewed. Aztreonam, an investigational agent nearing approval in the United States and Canada, is the first in a class of monobactam antimicrobials to be evaluated extensively in vitro and in vivo. It has a narrow spectrum of activity, encompassing only aerobic gram-negative microorganisms including Pseudomonas aeruginosa and most multiply resistant Enterobacteriaceae. Aztreonam has no useful activity against gram-positive or anaerobic microorganisms. In preliminary studies, aztreonam achieved high tissue concentrations and was usually well tolerated. Approximately 65-75% of an administered dose is excreted unchanged into the urine, and the elimination half-life is 1.6-2.2 hours in subjects with normal renal function. Dosage should be adjusted in patients with renal impairment. Aztreonam was shown equivalent to gentamicin and cefamandole for treating serious urinary-tract infections and produced cure rates greater than 85% in gonococcal, lower respiratory tract, orthopedic, serious urinary tract, acute uncomplicated lower urinary-tract, gynecologic, and intraabdominal infections. Development of resistance during therapy may be less likely with aztreonam than with other new cephalosporins. Aztreonam will probably have an important role in antimicrobial therapy, but much further study is necessary to assess clinical efficacy and toxicity. The clinical importance of aztreonam's superior activity under anaerobic conditions compared with aminoglycosides and the theoretical reduced alteration in GI colonization resistance must be assessed in controlled trials. Evaluation of aztreonam versus ceftazidime, the carbapenems, and the carboxyquinolones is needed, and the likelihood of gram-positive superinfection, especially with enterococci, must be further assessed.

Animals↗

PubMed1991

Aztreonam vs. cefotaxime in the treatment of gram-negative spontaneous peritonitis in cirrhotic patients.

Aztreonam and cefotaxime were compared in 44 cirrhotic patients who had 52 episodes of gram-negative spontaneous peritonitis. Patients were randomized into two therapeutic groups of similar characteristics. Group A (28 episodes) received 0.5 gm of aztreonam every 8 hr, and group B (24 episodes) received 1 gm of cefotaxime every 6 hr, for a planned 14-day period. Peak and trough serum and ascitic fluid levels of both antibiotics were several times higher than the minimum inhibitory concentrations of causative microorganisms. Eleven patients (21%) died within the first 48 hr after beginning therapy, which included seven in the aztreonam group and four in the cefotaxime group. In the remaining patients, signs and symptoms of infection were promptly controlled, and ascitic fluid cultures became negative after 48 hr in all cases, except in one patient from the aztreonam group, who was a clinical failure. Two patients from the aztreonam group and one from the cefotaxime group relapsed after treatment. The overall mortality rate was 50%, which was lower than classically reported: 12 patients (43%) died in the aztreonam group, and 14 (58%) died in the cefotaxime group (p = 0.265, NS). Hepatorenal syndrome and digestive tract hemorrhage were the most frequent causes of death occurring after the first 48 hr of treatment. Streptococcal superinfections developed in three patients (14.2%) in the aztreonam group. We conclude that both antibiotics at the low doses used in this study are similarly well tolerated and effective in controlling this infection. Because the use of aztreonam as the initial empirical treatment requires a concomitant antibiotic against gram-positive infections and the possibility of streptococcal superinfections, cefotaxime seems to be a more advantageous therapeutic alternative for this patient population.

Adult↗

PubMed1996

Stability of aztreonam in a portable pump reservoir used for home intravenous antibiotic treatment (HIVAT).

The stability of the monocyclic beta-lactam antibiotic aztreonam in portable pump reservoirs was studied during storage at temperatures of -20 degrees C and +5 degrees C and during drug delivery at 37 degrees C. Three 100-ml drug reservoirs and three glass containers containing 60 mg/ml aztreonam were stored at -20 degrees C and 2-ml samples were analysed in the freshly prepared solution and after thawing at days 7, 21, 28, 70 and after 6 months of storage. A separate triplicate batch of 100-ml prefilled drug reservoirs and glass containers containing a similar aztreonam concentration (60 mg/ml) were refrigerated and tested immediately after preparation and daily for 8 days and after 70 days. Solutions of aztreonam in duplicate freshly prepared reservoirs were tested for stability when the solution was pumped at 37 degrees C over a 24-h period. All solutions were inspected for visual changes and tested for pH. Drug concentration was analysed by high-performance liquid chromatography. No colour changes or pH differences were observed in any of the solutions in the reservoirs of containers. No statistically significant decrease in aztreonam concentration could be detected after 6 months of storage at -20 degrees C. Aztreonam was stable at 5 degrees C for at least 8 days. A 24-h pumping period at 37 degrees C showed a 3.6% decrease in aztreonam concentration. Aztreonam at a concentration of 60 mg/ml in a pump reservoir is sufficiently stable to be used in home intravenous antibiotic treatment programmes.

Aztreonam↗

PubMed1990

Aztreonam susceptibility testing. A retrospective analysis.

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

Ampicillin↗

PubMed1988

Aztreonam: the first monobactam.

There are several areas in which the use of aztreonam seems logical. Infections caused by organisms sensitive to aztreonam that are known to be multiresistant to other agents can be treated directly with aztreonam in single, directed therapy, thus making the use of more toxic agents unnecessary. In types of infection in which both gram positive and gram negative bacteria are present, aztreonam can replace the usual aminoglycoside component of the therapeutic regimen. In settings of mixed infections suspected of being caused by drug-resistant strains of Enterobacteriaceae and/or P. aeruginosa, aztreonam can be combined with an agent active against gram positive organisms or with one active against anaerobes. Aztreonam has proven to be effective, safe therapy for serious and life-threatening infections caused by multiresistant aerobic gram negative bacteria. It should be used in combination with drugs that inhibit gram positive species if the etiology of the infection is not known, particularly in the immunocompromised, neutropenic patient. Doses of 1 g every 8 to 12 hours will be adequate for treatment of infections caused by most Enterobacteriaceae. Whether 2 g doses every 8 hours would be preferred for treatment of systemic Pseudomonas infections remains to be determined. Urinary infections caused by gram negative bacteria can be treated with 500 mg administered IM once or twice daily. The dosage of aztreonam should be adjusted in patients with renal failure. Clearly, aztreonam is a useful addition to the antimicrobial agents available to the physician.

Aztreonam↗

PubMed1984

Aztreonam compared with gentamicin for treatment of serious urinary tract infections.

52 patients with serious urinary tract infections were randomised to receive either aztreonam (35) or gentamicin (17). In the aztreonam group 23 patients had unqualified cures, 6 cures with relapse, and 6 cures with reinfection; the comparable numbers in the gentamicin group were 9, 1, and 4. There were no failures with aztreonam and 3 with gentamicin. The most important determinant of outcome was the presence or absence of urological abnormalities. 11 further patients, with renal failure or gentamicin-resistant isolates, treated with aztreonam were all cured. Toxic effects were limited to symptomless liver-function-test abnormalities with aztreonam , whereas deterioration in renal function occurred in 4 gentamicin-treated subjects. Urinary colonisation with group D streptococci occurred in 14 of 46 aztreonam -treated patients (1 required treatment) compared with only 1 of 17 gentamicin-treated patients. 97% of 309 consecutive gram-negative urinary isolates tested, including 50 Pseudomonas aeruginosa, were susceptible in vitro to aztreonam and 91% to gentamicin. Aztreonam may prove an effective and safe alternative to the aminoglycosides.

Adolescent↗

PubMed2005

The efficacy and safety of tigecycline in the treatment of skin and skin-structure infections: results of 2 double-blind phase 3 comparison studies with vancomycin-aztreonam.

Two phase 3, double-blind studies in hospitalized adults with complicated skin and skin-structure infections (cSSSI) determined the safety and efficacy of tigecycline versus that of vancomycin-aztreonam. Patients received tigecycline (100 mg, followed by 50 mg intravenously twice daily) or vancomycin (1 g intravenously twice daily) plus aztreonam (2 g intravenously twice daily) for up to 14 days. Populations were as follows: 1116 patients (566 treated with tigecycline, and 550 treated with vancomycin-aztreonam) constituted the modified intent-to-treat (mITT) population, 1057 patients (538 treated with tigecycline, and 519 treated with vancomycin-aztreonam) constituted the clinical mITT (c-mITT) population, and 833 patients (422 treated with tigecycline, and 411 treated with vancomycin-aztreonam) constituted the clinically evaluable population. Clinical responses to tigecycline and vancomycin-aztreonam at test-of-cure were similar: c-mITT, 79.7% (95% confidence interval [CI], 76.1%-83.1%) versus 81.9% (95% CI, 78.3%-85.1%) (P = .4183); and clinically evaluable, 86.5% (95% CI, 82.9%-89.6%) versus 88.6% (95% CI, 85.1%-91.5%) (P = .4233). Adverse events were similar, with increased nausea and vomiting in the tigecycline group and increased rash and elevated hepatic aminotransferase levels in the vancomycin-aztreonam group. Tigecycline monotherapy is as safe and efficacious as the vancomycin-aztreonam combination in treating patients with cSSSI.

Adult↗