Aztreonam (Page 2 of 6)

Microbiology

Mechanism of Action

Aztreonam is a bactericidal agent that acts by inhibition of bacterial cell wall synthesis. Aztreonam has activity in the presence of some beta-lactamases, both penicillinases and cephalosporinases, of Gram-negative and Gram-positive bacteria.

Mechanism of Resistance

Resistance to aztreonam is primarily through hydrolysis by beta-lactamase, alteration of penicillin-binding proteins (PBPs), and decreased permeability.

Interaction with Other Antimicrobials

Aztreonam and aminoglycosides have been shown to be synergistic in vitro against most strains of P. aeruginosa , many strains of Enterobacteriaceae, and other Gram-negative aerobic bacilli.

Aztreonam has been shown to be active against most strains of the following microorganisms, both in vitro and in clinical infections as described in the INDICATIONS AND USAGE5 section.

Aerobic Gram-negative microorganisms:

Citrobacter species
Enterobacter species
Escherichia coli
Haemophilus influenzae (including ampicillin-resistant and other penicillinase-producing strains)
Klebsiella oxytoca
Klebsiella pneumoniae
Proteus mirabilis
Pseudomonas aeruginosa
Serratia species

The following in vitro data are available, but their clinical significance is unknown. At least 90% of the following microorganisms exhibit an in vitro minimum inhibitory concentration (MIC) less than or equal to the susceptible breakpoint for aztreonam. However, the efficacy of aztreonam in treating clinical infections due to these microorganisms has not been established in adequate and well-controlled clinical trials.

Aerobic Gram-negative microorganisms:

Aeromonas hydrophila
Morganella morganii
Neisseria gonorrhoeae (including penicillinase-producing strains)
Pasteurella multocida
Proteus vulgaris
Providencia stuartii
Providencia rettgeri Yersinia enterocolitica

Aztreonam and aminoglycosides have been shown to be synergistic in vitro against most strains of P. aeruginosa , many strains of Enterobacteriaceae, and other Gram-negative aerobic bacilli.

Alterations of the anaerobic intestinal flora by broad-spectrum antibiotics may decrease colonization resistance, thus permitting overgrowth of potential pathogens, e.g., Candida and Clostridium species. Aztreonam has little effect on the anaerobic intestinal microflora in in vitro studies. Clostridium difficile and its cytotoxin were not found in animal models following administration of aztreonam (see ADVERSE REACTIONS, Gastrointestinal).

Susceptibility Test Methods

When available, the clinical microbiology laboratory should provide the results of in vitro susceptibility test results for antimicrobial drug products used in resident hospitals to the physician as periodic reports that describe the susceptibility profile of nosocomial and community-acquired pathogens. These reports should aid the physician in selecting an antibacterial drug product for treatment.

Dilution Techniques

Quantitative methods are used to determine antimicrobial MICs. 1-3 These MICs provide estimates of the susceptibility of bacteria to antimicrobial compounds. The MICs should be determined using a standardized procedure. Standardized procedures are based on a dilution method 6 (broth or agar) or equivalent with standardized inoculum concentrations and standardized concentrations of aztreonam powder. The MIC values should be interpreted according to the criteria in Table 2.

Diffusion Techniques

Quantitative methods that require measurement of zone diameters also provide reproducible estimates of the susceptibility of bacteria to antimicrobial compounds. The zone size provides an estimate of the susceptibility of bacteria to antimicrobial compounds. The zone size should be determined using a standardized test method. 6,7 This procedure uses paper disks impregnated with 30 mcg aztreonam to test the susceptibility of microorganisms to aztreonam. The disk diffusion interpretive criteria are provided in Table 2.

Table 2: Susceptibility Test Interpretive Criteria for Aztreonam

Pathogen Minimum Inhibitory Concentrations (mcg/mL) Disk Diffusion Zone Diameters (mm)
(S) Susceptible (I) Intermediate (R) Resistant (S) Susceptible (I) Intermediate (R) Resistant
Enterobacteriaceae ≤ 4 8 ≥ 16 ≥ 21 18 to 20 ≤ 17
Haemophilus influenzae a ≤ 2 ≥ 26
Pseudomonas aeruginosa ≤ 8 16 ≥ 32 ≥ 22 16 to 21 ≤ 15

a The current absence of data on resistant isolates precludes defining any category other than “Susceptible”. If isolates yield MIC results other than susceptible, they should be submitted to a reference laboratory for additional testing.

Quality Control

Standardized susceptibility test procedures require the use of laboratory controls to monitor and ensure the accuracy and precision of supplies and reagents used in the assay, and the techniques of the individual performing the test. 6-8 Standard aztreonam powder should provide the following range of MIC values noted in Table 3. For the diffusion technique using the 30 mcg disk, the criteria in Table 3 should be achieved.

Table 3: Acceptable Quality Control Ranges for Aztreonam

QC Strain Minimum Inhibitory Concentrations (mcg/mL) Disk Diffusion Zone Diameters (mm)
Escherichia coli ATCC 25922 0.06 to 0.25 28 to 36
Haemophilus influenzae ATCC 49247 0.12 to 5 30 to 38
Pseudomonas aeruginosa ATCC 27853 2 to 8 23 to 29

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