Aztreonam

Abstract

Aztreonam, the first commercially available monobactam, has a wide range of activity against aerobic gram-negative bacilli. It can be administered two to three hours daily because its half-life is 1.6 to 2 hours. Excellent blood and tissue concentrations are attained. The MIC of aztreonam against most Enterobacteriaceae is less than or equal to 2 micrograms/ml and against P aeruginosa less than or equal to 16 micrograms g/ml. Aztreonam has been used in a wide array of infections of the urinary tract and respiratory tract, blood, intra-abdominal and gynecologic infections and infections of the skin, bones and joints. As empiric therapy, aztreonam is usually combined with another antimicrobial agent active against anaerobes and/or aerobic gram-positive cocci until culture results are available. One exception is empiric therapy for gram-negative urinary tract infections in which aztreonam can be used initially as monotherapy against susceptible gram-negative pathogens. In general, the efficacy of aztreonam is equal or superior to that of the aminoglycosides. Adverse reactions to aztreonam are unusual, and it as been shown to be a poor hapten, permitting its administration to patients with proven allergy to the penicillins and cephalosporins. Aztreonam is a useful addition to the available antibiotics for treatment of gram-negative infections.

Regulatory utility of pharmacometrics in the development and evaluation of antimicrobial agents and its recent progress in China

“…Pharmacometrics research can play a more important role in the PTA research, 4 as appropriate PK/PD targets can be determined by associating the microbiological and clinical efficacy with PK/PD indices based on in vitro and or in vivo studies, such as the percentage of time the free concentration of antibiotic is above the minimum inhibitory concentration (MIC; f T%>MIC), the ratio between the area under the plasma drug concentration‐time curve (AUC) and MIC ( f AUC/MIC), and the maximum plasma concentration (C max ) to MIC ratio ( f C max /MIC). Monte Carlo simulation based on population PK (PopPK) models developed in healthy volunteer and/or patients clinical studies can provide simulated drug concentration, C max , and AUC, so can be applied to calculate the PTA of different dosing regimens for the selection of optimal dosage and regimen to support registration 5,6 . Furthermore, pharmacometrics researches based on the understanding of tissue penetration can reveal the relationship between the concentration of antimicrobial agent at the site of infection and treatment efficacy, which is more relevant than plasma concentration in predicting the antimicrobial efficacy 7 …”

Focus of Regulatory Concerns Regarding Pharmacometric Review in the Development and Evaluation of Antimicrobial Agents

“…Appropriate PK-PD targets can be determined by associating the microbiological and clinical efficacy with PK-PD indices, such as the percentage of time the free concentration of antibiotic is above the MIC (fT%>MIC), the ratio between the area under the plasma drug concentration-time curve (AUC) and MIC (fAUC/MIC), and the maximum plasma concentration (Cmax) to MIC ratio (fCmax/MIC). Furthermore, Monte Carlo simulation can be applied to calculate the probability of target attainment (PTA) of different dosing regimens for the selection of optimal dosage and regimen [6,7]. Pharmacometric researches based on the understanding of tissue penetration can reveal the relationship between the concentration of antimicrobial agent at the site of infection and treatment efficacy, which is more precise than plasma concentration in predicting the antimicrobial efficacy [8].…”