Optimization of Aztreonam in Combination With Ceftazidime/Avibactam in a Cystic Fibrosis Patient With Chronic Stenotrophomonas maltophilia Pneumonia Using Therapeutic Drug Monitoring: A Case Study

Abstract

In this clinician-therapeutic drug monitoring (TDM) consultant interaction, the authors describe the use of TDM in an 11year-old female patient with cystic fibrosis receiving ceftazidime/ avibactam and aztreonam for the treatment of persistent pulmonary exacerbations caused by Stenotrophomonas pneumonia. Serum drug concentrations at a steady state confirmed inadequate antimicrobial exposure, and continuous infusions of both ceftazidime/avibactam and aztreonam were required to optimize the percentage of time when free drug remained above the minimum inhibitory concentration (MIC), known as fT . MIC. After dose adjustment, this continuous infusion strategy resulted in 100% target attainment for fT . MIC. This case illustrates the importance of TDM, and the logistical issues encountered with the use of alternative dosing strategies in pediatric patients with CF.

The Revival of Aztreonam in Combination with Avibactam against Metallo-β-Lactamase-Producing Gram-Negatives: A Systematic Review of In Vitro Studies and Clinical Cases

“…Of the remaining 90 studies, 37 were excluded due to the reasons listed in Figure 2 , wherein the entire process of article selection is illustrated. Overall, 35 in vitro studies [ 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 ] and 18 in vivo studies [ 4 , 47 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , …”

“…A total of 18 studies were retrieved addressing the clinical use of ATM plus CZA against MBL-producers, whose general features are detailed in Table 3 . The relative majority (7 out of 18) were conducted in the US [ 50 , 51 , 52 , 56 , 57 , 62 , 65 ]. The remaining were performed in the following countries: France (3), Italy (3), Australia (1), Greece (1), Mexico (1), Netherlands (1), Saudi Arabia (1), Spain (1) [ 4 , 47 , 53 , 54 , 55 , 58 , 59 , 60 , 61 , 63 , 64 ].…”

“…Overall, of the 94 included patients, 97% (91/94) are adults [ 55 , 62 , 65 ]. Precise data on gender were available for 82 patients: 72% were male (59/82); in the retrospective Italian study, the overall cohort, comprising the 12 cases of interest, was made up of males mostly (70%, 28/40) [ 47 ].…”

“…The large majority of causative agents were represented by bacteria belonging to Enterobacterales (96%, 90/94, mostly K. pneumoniae , E. coli or E. cloacae ). There were just three cases of non-fermenting Gram-negative bacteria involvement ( P. aeruginosa and S. maltophilia ) [ 50 , 51 , 62 ]. Bloodstream infections (BSIs), including the one related to central lines, were the most frequent type of clinical scenario (83%, 78/94).…”

Overcoming Stenotrophomonas maltophilia Resistance for a More Rational Therapeutic Approach

“…Similarly, Mojica et al reported the successful use of the same combination in a renal transplant recipient with prolonged bacteremia that failed colistin [ 94 ]. Cowart and Ferguson also successfully treated a pneumonia in a patient with cystic fibrosis [ 95 ].…”