Beta-Lactamase Inhibitors
M. Lindsay Grayson, Sara E. Cosgrove, Suzanne M. Crowe, M. Lindsay Grayson, William Hope, James S. McCarthy, John Mills, Johan W. Mouton, David L. Paterson in Kucers’ The Use of Antibiotics, 2017
In another prospective trial performed in Spain, ampicillin–sulbactam was found to be the most active agent against A. baumannii bacteremia (Cisneros et al., 1996). Treatment with imipenem demonstrated cure rates of 83% (35 of 42 patients), whereas cure rates with ampicillin–sulbactam were 87.5% (7 of 8 patients). However, this was not a randomized study. In a retrospective study from Israel of 94 cases of bloodstream infections due to A. baumannii, 51 (54%) involved multidrug-resistant strains; of these, 65% received ampicillin–sulbactam and 35% received inadequate antibiotic therapy. Of the 43 non-multidrug-resistant cases, 86% were treated according to susceptibility and 14% were treated inappropriately. Crude mortality was similar in the adequately treated groups. Among severely ill patients, ampicillin–sulbactam was associated with a decreased risk of death (Smolyakov et al., 2003). It is interesting that all multidrug-resistant isolates were susceptible to ampicillin–sulbactam; however, the drug was licensed in Israel shortly before the study.
Five-year surveillance and correlation of antibiotic consumption and resistance of Gram-negative bacteria at an intensive care unit in Serbia
Published in Journal of Chemotherapy, 2020
Radmila Popović, Zdenko Tomić, Ana Tomas, Nada Anđelić, Sanja Vicković, Gordana Jovanović, Dragica Bukumirić, Olga Horvat, Ana Sabo
A significant decrease in the consumption of 3rd and 4th generation cephalosporins and fluoroquinolones, driven mainly by a decrease in the use of ceftazidime and ciprofloxacin, respectively, with stable consumption of other antibiotics from these classes, was observed in the current study. Similarly, a study conducted in Kragujevac, Serbia, also noted a decrease in total antimicrobial consumption (2309.31 DDD/1000 PD in 2011 vs 1317.53 DDD/1000 PD in 2015).12 An increase in the use of combinations of penicillins and beta-lactamase inhibitors was mostly influenced by the consumption of ampicillin/sulbactam combination. Ampicillin-sulbactam is the empirically recommended antibiotic therapy for abdominal infections,28 and in high doses it demonstrates activity against multidrug-resistant (MDR) Acinetobacter baumannii. An increase in the use of tigecycline, another agent used in A. baumanni infections was also observed, which is in accordance with the results of the previous study conducted in Serbian ICUs.12
Pharmacokinetics-pharmacodynamics of β-lactamase inhibitors: are we missing the target?
Published in Expert Review of Anti-infective Therapy, 2019
Marguerite L Monogue, David P Nicolau
Specific to sulbactam’s β-lactamase inhibition, the antibacterial activity of ampicillin-sulbactam or piperacillin-sulbactam was lost when sulbactam concentration fell below a critical threshold [19,29]. In an in vitro model with TEM-1-producing E. coli, a loss in antibacterial activity was often observed at 4h post-dose when the sulbactam concentration fell below 10 µg/mL. Ampicillin concentration requirement increased significantly when the sulbactam concentration was below the critical threshold, and it was decreased significantly when the sulbactam concentration was above the critical threshold. The maintenance of sulbactam levels above enzyme inhibitory concentrations was a critical pharmacodynamic parameter affecting the activity of ampicillin-sulbactam. Notably, the pharmacodynamics did not change when sulbactam was dosed with or before the partner compound [29]. Similar findings were observed with piperacillin-sulbactam [19]. These studies suggest that sulbactam’s efficacy can be maximized by increasing the time its concentration remains above a specific threshold (fT > threshold), which varies between isolates. Similar to clavulanate, there are no available population PK models using a PK/PD index and target exposure specific to sulbactam.
Causative agents of bloodstream infections in two Croatian hospitals and their resistance mechanisms
Published in Journal of Chemotherapy, 2023
Branka Bedenić, Saša Likić, Marta Žižek, Vesna Bratić, Valentino D'Onofrio, Gordana Cavrić, Gordana Pavliša, Marijo Vodanović, Inge Gyssens, Ivan Barišić
Four A. baumannii isolates showed resistance to ceftazidime, cefepime, piperacillin/tazobactam, gentamicin and ciprofloxacin, and susceptibility to colistin as shown in Table 4. Three isolates were intermediate susceptible to ampicillin/sulbactam, whereas one exhibited resistance. The Hodge and CIM tests were positive indicating the production of carbapenemases. OXA-23 was the dominant carbapenem resistance determinant, identified in three isolates, while OXA-72, an allelic variant of OXA-24/40-like, was found in one isolate. blaOXA-23 and blaOXA-66 and genes possessed ISAba1 upstream of the genes. Chromosomal blaADH-25 was found as well. Among aminoglycoside resistance determinants: aph(3′), aac(3), armA, strB, and strA were found by WGS in the isolate 44921 (accession number CABFJO010000000). All isolates belonged to IC II (SG 1).
Related Knowledge Centers
- Ampicillin
- Antibiotic
- Bacteria
- Combination Drug
- Enzyme Inhibitor
- Infection
- Sulbactam
- Beta-Lactamase
- Intravenous Therapy
- Sultamicillin