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Beta-Lactamase Inhibitors
Published in 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, Kucers’ The Use of Antibiotics, 2017
Pascalis Vergidis, Matthew E. Falagas
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.
Extensively-drug resistant Acinetobacter baumannii bacteremia in neonates: effective treatment with the combination of colistin and ampicillin/sulbactam
Published in Journal of Chemotherapy, 2020
Despoina Gkentzi, Asimina Tsintoni, Irini Christopoulou, Ilias Mamalis, Fotini Paliogianni, Stelios F. Assimakopoulos, Markos Marangos, Gabriel Dimitriou
All patients completed a 10-day course of the combination of colistin (15000 IU/dose TDS) with ampicillin/sulbactam (100 mg/kg/dose TDS) following the first negative blood culture for A. baumannii except from the two siblings born at 27 weeks that received 14 days as per the clinical decision made at that point. In one of the two siblings there was a delay in the clearing of the bacteremia hence tigecycline was added at a dose of 1.2 mg/kg twice daily with favorable outcome (blood cultures negative 48 hours after treatment initiation). Of note, colistin was started early on in the first case that was diagnosed during this outbreak, whereas ampicillin/sulbactam was added thereafter due to lack of bacteremia clearance with colistin monotherapy (Table 1). Following the successful clinical and microbiological outcome of the first neonate, in the subsequent cases, ampicillin/sulbactam was started simultaneously with colistin. During this epidemic we had to permanently change our antibiotic guideline for Late Onset Sepsis from the combination of meropenem and vancomycin to colistin/ampicillin/sulbactam and vancomycin. Vancomycin was discontinued when A. baumannii bacteremia was confirmed and no gram positive bacteria were isolated. In addition, infection control measures were put in place and all positive cases were cohorted and had a barrier nurse.
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.
An evidence-based multidisciplinary approach focused at creating algorithms for targeted therapy of infection-related ventilator associated complications (IVACs) caused by Enterobacterales in critically ill adult patients
Published in Expert Review of Anti-infective Therapy, 2022
Milo Gatti, Bruno Viaggi, Gian Maria Rossolini, Federico Pea, Pierluigi Viale
Ampicillin-sulbactam [3 g q6h over 6 h by continuous infusion (CI) after 3 g loading dose [LD]] or ceftriaxone (2 g q24h)] are recommended as targeted therapy for IVACs caused by multi-susceptible Enterobacterales. Evidences supporting these choices are summarized in Table 1. Overall, five RCTs and one retrospective study [14–19] reported the efficacy of ampicillin-sulbactam for the treatment of lower respiratory tract infections. The settings included severe CAP, aspiration pneumonia, and lung abscess and Enterobacterales accounted for up to 53% of cases. Unfortunately, data on ICU admission rate were not available.