scholarly journals In-Vitro Evaluation of Different Antimicrobial Combinations with and without Colistin Against Carbapenem-Resistant Acinetobacter Baumannii

Molecules ◽  
2019 ◽  
Vol 24 (5) ◽  
pp. 886 ◽  
Author(s):  
Alessandra Oliva ◽  
Stefania Garzoli ◽  
Massimiliano De Angelis ◽  
Carolina Marzuillo ◽  
Vincenzo Vullo ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Bactericidal Activity ◽  
High Morbidity ◽  
Synergistic Activity ◽  
Carbapenem Resistant ◽  
Resistant Strains ◽  
High Level ◽  
University Of Rome ◽  
Antimicrobial Combinations

Carbapenem-resistant Acinetobacter baumannii (CR-Ab) infections are associated with high morbidity and mortality. The aim of the study was to evaluate the in-vitro activity of different antimicrobial combinations (with and without colistin, COL) against clinical isolates of CR-Ab collected from patients with CR-Ab infection, including unconventional combinations such as COL + VANcomycin (VAN) and COL + rifampin (RIF). CR-Ab strains were collected from hospitalized patients at Sapienza University of Rome. Antimicrobial susceptibility patterns were determined throughout MIC50/90s whereas the synergistic activity was evaluated by qualitative (i.e., checkerboard) and quantitative (i.e., killing studies) methods. All the strains were found oxacillinase (OXA) producers and tigecycline (TIG) sensitive whereas 2 strains were resistant to COL. Application of the checkerboard method indicated complete synergism in COL combinations at different extension: 21.4%, 57.1%, 42.8%, 35.7% for COL + meropenem (MEM), COL + RIF, COL + VAN and COL + TIG, respectively, with the non-conventional combinations COL + VAN and COL + RIF exhibiting the highest rate of synergism. Regarding COL-free combination, complete synergism was observed in 35.7% of the strains for MEM + TIG. Killing studies showed that the combinations COL + MEM, COL + TIG and MEM + TIG were bactericidal and synergistic against both colistin-sensitive and low colistin-resistant strains whereas only the combinations COL + VAN and COL + RIF showed an early and durable bactericidal activity against all the tested strains, with absence of growth at 24 h. This study demonstrated that COL-based combinations lead to a high level of synergic and bactericidal activity, especially COL + VAN and COL + RIF, even in the presence of high level of COL resistance.

scholarly journals In Vitro Synergistic Antimicrobial Activity of Combinations of Meropenem, Colistin, Tigecycline, Rifampin, and Ceftolozane/Tazobactam Against Carbapenem-Resistant Acinetobacter Baumannii

2021 ◽  
Author(s):  
Yong Guk Ju ◽  
Hak Joon Lee ◽  
Hong Soon Yim ◽  
Chang Kyu Lee ◽  
Mingoo Lee ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Bactericidal Effect ◽  
Drug Combinations ◽  
Synergistic Activity ◽  
Antibiotic Concentration ◽  
Carbapenem Resistant ◽  
Potential Alternative ◽  
Time Kill ◽  
Antimicrobial Combinations

Abstract The aim of this study was to investigate the in vitro activity of various antimicrobial combinations against carbapenem-resistant Acinetobacter baumannii (CRAB) isolates producing OXA-23 carbapenemases.In vitro activity of six two-drug combinations against CRAB isolates collected from patients with CRAB bacteremia was evaluated using the checkerboard method and time-kill assay [0.5 ×, 1 ×, 2 × minimum inhibitory concentrations (MIC)], to identify potential synergistic and bactericidal two-drug combinations against CRAB isolates, using meropenem, colistin, tigecycline, rifampin, and ceftolozane/tazobactam. All 10 CRAB isolates in our study carried the OXA-58-type and OXA-23-type carbapenem-hydrolyzing oxacillinase. The colistin-ceftolozane/tazobactam combination demonstrated a synergistic effect in both the time-kill assay (using an antibiotic concentration of 1 × MIC) and the checkerboard method, while simultaneously showing a bactericidal effect in the time-kill assay. For all 10 CRAB isolates, time-kill curves showed a significant synergistic bactericidal activity of the colistin-ceftolozane/tazobactam combination at 0.5 × MIC. Overall, there is substantial discordance of synergistic activity between the checkerboard microdilution and time-kill assay (with a concordance of 35%). Our study demonstrated that the two-drug combinations of colistin and ceftolozane/tazobactam can be a potential alternative for treating CRAB infections. The effect of these antibiotic combinations should be evaluated through clinical trials.

scholarly journals Semimechanistic Pharmacokinetic/Pharmacodynamic Modeling of Fosfomycin and Sulbactam Combination against Carbapenem-Resistant Acinetobacter baumannii

2021 ◽  
Vol 65 (5) ◽  
Author(s):  
Sazlyna Mohd Sazlly Lim ◽  
Aaron J. Heffernan ◽  
Jason A. Roberts ◽  
Fekade B. Sime
Keyword(s):  
Acinetobacter Baumannii ◽  
Treatment Options ◽  
Pharmacodynamic Modeling ◽  
Synergistic Activity ◽  
Bacterial Burden ◽  
Target Attainment ◽  
Content Type ◽  
Carbapenem Resistant ◽  
Time Kill

ABSTRACT Due to limited treatment options for carbapenem-resistant Acinetobacter baumannii (CR-AB) infections, antibiotic combinations are now considered potential treatments for CR-AB. This study aimed to explore the utility of fosfomycin-sulbactam combination (FOS/SUL) therapy against CR-AB isolates. Synergism of FOS/SUL against 50 clinical CR-AB isolates was screened using the checkerboard method. Thereafter, time-kill studies against two CR-AB isolates were performed. The time-kill data were described using a semimechanistic pharmacokinetic/pharmacodynamic (PK/PD) model. Monte Carlo simulations were then performed to estimate the probability of stasis, 1-log kill, and 2-log kill after 24 h of combination therapy. The FOS/SUL combination demonstrated a synergistic effect against 74% of isolates. No antagonism was observed. The MIC50 and MIC90 of FOS/SUL were decreased 4- to 8-fold, compared to the monotherapy MIC50 and MIC90. In the time-kill studies, the combination displayed bactericidal activity against both isolates and synergistic activity against one isolate at the highest clinically achievable concentrations. Our PK/PD model was able to describe the interaction between fosfomycin and sulbactam in vitro. Bacterial kill was mainly driven by sulbactam, with fosfomycin augmentation. FOS/SUL regimens that included sulbactam at 4 g every 8 h demonstrated a probability of target attainment of 1-log10 kill at 24 h of ∼69 to 76%, compared to ∼15 to 30% with monotherapy regimens at the highest doses. The reduction in the MIC values and the achievement of a moderate PTA of a 2-log10 reduction in bacterial burden demonstrated that FOS/SUL may potentially be effective against some CR-AB infections.

scholarly journals 1542. The Evaluation of the In Vitro Synergy of Colistin in Combination with Meropenem and Tigecycline against 50 Multi-Drug-resistant Acinetobacter baumannii strains

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S562-S563
Author(s):  
Jacinda Abdul-Mutakabbir ◽  
Juwom Yim ◽  
Logan Nguyen ◽  
Razieh Kebriaei ◽  
Kyle Stamper ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Bactericidal Activity ◽  
Single Agent ◽  
Resistance Mechanisms ◽  
Drug Resistant ◽  
Initial Inoculum ◽  
Log Reduction ◽  
Carbapenem Resistant ◽  
Time Kill

Abstract Background Acinetobacter baumannii possess inherent and acquired antibiotic resistance mechanisms that have rendered most antibiotics, including carbapenems, inactive. Colistin (COL) has risen as salvage therapy against these organisms due to its retained activity against A. baumannii. However, COL monotherapy is often met with suboptimal outcomes. Recently, combination therapy with COL and meropenem (MEM) or tigecycline (TGC) has been shown to be effective in eradicating multi-drug-resistant A. baumannii infections. The objective of this study was to further evaluate the efficacy of COL in combination with MEM or TGC against 50 multi-drug-resistant A. baumannii strains. Methods Fifty carbapenem-resistant A. baumannii strains were evaluated using combination minimum inhibitory concentration (MIC) testing and time-kill analysis (TKA). Single-drug MIC testing was performed for each strain by broth microdilution. Combination MIC testing was performed for COL+MEM and COL+TGC. Each strain was evaluated via 24-hour TKA to assess the synergistic capabilities of COL+MEM, and COL+TGC. Synergy was defined as a ≥ 2-log reduction CFU/mL in either combination from the most active single agent, while bactericidal activity was defined as a ≥ 3-log reduction CFU/mL of either combination from the initial inoculum. Results All 50 strains were resistant to MEM and TGC with MICs ≥ 64 µg/mL and ≥ 4 µg/mL respectively; while 3 strains were resistant to COL, MICs ≥ 2 µg/mL. MEM and TGC MIC values were reduced as much as 128-fold (median 2-fold) and 32-fold (median 2-fold),, respectively, in the presence of subinhibitory COL. COL MIC values were reduced as much as 512-fold (median 4-fold) from baseline in the presence of subinhibitory MEM, and as high as 16-fold (median 2-fold) in the presence of TGC. In TKAs, COL+MEM was synergistic in 45/50 (90%) strains and bactericidal against 43/50 (86%) strains. COL+TGC TKAs revealed synergy in 32/50 (64%) strains, and bactericidal activity against 28/50 (56%) strains. Conclusion The combinations of COL+MEM and COL+TGC demonstrate promise in combating highly resistant A. baumannii. Further research is mandated to explore other combinations that are capable of eradicating multi-drug-resistant A. baumannii. Disclosures All authors: No reported disclosures.

scholarly journals Synergistic activity of polymyxin B combined with vancomycin against carbapenem-resistant and polymyxin-resistant Acinetobacter baumannii: first in vitro study

2019 ◽  
Vol 68 (3) ◽  
pp. 309-315 ◽  
Author(s):  
Danielle Rosani Shinohara ◽  
Thatiany Cevallos Menegucci ◽  
Nayara Helisandra Fedrigo ◽  
Letícia Busato Migliorini ◽  
Floristher Elaine Carrara-Marroni ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
In Vitro Study ◽  
Polymyxin B ◽  
Vitro Study ◽  
Synergistic Activity ◽  
Carbapenem Resistant

scholarly journals Minocycline alone and in combination with polymyxin B, meropenem, and sulbactam against carbapenem- susceptible and resistant Acinetobacter baumannii in in vitro pharmacodynamic model

2020 ◽  
pp. AAC.01680-20
Author(s):  
Maya Beganovic ◽  
Kathryn E. Daffinee ◽  
Megan K. Luther ◽  
Kerry L. LaPlante
Keyword(s):  
Continuous Infusion ◽  
Acinetobacter Baumannii ◽  
Triple Therapy ◽  
Bactericidal Activity ◽  
Polymyxin B ◽  
Pharmacodynamic Model ◽  
High Dose ◽  
Resistance Development ◽  
Carbapenem Resistant

Acinetobacter baumannii is recognized as an urgent public health threat by the Centers for Disease Control and Prevention (CDC). Current treatment options are scarce, particularly against carbapenem-resistant Acinetobacter baumannii (CRAB). We simulated the impact of minocycline standard (200mg load+100mg Q12h) and high-dose (700mg load+ 350mg Q12h), polymyxin B (2.5mg/kg Q12h), sulbactam (1g Q6h and 9g/24h as continuous infusion) and meropenem (intermittent 1 or 2g Q8h and 6g/24h as continuous infusion) alone or in combination against CRAB and non-CRAB isolates by simulating human therapeutic dosing regimens in a 72-hour, in vitro pharmacodynamic model (IVPD). There were no monotherapy regimens that demonstrated bactericidal activity against the tested non-CRAB and CRAB. Resistance development was common in monotherapy regimens. Against the CRAB isolate, the triple combination of high-dose minocycline (fAUC/MIC 21.21), polymyxin B (fAUC/MIC 15.63), and continuous infusion sulbactam (67% T>MIC) was the most consistently active regimen. Against non-CRAB, the triple therapy regimen of high-dose minocycline (fAUC/MIC 84.84) with continuous infusion meropenem (100%T>MIC) and continuous infusion sulbactam (83%T>MIC), as well as the double therapy of high-dose minocycline (AUC/MIC 84.84) with continuous infusion meropenem (100%T>MIC) resulted persistently bactericidal activity. In conclusion, triple therapy with high dose minocycline, continuous infusion sulbactam, and polymyxin B produced the most significant kill against the carbapenem-resistant Acinetobacter baumannii, with no regrowth and minimal resistance development.

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