scholarly journals In Vitro Double and Triple Bactericidal Activities of Doripenem, Polymyxin B, and Rifampin against Multidrug-Resistant Acinetobacter baumannii, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Escherichia coli

2010 ◽  
Vol 54 (6) ◽  
pp. 2732-2734 ◽  
Author(s):  
Carl Urban ◽  
Noriel Mariano ◽  
James J. Rahal
Keyword(s):  
Escherichia Coli ◽  
Pseudomonas Aeruginosa ◽  
Klebsiella Pneumoniae ◽  
Acinetobacter Baumannii ◽  
Carbapenem Resistance ◽  
Polymyxin B ◽  
Multidrug Resistant ◽  
Carbapenem Resistant ◽  
Bactericidal Activities

ABSTRACT In vitro double and triple bactericidal activities of doripenem, polymyxin B, and rifampin were assessed against 20 carbapenem-resistant clinical isolates with different mechanisms of carbapenem resistance. Bactericidal activity was achieved in 90% of all bacteria assayed using combinations of polymyxin B, doripenem, and rifampin against five each of the carbapenem-resistant Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Escherichia coli isolates studied. Combinations with these antibacterials may provide a strategy for treatment of patients infected with such organisms.

scholarly journals In Vitro Activity of a Novel Siderophore-Cephalosporin LCB10-0200 (GT-1), and LCB10-0200/Avibactam, against Carbapenem-Resistant Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa Strains at a Tertiary Hospital in Korea

2021 ◽  
Vol 14 (4) ◽  
pp. 370
Author(s):  
Le Phuong Nguyen ◽  
Chul Soon Park ◽  
Naina Adren Pinto ◽  
Hyunsook Lee ◽  
Hyun Soo Seo ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Pseudomonas Aeruginosa ◽  
Klebsiella Pneumoniae ◽  
Acinetobacter Baumannii ◽  
Vitro Activity ◽  
In Vitro Activity ◽  
Strong Activity ◽  
E Coli ◽  
Carbapenem Resistant

The siderophore–antibiotic conjugate LCB10-0200 (a.k.a. GT-1) has been developed to combat multidrug-resistant Gram-negative bacteria. In this study, the in vitro activity of LCB10-0200 and LCB10-0200/avibactam (AVI) has been investigated against carbapenem-resistant Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa. Minimal inhibitory concentrations (MICs) of LCB10-0200, LCB10-0200/AVI, aztreonam, aztreonam/AVI, ceftazidime, ceftazidime/AVI, and meropenem were measured using the agar dilution method. Whole genome sequencing was performed using Illumina and the resistome was analyzed. LCB10-0200 displayed stronger activity than the comparator drugs in meropenem-resistant E. coli and K. pneumoniae, and the addition of AVI enhanced the LCB10-0200 activity to MIC ≤ 0.12 mg/L for 90.5% of isolates. In contrast, whereas LCB10-0200 alone showed potent activity against meropenem-resistant A. baumannii and P. aeruginosa at MIC ≤ 4 mg/L for 84.3% of isolates, the combination with AVI did not improve its activity. LCB10-0200/AVI was active against CTX-M-, SHV-, CMY-, and KPC- producing E. coli and K. pneumoniae, while LCB10-0200 alone was active against ADC-, OXA-, and VIM- producing A. baumannii and P. aeruginosa. Both LCB10-0200 and LCB10-0200/AVI displayed low activity against IMP- and NDM- producing strains. LCB10-0200 alone exhibited strong activity against selected strains. The addition of AVI significantly increased LCB10-0200 activity against carbapenem-resistant E. coli, K. pneumoniae.

scholarly journals Activity of cefiderocol against high-risk clones of multidrug-resistant Enterobacterales, Acinetobacter baumannii, Pseudomonas aeruginosa and Stenotrophomonas maltophilia

2020 ◽  
Vol 75 (7) ◽  
pp. 1840-1849 ◽  
Author(s):  
Mercedes Delgado-Valverde ◽  
M del Carmen Conejo ◽  
Lara Serrano ◽  
Felipe Fernández-Cuenca ◽  
Álvaro Pascual
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Acinetobacter Baumannii ◽  
Stenotrophomonas Maltophilia ◽  
Enterobacter Cloacae ◽  
Multidrug Resistant ◽  
In Vitro Activity ◽  
Carbapenem Resistant ◽  
Excellent Activity ◽  
In Vitro Antibacterial Activity

Abstract Background Cefiderocol is a novel siderophore cephalosporin, developed for activity against MDR Gram-negative bacilli (MDR-GNB). Objectives To assess the in vitro antibacterial activity of cefiderocol against a collection of MDR-GNB clinical isolates from hospitals in southern Spain. Methods Two hundred and thirty-one isolates of successful clones were tested: 125 Enterobacterales (121 ESBL- and/or carbapenemase-producing Klebsiella pneumoniae and 4 carbapenemase-producing Enterobacter cloacae), 80 Acinetobacter baumannii, 6 Pseudomonas aeruginosa and 20 Stenotrophomonas maltophilia. Ceftolozane/tazobactam, ceftazidime, ceftazidime/avibactam, cefepime, aztreonam, meropenem, amikacin, ciprofloxacin, colistin and tigecycline were used as comparators against Enterobacterales, P. aeruginosa and A. baumannii. Minocycline, levofloxacin and trimethoprim/sulfamethoxazole were studied against S. maltophilia instead of aztreonam, ciprofloxacin and cefepime. MICs were determined by broth microdilution according to CLSI guidelines. MIC determination was performed in CAMHB for all antimicrobials except cefiderocol, where iron-depleted CAMHB was used. Results Cefiderocol showed potent in vitro activity against the isolates analysed. MIC50 and MIC90 values were in the ranges 0.125–8 mg/L and 0.5–8 mg/L, respectively, and 98% of isolates were inhibited at ≤4 mg/L. Only five isolates showed cefiderocol MICs of >4 mg/L: three ST2/OXA-24/40-producing A. baumannii, one ST114/VIM-1-producing E. cloacae and one ST114/VIM-1 + OXA-48-producing E. cloacae. All KPC-3-producing K. pneumoniae were susceptible to cefiderocol, even those resistant to ceftazidime/avibactam. P. aeruginosa isolates showed cefiderocol MICs of <4 mg/L, including those resistant to ceftolozane/tazobactam. S. maltophilia isolates displayed cefiderocol MICs of <4 mg/L, including those resistant to levofloxacin and/or trimethoprim/sulfamethoxazole. Conclusions Cefiderocol showed excellent activity against MDR-GNB, including carbapenem-resistant isolates, and was the most active antimicrobial tested against this collection.

scholarly journals In vitro Bactericidal Activities of Combination Antibiotic Therapies Against Carbapenem-Resistant Klebsiella pneumoniae With Different Carbapenemases and Sequence Types

2021 ◽  
Vol 12 ◽  
Author(s):  
Jocelyn Qi-Min Teo ◽  
Nazira Fauzi ◽  
Jayden Jun-Yuan Ho ◽  
Si Hui Tan ◽  
Shannon Jing-Yi Lee ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Bactericidal Activity ◽  
Carbapenem Resistance ◽  
Polymyxin B ◽  
Apparent Difference ◽  
Initial Inoculum ◽  
Carbapenem Resistant ◽  
Limited Effectiveness ◽  
Sequence Types

Carbapenem-resistant Klebsiella pneumoniae (CRKP) is becoming increasingly problematic due to the limited effectiveness of new antimicrobials or other factors such as treatment cost. Thus, combination therapy remains a suitable treatment option. We aimed to evaluate the in vitro bactericidal activity of various antibiotic combinations against CRKP with different carbapenemase genotypes and sequence types (STs). Thirty-seven CRKP with various STs and carbapenemases were exposed to 11 antibiotic combinations (polymyxin B or tigecycline in combination with β-lactams including aztreonam, cefepime, piperacillin/tazobactam, doripenem, meropenem, and polymyxin B with tigecycline) in static time-kill studies (TKS) using clinically achievable concentrations. Out of the 407 isolate-combination pairs, only 146 (35.8%) were bactericidal (≥3 log10CFU/mL decrease from initial inoculum). Polymyxin B in combination with doripenem, meropenem, or cefepime was the most active, each demonstrating bactericidal activity in 27, 24, and 24 out of 37 isolates, respectively. Tigecycline in combination with β-lactams was rarely bactericidal. Aside from the lower frequency of bactericidal activity in the dual-carbapenemase producers, there was no apparent difference in combination activity among the strains with other carbapenemase types. In addition, bactericidal combinations were varied even in strains with similar STs, carbapenemases, and other genomic characteristics. Our findings demonstrate that the bactericidal activity of antibiotic combinations is highly strain-specific likely owing to the complex interplay of carbapenem-resistance mechanisms, i.e., carbapenemase genotype alone cannot predict in vitro bactericidal activity. The availability of WGS information can help rationalize the activity of certain combinations. Further studies should explore the use of genomic markers with phenotypic information to predict combination activity.

scholarly journals In Vitro Activity Comparison of Ceftazidime–Avibactam and Aztreonam–Avibactam Against Bloodstream Infections With Carbapenem-Resistant Organisms in China

2021 ◽  
Vol 11 ◽  
Author(s):  
Wei Yu ◽  
Luying Xiong ◽  
Qixia Luo ◽  
Yunbo Chen ◽  
Jinru Ji ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Pseudomonas Aeruginosa ◽  
Bloodstream Infections ◽  
Polymyxin B ◽  
Resistance Rate ◽  
In Vitro Activity ◽  
Carbapenem Resistant ◽  
Resistance Rates ◽  
Activity Comparison

ObjectivesThe aim of this work was to investigate the activity of ceftazidime–avibactam (CZA) and aztreonam–avibactam (AZA) against bloodstream infections caused by carbapenem-resistant organisms (CROs).MethodsNon-duplicate CROs, including 56 carbapenem-resistant Escherichia coli (CR-Eco), 318 carbapenem-resistant Klebsiella pneumoniae (CR-Kpn), and 65 carbapenem-resistant Pseudomonas aeruginosa (CR-Pae), were collected using the Blood Bacterial Resistant Investigation Collaborative System (BRICS) program in China. The minimum inhibitory concentrations (MICs) of 24 antibiotics were tested. Carbapenemase genes were amplified for CZA-resistant CROs by PCR. The MICs of CZA and AZA were further determined with avibactam at 8 and 16 mg/L, respectively.ResultsThe resistance rate of polymyxin B against CROs was less than 5%. Only one CR-Kpn was resistant to tigecycline. The resistance rates of CZA against CR-Eco, CR-Kpn, and CR-Pae were 75.0%, 12.6%, and 18.5%, respectively. The MIC90 values of AZA against CR-Eco, CR-Kpn, and CR-Pae were 2/4, 1/4, and 64/4 mg/L, respectively. Among the CZA-resistant CROs, 42 (100%) CR-Eco, 24 (60%) CR-Kpn, and 1 (8.3%) CR-Pae isolates harbored metallo-β-lactamase genes. The increase of avibactam concentration enhanced the susceptibility of CZA and AZA against CROs, especially for CR-Eco and CR-Kpn.ConclusionsThe in vitro activity of AZA was superior to that of CZA against CR-Eco and CR-Kpn, whereas CZA showed better effect against CR-Pae.

scholarly journals In VitroActivity of LYS228, a Novel Monobactam Antibiotic, against Multidrug-ResistantEnterobacteriaceae

2018 ◽  
Vol 62 (10) ◽  
Author(s):  
Johanne Blais ◽  
Sara Lopez ◽  
Cindy Li ◽  
Alexey Ruzin ◽  
Srijan Ranjitkar ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Klebsiella Pneumoniae ◽  
Carbapenem Resistance ◽  
Multidrug Resistant ◽  
Minimal Bactericidal Concentration ◽  
Content Type ◽  
Carbapenem Resistant ◽  
Time Kill ◽  
Reference Strains ◽  
M 14

ABSTRACTLYS228 is a novel monobactam with potent activity againstEnterobacteriaceae. LYS228 is stable to metallo-β-lactamases (MBLs) and serine carbapenemases, includingKlebsiella pneumoniaecarbapenemases (KPCs), resulting in potency against the majority of extended-spectrum β-lactamase (ESBL)-producing and carbapenem-resistantEnterobacteriaceaestrains tested. Overall, LYS228 demonstrated potent activity against 271Enterobacteriaceaestrains, including multidrug-resistant isolates. Based on MIC90values, LYS228 (MIC90, 1 μg/ml) was ≥32-fold more active against those strains than were aztreonam, ceftazidime, ceftazidime-avibactam, cefepime, and meropenem. The tigecycline MIC90was 4 μg/ml against the strains tested. AgainstEnterobacteriaceaeisolates expressing ESBLs (n= 37) or displaying carbapenem resistance (n= 77), LYS228 had MIC90values of 1 and 4 μg/ml, respectively. LYS228 exhibited potent bactericidal activity, as indicated by low minimal bactericidal concentration (MBC) to MIC ratios (MBC/MIC ratios of ≤4) against 97.4% of theEnterobacteriaceaestrains tested (264/271 strains). In time-kill studies, LYS228 consistently achieved reductions in CFU per milliliter of 3 log10units (≥99.9% killing) at concentrations ≥4× MIC forEscherichia coliandK. pneumoniaereference strains, as well as isolates encoding TEM-1, SHV-1, CTX-M-14, CTX-M-15, KPC-2, KPC-3, and NDM-1 β-lactamases.

scholarly journals In Vitro Synergism of Azithromycin Combination with Antibiotics against OXA-48-Producing Klebsiella pneumoniae Clinical Isolates

Antibiotics ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 1551
Author(s):  
Uthaibhorn Singkham-in ◽  
Netchanok Muhummudaree ◽  
Tanittha Chatsuwan
Keyword(s):  
Escherichia Coli ◽  
Klebsiella Pneumoniae ◽  
Outer Membrane Proteins ◽  
Carbapenem Resistance ◽  
Resistance Mechanisms ◽  
In Vitro Activity ◽  
Bacterial Regrowth ◽  
Antibiotic Development ◽  
Carbapenem Resistant

Carbapenem-resistant Klebsiella pneumoniae has globally emerged as an urgent threat leading to the limitation for treatment. K. pneumoniae carrying blaOXA-48, which plays a broad magnitude of carbapenem susceptibility, is widely concerned. This study aimed to characterize related carbapenem resistance mechanisms and forage for new antibiotic combinations to combat blaOXA-48-carrying K. pneumoniae. Among nine isolates, there were two major clones and a singleton identified by ERIC-PCR. Most isolates were resistant to ertapenem (MIC range: 2–>256 mg/L), but two isolates were susceptible to imipenem and meropenem (MIC range: 0.5–1 mg/L). All blaOXA-48-carrying plasmids conferred carbapenem resistance in Escherichia coli transformants. Two ertapenem-susceptible isolates carried both outer membrane proteins (OMPs), OmpK35 and OmpK36. Lack of at least an OMP was present in imipenem-resistant isolates. We evaluated the in vitro activity of an overlooked antibiotic, azithromycin, in combination with other antibiotics. Remarkably, azithromycin exhibited synergism with colistin and fosfomycin by 88.89% and 77.78%, respectively. Bacterial regrowth occurred after exposure to colistin or azithromycin alone. Interestingly, most isolates were killed, reaching synergism by this combination. In conclusion, the combination of azithromycin and colistin may be an alternative strategy in dealing with blaOXA-48-carrying K. pneumoniae infection during a recent shortage of newly effective antibiotic development.

scholarly journals In Vitro Activity of Colistin (Polymyxin E) against 3,480 Isolates of Gram-Negative Bacilli Obtained from Patients in Canadian Hospitals in the CANWARD Study, 2007-2008

2009 ◽  
Vol 53 (11) ◽  
pp. 4924-4926 ◽  
Author(s):  
A. Walkty ◽  
M. DeCorby ◽  
K. Nichol ◽  
J. A. Karlowsky ◽  
D. J. Hoban ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Pseudomonas Aeruginosa ◽  
Acinetobacter Baumannii ◽  
Multidrug Resistant ◽  
Vitro Activity ◽  
In Vitro Activity ◽  
Broth Microdilution ◽  
Gram Negative ◽  
Polymyxin E

ABSTRACT The in vitro activity of colistin was evaluated versus 3,480 isolates of gram-negative bacilli using CLSI broth microdilution methods. The MIC90 of colistin was ≤2 μg/ml against a variety of clinically important gram-negative bacilli, including Escherichia coli, Klebsiella spp., Enterobacter spp., Acinetobacter baumannii, and Pseudomonas aeruginosa. All multidrug-resistant (n = 76) P. aeruginosa isolates were susceptible to colistin (MIC, ≤2 μg/ml). These data support a role for colistin in the treatment of infections caused by multidrug-resistant P. aeruginosa.

scholarly journals In VitroPharmacodynamics of Polymyxin B and Tigecycline Alone and in Combination against Carbapenem-Resistant Acinetobacter baumannii

2013 ◽  
Vol 58 (2) ◽  
pp. 874-879 ◽  
Author(s):  
Mao Hagihara ◽  
Seth T. Housman ◽  
David P. Nicolau ◽  
Joseph L. Kuti
Keyword(s):  
Combination Therapy ◽  
Acinetobacter Baumannii ◽  
Population Analysis ◽  
Polymyxin B ◽  
Multidrug Resistant ◽  
Bacterial Killing ◽  
Content Type ◽  
Model Free ◽  
Carbapenem Resistant

ABSTRACTCarbapenem-resistantAcinetobacter baumanniiis increasing in prevalence. Polymyxin B and tigecycline are among the most active antibiotics used against this pathogenin vitro. Pastin vitrostudies, however, neglected the importance of simulating exposures observed in humans to determine their antibacterial effects. In this study, four carbapenem-resistantA. baumanniiisolates were evaluated using anin vitropharmacodynamic model. Free-drug exposures using 1 mg/kg of body weight of polymyxin B every 12 h (q12h), 100 and 200 mg tigecycline q12h, and the combination of these regimens were simulated. The microbiological responses to these treatments were measured by the change in log10CFU/ml over 24 h and the area under the bacterial killing and regrowth curve (AUBC). Resistance was assessed by a population analysis profile (PAP) conducted after 24 h of treatment. Polymyxin B achieved a reduction on the order of −2.05 ± 0.68 log10CFU/ml against theseA. baumanniiisolates, while all isolates grew to control levels with tigecycline monotherapy. Combination therapy with polymyxin B plus 200 mg tigecycline q12h achieved a greater reduction in bacterial density than did therapy with polymyxin B alone (−3.31 ± 0.71 versus −2.05 ± 0.68 log10CFU/ml,P< 0.001) but not significantly different than combination therapy with 100 mg tigecycline q12h (−2.45 ± 1.00 log10CFU/ml,P= 0.370). Likewise, combination therapy with polymyxin B plus 200 mg tigecycline q12h significantly reduced the AUBC compared to that with polymyxin B alone (62.8 ± 8.9 versus 79.4 ± 10.5 log10CFU/ml,P< 0.05). No changes in the PAP from baseline were observed for either antibiotic alone. In this study, combination therapy with simulated exposures of polymyxin B and tigecycline at an aggressive dose of 200 mg q12h produced synergistic or additive effects on humans against these multidrug-resistantA. baumanniistrains.

scholarly journals In Vitro Activity of Tigecycline against Multidrug-Resistant Acinetobacter baumannii and Selection of Tigecycline-Amikacin Synergy

2008 ◽  
Vol 52 (8) ◽  
pp. 2940-2942 ◽  
Author(s):  
Ellen S. Moland ◽  
David W. Craft ◽  
Seong-geun Hong ◽  
Soo-young Kim ◽  
Lucas Hachmeister ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Polymyxin B ◽  
Multidrug Resistant ◽  
Vitro Activity ◽  
Resistant Isolate ◽  
In Vitro Activity ◽  
Bactericidal Activities ◽  
Time Kill ◽  
Selection Of

ABSTRACT Polymyxin B, minocycline, and tigecycline were the most potent of 10 antibiotics against 170 isolates of multidrug-resistant Acinetobacter baumannii. In time-kill studies, the exposure of a highly tigecycline-resistant isolate to tigecycline resulted in enhanced susceptibility to amikacin and synergistic bactericidal activities of the two drugs.

scholarly journals In Vitro Antibacterial Interaction of Doripenem and Amikacin against Multidrug-Resistant Acinetobacter baumannii, Pseudomonas aeruginosa, and Klebsiella pneumoniae Isolates

2018 ◽  
Vol 2018 ◽  
pp. 1-6 ◽  
Author(s):  
Tonny Loho ◽  
Ninik Sukartini ◽  
Dalima A. W. Astrawinata ◽  
Suzanna Immanuel ◽  
Diana Aulia ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Klebsiella Pneumoniae ◽  
Acinetobacter Baumannii ◽  
Inhibitory Concentration ◽  
Multidrug Resistant ◽  
The Other ◽  
Additive Interaction ◽  
Class 1 ◽  
In Vitro Interaction

Evaluation of the in vitro interaction of doripenem and amikacin against Acinetobacter baumannii, Pseudomonas aeruginosa, and Klebsiella pneumoniae was done by classifying them into four groups: doripenem and amikacin sensitive (DOR-S/AMK-S), doripenem sensitive and amikacin resistant (DOR-S/AMK-R), doripenem resistant and amikacin sensitive (DOR-R/AMK-S), and both doripenem and amikacin resistant (DOR-R/AMK-R). The MIC of each antibiotic and their combination was obtained using the Etest method. The fractional inhibitory concentration index was calculated to classify the results as synergistic, additive, indifferent, or antagonistic interaction. In the DOR-S/AMK-S class, 1 isolate of A. baumannii showed synergy and the other 5 showed additive results, 5 isolates of P. aeruginosa showed additive and 1 isolate showed indifferent result, and 2 isolates of K. pneumoniae showed additive and the other 4 showed indifferent results. In the DOR-S/AMK-R class, 3 isolates of A. baumannii showed additive and the other 3 showed indifferent results, 2 isolates of P. aeruginosa showed indifferent results, and 1 isolate of K. pneumoniae showed additive and the other 5 showed indifferent results. In the DOR-R/AMK-S class, 1 isolate of A. baumannii showed additive and the other 5 showed indifferent results, 1 isolate of P. aeruginosa showed additive and the other 5 showed indifferent results, and 4 isolates of K. pneumoniae showed additive and the other 2 showed indifferent results. In the DOR-R/AMK-R class, 6 isolates of A. baumannii showed indifferent results, 1 isolate of P. aeruginosa showed additive and the other 5 showed indifferent results, and 1 isolate of K. pneumoniae showed additive and the other 5 showed indifferent results. Synergy occurred in only 1 (1.5%) isolate. Additive interaction occurred in 24 (35.3%) isolates, and indifferent interaction occurred in 43 (63.2%) isolates. Doripenem sensitive combined with amikacin sensitive reduced MIC significantly in all bacterial isolates when compared to single MIC of each antibiotic.

Sign in / Sign up

Export Citation Format

Share Document