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 1348. In vitro Activity of Plazomicin, a Next-Generation Aminoglycoside, Against Carbapenemase-Producing Klebsiella pneumoniae

2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S412-S413
Author(s):  
Michael R Jacobs ◽  
Caryn E Good ◽  
Ayman M Abdelhamed ◽  
Daniel D Rhoads ◽  
Kristine M Hujer ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Carbapenem Resistance ◽  
Vitro Activity ◽  
In Vitro Activity ◽  
Next Generation ◽  
Aminoglycoside Resistance ◽  
Carbapenem Resistant ◽  
Carbapenemase Gene ◽  
Research Grant

Abstract Background Plazomicin is a next-generation aminoglycoside with in vitro activity against multidrug-resistant Gram-negative species, including carbapenem-resistant isolates. The Consortium on Resistance Against Carbapenems in Klebsiella and other Enterobacteriaceae (CRACKLE) is a federally funded, prospective multicenter consortium of 20 hospitals from nine US healthcare systems to track carbapenem-resistant Enterobacteriaceae. Methods Minimum inhibitory concentrations (MICs) of plazomicin were determined by broth microdilution according to current CLSI guidelines against a collection of 697 carbapenem-resistant Klebsiella pneumoniae with defined carbapenem resistance mechanisms, including KPC and OXA carbapenemases. Isolates were submitted by participating CRACKLE centers. Results Carbapenemases present in study isolates included KPC-2 (n = 323), KPC-3 (n = 364), KPC-4 (n = 2), OXA-48 like (n = 7), and NDM (n = 1). Plazomicin MICs ranged from ≤0.12 to >32 mg/L, with MIC50 and MIC90 values of 0.25 and 1 mg/L, respectively (figure). MICs of 689 (98.8%) isolates were ≤4 mg/L, while MICs of the remaining eight isolates were >32 mg/L. Plazomicin MICs were related to specific carbapenemases present in isolates: of eight isolates with MICs >32 mg/L, seven contained OXA-48 like and one contained KPC-3, suggesting that these isolates possess an aminoglycoside-resistance mechanism on the same plasmid as their carbapenemase gene, such as a 16S ribosomal RNA methyltransferase, against which plazomicin is not active. Conclusion Plazomicin has good in vitro potency against a collection of carbapenemase-producing K. pneumoniae, with MIC90 value of 1 mg/L and MICs of ≤4 mg/L for 98.9% of isolates. Disclosures M. R. Jacobs, Achaogen: Investigator, Research grant. Shionogi: Investigator, Research grant. L. Connolly, Achaogen, Inc.: Consultant, Consulting fee. K. M. Krause, Achaogen: Employee, Salary. S. S. Richter, bioMerieux: Grant Investigator, Research grant. BD Diagnostics: Grant Investigator, Research grant. Roche: Grant Investigator, Research grant. Hologic: Grant Investigator, Research grant. Diasorin: Grant Investigator, Research grant. Accelerate: Grant Investigator, Research grant. Biofire: Grant Investigator, Research grant. D. Van Duin, achaogen: Scientific Advisor, Consulting fee. shionogi: Scientific Advisor, Consulting fee. Allergan: Scientific Advisor, Consulting fee. Astellas: Scientific Advisor, Consulting fee. Neumedicine: Scientific Advisor, Consulting fee. Roche: Scientific Advisor, Consulting fee. T2 Biosystems: Scientific Advisor, Consulting fee.

scholarly journals OmpK26, a Novel Porin Associated with Carbapenem Resistance in Klebsiella pneumoniae

2011 ◽  
Vol 55 (10) ◽  
pp. 4742-4747 ◽  
Author(s):  
Laura García-Sureda ◽  
Antonio Doménech-Sánchez ◽  
Mariette Barbier ◽  
Carlos Juan ◽  
Joan Gascó ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Outer Membrane Proteins ◽  
Systemic Infection ◽  
Carbapenem Resistance ◽  
Resistant Isolate ◽  
Identical Result ◽  
Sequencing Analysis ◽  
Content Type ◽  
Carbapenem Resistant

ABSTRACTClinical isolates ofKlebsiella pneumoniaeresistant to carbapenems are being isolated with increasing frequency. Loss of the expression of the major nonspecific porins OmpK35/36 is a frequent feature in these isolates. In this study, we looked for porins that could compensate for the loss of the major porins in carbapenem-resistant organisms. Comparison of the outer membrane proteins from twoK. pneumoniaeclinical isogenic isolates that are susceptible (KpCS-1) and resistant (KpCR-1) to carbapenems revealed the absence of OmpK35/36 and the presence of a new 26-kDa protein in the resistant isolate. An identical result was obtained when another pair of isogenic isolates that are homoresistant (Kpn-3) and heteroresistant (Kpn-17) to carbapenems were compared. Mass spectrometry and DNA sequencing analysis demonstrated that this new protein, designated OmpK26, is a small monomeric oligogalacturonate-specific porin that belongs to the KdgM family of porins. Insertion-duplication mutagenesis of the OmpK26 coding gene,yjhA, in the carbapenem-resistant, porin-deficient isolate KpCR-1 caused the expression of OmpK36 and the reversion to the carbapenem-susceptible phenotype, suggesting that OmpK26 is indispensable for KpCR-1 to lose OmpK36 and become resistant to these antibiotics. Moreover, loss of the major porin and expression of OmpK26 reducedin vitrofitness and attenuated virulence in a murine model of acute systemic infection. Altogether, these results indicate that expression of the oligogalacturonate-specific porin OmpK26 compensates for the absence of OmpK35/36 and allows carbapenem resistance inK. pneumoniaebut cannot restore the fitness of the microorganism.

Comparison of in vitro activities of plazomicin and other aminoglycosides against clinical isolates of Klebsiella pneumoniae and Escherichia coli

2021 ◽  
Author(s):  
Gizem İnce ◽  
Hasan Cenk Mirza ◽  
Aylin Üsküdar Güçlü ◽  
Hale Gümüş ◽  
Çiğdem Erol ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Klebsiella Pneumoniae ◽  
Resistance Rate ◽  
Vitro Activity ◽  
Diffusion Method ◽  
In Vitro Activity ◽  
Carbapenem Resistant ◽  
Gradient Diffusion ◽  
Susceptibility Rate

Abstract Objectives To compare the in vitro activity of plazomicin and two older aminoglycosides (gentamicin and amikacin) against 180 isolates of Escherichia coli and Klebsiella pneumoniae, including subsets of 60 non-ESBL-producing, 60 ESBL-producing and 60 carbapenem-resistant (46 carrying blaOXA-48, 11 carrying blaNDM and 3 carrying blaOXA-48 and blaNDM) strains. Methods MICs of plazomicin, gentamicin and amikacin were determined by a gradient diffusion method. Gentamicin and amikacin MICs were interpreted according to CLSI criteria and EUCAST breakpoint tables. Plazomicin MICs were interpreted using FDA-defined breakpoints. Results All non-ESBL-producing and ESBL-producing isolates were susceptible to plazomicin. The plazomicin susceptibility rate (71.7%) in carbapenem-resistant isolates was significantly higher than those observed for gentamicin (45%) and amikacin (56.7% and 51.7% according to CLSI and EUCAST breakpoints, respectively). Gentamicin, amikacin and plazomicin susceptibility rates (35.6% for gentamicin; 44.4% and 37.8% for amikacin according to CLSI and EUCAST breakpoints, respectively; 64.4% for plazomicin) in carbapenem-resistant K. pneumoniae were significantly lower than those observed for carbapenem-resistant E. coli isolates (73.3% for gentamicin; 93.3% for amikacin and plazomicin). Gentamicin, amikacin and plazomicin susceptibility rates for blaNDM-positive isolates were lower than those observed for blaOXA-48-positive isolates, but differences were not statistically significant. Among the isolates that were non-susceptible to both gentamicin and amikacin, the plazomicin susceptibility rate was less than 30%. Conclusions Although plazomicin showed excellent in vitro activity against carbapenem-susceptible isolates, the plazomicin resistance rate increased to 35.6% among carbapenem-resistant K. pneumoniae and further increased to 45.5% among blaNDM-positive isolates.

scholarly journals In Vitro Activity of Cefotetan against ESBL-Producing Escherichia coli and Klebsiella pneumoniae Bloodstream Isolates from the MERINO Trial

2021 ◽  
Author(s):  
Adam G. Stewart ◽  
Kyra Cottrell ◽  
Andrew Henderson ◽  
Kanthi Vemuri ◽  
Michelle J. Bauer ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Klebsiella Pneumoniae ◽  
Severe Infection ◽  
Vitro Activity ◽  
In Vitro Activity ◽  
Gram Negative ◽  
Carbapenem Resistant

Carbapenem antibiotics remain the treatment of choice for severe infection due to ESBL- and AmpC-producing Enterobacterales . The use of carbapenems is a major driver of the emergence of carbapenem-resistant Gram-negative bacilli, which are often resistant to most available antimicrobials.

scholarly journals Antimicrobial agents active against carbapenem-resistant Escherichia coli and Klebsiella pneumoniae isolates in Lebanon

2018 ◽  
Vol 12 (03) ◽  
pp. 164-170 ◽  
Author(s):  
George Farah Araj ◽  
Aline Z Avedissian ◽  
Lina Y Itani ◽  
Jowana A Obeid
Keyword(s):  
Escherichia Coli ◽  
Retrospective Study ◽  
Klebsiella Pneumoniae ◽  
Antimicrobial Agents ◽  
Medical Center ◽  
In Vitro Activity ◽  
E Coli ◽  
Carbapenem Resistant ◽  
Promising Treatment

Introduction: It is not yet clear which antimicrobial agents should be used to treat the ominously increasing infections with carbapenem-resistant (CR) bacteria. We therefore investigated the activity of different antimicrobial agents against CR Escherichia coli and Klebsiella pneumoniae in Lebanon. Methodology: This retrospective study assessed the minimum inhibitory concentrations (MICs) of three carbapenems (by Etest), as well as the in vitro activity of eight other antimicrobials (by disk diffusion) against CR E. coli (n = 300) and K. pneumoniae (n = 232) isolates recovered at a major University Medical Center in Lebanon. Results: Higher percentages of isolates showing carbapenem MICs of ≤ 8 µg/mL were noted among the CR E. coli compared to the CR K. pneumoniae for ertapenem (48% vs 27%), imipenem (74 % vs 58%) and meropenem (82% vs 63%). Among the eight other antimicrobials, activity was generally higher when the MICs for the three carbapenems were ≤ 8 µg/mL. Regardless of the MIC level of the three carbapenems, very low susceptibility rates (≤ 33%) were noted for ciprofloxacin, trimethoprim-sulfamethoxazole and aztreonam against both E. coli and K. pneumoniae isolates. With Amikacin, higher susceptibility rates were seen against E. coli isolates (81%-97%) than against K. pneumoniae isolates (55%-86%), also reflecting higher activity than gentamicin (44%-54%). The best activity (66%-100%) was observed for tigecycline, colistin and fosfomycin against both CR species. Conclusions: Based on the in vitro findings in this study, the combination of a carbapenem showing an MIC of ≤ 8 µg/mL together with an active colistin, tigecycline, or fosfomycin, would offer a promising treatment option for patients infected with CR E. coli or K. pneumoniae.

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 Cefiderocol: A Novel Siderophore Cephalosporin Defeating Carbapenem-resistant Pathogens

2019 ◽  
Vol 69 (Supplement_7) ◽  
pp. S519-S520 ◽  
Author(s):  
Robert A Bonomo
Keyword(s):  
Late Stage ◽  
Transport Mechanism ◽  
Carbapenem Resistance ◽  
Resistance Mechanisms ◽  
Clinical Development ◽  
In Vitro Activity ◽  
Gram Negative ◽  
Carbapenem Resistant ◽  
Active Transport Mechanism

AbstractCefiderocol, a novel siderophore cephalosporin in late-stage clinical development, utilizes a “Trojan horse” active transport mechanism to enter bacteria and has proven in vitro activity against carbapenem-resistant gram-negative pathogens, including those with major carbapenem-resistance mechanisms, and stability against all carbapenemases.

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.

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