In Vitro Activity of β-Lactam Antimicrobial Agents in Combination with Aztreonam Tested Against Metallob-β-Lactamase-Producing Pseudomonas aeruginosa and Acinetobacter baumannii

Abstract Background Multidrug-resistant Enterobacteriaceae (Ent) and Pseudomonas aeruginosa (Pae) are involved in a considerable number of healthcare-associated infections, thus representing a therapeutic challenge. Ceftolozane–tazobactam (C/T) is a combination of a novel cephalosporin with a known β-lactamase inhibitor. Ceftolozane has high affinity for penicillin-binding proteins, improved outer membrane permeability, increased stability against efflux and enhanced stability against chromosomal AmpC β-lactamases compared with other β-lactam antibiotics. This agent is not active against carbapenemases. We evaluated the in vitro activity of C/T against clinical isolates of Ent and Pae collected from 2016- 2017 and compared it to the activity of broad-spectrum antimicrobial agents. Methods 1.644 Ent and Pae non-duplicate clinical isolates were collected in 13 medical centers located in 12 Colombian cities. Minimum inhibitory concentrations (MIC) were performed by broth microdilution and interpreted according to current CLSI guidelines. Isolates tested included 813 Escherichia coli (Eco), 441 Klebsiella pneumoniae (Kpn), 82 Enterobacter spp., (Enb); 60 Serratia marcescens (Sma) and 248 Pae. Comparator agents were ceftriaxone (CRO), cefotaxime (CTX), ceftazidime (CAZ), cefepime (FEP), piperacillin/tazobactam (TZP), ertapenem (ETP), imipenem (IMI), meropenem (MEM). Results Susceptibilities to C/T and comparators of 4 Ent species and Pae are shown in Table 1. Compared with other β-lactams such as CRO, CAZ, TZP, and FEP, C/T had considerably higher susceptibility rates against ESBL, non-carbapenem-resistant (CR) Eco and Kpn isolates. C/T MIC50/90 were: Eco (≤1/≤1); Kpn (≤1/128); Enb (≤1/64); Sma (≤1/≥256); Pae (≤1/≥256). In the case of P.aeruginosa despite the high resistance rates observed in the study, C/T had the best susceptibility, even higher than the carbapenems. Conclusion Overall, C/T demonstrated higher in vitro activity than currently available cephalosporins and TZP when tested against Ent and Pae. C/T provides an important treatment option against infections caused by non-carbapenemase producing Gram-negative pathogens. Further studies are warranted to identify an emerging mechanism of resistance in Colombia. Disclosures All authors: No reported disclosures.

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In-vitro activity of cationic peptides alone and in combination with clinically used antimicrobial agents against Pseudomonas aeruginosa

Journal of Antimicrobial Chemotherapy ◽

10.1093/jac/44.5.641 ◽

1999 ◽

Vol 44 (5) ◽

pp. 641-645 ◽

Cited By ~ 68

Author(s):

A. Giacometti ◽

O. Cirioni ◽

F. Barchiesi ◽

M. Fortuna ◽

G. Scalise

Keyword(s):

Pseudomonas Aeruginosa ◽

Antimicrobial Agents ◽

Vitro Activity ◽

Cationic Peptides ◽

In Vitro Activity

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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

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00786-09 ◽

2009 ◽

Vol 53 (11) ◽

pp. 4924-4926 ◽

Cited By ~ 42

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.

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In Vitro Activities of Tritrpticin Alone and in Combination with Other Antimicrobial Agents against Pseudomonas aeruginosa

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00652-06 ◽

2006 ◽

Vol 50 (11) ◽

pp. 3923-3925 ◽

Cited By ~ 16

Author(s):

Oscar Cirioni ◽

Andrea Giacometti ◽

Carmela Silvestri ◽

Agnese Della Vittoria ◽

Alberto Licci ◽

...

Keyword(s):

Pseudomonas Aeruginosa ◽

Antimicrobial Agents ◽

Inhibitory Concentration ◽

Multidrug Resistant ◽

Procoagulant Activity ◽

Vitro Activity ◽

In Vitro Activity

ABSTRACT The in vitro activity of the cathelicidin tritrpticin was investigated against multidrug-resistant Pseudomonas aeruginosa. The isolates were susceptible to the peptide at concentrations of 0.50 to 8 mg/liter. Tritrpticin completely inhibits lipopolysaccharide procoagulant activity at a 10 μM concentration. Fractionary inhibitory concentration indexes (0.385, 0.312, and 0.458) demonstrated synergy between the peptide and β-lactams.

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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

Pharmaceuticals ◽

10.3390/ph14040370 ◽

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.

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