In vitro synergistic activities of tobramycin and selected beta-lactams against 75 gram-negative clinical isolates.

1997 ◽  
Vol 41 (11) ◽  
pp. 2586-2588 ◽  
Author(s):  
R C Owens ◽  
M A Banevicius ◽  
D P Nicolau ◽  
C H Nightingale ◽  
R Quintiliani

The microdilution checkerboard technique was utilized to distinguish synergistic activity between tobramycin and four beta-lactams: piperacillin-tazobactam, ticarcillin-clavulanate, ceftazidime, and ceftriaxone. Beta-lactam-aminoglycoside combinations were tested against 75 clinical isolates of Pseudomonas aeruginosa, Acinetobacter baumanii, Citrobacterfreundii, Serratia marcescens, and Enterobacter cloacae. Despite in vitro susceptibilities, all isolates demonstrated either synergism or indifference; no antagonism was observed. Against pathogenic gram-negative nosocomial isolates, a greater percentage of synergy was consistently observed with combination regimens containing tobramycin and piperacillin-tazobactam or ticarcillin-clavulanate than with the cephalosporin-containing regimens.

Author(s):  
Olga Lomovskaya ◽  
Debora Rubio-Aparicio ◽  
Kirk Nelson ◽  
Dongxu Sun ◽  
Ruslan Tsivkovski ◽  
...  

QPX7728 is an ultra-broad-spectrum beta-lactamase inhibitor with potent inhibition of key serine and metallo beta-lactamases. QPX7728 enhances the potency of multiple beta-lactams in beta-lactamase producing Enterobacterales and Acinetobacter spp. In this study we evaluated the in vitro activity of QPX7728 (8 μg/ml) combined with multiple beta-lactams against clinical isolates of Pseudomonas aeruginosa with varying beta-lactam resistance mechanisms. Seven-hundred-ninety clinical isolates were included in this study; 500 isolates, termed a “representative panel”, were selected to be representative the MIC distribution of meropenem (MEM), ceftazidime-avibactam (CAZ-AVI), and ceftolozane-tazobactam (TOL-TAZ) resistance for clinical isolates according to 2017 SENTRY surveillance data (representative panel). An additional 290 selected isolates (“challenge panel”), that were either non-susceptible to MEM or were resistant to TOL-TAZ or CAZ-AVI were also tested; 61 strains carried metallo beta-lactamases (MBLs), 211 strains were defective in the carbapenem porin OprD and 185 strains had the MexAB-OprM efflux pump overproduced based on a phenotypic test. Against the representative panel, susceptibility for all QPX7728/beta-lactam combinations was >90%. For the challenge panel, QPX-ceftolozane (TOL) was the most active combination (78.6% susceptible) followed by equipotent QPX-piperacillin (PIP) and QPX-cefepime (FEP), restoring susceptibility in 70.3% of strains (CLSI breakpoints for the beta-lactam compound alone). For MBL-negative strains, QPX-TOL and QPX-FEP restored the MIC values to susceptibility rates in ∼90% and ∼80% of strains, respectively, vs 68-70% for QPX-MEM and QPX-PIP and 63-65% for TOL-TAZ and CAZ-AVI. For MBL-positive strains, QPX-PIP restored the MIC to susceptibility values for ∼70% of strains vs 2-40% for other combinations. Increased efflux and impaired OprD had varying effect on QPX7728 combination depending on the partner beta-lactam tested. QPX7728 enhanced the potency of multiple beta-lactams against P. aeruginosa, with varying results according to the beta-lactamase production and other intrinsic resistance mechanisms.


2008 ◽  
Vol 52 (11) ◽  
pp. 4023-4029 ◽  
Author(s):  
Gian Maria Rossolini ◽  
Francesco Luzzaro ◽  
Roberta Migliavacca ◽  
Claudia Mugnaioli ◽  
Beatrice Pini ◽  
...  

ABSTRACT Metallo-β-lactamases (MBLs) can confer resistance to most β-lactams, including carbapenems. Their emergence in gram-negative pathogens is a matter of major concern. Italy was the first European country to report the presence of acquired MBLs in gram-negative pathogens and is one of the countries where MBL producers have been detected repeatedly. Here, we present the results of the first Italian nationwide survey of acquired MBLs in gram-negative pathogens. Of 14,812 consecutive nonreplicate clinical isolates (12,245 Enterobacteriaceae isolates and 2,567 gram-negative nonfermenters) screened for reduced carbapenem susceptibility during a 4-month period (September to December 2004), 30 isolates (28 Pseudomonas aeruginosa isolates, 1 Pseudomonas putida isolate, and 1 Enterobacter cloacae isolate) carried acquired MBL determinants. MBL producers were detected in 10 of 12 cities, with a predominance of VIM-type enzymes over IMP-type enzymes (4:1). Although having an overall low prevalence (1.3%) and significant geographical differences, MBL-producing P. aeruginosa strains appeared to be widespread in Italy, with a notable diversity of clones, enzymes, and integrons carrying MBL gene cassettes.


2020 ◽  
Vol 75 (9) ◽  
pp. 2609-2615 ◽  
Author(s):  
Yawei Zhang ◽  
Chunjiang Zhao ◽  
Qi Wang ◽  
Xiaojuan Wang ◽  
Hongbin Chen ◽  
...  

Abstract Background SPR206 is a novel polymyxin analogue. Activity against clinical isolates is little documented. Methods A collection of 200 MDR, carbapenem-resistant, tigecycline-resistant, colistin-resistant and non-MDR clinical isolates of Acinetobacter baumannii, Pseudomonas aeruginosa, Klebsiella pneumoniae, Escherichia coli, Enterobacter cloacae and Stenotrophomonas maltophilia was obtained from 50 centres across China (2016–17). All isolates were derived from respiratory tract, urine and blood samples. Strains were purposely selected on the basis of phenotypes, genotypes and specimen origins. MICs of SPR206 and other antimicrobials were determined. Results SPR206 was active against all bacteria tested except colistin-resistant isolates. The MIC50/90 values of SPR206 for colistin-resistant strains were comparable to known polymyxins (16/128 versus 8/128 mg/L). SPR206 exhibited potent activity against colistin-susceptible OXA-producing A. baumannii (MIC50/90 = 0.064/0.125 mg/L), NDM-producing Enterobacteriaceae (MIC50/90 = 0.125/0.25 mg/L) and KPC-2-producing Enterobacteriaceae (MIC50/90 = 0.125/0.5 mg/L). In fact, SPR206 was the most potent agent tested, with 2- to 4-fold lower MICs than colistin and polymyxin B for A. baumannii, P. aeruginosa and Enterobacteriaceae. Additionally, MIC values of SPR206 (MIC50/90 = 0.064/0.125 mg/L) were 16- to 32-fold lower than those of tigecycline (MIC50/90 = 2/2 mg/L) for tigecycline-susceptible carbapenem-resistant A. baumannii. Conclusions SPR206 showed good in vitro activity against MDR, tigecycline-resistant and non-MDR clinical isolates of Gram-negative pathogens. SPR206 also exhibited superior potency to colistin and polymyxin B, with 2- to 4-fold lower MIC50/90 values.


1984 ◽  
Vol 37 (12) ◽  
pp. 1681-1686 ◽  
Author(s):  
KOZO KITAURA ◽  
KAZUYUKI MINEURA ◽  
NOBUHIRO NAKAMIZO ◽  
KHOYA SHIBA ◽  
MASAHISA OHMORI ◽  
...  

2010 ◽  
Vol 59 (5) ◽  
pp. 511-520 ◽  
Author(s):  
Thomas S. Murray ◽  
Michel Ledizet ◽  
Barbara I. Kazmierczak

Pseudomonas aeruginosa is an opportunistic Gram-negative pathogen capable of acutely infecting or persistently colonizing susceptible hosts. P. aeruginosa colonizes surfaces in vitro by either biofilm formation or swarming motility. The choice of behaviour is influenced by the physical properties of the surface and specific nutrient availability, and subject to regulatory networks that also govern type 2 and type 3 protein secretion. Biofilm formation by clinical isolates has been well-studied. However, the swarming behaviour of human isolates has not been extensively analysed. We collected isolates from 237 hospitalized patients without cystic fibrosis and analysed motility and secretion phenotypes of each isolate. We found biofilm formation and swarming to be negatively associated, while swarming was positively associated with the secretion of both proteases and type 3 exoenzymes. Most isolates were capable of type 3 secretion and biofilm formation, even though these traits are considered to favour distinct modes of pathogenesis. Our data demonstrate that while clinical isolates display diverse motility, biofilm and secretion phenotypes, many of the predicted relationships between swarming motility and other phenotypes observed in laboratory strains also hold true for bacteria isolated from human patients.


2006 ◽  
Vol 55 (1) ◽  
pp. 59-63 ◽  
Author(s):  
Margaret Ip ◽  
Sau Lai Lui ◽  
Vincent K. M. Poon ◽  
Ivan Lung ◽  
Andrew Burd

A range of silver-coated or -impregnated dressings are now commercially available for use but comparative data on their antimicrobial efficacies are limited. The antibacterial activities of five commercially available silver-coated/impregnated dressings were compared against nine common burn-wound pathogens, namely methicillin-sensitive and -resistant Staphylococcus aureus (MRSA), Enterococcus faecalis, Pseudomonas aeruginosa, Escherichia coli, Enterobacter cloacae, Proteus vulgaris, Acinetobacter baumannii and a multi-drug-efflux-positive Acinetobacter baumannii (BM4454), using a broth culture method. The rapidity and extent of killing of these pathogens under in vitro conditions were evaluated. All five silver-impregnated dressings investigated exerted bactericidal activity, particularly against Gram-negative bacteria, including Enterobacter species, Proteus species and E. coli. The spectrum and rapidity of action, however, ranged widely for different dressings. Acticoat and Contreet had a broad spectrum of bactericidal activities against both Gram-positive and -negative bacteria. Contreet was characterized by a very rapid bactericidal action and achieved a reduction of ⩾10 000 c.f.u. ml−1 in the first 30 min for Enterobacter cloacae, Proteus vulgaris, Pseudomonas aeruginosa and Acinetobacter baumanii. Other dressings demonstrated a narrower range of bactericidal activities. Understanding the characteristics of these dressings may enable them to be targeted more appropriately according to the specific requirements for use of a particular dressing, as in for prophylaxis in skin grafting or for an infected wound with MRSA.


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