scholarly journals In VitroActivity of Telavancin in Combination with Colistin versus Gram-Negative Bacterial Pathogens

2012 ◽  
Vol 56 (6) ◽  
pp. 3080-3085 ◽  
Author(s):  
Michael Hornsey ◽  
Christopher Longshaw ◽  
Lynette Phee ◽  
David W. Wareham
Keyword(s):  
Therapeutic Option ◽  
Multidrug Resistant ◽  
Clinical Isolates ◽  
Dilution Method ◽  
Agar Dilution Method ◽  
Gram Negative ◽  
Content Type ◽  
Log Reduction ◽  
Time Kill

ABSTRACTThe treatment of Gram-negative infections is increasingly compromised by the spread of resistance. With few agents currently in development, clinicians are now considering the use of unorthodox combination therapies for multidrug-resistant strains. Here we assessed thein vitroactivity of the novel lipoglycopeptide telavancin (TLV) when combined with colistin (COL) versus 13 Gram-negative type strains and 66 clinical isolates. Marked synergy was observed in either checkerboard (fractional inhibitory concentration index [FICI], <0.5; susceptibility breakpoint index [SBPI], >2) or time-kill assays (>2-log reduction in viable counts compared with starting inocula at 24 h) versus the majority of COL-susceptible enterobacteria,Stenotrophomonas maltophilia, andAcinetobacter baumanniiisolates, but only limited effects were seen againstPseudomonas aeruginosaor strains with COL resistance. Using an Etest/agar dilution method, the activity of TLV was potentiated by relatively low concentrations of COL (0.25 to 0.75 μg/ml), reducing the MIC of TLV from >32 μg/ml to ≤1 μg/ml for 35% of the clinical isolates. This provides further evidence that glycopeptide-polymyxin combinations may be a useful therapeutic option in the treatment of Gram-negative infections.

In vitro activity of a novel antibacterial agent, levonadifloxacin, against clinical isolates collected in a prospective, multicentre surveillance study in India during 2016–18

2019 ◽  
Vol 75 (3) ◽  
pp. 600-608 ◽  
Author(s):  
Boppe Appalaraju ◽  
Sujata Baveja ◽  
Shrikala Baliga ◽  
Suchitra Shenoy ◽  
Renu Bhardwaj ◽  
...  
Keyword(s):  
Therapeutic Option ◽  
Tertiary Care ◽  
Vitro Activity ◽  
Clinical Isolates ◽  
Surveillance Study ◽  
Dilution Method ◽  
Agar Dilution Method ◽  
In Vitro Activity ◽  
Broth Microdilution Method

Abstract Background Levonadifloxacin is a novel antibiotic belonging to the benzoquinolizine subclass of fluoroquinolones with potent activity against MRSA and quinolone-resistant Staphylococcus aureus. IV levonadifloxacin and its oral prodrug alalevonadifloxacin have recently been approved in India for the treatment of acute bacterial skin and skin structure infections (ABSSSIs) including diabetic foot infections. Objectives To investigate the in vitro activity of levonadifloxacin against contemporary clinical isolates collected from multiple tertiary care hospitals across India in the Antimicrobial Susceptibility Profiling of Indian Resistotypes (ASPIRE) surveillance study. Methods A total of 1376 clinical isolates, consisting of staphylococci (n = 677), streptococci (n = 178), Enterobacterales (n = 320), Pseudomonas aeruginosa (n = 140) and Acinetobacter baumannii (n = 61), collected (2016–18) from 16 tertiary hospitals located across 12 states in India, were included in the study. The MICs of levonadifloxacin and comparator antibiotics were determined using the reference agar dilution method and broth microdilution method. Results Levonadifloxacin exhibited potent activity against MSSA (MIC50/90: 0.5/1 mg/L), MRSA (MIC50/90: 0.5/1 mg/L) and levofloxacin-resistant S. aureus (MIC50/90: 1/1 mg/L) isolates. Similarly, potent activity of levonadifloxacin was also observed against CoNS including MDR isolates (MIC50/90: 1/2 mg/L). Against Streptococcus pneumoniae, levonadifloxacin (MIC50/90: 0.5/0.5 mg/L) showed superior activity compared with levofloxacin (MIC50/90: 1/2 mg/L). Among levofloxacin-susceptible Enterobacterales, 80.6% of isolates were inhibited at ≤2 mg/L levonadifloxacin. Conclusions Levonadifloxacin displayed potent activity against contemporary MRSA and fluoroquinolone-resistant staphylococcal isolates, thus offering a valuable IV as well as an oral therapeutic option for the treatment of ABSSSIs. Furthermore, levonadifloxacin exhibited a broad-spectrum activity profile as evident from its activity against streptococci and levofloxacin-susceptible Gram-negative isolates.

scholarly journals Efficacy of Humanized Exposures of Cefiderocol (S-649266) against a Diverse Population of Gram-Negative Bacteria in a Murine Thigh Infection Model

2017 ◽  
Vol 61 (11) ◽  
Author(s):  
Marguerite L. Monogue ◽  
Masakatsu Tsuji ◽  
Yoshinori Yamano ◽  
Roger Echols ◽  
David P. Nicolau
Keyword(s):  
Antibacterial Activity ◽  
Multidrug Resistant ◽  
Infection Model ◽  
Gram Negative Bacteria ◽  
Diverse Population ◽  
Gram Negative ◽  
Content Type ◽  
Log Reduction

ABSTRACT Cefiderocol (S-649266) is a novel siderophore cephalosporin with potent in vitro activity against clinically encountered multidrug-resistant (MDR) Gram-negative isolates; however, its spectrum of antibacterial activity against these difficult-to-treat isolates remains to be fully explored in vivo. Here, we evaluated the efficacy of cefiderocol humanized exposures in a neutropenic murine thigh model to support a suitable MIC breakpoint. Furthermore, we compared cefiderocol's efficacy with humanized exposures of meropenem and cefepime against a subset of these phenotypically diverse isolates. Ninety-five Gram-negative isolates were studied. Efficacy was determined as the change in log10 CFU at 24 h compared with 0-h controls. Bacterial stasis or ≥1 log reduction in 67 isolates with MICs of ≤4 μg/ml was noted in 77, 88, and 85% of Enterobacteriaceae, Acinetobacter baumannii, and Pseudomonas aeruginosa, respectively. For isolates with MICs of ≥8 μg/ml, bacterial stasis or ≥1 log10 reduction was observed in only 2 of 28 (8 Enterobacteriaceae, 19 A. baumannii, and 1 P. aeruginosa) strains. Against highly resistant meropenem and cefepime organisms, cefiderocol maintained its in vivo efficacy. Overall, humanized exposures of cefiderocol produced similar reductions in bacterial density for organisms with MICs of ≤4 μg/ml, whereas isolates with MICs of ≥8 μg/ml generally displayed bacterial growth in the presence of the compound. Data derived in the current study will assist with the delineation of MIC susceptibility breakpoints for cefiderocol against these important nosocomial Gram-negative pathogens; however, additional clinical data are required to substantiate these observations.

scholarly journals 616. Evaluation of In Vitro Susceptibility to Ceftazidime/Avibactam of Clinical Isolates of Carbapenem Nonsusceptible Gram-Negative Bacilli from Colombia

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S287-S287
Author(s):  
Tobias M Appel ◽  
Maria F Mojica ◽  
Elsa De La Cadena ◽  
Christian Pallares ◽  
Maria Virginia Villegas
Keyword(s):  
Therapeutic Option ◽  
Generation Cephalosporin ◽  
Multidrug Resistant ◽  
Resistance Mechanisms ◽  
Clinical Isolates ◽  
In Vitro Susceptibility ◽  
Gram Negative ◽  
Fixed Concentration ◽  
Class B

Abstract Background Ceftazidime/avibactam (CZA) is a combination of a third-generation cephalosporin and a diazabicyclooctane β-lactamase inhibitor, which is active against a broad range of class A, C and D β-lactamases. In Colombia, high rates of multidrug-resistant Enterobacteriaceae (Ent)and P. aeruginosa (Pae) have been reported. Of special concern are KPC enzymes endemic in Ent and found in Pae, which are associated with higher mortality and healthcare costs, as well as limited therapeutic options. Herein, we evaluate the susceptibility of clinical isolates of carbapenem nonsusceptible Ent (CNS-E) and Pae (CNS-P) to CZA with the aim of understanding its role as a therapeutic option for these bacteria. Methods Three hundred ninety-nine nonduplicate clinical isolates of carbapenem nonsusceptible Gram-negative bacilli were collected in 13 medical centers from 12 Colombian cities, from January 2016 to October 2017 (137 K. pneumoniae [Kpn], 76 E. coli, 34 Enterobacter spp., 21 S. marcescens [Sma] and 131 Pae). CNS-E was defined as minimum inhibitory concentrations (MIC) ≥1 mg/L for ertapenem and CNS-P was defined as MIC ≥4 mg/L for meropenem. MIC were determined by broth microdilution and interpreted according to current CLSI guidelines. CZA MIC were determined using double dilutions of ceftazidime and a fixed concentration of avibactam of 4 mg/L. Comparator agents were ceftazidime, cefepime, piperacillin/tazobactam, imipenem, meropenem, tigecycline (TGC), and fosfomycin (FOS). Results Antimicrobial activity of CZA and comparators is shown in Table 1. CZA susceptibility ranged from 69% in Kpn to 81% in Sma, whereas 49% of CNS-P were susceptible to CZA. In both, CNS-E and CNS-P, CZA was superior to all other tested β-lactam compounds. Notably, in CNS-E CZA susceptibility was comparable to FOS and TGC (except for TGC in Sma). Conclusion CZA is the most active β-lactam against CNS-E and CNS-P. CZA nonsusceptibility suggests the presence of other resistance mechanisms, such as class B β-lactamases that are not inhibited by avibactam, and which are more frequently reported in CNS-P. Our results highlight the key role of new agents such as CZA in KPC endemic countries and the need for surveillance studies to determine the nature of resistance mechanisms. Disclosures All authors: No reported disclosures.

scholarly journals In Vitro Activity of Ceftolozane-Tazobactam against Multidrug-Resistant Nonfermenting Gram-Negative Bacilli Isolated from Patients with Cystic Fibrosis

2017 ◽  
Vol 61 (4) ◽  
Author(s):  
Patrick Grohs ◽  
Gary Taieb ◽  
Philippe Morand ◽  
Iheb Kaibi ◽  
Isabelle Podglajen ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Stenotrophomonas Maltophilia ◽  
Active Agent ◽  
Multidrug Resistant ◽  
In Vitro Activity ◽  
Gram Negative ◽  
Content Type ◽  
Time Kill

ABSTRACT Ceftolozane-tazobactam was tested against 58 multidrug-resistant nonfermenting Gram-negative bacilli (35 Pseudomonas aeruginosa, 11 Achromobacter xylosoxydans, and 12 Stenotrophomonas maltophilia isolates) isolated from cystic fibrosis patients and was compared to ceftolozane alone, ceftazidime, meropenem, and piperacillin-tazobactam. Ceftolozane-tazobactam was the most active agent against P. aeruginosa but was inactive against A. xylosoxydans and S. maltophilia. In time-kill experiments, ceftolozane-tazobactam had complete bactericidal activity against 2/6 clinical isolates (33%).

scholarly journals In Vitro Activity of Ceftaroline Alone and in Combination against Clinical Isolates of Resistant Gram-Negative Pathogens, Including β-Lactamase-Producing Enterobacteriaceae and Pseudomonas aeruginosa

2009 ◽  
Vol 53 (6) ◽  
pp. 2360-2366 ◽  
Author(s):  
Céline Vidaillac ◽  
Steve N. Leonard ◽  
Helio S. Sader ◽  
Ronald N. Jones ◽  
Michael J. Rybak
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Therapeutic Option ◽  
Multidrug Resistant ◽  
Vitro Activity ◽  
In Vitro Activity ◽  
Clinical Value ◽  
Gram Negative ◽  
E Coli ◽  
Time Kill

ABSTRACT Ceftaroline is a novel broad-spectrum cephalosporin that exhibits bactericidal activity against many gram-positive and -negative pathogens. However, the activity of ceftaroline cannot be solely relied upon for eradication of multidrug-resistant gram-negative isolates, such as Pseudomonas aeruginosa and extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae, which represent a current clinical concern. As drug combinations might be beneficial by potential synergy, we evaluated the in vitro activity of ceftaroline combined with meropenem, aztreonam, cefepime, tazobactam, amikacin, levofloxacin, and tigecycline. Susceptibility testing was performed for 20 clinical P. aeruginosa isolates, 10 ESBL-producing Escherichia coli isolates, 10 ESBL-producing Klebsiella pneumoniae isolates, and 10 AmpC-derepressed Enterobacter cloacae isolates. Time-kill experiments were performed for 10 isolates using antimicrobials at one-fourth the MIC. Ceftaroline exhibited a MIC range of 0.125 to 1,024 μg/ml and was reduced 2- to 512-fold by combination with tazobactam (4 μg/ml) for ESBL-producing strains. In time-kill experiments, ceftaroline plus amikacin was synergistic against 90% of the isolates (and indifferent for one P. aeruginosa isolate). Ceftaroline plus tazobactam was indifferent for E. cloacae and P. aeruginosa strains but synergistic against 100% of E. coli and K. pneumoniae isolates. Combinations of ceftaroline plus meropenem or aztreonam were also synergistic for all E. coli and E. cloacae isolates, respectively, but indifferent against 90% of the other isolates. Finally, combinations of ceftaroline plus either tigecycline, levofloxacin, or cefepime were indifferent for 100% of the isolates. No antagonism was observed with any combination. Ceftaroline plus amikacin appeared as the most likely synergistic combination. This represents a promising therapeutic option, and further studies are warranted to elucidate the clinical value of ceftaroline combinations against resistant gram-negative pathogens.

scholarly journals Novel Phage Lysin Capable of Killing the Multidrug-Resistant Gram-Negative Bacterium Acinetobacter baumannii in a Mouse Bacteremia Model

2015 ◽  
Vol 59 (4) ◽  
pp. 1983-1991 ◽  
Author(s):  
Rolf Lood ◽  
Benjamin Y. Winer ◽  
Adam J. Pelzek ◽  
Roberto Diez-Martinez ◽  
Mya Thandar ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Genomic Library ◽  
Multidrug Resistant ◽  
Clinical Isolates ◽  
Gram Negative ◽  
Content Type ◽  
Highly Active ◽  
Genes Encoding

ABSTRACTAcinetobacter baumannii, a Gram-negative multidrug-resistant (MDR) bacterium, is now recognized as one of the more common nosocomial pathogens. Because most clinical isolates are found to be multidrug resistant, alternative therapies need to be developed to control this pathogen. We constructed a bacteriophage genomic library based on prophages induced from 13A. baumanniistrains and screened it for genes encoding bacteriolytic activity. Using this approach, we identified 21 distinct lysins with different activities and sequence diversity that were capable of killingA. baumannii. The lysin (PlyF307) displaying the greatest activity was further characterized and was shown to efficiently kill (>5-log-unit decrease) all testedA. baumanniiclinical isolates. Treatment with PlyF307 was able to significantly reduce planktonic and biofilmA. baumanniibothin vitroandin vivo. Finally, PlyF307 rescued mice from lethalA. baumanniibacteremia and as such represents the first highly active therapeutic lysin specific for Gram-negative organisms in an array of native lysins found inAcinetobacterphage.

scholarly journals WCK 5222 (Cefepime-Zidebactam) Antimicrobial Activity against Clinical Isolates of Gram-Negative Bacteria Collected Worldwide in 2015

2017 ◽  
Vol 61 (5) ◽  
Author(s):  
Helio S. Sader ◽  
Mariana Castanheira ◽  
Michael Huband ◽  
Ronald N. Jones ◽  
Robert K. Flamm
Keyword(s):  
Antimicrobial Activity ◽  
Bacterial Infections ◽  
The United States ◽  
Multidrug Resistant ◽  
Clinical Isolates ◽  
Asia Pacific ◽  
Gram Negative ◽  
Content Type ◽  
Broth Microdilution Method

ABSTRACT WCK 5222 consists of cefepime combined with zidebactam, a bicyclo-acyl hydrazide β-lactam enhancer antibiotic with a dual action involving binding to Gram-negative bacterial PBP2 and β-lactamase inhibition. We evaluated the in vitro activity of cefepime-zidebactam against 7,876 contemporary (2015) clinical isolates of Enterobacteriaceae (n = 5,946), Pseudomonas aeruginosa (n = 1,291), and Acinetobacter spp. (n = 639) from the United States (n = 2,919), Europe (n = 3,004), the Asia-Pacific (n = 1,370), and Latin America (n = 583). The isolates were tested by a reference broth microdilution method for susceptibility against cefepime-zidebactam (1:1 and 2:1 ratios) and comparator agents. Cefepime-zidebactam was the most active compound tested against Enterobacteriaceae (MIC50/90, ≤0.03/0.12 μg/ml [1:1] and 0.06/0.25 μg/ml [2:1]; 99.9% of isolates were inhibited at ≤4 [1:1] and ≤8 μg/ml [2:1]). Cefepime-zidebactam was active against individual Enterobacteriaceae species (MIC50/90, ≤0.03 to 0.06/≤0.03 to 0.5 μg/ml [1:1]) and retained potent activity against carbapenem-resistant isolates (MIC50/90, 1/4 μg/ml; 99.3% of isolates were inhibited at ≤8 μg/ml [1:1]). Cefepime-zidebactam activity was consistent among geographic regions, and only one isolate showed MIC values of >8 μg/ml (1:1). Cefepime-zidebactam was also very active against P. aeruginosa with MIC50/90 values of 1/4 μg/ml, and 99.5% of isolates were inhibited at ≤8 μg/ml (1:1). The MIC values for cefepime-zidebactam at the 1:1 ratio were generally 2-fold lower than those for cefepime-zidebactam at the 2:1 ratio (MIC50/90, 2/8 μg/ml) and zidebactam alone (MIC50/90, 4/8 μg/ml). Against Acinetobacter spp., cefepime-zidebactam at 1:1 and 2:1 ratios (MIC50/90, 16/32 μg/ml for both) was 4-fold more active than cefepime or ceftazidime. Zidebactam exhibited potent in vitro antimicrobial activity against some organisms. These results support the clinical development of WCK 5222 for the treatment of Gram-negative bacterial infections, including those caused by multidrug-resistant isolates.

scholarly journals Comparative In Vivo Antibacterial Activity of Human-Simulated Exposures of Cefiderocol and Ceftazidime against Stenotrophomonas maltophilia in the Murine Thigh Model

2019 ◽  
Vol 63 (12) ◽  
Author(s):  
Iris H. Chen ◽  
James M. Kidd ◽  
Kamilia Abdelraouf ◽  
David P. Nicolau
Keyword(s):  
Stenotrophomonas Maltophilia ◽  
Multidrug Resistant ◽  
Bacterial Reduction ◽  
Bacterial Killing ◽  
Gram Negative ◽  
Content Type ◽  
Log Reduction ◽  
Gram Negative Organisms

ABSTRACT Cefiderocol is a novel siderophore cephalosporin that utilizes bacterial ferric iron transports to cross the outer membrane. Cefiderocol shows high stability against all classes of β-lactamases, rendering it extremely potent against carbapenem- and multidrug-resistant Gram-negative organisms. Using a neutropenic murine thigh model, we compared the efficacies of human-simulated exposures of cefiderocol (20-g, 3-h infusion every 8 h [Q8H]) and ceftazidime (2-g, 2-h infusion Q8H) against Stenotrophomonas maltophilia, an emerging opportunistic Gram-negative organism associated with serious and often fatal nosocomial infections. Twenty-four S. maltophilia isolates were studied, including isolates resistant to ceftazidime, trimethoprim-sulfate, and/or levofloxacin. The thighs were inoculated with bacterial suspensions of 108 CFU/ml, and the human-simulated regimens were administered over 24 h. Efficacy was measured as the change in log10 CFU/thigh at 24 h compared to 0-h controls. Cefiderocol human-simulated exposure demonstrated potent bacterial killing; the mean bacterial reduction at 24 h was −2.67 ± 0.68 log10 CFU/thigh with ≥2-log reduction achieved in 21 isolates (87.5%) and a ≥1-log reduction achieved in the remaining 3 isolates (12.5%). In comparison, ceftazidime human-simulated exposure produced a mean bacterial reduction of −1.38 ± 1.49 log10 CFU/thigh among 10 ceftazidime-susceptible isolates and a mean bacterial growth of 0.64 ± 0.79 log10 CFU/thigh among 14 ceftazidime-nonsusceptible isolates. Although ceftazidime showed modest efficacy against most susceptible isolates, humanized cefiderocol exposures resulted in remarkable in vivo activity against all S. maltophilia isolates examined, inclusive of ceftazidime-nonsusceptible isolates. The potent in vitro and in vivo activity of cefiderocol supports the development of this novel compound for managing S. maltophilia infections.

scholarly journals In Vitro Activity of Eravacycline against Gram-Negative Bacilli Isolated in Clinical Laboratories Worldwide from 2013 to 2017

2019 ◽  
Vol 64 (3) ◽  
Author(s):  
Ian Morrissey ◽  
Melanie Olesky ◽  
Stephen Hawser ◽  
Sibylle H. Lob ◽  
James A. Karlowsky ◽  
...  
Keyword(s):  
Antimicrobial Agents ◽  
Multidrug Resistant ◽  
Clinical Isolates ◽  
Gram Negative ◽  
Content Type ◽  
Microdilution Method ◽  
Clinical Laboratories ◽  
Serious Infections ◽  
Broth Microdilution Method

ABSTRACT Eravacycline is a novel, fully synthetic fluorocycline antibiotic developed for the treatment of serious infections, including those caused by multidrug-resistant (MDR) pathogens. Here, we evaluated the in vitro activities of eravacycline and comparator antimicrobial agents against a global collection of frequently encountered clinical isolates of Gram-negative bacilli. The CLSI broth microdilution method was used to determine MIC data for isolates of Enterobacterales (n = 13,983), Acinetobacter baumannii (n = 2,097), Pseudomonas aeruginosa (n = 1,647), and Stenotrophomonas maltophilia (n = 1,210) isolated primarily from respiratory, intra-abdominal, and urinary specimens by clinical laboratories in 36 countries from 2013 to 2017. Susceptibilities were interpreted using both CLSI and EUCAST breakpoints. Multidrug-resistant (MDR) isolates were defined by resistance to agents from ≥3 different antimicrobial classes. The MIC90s ranged from 0.25 to 1 μg/ml for Enterobacteriaceae and were 1 μg/ml for A. baumannii and 2 μg/ml for S. maltophilia, Proteus mirabilis, and Serratia marcescens. Eravacycline’s potency was up to 4-fold greater than that of tigecycline against genera/species of Enterobacterales, A. baumannii, and S. maltophilia. The MIC90s for five of six individual genera/species of Enterobacterales and A. baumannii were within 2-fold of the MIC90s for their respective subsets of MDR isolates, while the MDR subpopulation of Klebsiella spp. demonstrated 4-fold higher MIC90s. Eravacycline demonstrated potent in vitro activity against the majority of clinical isolates of Gram-negative bacilli, including MDR isolates, collected over a 5-year period. This study further underscores the potential benefit of eravacycline in the treatment of infections caused by MDR Gram-negative pathogens.

scholarly journals Activity of Meropenem Combined with RPX7009, a Novel β-Lactamase Inhibitor, against Gram-Negative Clinical Isolates in New York City

2015 ◽  
Vol 59 (8) ◽  
pp. 4856-4860 ◽  
Author(s):  
Amabel Lapuebla ◽  
Marie Abdallah ◽  
Olawole Olafisoye ◽  
Christopher Cortes ◽  
Carl Urban ◽  
...  
Keyword(s):  
New York ◽  
New York City ◽  
York City ◽  
Carbapenem Resistance ◽  
Multidrug Resistant ◽  
Clinical Isolates ◽  
Gram Negative ◽  
Content Type ◽  
Lactamase Inhibitor

ABSTRACTMultidrug-resistantKlebsiella pneumoniaecarbapenemase (KPC)-producingEnterobacteriaceaeare endemic to hospitals in New York City and other regions. RPX7009 is a novel β-lactamase inhibitor with activity against serine carbapenemases. We tested the activity of meropenem plus RPX7009 against 4,500 recent Gram-negative clinical isolates from 11 New York City hospitals. The meropenem-RPX7009 combination was found to have excellentin vitroactivity againstEscherichia coli,K. pneumoniae, andEnterobacterspp., including multidrug-resistant (MDR) KPC-producing strains. Overall, 131/133 (98.5%) KPC-producingEnterobacteriaceaestrains were inhibited by meropenem (≤1 μg/ml) plus RPX7009 (8 μg/ml). In a limited number of strains, the combination appeared to have reduced activity against KPC-producingK. pneumoniaeisolates with diminishedompK35andompK36expression. The addition of RPX7009 did not affect the activity of meropenem againstAcinetobacter baumanniiandPseudomonas aeruginosa. The meropenem-RPX7009 combination shows promise as a novel agent against KPC-producingEnterobacteriaceaeand deserves further study. Other approaches will be needed to address multidrug-resistantA. baumanniiandP. aeruginosa, which typically possess different mechanisms of carbapenem resistance.

Sign in / Sign up

Export Citation Format

Share Document