In Vitro Susceptibility of Gram-negative Pathogens to Cefiderocol in Five Consecutive Annual Multinational SIDERO-WT Surveillance Studies (2014-2019)

2021 ◽  
Author(s):  
James A. Karlowsky ◽  
Meredith A. Hackel ◽  
Miki Takemura ◽  
Yoshinori Yamano ◽  
Echols Roger ◽  
...  
Keyword(s):  
North America ◽  
Burkholderia Cepacia ◽  
Stenotrophomonas Maltophilia ◽  
Clinical Isolates ◽  
In Vitro Susceptibility ◽  
Gram Negative ◽  
Surveillance Studies ◽  
Susceptibility Data ◽  
Clinical Breakpoints

We report in vitro susceptibility data from five consecutive annual SIDERO-WT surveillance studies (2014-2019) for cefiderocol and comparators tested against Gram-negative clinical isolates from North America and Europe. CLSI broth microdilution was used to determine MICs for Enterobacterales ( n =31,896), Pseudomonas aeruginosa ( n =7,700), Acinetobacter baumannii complex ( n =5,225), Stenotrophomonas maltophilia ( n =2,030), and Burkholderia cepacia complex ( n =425). MICs were interpreted by CLSI-approved clinical breakpoints (February 2021). Cefiderocol inhibited 99.8%, 96.7%, 91.6%, and 97.7% of all Enterobacterales , meropenem-nonsusceptible, ceftazidime-avibactam-nonsusceptible, and ceftolozane-tazobactam-nonsusceptible isolates, respectively, at ≤4 μg/ml (susceptible breakpoint). Cefiderocol inhibited 99.9%, 99.8%, 100%, and 99.8% of all P. aeruginosa , meropenem-nonsusceptible, ceftazidime-avibactam-nonsusceptible, and ceftolozane-tazobactam-nonsusceptible isolates, respectively, at ≤4 μg/ml (susceptible breakpoint). Cefiderocol inhibited 96.0% of all A. baumannii complex isolates and 94.2% of meropenem-nonsusceptible isolates at ≤4 μg/ml (susceptible breakpoint), and 98.6% of S. maltophilia isolates at ≤1 μg/ml (susceptible breakpoint). B. cepacia complex isolates tested with a MIC 50 of ≤0.03 μg/ml and MIC 90 of 0.5 μg/ml. Annual cefiderocol percent susceptible rates for Enterobacterales (North America, range 99.6-100%/year; Europe, range 99.3-99.9%/year) and P. aeruginosa (99.8-100%; 99.9-100%) were unchanged from 2014 to 2019. Annual percent susceptible rates for A. baumannii complex demonstrated sporadic, non-directional differences (97.5-100%; 90.4-97.5%); the wider range for Europe (∼7%) was due to isolates from Russia. Annual percent susceptible rates for S. maltophilia showed minor, non-directional differences (96.4-100%; 95.6-100%). We conclude that clinical isolates of Enterobacterales (99.8% susceptible), P. aeruginosa (99.9%), A. baumannii (96.0%), and S. maltophilia (98.6%) collected in North America and Europe from 2014 to 2019 were highly susceptible to cefiderocol.

scholarly journals Burkholderia pseudomallei clinical isolates are highly susceptible in vitro to cefiderocol, a novel siderophore cephalosporin

2020 ◽  
Author(s):  
Delaney Burnard ◽  
Gemma Robertson ◽  
Andrew Henderson ◽  
Caitlin Falconer ◽  
Michelle Bauer-Leo ◽  
...  
Keyword(s):  
Burkholderia Pseudomallei ◽  
Multidrug Resistant ◽  
Clinical Isolates ◽  
Transport Systems ◽  
Gram Negative ◽  
Highly Active ◽  
Amoxicillin Clavulanate ◽  
Clinical Breakpoints ◽  
Species Specific

AbstractCefiderocol is a novel cephalosporin designed to treat multidrug resistant Gram-negative infections. By forming a chelated complex with ferric iron, cefiderocol is transported into the periplasmic space via bacterial iron transport systems and primarily binds to penicillin-binding protein 3 (PBP3) to inhibit peptidoglycan synthesis. This mode of action results in cefiderocol having greater in vitro activity against many Gram-negative bacilli than currently used carbapenems, β-lactam/β-lactamase inhibitor combinations, and cephalosporins. Thus, we investigated the in vitro activity of cefiderocol (S-649266) against a total of 271 clinical isolates of Burkholderia pseudomallei from Australia. The collection was comprised of primary isolates (92.3%) and subsequent isolates (7.7%). Minimum inhibitory concentrations (MIC) of cefiderocol ranged from ≤0.03 to 32 mg/L, where the MIC90 was 1 mg/L and 16 mg/L for primary and subsequent isolates, respectively. Based upon non-species specific (Gram-negative bacilli) clinical breakpoints for cefiderocol (MIC ≤ 4 mg/L), twelve isolates (4.4%) would be classified as non-susceptible. Further testing for co-resistance to meropenem, ceftazidime, trimethoprim-sulfamethoxazole, amoxicillin-clavulanate and doxycycline was performed on a subset of isolates with elevated cefiderocol MICs (≥2 mg/L, 4.8%) and 84.6% of these isolates exhibited resistance to at least one of these antimicrobials. Cefiderocol was found to be highly active in vitro against B. pseudomallei primary clinical isolates. This novel compound shows great potential for the treatment of melioidosis in endemic countries and should be explored further.

scholarly journals 1349. Global Surveillance of Cefiderocol Against Gram-Negative Clinical Strains Collected in North America: SIDERO-WT-2015

2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S413-S413 ◽  
Author(s):  
Masakatsu Tsuji ◽  
Meredith Hackel ◽  
Roger Echols ◽  
Yoshinori Yamano ◽  
Dan Sahm
Keyword(s):  
North America ◽  
Burkholderia Cepacia ◽  
Dose Range ◽  
The United States ◽  
Vitro Activity ◽  
In Vitro Activity ◽  
Gram Negative ◽  
Wide Range

Abstract Background Cefiderocol (CFDC) is a novel parenteral siderophore cephalosporin with potent activity against a wide range of Gram-negative pathogens, including carbapenem-resistant strains. Additionally, a recently conducted in vivo murine-based study has demonstrated an incremental exposure-response profile over a dose range without the appearance of adaptive resistance. In this study, we evaluated the in vitro activity of CFDC and comparator agents against clinical isolates collected in 2015–2016 from North America from SIDERO-WT-2015 surveillance study. Methods A total of 3,602 isolates (2,470 Enterobacteriaceae, 223 A. baumannii, 85 Acinetobacter spp., 619 P. aeruginosa, 165 S. maltophilia and 17 Burkholderia cepacia, and 23 Burkholderia spp.) collected from the United States and Canada in 2015–2016 were tested. MICs were determined for CFDC, cefepime (FEP), ceftazidime–avibactam (CZA), ceftolozane–tazobactam (C/T), ciprofloxacin (CIP), colistin (CST), and meropenem (MEM) by broth microdilution and interpreted according to CLSI guidelines. As recommended by CLSI, cefiderocol was tested in iron-depleted cation-adjusted Mueller–Hinton broth (ID-CAMHB). Carbapenem nonsusceptible (Carb-NS) strains were defined as MEM MIC ≥2 µg/mL for Enterobacteriaceae, and ≥4 µg/mL for nonfermenters. Results CFDC exhibited potent in vitro activity against 3,602 strains of Gram-negative bacteria with an overall MIC90 of 0.5 mg/mL. As shown in the following table, MIC90 of CFDC against P. aeruginosa, A. baumannii, S. maltophilia, and Enterobacteriaceae including the subset of Carb-NS isolates were 0.5, 2, 0.5 and 0.5 mg/mL, respectively. At 4 mg/mL, CFDC inhibited the growth of 99.6% of the isolates while 18.1%, 12.6%, and 13.8% showed resistance to CZA, C/T, and CST, respectively. Conclusion CFDC demonstrated potent in vitro activity against the teat isolates collected from North America with greater than 99.6% of isolates having MIC values ≤4 mg/mL, including Carb-NS isolates of A. baumannii, P. aeruginosa, and Enterobacteriaceae. These findings indicate that this agent has high potential for treating infections caused by these problematic organisms. Disclosures M. Tsuji, Shionogi & Co., Ltd.: Employee, Salary. M. Hackel, IHMA, Inc.: Employee, Salary. Y. Yamano, Shionogi & Co., Ltd.: Employee, Salary. D. Sahm, IHMA, Inc.: Employee, Salary.

scholarly journals In Vitro Activity of the Siderophore Cephalosporin, Cefiderocol, against a Recent Collection of Clinically Relevant Gram-Negative Bacilli from North America and Europe, Including Carbapenem-Nonsusceptible Isolates (SIDERO-WT-2014 Study)

2017 ◽  
Vol 61 (9) ◽  
Author(s):  
Meredith A. Hackel ◽  
Masakatsu Tsuji ◽  
Yoshinori Yamano ◽  
Roger Echols ◽  
James A. Karlowsky ◽  
...  
Keyword(s):  
North America ◽  
North American ◽  
Clinical Isolates ◽  
In Vitro Activity ◽  
Gram Negative ◽  
Content Type ◽  
Mueller Hinton ◽  
Recent Collection ◽  
Mueller Hinton Broth

ABSTRACT Cefiderocol (formerly S-649266) is an investigational siderophore cephalosporin. Iron-depleted cation-adjusted Mueller-Hinton broth (ID-CAMHB) was prepared according to the Clinical and Laboratory Standards Institute (CLSI) protocol and used to perform broth microdilution testing of cefiderocol against a 2014-2015 collection of clinical isolates of Gram-negative bacilli from North America (n = 4,239) and Europe (n = 4,966). The concentrations of cefiderocol inhibiting 90% of isolates tested (MIC90s) were 0.5 μg/ml (North America; n = 3,007) and 1 μg/ml (Europe; n = 3,080) for all isolates of Enterobacteriaceae; 1 μg/ml (North America; n = 30) and 4 μg/ml (Europe; n = 139) for meropenem-nonsusceptible (MIC ≥ 2 μg/ml) isolates of Enterobacteriaceae; 0.5 μg/ml for both North American (n = 765) and European (n = 765) isolates of Pseudomonas aeruginosa; 0.5 μg/ml (North America; n = 151) and 1 μg/ml (Europe; n = 202) for meropenem-nonsusceptible (MIC ≥ 4 μg/ml) isolates of P. aeruginosa; 1 μg/ml for both North American (n = 309) and European (n = 839) isolates of all Acinetobacter baumannii strains as well as for both North American (n = 173) and European (n = 595) isolates of meropenem-nonsusceptible A. baumannii; and 0.5μg/ml (North America; n = 152) and 0.25 μg/ml (Europe; n = 276) for isolates of Stenotrophomonas maltophilia. MICs of cefiderocol were ≤4 μg/ml for 99.9% (6,078/6,087) of all Enterobacteriaceae, 97.0% (164/169) of meropenem-nonsusceptible Enterobacteriaceae, 99.9% (1,529/1,530) of all P. aeruginosa isolates, 100% (353/353) of meropenem-nonsusceptible P. aeruginosa isolates, 97.6% (1,120/1,148) of all A. baumannii isolates, 96.9% (744/768) of meropenem-nonsusceptible A. baumannii isolates, 100% of isolates of S. maltophilia (428/428) and 93.8% of isolates of Burkholderia cepecia (11/12). We conclude that cefiderocol demonstrated potent in vitro activity against a recent collection of clinical isolates of commonly encountered Gram-negative bacilli, including carbapenem-nonsusceptible isolates.

Evaluation of the in vitro activity of new polymyxin B analogue SPR206 against clinical MDR, colistin-resistant and tigecycline-resistant Gram-negative bacilli

2020 ◽  
Vol 75 (9) ◽  
pp. 2609-2615 ◽  
Author(s):  
Yawei Zhang ◽  
Chunjiang Zhao ◽  
Qi Wang ◽  
Xiaojuan Wang ◽  
Hongbin Chen ◽  
...  
Keyword(s):  
Stenotrophomonas Maltophilia ◽  
Enterobacter Cloacae ◽  
Polymyxin B ◽  
Vitro Activity ◽  
Clinical Isolates ◽  
In Vitro Activity ◽  
Gram Negative ◽  
Carbapenem Resistant ◽  
Resistant Strains

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.

scholarly journals In Vitro Susceptibility of Ureaplasma urealyticum and Mycoplasma hominis Isolates in Argentina

1995 ◽  
Vol 3 (6) ◽  
pp. 236-240
Author(s):  
Jorgelina Smayevsky ◽  
Silvia Relloso ◽  
Mariela Pundik ◽  
Alejandra Lanza ◽  
Gabriela Weltman ◽  
...  
Keyword(s):  
Ureaplasma Urealyticum ◽  
Mycoplasma Hominis ◽  
Clinical Isolates ◽  
Broth Microdilution ◽  
In Vitro Susceptibility ◽  
Surveillance Studies ◽  
Agar Dilution ◽  
High Mics

Objective: Our goal was to determine the in vitro susceptibility of Ureaplasma urealyticum and Mycoplasma hominis isolates to several antibiotics in Argentina.Methods: Ninety-four strains of U. urealyticum and 18 strains of M. hominis isolated from cervical and urethral specimens were studied. Broth microdilution and agar dilution tests for minocycline, tetracycline, erythromycin, ciprofloxacin, and ofloxacin were performed.Results: Both methods proved to be reliable and reproducible for U. urealyticum and M. hominis, with no major differences in results. The U. urealyticurn strains were inhibited by erythromycin at MICs ranging from ≤0.5 to >8 μ/ml. Ofloxacin showed the highest activity against this latter organism. No differences between tetracycline and minocycline MICs were observed with U. urealyticum. Two M. hominis strains displaying high MICs both to tetracycline and to minocycline were detected.Conclusions: The emerging resistance of mycoplasmas to certain antibiotics emphasizes the need to undertake further surveillance studies on the clinical isolates of such organisms.

scholarly journals Burkholderia pseudomallei clinical isolates are highly susceptible in vitro to cefiderocol, a siderophore cephalosporin

2020 ◽  
Author(s):  
Delaney Burnard ◽  
Gemma Robertson ◽  
Andrew Henderson ◽  
Caitlin Falconer ◽  
Michelle J. Bauer ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Burkholderia Pseudomallei ◽  
Multidrug Resistant ◽  
Clinical Isolates ◽  
Transport Systems ◽  
Gram Negative ◽  
Highly Active ◽  
Amoxicillin Clavulanate ◽  
Clinical Breakpoints

Cefiderocol is a cephalosporin designed to treat multidrug resistant Gram-negative infections. By forming a chelated complex with ferric iron, cefiderocol is transported into the periplasmic space via bacterial iron transport systems and primarily binds to penicillin-binding protein 3 (PBP3) to inhibit peptidoglycan synthesis. This mode of action results in cefiderocol having greater in vitro activity against many Gram-negative bacilli than currently used carbapenems, β-lactam/β-lactamase inhibitor combinations, and cephalosporins. Thus, we investigated the in vitro activity of cefiderocol against a total of 246 clinical isolates of Burkholderia pseudomallei from Queensland, Australia. The collection was comprised primarily of bloodstream (56.1%), skin and soft tissue (16.3%) and respiratory isolates (15.9%). Minimum inhibitory concentrations (MIC) of cefiderocol ranged from ≤0.03 to 16 mg/L, where the MIC90 was 0.125 mg/L. Based upon CLSI clinical breakpoints for cefiderocol against Pseudomonas aeruginosa, Acinetobacter baumannii and Stenotrophomonas maltophilia, three isolates (1.2%) would be classified as non-susceptible (MIC >4 mg/L). Using EUCAST non-species specific (PK/PD) clinical breakpoints, or those set for Pseudomonas aeruginosa, four isolates (1.6%) would be resistant (MIC >2 mg/L). Further testing for co-resistance to meropenem, ceftazidime, trimethoprim-sulfamethoxazole, amoxicillin-clavulanate and doxycycline was performed on the four isolates with elevated cefiderocol MICs (>2 mg/L), all isolates exhibited resistance to amoxicillin-clavulanic acid, while three isolates also displayed resistance to at least one other antimicrobial. Cefiderocol was found to be highly active in vitro against B. pseudomallei primary clinical isolates. This compound shows great potential for the treatment of melioidosis in endemic countries and should be explored further.

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 Susceptibility Pattern of Major Gram Negative Isolates to Selected Antimicrobial Agents

2019 ◽  
pp. 1-8
Author(s):  
Shalini Gupta ◽  
Pankaj Mandale
Keyword(s):  
Antimicrobial Susceptibility ◽  
Bacterial Infections ◽  
Therapeutic Option ◽  
Polymyxin B ◽  
Susceptibility Pattern ◽  
In Vitro Susceptibility ◽  
Gram Negative ◽  
E Coli ◽  
Susceptibility Data

Background: The choice of choosing right anti-microbial therapy in hospitals depends on the knowledge of local anti-microbial susceptibility profile. This retrospective study was conducted to assess the in vitro susceptibility pattern of different pathogen isolates to various antibiotics including Cefepime-Amikacin-Antibiotic resistant breakers (ARBs)* in various hospitals across the Jaipur City. Methods: To characterize the antimicrobial susceptibility pattern of different isolates from various hospitals across the Jaipur City, a retrospective, observational analysis was done for antibiogram data. A total of 1201 Gram negative isolates collected during the period from January 2017 to December 2017 were included in the study. Antibiotic sensitivity testing was done in accordance with the recommendations of Clinical Laboratory Standard Institute (CLSI) guidelines. Results: Of the total 1201 Gram negative isolates included in this study, 51.6% were from wounds and pus specimens, 40.1% were from respiratory and 8.2% from blood. P. aeruginosa (49.7%) was the most frequently isolated pathogen distantly followed by A. baumannii (21.6%), K. pneumoniae (16.6%) and E. coli (12.1%). The highest susceptibility was reported to polymyxins (100%) including Colistin and Polymyxin B, among all the tested bacteria’s and system wise. Among all the antibiotic tested, (Cefepime-Amikacin-ARBs*) sensitivity ranged for 87.9% to 52% on pathogens (E. coli, K. pneumonia, P. aeruginosa) tested from samples of skin and soft tissue, respiratory tract, blood stream, followed by Meropenem ranged for 78.4% to 55% on pathogens (E. coli, K. pneumonia, P. aeruginosa), followed by ceftazidime-tazobactam ranged for 82.7% to 58% on pathogens (E. coli, K. pneumonia, P. aeruginosa) and 22.7% sensitive for A. baumannii to Cefoperazone sulbactam. Based on pathogen type, E. coli exhibited highest overall susceptibility and the lowest was reported by A. baumannii. The susceptibility of A. baumannii ranged from 1-26% to all the tested antibiotics except polymyxins with 100% susceptibility. Conclusions: This in vitro susceptibility data suggests that Cefepime-Amikacin-ARBs* can serve as important therapeutic option for the treatment of various resistant Gram-negative bacterial infections to relieve the excess pressure on last resort antibiotics, carbapenems and other drugs including Colistin and polymyxin B. Cefepime-Amikacin-ARBs*on the basis of antimicrobial susceptibility data can be considered as an effective therapeutic option for carbapenems in treating gram negative bacterial infections, and could be considered as a broad spectrum antibiotic sparer’s like carbapenem, colistin and Polymyxin B.

scholarly journals 2477. Antimicrobial Resistance patterns of Enterobacteriaceae and Pseudomonas aeruginosa from Colombian clinical isolates. 2017–2018

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S858-S858
Author(s):  
Monica Maria Rojas Rojas ◽  
Catalina López ◽  
Jaime Ruiz ◽  
Jacquleine Pavía ◽  
Jose Oñate ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Antimicrobial Resistance ◽  
Antimicrobial Agents ◽  
Clinical Isolates ◽  
In Vitro Susceptibility ◽  
Gram Negative ◽  
Guidelines Development ◽  
Resistance Patterns ◽  
Tract Infections

Abstract Background The Study for Monitoring Antimicrobial Resistance Trends (SMART) is a worldwide initiative to monitor in vitro susceptibility of clinical Gram-negative isolates to several antimicrobial agents. Surveillance initiatives are essential to provide real-world evidence to support local guidelines development. Colombia has participated since 2012 with isolates from complicated intrabdominal infections (cIAI), complicated urinary tract infections (cUTI) and respiratory tract infections (RTI). This study describes resistant patterns of Escherichia coli (Eco), Klebsiella pneumoniae (Kpn) and Pseudomonas aeruginosa (Pae) clinical isolates collected in Colombian hospitals in a 2 years period (2017–2018). Methods Isolates from patients with cIAI, cUTI and RTI were collected. Identification confirmation was done in central laboratory. Minimum inhibitory concentrations (MIC) were performed by broth microdilution and interpreted according to 2018 CLSI guidelines, same criteria for Extended-spectrum β-lactamase (ESBL) classification. The antimicrobial activity was evaluated for aztreonam (ATM), ceftolozane/tazobactam (C/T), ceftazidime (CAZ), colistin (COL), ertapenem (ETP), cefepime (FEP), imipenem (IMP), meropenem (MEM) and piperacillin–tazobactam (TZP). Results During 2017–2018, 1492 isolates were collected. The main organism was Eco (51%) followed by Kpn (29%) and Pae (20%). In vitro susceptibility activity is presented in Table 1. COL, C/T, ETP, MEM and IPM exhibited over 95% susceptibility in Eco. ESBL prevalence was 18% for Eco (53/314) and 22% for Kpn (36/165). COL and C/T were the most active agents against Pae isolates. For Kpn, MIC50/90 values were: MEM (0.12 / 8), C/T (0.5 / 8) and for TZP (8 / > 64), meanwhile for Pae were MEM (0.5 / 32), C/T (0.5 / 32) and for TZP (8 / > 64). Conclusion Continued antimicrobial resistance surveillance initiatives are critical to guide the empiric treatments decision in a multidrug resistance era. This study shows that Ceftolozane/Tazobactam, MEM and COL have the best susceptibility profile against Eco, Kpn and Pae of cIAI, cUTI and RTI cases in Colombia. The C/T susceptibility rates and low MIC distribution provide evidence to support its use as a non-carbapenem therapeutic alternative for Gram-negative infections. Disclosures All authors: No reported disclosures.

Clinical and Laboratory Standards Institute and European Committee on Antimicrobial Susceptibility Testing Position Statements on Polymyxin B and Colistin Clinical Breakpoints

2020 ◽  
Author(s):  
Michael J Satlin ◽  
James S Lewis ◽  
Melvin P Weinstein ◽  
Jean Patel ◽  
Romney M Humphries ◽  
...  
Keyword(s):  
Antimicrobial Susceptibility ◽  
Susceptibility Testing ◽  
Polymyxin B ◽  
Antimicrobial Susceptibility Testing ◽  
In Vitro Susceptibility ◽  
Susceptibility Data ◽  
European Committee ◽  
Clinical Breakpoints ◽  
State Concentration

Abstract Recent data on polymyxin pharmacokinetics, pharmacodynamics, toxicity, and clinical outcomes suggest these agents have limited clinical utility. Pharmacokinetics-pharmacodynamics data show a steady-state concentration of 2 μg/mL is required for killing bacteria with colistin minimum inhibitory concentrations of 2 μg/mL. Less than 50% of patients with normal renal function achieve this exposure, and it is associated with high risk of nephrotoxicity. This exposure does not achieve bacterial stasis in pneumonia models. Randomized and observational studies consistently demonstrate increased mortality for polymyxins compared with alternative agents. The Clinical and Laboratory Standards Institute (CLSI) and European Committee on Antimicrobial Susceptibility Testing (EUCAST) are 2 global organizations that establish interpretive criteria for in vitro susceptibility data. CLSI has recently taken the step to eliminate the “susceptible” interpretive category for the polymyxins, whereas EUCAST maintains this interpretive category. This viewpoint describes the opinions of these organizations and the data that were used to inform their perspectives.

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