Aztreonam/avibactam activity against clinical isolates of Enterobacterales collected in Europe, Asia and Latin America in 2019

2020 ◽  
Author(s):  
Helio S Sader ◽  
Cecilia G Carvalhaes ◽  
S J Ryan Arends ◽  
Mariana Castanheira ◽  
Rodrigo E Mendes
Keyword(s):  
Latin America ◽  
Western Europe ◽  
Multidrug Resistant ◽  
Clinical Development ◽  
Asia Pacific ◽  
Asia Pacific Region ◽  
Carbapenem Resistant ◽  
Serious Infections ◽  
Susceptibility Tests

Abstract Background Aztreonam is a monobactam stable to hydrolysis by metallo-β-lactamases (MBLs) and avibactam is a non-β-lactam β-lactamase inhibitor that effectively inhibits serine carbapenemases (CPs). Aztreonam/avibactam is under clinical development for treatment of serious infections caused by Gram-negative bacteria, including MBL-producers. Objectives To evaluate the in vitro activity of aztreonam/avibactam against clinical Enterobacterales isolates. Methods 8787 Enterobacterales were collected consecutively from 64 medical centres located in Western Europe (W-EU; n = 4616; 26 centres in 10 nations), Eastern Europe (E-EU; n = 1554; 11 centres in 9 nations), the Asia-Pacific region (APAC; n = 1456; 17 centres in 9 nations), and Latin America (LATAM; n = 1161; 10 centres in 6 nations). Susceptibility tests were performed by reference broth microdilution methods and interpreted according to EUCAST criteria. Results 99.9% of isolates were inhibited at aztreonam/avibactam MIC of ≤8 mg/L (MIC50/90, ≤0.03/0.12 mg/L), including 99.7% of carbapenem-resistant (CRE; n = 396; MIC50/90, 0.25/0.5 mg/L) and 99.7% of multidrug-resistant isolates (n = 1706; MIC50/90, 0.06/0.5 mg/L). CRE rates were 1.2%, 12.9%, 5.2%, and 5.8% in W-EU, E-EU, APAC, and LATAM, respectively (4.5% overall). A CP was identified in 90.2% of CRE isolates. The most common CPs were variants of KPC (35.9% of CRE), NDM (29.0%), and OXA-48 (26.8%). The highest aztreonam/avibactam MIC value among MBL-producers (n = 110; MIC50/90, 0.12/0.5 mg/L) was 2 mg/L. Susceptibility rates for ceftriaxone, meropenem, levofloxacin, and amikacin were highest in W-EU (80.9%, 99.0%, 80.7% and 97.9%, respectively) and lowest in E-EU (52.0%, 88.9%, 54.1%, and 84.2%, respectively). Conclusions Our results support clinical development of aztreonam/avibactam to treat infections caused by Enterobacterales, including MBL-producers.

Geographic Patterns of Carbapenem-resistant Pseudomonas aeruginosa in the Asia-Pacific Region: Results from the Antimicrobial Testing Leadership and Surveillance (ATLAS) program, 2015–2019

2021 ◽  
Author(s):  
Yu-Lin Lee ◽  
Wen-Chien Ko ◽  
Po-Ren Hsueh
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Antimicrobial Agents ◽  
Carbapenem Resistance ◽  
Multidrug Resistant ◽  
Asia Pacific ◽  
Pacific Region ◽  
Asia Pacific Region ◽  
Carbapenem Resistant ◽  
Broth Microdilution Method ◽  
Resistance Patterns

Pseudomonas aeruginosa is a common pathogen that is associated with multidrug-resistant (MDR) and carbapenem-resistant (CR) phenotypes; therefore, we investigated its resistance patterns and mechanisms by using data from the Antimicrobial Testing Leadership and Surveillance (ATLAS) program in the Asia-Pacific region during 2015–2019. MICs were determined using the broth microdilution method. Genes encoding major extended-spectrum β-lactamases and carbapenemases were investigated by multiplex PCR assays. Susceptibility was interpreted using the Clinical and Laboratory Standards Institute (CLSI) breakpoints. A total of 6,349 P. aeruginosa isolates were collected in the ATLAS program between 2015 and 2019 from 14 countries. According to the CLSI definitions, the numbers (and rates) of CR and MDR P. aeruginosa were 1,198 (18.9%) and 1,303 (20.5%), respectively. For 747 of the CR P. aeruginosa strains that were available for gene screening, 253 β-lactamases genes were detected in 245 (32.8%) isolates. The most common gene was bla VIM (29.0, 71/245), followed by bla NDM (24.9%, 61/245) and bla VEB (20.8%, 51/245). The resistance patterns and associated genes varied significantly between the countries in the Asia-Pacific region. India had the highest rates of carbapenem resistance (29.3%, 154/525) and gene detection (17.7%, 93/525). Compared to those harboring either class A or B β-lactamase genes, the CR P. aeruginosa without detected β-lactamase genes had lower MICs for most of the antimicrobial agents, including ceftazidime/avibactam and ceftolozane/tazobactam. In conclusion, MDR and CR P. aeruginosa infections pose a major threat, particularly those with detected carbapenemase genes. Continuous surveillance is important for improving antimicrobial stewardship and antibiotic prescriptions.

scholarly journals In Vitro Activity of Ceftazidime-Avibactam against Clinical Isolates of Enterobacteriaceae and Pseudomonas aeruginosa Collected in Asia-Pacific Countries: Results from the INFORM Global Surveillance Program, 2012 to 2015

2018 ◽  
Vol 62 (7) ◽  
Author(s):  
James A. Karlowsky ◽  
Krystyna M. Kazmierczak ◽  
Samuel K. Bouchillon ◽  
Boudewijn L. M. de Jonge ◽  
Gregory G. Stone ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Hong Kong ◽  
Multidrug Resistant ◽  
Clinical Isolates ◽  
Asia Pacific ◽  
Surveillance Program ◽  
Asia Pacific Region ◽  
Content Type ◽  
Medical Centers

ABSTRACT The in vitro activities of ceftazidime-avibactam and comparators against 9,149 isolates of Enterobacteriaceae and 2,038 isolates of Pseudomonas aeruginosa collected by 42 medical centers in nine countries in the Asia-Pacific region from 2012 to 2015 were determined as part of the International Network for Optimal Resistance Monitoring (INFORM) global surveillance program. Antimicrobial susceptibility testing was conducted by Clinical and Laboratory Standards Institute (CLSI) broth microdilution, and isolate subset analysis was performed on the basis of the resistant phenotypes and β-lactamase content. Ceftazidime-avibactam demonstrated potent in vitro activity (MIC, ≤8 μg/ml) against all Enterobacteriaceae tested (99.0% susceptible) and was the most active against isolates that were metallo-β-lactamase (MBL) negative (99.8% susceptible). Against P. aeruginosa , 92.6% of all isolates and 96.1% of MBL-negative isolates were susceptible to ceftazidime-avibactam (MIC, ≤8 μg/ml). The rates of susceptibility to ceftazidime-avibactam ranged from 97.0% (Philippines) to 100% (Hong Kong, South Korea) for Enterobacteriaceae and from 83.1% (Thailand) to 100% (Hong Kong) among P. aeruginosa isolates, with lower susceptibilities being observed in countries where MBLs were more frequently encountered (Philippines, Thailand). Ceftazidime-avibactam inhibited 97.2 to 100% of Enterobacteriaceae isolates, per country, that carried serine β-lactamases, including extended-spectrum β-lactamases, AmpC cephalosporinases, and carbapenemases (KPC, GES, OXA-48-like). It also inhibited 91.3% of P. aeruginosa isolates that were carbapenem nonsusceptible in which no acquired β-lactamase was detected. Among MBL-negative Enterobacteriaceae isolates that were ceftazidime nonsusceptible, meropenem nonsusceptible, colistin resistant, and multidrug resistant, ceftazidime-avibactam inhibited 96.1, 87.7, 100, and 98.8% of isolates, respectively, and among MBL-negative P. aeruginosa isolates that were ceftazidime nonsusceptible, meropenem nonsusceptible, colistin resistant, and multidrug resistant, ceftazidime-avibactam inhibited 79.6, 83.6, 83.3, and 68.2% of isolates, respectively. Overall, clinical isolates of Enterobacteriaceae and P. aeruginosa collected in nine Asia-Pacific countries from 2012 to 2015 were highly susceptible to ceftazidime-avibactam.

scholarly journals In Vitro Activity of KBP-7072, a Novel Third-Generation Tetracycline, against 531 Recent Geographically Diverse and Molecularly Characterized Acinetobacter baumannii Species Complex Isolates

2020 ◽  
Vol 64 (5) ◽  
Author(s):  
Michael D. Huband ◽  
Rodrigo E. Mendes ◽  
Michael A. Pfaller ◽  
Jill M. Lindley ◽  
Gregory J. Strand ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Species Complex ◽  
Phase 1 ◽  
The United States ◽  
Clinical Development ◽  
Asia Pacific ◽  
Third Generation ◽  
Content Type ◽  
Carbapenem Resistant

ABSTRACT KBP-7072 is a novel third-generation tetracycline (aminomethylcycline) antibacterial that overcomes common efflux and ribosomal protection resistance mechanisms that cause resistance in older-generation tetracyclines. KBP-7072 completed phase 1 clinical development studies for safety, tolerability, and pharmacokinetics (ClinicalTrials.gov identifier NCT02454361) and multiple ascending doses in healthy subjects (ClinicalTrials.gov identifier NCT02654626) in December 2015. Both oral and intravenous formulations of KBP-7072 are being developed. In this study, we evaluated the in vitro activities of KBP-7072 and comparator agents by CLSI document M07 (2018) broth microdilution against 531 recent geographically diverse and/or molecularly characterized Acinetobacter baumannii-A. calcoaceticus species complex (A. baumannii) isolates from the United States, Europe, Asia-Pacific (excluding China), and Latin America. A. baumannii isolates included carbapenem-resistant, colistin-resistant, tetracycline-resistant, and extended-spectrum-β-lactamase (ESBL)- and metallo-β-lactamase (MBL)-producing isolates. Overall, KBP-7072 (MIC50/90, 0.25/1 mg/liter) was comparable in activity to colistin (92.8%/92.8% susceptible [S] [CLSI/EUCAST]) against A. baumannii isolates, inhibiting 99.2% of isolates at ≤2 mg/liter and 97.6% of isolates at ≤1 mg/liter. KBP-7072 was equally active against A. baumannii isolates, including carbapenem-resistant, colistin-resistant, and tetracycline-resistant isolates, regardless of geographic location, and maintained activity against ESBL- and MBL-producing isolates. KBP-7072 outperformed comparator agents, including ceftazidime (40.3% S [CLSI]), gentamicin (48.2%/48.2% S [CLSI/EUCAST]), levofloxacin (39.5%/37.9% S [CLSI/EUCAST]), meropenem (42.0%/42.0% S [CLSI/EUCAST]), piperacillin-tazobactam (33.3% S [CLSI]), and all tetracycline-class comparator agents, which include doxycycline (67.3% S [CLSI]), minocycline (73.8% S [CLSI]), tetracycline (37.2% S [CLSI]), and tigecycline (79.5% inhibited by ≤2 mg/liter). The potent in vitro activity of KBP-7072 against recent geographically diverse, molecularly characterized, and drug-resistant A. baumannii isolates supports continued clinical development for the treatment of serious infections, including those caused by A. baumannii.

scholarly journals 1261. Antimicrobial Activity of Aztreonam-Avibactam against Gram-negative Bacteria Isolated from Patients Hospitalized with Pneumonia in Europe, Latin America, and Asia in 2019

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S647-S647
Author(s):  
Helio S Sader ◽  
Mariana Castanheira ◽  
Cecilia G Carvalhaes ◽  
Timothy B Doyle ◽  
Rodrigo E Mendes
Keyword(s):  
Latin America ◽  
Western Europe ◽  
Clinical Development ◽  
Chemical Diversity ◽  
Asia Pacific ◽  
Gram Negative Bacteria ◽  
Services Research ◽  
Gram Negative ◽  
Center Research ◽  
Research Grant

Abstract Background Aztreonam (ATM) is a monobactam stable to hydrolysis by metallo-β-lactamases (MBL). Avibactam (AVI) is a non-β-lactam β-lactamase inhibitor that inhibits serine carbapenemases (CPEs), such as ESBLs, KPCs, AmpC, and some OXAs. ATM-AVI is under clinical development for treatment of serious infections caused by Gram-negative bacteria (GNB), including MBL-producers. Methods 2,582 GNB (1,630 Enterobacterales [ENT] and 952 nonfermentative-GNB) were consecutively collected (1/patient) from 56 medical centers located in Western Europe (W-EU; 22 centers in 10 nations), Eastern Europe (E-EU; 12 centers in 9 nations), Latin America (LATAM; 10 centers 6 nations), and the Asia-Pacific region (APAC; 12 centers in 8 nations) in 2019 and susceptibility (S) tested against ATM-AVI and comparators at a central laboratory by reference broth microdilution methods. Results Overall, 99.9% of ENT (MIC50/90, 0.06/0.25 mg/L), including 99.1% of carbapenem-resistant ENT (CRE; MIC50/90, 0.25/0.5 mg/L), were inhibited at an ATM-AVI MIC of ≤ 8 mg/L (Table). CRE rates were 1.4%, 23.7%, 6.3%, and 9.6% in W-EU, E-EU, LATAM, and APAC, respectively (6.9% overall). A CPE was identified in 95 of 113 CRE isolates (84.1%). These CPEs included NDM-like (31.0% of CRE), KPC-like (26.5%), OXA-48-like (24.8%), and VIM-like (7.1%). Six isolates produced 2 CPEs. The highest ATM-AVI MIC value among MBL-producers (n=43; MIC50/90, 0.12/0.5 mg/L) was 4 mg/L. Among P. aeruginosa, 75.1% were inhibited at ≤ 8 mg/L of ATM-AVI; S to meropenem (MEM), piperacillin-tazobactam, and ceftazidime were 69.4%, 72.5%, and 75.7%, respectively, and ranged from 64.3% in E-EU to 82.0% in W-EU. MEM non-S P. aeruginosa varied from 22.2% in W-EU to 54.8% in E-EU. ATM-AVI was highly active against S. maltophilia, inhibiting 95.0%, 100.0%, 100.0%, and 90.0% of isolates from W-EU, E-EU, LATAM, and APAC, respectively, at ≤8 mg/L. S. maltophilia S to cotrimoxazole were 90.0%, 97.7%, 85.7%, and 100.0% in W-EU, E-EU, LATAM, and APAC, respectively. ATM-AVI also was very active against Burkholderia spp. (highest MIC, 8 mg/L). Conclusion Our results support clinical development of ATM-AVI to treat pneumonia caused by ENT (including MBL-producers), P. aeruginosa, S. maltophilia, and Burkholderia spp. Table 1 Disclosures Helio S. Sader, MD, PhD, A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Allergan (Research Grant or Support)Allergan (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Melinta (Research Grant or Support)Merck (Research Grant or Support)Merck (Research Grant or Support)Paratek Pharma, LLC (Research Grant or Support)Pfizer (Research Grant or Support) Mariana Castanheira, PhD, 1928 Diagnostics (Research Grant or Support)A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Allergan (Research Grant or Support)Amplyx Pharmaceuticals (Research Grant or Support)Cidara Therapeutics (Research Grant or Support)Cidara Therapeutics (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Fox Chase Chemical Diversity Center (Research Grant or Support)GlaxoSmithKline (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Merck (Research Grant or Support)Merck (Research Grant or Support)Merck & Co, Inc. (Research Grant or Support)Merck & Co, Inc. (Research Grant or Support)Paratek Pharma, LLC (Research Grant or Support)Pfizer (Research Grant or Support)Qpex Biopharma (Research Grant or Support) Cecilia G. Carvalhaes, MD, PhD, A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Cidara Therapeutics (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Fox Chase Chemical Diversity Center (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Merck (Research Grant or Support)Merck (Research Grant or Support)Merck & Co, Inc. (Research Grant or Support)Pfizer (Research Grant or Support) Timothy B. Doyle, Allergan (Research Grant or Support)Allergan (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Pfizer (Research Grant or Support)Qpex Biopharma (Research Grant or Support) Rodrigo E. Mendes, PhD, A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Allergan (Research Grant or Support)Basilea Pharmaceutica International, Ltd (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Department of Health and Human Services (Research Grant or Support)GlaxoSmithKline (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Merck (Research Grant or Support)Merck (Research Grant or Support)Pfizer (Research Grant or Support)

scholarly journals In Vitro Properties of BAL30072, a Novel Siderophore Sulfactam with Activity against Multiresistant Gram-Negative Bacilli

2010 ◽  
Vol 54 (6) ◽  
pp. 2291-2302 ◽  
Author(s):  
Malcolm G. P. Page ◽  
Clothilde Dantier ◽  
Eric Desarbre
Keyword(s):  
Multidrug Resistant ◽  
Unusual Property ◽  
Gram Negative ◽  
Penicillin Binding Proteins ◽  
High Affinity ◽  
Class A ◽  
Carbapenem Resistant ◽  
Lactam Antibiotic ◽  
Resistant Strains

ABSTRACT BAL30072 is a new monocyclic β-lactam antibiotic belonging to the sulfactams. Its spectrum of activity against significant Gram-negative pathogens with β-lactam-resistant phenotypes was evaluated and was compared with the activities of reference drugs, including aztreonam, ceftazidime, cefepime, meropenem, imipenem, and piperacillin-tazobactam. BAL30072 showed potent activity against multidrug-resistant (MDR) Pseudomonas aeruginosa and Acinetobacter sp. isolates, including many carbapenem-resistant strains. The MIC90s were 4 μg/ml for MDR Acinetobacter spp. and 8 μg/ml for MDR P. aeruginosa, whereas the MIC90 of meropenem for the same sets of isolates was >32 μg/ml. BAL30072 was bactericidal against both Acinetobacter spp. and P. aeruginosa, even against strains that produced metallo-β-lactamases that conferred resistance to all other β-lactams tested, including aztreonam. It was also active against many species of MDR isolates of the Enterobacteriaceae family, including isolates that had a class A carbapenemase or a metallo-β-lactamase. Unlike other monocyclic β-lactams, BAL30072 was found to trigger the spheroplasting and lysis of Escherichia coli rather than the formation of extensive filaments. The basis for this unusual property is its inhibition of the bifunctional penicillin-binding proteins PBP 1a and PBP 1b, in addition to its high affinity for PBP 3, which is the target of monobactams, such as aztreonam.

scholarly journals 694. In vitro Antibacterial Activity of Sulbactam–Durlobactam (ETX2514SUL) Against 121 Recent Acinetobacter baumannii Isolated from Patients in India

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S314-S314
Author(s):  
Alita Miller ◽  
Sarah McLeod ◽  
Tarun Mathur ◽  
Ian Morrissey
Keyword(s):  
Antibacterial Activity ◽  
Acinetobacter Baumannii ◽  
Package Insert ◽  
Multidrug Resistant ◽  
Antibiotic Resistant ◽  
Carbapenem Resistant ◽  
In Vitro Antibacterial Activity ◽  
Spectrum Activity ◽  
Broad Spectrum Activity

Abstract Background The incidence of infections caused by multidrug-resistant Acinetobacter baumannii is increasing at an alarming rate in Southeast Asia and other parts of the world. Sulbactam (SUL) has intrinsic antibacterial activity against A. baumannii; however, the prevalence of β-lactamases in this species has limited its therapeutic use. Durlobactam (ETX2514, DUR) is a novel β-lactamase inhibitor with broad-spectrum activity against Ambler class A, C and D β-lactamases. DUR restores SUL in vitro activity against multidrug-resistant A. baumannii. Against >3,600 globally diverse, clinical isolates from 2012–2017, addition of 4 mg/L DUR reduced the SUL MIC90 from >32 to 2 mg/L. SUL-DUR is currently in Phase 3 clinical development for the treatment of infections caused by carbapenem-resistant Acinetobacter spp.The goal of this study was to determine the activity of SUL-DUR and comparator antibiotics (amikacin (AMK), ampicillin-sulbactam (AMP-SUL), cefoperazone-sulbactam (CFP-SUL) and meropenem (MEM)) against A. baumannii isolated from hospitalized patients in India. Methods A total of 121 clinical A. baumannii isolates from multiple hospital settings and infection sources were collected between 2016–2019 from six geographically diverse hospitals in India. Species identification was performed by MALDI-TOF. Susceptibility of these isolates to SUL-DUR (10µg/10µg) and comparator antibiotics was determined by disk diffusion using CLSI methodology and interpretive criteria, except for CFP-SUL, for which resistance was defined using breakpoints from the CFP-SUL package insert. Results As shown in Table 1, resistance of this collection of isolates to marketed agents was extremely high. In contrast, based on preliminary breakpoint criteria, only 11.5% of isolates were resistant to SUL-DUR. Conclusion The in vitro antibacterial activity of SUL-DUR was significantly more potent than comparator agents against multidrug-resistant A. baumannii isolates collected from diverse sites in India. These data support the continued development of SUL-DUR for the treatment of antibiotic-resistant infections caused by A. baumannii. Disclosures All authors: No reported disclosures.

scholarly journals Pilot Ex Vivo and In Vitro Evaluation of a Novel Foley Catheter with Antimicrobial Periurethral Irrigation for Prevention of Extraluminal Biofilm Colonization Leading to Catheter-Associated Urinary Tract Infections (CAUTIs)

2019 ◽  
Vol 2019 ◽  
pp. 1-10
Author(s):  
Nylev Vargas-Cruz ◽  
Joel Rosenblatt ◽  
Ruth A Reitzel ◽  
Anne-Marie Chaftari ◽  
Ray Hachem ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Foley Catheter ◽  
Irrigation Treatment ◽  
Multidrug Resistant ◽  
Indwelling Catheter ◽  
Carbapenem Resistant ◽  
Colonization Model ◽  
Tract Infections

CAUTI remains a serious healthcare issue for incontinent patients whose urine drainage is managed by catheters. A novel double-balloon Foley catheter was developed which was capable of irrigating the extraluminal catheter surfaces within the periurethral space between the urethral-bladder junction and meatus. The catheter has a retention cuff that is inflated to secure the catheter in the bladder and a novel irrigation cuff proximal to the urethral-bladder junction capable of providing periurethral irrigation from the urethral-bladder junction to the meatus. Uniform periurethral irrigation was demonstrated in an ex vivo porcine model by adding a dye to the antimicrobial urethral irrigation solution. An in vitro biofilm colonization model was adapted to study the ability of periurethral irrigation with a newly developed antimicrobial combination consisting of polygalacturonic acid + caprylic acid (PG + CAP) to prevent axial colonization of the extraluminal urethral indwelling catheter shaft by common uropathogens. The extraluminal surface of control catheters that were not irrigated formed biofilms along the entire axial urethral tract after 24 hours. Significant (p<0.001) inhibition of colonization was seen against multidrug-resistant Pseudomonas aeruginosa (PA), carbapenem-resistant Escherichia coli (EC), and carbapenem-resistant Klebsiella pneumoniae (KB). For other common uropathogens including Candida albicans (CA), Proteus mirabilis (PR), and Enterococcus faecalis (EF), a first irrigation treatment completely inhibited colonization of half of the indwelling catheter closest to the bladder and a second treatment largely disinfected the remaining intraurethral portion of the catheter towards the meatus. The novel Foley catheter and PG + CAP antimicrobial irrigant prevented biofilm colonization in an in vitro CAUTI model and merits further testing in an in vivo CAUTI prevention model.

scholarly journals 129. Antimicrobial Activity of Ceftazidime–avibactam and Comparator Agents Tested against Gram-Negative Organisms Isolated from Patients with Bloodstream Infections in United States Medical Centers (2017–2018)

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S93-S94
Author(s):  
Cecilia G Carvalhaes ◽  
Mariana Castanheira ◽  
Rodrigo E Mendes ◽  
Helio S Sader
Keyword(s):  
United States ◽  
New York ◽  
Bloodstream Infections ◽  
The United States ◽  
Multidrug Resistant ◽  
Medical Centers ◽  
Carbapenem Resistant ◽  
Gram Negative Organisms ◽  
Esbl Producers

Abstract Background We evaluated the antimicrobial susceptibility of Enterobacterales (ENT) and P. aeruginosa (PSA) causing bloodstream infections (BSIs) in the United States (US) hospitals. Methods A total of 3,317 ENT and 331 PSA isolates were consecutively collected (1/patient) from patients with BSI in 68 US medical centers in 2017–2018 and tested for susceptibility (S) by reference broth microdilution methods in a central laboratory as part of the International Network for Optimal Resistance Monitoring (INFORM) Program. β-Lactamase screening was performed by whole-genome sequencing on ENT with decreased S to broad-spectrum cephalosporins (ESBL phenotype). Results The most common ENT species isolated from BSI were E. coli (EC; 41.9% of ENT), K. pneumoniae (KPN; 24.4%), and E. cloacae (ECL; 8.7%), and the most active agents against ENT were ceftazidime–avibactam (CAZ-AVI; 99.9%S), amikacin (AMK; 99.6%S) and meropenem (MEM; 99.3%S). CAZ-AVI was active against all EC and KPN isolates (100.0%S). Only 2 ENT isolates (0.06%) were CAZ-AVI resistant, 2 NDM-1-producing ECL isolated in the New York City area. Ceftolozane–tazobactam (C-T) and piperacillin–tazobactam (PIP-TAZ) showed good activity against EC and KPN (92.2–98.9%S; Table), with limited activity against ECL (81.9–83.7%S). The most common ESBLs were CTX-M-type, which was observed in 93% of ESBL producers (mainly CTX-M-15 [64% of ESBL producers] and CTX-M-27 [13%]), and OXA-1/OXA-30 (42%); 42% of ESBL producers (n = 333, excluding carbapenemase producers) displayed ≥2 ESBL genes, mainly CTX-M-15 and OXA-1/OXA-30 (40% of ESBL producers). The most active agents against ESBL producers were CAZ-AVI (100.0%S), imipenem (99.4%S), and colistin (COL; 99.1%S). Only CAZ-AVI (99.4%S), AMK (96.2%S) and MEM (92.8%S) were active against >90% of multidrug-resistant (MDR) ENT. Among 19 carbapenem-resistant ENT (CRE; 0.6% of ENT), 9 produced a KPC-like, 2 an NDM-1, and 2 an NMC-A; carbapenemase genes were not found in 6 CRE isolates. COL (100.0%S), CAZ-AVI (98.5%S), AMK (98.5%S), C-T (98.1%S), and tobramycin (97.0%S) were very active against PSA. Conclusion CAZ-AVI exhibited potent in vitro activity and great spectrum against ENT (99.9%S) and PSA (98.5%) isolated from patients with BSI from US hospitals. Disclosures All authors: No reported disclosures.

scholarly journals In Vitro Activity of Imipenem and Colistin against a Carbapenem-ResistantKlebsiella pneumoniaeIsolate Coproducing SHV-31, CMY-2, and DHA-1

2015 ◽  
Vol 2015 ◽  
pp. 1-5 ◽  
Author(s):  
Hung-Jen Tang ◽  
Yee-Huang Ku ◽  
Mei-Feng Lee ◽  
Yin-Ching Chuang ◽  
Wen-Liang Yu
Keyword(s):  
Outer Membrane ◽  
Multidrug Resistant ◽  
In Vitro Activity ◽  
Carbapenem Resistant ◽  
Hip Infection ◽  
Outer Membrane Porin ◽  
The Common ◽  
Inoculum Effect ◽  
Time Kill

We investigated the synergism of colistin and imipenem against a multidrug-resistantK. pneumoniaeisolate which was recovered from a severe hip infection. PCR and DNA sequencing were used to characterize the outer membrane porin genes and the resistance genes mediating the commonβ-lactamases and carbapenemases. Synergism was evaluated by time-kill studies. TheblaSHV-31,blaCMY-2, andblaDHA-1were detected. Outer membrane porin genes analysis revealed loss ofompK36and frame-shift mutation ofompK35. The common carbapenemase genes were not found. Time-kill studies demonstrated that a combination of 1x MIC of colistin (2 mg/L) and 1x MIC of imipenem (8 mg/L) was synergistic and bactericidal but with inoculum effect. Bactericidal activity without inoculum effect was observed by concentration of 2x MIC of colistin alone or plus 2x MIC of imipenem. In conclusion, colistin plus imipenem could be an alternative option to treat carbapenem-resistantK. pneumoniaeinfections.

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