scholarly journals Antimicrobial Activity of Ceftolozane–Tazobactam Tested against Contemporary (2012–2016) Enterobacteriaceae and Pseudomonas aeruginosa Isolates by US Census Division

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S371-S372
Author(s):  
Dee Shortridge ◽  
Leonard R Duncan ◽  
Michael A Pfaller ◽  
Robert K Flamm
Keyword(s):  
Pseudomonas Aeruginosa ◽  
The United States ◽  
Gram Negative ◽  
Carbapenem Resistant ◽  
Tract Infections ◽  
Abdominal Infections ◽  
Us Census ◽  
Phenotype Screen ◽  
Lactamase Inhibitor ◽  
Research Grant

Abstract Background Ceftolozane-tazobactam (C-T) is a combination of a novel antipseudomonal cephalosporin and a well-described β-lactamase inhibitor. C-T was approved by the United States (US) Food and Drug Administration in 2014 for complicated urinary tract infections, including acute pyelonephritis and complicated intra-abdominal infections. C-T is currently in clinical trials for the treatment of nosocomial pneumonia. The Program to Assess Ceftolozane-Tazobactam Susceptibility (PACTS) monitors C-T resistance to gram-negative (GN) isolates worldwide. In this study, the activities of C-T and comparators vs. GN isolates from each of the 9 US Census divisions were compared. Methods A total of 18,856 Enterobacteriaceae (ENT) and 4,735 Pseudomonas aeruginosa (PSA) isolates were collected from 32 US hospitals in 2012–2016. Isolates were tested for susceptibility (S) to C-T and comparators by CLSI broth microdilution methodology in a central monitoring laboratory. Other antibiotics tested included amikacin (AMK), ceftazidime (CAZ), colistin (COL), meropenem (MER), and piperacillin-tazobactam (TZP). The following resistant phenotypes were analyzed for ENT: carbapenem resistant (CRE); extended-spectrum β-lactamase phenotype screen-positive (ESBL); and ESBL, nonCRE. or PSA, MER-nonsusceptible (NS), TZP-NS, and CAZ-NS isolates were analyzed. CLSI (2017) interpretive criteria were used. Results For all ENT, 94.2% were S to C-T, 91.5% were S to TZP, 98.0% were S to MER, and 98.8% were S to AMK; 1,697 (9.0%) were ESBL, nonCRE and 356 (1.9%) were CRE. For all PSA isolates, 97.4% were S to C-T, 99.3% were S to COL, 96.9% were S to AMK, and 81.2% were S to MER. The % C-T S for each division (DIV) are shown in the table. The % C-T S for ENT ranged from 98.1% (DIV 4) to 87.4% (DIV 2) and % C-T S for ESBL, nonCRE ranged from 93.8% in DIV 4 to 79.8% in DIV 7. For PSA, the % C-T S ranged from 99.6% in DIV 4 to 94.9% in DIV 9. Activity of C-T against PSA NS to MER, CAZ or TZP varied by division and was >80% for all except DIV 9. Conclusion Against PSA, only COL was more active than C-T. C-T demonstrated potent activity against PSA NS to other β-lactams. For ENT, overall activity was good. For both PSA and ENT, C-T varied by DIV. Disclosures D. Shortridge, Merck: Research Contractor, Research grant; L. R. Duncan, Merck: Research Contractor, Research grant; M. A. Pfaller, Merck: Research Contractor, Research grant; R. K. Flamm, Merck: Research Contractor, Research grant

scholarly journals Antimicrobial Activity of Ceftolozane–Tazobactam Tested against Contemporary (2012–2016) Enterobacteriaceae and Pseudomonas aeruginosa from ICU vs. non-ICU Isolates Collected in US Medical Centers

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S366-S366
Author(s):  
Dee Shortridge ◽  
Leonard R Duncan ◽  
Michael A Pfaller ◽  
Robert K Flamm
Keyword(s):  
Pseudomonas Aeruginosa ◽  
The United States ◽  
Icu Patients ◽  
Medical Centers ◽  
Hospital Acquired Pneumonia ◽  
Tract Infections ◽  
Abdominal Infections ◽  
Hospital Acquired ◽  
Lactamase Inhibitor ◽  
Research Grant

Abstract Background Ceftolozane-tazobactam (C-T) is a combination of a novel antipseudomonal cephalosporin and a well-described β-lactamase inhibitor. C-T was approved by the United States (US) Food and Drug Administration in 2014 for complicated urinary tract infections, including acute pyelonephritis and complicated intra-abdominal infections. C-T is currently in clinical trials for the treatment of hospital-acquired pneumonia. The Program to Assess Ceftolozane-Tazobactam Susceptibility (PACTS) monitors C-T resistance to gram-negative (GN) isolates worldwide. This study compares the activities of C-T and comparators against GN isolates from ICU patients and non-ICU patients. Methods A total of 3,100 GN ICU isolates and 3,271 isolates from non-ICU patients were collected from 30 US hospitals in 2012–2016. Isolates were tested for susceptibility (S) to C-T and comparators by CLSI broth microdilution methodology in a central monitoring laboratory. Other antibiotics tested included amikacin (AMK), cefepime (FEP), ceftazidime (CAZ), colistin (COL), meropenem (MER), and piperacillin-tazobactam (TZP). CLSI (2017) interpretive criteria were used for all except COL with Enterobacteriaceae (ENT), for which EUCAST (2017) criteria were used. Results The most common ENT species from ICU and non-ICU patients were similar. The 3 most common ENT for ICU and non-ICU isolates were Klebsiella pneumoniae, 24.1% and 25.8%; Escherichia coli, 19.4% and 18.2%; and Serratia marcescens, 14.7% and 14.3%, respectively. The most common non-enteric species was Pseudomonas aeruginosa (PSA) for ICU and non-ICU (72.7% and 78.2%). ICU ENT isolates generally had a lower %S than non-ICU (Table). ENT showed more variability than PSA for %S between ICU and non-ICU. Conclusion For ENT overall, MER and AMK were the most active, followed by C-T. Comparing ICU and non-ICU, MER and C-T were slightly more active vs. non-ICU ENT, while AMK %S was similar for both. For PSA, COL was the most active; C-T and AMK were similar. Activities between ICU and non-ICU isolates were similar for C-T and COL while AMK was more active vs. ICU isolates, and MER was more active vs. non-ICU. C-T showed potent activity against ICU and non-ICU isolates for ENT and PSA. Disclosures D. Shortridge, Merck: Research Contractor, Research grant; L. R. Duncan, Merck: Research Contractor, Research grant; M. A. Pfaller, Merck: Research Contractor, Research grant; R. K. Flamm, Merck: Research Contractor, Research grant

scholarly journals Ceftazidime/Avibactam: Who Says You Can’t Teach an Old Drug New Tricks?

2016 ◽  
Vol 19 (4) ◽  
pp. 448 ◽  
Author(s):  
Katie E. Barber ◽  
Jessica K. Ortwine ◽  
Ronda L Akins
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Urinary Tract ◽  
Urinary Tract Infections ◽  
The United States ◽  
Phase Iii ◽  
In Vitro Susceptibility ◽  
Gram Negative ◽  
Tract Infections ◽  
Abdominal Infections

Purpose: Gram-negative resistance continues to rise with treatment options becoming more limited. Ceftazidime/avibactam was recently approved in the United States and Europe, which combines an established third-generation cephalosporin with a new, unique, non-β-lactam β-lactamase inhibitor. This review conducts a thorough examination of structure, pharmacology, spectrum of activity, pharmacokinetics/pharmacodynamics, in vitro and clinical efficacy and safety/tolerability of ceftazidime/avibactam, as well as detailed future directions for the agent. Methods: Pubmed and clinicaltrials.gov searches, as well as abstracts from the 2015 Interscience Conference on Antimicrobial Agents and Chemotherapy/International Society of Chemotherapy (ICAAC/ICC) and ID Week meetings and the 2016 American Society of Microbiology Microbe meeting, were conducted from January 2004 – September 2016. Relevant search terms included ceftazidime, ceftazidime/avibactam, avibactam, NXL104 and AVE1330A. The US package insert for ceftazidime/avibactam (02/2015) and European public assessment report (06/2016) were also reviewed. Results: In vitro susceptibility for ceftazidime/avibactam displayed potent activity against many Enterobacteriaceae including extended-spectrum-β-lactamase (ESBL) and carbapenemase-producing strains, as well as Pseudomonas aeruginosa. Phase II clinical trials utilized for approval demonstrated comparable safety and efficacy to imipenem/cilistatin for treatment of complicated urinary tract infections (70.4% vs. 71.4%) and combined with metronidazole compared to meropenem in complicated intra-abdominal infections (91.2% vs 93.4%). Phase III data displayed non-inferior efficacy of ceftazidime/avibactam compared to doripenem for complicated urinary tract infections (70.2% vs 66.2%) and combined with metronidazole compared to meropenem in complicated intra-abdominal infections (82.5% vs 84.9%), as well as comparable safety. Ceftazidime/avibactam was well-tolerated but does require renal adjustments. Additionally, 3 case series and a single case report have demonstrated the potential for ceftazidime/avibactam against multidrug resistant organisms for compassionate use or failure after previous therapy. Conclusion: By adding avibactam to ceftazidime, clinicians’ antimicrobial armamentarium is expanded, potentially increasing the ability to combat multi-drug resistant gram-negative pathogens, particularly ESBL and carbapenemase-producing organisms, as well as Pseudomonas aeruginosa. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

scholarly journals 1589. Ceftolozane–Tazobactam Activity Against Difficult-to-Treat Resistance in Pseudomonas aeruginosa from Bloodstream Infections in US Hospitals

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S580-S580
Author(s):  
Dee Shortridge ◽  
S J Ryan Arends ◽  
Leonard R Duncan ◽  
Jennifer M Streit ◽  
Robert K Flamm
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Bloodstream Infections ◽  
The United States ◽  
Multidrug Resistant ◽  
First Line ◽  
Microdilution Method ◽  
Drug Classes ◽  
Broth Microdilution Method ◽  
Tract Infections ◽  
Abdominal Infections

Abstract Background Infections caused by Pseudomonas aeruginosa (PSA) resistant to first-line agents are difficult to treat and require using more toxic antimicrobials, such as amikacin (AMK) and colistin (COL). Kadri et al. recently described the category of difficult-to-treat resistance (DTR) as intermediate or resistant to all tested first-line agents (fluoroquinolones, carbapenems, and extended-spectrum cephalosporins). Ceftolozane–tazobactam (C-T) is an antibacterial combination of an antipseudomonal cephalosporin and a β-lactamase inhibitor. C-T has been approved in >60 countries to treat complicated urinary tract infections, acute pyelonephritis, and complicated intra-abdominal infections. The filing is in progress for treatment of hospital-acquired pneumonia, including ventilator-associated pneumonia. The Program to Assess Ceftolozane–Tazobactam Susceptibility (PACTS) monitors gram-negative (GN) isolates resistant to C-T worldwide. In this study, the activity of C-T and comparators against PSA bloodstream isolates that are DTR, multidrug-resistant (MDR), or extensively drug-resistant (XDR) were analyzed. Methods A total of 922 PSA isolates from BSI were collected between 2011 and 2018 from 35 PACTS hospitals in the United States. Isolates were tested for C-T susceptibility (S) by the CLSI broth microdilution method. Other antibiotics tested included cefepime (FEP), ceftazidime (CAZ), ciprofloxacin, levofloxacin (LEV), doripenem, imipenem, meropenem (MEM), piperacillin–tazobactam (PIP-TAZ), AMK and COL. Antibiotic-resistant phenotypes analyzed using CLSI (2019) breakpoints included MDR (nonsusceptible to ≥ 1 agent in ≥ 3 drug classes), XDR (susceptible to ≤ 1 agent in ≤ 2 drug classes), or DTR. Results The percent of DTR isolates was 4.8% when compared with 15.2% MDR and 9.3% XDR. The %S for C-T and other first- and second-line agents are shown in the table for each phenotype. Conclusion C-T demonstrated 97.1%S overall for BSI isolates, similar to AMK (97.8%) and COL (99.5%). C-T had better coverage than first-line drugs against MDR (81.4%) and XDR (72.1%), and 50% for the DTR isolates, which represented only 4.8% of isolates. Only AMK and COL had > 75%S for DTR isolates. Disclosures All authors: No reported disclosures.

scholarly journals Colistin- and Carbapenem-Resistant Escherichia coli Harboring mcr-1 and bla NDM-5 , Causing a Complicated Urinary Tract Infection in a Patient from the United States: TABLE 1 

mBio ◽  
2016 ◽  
Vol 7 (4) ◽  
Author(s):  
José R. Mediavilla ◽  
Amee Patrawalla ◽  
Liang Chen ◽  
Kalyan D. Chavda ◽  
Barun Mathema ◽  
...  
Keyword(s):  
United States ◽  
Escherichia Coli ◽  
Urinary Tract ◽  
The United States ◽  
Clinical Samples ◽  
Isolation And Identification ◽  
Gram Negative ◽  
E Coli ◽  
Carbapenem Resistant ◽  
Tract Infections

ABSTRACT Colistin is increasingly used as an antibiotic of last resort for the treatment of carbapenem-resistant Gram-negative infections. The plasmid-borne colistin resistance gene mcr-1 was initially identified in animal and clinical samples from China and subsequently reported worldwide, including in the United States. Of particular concern is the spread of mcr-1 into carbapenem-resistant bacteria, thereby creating strains that approach pan-resistance. While several reports of mcr-1 have involved carbapenem-resistant strains, no such isolates have been described in the United States. Here, we report the isolation and identification of an Escherichia coli strain harboring both mcr-1 and carbapenemase gene bla NDM-5 from a urine sample in a patient without recent travel outside the United States. The isolate exhibited resistance to both colistin and carbapenems, but was susceptible to amikacin, aztreonam, gentamicin, nitrofurantoin, tigecycline, and trimethoprim-sulfamethoxazole. The mcr-1 - and bla NDM-5 -harboring plasmids were completely sequenced and shown to be highly similar to plasmids previously reported from China. The strain in this report was first isolated in August 2014, highlighting an earlier presence of mcr-1 within the United States than previously recognized. IMPORTANCE Colistin has become the last line of defense for the treatment of infections caused by Gram-negative bacteria resistant to multiple classes of antibiotics, in particular carbapenem-resistant Enterobacteriaceae (CRE). Resistance to colistin, encoded by the plasmid-borne gene mcr-1 , was first identified in animal and clinical samples from China in November 2015 and has subsequently been reported from numerous other countries. In April 2016, mcr-1 was identified in a carbapenem-susceptible Escherichia coli strain from a clinical sample in the United States, followed by a second report from a carbapenem-susceptible E. coli strain originally isolated in May 2015. We report the isolation and identification of an E. coli strain harboring both colistin ( mcr-1 ) and carbapenem ( bla NDM-5 ) resistance genes, originally isolated in August 2014 from urine of a patient with recurrent urinary tract infections. To our knowledge, this is the first report in the United States of a clinical bacterial isolate with both colistin and carbapenem resistance, highlighting the importance of active surveillance efforts for colistin- and carbapenem-resistant organisms.

scholarly journals 1278. Impact of Different Breakpoint Criteria on the Susceptibility Rates of Enterobacterales resistant Subsets to the Aminoglycosides

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S654-S655
Author(s):  
Helio S Sader ◽  
S J Ryan Arends ◽  
Jaideep Gogtay ◽  
Cecilia G Carvalhaes ◽  
Mariana Castanheira
Keyword(s):  
The United States ◽  
Multidrug Resistant ◽  
Chemical Diversity ◽  
Asia Pacific ◽  
Medical Centers ◽  
Carbapenem Resistant ◽  
Us Fda ◽  
Tract Infections ◽  
Center Research ◽  
Research Grant

Abstract Background Plazomicin (PLZ) is an aminoglycoside recently approved by the United States (US) Food and Drug Administration (FDA) for the treatment of complicated urinary tract infections, including pyelonephritis. We evaluated the susceptibility (S) rates of PLZ, amikacin (AMK), gentamicin (GEN) and tobramycin (TOB) by applying current breakpoints published by different organizations. Methods A total of 9,303 Enterobacterales (ENT) isolates (1/patient) were collected in 2018-2019 from medical centers located in the US (n=3,899; 33 centers), Europe (n=3,782; 39 centers in 19 nations), Asia-Pacific (n=795; 13 centers in 7 nations [2018 only]), and Latin America (n=827; 10 centers in 6 nations [2018 only]). PLZ and comparator agents were S tested by reference broth microdilution methods at a central laboratory. Breakpoints for the following organizations were applied when available: CLSI, EUCAST, USCAST, and US FDA. Results PLZ was active against 95.5% and 98.0% of isolates as per US FDA (≤2 mg/L) and USCAST (≤4 mg/L) criteria, respectively. S rates as per US FDA and USCAST criteria were 97.4% and 90.2% for AMK, 86.4% and 85.6% for GEN, and 83.8% and 81.1% for TOB, respectively (Table). CLSI and US FDA breakpoints were identical for these three older aminoglycosides, and EUCAST breakpoints were identical for GEN and TOB and one doubling dilution higher for AMK when compared with USCAST. Per US FDA criteria, carbapenem-resistant ENT (CRE) S rates to PLZ and AMK were 71.5% and 58.3%, respectively. Differences in S rates between PLZ and AMK were higher when applying USCAST for resistant subsets, such as CRE (72.2% versus 38.5%, respectively), ESBL-phenotype (92.7% versus 72.4%, respectively), and multidrug-resistant isolates (n=1,348; 88.6% versus 59.6%, respectively). GEN and TOB exhibited limited activity against ENT resistant subsets. Conclusion PLZ retained potent activity against ENT, including resistant subsets. The discrepancies among the S rates for aminoglycosides were greater when applying breakpoints generated using the same stringent contemporary methods applied to determine PLZ breakpoints. 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) S. J. Ryan Arends, PhD, Allergan (Research Grant or Support)Cipla Ltd. (Research Grant or Support)GlaxoSmithKline (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support) Jaideep Gogtay, n/a, Cipla Ltd. (Employee) 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) 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)

scholarly journals Susceptibility to Imipenem/Relebactam of Pseudomonas Aeruginosa and Acinetobacter Baumannii Isolates From Chinese Intra-Abdominal, Respiratory and Urinary Tract Infections: SMART 2015 To 2018

2021 ◽  
Author(s):  
Hui Zhang ◽  
Peiyao Jia ◽  
Ying Zhu ◽  
Ge Zhang ◽  
Jingjia Zhang ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Urinary Tract ◽  
Acinetobacter Baumannii ◽  
Urinary Tract Infections ◽  
Surveillance Program ◽  
College Hospital ◽  
Medical College ◽  
Carbapenem Resistant ◽  
Tract Infections ◽  
Abdominal Infections

Abstract Background In recent years, less options are available for treating carbapenem-resistant Acinetobacter baumannii and carbapenem-resistant Pseudomonas aeruginosa. The present study investigatesthe susceptibility rates to imipenem/relebactamfor the treatment of intra-abdominal infections (IAIs), respiratory tract infections (RTIs) and urinary tract infections (UTIs) caused by A. baumannii and P. aeruginosain China. Methods 1,886 P. aeruginosa and 1,889 A.baumanniiisolates were collected in 21 centers (7 regions) as part of the global SMART surveillance program between 2015 and 2018. Antimicrobial susceptibility testing was performed according tothe Clinical and Laboratory Standards Institute (CLSI) recommendations using the broth microdilution methodology in the Peking Union Medical College Hospital. Results Rates of imipenem-non-susceptibilities of P. aeruginosa and A. baumanniiisolates were 44.3% and 79.0%, whereas the multidrug-resistance (MDR) rateswere 44.3% and 81.9%, respectively.For P. aeruginosa, susceptibility rates to imipenem/relebactamwere 84.2% at aCLSI breakpoint of ≤ 2 mg/L compared to 55.7% for imipenem. The MIC90 of imipenem/relebactam(8 mg/L) was one fourth of that of imipenem (32 mg/L).The susceptibilities of imipenem-non-susceptible and MDRP.aeruginosastrains were similarly restored by imipenem/relebactam in non-ICU and ICU wards.The susceptiblity rate of A. baumannii isolates to imipenem was 21.0% and to imipenem/relebactam 22.2%. Conclusions Imipenem/relebactam provides a therapy option for infections caused by MDRor imipenem-non-susceptible P. aeruginosa infections in China.

scholarly journals Activity of Plazomicin against Enterobacteriaceae Isolates Collected in the United States Including Isolates Carrying Aminoglycoside-Modifying Enzymes Detected by Whole Genome Sequencing

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S377-S377 ◽  
Author(s):  
Mariana Castanheira ◽  
Lalitagauri M Deshpande ◽  
Cory M Hubler ◽  
Rodrigo E Mendes ◽  
Alisa W Serio ◽  
...  
Keyword(s):  
De Novo ◽  
Infection Type ◽  
The United States ◽  
E Coli ◽  
Carbapenem Resistant ◽  
Serious Infections ◽  
Tract Infections ◽  
Encoding Genes ◽  
Carbapenem Resistant Enterobacteriaceae ◽  
Research Grant

Abstract Background Plazomicin (PLZ) is a next-generation aminoglycoside (AMG) stable against aminoglycoside-modifying enzymes (AME) that completed Phase 3 studies for complicated urinary tract infections and serious infections due to carbapenem-resistant Enterobacteriaceae (ENT). We evaluated the activity of PLZ and AMGs against ENT collected in US hospitals during 2016. Methods A total of 2,097 ENT were susceptibility (S) tested by CLSI reference broth microdilution methods. E. coli, Klebsiella spp. Enterobacter spp., and P. mirabilis isolates displaying non-S MICs (CLSI criteria) for gentamicin (GEN), amikacin (AMK), and/or tobramycin (TOB) were submitted to WGS, de novo assembly and screening for AME genes. Results Against ENT, PLZ was more active than all 3 clinically available AMGs (Table). PLZ and AMK activities were stable regardless of the infection type; however, differences were observed for GEN and TOB. Bloodstream isolates displayed higher GEN MICs when compared with the other infection sites. TOB activity varied 4-fold, being higher for bloodstream and pneumonia infections and lower for skin/soft tissue and other/unknown specimens. Against 198 isolates carrying 1 or more AME-encoding genes detected among 208 AMG-non-S isolates, the activity of PLZ was 8- to 16-fold greater when compared with the activity of AMK and at least 16-fold higher than the activity of GEN or TOB. Conclusion PLZ was active against ENT isolates from US hospitals regardless of infection type. PLZ displayed activity against isolates carrying AME genes that represent 12.0% of selected species. AME-carrying isolates were considerably more resistant to AMK, GEN, and TOB, highlighting the potential value of PLZ to treat infections caused by these organisms. This project has been funded under BARDA Contract No. HHSO100201000046C. Disclosures M. Castanheira, Achaogen: Research Contractor, Research grant; L. M. Deshpande, Achaogen: Research Contractor, Research grant; C. M. Hubler, Achaogen: Research Contractor, Research grant; R. E. Mendes, Achaogen: Research Contractor, Research grant; A. W. Serio, Achaogen: Employee, Salary; K. M. Krause, Achaogen: Employee, Salary; R. K. Flamm, Achaogen: Research Contractor, Research grant

scholarly journals Prevalence of Carbapenem-Resistant Gram-Negative Infections in the United States Predominated by Acinetobacter baumannii and Pseudomonas aeruginosa

2017 ◽  
Vol 4 (3) ◽  
Author(s):  
Bin Cai ◽  
Roger Echols ◽  
Glenn Magee ◽  
Juan Camilo Arjona Ferreira ◽  
Gareth Morgan ◽  
...  
Keyword(s):  
United States ◽  
Pseudomonas Aeruginosa ◽  
Hospital Mortality ◽  
Acinetobacter Baumannii ◽  
The United States ◽  
Infection Site ◽  
Pathogen Infection ◽  
Gram Negative ◽  
Carbapenem Resistant ◽  
Hospital Stays

Abstract Background Carbapenem-resistant (CR) Gram-negative pathogens are recognized as a major health concern. This study examined the prevalence of infections due to 4 CR Gram-negative species (Acinetobacter baumannii, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Escherichia coli) in the United States and assessed their impact on hospital stays and mortality. Methods Hospitalized patients with laboratory-confirmed infection due to any of the 4 Gram-negative pathogens were identified from the Premier Healthcare Database. Proportions of CR were calculated by pathogen and infection site (blood, respiratory, urinary, or other) for the United States as whole and by census regions. Crude and adjusted odds ratios for in-hospital mortality were produced using logistic regression. Results From 2009 to 2013, 13 262 (4.5%) of 292 742 infections due to these 4 Gram-negative pathogens were CR. Of these CR infections, 82.3% were caused by A. baumannii (22%) or P. aeruginosa (60.3%), while 17.7% were caused by K. pneumoniae or E. coli. CR patients had longer hospital stays than carbapenem-susceptible (CS) patients in all pathogen-infection site cohorts, except in the A. baumannii-respiratory cohort. The crude all cause in-hospital mortality was greater for most pathogen-infection site cohorts of the CR group compared with the CS group, especially for A. baumannii infection in the blood (crude odds ratio [OR], 3.91; 95% confidence interval [CI], 2.69–5.70). This difference for the A. baumannii-blood cohort remained after adjusting for the relevant covariates (adjusted OR, 2.46; 95% CI, 1.43–4.22). Conclusion The majority of CR infections and disease burden in the United States was caused by nonfermenters A. baumannii and P. aeruginosa. Patients with CR infections had longer hospital stays and higher crude in-hospital mortality.

Imipenem/cilastatin/relebactam: A new carbapenem β-lactamase inhibitor combination

2021 ◽  
Author(s):  
Hanine Mansour ◽  
Ahmad El Ouweini ◽  
Elias B Chahine ◽  
Lamis R Karaoui
Keyword(s):  
Clinical Trials ◽  
Drug Therapy ◽  
Drug Combination ◽  
Bacterial Pneumonia ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Carbapenem Resistant ◽  
Tract Infections ◽  
Inhibitor Combination ◽  
Lactamase Inhibitor

Abstract Purpose The pharmacology, pharmacokinetics, pharmacodynamics, antimicrobial activity, efficacy, safety, and current regulatory status of a recently approved triple-drug therapy for complicated infections are reviewed. Summary Imipenem/cilastatin/relebactam is a newly approved anti-infective combination of a well-established β-lactam and a new β-lactamase inhibitor for the treatment of complicated urinary tract infections (cUTIs), including pyelonephritis, and complicated intra-abdominal infections (cIAIs) caused by susceptible gram-negative bacteria in patients 18 years of age or older with limited or no alternative treatment options; the medication is also indicated for use in treating hospital-acquired bacterial pneumonia (HABP) and ventilator-associated bacterial pneumonia (VABP). The medication is active in vitro against a wide range of pathogens, including multidrug-resistant (MDR) Pseudomonas aeruginosa and carbapenemase-resistant Enterobacterales such as Klebsiella pneumoniae carbapenemase. The addition of relebactam does not restore the activity of imipenem against metallo-β-lactamase (MBL)–producing Enterobacterales and carbapenem-resistant Acinetobacter baumannii. Two phase 3 clinical trials of imipenem/cilastatin/relebactam were conducted. In the RESTORE-IMI 1 trial, the efficacy and safety of the triple-drug combination was found to be comparable to that of colistin/imipenem for treatment of infections caused by imipenem-nonsusceptible gram-negative bacteria in patients with HABP or VABP, cUTIs, and cIAIs, with a significantly lower incidence of nephrotoxicity reported with triple-drug therapy. The RESTORE-IMI 2 trial demonstrated the noninferiority of the triple-drug combination to piperacillin/tazobactam for the treatment of HABP and VABP. Commonly reported adverse events in clinical trials included anemia, elevated liver enzymes, electrolyte imbalances, nausea, vomiting, diarrhea, headache, fever, phlebitis and/or infusion-site reactions, and hypertension. Conclusion Imipenem/cilastatin/relebactam is a new β-lactam/β-lactamase inhibitor combination with activity against MDR gram-negative bacteria, including many CRE but not including MBL-producing Enterobacterales and carbapenem-resistant Acinetobacter isolates. It is approved for the treatment of cUTIs, cIAIs, HABP, and VABP.

scholarly journals 1463. Activity of Delafloxacin against Multi-Drug-Resistant Fastidious Respiratory Pathogens from European Medical Centers (2014-2019)

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S733-S733
Author(s):  
Dee Shorttidge ◽  
Jennifer M Streit ◽  
Michael D Huband ◽  
Robert K Flamm
Keyword(s):  
Active Agent ◽  
The United States ◽  
Multidrug Resistant ◽  
Respiratory Pathogens ◽  
Services Research ◽  
In Vitro Susceptibility ◽  
Amoxicillin Clavulanate ◽  
Tract Infections ◽  
Research Grant

Abstract Background Delafloxacin (DLX) is an anionic fluoroquinolone (FQ) that has been approved in the United States and in Europe for the treatment of acute bacterial skin and skin structure infections and was recently approved in the US for treatment of community-acquired bacterial pneumonia (CABP). In the present study, in vitro susceptibility (S) results for DLX and comparator agents were determined for CABP pathogens including Streptococcus pneumoniae (SPN), Haemophilus influenzae (HI), H. parainfluenzae (HP) and Moraxella catarrhalis (MC) clinical isolates from European hospitals participating in the SENTRY Program during 2014-2019. Methods A total of 2,835 SPN, 1,484 HI, 959 MC, and 20 HP isolates were collected from community-acquired respiratory tract infections (CARTI) during 2014-2019 from European hospitals. Sites included only 1 isolate/patient/infection episode. Isolate identifications were confirmed at JMI Laboratories. Susceptibility testing was performed according to CLSI broth microdilution methodology, and EUCAST (2020) breakpoints were applied where applicable. Other antimicrobials tested included levofloxacin (LEV) and moxifloxacin (MOX; not tested in 2015). Multidrug-resistant (MDR) SPN isolates were categorized as being nonsusceptible (NS) to amoxicillin-clavulanate, erythromycin (ERY), and tetracycline; other SPN phenotypes were ERY-NS, or penicillin (PEN)-NS. β-lactamase (BL) presence was determined for HI, HP, and MC. Results The activities of the 3 FQs are shown in the table. The most active agent against SPN was DLX, with the lowest MIC50/90 values of 0.015/0.03 mg/L. DLX activities were the same when tested against the MDR or PEN-NS for SPN phenotypes. ERY-NS isolates had DLX MIC50/90 results of 0.015/0.03 mg/L. DLX was the most active FQ against HI, HP, and MC. BL presence did not affect FQ MIC values for HI or MC; only 1 HP isolate was BL-positive. Conclusion DLX demonstrated potent in vitro antibacterial activity against SPN, HI, HP, and MC. DLX was active against MDR SPN that were NS to the agents commonly used as treatments for CABP. These data support the utility of DLX in CABP including when caused by antibiotic resistant strains. Table 1 Disclosures Jennifer M. Streit, BS, A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (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)Paratek Pharma, LLC (Research Grant or Support) Robert K. Flamm, PhD, A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Amplyx Pharmaceuticals (Research Grant or Support)Basilea Pharmaceutica International, Ltd (Research Grant or Support)Department of Health and Human Services (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)

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