scholarly journals Carbapenem-resistant Gram-negative pathogens in a German university medical center: Prevalence, clinical implications and the role of novel β-lactam/β-lactamase inhibitor combinations

PLoS ONE ◽  
2018 ◽  
Vol 13 (4) ◽  
pp. e0195757 ◽  
Author(s):  
Juri Katchanov ◽  
Lucia Asar ◽  
Eva-Maria Klupp ◽  
Anna Both ◽  
Camilla Rothe ◽  
...  
Keyword(s):  
Medical Center ◽  
Clinical Implications ◽  
Gram Negative ◽  
Carbapenem Resistant ◽  
Lactamase Inhibitor

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 Treatment Options for Carbapenem-resistant Gram-negative Bacterial Infections

2019 ◽  
Vol 69 (Supplement_7) ◽  
pp. S565-S575 ◽  
Author(s):  
Yohei Doi
Keyword(s):  
Bacterial Infections ◽  
Treatment Options ◽  
Clinical Development ◽  
Gram Negative Bacteria ◽  
First Line ◽  
Safe Alternative ◽  
New Agents ◽  
Gram Negative ◽  
Carbapenem Resistant

AbstractAntimicrobial resistance has become one of the greatest threats to public health, with rising resistance to carbapenems being a particular concern due to the lack of effective and safe alternative treatment options. Carbapenem-resistant gram-negative bacteria of clinical relevance include the Enterobacteriaceae, Pseudomonas aeruginosa, Acinetobacter baumannii, and more recently, Stenotrophomonas maltophilia. Colistin and tigecycline have been used as first-line agents for the treatment of infections caused by these pathogens; however, there are uncertainties regarding their efficacy even when used in combination with other agents. More recently, several new agents with activity against certain carbapenem-resistant pathogens have been approved for clinical use or are reaching late-stage clinical development. They include ceftazidime-avibactam, ceftolozane-tazobactam, meropenem-vaborbactam, imipenem-cilastatin-relebactam, plazomicin, eravacycline, and cefiderocol. In addition, fosfomycin has been redeveloped in a new intravenous formulation. Data regarding the clinical efficacy of these new agents specific to infections caused by carbapenem-resistant pathogens are slowly emerging and appear to generally favor newer agents over previous best available therapy. As more treatment options become widely available for carbapenem-resistant gram-negative infections, the role of antimicrobial stewardship will become crucial in ensuring appropriate and rationale use of these new agents.

scholarly journals Infections in patients colonized with carbapenem-resistant Gram-negative bacteria in a medium Spanish city

2021 ◽  
Author(s):  
Carmen Soria-Segarra ◽  
Mercedes Delgado-Valverde ◽  
María Luisa Serrano-García ◽  
Inmaculada López-Hernández ◽  
José María Navarro-Marí ◽  
...  
Keyword(s):  
Predictive Value ◽  
Stenotrophomonas Maltophilia ◽  
Sanger Sequencing ◽  
Clinical Samples ◽  
Clinical Implications ◽  
Gram Negative Bacteria ◽  
Cross Sectional ◽  
Gram Negative ◽  
Carbapenem Resistant ◽  
Pulsed Field Electrophoresis

Objective. Because there are few studies on the clinical implications of colonization by carbapenem-resistant gram-negative bacteria (CRB) this was analyzed in rectal smears (RS) and pharyngeals (PS) and its ability to predict infection/colonization. Methodology. A cross-sectional, retrospective study from adult inpatients between January 2016 and December 2019 was conducted. The isolates were characterized by MicroScan and spectrometry of masses applying EUCAST 2018 cutoff points. The detection of carbapenemases was performed by PCR and Sanger sequencing; sequencies was assigned by MLST. The genetic relationship between the clinical isolates was made by pulsed field electrophoresis using the enzymes Xbal, Spel or Apal. Results. A total of 308 (86.03%) RS and 50 (13.97%) positive PS were detected, the RS had a 85% sensibility, 100% specificity, 100% positive predictive value and 97% negative predictive value. In RS, the following were isolated: 44% (n=135) Acinetobacter baumannii, 26% (n =80) Enterobacterales (20 KPC, 29 OXA-48, 22 VIM, 2 IMP, 7 NDM), 17% (n=53) Pseudomonas aeruginosa and 13% (n=40) Stenotrophomonas maltophilia. In the PS were isolated 44% (n=22) S. maltophilia, 40% (n = 20) A. baumannii, 8% (n=4) P. aeruginosa and 8% (n=4) Enterobacterales (3 VIM, 1 OXA). From the patients with simultaneous RS and PS, 41 (40.6%) had positivity in both smears, 45 (44.6%) only in RS and 15 (14.9%) only in PS. Colonization preceded infection in 81.3% (n=13) of the isolates; association between infection and colonization was found (p<0.001; χ2); and the episodes where the information was found all the isolates from the clinical samples and from the smears were similar. Conclusions. The probability of predicting infection through the CRB colonized in different clinical samples is feasible. The RS has a major sensibility to detect colonization.

scholarly journals 1253. Antimicrobial Activity of Cefepime in Combination with Taniborbactam Against Clinical Isolates of Enterobacterales from 2018-2020 Global Surveillance

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S715-S715
Author(s):  
Meredith Hackel ◽  
Mark G G Wise ◽  
Daniel F Sahm
Keyword(s):  
Clinical Isolates ◽  
Hospital Infections ◽  
In Vitro Activity ◽  
Penicillin Binding Protein ◽  
Independent Contractor ◽  
Gram Negative ◽  
Carbapenem Resistant ◽  
New Treatment ◽  
Lactamase Inhibitor

Abstract Background Taniborbactam (formerly VNRX-5133) is a novel cyclic boronate-based broad-spectrum β-lactamase inhibitor with potent and selective direct inhibitory activity against both serine- and metallo-β-lactamases (Ambler Classes A, B, C and D). Taniborbactam restores the activity of cefepime against many difficult to treat organisms, including cephalosporin- and carbapenem-resistant Enterobacterales and Pseudomonas aeruginosa. The activity of the investigational combination cefepime-taniborbactam (FTB) and comparator agents was evaluated against clinical isolates of Enterobacterales from a 2018-2020 global surveillance study. Methods MICs of cefepime with taniborbactam fixed at 4 µg/mL and comparators were determined following CLSI M07-A11 guidelines against 10,543 Enterobacterales. Isolates were from community and hospital infections collected from 259 sites in 56 countries in 2018-2020. Resistant phenotypes were based on 2021 CLSI breakpoints. A set of 827 isolates with meropenem MIC ≥4 µg/mL (n=421) or with cefepime and/or ceftazidime MIC ≥2 µg/mL (n=406) was evaluated for the presence of MBLs, KPC, ESBLs, and OXA-48 group genes via PCR and sequencing. Forty-eight isolates with FTB MIC values of 16 µg/mL or greater were interrogated by WGS. Results Overall, 23.0% and 15.9% of isolates were nonsusceptible (NS) to cefepime and piperacillin-tazobactam (TZP), respectively (Table). FTB had potent activity against all Enterobacterales, with MIC50/90 values of 0.06/0.25 µg/mL and 99.5% inhibited at ≤8 µg/mL. FTB maintained activity against MBL-, KPC-, OXA-48 group, and ESBL-positive isolates (MIC90 range, 1 to &gt;16 µg/mL; 80.5% to 100% inhibited at ≤8 µg/mL). Isolates with elevated FTB MICs had IMP-type enzymes, variation in the cefepime target (penicillin binding protein 3), permeability defects in combination with acquired β-lactamases, and/or possible up-regulated efflux. Results Table Conclusion Taniborbactam significantly restored the in vitro activity of cefepime against Enterobacterales, including isolates nonsusceptible to recently-approved BL/BLI combinations and expressing serine and metallo-β-lactamases. This support the continued development of FTB as a potential new treatment option for challenging infections due to resistant Gram-negative pathogens. Disclosures Meredith Hackel, PhD MPH, IHMA (Employee)Pfizer, Inc. (Independent Contractor) Mark G G. Wise, PhD, IHMA (Employee)Pfizer, Inc. (Independent Contractor) Daniel F. Sahm, PhD, IHMA (Employee)Pfizer, Inc. (Independent Contractor)

scholarly journals In VivoEfficacy of Humanized Exposures of Ceftazidime-Avibactam in Comparison with Ceftazidime against Contemporary Enterobacteriaceae Isolates

2014 ◽  
Vol 58 (11) ◽  
pp. 6913-6919 ◽  
Author(s):  
Shawn H. MacVane ◽  
Jared L. Crandon ◽  
Wright W. Nichols ◽  
David P. Nicolau
Keyword(s):  
Gram Negative ◽  
Content Type ◽  
Carbapenem Resistant ◽  
Class D ◽  
Variable Activity ◽  
Resistant Strains ◽  
The Impact ◽  
Inhibitor Combination ◽  
Lactamase Inhibitor

ABSTRACTCeftazidime-avibactam is a β-lactam β-lactamase inhibitor combination under investigation for the treatment of serious Gram-negative infections. When combined with avibactam, a novel non-β-lactam β-lactamase inhibitor, ceftazidime has activity against isolates that produce Ambler class A, class C, and some class D β-lactamases. However, little is known of thein vivoefficacy of the combination against these targeted ceftazidime- and carbapenem-resistantEnterobacteriaceae. Using humanized exposures in the murine thigh model, we evaluated the efficacy of ceftazidime-avibactam againstEnterobacteriaceaeexhibiting MICs of ≥8 μg/ml to aid in the assignment of interpretive susceptibility criteria. Eighteen clinicalEnterobacteriaceaeisolates, including nine carbapenem-resistant strains, were evaluated against ceftazidime-avibactam (2,000 mg/500 mg) as a 2-h infusion every 8 h. To highlight the impact of avibactam, 13 select isolates were tested in the neutropenic model against a humanized regimen of 2,000 mg ceftazidime every 8 h (2-h infusion). Additionally, nine isolates were evaluated in immunocompetent animals. The efficacy was evaluated as the change in log10CFU compared with that of 0-h controls after 24 h. The vast majority (17/18, 94%) of the isolates were resistant to ceftazidime alone. The ceftazidime monotherapy failed to have activity against 10 of 13 isolates, while ceftazidime-avibactam produced reductions in bacterial density against 16 of 18 isolates. Ceftazidime-avibactam (2,000 mg/500 mg) every 8 h (2-h infusion) displayed dependable activity against theEnterobacteriaceaeisolates, exhibiting MICs of ≤16 μg/ml (free drug concentration above the MIC [fT>MIC] of ≥62%) and variable activity was noted at an MIC of 32 μg/ml (fT>MICof 34%). The presence of a functioning immune system enhanced the efficacy for both regimens against all tested isolates. These data support further examination of the use of ceftazidime-avibactam as an effective therapy against infections due to Gram-negative infections, including carbapenem-resistantEnterobacteriaceae.

Sign in / Sign up

Export Citation Format

Share Document