scholarly journals Multicenter Study of Outcomes with Ceftazidime-Avibactam in Patients with Carbapenem-Resistant Enterobacteriaceae Infections

2017 ◽  
Vol 61 (7) ◽  
Author(s):  
Madeline King ◽  
Emily Heil ◽  
Safia Kuriakose ◽  
Tiffany Bias ◽  
Vanthida Huang ◽  
...  
Keyword(s):  
Chart Review ◽  
Clinical Success ◽  
Retrospective Chart Review ◽  
Beta Lactamase ◽  
Content Type ◽  
Carbapenem Resistant ◽  
Enterobacteriaceae Infections ◽  
Microbiological Cure ◽  
Inhibitor Combination ◽  
Carbapenem Resistant Enterobacteriaceae

ABSTRACT Ceftazidime-avibactam is a novel cephalosporin–beta-lactamase inhibitor combination that is active against many carbapenem-resistant Enterobacteriaceae (CRE). We describe a retrospective chart review for 60 patients who received ceftazidime-avibactam for a CRE infection. In-hospital mortality was 32%, 53% of patients had microbiological cure, and 65% had clinical success. In this severely ill population with CRE infections, ceftazidime-avibactam was an appropriate option.

scholarly journals 662. Recurrence of Infection and Emergence of Drug Resistance After Treatment with Meropenem/Vaborbactam Compared with Ceftazidime/Avibactam in Carbapenem-Resistant Enterobacteriaceae Infections

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S303-S303 ◽  
Author(s):  
Renee Ackley ◽  
Danya Roshdy ◽  
Jacqueline Isip ◽  
Sarah B, Minor ◽  
Amanda L Elchynski ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Combination Therapy ◽  
Clinical Success ◽  
Recurrent Infection ◽  
Signs And Symptoms ◽  
Development Of Resistance ◽  
Carbapenem Resistant ◽  
Enterobacteriaceae Infections ◽  
Post Hoc ◽  
Carbapenem Resistant Enterobacteriaceae

Abstract Background Options for treatment of carbapenem-resistant Enterobacteriaceae (CRE) infections were historically limited to antibiotics with limited efficacy and significant toxicities. Ceftazidime/avibactam (CA) and meropenem/vaborbactam (MV) are superior to older regimens; however, a direct comparison of the agents is lacking. This study compared clinical outcomes including recurrence of infection and emergence of drug resistance in patients who received CA vs. MV for CRE infections. Methods This was a multicenter, retrospective cohort study of adults with CRE infections who received CA or MV for ≥72 hours from February 2015 to October 2018. Patients with localized urinary tract infection were excluded. The primary endpoint was clinical success (30-day survival, resolution of signs and symptoms of infection, sterilization of blood cultures within 7 days in patients with bacteremia, absence of recurrent infection). Secondary endpoints included 30- and 90-day mortality, adverse events (AE), recurrent CRE infection within 90 days, and development of resistance in patients with recurrent infection. We conducted a post hoc subgroup analysis in patients with recurrence to compare development of resistance in those who received CA monotherapy, CA combination therapy, and MV monotherapy. Results 131 patients were included (CA: 105 patients, MV: 26 patients), 40% had bacteremia. No statistical difference in clinical success was observed between groups (62% vs. 69%, respectively, P = 0.49). Patients in the CA arm received combination therapy more often than patients in the MV arm (61% vs. 15%, P < 0.01). No difference in 30- and 90-day mortality resulted among groups, but numerically higher rates of AE were observed in the CA group (38% vs. 23%, P = 0.17). In patients with recurrent infection, development of resistance occurred more often with CA monotherapy, though not statistically significant (Table 1). One case of MV resistance was observed in a patient who had received 4 prior courses of MV, but this episode was outside of the study period. Conclusion Clinical success was similar between the groups despite MV being used more often as monotherapy. Development of resistance and rates of AE were higher in the CA group compared with MV therapy. Disclosures All authors: No reported disclosures.

scholarly journals Early Experience With Meropenem-Vaborbactam for Treatment of Carbapenem-resistant Enterobacteriaceae Infections

2019 ◽  
Vol 71 (3) ◽  
pp. 667-671 ◽  
Author(s):  
Ryan K Shields ◽  
Erin K McCreary ◽  
Rachel V Marini ◽  
Ellen G Kline ◽  
Chelsea E Jones ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Clinical Success ◽  
Survival Rates ◽  
Recurrent Infection ◽  
Early Experience ◽  
Carbapenem Resistant ◽  
Enterobacteriaceae Infections ◽  
Carbapenem Resistant Enterobacteriaceae

Abstract Twenty patients with carbapenem-resistant Enterobacteriaceae infections were treated with meropenem-vaborbactam. Thirty-day clinical success and survival rates were 65% (13/20) and 90% (18/20), respectively. Thirty-five percent of patients had microbiologic failures within 90 days. One patient developed a recurrent infection due to meropenem-vaborbactam–nonsusceptible, ompK36 porin mutant Klebsiella pneumoniae.

scholarly journals Phenotypic and Molecular Characterization of Carbapenem-Resistant Enterobacteriaceae from Clinical Bacterial Isolates: A Multicenter Retrospective Chart Review Study in western of Saudi Arabia

2020 ◽  
Author(s):  
Rbab Taha ◽  
Abdulfattah W Alamri ◽  
Areej H Mufti ◽  
Abdulhakim Al thaqafi ◽  
Asif Jiman Fatani Fatani ◽  
...  
Keyword(s):  
Saudi Arabia ◽  
Antimicrobial Resistance ◽  
Chart Review ◽  
Antimicrobial Agents ◽  
Retrospective Chart Review ◽  
Clinical Isolates ◽  
Major Health Problem ◽  
E Coli ◽  
Carbapenem Resistant ◽  
Carbapenem Resistant Enterobacteriaceae

Abstract Background: Carbapenemase-producing bacteria are a major health problem because of its limited treatment options. Carbapenem-Resistant Enterobacteriaceae (CRE) are non-susceptible to carbapenem, which serves as the most potent class of antimicrobial agents available for multidrug-resistant bacterial infections. The aim of our study was to determine the prevalence of CRE and determine the type of carbapenemase genes present among patients in tertiary care hospitals in Jeddah, Saudi Arabia.Methods: We performed a retrospective chart review on 180 patients in two sites. Primarily, we evaluated the prevalence of KPC, NDM, VIM, OXA-48, and IMP genes of CRE from clinical isolates tested by Xpert® Carba-R. Secondly, we assessed the prevalence of CRE based on antibiogram reports and described the susceptibility of CRE and the aforementioned CRE genes to antimicrobial agents.Results: CRE clinical isolates showed no occurrence of KPC, VIM, and IMP genes. OXA-48 gene was predominantly prevalent, with 76.1%, followed by NDM 13.9%, and both genes co-existed in 6.1% of the isolates. The CRE percent prevalence in one site in 2017 was 3.8%, and increased to 6.03% in 2018, whereas in the second site, the percentage was much higher, reaching 22.9% in 2018 and 18.9% in 2019. The CRE prevalence was dominated by Klebsiella pneumoniae (K. pne), occurring in 92.8% of the isolates, followed by E. coli in 6.7%. K. pne showed a higher frequency of OXA-48 (79%) than NDM (11.7%) genes, with a p-value of 0.007, while E. coli showed an equal frequency of both genes (41.7%). K. pne and E. coli showed high antimicrobial resistance to imipenem, meropenem, tazocin, and ciprofloxacin. However, they showed less resistance to amikacin, gentamycin, and tigecycline. NDM and OXA-48 genes showed 100% resistance to imipenem, meropenem, tazocin, ciprofloxacin and amikacin and the lowest resistance to gentamycin, tigecycline, and colistin.Conclusion: Over the two year retrospective study period, the CRE percent prevalence in the evaluated clinical isolates has remarkably increased. K. pne and E. coli were the most prevalent CRE organisms with OXA-48 and NDM as the predominant genes. CRE organisms and genes showed high antimicrobial resistance to imipenem, meropenem and tazocin, and lower resistance to gentamycin and tigecycline.

scholarly journals The characteristics of antimicrobial resistance and treatment of carbapenem-resistant Enterobacteriaceae infections in children from 2013 to 2018 in a chinese tertiary hospital

2019 ◽  
Author(s):  
Xiu-Qin Jia ◽  
Feng Pang ◽  
Xin Luo ◽  
Jian Zhang
Keyword(s):  
Antimicrobial Resistance ◽  
Adjuvant Therapy ◽  
Pathogenic Bacteria ◽  
Antimicrobial Agents ◽  
Pediatric Patients ◽  
Tertiary Hospital ◽  
Invasive Procedures ◽  
Carbapenem Resistant ◽  
Enterobacteriaceae Infections ◽  
Carbapenem Resistant Enterobacteriaceae

Abstract Background The aim of this study was to performe a retrospective analysis of prevalence and treatment of carbapenem-resistant Enterobacteriaceae (CRE) infections in children in a tertiary hospital. Methods The non-repeat clinical isolates of CRE in children were collected in Liaocheng People's Hospital from January, 2013 to December, 2018. The bacterial identification and antibiotic susceptibility was performed according to the standard methods. The isolated strains will be detected carbapenemases genotypes and homology analysis. All data on the culture-positive strains and associated clinical infection from different pediatric wards were reviewed. Results A total of 20 CRE strains isolated from pediatric patients, which derived from different infection sites and present a classification of multiple species of Enterobacteriaceae. And the production of IMP-type carbapenemase in these strains is the main reason of antimicrobial resistance. Most of the infected patients have severe comorbidities and invasive procedures, and use insensitive drugs due to the high resistance rates and medication restrictions. Nevertheless, most infected children have been treated despite the resistance of pathogens to multiple antimicrobial agents. In our follow-up survey, most children received adjuvant therapy such as human intravenous immunoglobulin, which may be an important factor in helping patients defeat pathogenic bacteria. Conclusions This study demonstrates a high prevalence of IMP-mediated CRE infection in pediatric patients with severe comorbidities and invasive procedures. Most children have been cured, which may be related to application of adjuvant therapy and weaker pathogenicity of the IMP-type Enterobacteriaceae.

scholarly journals Detection of New Delhi metallo-beta-lactamase enzyme gene bla NDM-1 associated with the Int-1 gene in Gram-negative bacteria collected from the effluent treatment plant of a tuberculosis care hospital in Delhi, India

2020 ◽  
Vol 2 (6) ◽  
Author(s):  
Amit Aggarwal ◽  
Manpreet Bhalla ◽  
Khan Hena Fatima
Keyword(s):  
Treatment Plant ◽  
Effluent Treatment ◽  
Diffusion Method ◽  
Care Hospital ◽  
Beta Lactamase ◽  
Genotypic Resistance ◽  
Content Type ◽  
Link Type ◽  
Carbapenem Resistant ◽  
Effluent Treatment Plant

Background. Organisms possessing the bla NDM-1 gene (responsible for carbapenem resistance) with a class-1 integron can acquire many other antibiotic resistance genes from the community sewage pool and become multidrug-resistant superbugs. In this regard, hospital sewage, which contains a large quantity of residual antibiotics, metals and disinfectants, is being recognized as a significant cause of antimicrobial resistance (AMR) origination and spread across the major centres of the world and is thus routinely investigated as a marker for tracing the origin of drug resistance. Therefore, in this study, an attempt has been made to identify and characterize the carbapenem-resistant microbes associated with integron genes amongst the organisms isolated from the effluent treatment plant (ETP) installed in a tertiary respiratory care hospital in Delhi, India. Methods. One hundred and thirty-eight organisms belonging to Escherichia , Klebsiella , Pseudomonas and Acinetobacter spp. were collected from the incoming and outgoing sewage lines of the ETP. Carbapenem sensitivity and characterization was performed by the imipenem and imipenem-EDTA disc diffusion method. Later DNA extraction and PCR steps were performed for the Int-1 and bla NDM-1 genes. Results. Of the 138 organisms, 86 (62.3 %) were imipenem-resistant (P<0.05). One hundred and twenty-four (89.9 %) organisms had one or both of the genes. Overall, the bla NDM-1 gene (genotypic resistance) was present in 71 % (98/138) of organisms. 53.6 % (74/138) organisms were double gene-positive (bla NDM-1 + Int-1), of which 40 were producing the metallo-beta-lactamase enzyme, making up almost 28.9 % (40/138) of the collected organisms. Conclusion. The current study strengthens the hypothesis that Carbapenem resistant organisms are in a high-circulation burden through the human gut and hospital ETPs are providing an environment for resistance origination and amplification.

scholarly journals Determining the Optimal Carbapenem MIC That Distinguishes Carbapenemase-Producing and Non-Carbapenemase-Producing Carbapenem-Resistant Enterobacteriaceae

2016 ◽  
Vol 60 (10) ◽  
pp. 6425-6429 ◽  
Author(s):  
Pranita D. Tamma ◽  
Yanjie Huang ◽  
Belita N. A. Opene ◽  
Patricia J. Simner
Keyword(s):  
Infection Control ◽  
Content Type ◽  
Carbapenem Resistant ◽  
Rapid Spread ◽  
Carbapenem Resistant Enterobacteriaceae

ABSTRACTCarbapenemase-producing (CP)Enterobacteriaceaeare largely responsible for the rapid spread of carbapenem-resistantEnterobacteriaceae(CRE). Distinguishing CP-CRE from non-CP-CRE has important infection control implications. In a cohort of 198 CRE isolates, for isolates that remained susceptible or intermediate to some carbapenem antibiotics, an ertapenem MIC of 0.5 μg/ml and meropenem, imipenem, and doripenem MICs of 2 μg/ml were best able to distinguish CP-CRE from non-CP-CRE isolates.

scholarly journals Treatment of Carbapenem-Resistant Enterobacteriaceae Infections with Ceftazidime-Avibactam

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S286-S286
Author(s):  
Elham Rahmati ◽  
Emily Blodget ◽  
Rosemary C She ◽  
Jennifer Cupo Abbott ◽  
Robert A Bonomo ◽  
...  
Keyword(s):  
Carbapenem Resistant ◽  
Enterobacteriaceae Infections ◽  
Carbapenem Resistant Enterobacteriaceae

scholarly journals In Vivo Activity of QPX7728, an Ultrabroad-Spectrum Beta-Lactamase Inhibitor, in Combination with Beta-Lactams against Carbapenem-Resistant Klebsiella pneumoniae

2020 ◽  
Vol 64 (11) ◽  
Author(s):  
Mojgan Sabet ◽  
Ziad Tarazi ◽  
David C. Griffith
Keyword(s):  
Klebsiella Pneumoniae ◽  
Beta Lactamase ◽  
Beta Lactam ◽  
Beta Lactams ◽  
Bacterial Killing ◽  
Clinical Issue ◽  
Content Type ◽  
Beta Lactam Antibiotics ◽  
Carbapenem Resistant ◽  
Lactamase Inhibitor

ABSTRACT Resistance to beta-lactams has created a major clinical issue. QPX7728 is a novel ultrabroad-spectrum cyclic boronic acid beta-lactamase inhibitor with activity against both serine and metallo-beta-lactamases developed to address this resistance for use in combination with beta-lactam antibiotics. The objective of these studies was to evaluate the activity of QPX7728 in combination with multiple beta-lactams against carbapenem-resistant Klebsiella pneumoniae isolates in a neutropenic mouse thigh infection model. Neutropenic mice were infected with strains with potentiated beta-lactam MICs of ≤2 mg/liter in the presence of 8 mg/liter QPX7728. Two strains of carbapenem-resistant K. pneumoniae were tested with aztreonam, biapenem, cefepime, ceftazidime, ceftolozane, and meropenem alone or in combination with 12.5, 25, or 50 mg/kg of body weight of QPX7728 every 2 hours for 24 hours. Treatment with all beta-lactams alone either was bacteriostatic or allowed for bacterial growth. The combination of QPX7728 plus each of these beta-lactams produced bacterial killing at all QPX7728 doses tested. Overall, these data suggest that QPX7728 administered in combination with different partner beta-lactam antibiotics may have utility in the treatment of bacterial infections due to carbapenem-resistant K. pneumoniae.

scholarly journals Estimating the Size of the U.S. Market for New Antibiotics with Activity against Carbapenem-Resistant Enterobacteriaceae

2019 ◽  
Vol 63 (12) ◽  
Author(s):  
Cornelius J. Clancy ◽  
M. Hong Nguyen
Keyword(s):  
United States ◽  
The United States ◽  
Content Type ◽  
Antibiotic Development ◽  
Development Models ◽  
Carbapenem Resistant ◽  
Financial Difficulties ◽  
New Antibiotics ◽  
The U.S ◽  
Carbapenem Resistant Enterobacteriaceae

ABSTRACT New antibiotics with activity against carbapenem-resistant Enterobacteriaceae (CRE) improve outcomes of CRE-infected patients. However, companies developing these drugs have faced financial difficulties. Sales of ceftazidime-avibactam, meropenem-vaborbactam, and plazomicin in the United States totaled $101 million from February 2018 to January 2019. We estimate that the current annual U.S. market for new anti-CRE antibiotics is $289 million (range, $169 to $439 million). Without new antibiotic development models and/or reimbursement reform, the majority of anti-CRE drugs will be commercially inviable.

scholarly journals Activity of Meropenem-Vaborbactam in Mouse Models of Infection Due to KPC-Producing Carbapenem-Resistant Enterobacteriaceae

2017 ◽  
Vol 62 (1) ◽  
Author(s):  
Mojgan Sabet ◽  
Ziad Tarazi ◽  
Thomas Nolan ◽  
Jonathan Parkinson ◽  
Debora Rubio-Aparicio ◽  
...  
Keyword(s):  
Body Weight ◽  
Lung Infection ◽  
Infection Model ◽  
Bacterial Killing ◽  
Gram Negative ◽  
Content Type ◽  
Highly Active ◽  
Carbapenem Resistant ◽  
Infection Models ◽  
Carbapenem Resistant Enterobacteriaceae

ABSTRACT Meropenem-vaborbactam (Vabomere) is highly active against Gram-negative pathogens, especially Klebsiella pneumoniae carbapenemase (KPC)-producing, carbapenem-resistant Enterobacteriaceae. The objective of these studies was to evaluate the efficacy of meropenem alone and in combination with vaborbactam in mouse thigh and lung infection models. Thighs or lungs of neutropenic mice were infected with KPC-producing carbapenem-resistant Enterobacteriaceae, with meropenem MICs ranging from ≤0.06 to 8 mg/liter in the presence of 8 mg/liter vaborbactam. Mice were treated with meropenem alone or meropenem in combination with vaborbactam every 2 h for 24 h to provide exposures comparable to 2-g doses of each component in humans. Meropenem administered in combination with vaborbactam produced bacterial killing in all strains tested, while treatment with meropenem alone either produced less than 0.5 log CFU/tissue of bacterial killing or none at all. In the thigh model, 11 strains were treated with the combination of meropenem plus vaborbactam (300 plus 50 mg/kg of body weight). This combination produced from 0.8 to 2.89 logs of bacterial killing compared to untreated controls at the start of treatment. In the lung infection model, two strains were treated with the same dosage regimen of meropenem and vaborbactam. The combination produced more than 1.83 logs of bacterial killing against both strains tested compared to untreated controls at the start of treatment. Overall, these data suggest that meropenem-vaborbactam may have utility in the treatment of infections due to KPC-producing carbapenem-resistant Enterobacteriaceae.

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