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 Meropenem-Vaborbactam versus Ceftazidime-Avibactam for Treatment of Carbapenem-Resistant Enterobacteriaceae Infections

2020 ◽  
Vol 64 (5) ◽  
Author(s):  
Renee Ackley ◽  
Danya Roshdy ◽  
Jacqueline Meredith ◽  
Sarah Minor ◽  
William E. Anderson ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Clinical Success ◽  
Recurrent Infection ◽  
Study Drug ◽  
First Episode ◽  
Development Of Resistance ◽  
Carbapenem Resistant ◽  
Significant Difference ◽  
Enterobacteriaceae Infections ◽  
Post Hoc

ABSTRACT The comparative efficacy of ceftazidime-avibactam and meropenem-vaborbactam for treatment of carbapenem-resistant Enterobacteriaceae (CRE) infections remains unknown. This was a multicenter, retrospective cohort study of adults with CRE infections who received ceftazidime-avibactam or meropenem-vaborbactam for ≥72 hours from February 2015 to October 2018. Patients with a localized urinary tract infection and repeat study drug exposures after the first episode were excluded. The primary endpoint was clinical success compared between treatment groups. Secondary endpoints included 30- and 90-day mortality, adverse events (AE), 90-day CRE infection recurrence, and development of resistance in patients with recurrent infection. A post hoc subgroup analysis was completed comparing patients who received ceftazidime-avibactam monotherapy, ceftazidime-avibactam combination therapy, and meropenem-vaborbactam monotherapy. A total of 131 patients were included (ceftazidime-avibactam, n = 105; meropenem-vaborbactam, n = 26), 40% of whom had bacteremia. No significant difference in clinical success was observed between groups (62% versus 69%; P = 0.49). Patients in the ceftazidime-avibactam arm received combination therapy more often than patients in the meropenem-vaborbactam arm (61% versus 15%; P < 0.01). No difference in 30- and 90-day mortality resulted, and rates of AE were similar between groups. In patients with recurrent infection, development of resistance occurred in three patients that received ceftazidime-avibactam monotherapy and in no patients in the meropenem-vaborbactam arm. Clinical success was similar between patients receiving ceftazidime-avibactam and meropenem-vaborbactam for treatment of CRE infections, despite ceftazidime-avibactam being used more often as a combination therapy. Development of resistance was more common with ceftazidime-avibactam monotherapy.

scholarly journals 1601. Combination Therapy versus Monotherapy for Carbapenem-resistant Organisms: Is More Really Better?

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S796-S797
Author(s):  
Laila Najia ◽  
Amy Carr ◽  
Jose Alexander ◽  
Sarah B Minor
Keyword(s):  
Combination Therapy ◽  
Clinical Success ◽  
Treatment Success ◽  
Recurrent Infection ◽  
Signs And Symptoms ◽  
Definitive Treatment ◽  
Secondary Source ◽  
Source Of Infection ◽  
Carbapenem Resistant ◽  
Length Of Therapy

Abstract Background Carbapenem-resistant organisms (CROs) represent an urgent public health threat and associated with mortality rates up to 60%. Pharmacotherapy for these infections remain challenging and historically included multiple agents. Meropenem/vaborbactam and ceftazidime/avibactam are options to treat CRO infections as monotherapy; however, combination therapy is still frequently utilized. Data evaluating outcomes of patients who received combination therapy compared to those receiving monotherapy for CRO infections is limited. Methods This retrospective analysis was completed across 7 campuses at AdventHealth Orlando (AHO) from March 2018-October 2019. AHO implemented CRO PCR testing in March 2018, to identify carbapenemase producing CROs (CP-CROs). Inclusion criteria were hospitalization, age ≥ 18 years, culture with CP-CRO detected by PCR, and ≥ 72 hours of either monotherapy or combination therapy. Primary outcome was clinical success, defined as resolution of signs and symptoms of infection and absence of recurrent infection. Secondary outcomes included mean length of therapy, mean length of stay, inpatient mortality, adverse reactions and 30-day all cause readmissions. Results CRO was isolated 68 times in 59 unique patients (56% male, mean age 62 years). Most common sources included urine (41%), sputum (24%) and wound (22%). Commonly isolated organisms include K. pneumoniae (44%) and E. cloacae (29%). Thirty infections (44%) were polymicrobial and 28 patients (41%) had a secondary source of infection. Forty-three patients (63%) received definitive treatment therapy with a single antibiotic. Monotherapy treated patients had higher rates of treatment success (79% vs 68%, p=0.39), lower in-hospital mortality (4% vs 9%, p=0.066), less nephrotoxicity (6% vs 10%, p=0.084), shorter length of therapy (9.6 vs 13.4 days, p=0.034) and shorter hospital stay (20 vs 34 days, p=0.056). All-cause readmission rates were higher in the monotherapy group (18% vs 9%, p=0.78). Minimum inhibitory concentrations (MIC) were reported in 97% of patients. Conclusion Treatment with a single antibiotic for carbapenem-resistant infections can lead to treatment success, while minimizing adverse events, compared to utilizing combination 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 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 Ceftazidime-Avibactam Therapy Versus Ceftazidime-Avibactam-Based Combination Therapy in Patients With Carbapenem-Resistant Gram-Negative Pathogens: A Meta-Analysis

2021 ◽  
Vol 12 ◽  
Author(s):  
Dan Li ◽  
Fan Fei ◽  
Hua Yu ◽  
Xiangning Huang ◽  
Shanshan Long ◽  
...  
Keyword(s):  
Mortality Rate ◽  
Combination Therapy ◽  
Clinical Success ◽  
Meta Analysis ◽  
Current Evidence ◽  
Gram Negative ◽  
Beneficial Effects ◽  
Development Of Resistance ◽  
Carbapenem Resistant ◽  
Significant Difference

Objective: To systematically review and compare the efficacy and posttreatment resistance of ceftazidime-avibactam therapy and ceftazidime-avibactam-based combination therapy in patients with Gram-negative pathogens.Methods: PubMed, Embase, Web of Science, CNKI, and Wanfang Data databases were searched from their inception up to March 31, 2021, to obtain studies on ceftazidime-avibactam therapy versus ceftazidime-avibactam-based combination therapy in patients with carbapenem-resistant Gram-negative pathogens. The primary outcome was mortality rate, and the second outcomes were microbiologically negative, clinical success, and the development of resistance after ceftazidime-avibactam treatment.Results: Seventeen studies representing 1,435 patients (837 received ceftazidime-avibactam-based combination therapy and 598 received ceftazidime-avibactam therapy) were included in the meta-analysis. The results of the meta-analysis showed that no statistically significant difference was found on mortality rate (Petos odds ratio (OR) = 1.03, 95% confidence interval (CI) 0.79–1.34), microbiologically negative (OR = 0.99, 95% CI 0.54–1.81), and clinical success (OR =0.95, 95% CI 0.64–1.39) between ceftazidime-avibactam-based combination therapy and ceftazidime-avibactam therapy. Although there was no difference in posttreatment resistance of ceftazidime-avibactam (OR = 0.65, 95% CI 0.34–1.26) in all included studies, a trend favoring the combination therapy was found (according to the pooled three studies, OR = 0.18, 95% CI 0.04–0.78).Conclusions: The current evidence suggests that ceftazidime-avibactam-based combination therapy may not have beneficial effects on mortality, microbiologically negative, and clinical success to patients with carbapenem-resistant Gram-negative pathogens. A trend of posttreatment resistance occurred more likely in ceftazidime-avibactam therapy than the combination therapy. Due to the limited number of studies that can be included, additional high-quality studies are needed to verify the above conclusions.

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 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 Increased 30-Day Mortality Associated With Carbapenem-Resistant Enterobacteriaceae in Children

2018 ◽  
Vol 5 (10) ◽  
Author(s):  
Kathleen Chiotos ◽  
Pranita D Tamma ◽  
Kelly B Flett ◽  
Manjiree V Karandikar ◽  
Koorosh Nemati ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Antibiotic Treatment ◽  
Multicenter Study ◽  
Significant Variation ◽  
Hospitalized Children ◽  
Carbapenem Resistant ◽  
Increased Risk ◽  
Carbapenem Resistant Enterobacteriaceae

Abstract In this multicenter study, we identified an increased risk of 30-day mortality among hospitalized children with carbapenem-resistant Enterobacteriaceae (CRE) isolated from clinical cultures compared with those with carbapenem-susceptible Enterobacteriaceae. We additionally report significant variation in antibiotic treatment for children with CRE infections with infrequent use of combination therapy.

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