CRE Infections Research Articles

Systematic Review and Meta-Analysis of Clinical Efficacy and Safety of Meropenem-Vaborbactam versus Best-Available Therapy in Patients with Carbapenem-Resistant Enterobacteriaceae Infections.

Antimicrobial resistance is increasingly concerning, causing millions of deaths and a high cost burden. Given that carbapenemase-producing Enterobacterales are particularly concerning due to their ability to develop structural modifications and produce antibiotic-degrading enzymes, leading to high resistance levels, we sought to summarize the available data on the efficacy and safety regarding the combination of meropenem-vaborbactam (MV) versus the best available therapy (BAT). Articles related to our objective were searched in the PubMed and Scopus databases inception to July 2024. To assess the quality of the studies, we used the Cochrane risk-of-bias tool, RoB2. The outcomes were pooled as a risk ratio (RR) and a 95% confidence interval (95%CI). A total of four published studies were involved: one retrospective cohort study and three phase 3 trials, including 432 patients treated with MV and 426 patients treated with BAT (mono/combination therapy with polymyxins, carbapenems, aminoglycosides, colistin, and tigecycline; or ceftazidime-avibactam; or piperacillin-tazobactam). No significant difference in the clinical response rate was observed between MV and the comparators at the TOC (RR = 1.29, 95%CI [0.92, 1.80], p = 0.14) and EOT (RR = 1.66, 95%CI [0.58, 4.76], p = 0.34) visits. MV was associated with a similar microbiological response as the comparators at TOC (RR = 1.63, 95%CI [0.85, 3.11], p = 0.14) and EOT assessment (RR = 1.16, 95%CI [0.88, 1.54], p = 0.14). In the pooled analysis of the four studies, 28-day all-cause mortality was lower for MV than the control groups (RR = 0.47, 95%CI [0.24, 0.92], p = 0.03). MV was associated with a similar risk of adverse events (AEs) as comparators (RR = 0.79, 95%CI [0.53, 1.17], p = 0.23). Additionally, MV was associated with fewer renal-related AEs than the comparators (RR = 0.32, 95%CI [0.15, 0.66], p = 0.002). MV was associated with a similar risk of treatment discontinuation due to AEs (RR = 0.76, 95%CI [0.38, 1.49], p = 0.42) or drug-related AEs (RR = 0.56, 95%CI [0.28, 1.10], p = 0.09) as the comparators. In conclusion, MV presents a promising therapeutic option for treating CRE infections, demonstrating similar clinical and microbiological responses as other comparators, with potential advantages in mortality outcomes and renal-related AEs.

Management of CRE Infections: High Time for an RCT?

How to cite this article: Kundu R, Chowdhury SR. Management of CRE Infections: High Time for an RCT? Indian J Crit Care Med 2024;28(5):511.

2779. Early Administration of Ceftazidime-Avibactam for Carbapenem-Resistant Enterobacterales Is Associated with Improved Clinical Success

Abstract Background Carbapenem-resistant Enterobacterales (CRE) are a significant public health threat. Ceftazidime-avibactam (CZA) retains activity against most carbapenemase-producing CRE and demonstrates favorable health outcomes compared to historically best available therapy. While early initiation of effective therapy is critical in serious infections, the impact of time to CZA initiation on CRE infection-related outcomes has yet to be assessed. Aim: to evaluate clinical outcomes of patients with CRE infections receiving early vs. late CZA as the first active β-lactam. Methods Multicenter, retrospective cohort of hospitalized adult patients from 2019-2022 with culture-positive CRE and infectious symptoms receiving early vs. late CZA as the first active β-lactam. Early and late CZA were defined as CZA administration within or after 48 hours of index culture collection, respectively. Primary outcome was a composite of clinical success defined as i) the absence of all-cause mortality or microbiological recurrence requiring therapy within 30 days from the end of CZA therapy and ii) continued infectious symptoms during CZA therapy. Results In total, 174 patients were included (≤48 hours n=52, >48 hours n=122). Median (IQR) age was 61 (53, 73) years and 56.3% were male. ICU admission rates were similar between early vs. late CZA (73.1% vs. 72.1%; P=0.921). Most common infection sources were respiratory (59.8%) and skin and skin structure (9.2%). Klebsiella pneumoniae was the most common CRE isolated (66%). The overall median (IQR) of CZA MIC was 2 (1,4). and there was no difference in the receipt of package insert CZA doses in the first 48 hours of CZA therapy between the early vs. late groups, respectively (1.9% vs. 5.2%; P=0.311). In total, 40/52 (76.9%) early and 68/122 (55.7%) late CZA patients met the clinical endpoint of clinical success (P< 0.001). The early and late CZA groups demonstrated similar ICU length of stay (LOS) (26 [9, 46] vs. 22 [12, 40]; P=0.431, respectively). Table 1. Baseline and Clinical Characteristics Conclusion In hospitalized adult patients with CRE infections, CZA administration within 48 hours of culture collection was associated with a higher rate of clinical success compared to CZA administered after 48 hours. Further studies in a larger patient cohort are warranted to verify these results. Disclosures Wesley D. Kufel, Pharm.D., BCPS, BCIDP, AAHIVP, Merck: Grant/Research Support Bryan White, PharmD, BCPS, BCIDP, Gilead Sciences: Advisor/Consultant Michael J. Rybak, PharmD, PhD, MPH, Abbvie, Merck, Paratek, Shionogi, Entasis, La Jolla, T2 Biosystems: Advisor/Consultant

Carbapenemase genes and mortality in patients with carbapenem-resistant Enterobacterales, Atlanta, Georgia, 2011–2020

Background: Carbapenemase genes in carbapenem-resistant Enterobacterales (CP-CRE) may be transmitted between patients and bacteria. Reported rates of carbapenemase genes vary widely, and it is unclear whether having a carbapenemase gene portends worse outcomes given that all patients with CRE infections have limited treatment options. Methods: Using active population- and laboratory-based active surveillance data collected by the US CDC-funded Georgia Emerging Infections Program from 2011 to 2020, we assessed the frequency of carbapenemase genes in a convenience sample of CRE isolates using whole-genome sequencing (WGS), and we investigated risk factors for carbapenemase positivity. Only the first isolate per patient in a 30-day period was included. We compared characteristics of patients with CP-CRE and non–CP-CRE. Using multivariable log binomial regression, we assessed the association of carbapenemase gene positivity and 90-day mortality. Results: Of 284 CRE isolates, 171 isolates (60.2%) possessed a carbapenemase gene (Table 1), and KPC-3 was the most common carbapenemase gene (80.7%), with only 7 isolates possessing NDM (Table 2). No isolates possessed >1 carbapenemase gene, and most isolates were from urine (82.4%) (Table 1). Carbapenemase gene positivity was associated with lower age, male sex, black race, infection with Klebsiella pneumoniae, polymicrobial infection, having an indwelling medical device, receiving chronic dialysis, and prior stay in a long-term acute-care hospital, long-term care facility, and/or prior hospitalization in the last year. The 90-day mortality rates were similar in patients with non–CP-CRE and CP-CRE: 24.8% versus 25.7% (P = .86). In multivariable analysis, carbapenemase gene presence was not associated with 90-day mortality (adjusted risk ratio, 0.82; 95% CI, 0.50–1.35) when adjusting for CCI, infection with Klebsiella pneumoniae, and chronic dialysis use. Conclusions: The frequency of CP-CRE among CRE was high in this study, but unlike prior studies, the 90-day mortality rates wer similar in patients with CP-CRE compared to non–CP-CRE. Our results provide novel associations (eg, lower age, male sex, infection with Klebsiella pneumoniae, and indwelling medical devices) that infection preventionists could use to target high-risk patients for screening or isolation prior to CP-CRE detection.Disclosure: None

Synergy between infection control and antimicrobial stewardship programs to control carbapenem-resistant Enterobacterales.

Argentina is the third country in the world with the higher levels of CRE. The primary objective is to achieve an optimal result in the CRE infection rate after the implementation of an IPC program and antimicrobial stewardship programs (ASP) in a large teaching hospital in Argentina. Retrospective, observational study from January 2018 to December 2021, in a 220-bed tertiary care teaching hospital in Buenos Aires province. Actions aimed at CRE control and prevention included CRE and healthcare-associated infection (HAI) surveillance; compliance with hand hygiene, hospital hygiene, contact isolation precautions, and care bundles for the prevention of device-associated infections; optimization of antimicrobial treatments, antimicrobial consumption, education, and feedback. Synergy between an ICP and ASP achieved controlled rate of CRE infections reaching the lowest levels during 2020 (0.08 episodes/1000 patient days). Colonization rate remained stable throughout the study period. Ventilator-associated pneumonia (VAP) rate showed a trend toward lower rates. Compliance with care bundles showed rates >85%. Antimicrobial consumption increased slightly during the study period (15%). Among high-impact antimicrobials, only colistin consumption increased. Our study demonstrates the sustained and beneficial impact of an IPC Program and an ASP to control CRE infection.

417. Factors associated with 30-day Mortality in Carbapenems-resistant Enterobacteriaceae Infections

Abstract Background Carbapenem-resistant Enterobacteriaceae (CRE) infections are the serious conditions and provide high mortality. The studies of risk factors of death in CRE infection have been limited particularly in our center. Hence, the study was conducted for evaluating mortality and factors associated with CRE infection. Methods A retrospective cohort study was conducted between January 1st, 2015, and December 31st, 2019 in sigle center medical university. All patients diagnosed CRE infections who aged ≥ 18 years were included and reviewed. The multivariate logistic regression was used for evaluating the factors associated with 30-day mortality. Results Ninety-three patients enrolled in the study. The 30-day mortality occurred in thirty-five patients (37.6%). The non-survive patients had significantly higher simplified acute physiology (SAP) II score, sepsis at the time of diagnosis, and pneumonia (p< 0.05) than survive patients. The most common pathogen was Klebsiella pneumoniae, Escherichia coli and Enterobacter spp. The most common CRE isolates were susceptible to fosfomycin, tigecycline, and colistin (96.7%, 95.7%, 90.3%, respectively). The independent factors associated with 30-day mortality were having simplified acute physiology (SAP) II score > 30 [adjusted odds ratio (aOR) of 12.98 (95% confidence interval (CI), 2.84-59.34, p=0.001)], sepsis at the time of diagnosis [aOR of 4.77 (CI 1.19-19.20, p=0.03)], pneumonia [aOR of 4.64 (CI 1.31-16.47, p=0.01)], and improper empiric antibiotic [aOR of 7.83 (CI 1.84-33.37, p=0.01)]. Conclusion The mortality of CRE infections were high. The factors associated with 30-day mortality were having SAP II score > 30, sepsis at the time of diagnosis, pneumonia, and improper empiric antibiotic. Disclosures All Authors: No reported disclosures.

416. Evaluating Indwelling Devices and Mortality in Invasive Carbapenem-Resistant Enterobacterales Infections, Atlanta, GA, 2012–2019.

Abstract Background Carbapenem-resistant Enterobacterales (CRE) infections pose a grave public health threat due to the potentially silent transmission leading to outbreaks, limited therapeutic options and high mortality. We sought to identify risk factors for mortality in patients with invasive CRE infections and describe the association between indwelling medical devices and 90-day mortality. Methods The Georgia Emerging Infections Program performs active population and laboratory based surveillance for CRE in the Atlanta, Georgia metropolitan area. Using this data we created a retrospective observational cohort of patients with invasive CRE infections between 2012 and 2019. Invasive infections were defined as resistant isolates obtained from a normally sterile site (Table 1). Indwelling medical devices, including central venous catheters (CVCs), were present within two calendar days prior to infection. We completed bivariate analyses examining the relationship between covariates and mortality. Multivariable log binomial regression was used to estimate adjusted risk ratios (aRR) for the association of covariates and all-cause 90-day mortality. Sub-group analyses were completed evaluating only those patients with CVCs and those with at least two indwelling devices. Table 1.Definition of Carbapenem-resistant Enterobacterales Abbreviations: MIC – minimum inhibitory concentration Results There were 154 invasive CRE infections (Table 2) with 87.7% having at least one indwelling device and an overall mortality of 23.4%. Intensive care unit (ICU) admission, having at least two indwelling devices, and requiring chronic dialysis were associated with mortality on bivariate analysis. The presence of any indwelling device (aRR 1.02, 95% CI 0.36, 2.89) or specifically a CVC (aRR 1.13, 95% CI 0.54, 2.37) were not associated with increased risk of 90-day mortality in unadjusted or multivariable analysis (Table 3). Having at least two indwelling devices was associated with increased risk of mortality (aRR 2.48, 95% CI: 1.02, 5.99) (Table 3). Characteristics of Patients with Invasive CRE Infections in Atlanta, Georgia 2012-2019 Race: 6 unknowns, Ethnicity: 28 unknowns Other race: American Indian or Alaska Native, Asian, Native Hawaiian or Pacific Islander Other sites of infection: deep tissue, sterile fluid, or other sterile site Other indwelling devices: endotracheal or nasotracheal tube, nephrostomy tube, nasogastric tube, other * 1 missing **16 patients never admitted to the hospital and 2 with missing data Risk Ratios for Invasive Devices and Mortality Including Subgroup Analyses 1 Adjusted for indwelling device, Charlson comorbidity score, intensive care admission, previous stay at LTACH 2 Adjusted for central venous catheter, Charlson comorbidity score, intensive care admission, previous stay at LTACH 3 Adjusted for at least two indwelling devices, Charlson comorbidity score, previous stay at LTACH Abbreviations: LTACH - Long Term Acute Care hospital Conclusion In patients with invasive CRE infections, indwelling medical device use was frequent but only associated with mortality in patients with multiple devices. Stewardship of medical devices may be an important target for intervention in this population. Disclosures All Authors: No reported disclosures.

The Distribution and Source of MRDOs Infection: A Retrospective Study in 8 ICUs, 2013-2019.

BackgroundTo analyze the distribution and source of MDROs infection in the ICUs and to provide a basis for formulating more effective prevention and control programs for MDROs.MethodsA retrospective investigation was conducted on MDROs infection in 8 ICUs of a large tertiary hospital from July 2013 to June 2019. A total of 2629 strains of MDROs isolated from 1701 inpatients were selected for analysis. The MDROs of the 8 ICUs were divided into two types of four categories according to source: out-of-hospital (out-of-hospital transfer and community acquisition) and in-hospital (in-hospital transfer and department acquisition) infections.ResultsCRAB (41.84%) and CRE (35.07%) accounted for the majority of the infecting MDROs. The detection rates of MRSA, CRAB, CRPA and CRE were 61.24%, 83.75%, 43.01% and 30.15%, respectively. The top three infection sites of MDROs were the lower respiratory tract (81.10%), blood (6.70%) and abdominal cavity (5.80%). The out-of-hospital and in-hospital infection rates of MDROs were 50.51% and 49.49%, respectively; the out-of-hospital infection rates for MRSA, CRAB, CRPA and CRE were 43.56%, 55.91, 64.44% and 44.58%, respectively. The proportions of MRSA, CRAB, CRPA and CRE infections contracted in the department were 40.98%, 36.27%, 25.56% and 46.62%, respectively. There was a statistically significant difference between comprehensive ICU and specialized ICU wards as sources for CRAB infections (P < 0.001).ConclusionThe main source of MDROs in the ICU is not the hospital itself entirely. It is particularly important to strengthen the identification of MDRO sources and implement more effective and accurate infection prevention and control measures.

Escalating antimicrobial resistance among Enterobacteriaceae: focus on carbapenemases

ABSTRACT Introduction: Over the past few decades, antimicrobial resistance (AMR) has skyrocketed globally among bacteria within the Family Enterobacteriaceae (i.e. Enterobacter spp, Klebsiella spp, Escherichia coli, Proteus spp, Serratia marcescens, Citrobacter spp, and others). Enterobacteriaceae are intestinal flora and are important pathogens in nosocomial and community settings. Enterobacteriaceae spread easily between humans and may acquire AMR via plasmids or other mobile resistance elements. The emergence and spread of multidrug resistant (MDR) clones have greatly limited therapeutic options. Some infections are untreatable with existing antimicrobials. Areas covered: The authors discuss the escalation of CRE globally, the epidemiology and outcomes of CRE infections, the optimal therapy, and the potential role of several new antimicrobials to combat MDR organisms. An exhaustive search for literature related to Enterobacteriaceae was performed using PubMed, using the following key words: antimicrobial resistance; carbapenemases; Enterobacterales; Enterobacteriaceae; Klebsiella pneumoniae; Escherichia coli; global epidemiology; metallo-β-lactamases; multidrug resistance; New Delhi Metalloproteinase-1 (NDM-1); plasmids Expert opinion: Innovation and development of new classes of antibacterial agents are critical to expand effective therapeutic options. The authors encourage the judicious use of antibiotics and aggressive infection-control measures are essential to minimize the spread of AMR.

Pharmacodynamic evaluation of meropenem, cefepime, or aztreonam combined with a novel β-lactamase inhibitor, nacubactam, against carbapenem-resistant and/or carbapenemase-producing Klebsiella pneumoniae and Escherichia coli using a murine thigh-infection model

BackgroundCarbapenem-resistant Enterobacterales (CRE) and carbapenemase-producing Enterobacterales (CPE) are difficult to treat and are a serious public health threat. Nacubactam (NAC) is a novel non-β-lactam diazabicyclooctane β-lactamase inhibitor with in vitro activity against some Enterobacterales expressing classes of β-lactamases. MethodsThe antimicrobial efficacy of meropenem (MEM), cefepime (FEP), and aztreonam (ATM), each in combination with NAC, were assessed in vitro and in vivo against Klebsiella pneumoniae and Escherichia coli. Ten isolates, including CRE and/or CPE with β-lactamase genes, were used in this study. The relationship between phenotype and in vivo efficacy was assessed in a murine neutropenic thigh-infection model. Efficacy was determined by the change in bacterial quantity. ResultsThe results of the in vitro study showed the minimum inhibitory concentrations of the combination of NAC with either MEM, FEP, or ATM in a 1:1 ratio were 2 to >128-fold lower than those of MEM, FEP, or ATM alone against CRE+ isolates. In addition, combinations of β-lactams and NAC administered in the murine thigh-infection model showed greater efficacy against CRE+/CPE+, CRE+/CPE-, and CRE-/CPE+ isolates harboring various β-lactamase genes (IMP-1, IMP-6, KPC, DHA-1, or OXA-48) compared with MEM, FEP, ATM, and NAC alone. ConclusionMEM, FEP, or ATM in combination with NAC showed potent in vivo antimicrobial activity in a murine thigh-infection model caused by K. pneumoniae and E. coli, including CRE and/or CPE isolates. These findings indicate that these combinations of β-lactams and NAC are potential candidates for the treatment of CRE and/or CPE infections.

Predominance of Non-carbapenemase Producing Carbapenem-Resistant Enterobacterales in South Texas.

BackgroundCarbapenem-resistant Enterobacterales (CRE) pose a significant global public health threat. Resistance among CRE is particularly complex, owing to numerous possible resistance mechanisms and broad definitions. We aimed to characterize the clinical and molecular profiles of CRE in the South Texas region.Materials and methodsWe compared the clinical, genotypic, and phenotypic profiles of carbapenemase producing Enterobacterales (CPE) with those of non-carbapenemase producers (NCPE) isolated from South Texas, United States between 2011 and 2019. Molecular characteristics and resistance mechanisms were analyzed using whole-genome sequences.ResultsThe majority (59%) of the CRE isolates were NCPE while 41% of isolates harbored carbapenemases, predmonantly blaKPC-type. The most common CPE was Klebsiella pneumoniae while majority of Enterobacter cloacae and Escherichia coli were NCPE Among K. pneumoniae, the clonal group 307 has emerged as a predmoninant group and was associated with as many CRE infections as the previous common clonal group 258. Patients with NCPE compared to CPE infections were associated with higher antimicrobial exposure prior to culture collection (days of therapy, 795 vs. 242; p < 0.001) and emergency department visits within past 90 days (22% vs. 4%; p = 0.011). The all cause 30-day mortality was 21%.ConclusionsThis study highlights the diversity of resistance mechanisms underlying CRE in South Texas, with 59% not harboring a carbapenemase. Individuals with NCPE infections were more likely to have had prior antimicrobial therapy and emergency department visits compared to those with CPE. Identification and distinction of these mechanisms by rapid identification of species and carbapenemase would allow for optimal treatment and infection control efforts.

1591. Antibiotic Utilization Trends in Veterans Affairs (VA) Patients with Carbapenem Resistant Enterobacteriaceae (CRE) Infections

BackgroundCarbapenem-resistant Enterobacteriaceae (CRE) are classified as an “urgent threat” to public health. Historically, colistin and tigecycline had been considered the drugs of choice for CRE infections, while other agents such as aminoglycosides and carbapenems had been used as adjunctive therapy. However, the FDA approval of ceftazidime-avibactam in 2015, meropenem-vaborbactam in 2017, and plazomicin in 2018 has expanded treatment options. Our purpose was to assess trends in CRE treatment for “new” antibiotics (ceftazidime-avibactam, meropenem-vaborbactam, plazomicin) as compared with other antibiotics with CRE activity.MethodsThis was a retrospective cohort study describing treatment of CRE blood stream infections (BSI) across 134 VA facilities from 2012-2018. Patients were censored at their first positive blood culture with CRE. Categorical data was assessed with a Fisher’s exact test or chi-square test. Trends test and logistic regression were used to describe changes in CRE treatment over time.Results724 patients with positive blood cultures for CRE were identified during the study period. Most patients were male (94%), white (32%) or Hispanic (38%), and the mean age was 71.5+11.9. Of those patients that received antibiotics (N=697), 53.4% carbapenems, 40.3% received aminoglycosides, 39.3% received polymyxins, 32.9% penicillins, 32.6% extended spectrum cephalosporins, 26.1% fluoroquinolones, 11.6% ceftazidime/avibactam, and 0.4% ceftolazone/tazobactam. Over the study period, there was decreased utilization of aminoglycosides (P < 0.0026) and colistin (P< 0.002) and increases in extended spectrum cephalosporins (P < 0.001) and ceftazidime/avibactam (P < 0.001).ConclusionUtilization of “older” agents such as aminoglycosides and polymyxins for the treatment of CRE blood stream infections is decreasing in the VA. Treating CRE with ceftazidime/avibactam, a newly approved antibiotic, and extended spectrum cephalosporins are increasing.Disclosures All Authors: No reported disclosures

Performance quality control of carbapenem-resistant enterobacteriaceae using multiplex polymerase chain reaction and BD max assay

Background: Carbapenem-resistance is marked as a major challenge to clinicians considering that carbapenems are considered as the last-line treatment for Enterobacteriaceae treatment. Molecular classification, with consideration of their geographical origin, of these organisms are found to be relevant to the drug of choice for the affected individuals. Methods and materials: A total of 27 clinical strains were tested in this study and 5 reference strains were used as positive controls of the study. Thus, this study focused on the detection of the different carbapenamase genes in the western province of Thailand namely blaKPC, blaOXA-48, blaNDM, and blaVIM using real-time PCR and multiplex PCR assay. Results: In this study, I demonstrated that among all clinical strains, 24 strains were positive for blaNDM gene which is about 77% while 5 strains were positive for blaOXA-48 which is 16%. However, among all the strains, 2 CRE strains were negative for any carbapenamase gene which showed 7% of all the clinical strains tested. Furthermore, 4 clinical strains were positive for 2 carbapenamase genes. Therefore, among all the clinical strains tested, only blaNDM and blaOXA-48 genes were detected. Conclusion: Overall, blaNDM is considered to be the dominant gene that is prevalent in Thailand. The data would help medical professionals in considering drug therapy for a patient with CRE infections. Further studies should consider testing more clinical strains and to analyze it with high precision and expertise. Surveillance and proper identification of carbapenem-resistant Enterobacteriaceae will benefit the good prognosis of the future patients in Thailand.

PIN43 IMPACT of CRE Infections on Hospital LOS and Mortality in ASIA

PIN43 IMPACT of CRE Infections on Hospital LOS and Mortality in ASIA

In vivo study assessed meropenem and amikacin combination therapy against carbapenem-resistant and carbapenemase-producing Enterobacteriaceae strains

BackgroundCarbapenem-resistant Enterobacteriaceae (CRE), especially for carbapenemase-producing Enterobacteriaceae (CPE), is an emerging cause that pose a significant threat to public health. However, efficient therapy has not been established. We assessed the antimicrobial efficacy of meropenem (MEPM) and amikacin (AMK) combination therapy. Material and methodsTotal eight isolates of Escherichia coli or Klebsiella pneumoniae, including CRE and/or CPE have carbapenemase genes were used. The relationship between phenotype and in vivo efficacy was assessed in neutropenic murine thigh infection model. Efficacy was determined using the change in bacterial density and survival rate. ResultsThe combination therapy showed enhanced antimicrobial activities against CRE+/CPE+ and CRE+/CPE-K. pneumoniae isolates than MEPM monotherapy (0.63 ± 0.04 vs. 2.56 ± 0.24 ⊿log10 cfu/mL, p < 0.05; −1.05 ± 0.15 vs. −0.48 ± 0.30 ⊿log10 cfu/mL, p < 0.05). Likewise, the combination therapy showed enhanced antimicrobial activities against CRE+/CPE+ and CRE+/CPE-E. coli isolates than MEPM monotherapy (0.90 ± 0.68 vs. 1.86 ± 0.23 ⊿log10 cfu/mL, p < 0.05; −1.81 ± 0.06 vs. −0.88 ± 0.23 ⊿log10 cfu/mL, p < 0.05). Also, combination therapy group showed similar to higher survival rates in CRE + E. coli infection mice, compared to MEPM monotherapy group. ConclusionOur results are the first supportive data to threat CRE infections with combination therapy of MEPM and AMK with in vivo model. The current results verify the promising utility of the combination therapy with MEPM and AMK against CRE isolates with a wide range of MEPM MICs.

2130. Detection of Carbapenemase-Producing Organisms and Impact on Antimicrobial Utilization for Carbapenem-Resistant Enterobacteriaceae (CRE) Infections

BackgroundCREs are feared pathogens with resistance occurring through the production of carbapenemases. Identification of carbapenemase-producing (CP) organisms assists with proper antimicrobial selection of commonly used agents, such as ceftazidime/avibactam (CA), meropenem/vaborbactam (MV), and tigecycline (TG). AdventHealth Orlando implemented a CRE screening method based on meropenem (MER) and a confirmatory CRE PCR testing in March 2018. Prior to implementing this test, patients were deemed to have CRE infections (CREI) if the organism demonstrated resistance to any carbapenem. The objective of this study was to evaluate the impact of this testing on the utilization of anti-CRE antibiotics.MethodsThis was a retrospective pre (March 2017–February 2018)- and post (March 2018–February 2019)-implementation study examining the impact of CRE PCR testing. Outcomes included the number of antibiotic days saved, average duration of therapy (DOT), median length of stay (LOS), and change in CP-CRE prevalence. The intervention consisted of the implementation of CRE PCR testing and included inpatients > 18 years old who received either CA, MV, or TG for the treatment of a CREI.ResultsPost-implementation, 30 unique patients were identified as having a positive K. pneumoniae carbapenemase gene by PCR, indicating a CP-CRE and received CA, MV, or TG; whereas, 42 patients in the pre-implementation group had a CREI and received CA, MV, or TG. Testing to identify CP-CREs led to a 50% reduction in the number of antibiotic days for CA, MV, and TG (575 vs. 287 days, P < 0.0001). Additionally, the average DOT decreased by 2.5 days in the post-implementation group (10.5 days vs. 8 days, P = 0.18) along with a 3.5-day shorter median LOS (15 days vs. 11.5 days, P = 0.48). The CRE prevalence based on resistance only to MER is 0.27%, compared with the previously reported rate of 2.5% that included resistance to ertapenem or MER.ConclusionImplementing CRE PCR testing to identify CP-CRE organisms resulted in a significant reduction in utilization of anti-CRE agents for CREIs. Additionally, the testing algorithm allowed for accurate reporting of our local CRE prevalence. By avoiding CA, MV, or TG in patients without CP-CREs, this has the potential to optimize therapy while reducing collateral damage associated with broad-spectrum agents.Disclosures All authors: No reported disclosures.

191. Appropriateness of Empiric Antibiotics for Enterobacteriaceae Bacteremia

BackgroundAppropriate empiric antibiotic therapy is associated with decreased mortality and recurrence in patients with Enterobacteriaceae bacteremia (EB). Increasing bacterial resistance adds an additional layer to this complex clinical scenario. Swift utilization of appropriate antibiotics is crucial for improved patient outcomes. However, prolonged and excessively broad antibiotic coverage is not without its own complications. Our study aimed to review the appropriateness of empiric antibiotics for EB.MethodsA retrospective chart review of all patients >18 years of age who were admitted to a single academic community hospital during 2018 EB anytime throughout their hospitalization. The primary endpoint was the appropriateness of empiric antibiotic therapy, defined as receiving active therapy prior to the return of antimicrobial sensitivities that were susceptible to the empiric agents used. Appropriateness was further adjusted for standard of care (SOC) practices. Specifically, despite in vitro susceptibility of piperacillin/tazobactam and cefepime, carbapenem therapy is preferred for ESBL infections.ResultsOur study identified 178 patients with EB. Most common organisms included E.coli (64.6%), K. pneumoniae (11.8%) and P. mirabilis (7.3%). Resistance patterns included 1 CRE (0.57%) and 17 ESBL (9.7%) isolates. Most common sources of infection included urinary (63.5%) and intraabdominal (13.5%). Based on the sensitivity reports of tested isolates, 83.7% of patients received appropriate empiric antibiotics. After adjustment for SOC, 11.8% of ESBL patients (2/17) and 0% of CRE (0/1) patients received appropriate therapy. Comparatively 89.0% of patients without ESBL or CRE (137/154) received appropriate care (P < 0.0001).ConclusionThe results of this study demonstrate that across our patient population, over 80% of patients received appropriate empiric antibiotics for EB; however, this percentage was dramatically lower for patients with ESBL or CRE infections. This highlights room for improved rapid diagnosis and identification of risk factors predisposing to resistant organisms thereby decreasing the time to appropriate antibiotic therapy. Disclosures All authors: No reported disclosures.

2247. Real-world Experience with Meropenem–Vaborbactam (M/V) for Treatment of Carbapenem-Resistant Enterobacteriaceae (CRE) Infections

BackgroundM/V demonstrates in vitro activity against KPC-producing CRE, but real-world clinical experience is limited.MethodsPatients treated for > 48 hours with M/V for CRE infections were included. Success was defined as improved symptoms, absence of recurrent infection, and survival at 30 days. Microbiologic failures (MF) were defined as isolation of the same species post-treatment (tx). KPC and ompK36 mutations were detected by sequencing of PCR products.Results19 patients were included; 58% were men; median age was 53. 11% were transplant recipients and median Charlson score was 3 (range: 0–10). Infection types included bacteremia (n = 7), pneumonia (6; 5 ventilator-associated), soft tissue (2), tracheobronchitis (2), intra-abdominal (1), and pyelonephritis (1). 68% of patients were in the ICU; median APACHE II and SOFA scores were 18 (7–40) and 4 (1–13), respectively. CR pathogens included K. pneumoniae (14), K. oxytoca (2), E. coli (2), and C. freundii (1); 89% harbored KPC, including KPC-2 (6), KPC-3 (10), and KPC-3 with a D179Y mutation (1). All were susceptible to M/V (median MIC = 0.03 µg/mL [0.015–0.12]). Median duration of tx was 8 days (3 – 28); 89% received monotherapy. Success and survival rates at 30d were 63% and 89%, respectively. Failures were due to death (2), recurrent infection (2), worse symptoms (2), and persistent bacteremia (1). Success rates for bacteremia and pneumonia were 57% and 67%, respectively. MF within 90 days occurred in 32% due to K. pneumoniae (5) or E. coli (1). MF were classified as intra-abdominal abscess (3), pneumonia (1), and respiratory (1) or urinary (1) colonization. The median time to MF was 32 days (15 – 67). M/V MICs were increased ≥8-fold against 67% (4/6) of recurrent isolates. 1 pt developed intra-abdominal infection due to M/V non-susceptible KPC-3 K. pneumoniae isolate (MIC = 8) following a 12-day of M/V; the recurrent isolate differed from the parent by an IS5 insertion in the ompK36 gene promoter. M/V was well-tolerated, 1 patient developed eosinophilia.ConclusionIn this cohort of critically-ill patients with CRE infection, tx with M/V yielded outcomes comparable to prior cohorts treated with ceftazidime–avibactam. M/V non-susceptibility emerged in 1 isolate. Our findings require validation in future studies.Disclosures All authors: No reported disclosures.

2276. Clinical Epidemiology of the Carbapenem-Resistant Enterobacteriaceae (CRE) Epidemic in Colombia: A Multicenter Prospective Study

BackgroundThe CRE epidemic in Colombia is amplified by horizontal transmission of mobile genetic elements encoding KPC among Enterobacteriaeae and clonal expansion of K. pneumoniae clonal group (CG) 258, making the country hyperendemic for CRE. However, the clinical impact of CRE infections has not been comprehensively assessed.MethodsIn the framework of a prospective study assessing the clinical epidemiology of CRE (CRACKLE II), we report the results of the first 246 patients enrolled in 5 Colombian hospitals (from July 2017 to November 2018). Clinical variables, outcomes at 90 days post-hospitalization and susceptibility patterns were collected. Resistance to carbapenems was defined per CDC guidelines. Infection was defined with standardized criteria. All isolates which did not meet these criteria were considered colonizationResultsThe majority of patients were men (66%); median age was 62 years [IQR 37–73]); 67% were admitted from home and 33% were hospital transfers. The mean Charlson Comorbidity Index and Pitt Bacteremia scores were 2 (SD = 2) and 3 (SD = 3), respectively. Most patients (60%; n = 148) were considered to be infected. The most frequent source of culture was urine (36%), followed by blood (30%) and wound secretions (13%). A respiratory source was found in the minority (6%) of patients. Species of CRE are summarized in Table 1 with the majority being K. pneumoniae. The best in vitro activity against CRE was found for fosfomycin (80% susceptible (47/59)), tigecycline (75% (67/89)), colistin (70% (35/50)) and amikacin (67% (148/220)). From 234 patients with available information at 90 days of follow-up, 13% were readmitted after discharge. Mortality at 30 and 90 days after a positive culture was 31% and 35%, respectively.Conclusion K. pneumoniae are the main drivers of the CRE epidemic in Colombia isolated mainly from non-respiratory sources. Non-susceptibility to last resource antibiotics (tigecycline, colistin and fosfomycin) is substantial among the Colombian isolates leaving few therapeutic options, a finding that correlates with high mortality. Our findings indicate that introduction of novel therapeutics in Colombia is urgently needed with a rampant epidemic of CRE causing high burden of disease.Disclosures All authors: No reported disclosures.

Efficacy of ceftazidime-avibactam in the treatment of infections due to Carbapenem-resistant Enterobacteriaceae

BackgroundCarbapenem-resistant Enterobacteriaceae (CRE) represent an important global threat. The aim of this study is to describe the clinical course and outcomes of patients with CRE infections treated with ceftazidime-avibactam (CAZ-AVI) compared to patients treated with other agents.MethodsA retrospective cohort study of patients with established CRE infections from January 2017 until August 2018 was conducted. All patients who received CAZ-AVI and all cultures with carbapenem-resistant isolates were screened. We compared patients who received CAZ-AVI for CRE infections with patients who received other agents.ResultsA total of 38 consecutive patients with CRE infections were identified. Age and baseline comorbidities were similar between the two groups. The median time from admission to isolation of CRE culture was 22.5 days in the CAZ-AVI group and 17 days in the comparative group (P = 0.7). The incidence of CRE bacteremia was similar between the two groups: 7 patients (70%) in the CAZ-AVI group and 15 patients (53.6%) in the comparative group (P = 0.47). The most common type of CRE infections in both groups was hospital acquired pneumonia (HAP). Klebsiella pneumoniae was the predominant pathogen in both groups. A carbapenemase gene was detected in 35 (92%) patients; the OXA-48 gene was the predominant gene identified in 28 (74%) isolates. Eight out of ten patients in the CAZ-AVI group and fifteen out of twenty-eight in the comparative group achieved clinical remission (P = 0.14). After thirty days, all-cause mortality was observed in five patients in the CAZ-AVI group and 16 patients in the comparative group, accounting for 50 and 57% respectively.ConclusionsIn patients with established OXA-48-type CRE infection, CAZ-AVI is a reasonable alternative to standard therapy. These findings need to be confirmed in prospective studies.