Carbapenem Therapy Research Articles

38. Predicting stenotrophomonas Maltophilia bloodstream Infections (BSI) in the Hematologic Malignancy Population

BackgroundTrimethoprim-sulfamethoxazole (TMP-SMX) is the preferred treatment for S. maltophilia BSI. Hematologic malignancy patients are at increased risk of S. maltophilia BSI but because of the TMP-SMX adverse event profile, this agent is not routinely included in empiric treatment regimens. We sought to identify risk factors for S. maltophilia BSI in hematologic malignancy patients to guide empiric treatment decisions in this population.MethodsInpatients ≥ 12 years at Johns Hopkins Health System hospitals between 7/1/16-12/1/19 with a hematologic malignancy and/or stem cell transplant (SCT) within 12 months were included. Cases were patients with S. maltophilia BSI and controls were patients with BSI from Gram-negative organisms other than S. maltophilia. Demographics, pre-existing medical conditions, antibiotic use (including prophylaxis) in the previous 3 months, and hospitalization in the previous 3 months were compared between cases and controls using non-parametric methods and multivariable logistic regression.ResultsThere were 20 cases and 105 controls. Cases and controls were similar in terms of age, sex, type of underlying malignancy, proportion with recent SCT, absolute neutrophil count, (ANC), central venous catheter, and severity of illness. Cases were more likely to have received ≥ 72 hours of a carbapenem within the preceding 3 months, controlling for age, recent SCT, ANC, and central venous catheter (OR=3.11, 95% 1.05–9.16, p=0.04). There were no significant differences in prior cefepime or piperacillin/tazobactam use in the preceding 3 months between cases and controls.ConclusionHematologic malignancy patients who received ≥ 72 hours of carbapenem therapy, but not other broad spectrum antibiotic use within the previous 3 months were more likely to be infected with S. maltophilia BSI. Identifying patients at high risk for S. maltophilia BSI can ensure early, appropriate empiric therapy – ultimately improving clinical outcomes.Disclosures All Authors: No reported disclosures

835. Comparison of the outcomes of patients with KPC and NDM-1-producing Enterobacteriaceae

BackgroundCarbapenemase-producing Enterobacteriaceae infections are associated with high mortality. We aimed to compare the clinical outcomes of patients with Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae and those with New-Delhi-Metallo-beta-lactamase-1 (NDM-1)-producing Enterobacteriaceae.MethodsWe performed a retrospective cohort study of all adult patients (> 16 years old) with KPC or NDM-1-producing Enterobacteriaceae isolates in a 2,700-bed tertiary referral hospital in Seoul, South Korea between 2010 and 2019. Primary outcomes were infection within 30 days and 30-day mortality after the first isolation of KPC or NDM-1-producing Enterobacteriaceae.ResultsA total of 859 patients were identified during the study period. Of them, 475 (55%) were KPC group and 384 (45%) were NDM-1 group. KPC group tended to develop infection within 30 days after first isolation more frequently than NDM-1 group (31% vs. 26%; P = 0.07). Thirty-day mortality was significantly higher in KPC group compared to NDM-1 group (KPC, 17% (81/475) versus NDM-1, 9% (33/384), P < 0.001). Multivariate analysis revealed that APACHE II score (adjusted odds ratio [aOR], 1.12; P < 0.001), solid cancer (aOR, 2.56; P < 0.001), previous carbapenem therapy (aOR, 1.93; P = 0.004), development of infection of KPC or NDM-1-producing Enterobacteriaceae within 30 days (aOR, 2.63; P < 0.001), and KPC-producing Enterobacteriaceae (aOR, 1.62; P = 0.045) were independent risk factors for 30-day mortality.Table 1. Results of analyses of risk factors for 30-day mortality from initial positive culture date in patients with KPC or NDM-1- producing Enterobacteriaceae Figure 1. Kaplan–Meier survival estimates of patients with KPC or NDM-1-producing Enterobacteriaceae for 30-day mortality after first isolation: KPC (continuous line) versus NDM (dotted line). (log-rank test). ConclusionOur study suggests that KPC-producing Enterobacteriaceae is associated with poorer outcome compared to NDM-1-producing Enterobacteriaceae. Therefore, patients with KPC-producing Enterobacteriaceae colonization should be monitored carefully for development of infection, and appropriate antibiotics should be initiated as soon as possible.Disclosures All Authors: No reported disclosures

115. Influence of Antimicrobial Stewardship and Molecular Rapid Diagnostic Test on Antimicrobial Prescribing for Extended-spectrum Beta-lactamase and Carbapenemase-producing Bacteria in Bloodstream Infections

BackgroundMolecular rapid diagnostic tests (mRDT) may help expedite the time to optimal antimicrobial therapy (TTOT) for extended-spectrum beta-lactamase (ESBL)- and carbapenemase-producing bacteria in bloodstream infections (BSI). The greatest impact of mRDT appears to occur when combined with antimicrobial stewardship program (ASP) intervention. The purpose of this study was to evaluate if mRDT + ASP influences the TTOT for patients with ESBL- and carbapenemase-producing E. coli and K. pneumoniae in BSI compared to conventional microbiological methods with ASP (CONV + ASP).MethodsMulticenter, retrospective, cohort study evaluating five years of patients that had a positive E. coli or K. pneumoniae blood culture determined to be ESBL- or carbapenemase-producing by mRDT and/or CONV. Patients were excluded if they had polymicrobial BSI, transferred–in with previously identified positive blood cultures, were immunosuppressed, or died before culture results.Primary outcome was TTOT defined as time from blood culture draw to start of carbapenem therapy for ESBL-producing BSI and ceftazidime-avibactam, meropenem-vaborbactam, or at least one drug active in-vitro with the most-narrow spectrum for carbapenemase-producing BSI. Secondary outcomes were time to microbial clearance (TTMC) defined as the time from index blood culture draw to the time of first negative blood culture or hospital discharge, all-cause hospital mortality, 30-, 60- and 90-day readmission rates, and Clostridioides difficile rates.ResultsA total of 378 patients were included for analysis. Baseline characteristics were balanced between mRDT + ASP (n=164) and CONV + ASP (n=214). Infectious diseases consults were significantly greater for CONV + ASP compared to mRDT + ASP (82.2% vs 34.8%; p< 0.001). The mRDT + ASP demonstrated a statistically significant decrease in TTOT (20.5 hrs [(IQR 17.0–42.2 hrs)] vs 50.1 hrs [(IQR 27.6–77.9 hrs)]; p< 0.001) and TTMC (71.9 hrs [(IQR 54.1–108.5 hrs)] vs 91.2 hrs [(IQR 64.6–134.3 hrs)]; p=0.007). Other secondary endpoints were similar between groups.Table 1. Comparison of baseline characteristics for the mRDT+ASP and CONV+ASP groups Graph 1. Kaplan Meier time to optimal antimicrobial therapy Graph 2. Kaplan Meier time to microbial clearance ConclusionOur study supports the additional benefit of mRDT to ASP on shortening the TTOT and TTMC in patients with ESBL- or carbapenemase-producing E. coli and K. pneumoniae in BSI compared to CONV + ASP.Disclosures All Authors: No reported disclosures

Clinical syndromes and treatment location predict utility of carbapenem sparing therapies in ceftriaxone-non-susceptibleEscherichia colibloodstream infection

BackgroundCefiderocol, ceftazidime-avibactam, ceftolozane-tazobactam, intravenous fosfomycin and plazomicin represent potential carbapenem sparing agents for extended-spectrum-beta-lactamase or AmpC beta-lactamase producing Escherichia coli infection. However, available data is limited in predicting the volume of carbapenem therapy which could be substituted and real-world contraindications.MethodsWe determined the number of carbapenem days of therapy (DOT) which could be substituted and frequent contraindications accounting for antimicrobial susceptibility and site of infection in an unselected cohort with ceftriaxone-non-susceptible E. coli bacteremia at a single health network from 2015 to 2016. Individual patient data was used to calculate DOT and substitution for each agent.ResultsThere were 108 episodes of E. coli bacteremia resulting in 67.2 carbapenem DOT/100 patient-days of antimicrobial therapy administered. Ceftazidime-avibactam could be used to substitute 36.2 DOT/100 patient-days (54%) for inpatient definitive therapy, ceftolozane-tazobactam for 34.7 DOT/100 patient-days (52%), cefiderocol for 27.1 DOT/100 patient-days (40%), fosfomycin for 23.3 DOT /100 patient-days (35%) and plazomicin for 27.1 DOT/100 patient-days (40%). Non-urinary tract source of infection was the most frequent contraindication to fosfomycin (25), plazomicin (26) and cefiderocol (26). Use in outpatient parenteral antimicrobial therapy (OPAT) programs accounted for 40% of DOT, all of which could be substituted if stability data allowed for ceftazidime-avibactam and ceftolozane-tazobactam.ConclusionsAll tested agents could be used to replace a significant volume of carbapenem therapy. Establishing stability of these agents for use in OPAT is required for maximizing their use as carbapenem sparing agents while randomized clinical data is awaited for some of these agents in resistant E. coli bacteremia.

Infections Caused by Carbapenem-Resistant Enterobacterales: Epidemiology, Clinical Significance, and Possibilities for Antibiotic Therapy Optimization

The resistance of Enterobacterales to carbapenems can be realized by different mechanisms, but the most common one is enzymatic, associated with the production of carbapenemases. Carbapenemases of enterobacteria are characterized by a wide variety;they are represented in three classes of beta-lactamases. The most well-known carbapenemases belong to classes A (KPC, GESenzymes), D (OXA-48), and B (metalloenzymes — NDM, VIM, IMP). Detailed clinical and microbiological characteristics of carbapenemases are given, as well as recommendations for their detection. Carbapenemases are widespread, and the paper discusses the geographical distribution of carbapenemases in different regions of the world; OXA-48 and NDM are the most widelydistributed enzymes in Russia. The clinical significance of carbapenemases and risk factors for these infections are discussed,including the following: 1) previous carbapenem therapy; 2) high levels of carbapenemases in the Department; 3) colonization of theintestine with carbapenemase-producing enterobacteria; 4) traveling to regions with a high prevalence of carbapenemases (4th and5th epidemiological levels). The possibilities of antibacterial therapy of infections caused by carbapenem-resistant enterobacteriaare discussed, the clinical and pharmacological characteristics of different antibiotics (ceftazidime/avibactam, aztreonam, carbapenems, polymyxins, tigecycline, fosfomycin), their effectiveness and treatment options are analyzed in detail. Current clinicaldata showing the effectiveness of ceftazidime/avibactam monotherapy for infections caused by carbapenemase producers OXA-48and KPC are presented. Practical issues of management of such patients are discussed. Algorithms for empirical and targeted therapy of infections caused by carbapenem-resistant enterobacteria are presented.

Impact of reflex fosfomycin susceptibility testing on the utilization of carbapenems for definitive extended-spectrum β-lactamase Escherichia coli urinary tract infection treatment

A protocol was started within a large health system to automatically test all confirmed extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli urine isolates for susceptibility to fosfomycin, an antibiotic not routinely included in such testing in most institutions. This study assessed the effectiveness of the protocol at reducing carbapenem use for the definitive treatment of ESBL E. coli urinary tract infection (UTI) through several endpoints. Eighty and 99 patients were compared pre- and postintervention, respectively. The primary outcome was the proportion of patients who received definitive carbapenem therapy. Key secondary outcomes included median total carbapenem days of therapy (DOT), discharge on intravenous UTI antibiotics, and median total antibiotic DOT. Preprotocol vs postprotocol definitive carbapenem use was seen in 59 of 80 patients (73.8%) and 71 of 99 patients (71.7%) (95% confidence interval [CI] for difference, -11.1% to 15.1%; P = 0.76). The rates of step-down to oral agents pre- and postintervention were 15 of 59 (25.4%) and 35 of 71 (49.3%) (P = 0.004). Median carbapenem DOT in those receiving carbapenems decreased from 8 to 4 days (95% CI, -5 to -1 days; P = 0.001). Median total DOT decreased from 10 to 8 days (95% CI, -3 to -1 days; P = 0.002). Implementation of a laboratory policy to automatically test ESBL positive E. coli for fosfomycin susceptibility did not reduce the percentage of patients receiving at least 1 dose of carbapenem treatment. It did result in a larger percentage reduction in step-down use of intravenous antibiotics for UTI prior to discharge, reduction in carbapenem DOT, and reduction in total antibiotic DOT.

Minimizing Time to Optimal Antimicrobial Therapy for Enterobacteriaceae Bloodstream Infections: A Retrospective, Hypothetical Application of Predictive Scoring Tools vs Rapid Diagnostics Tests.

BackgroundBloodstream infections (BSIs) due to ceftriaxone (CRO)-resistant Enterobacteriaceae are associated with delays in time to appropriate therapy and worse outcomes compared with infections due to susceptible isolates. However, treating all at-risk patients with empiric carbapenem therapy risks overexposure. Strategies are needed to appropriately balance these competing interests. The purpose of this study was to compare 4 methods for achieving this balance.MethodsThis was a retrospective hypothetical observational study of patients at the Detroit Medical Center with monomicrobial BSIs due to E. coli, K. oxytoca, K. pneumoniae, or P. mirabilis. This study compared the effectiveness of 4 methods to predict CRO resistance at the time of organism isolation. Three methods were based on applying published extended-spectrum beta-lactamase (ESBL) scoring tools. The fourth method was based on the presence or absence of the CTX-M marker from Verigene.ResultsFour hundred fifty-one Enterobacteriaceae BSIs were included, 73 (16%) of which were CRO-resistant. Verigene accurately predicted ceftriaxone susceptibility for 97% of isolates, compared with 70%–81% using the scoring tools (P < .001). Verigene was associated with fewer cases of treatment with CRO when the isolate was CRO-resistant (15% vs 63%–71% with scoring tools) and fewer cases of overtreatment with a carbapenem for CRO-susceptible strains (0.3% vs 10%–12%).ConclusionsVerigene significantly outperformed published ESBL scoring tools for identifying CRO-resistant Enterobacteriaceae BSI. Institutions should validate scoring tools before implementation. Stewardship programs should consider adoption of rapid diagnostic tests to optimize early therapy.

Opportunities for antimicrobial stewardship among carbapenem-treated patients in 18 North American hospitals

Here we describe the characteristics of carbapenem use at 18 hospitals across North America. Adult inpatients treated with a carbapenem for ≥24 h were included in this multicentre, retrospective, cross-sectional study. Outcomes evaluated included classification of therapy as empirical or definitive, discharge disposition and 30-day re-admission. A total of 621 patients were included in this study. Of these, 467 patients (75.2%) received a carbapenem empirically, among whom negative cultures occurred in 313 (67.0%) and 93% were eligible for de-escalation of therapy. In-hospital mortality occurred in 72 patients (11.6%) and 549 patients (88.4%) were discharged. Of the 549 patients who were discharged, 349 patients (63.6%) went home and 30-day infection-related re-admission occurred in 95 patients (17.3%). This population represents a significant need for carbapenem stewardship. Institutional guidelines should focus on four common disease states (respiratory, genitourinary, intra-abdominal and bloodstream), and diagnostic stewardship should be employed to aid in rapid de-escalation of carbapenem therapy. Additional studies aiming to identify antimicrobial stewardship techniques that may help to optimise carbapenem therapy and increase education about the importance of utilising carbapenem-sparing regimens are required.

Acquisition of plasmids conferring carbapenem and aminoglycoside resistance and loss of surface-exposed macromolecule structures as strategies for the adaptation of Acinetobacter baumannii CC104O/CC15P strains to the clinical setting.

Acinetobacter baumannii (Aba) is an emerging opportunistic pathogen associated to nosocomial infections. The rapid increase in multidrug resistance (MDR) among Aba strains underscores the urgency of understanding how this pathogen evolves in the clinical environment. We conducted here a whole-genome sequence comparative analysis of three phylogenetically and epidemiologically related MDR Aba strains from Argentinean hospitals, assigned to the CC104O/CC15P clonal complex. While the Ab244 strain was carbapenem-susceptible, Ab242 and Ab825, isolated after the introduction of carbapenem therapy, displayed resistance to these last resource β-lactams. We found a high chromosomal synteny among the three strains, but significant differences at their accessory genomes. Most importantly, carbapenem resistance in Ab242 and Ab825 was attributed to the acquisition of a Rep_3 family plasmid carrying a bla OXA-58 gene. Other differences involved a genomic island carrying resistance to toxic compounds and a Tn10 element exclusive to Ab244 and Ab825, respectively. Also remarkably, 44 insertion sequences (ISs) were uncovered in Ab825, in contrast with the 14 and 11 detected in Ab242 and Ab244, respectively. Moreover, Ab825 showed a higher killing capacity as compared to the other two strains in the Galleria mellonella infection model. A search for virulence and persistence determinants indicated the loss or IS-mediated interruption of genes encoding many surface-exposed macromolecules in Ab825, suggesting that these events are responsible for its higher relative virulence. The comparative genomic analyses of the CC104O/CC15P strains conducted here revealed the contribution of acquired mobile genetic elements such as ISs and plasmids to the adaptation of A. baumannii to the clinical setting.

The impact of nephrostomy drainage prior to mini-percutaneous nephrolithotomy in patients with ESBL-positive Escherichia coli.

Extended-spectrum β-lactamase-producing Escherichia coli (ESBL-EC) is one of the most frightening multidrug-resistant bacteria that usually causes sepsis. Herein we explored the benefits of nephrostomy drainage prior to percutaneous nephrolithotomy (PCNL) on infection outcomes in patients with ESBL-EC. Between June 2016 and April 2019, 43 consecutive patients with ESBL-EC who received nephrostomy drainage for > 24h prior to PCNL were retrospectively evaluated as group 1. 86 patients were randomly selected from patients with ESBL-EC who received concurrent percutaneous access during PCNL as group 2. The postoperative infection complications were compared. Although the total infection complications were not statistically different (11.6% vs. 25.6%, p = 0.066), the severity seemed to be worse among group 2 subjects. Severe infections, including urosepsis (4.7% vs.13.9%) and septic shock (2.3% vs 4.6%), were observed at twice or greater rates in group 2. Blood transfusions were also more frequent (2.3% vs. 13.9%, p = 0.039). Multivariate analysis demonstrated that preoperative drainage was an independent risk factor for postoperative infection events (OR 2.31 CI 1.14-3.48, p = 0.017). Subgroup analyses indicated that preoperative drainage may largely reduce the incidence of urosepsis in patients with hydronephrosis or without receiving preoperative carbapenem therapy. Because of the high rate of severe infection after PCNL in patients with ESBL‑positive E. coli, preoperative nephrostomy drainage for > 24h is an effective measure to reduce the risk of severe infection complications, especially in patients with hydronephrosis or those without preoperative carbapenem therapy.

Quantifying risk of disease due to extended-spectrum β-lactamase producing Enterobacteriaceae in patients who are colonized at ICU admission

BackgroundThe prevalence of extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-PE) has globally increased and spread to the community. No clinical score is available to select carriers in whom these organisms can be empirically targeted at ICU admission. MethodsWe prospectively assessed between 2009 and 2017 the prevalence of ESBL-PE infection in carriers at ICU admission. A logistic regression was used to determine independent risk factors associated with ESBL-PE infection, and to build a clinical risk score. ResultsOf the 8,061 admissions over the study 7-year period, 745 (9%) patients were ESBL-PE carriers at admission, of whom 395 had infections at ICU admission including 59 (15%) who had culture-proven ESBL-PE related infection. By multivariable analysis, age >60 years, cirrhosis, being on broad-spectrum antibiotics within the past three months, urinary or intra-abdominal source of infection, and the absence of chronic pulmonary disease, were the five independent factors associated with ESBL-PE infection in carriers. A clinical risk score ranging from 0 to 7 was built based on these variables, with an area under the receiver operating characteristic curve (ROC) of 0.82 (95% CI 0.78–0.86); p <0.001. The prevalence of ESBL-PE infection for clinical risk scores of 0–1, 2–3, 4–5, or 6–7 was 0%, 4%, 26%, and 49%, respectively. The negative predictive value when Mondor ESBL risk score is <4 was 97%. ConclusionESBL-PE related infection was not common in carriers at ICU admission. A clinical risk score may spare ESBL-PE carriers with lower risk of ESBL-PE infection at ICU admission unnecessary empiric carbapenem therapy.

Incidence, risk factors and healthcare costs of central line-associated nosocomial bloodstream infections in hematologic and oncologic patients

Non-implanted central vascular catheters (CVC) are frequently required for therapy in hospitalized patients with hematological malignancies or solid tumors. However, CVCs may represent a source for bloodstream infections (central line-associated bloodstream infections, CLABSI) and, thus, may increase morbidity and mortality of these patients. A retrospective cohort study over 3 years was performed. Risk factors were determined and evaluated by a multivariable logistic regression analysis. Healthcare costs of CLABSI were analyzed in a matched case-control study. In total 610 patients got included with a CLABSI incidence of 10.6 cases per 1,000 CVC days. The use of more than one CVC per case, CVC insertion for conditioning for stem cell transplantation, acute myeloid leukemia, leukocytopenia (≤ 1000/μL), carbapenem therapy and pulmonary diseases were independent risk factors for CLABSI. Hospital costs directly attributed to the onset of CLABSI were 8,810 € per case. CLABSI had a significant impact on the overall healthcare costs. Knowledge about risk factors and infection control measures for CLABSI prevention is crucial for best clinical practice.

Incidence and risk factors for acquired colonization and infection due to extended-spectrum beta-lactamase-producing Gram-negative bacilli: a retrospective analysis in three ICUs with low multidrug resistance rate.

The purpose of this study is to assess risk factors for the acquisition of extended-spectrum β-lactamase-producing Gram-negative bacilli (ESBL-GNB) colonization and infection (AI) in ICUs with low ESBL-GNB prevalence rate. We conducted a retrospective observational study in three ICUs in Bretagne, France. All patients admitted from January 2016 to September 2017 with a length of stay of 2 days or more were included. Universal screening for ESBL-GNB colonization was performed in all participating ICUs. Of the 3250 included patients, 131 (4.0%) were colonized at admission, 59 acquired colonization while hospitalized (1.9%; 95% CI [1.5–2.5%]), and 15 (0.5%; 95% CI [0.3–0.8%]) acquired ESBL-GNB infections. In the case of infection, the specificity and the negative predictive values of preexistent colonization for the ESBL-GNB etiology were 93.2% [91.5–95.1%] and 95.2% [93.5–97.1%], respectively. Colonization was the main risk factor for ESBL-GNB AI (OR = 9.61; 95% CI [2.86–32.29]; p < 0.001). Antimicrobial susceptibility of non-ESBL-GNB isolates responsible for AI was similar for any non-carbapenem β-lactam (95%) and imipenem (94%). ESBL-GNB AIs were rare in ICUs with low ESBL-GNB prevalence rate. Prior colonization was the main risk factor for subsequent infection. Empirical carbapenem therapy could be avoided in non ESBL-GNB colonized patients with suspected AI.Electronic supplementary materialThe online version of this article (10.1007/s10096-019-03800-y) contains supplementary material, which is available to authorized users.

Expressed and Silent Carbapenemase Genes Detected by Multiplex PCR in both Carbapenem-Resistant and Phenotypically-Susceptible Gram Negative Bacilli

ABSTRACT Introduction Carbapenemase-producing Gram-negative bacilli have been major culprits in hospital-associated infections (HAIs), particularly in critically ill patients suffering device-associated infections (DAIs). The current study aimed to investigate the performance of the modified Hodge test (MHT) as a phenotypic confirmatory method for the detection of carbapenemase-producing Gram-negative bacilli and to compare it to the gold standard PCR for the detection of carbapenemase production in both non-susceptible and phenotypically susceptible isolates. The latter were expected to harbor silent carbapenemase genes, as suspected from the inappropriate response to carbapenem therapy. Methods Ninety-five bacterial isolates from 75 critically ill patients were collected over 6 months from several ICUs at Cairo University Hospitals. The isolates were subjected to antibiotic susceptibility testing (AST) for carbapenems and were further screened by MHT, followed by genotypic analysis via multiplex PCR. Results Enterobacteriaceae were the most commonly isolated pathogens (55.8% of the total isolates), followed by Acinetobacter spp. (24%). Lower respiratory tract infections were the most common HAIs (42.11%), followed by surgical site infections (27.37%). All isolates demonstrating carbapenem resistance by AST were found to harbor at least one of the following carbapenemase genes: blaKPC, blaOXA-48, blaIPM, blaVIM, and blaNDM-1 . Alarmingly, 97.8% of the isolates which exhibited carbapenem-susceptible profile and negative MHT were harboring carbapenemase genes as confirmed by multiplex PCR. With the exception of one isolate (E. coli) which was not harboring any carbapenemase gene, the remaining 94 bacterial isolates were found to carry either a single or multiple carbapenemase genes. Conclusion The silent dissemination of different classes of carbapenemases even in isolates with negative MHT is a daunting challenge. It necessitates the implementation of strict antibiotic stewardship along with updated and actionable approach to detect non-expressed carbapenemase genes in phenotypically susceptible isolates.

Is Piperacillin-Tazobactam Effective for the Treatment of Pyelonephritis Caused by Extended-Spectrum β-Lactamase-Producing Organisms?

Limited data exist regarding the efficacy of piperacillin-tazobactam (TZP) for the management of nonbacteremic pyelonephritis caused by extended-spectrum β-lactamase (ESBL)-producing organisms. We conducted a multicenter observational study comparing clinical outcomes of adults hospitalized with ESBL-producing pyelonephritis who were receiving TZP versus carbapenems, using an inverse probability of treatment weighted propensity score analysis. Patients were eligible for inclusion if all of the following criteria were met: (1) urine cultures growing Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, or Proteus mirabilis at ≥50 000 colony-forming units/mL; (2) identification of an ESBL gene; (3) pyuria (≥10 white blood cells per high powered field in the urine); and (4) dysuria and fever plus at least 1 of the following symptoms: emesis, rigors, hypotension, or flank pain. There were 186 patients included in the propensity score-weighted cohort; 45 (24%) received TZP and 141 (76%) received a carbapenem. Of these 186 patients, 27% were admitted to the intensive care unit, 48% were immunocompromised, and 45% had underlying urologic abnormalities. There were no differences between the 2 groups in the proportion of patients (20% vs 25%) with recurrent cystitis or pyelonephritis with the same ESBL-producing organism within 30 days (odds ratio, 0.75; 95% confidence interval, .31-1.81; P = .52). There were no differences in the resolution of clinical symptoms by Day 7 or in 30-day mortality. There was 1 (2%) patient in the TZP arm and 11 (8%) patients in the carbapenem arm who had incident carbapenem-resistant organisms isolated within 30 days (P = .09). TZP may be a reasonable alternative to carbapenems for the management of ESBL-producing pyelonephritis and may mitigate the risk of emergence of carbapenem-resistant organisms, compared with carbapenem therapy.

Outcomes of treating AmpC-producing Enterobacterales bacteraemia with carbapenems vs. non-carbapenems

IntroductionAmpC β-lactamases are found in Enterobacter species, Serratia species, Citrobacter freundii, Providencia species and Morganella morganii (‘ESCPM’). Carbapenems are commonly used to treat severe ‘ESCPM’ infections. Carbapenem-sparing agents are needed because of increasing carbapenem resistance worldwide. Use of cefepime and piperacillin-tazobactam has limited supportive clinical data. We evaluated the efficacy of non-carbapenems vs. carbapenems in ‘ESCPM’ bacteraemia. MethodsA retrospective cohort study was conducted on patients with ‘ESCPM’ bacteraemia. Primary outcome was 30-day mortality. Analyses were performed on patients who received carbapenems vs. piperacillin-tazobactam or cefepime monotherapy as empirical and definitive therapy. Propensity score for carbapenem therapy was adjusted for in multivariate analyses for 30-day mortality. ResultsA total of 241 patients were included. The most common bacterium isolated was Enterobacter species (58.1%). Common sources were urinary (22.8%) and vascular lines (22.0%). Carbapenems (28.6%) and piperacillin-tazobactam (28.6%) were the commonest empirical antibiotics. Carbapenems (54.8%) and cefepime (23.7%) were the most common definitive antibiotics. Median Pitt bacteraemia score was 1 (interquartile range [IQR], 0-2). Overall, 30-day mortality was 12.9%.Adjusted multivariate analyses for empirical and definitive antibiotic treatment models yielded risk factors for 30-day mortality, including higher Pitt bacteraemia score (empirical: adjusted OR [aOR] 1.21 for each point increase, 95% confidence interval [CI]:1.01-1.45; definitive: aOR 1.33 for each point increase, 95% CI:1.06-1.69) and age (empirical: aOR 1.04 for each year increase, 95% CI:1.01-1.08). Empirical piperacillin-tazobactam (aOR 0.29, 95% CI:0.07-1.27) and definitive cefepime (aOR 0.65, 95% CI:0.12-3.55) were not associated with 30-day mortality. ConclusionsCompared with carbapenem therapy, empirical piperacillin-tazobactam and definitive cefepime were not associated with 30-day mortality in ‘ESCPM’ bacteraemia.

Colistin Plus Carbapenem versus Colistin Monotherapy in the Treatment of Carbapenem-Resistant Acinetobacter baumannii Pneumonia.

PurposeColistin alone may not be sufficient for treating carbapenem-resistant Acinetobacter baumannii (CRAB); thus, efforts are needed to increase treatment success rates. We compared the effects of colistin plus carbapenem therapy versus colistin monotherapy in treating pneumonia caused by CRAB and attempted to identify specific populations or factors that could benefit from combination therapy.MethodsWe retrospectively collected data on cases of CRAB pneumonia. The patients were divided into colistin plus carbapenem therapy and colistin monotherapy groups. The primary outcome was 14-day mortality. The secondary outcomes were in-hospital mortality, clinical improvement at days 2 and 14, and microbiological improvement at day 14.ResultsOf 160 cases meeting criteria for CRAB pneumonia, 83 (52%) and 77 (48.0%) were treated with carbapenem combination therapy or colistin monotherapy, respectively. Among these patients, 50 (63.3%) in the combination group and 27 (39.7%) in the monotherapy group had Acute Physiologic Assessment and Chronic Health Evaluation (APACHE) II scores >24 points (p=0.010). Overall, there was no significant difference in 14-day mortality between the combination and monotherapy groups (24.1% vs 20.8%, p=0.616). Clinical improvement and sputum-negative conversion also showed no significant difference. After adjusting for disease severity according to APACHE II score, the 14-day mortality was significantly lower in the combination group than in the monotherapy group among patients with APACHE II scores of 25–29 points (9.1% vs 53.8%, P=0.020).ConclusionDespite more severe conditions, compared with colistin monotherapy, colistin plus carbapenem combination therapy showed equivalent primary mortality outcome in treating CRAB pneumonia. Combination therapy was more effective in patients with APACHE II score ranging from 25 to 29 points.

2290. Carbapenem vs. Piperacillin–tazobactam Definitive Therapy for Patients with Bloodstream Infections Due to Ceftriaxone Not Susceptible Escherichia coli or Klebsiella species

BackgroundDefinitive therapy with piperacillin–tazobactam (TZP) for ceftriaxone (CRO)-resistant E. coli or K. pneumoniae bloodstream infections (BSI) has been shown to be inferior to carbapenem therapy in a randomized trial.MethodsThe Premier US database was queried for hospitalized patients with monomicrobial E. coli or Klebsiella spp BSI that were not susceptible (NS) to CRO between June 2015 and May 2018. Adults with index positive blood culture(s) drawn within the first 2 hospital days who were treated with active antibiotic therapy that continued for ≥3 consecutive days were included. We defined antibiotics administered on or prior to Day 3 as empirical therapy and all subsequent days as definitive therapy. Outcomes among patients who received definitive therapy with a carbapenem vs. TZP were evaluated.ResultsThere were 954 patients (mean age, 67.6 years; 52.4% women) who met selection criteria and received active empirical therapy. 729/954 received carbapenem definitive therapy and 38/954 received TZP definitive therapy. Median Charlson Comorbidity Index scores were similar between carbapenem and TZP definitive therapy groups (6 vs. 5, P = 0.78). Crude 14-day in-hospital mortality for CRO-NS BSI due to E. coli or Klebsiella spp. was 4.4%. Definitive therapy with TZP (6/38; 15.8%) was associated with an increased likelihood of 14-day mortality relative to that of a carbapenem (22/729; 3.0%; P < 0.0001). The increased 14-day mortality observation was consistent in a multivariate cox proportional hazards model (adjusted hazard ratio, 5.70; 95% CI, 2.09 to 13.23; P = 0.002). Of patients who received carbapenem definitive therapy, 14-day mortality was 2.7% (19/693) if a carbapenem was part of empirical therapy and 8.3% (3/36; P = 0.06) if empirical therapy did not include a carbapenem. Median post-blood culture length of stay (7 vs. 6 days, P = 0.65) and hospital costs ($13,886 vs. $13,559, P = 0.62) were similar between carbapenem and TZP definitive therapy groups<./p>ConclusionIn this large US database, definitive therapy with TZP was associated with an increased likelihood of 14-day mortality relative to that of definitive carbapenem therapy in patients with CRO-NS BSI due to E. coli or Klebsiella spp. These findings support recent clinical evidence in favor of definitive carbapenem therapy for CRO-NS BSI due to E. coli or Klebsiella spp.Disclosures All authors: No reported disclosures.

1452. Is Carbapenem-Sparing Therapy as Effective as Carbapenems Against Extended-Spectrum β-Lactamase Producing Enterobacteriaceae in UTI?

BackgroundWith the emergence of carbapenem-resistant strains of Enterobacteriaceae, non-carbapenem antibiotics are suggested as the alternative treatment of extended-spectrum β-lactamase (ESBL) producing Enterobacteriaceae infection. In this study, efficacy of non-carbapenem antibiotics on acute pyelonephritis (APN) with ESBL-producing Enterobacteriaceae was compared with that of carbapenems.MethodsThe medical records of patients who had diagnosed to have acute pyelonephritis with ESBL-producing Enterobacteriaceae on their urine culture, from January 2011 to December 2018, were reviewed retrospectively. Patients were classified as carbapenem and non-carbapenem group according to the definitive antibiotics they had treated with.ResultsTotal number of patients was 141, including 112 (79.4%) who had received carbapenem, and 29 (20.6%) received non-carbapenem as definitive therapy against to APN with ESBL-producing Enterobacteriaceae. The duration of hospitalization was shorter for non-carbapenem group (median 9.93 days) than for carbapenem group (median 14.39 days) (P < 0.001). The duration of negative conversion of culture was shorter for carbapenem group (median 40.73 hours) than for non-carbapenem group (median 56.79 hours). There was no significant difference in time to febrile period and duration of definitive therapy between two groups.ConclusionNon-carbapenem therapy against APN with ESBL-producing Enterobacteriaceae has no significant difference in clinical outcome compared with carbapenem therapy.Disclosures All authors: No reported disclosures.

2297. Epidemiology of Antibiotic-resistant Pathogens and Empiric Treatment Patterns in Community-Onset Sepsis

BackgroundGuidelines recommend immediate empiric broad-spectrum antibiotics for all patients with suspected sepsis. Understanding the epidemiology of antibiotic-resistant pathogens and empiric treatment patterns in sepsis could inform improvements in antibiotic utilization and outcomes.MethodsWe identified adults admitted during 2009–2015 to 104 US hospitals in the Cerner HealthFacts dataset who met CDC Adult Sepsis Event criteria and had positive clinical cultures within 2 days of admission. We characterized prevalence and empiric treatment rates for methicillin-resistant S. aureus (MRSA), vancomycin-resistant enterococcus (VRE), ceftriaxone-resistant Gram-negative organisms (CRO) (including P. aeruginosa), and extended-spectrum β-lactamase Gram-negative organisms (ESBL). We evaluated associations between in-hospital mortality and either inappropriate empiric therapy (antibiotics inactive against any isolated pathogen) or excessively broad therapy (empiric MRSA or VRE coverage, extended spectrum β-lactam, or carbapenem therapy when targeted organisms were absent), adjusting for baseline characteristics and severity-of-illness.ResultsThe cohort included 17,962 patients with culture-positive sepsis; 2,965 (16.5%) died in-hospital. The most common culture-positive sites were urine (51.2%), blood (41.8%), and respiratory (16.5%). The most common pathogens were E. coli (33.0%), S. aureus (20.9%), and Streptococcus (13.2%) (Figure 1). Most (81.6%) patients received empiric antibiotics active against all isolated pathogens. Empiric therapy was directed at resistant organisms in 67.5% of cases (primarily vancomycin and extended spectrum β-lactams, Figure 2), but resistant organisms were isolated in only 25.2% (MRSA 11.5%, CRO 12.9%, VRE 2.0%, ESBL 0.8%). Both inappropriate empiric therapy and excessively broad empiric therapy were associated with higher mortality on multivariate analysis (OR 1.30, 95% CI 1.14–1.48 and OR 1.20, 95% CI 1.05–1.38, respectively).ConclusionMost patients with community-onset sepsis do not have resistant pathogens, yet empiric broad-spectrum antibiotics are frequently prescribed. Both inappropriate empiric therapy and excessively broad therapy are associated with worse outcomes. Disclosures All authors: No reported disclosures.