bluuebunny/crossref_metadata_2025 huggingface dataset:
2136. Rapid Antimicrobial Susceptibility Testing using ATP Luminescence and Machine Learning Methods
Authors: Kawabe Shunsuke , Uchiho Yuichi , Noda Hideyuki , Matsui Atsushi , Niimi Hideki , Kitajima Isao
Published: October 2019

Background

To prevent the spread of drug-resistant bacteria, a rapid and accurate antimicrobial susceptibility test (AST) is necessary. Recently, morphokinetic microscopy approaches have been reported as a rapid AST method. However, these still require several hours to obtain a minimum inhibitory concentration (MIC). Adenosine triphosphate (ATP) luminescence has also been reported as a rapid AST method that can detect bacterial growth more rapidly than morphokinetic approaches, since ATP in bacteria increases prior to bacterial division. In this study, we designed a new machine learning-based algorithm that predicts MIC rapidly, using a dataset that contains ATP luminescence patterns and conventional MICs determined by turbidity. Essential agreement (EA) rates between rapid and conventional MIC were then evaluated.

Methods

Sixty-three strains of E. coli (ATCC 25922 and clinical isolates from Toyama University Hospital) were tested. Bacterial suspensions were diluted 500-fold in Mueller–Hinton broth from 0.5 McF solutions, and the final concentration of bacteria was 3×105 CFU/mL. The suspensions were dispensed into a 96-well microplate, which had 12 antimicrobials in two-fold dilution series, and the microplate was incubated at 35°C. At each measurement time point, the amount of ATP in a 10 μL aliquot from each well was evaluated by our original measurement system, which can sensitively detect ATP luminescence equivalent to a single bacterium. After 22 hours, MIC was determined conventionally by measuring turbidity. A rapid MIC for each bacterium was estimated by the algorithm based on the dataset consisting of the rest of the 62 strains (leave-one-out cross validation).

Results

Table 1 shows the EA rate for the 12 antimicrobials; EA rates > 90% were achieved for 7 antimicrobials in 2 hours and for 12 antimicrobials in 3 hours. In 6 hours, an average EA rate > 97% was achieved.

Conclusion

Using the dataset, our new machine learning-based algorithm predicted MIC rapidly within 2 hours with an EA rate > 90% for 7 antimicrobials. The rapid AST detected by the ATP luminescence method will contribute toward both appropriate antimicrobial treatment and reduction in medication and admission charges. In the future, other species of bacteria will be evaluated by our ATP method.

Disclosures

All authors: No reported disclosures.
2143. Attempting to Add Clarity to “Indeterminates” on a Deployed Rapid Diagnostic with Antimicrobial Stewardship Program (ASP) Intervention
Authors: Cox Heather L , Attai April E , Stilwell Allison M , Vegesana Kasi B , Brewster Frankie , Poulter Melinda D , Mathers Amy J
Published: October 2019

Background

Rapid diagnostic testing paired with ASP intervention optimizes therapy and improves outcomes but few data guide ASP response in the absence of organism identification (ID). We describe the microbiology for organisms unidentified by Accelerate Pheno™ Gram-negative platform (AXDX) in order to inform ASP-provider team communication (PTC).

Methods

Consecutive, non-duplicate inpatient blood cultures with Gram-negative bacilli (GNB) following AXDX implementation at a single university hospital between April 2018 and March 2019 were included. Standard of care (SOC) ID and susceptibility followed AXDX. Clinical Microbiology emailed AXDX results to the ASP in real time; results were released into the EMR paired with telephone PTC or withheld after ASP review. Bloodstream Infections (BSIs) and patient outcomes for organisms labeled no/indeterminate ID by the AXDX were characterized.

Results

AXDX was performed on 351 blood cultures. Among 52 (15%) labeled no/indeterminate ID, SOC methods revealed: Enterobacteriaceae (40%; 9 monomicrobial with AXDX targets), anaerobes (21%), non-lactose fermenters (NLFs) other than Pseudomonas aeruginosa (21%), and fastidious GNB (10%). Frequent organisms without AXDX targets included: Raoultella planticola (4); Bacteroides fragilis, Cupriavidus spp., Haemophilus spp., Prevotella spp., Providencia spp., non-aeruginosa Pseudomonas spp., Salmonella spp. (3 each); Pasteurella multocida, Stenotrophomonas maltophilia (2 each). BSI sources were most commonly intra-abdominal (21%), central line-associated (17%), or unknown (17%). CLABSIs were associated with immune suppression and/or substance abuse in all but 1 case. BSIs without active empiric therapy included: NDM-producing Providencia stuartii SSSI; OXA-48-producing R. planticola intraabdominal infection (IAI); Pandoraea spp. CLABSI after liver transplant; enteric fever; B. fragilis, Leptotrichia wadei, and S. maltophilia, each of unknown source. In-hospital mortality occurred in 4 of these cases.

Conclusion

When AXDX yields no/indeterminate ID, ASP chart review for possible anaerobic/IAI, unique environmental exposures, and travel history may assist in guiding empiric therapy. GNB with AXDX targets are not excluded.

Disclosures

All authors: No reported disclosures.
2151. Biofilm and Metallo-β-Lactamase (MBL) Production Among Imipenem-Resistant Pseudomonas aeruginosa and Acinetobacter spp.
Authors: Metok Yang , Hosuru Subramanya Supram , Thapa Shrestha Upendra , Reus Rodrigues Perez Leandro , Adhikari Nabaraj , Nayak Niranjan , Gokhale Shishir
Published: October 2019

Background

Pseudomonas aeruginosa and Acinetobacter spp. head the list of hospital-acquired infections. Resistance to carbapenem as reserve drug is under threat with the emergence of Metallo-β-lactamase (MBL) and biofilm producing bacterial strains. This study was thus undertaken to determine the rate of MBL and biofilm production among imipenem-resistant P. aeruginosa (IRPA) and imipenem-resistant Acinetobacter spp. (IRAS) isolates.

Methods

A total of 79 P. aeruginosa and 117 Acinetobacter spp. were isolated from different clinical specimens of patients visiting Manipal Teaching Hospital, Pokhara Nepal from July 2016 to January 2017. Isolation, identification and antibiotic susceptibility testing of the isolates were performed by standard microbiological techniques. Combined disc test and Epsilometer test (E-test) were employed to detect MBL in IRPA and IRAS isolates. Microtiter plate using crystal violet method was employed for detection of biofilm in imipenem-resistant isolates.

Results

9 (11.4%) of P. aeruginosa and 49 (41.9%) of Acinetobacter spp. were Multidrug Resistant (MDR). Similarly, 22 (27.8%) of P. aeruginosa and 23 (19.7%) of Acinetobacter spp. were Extensively Drug Resistant (XDR). Imipenem resistance was detected among 15 (19%) P. aeruginosa and 57 (48.7%) Acinetobacter spp. isolates. 8 (53.3%) of IRPA and 22 (38.6%) of IRAS isolates were MBL producers while all (100%) of IRPA and 47 (82.5%) of IRAS were biofilm producers. All the biofilm producer IRPA isolates were XDR and 62.5% of XDR IRAS strains were moderate biofilm producers. However, 80% of IRPA, 49.1% of IRAS and 63% of both MBL producer isolates were weak biofilm formers. Polymyxin B and ampicillin-sulbactam showed a better degree of susceptibility against MBL cum biofilm producer IRPA and IRAS isolates respectively.

Conclusion

The study showed high propensity of IRPA and IRAS to form biofilm, which is strongly associated with higher drug resistance. Such high rate of MBL and biofilm producing P. aeruginosa and Acinetobacter spp. alarms the rapid spread of such strains in our hospital setting.

Disclosures

All authors: No reported disclosures.
2156. To Evaluate the Role of Kit-Based Loop-Mediated Isothermal Amplification (TB-LAMP) Assay in the Diagnosis of Tubercular Lymphadenitis
Authors: Nischal Neeraj , Das Saurav , Kumar Singh Binit , Wig Naveet , Soneja Manish , Jorwal Pankaj , Saini Rahul
Published: October 2019

Background

Tuberculosis (TB) is the leading cause of death as a single infectious agent worldwide. In 2017, there were an estimated 1.3 million TB deaths among HIV-negative people and 300,000 deaths among HIV-positive people. The rapid and accurate diagnosis of TB in lymphnode specimens remains a challenging task today. In 2016, World Health Organization endorsed a commercial molecular assay, the LoopAMP™ Mycobacterium tuberculosis complex (MTBC) detection kit (Eiken Chemical Company, Tokyo, Japan), which uses loop-mediated isothermal amplification (LAMP) for sputum samples only. No prospective studies on LAMP in diagnosis of Tubercular Lymphadenitis in adults have been done yet.

Methods

A prospective observational study with a total of 70 lymph-node aspirate specimens from suspected cases of Tubercular Lymphadenitis with age >18 years were selected and subjected to Ziehl–Neelsen staining, LAMP and culture in mycobacterial growth indicator tube (MGIT960). The immunochromatographic test was used to confirm MTB complex (MTBC) in culture positive samples and phenotypic drug susceptibility testing was done using MGIT-960. The composite reference standard (CRS) used in the study includes symptoms, radiological evidence and follow-up of 2 months. 2 × 2 tables were made and Sensitivity, Specificity, PPV, NPV of TB-LAMP were calculated with respect to AFB smear and composite reference standard (CRS).

Results

LAMP assay was able to detect MTBC in 34.3% (24/70) of lymph-node specimens. Sensitivity and specificity of the assay were 100% and 69.7%, respectively, considering smear as gold standard. On comparing with CRS, the assay showed 100% sensitivity and 100% specificity in the diagnosis of MTBC.

Conclusion

In our study, LAMP assay was found to be a promising tool for the diagnosis of Tubercular Lymphadenitis and could be used for rapid and cost-effective diagnosis of Tubercular Lymphadenitis in resource-limited settings.

Disclosures

All authors: No reported disclosures.
2160. Performance of the Cepheid Rapid PCR Test for Patient Screening and Association with Efficacy of Suvratoxumab, A Novel Anti-Staphylococcus aureus Monoclonal Antibody, During the Phase 2 SAATELLITE study
Authors: Ruzin Alexey , Yu Li , Barraud Olivier , François Bruno , Sánchez Garcia Miguel , Eggimann Philippe , Dequin Pierre-Francois , Laterre Pierre-François , Huberlant Vincent , Viña Lucia , Boulain Thierry , Bretonnière Cédric , Pugin Jérôme , Trenado Álvarez José , Catalina Hernandez Padilla Ana , Vignaud Julie , Vandamme Drieke , Ali Omar , Shoemaker Kathryn , Colbert Susan , Sellman Bret R , McCarthy Michael , Jafri Hasan S , Esser Mark T
Published: October 2019

Background

Patients with lower airway Staphylococcus aureus (SA) colonization are at great risk (> 20%) of early-onset ventilator-associated pneumonia (VAP). Thus, a rapid test is required to identify patients at risk. Suvratoxumab (formerly MEDI4893) is a human monoclonal antibody that neutralizes SA alpha toxin. SAATELLITE, a phase 2 study of safety and efficacy of suvratoxumab for reducing the incidence of SA pneumonia (NCT02296320) was conducted and recently completed within the consortium for Combatting Bacterial Resistance in Europe. We investigated the performance of a rapid PCR test (Xpert MRSA/SA SSTI™, Cepheid) as a screening tool during the study and the association between SA load and suvratoxumab efficacy.

Methods

The PCR assay was used to detect SA and methicillin-resistant SA (MRSA) in lower respiratory tract (LRT) samples. Culture was performed on PCR SA+ LRT samples according to local procedures. PCR SA+ subjects were randomized 1:1 to either a single intravenous infusion of 5000 mg suvratoxumab (n = 96) or placebo (n = 100) and followed for 190 days post dose. Efficacy of suvratoxumab was defined as relative risk reduction (RRR) in incidence of SA pneumonia within 30 days post-dose compared with placebo.

Results

299 (41.5%) out of 720 screened subjects were SA+ by PCR. Of 209 subjects with culture data, there were 162 (77.5%) SA+, 47 (22.5%) SA- and 9 (5.6%) MRSA by culture. Culture results could have been affected by antibiotic use and site variability in limits of detection ranging from 3.3 to 100,000 colony-forming units per mL (CFU/mL). No discordance was noted between PCR and culture for MRSA detection. An inverse linear correlation was observed between the PCR cycle threshold (Ct) values for SA protein A gene (spa) and SA CFU/mL counts from quantitative culture. In subjects with low SA load (Ct ≥ 29; n = 72), suvratoxumab provided 66.7% RRR [90% confidence interval (CI): 21.3%, 86.2%] compared with 31.9% RRR [90% CI: -7.5%, 56.8%] in total study population.

Conclusion

Cepheid Xpert PCR assay was easy to perform, sensitive and standardized, and provided better sensitivity than conventional culture for detection of SA. Additionally, quantitative PCR Ct output was associated with the efficacy of suvratoxumab in reducing SA pneumonia incidence.

Disclosures

All authors: No reported disclosures.
2175. Rapid Detection of Carbapenemase Producing Organisms Directly from Blood Cultures Positive for Gram-Negative Bacilli
Authors: Stokes William , Pitout Johann , Campbell Lorraine , Church Deirdre , Gregson Dan
Published: October 2019

Background

The rapid detection of carbapenemase-producing organisms (CPOs) directly from blood cultures (BC) positive for Gram-negative bacilli (GNB) may accelerate the appropriate treatment of at-risk patients. Our objective was to evaluate the performance of two commercial assays in the rapid detection of CPOs directly from BC positive for GNB.

Methods

BC positive for GNB, taken from patients within the Calgary Health Zone over a 3 month period, were tested for the presence of CPOs with βCARBA® and NG-Test® CARBA 5. A subset of sterile BC samples was seeded with multi-drug-resistant (MDR) GNB. BC were incubated using the Bact-Alert™ system. Positive BC from clinical and seeded samples was tested directly with βCARBA and CARBA 5 from BC pellets processed for direct testing using an ammonium chloride lysis and wash method. Sensitivity, specificity, negative predictive value (NPV) and positive predictive value (PPV) were calculated with 95% confidence intervals for binomial proportions.

Results

65 samples were tested (30 clinical, 35 seeded). Seeded samples included 1 GES, 4 IMP, 6 KPC, 1 co-producing KPC and NDM, 9 OXA, 4 VIM, 5 NDM, and 5 non-CPO carbapenem-resistant organisms. βCARBA had a sensitivity, specificity, NPV and PPV of 100% (88.4% - 100%), 65.7% (47.8–80.9%), 100%, and 71.4% (61.3%–79.8%), respectively. CARBA 5 had a sensitivity, specificity, NPV and PPV of 90.0% (73.5%–97.9%), 100% (90.0%–100%), 92.1% (80.0%–97.2%), and 100%. When excluding GES, which is known not to be detected by CARBA 5, sensitivity and NPV increased to 93.1% (77.2%–99.2%) and 93.1% (78.0%–98.1%), respectively. False negatives for βCARBA occurred with 1 VIM-1 and IMP-14.

Conclusion

This study demonstrates that the detection of CPOs directly from positive BC can be accurately achieved. βCARBA had excellent sensitivity but suffered from poor specificity. CARBA 5 had good sensitivity and specificity but is unable to detect certain CPOs. Testing positive BC directly using βCARBA and/or CARBA 5 may be useful in rapidly detecting CPOs. Results of direct testing from the CARBA5 assay would quickly identify patients amenable to treatment with avibactam combination compounds.

Disclosures

All authors: No reported disclosures.
2178. Sensitivity of Blood Cultures in Detection of Bacteremia in Febrile Neutropenia
Authors: Patel Vanisha , Ferrolino Jose Amadeo A , Hayden Randall , Hayden Randall , Gaur Aditya H
Published: October 2019

Background

Febrile neutropenia (FN) secondary to bacteremia is a treatable complication of chemotherapy that increases mortality if not promptly recognized and managed.

Methods

The sensitivity of blood cultures collected in pediatric oncology patients with FN was assessed and stratified based on the day of FN episode, culture media type, and the source of blood culture draw at a single US center between 2013 and 2018. Paired aerobic and lytic media bottles were inoculated with each culture draw using a weight-based volume of blood; anaerobic cultures were included with initial cultures starting in September of 2015.

Results

In a retrospective analysis of 10,596 patients, a total of 3,039 episodes of FN were identified. Of the FN episodes, 17.7% had at least one positive blood culture; 84.5%, 1.3%, 0.9% and 13.3% of positive cultures were collected on day 0, day 1, day 2 and ≥ day 3 of a febrile episode. Among the positive day 0 cultures, the median time to detection of an organism was 14.1 hours. Host characteristics of blood culture-positive FN episodes are summarized in Table 1. Bacteremia was identified in 537 FN cases; 18.1%, 11.9% and 2.6% of cultures were positive in only aerobic, lytic or anaerobic media cultures, respectively. The most commonly isolated organisms were Escherichia coli, coagulase-negative Staphylococcus, viridans group streptococcus, Klebsiella pneumoniae and Pseudomonas aeruginosa. Fifteen percent of infectious episodes with a positive blood culture were polymicrobial.

Conclusion

In summary, the study findings have important clinical implications such as emphasizing the value of day 0 cultures and highlighting the importance of routinely collecting blood cultures in more than one media type. Despite an optimized blood culture approach, less than a fifth of FN episodes had a blood culture-based diagnosis.

Disclosures

Randall Hayden, MD, Abbott Molecular: Advisory Board; Quidel: Advisory Board; Roche Diagnostics: Advisory Board.
111. Pediatric and Adolescent Sepsis Epidemiology and Clinical Characteristics, Emerging Infections Program, 2014–2015
Authors: Gokhale Runa Hatti , Sapiano Matthew , Dantes Raymund , Abanyie-Bimbo Francisca , Wilson Lucy E , Thompson Nicola , Perlmuter Rebecca , Nadle Joelle , Frank Linda , Brousseau Geoff , Johnston Helen , Bamberg Wendy M , Dumyati Ghinwa , Lynfield Ruth , DaSilva Malini , Kainer Marion A , Zhang Alexia Y , Ocampo Valerie , Samper Monika , Irizarry Lourdes , Sievers Marla M , Maloney Meghan , Ray Susan , Magill Shelley , Katz David , Epstein Lauren
Published: October 2019

Background

Sepsis is an important contributor to mortality among children and young adults. However, recent studies focused on hospital management and burden estimation do not provide critical data to inform prevention efforts. We conducted detailed medical record reviews to describe the epidemiology and clinical characteristics of children and young adults with sepsis to inform prevention and early recognition targets.

Methods

We utilized the Emerging Infections Program (EIP) to collect comprehensive data via retrospective record review for patients with severe sepsis or septic shock discharge diagnosis codes from a nonrandom sample of hospitals across 10 states. Children and young adults, aged 30 days through 21 years, discharged between September 30, 2014 and October 1, 2015, were randomly selected for inclusion. We performed a descriptive analysis of these data.

Results

Among 734 patients hospitalized with sepsis, 92% were living in a private residence 4 days before admission, 38% had an outpatient medical encounter in the 7 days before admission, 14% had sepsis onset after hospital day 3, and 11% died within 90 days of sepsis diagnosis. The most frequently identified infection was lower respiratory tract infection (14%); for 317 (43%) no infection was documented as a cause of sepsis. The most frequently identified pathogen was Staphylococcus aureus (10%); for 326 (44%) no pathogen was identified as a cause of sepsis. Among 394 (54%) patients with ≥1 chronic underlying medical condition (CUMC), the most common were pulmonary disease (35%), hematologic/oncologic disease (31%), immune compromise (24%), and cardiovascular disease (20%). Patients with CUMC had a higher percentage of their sepsis onset after hospital day 3, death within 90 days of sepsis diagnosis, and Pseudomonas aeruginosa as a cause of sepsis (table). The percentage of patients with no pathogen identified was similar between those with CUMC and those without.

Conclusion

In our large cohort of children and young adults with sepsis, most had sepsis onset outside of the hospital and over half had chronic conditions. Our data suggest that distinct approaches may be needed to develop effective prevention and early recognition strategies for children and young adults depending on the presence of chronic conditions.

Disclosures

All authors: No reported disclosures.
2203. Patient-Specific Risk Stratification to Identify Patients at High and Low Risk for P. aeruginosa in Community-Acquired Pneumonia
Authors: Justin Moore William , Cruce Caroline , Harkabuz Karolina , Salama Shereen , Sutton Sarah , Zembower Teresa , Postelnick Michael J , Wunderink Richard G , Rhodes Nathaniel J
Published: October 2019

Background

Pseudomonas aeruginosa (PsA) is an infrequent pathogen associated with poor outcomes in community-acquired pneumonia (CAP). Identifying patients at high and low-risk for PsA in CAP is necessary to reduce inappropriate and overly broad-spectrum antibiotic use. We evaluated the distribution of risk-factors in hospitalized CAP patients with and without PsA infection.

Methods

Design: retrospective, single-center, case–control study. Inclusion: hospitalized CAP patients admitted to the general medicine wards between January 1, 2014 and May 29, 2018. Exclusion: cystic fibrosis, ≥ 3 admissions within 30 days, CAP requiring ICU admission, and death within 48 hours of admission. Case patients had PsA in respiratory or blood cultures during the index CAP admission. Controls were randomly selected targeting a 3:1 ratio. Comorbidities, pneumonia severity index, and m-APACHE II were assessed. Gram-negative risk factors defined by Shindo et al. 2013 (PMID: 23855620) and validated by Kobayashi et al. (2018; PMID: 30349327) were scored for each patient. Stepwise logistic regression was used to identify covariates that distinguished cases from controls at a P < 0.2; these were then used to generate propensity weights (i.e., inverse-probability conditioned on covariates). Unadjusted and adjusted odds ratios for case status were estimated using logistic regression according to: the total number of risk factors present and threshold values, respectively. All analyses were conducted using IC Stata (v.14.2).

Results

54 cases and 152 controls were included. The distribution of the patient-specific sum of risk factors for PsA is shown in Figure 1. The univariate OR for case status was 4.29 (95% CI:1.55–11.9) at n = 3 risk factors, which was similar after propensity weight adjustment [aOR = 4.64 (95% CI: 1.32–16.3)]. The univariate OR of case status was 2.98 among patients with ≥ 3 risk factors (95% CI: 1.34–6.62), which was similar after propensity weight adjustment [aOR = 2.8 (95% CI: 1.02–7.72)], and correct classification was 73.8%.

Conclusion

At a threshold of ≥ 3 PsA risk factors, cases and controls were well classified, even after adjusting for propensity weights. The impact of patient-specific PsA risk-stratification on CAP outcomes and appropriate antibiotic use should be evaluated.

Disclosures

All authors: No reported disclosures.
2209. Charlson Comorbidity Index Scores and In-hospital Prognosis in Severe Acute Respiratory Infections Patients
Authors: Wisniewski Setter Nicholas , Latarini Peres Marcos , Machado de Almeida Bernardo Montesanti , Mara Raboni Sonia
Published: October 2019

Background

Respiratory infections are one of the leading causes of mortality, and comorbid conditions play a significant role in the severity and fatality of these infections. The Charlson Comorbidity index (CCI) is the most used comorbidity index, presenting a few updated versions since its establishment. In the present study, we evaluated the CCI score and possible predictors of mortality in hospitalized patients with Severe Acute Respiratory Infection (SARI), aiming to test whether the CCI is a valid in-hospital prognostic indicator.

Methods

Patients older than 14 years, hospitalized from 2010 to 2016 due to SARI by viral infection, and who were submitted to respiratory virus testing were included. We assessed comorbidity retrospectively through chart review, and calculated 4 variants of the CCI.

Results

Of the 291 patients assessed, 72.8% (n = 212) presented comorbidities and 24% died (n = 70). The most recurrent comorbidities were Chronic Pulmonary Disease (n = 76/212, 36%) and HIV (n = 50/212, 23.6%). Respiratory virus testing was positive in 38.1% of patients (n = 111), Influenza and Rhinoviruses being the most frequent. The 1994 Age-adjusted CCI predicted in-hospital mortality in SARI patients (P = 0.04), and HIV was independently associated with in-hospital mortality (P = 0.032).

Conclusion

The comorbidity scores used to assess mortality risk in hospitalized patients with SARI displayed poor results, but HIV infection was considered a marker of severity. However, other factors should be considered in order to compose a scoring system that allows us to specifically assess the risk of mortality in patients with SARI.

Disclosures

All authors: No reported disclosures.
2217. Frequency and Antimicrobial Susceptibility of Bacteria Isolated from Patients Hospitalized with Pneumonia in US Medical Centers During 2018
Authors: Sader Helio S , Huband Michael D , Carvalhaes Cecilia G , Castanheira Mariana
Published: October 2019

Background

Rapidly introducing appropriate antimicrobial therapy is crucial to reduce morbidity and mortality of patients hospitalized with pneumonia (PHP), and therapy is determined mostly by understanding causative pathogens. Ceftazidime–avibactam (CAZ-AVI) was recently approved and ceftolozane–tazobactam (C-T) is in late-stage clinical development for treating nosocomial pneumonia, including ventilator-associated.

Methods

Bacterial isolates were consecutively collected from PHP (1/patient) in 67 US medical centers in 2018 and the Gram-negative bacilli (GNB) were tested by reference broth microdilution methods for susceptibility (S) to CAZ-AVI, C-T, and many comparators at a central laboratory.

Results

The most common organisms isolated from PHP were S. aureus (27.0%), P. aeruginosa (PSA) (24.6%), K. pneumoniae (KPN; 7.6%), E. coli (6.8%), S. marcescens (5.4%), and S. maltophilia (XM; 4.5%). Colistin (99.7%S), CAZ-AVI (95.7%S), and C-T (94.9%S) were the most active compounds against PSA; CAZ-AVI (99.9%S), amikacin (AMK; 98.8%S), and meropenem (MEM; 97.6%S) were the most active compounds against Enterobacterales (ENT). CAZ-AVI and C-T retained activity against PSA isolates non-S (NS) to piperacillin–tazobactam (PIP-TAZ), MEM, and cefepime (FEP), whereas PSA isolates NS to PIP-TAZ, MEM, or FEP exhibited low S rates to PIP-TAZ (≤ 39.2%), MEM (≤ 37.8%), and FEP (≤ 38.0%; Table). CAZ-AVI and tigecycline were the only compounds with good activity against carbapenem-resistant ENT (CRE), both with 96.6%S. Among ENT, the most common ESBL and carbapenemase were CTX-M-15 (73%) and KPC-2/3 (76%), respectively. CAZ-AVI was active against all ESBL producers (100.0%S), whereas the S rate to C-T was 82.4%. The most active compounds against multidrug-resistant (MDR) ENT were CAZ-AVI (98.9%S), AMK (91.5%S), and MEM (80.8%S). XM and A. baumannii exhibited low S rates to most antimicrobials tested.

Conclusion

Gram-negative bacteria were isolated from 70% of PHP, and PSA and ENT represented >80% of these organisms. CAZ-AVI and C-T showed similar coverage (%S) against PSA (95.7–94.9%S). In contrast, C-T was less active than CAZ-AVI against ENT in general and exhibited limited activity against ENT-resistant subsets.

Disclosures

All authors: No reported disclosures.
2233. Efficacy and Symptom Resolution by Visit in Adults With Community-Acquired Bacterial Pneumonia (CABP) Treated With Lefamulin (LEF) or Moxifloxacin (MOX): Pooled Analysis of Lefamulin Evaluation Against Pneumonia (LEAP) 1 and LEAP 2 Study Results
Authors: Schranz Jennifer , Das Anita F , Alexander Elizabeth , Moran Gregory J , Sandrock Christian , File Thomas M , Gelone Steven P
Published: October 2019

Background

Efficacy and safety of LEF were shown in 2 noninferiority trials (LEAP 1/2) vs. MOX in adults with CABP. We assessed the efficacy of LEF by visit based on a pooled analyses of LEAP 1/2 data.

Methods

In LEAP 1, PORT III–V patients (patients) received LEF 150 mg IV q12h for 5–7 days or MOX 400 mg IV q24h for 7 days, with optional IV-to-oral switch (600 mg LEF q12h or 400 mg MOX q24h). In LEAP 2, PORT II–IV patients received oral LEF 600 mg q12h for 5 days or oral MOX 400 mg q24h for 7 days. Criteria for defining the FDA primary endpoint of early clinical response (ECR) at 96 ± 24 hours after first dose were applied to each visit through late follow-up (LFU; days 27–34) in the intent-to-treat (ITT; all randomized patients) population. Investigator assessment of clinical response (IACR) was examined at end of treatment (EOT; within 2 days after last dose), test-of-cure (TOC; 5–10 days after last dose; EMA primary endpoint), and LFU in the modified ITT (mITT; received ≥1 dose of study drug) and clinically evaluable (CE; met predefined evaluability criteria) populations. Results are presented by visit for pooled LEAP 1/2 data.

Results

1289 ITT patients were randomized (LEF, n = 646; MOX, n = 643). Most patients in both groups achieved ECR at Day 3, with further increases through Day 7 and sustained efficacy through LFU (Fig 1). In mITT patients, IACR success rates at EOT/TOC/LFU were 87.1/85.0/83.2% with LEF and 88.1/87.1/86.1% with MOX; results were consistent in CE patients. The proportions of ITT patients with resolution of all baseline signs/symptoms of CABP increased similarly by visit in both treatment groups (Fig 2). Most patients did not achieve complete sign/symptom resolution until TOC, with fever generally being the first and cough the last to resolve. There was no apparent relationship between ECR and age, gender, renal status, SIRS, PORT, prior antibiotic use, baseline pathogens, typical/atypical pathogens, or mono/polymicrobial pathogens. The high percentage of patients at LFU with baseline symptom resolution suggests that symptom resolution was sustained.

Conclusion

In this pooled analysis, efficacy results were similar by visit in the LEF and MOX groups, with high ECR rates maintained through LFU. LEF will provide a potential new effective systemic monotherapy alternative to fluoroquinolones for the empiric treatment of CABP.

Disclosures

All authors: No reported disclosures.
2237. Early Discontinuation of Antibacterials Is Safe for Patients with Community-Acquired Pneumonia (CAP) Who Have a Positive Viral Test, Negative Tests for Bacteria, and Low Procalcitonin
Authors: Politis Paula Ann , Kallstrom George , Tan Michael , File Thomas M
Published: October 2019

Background

Studies using molecular testing methods have found monomicrobial infection with a virus as the etiology of CAP in adult patients admitted to the hospital in 6–30% of cases. The use of antibacterial agents in such patients is unnecessary, and can lead to untoward consequences. A test confirming a viral etiology may reduce the needless use of antibiotics, especially if the procalcitonin (PCT) level is low, suggesting that bacterial co-infection is unlikely. Our Antimicrobial Stewardship Program (ASP) routinely follows patients admitted with respiratory tract infections, and provides recommendations for appropriate therapy based on diagnostic test results as well as PCT levels. We present a retrospective evaluation of our experience.

Methods

A retrospective review of ASP interventions on patients admitted to Summa Health System—Akron Campus was performed for the time frame of January 2018–March 2019. Patients were included if they had a positive viral PCR result (VERIGENE™, BioFire™), a PCT level <0.25 ng/mL (BioMérieux™, Abbott™), negative bacterial studies, and an accepted intervention to discontinue antimicrobial therapy made by the ASP.

Results

The ASP assessed 131 patients with positive viral PCR studies and low PCT levels who had antimicrobials discontinued based on ASP recommendations; 68 with CAP and 63 without pneumonia (WPNA) as demonstrated on imaging. Most patients in the WPNA category had acute exacerbation of COPD. Common viruses identified were Influenza A or B, Rhinovirus and RSV. Mean duration of antibiotics was 2.6 days for CAP and 2.4 days for WPNA (Table 1). The 30-day readmission rate was similar for each group, and for CAP patients was similar for all-cause pneumonia patients at our institution (14% during similar time period). 30-day Mortality of CAP patients was low.

Conclusion

While national guidelines recommend a minimum of 5 days of antimicrobial therapy for CAP patients, we have observed that discontinuing antibiotics well before that is safe if a viral etiology is identified without evidence of bacterial co-infection (including low PCT) and results in less antibiotic usage. Reduction in unnecessary antibiotic use has the potential to improve the quality of care for adults with CAP.

Disclosures

All authors: No reported disclosures.
2247. Real-world Experience with Meropenem–Vaborbactam (M/V) for Treatment of Carbapenem-Resistant Enterobacteriaceae (CRE) Infections
Authors: Shields Ryan K , McCreary Erin K , Marini Rachel V , Kline Ellen G , Jones Chelsea E , Hao Binghua , Clancy Cornelius J , Nguyen Minh-Hong
Published: October 2019

Background

M/V demonstrates in vitro activity against KPC-producing CRE, but real-world clinical experience is limited.

Methods

Patients 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.

Results

19 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.

Conclusion

In 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.
2248. Clinical and Microbiological Outcomes Associated with Real-World Use of Ceftolozane/Tazobactam
Authors: Cabrera Nicolo , Tran Truc T , Miller William R , Dinh An Q , Hanson Blake , Munita Jose M , Shelburne Samuel A , Shelburne Samuel A , Aitken Samuel L , Aitken Samuel L , Garey Kevin W , Puzniak Laura A , Arias Cesar A
Published: October 2019

Background

Ceftolozane/tazobactam (C/T) is a novel cephalosporin/β-lactamase inhibitor combination for treating Gram-negative infections, particularly Pseudomonas aeruginosa (PA). C/T has been FDA-approved for complicated intra-abdominal and urinary tract infections and has just completed a trial in ventilator nosocomial pneumonia, but real-world outcome data are still emerging.

Methods

Demographic, microbiologic, treatment and outcome data of patients who received C/T for ≥48 hours from January 2016 to August 2018 at multiple centers within a single hospital system were retrospectively collected. Available isolates were analyzed for C/T susceptibility (by Etest) and whole-genome sequencing (WGS). Spades v.3.11.1 was used for assembly, multi-locus sequence typing v2.10 performed for in silico MLST with the PubMLST database and Abricate v0.7 was used for resistance gene screening with the CARD database.

Results

Among 45 patients, 58% were non-white, 53% were female and 13% were immunocompromised. The median age was 64 years (IQR, 50 to 69). At the time of the index event, a high proportion of patients required ICU care (42%) and pressor support (13%) as well as had invasive devices in place (64%). A minority (2.4%) had prior exposure to C/T. Respiratory infections were most common (38%) followed by urinary tract (20%). Concomitant Gram-negative agents were used in 18%. 69% achieved clinical success (i.e., recovery from infection-related signs and symptoms). The in-hospital mortality rate was 16% of which 5 out of 7 were attributed to infection. Microbiology was available for 91% of patients; 84% had PA isolates resistant to at least 3 antipseudomonal classes (Figures 1 and 2). Ten PA isolates were analyzed with WGS (Table 1). C/T resistance arose during therapy in one patient (MIC increase from 1 to 128 µg/mL). WGS showed a substitution in AmpC β-lactamase (A46D) and presence of blaCARB-2.

Conclusion

Although C/T was used in a critically ill population with highly resistant organisms, cure rates were high and mortality was low. Acquired β-lactamases were not frequently seen among the PA isolates. C/T is a vital therapeutic option, particularly on MDR isolates for which options are limited.

Disclosures

Samuel L. Aitken, PharmD, Melinta Therapeutoics: Grant/Research Support, Research Grant; Merck, Sharpe, and Dohme: Advisory Board; Shionogi: Advisory Board.
2250. Combination Vancomycin Plus Cefazolin for Methicillin-Resistant Staphylococcus aureus Bloodstream Infections
Authors: Jorgensen Sarah C J , Trinh Trang D , Zasowski Evan J , Alosaimy Sara , Melvin Sarah , Bhatia Sahil , Dhar Sorabh , Mynatt Ryan P , Pogue Jason M , Rybak Michael J
Published: October 2019

Background

Combination β-lactam and vancomycin (VAN) prevent the emergence of resistance and result in synergistic antimicrobial activity against methicillin-resistant Staphylococcus aureus (MRSA) in vitro. We sought to provide clinical translation to these data and determine if patients with MRSA bloodstream infection (BSI) treated with VAN + cefazolin (VAN/CFZ) via our MRSA BSI clinical pathway had improved clinical outcomes compared VAN alone.

Methods

Multicenter, retrospective, comparative cohort study from 2006 to 2019 in adults with MRSA BSI treated with VAN for ≥ 72 hours. VAN/CFZ was defined as VAN + CFZ within ≤ 72 hours of index culture for ≥ 24 hours. Other β-lactams were allowed for < 48 h in the VAN/CFZ group. The VAN alone group could not have other β-lactams within 7 days of treatment initiation. The primary outcome was clinical failure defined as a composite of 30-d all-cause mortality, 60-day recurrence, and persistent BSI (≥ 7 days). The independent effect of VAN/CFZ on clinical failure was evaluated with multivariable logistic regression. The primary safety endpoint was nephrotoxicity within 7 days of treatment initiation.

Results

A total of 237 patients were included (104 VAN/CFZ, 133 VAN). The most common BSI sources were skin/soft tissue (29.1%), IV catheter (21.9%), osteoarticular (20.3%) and infective endocarditis (16.0%). Demographic and clinical characteristics were similar between groups except VAN/CFZ had a higher median APACHE II score (18 vs. 13, P = 0.011). VAN/CFZ patients were also more likely to have received an infectious disease consult (100% vs. 81.2%, P < 0.001). Median (IQR) duration of CFZ was 115 (87–164) hours. After controlling for age, APACHE II score, ID consult and infection source, VAN/CFZ was associated with reduced odds of clinical failure (aOR 0.425, 95% CI 0.228, 0.792). Bivariate outcomes are shown in the table:

Conclusion

Patients with MRSA BSI treated with VAN/CFZ vs. VAN experienced fewer clinical failures, supporting additional studies evaluating the role of adjuvant CFZ for MRSA BSI.

Disclosures

All authors: No reported disclosures.
2254. Multicenter Evaluation of Ceftazidime–Avibactam for Multidrug-Resistant Pseudomonas aeruginosa Infections
Authors: Jorgensen Sarah C J , Trinh Trang D , Zasowski Evan J , Alosaimy Sara , Lagnf Abdalhamid M , Bhatia Sahil , Melvin Sarah , Simon Samuel , Steed Molly E , Rosenberg Joshua R , Estrada Sandra J , Davis Susan L , Rybak Michael J
Published: October 2019

Background

Ceftazidime–avibactam (CZA) is a novel cephalosporin/β-lactamase inhibitor with activity against carbapenem-resistant Enterobacteriaceae (CRE) and multidrug-resistant (MDR) Pseudomonas aeruginosa (PA). Real-world experience with CZA for CRE infections is accumulating but data on its use for MDR PA infections remains limited.

Methods

Retrospective, multicenter cohort study describing the clinical characteristics and outcomes of patients treated with CZA (≥ 72 hours) for MDR PA infections between 2015 and 2018.

Results

Fifty-one patients were included. The median (IQR) age was 61 (43, 71) years. Most patients had MDR risk factors including recent hospitalization (74.5%), recent antimicrobial exposure (84.3%), and/or previous infection or colonization with an MDR pathogen (58.8%). The median Charlson Comorbidity score was 4 (2, 6) and the median APACHE II score was 20 (12, 29). Infections were predominantly (68.6%) hospital-acquired and 52.9% of patients were in the ICU at infection onset. The common sources were respiratory tract (60.8%), osteoarticular (11.8%) and skin and soft tissue (11.8%). Two patients had positive blood cultures. PA antibiotic susceptibilities were as follows: ceftazidime 52.6% (n = 51), CZA 92.0% (n = 25), ciprofloxacin 10% (n = 30), meropenem 19.6% (n = 46), piperacillin–tazobactam 30.4% (n = 4) and tobramycin 72.9% (n = 48). Most (60.8%) infections were polymicrobial including 15 (29.4) CRE co-infections. CZA was started 97 (50, 170) hours after culture collection and continued for 9 (7, 14) days. Only 8 patients (15.7%) received active antibiotic therapy before CZA. Combination CZA therapy was used 35.3%, most often an aminoglycoside (8/18, 44.4%). Clinical cure or improvement was achieved in 40 patients (78.4%), and 42 (82.4%) were discharged alive. Among patients with repeat cultures (n = 11), CZA resistance development was not detected. Three patients (5.9%) experienced infection recurrence within 30 days of completing therapy.

Conclusion

The use of CZA was associated with high rates of favorable outcomes in complex patients with MDR PA infections. Future studies evaluating long-term outcomes and comparative studies are needed to more precisely define the role of CZA for MDR PA infections.

Disclosures

All authors: No reported disclosures.
2255. The Use of Dalbavancin for Staphylococcus aureus Bacteremia in Persons Who Inject Drugs (PWID)
Authors: Van Hise Nicholas W , Anderson Michael , McKinsey David , McKinsey Joel , Harting Brian , Belmares Jaime , Petrak Russell M
Published: October 2019

Background

Staphylococcus aureus is a significant cause of bacteremia and is associated with high morbidity and mortality rates. In patients with S. aureus bacteremia, studies have proven that intravenous antibiotics are needed for the entire course of therapy. For some groups of patients, specifically in persons who inject drugs (PWID), the long-term use of IV antibiotics is not safe or feasible. In this population, the current options would be obtaining intravenous access daily for antibiotic infusions, oral antibiotics, or being admitted to a facility that can monitor the patient. Data concerning the utilization of dalbavancin for the treatment of S. aureus bacteremia are limited.

Methods

This was a multicenter, retrospective case series of patients treated with four to six weekly doses of dalbavancin at 5 infusion centers in 3 states under the care of Metro Infectious Disease Consultant (MIDC) physicians between January 1 and December 31, 2018. All patients received intravenous therapy through a peripherally inserted catheter that was removed immediately after the infusion was completed. All patients were evaluated by an MIDC physician at the time of the initial dalbavancin dose, and weekly through their course of therapy. Cure was defined as negative blood cultures and no clinical evidence of persistent or relapsing infection. All patients completed their prescribed dosing and had phone follow-up to assess treatment efficacy at weeks 4, 8, 12, and 24.

Results

Twenty-one patients were included in the analysis. All patients began therapy for S. aureus bacteremia as inpatients and were transitioned to dalbavancin as outpatients. All patients received dalbavancin 1 g followed by 500 mg doses for at least 3 more weeks with an average of 4 weeks of therapy. Of the 21 patients, 16 were able to be contacted post therapy. Of the 16 patients, 2 patients were readmitted within the 6 month time frame for recurrent bacteremia related to intravenous drug usage. The remaining 14 patients remained disease free at the 6 month interval. No patients experienced a line related issue or C. difficile infection during the course of therapy.

Conclusion

Use of dalbavancin to treat S. aureus bacteremia infections resulted in clinical cure and markedly decreased healthcare costs.

Disclosures

All authors: No reported disclosures.