JMI Laboratories Research Articles

1582. Delafloxacin Activity Against Drug-Resistant Streptococcus pneumoniae, Haemophilus influenzae, Haemophilus parainfluenzae, and Moraxella catarrhalis from US Medical Centers (2014–2018)

BackgroundDelafloxacin (DLX) is an anionic fluoroquinolone (FQ) antimicrobial that was approved in 2017 by the United States (US) Food and Drug Administration for the treatment of acute bacterial skin and skin structure infections. DLX recently successfully completed a clinical trial for the treatment of community-acquired bacterial pneumonia (CABP). In the present study, in vitro susceptibility (S) results for DLX and comparator agents were determined for CABP pathogens including Streptococcus pneumoniae (SPN), Haemophilus influenzae (HI), H. parainfluenzae (HP) and Moraxella catarrhalis (MC) clinical isolates from US hospitals participating in the SENTRY Program during 2014–2018.MethodsA total of 1,975 SPN, 1,128 HI, 684 MC, and 43 HP isolates were collected from community-acquired respiratory tract infections (CARTI) during 2014–2018 from US hospitals. Sites included only 1 isolate/patient/infection episode. Isolate identifications were confirmed at JMI Laboratories. Susceptibility testing was performed according to CLSI broth microdilution methodology, and CLSI (2019) breakpoints were applied where applicable. Other antimicrobials tested included levofloxacin (LEV) and moxifloxacin (MOX; not tested in 2015). Multidrug-resistant (MDR) SPN isolates were categorized as being nonsusceptible (NS) to amoxicillin-clavulanate, erythromycin, and tetracycline; other SPN phenotypes were LEV-NS or penicillin (PEN)-NS. β-Lactamase (BL) presence was determined for HI, HP, and MC.ResultsThe activities of the 3 FQs are shown in the table. The most active agent against SPN was DLX, with the lowest MIC50/90 values of 0.015/0.03 mg/L. DLX activities were similar when tested against the MDR or PEN-NS for SPN phenotypes. LEV-NS isolates had DLX MIC50/90 results of 0.12/0.25 mg/L. DLX was the most active FQ against HI, HP, and MC. BL presence did not affect FQ MIC values for HI or MC; only 2 HP isolates were BL-positive.ConclusionDLX demonstrated potent in vitro antibacterial activity against SPN, HI, HP, and MC. DLX was active against MDR SPN that were NS to the agents commonly used as treatments for CABP. DLX had excellent activity against LEV-NS SPN. These data support the continued study of DLX as a potential treatment for CABP. Disclosures All authors: No reported disclosures.

1584. Minocycline Activity Against Stenotrophomonas maltophilia Isolated From Patients in US Hospitals

Background Stenotrophomonas maltophilia (SM) has emerged as a common hospital-associated opportunistic pathogen found in immunocompromised and immunocompetent patients. SM is intrinsically resistant to many common drug classes, including carbapenems, cephalosporins, and aminoglycosides. Only 4 antibiotics have CLSI breakpoints for SM: minocycline (MIN), ceftazidime (CAZ), levofloxacin (LVX) and trimethoprim-sulfamethoxazole (TMP-SMX). Minocycline is frequently used to treat SM infections. In this study, we analyzed susceptibilities of SM isolates collected as part of the SENTRY Program. We also examined the frequency of SM isolation from pneumonia in hospitalized patients (PIHP) among all Gram-negative (GN) species.MethodsFrom 2014 to 2018, 990 SM isolates were collected from hospitalized patients in 32 US hospitals. Hospitals submitted 1 isolate per patient per infection episode that met local criteria for being the likely causative pathogen and submitted consecutive isolates from pneumonia. Isolates were tested for MIN susceptibility (S) using the CLSI broth microdilution method at JMI Laboratories. Other antimicrobials tested were CAZ, LVX, and TMP-SMX. TMP-SMX was tested 3 of 5 years. All infection types were included in the susceptibility analysis. The prevalence of SM isolates in PIHP during this period was also analyzed.ResultsThere were 9,120 GN pathogens isolated from PIHP. The most commonly isolated species was P. aeruginosa (34.7%), followed by Klebsiella pneumoniae (12.6%), Escherichia coli (10.1%), and SM (7.9%). Among the 990 infections caused by SM, PIHP was the most common at 72.4%, followed by bloodstream infections (14.4%) and skin/skin structure infections (6.9%). The %S and MIC50/90 values of the 4 antimicrobials tested in this study are shown in the table.ConclusionSM was the fourth most frequent cause of GN PIHP in US medical centers. MIN was the most active drug tested against SM with 99.5%S, followed by TMP-SMX (94.7%), and CAZ was the least active with 28.5%S. This study suggests that MIN may be a consideration as a treatment for infections caused by SM, with a very low resistance rate based on CLSI breakpoints. Disclosures All authors: No reported disclosures.

Antimicrobial activity of ceftolozane/tazobactam tested against contemporary (2015–2017) Pseudomonas aeruginosa isolates from a global surveillance programme

ObjectivesCeftolozane/tazobactam (C–T) is an antimicrobial combination of an antipseudomonal cephalosporin and a β-lactamase inhibitor. C–T has been approved in >60 countries for complicated urinary tract infections, acute pyelonephritis, complicated intra-abdominal infections in combination with metronidazole, and was recently approved for hospital-acquired bacterial pneumonia. In this study, data for Pseudomonas aeruginosa isolates consecutively collected from various infection types in hospitalised patients from 2015 to 2017 were analysed. MethodsA total of 6836 P. aeruginosa isolates were collected from 104 hospitals in four continents and were tested for susceptibility to C–T by CLSI broth microdilution methodology at JMI Laboratories using CLSI (2018) breakpoints. Other agents tested included amikacin, ceftazidime (CAZ), colistin (COL), levofloxacin (LVX), meropenem (MEM) and piperacillin/tazobactam (TZP). Resistance phenotypes analysed included CAZ-non-susceptible (CAZ-NS), COL-NS, MEM-NS, LVX-NS, TZP-NS and β-lactam-NS. Multidrug resistance (MDR) was defined as NS to ≥1 drug in ≥3 drug classes, and extensively drug-resistant (XDR) was defined as NS to ≥1 agent in all but 2 or fewer antimicrobial classes. ResultsThe most common infection from which P. aeruginosa was isolated was pneumonia (51.6%), followed by skin and skin-structure infection (22.2%) and bloodstream infection (15.3%). Percentage susceptibility to C–T varied by region: 98.2% in North America; 94.8% in Asia-Pacific; 90.8% in Latin America; and 89.1% in Europe. ConclusionC–T had potent activity against P. aeruginosa isolated from patients in hospitals in four continents. C–T was more active than all comparators, except COL, and maintained activity against MDR and XDR isolates and isolates NS to all four tested β-lactams. C–T was active against 13/16 COL-NS isolates.

Antimicrobial Activity of Omadacycline Tested against Clinical Bacterial Isolates from Hospitals in Mainland China, Hong Kong, and Taiwan: Results from the SENTRY Antimicrobial Surveillance Program (2013 to 2016).

Omadacycline is a derivative of minocycline and the first agent of the aminomethylcycline class. A total of 3,282 organisms (1 per patient) were consecutively collected from patients hospitalized in China (including Hong Kong) and Taiwan. Susceptibility testing was performed by broth microdilution methods in a central laboratory (JMI Laboratories). The collection included Gram-positive and Gram-negative organisms from patients with pneumonia, bloodstream, skin, community-acquired respiratory, and other infections. Omadacycline was very potent against Staphylococcus aureus (n = 689; MIC50/90, 0.12/0.25 mg/liter), including methicillin-resistant Staphylococcus aureus (MRSA; n = 299; MIC50/90, 0.12/0.5 mg/liter), and had similar activity across geographic regions. Omadacycline was very active against Streptococcus pneumoniae (highest MIC, 0.25 mg/liter), β-hemolytic streptococci (highest MIC, 1 mg/liter), viridans group streptococci (highest MIC, 0.25 mg/liter), and Enterococcus spp. (highest MIC, 0.5 mg/liter) from all geographic regions. Overall, 53.8% of S. pneumoniae isolates were penicillin resistant (penicillin MIC, ≥2 mg/liter) and 10.7% of enterococci (21.2% among E. faecium isolates) were vancomycin resistant. Omadacycline was active against Haemophilus influenzae (MIC50/90, 0.5/1 mg/liter) regardless of β-lactamase production and was active against Moraxella catarrhalis (MIC50/90, ≤0.12/0.25 mg/liter). Against Enterobacteriaceae, omadacycline was most active against Escherichia coli (MIC50/90, 1/2 mg/liter), Klebsiella oxytoca (MIC50/90, 1/4 mg/liter), and Enterobacter cloacae (MIC50/90, 2/4 mg/liter). Omadacycline had potent in vitro activity against Gram-positive and Gram-negative pathogens isolated from China and Taiwan and retained activity against problem pathogens, such as MRSA, vancomycin-resistant enterococci (VRE), penicillin-resistant S. pneumoniae (PRSPN), and extended-spectrum β-lactamase-producing E. coli The observed MIC profile in Chinese isolates was very similar to that seen in the U.S. and European surveillance studies.

1375. In vitro Activity of Cefiderocol and Comparator Agents against Gram-Negative Isolates from Cancer Patients

BackgroundGram-negative bacilli (GNB) are now the predominant cause of bacterial infection in cancer patients (CP). Many GNB are problematic because they have become resistant to commonly used antibiotics. Cefiderocol (CFDC), a novel siderophore cephalosporin, is active against a wide spectrum of GNB. We evaluated its in vitro activity and that of eleven comparator agents against GNB isolated from CP.MethodsA total of 341 recent GNB blood isolates from CP were tested using CLSI approved methods for MIC determination by broth microdilution. Comparator agents were amikacin (A), aztreonam (AZ), ceftazidime (CZ), ceftazidime/avibactam (CAV), cefepime (CEF), ciprofloxacin (CIP), colistin (CL), meropenem (MR), ceftolozane/tazobactam (C/T), tigecycline (TG), and trimethoprim/sulfamethoxazole (T/S).ResultsCFDC MIC90s as mg/L were: S. maltophilia [50 isolates] 0.25, E. coli (ESBL−) [50 isolates] 0.5, E. coli (ESBL+) [51 isolates] 2.0, K. pneumoniae (ESBL− and +) [60 isolates] 0.5; K. pneumoniae (CRE) [22 isolates] 2.0; P. aeruginosa (MDR) [32 isolates] 1.0; E. cloacae [27 isolates] 4.0; Achromobacter spp. [15 isolates] 0.12. CFDC inhibited P. agglomerans, Burkholderia spp., Sphingomonas spp., Ochrobactrum spp. at ≤1 mg/L [23 total isolates] and Elizabethkingia spp. and R. radiobacter at ≤8 mg/L [11 total isolates]. Among comparator agents, only T/S had consistent activity against S. maltophilia. For E. coli (ESBL− and +) MR, TG, CAV, CL were most active. For K. pneumoniae (ESBL–and +) MR, CAV were most active. For K. pneumoniae (CRE) and P. aeruginosa (MDR), none of the comparators had significant activity. For E. cloacae, MR, A, CAV, TG were most active. Among the uncommon organisms, MR and TG had the greatest activity.ConclusionAlthough susceptibility breakpoints have yet to be determined, CFDC has significant activity (≤4 mg/L) against most problematic Gram-negative organisms causing infections in CP based on available pharmacokinetic/pharmacodynamic data. In particular, its activity against S. maltophilia was superior to the comparators. Also, it was the most active agent against P. aeruginosa (MDR) and K. pneumoniae (CRE). Based on our results, CFDC warrants clinical evaluation for the treatment of blood stream infections caused by GNB in CP.Disclosures K. V. I. Rolston, Merck: Investigator, Research grant; JMI Laboratories: Investigator, Research grant; Shionogi (Japan): Investigator, Research grant. B. Gerges, Shionogi: Collaborator, Research support. S. L. Aitken, Shionogi: Scientific Advisor, Consulting fee; Merck: Scientific Advisor, Consulting fee; Medicines Co: Scientific Advisor, Consulting fee; Achaogen: Scientific Advisor, Consulting fee; Zavante: Scientific Advisor, Consulting fee; R. Prince, Shionogi: Investigator, Research support. Merck: Investigator, Research support.

1004. Frequency of Occurrence and Antimicrobial Susceptibility of Bacteria Isolated From Patients Hospitalized With Bloodstream Infections in United States Medical Centers (2015–2017)

BackgroundBloodstream infections (BSIs) cause significant morbidity and mortality. We evaluated the frequency and antimicrobial susceptibility of bacteria causing BSIs in the United States.MethodsA total of 9,210 bacterial isolates were consecutively collected (1/patient) from 33 US medical centers in 2015–2017 and tested for susceptibility by reference broth microdilution methods in a central laboratory (JMI Laboratories) as part of the International Network for Optimal Resistance Monitoring (INFORM) program. Whole-genome sequencing was performed on carbapenem-resistant Enterobacteriaceae (CRE).ResultsThe most common organisms were S. aureus (SA; 24.3%), E. coli (EC; 20.8%), K. pneumoniae (KPN; 9.1%), coagulase-negative staphylococci (7.3%), E. faecalis (5.5%), P. aeruginosa (PSA; 4.7%), and β-hemolytic streptococci (4.7%). Overall, 50.0% of isolates were Gram-negative bacilli (GNB) and 41.4% were Enterobacteriaceae (ENT). All SA were susceptible (S) to dalbavancin (MIC90, 0.03 μg/mL), linezolid, tigecycline (TGC), and vancomycin; >99.9% S to daptomycin, 97.6% S to ceftaroline, and 57.8% S to oxacillin. The most active agents against ENT were CAZ-AVI (99.9% S; table), amikacin (AMK; 99.7% S), and the carbapenems meropenem (MEM) and doripenem (99.1% S). Ceftolozane-tazobactam (C-T; tested in 2017 only) was active against 96.9% of ENT. Ceftriaxone (CRO)-S rates were 83.0% and 86.5% among EC and KPN, respectively. CRO-non-S KPN exhibited low S rates to most agents, except CAZ-AVI (99.1% S), TGC (93.6%), AMK (93.8%), and colistin (COL; 93.4%). Among 28 CRE isolates (0.7% of ENT), 21 produced a KPC-like, 2 an NMD-like, and 1 a KPC-17 and an NDM-1. COL (100.0% S), C-T (98.7%S), CAZ-AVI (98.2% S), AMK (97.9% S), and tobramycin (95.6% S) were very active against PSA. CAZ-AVI and C-T remained active against most PSA isolates non-S to MEM (93.0 and 95.0% S, respectively) and/or piperacillin–tazobactam (P-T; 88.9 and 91.3% S) and/or CAZ (86.9 and 88.2% S).ConclusionGNB represented 50.0% of bacteria isolated from patients with BSIs and the most active agents against these organisms were CAZ-AVI and AMK. Various agents exhibited excellent overall coverage against Gram-positives, including dalbavancin, daptomycin, linezolid, and TGC. Disclosures H. S. Sader, Allergan: Research Contractor, Research support. R. K. Flamm, Allergan: Research Contractor, Research support. M. A. Pfaller, Allergan: Research Contractor, Research support. M. Castanheira, Allergan: Research Contractor, Research support.

1047. Global Surveillance: Susceptibility of Ceftolozane–Tazobactam Against Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa Isolates Collected From Bloodstream Infections in the United States From 2015 to 2017

BackgroundCeftolozane–tazobactam (C-T) is an antibacterial combination of a novel antipseudomonal cephalosporin and a β-lactamase inhibitor. C-T was approved by the US Food and Drug Administration in 2014 and by the European Medicines Agency in 2015 to treat complicated urinary tract infections, acute pyelonephritis, and complicated intra-abdominal infections. The Program to Assess Ceftolozane-Tazobactam Susceptibility (PACTS) monitors Gram-negative (GN) isolates resistant to C-T worldwide. In the current study, isolates were collected from patients hospitalized with bloodstream infections (BSIs) from 2015 to 2017 within the United States.MethodsA total of 3,377 prevalence-based BSI GN isolates, including Escherichia coli (EC; 1,422), Klebsiella pneumoniae (KPN, 630), and Pseudomonas aeruginosa (PSA; 344), were collected during 2015 to 2017 from 32 PACTS hospitals in the United States. Isolates were tested for C-T susceptibility by CLSI broth microdilution method in a central monitoring laboratory (JMI Laboratories). Other antibiotics tested were amikacin (AMK), cefepime (FEP), ceftazidime (CAZ), colistin (COL), levofloxacin (LVX), meropenem (MEM), and piperacillin–tazobactam (TZP). Antibiotic-resistant phenotypes analyzed (CLSI, 2018) for EC and KPN included carbapenem-R (CR) and non-CR extended-spectrum β-lactamase (ESBL); as well as CAZ-nonsusceptible (CAZ-NS), MEM-NS, and COL-NS PSA.ResultsOf the 3,377 BSI GN isolates, 3,219 (95.3%) had a C-T MIC ≤ 4 mg/L. The three most prevalent GN species isolated from BSIs were EC (42.1%), KPN (18.7%), and PSA (10.2%). The %S of C-T and comparators for the top three pathogens are shown in the table. C-T showed activity against these isolates with %S of ≥96.0% against all three species. Of the comparators tested, AMK and COL also had high %S against these isolates.ConclusionC-T demonstrated activity against the most prevalent contemporary GN isolates from BSIs in the US. C-T was the only beta-lactam that had ≥96%S against all three species: EC, KPN, and PSA. For PSA, C-T maintained activity (>90%S) against isolates resistant to CAZ, TZP, and MEM. These data suggest that C-T may be a useful treatment for GN BSI. Disclosures S. J. R. Arends, Merck: Research Contractor, Research support. D. Shortridge, Merck: Research Contractor, Research support. M. Castanheira, Merck: Research Contractor, Research support. J. M. Streit, Merck: Research Contractor, Research support. R. K. Flamm, Merck: Research Contractor, Research support.

1016. Bloodstream Infection Survey in High-Risk Oncology Patients (BISHOP) With Fever and Neutropenia (FN): Predictors for Morbidity and Mortality

BackgroundBlood stream infection (BSI) during neutropenia is associated with high risk for morbidity and mortality in patients with hematologic malignancies receiving chemotherapy or undergoing hematopoietic cell transplant (HCT). We sought to identify factors associated with increased risk for critical illness (CI) morbidities within 7 days of BSI with index FN following chemotherapy.MethodsA prospective ongoing survey among 14 high-volume US cancer centers submitting clinical and microbiologic data from consecutive HM patients with blood stream infection (BSI) during first FN after cytotoxic chemotherapy or HCT. We evaluated factors influencing poor outcomes defined as critical illness (need for pressor support, mechanical ventilation, new pneumonia or new BSI) within 7 days of BSI with index FN. Concordance between antibiotic and BSI isolate was determined by investigator (AZ, AF) interpretation of susceptibility reports provided by each center compared with the initial antimicrobial regimen (IAR) used, for single organism bacteremias only.ResultsAmong 294 FN bacteremic episodes (93 HCT) were 336 bacterial pathogens (48.5% Gram-negative [GN], 46.5% Gram-positive [GP], and 6% anaerobes). Death occurred in 11/294 (4%) and 41/294 (14%) had CI by day 8. At FN presentation, mean MASCC score of those with CI vs. those without was 16.9 vs. 18.6 (P = 0.03) and there was a trend toward higher mean PITT scores for patients with CI by day 8 vs. those without (1.54 vs. 0.82 (P = 0.08)). Among GN bacteremias, 15% developed CI vs. 14.5% in nonviridans group Streptococci (VGS) GP bacteremias, and 10.9% in VGS bacteremias (NS). Among patients with single organism bacteremias (88% of all BSI), mismatch of IAR coverage with isolate susceptibilities occurred in 16.7% (38/227). Among patients whom IAR was active vs. inactive against BSI isolate, 16% vs 14.3%, respectively, developed CI (P = 0.81).ConclusionThese data indicate that the MASCC score applied to high-risk inpatients may be a predictor for CI in the first week after bacteremia FN. The PITT shows less correlation with poor outcomes. There was no association between isolate type (GN, GP, or VGS) and CI. Notably there was no association between mismatched BSI susceptibility and antimicrobial spectrum of the IAR and early CI.Disclosures A. G. Freifeld, Merck: Investigator, Research grant. A. Zimmer, Merck: Investigator, Research grant. S. Pergam, Merck: Consultant, Consulting fee. Chimerix: Consultant, Consulting fee. K. V. Rolston, Merck: Investigator, Research grant. JMI Laboratories: Investigator, Research grant. Shionogi (Japan): Investigator, Research grant. S. Shoham, Merck: Investigator and Scientific Advisor, Consulting fee and Grant recipient. Astellas: Investigator, Grant recipient. Shionogi (Japan): Investigator, Grant recipient. Gilead: Investigator, Grant recipient. Shire: Investigator, Grant recipient. T. J. Walsh, Merck: Grant Investigator, Research grant. Atellas: Consultant, Grant Investigator and Scientific Advisor, Consulting fee and Research grant. Gilead: Scientific Advisor, Consulting fee. Allergan: Grant Investigator and Scientific Advisor, Consulting fee and Research grant. Scynexis: Grant Investigator, Research grant. Amplyx: Grant Investigator, Research grant. Shionogi: Scientific Advisor, Consulting fee. J. A. Young, GSK: Investigator, The University of Minnesota is reimbursed for contract costs associated with conducting clinical trials of vaccine. I receive no personal financial benefit. Y. Zhang, Merck: Investigator, Research grant. J. Meza, Merck: Investigator, Research grant.

1363. Sulopenem Activity Against Enterobacteriaceae Isolates From Patients With Urinary Tract Infection or Intra-Abdominal Infection

BackgroundSulopenem is a thiopenem antibacterial with oral and parenteral formulations being developed for the treatment of urinary tract infection (UTI) or complicated intra-abdominal infection (cIAI). The activity of sulopenem aligns with the most urgent drug-resistant antimicrobial threats defined by the Centers for Disease Control (CDC), including ESBL-producing strains of Escherichia coli and Klebsiella species. We evaluated the in vitro antibacterial activity of sulopenem against clinical Enterobacteriaceae isolates from patients in North America with UTI or cIAI collected during 2016–2017.MethodsSulopenem and other antimicrobial agents were tested for in vitro activity against 1,008 recent (2016–2017) consecutive Enterobacteriaceae isolates collected through the SENTRY Antimicrobial Surveillance Program from patients in North America with UTI (906 isolates) or cIAI (102 isolates). Reference broth microdilution susceptibility testing was conducted using frozen-form panels produced by JMI Laboratories according to CLSI (M07, 2018) guidelines using cation-adjusted Mueller–Hinton broth. Quality control (QC) and interpretation of results were performed in accordance with CLSI M100 (2018) guidelines.ResultsTable 1. Activity of sulopenem and comparator antimicrobial agents against 1,008 Enterobacteriaceae North American isolatesCLSIAntibioticMIC50MIC90%S%I%RSulopenem–––0.030.25Meropenem99.60.10.30.030.06Ertapenem99.30.30.4≤0.0080.03Ceftriaxone87.30.612.1≤0.06>8Piperacillin–tazobactam96.32.21.528Amoxicillin–clavulanate (2:1)75.87.716.5464Levofloxacin82.81.815.40.0616Nitrofurantoin63.822.214.032128The sulopenem MIC50/90 values for Enterobacteriaceae were 0.03/0.25 µg/mL. For Escherichia coli, Klebsiella species and Proteus mirabilis, the MIC50/90 results were 0.03/0.03 µg/mL, 0.03/0.06 µg/mL, and 0.12/0.25 µg/mL, respectively.ConclusionSulopenem demonstrated potent in vitro activity against organisms commonly implicated in UTI and cIAI. These data support the further clinical development of sulopenem for Gram-negative infections.Disclosures S. Puttagunta, Iterum Therapeutics: Employee and Shareholder, Salary. S. Aronin, Iterum Therapeutics: Employee and Shareholder, Salary. M. Huband, JMI Labs: Research Contractor, Grant recipient. R. K. Flamm, Allergan: Research Contractor, Research support. M. Dunne, Iterum Therapeutics: Employee and Shareholder, Salary.

1585. Bloodstream Infection Survey in High-Risk Oncology Patients (BISHOP) with Fever and Neutropenia (FN): Correlation Between Initial Empiric Antibiotic Regimen Correlation and Susceptibility Patterns

BackgroundThe empiric initial antibiotic regimen (IAR) for treatment of febrile neutropenia (FN) relies on a knowledge of epidemiology and susceptibility patterns of bacterial bloodstream infections (BSI), especially in high-risk patient populations, i.e., those receiving chemotherapy for hematologic malignancies (HM) or undergoing hematopoietic stem cell transplant (HCT). As the last US national survey of BSI epidemiology in cancer patients was published in 2003, we sought to update these data focusing exclusively on high-risk patients with attention to IARs used and their concordance with susceptibilities of isolated bloodstream pathogens.MethodsA prospective ongoing survey among 14 high-volume US cancer centers submitting clinical and microbiologic data from consecutive HM patients with BSI during first FN after cytotoxic chemotherapy or HCT. Concordance between antibiotic and BSI was determined by investigator (AZ, AF) interpretation of susceptibility reports provided by each center compared with IAR used, for single organism bacteremias only.ResultsAmong 294 FN bacteremic episodes (93 HCT), there were 336 bacterial pathogens (48.5% Gram negative [GN] 46.5% Gram positive [GP] and 6% anaerobes), with 88% monomicrobial episodes. E. coli and viridans group Streptococci (VGS) were the most commonly isolated GN and GP, respectively, each accounting for nearly 25% of total organisms identified. IARs included cefepime 61%, piperacillin–tazobactam 24%, and meropenem 8%. Isolates were nonsusceptible to the IAR in 38/227 (17%) of FN episodes. Antibiotic mismatch was more likely to occur with a non-VGS GP (37%) vs. GN (13%) or VGS (2%) P < 0.001.ConclusionThis is the first US national survey of high-risk BSI in FN. Although mismatch between BSI and IAR occurs in 17% of FN bacteremia episodes, this is driven primarily by non-VGS GP isolates such as CoNS and MRSA. Currently used IARs, comprised primarily of cefepime and piperacillin–tazobactam, generally provide reliable coverage for GN isolates across the United States (87%) but careful tracking of this rate is essential to identify further erosion of coverage in the current era of antimicrobial resistance.Disclosures A. Zimmer, Merck: Investigator, Research grant. A. G. Freifeld, Merck: Investigator, Research grant. S. Pergam, Merck: Consultant, Consulting fee; Chimerix: Consultant, Consulting fee. K. V. Rolston, Merck: Investigator, Research grant; JMI Laboratories: Investigator, Research grant; Shionogi (Japan): Investigator, Research grant. S. Shoham, Merck: Investigator and Scientific Advisor, Consulting fee and Grant recipient; Astellas: Investigator, Grant recipient; Shionogi (Japan): Investigator, Grant recipient; Gilead: Investigator, Grant recipient; Shire: Investigator, Grant recipient. T. J. Walsh, Merck: Grant Investigator, Research grant; Atellas: Consultant, Grant Investigator and Scientific Advisor, Consulting fee and Research grant; Gilead: Scientific Advisor, Consulting fee; Allergan: Grant Investigator and Scientific Advisor, Consulting fee and Research grant; Scynexis: Grant Investigator, Research grant; Amplyx: Grant Investigator, Research grant; Shionogi: Scientific Advisor, Consulting fee. J. A. Young, GSK: Investigator, The University of Minnesota is reimbursed for contract costs associated with conducting clinical trials of vaccine. I receive no personal financial benefit.. J. Meza, Merck: Investigator, Research grant. Y. Zhang, Merck: Investigator, Research grant.

1485. Antimicrobial Activity of Ceftolozane-Tazobactam Tested Against Contemporary (2015–2017) Gram-Negative Isolates from Patients with Pneumonia in US Medical Centers

BackgroundCeftolozane-tazobactam (C-T) is a combination antipseudomonal cephalosporin and β-lactamase inhibitor. C-T has been approved in >50 countries for treating adults with complicated urinary tract infections, acute pyelonephritis, and complicated intra-abdominal infections in combination with metronidazole. The Program to Assess Ceftolozane-Tazobactam Susceptibility (PACTS) monitors C-T resistance among Gram-negative (GN) isolates worldwide. In the current study, isolates were collected from US patients hospitalized with pneumonia (PIHP) from 2015–2017.MethodsA total of 4,337 GN isolates, including 2,102 Enterobacteriaceae (ENT) and 1,528 Pseudomonas aeruginosa (PSA) isolates, were collected in 2015–2017 from 30 US hospitals and tested for C-T susceptibility (S) by CLSI broth microdilution at JMI Laboratories. Only 1 isolate per patient per infection episode was included. Other antibiotics tested were amikacin (AMK), cefepime (FEP), ceftazidime (CAZ), colistin (COL), levofloxacin (LVX), meropenem (MEM), and piperacillin–tazobactam (TZP).-resistant (R) phenotypes analyzed were ENT R to doripenem, imipenem, or meropenem (CRE) and extended-spectrum β-lactamase (ESBL, non-CRE). Multidrug-resistant (MDR) isolates were identified as nonsusceptible (NS) to 3 or more antimicrobial classes. PSA phenotypes analyzed were CAZ-NS, MEM-NS, and TZP-NS.ResultsOf the 4,337 GN isolates, 3,820 (88.1%) had a C-T MIC ≤8 mg/L. The three most prevalent GN species isolated from PIHP were PSA (n = 1,528; 35.2%), Klebsiella pneumoniae (KPN, n = 562; 13.0%), and Escherichia coli (EC, n = 434; 10.0%). The %S of C-T and comparators for the top 3 pathogens are shown in the table. C-T showed activity against these isolates with %S of 96.5, 88.6, and 97.5% against EC, KPN, and PSA, respectively.ConclusionC-T demonstrated activity against the most prevalent contemporary GN isolates from PIHP in the US. C-T was the only β-lactam that had >88%S against all 3 species: EC, KPN, and PSA. C-T and COL were the only agents tested that had >95%S for EC and PSA pathogens in PIHP. For PSA, C-T maintained activity against isolates resistant to CAZ, TZP, and MEM. These data suggest that C-T may be a useful treatment for GN infections causing PIHP. Disclosures S. J. R. Arends, Merck: Research Contractor, Research support. D. Shortridge, Merck: Research Contractor, Research support. L. R. Duncan, Merck: Research Contractor, Research support. J. M. Streit, Merck: Research Contractor, Research support. R. K. Flamm, Merck: Research Contractor, Research support.

Antimicrobial Susceptibility of Enterobacteriaceae and Pseudomonas aeruginosa Isolates from United States Medical Centers Stratified by Infection Type: Results from the International Network for Optimal Resistance Monitoring (INFORM) Surveillance Program, 2015–2016

A total of 18,656 Enterobacteriaceae and 4,175 Pseudomonas aeruginosa were consecutively collected from 85 US hospitals and tested for susceptibility by broth microdilution methods in a central monitoring laboratory (JMI Laboratories). The antimicrobial susceptibility and frequency of key resistance phenotypes were assessed and stratified by infection type as follows: bloodstream (BSI; 3,434 isolates; 15.0%), pneumonia (6,439; 28.2%), skin and skin structure (SSSI; 4,134; 18.1%), intra-abdominal (IAI; 951; 4.2%), and urinary tract (UTI; 7,873; 34.5%). Ceftazidime-avibactam was active against 99.9% to 100.0% of Enterobacteriaceae and 97.0% (pneumonia) to 99.4% (UTI) of P. aeruginosa isolates. Susceptibility rates were consistently lower for β-lactams, such as ceftazidime (82.3% vs. 87.1–90.8%), piperacillin-tazobactam (87.5% vs. 90.2–95.6%), and meropenem (96.8% vs. 98.4–99.4%) among Enterobacteriaceae from pneumonia compared to other infection types. Susceptibility to gentamicin was also generally lower among isolates from pneumonia, whereas susceptibility to levofloxacin and colistin were lowest among BSI and SSSI isolates, respectively. The occurrence of multidrug-resistance (MDR; 8.2% overall), extensively drug-resistance (XDR; 1.1% overall), and carbapenem-resistant Enterobacteriaceae (CRE; 1.3% overall) phenotypes were markedly higher among isolates from patients with pneumonia compared to other infection types. Among P. aeruginosa, susceptibility rates for ceftazidime, piperacillin-tazobactam, and gentamicin were lowest among isolates from pneumonia, whereas susceptibility to meropenem was similar among isolates from BSI, pneumonia, and IAI (77.3–77.9%), and susceptibility to levofloxacin was markedly lower among UTI isolates (67.1%). The frequencies of P. aeruginosa isolates with MDR and XDR phenotypes were highest among isolates from patients with pneumonia.

Antimicrobial Activity of Ceftazidime-Avibactam Tested against Multidrug-Resistant Enterobacteriaceae and Pseudomonas aeruginosa Isolates from U.S. Medical Centers, 2013 to 2016.

The in vitro activity of ceftazidime-avibactam and many comparator agents was determined against various resistant subsets of organisms selected among 36,380 Enterobacteriaceae and 7,868 Pseudomonas aeruginosa isolates. The isolates were consecutively collected from 94 U.S. hospitals, and all isolates were tested for susceptibility by reference broth microdilution methods in a central monitoring laboratory (JMI Laboratories). Enterobacteriaceae isolates resistant to carbapenems (CRE) and/or ceftazidime-avibactam (MIC ≥ 16 μg/ml) were evaluated for the presence of genes encoding extended-spectrum β-lactamases and carbapenemases. Ceftazidime-avibactam inhibited >99.9% of all Enterobacteriaceae at the susceptible breakpoint of ≤8 μg/ml and was active against multidrug-resistant (MDR; n = 2,953; MIC50/90, 0.25/1 μg/ml; 99.2% susceptible), extensively drug-resistant (XDR; n = 448; MIC50/90, 0.5/2 μg/ml; 97.8% susceptible), and CRE (n = 513; MIC50/90, 0.5/2 μg/ml; 97.5% susceptible) isolates. Only 82.2% of MDR Enterobacteriaceae (n = 2,953) and 64.2% of ceftriaxone-nonsusceptible Klebsiella pneumoniae (n = 1,063) isolates were meropenem susceptible. Among Enterobacter cloacae (22.2% ceftazidime nonsusceptible), 99.8% of the isolates, including 99.3% of the ceftazidime-nonsusceptible isolates, were ceftazidime-avibactam susceptible. Only 23 of 36,380 Enterobacteriaceae (0.06%) isolates were ceftazidime-avibactam nonsusceptible, including 9 metallo-β-lactamase producers and 2 KPC-producing strains with porin alteration; the remaining 12 strains showed negative results for all β-lactamases tested. Ceftazidime-avibactam showed potent activity against P. aeruginosa (MIC50/90, 2/4 μg/ml; 97.1% susceptible), including MDR (MIC50/90, 4/16 μg/ml; 86.5% susceptible) isolates, and inhibited 71.8% of isolates nonsusceptible to meropenem, piperacillin-tazobactam, and ceftazidime (n = 628). In summary, ceftazidime-avibactam demonstrated potent activity against a large collection (n = 44,248) of contemporary Gram-negative bacilli isolated from U.S. patients, including organisms resistant to most currently available agents, such as CRE and meropenem-nonsusceptible P. aeruginosa.

Activity of Ceftolozane-Tazobactam and Comparators When Tested against Bacterial Surveillance Isolates Collected from Pediatric Patients in the US during 2012–2016 as Part of a Global Surveillance Program

BackgroundCeftolozane-tazobactam (C-T) is an antibacterial combination of a novel antipseudomonal cephalosporin and a β-lactamase inhibitor. C-T was approved by the US Food and Drug Administration in 2014 and by the European Medicine Agency in 2015 to treat complicated urinary tract infections, acute pyelonephritis, and complicated intra-abdominal infections in adults. The Program to Assess Ceftolozane-Tazobactam Susceptibility (PACTS) monitors C-T resistance to gram-negative (GN) isolates worldwide.MethodsA total of 4121 GN isolates were collected during 2012–2016 from pediatric patients (<18 years old) in 31 US hospitals and tested for C-T susceptibility (S) by CLSI broth microdilution method in a central monitoring laboratory (JMI Laboratories). Other antibiotics tested were amikacin (AMK), cefepime (FEP), ceftazidime (CAZ), colistin (COL), levofloxacin (LVX), meropenem (MER), and piperacillin-tazobactam (TZP). Antibiotic-resistant phenotypes identified using CLSI (2017) clinical breakpoints included: carbapenem-resistant Enterobacteriaceae (CRE), non-CRE extended-spectrum β-lactamase screen positive (ESBL, non-CRE), ceftazidime-nonsusceptible (CAZ-NS), and meropenem-NS (MER-NS). EUCAST (2017) COL clinical breakpoints were used for Enterobacteriaceae (ENT).ResultsThe most common infection type in hospitalized pediatric patients was pneumonia (n = 1,488) followed by urinary tract infection (n = 1,143) and bloodstream infection (n = 767). A total of 2,969 ENT and 1,152 non-enterics were isolated. The 5 most common species were Escherichia coli (EC: 1,311), Pseudomonas aeruginosa (PSA: 821 isolates), Klebsiella pneumoniae (KPN: 429), Enterobacter cloacae complex (ECC: 360), and Serratia marcescens (SM: 264). Susceptibilities of C-T and comparators for the main species and resistant phenotypes are shown in the Table. Only 7 isolates were CRE in this study.Conclusion C-T demonstrated good activity against pediatric ENT isolates (96.1%S), EC (99.2%S), and KPN (97.9%S). For ENT, all agents but COL had >90% S. For PSA, C-T demonstrated potent activity (99.5%S) and was the most potent antibiotic tested with activity similar to COL.Disclosures D. Shortridge, Merck: Research Contractor, Research grant; L. R. Duncan, Merck: Research Contractor, Research grant; M. A. Pfaller, Merck: Research Contractor, Research grant; R. K. Flamm, Merck: Research Contractor, Research grant

Antimicrobial Activity of Ceftazidime-Avibactam and Comparator Agents Tested against Enterobacteriaceae and Pseudomonas aeruginosa from United States (US) Medical Centers Stratified by Infection Type (2015–2016)

BackgroundWe evaluated and compared the in vitro activities of ceftazidime-avibactam (CAZ-AVI) and comparators against of Enterobacteriaceae (ENT) and P. aeruginosa (PSA) from various infection types.Methods23,440 isolates composed of 19,249 ENT and 4,191 PSA were consecutively collected from 85 US hospitals and tested for susceptibility (S) by broth microdilution methods in a central monitoring laboratory (JMI Laboratories). The antimicrobial S and frequency of key resistance (R) phenotypes, such as multidrug-R (MDR) and extensively drug-R (XDR) among others, were assessed and stratified by these infection types: bloodstream (BSI; 3,434 isolates; 14.7%), pneumonia (6,439; 27.5%), skin/skin structure (SSSI; 4,134; 17.6%), intra-abdominal (IAI; 951; 4.1%), urinary tract (UTI; 7,873; 33.6%), and others combined (609; 2.6%).ResultsCAZ-AVI was active against 99.9% to 100.0% of ENT and 97.0% (pneumonia) to 99.4% (UTI) of PSA isolates. S rates were consistently lower among ENT from pneumonia compared with other infection types for β-lactams such as CAZ (82.3% vs. 87.1–90.8%), piperacillin-tazobactam (P-T; 87.5% vs. 90.2–95.6%) and meropenem (MEM; 96.8% vs. 98.4–99.4%). S to gentamicin (GEN) was also generally lower among isolates from pneumonia, whereas S to levofloxacin (LEV) and colistin (COL) were lowest among BSI and SSSI isolates, respectively. The occurrence of MDR, XDR, and carbapenem-resistant ENT (CRE) phenotypes were markedly higher among isolates from patients with pneumonia compared with other infection types (Table). Among PSA, S rates for CAZ, P-T, and GEN were lowest among isolates from pneumonia, whereas S to MEM was similar among isolates from BSI, pneumonia, and IAI (77.3–77.9%), and S to LEV was markedly lower among UTI isolates (67.1%). The frequency of PSA isolates with MDR and XDR phenotypes, as well as non-S to CAZ, MER, and P-T, were also highest among isolates from patients with pneumonia (Table).ConclusionAntimicrobial S rates were generally lower among ENT and PSA isolates from patients with pneumonia compared with other infections. CAZ-AVI was highly active against a large collection of contemporary ENT and PSA isolates from US hospitals (2015–2016), including MDR and XDR organisms, regardless of the infection type.Disclosures H. S. Sader, Allergan: Research Contractor, Research grant; M. Castanheira, Allergan: Research Contractor, Research grant; L. R. Duncan, Allergan: Research Contractor, Research grant; R. K. Flamm, Allergan: Research Contractor, Research grant

In Vitro Evaluation of Delafloxacin Activity when Tested Against Contemporary community-Acquired Bacterial Respiratory Tract Infection Isolates (2014–2016): Results from the Sentry Antimicrobial Surveillance Program

BackgroundDelafloxacin (DLX) is a broad-spectrum fluoroquinolone (FQ) antibacterial that has completed clinical development (oral and intravenous formulations) with the new drug application currently under the Food and Drug Administration review for the treatment of acute bacterial skin and skin structure infections (ABSSSI). DLX is also in clinical trials for community-acquired bacterial pneumonia. In this study, in vitro susceptibility results for DLX and comparator agents were determined for clinical isolates from community-acquired respiratory tract infections (CA-RTI) collected in medical centers in the United States and Europe participating in the SENTRY surveillance program during 2014–2016.MethodsA total of 3,093 isolates that included 1,673 Streptococcus pneumoniae (SPN), 805 Haemophilus influenzae (HI) and 555 Moraxella catarrhalis (MC) were collected during 2014–2016 and included only 1 isolate/patient/infection episode. Isolate identifications were confirmed at JMI Laboratories. Susceptibility testing was performed according to CLSI reference broth microdilution methodology, and results were interpreted per CLSI (2017) breakpoints. Other antibacterials tested included levofloxacin (LVX) and penicillin. Β-lactamase production for HI and MC was determined by the nitrocephin disk test.ResultsDLX demonstrated potent in vitro activity against SPN (MIC50/90 0.015/0.03 mg/L). Activity remained the same for penicillin-intermediate or -resistant isolates. For 23 LVX nonsusceptible SPN, the DLX MIC50/90 were 0.12/0.25 mg/L with all isolates having DLX MIC values ≤1 mg/L. For HI, the DLX MIC50/90 were ≤0.001/0.004 mg/L, and for MC the MIC50/90 were 0.008/0.008 mg/L. DLX activity was unaffected by the presence of β-lactamase for either HI or MC. Activity of DLX was similar for US and European isolates.ConclusionDelafloxacin demonstrated potent in vitro antibacterial activity against CA-RTI pathogens, including SPN, HI, and MC. These data support the continued study of DLX as a potential treatment for community-acquired pneumonia.Disclosures D. Shortridge, Melinta Therapeutics: Research Contractor, Research grant; J. M. Streit, Melinta Therapeutics: Research Contractor, Research grant; M. D. Huband, Melinta Therapeutics: Research Contractor, Research grant; P. R. Rhomberg, Melinta Therapeutics: Research Contractor, Research grant; R. K. Flamm, Melinta Therapeutics: Research Contractor, Research grant

Antimicrobial Activity of Ceftazidime-Avibactam Tested against Multidrug-Resistant Enterobacteriaceae and Pseudomonas aeruginosa Isolates from United States (US) Medical Centers (2013–2016)

BackgroundThe in vitro activity of ceftazidime-avibactam (CAZ-AVI) and many comparator agents were tested against various resistant subsets of organisms selected among 36,380 Enterobacteriaceae and 7,868 P. aeruginosa isolates.MethodsIsolates were consecutively collected from 94 US hospitals in 2013–2016 and tested for susceptibility by reference broth microdilution methods in a central monitoring laboratory (JMI Laboratories) as part of the International Network for Optimal Resistance Monitoring (INFORM) program. Enterobacteriaceae strains with elevated CAZ-AVI MIC values (≥16 μg/mL) were evaluated for the presence of genes encoding extended-spectrum β-lactamases, KPC, NDM, and transferable AmpC enzymes.ResultsCAZ-AVI inhibited >99.9% of all Enterobacteriaceae at the susceptible (S) breakpoint of ≤8 μg/mL and was active against multidrug-resistant (MDR; n = 2,953; MIC50/90, 0.25/1 μg/mL; 99.2%S, extensively drug-resistant (XDR; n = 448; MIC50/90, 0.5/2 μg/mL; 97.8%S), and carbapenem-resistant isolates (CRE; n = 513; MIC50/90, 0.5/2 μg/mL; 97.5%S). Only 82.2% of MDR Enterobacteriaceae and 64.2% of ceftriaxone-nonsusceptible (NS) Klebsiella pneumoniae (n = 1,063) were meropenem-S. Among Enterobacter cloacae (n = 3,740; 22.2% ceftazidime-NS), 99.8% of isolates, including 99.3% of ceftazidime-NS isolates, were CAZ-AVI-S. Only 22 of 36,380 Enterobacteriaceae (0.06%) isolates were CAZ-AVI-NS, including 8 MBL-producers (0.02%) and 2 KPC-producing strains with porin alteration; the remaining 12 strains showed negative results for all β-lactamases tested. CAZ-AVI showed potent activity against P. aeruginosa (n = 7,868; MIC50/90, 2/4 μg/mL; 97.1% S), including meropenem-NS (n = 1,471; MIC50/90, 4/16 μg/mL; 87.2%S) and MDR (n = 1,562; MIC50/90, 4/16 μg/mL; 86.5%S) isolates, and inhibited 71.8% of isolates NS to meropenem, piperacillin-tazobactam, and ceftazidime (n = 628).ConclusionCAZ-AVI demonstrated potent activity against a large US collection (n = 44,248) of contemporary gram-negative bacilli, including organisms resistant to most currently available agents, such as CRE and meropenem-NS P. aeruginosa.Disclosures H. S. Sader, Allergan: Research Contractor, Research grant; M. Castanheira, Allergan: Research Contractor, Research grant; D. Shortridge, Allergan: Research Contractor, Research grant; R. E. Mendes, Allergan: Research Contractor, Research grant; R. K. Flamm, Allergan: Research Contractor, Research grant

Antimicrobial Activity of Aztreonam-Avibactam and Comparator Agents Tested against Contemporary (2016) Clinical Enterobacteriaceae Isolates

BackgroundAvibactam (AVI) is a non-β-lactam β-lactamase (BL) inhibitor that inhibits Ambler class A, C, and some class D enzymes (eg, ESBL, KPC, and AmpC), and aztreonam (ATM) is a monobactam stable to hydrolysis by metallo-β-lactamases (MBL).MethodsA total of 10,451 Enterobacteriaceae(ENT) consecutively collected from 84 United States (US) medical centers and 250 carbapenem-resistant ENT (CRE) collected from 38 centers in 25 other countries (ex-US) were tested for susceptibility (S) by reference broth microdilution methods in a central monitoring laboratory (JMI Laboratories). CRE strains were screened for the presence of carbapenemase (CBP)-encoding genes using whole genome sequencing analysis.ResultsAll ENT isolates from US (MIC50/90, ≤0.03/0.12 μg/mL), except for 1 Escherichia coli strain with an ATM-AVI MIC of 8 μg/mL, and all ex-US CRE isolates (MIC50/90, 0.25/0.5 μg/mL) were inhibited at ATM-AVI MIC of ≤4 µg/mL (CLSI S breakpoint for ATM). Among US isolates, ATM-AVI was also very active against CRE (n = 120; MIC50/90, 0.12/0.5 μg/mL; highest MIC, 4 μg/mL), multidrug-resistant (MDR; n = 876; MIC50/90, 0.06/0.25 μg/mL), extensively drug-resistant (XDR; n = 111; MIC50/90, 0.12/0.5 μg/mL), pan-drug resistant (n = 2; MICs ≤0.03 and 0.12 μg/mL), and ceftazidime-non-S Enterobacter cloacae (MIC50/90, 0.25/1 μg/mL) isolates. Meropenem was very active against US ENT overall (MIC50/90, 0.03/0.06 μg/mL; 98.8%S per CLSI), but showed limited activity against MDR (86.2%S) and XDR (30.6%S) isolates. Amikacin and colistin were active against 74.2% and 81.7% of US CRE, 93.4% and 58.3% US MDR, 65.8% and 57.7% of US XDR, and 58.0% and 79.2% of ex-US CRE isolates, respectively. A total of 106 CBPs were detected in 106 US CRE isolates, including 102 KPC-like, 2 SME-4, 1 NDM-1, and 1 IMP-27. Also, 248 CBPs were identified on 241 ex-US CRE isolates, including 124 KPC-like, 64 OXA-like, 50 NDM-like, 7 VIM-1, 2 IMP-4, and 1 SME-4. All CRE isolates, including all CBP-producing ENT (US and ex-US), were inhibited at ATM-AVI MIC of ≤4 μg/mL.ConclusionATM-AVI demonstrated potent in vitro activity against a large collection of contemporary (2016) ENT isolated from patients in US hospitals and CRE isolates collected worldwide, including NDM, KPC, OXA, VIM, and SME producers.Disclosures H. S. Sader, Allergan: Research Contractor, Research grant; R. E. Mendes, Allergan: Research Contractor, Research grant; D. Shortridge, Allergan: Research Contractor, Research grant; R. K. Flamm, Allergan: Research Contractor, Research grant; M. Castanheira, Allergan: Research Contractor, Research grant

Evaluation of the Rapid Polymyxin NP Test for Polymyxin B Resistance Detection Using Enterobacter cloacae and Enterobacter aerogenes Isolates.

Polymyxin resistance is an increasing problem worldwide. Currently, determining susceptibility to polymyxins is problematic and lengthy. Polymyxins diffuse poorly into agar, potentially giving inaccurate disk diffusion and Etest results. A rapid screening test (2 h) for the detection of polymyxin resistance in Enterobacteriaceae, developed by P. Nordmann and L. Poirel (rapid polymyxin NP test) in 2016, detects glucose metabolization in the presence of polymyxin E (PE) and PB via pH-induced color change. The sensitivity and specificity were 99.3 and 95.4%, respectively, with results obtained in ≤2 h. Our goal was to evaluate this test using PB against larger numbers of Enterobacter A total of 143 nonduplicate Enterobacter isolates (102 E. cloacae complex, 41 E. aerogenes) were tested, including 136 collected from Ochsner Health System patients from March to May 2016 and 7 previously determined PB-resistant E. cloacae isolates from JMI Laboratories. MICs were determined via broth microdilution. For the rapid polymyxin NP test, a color change from orange to yellow is positive; a weak/no color change is deemed negative after 4 h. Of 143 Enterobacter isolates, 25 were determined to be PB resistant by broth microdilution (MIC > 2 μg/ml), including all 7 JMI isolates. Of these 25, 7 were positive by the rapid polymyxin NP test (included 3/7 JMI isolates). All 118 isolates determined to be PB susceptible by broth microdilution were NP test negative. The sensitivity and specificity for the rapid polymyxin NP test were 25 and 100%, respectively, compared to broth microdilution. Although the rapid polymyxin NP test is a much faster method (2 to 4 h) for polymyxin resistance determination compared to broth microdilution (16 to 20 h), our study indicates that it may be subject to limitations when testing Enterobacter.

Activity of oritavancin tested against uncommonly isolated Gram-positive pathogens responsible for documented infections in hospitals worldwide

To assess the oritavancin spectrum and activity against 2811 rarer species of coagulase-negative staphylococci (CoNS), streptococci and other Gram-positive species. A total of 2057 CoNS (14 species), 674 streptococci (7 groups) and 80 other Gram-positive species (3 genera) collected over a 5 year period as part of the SENTRY Program (2008-12) were included. Isolates were primarily identified by the participating laboratory and identification was confirmed by the reference monitoring laboratory (JMI Laboratories, North Liberty, IA, USA). Isolates were tested for susceptibility by broth microdilution following the CLSI M07-A9 and M100-S23 documents. Overall, oritavancin was active against all CoNS (MIC50/MIC90, 0.015/0.06 mg/L), with MIC50 values of ≤0.008-0.03 mg/L. Streptococci exhibited oritavancin MIC50 results of ≤0.008 mg/L, except for the Streptococcus bovis (0.03 mg/L), Streptococcus dysgalactiae (0.06 mg/L) and Streptococcus salivarius/vestibularis (0.06 mg/L) groups. Micrococcus spp., Listeria monocytogenes and Corynebacterium spp. had oritavancin MIC50 results of ≤0.008 mg/L. This study expands the oritavancin in vitro data against several species of Gram-positive organisms.