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Aims: We evaluated a novel disinfectant (VR) and seven comparators (disinfectants A–G) against resistant pathogens common in healthcare settings. Methods and Results: VR at different dilutions, along with commercial disinfectants A–G, was tested against surrogate viruses, and resistant bacterial and fungal pathogens. Surrogate viruses had an initial concentration of ~1 × 108 mL−1, and bacterial and fungal isolates had an initial concentration of ~1 × 106 mL−1 on Siliconee surfaces. After the application of VR or a comparator disinfectant, surfaces were tested for the reduction in microbial loads after 30 s and 5 min wet exposures, and after a 24 h dry residue exposure. Sterile deionized water was used as a control. The VR at a concentration of 4.68% was superior to all comparator disinfectants against most pathogens in wet and dry testing. The VR at 7.8% concentration showed the highest pathogen-reduction rate among all comparator disinfectants when tested against all pathogens. Conclusions: Overall, the novel VR disinfectant was the most effective disinfectant in both wet and dry residue states against the range of tested pathogens. Significance and Impact of the Study: VR is a broadly effective disinfectant combination for use in high-risk settings, particularly those in which intervals between applications of disinfectant can be lengthy or inconsistent.

BackgroundBacterial infections are common in patients with cancer, and many bacteria have developed resistance to currently used antibiotics.ObjectivesWe evaluated the in vitro activity of eravacycline (a recently developed fluorocycline) and comparators against bacterial pathogens isolated from patients with cancer.MethodsAntimicrobial susceptibility testing was performed using CLSI-approved methodology and interpretive criteria for 255 Gram-positive and 310 Gram-negative bacteria. MIC and susceptibility percentage were calculated according to CLSI and FDA breakpoints when available.ResultsEravacycline had potent activity against most Gram-positive bacteria, including MRSA. Of 80 Gram-positive isolates with available breakpoints, 74 (92.5%) were susceptible to eravacycline. Eravacycline had potent activity against most Enterobacterales, including ESBL-producing organisms. Of 230 Gram-negative isolates with available breakpoints, 201 (87.4%) were susceptible to eravacycline. Eravacycline had the best activity among comparators against carbapenem-resistant Enterobacterales, with 83% susceptibility. Eravacycline was also active against many non-fermenting Gram-negative bacteria, with the lowest MIC90 value among comparators.ConclusionsEravacycline was active against many clinically significant bacteria isolated from patients with cancer, including MRSA, carbapenem-resistant Enterobacterales, and non-fermenting Gram-negative bacilli. Eravacycline might play an important role in the treatment of bacterial infections in patients with cancer, and additional clinical evaluation is warranted.

BackgroundFluoroquinolones are used for infection prevention in high-risk patients with haematological malignancies. Fluoroquinolones are active against many Gram-negative bacilli (GNB) but are less active against Gram-positive organisms. We evaluated the in vitro activity of delafloxacin and selected comparators against 560 bacterial pathogens isolated exclusively from patients with cancer.MethodsAntimicrobial susceptibility testing and time-kill studies were performed using CLSI-approved methodology and interpretive criteria for 350 Gram-positive organisms and 210 GNB that had been recently isolated from patients with cancer.ResultsDelafloxacin was more active than ciprofloxacin and levofloxacin against Staphylococcus aureus and CoNS. Overall, 63% of staphylococcal isolates were susceptible to delafloxacin, 37% to ciprofloxacin and 39% to levofloxacin. Activity of delafloxacin against most Enterobacterales was similar to that of ciprofloxacin and levofloxacin. Escherichia coli and MDR Pseudomonas aeruginosa isolates had low susceptibility rates to the three tested fluoroquinolones. In time-kill studies delafloxacin and levofloxacin decreased the bacterial load to 3.0 log10 in 8 and 13 h, respectively, using 8 × MIC.ConclusionsDelafloxacin is more active than ciprofloxacin and levofloxacin against S. aureus but has substantial gaps in coverage against GNB. Resistance to all three fluoroquinolones could be high among leading GNB such as E. coli and P. aeruginosa, particularly in cancer centres where these agents are widely used as prophylactic agents.

Background Contamination of surfaces with virions remains an important medical issues because they can serve as fomites for viral transmission. Long acting disinfectants are important because viruses can remain viable for extended durations. Here we assessed the anti-viral efficacy of various environmental spray disinfectants against F specific coliphage MS2, and Feline Calicivirus (FCV) as surrogate non-enveloped viruses. Methods MS2 was grown and titrated according to Environmental Protection Agency method 1601 and counted as plague forming unit per milliliter (PFU/mL.). Strain F9 of FCV was propagated and titrated in monolayers of Crandell-Reese Feline Kidney cells. Commercially available and an experimental disinfectant based on a biguanide combination were tested. The disinfectants, both wet and as dried residues, were compared on silicone surfaces for reduction of viral loads following 1-minute exposure to high viral load challenges (106-107 PFU/ml). Sterilized deionized water was used as a control. Results Results (as log10 reduction relative to sterilized deionized water control) are tabulated below for the disinfectants in wet and dry states following 1-minute viral challenges. Log10 reductions of MS2 and FCV viral loads following 1-minute exposures to disinfectants in wet and dry residue states. Conclusion The disinfectants were generally much less effective as dried residues than wet. The biguanide-combination and hydrogen peroxide-combination disinfectants were the most effective disinfectants tested in both wet and dry residue states. Both warrant further study for extended eradication of highly infectious viruses on surfaces. Disclosures All Authors: No reported disclosures

Background Bacterial infections are common in patients with cancer (PWC). Many bacteria have developed resistance to currently used antibiotics, posing therapeutic challenges. we evaluated the in vitro activity of eravacycline (a novel fluorocycline) against clinical bacteria recently (2018-2019) isolated from PWC. Methods All 565 isolates tested were from blood cultures. CLSI approved broth microdilution method was used. Appropriate ATCC controls were included. MIC50, MIC90, MIC ranges and percent susceptibility calculations were made using FDA breakpoints when available. Eravacycline susceptibility breakpoint for most Gram-positive organisms (GPO) is ≤ 0.06 mg/L and for Enterobacterales is ≤ 0.5 mg/L. Results Eravacycline had potent activity against Staphylococcus aureus (methicillin-susceptible and resistant strains), oxacillin-susceptible coagulase-negative staphylococci (CoNS) including Staphylococcus lugdunensis, viridans group streptococci, beta-hemolytic streptococci. Streptococcus pneumoniae. Bacillus spp., Corynebacterium spp., and Micrococcus spp. It was slightly less active against oxacillin-resistant CoNS, and vancomycin-susceptible Enterococcus faecalis (MIC90 0,125 mg/L respectively) and was moderately active against vancomycin-resistant Enterococcus faecium (MIC50, 0.06, and MIC90. 0.25 mg/L). Eravacycline had potent activity against Escherichia coli (including ESBL producing strains), Citrobacter spp., and non-ESBL Klebsiella spp. Eravacycline inhibited 83% of ESBL positive K. pneumoniae, 83% of Enterobacter cloacae, and 80% of carbapenem-resistant Enterobacteriaceae (CRE) isolates at ≤ 0.5 mg/L. The presence of ESBLs increased MIC90 value no more than 2 fold. Eravacycline was also active against many non-fermentative GNB (Achromobacter spp., Acinetobacter spp., Sphingomonas paucimobilis, and Stenotrophomonas maltophilia). Table 1. Percent Susceptibility of Gram-negative isolates to Eravacycline Table 2. Percent Susceptibility of Gram-positive isolates to Eravacycline Conclusion Our data demonstrate that eravacycline has promising activity against clinically significant bacterial pathogens isolated from PWC including many drug resistant strains such as CRE and non--fermentative GNB. it might play an important role in the treatment of bacterial infections in PWC and warrants clinical evolution in this setting. Disclosures Samuel L. Aitken, PharmD, MPH, BCIDP, Melinta Therapeutoics (Individual(s) Involved: Self): Consultant, Grant/Research Support Kenneth Rolston, MD, Tetraphase Pharmaceuticals (Grant/Research Support)

Background Fluoroquinolones have been used for infection prevention in patients with cancer (PWC). They are active against many Gram-negative bacilli (GNB) but are less active against Gram-positive organisms (GPO). Quinolone resistance is increasing and many institutions are using combination regimens for antimicrobial prophylaxis. We evaluated the in vitro activity of delafloxacin (DLX), a novel fluoroquinolone, and selected comparators against 560 bacterial isolates from PWC. Methods Isolates were from recent blood cultures. Susceptibility testing and time kill studies (TKS) were performed using CLSI approved methodology. Appropriate ATCC control strains were used. We calculated MIC50, MIC90, MIC ranges and percent susceptibility using FDA breakpoints when available. TKS were performed on 4 streptococcus mitis isolates at concentrations of MIC, 4x MIC, and 8x MIC. Results DLX was more active than ciprofloxacin (CIP) and levofloxacin (LEV) against methicillin-susceptible (MSSA), and resistant (MRSA) S. aureus, coagulase-negative staphylococci (CoNS), and viridans group streptococci (VGS), and had similar activity against beta-hemolytic streptococci. It also had low MICs for Bacillus species (SPP.), Listeria monocytogenes, Micrococcus spp., and Rothia spp. Overall GPO susceptibility was 73% to DLX, 42% to CIP, and 52% to LEV. The activity of DLX against Enterobacterales was similar to CIP and LEV. All 3 agents had moderate activity against Citrobacter spp., and non-MDR P. aeruginosa. Notably, all 3 quinolones had poor activity against E. coli, P. mirabilis, and MDR P. aeruginosa, all common pathogens in PWC. All 3 had low MICs for Acinetobacter spp. DLX and LEV achieved peak bactericidal activity at 6-8 h against all 4 VGS isolates (maximum activity at 8x MIC) but this was not always sustained at 24 h. Table 1. Percent Susceptibility of selected Gram-positive isolates to Delafloxacin, Ciprofloxacin and Levofloxacin Table 2. Percent Susceptibility of selected Gram-negative isolates to Delafloxacin, Ciprofloxacin and Levofloxacin Figure 1. Bactericidal Activity of DLX at 1x , 4x, and 8x MIC against VGS - Time Kill Study Conclusion DLX is more active than CIP and LEV against many GPO from PWC (including S. aureus and VGS), but like these agents there are significant gaps in its coverage against GNB. It is probably not suitable as a single agent for antimicrobial prophylaxis in high-risk PWC. The current practice of combining a quinolone with a beta-lactam probably still represents the best option in PWC who need prophylaxis. Disclosures Kenneth Rolston, MD, Tetraphase Pharmaceuticals (Grant/Research Support)

Background Gram negative (GN) bacterial infections are on the rise in patients with cancer and frequently require extended hospital stays that may lead to a major increase in healthcare cost. This study aimed to evaluate the in vitro activity of a novel oral carbapenem, tebipenem against recent gram-negative clinical isolates from our cancer patients. Methods All 173 clinical isolates from our cancer patients including 36 Extended Spectrum Beta-Lactamase (ESBL) isolates from blood cultures were tested against tebipenem and other comparators. Clinical and Laboratory Standards Institute (CLSI) approved broth microdilution method was used. Appropriate ATCC controls were included. MIC50, MIC90, MIC ranges and percent of susceptibility calculations ware made using FDA breakpoints when available. The tebipenem provisional susceptibility breakpoint for most GN organism is ≤ 0.125 mg/L. Results Tebipenem and comparators antibiotics susceptibility percent (S: %), and MIC90 are shown in the table below. Tebipenem demonstrated highly potent activity against Escherichia coli, Klebsiella pneumoniae (including ESBL producing strains), Enterobacter cloacae and inhibited 90% of the Enterobacter aerogenes strains screened. MIC90s ranged from 0.06-0.25 mg/L for all tested Enterobacteriaceae. At a provisional breakpoints of 0.125 mg/L, the susceptibilities, MICs and ranges were comparable to meropenem, and ertapenem. Comparative study between Tebipenem and comparators for MIC90 (mg/L.) and Susceptibility (%) results against Gram-Negative Bacteria Isolated from Patients with Cancer Conclusion Our data demonstrate that oral tebipenem has promising activity against clinically significant bacterial pathogens isolated from cancer patients, and it has similar activity to that of other tested carbapenem. Further clinical evaluation for oral carbapenem treatment of bacterial infections is warranted. Disclosures All Authors: No reported disclosures

Background Central Line Associated Bloodstream Infections (CLABSIs) remain a significant medical problem for critically ill cancer patients who required catheters for extended durations. Minocycline (M) -Rifampin (R) loaded catheters have shown the greatest impact on reducing CLABSIs; however, there is a risk for developing antibiotic resistant organisms when exposed to catheters whose concentration becomes depleted below antimicrobially effective levels due to extended indwells. Chlorhexidine (CH) and M-R combination catheters (MRCH) have been proposed as a next generation catheter with improved performance. Here we studied whether bacteria that were Tetracycline and Rifampin resistant became resistant to MRCH when allowed to form biofilms on MRCH catheters depleted below antimicrobially effective MRCH concentrations. Methods Minimum inhibitory concentrations (MICs) of Tetracycline and/or Rifampin resistant stock isolates were measured by standard microbroth dilution methods. MRCH catheters were depleted to below antimicrobially effective concentrations by soaking in serum for 6 weeks. The resistant bacteria were then allowed to form biofilm for 24 hrs on the depleted catheters in broth. Following 24 hour incubation the adherent (breakthrough) bacteria were removed by sonication and MICs were remeasured. The same organisms grown on non-antimicrobial catheters were used as controls. Results MICs (ug/mL) of the organisms against each agent and the combination are tabulated below: MICs (ug/mL) of the organisms against each agent and the combination Conclusion The M and R resistant bacteria did not develop in vitro resistance to the MRCH combination after forming biofilms on MRCH catheters depleted below antimicrobially effective concentrations. Disclosures Joel Rosenblatt, PhD, Cook Medical (Shareholder, Other Financial or Material Support, Inventor of the MRCH catheter technology which is owned by the University of Texas MD Anderson Cancer Center and has been licensed to Cook Medical)Novel Anti-Infective Technologies (Shareholder, Other Financial or Material Support, Inventor of the MRCH catheter technology which is owned by the University of Texas MD Anderson Cancer Center and has been licensed to Cook Medical) Issam I. Raad, MD, Citius (Other Financial or Material Support, Ownership interest)Cook Medical (Grant/Research Support)Inventive Protocol (Other Financial or Material Support, Ownership interest)Novel Anti-Infective Technologies (Shareholder, Other Financial or Material Support, Ownership interest)