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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 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)

Surgical site infections (SSI) are the most common complications of breast cancer surgery. The authors identified 35 cases of SSI in the M.D. Anderson Cancer Center (Houston, TX) over a 7-month study period. Monomicrobial infections predominated (69%) with Staphylococcus aureus being isolated most often. A wide variety of gram-positive and gram-negative organisms were isolated from the 31% of polymicrobial infections, suggesting the need for broad-spectrum coverage at least until culture results become available. Although all S aureus isolates were susceptible to vancomycin (minimal inhibitory concentration [MIC] ≤ 2.0 µg/mL), 63% of methicillin-susceptible isolates and 82% of methicillin-resistant isolates had MIC values of ≥ 1.0 µg/mL for this agent, indicating the need for alternative therapeutic agents. The organisms were susceptible to trimethoprim/sulfamethoxazole, rifampin, linezolid, daptomycin, and tigecycline.

BACKGROUND Stenotrophomonas maltophilia bacteremia is frequently found in cancer patients. This study attempted to determine how often the catheters were the source of this infection and the risk factors associated with catheter-related bacteremias. METHODS The microbiology records were retrospectively reviewed of all cancer patients having S. maltophilia bacteremia and indwelling central venous catheters seen between January 1998 and January 2004. In a multivariate analysis the patients' clinical characteristics, antimicrobial therapy, outcome, and source of bacteremia that were significantly associated with definite catheter-related S. maltophilia bacteremia as opposed to secondary bacteremia were identified. RESULTS A total of 217 bacteremias were identified in 207 patients: 159 (73%) were primary catheter-related (53 definite, 89 probable, and 17 possible), 11 (5%) were primary noncatheter-related, and 47 (22%) were secondary. Multivariate analysis showed the following factors to be independently associated with definite catheter-related bacteremias: 1) polymicrobial bacteremia (odds ratio [OR], 7.6; 95% confidence interval [95% CI], 1.3–45.5); 2) no prior intensive care unit admission (OR, 0.06; 95% CI, 0.005–0.578); and 3) nonneutropenic status at onset (OR, 0.07; 95% CI, 0.013–0.419). The response rate to appropriate antibiotics and catheter removal was 95% in the patients with definite catheter-related bloodstream infections, compared with only 56% in the patients with secondary bacteremias (P = .001). CONCLUSIONS The majority of the S. maltophilia bacteremias occurring in cancer patients with indwelling central venous catheters appear to be catheter-related and are often polymicrobial. Catheter-related S. maltophilia bacteremias occurred more frequently in noncritically ill, nonneutropenic patients, and prompt removal of the catheter was found to be associated with a better prognosis. Cancer 2006. © 2006 American Cancer Society.

Influenza is one of the most important respiratory diseases of mankind, yet scant data exist concerning the frequency and clinical course of influenza in severely immunocompromised adults. From October 1993 to September 1994, we cultured the respiratory secretions of all adults with leukemia who were hospitalized with an acute respiratory illness at The University of Texas M.D. Anderson Cancer Center in Houston. During a 9-week period from 29 November 1993 to 29 January 1994, influenza virus type A (H3N2) was isolated from 15 (33%) of these 45 hospitalized adults. Twelve (80%) of the cases of influenza were associated with pneumonia, and four patients (33%) with pneumonia died. Patients who died tended to have received chemotherapy more recently and to be more myelosuppressed. Autopsy examination in two cases revealed histopathologic changes consistent with viral pneumonia. During community outbreaks, influenza is a frequent cause of serious respiratory disease in hospitalized adults with leukemia. Effective prophylactic and therapeutic regimens need to be defined for immunocompromised patients.