In Vitro Activity of Ceftazidime-Avibactam (CAZ-AVI) Against 511 Gram-Negative Clinical Isolates Obtained From Cancer Patients

Abstract 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

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

Open Forum Infectious Diseases ◽

10.1093/ofid/ofy210.1206 ◽

2018 ◽

Vol 5 (suppl_1) ◽

pp. S421-S422 ◽

Cited By ~ 2

Author(s):

Kenneth V I Rolston ◽

Bahgat Gerges ◽

Issam Raad ◽

Samuel L Aitken ◽

Ruth Reitzel ◽

...

Keyword(s):

Cancer Patients ◽

Active Agent ◽

Vitro Activity ◽

Significant Activity ◽

In Vitro Activity ◽

Research Support ◽

Gram Negative ◽

E Coli ◽

Research Grant

Abstract Background Gram-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. Methods A 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). Results CFDC 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. Conclusion Although 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.

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