1278. Testing the Synergistic Effect of Ceftazidime-Avibactam Plus Aztreonam on Metallobetalactamase-Producing Non-Fermenting Gram-negative Bacteria

Abstract Background Metallo-betalactamases (MBL) are rapidly becoming a more widespread form of antimicrobial resistance. MBL are class B betalactamases that use zinc rather than serine in their active site and are only inactivated by monobactams, such as aztreonam. Unfortunately, most MBL-producing organisms also produce aztreonam-inactivating beta-lactamases. Synergy between ceftazidime-avibactam and aztreonam is well documented for MBL-producing Enterobacteriaceae but has not been tested extensively in non-fermenting Gram-negative bacteria. This study evaluates the susceptibilities of non-fermenting Gram-negative bacteria via E-test to this combination in vitro, in order to provide support for use to treat infections from these organisms. Methods The antibiotic combination ceftazidime-avibactam+aztreonam was tested against a total of 33 isolates, including MBL-producing Pseudomonas aeruginosa, Pseudomonas putida, and the intrinsically aztreonam resistant Acinetobacter baumanii using the E-test method. MBL-producing Enterobacteriaceae were included as positive controls. All isolates were also tested against ceftazidime alone, aztreonam alone, and ceftazidime-avibactam. Bacterial isolates were procured from the Multidrug-resistant organism Repository & Surveillance Network at the Walter Reed Army Institute of Research. Antimicrobial resistance genes were previously identified by whole genome sequencing Results Of 13 Pseudomonas spp. isolates tested, 9 were resistant, 3 were intermediate, and 1 was susceptible to aztreonam. Synergistic testing of ceftazidime-avibactam+aztreonam reduced the MIC of 4 Pseudomonas isolates by 1-2 doubling dilutions. While Acinetobacter spp. are usually considered intrinsically resistant to aztreonam, synergistic testing of ceftazidime-avibactam+aztreonam reduced the MIC of all 12 isolates tested by 1 to 3 doubling dilutions. Conclusion The ability of ceftazidime-avibactam+aztreonam to reduce the MICs of Acinetobacter baumanii and MBL-producing Pseudomonas aeruginosa is a potentially promising therapeutic option when faced with growing antimicrobial resistance. Disclosures All Authors: No reported disclosures

Background. Characterization of antimicrobial-resistant organism (ARO) colonization is critical to understand transmission dynamics and infection risk, however data in resource-limited settings are scare. We estimated the prevalence of Enterobacterales colonization with extended-spectrum cephalosporin-resistance (ESCrE), carbapenem-resistance (CRE) and methicillin-resistant Staphylococcus aureus (MRSA) among community residents and hospitalized patients in rural (Siaya County) and urban (Kibera) Kenya.
Methods. Community-dwelling adults and children were enrolled via cluster randomized sampling. Inpatients of all ages were enrolled by simple random sampling. Stool/ rectal and nasal swabs were collected and screened for ESCrE, CRE and MRSA, respectively, using HardyChrom™ media. Vitek2 ® was used for isolate confirmation and antibiotic susceptibility testing. Fisher's exact tests were used to compare prevalence of AROs.
Conclusion. Colonization with AROs were widespread in households and hospitals in urban and rural areas. Hospitals with elevated prevalence of highly transmissible AROs should consider whether implementation of colonization screening can be incorporated as part of their infection prevention and control programs. Risk factors for ARO colonization should be elucidated to identify novel prevention strategies.
Disclosures. Background. Metallo-betalactamases (MBL) are rapidly becoming a more widespread form of antimicrobial resistance. MBL are class B betalactamases that use zinc rather than serine in their active site and are only inactivated by monobactams, such as aztreonam. Unfortunately, most MBL-producing organisms also produce aztreonam-inactivating beta-lactamases. Synergy between ceftazidime-avibactam and aztreonam is well documented for MBL-producing Enterobacteriaceae but has not been tested extensively in non-fermenting Gram-negative bacteria. This study evaluates the susceptibilities of non-fermenting Gram-negative bacteria via E-test to this combination in vitro, in order to provide support for use to treat infections from these organisms.
Methods. The antibiotic combination ceftazidime-avibactam+aztreonam was tested against a total of 33 isolates, including MBL-producing Pseudomonas aeruginosa, Pseudomonas putida, and the intrinsically aztreonam resistant Acinetobacter baumanii using the E-test method. MBL-producing Enterobacteriaceae were included as positive controls. All isolates were also tested against ceftazidime alone, aztreonam alone, and ceftazidime-avibactam. Bacterial isolates were procured from the Multidrug-resistant organism Repository & Surveillance Network at the Walter Reed Army Institute of Research. Antimicrobial resistance genes were previously identified by whole genome sequencing Results. Of 13 Pseudomonas spp. isolates tested, 9 were resistant, 3 were intermediate, and 1 was susceptible to aztreonam. Synergistic testing of ceftazidime-avibac-tam+aztreonam reduced the MIC of 4 Pseudomonas isolates by 1-2 doubling dilutions. While Acinetobacter spp. are usually considered intrinsically resistant to aztreonam, synergistic testing of ceftazidime-avibactam+aztreonam reduced the MIC of all 12 isolates tested by 1 to 3 doubling dilutions.
Conclusion. The ability of ceftazidime-avibactam+aztreonam to reduce the MICs of Acinetobacter baumanii and MBL-producing Pseudomonas aeruginosa is a potentially promising therapeutic option when faced with growing antimicrobial resistance.
Disclosures. All Authors: No reported disclosures Methods. CRKP clinical cultures were collected from 21 Kindred Healthcare LTACHs in 4 US states (California, Texas, Florida, Kentucky) from 8/1/14-7/25/15. Cultures collected within 30 days of a prior CRKP culture from the same patient were excluded. Colistin resistance (minimum inhibitory concentration ≥4) was determined using a custom Sensititre TM broth microdilution assay (ThermoFisher Scientific, Waltham, MA). Multivariate logistic regression was performed to evaluate candidate risk factors of age, sex, cirrhosis, chronic kidney disease, culture source, length of stay, indwelling line or tracheostomy, and antibiotic exposure (colistin, fluoroquinolones, 3 rd -5 th generation cephalosporins, piperacillin-tazobactam, carbapenems, and aminoglycosides) for ≥48 hours in the prior 30 days.