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2021 ECCMID | 00751 in Vitro Activities of Ceftazidime-Avibactam

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2021 ECCMID | 00751 in Vitro Activities of Ceftazidime-Avibactam IHMA In Vitro Activities of Ceftazidime-avibactam and Comparator Agents against Enterobacterales Isolates 2122 Palmer Drive 00751 Schaumburg, IL 60173 USA Collected in Europe Stratified by Infection Type from the ATLAS Global Surveillance Program 2016-2019 www.ihma.com M. Estabrook1, K. Kazmierczak1, G. Stone2, D. Sahm1 1IHMA, Inc., Schaumburg IL, USA, 2Pfizer Inc., Groton, CT USA Introduction Results Results Summary The global spread of multi-drug Table 1: Distribution of organisms collected for this Figure 1A: Ceftazidime-avibactam MIC distribution against all isolates, by infection Figure 1C: Ceftazidime-avibactam MIC distribution against colistin-resistant . Ceftazidime-avibactam was active against more a resistant (MDR) Enterobacterales study source isolates, by infection source isolates from each infection type than the tested has limited the number of options Genus (% of total) Species N LRTI (n=7,625) UTI (n=7,147) SSTI (n=6,973) IAI (n=5,097) Blood (n=5,499) LRTI (n=191) UTI (n=108) SSTI (n=125) IAI (n=68) Blood (n=116) comparators (98.3-99.1% susceptible; MIC90 available to treat infections caused Escherichia (29%) Escherichia coli 9,441 40 30 values 0.5 mg/L) (Table 2; Figure 1A). by Gram-negative pathogens. Klebsiella (26%) Klebsiella pneumoniae 8,271 SR SR . Ceftazidime-avibactam was more consistently Ceftazidime-avibactam (CAZ-AVI) 35 active against isolates from various infection Enterobacter cloacae 2,952 25 is a β-lactam-β-lactamase inhibitor sources than comparators, with the percentage Enterobacter asburiae combination developed for 205 30 of susceptible isolates varying by 0.8% between ) Enterobacter kobei ) % 96 % ( sources, compared to 1.9-13.8% for other agents treatment of carbapenem-resistant ( 20 s Enterobacter cloacae complex s e 73 e (Table 2). t and MDR infections caused by β- 25 t a a l l o lactamase-producing Gram- Enterobacter (11%) Enterobacter ludwigii 55 o . While 70.8% of meropenem-non-susceptible s s i i f f isolates were susceptible to ceftazidime- o negative bacteria. CAZ-AVI has Enterobacter xiangfangensis 20 o 15 32 e e * g activity against Enterobacterales g avibactam, activity was improved against those a Enterobacter bugandensis a t 24 t n that carry Class A, C and some n isolates that were MBL-negative (98.6% e 15 e c Enterobacter hormaechi c r 6 r 10 e Class D β-lactamases, but not e susceptible; MIC90, 4 mg/L) (Table 2; Figure 1B). P Species undefined 153 P Class B metallo-β-lactamases 10 . Ceftazidime-avibactam demonstrated activity (MBLs). The in vitro activity of Klebsiella oxytoca 1,797 * against colistin-resistant isolates (93.1% 5 CAZ-AVI against Enterobacterales Klebsiella aerogenes 1,100 susceptible; MIC90, 4 mg/L). In contrast, only Klebsiella (11%) 5 isolates collected from patients in Klebsiella variicola 520 61.8% of these isolates were susceptible to Europe from various body sites for *** **** meropenem (Table 2; Figure 1C). Species undefined 9 0 0 the ATLAS Global Surveillance Citrobacter freundii ≤0.03 0.06 0.12 0.25 0.5 1 2 4 8 16 32 64 128 >128 ≤0.03 0.06 0.12 0.25 0.5 1 2 4 8 16 32 64 128 >128 Program in 2016-2019 is evaluated 1,194 herein. Citrobacter koseri 833 MIC (mg/L) MIC (mg/L) Conclusions Citrobacter braakii 164 *MBLs were detected in isolates testing with CAZ-AVI MICs ≥16 mg/L: LRTI (124/130, 95.4%); UTI (85/88, *MBLs were detected in isolates testing with CAZ-AVI MICs ≥16 mg/L: LRTI (10/14, 71.4%); UTI (12/12, . Ceftazidime-avibactam demonstrated potent in Citrobacter amalonaticus 32 96.6%); SSTI (58/65, 89.2%); IAI (53/57, 93%); Blood (64/71, 90.1%). 100%); SSTI (4/6, 66.7%); IAI (4/4, 100%); Blood (5/6, 83.3%). Dashed line represents the EUCAST 2021 susceptibility breakpoint for CAZ-AVI. S, susceptible; R, resistant. Dashed line represents the EUCAST 2021 susceptibility breakpoint for CAZ-AVI. S, susceptible; R, resistant. vitro activity against Enterobacterales isolates Methods Citrobacter farmeri 22 a Citrobacter (7%) Poorly visible due to low numbers, isolates testing with CAZ-AVI MIC 16 mg/L: LRTI (0.04%); UTI (0.03%); Isolates of Morganellaceae and Serratia spp. were not included in this subset due to intrinsic colistin- collected from patients in Europe with LRTI, UTI, resistance. 32,341 non-duplicate Entero- Citrobacter sedlakii 9 SSTI (0.04%), 32 mg/L: LRTI (0.03%); UTI (0.01%); SSTI (0.03%); blood (0.02%), 64 mg/L: LRTI (0.03%); UTI (0.01%); IAI (0.04%); blood (0.02%), and 128 mg/L: SSTI (0.03%). SSTI, IAI and bloodstream infections as part of bacterales isolates were Citrobacter gillenii 6 the ATLAS Global Surveillance Program in 2016- collected from 123 sites in 24 Figure 1B: Ceftazidime-avibactam MIC distribution against meropenem-non- Table 2 : In vitro susceptibility to ceftazidime-avibactam and comparator agentsa Citrobacter youngae 2 2019. countries in Europe from susceptible MBL-negative isolates, by infection source Citrobacter murliniae 1 Drug (MIC90 [% Susceptible]) . MBL-positive Enterobacterales compromise the patients with lower-respiratory- LRTI (n=242) UTI (n=152) SSTI (n=175) IAI (n=118) Blood (n=220) Species undefined Phenotype/ in vitro activity of ceftazidime-avibactam and tract infections (LRTI), urinary- 12 35 N CAZ-AVI CAZ FEP MEM CST TZP Infection source other important agents. The spread of MBLs tract infections (UTI), skin/soft- Proteus mirabilis 1,428 SR MIC %S MIC %S MIC %S MIC %S MIC %S MIC %S must continue to be monitored. Proteus vulgaris 90 90 90 90 90 90 tissue infections (SSTI), intra- 701 30 . Ceftazidime-avibactam is a valuable treatment abdominal infections (IAI) and Proteus hauseri 131 All 32,341 0.5 98.7 64 73.8 >16 78.2 0.12 96.1 >8 82.1 >64 79.6 option for infections caused by Enterobacterales bloodstream infections for the Proteus (7%) Proteus penneri 12 that are resistant to last resort agents such as ) 25 MEM-NS 1,269 >128 70.8 >128 4.3 >16 2.6 >8 0.0 >8 77.6 >64 0.9 ATLAS global surveillance % ( colistin, which is nephrotoxic, or meropenem, Proteus rettgeri 1 program from 2016-2019. s e Species undefined t which is inactivated by carbapenemases. a MEM-NS, MBL-NEG 907 4 98.6 >128 6.0 >16 3.5 >8 0.0 >8 76.4 >64 1.2 Isolates collected in Turkey are 2 l o 20 s i Serratia marcescens not included in this analysis. 1,231 f o b CST-R 608 4 93.1 >128 33.9 >16 42.1 >8 61.8 >8 0 >64 38.5 . Antimicrobial susceptibility was Serratia liquefaciens 9 e g References Serratia (4%) a 15 t determined by broth micro- Serratia ureilytica 8 n 1. CLSI. Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that e LRTI, All 7,625 0.5 98.3 128 71.5 >16 76.7 0.12 95.3 >8 83.2 >64 76.0 c Grow aerobically. 11th ed. CLSI standard M07. Wayne, PA: Clinical and dilution according to CLSI r Serratia fonticola 1 e Laboratory Standards Institute; 2018. guidelines and analyzed with P 10 UTI, All 7,147 0.5 98.8 64 72.6 >16 76.5 0.12 96.7 >8 78.6 64 80.6 2. The European Committee on Antimicrobial Susceptibility Testing. Breakpoint Morganella (3%) Morganella morganii 942 tables for interpretation of MICs and zone diameters. Version 11.0, 2021. EUCAST 2021 breakpoints [1- http://www.eucast.org. Providencia stuartii 463 3. Lob SH, Kazmierczak KM, Badal RE, Hackel MA, Bouchillon SK, Biedenbach DJ, 2]. Avibactam was tested at a 5 SSTI, All 6,973 0.5 99.1 64 76.2 >16 80.6 0.12 96.7 >8 75.6 64 82.1 Providencia rettgeri Sahm, DF. 2015. Trends in susceptibility of Escherichia coli from intra-abdominal fixed concentration of 4 mg/L. 312 infections to ertapenem and comparators in the United States according to data from the SMART program, 2009 to 2013. Antimicrob Agents Chemother 59:3606- β-lactamase screening by PCR Providencia (2%) Providencia alcalifaciens 12 IAI, All 5,097 0.5 98.9 64 77.0 >16 82.0 0.12 96.8 >8 89.4 >64 81.7 0 3610. and sequencing was performed Providencia rustigianii 2 on isolates with meropenem ≤0.03 0.06 0.12 0.25 0.5 1 2 4 8 16 32 64 128 >128 Blood, All 5,499 0.5 98.7 64 72.4 >16 76.1 0.12 94.9 >8 86.7 >64 77.9 Species undefined 9 MIC values ≥2 mg/L as MIC (mg/L) aAbbreviations: CAZ-AVI, ceftazidime-avibactam; CAZ, ceftazidime; FEP, cefepime; MEM, meropenem; CST, Raoultella ornithinolytica 38 colistin; TZP, piperacillin-tazobactam; NS, non-susceptible; R, resistant; MBL-NEG, metallo-β-lactamase negative; Disclosures described previously [3]. LRTI, lower-respiratory-tract infection; UTI, urinary-tract infection; SSTI, skin/soft-tissue infection; IAI, intra- Other (<1%) Raoultella planticola Dashed line represents the EUCAST 2021 susceptibility breakpoint for CAZ-AVI. S, susceptible; R, resistant This study was sponsored by Pfizer. IHMA received financial support from Pfizer 15 abdominal infection. in connection with the study and the development of this poster. ME, KK, and DS b Other 15 Isolates of Morganellaceae and Serratia spp. were not included in this subset due to intrinsic colistin-resistance. are employees of IHMA. GS is an employee of Pfizer. Presented at ECCMID 2021, July 9-12, 2021 Online.
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