scholarly journals 1245. In Vitro Activities of Ceftaroline and Comparator Agents Against Bacterial Pathogens Collected from Patients with Skin and Skin Structure Infections: ATLAS Global Surveillance Program 2012-2019

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S711-S711
Author(s):  
Meredith Hackel ◽  
Gregory Stone ◽  
Daniel F Sahm

Abstract Background Ceftaroline fosamil, the prodrug of ceftaroline, is a parenteral cephem approved for the treatment of patients with skin and skin structure infections (SSSIs) caused by Staphylococcus aureus (both methicillin-susceptible [MSSA] and methicillin-resistant [MRSA] isolates), β-hemolytic streptococci (Streptococcus pyogenes, S. agalactiae, S. dysgalactiae), and select species of Enterobacterales (Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca). The current study is part of the ATLAS (Antimicrobial Testing Leadership and Surveillance) program and evaluated the current activities of ceftaroline and comparator agents against commonly encountered bacterial isolates associated with SSSIs. Methods From 2012 to 2019 the ATLAS program received 124,694 bacterial isolates that had been cultured by 493 clinical laboratories in 71 countries from samples of patients diagnosed with SSSIs. All isolates were transported to IHMA, (Schaumburg, IL, USA) where their identities were confirmed using MALDI-TOF mass spectrometry and antimicrobial susceptibility testing performed following standardized CLSI broth microdilution methodology (M07). Percent susceptibilities were determined using 2021 CLSI MIC breakpoints. Phenotypic extended-spectrum β-lactamase (ESBL) screening and confirmatory testing were performed using the CLSI M100 method. Results The in vitro activity of ceftaroline is summarized in the following table. Overall, >99.9% of MSSA and 92.8% of MRSA from SSSI were susceptible to ceftaroline (MIC ≤1 µg/ml); 7.1% of MRSA isolates were ceftaroline-susceptible dose-dependent (MIC 2-4 µg/ml) with greatest proportion being from Chile (53.3% of 392 isolates), S. Korea (29.3% of 321 isolates), and China (24.7% of 652 isolates). Twelve ceftaroline-resistant MRSA were observed, consisting of 11 of 109 isolates from Thailand (10.1%) and 1 of 161 from China (0.6%). All S. pyogenes and 88.0% of ESBL-negative Enterobacterales were susceptible to ceftaroline. Results Table Conclusion Ceftaroline continues to demonstrate potent in vitro activity against clinically relevant pathogens associated with SSSIs. Disclosures Meredith Hackel, PhD MPH, IHMA (Employee)Pfizer, Inc. (Independent Contractor) Gregory Stone, PhD, AztraZeneca (Shareholder, Former Employee)Pfizer, Inc. (Employee) Daniel F. Sahm, PhD, IHMA (Employee)Pfizer, Inc. (Independent Contractor)

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S782-S782
Author(s):  
Meredith Hackel ◽  
Greg Stone ◽  
Daniel F Sahm

Abstract Background Ceftaroline fosamil, the prodrug of ceftaroline, is a parenteral cephem approved for the treatment of patients with skin and skin structure infections (SSSIs) caused by Staphylococcus aureus (both methicillin-susceptible [MSSA] and methicillin-resistant [MRSA] isolates), β-hemolytic streptococci (Streptococcus pyogenes, Streptococcus agalactiae), and select species of Enterobacterales (Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca). The current study is part of the ATLAS (Antimicrobial Testing Leadership and Surveillance) program and evaluated the current activities of ceftaroline and comparator agents against commonly encountered bacterial isolates associated with SSSIs. Methods From 2012 to 2018 the ATLAS program received 90,119 bacterial isolates that had been cultured by 370 clinical laboratories in 56 countries from samples of patients diagnosed with SSSIs. All isolates were transported to IHMA, Inc., (Schaumburg, IL, USA) where their identities were confirmed using MALDI-TOF mass spectrometry and antimicrobial susceptibility testing performed following standardized CLSI broth microdilution methodology (M07). Percent susceptibilities were determined using 2020 CLSI MIC breakpoints. Phenotypic ESBL screening and confirmatory testing were performed using the CLSI M100 method. Results The in vitro activity of ceftaroline is summarized in the following table. Overall, 100% of MSSA and 93.8% of MRSA from SSSI were susceptible to ceftaroline (MIC ≤1 µg/ml); 6.2% of MRSA isolates were ceftaroline -susceptible dose-dependent (MIC 2-4 µg/ml) with greatest proportion being from Chile (57.1% of 1,669 isolates), Thailand (36.5% of 2,318 isolates), and S. Korea (29.3% of 1,231 isolates). No ceftaroline-resistant MRSA were observed. All S. pyogenes and 88.5% of ESBL-negative Enterobacterales were also susceptible to ceftaroline. Table Conclusion Ceftaroline continues to demonstrate potent in vitro activity against clinically relevant pathogens associated with SSSIs. Disclosures Greg Stone, PhD, AztraZeneca (Shareholder, Former Employee)Pfizer, Inc. (Employee) Daniel F. Sahm, PhD, IHMA (Employee)Pfizer, Inc. (Consultant)Shionogi & Co., Ltd. (Independent Contractor)


2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S724-S724
Author(s):  
Meredith Hackel ◽  
Gregory Stone ◽  
Daniel F Sahm

Abstract Background Community-acquired bacterial pneumonia (CABP) is a frequent cause of patient morbidity and mortality. Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis are frequent etiologic agents of CABP. Ceftaroline fosamil is a parenteral cephem approved for treatment of patients with CABP caused by S. pneumoniae (including cases with concurrent bacteremia), methicillin-susceptible Staphylococcus aureus (MSSA), H. influenzae, and some species of Enterobacterales. In this study we report the in vitro activity of ceftaroline and comparators against isolates from community-acquired respiratory tract infections (CARTI) collected through a global surveillance program. Methods Clinically relevant, non-duplicate, isolates cultured from respiratory specimens by clinical laboratories in 54 countries in 2016-2019 were collected by the ATLAS Surveillance Program central laboratory (IHMA, Schaumburg, IL, USA). In total, 2,636 isolates of S. pneumoniae, H. influenzae, M. catarrhalis, MSSA, and methicillin-resistant S. aureus (MRSA) were tested. The isolates (n/percent of total) originated from Asia/South Pacific (722/27.4%); Europe (1481/56.2%); Latin America (292/11.1%); Middle East/Africa (57/2.2%); and North America (Canada only) (84/3.2%). Ceftaroline and comparator agent MICs were determined by CLSI M07 broth microdilution methodology. MICs were interpreted using 2021 CLSI M100 MIC breakpoints. Results Ceftaroline and comparator agent in vitro activities are summarized in the table. Greater than 98% of S. pneumoniae and >99% of MSSA were susceptible to ceftaroline, including penicillin-nonsusceptible S. pneumoniae based on a dosage of 600 mg every 12h. Sixty-four (24.4%) MRSA were ceftaroline-susceptible-dose-dependent (MIC 2-4 µg/mL) based on a dosage of 600 mg every 8h administered over 2h, with the majority from (n) China (70), S. Korea (19), Japan (10), and Chile (8). Three isolates, all from China, were resistant to CPT (MIC of 8 µg/mL). 99.2% of H. influenzae were susceptible to ceftaroline. Results Table Conclusion Ceftaroline demonstrated potent in vitro activity against current pathogens associated with CABP from a global collection. Disclosures Meredith Hackel, PhD MPH, IHMA (Employee)Pfizer, Inc. (Independent Contractor) Gregory Stone, PhD, AztraZeneca (Shareholder, Former Employee)Pfizer, Inc. (Employee) Daniel F. Sahm, PhD, IHMA (Employee)Pfizer, Inc. (Independent Contractor)


2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S701-S702
Author(s):  
Meredith Hackel ◽  
Gregory Stone ◽  
Daniel F Sahm

Abstract Background Typical gram-positive organisms causing bloodstream infections (BSI) include Staphylococcus aureus (methicillin-susceptible [MSSA] and -nonsusceptible [MRSA]), coagulase negative staphylococci, Streptococcus pneumoniae and beta hemolytic streptococci. The parenteral cephem ceftaroline fosamil is approved for treatment of patients with community-acquired bacterial pneumonia caused by S. pneumoniae (including cases with concurrent bacteremia), MSSA, Haemophilus influenzae, and some species of Enterobacterales. Limited data have been published on the in vitro activity of ceftaroline against recent gram-positive clinical isolates known to be frequent bacterial causes of blood stream infections. Methods Standard CLSI broth microdilution MIC determinations (M07) were performed with ceftaroline and comparator agents. MICs were interpreted using 2021 CLSI MIC breakpoints. Clinically relevant, non-duplicate, isolates cultured from blood by clinical laboratories in 2012-2019 were tested by the ATLAS (Antimicrobial Testing Leadership and Surveillance) program central laboratory (IHMA, Inc., Schaumburg, IL, USA). In total, 21,967 non-duplicate isolates of S. aureus, S. epidermidis, S. pneumoniae and beta hemolytic streptococci from BSI collected between 2012 and 2019 were tested. Isolates came from (n/%): Asia/South Pacific (2,970/13.5%), Europe (13,691/62.3%), Latin America (2,824/12.9%), MidEast/Africa (1,498/6.8%), and North America (Canada only) (984/4.5%). Results Ceftaroline and comparator agent activities are summarized in the following table. Results Table Conclusion Greater than 99% of S. pneumoniae, beta-hemolytic streptococci and MSSA isolates included in a 2012-2019 collection of gram-positive blood stream pathogens were susceptible to ceftaroline. 90.8% of MRSA were susceptible, and 9.1% isolates categorized as susceptible-dose dependent (MIC, 2-4 µg/mL); four isolates (two from Thailand and one each from China and S. Korea) were resistant to ceftaroline (MIC >4 µg/mL). The ceftaroline MIC90 for S. epidermidis was 0.5 µg/mL, with 97.7% of MICs ≤1 µg/mL. Ceftaroline continues to demonstrate potent in vitro activity against clinically relevant pathogens associated with BSI. Disclosures Meredith Hackel, PhD MPH, IHMA (Employee)Pfizer, Inc. (Independent Contractor) Gregory Stone, PhD, AztraZeneca (Shareholder, Former Employee)Pfizer, Inc. (Employee) Daniel F. Sahm, PhD, IHMA (Employee)Pfizer, Inc. (Independent Contractor)


2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S782-S783
Author(s):  
Meredith Hackel ◽  
Greg Stone ◽  
Daniel F Sahm

Abstract Background Typical gram-positive organisms causing bloodstream infections (BSI) include Staphylococcus aureus (methicillin-susceptible [MSSA] and -nonsusceptible [MRSA]), coagulase negative staphylococci, Streptococcus pneumoniae and beta hemolytic streptococci. The parenteral cephem ceftaroline fosamil is approved for treatment of patients with community-acquired bacterial pneumonia caused by S. pneumoniae (including cases with concurrent bacteremia), MSSA, Haemophilus influenzae, and some species of Enterobacterales. Limited data have been published on the in vitro activity of ceftaroline against recent gram-positive clinical isolates known to be frequent bacterial causes of blood stream infections. Methods Standard CLSI broth microdilution MIC determinations (M07) were performed with ceftaroline and comparator agents. MICs were interpreted using 2020 CLSI MIC breakpoints. Clinically relevant, non-duplicate, isolates cultured from blood by clinical laboratories in 2012-2018 were tested by the ATLAS (Antimicrobial Testing Leadership and Surveillance) program central laboratory (IHMA, Inc., Schaumburg, IL, USA). In total, 10,998 non-duplicate isolates of S. aureus, S. epidermidis, S. pneumoniae and beta hemolytic streptococci from BSI collected between 2012 and 2018 were tested. Isolates came from (n/%): Asia/South Pacific (1,739/15.8%), Europe (5,448/49.5%), Latin America (1,805/16.4%), MidEast/Africa (861/7.8%), and North America (1,145/10.4%). Results Ceftaroline and comparator agent activities are summarized in the following table. Table Conclusion Greater than 98% of S. pneumoniae, S. epidermidis, beta-hemolytic streptococci and MSSA isolates included in a 2012-2018 collection of gram-positive blood stream pathogens were susceptible to ceftaroline. 91.4% of MRSA were susceptible, and 8.6% isolates categorized as susceptible-dose dependent (MIC, 2-4 ug/mL); two isolates (one each from Thailand and S. Korea) were resistant to ceftaroline (MIC >4 ug/mL). Ceftaroline continues to demonstrate potent in vitro activity against clinically relevant pathogens associated with BSI. Disclosures Greg Stone, PhD, AztraZeneca (Shareholder, Former Employee)Pfizer, Inc. (Employee) Daniel F. Sahm, PhD, IHMA (Employee)Pfizer, Inc. (Consultant)Shionogi & Co., Ltd. (Independent Contractor)


2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S783-S784
Author(s):  
Krystyna Kazmierczak ◽  
Sibylle Lob ◽  
Greg Stone ◽  
Daniel F Sahm

Abstract Background Avibactam (AVI) is a β-lactamase inhibitor with potent inhibitory activity against Class A, Class C, and some Class D serine β-lactamases. The combination of ceftazidime (CAZ) with AVI has been approved in Europe and in the United States for several indications. This study evaluated the in vitro activity of CAZ-AVI and comparators against Enterobacterales (Eba) and Pseudomonas aeruginosa (Pae) isolates collected from patients with bloodstream infections as part of the ATLAS surveillance program in 2015-2018. Methods A total of 57048 Eba and 15813 Pae non-duplicate clinically significant isolates, including 7720 Eba and 1286 Pae isolated from bloodstream infections, were collected in 52 countries in Europe, Latin America, Asia/Pacific (excluding mainland China), and the Middle East/Africa region. Susceptibility testing was performed by CLSI broth microdilution. CAZ-AVI was tested at a fixed concentration of 4 µg/ml AVI. Meropenem-nonsusceptible (MEM-NS) Eba and Pae isolates were screened for the presence of β-lactamase genes. Results Susceptibility data are shown in the Table. Percentages of susceptibility (% S) to the tested agents were 0.3-2.9% lower among Eba and Pae from bloodstream infections compared to isolates from combined sources in most cases. CAZ-AVI showed potent in vitro activity against all Eba bloodstream isolates and the CAZ-NS subset (MIC90, 0.5-2 µg/ml, 93.4-98.1% S). Reduced activity against MEM-NS Eba was attributable to carriage of class B metallo-β-lactamases (MBLs) because 99% of MEM-NS MBL-negative isolates were susceptible to CAZ-AVI. None of the tested comparators exceeded the activity of CAZ-AVI. CAZ-AVI also showed good in vitro activity against the majority of Pae bloodstream isolates (MIC90, 16 µg/ml, 89.4% S). Activity was reduced against CAZ-NS and MEM-NS subsets (54.2-63.8% S), which included isolates carrying MBLs, but exceeded the activity of CAZ and MEM against these subsets by 26-31 percentage points. Amikacin was the only tested comparator that demonstrated comparable activity against Pae bloodstream isolates. Table Conclusion CAZ-AVI provides a valuable therapeutic option for treating bloodstream infections caused by MBL-negative Eba and Pae isolates. Disclosures Krystyna Kazmierczak, PhD, IHMA (Employee)Pfizer, Inc. (Consultant) Sibylle Lob, PhD, IHMA (Employee)Pfizer, Inc. (Consultant) Greg Stone, PhD, AztraZeneca (Shareholder, Former Employee)Pfizer, Inc. (Employee) Daniel F. Sahm, PhD, IHMA (Employee)Pfizer, Inc. (Consultant)Shionogi & Co., Ltd. (Independent Contractor)


2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S784-S784
Author(s):  
Sibylle Lob ◽  
Krystyna Kazmierczak ◽  
Greg Stone ◽  
Daniel F Sahm

Abstract Background Ceftazidime-avibactam (CAZ-AVI) is a β-lactam/non-β-lactam β-lactamase inhibitor combination with activity against Enterobacterales producing class A, C and some class D β-lactamases. Resistance caused by these β-lactamases is especially high in ICUs. This study evaluated the in vitro activity of CAZ-AVI and comparators against Enterobacterales isolates from patients in ICU and non-ICU wards. Methods Non-duplicate clinical isolates were collected in 2017-2018 from patients in Asia/Pacific, Europe, Latin America, and Middle East/Africa. Susceptibility testing was performed using CLSI broth microdilution and interpreted using CLSI 2020 and FDA (tigecycline) breakpoints. PCR and sequencing were used to determine the β-lactamase genes present in all isolates with meropenem (MEM) MIC >1 µg/ml, and Escherichia coli, Klebsiella spp. and Proteus mirabilis with aztreonam or ceftazidime MIC >1 µg/ml. Results The activity of CAZ-AVI and comparators is shown in the table. Susceptibility rates among global Enterobacterales were generally lower for isolates from patients in ICU than non-ICU wards, but this difference was small for CAZ-AVI, which inhibited ≥97% of isolates from both ward types. Among MEM-nonsusceptible (NS) isolates, CAZ-AVI was active against 66.5% and 68.1% of ICU and non-ICU isolates, respectively (of which 31.8% and 30.8%, respectively, carried metallo-β-lactamases [MBLs]). CAZ-AVI inhibited >97% of MEM-NS MBL-negative isolates collected globally. Antimicrobial activity against all Enterobacterales from both ICU and non-ICU wards in Latin America (LA) was generally similar to the global average. Among MEM-NS isolates, antimicrobial activity of CAZ-AVI and TGC was higher in LA than the global average among isolates from both ward types, at least partly because of a lower proportion of MBL-positive isolates in this subset (15.8% and 17.9% in ICU and non-ICUs, respectively). CAZ-AVI inhibited 100% of MEM-NS MBL-negative isolates from LA. Table Conclusion CAZ-AVI provides a valuable treatment option for infections caused by Enterobacterales that do not carry MBLs, including those among patients in ICU wards, where antimicrobial resistance is typically higher. Disclosures Sibylle Lob, PhD, IHMA (Employee)Pfizer, Inc. (Consultant) Krystyna Kazmierczak, PhD, IHMA (Employee)Pfizer, Inc. (Consultant) Greg Stone, PhD, AztraZeneca (Shareholder, Former Employee)Pfizer, Inc. (Employee) Daniel F. Sahm, PhD, IHMA (Employee)Pfizer, Inc. (Consultant)Shionogi & Co., Ltd. (Independent Contractor)


2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S783-S783
Author(s):  
Krystyna Kazmierczak ◽  
Greg Stone ◽  
Daniel F Sahm

Abstract Background Ceftazidime-avibactam (CAZ-AVI) is a β-lactam/non-β-lactam β-lactamase inhibitor combination with in vitro activity against Enterobacterales (Ent) and Pseudomonas aeruginosa (Psa) carrying Class A, C and some Class D β-lactamases. We examined the in vitro activity of CAZ-AVI and comparators against presumed community-acquired (CA; cultured < 48 h after hospital admission) and hospital-acquired (HA; cultured ≥48 h post-admission) isolates collected from pediatric patients as part of the ATLAS surveillance program. Methods 6023 non-duplicate isolates were collected in 50 countries in Europe (n=3122), Latin America (n=1220), Middle East/Africa (n=1007), and Asia/Pacific (excluding China; n=674) from patients (newborn to 17 y) with lower respiratory tract (LRTI; n=1641), urinary tract (UTI; n=1595), skin and soft tissue (SSTI; n=1027), intra-abdominal (IAI; n=949), and bloodstream (BSI; n=811) infections. Susceptibility testing was performed by CLSI broth microdilution and values were interpreted using CLSI 2020 breakpoints. CAZ-AVI was tested at a fixed concentration of 4 µg/mL AVI. Isolates with CAZ or aztreonam MICs ≥2 µg/mL (Escherichia coli, Klebsiella spp., Proteus mirabilis) or meropenem MICs ≥2 µg/mL (all Ent species) or ≥4 µg/mL (Psa) were screened for β-lactamase genes. Results The in vitro activity of CAZ-AVI exceeded that of meropenem and other tested β-lactams against Ent (98.5% susceptible (S)) and Psa (93.1% S) collected globally from pediatric patients (Table). Percentages of susceptibility to CAZ-AVI ranged from 96.8-99.3% among CA Ent from different infection types and were reduced 0.4-1.0% among HA isolates from SSTI, IAI and BSI. Susceptibility to CAZ-AVI was also similar (92.7-95.4% S) among CA Psa from different infection types and was reduced 0.1-4.4% among HA isolates. For both Ent and Psa, the lowest percentages of susceptibility to the tested β-lactams were observed among isolates from BSI, which included a higher proportion of isolates carrying extended-spectrum β-lactamases and/or carbapenemases than isolates from other infection types. Table Conclusion CAZ-AVI could provide a valuable therapeutic option for treatment of CA and HA infections caused by Ent and Psa in pediatric patients. Disclosures Krystyna Kazmierczak, PhD, IHMA (Employee)Pfizer, Inc. (Consultant) Greg Stone, PhD, AztraZeneca (Shareholder, Former Employee)Pfizer, Inc. (Employee) Daniel F. Sahm, PhD, IHMA (Employee)Pfizer, Inc. (Consultant)Shionogi & Co., Ltd. (Independent Contractor)


2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S711-S711
Author(s):  
Sibylle Lob ◽  
Meredith Hackel ◽  
Gregory Stone ◽  
Daniel F Sahm

Abstract Background Ceftazidime-avibactam (CAZ-AVI) is a β-lactam/non-β-lactam β-lactamase inhibitor combination that can inhibit class A, C, and some class D β-lactamases. Resistance caused by these β-lactamases often results in multidrug-resistance (MDR). This study evaluated the in vitro activity of CAZ-AVI and comparators against MDR Enterobacterales and Pseudomonas aeruginosa isolates collected from patients in Latin America. Methods Non-duplicate clinical isolates were collected in 2018-2019 in 10 countries in Latin America. Susceptibility testing was performed using CLSI broth microdilution and interpreted using CLSI 2021 and FDA (tigecycline) breakpoints. MDR was defined as resistant (R) to ≥3 of 7 sentinel drugs: amikacin (AMK), aztreonam (ATM), cefepime (FEP), colistin (CST), levofloxacin (LVX), meropenem (MEM), and piperacillin-tazobactam (TZP). Results The activity of CAZ-AVI and comparators against all isolates and MDR subsets is shown in the table. MDR rates for the studied species ranged from 16.3% among E. cloacae to 35.7% among K. pneumoniae. CAZ-AVI was active against 98% of Enterobacterales isolates and maintained activity against 74-98% of MDR isolates of the examined Enterobacterales species. Only tigecycline showed higher activity. Among P. aeruginosa, CAZ-AVI was active against 87% of all isolates and 47% of MDR isolates; no other studied drug was more active. The three most common MDR phenotypes among Enterobacterales were 1) R to ATM, FEP, and LVX (n=544, 44.8% of all MDR Enterobacterales; 100% susceptible (S) to CAZ-AVI), 2) R to ATM, FEP, LVX, and TZP (n=150, 12.4% of all MDR Enterobacterales; 99.3% S to CAZ-AVI), and 3) R to all sentinel drugs except AMK and CST (n=145, 11.9% of all MDR isolates; 78.6% S to CAZ-AVI). The three most common MDR phenotypes among P. aeruginosa were 1) R to all sentinel drugs except CST (n=85, 19.7% of all MDR isolates; 24.7% S to CAZ-AVI), 2) R to all sentinel drugs except AMK and CST (n=42, 9.7% of all MDR isolates; 66.7% S to CAZ-AVI), and 3) R to AMK, LVX, and MEM (n=37, 8.6% of all MDR isolates; 24.3% S to CAZ-AVI). Conclusion These in vitro data suggest that CAZ-AVI can be an effective treatment option for infections caused by MDR Enterobacterales and P. aeruginosa collected in Latin America. Disclosures Sibylle Lob, PhD, IHMA (Employee)Pfizer, Inc. (Independent Contractor) Meredith Hackel, PhD MPH, IHMA (Employee)Pfizer, Inc. (Independent Contractor) Gregory Stone, PhD, AztraZeneca (Shareholder, Former Employee)Pfizer, Inc. (Employee) Daniel F. Sahm, PhD, IHMA (Employee)Pfizer, Inc. (Independent Contractor)


2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S784-S785
Author(s):  
Krystyna Kazmierczak ◽  
Sibylle Lob ◽  
Greg Stone ◽  
Daniel F Sahm

Abstract Background Ceftazidime-avibactam (CAZ-AVI) is a β-lactam/non-β-lactam β-lactamase inhibitor combination that can inhibit class A, C and some class D β-lactamases. Resistance caused by these β-lactamases often results in multidrug-resistance (MDR). This study evaluated the in vitro activity of CAZ-AVI and comparators against MDR Enterobacterales and Pseudomonas aeruginosa isolates collected from patients in Latin America. Methods Non-duplicate clinical isolates were collected in 2017-2018 in 10 countries in Latin America. Susceptibility testing was performed using CLSI broth microdilution and interpreted using CLSI 2020 and FDA (tigecycline) breakpoints. MDR was defined as resistant (R) to ≥3 of 7 sentinel drugs: amikacin (AMK), aztreonam (ATM), cefepime (FEP), colistin (CST), levofloxacin (LVX), meropenem (MEM), and piperacillin-tazobactam (TZP). Results The activity of CAZ-AVI and comparators against all isolates and MDR subsets is shown in the table. MDR rates for the studied species ranged from 17.6% among E. cloacae to 31.0% among K. pneumoniae. CAZ-AVI was active against 99% of Enterobacterales isolates and maintained activity against 85-99% of MDR isolates of the examined species. Only tigecycline showed comparable or higher activity. Among P. aeruginosa, CAZ-AVI was active against 86% of all isolates and 45% of MDR isolates; no other studied drug was more active. The three most common MDR phenotypes among Enterobacterales were 1) R to ATM, FEP, and LVX (n=538, 50% of all MDR Enterobacterales; 100% susceptible (S) to CAZ-AVI), 2) R to all sentinel drugs except AMK and CST (n=112, 10% of all MDR isolates; 88% S to CAZ-AVI), and 3) R to ATM, FEP, LVX, and TZP (n=111, 10% of all MDR Enterobacterales; 100% S to CAZ-AVI). The three most common MDR phenotypes among P. aeruginosa were 1) R to all sentinel drugs except CST (n=70, 22% of all MDR isolates; 20% S to CAZ-AVI), 2) R to AMK, LVX, and MEM (n=33, 10% of all MDR isolates; 33% S to CAZ-AVI), and 3) R to all sentinel drugs except AMK and CST (n=30, 9% of all MDR isolates; 70% S to CAZ-AVI). Table Conclusion These in vitro data suggest that CAZ-AVI can be an effective treatment option for infections caused by MDR Enterobacterales and P. aeruginosa collected in Latin America. Disclosures Krystyna Kazmierczak, PhD, IHMA (Employee)Pfizer, Inc. (Consultant) Sibylle Lob, PhD, IHMA (Employee)Pfizer, Inc. (Consultant) Greg Stone, PhD, AztraZeneca (Shareholder, Former Employee)Pfizer, Inc. (Employee) Daniel F. Sahm, PhD, IHMA (Employee)Pfizer, Inc. (Consultant)Shionogi & Co., Ltd. (Independent Contractor)


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