P-1318. Antimicrobial Activity of Aztreonam-Avibactam and Comparator Agents against Stenotrophomonas maltophilia Isolates from Patients Hospitalized with Pneumonia in Europe, Latina America, and Asia (2020-2024)

TL;DR

This study tested how well aztreonam-avibactam and other antibiotics work against a type of bacteria called Stenotrophomonas maltophilia in patients with pneumonia across different regions.

Contribution

The study provides new data on the effectiveness of aztreonam-avibactam against S. maltophilia, a bacteria that is often resistant to other antibiotics.

Findings

Aztreonam-avibactam inhibited 98.7% of S. maltophilia isolates at a concentration of ≤8 mg/L.

Trimethoprim-sulfamethoxazole and minocycline were also highly effective, but ceftazidime and colistin showed limited activity.

Aztreonam-avibactam remained effective against isolates resistant to other antibiotics like TMP-SMX and levofloxacin.

Abstract

Aztreonam-avibactam (ATM-AVI) has recently been approved for clinical use in the European Union and United States to treat Enterobacterales infections, including those caused by metallo-β-lactamase (MBL) producers. We evaluated the activity of ATM-AVI against S. maltophilia isolated from patients with pneumonia.Table 1.Aztreonam-avibactam (ATM-AVI) activity stratified by region and yearAbbreviations: W-EU, Western Europe; E-EU, Eastern Europe; APAC, Asia Pacific region; LATAM, Latin America.Antimicrobial activity of aztreonam-avibactam (ATM-AVI) and comparators against S. maltophilia isolates from patients with pneumonia stratified by region* % inhibited at ≤8 mg/L. ** % inhibited at ≤2 mg/L.Abbreviations: ATM-AVI, aztreonam-avibactam; TMP-SMX, trimethoprim-sulfamethoxazole; W-EU, Western Europe; E-EU, Eastern Europe, APAC, Asia-Pacific region; LATAM; Latin America.

Aztreonam-avibactam (ATM-AVI) activity stratified by region and year

Abbreviations: W-EU, Western Europe; E-EU, Eastern Europe; APAC, Asia Pacific region; LATAM, Latin America.

Antimicrobial activity of aztreonam-avibactam (ATM-AVI) and comparators against S. maltophilia isolates from patients with pneumonia stratified by region

* % inhibited at ≤8 mg/L. ** % inhibited at ≤2 mg/L.

Abbreviations: ATM-AVI, aztreonam-avibactam; TMP-SMX, trimethoprim-sulfamethoxazole; W-EU, Western Europe; E-EU, Eastern Europe, APAC, Asia-Pacific region; LATAM; Latin America.

784 clinical isolates were collected from 60 medical centers located in Western Europe (W-EU; n=457; 25 centers in 10 countries), Eastern Europe (E-EU; n=179; 16 centers in 9 countries), the Asia-Pacific region (APAC; n=89; 10 centers in 5 countries), and Latin America (LATAM; n=59; 9 centers in 6 countries), and as part of the SENTRY Antimicrobial Surveillance Program. Isolates were susceptibility tested by CLSI M07 broth microdilution method. An ATM-AVI pharmacodynamic/pharmacokinetic (PK/PD) susceptible breakpoint of ≤ 8 mg/L was applied for comparison. CLSI breakpoints were applied to comparators when available.Antimicrobial activity of aztreonam-avibactam (ATM-AVI) and comparators against S. maltophilia isolates from patients with pneumonia stratified by year* % inhibited at ≤8 mg/L. ** % inhibited at ≤2 mg/L.Abbreviations: ATM-AVI, aztreonam-avibactam; TMP-SMX, trimethoprim-sulfamethoxazole.Antimicrobial activity of aztreonam-avibactam (ATM-AVI) and comparators against resistant subsets* % inhibited at ≤8 mg/L. ** % inhibited at ≤2 mg/L.Abbreviations: ATM-AVI, aztreonam-avibactam; TMP-SMX, trimethoprim-sulfamethoxazole; NS, not susceptible.

Antimicrobial activity of aztreonam-avibactam (ATM-AVI) and comparators against S. maltophilia isolates from patients with pneumonia stratified by year

* % inhibited at ≤8 mg/L. ** % inhibited at ≤2 mg/L.

Abbreviations: ATM-AVI, aztreonam-avibactam; TMP-SMX, trimethoprim-sulfamethoxazole.

Antimicrobial activity of aztreonam-avibactam (ATM-AVI) and comparators against resistant subsets

* % inhibited at ≤8 mg/L. ** % inhibited at ≤2 mg/L.

Abbreviations: ATM-AVI, aztreonam-avibactam; TMP-SMX, trimethoprim-sulfamethoxazole; NS, not susceptible.

ATM-AVI demonstrated potent activity against isolates from all geographic regions (overall MIC50/90, 4/4 mg/L; 98.7% inhibited at ≤ 8 mg/L), and its activity remained stable during the study period (Table 1 and Figures 1 and 2). The percentage inhibited at ≤8 mg/L ranged from 97.2% in E-EU to 100.0% in LATAM. Trimethoprim-sulfamethoxazole (TMP-SMX; MIC50/90, ≤ 0.12/0.5 mg/L; 95.4% susceptible) and minocycline (MIC50/90, 0.5/1 mg/L; 94.5% susceptible) also were very active. Levofloxacin was active against 84.8% of isolates per CLSI criteria. Ceftazidime (MIC50/90, > 32/ > 32 mg/L; 13.5% inhibited at ≤ 8 mg/L) and colistin (MIC50/90, 4/ > 8 mg/L; 38.8% inhibited at ≤ 2 mg/L) showed limited activity. ATM-AVI retained potent activity against isolates not susceptible to TMP-SMX, minocycline, and/or levofloxacin (Figure 3).

Our results indicated that ATM-AVI may represent a valuable option to treat S. maltophilia infections, addressing a major unmet medical need. S. maltophilia susceptibility rates for comparator agents should be interpreted with caution since breakpoints were established in the 1980s; i.e. before the knowledge of PK/PD parameters that are currently used to establish breakpoints.

Helio Sader, United States Food and Drug Administration: FDA Contract Number: 75F40123C00140 Mariana Castanheira, PhD, Melinta Therapeutics: Advisor/Consultant|Melinta Therapeutics: Grant/Research Support Marisa Winkler, MD, PhD, Basilea: Advisor/Consultant|Basilea: Grant/Research Support|GSK: Advisor/Consultant|GSK: Grant/Research Support|Melinta Therapeutics: Advisor/Consultant|Melinta Therapeutics: Grant/Research Support|Mundipharma: Advisor/Consultant|Mundipharma: Grant/Research Support|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support|Pulmocide: Advisor/Consultant|Pulmocide: Grant/Research Support Rodrigo E. Mendes, PhD, GSK: Grant/Research Support|Shionogi & Co., Ltd.: Grant/Research Support|United States Food and Drug Administration: FDA Contract Number: 75F40123C00140

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