The Revival of Aztreonam in Combination with Avibactam against Metallo-β-Lactamase-Producing Gram-Negatives: A Systematic Review of In Vitro Studies and Clinical Cases
Infections caused by metallo-β-lactamase (MBL)-producing <i>Enterobacterales</i> and <i>Pseudomonas</i> are increasingly reported worldwide and are usually associated with high mortality rates (>30%). Neither standard therapy nor consensus for the management of these infec...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-08-01
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| Series: | Antibiotics |
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| Online Access: | https://www.mdpi.com/2079-6382/10/8/1012 |
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| author | Carola Mauri Alberto Enrico Maraolo Stefano Di Bella Francesco Luzzaro Luigi Principe |
| author_facet | Carola Mauri Alberto Enrico Maraolo Stefano Di Bella Francesco Luzzaro Luigi Principe |
| author_sort | Carola Mauri |
| collection | DOAJ |
| description | Infections caused by metallo-β-lactamase (MBL)-producing <i>Enterobacterales</i> and <i>Pseudomonas</i> are increasingly reported worldwide and are usually associated with high mortality rates (>30%). Neither standard therapy nor consensus for the management of these infections exist. Aztreonam, an old β-lactam antibiotic, is not hydrolyzed by MBLs. However, since many MBL-producing strains co-produce enzymes that could hydrolyze aztreonam (e.g., AmpC, ESBL), a robust β-lactamase inhibitor such as avibactam could be given as a partner drug. We performed a systematic review including 35 in vitro and 18 in vivo studies on the combination aztreonam + avibactam for infections sustained by MBL-producing Gram-negatives. In vitro data on 2209 Gram-negatives were available, showing the high antimicrobial activity of aztreonam (MIC ≤ 4 mg/L when combined with avibactam) in 80% of MBL-producing <i>Enterobacterales</i>, 85% of <i>Stenotrophomonas</i> and 6% of MBL-producing <i>Pseudomonas</i>. Clinical data were available for 94 patients: 83% of them had bloodstream infections. Clinical resolution within 30 days was reported in 80% of infected patients. Analyzing only patients with bloodstream infections (64 patients), death occurred in 19% of patients treated with aztreonam + ceftazidime/avibactam. The combination aztreonam + avibactam appears to be a promising option against MBL-producing bacteria (especially <i>Enterobacterales</i>, much less for <i>Pseudomonas</i>) while waiting for new antimicrobials. |
| first_indexed | 2024-03-10T09:03:38Z |
| format | Article |
| id | doaj.art-bd8b33287a68407788d0ba9ddeb86865 |
| institution | Directory Open Access Journal |
| issn | 2079-6382 |
| language | English |
| last_indexed | 2024-03-10T09:03:38Z |
| publishDate | 2021-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antibiotics |
| spelling | doaj.art-bd8b33287a68407788d0ba9ddeb868652023-11-22T06:34:40ZengMDPI AGAntibiotics2079-63822021-08-01108101210.3390/antibiotics10081012The Revival of Aztreonam in Combination with Avibactam against Metallo-β-Lactamase-Producing Gram-Negatives: A Systematic Review of In Vitro Studies and Clinical CasesCarola Mauri0Alberto Enrico Maraolo1Stefano Di Bella2Francesco Luzzaro3Luigi Principe4Clinical Microbiology and Virology Unit, “A. Manzoni” Hospital, 23900 Lecco, ItalyFirst Division of Infectious Diseases, Cotugno Hospital, AORN dei Colli, 80131 Naples, ItalyClinical Department of Medical, Surgical and Health Science, Trieste University, 34128 Trieste, ItalyClinical Microbiology and Virology Unit, “A. Manzoni” Hospital, 23900 Lecco, ItalyClinical Pathology and Microbiology Unit, “S. Giovanni di Dio” Hospital, 88900 Crotone, ItalyInfections caused by metallo-β-lactamase (MBL)-producing <i>Enterobacterales</i> and <i>Pseudomonas</i> are increasingly reported worldwide and are usually associated with high mortality rates (>30%). Neither standard therapy nor consensus for the management of these infections exist. Aztreonam, an old β-lactam antibiotic, is not hydrolyzed by MBLs. However, since many MBL-producing strains co-produce enzymes that could hydrolyze aztreonam (e.g., AmpC, ESBL), a robust β-lactamase inhibitor such as avibactam could be given as a partner drug. We performed a systematic review including 35 in vitro and 18 in vivo studies on the combination aztreonam + avibactam for infections sustained by MBL-producing Gram-negatives. In vitro data on 2209 Gram-negatives were available, showing the high antimicrobial activity of aztreonam (MIC ≤ 4 mg/L when combined with avibactam) in 80% of MBL-producing <i>Enterobacterales</i>, 85% of <i>Stenotrophomonas</i> and 6% of MBL-producing <i>Pseudomonas</i>. Clinical data were available for 94 patients: 83% of them had bloodstream infections. Clinical resolution within 30 days was reported in 80% of infected patients. Analyzing only patients with bloodstream infections (64 patients), death occurred in 19% of patients treated with aztreonam + ceftazidime/avibactam. The combination aztreonam + avibactam appears to be a promising option against MBL-producing bacteria (especially <i>Enterobacterales</i>, much less for <i>Pseudomonas</i>) while waiting for new antimicrobials.https://www.mdpi.com/2079-6382/10/8/1012aztreonamavibactamceftazidime/avibactam<i>Enterobacterales</i><i>Pseudomonas</i><i>Stenotrophomonas</i> |
| spellingShingle | Carola Mauri Alberto Enrico Maraolo Stefano Di Bella Francesco Luzzaro Luigi Principe The Revival of Aztreonam in Combination with Avibactam against Metallo-β-Lactamase-Producing Gram-Negatives: A Systematic Review of In Vitro Studies and Clinical Cases Antibiotics aztreonam avibactam ceftazidime/avibactam <i>Enterobacterales</i> <i>Pseudomonas</i> <i>Stenotrophomonas</i> |
| title | The Revival of Aztreonam in Combination with Avibactam against Metallo-β-Lactamase-Producing Gram-Negatives: A Systematic Review of In Vitro Studies and Clinical Cases |
| title_full | The Revival of Aztreonam in Combination with Avibactam against Metallo-β-Lactamase-Producing Gram-Negatives: A Systematic Review of In Vitro Studies and Clinical Cases |
| title_fullStr | The Revival of Aztreonam in Combination with Avibactam against Metallo-β-Lactamase-Producing Gram-Negatives: A Systematic Review of In Vitro Studies and Clinical Cases |
| title_full_unstemmed | The Revival of Aztreonam in Combination with Avibactam against Metallo-β-Lactamase-Producing Gram-Negatives: A Systematic Review of In Vitro Studies and Clinical Cases |
| title_short | The Revival of Aztreonam in Combination with Avibactam against Metallo-β-Lactamase-Producing Gram-Negatives: A Systematic Review of In Vitro Studies and Clinical Cases |
| title_sort | revival of aztreonam in combination with avibactam against metallo β lactamase producing gram negatives a systematic review of in vitro studies and clinical cases |
| topic | aztreonam avibactam ceftazidime/avibactam <i>Enterobacterales</i> <i>Pseudomonas</i> <i>Stenotrophomonas</i> |
| url | https://www.mdpi.com/2079-6382/10/8/1012 |
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