Treatment of Multidrug-resistant Gram-Negative Skin and Soft Tissue Infections

Jean-Francois Jabbour; Sima L. Sharara; Souha S. Kanj


Curr Opin Infect Dis. 2020;33(2):146-154. 

In This Article

Management of Skin and Soft Tissue Infection by Metallo-beta-lactamase-producing Carbapenem-resistant Enterobacteriaceae

An intrinsic resistance is conferred to β-lactam antibiotics for NDM producers, except for aztreonam. Avibactam does not possess the ability to inhibit MBL Class B and many Class D enzymes.[16] Hence, the combination of ceftazidime–avibactam and aztreonam was investigated and found to be synergistic[42] and safe[43] in most cases of NDM-CREs.

The combination of aztreonam–avibactam protects aztreonam from hydrolysis and provides synergy in antimicrobial activity against multiple β-lactamase-expressing strains with a wide MIC range.[44] In-vitro studies have shown that aztreonam-avibactam was highly active against all CRE strains (KPC, OXA-48, MBL) and MDR strains,[45–47] but showed diminished activity against some Escherichia coli isolates, which harbor an amino-acid insertion in PBP3.[47,48] An ongoing multicenter phase 3 clinical trial is assessing the safety and tolerability of aztreonam–avibactam with metronidazole to meropenem and colistin for cIAI ( Identifier: NCT03329092). A similar phase 3 trial is examining aztreonam–avibactam compared with BAT for hospitalized patients with infections including cIAI, cUTI, nosocomial pneumonia and bloodstream infections with MBL-producing GNB ( Identifier: NCT03580044). The results of these studies could provide insight into the role of aztreonam–avibactam in the management of MDR-GNB infections, although its use in SSTIs remains unknown.