Therapeutic approach in the critically ill patient with suspected multidrug resistance.

The treatment of infections caused by multidrug-resistant microorganisms (MDROs) in critically ill patients remains a major clinical challenge due to the high mortality associated with therapeutic failure. Delays in administering effective antibiotics is a determining factor, especially in patients with sepsis. The presence of MDROs is one of the main causes of failure of empirical treatment. Identifying patients at risk of MDRO infection is essential, although complex. Factors such as prior use of antibiotics disrupt the intestinal microbiome balance and promote colonization by MDROs. Immunosuppression, disruption of physical barrier, systemic or organ-specific frailty, and the length of hospital stay increase the risk of colonization and infection by MDROs. In patients with sepsis and a high risk of MDRO infection, empirical therapy should be broad-spectrum and administered early. Traditionally, combination therapy has been recommended, preferably including a classical β-lactam together with aminoglycosides or colistin-drugs that may be suboptimal in certain infection sites and are associated with significant toxicity risks. The new broad-spectrum β-lactams, already validated as first-line targeted treatment, are emerging as a promising empirical option in selected patients. Their early use, guided by colonization status, can optimize initial coverage in terms of spectrum and pharmacokinetic/pharmacodynamic, and reduces delays in the initiation of effective treatment. This strategy should be integrated into antimicrobial stewardship programs and be followed by deescalation once microbiological results are available.