Antibiotic Treatment of Severe Infections with Multiresistant Bacteria

Approximately 10 000 people die in Germany each year because of infections with multidrug-resistant organisms (MDRO) such as carbapenem-resistant Enterobacterales (CRE), difficult-to-treat resistant Pseudomonas aeruginosa (DTR-PA), carbapenem-resistant Acinetobacter baumannii (CRAB), methicillin-resistant Staphylococcus aureus (MRSA), and vancomycin-resistant enterococci (VRE). Such infections are a diagnostic and therapeutic challenge. This clinical practice guideline contains evidence-based recommendations for the antibiotic treatment of severe MDRO infections.

This guideline is based on findings in publications retrieved by a systematic search in PubMed, Embase, and the Cochrane Library. The evidence was evaluated according to the GRADE system, and a structured nominal group process was carried out under moderation by the Association of the Scientific Medical Societies in Germany (Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften, AWMF).

In cases of suspected MDRO, the species of the pathogen and its MDRO-defining resistance should be identified and confirmed, and sensitivity to other antibiotics should be tested. In cases of severe Gram-negative MDRO infection, metallo-β-lactamases must be either detected or ruled out. Treatment tailored to the pathogen and its sensitivity pattern increases the likelihood of success and lowers selection pressure that can lead to the development of resistance. For MDRO not involving metallo-β-lactamase, the drugs of first choice are ceftazidime-avibactam, meropenem-vaborbactam, and imipenem-relebactam; for MDRO with metallo-β-lactamase or drug resistance, cefiderocol or aztreonam-avibactam may be considered. Ceftolozan-tazobactam, ceftazidime-avibactam, imipenem-relebactam, and cefiderocol are suitable for DTR-PA; ceftolozan-tazobactam is the preferred choice, while cefiderocol should be reserved for metallo-β-lactamase-producing strains. For CRAB, cefiderocol is recommended; sulbactam-durlobactam plus a carbapenem is an alternative that is not approved in Europe. MRSA bloodstream infections should be treated with intravenous daptomycin or vancomycin, and MRSA pneumonia with linezolid or vancomycin. For VRE bloodstream infections, linezolid or daptomycin at a dosage of 10-12 mg/kg is indicated.

The treatment should be tailored in consideration of the site of infection, the antibiotic sensitivity profile, the resistance mechanism, and the clinical situation. New reserve antibiotics should be used selectively and in the framework of antimicrobial stewardship.