Ceftobiprole in the Management of Severe Legionella pneumophila Pneumonia in Critically Ill Patients: Two Illustrative Case Reports

Legionella pneumophila is a pathogen responsible for severe ‘atypical pneumonia’ and is often associated with high mortality rates in hospitalized patients. Atypical pneumonia can progress to severe forms with fatal outcomes, causing multi-organ damage. The standard of care involves antibiotics such as fluoroquinolones and macrolides, therapies which can be limited by toxicity or emerging resistance. We report two complex cases of Legionella pneumonia not responsive to other antibiotics. Both cases involved ceftobiprole administration in combination with or following macrolide therapy, and in one case, also addressed a documented co-infection. In the first case, levofloxacin was discontinued due to neurotoxicity, and treatment was successfully switched to ceftobiprole combined with azithromycin, leading to complete clinical and radiological recovery. In the second case, ceftobiprole was administered for a concurrent Staphylococcus aureus infection, and a carbapenem-resistant Acinetobacter baumannii (CRAB) was subsequently managed with an alternative agent, eravacycline. This highlights the complexity of managing polymicrobial infections and the need for adaptable antimicrobial strategies. Ceftobiprole may represent a useful component of an individualized antimicrobial strategy in selected critically ill patients with severe Legionella pneumonia, particularly when first-line agents are contraindicated or concomitant bacterial infections require additional coverage. Although beta-lactams are generally not favored for Legionella due to poor intracellular penetration, the successful outcome in our first case suggests potential benefits in combination therapy. Furthermore, regional antibiotic resistance patterns, such as those observed in Campania (Italy), may favor the use of broad-spectrum agents like ceftobiprole. However, further clinical studies are warranted to define its precise role in this setting.