Optimizing TB treatment with Beta-lactams in intensive care settings
Optimizing TB treatment with Beta-lactams in intensive care settings
This thesis of investigates the treatment of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB), focusing on the use of beta-lactam antibiotics and the management of critically ill TB patients in the intensive care unit (ICU).
The first part explores the role of beta-lactam antibiotics, especially carbapenems combined with clavulanic acid, in the treatment of resistant TB. Several studies demonstrated that meropenem/clavulanate is an effective and well-tolerated treatment option for patients with MDR- and XDR-TB. Compared with imipenem/clavulanate, meropenem/clavulanate was associated with higher sputum and culture conversion rates and improved treatment outcomes. Adverse events were generally mild and mainly gastrointestinal in nature. In contrast, the addition of imipenem/clavulanate to an optimized background regimen did not significantly improve treatment success. The thesis also discusses the pharmacodynamic advantages of meropenem and the potential of emerging and repurposed oral carbapenems, which could expand access to effective treatment and reduce the need for hospitalization.
The second part focuses on TB patients admitted to the ICU. A systematic review and a large international multicentre study found mortality rates of approximately 50% among critically ill TB patients. Key predictors of poor outcomes included respiratory failure, organ dysfunction, hospital-acquired infections, and delays in treatment initiation. Intravenous administration of anti-TB drugs, particularly rifampicin, was associated with improved outcomes and lower mortality.
Overall, the thesis supports the use of beta-lactams as valuable components of MDR/XDR-TB treatment and highlights the need for further clinical research, optimized dosing strategies, resistance surveillance, and standardized treatment protocols, especially for critically ill patients.