30-Second Takeaway
- High-dose rifampicin significantly reduces linezolid exposure in TB meningitis; twice-daily dosing preserves therapeutic CNS levels.
- Ceftazidime–avibactam plus aztreonam is strongly associated with lower mortality in MBL-producing Enterobacterales bloodstream infection.
- MRSA nasal PCR with pharmacist-driven protocols shortens anti-MRSA therapy and reduces vancomycin nephrotoxicity in LRTI.
- Severe mpox, tecovirimat failure, and resistance cluster in advanced HIV with very low CD4 counts.
- Post-COVID shifts in Candida, Klebsiella, Salmonella Typhi, TB, and C. difficile require updated screening and empiric strategies.
Week ending April 18, 2026
Targeted strategies for TB, resistant Gram-negatives, fungal threats, and viral infections
High-dose rifampicin accelerates linezolid clearance and undermines once-daily dosing in TB meningitis
In this phase II TB meningitis PK analysis, high-dose rifampicin (35 mg/kg) increased linezolid clearance by 34.2%. Higher clearance reduced both plasma and CSF linezolid exposure, threatening sustained therapeutic CNS concentrations. Simulations showed linezolid 1200 mg once daily failed to maintain target plasma and CSF levels with high-dose rifampicin. In contrast, 600 mg twice daily achieved adequate exposures despite rifampicin-induced clearance. These findings support twice-daily linezolid and potential TDM when combined with high-dose rifampicin in TB meningitis regimens.
Ceftazidime–avibactam plus aztreonam associated with markedly lower mortality in MBL-Enterobacterales bacteremia
This Argentine multicenter cohort included 140 adults with bloodstream infection from metallo-β-lactamase–producing Enterobacterales, mainly Klebsiella pneumoniae. Patients were critically ill; most were in intensive care, many ventilated, and over one-third presented with shock. Thirty-day mortality reached 41%, underscoring the lethality of these infections. Propensity score–adjusted analysis showed ceftazidime–avibactam plus aztreonam therapy was associated with lower mortality (OR 0.18; 95% CI .05–.58). An INCREMENT-CPE score ≥8 independently predicted higher mortality (OR 3.63; 95% CI 1.13–11.7).
MRSA nasal PCR plus pharmacist protocols safely reduce MRSA therapy and nephrotoxicity in LRTI
This systematic review and meta-analysis included 15 studies with 2872 hospitalized adults with lower respiratory tract infections. Pharmacist-driven protocols using MRSA nasal PCR shortened anti-MRSA therapy by about 1.5 days versus no testing. The bundle reduced vancomycin trough monitoring (OR 0.21) and acute kidney injury (OR 0.54). In-hospital mortality was lower with pharmacist-driven PCR protocols (OR 0.70), though Bayesian analysis suggested limited certainty for mortality benefit. PCR or culture alone without stewardship protocols did not significantly change MRSA therapy duration.
References
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Additional Reads
Optional additional studies from this edition.