Bacterial Infections

Abstract

AbstractHCT patients are at risk for severe bacterial infection, the most frequent of them are bloodstream infections (BSI). The majority occur at the pre-engraftment period. Primary BSIs are mainly central line catheter-related (CRBSI) or mucosal barrier injury-associated. Secondary BSI accompanies site-specific infection (e.g., Pseudomonas aeruginosa pneumonia and BSI). GNB has become an increasingly common cause of BSI, and are associated with high mortality. Specifically, an increase in infections due to resistant GNB, such as ESBL Enterobacterales, carbapenemase-producing Enterobacterales (CPE), MDR GNB, or difficult-to-treat (DTR) Pseudomonas aeruginosa, leads to delay in appropriate therapy and increases mortality. Empirical antibiotic therapy should be started immediately when bacterial infection is suspected. It should be based on escalation/de-escalation principles reflecting the patient’s clinical condition, prior colonization or infection with resistant bacteria, and local epidemiology. Main targeted therapy options for severe infections caused by resistant GNB include: carbapenems for ESBL Enterobacterales; meropenem-vaborbactam or ceftazidime-avibactam for KPC-producing Enterobacterales; ceftazidime-avibactam for OXA-48-like-producing Enterobacterales; aztreonam plus ceftazidime–avibactam, or cefiderocol for Metallo-β-lactamases-producing Enterobacterales; ceftolozane-tazobactam for DTR Pseudomonas aeruginosa. Routine combination therapy of β-lactams with aminoglycosides/fluoroquinolone (FQ)/polymyxins for infection due to MDR GNB susceptible to β-lactam is not recommended (with a possible exception of a severe infections due to Pseudomonas aeruginosa in neutropenic patients). High-dose prolonged β-lactam infusion can maximize efficacy. Source control with CVC removal is important. Antibiotic treatment should be continued for at least 7 days until the infection is microbiologically eradicated and all clinical signs resolved, with the patient afebrile for at least 4 days. Antimicrobial stewardship aims to individualize an empirical approach to patients with suspected infection, limiting unnecessary antibiotic use, and optimizing treatment based on pharmacokinetic/pharmacodynamic principles. Infection control is crucial to limit the spread of MDR pathogens. Fluoroquinolone prophylaxis is controversial. Encapsulated bacteria (Streptococcus pneumoniae and Haemophilus influenzae) cause infection during the late post-engraftment period. Preventive measures include oral prophylaxis, IVIg, and vaccinations.