ABSTRACT
Aim: To elucidate the factors that influence beta-lactam pharmacokinetic (PK) and pharmacodynamic (PD) variability in infective endocarditis (IE) and to examine optimal PK/PD target parameters for therapy. Background(s): Beta-lactam antibiotics are the mainstay of therapy for most bacterial causes of IE. Traditionally considered as agents with a broad therapeutic index there has been increasing recognition that standard doses may be subtherapeutic or toxic in critically ill patients. Optimising therapy for efficacy requires an established PK/PD target associated with clinical and microbiological cure. Method(s): Clinical and laboratory in vivo animal or human studies examining PK and/or PD of beta-lactam antibiotics in IE were eligible. Ovid MEDLINE, Embase and Cochrane Central Registry were searched using defined terms. Two authors reviewed s and full texts using Covidence software. Result(s): 62 articles were selected for review and synthesis. We identified 45 animal studies investigating the broad categories of beta-lactam diffusion into vegetations, PK/PD determinants of outcome, mode of antibiotic delivery and synergistic impact of agents. 17 human case studies/series totalling 347 participants reported antibiotic serum concentrations and clinical outcomes. Findings generally supported the importance of time-dependent killing for beta-lactams but heterogeneous data limited the determination of an optimal PK/PD target for IE treatment. Conclusion(s): Beta-lactam PK and PD in endocarditis is variable and specific to the particular antibiotic-organism combination. Timedependent killing is important, consistent with non-endocarditis studies, but there is little agreement on optimal drug exposure. Clinical studies examining various PK/PD targets in endocarditis patients are required to further inform drug selection and dosing.Copyright © 2023 Southern Society for Clinical Investigation.
ABSTRACT
BACKGROUND: Wards caring for COVID-19 patients, including intensive care units (ICUs), have an important focus on preventing transmission of SARS-CoV-2 to other patients and healthcare workers. AIM: To describe an outbreak of carbapenemase-producing Enterobacterales (CPE) in a COVID-19 ICU and to discuss key infection control measures enabling prompt termination of the cluster. METHODS: CPE were isolated from clinical specimens and screening swabs from intensive care patients with COVID-19 disease and from environmental screening. Whole-genome sequencing analysis was instrumental in informing phylogenetic relationships. FINDINGS: Seven clinical isolates and one environmental carbapenemase-producing Klebsiella pneumoniae isolate - all carrying OXA-48, CTX-M-15 and outer membrane porin mutations in ompK35/ompK36 - were identified with ≤1 single nucleotide polymorphism difference, indicative of clonality. A bundle of infection control interventions including careful adherence with contact precautions and hand hygiene, twice weekly screening for multidrug-resistant organisms, strict antimicrobial stewardship, and enhanced cleaning protocols promptly terminated the outbreak. CONCLUSION: Prolonged use of personal protective equipment is common with donning and doffing stations at the ward entrance, leaving healthcare workers prone to reduced hand hygiene practices between patients. Minimizing transmission of pathogens other than SARS-CoV-2 by careful adherence to normal contact precautions including hand hygiene, even during high patient contact manoeuvres, is critical to prevent outbreaks of multidrug-resistant organisms. Appropriate antimicrobial stewardship and screening for multidrug-resistant organisms must also be maintained throughout surge periods to prevent medium-term escalation in antimicrobial resistance rates. Whole-genome sequencing is highly informative for multidrug-resistant Enterobacterales surveillance strategies.