Background: Infections due to antibiotic resistant bacteria are increasing worldwide and while, the epidemiology of these pathogens is well described in adults, pediatric specific data are lacking. We sought to gain an understanding of the risk factors for multi-drug resistant Gram-negative (MDRGN) infections in our pediatric population. Methods: We performed a retrospective review of pediatric patients seen at a pediatric hospital system in 2022 who had a culture-positive MDRGN, which was defined as a gram-negative bacteria resistant or intermediate to at least 1 antibiotic in ≥ 3 antibiotic groups. Repeat positive cultures for the same MDRGN were considered a single infection episode if occurring within a 14-day period. Demographic, clinical, and microbiologic data was obtained from the electronic medical record. Fisher’s exact was used for analysis. Results: One hundred and seventy-nine children had 237 infection episodes during the study period. Eighty-one patients (45%) were male and the median age was 5.3 years. The most prevalent MDRGNs included: Escherichia coli (154, 65%), Klebsiella spp (52, 22%), and Enterobacter spp (16, 7%). Escherichia coli was significantly more likely than other pathogens to be isolated from the urine (P = 0.008). Compared to multi-drug resistant E. coli, patients with a non-E. coli MDRGN were significantly more likely to have an underlying medical condition, recent hospitalization and antibiotic use (P≤0.001 for each, Table 1). A carbapenem was administered in 32% (75/237) of infection episodes. There were only 6 carbapenem resistant organisms. Conclusions: In our study, E. coli was the most frequent MDRGN. Most patients with a non-E. coli MDRGN infection episode had an underlying medical condition, recent hospitalization and antibiotic use. Carbapenem resistance was infrequent, though surveillance studies are needed to identify changing antibiotic resistance patterns and to direct prevention measures.

Background: Carbapenem-resistant Pseudomonas aeruginosa (CRPA) is a frequent cause of healthcare-associated infections (HAIs). The CDC Emerging Infections Program (EIP) conducted population and laboratory-based surveillance of CRPA in selected areas in 8 states from August 1, 2016, through July 31, 2018. We aimed to describe the molecular epidemiology and mechanisms of resistance of CRPA isolates collected through this surveillance. Methods: We defined a case as the first isolate of P. aeruginosa resistant to imipenem, meropenem, or doripenem from the lower respiratory tract, urine, wounds, or normally sterile sites identified from a resident of the EIP catchment area in a 30-day period; EIP sites submitted a systematic random sample of isolates to CDC for further characterization. Of 1,021 CRPA clinical isolates submitted, 707 have been sequenced to date using an Illumina MiSeq. Sequenced genomes were classified using the 7-gene multilocus sequence typing (MLST) scheme, and a core genome MLST (cgMLST) scheme was used to determine phylogeny. Antimicrobial resistance genes were identified using publicly available databases, and chromosomal mechanisms of carbapenem resistance were determined using previously validated genetic markers. Results: There were 189 sequence types (STs) among the 707 sequenced genomes (Fig. 1). The most frequently occurring were high-risk clones ST235 (8.5%) and ST298 (4.7%), which were found across all EIP sites. Carbapenemase genes were identified in 5 (<1%) isolates. Overall, 95.6% of the isolates had chromosomal mutations associated with carbapenem resistance: 93.2% had porinD-associated mutations that decrease membrane permeability to the drugs; 24.8% had mutations associated with overexpression of the multidrug efflux pump MexAB-OprM; and 22.9% had mutations associated with overexpression of the endogenous β-lactamase ampC. More than 1 such chromosomal resistance mutation type was present in 37.8% of the isolates. Conclusions: The diversity of the sequence types demonstrates that HAIs caused by CRPA can arise from a variety of strains and that high-risk clones are broadly disseminated across the EIP sites but are a minority of CRPA strains overall. Carbapenem resistance in P. aeruginosa was predominantly driven by chromosomal mutations rather than acquired mechanisms (ie, carbapenemases). The diversity of the CRPA isolates and the lack of carbapenemase genes suggest that this ubiquitous pathogen can readily evolve chromosomal resistance mechanisms, but unlike carbapenemases, these cannot be easily spread through horizontal transfer.

Funding: None

Disclosures: None

A widespread view in the philosophy of mind and action holds that intentions are propositional attitudes. Call this view ‘Propositionalism about Intention’. The key alternative holds that intentions have acts, or do-ables, as their contents. Propositionalism is typically accepted by default, rather than argued for in any detail. By appealing to a key metaphysical constraint on any account of intention, I argue that on the contrary, it is the Do-ables View which deserves the status of the default position, and Propositionalism which bears the burden of proof. I go on to show that this burden has not been met in the literature.

Anscombe thought that practical knowledge – a person’s knowledge of what she is intentionally doing – displays formal differences to ordinary empirical, or ‘speculative’, knowledge. I suggest these differences rest on the fact that practical knowledge involves intention analogously to how speculative knowledge involves belief. But this claim conflicts with the standard conception of knowledge, according to which knowledge is an inherently belief-involving phenomenon. Building on John Hyman’s account of knowledge as the ability to use a fact as a reason, I develop an alternative, two-tier, epistemology which allows that knowledge might really come in a belief-involving and an intention-involving form.

Adaptive management (AM) emerged in the literature in the mid-1970s in response both to a realization of the extent of uncertainty involved in management, and a frustration with attempts to use modelling to integrate knowledge and make predictions. The term has since become increasingly widely used in scientific articles, policy documents and management plans, but both understanding and application of the concept is mixed. This paper reviews recent literature from conservation and natural resource management journals to assess diversity in how the term is used, highlight ambiguities and consider how the concept might be further assessed. AM is currently being used to describe many different management contexts, scales and locations. Few authors define the term explicitly or describe how it offers a means to improve management outcomes in their specific management context. Many do not adhere to the idea as it was originally conceived, despite citing seminal work. Significant confusion exists over the distinction between active and passive approaches. Over half of the studies reporting to implement AM claimed to have done so successfully, yet none quantified specific benefits, or costs, in relation to possible alternatives. Similarly those studies reporting to assess the approach did so only in relation to specific models and their parameterizations; none assessed the benefits or costs of AM in the field. AM is regarded by some as an effective and well-established framework to support the management of natural resources, yet by others as a concept difficult to realize and fraught with implementation challenges; neither of these observations is wholly accurate. From a scientific and technical perspective many practical questions remain; in particular real-world assessments of the value of experimentation within a management framework, as well as of identified challenges and pathologies, are needed. Further discussion and systematic assessment of the approach is required, together with greater attention to its definition and description, enabling the assessment of new approaches to managing uncertainty, and AM itself.