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Background Prosthetic joint infection (PJI) of the knee carries significant morbidity, mortality, and economic cost. We hypothesize that obese and poor medical hosts will have a significant and additive increase in failure rate undergoing 2-stage revision total knee arthroplasty for PJI. Methods All 2-stage revision total knee arthroplasty procedures for PJI performed at one institution were identified between 2005 and 2020. In total, 144 patients were included and defined as success or failure based on published criteria regarding infection eradication, further intervention, or mortality. The American Society of Anesthesiologists score and the Charlson Comorbidity Index were utilized to assess host grade. Patient, surgical, and microbiologic variables were investigated with univariable and multivariable analysis to explore association with risk of failure. Results In the cohort, 32.4% of patients failed with mean follow-up of 5.1 years. In multivariable analysis, the number of major operations requiring arthrotomy and implantation of new material between the primary and first stage, host grade, and elevated body mass index were the major contributors to failure. Combining these factors, with body mass index >30 and 2 or more major operations, the failure rate increased to 76.5% and 71.4% respectively for American Society of Anesthesiologists score 3 (P ≤ .001) and Charlson Comorbidity Index ≥2 (P ≤ .001). Conclusion In this cohort, multiple major operations between the primary and first stage, host grade, and obesity were the major contributors to failure. When combining these factors, patients had an additive increase in failure rate. Treatments such as amputation or less invasive options and suppression should be discussed and considered in these patients.

Mycobacterium tuberculosis is a facultative anaerobe and its characteristic pathological hallmark, the granuloma, exhibits hypoxia in humans and in most experimental models. Thus the host and bacillary adaptation to hypoxia is of central importance in understanding pathogenesis and thereby to derive new drug treatments and vaccines.

Gene-directed enzyme prodrug therapy (GDEPT) aims to achieve highly selective tumor-cell killing through the use of tumor-tropic gene delivery vectors coupled with systemic administration of otherwise inert prodrugs. Nitroaromatic prodrugs such as CB1954 hold promise for GDEPT as they are readily reduced to potent DNA alkylating agents by bacterial nitroreductase enzymes (NTRs). Transfection with the nfsB gene from Escherichia coli can increase the sensitivity of tumor cells to CB1954 by greater than 1000-fold. However, poor catalytic efficiency limits the activation of CB1954 by NfsB at clinically relevant doses. A lack of flexible, high-throughput screening technology has hindered efforts to discover superior NTR candidates. Here we demonstrate how the SOS chromotest and complementary screening technologies can be used to evaluate novel enzymes that activate CB1954 and other bioreductive and/or genotoxic prodrugs. We identify the major E. coli NTR, NfsA, as 10-fold more efficient than NfsB in activating CB1954 as purified protein (k(cat)/K(m)) and when over-expressed in an E. coli nfsA(-)/nfsB(-) gene deleted strain. NfsA also confers sensitivity to CB1954 when expressed in HCT-116 human colon carcinoma cells, with similar efficiency to NfsB. In addition, we identify two novel E. coli NTRs, AzoR and NemA, that have not previously been characterized in the context of nitroaromatic prodrug activation.