Escherichia coli K-12 strains are normally tolerant to n-hexane and susceptible to cyclohexane. Constitutive expression of marA of the multiple antibiotic resistance (mar) locus or of the soxS or robA gene product produced tolerance to cyclohexane. Inactivation of the mar locus or the robA locus, but not the soxRS locus, increased organic solvent susceptibility in the wild type and Mar mutants (to both n-hexane and cyclohexane). The organic solvent hypersusceptibility is a newly described phenotype for a robA-inactivated strain. Multicopy expression of mar, soxS, or robA induced cyclohexane tolerance in strains with a deleted or inactivated chromosomal mar, soxRS, or robA locus; thus, each transcriptional activator acts independently of the others. However, in a strain with 39 kb of chromosomal DNA, including the mar locus, deleted, only the multicopy complete mar locus, consisting of its two operons, produced cyclohexane tolerance. Deletion of acrAB from either wild-type E. coli K-12 or a Mar mutant resulted in loss of tolerance to both n-hexane and cyclohexane. Organic solvent tolerance mediated by mar, soxS, or robA was not restored in strains with acrAB deleted. These findings strongly suggest that active efflux specified by the acrAB locus is linked to intrinsic organic solvent tolerance and to tolerance mediated by the marA, soxS, or robA gene product in E. coli.

Background and objectives The calcimimetic cinacalcet reduced the risk of death or cardiovascular (CV) events in older, but not younger, patients with moderate to severe secondary hyperparathyroidism (HPT) who were receiving hemodialysis. To determine whether the lower risk in younger patients might be due to lower baseline CV risk and more frequent use of cointerventions that reduce parathyroid hormone (kidney transplantation, parathyroidectomy, and commercial cinacalcet use), this study examined the effects of cinacalcet in older ($65 years, n=1005) and younger (,65 years, n=2878) patients.Design, setting, participants, & measurements Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events (EVOLVE) was a global, multicenter, randomized placebo-controlled trial in 3883 prevalent patients on hemodialysis, whose outcomes included death, major CV events, and development of severe unremitting HPT. The age subgroup analysis was prespecified.Results Older patients had higher baseline prevalence of diabetes mellitus and CV comorbidity. Annualized rates of kidney transplantation and parathyroidectomy were .3-fold higher in younger relative to older patients and were more frequent in patients randomized to placebo. In older patients, the adjusted relative hazard (95% confidence interval) for the primary composite (CV) end point (cinacalcet versus placebo) was 0.70 (0.60 to 0.81); in younger patients, the relative hazard was 0.97 (0.86 to 1.09). Corresponding adjusted relative hazards for mortality were 0.68 (0.51 to 0.81) and 0.99 (0.86 to 1.13). Reduction in the risk of severe unremitting HPT was similar in both groups. ConclusionsIn the EVOLVE trial, cinacalcet decreased the risk of death and of major CV events in older, but not younger, patients with moderate to severe HPT who were receiving hemodialysis. Effect modification by age may be partly explained by differences in underlying CV risk and differential application of cointerventions that reduce parathyroid hormone.

The multiple antibiotic resistance (mar) locus in Escherichia coli consists of two divergently expressed operons (marC and marRAB), both of which contribute to the Mar phenotype. Overexpression of the marRAB operon protected E. coli against rapid cell killing by fluoroquinolones. Inactivation of the operon in mar mutants restored a wild-type bactericidal susceptibility. Both operons of the locus were required for protection from the quinolone-mediated bactericidal activity in mar locus deletion mutants. The effect was lost at high concentrations of fluoroquinolones, unlike the case for the previously described genes hipA and hipQ. The inducible mar locus appears to specify a novel antibactericidal mechanism which may play a role in the emergence of fluoroquinolone-resistant clinical E. coli isolates.

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Fluoroquinolone resistance in Escherichia coli is principally caused by two kinds of mutation: those affecting the target proteins of the drugs, i.e. DNA gyrase and topoisomerase IV, and those affecting regulatory genes such as marA, soxS or robA. Recently, overexpression of the latter genes was linked to increased organic solvent tolerance in E. coli. Among 138 clinical fluoroquinolone-resistant and -susceptible clinical isolates of E. coli we found a high association between fluoroquinolone resistance and organic solvent tolerance. This finding suggests that E. coli may undergo an adaptive response to extrinsic substances other than quinolones, while mutating to fluoroquinolone resistance.

Background: Acute kidney injury (AKI) is a serious complication of COVID-19. Methods: Records of hospitalized adult patients with confirmed SARS-CoV-2 infection from 1 March to 31 May 2020 were retrospectively reviewed. Results: Of 283 patients, AKI occurred in 40.6%. From multivariate analyses, the risk factors of AKI in COVID-19 can be divided into: (1) demographics/co-morbidities (male, increasing age, diabetes, chronic kidney disease); (2) other organ involvements (transaminitis, elevated troponin I, ST segment/T wave change on electrocardiography); (3) elevated biomarkers (ferritin, lactate dehydrogenase); (4) possible bacterial co-infection (leukocytosis, elevated procalcitonin); (5) need for advanced oxygen delivery (non-invasive positive pressure ventilation, mechanical ventilation); and (6) other critical features (ICU admission, need for vasopressors, acute respiratory distress syndrome). Most AKIs were due to pre-renal (70.4%) and intrinsic (34.8%) causes. Renal replacement therapy was more common in intrinsic AKI. Both pre-renal (HR 3.2; 95% CI 1.7–5.9) and intrinsic AKI (HR 7.7; 95% CI 3.6–16.3) were associated with higher mortality. Male, stage 3 AKI, higher baseline and peak serum creatinine and blood urea nitrogen were prevalent in intrinsic AKI. Urine analysis and the fractional excretion of sodium and urea were not helpful in distinguishing intrinsic AKI from other causes. Conclusions: AKI is very common in COVID-19 and is associated with higher mortality. Characterization of AKI is warranted due to its diverse nature and clinical outcome.

Hospital-acquired infections (HAIs) pose a serious threat to patients, and hospitals spend billions of dollars each year to reduce and treat these infections. Many HAIs are due to contamination from workers’ hands and contact with high-touch surfaces. Therefore, we set out to test the efficacy of a new preventative technology, AIONX® Antimicrobial Technologies, Inc’s cleanSURFACES®, which is designed to complement daily chemical cleaning events by continuously preventing re-colonization of surfaces. To that end, we swabbed surfaces before (Baseline) and after (Post) application of the cleanSURFACES® at various time points (Day 1, Day 7, Day 14, and Day 28). To circumvent limitations associated with culture-based and 16S rRNA gene amplicon sequencing methodologies, these surface swabs were processed using metatranscriptomic (RNA) analysis to allow for comprehensive taxonomic resolution and the detection of active microorganisms. Overall, there was a significant (P < 0.05) global reduction of microbial diversity in Post-intervention samples. Additionally, Post sample microbial communities clustered together much more closely than Baseline samples based on pairwise distances calculated with the weighted Jaccard distance metric, suggesting a defined shift after product application. This shift was characterized by a general depletion of several microbes among Post samples, with multiple phyla also being reduced over the duration of the study. Notably, specific clinically relevant microbes, including Staphylococcus aureus, Clostridioides difficile and Streptococcus spp., were depleted Post-intervention. Taken together, these findings suggest that chemical cleaning events used jointly with cleanSURFACES® have the potential to reduce colonization of surfaces by a wide variety of microbes, including many clinically relevant pathogens.

Septic arthritis of the temporomandibular joint (TMJ) is a rare event that has only been reported a few dozen times worldwide. This case is remarkable for septic arthritis of the TMJ joint in an otherwise healthy male.Case Report:A 24-year-old male presented to the emergency department with periauricular swelling, erythema, fever, myalgia's and generalized joint pain. He had previously sought medical attention and was placed on ciprofloxacin. However, he developed facial swelling and a rash and had to discontinue the antibiotic. On physical exam the patient had a large swelling and tenderness in his left periauricular area, with erythema and deviation of the right mandible which limited his ability to open the mouth. A computed tomography showed mild asymmetric soft tissue swelling in the left pharyngeal region but did not show joint effusion. Subsequent magnetic resonance imaging did show effusion of the joint space. The effusion was drained, and the synovial fluid was submitted for gram stain, culture, and sensitivity. The cultures grew menthicillin sensitive Staphyloccocus Aureus. The patient was discharged to complete a two week course of intravenous (IV) Ceftriaxone and IV Vancomycin via home infusion.Conclusion:Septic Arthritis of the TMJ is a rare event with very specific clinical symptoms. Due to the low sensitivity of the computed tomography scan, magnetic resonance imaging should be considered when computed tomography scan is negative for TMJ effusion.