Genomics of Aminoglycoside Resistance in Pseudomonas aeruginosa Bloodstream Infections at a United States Academic Hospital.

Pseudomonas aeruginosa frequently becomes resistant to aminoglycosides by the acquisition of aminoglycoside modifying enzyme (AME) genes and the occurrence of mutations in the mexZ, fusA1, parRS, and armZ genes. We examined resistance to aminoglycosides in a collection of 227 P. aeruginosa bloodstream isolates collected over 2 decades from a single United States academic medical institution. Resistance rates of tobramycin and amikacin were relatively stable over this time, while the resistance rates of gentamicin were somewhat more variable. For comparison, we examined resistance rates to piperacillin-tazobactam, cefepime, meropenem, ciprofloxacin, and colistin. Resistance rates to the first four antibiotics were also stable, although uniformly higher for ciprofloxacin. Colistin resistance rates were initially quite low, rose substantially, and then began to decrease at the end of the study. Clinically relevant AME genes were identified in 14% of isolates, and mutations predicted to cause resistance were relatively common in the mexZ and armZ genes. In a regression analysis, resistance to gentamicin was associated with the presence of at least one gentamicin-active AME gene and significant mutations in mexZ, parS, and fusA1. Resistance to tobramycin was associated with the presence of at least one tobramycin-active AME gene. An extensively drug-resistant strain, PS1871, was examined further and found to contain five AME genes, most of which were within clusters of antibiotic resistance genes embedded in transposable elements. These findings demonstrate the relative contributions of aminoglycoside resistance determinants to P. aeruginosa susceptibilities at a United States medical center. IMPORTANCE Pseudomonas aeruginosa is frequently resistant to multiple antibiotics, including aminoglycosides. The rates of resistance to aminoglycosides in bloodstream isolates collected over 2 decades at a United States hospital remained constant, suggesting that antibiotic stewardship programs may be effective in countering an increase in resistance. Mutations in the mexZ, fusA1, parR, pasS, and armZ genes were more common than acquisition of genes encoding aminoglycoside modifying enzymes. The whole-genome sequence of an extensively drug resistant isolate indicates that resistance mechanisms can accumulate in a single strain. Together, these results suggest that aminoglycoside resistance in P. aeruginosa remains problematic and confirm known resistance mechanisms that can be targeted for the development of novel therapeutics.

Painful Convictions: Examining Pain Management Malpractice Claims From Incarcerated Patients, 2000-2020.

We aim to characterize the legal landscape of incarcerated patients' pain management malpractice claims and to discuss the ethical and policy implications that result. The most common rationales for lawsuits were failure to completely treat (38 [46.3%]), failure to offer (34 [41.4%]), and delay of treatment (6 [7.3%]). In cases won by defendants, the most common rationale for verdicts was no deliberate indifference occurred (74 [86.6%]). We found that incarcerated individuals were often unsuccessful in litigating claims for inadequate pain management despite several cases pointing toward treatment strategies far below what would be ethically accepted as standard of care in the community setting.

Off-Label studies on anakinra in dermatology: a review.

PURPOSE: Anakinra (Kineret®) is an interleukin-1 receptor antagonist (IL-1Ra) FDA approved for use in rheumatoid arthritis and in neonatal-onset multisystem inflammatory disease (NOMID). It has been used off-label for a variety of dermatologic conditions. A review of the available studies and cases of these off-label uses would be valuable to the dermatologist considering alternative treatments for these oftentimes poorly studied conditions. MATERIALS AND METHODS: The PubMed/MEDLINE, EMBASE, Scopus, and ClinicalTrials.gov databases were searched with the term 'anakinra.' Results were manually screened to identify published data on off-label uses of anakinra in dermatologic conditions and systemic conditions with prominent dermatologic manifestations. RESULTS: Anakinra appears to show efficacy for numerous dermatologic conditions, with the strongest evidence for hidradenitis suppurativa, Bechet's disease, Muckle-Wells syndrome, and SAPHO syndrome. Case reports and case series data are available for numerous other dermatologic conditions. CONCLUSION: Anakinra is a potential option for patients with certain difficult-to-treat dermatologic diseases, given its relatively benign adverse effect profile and its effectiveness in a wide array of conditions. Overall, anakinra appears to be a promising option in the treatment of numerous dermatologic inflammatory conditions refractory to first line therapies, but further and higher-quality data is needed to clarify its therapeutic role.

The Effect of Homelessness on Patient Wait Times in the Emergency Department.

BACKGROUND: Prolonged emergency department (ED) wait times could potentially lead to increased morbidity and mortality. While previous work has demonstrated disparities in wait times associated with race, information about the relationship between experiencing homelessness and ED wait times is lacking. OBJECTIVES: The purpose of this study was to explore the relationship between residence status (undomiciled vs. domiciled) and ED wait times. We hypothesized that being undomiciled would be associated with longer wait times. METHODS: We obtained data from the National Hospital Ambulatory Medical Care Survey from 2014 to 2017. We compared wait times in each triage category using t tests. We used multivariate linear regression to explore associations between residence status and wait times while controlling for other patient- and hospital-level variables. RESULTS: On average, undomiciled patients experienced significantly longer mean ED wait times than domiciled patients (53.4 vs. 38.9 min; p < 0.0001). In the multivariate model, undomiciled patients experienced significantly different wait times by 15.5 min (p = 0.0002). Undomiciled patients experienced increasingly longer waits vs. domiciled patients for the emergent and urgent triage categories (+33.5 min, p < 0.0001, and +22.7 min, p < 0.0001, respectively). CONCLUSIONS: Undomiciled patients experience longer ED wait times when compared with domiciled patients. This disparity is not explained by undomiciled patients seeking care in the ED for minor illness, because the disparity is more pronounced for urgent and emergent triage categories.

Off-label studies on tofacitinib in dermatology: a review.

PURPOSE: Tofacitinib citrate is an oral Janus kinase 1/3 inhibitor approved for rheumatoid arthritis, ulcerative colitis, and active psoriatic arthritis. Tofacitinib is being increasingly used off-label for dermatological conditions, with varying efficacy across recent studies. A review of these studies will be a helpful resource for dermatologists considering the use of tofacitinib for conditions refractory to first-line therapies. MATERIALS AND METHODS: MEDLINE, Embase, CINAHL Plus, Cochrane Library, Scopus, Web of Science, Clinicaltrials.gov, and the WHO International Clinical Trials Registry Platform were all searched for articles and trials mentioning the term 'tofacitinib', then manually reviewed to identify published data on off-label uses of tofacitinib. The article was structured according to the quality of the evidence available. RESULTS: Tofacitinib appears to show strong efficacy for numerous dermatologic conditions. Randomized controlled trial data is available for atopic dermatitis, alopecia areata, and plaque psoriasis. Case report and case series data is available for numerous other dermatologic conditions. CONCLUSION: While tofacitinib has a wide array of immunoregulatory properties, making it a possible candidate for treating many dermatologic conditions refractory to other treatments, further testing is needed to better characterize its efficacy and utility moving forward, as well as its safety and adverse effect profile.

Severe Shivering on Venoarterial Extracorporeal Membrane Oxygenation-Raising the Circuit Temperature to Stop Rhabdomyolysis: A Case Report.

We report a case of severe shivering resulting in rhabdomyolysis while on venoarterial extracorporeal membrane oxygenation (ECMO) that resolved after hyperthermia was induced using the ECMO circuit. The patient developed shivering approximately 24 hours after venoarterial ECMO cannulation for refractory ventricular tachycardia. The shivering caused rhabdomyolysis and necessitated cisatracurium infusion. The shivering failed to resolve after the patient was diagnosed and treated for ventilator-associated pneumonia. Suspecting sepsis as the etiology of shivering, the ECMO circuit temperature was increased to 38 °C, and the shivering was resolved. This case demonstrates therapeutic hyperthermia to treat infection-induced severe shivering and rhabdomyolysis while on ECMO.