Safety and tolerability of tedizolid as oral treatment for bone and joint infections.

Bone and joint infections (BJIs) are common infections increasingly managed with oral therapy. However, there are limited safe oral options for many Gram-positive pathogens. In animal studies and short-term human use, tedizolid lacks the hematologic and neurologic toxicity of the other available oxazolidinone, linezolid. However, there are limited prospective safety data. We conducted an open-label, non-comparative trial of oral tedizolid for BJI treatment. Primary outcomes were safety and cure rate. Eligible patients had a BJI caused by documented or suspected Gram-positive pathogen, required 4-12 weeks of therapy, and did not have myelosuppression or peripheral/optic neuropathy. Subjects underwent weekly evaluation for cytopenias and neuropathy. We enrolled 44 subjects; five were lost to follow-up. Two subjects did not complete planned treatment because of rash (n = 1) and urgent surgery (n = 1). Of 37 patients with evaluable outcomes, 17 (46%) had hardware-associated infection, 13 (35%) had osteomyelitis, 5 (14%) had prosthetic joint infection, and 2 (5%) had other BJIs. Median (mean, range) treatment duration was 12 (10.1, 4-12) weeks. There were no cases of cytopenias or peripheral or optic neuropathy. Treatment cure occurred in 13 (35%); 19 (51%) required antibiotic continuation after 12 weeks of tedizolid related to retained hardware at the BJI site, and failure occurred in four (11%), two unlikely, one possibly, and one probably due to tedizolid. We found that oral tedizolid was well tolerated for prolonged BJI treatment without significant toxicity. Clinical failure rate was similar to that of other published BJI investigations. (This study has been registered at Clinicaltrials.gov under identifier NCT03009045.) IMPORTANCE Bone and joint infections are common infections with limited effective and safe oral options for Gram-positive infections. The largest prospective clinical trial of tedizolid therapy for bone and joint infections enrolled 44 patients and tested each in person weekly with detailed safety monitoring including tests for leukopenia, anemia, thrombocytopenia, peripheral neuropathy, and optic neuropathy for up to 12 weeks. Findings demonstrated tedizolid was generally well tolerated and there were no incident cases of cytopenias or neuropathy. Cure rates were similar to that in other bone and joint infection studies. In summary, oral tedizolid appears to be a well-tolerated oral option for Gram-positive bone and joint infections.

A Disease-Specific Antibiogram to Evaluate Empiric Coverage Patterns in Fournier's Gangrene.

OBJECTIVE: To analyze our local antibiogram and antibiotic resistance patterns given concern for multidrug-resistant and fungal organisms in contemporary series detailing causative organisms in Fournier's Gangrene (FG). METHODS: All patients from 2018 to 2022 were identified from the institutional FG registry. Microorganisms and sensitivities were collected from operative tissue cultures. The primary outcome of this study was the adequacy of our empiric. Secondary outcomes included the rate of bacteremia, the concordance of blood cultures and tissue cultures, and the rate of fungal tissue infections. RESULTS: Escherichia coli and Streptococcus anginosus were most common, identified in 12 patients each (20.0%). Enterococcus faecalis (9, 15.0%), S agalactiae (8, 13.3%) and mixed cultures without a predominant organism (9, 15.0%) were also common. A fungal organism was identified in 9 (15.0%) patients. Patients who were started on Infectious Diseases Society of America guideline adherent antibiotic regimen were not significantly different in terms of bacteremia rate (P = .86), mortality (P = .25), length of stay (P = .27), or final antibiotic duration (P = .43) when compared to those on alternative regimens. Patients with a tissue culture positive for a fungal organism were not significantly different in terms of Fournier's Gangrene Severity Index (P = .25) or length of stay (P = .19). CONCLUSION: Local disease-specific antibiograms can be a powerful tool to guide empiric antibiotic therapy in FG. Although fungal infections are responsible for a majority of the gaps in empiric antimicrobial coverage at our institution they were present in only 15% of patients and their effect on outcomes does not justify addition of empiric antifungal agents.

Chlorhexidine and Mupirocin for Clearance of Methicillin-Resistant Staphylococcus aureus Colonization After Hospital Discharge: A Secondary Analysis of the Changing Lives by Eradicating Antibiotic Resistance Trial.

BACKGROUND: The CLEAR Trial demonstrated that a multisite body decolonization regimen reduced post-discharge infection and hospitalization in methicillin-resistant Staphylococcus aureus (MRSA) carriers. Here, we describe decolonization efficacy. METHODS: We performed a large, multicenter, randomized clinical trial of MRSA decolonization among adult patients after hospital discharge with MRSA infection or colonization. Participants were randomized 1:1 to either MRSA prevention education or education plus decolonization with topical chlorhexidine, oral chlorhexidine, and nasal mupirocin. Participants were swabbed in the nares, throat, axilla/groin, and wound (if applicable) at baseline and 1, 3, 6, and 9 months after randomization. The primary outcomes of this study are follow-up colonization differences between groups. RESULTS: Among 2121 participants, 1058 were randomized to decolonization. By 1 month, MRSA colonization was lower in the decolonization group compared with the education-only group (odds ration [OR] = 0.44; 95% confidence interval [CI], .36-.54; P ≤ .001). A similar magnitude of reduction was seen in the nares (OR = 0.34; 95% CI, .27-.42; P < .001), throat (OR = 0.55; 95% CI, .42-.73; P < .001), and axilla/groin (OR = 0.57; 95% CI, .43-.75; P < .001). These differences persisted through month 9 except at the wound site, which had a relatively small sample size. Higher regimen adherence was associated with lower MRSA colonization (P ≤ .01). CONCLUSIONS: In a randomized, clinical trial, a repeated post-discharge decolonization regimen for MRSA carriers reduced MRSA colonization overall and at multiple body sites. Higher treatment adherence was associated with greater reductions in MRSA colonization.

Sociodemographic index and global trends in prostate cancer: 1990-2017.

BACKGROUND: Considered globally, prostate cancer is a disease of the aging male that increases in prevalence with exposure to screening and diagnostic testing, and which requires a population with the health and longevity to encounter it. The Global Burden of Disease (GBD) dataset is an aggregation of worldwide registries and health data systems that reports global and regional assessment of disease impact. METHODS: Using the GBD database, 1171 worldwide registries and health registration systems from 1990 to 2016 were aggregated for prostate cancer disease codes and outcomes. Disease-Adjusted Life Years (DALYs) were calculated and segregated by sociodemographic index (SDI) quintile, and compared to other urologic diseases and tuberculosis (TB). RESULTS: Prostate cancer exerts a burden of disease that is vastly higher in the top quintile of SDI. The three lowest SDI quintiles represent the majority of global population but are currently less impacted by prostate cancer. Conversely, TB has its highest impact on the lowest SDI levels, although these rates are declining. CONCLUSIONS: As a global disease, prostate cancer predominantly affects high SDI men who enjoy a longer life expectancy in which to suffer from this disease and a greater exposure to screening and diagnosis. As lower SDI men are elevated in health and income, reallocation of DALYs will occur, and a greater burden of prostate cancer can be expected. These epidemiologic trends have great implications for the allocation of resources, as the population of men affected by prostate cancer outpaces urologic workforce growth.

Long-term Follow Up of Ileal Ureteral Replacement for Complex Ureteral Strictures: Single Institution Study.

OBJECTIVE: To report our 16-year experience with ileal ureter interposition for complex ureteral stricture. Ureteral reconstruction continues to evolve to include less invasive techniques to successfully manage ureteral stricture. However, long, complex, obliterative and especially radiated ureteral strictures are not amenable to less invasive techniques and may require Ileal ureter interposition. MATERIALS AND METHODS: Retrospective review of a single institution's ureteral reconstruction database was performed. Demographics, operative details, success rate, complication rate, and length of follow-up were noted. Unilateral replacements utilized ileal ureteral interposition. Success rate was defined as no need for further open intervention. RESULTS: Between 2003 and 2019, 188 ureteral reconstructions were performed, of which 46 required ileal ureter interposition. Of these 46 patients, 10 required bilateral reconstruction. Average age was 53 years, 26 (57%) were female. The average stricture length was 9.1 cm (2-20 cm). Stricture etiology included iatrogenic causes (n = 24, 52%), radiation causes (n = 12; 26%), vascular disease (n = 3; 7%), and idiopathic retroperitoneal fibrosis (n = 3; 7%). Forty-three surgeries were performed by open abdominal approach; 3 were performed robotically. The average length of operation was 412 minutes, blood loss 417 mL and LOS was 10 days. At mean follow up of 4.4 years (1-16 years), overall success rate was 83%, with 17% (n = 8) patients requiring subsequent major surgery (5 successful ureteral revision, 3 nephrectomy) and 11 (24%) patients experiencing a major complication. CONCLUSION: In our long-term follow up of over 4 years, ileal ureteral interposition remains a successful option for complex ureteral strictures in properly selected patients.

The rising worldwide impact of benign prostatic hyperplasia.

OBJECTIVES: To describe the trend in the impact of lower urinary tract symptoms attributed to benign prostatic hyperplasia (LUTS/BPH) on a global scale using the Global Burden of Disease (GBD) database. MATERIALS AND METHODS: Using the GBD database, worldwide data aggregated from registries and health systems from 1990 to 2017 were filtered for LUTS/BPH diagnoses. Calculation of years lived with disability (YLD) were compared with other urological diseases. YLD were calculated by a standardized method using assigned disability weights. The GBD-defined sociodemographic index (SDI) was used to assess impact of LUTS/BPH by global SDI quintile. RESULTS: Global Burden of Disease data over the 1990-2017 study period were summarized and global numbers and trends noted with other urological diseases for comparison. A total of 2 427 334 YLD were attributed to BPH in 2017 alone, almost three times more than those attributed to the next highest urological disease, prostate cancer (843 227 YLD). When stratified by SDI quintile, a much lower impact of BPH was found in the bottom three quintiles, despite this subset representing 66.9% of the 2017 world population. CONCLUSIONS: Lower urinary tract symptoms attributed to benign prostatic hyperplasia exert a rapidly rising human burden far exceeding other urological diseases. As the population ages and men in a lower SDI enjoy increased life expectancy and decreased competing mortalities, a continually accelerating wave of LUTS/BPH can be forecast. These epidemiological trends have serious implications for the future allocation of resources and the global urological workforce.

Detection of carbapenem resistant enterobacteriace from fomite surfaces.

Accurately identifying carbapenem resistant enterobacteriace (CRE) from fomites is critical for infection control practices, research, and assessing patient risk. We compared a commercial CRE agar intended for patient use with a modified MacConkey agar. We found that our modified MacConkey agar was more selective at identifying CRE from environmental sources.

A Retrospective Study of Patients Undergoing Radical Cystectomy and Receiving Peri-Operative Naloxegol or Alvimopan: Comparison of Length of Stay.

Alvimopan is a µ-opioid receptor antagonist used in the post-operative period to decrease rates of post-operative ileus (POI) following radical cystectomy (RC) and thereby shorten length of stay (LOS). Naloxegol is a much less expensive drug of the same class that has yet to be studied for prevention of POI in the peri-operative period. The purpose of the current study is to evaluate the differences in LOS and development of POI in patients post-RC who take alvimopan versus those who take naloxegol, with the hope that drug efficacy can be evaluated against the significant difference in cost burden between the two drugs. The study population included all adult patients between 18-89 years of age with bladder cancer undergoing radical cystectomy with urostomy at University of Colorado Hospital. Those patients who received usual post-operative care as well as either alvimopan or naloxegol between September 2011 and December 2017 were selected for analysis. Patients who did not take either medication or were switched from one drug to the other were excluded from the study. A zero-truncated binomial regression analysis was used to analyze differences in length of stay in patients who received alvimopan versus those who received naloxegol. Additionally, the incidence of post-operative ileus was compared between treatment groups. 130 patients who underwent RC and received either alvimopan or naloxegol were included in the study: 75 (58%) received alvimopan and 55 (42%) received naloxegol. Baseline characteristics were similar between treatment groups. There was no significant difference in the length of stay between patients who received alvimopan and patients who received naloxegol after adjusting for age, sex, BMI, length of surgical time, or stage of disease (p = 0.41). There was no significant between the two drugs for development of POI (p = 0.85). Development of POI was significantly associated with a longer LOS (p = 0.007). The analysis showed that naloxegol was comparable to alvimopan when it came to length of hospital stay following RC. Therefore, naloxegol may be offered as a less expensive, effective alternative to alvimopan.

Denial of a sleep deprivation message: situational and dispositional influences on message rejection.

Two studies investigated situational and dispositional influences on rejection of a sleep deprivation warning message for young adults. The hassle of protection (Study 1) and the self-relevance of the problem (Study 2) were manipulated; the disposition to use denial (threat orientation) for warning messages was measured. In both studies, it was found that both dispositional denial and the situational manipulation (more protection-hassle or self-relevance) showed at least one denial effect by reducing perceived susceptibility, perceived severity, or credibility. Indirect (mediational) effects were tested with the bootstrap method. In Study 1, judgments of credibility and severity mediated the effects of the hassle manipulation and denial orientation on message outcomes. In Study 2, credibility mediated the effects of the self-relevance manipulation and denial orientation on message outcomes of intentions to change and priority given to sleep. These studies show that both situational and dispositional sources of denial work in similar ways by lowering key message judgments and that the lower judgments lead to less priority given to a health risk and lower intentions to protect oneself.

Escherichia coli Sequence Type 131 H30 Is the Main Driver of Emerging Extended-Spectrum-ß-Lactamase-Producing E. coli at a Tertiary Care Center.

The H30 strain of Escherichia coli sequence type 131 (ST131-H30) is a recently emerged, globally disseminated lineage associated with fluoroquinolone resistance and, via its H30Rx subclone, the CTX-M-15 extended-spectrum beta-lactamase (ESBL). Here, we studied the clonal background and resistance characteristics of 109 consecutive recent E. coli clinical isolates (2015) and 41 historical ESBL-producing E. coli blood isolates (2004 to 2011) from a public tertiary care center in California with a rising prevalence of ESBL-producing E. coli isolates. Among the 2015 isolates, ST131, which was represented mainly by ST131-H30, was the most common clonal lineage (23% overall). ST131-H30 accounted for 47% (8/17) of ESBL-producing, 47% (14/30) of fluoroquinolone-resistant, and 33% (11/33) of multidrug-resistant isolates. ST131-H30 also accounted for 53% (8/14) of dually fluoroquinolone-resistant, ESBL-producing isolates, with the remaining 47% comprised of diverse clonal groups that contributed a single isolate each. ST131-H30Rx, with CTX-M-15, was the major ESBL producer (6/8) among ST131-H30 isolates. ST131-H30 and H30Rx also dominated (46% and 37%, respectively) among the historical ESBL-producing isolates (2004 to 2011), without significant temporal shifts in relative prevalence. Thus, this medical center's recently emerging ESBL-producing E. coli strains, although multiclonal, are dominated by ST131-H30 and H30Rx, which are the only clonally expanded fluoroquinolone-resistant, ESBL-producing lineages. Measures to rapidly and effectively detect, treat, and control these highly successful lineages are needed. IMPORTANCE The ever-rising prevalence of resistance to first-line antibiotics among clinical Escherichia coli isolates leads to worse clinical outcomes and higher health care costs, thereby creating a need to discover its basis so that effective interventions can be developed. We found that the H30 subset within E. coli sequence type 131 (ST131-H30) is currently, and has been since at least 2004, the main E. coli lineage contributing to key resistance phenotypes-including extended-spectrum-beta-lactamase (ESBL) production, fluoroquinolone resistance, multidrug resistance, and dual ESBL production-plus-fluoroquinolone resistance-at a United States tertiary care center with a rising prevalence of ESBL-producing E. coli isolates. This identifies ST131-H30 as a target for diagnostic tests and preventive measures designed to curb the emergence of multidrug-resistant E. coli isolates and/or to blunt its clinical impact.

Prevalence of and Factors Associated With Multidrug Resistant Organism (MDRO) Colonization in 3 Nursing Homes.

Nursing home residents are at risk for acquiring and transmitting MDROs. A serial point-prevalence study of 605 residents in 3 facilities using random sampling found MDRO colonization in 45% of residents: methicillin-resistant Staphylococcus aureus (MRSA, 26%); extended-spectrum ß-lactamase-producing Enterobacteriaceae (ESBL, 17%); vancomycin-resistant Enterococcus spp. (VRE, 16%); carbapenem-resistant Enterobacteriaceae (CRE, 1%). MDRO colonization was associated with history of MDRO, care needs, incontinence, and catheters. Infect Control Hosp Epidemiol 2016;1485-1488.