Molecular genetic testing does not improve the detection of fluoroquinolone resistance before transrectal prostate biopsy.

Background: Fluoroquinolone-resistant (FQR) Escherichia coli (E. coli) causes transrectal prostate biopsy infections. We seek to further identify fluoroquinolones resistance by the incorporation of genetic profiling to influence antibiotic selection for transrectal prostate biopsy and whether the addition of this genetic testing could improve the prediction of FQR detection at the time of biopsy. Materials and methods: In this prospective observational cohort study, rectal swabs were collected within 30 days of an upcoming prostate biopsy. These swabs were sent for phenotypic and genotypic assessment to predict FQR on the day of the biopsy. Phenotype: Specimens were inoculated onto MacConkey agar containing ciprofloxacin using standard culture techniques to determine FQR status. Genotype: We compared cultures to polymerase chain reaction (PCR) sequence typing (E.coli- ST131/H30/ST69) and bacterial plasmids (gyrA, qnrQ, and qnrS). The presence of FQR on this testing was compared to the second rectal swab collected just before biopsy (2 hours after ciprofloxacin prophylaxis), which served as the gold standard for FQR. Results: Overall, the FQR rate was 23.6%. The bacterial plasmids (qnr) were present in 54.1% of samples, and multidrug-resistant E. coli ST131 was present in 12.5% of samples. In comparison, phenotypic assessment using rectal culture had a better prediction for the presence of FQR as compared to genotypic testing [area under the curve (AUC) = 0.85 in phenotype arm vs. AUC = 0.45 in genotype arm]. Conclusion: We detected a high prevalence of FQR genes in the rectum, but the addition of PCR-based genotyping did not improve the prediction of culture-based FQR at the time of biopsy.

Efficacy of interferon beta-1a plus remdesivir compared with remdesivir alone in hospitalised adults with COVID-19: a double-bind, randomised, placebo-controlled, phase 3 trial.

BACKGROUND: Functional impairment of interferon, a natural antiviral component of the immune system, is associated with the pathogenesis and severity of COVID-19. We aimed to compare the efficacy of interferon beta-1a in combination with remdesivir compared with remdesivir alone in hospitalised patients with COVID-19. METHODS: We did a double-blind, randomised, placebo-controlled trial at 63 hospitals across five countries (Japan, Mexico, Singapore, South Korea, and the USA). Eligible patients were hospitalised adults (aged ≥18 years) with SARS-CoV-2 infection, as confirmed by a positive RT-PCR test, and who met one of the following criteria suggestive of lower respiratory tract infection: the presence of radiographic infiltrates on imaging, a peripheral oxygen saturation on room air of 94% or less, or requiring supplemental oxygen. Patients were excluded if they had either an alanine aminotransferase or an aspartate aminotransferase concentration more than five times the upper limit of normal; had impaired renal function; were allergic to the study product; were pregnant or breast feeding; were already on mechanical ventilation; or were anticipating discharge from the hospital or transfer to another hospital within 72 h of enrolment. Patients were randomly assigned (1:1) to receive intravenous remdesivir as a 200 mg loading dose on day 1 followed by a 100 mg maintenance dose administered daily for up to 9 days and up to four doses of either 44 µg interferon beta-1a (interferon beta-1a group plus remdesivir group) or placebo (placebo plus remdesivir group) administered subcutaneously every other day. Randomisation was stratified by study site and disease severity at enrolment. Patients, investigators, and site staff were masked to interferon beta-1a and placebo treatment; remdesivir treatment was given to all patients without masking. The primary outcome was time to recovery, defined as the first day that a patient attained a category 1, 2, or 3 score on the eight-category ordinal scale within 28 days, assessed in the modified intention-to-treat population, defined as all randomised patients who were classified according to actual clinical severity. Safety was assessed in the as-treated population, defined as all patients who received at least one dose of the assigned treatment. This trial is registered with ClinicalTrials.gov, NCT04492475. FINDINGS: Between Aug 5, 2020, and Nov 11, 2020, 969 patients were enrolled and randomly assigned to the interferon beta-1a plus remdesivir group (n=487) or to the placebo plus remdesivir group (n=482). The mean duration of symptoms before enrolment was 8·7 days (SD 4·4) in the interferon beta-1a plus remdesivir group and 8·5 days (SD 4·3) days in the placebo plus remdesivir group. Patients in both groups had a time to recovery of 5 days (95% CI not estimable) (rate ratio of interferon beta-1a plus remdesivir group vs placebo plus remdesivir 0·99 [95% CI 0·87-1·13]; p=0·88). The Kaplan-Meier estimate of mortality at 28 days was 5% (95% CI 3-7%) in the interferon beta-1a plus remdesivir group and 3% (2-6%) in the placebo plus remdesivir group (hazard ratio 1·33 [95% CI 0·69-2·55]; p=0·39). Patients who did not require high-flow oxygen at baseline were more likely to have at least one related adverse event in the interferon beta-1a plus remdesivir group (33 [7%] of 442 patients) than in the placebo plus remdesivir group (15 [3%] of 435). In patients who required high-flow oxygen at baseline, 24 (69%) of 35 had an adverse event and 21 (60%) had a serious adverse event in the interferon beta-1a plus remdesivir group compared with 13 (39%) of 33 who had an adverse event and eight (24%) who had a serious adverse event in the placebo plus remdesivir group. INTERPRETATION: Interferon beta-1a plus remdesivir was not superior to remdesivir alone in hospitalised patients with COVID-19 pneumonia. Patients who required high-flow oxygen at baseline had worse outcomes after treatment with interferon beta-1a compared with those given placebo. FUNDING: The National Institute of Allergy and Infectious Diseases (USA).

Microbiome diversity in carriers of fluoroquinolone resistant Escherichia coli.

Purpose: Fluoroquinolone-resistant (FQR) Escherichia coli causes transrectal prostate biopsy infections. In order to reduce colonization of these bacteria in carriers, we would like to understand the surrounding microbiome to determine targets for decolonization. Materials and Methods: We perform an observational study to investigate the microbiome differences in men with and without FQR organisms found on rectal culture. A rectal swab with two culturettes was performed on men before an upcoming prostate biopsy procedure as standard of care to perform "targeted prophylaxis." Detection of FQR was performed by the standard microbiology lab inoculates the swab onto MacConkey agar containing ciprofloxacin. The extra swab was sent for 16S rRNA amplicon sequencing (MiSeq paired-end) using the V1V2 primer. Alpha and beta-diversity analysis were performed using QIIME. We used PERMANOVA to evaluate the statistical significance of beta-diversity distances within and between groups of interest. Results: We collected 116 rectal swab samples before biopsy for 16S rRNA amplicon sequencing. We identified 18 isolates (15.5%, 18/116) that were positive and had relative reduced diversity profiles (p<0.05). Enterobacteriaceae were significantly over-represented in the FQR subjects (adjusted p=0.03). Conclusions: Microbiome analysis determined that men colonized with FQR bacteria have less diverse bacterial communities (dysbiosis), higher levels of Enterobacteriaceae and reduced levels of Prevotella disiens. These results may have implications in pre/probiotic intervention studies.

Effectiveness of an Antimicrobial Stewardship Approach for Urinary Catheter-Associated Asymptomatic Bacteriuria.

IMPORTANCE: Overtreatment of asymptomatic bacteriuria (ASB) in patients with urinary catheters remains high. Health care professionals have difficulty differentiating cases of ASB from catheter-associated urinary tract infections. OBJECTIVES: To evaluate the effectiveness and sustainability of an intervention to reduce urine culture ordering and antimicrobial prescribing for catheter-associated ASB compared with standard quality improvement methods. DESIGN, SETTING, AND PARTICIPANTS: A preintervention and postintervention comparison with a contemporaneous control group from July 2010 to June 2013 at 2 Veterans Affairs health care systems. Study populations were patients with urinary catheters on acute medicine wards and long-term care units and health care professionals who order urine cultures and prescribe antimicrobials. INTERVENTION: A multifaceted guidelines implementation intervention. MAIN OUTCOMES AND MEASURES: The primary outcomes were urine cultures ordered per 1000 bed-days and cases of ASB receiving antibiotics (overtreatment) during intervention and maintenance periods compared with baseline at both sites. Patient-level analysis of inappropriate antimicrobial use adjusted for individual covariates. RESULTS: Study surveillance included 289,754 total bed-days. The overall rate of urine culture ordering decreased significantly during the intervention period (from 41.2 to 23.3 per 1000 bed-days; incidence rate ration [IRR], 0.57; 95% CI, 0.53-0.61) and further during the maintenance period (to 12.0 per 1000 bed-days; IRR, 0.29; 95% CI, 0.26-0.32) (P < .001 for both). At the comparison site, urine cultures ordered did not change significantly across all 3 periods. There was a significant difference in the number of urine cultures ordered per month over time when comparing the 2 sites using longitudinal linear regression (P < .001). Overtreatment of ASB at the intervention site fell significantly during the intervention period (from 1.6 to 0.6 per 1000 bed-days; IRR, 0.35; 95% CI, 0.22-0.55), and these reductions persisted during the maintenance period (to 0.4 per 1000 bed-days; IRR, 0.24; 95% CI, 0.13-0.42) (P < .001 for both). Overtreatment of ASB at the comparison site was similar across all periods (odds ratio, 1.32; 95% CI, 0.69-2.52). When analyzed by type of ward, the decrease in ASB overtreatment was significant in long-term care. CONCLUSIONS AND RELEVANCE: A multifaceted intervention targeting health care professionals who diagnose and treat patients with urinary catheters reduced overtreatment of ASB compared with standard quality improvement methods. These improvements persisted during a low-intensity maintenance period. The impact was more pronounced in long-term care, an emerging domain for antimicrobial stewardship.

Clindamycin-resistant methicillin-resistant Staphylococcus aureus: epidemiologic and molecular characteristics and associated clinical factors.

In this prospective, observational study of 618 consecutive adult patients with skin and soft tissue infections (SSTI) caused by methicillin-resistant Staphylococcus aureus (MRSA), the clinical characteristics, molecular epidemiology, and outcome of patients with clindamycin-resistant MRSA (n = 64) and clindamycin-susceptible MRSA (n = 554) were compared (including factors predictive of clindamycin-resistant MRSA SSTI). Patients with clindamycin-resistant MRSA were more likely to have had antibiotic exposure within 3 months (37.5% versus 17%, P < 0.01), surgery (25% versus 8%, P < 0.01), MRSA infection/colonization within 12 months (23% versus 7%, P < 0.01), or intravascular catheters (5% versus 0.5%, P = 0.02). On multivariate analysis, previous surgery (adjusted odds ratio [AOR] 2.97; 95% confidence interval [CI] 1.5-6.0), history of MRSA (AOR 3.4; 95% CI 1.7-7.1), and exposure to clindamycin (AOR 8.5; 95% CI 2.3-32) and to macrolides (AOR 7.2, 95% CI 1.6-31.8) were independently associated with presence of clindamycin-resistant MRSA. Clinical resolution was similar between groups (77% versus 68%; P = 0.26). Clindamycin-resistant MRSA was less often USA-300 (82% versus 98%, P = 0.004). Clindamycin resistance did not affect MRSA-SSTI clinical outcomes.

Recurrent skin and soft tissue infections due to methicillin-resistant Staphylococcus aureus requiring operative debridement.

BACKGROUND: The aim of this study was to examine clinical factors associated with the recurrence of community-onset skin and soft tissue infections caused by methicillin-resistant Staphylococcus aureus. METHODS: An observational case-comparison study based on a retrospective review of medical records was conducted in a public health system. All patients with community-onset skin and soft tissue infections caused by methicillin-resistant S aureus who underwent operative debridement from January 1999 to December 2003 were included. The outcome of interest was recurrence within 1 year. RESULTS: Two hundred fifty-three patients met the criteria for inclusion. Fifty-three (21%) patients returned with recurrent episodes. These patients were compared with 200 patients (79%) who did not develop recurrence. On multivariate analysis, factors independently predictive of recurrence were medical history of abscess requiring surgical debridement within the previous year (adjusted odds ratio, 2.6; 95% confidence interval, 1.4-5.0; P = .002) and obesity (adjusted odds ratio, 3.4; 95% confidence interval, 1.4-8.8; P = .008). CONCLUSIONS: Patients with obesity or histories of methicillin-resistant S aureus infection are at significantly increased risk for recurrent soft tissue infection.

Correlation between respiratory colonization with gram-negative bacteria and development of gram-negative bacterial infection after cardiac surgery.

This pilot, observational study involving 286 patients who underwent cardiac surgery found that patients who had endotracheal colonization with gram-negative bacteria at 1 week after surgery were more likely to develop subsequent infection compared to those without colonization (8 of 23 vs. 4 of 40; relative risk 2.3 [95% confidence interval, 1.3-4.1; P value <.05]).