In vitro identification of underutilized ß-lactam combinations against methicillin-resistant Staphylococcus aureus bacteremia isolates.

Methicillin-resistant Staphylococcus aureus (MRSA) bacteremia is a serious clinical challenge with high mortality rates. Antibiotic combination therapy is currently used in cases of persistent infection; however, the limited development of new antibiotics will likely increase the need for combination therapy, and better methods are needed for identifying effective combinations for treating persistent bacteremia. To identify pairwise combinations with the most consistent potential for benefit compared to monotherapy with a primary anti-MRSA agent, we conducted a systematic study with an in vitro high-throughput methodology. We tested daptomycin and vancomycin each in combination with gentamicin, rifampicin, cefazolin, and oxacillin, and ceftaroline with daptomycin, gentamicin, and rifampicin. Combining cefazolin with daptomycin lowered the daptomycin concentration required to reach 95% growth inhibition (IC95) for all isolates tested and lowered daptomycin IC95 below the sensitivity breakpoint for five out of six isolates that had daptomycin minimum inhibitory concentrations at or above the sensitivity breakpoint. Similarly, vancomycin IC95s were decreased when vancomycin was combined with cefazolin for 86.7% of the isolates tested. This was a higher percentage than was achieved by adding any other secondary antibiotic to vancomycin. Adding rifampicin to daptomycin or vancomycin did not always reduce IC95s and failed to produce synergistic interaction in any of the isolates tested; the addition of rifampicin to ceftaroline was frequently synergistic and always lowered the amount of ceftaroline required to reach the IC95. These analyses rationalize further in vivo evaluation of three drug pairs for MRSA bacteremia: daptomycin+cefazolin, vancomycin+cefazolin, and ceftaroline+rifampicin.IMPORTANCEBloodstream infections caused by methicillin-resistant Staphylococcus aureus (MRSA) have a high mortality rate despite the availability of vancomycin, daptomycin, and newer antibiotics including ceftaroline. With the slow output of the antibiotic pipeline and the serious clinical challenge posed by persistent MRSA infections, better strategies for utilizing combination therapy are becoming increasingly necessary. We demonstrated the value of a systematic high-throughput approach, adapted from prior work testing antibiotic combinations against tuberculosis and other mycobacteria, by using this approach to test antibiotic pairs against a panel of MRSA isolates with diverse patterns of antibiotic susceptibility. We identified three antibiotic pairs-daptomycin+cefazolin, vancomycin+cefazolin, and ceftaroline+rifampicin-where the addition of the second antibiotic improved the potency of the first antibiotic across all or most isolates tested. Our results indicate that these pairs warrant further evaluation in the clinical setting.

The clinical effectiveness of Fidaxomicin compared to Vancomycin in the treatment of Clostridioides difficile infection, a single center real-world experience.

BACKGROUND: The use of fidaxomicin is recommended as first line therapy for all patients with Clostridioides difficile infection (CDI). However, real-world studies have shown conflicting evidence of superiority. METHODS: We conducted a retrospective single center study of patients diagnosed with CDI between 2011-2021. A primary composite outcome of clinical failure, 30-day relapse or CDI-related death was used. A multivariable cause specific Cox proportional hazards model was used to evaluate fidaxomicin compared to vancomycin in preventing the composite outcome. A separate model was fit on a subset of patients with C. difficile ribotypes adjusting for ribotype. RESULTS: There were 598 patients included, of whom 84 received fidaxomicin. The primary outcome occurred in 8 (9.5%) in the fidaxomicin group compared to 111 (21.6%) in the vancomycin group. The adjusted multivariable model showed fidaxomicin was associated with 63% reduction in the risk of the composite outcome compared to vancomycin (HR = 0.37, 95% CI 0.17-0.80). In the 337 patients with ribotype data after adjusting for ribotype 027, the results showing superiority of fidaxomicin were maintained (HR = 0.19, 95% CI 0.05-0.77). CONCLUSION: In the treatment of CDI, we showed that real-world use of fidaxomicin is associated with lower risk of a composite endpoint of treatment failure.

Connecting the Dots between Barriers to W.I.C. Access and Adult and Child Food Insecurity: A Survey of Missouri Residents.

Background. Previous research has explored the impact of W.I.C. on recipients' health, but less is known about the connection between barriers to W.I.C. access and health outcomes. We fill in a gap in the literature by studying the relationship between barriers to Special Supplemental Nutrition Program for Women, Infants, and Children (W.I.C.) access and adult and child food insecurity. Methods. After survey administration, we analyzed a cross-sectional sample of 2244 residents in Missouri who have used W.I.C. or lived in a household with a W.I.C. recipient in the past three years. We ran logistic regression models to understand the relationships among barriers to W.I.C. utilization, adult food insecurity, and child food insecurity. Results. Having special dietary needs (for adults), lacking access to technology, encountering inconvenient clinic hours of operation, and experiencing difficulties taking off work were associated with increased adult food insecurity. Difficulties finding WIC-approved items in the store, technological barriers, inconvenient clinic hours, difficulties taking off work, and finding childcare were associated with increased child food insecurity. Conclusion. Barriers to accessing and utilizing W.I.C. are associated with adult and child food insecurity. However, current policies suggest promising approaches to curbing these barriers.

Impact of antimicrobial use in dogs on antimicrobial resistance and shared flora with human owners.

Transmission of bacteria between animals and humans in domestic households is increasingly recognized. We evaluated the presence of antimicrobial-resistant fecal bacteria in 8 dog-owner-dog pairs before and after the dog received amoxicillin-clavulanate. The study identified shared flora in the humans and dogs that were affected by antimicrobial administration.

Attitudes and awareness of Australian women regarding peripartum antibiotic use: A multicentre survey.

BACKGROUND: Peripartum antibiotics are commonly administered. Little is known of the attitudes of pregnant women toward peripartum antibiotics. AIM: We aimed to assess the awareness of and attitudes toward peripartum antibiotic use in Australian women. MATERIALS AND METHODS: We surveyed post-partum women at three hospitals over six months. Women reported if they received antibiotics 48 h either side of delivery and responded to statements assessing attitudes to peripartum antibiotic use. Administered antibiotics were recorded. We reported the proportion receiving antibiotics and the proportion aware of receiving them. Participants responded on five-point Likert scales and selected side effects of concern. RESULTS: Participants responding were 248 of 299 (83%, Royal Brisbane and Women's Hospital), 56 of 106 (53%, Caboolture Hospital) and 17 (Redcliffe Hospital, denominator not recorded). Of 183 (57%) receiving antibiotics, 134 (73%) received them pre-delivery only, 18 (10%) post-delivery only and 31 (17%) pre- and post-delivery. Pre-delivery, the most common indication was pre-incisional prophylaxis for caesarean delivery (93 of 160 responses, 58%). Seventy-nine (51%, 156 responses) of those receiving pre-delivery antibiotics were aware. Of 49 women receiving post-delivery antibiotics, 36 (73%) were aware. Most agreed they were worried that pre-delivery antibiotics would affect their baby (198, 62%) and 160 (50%) were concerned about effects on their own microbiome. Most (204, 65%) agreed they would rather not take antibiotics while breastfeeding. CONCLUSION: Many women were unaware of receiving pre-delivery antibiotics. Most had concerns about side effects. Improved communication regarding peripartum antibiotic use would improve patient-centred care.

Single-centre survey of women reflecting on recent experiences and preferences of oral intake during labour.

BACKGROUND: Consensus-based recommendations guiding oral intake during labour are lacking. AIMS: We surveyed women at a tertiary women's hospital about preferences for and experiences of oral intake during labour, gastrointestinal symptoms during labour and recalled advice about oral intake. MATERIALS AND METHODS: Women who experienced labour completed a postpartum survey with responses as free text, yes-no questions and five-point Likert scales. We identified demographic data and risk factors for surgical or anaesthetic intervention at delivery from medical records. We summarised free text comments using conventional content analysis. RESULTS: One hundred and forty-nine women completed the survey (47% response rate). Their mean (SD) age was 31 (four) years, birthing at median gestation of 39 weeks (interquartile range: 38-40). One hundred and twenty-two (83%) and 44 (30%) women strongly agreed or agreed they felt like drinking and eating respectively during labour. Ninety women (61%) reported nausea and 47 women (32%) reported vomiting in labour. Forty-one women (28%) did not receive advice on oral intake during labour. Maternal risk factors for surgical intervention were identified in 72 (48%) women and fetal risk factors in 27 (18%) women. Thirty-one women (21%) delivered by emergency caesarean section. CONCLUSION: Pregnant women received variable advice regarding oral intake during labour, from variable sources. Most women felt like drinking but not eating during labour. Guidelines on oral intake in labour may be beneficial to women, balancing the preferences of women with risks of surgical intervention.

In Vitro Evaluation of the Activity of Aztreonam-Avibactam against 341 Recent Clinical Isolates of Anaerobes.

Aztreonam-avibactam is under clinical development for multidrug-resistant Gram-negative infections. We evaluated in vitro activity against 341 recent clinical isolates. The addition of avibactam to aztreonam had no effect on the anaerobic activity of aztreonam. IMPORTANCE This work shows that aztreonam-avibactam lacks activity against anaerobic organisms.

How Did School Meal Access Change during the COVID-19 Pandemic? A Two-Step Floating Catchment Area Analysis of a Large Metropolitan Area.

SARS-CoV-2 (COVID-19) resulted in school closures and contingencies across the U.S. that limited access to school meals for students. While some schools attempted to provide alternative meal access points where students or parents could pick up meals, many students-especially those in low-income households-lacked adequate transportation to these access points. Thus, physical proximity to meal access points was particularly important during the pandemic. In this study, we explore how school meal access changed during the COVID-19 pandemic, especially as it relates to race/ethnicity and socio-economic status. Taking into account both the "supply" (meal access points) and the "demand" (low-income students) for free meals, we employed a two-step floating catchment area analysis to compare meal accessibility in St. Louis, Missouri before and during the pandemic in the spring and summer of 2019 and 2020. Overall, while school meal access decreased during the spring of 2020 during the early months of the pandemic, it increased during the summer of 2020. Moreover, increased access was greatest in low-income areas and areas with a higher proportion of Black residents. Thus, continuing new policies that expanded access to school meals-especially for summer meal programs-could lead to positive long-term impacts on children's health and well-being.

The Readability of Patient Education Materials Pertaining to Gastrointestinal Procedures.

Introduction: Due to the ubiquity and ease of access of Internet, patients are able to access online health information more easily than ever. The American Medical Association recommends that patient education materials be targeted at or below the 6th grade level in order to accommodate a wider audience. In this study, we evaluate the difficulty of educational materials pertaining to common GI procedures; we analyze on the readability of online education materials for colonoscopy, flexible sigmoidoscopy, and esophagogastroduodenoscopy (EGD). Methods: Google search was performed using keywords of "colonoscopy," "sigmoidoscopy," and "EGD" with "patient information" at the end of each search term. The texts from a total of 18 studies, 6 for each of the procedures, were then saved. Each study was also subdivided into "Introduction," "Preparation," "Complications," and if available, "Alternatives." Furthermore, medical terminology that was properly explained, proper nouns, medication names, and other copyright text were removed in order to prevent inflation of the difficulty. Five validated readability tests were used to analyze each study and subsections: Coleman-Liau, New Dale-Chall, Flesch-Kincaid, Gunning Fog, SMOG. Results: Studies on colonoscopy, flexible sigmoidoscopy, and EGD had median readability grades of 9.7, 10.2, and 11.0, respectively. Analysis of the subsections revealed that the "Alternative" subsection was the most difficult to comprehend with a readability score of 11.4, whereas the "Introduction" subsection was the easiest to comprehend with a readability score of 9.5. Conclusion: Despite modifications to the studies that improved the readability scores, patient education materials were still significantly above the recommended 6th grade level across all websites. This study emphasizes that clear and simple language is warranted in order to create information that is suitable for most patients.

Opioid Prescribing in Canada following the Legalization of Cannabis: A Clinical and Economic Time-Series Analysis.

PURPOSE: On 17 October 2018 recreational cannabis became legal in Canada, thereby increasing access and reducing the stigma associated with its use for pain management. This study assessed total opioid prescribing volumes and expenditures prior to and following cannabis legalization. METHODS: National monthly claims data for public and private payers were obtained from January 2016 to June 2019. The drugs evaluated consisted of morphine, codeine, fentanyl, hydrocodone, hydromorphone, meperidine, oxycodone, tramadol, and the non-opioids gabapentin and pregabalin. All opioid volumes were converted to a mean morphine equivalent dose (MED)/claim, which is analogous to a prescription from a physician. Gabapentin and pregabalin claims data were analyzed separately from the opioids. Time-series regression modelling was undertaken with dependent variables being mean MED/claim and total monthly spending. The slopes of the time-series curves were then compared pre- versus post-cannabis legalization. RESULTS: Over the 42-month period, the mean MED/claim declined within public plans (p < 0.001). However, the decline in MED/claim was 5.4 times greater in the period following legalization (22.3 mg/claim post vs. 4.1 mg/claim pre). Total monthly opioid spending was also reduced to a greater extent post legalization ($Can267,000 vs. $Can95,000 per month). The findings were similar for private drug plans; however, the absolute drop in opioid use was more pronounced (76.9 vs. 30.8 mg/claim). Over the 42-month period, gabapentin and pregabalin usage also declined. CONCLUSIONS: Our findings support the hypothesis that easier access to cannabis for pain may reduce opioid use for both public and private drug plans.

Antimicrobial susceptibility and ribotypes of Clostridium difficile isolates from a Phase 2 clinical trial of ridinilazole (SMT19969) and vancomycin.

Objectives: We evaluated the antimicrobial susceptibility and ribotypes of Clostridium difficile isolates from participants in a Phase 2 study of ridinilazole, a novel targeted-spectrum agent for treatment of C. difficile infection. Methods: Participants received ridinilazole (200 mg twice daily) or vancomycin (125 mg four times daily) for 10 days (ClinicalTrials.gov: NCT02092935). The MICs of ridinilazole and comparators for C. difficile isolates from stool samples were determined by agar dilution. Toxin gene profiling was performed by multiplex PCR and ribotype identification by capillary electrophoresis. Results: Eighty-nine isolates were recovered from 88/100 participants (one participant had two strains at baseline). The median colony count (cfu/g stool) was 1.9 × 104 (range: 2.5 × 102-7.0 × 106). Twelve participants (three received ridinilazole and nine received vancomycin) experienced recurrence, confirmed by immunoassays for free toxin in stool samples. The ribotype of eight out of nine isolates obtained at recurrence matched those of the initial isolates. All isolates, including those obtained at recurrence, were susceptible to ridinilazole within the expected range [median (range) MIC: 0.12 (0.06-0.5) mg/L]. The median (range) vancomycin MIC was 1 (0.5-4.0) mg/L. At baseline, 13.6% and 13.3% of samples in the ridinilazole and vancomycin groups were positive for VRE, increasing to 23.7% and 29.7% by day 40, respectively. Common ribotypes included 014-20 (14 isolates), 027 (13), 106 (7), 002 (7), 078-126 (4), 001 (4), 087 (3) and 198 (3). Toxin gene profiling of nearly all baseline isolates (98.9%) revealed a binary toxin gene (cdtA/cdtB) prevalence of 35%. Conclusions: Ridinilazole potently inhibited recovered C. difficile isolates. Recurrence was not associated with altered susceptibility.

A repeat offender: Recurrent extraintestinal Clostridium difficile infection following fecal microbiota transplantation.

Extraintestinal infection with Clostridium difficile has been reported but remains uncommon. Treatment of this unusual complication is complex given the limitations of current therapeutic options. Here we report a novel case of recurrent extraintestinal C. difficile infection that occurred following fecal microbiota transplantation. Using whole genome sequencing, we confirmed recrudescence rather than reinfection was responsible. The patient ultimately responded to prolonged, targeted antimicrobial therapy informed by susceptibility testing.

Evaluation of the In Vitro Activity of Eravacycline against a Broad Spectrum of Recent Clinical Anaerobic Isolates.

The novel fluorocycline antibiotic eravacycline is in development for use in the treatment of serious infections caused by susceptible and multidrug-resistant (MDR) aerobic and anaerobic Gram-negative and Gram-positive pathogens. Eravacycline and 11 comparator antibiotics were tested against recent anaerobic clinical isolates, including MDR Bacteroides spp. and Clostridium difficile Eravacycline was potent in vitro against all the isolates tested, including strains with tetracycline-specific resistance determinants and MDR anaerobic pathogens resistant to carbapenems and/or ß-lactam-ß-lactamase inhibitor combinations.

In Vitro Evaluation of the Activity of Imipenem-Relebactam against 451 Recent Clinical Isolates of Bacteroides Group and Related Species.

We evaluated the in vitro activity of imipenem-relebactam (imipenem-MK7655) against 451 recent clinical isolates within the Bacteroides group and related species. Relebactam did not enhance or inhibit the activity of imipenem against Bacteroides fragilis or other Bacteroides species. No synergistic or antagonistic effect was observed. The MICs of imipenem-relebactam were equal to or within one dilution of the MICs of these isolates to imipenem.

Differences in the Molecular Epidemiology and Antibiotic Susceptibility of Clostridium difficile Isolates in Pediatric and Adult Patients.

The rising incidence of Clostridium difficile infections (CDIs) in adults is partly related to the global spread of fluoroquinolone-resistant strains, namely, BI/NAP1/027. Although CDIs are also increasingly diagnosed in children, BI/NAP1/027 is relatively uncommon in children. Little is known about the antibiotic susceptibility of pediatric CDI isolates. C. difficile was cultured from tcdB-positive stools collected from children diagnosed with CDI between December 2012 and December 2013 at an academic children's hospital. CDI isolates were grouped by restriction endonuclease analysis (REA). MICs were measured by agar dilution method for 7 antibiotics. Susceptibility breakpoints were based on guidelines from CLSI and/or the European Committee on Antimicrobial Susceptibility Testing (EUCAST). MICs and REA groupings of C. difficile isolates from 74 adult patients (29 isolates underwent REA) from a temporally and geographically similar adult cohort were compared to those of pediatric isolates. Among 122 pediatric and 74 adult isolates, respectively, the rates of resistance were as follows: metronidazole, 0% and 0%; vancomycin, 0% and 8% (P = 0.003); rifaximin, 1.6% and 6.7% (P = 0.11); clindamycin, 18.9% and 25.3% (P = 0.29); and moxifloxacin, 2.5% and 36% (P = <0.0001). Only 1 of 122 (0.8%) BI/NAP1/027 isolates was identified among the children, compared to 9 of 29 (31%) isolates identified among the adults (P = <0.0001). The 3 moxifloxacin-resistant pediatric isolates were of REA groups BI and CF and a nonspecific group. The 2 rifaximin-resistant pediatric isolates were of REA groups DH and Y. The 21 clindamycin-resistant pediatric isolates were distributed among 9 REA groups (groups A, CF, DH, G, L, M, and Y and 2 unique nonspecific REA groups). These data suggest that a diverse array of relatively antibiotic-susceptible C. difficile strains predominate in a cohort of children with CDI compared to adults.

Mucocutaneous Findings and Course in an Adult With Zika Virus Infection.

IMPORTANCE: The Zika virus epidemic has been declared a public health emergency of international concern by the World Health Organization. We describe the mucocutaneous features and histologic correlation in a patient with the acute Zika virus infection. OBSERVATIONS: We observed the presence of a diffuse papular descending eruption, petechiae on the palate, and hyperemic sclerae in a 44-year-old man returning from Puerto Rico with confirmatory testing for the Zika virus. CONCLUSIONS AND RELEVANCE: A detailed awareness of mucocutaneous findings associated with Zika virus infection will support its early recognition and will facilitate elimination of Zika infection from consideration for concerned patients who present with other, more common erythematous eruptions.

A Review of Indigo Naturalis as an Alternative Treatment for Nail Psoriasis.

INTRODUCTION: Nail psoriasis is challenging to treat. The few currently available therapies are limited in efficacy, and often produce unfavorable side effects. A plant extract widely used in Traditional Chinese Medicine, indigo naturalis (Qing Dai), is presented in this review as an alternative topical treatment for skin and nail psoriasis. The purpose of this article is to present information on a viable alternative treatment with a favorable side effect profile for a difficult disease to treat. METHODS: A PubMed search for the term "indigo naturalis" was performed, and literature from 2006 to the present relevant to indigo naturalis and treatment of psoriasis and nail psoriasis was reviewed. RESULTS: Indigo naturalis shares several therapeutic mechanisms with current psoriasis treatments, such as regulation of keratinocyte proliferation and differentiation, restoration of epidermal barrier function, and reduction of inflammatory processes. Clinically, it is well tolerated. CONCLUSION: Recent research of indigo naturalis suggests that it is a safe, inexpensive, and effective alternative topical treatment for skin and nail psoriasis.

Use of tumor necrosis factor (TNF) inhibitors in patients with HIV/AIDS.

Patients with HIV and AIDS are living longer because of advancements in antiretroviral therapy. These patients are often susceptible to debilitating inflammatory disorders that are refractory to standard treatment. We discuss the relationship of tumor necrosis factor-alpha and HIV and then review 27 published cases of patients with HIV being treated with tumor necrosis factor-alpha inhibitors. This review is limited because no randomized controlled trials have been performed with this patient population. Regardless, we propose that reliable seropositive patients, who are adherent to medication regimens and frequent monitoring and have failed other treatment modalities, should be considered for treatment with tumor necrosis factor-alpha inhibitors.