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  • Best Movies of Fall 2025

    Best Movies of Fall 2025

    From a Bruce Springsteen biopic to a new PTA drama, a new ‘Avatar’ and the ‘Wicked’ sequel — everything you need to see this awards season

    Ah yes, the autumn months — when the leaves turn brown, the air becomes chillier, school is back in session, and talk turns to “BUT WHAT ARE ITS OSCAR CHANCES?!?” Looking over the year’s final moviegoing stretch, there are certainly a few films that aren’t actively gunning for all the gold statues; we doubt the horror-film sequels and blockbuster remakes hitting screens between Labor Day and New Year’s Eve are crossing their fingers over nominations. But there’s an abundance of stuff that carries a patina of prestige, a handful of film festival laurels, and an already active For Your Consideration campaign with a budget the size of Paraguay’s gross national product that’s ready to jockey for your eyeballs. Some will be modern classics. Some will be instantly forgettable. And some will even have Cynthia Erivo in green make-up and hitting notes that break car windows in the multiplex parking lot. Forget it, Jake. It’s the Fall Movie Season.

    We’ve rounded up 50 movies, ranging from recognizable-I.P. franchise entries to a Bruce Springsteen biopic, auteur-driven pet projects (New PTA! New Guillermo del Toro!! New Kathryn Freakin’ Bigelow!!!) to best-of-fest-circuit imports, that you’ll want to pay attention to over the next four months. It’s curated, not comprehensive, so don’t consider this a complete guide to the remainder of your moviegoing year — just the only one you need. And, as always, dates are subject to change (we promise to update them when they inevitably do).

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  • Prince Harry and Meghan Markle’s History with José Andrés, Explained

    Prince Harry and Meghan Markle’s History with José Andrés, Explained

    In the finale of With Love, Meghan season two, Chef José Andrés and Meghan Markle make a paella for the crew of the Netflix show.

    “I love them,” Andrés told People of the Duke and Duchess of Sussex in 2022. “I have been able to spend time with them, working with them and they are very hands-on and highly knowledgeable of what’s happening in the world, what the issues are, and what the needs are.”

    He continued, “For me, it is a pleasure to call them friends. All my life I have been trying to learn what exactly we are missing because why is there still hunger? What are we missing? We have to make the most of the opportunities of goodness, and I believe that with people like Meghan and Harry, we can make it happen.”

    Here, what to know about the Sussexes’ friendship with Chef José Andrés:

    The Archewell Foundation launches partnership with the World Central Kitchen.

    Harry and Meghan’s Archewell Foundation first teamed up with Andrés’s World Central Kitchen (WCK) in 2020; it was Archewell’s first public partnership. In their partnership, the Duke and Duchess of Sussex announced they were funding a series of Community Relief Centers for World Central Kitchen. “The health of our communities depends on our ability to connect to our shared humanity,” Meghan and Harry said in an emailed statement to Bloomberg in December 2020. “When we think about Chef Andrés and his incredible team at World Central Kitchen, we’re reminded that even during a year of unimaginable hardship, there are so many amazing people willing—and working tirelessly—to support each other. World Central Kitchen inspires us through compassion in action.”

    Andrés said at the time, “We are more energized than ever to continue this vital work, and we’re proud that it will be hand in hand with Archewell Foundation and The Duke and Duchess of Sussex. I have come to know both of them well, and believe that their values are directly aligned with what we stand for at World Central Kitchen.”

    This is likely around when Andrés and the Sussexes first met. “It was very refreshing the first time I met them,” Andrés said a few years later. “They contacted me and said, ‘We want to be a partner with you.’ For me, it is amazing. They are very good people.”

    In 2022, Archewell announced they had donated to WCK to support their Ukraine relief efforts, and again in early 2025, they supported WCK in their response to the wildfires in California.

    Meghan contributes a recipe to The World Central Kitchen Cookbook.

    The World Central Kitchen Cookbook: Feeding Humanity, Feeding Hope

    Her lemon olive oil cake appears in the cookbook.

    Meghan had previously baked the cake for “a group of female restaurateurs who partnered with WCK to provide meals to their community during the pandemic,” per Sussex.com.

    With the cake, she wrote them a note that read, “Sometimes we overlook how much it matters to express thanks and show appreciation. Perhaps we realize now more than ever that fundamental human moments, like enjoying a meal together, fill us up with more than just food (even if that food is delicious!). To that point, we hope you enjoy the offering we baked for you—a small token of thanks, from our home to yours. Our hope with this effort is to show that, when we all participate, even the smallest actions can have a ripple effect. Even individual actions can impact the whole of us.”

    Harry and Andrés reunite in New York City in September 2024.

    Both the Duke of Sussex and the chef spoke at the 2024 edition of the Clinton Global Initiative.

    Andrés and the Sussexes volunteer together in California.

    Amid the wildfires in California in January 2025, Harry, Meghan, and Andrés were pictured volunteering together. “I mean, listen, I consider them friends,” Andrés told People. “I know they are in the spotlight — not in America, but in Britain — and what I can tell you from what I know is that they don’t have to, but they decide to do it.”

    He added, “Probably, you feel like it’s better that nobody does anything, because nobody criticizes you for showing up — but the amazing thing is that they show up. The hugs I saw [them] give to the people that recognize them and even the people that don’t recognize them, it’s people that just want somebody to listen to them, and give them a hug. I’m just glad that they show up like so many others.”

    Andrés appears in With Love, Meghan.

    with love, meghan l to r meghan, duchess of sussex, josé andrés in episode 208 of with love, meghan cr courtesy of netflix © 2025

    Courtesy Netflix

    Andrés and Meghan while they make a paella.

    José Andrés is the final guest in With Love, Meghan, and he joins Meghan in the finale of season two to create a dinner to celebrate the crew.

    with love, meghan l to r josé andrés, meghan, duchess of sussex in episode 208 of with love, meghan cr courtesy of netflix © 2025
    Headshot of Emily Burack

    Emily Burack (she/her) is the Senior News Editor for Town & Country, where she covers entertainment, celebrities, the royals, and a wide range of other topics. Before joining T&C, she was the deputy managing editor at Hey Alma, a Jewish culture site. Follow her @emburack on Twitter and Instagram.

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  • KVM Evolves for an IP and Cloud-Based Media Future

    KVM Evolves for an IP and Cloud-Based Media Future

    As broadcasters and producers deploy IP, cloud and artificial intelligence technologies to more efficiently produce and deliver content to multiple different platforms, KVM systems are helping them revamp their operations and tap into the benefits of newer technologies.

    In the process, KVM (keyboard, video, mouse) systems, originally conceived of as a simple way to control multiple computers, are undergoing a rapid transformation, adding capabilities and tools designed to help producers and broadcasters manage increasingly large operations, handle higher-resolution content, control large remote productions and oversee complex arrays of devices, networks and processes relying on IP and cloud workflows.

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  • Gorillaz review – after 25 years, Damon Albarn and Jamie Hewlett’s cartoon band are still riveting and relevant | Gorillaz

    Gorillaz review – after 25 years, Damon Albarn and Jamie Hewlett’s cartoon band are still riveting and relevant | Gorillaz

    Gorillaz are 25. In 2000, this cartoon-fronted project seemed like something fun for Damon Albarn to do between Blur albums, hiding behind Jamie Hewlett’s comic-book animations, but they’ve overtaken Blur almost everywhere but Britain. The number of children in the audience testifies to Gorillaz’s powers of self-rejuvenation – an ever-changing vehicle for Albarn’s ceaseless curiosity.

    Gorillaz are marking the occasion with an immersive exhibition, House of Kong, and four era-specific shows. This second night revives 2005’s Demon Days. Co-produced by Danger Mouse, it remains the most satisfying expression of the Gorillaz concept: focused in both its themes (innocence and violence) and personnel (rappers and the rap-adjacent). Dressed like a hip vicar, Albarn serves double duty as a frontman and a conscientious host, although the original cast of vocalists is inevitably depleted. The late MF DOOM and awol Shaun Ryder appear only on screen, while Skye Edwards replaces Martina Topley-Bird on All Alone. Thank goodness for the old-school stalwarts. Bootie Brown enters Dirty Harry like a red-and-white firework before De La Soul boom and cackle through Feel Good Inc.

    Gorillaz with London Community Gospel Choir at Copper Box Arena, London. Photograph: Phoebe Fox

    Straight replication, though, is not the point. Beneath Hewlett’s helter-skelter videos, the band, choir and string quartet give the songs new mass and drama. O Green World builds to a startling frenzy and the climactic title track blossoms gloriously. As stained-glass windows fill the screen and the London Community Gospel Choir chant the cathartic refrain, “To the sun”, Albarn’s vicar gear suddenly makes sense. The encore of three contemporary B-sides, while admirably disciplined, is somewhat anticlimactic. The luminous Hong Kong, starring the guzheng virtuoso Qing Du, ends the night on a melancholy question mark rather than an exclamation point.

    Then again, the singles notwithstanding, Demon Days isn’t exactly a party record. This product of the Bush-and-Blair years was pitched as “the world in a state of night,” drawing inspiration from horror soundtracks and the Specials’ queasy crisis-pop. The show opens with a wartorn newsreel montage and sporadically drenches the crowd in hell-red light. For obvious reasons, the album’s haunting protest against humanity’s appetite for destruction – of people and planet alike – sounds no less apt tonight. Demon days are here again.

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  • Factors influencing the number of Clostridioides difficile spores dete

    Factors influencing the number of Clostridioides difficile spores dete

    Chun-Wei Chiu,1 Shiang-En Chen,2 Yu-Ting Lin,2 Ching-Chi Lee,3– 5 Jen-Chieh Lee,4,5 Chin-Shiang Tsai,4– 6 Wen-Chien Ko,4,5 Chih-Hsuan Tsai,2,5,* Yuan-Pin Hung1,2,4,5,*

    1Department of Internal Medicine, Tainan Hospital, Ministry of Health and Welfare, Tainan, Taiwan; 2Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 3Clinical Medicine Research Center, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 4Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 5Department of Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 6Department of Internal Medicine, National Cheng Kung University Hospital, Dou-Liou Branch, College of Medicine, National Cheng Kung University, Yunlin, Taiwan

    Correspondence: Chih-Hsuan Tsai, Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Medical College, No. 1, University Road, Tainan, 70101, Taiwan, Tel +886-6-2353535 ext 5626, Email [email protected] Yuan-Pin Hung, Department of Internal Medicine, Tainan Hospital, Ministry of Health and Welfare, No. 125, Jhongshan Road, West Central Dist, Tainan, Taiwan, Tel +886-6-2200055 ext. 6215, Email [email protected]

    Objective: Clostridioides difficile is the most common cause of antibiotic-associated diarrhea. Wastewater from hospitals may be an important source of C. difficile transmission between hospitals and communities. The objective of this study is to quantify C. difficile spores and to elucidate their potential transmission risk via hospital wastewater.
    Methods: A prospective study of wastewater from a teaching hospital was conducted weekly, from July 2023 to June 2024. The number of C. difficile spores detected in wastewater from hospital settings fluctuated weekly during the study period.
    Results: There was a borderline association between the number of C. difficile spores detected in wastewater at room temperature in hospitals (p = 0.02) and the consumption of antimicrobial agents (p value = 0.04), particularly cephalosporins (p = 0.001). Specifically, the number of C. difficile spores detected in the wastewater was highly correlated with first-generation cephalosporin consumption (p = 0.002), particularly the consumption of first-generation intravenous cephalosporin (cefazolin) (p < 0.001).
    Conclusion: The number of C. difficile spores detected in wastewater from hospital settings is strongly associated with the consumption of antimicrobial agents, particularly cephalosporins. Further evaluation is needed to assess whether antibiotic stewardship programs can reduce the burden of C. difficile spores in wastewater.

    Plain Language Summary: Consumption of antimicrobial agents influences Clostridioides difficile spores in hospital wastewater.

    Keywords: Clostridioides difficile, spore, wastewater, cephalosporins, cefazolin, hospital setting

    Introduction

    Clostridioides difficile remains the most common etiology of healthcare-associated infections in recent years, and significant complications have been observed in severe cases.1–4 In a review of 59 studies encompassing data from 24 countries across North America, Europe, the Asia-Pacific region, Latin America, and the Middle East, in year 2016–2024, the highest incidence of C. difficile infection (CDI) was observed in hospital-onset health-care facility settings, with 5.31 cases per 1,000 admissions (95% CI: 3.76–7.12) and 5.00 cases per 10,000 patient-days (95% CI: 3.96–6.15). Recurrence rates were highest among community-acquired CDI cases at 16.22%. The 30-day all-cause mortality and the overall mortality (unspecified duration) were reported at 8.32% and 16.05%, respectively.5 Despite important advances in the development of new therapeutic agents and preventative methods, the worldwide prevalence of CDI remains high.1 In addition to unfavorable outcomes, it poses a global concern owing to its resistance to common antibiotics and ease of transmission.6,7

    C. difficile is commonly transmitted via the fecal-oral route. Transmission can even occur due to spore ingestion, because spores can endure extremely acidic conditions within the stomach, germinate into vegetative forms in the intestine, and colonize the host colon.8 The outermost layer of C. difficile spores has an extremely low permeability to small compounds and defends its core against DNA-damaging chemicals or antimicrobials.9 Owing to its ability to withstand harsh environments, the infectious and transmissible potential of C. difficile depends largely on dormant spores, which are characterized by resistance to heat, oxygen, and common disinfectants, such as ethanol-based hand sanitizers.9–11

    When spores are ingested, C. difficile initiates a sporulation pathway that yields dormant spores, resulting in prolonged colonization and further dissemination among patients.9,12 Germination of C. difficile spores and growth of vegetative forms may occur in the intestine, where some compounds such as bile acids and taurocholate can induce germination of spores into dynamically duplicating vegetative bacteria.13,14 Another primary bile acid, chenodeoxycholate, is a competitive taurocholate inhibitor that inhibits the germination of C. difficile spores.14,15 The sporulation and germination abilities of different clinical strains of C. difficile differ.13,16

    According to the updated international guidelines issued by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA) in 2017, vancomycin and fidaxomicin are recommended therapeutic agents for CDIs.17 In clinical settings, the high recurrence rate of CDI is mainly not due to the development of antibiotic resistance, but rather due to the formation of spores. Treating CDIs with vancomycin or fidaxomicin is associated with a high recurrence rate because neither antibiotic is effective against spores.17 The residual spores germinated into vegetative bacteria after the cessation of antibiotics.18

    Previously, CDIs were often regarded as important healthcare-associated infections. Currently, the majority of CDI cases are acquired within the community as determined by whole-genome sequencing.19 The origin of community-acquired CDIs is still a topic of debate and is possibly attributed to foodborne transmission since they are usually found in a wide range of foods, including meat, seafood, and fresh products.20 However, the role of these foods as potential transmission vehicles remains clear.20 Environmental contamination and the persistence of C. difficile in hospital wastewater systems have been reported in German hospital.21 A genomic survey of C. difficile reservoirs in eastern England suggested that environmental contamination of wastewater treatment plants from clinical sources was possible.22 Therefore, wastewater from health-care facilities may be an important source of CDI transmission. This study aimed to monitor the number of C. difficile spores in hospital wastewater and determine the factors associated with the alteration of spore amounts in wastewater.

    Materials and Methods

    The amount and characteristics of C. difficile spores in hospital wastewater were monitored. C. difficile spores from the wastewater of a teaching hospital were collected at 5 p.m. on Wednesdays every week from July 2023 to June 2024. C. difficile spores from wastewater were monitored using a culture method.23

    Wastewater Sample Collection

    Wastewater sampling was conducted at the hospital basement wastewater treatment facility. The source of the wastewater was untreated hospital effluent prior to chlorination. Samples were collected using a water scoop (purchased from Techni Trade@, D8QA-108000), which was used to retrieve wastewater from the collection tank. The wastewater was transferred into sterile sampling bags (purchased from Techni Trade@, DP-SB1930W), with each bag containing 1 liter. A total of three bags were collected. One bag was used for subsequent experiments, while the remaining two were stored at 4°C for backup purposes. We first conducted a preliminary test by collecting wastewater samples on several different days within the same week to quantify spore counts. After identifying the day with the highest spore load, we subsequently performed weekly wastewater sampling on that specific day.

    Counting C. difficile Spores in Wastewater23

    Hospital wastewater was collected and concentrated using a 0.45 µm pore-size cellulose acetate membrane filter (Tak Kee Instruments, ADVANTEC@). After the entire volume passed through the filter, the membrane was removed and placed into a 50 mL centrifuge tube containing Brain Heart Infusion-supplemented (BHIS) medium, 0.1% taurocholic acid (TA), and an antibiotic cocktail. The tube was then incubated anaerobically at 37°C for ten days. After ten days, 2 mL of bacterial sediment from the bottom of the centrifuge tube was transferred using a micropipette into a 15 mL centrifuge tube. A heat shock treatment (65°C for 20 minutes) was performed, followed by an ethanol shock treatment (2 mL of 99% ethanol, incubated at room temperature for one hour). The sample was then centrifuged at room temperature (4000 rpm for 10 minutes), and the supernatant was discarded. The spore pellet was resuspended in 1 mL of taurocholic acid (TA) solution. From each tube, 20 µL was plated onto Cycloserine-Cefoxitin Fructose Agar (CCFA) in duplicate. Additionally, 200 µL was plated per tube onto CCFA to prevent false negatives due to low spore counts in the solution. The plates were incubated anaerobically at 37°C for two days. After incubation, colonies were subcultured onto blood agar under anaerobic conditions for confirmation. Colonies identified as C. difficile according to the morphology: The colonies are usually circular, slightly raised, and have an irregular edge, and often exhibit a matte or ground-glass appearance and are grayish to yellowish-white in color. These colonies were scraped into BHIS cryovials and stored at –80°C. Statistical analysis was performed using the Prism statistical software (version 10.0). The linear-by-linear associations between the risk factors and spore amounts in wastewater were analyzed using Spearman correlation. Statistical P was set less than 0.05.

    The Amount of Antibiotics Consumed

    Hospital-wide antibiotic consumption was recorded using electronic medical records. The most often prescribed antibiotics were grouped into the following classes: cephalosporins, fluoroquinolones, penicillins, and carbapenems. Cephalosporins include first-generation cephalosporins (eg, intravenous cefazolin and oral cephalexin), second-generation cephalosporins (eg, cefuroxime), third-generation cephalosporins (eg, ceftriaxone, cefotaxime, and ceftazidime), and fourth-generation cephalosporins (eg, cefepime). The antibiotic consumption was calculated using the defined daily dose (DDD), which is the assumed average maintenance dose per day for a drug used for its main indication in adults.24

    The Number of Patients with CDI, Temperature and Humidity in the Hospital

    The number of patients with CDI in the hospital was obtained from the electronic medical records. The Institutional Review Board of the National Cheng Kung University Hospital, Taiwan approved the collection of data from patients with CDI (approval number: B-ER-103-098). Because of the retrospective review of the medical records of hospitalized patients, inability to obtain informed consent, and no specific ethical concerns and minimal safety risks, the study was allowed to waive informed consent in compliance with the Declaration of Helsinki from legally authorized representatives. The weekly temperature and humidity in the study hospital were recorded using a hospital-installed temperature and humidity monitoring device on the first floor, which provides institution-wide data. Since the hospital uses a centralized air conditioning system, the temperature and humidity do not vary significantly across different areas.

    Statistical Analysis

    Statistical analysis was performed using the Prism statistical software (version 10.0). The linear-by-linear associations between the risk factors and spore amounts in wastewater were analyzed using Spearman correlation. Statistical P was set less than 0.05.

    Results

    Weekly Amount of C. difficile Spores in Wastewater

    We collected wastewater samples on the following three days within the same week, and the corresponding spore concentrations were as follows:

    March 27, 2023 (Monday), 09:00—21,660 CFU/mL

    April 12, 2023 (Wednesday), 17:00—113,807 CFU/mL

    April 14, 2023 (Friday), 13:00—16,942 CFU/mL

    Among these, the sample collected on Wednesday showed the highest spore concentration. Therefore, all subsequent weekly wastewater sampling was performed around 17:00 on Wednesdays.

    The number of C. difficile spores detected in wastewater from July 2023 to June 2024 fluctuated every week from 95 CFU/mL to 10500 CFU/mL (Figure 1). Many factors may contribute to variations in the detected C. difficile spores in wastewater, such as patients with CDI in hospitals, temperature and humidity in hospital settings, and antimicrobial agent consumption.

    Figure 1 C. difficile spores were detected in wastewater every week from July 2023 to June 2024.

    Analysis of the Factors Contributing to the Variations in the Detected Spores in Wastewater

    There was no association between room temperature and the number of detected C. difficile spores in wastewater (p value = 0.02, ⍴ = −0.685) (Figure 2A), but there was no correlation between room humidity and the number of detected C. difficile spores in wastewater (p value = 0.22, ⍴ = −0.253) (Figure 2B). There was no correlation between patients with CDI and the number of C. difficile spores detected in wastewater (p value = 0.32, ⍴ = 0.155) (Figure 3A). Finally, there was association between the consumption of antimicrobial agents and the number of C. difficile spores detected in wastewater (p = 0.04, ⍴ = 0.627) (Figure 3B).

    Figure 2 Factors contributing to the detection of C. difficile spores in wastewater. Correlations between C. difficile spores detected in wastewater and room temperature (A), and room humidity (B). The linear-by-linear associations between the contributing factors and the spore amounts in wastewater were analyzed via Pearson correlation. A two-tailed P value of less than 0.05 was considered statistically significant.

    Figure 3 Factors contributing to the detection of C. difficile spores in wastewater. Correlations between C. difficile spores detected in wastewater and patients with CDI (A), and antimicrobial agent consumption (B). The linear-by-linear associations between the contributing factors and the spore amounts in wastewater were analyzed via Pearson correlation. A two-tailed P value of less than 0.05 was considered statistically significant.

    Association Between the Consumption of Antimicrobial Agents and Spores in Wastewater

    C. difficile spores in wastewater were associated with cephalosporin consumption (p value = 0.001, ⍴ = 0.8636) (Figure 4A) but not with penicillin (p value = 0.69, ⍴ = −0.1364) (Figure 4B), carbapenem (p value = 0.22, ⍴ = 0.4) (Figure 4C), or fluoroquinolone (p value = 0.56, ⍴ = 0.2) (Figure 4D).

    Figure 4 Associations between the consumption of different classes of antimicrobial agents, including cephalosporins (A), penicillins (B), carbapenems (C), or fluoroquinolones (D), and the number of detected C. difficile spores in wastewater. The linear-by-linear associations between the contributing factors and the spore amounts in wastewater were analyzed via Pearson correlation. A two-tailed P value of less than 0.05 was considered statistically significant.

    A detailed analysis of the consumption of cephalosporins revealed that C. difficile spores detected in wastewater were associated with first-generation cephalosporin consumption (p value = 0.002, ⍴ = 0.8455) (Figure 5A) but not with second-generation cephalosporin consumption (p value = 0.95, ⍴ = 0.0273) (Figure 5B), third-generation cephalosporin consumption (p value = 0.08, ⍴ = 0.5636) (Figure 5C), or fourth-generation cephalosporin consumption (p value = 0.56, ⍴ = 0.2) (Figure 5D).

    Figure 5 The correlation between the consumption of different generations of cephalosporins and the number of detected C. difficile spores in wastewater, including first-generation cephalosporins (A), second-generation cephalosporins (B), third-generation cephalosporins (C), or fourth-generation cephalosporins (D). The linear-by-linear associations between the contributing factors and the spore amounts in wastewater were analyzed via Pearson correlation. A two-tailed P value of less than 0.05 was considered statistically significant.

    In terms of the association between the number of detected C. difficile spores in wastewater and first-generation cephalosporin consumption, there was a correlation between the number of detected C. difficile spores in wastewater and the consumption of intravenous first-generation cephalosporins (cefazolin) (p value ≤ 0.001, ⍴ = 0.8909) (Figure 6A) but not with the consumption of first-generation cephalosporins (cephalexin) in the oral form (p value = 0.15, ⍴ = 0.4636) (Figure 6B).

    Figure 6 Associations between C. difficile spores detected in wastewater and the consumption of different first-generation cephalosporins, including intravenous first-generation cephalosporins (cefazolin) (A) and oral first-generation cephalosporins (cephalexin) (B).

    Discussion

    The number of C. difficile spores detected in the wastewater fluctuated every week during the study period, which was primarily related to differences in antimicrobial agent consumption (Figure 7). Owing to their ability to overcome harsh environments, spores of C. difficile can persist in the environment even after exposure to heat, oxygen, and common disinfectants, such as ethanol-based hand sanitizers.9–11 Therefore, C. difficile spores are frequently found in wastewater from wastewater treatment plants.23,25–27 In a study of 12 wastewater treatment plants in western Australia, spores of C. difficile were found in 90.5% of raw sewage influent.25 C. difficile spores in wastewater treatment plants might originate from different sources, including the environment, food, animals, or humans; however, the most important source is the hospital setting.22,28 A genomic survey of C. difficile reservoirs in East England suggested that a major source of environmental contamination in wastewater treatment plants is the clinical settings.22 Therefore, it is important to monitor the number of C. difficile spores in wastewater from hospital settings. Data concerning the weekly amount of C. difficile spores in wastewater from a hospital setting and the possible influencing factors analyzed in our study could help manage C. difficile spores in hospital wastewater.

    Figure 7 The number of detected C. difficile spores in wastewater fluctuated every week during the study period, which was primarily related to differences in antimicrobial agent consumption.

    In our study, the consumption of antimicrobial agents, especially first-generation cephalosporins, was associated with the number of spores in wastewater from the hospital setting. Almost all classes of antibiotics, including cephalosporins, penicillins, clindamycin, and quinolones, have been associated with CDI.29–32 Cefazolin, the most popular first-generation cephalosporin, is widely used as perioperative antibiotic prophylaxis in many surgeries.33,34 The use of cefazolin as a prophylactic antimicrobial agent has been associated with the development of fulminant CDI after surgery.34 Therefore, we hypothesize that the widespread use of cefazolin as a prophylactic antibiotic for surgical procedures in our hospital may contribute to an increase in C. difficile colonization. However, we do not have direct evidence to support this hypothesis. Although antibiotic therapy is indispensable for treating bacterial infections, it profoundly disrupts the gut microbiota—characterized by reduced microbial diversity and alterations in community composition, particularly affecting beneficial genera such as Bifidobacterium and Eubacterium.35 These changes promote the emergence of antibiotic-resistant strains and facilitate the horizontal transfer of resistance genes.35 Consequently, the disruption impairs colonization resistance, increases intestinal permeability, and heightens susceptibility to opportunistic pathogens such as C. difficile. So the reason for the association between antibiotic consumption and the development of CDI is that antibiotic use changes the indigenous intestinal microbiota and creates an environment where C. difficile easily colonizes the host colon and influences the bile acid composition in the colon of the host, thereby promoting the growth of C. difficile.36 The correlation between antibiotic consumption and the number of C. difficile spores in wastewater indicates an opportunity to decrease the burden of C. difficile spores in wastewater through antibiotic stewardship, as up to 30% of the antibiotics prescribed in the United States are unnecessary or inappropriate.37

    There was no association between room temperature and the number of C. difficile spores detected in wastewater in our study. In a population-based spatiotemporal study of CDI in Queensland, Australia, over a 10-year period, peaks in CDI were found in summer.38 In a study of C. difficile spore viability in stored meat products, the change in viability was not significant at 4°C but increased significantly at 23°C.39 In another in vitro study, the germination rate of C. difficile spores was found to be significantly higher at 37°C than at 20°C.40 Therefore, the potential impact of lowering room temperature on reducing the incidence of CDI and the concentration of C. difficile spores in hospital wastewater requires further evaluation.

    Although C. difficile spore concentration in the wastewater was relatively high in our study, the data did not represent the actual number of spores emitted from hospitals into the environment. First, the spore number was calculated after adding sodium taurocholate to the wastewater to improve the spore germination. Second, the number of spores increased during the culture procedure. Third, C. difficile spore concentrations were analyzed in raw sewage wastewater in our study. The number of spores decreased to a small number after treatment before emission from hospitals into the environment. In a study of wastewater treatment plants in western Australia, spores of C. difficile were found in 90.5% of the raw sewage influent but decreased to 48.1% in the treated effluent.25 The actual number of spores expelled from the hospital setting is expected to be very small.

    This study had several limitations. First, wastewater was sampled only once per week. As there were fluctuations in the number of spores present in the wastewater at every time point, our data did not represent the number of spores present throughout the week. Continuous monitoring of all spores in wastewater is needed to determine the exact number of spores present throughout the week. Second, CDI spores can exist in the feces of colonized patients. Prospective stool cultures of all patients without diarrhea in the hospital may be needed to determine the exact number of patients with C. difficile colonization. Combining patients with CDI and those with C. difficile colonization will provide the real number of patients with C. difficile spores in feces. Third, the toxin genes and ribotypes of the C. difficile isolates from wastewater were not analyzed in our study because the sporulation ability was diverse among different C. difficile ribotypes. Fourth, the impact of potential confounding factors, such as differences in patient population, infection control measures, or seasonal variations in prescribing patterns, which might influence the prevalence of CDI, was not analyzed in our study. Finally, since all samples were subjected to sodium taurocholate stimulation, our focus was on the relative changes in values and their potential association with antibiotic use. However, as the reviewer rightly pointed out, these values do not represent the absolute number of spores being shed.

    In conclusion, the number of C. difficile spores detected in wastewater from hospital settings fluctuated weekly during the study period, which was primarily related to the consumption of different antimicrobial agents, particularly cephalosporins. The effect of reducing unnecessary antibiotic use through antibiotic stewardship on decreasing the burden of C. difficile spores in wastewater requires further evaluation.

    Data Sharing Statement

    Available from the corresponding author upon reasonable request.

    Funding

    This study was partially supported by research grants from the National Science and Technology Council (NSTC 111-2314-B-675-001-MY3, 112-2314-B-006-089-MY3, 112-2320-B-006-056, 113-2320-B-006-027-MY3, and 114-2314-B-675-001-MY3), National Cheng Kung University Hospital (NCKUMCS2024059, NCKUH-11304002, and NCKUH-11310024), Tainan, Taiwan, and Tainan Hospital, Ministry of Health and Welfare, Tainan, Taiwan (PG11104-0146, PG11205-0117, PG11202-0281, PG11306-0010, PG11304-0336, PG11402-0325, PG11402-0323, PG11403-0361, and PG11402-0271).

    Disclosure

    The authors have no conflicts of interest to declare for this work.

    References

    1. Clarke LM, Allegretti JR. Review article: the epidemiology and management of Clostridioides difficile infection-A clinical update. Aliment Pharmacol Ther. 2024;59(11):1335–1349. doi:10.1111/apt.17975

    2. Tsai BY, Tsai PJ, Lee CC, et al. Association of single nucleotide polymorphisms in nucleotide-binding domain leucine-rich repeat protein 1 with Clostridioides difficile colonization or infection. Infect Drug Resist. 2023;16:413–421. doi:10.2147/IDR.S392510

    3. Lee CC, Lee JC, Chiu CW, Tsai PJ, Ko WC, Hung YP. Impacts of corticosteroid therapy at acute stage of hospital-onset Clostridioides difficile infections. Infect Drug Resist. 2022;15:5387–5396. doi:10.2147/IDR.S377967

    4. Lee JC, Lee CC, Chiu CW, et al. Reappraisal of the clinical role of metronidazole therapy for Clostridioides difficile infection in Taiwan: a multicenter prospective study. J Formos Med Assoc. 2022;121(12):2608–2616. doi:10.1016/j.jfma.2022.07.004

    5. Akorful RAA, Odoom A, Awere-Duodu A, Donkor ES. The global burden of Clostridioides difficile infections, 2016-2024: a systematic review and meta-analysis. Infect Dis Rep. 2025;17(2). doi:10.3390/idr17020031

    6. Kuijper EJ, van Dissel JT, Wilcox MH. Clostridium difficile: changing epidemiology and new treatment options. Curr Opin Infect Dis. 2007;20(4):376–383. doi:10.1097/QCO.0b013e32818be71d

    7. Lee CC, Chiu CW, Lee JC, Tsai PJ, Ko WC, Hung YP. Risk factors and clinical impact of carbapenem-resistant enterobacterales coinfections among hospitalized patients with Clostridioides difficile infection. Infect Drug Resist. 2022;15:6287–6295. doi:10.2147/IDR.S386309

    8. Sandhu BK, McBride SM. Clostridioides difficile. Trends in microbiology. 2018;26(12):1049–1050.

    9. Paredes-Sabja D, Shen A, Sorg JA. Clostridium difficile spore biology: sporulation, germination, and spore structural proteins. Trends Microbiol. 2014;22(7):406–416. doi:10.1016/j.tim.2014.04.003

    10. Dawson LF, Valiente E, Donahue EH, Birchenough G, Wren BW. Hypervirulent Clostridium difficile PCR-ribotypes exhibit resistance to widely used disinfectants. PLoS One. 2011;6(10):e25754. doi:10.1371/journal.pone.0025754

    11. Rodriguez-Palacios A, Lejeune JT. Moist-heat resistance, spore aging, and superdormancy in Clostridium difficile. Appl Environ Microbiol. 2011;77(9):3085–3091. doi:10.1128/AEM.01589-10

    12. Higgins D, Dworkin J. Recent progress in Bacillus subtilis sporulation. FEMS Microbiol Rev. 2012;36(1):131–148. doi:10.1111/j.1574-6976.2011.00310.x

    13. Abt MC, McKenney PT, Pamer EG. Clostridium difficile colitis: pathogenesis and host defence. Nat Rev Microbiol. 2016;14(10):609–620. doi:10.1038/nrmicro.2016.108

    14. Wilson KH, Kennedy MJ, Fekety FR. Use of sodium taurocholate to enhance spore recovery on a medium selective for Clostridium difficile. J Clin Microbiol. 1982;15(3):443–446. doi:10.1128/jcm.15.3.443-446.1982

    15. Sorg JA, Sonenshein AL. Inhibiting the initiation of Clostridium difficile spore germination using analogs of chenodeoxycholic acid, a bile acid. J Bacteriol. 2010;192(19):4983–4990. doi:10.1128/JB.00610-10

    16. Moore P, Kyne L, Martin A, Solomon K. Germination efficiency of clinical Clostridium difficile spores and correlation with ribotype, disease severity and therapy failure. J Med Microbiol. 2013;62(Pt 9):1405–1413. doi:10.1099/jmm.0.056614-0

    17. McDonald LC, Gerding DN, Johnson S, et al. clinical practice guidelines for Clostridium difficile infection in adults and children: 2017 update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA). Clin Infect Dis. 2018;66(7):987–994. doi:10.1093/cid/ciy149

    18. Kelly CP, LaMont JT. Clostridium difficile–more difficult than ever. N Engl J Med. 2008;359(18):1932–1940. doi:10.1056/NEJMra0707500

    19. Knight DR, Elliott B, Chang BJ, Perkins TT, Riley TV. Diversity and evolution in the genome of Clostridium difficile. Clin Microbiol Rev. 2015;28(3):721–741. doi:10.1128/CMR.00127-14

    20. Warriner K, Xu C, Habash M, Sultan S, Weese SJ. Dissemination of Clostridium difficile in food and the environment: significant sources of C. difficile community-acquired infection? J Appl Microbiol. 2017;122(3):542–553. doi:10.1111/jam.13338

    21. Freier L, Zacharias N, Gemein S, et al. Environmental contamination and persistence of Clostridioides difficile in hospital wastewater systems. Appl Environ Microbiol. 2023;89(5):e0001423. doi:10.1128/aem.00014-23

    22. Moradigaravand D, Gouliouris T, Ludden C, et al. Genomic survey of Clostridium difficile reservoirs in the East of England implicates environmental contamination of wastewater treatment plants by clinical lineages. Microb Genom. 2018;4(3). doi:10.1099/mgen.0.000162

    23. Baghani A, Alimohammadi M, Aliramezani A, Talebi M, Mesdaghinia A, Douraghi M. Isolation and characterization of a multidrug-resistant Clostridioides difficile toxinotype V from municipal wastewater treatment plant. J Environ Health Sci Eng. 2020;18(2):1281–1288. doi:10.1007/s40201-020-00546-0

    24. Nagassar RP, Jalim N, Mitchell A, et al. Antimicrobial consumption from 2017 to 2021 in East trinidad and tobago: a study in the english-speaking caribbean. Antibiotics. 2023;12(3). doi:10.3390/antibiotics12030466

    25. Chisholm JM, Putsathit P, Riley TV, Lim SC. Spore-Forming Clostridium (Clostridioides) difficile in Wastewater Treatment Plants in Western Australia. Microbiol Spectr. 2023;11(1):e0358222. doi:10.1128/spectrum.03582-22

    26. Nikaeen M, Aghili Dehnavi H, Hssanzadeh A, Jalali M. Occurrence of Clostridium difficile in two types of wastewater treatment plants. J Formos Med Assoc. 2015;114(7):663–665. doi:10.1016/j.jfma.2014.12.005

    27. Romano V, Pasquale V, Krovacek K, Mauri F, Demarta A, Dumontet S. Toxigenic Clostridium difficile PCR ribotypes from wastewater treatment plants in southern Switzerland. Appl Environ Microbiol. 2012;78(18):6643–6646. doi:10.1128/AEM.01379-12

    28. Romano V, Pasquale V, Lemee L, et al. Clostridioides difficile in the environment, food, animals and humans in southern Italy: occurrence and genetic relatedness. Comp Immunol Microbiol Infect Dis. 2018;59:41–46. doi:10.1016/j.cimid.2018.08.006

    29. Spencer RC. The role of antimicrobial agents in the aetiology of Clostridium difficile-associated disease. J Antimicrob Chemother. 1998;41:21–27. doi:10.1093/jac/41.suppl_3.21

    30. Pepin J, Saheb N, Coulombe MA, et al. Emergence of fluoroquinolones as the predominant risk factor for Clostridium difficile-associated diarrhea: a cohort study during an epidemic in Quebec. Clin Infect Dis. 2005;41(9):1254–1260. doi:10.1086/496986

    31. Bartlett JG. Antibiotic-associated diarrhea. Clin Infect Dis. 1992;15(4):573–581. doi:10.1093/clind/15.4.573

    32. Thomas C, Stevenson M, Riley TV. Antibiotics and hospital-acquired Clostridium difficile-associated diarrhoea: a systematic review. J Antimicrob Chemother. 2003;51(6):1339–1350. doi:10.1093/jac/dkg254

    33. Bukowski BR, Torres-Ramirez RJ, Devine D, et al. Perioperative cefazolin for total joint arthroplasty patients who have a penicillin allergy: is it safe? J Arthroplasty. 2024;39:S110–S116. doi:10.1016/j.arth.2024.04.058

    34. Nakamura I, Yamaguchi T, Tsukimori A, et al. Fulminant colitis from Clostridium difficile infection, the epidemic strain ribotype 027, in Japan. J Infect Chemother. 2014;20(6):380–383. doi:10.1016/j.jiac.2013.11.009

    35. Cusumano G, Flores GA, Venanzoni R, Angelini P. The impact of antibiotic therapy on intestinal microbiota: dysbiosis, antibiotic resistance, and restoration strategies. Antibiotics. 2025;14(4):371. doi:10.3390/antibiotics14040371

    36. Britton RA, Young VB. Role of the intestinal microbiota in resistance to colonization by Clostridium difficile. Gastroenterology. 2014;146(6):1547–1553. doi:10.1053/j.gastro.2014.01.059

    37. Loo VG, Bourgault AM, Poirier L, et al. Host and pathogen factors for Clostridium difficile infection and colonization. N Engl J Med. 2011;365(18):1693–1703. doi:10.1056/NEJMoa1012413

    38. Furuya-Kanamori L, Robson J, Soares Magalhaes RJ, et al. A population-based spatio-temporal analysis of Clostridium difficile infection in Queensland, Australia over a 10-year period. J Infect. 2014;69(5):447–455. doi:10.1016/j.jinf.2014.06.014

    39. Deng K, Plaza-Garrido A, Torres JA, Paredes-Sabja D. Survival of Clostridium difficile spores at low temperatures. Food Microbiol. 2015;46:218–221. doi:10.1016/j.fm.2014.07.022

    40. Wheeldon LJ, Worthington T, Hilton AC, Elliott TS, Lambert PA. Physical and chemical factors influencing the germination of Clostridium difficile spores. J Appl Microbiol. 2008;105(6):2223–2230. doi:10.1111/j.1365-2672.2008.03965.x

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  • 5 mysteries of the solar system that still baffle scientists

    5 mysteries of the solar system that still baffle scientists

    In 2017, astronomers detected ‘Oumuamua, an interstellar object passing through our solar system. Its unusual shape and acceleration patterns defy conventional explanations, leading to various hypotheses, including the possibility of it being an artificial object. However, no consensus has been reached, and ‘Oumuamua remains an unresolved enigma in modern astronomy.

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  • You Can Get the Nothing Phone 2a for Just Rs. 5,917/Month With Free Earbuds

    You Can Get the Nothing Phone 2a for Just Rs. 5,917/Month With Free Earbuds

    Faysal Bank has introduced a financing plan for the Nothing Phone 2a (12 GB RAM / 256 GB storage) through its online outlet Faysal Digimall, allowing customers to purchase via installments with a promotional zero-profit option for the first three months and extending up to 48 months.

    The retail price for the phone is set at Rs. 144,990.

    Pricing and EMI Details

    Here is the installment breakdown based on payment duration:

    Tenure Monthly Installment (PKR)
    3 Months @ 0% 48,300
    6 Months 27,484
    12 Months 14,973
    24 Months 9,345
    36 Months 6,923
    48 Months 5,917

     

    As the table shows, the 0% profit applies only to the 3-month tenure.

    Key Benefits

    • Each purchase includes CMF Buds at no added cost.
    • All units are PTA-approved
    • Customers receive free shipping across the country.

    The offer is available exclusively to Faysal Bank credit card holders.

    How to Apply

    Prospective buyers can apply through Faysal Digimall using the following options:

    • Online Portal
    • Contact Faysal Bank at 111‑06 06 06 for assistance

    Applicants are encouraged to review the full Terms & Conditions on the site before submitting a request.


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  • Europe’s central bank boss joins warnings about threat to Fed’s independence from White House ‘intervention’

    Europe’s central bank boss joins warnings about threat to Fed’s independence from White House ‘intervention’

    By Jules Rimmer

    Threats to the Federal Reserve’s independence have been coming thick and fast of late

    A poll of economists in the Financial Times called it “long-term damage” while the President of the European Central Bank referred to it as “serious damage”, but the conclusion drawn by both parties about the threat to U.S. Federal Reserve independence was essentially the same – and unequivocal: it’s bad news.

    The observations come as U.S. President Donald Trump continues to harangue the Fed to sharply lower interest rates, in a campaign that has included ad hominem attacks on Fed Chair Jerome Powell alongside accusations he overspent in the renovations to the Federal reserved building, and also an attempt to sack Fed governor Lisa Cook.

    Ninety-four percent of respondents in the FT’s survey did not feel financial markets have adequately priced in the risks posed by the White House interventions in the Fed’s policy.

    While ECB President Christine Lagarde is just one economist (albeit a very important one) the alarm bell she sounded in a radio interview Monday morning coincided in timing and message with the FT survey of 94 U.S. and E.U. economists.

    Given that Lagarde took the trouble of attaching a link to her interview in a posting on X, it’s clear that she wanted her views to be widely disseminated.

    Lagarde posited, “If U.S. monetary policy were no longer independent and instead dependent on the dictates of this or that person, then I believe that the effect on the balance of the American economy could, as a result of the effects this would have around the world, be very worrying, because it is the largest economy in the world”.

    The FT survey published Monday articulates these economists’ fears that higher inflation and a loss of confidence in U.S. government debt are the most probable outcomes of White House pressure and interference.

    What’s the single-biggest economic risk if the Fed’s independence is eroded?

    The FT’s survey found 89 economists already believe the Fed’s credibility was already impaired and more than a quarter expressed their doubts that by the end of Trump’s second term in 2029, “the Fed will be able to fulfil its mandate to set U.S. borrowing costs free from political influence.”

    The FT’s article notes consensus among economists that weakening the central bank’s independence would inflict significant damage on the U.S. economy because it pursues its mandate to lower inflation and maintain financial stability. These principles may be sacrificed on the altar of Trump’s determination to lower borrowing costs, the column reports.

    -Jules Rimmer

    This content was created by MarketWatch, which is operated by Dow Jones & Co. MarketWatch is published independently from Dow Jones Newswires and The Wall Street Journal. 

    
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  • The Critical Communications Review – Synch Launches Version 6.6, Enhancing Incident Management and Frontline Safety

    The Critical Communications Review – Synch Launches Version 6.6, Enhancing Incident Management and Frontline Safety

    Broadband  |  2025-09-01

    The enhancements are designed to help organizations streamline operations, reduce information overload, and strengthen situational awareness during high-pressure events.

    Synch, a leading provider of mission-critical communication and incident management solutions, has announced the release of Synch 6.6, marking another significant advancement in the company’s mission to make frontline operations faster, safer, and easier to manage.

    With this latest version, Synch introduces a suite of updates across its Admin, Dispatcher, Android, and iOS platforms. The enhancements are designed to help organizations streamline operations, reduce information overload, and strengthen situational awareness during high-pressure events.

    Reducing Noise and Streamlining Incidents

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    Empowering Safe Workers and Compliance

    Building on its Safe Worker features, Synch 6.6 introduces a new SOS widget that gives frontline staff direct access to an emergency panic button from their device home screen. Organizations also benefit from improved transcript capabilities across platforms, simplifying documentation, playback, and compliance reporting.

    Additional Operational Enhancements

    The release also includes auto-incident creation, streamlined group management, expanded admin control through a new Incidents tab, and bulk user update options. Mobile users gain improved notification visibility, with full message history accessible directly from the notification drawer.

    With over 80 bug fixes and performance improvements, Synch 6.6 delivers a more stable, reliable, and responsive platform.

    By combining advanced technology with user-focused design, Synch continues to position itself as a trusted partner for organizations operating in demanding environments.

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  • Treatment outcomes and associated influencing factors among elderly patients with rifampicin-resistant tuberculosis: a multicenter, retrospective, cohort study in China | BMC Infectious Diseases

    Treatment outcomes and associated influencing factors among elderly patients with rifampicin-resistant tuberculosis: a multicenter, retrospective, cohort study in China | BMC Infectious Diseases

  • World Health Organization. Global Tuberculosis Report 2024. 2024. https://www.who.int/teams/global-tuberculosis-programme/tb-reports/global-tuberculosis-report-2024

  • Bureau SS. Statistical bulletin of the National economic and social development of the people’s Republic of China in 2023. Chin Stat. 2024;03:4–21.

    Google Scholar 

  • Donald PR, Marais BJ, Barry CE. 3rd. Age and the epidemiology and pathogenesis of tuberculosis. Lancet (London England). 2010;375(9729):1852–4.

    PubMed 

    Google Scholar 

  • Pratt RH, Winston CA, Kammerer JS, Armstrong LR. Tuberculosis in older adults in the united states, 1993–2008. J Am Geriatr Soc. 2011;59(5):851–7.

    PubMed 

    Google Scholar 

  • Rajagopalan S. Tuberculosis in older adults. Clin Geriatr Med. 2016;32(3):479–91.

    PubMed 

    Google Scholar 

  • Wang L, Zhang H, Ruan Y, et al. Tuberculosis prevalence in china, 1990–2010; a longitudinal analysis of National survey data. Lancet (London England). 2014;383(9934):2057–64.

    PubMed 

    Google Scholar 

  • Mori T, Leung CC. Tuberculosis in the global aging population. Infect Dis Clin N Am. 2010;24(3):751–68.

    Google Scholar 

  • Negin J, Abimbola S, Marais BJ. Tuberculosis among older adults–time to take notice. Int J Infect Diseases: IJID : Official Publication Int Soc Infect Dis. 2015;32:135–7.

    Google Scholar 

  • Lv H, Zhang X, Zhang X, et al. Global prevalence and burden of multidrug-resistant tuberculosis from 1990 to 2019. BMC Infect Dis. 2024;24(1):243.

    PubMed 
    PubMed Central 

    Google Scholar 

  • Chaves-Torres NM, Fadul S, Patiño J, Netto E. Factors associated with unfavorable treatment outcomes in patients with rifampicin-resistant tuberculosis in Colombia 2013–2015: A retrospective cohort study. PLoS ONE. 2021;16(4):e0249565.

    PubMed 
    PubMed Central 

    Google Scholar 

  • Makhmudova M, Maxsumova Z, Rajabzoda A, Makhmadov A, van den Hof S, Mirtskhulava V. Risk factors for unfavourable treatment outcomes among rifampicin-resistant tuberculosis patients in Tajikistan. Int J Tuberculosis Lung Disease: Official J Int Union against Tuberculosis Lung Disease. 2019;23(3):331–6.

    Google Scholar 

  • Alemu A, Bitew ZW, Worku T. Poor treatment outcome and its predictors among drug-resistant tuberculosis patients in ethiopia: A systematic review and meta-analysis. Int J Infect Diseases: IJID : Official Publication Int Soc Infect Dis. 2020;98:420–39.

    Google Scholar 

  • Li H, Mei J, Su W. Analysis of the treatment outcomes and influencing factors of rifampicin-resistant pulmonary tuberculosis patients aged 65 and above in China from 2015 to 2021. Chin J Tuberculosis. 2025;47(04):408–15.

    Google Scholar 

  • Ye Z, Ren F, Wang H. Treatment outcomes and influencing factors in elderly patients with multidrug/rifampicin-resistant pulmonary tuberculosis: a National multicenter, retrospective cohort study. Chin J Tuberculosis. 2024;46(09):1023–9.

    Google Scholar 

  • Cantalice Filho JP, Bóia MN, Sant Anna CC. [Analysis of the treatment of pulmonary tuberculosis in elderly patients at a university hospital in Rio de janeiro, brazil]. Jornal Brasileiro De Pneumologia: Publicacao Oficial Da Sociedade Brasileira De Pneumologia E Tisilogia. 2007;33(6):691–8.

    PubMed 

    Google Scholar 

  • Bele S, Jiang W, Lu H, et al. Population aging and migrant workers: bottlenecks in tuberculosis control in rural China. PLoS ONE. 2014;9(2):e88290.

    PubMed 
    PubMed Central 

    Google Scholar 

  • Organization WH. World Health Organization. Global Tuberculosis Report. 2018. https://www.who.int/publications/i/item/9789241565646

  • Topalian SL, Hodi FS, Brahmer JR, et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med. 2012;366(26):2443–54.

    PubMed 
    PubMed Central 

    Google Scholar 

  • Workneh MH, Bjune GA, Yimer SA. Prevalence and associated factors of tuberculosis and diabetes mellitus comorbidity: A systematic review. PLoS ONE. 2017;12(4):e0175925.

    PubMed 
    PubMed Central 

    Google Scholar 

  • Liu Q, Li W, Xue M, et al. Diabetes mellitus and the risk of multidrug resistant tuberculosis: a meta-analysis. Sci Rep. 2017;7(1):1090.

    PubMed 
    PubMed Central 

    Google Scholar 

  • Zou L, Kang W, Guo C, et al. Treatment outcomes and associated influencing factors among patients with Rifampicin-Resistant tuberculosis: A multicenter, retrospective, cohort study in China. Infect Drug Resist. 2024;17:3737–49.

    PubMed 
    PubMed Central 

    Google Scholar 

  • Lecai J, Mijiti P, Chuangyue H, Qian G, Weiguo T, Jihong C. Treatment outcomes of multidrug-resistant tuberculosis patients receiving ambulatory treatment in shenzhen, china: a retrospective cohort study. Front Public Health. 2023;11:1134938.

    PubMed 
    PubMed Central 

    Google Scholar 

  • Ma JB, Zeng LC, Ren F, et al. Treatment outcomes and risk factors of Multidrug-Resistant tuberculosis patients in xi’an china, a retrospective cohort study. Infect Drug Resist. 2022;15:4947–57.

    PubMed 
    PubMed Central 

    Google Scholar 

  • Conradie F, Diacon AH, Ngubane N, et al. Treatment of highly Drug-Resistant pulmonary tuberculosis. N Engl J Med. 2020;382(10):893–902.

    PubMed 
    PubMed Central 

    Google Scholar 

  • Guglielmetti L, Khan U, Velásquez GE, et al. Oral regimens for Rifampin-Resistant, Fluoroquinolone-Susceptible tuberculosis. N Engl J Med. 2025;392(5):468–82.

    PubMed 
    PubMed Central 

    Google Scholar 

  • Tola H, Holakouie-Naieni K, Mansournia MA, et al. National treatment outcome and predictors of death and treatment failure in multidrug-resistant tuberculosis in ethiopia: a 10-year retrospective cohort study. BMJ Open. 2021;11(8):e040862.

    PubMed 
    PubMed Central 

    Google Scholar 

  • Kuaban A, Balkissou AD, Ekongolo MCE, Nsounfon AW, Pefura-Yone EW, Kuaban C. Incidence and factors associated with unfavourable treatment outcome among patients with rifampicin-resistant pulmonary tuberculosis in yaoundé, Cameroon. Pan Afr Med J. 2021;38:229.

    PubMed 
    PubMed Central 

    Google Scholar 

  • Caraux-Paz P, Diamantis S, de Wazières B, Gallien S. Tuberculosis in the elderly. J Clin Med. 2021;10(24). https://doi.org/10.3390/jcm10245888

  • Udwadia Z, Vendoti D. Totally drug-resistant tuberculosis (TDR-TB) in india: every dark cloud has a silver lining. J Epidemiol Commun Health. 2013;67(6):471–2.

    Google Scholar 

  • Yin J, Wang X, Zhou L, Wei X. The relationship between social support, treatment interruption and treatment outcome in patients with multidrug-resistant tuberculosis in china: a mixed-methods study. Trop Med Int Health: TM IH. 2018;23(6):668–77.

    PubMed 

    Google Scholar 

  • Wagnew F, Alene KA, Kelly M, Gray D. The effect of undernutrition on sputum culture conversion and treatment outcomes among people with multidrug-resistant tuberculosis: a systematic review and meta-analysis. Int J Infect Diseases: IJID : Official Publication Int Soc Infect Dis. 2023;127:93–105.

    Google Scholar 

  • Chakhaia T, Blumberg HM, Kempker RR et al. Lack of weight gain and increased mortality during and after treatment among adults with drug-resistant tuberculosis in Georgia, 2009–2020. medRxiv: the preprint server for health sciences. 2024.

  • Badawi A, Gregg B, Vasileva D. Systematic analysis for the relationship between obesity and tuberculosis. Public Health. 2020;186:246–56.

    PubMed 

    Google Scholar 

  • Hu S, Guo J, Chen Z, Gong F, Yu Q. Nutritional indices predict all cause mortality in patients with Multi-/Rifampicin-Drug resistant tuberculosis. Infect Drug Resist. 2024;17:3253–63.

    PubMed 
    PubMed Central 

    Google Scholar 

  • Johnston JC, Shahidi NC, Sadatsafavi M, Fitzgerald JM. Treatment outcomes of multidrug-resistant tuberculosis: a systematic review and meta-analysis. PLoS ONE. 2009;4(9):e6914.

    PubMed 
    PubMed Central 

    Google Scholar 

  • Chiang CY, Enarson DA, Yu MC, et al. Outcome of pulmonary multidrug-resistant tuberculosis: a 6-yr follow-up study. Eur Respir J. 2006;28(5):980–5.

    PubMed 

    Google Scholar 

  • Keshavjee S, Gelmanova IY, Farmer PE, et al. Treatment of extensively drug-resistant tuberculosis in tomsk, russia: a retrospective cohort study. Lancet (London England). 2008;372(9647):1403–9.

    PubMed 

    Google Scholar 

  • Chan ED, Strand MJ, Iseman MD. Treatment outcomes in extensively resistant tuberculosis. N Engl J Med. 2008;359(6):657–9.

    PubMed 

    Google Scholar 

  • Stephanie F, Saragih M, Tambunan USF. Recent progress and challenges for Drug-Resistant tuberculosis treatment. Pharmaceutics. 2021;13(5).

  • Wallis RS, O’Garra A, Sher A, Wack A. Host-directed immunotherapy of viral and bacterial infections: past, present and future. Nat Rev Immunol. 2023;23(2):121–33.

    PubMed 

    Google Scholar 

  • Mi J, Liang Y, Liang J, et al. The research progress in immunotherapy of tuberculosis. Front Cell Infect Microbiol. 2021;11:763591.

    PubMed 
    PubMed Central 

    Google Scholar 

  • Barzegari S, Afshari M, Movahednia M, Moosazadeh M. Prevalence of anemia among patients with tuberculosis: A systematic review and meta-analysis. Indian J Tuberc. 2019;66(2):299–307.

    PubMed 

    Google Scholar 

  • Singla R, Raghu B, Gupta A, et al. Risk factors for early mortality in patients with pulmonary tuberculosis admitted to the emergency room. Pulmonology. 2021;27(1):35–42.

    PubMed 

    Google Scholar 

  • Ashenafi S, Bekele A, Aseffa G, et al. Anemia is a strong predictor of wasting, disease severity, and progression, in clinical tuberculosis (TB). Nutrients. 2022;14:16.

    Google Scholar 

  • de Mendonça EB, Schmaltz CA, Sant’Anna FM, et al. Anemia in tuberculosis cases: A biomarker of severity? PLoS ONE. 2021;16(2):e0245458.

    PubMed 
    PubMed Central 

    Google Scholar 

  • Nagu TJ, Spiegelman D, Hertzmark E, et al. Anemia at the initiation of tuberculosis therapy is associated with delayed sputum conversion among pulmonary tuberculosis patients in Dar-es-Salaam, Tanzania. PLoS ONE. 2014;9(3):e91229.

    PubMed 
    PubMed Central 

    Google Scholar 

  • Isanaka S, Mugusi F, Urassa W, et al. Iron deficiency and anemia predict mortality in patients with tuberculosis. J Nutr. 2012;142(2):350–7.

    PubMed 

    Google Scholar 

  • Morris CD, Bird AR, Nell H. The haematological and biochemical changes in severe pulmonary tuberculosis. Q J Med. 1989;73(272):1151–9.

    PubMed 

    Google Scholar 

  • Shin DM, Jo EK. Antimicrobial peptides in innate immunity against mycobacteria. Immune Netw. 2011;11(5):245–52.

    PubMed 
    PubMed Central 

    Google Scholar 

  • Hella J, Cercamondi CI, Mhimbira F, et al. Anemia in tuberculosis cases and household controls from tanzania: contribution of disease, coinfections, and the role of Hepcidin. PLoS ONE. 2018;13(4):e0195985.

    PubMed 
    PubMed Central 

    Google Scholar 

  • Kerkhoff AD, Meintjes G, Burton R, Vogt M, Wood R, Lawn SD. Relationship between blood concentrations of Hepcidin and anemia severity, mycobacterial burden, and mortality among patients with HIV-Associated tuberculosis. J Infect Dis. 2016;213(1):61–70.

    PubMed 

    Google Scholar 

  • Gil-Santana L, Cruz LAB, Arriaga MB, et al. Tuberculosis-associated anemia is linked to a distinct inflammatory profile that persists after initiation of antitubercular therapy. Sci Rep. 2019;9(1):1381.

    PubMed 
    PubMed Central 

    Google Scholar 

  • Gu P, Lu P, Ding H, et al. Effectiveness, cost, and safety of four regimens recommended by WHO for RR/MDR-TB treatment: a cohort study in Eastern China. Ann Med. 2024;56(1):2344821.

    PubMed 
    PubMed Central 

    Google Scholar 

  • Lan Z, Ahmad N, Baghaei P, et al. Drug-associated adverse events in the treatment of multidrug-resistant tuberculosis: an individual patient data meta-analysis. Lancet Respiratory Med. 2020;8(4):383–94.

    Google Scholar 

  • Zou F, Cui Z, Lou S, et al. Adverse drug events associated with linezolid administration: a real-world pharmacovigilance study from 2004 to 2023 using the FAERS database. Front Pharmacol. 2024;15:1338902.

    PubMed 
    PubMed Central 

    Google Scholar 

  • Guglielmetti L, Jaspard M, Le Dû D et al. Long-term outcome and safety of prolonged bedaquiline treatment for multidrug-resistant tuberculosis. Eur Respir J. 2017;49(3).

  • Brust JCM, Gandhi NR, Wasserman S, et al. Effectiveness and cardiac safety of Bedaquiline-Based therapy for Drug-Resistant tuberculosis: A prospective cohort study. Clin Infect Diseases: Official Publication Infect Dis Soc Am. 2021;73(11):2083–92.

    Google Scholar 

  • Jin Y, Benkeser D, Kipiani M, et al. The effect of anti-tuberculosis drug pharmacokinetics on QTc prolongation. Int J Antimicrob Agents. 2023;62(4):106939.

    PubMed 
    PubMed Central 

    Google Scholar 

  • Kuhlin J, Davies Forsman L, Osman A, et al. Increased risk of adverse drug reactions by higher linezolid dose per weight in multidrug-resistant tuberculosis. Int J Antimicrob Agents. 2024;64(4):107302.

    PubMed 

    Google Scholar 

  • Frippiat F, Bergiers C, Michel C, Dujardin JP, Derue G. Severe bilateral optic neuritis associated with prolonged linezolid therapy. J Antimicrob Chemother. 2004;53(6):1114–5.

    PubMed 

    Google Scholar 

  • Korotych O, Achar J, Gurbanova E, et al. Effectiveness and safety of modified fully oral 9-month treatment regimens for rifampicin-resistant tuberculosis: a prospective cohort study. Lancet Infect Dis. 2024;24(10):1151–61.

    PubMed 
    PubMed Central 

    Google Scholar 

  • Sotgiu G, Centis R, D’Ambrosio L, et al. Efficacy, safety and tolerability of linezolid containing regimens in treating MDR-TB and XDR-TB: systematic review and meta-analysis. Eur Respir J. 2012;40(6):1430–42.

    PubMed 

    Google Scholar 

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