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Abstract Background The breast milk bank is a professional organization that collects donor human milk (DHM) for special medical needs by recruiting qualified breast milk donors. Such organizations are also responsible for the disinfection, processing, testing, storage, distribution, and use of breast milk. As DHM is a biological product, it may get contaminated. Microbiological testing is the final step to determine microbial contamination of DHM. However, a universal method for the microbiological analysis of DHM in breast milk banks globally is lacking.DHM without strict screening may become a potential carrier of pathogens and seriously threaten the health of infants. Clostridium perfringens, a gram-positive anaerobic bacterium, is capable of causing wound infections, including gas gangrene, enteritis/enterocolitis, and enterotoxemia. Here, the first case of C. perfringens detected in DHM has been reported to facilitate the identification of such contamination in breast milk banks. Case presentation A breastfeeding mother donated 3000 mL of milk to the breast milk bank of the First Affiliated Hospital of the Army Medical University(over 2900 beds and patient receiving capacity of over 132,000), Chongqing, China. The milk sample was subjected to microbiological screening using liquid enrichment, followed by anaerobic and aerobic culturing. The results revealed the growth of C. perfringens in the anaerobic culture medium, but no bacteria or yeast-like fungi were observed in the aerobic culture medium. The donor did not exhibit any clinical symptoms, and her routine blood results and body temperature were normal. However, the infant fed with her milk had recurrent bloody stools. Breast milk bank infection control emergency handling as well as environmental sampling and investigation revealed that the cause was contamination of the donor’s home-use breast pump with C. perfringens. The infant no longer experienced bloody stool once the donor changed the breast pump. Conclusions C. perfringens can enter breast milk from contaminated pumping environments or devices, thus causing illness in infants. The microbiological testing of DHM in breast milk banks can be accomplished using liquid enrichment, along with anaerobic and aerobic culture, which is of immense significance in improving the standards for microbiological screening, DHM safety, and infant health. …

Abstract Background Approximately 10% of patients experience prolonged symptoms after Lyme disease. PTLDS (post treatment Lyme disease syndrome) is a controversial topic. It has been described as a source of overdiagnosis and off-label treatment. This review aims to describe the diagnostic errors and adverse events associated with the diagnosis and treatment of PTLDS. Methods systematic review of the literature in the Medline and Cochrane Library databases, according to PRISMA criteria, including randomized clinical trials (RCT), observational studies, and case reports addressing diagnostic errors and adverse events published between January 2010 and November 2020 in English or French. Selection used a quadruple reading process on the basis of the titles and abstracts of the different articles, followed by a full reading. Results 17 studies were included: 1 RCT, 6 observational studies and 10 case reports. In the 6 observational studies, overdiagnosis rates were very high, ranging from 80 to 100%. The new diagnoses were often psychiatric, rheumatological and neurological. Disorders with somatic symptoms were often cited. Diagnostic delays were identified for cancers and frontoparietal dementia. In the RCT and observational studies, prolonged anti-infective treatments were also responsible for adverse events, with emergency room visits and/or hospitalization. The most common adverse events were diarrhea, sometimes with Clostridium difficile colitis, electrolyte abnormalities, sepsis, bacterial and fungal infections, and anaphylactic reactions. Conclusion This review highlights the risks of prolonged anti-infective treatments that have not been proven to be beneficial in PTLDS. It emphasizes the ethical imperative of the “primum non nocere” principle, which underscores the importance of not causing harm to patients. Physicians should exercise caution in diagnosing PTLDS and consider the potential risks associated with off-label treatments. …

Science Advances, Volume 9, Issue 39, September 2023.

by Difei Yao, Wei He, Yangmin Hu, Ying Yuan, Huimin Xu, Juan Wang, Haibin Dai Probiotics have become increasingly popular among cancer patients. However, there is limited data from a real-world setting. This study aims to conduct a retrospective analysis to understand the trend of probiotic prescriptions in Chinese colorectal cancer patients. The Mann-Kendall and Cochran-Armitage trend test was applied to estimate the trend significance. Gephi software identified the combination of probiotic strains. The binary logistic regression investigated influence factors, and Spearman’s rank correlation coefficient calculated correlations between probiotics and antitumor drug usage. The probiotic prescription percentage increased from 3.3% in 2015 to 4.2% in 2021 (Z = 12.77, p < 0.001). Although 48.3% of probiotic prescriptions had no indication-related diagnosis, diarrhea (OR 10.91, 95% CI 10.57–11.26) and dyspepsia (3.97, 3.82–4.12) included prescriptions most likely to contain probiotics. Prescriptions from the tertiary hospital (1.43,1.36–1.50), clinics (1.30, 1.28–1.33), and senior patients (1.018 per year, 1.017–1.019) were more likely to contain probiotics. Most probiotic prescriptions (95.0%) contained one probiotic product but multiple strains (69.3%). Enterococcus faecalis (49.7%), Lactobacillus acidophilus (39.4%), and Clostridium butyricum (27.9%) were the most prescribed strains. The probiotics co-prescribed with antitumor agents increased rapidly from 6.6% to 13.8% in seven years (Z = 15.31, p < 0.001). Oral fluorouracil agents (2.35, 2.14–2.59), regorafenib (1.70,1.27–2.26), and irinotecan (1.27,1.15–1.41) had a higher probability to co-prescribed with probiotics. There was no correlation between probiotic strain selection and specific antitumor drug use. The increasing prescription of probiotics in colorectal cancer patients in China may be related to treating the gastrointestinal toxicity of anti-cancer drugs. With unapproved indications and a lack of strain selectivity, evidence-based guidelines are urgently needed to improve probiotic use in this population.

by Jia Ouyang, Qinghua Miao, Dong Wei, Xinxin Zhang, Erming Luo, Chunying Li, Li Wei The treatment efficiency of Chromium (Cr)-containing Printed Circuit Board (PCB) wastewater is significantly hampered by the limited physiological activity of microorganisms when activated sludge is applied. In this study, the biodegradation and electron transfer based on sulfur metabolism in the integrated (BESI®) process use sulfur as the electron acceptor to achieve sulfate reduction and sulfide oxidation, leading to efficient removal of Cr. The concentrations of total Cr and Cr(VI) in the effluent were reduced to 0.5 mg/L and 0.1 mg/L, respectively, from an initial range of 25–32 mg/L in the influent. The removal of Cr (ΔC(Cr(VI))) mainly occurred in the Sulfate Reduction (SR) reactor, which was significantly correlated with the generation of sulphide (ΔC(S2−)) (R2 = 0.9987). Meantime, analysis of the microbial community showed that Cr (VI) stress increased the diversity of the bacterial community in sludge. The presence of Clostridium (52.54% and 47.78%) in SR & Sulfide Oxidation (SO) reactor, along with the Synergistaceae (31.90%) and Trichococcus (26.59%) in aerobic reactor, might contribute to the gradient degradation of COD, resulting in a removal efficiency exceeding 80% when treating an influent with a concentration of 1000 mg/L. In addition, the main precipitation components in the SR reactor were identified by scanning electron microscope, indicating that Cr has been removed from wastewater as Cr(OH)3 precipitation. This study sheds light on the potential of using the BESI® process for the real PCB wastewater treatment.

Purpose of review The aim of this study was to review recently published diagnostic stewardship studies of common clinical infectious syndromes and the impact on antibiotic prescribing. Recent findings Diagnostic stewardship can be implemented within healthcare systems and tailored to infectious syndromes, including urinary tract, gastrointestinal, respiratory and bloodstream infections. In urinary syndromes, diagnostic stewardship can decrease unnecessary urine culturing and associated antibiotic prescribing. Diagnostic stewardship of Clostridium difficile testing can decrease antibiotics and test ordering with a reduction in healthcare-associated C. difficile infections. Respiratory syndrome multiplex arrays can decrease time to results and increase detection of clinically relevant pathogens but may not decrease antibiotics use, or worse, could increase over-prescribing if diagnostic stewardship of ordering practices is not exercised. Lastly, blood culturing practices can be improved by clinical decision support to safely decrease collection and broad-spectrum antibiotic use. Summary Diagnostic stewardship decreases unnecessary antibiotic use in a way that is different from and complementary to antibiotic stewardship. Further studies are needed to quantify the full impact on antibiotic use and resistance. Future considerations should be to institutionalize diagnostic stewardship in patient care activities to leverage integration into systems-based interventions.

AbstractBackgroundDespite intensive prophylactic and pre-emptive measures, infections remain an important cause of morbidity and mortality in pediatric recipients of allogeneic hematopoietic cell transplantation (allo-HCT). Disruption of the gut microbiota has been linked to clinical outcomes after adult allo-HCT. This study evaluated whether these or differing microbiota disruptions or signatures were associated with risk of infection in pediatric allo-HCT.MethodsIn a prospective observational study, fecal samples from 74 children were collected prior to conditioning and at the time of neutrophil recovery and profiled by means of 16S ribosomal rRNA sequencing. The associations between microbiome signatures and infections or acute graft-versus-host disease (aGVHD) were examined using Cox proportional-hazards analysis.ResultsPreviously associated indices of microbiome disruption in adults, including diversity and butyrate producer frequency, did not predict infection risk in pediatric allo-HCT. Unique microbiota signatures were associated with different infections or aGVHD. A ratio of strict and facultative anaerobes (e.g. Lachnoclostridium, Parabacteroides, Clostridium spp.) prior to conditioning predicted likelihood of bacteremia (cox hazards ratio 3.89) in first year post HCT. A distinct ratio of oral (e.g. Rothia, Veillonella spp.) to colonic anaerobes (e.g. Anaerobutyricum, Dorea, Romboutsia spp.) at neutrophil recovery predicted likelihood of bacterial infections (cox hazards ratio 1.81) and viral enterocolitis (cox hazards ratio 1.96) through first year post transplant.ConclusionsInteractions between medical interventions, pediatric hosts and microbial communities may be responsible for these consistent microbiota signatures that predict infections. A future multi-center investigation will be needed to demonstrate whether these ratios can be generalized to other pediatric cohorts.

Infection and Immunity, Ahead of Print.

Objective: To investigate temporal trends and outcomes associated with early antibiotic prescribing in patients hospitalized with COVID-19. Design: Retrospective propensity-matched cohort study using the National COVID Cohort Collaborative (N3C) database. Setting: Sixty-six health systems throughout the United States that were contributing to the N3C database. Centers that had fewer than 500 admissions in their dataset were excluded. Patients: Patients hospitalized with COVID-19 were included. Patients were defined to have early antibiotic use if they received at least 3 calendar days of intravenous antibiotics within the first 5 days of admission. Interventions: None. Measurements and Main Results: Of 322,867 qualifying first hospitalizations, 43,089 patients received early empiric antibiotics. Antibiotic use declined across all centers in the data collection period, from March 2020 (23%) to June 2022 (9.6%). Average rates of early empiric antibiotic use (EEAU) also varied significantly between centers (deviance explained 7.33% vs 20.0%, p < 0.001). Antibiotic use decreased slightly by day 2 of hospitalization and was significantly reduced by day 5. Mechanical ventilation before day 2 (odds ratio [OR] 3.57; 95% CI, 3.42–3.72), extracorporeal membrane oxygenation before day 2 (OR 2.14; 95% CI, 1.75–2.61), and early vasopressor use (OR 1.85; 95% CI, 1.78–1.93) but not region of residence was associated with EEAU. After propensity matching, EEAU was associated with an increased risk for in-hospital mortality (OR 1.27; 95% CI, 1.23–1.33), prolonged mechanical ventilation (OR 1.65; 95% CI, 1.50–1.82), late broad-spectrum antibiotic exposure (OR 3.24; 95% CI, 2.99–3.52), and late Clostridium difficile infection (OR 1.60; 95% CI, 1.37–1.87). Conclusions: Although treatment of COVID-19 patients with empiric antibiotics has declined during the pandemic, the frequency of use remains high. There is significant inter-center variation in antibiotic prescribing practices and evidence of potential harm. Our findings are hypothesis-generating and future work should prospectively compare outcomes and adverse events.

Abstract Background Disseminated Clostridium septicum infection is an uncommon complication associated with malignancies, particular colonic adenocarcinoma. The organism appears to preferentially colonize large masses in rare individuals and subsequently seed the blood via mucosal ulceration. This has rarely been reported to lead to central nervous system infection and, in several cases, rapidly progressive pneumocephalus. In the few cases reported, this was a universally fatal condition. The current case adds to the reports of this extremely rare complication and provides a unique and complete clinicopathologic characterization with autopsy examination, microscopy, and molecular testing. Case Presentation A 60-year-old man with no known past medical history was discovered having seizure-like activity and stroke-like symptoms. Blood cultures turned positive after six hours. Imaging revealed a large, irregular cecal mass as well as 1.4 cm collection of air in the left parietal lobe that progressed to over 7 cm within 8 h. By the following morning, the patient had lost all neurologic reflexes and died. Post-mortem examination revealed brain tissue with multiple grossly evident cystic spaces and intraparenchymal hemorrhage, while microscopic exam showed diffuse hypoxic-ischemic injury and gram-positive rods. Clostridium septicum was identified on blood cultures and was confirmed in paraffin embedded tissue from the brain by 16 S ribosomal sequencing and from the colon by C. septicum specific PCR. Conclusions C. septicum is an anaerobic, gram-positive rod that can become invasive and is strongly associated with gastrointestinal pathology including colonic adenocarcinomas. Central nervous system infection with rapidly progressive pneumocephalus is a rarely reported and universally fatal complication of disseminated C. septicum infection. …