Studies on the Catechin Constituents of Bark of Cinnamomum sieboldii.

Screening for bioactivity related to anti-infective, anti-methicillin-resistant Staphylococcus aureus (MRSA) and anti-viral activity, led us to identify active compounds from a methanol extract of Litsea japonica (Thub.) Juss. and the hot water extract of bark of Cinnamomum sieboldii Meisn (also known as Karaki or Okinawa cinnamon). The two main components in these extracts were identified as the catechin trimers (+)-cinnamtannin B1 and pavetannin B5. Moreover, these extracts exhibited anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) activity. The structures of these catechin trimers were previously determined by chemical and spectroscopic methods. Pavetanin B5 has never been reported to be isolated as a pure form and has been obtained as a mixture with another component. Although other groups have reported the putative structure of pavetannin B5, preparation of the methylated derivative of pavetannin B5 in this study allowed us to obtain the pure form for the first time as the undecamethyl derivative and confirm its exact structure. Commercially available (+)-cinnamtannin B1 and aesculitannin B (C2'-epimer of cinnamtannin B1) both of which contained pavetannin B5 as a minor component, and C. sieboldii bark extract (approx. 5/2 mixture of (+)-cinnamtannin B1/pavetannin B5) were assessed for anti-SARS-CoV-2 activity. Both C. sieboldii bark extract and commercially available aesculitannin B showed viral growth inhibitory activity.

Bioactive metabolites of Streptomyces misakiensis display broad-spectrum antimicrobial activity against multidrug-resistant bacteria and fungi.

Background: Antimicrobial resistance is a serious threat to public health globally. It is a slower-moving pandemic than COVID-19, so we are fast running out of treatment options. Purpose: Thus, this study was designed to search for an alternative biomaterial with broad-spectrum activity for the treatment of multidrug-resistant (MDR) bacterial and fungal pathogen-related infections. Methods: We isolated Streptomyces species from soil samples and identified the most active strains with antimicrobial activity. The culture filtrates of active species were purified, and the bioactive metabolite extracts were identified by thin-layer chromatography (TLC), preparative high-performance liquid chromatography (HPLC), nuclear magnetic resonance (NMR) spectroscopy, and gas chromatography-mass spectrometry (GC-MS). The minimum inhibitory concentrations (MICs) of the bioactive metabolites against MDR bacteria and fungi were determined using the broth microdilution method. Results: Preliminary screening revealed that Streptomyces misakiensis and S. coeruleorubidus exhibited antimicrobial potential. The MIC50 and MIC90 of S. misakiensis antibacterial bioactive metabolite (ursolic acid methyl ester) and antifungal metabolite (tetradecamethylcycloheptasiloxane) against all tested bacteria and fungi were 0.5 µg/ml and 1 µg/mL, respectively, versus S. coeruleorubidus metabolites: thiocarbamic acid, N,N-dimethyl, S-1,3-diphenyl-2-butenyl ester against bacteria (MIC50: 2 µg/ml and MIC90: 4 µg/mL) and fungi (MIC50: 4 µg/ml and MIC90: 8 µg/mL). Ursolic acid methyl ester was active against ciprofloxacin-resistant strains of Streptococcus pyogenes, S. agalactiae, Escherichia coli, Klebsiella pneumoniae, and Salmonella enterica serovars, colistin-resistant Aeromonas hydrophila and K. pneumoniae, and vancomycin-resistant Staphylococcus aureus. Tetradecamethylcycloheptasiloxane was active against azole- and amphotericin B-resistant Candida albicans, Cryptococcus neoformans, C. gattii, Aspergillus flavus, A. niger, and A. fumigatus. Ursolic acid methyl ester was applied in vivo for treating S. aureus septicemia and K. pneumoniae pneumonia models in mice. In the septicemia model, the ursolic acid methyl ester-treated group had a significant 4.00 and 3.98 log CFU/g decrease (P < 0.05) in liver and spleen tissue compared to the infected, untreated control group. Lung tissue in the pneumonia model showed a 2.20 log CFU/g significant decrease in the ursolic acid methyl ester-treated group in comparison to the control group. The haematological and biochemical markers in the ursolic acid methyl ester-treated group did not change in a statistically significant way. Moreover, no abnormalities were found in the histopathology of the liver, kidneys, lungs, and spleen of ursolic acid methyl ester-treated mice in comparison with the control group. Conclusion: S. misakiensis metabolite extracts are broad-spectrum antimicrobial biomaterials that can be further investigated for the potential against MDR pathogen infections. Hence, it opens up new horizons for exploring alternative drugs for current and reemerging diseases.

Health Care-Associated Infections Among Hospitalized Patients With COVID-19, March 2020-March 2022.

Importance: The reported incidence of many health care-associated infections (HAIs) increased during the COVID-19 pandemic; however, it is unclear whether this is due to increased patient risk or to increased pressure on the health care system. Objective: To assess HAI occurrence among patients admitted to hospitals with and without COVID-19. Design, Setting, and Participants: A cross-sectional retrospective analysis of inpatients discharged both with and without laboratory-confirmed COVID-19 infection was conducted. Data were obtained between January 1, 2019, and March 31, 2022, from community hospitals affiliated with a large health care system in the US. Exposure: COVID-19 infection. Main Outcomes and Measures: Occurrence of central line-associated bloodstream infection (CLABSI), catheter-associated urinary tract infection (CAUTI), methicillin-resistant Staphylococcus aureus (MRSA) bacteremia, and Clostridioides difficile infection as reported to the National Healthcare Safety Network. Results: Among nearly 5 million hospitalizations in 182 hospitals between 2020 and 2022, the occurrence of health care-associated infections (HAIs) was high among the 313 200 COVID-19 inpatients (median [SD] age, 57 [27.3] years; 56.0% women). Incidence per 100 000 patient-days showed higher HAIs among those with COVID-19 compared with those without. For CLABSI, the incidence for the full 9 quarters of the study was nearly 4-fold higher among the COVID-19 population than the non-COVID-19 population (25.4 vs 6.9). For CAUTI, the incidence in the COVID-19 population was 2.7-fold higher in the COVID-19 population (16.5 vs 6.1), and for MRSA, 3.0-fold higher (11.2 vs 3.7). Quarterly trends were compared with the same quarter in 2019. The greatest increase in the incidence of HAI in comparison with the same quarter in 2019 for the entire population occurred in quarter 3 of 2020 for CLABSI (11.0 vs 7.3), quarter 4 of 2021 for CAUTI (7.8 vs 6.8), and quarter 3 of 2021 for MRSA (5.2 vs 3.9). When limited to the non-COVID-19 population, the increase in CLABSI incidence vs the 2019 incidence was eliminated, and the quarterly rates of MRSA and CAUTI were lower vs the prepandemic 2019 comparator quarter. Conclusions and Relevance: In this cross-sectional study of hospitals during the pandemic, HAI occurrence among inpatients without COVID-19 was similar to that during 2019 despite additional pressures for infection control and health care professionals. The findings suggest that patients with COVID-19 may be more susceptible to HAIs and may require additional prevention measures.

Success and failures in MRSA infection control during the COVID-19 pandemic.

Private sector facilities in the United States have experienced a resurgence of Methicillin-resistant Staphylococcus aureus (MRSA) hospital-onset infections during the COVID-19 pandemic, which eliminated all gains that were achieved over the last decade. The third quarter of 2021, the Standardized Infection Ratio for hospital onset MRSA bloodstream infections was 1.17, well above the baseline value of 1.0. In contrast, the Veterans Health Administration (VHA) has been able to maintain its mitigation efforts and low rates of MRSA hospital-onset infections through the second quarter of fiscal year 2022 (Mar. 31, 2022), the most recent available data. The difference may be explained not only by the VHA's use of uniform mitigating policies which rely on active surveillance and contact precautions, but also on the VAH's ability to maintain adequate staffing during the pandemic. Future research into MRSA mitigation is warranted and this data supports the need for healthcare system transformation.

Multidrug-Resistant Kocuria rosea and Methicillin-Resistant Staphylococcus aureus Co-Infection in a Nigerian Patient with COVID-19: A Case Report.

BACKGROUND Bacterial Infections, especially, of the respiratory system, have been reported as one of the medical concerns in patients with the Coronavirus Disease-2019 (COVID-19), particularly those with multiple co-morbidities. We present a case of a diabetic patient with co-infection of multi-drug-resistant Kocuria rosea and methicillin-resistant Staphylococcus aureus (MRSA) who contracted COVID-19. CASE REPORT A 72-year-old man with diabetes presented with symptoms including cough, chest pain, urinary incontinence, respiratory distress, sore throat, fever, diarrhea, loss of taste, and anosmia and was confirmed to have COVID-19. At admission, he was also found to have sepsis. MRSA was isolated in conjunction with another organism, resembling coagulase-negative Staphylococcus, which was misidentified using commercial biochemical testing systems. The strain was finally confirmed to be Kocuria rosea by 16S rRNA gene sequencing. Both strains were highly resistant to multiple classes of antibiotics, but the Kocuria rosea was resistant to all the cephalosporins, fluoroquinolones, and macrolides tested. The use of ceftriaxone and ciprofloxacin did not improve his condition, which ultimately led to his death. CONCLUSIONS This case report shows that the presence of multi-drug-resistant bacteria infections can be fatal in patients with COVID-19, especially in patients with other co-morbidities like diabetes. This case report also shows that biochemical testing may be inadequate in identifying emerging bacterial infections and there is a need to include proper bacterial screening and treatment in the management of COVID-19, especially in patients with other co-morbidities and with indwelling devices.

A Bifunctional Spray Coating Reduces Contamination on Surfaces by Repelling and Killing Pathogens.

Surface-mediated transmission of pathogens is a major concern with regard to the spread of infectious diseases. Current pathogen prevention methods on surfaces rely on the use of biocides, which aggravate the emergence of antimicrobial resistance and pose harmful health effects. In response, a bifunctional and substrate-independent spray coating is presented herein. The bifunctional coating relies on wrinkled polydimethylsiloxane microparticles, decorated with biocidal gold nanoparticles to induce a "repel and kill" effect against pathogens. Pathogen repellency is provided by the structural hierarchy of the microparticles and their surface chemistry, whereas the kill mechanism is achieved using functionalized gold nanoparticles embedded on the microparticles. Bacterial tests with methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa reveal a 99.9% reduction in bacterial load on spray-coated surfaces, while antiviral tests with Phi6─a bacterial virus often used as a surrogate to SARS-CoV-2─demonstrate a 98% reduction in virus load on coated surfaces. The newly developed spray coating is versatile, easily applicable to various surfaces, and effective against various pathogens, making it suitable for reducing surface contamination in frequently touched, heavy traffic, and high-risk surfaces.

A parallel and silent emerging pandemic: Antimicrobial resistance (AMR) amid COVID-19 pandemic.

World is in the middle of the pandemic (COVID-19), caused by SARS-COV-2 virus, which is a significant global health crisis after Spanish influenza in the beginning of 20th century. Progressive drastic steps have been enforced to minimize the transmission of the disease. Likewise, in the current years, antimicrobial resistance (AMR) has been referred as one of the potential perils to the global economy and health; however, it is now veiled under the present pandemic. During the current pandemic, AMR to available frontline antibiotics may prove fatal and life threatening to bacterial and fungal infections during routine procedures like elective surgery, C-sections, etc. Currently, a swift elevation in multidrug-resistant organisms (MDROs), like carbapenem-resistant New Delhi metallo-ß-lactamase (NDM)-producing Acinetobacter baumannii, Enterobacterales, extended-spectrum ß-lactamase (ESBL)-producing Klebsiella pneumoniae, methicillin-resistant Staphylococcus aureus (MRSA), multi-triazole-resistant Aspergillus fumigatus and pan-echinocandin-resistant Candida glabrata has been seen. Thereupon, the global outbreak of COVID-19 also offers some important ramification for developing antimicrobial drug resistance. This article aims to highlights episodes and aspects of AMR prevalence, impact of management and mismanagement of COVID-19 crisis, hospital settings, community, environment, and travel on the AMR during the current pandemic.

Eremoxylarins D-J, Antibacterial Eremophilane Sesquiterpenes Discovered from an Endolichenic Strain of Xylaria hypoxylon.

An endolichenic strain of the Ascomycetaceous Xylaria hypoxylon, cultivated alone or in coculture with another endolichenic fungus Dendrothyrium variisporum, produced seven new bioactive eremophilane sesquiterpenes eremoxylarins D-J (1-7). The isolated compounds disclosed a high similarity with the eremophilane core of the bioactive integric acid, and structures were elucidated by 1D and 2D NMR spectra and electronic circular dichroism (ECD) analyses. Eremoxylarins D, F, G, and I showed a selective activity against Gram-positive bacteria such as methicillin-resistant Staphylococcus aureus with minimum inhibitory concentration (MIC) values between 0.39 and 12.5 µg/mL. Eremoxylarin I, the most antibacterial active sesquiterpene, was also active against HCoV-229E at a concentration nontoxic to the hepatoma Huh-7 cell line with an 50% inhibitory concentration (IC50) of 18.1 µM and a 50% cytotoxic concentration (CC50) of 46.6 µM.

Evidence of Antimicrobial Resistance in Bats and Its Planetary Health Impact for Surveillance of Zoonotic Spillover Events: A Scoping Review.

As a result of the COVID-19 pandemic, as well as other outbreaks, such as SARS and Ebola, bats are recognized as a critical species for mediating zoonotic infectious disease spillover events. While there is a growing concern of increased antimicrobial resistance (AMR) globally during this pandemic, knowledge of AMR circulating between bats and humans is limited. In this paper, we have reviewed the evidence of AMR in bats and discussed the planetary health aspect of AMR to elucidate how this is associated with the emergence, spread, and persistence of AMR at the human-animal interface. The presence of clinically significant resistant bacteria in bats and wildlife has important implications for zoonotic pandemic surveillance, disease transmission, and treatment modalities. We searched MEDLINE through PubMed and Google Scholar to retrieve relevant studies (n = 38) that provided data on resistant bacteria in bats prior to 30 September 2022. There is substantial variability in the results from studies measuring the prevalence of AMR based on geographic location, bat types, and time. We found all major groups of Gram-positive and Gram-negative bacteria in bats, which are resistant to commonly used antibiotics. The most alarming issue is that recent studies have increasingly identified clinically significant multi-drug resistant bacteria such as Methicillin Resistant Staphylococcus aureus (MRSA), ESBL producing, and Colistin resistant Enterobacterales in samples from bats. This evidence of superbugs abundant in both humans and wild mammals, such as bats, could facilitate a greater understanding of which specific pathways of exposure should be targeted. We believe that these data will also facilitate future pandemic preparedness as well as global AMR containment during pandemic events and beyond.

Evaluating Methicillin-Resistant Staphylococcus aureus Polymerase Chain Reaction Nasal Screening as a Tool for Antimicrobial Stewardship.

INTRODUCTION: Initiation of broad-spectrum empiric antibiotics is common when infection is suspected in hospitalized adults. The benefits of early utilization of effective antibiotics are well documented. However, the negative effects of inappropriate antibiotic use have led to antimicrobial stewardship mandates. Recent data demonstrate the utility of methicillin-resistant Staphylococcus aureus (MRSA) polymerase chain reaction (PCR) nasal screening to steward anti-MRSA empiric antibiotics in pneumonia. We hypothesize that MRSA PCR nasal swabs would also be effective to rule out other MRSA infection to effectively limit unnecessary antibiotics for any infectious source. METHODS: We performed a single-center retrospective chart review of all adult patient encounters from October 2019-July 2021 with MRSA PCR nasal testing. We then reviewed all charts to evaluate for the presence of infections based on source cultures results, as the gold standard. Sensitivity, specificity, negative predictive value, and positive predictive value were calculated from 2 × 2 contingency tables. RESULTS: Among all patients with MRSA nasal screening, 1189 patients had any infection. Prevalence of MRSA nasal carriage among patients screened was 12%. Prevalence of MRSA infection among all infections was 7.5%. MRSA nasal swabs demonstrated a negative predictive value of 100% for MRSA urinary tract infection, 97.9% for MRSA bacteremia, 97.8% for MRSA pneumonia, 92.1% for MRSA wound infection, and 96.6% for other MRSA infections. Overall, MRSA PCR nasal swabs had a sensitivity of 68.5%, specificity of 90.1%, positive predictive value of 23.7%, and negative predictive value of 98.5% for any infections. CONCLUSIONS: MRSA PCR nasal swabs have a high negative predictive value for all infections. Our data support the use of MRSA PCR nasal swabs to rule out MRSA infection and thereby allow early de-escalation of MRSA coverage in hospitalized patients requiring empiric antibiotics. Implementation of MRSA screening could decrease antibiotic-associated morbidity, resistance, and costs. More studies should be conducted to validate these results and support these findings.

Impact of COVID-19 pandemic on multidrug resistant gram positive and gram negative pathogens: A systematic review.

BACKGROUND: There is paucity of data describing the impact of COVID-19 pandemic on antimicrobial resistance. This review evaluated the changes in the rate of multidrug resistant gram negative and gram positive bacteria during the COVID-19 pandemic. METHODS: A search was conducted in PubMed, Science Direct, and Google Scholar databases to identify eligible studies. Studies that reported the impact of COVID-19 pandemic on carbapenem-resistant Acinetobacter baumannii (CRAB), carbapenem-resistant Enterobacteriaceae (CRE), extended-spectrum beta-lactamase inhibitor (ESBL)-producing Enterobacteriaceae, vancomycin-resistant enterococci (VRE), methicillin-resistant Staphylococcus aureus (MRSA) and carbapenem-resistant Pseudomonas aeruginosa (CPE) were selected. Studies published in English language from the start of COVID-19 pandemic to July 2022 were considered for inclusion. RESULTS: Thirty eligible studies were selected and most of them were from Italy (n = 8), Turkey (n = 3) and Brazil (n = 3). The results indicated changes in the rate of multidrug resistant bacteria, and the changes varied between the studies. Most studies (54.5%) reported increase in MRSA infection/colonization during the pandemic, and the increase ranged from 4.6 to 170.6%. Five studies (55.6%) reported a 6.8-65.1% increase in VRE infection/colonization during the pandemic. A 2.4-58.2% decrease in ESBL E. coli and a 1.8-13.3% reduction in ESBL Klebsiella pneumoniae was observed during the pandemic. For CRAB, most studies (58.3%) reported 1.5-621.6% increase in infection/colonization during the pandemic. Overall, studies showed increase in the rate of CRE infection/colonization during the pandemic. There was a reduction in carbapenem-resistant E. coli during COVID-19 pandemic, and an increase in carbapenem-resistant K. pneumoniae. Most studies (55.6%) showed 10.4 - 40.9% reduction in the rate of CRPA infection during the pandemic. CONCLUSION: There is an increase in the rate of multidrug resistant gram positive and gram negative bacteria during the COVID-19 pandemic. However, the rate of ESBL-producing Enterobacteriaceae and CRPA has decrease during the pandemic. Both infection prevention and control strategies and antimicrobial stewardship should be strengthen to address the increasing rate of multidrug resistant gram positive and gram negative bacteria.

Antibiotic resistance associated with the COVID-19 pandemic: a systematic review and meta-analysis.

BACKGROUND: COVID-19 and antimicrobial resistance (AMR) are two intersecting global public health crises. OBJECTIVE: We aimed to describe the impact of the COVID-19 pandemic on AMR across health care settings. DATA SOURCE: A search was conducted in December 2021 in WHO COVID-19 Research Database with forward citation searching up to June 2022. STUDY ELIGIBILITY: Studies evaluating the impact of COVID-19 on AMR in any population were included and influencing factors were extracted. Reporting of enhanced infection prevention and control and/or antimicrobial stewardship programs was noted. METHODS: Pooling was done separately for Gram-negative and Gram-positive organisms. Random-effects meta-analysis was performed. RESULTS: Of 6036 studies screened, 28 were included and 23 provided sufficient data for meta-analysis. The majority of studies focused on hospital settings (n = 25, 89%). The COVID-19 pandemic was not associated with a change in the incidence density (incidence rate ratio 0.99, 95% CI: 0.67-1.47) or proportion (risk ratio 0.91, 95% CI: 0.55-1.49) of methicillin-resistant Staphylococcus aureus or vancomycin-resistant enterococci cases. A non-statistically significant increase was noted for resistant Gram-negative organisms (i.e. extended-spectrum beta-lactamase, carbapenem-resistant Enterobacterales, carbapenem or multi-drug resistant or carbapenem-resistant Pseudomonas aeruginosa or Acinetobacter baumannii, incidence rate ratio 1.64, 95% CI: 0.92-2.92; risk ratio 1.08, 95% CI: 0.91-1.29). The absence of reported enhanced infection prevention and control and/or antimicrobial stewardship programs initiatives was associated with an increase in gram-negative AMR (risk ratio 1.11, 95% CI: 1.03-1.20). However, a test for subgroup differences showed no statistically significant difference between the presence and absence of these initiatives (p 0.40). CONCLUSION: The COVID-19 pandemic may have hastened the emergence and transmission of AMR, particularly for Gram-negative organisms in hospital settings. But there is considerable heterogeneity in both the AMR metrics used and the rate of resistance reported across studies. These findings reinforce the need for strengthened infection prevention, antimicrobial stewardship, and AMR surveillance in the context of the COVID-19 pandemic.

Biopolymer Coating Imparts Sustainable Self-Disinfecting and Antimicrobial Properties to Fabric: Translated to Protective Gears for the Pandemic and Beyond.

The global pandemic of COVID-19 and emerging antimicrobial drug resistance highlights the need for sustainable technology that enables more preparedness and active control measures. It is thus important to have a reliable solution to avert the present situations as well as preserve nature for habitable life in the future. One time use of PPE kits is promoting the accumulation of nondegradable waste, which may pose an unforeseen challenge in the future. We have developed a biocompatible, biodegradable, and nonirritating nanoemulsion coating for textiles. The study focused on coating cotton fabric to functionalize it with broad spectrum antimicrobial, antibiofilm, and anti-SARS-CoV-2 activity. The nanoemulsion comprises spherical particles of chitosan, oleic acid, and eugenol that are cross-linked to fibers. The nanoemulsion caused complete destruction of pathogens even for the most rigid biofilms formed by drug resistant Staphylococcus aureus, Pseudomonas aeruginosa, and Candida albicans on the surface of the coated fabric. The secondary coat with beeswax imparts super hydrophobicity and 20 wash cycle resistance and leads to enhanced barrier properties with superior particulate filtration, bacterial filtration, and viral penetration efficiency as compared to an N95 respirator. The coated fabric qualifies as per standard parameters like breathability, flammability, splash resistance, and filtration efficiency for submicrometer particles, bacteria, and viruses. The scaleup and bulk manufacturing of the coating technology on fabric masks complied with standards. The consumer feedback rated the coated mask with high scores in breathability and comfortability as compared to an N95. The strategy promises to provide a long-term sustainable model compared to single use masks and PPE that will remain a nondegradable burden on the ecosystem for years to come.

Skin and soft tissue infections in the elderly.

PURPOSE OF REVIEW: To highlight the peculiarity of skin and soft tissue infections (SSTIs) in elderly patients and to provide useful elements for their optimal management. RECENT FINDINGS: In the COVID-19 era, early discharge from the hospital and implementation of outpatient management is of key importance. SUMMARY: Elderly patients are at high risk of SSTIs due to several factors, including presence of multiple comorbidities and skin factors predisposing to infections. Clinical presentation may be atypical and some signs of severity, such as fever and increase in C-reactive protein, may be absent or aspecific in this patients population. An appropriate diagnosis of SSTIs in the elderly is crucial to avoid antibiotic overtreatment. Further studies should explore factors associated with bacterial superinfections in patients with pressure ulcers or lower limb erythema. Since several risk factors for methicillin-resistant Staphylococcus aureus (MRSA) may coexist in elderly patients, these subjects should be carefully screened for MRSA risk factors and those with high risk of resistant etiology should receive early antibiotic therapy active against MRSA. Physicians should aim to several objectives, including clinical cure, patient safety, early discharge and return to community. SSTIs in the elderly may be managed using long-acting antibiotics, but clinical follow-up is needed.

Tetrahedral Framework Nucleic Acids: A Novel Strategy for Antibiotic Treating Drug-Resistant Infections.

Antibiotic multiresistance (AMR) has emerged as a major threat to human health as millions of people die from AMR-related problems every year. As has been witnessed during the global COVID-19 pandemic, the significantly increased demand for antibiotics has aggravated the issue of AMR. Therefore, there is an urgent need to find ways to alleviate it. Tetrahedral framework nucleic acids (tFNAs) are novel nanomaterials that are often used as drug delivery platforms because of their structural diversity. This study formed a tFNAs-antibiotic compound (TAC) which has a strong growth inhibitory effect on Escherichia coli and methicillin-resistant Staphylococcus aureus (MRSA) in vitro owing to the increased absorption of antibiotics by bacteria and improved drug movement across cell membranes. We established a mouse model of systemic peritonitis and local wound infections. The TAC exhibited good biosafety and improved the survival rate of severely infected mice, promoting the healing of local infections. In addition to the better transport of antibiotics to the target, the TAC may also enhance immunity by regulating the differentiation of M1 and M2 macrophages, providing a new option for the treatment of infections.

Waterhouse-Friderichsen Syndrome with Bilateral Adrenal Hemorrhage Associated with Methicillin-Resistant Staphylococcus aureus (MRSA) Bacteremia in an Adult Patient with History of Intravenous Drug Use.

BACKGROUND Waterhouse-Friderichsen syndrome, also known as acute adrenal insufficiency due to adrenal gland hemorrhage, is an uncommon and frequently fatal condition classically presenting with fever, shock, rash, and coagulopathy. Although most often associated with Meningococcemia, many other etiologies have been implicated, including reports of Staphylococcus aureus infection on autopsy examinations. This report details an adult intravenous drug user with adrenal hemorrhage associated with methicillin-resistant Staphylococcus aureus (MRSA) bacteremia. CASE REPORT A 58-year-old man with a history of intravenous drug use presented to the hospital with weakness. Vitals were initially normal and exam findings were notable for decreased right-sided motor strength. Magnetic resonance imaging (MRI) revealed a cervical epidural abscess with spinal cord compression. Despite initiation of broad-spectrum antibiotics and intravenous fluids, the patient progressed to shock, requiring vasopressor administration, and his blood cultures later grew MRSA. Further imaging of the abdomen/pelvis was completed, revealing bilateral adrenal hemorrhage. Random cortisol at that time was 5.6 µg/dL, confirming a diagnosis of critical illness-related corticosteroid insufficiency in addition to likely septic and spinal shock. The patient was initiated on hydrocortisone with improvement in his hypotension. He was transitioned to prednisone and fludrocortisone in addition to 8 weeks of antibiotics after achieving clinical stability. CONCLUSIONS This report brings to attention the risk of adrenal hemorrhage and acute adrenal insufficiency as a sequela of the relatively common illness of Staphylococcus aureus bacteremia. As symptoms of adrenal insufficiency can overlap with septic shock related to the primary condition, this diagnosis requires a high index of suspicion in the critically ill patient.

Healthcare microenvironments define multidrug-resistant organism persistence.

BACKGROUND: Multidrug-resistant organisms (MDROs) colonizing the healthcare environment have been shown to contribute to risk for healthcare-associated infections (HAIs), with adverse effects on patient morbidity and mortality. We sought to determine how bacterial contamination and persistent MDRO colonization of the healthcare environment are related to the position of patients and wastewater sites. METHODS: We performed a prospective cohort study, enrolling 51 hospital rooms at the time of admitting a patient with an eligible MDRO in the prior 30 days. We performed systematic sampling and MDRO culture of rooms, as well as 16S rRNA sequencing to define the environmental microbiome in a subset of samples. RESULTS: The probability of detecting resistant gram-negative organisms, including Enterobacterales, Acinetobacter spp, and Pseudomonas spp, increased with distance from the patient. In contrast, Clostridioides difficile and methicillin-resistant Staphylococcus aureus were more likely to be detected close to the patient. Resistant Pseudomonas spp and S. aureus were enriched in these hot spots despite broad deposition of 16S rRNA gene sequences assigned to the same genera, suggesting modifiable factors that permit the persistence of these MDROs. CONCLUSIONS: MDRO hot spots can be defined by distance from the patient and from wastewater reservoirs. Evaluating how MDROs are enriched relative to bacterial DNA deposition helps to identify healthcare micro-environments and suggests how targeted environmental cleaning or design approaches could prevent MDRO persistence and reduce infection risk.