Broad Spectrum Research Articles

Two Enterococcus faecium Isolates Demonstrated Modulating Effects on the Dysbiosis of Mice Gut Microbiota Induced by Antibiotic Treatment

Broad-spectrum antibiotics are frequently used to treat bacteria-induced infections, but the overuse of antibiotics may induce the gut microbiota dysbiosis and disrupt gastrointestinal tract function. Probiotics can be applied to restore disturbed gut microbiota and repair abnormal intestinal metabolism. In the present study, two strains of Enterococcus faecium (named DC-K7 and DC-K9) were isolated and characterized from the fecal samples of infant dogs. The genomic features of E. faecium DC-K7 and DC-K9 were analyzed, the carbohydrate-active enzyme (CAZyme)-encoding genes were predicted, and their abilities to produce short-chain fatty acids (SCFAs) were investigated. The bacteriocin-encoding genes in the genome sequences of E. faecium DC-K7 and DC-K9 were analyzed, and the gene cluster of Enterolysin-A, which encoded a 401-amino-acid peptide, was predicted. Moreover, the modulating effects of E. faecium DC-K7 and DC-K9 on the gut microbiota dysbiosis induced by antibiotics were analyzed. The current results demonstrated that oral administrations of E. faecium DC-K7 and DC-K9 could enhance the relative abundances of beneficial microbes and decrease the relative abundances of harmful microbes. Therefore, the isolated E. faecium DC-K7 and DC-K9 were proven to be able to alter the gut microbiota dysbiosis induced by antibiotic treatment.

Secondary metabolite fingerprinting, anti-pathogenic activity, elite chemotype selection and conservation of Curcuma caesia- an ethnomedicinally underutilized species.

Curcuma caesia Roxb. is an ethnomedicinally important, essential oil (EO) yielding aromatic plant. A total of twelve accessions of this plant rhizome were collected from six different agro-climatic zones of West Bengal, India and evaluated for their antimicrobial activities against eight disease-causing, multi-drug-resistant pathogenic strains of urinary-tract infection and respiratory-tract infection. The EO and extracts demonstrated antibacterial activity, with the highest inhibition zone of 18.00 ± 0.08 and 17.50 ± 0.14mm against Klebsiella pneumoniae by accession 06, even where all the broad-spectrum antibiotics failed to respond. In this study, we employed high-performance thin-layer chromatography (HPTLC) to quantify curcumin, the primary secondary metabolite of C. caesia, and the highest 0.228mg/gm of curcumin resulted from accession 06. Hence, on the basis of all aspects, accession 06 was identified as the elite chemotype among all twelve accessions. The chemical profiling of EO from accession 06 was done using gas chromatography-mass spectroscopy (GC-MS). Conceivably, about 13 medicinally significant compounds were detected. As this plant species is seasonal and has difficulties in conventional breeding due to dormancy, it must be conserved through in vitro tissue culture for a steady supply throughout the year in massive amounts for agricultural demand. A maximum number of 19.28 ± 0.37 shoots has been obtained in MS medium fortified with 6-Benzylaminopurine, Kinetin, and Naphthalene acetic acid. The genetic uniformity of the plants has been studied through Start Codon Targeted Polymorphism. Therefore, this study must help meet the need for essential phytoactive compounds through a simple, validated, and reproducible plant tissue culture protocol throughout the year.

Outcomes associated with initial narrow-spectrum versus broad-spectrum antibiotics in children hospitalized with urinary tract infections.

The aim of this study is to describe the proportion of children hospitalized with urinary tract infections (UTIs) who receive initial narrow- versus broad-spectrum antibiotics across children's hospitals and explore whether the use of initial narrow-spectrum antibiotics is associated with different outcomes. We performed a retrospective cohort analysis of children aged 2 months to 17 years hospitalized with UTI (inclusive of pyelonephritis) using the Pediatric Health Information System (PHIS) database. We analyzed the proportions of children initially receiving narrow- versus broad-spectrum antibiotics; additionally, we compiled antibiogram data for common uropathogenic organisms from participating hospitals to compare with the observed antibiotic susceptibility patterns. We examined the association of antibiotic type with adjusted outcomes including length of stay (LOS), costs, and 7- and 30-day emergency department (ED) revisits and hospital readmissions. We identified 10,740 hospitalizations for UTI across 39 hospitals. Approximately 5% of encounters demonstrated initial narrow-spectrum antibiotics, with hospital-level narrow-spectrum use ranging from <1% to 25%. Approximately 80% of hospital antibiograms demonstrated >80% Escherichia coli susceptibility to cefazolin. In adjusted models, those who received initial narrow-spectrum antibiotics had shorter LOS (narrow-spectrum: 33.1 (95% confidence interval [CI]: 30.8-35.4) h versus broad-spectrum: 46.1 (95% CI: 44.1-48.2) h) and reduced costs [narrow-spectrum: $4570 ($3751-5568) versus broad-spectrum: $5699 ($5005-$6491)]. There were no differences in ED revisits or hospital readmissions. In summary, children's hospitals have low rates of narrow-spectrum antibiotic use for UTIs despite many reporting high rates of cefazolin-susceptible E. coli. These findings, coupled with the observed decreased LOS and costs among those receiving narrow-spectrum antibiotics, highlight potential antibiotic stewardship opportunities.

Gut Microbiota and Immune System in Necrotizing Enterocolitis and Related Sepsis

A severe condition of sepsis can be a complication of necrotizing enterocolitis (NEC), which can occur in premature infants and becomes a medical challenge in the neonatal intensive care unit (NICU). It is a multifactorial intestinal disease (can affect both the small and large intestine) that can lead to ischemia of the intestinal tissues that evolves into acute organ necrosis. One of these factors is that different types of nutrition can influence the onset or the progression of the disease. Cow-milk-based infant formulas have been shown to cause it in premature infants more frequently than human milk. Recently, nutrition has been shown to be beneficial after surgery. Several issues still under study, such as the pathogenesis and the insufficient and often difficult therapeutic approach, as well as the lack of a common and effective prevention strategy, make this disease an enigma in daily clinical practice. Recent studies outlined the emerging role of the host immune system and resident gut microbiota, showing their close connection in NEC pathophysiology. In its initial stages, broad-spectrum antibiotics, bowel rest, and breastfeeding are currently used, as well as probiotics to help the development of the intestinal microbiota and its eubiosis. This paper aims to present the current knowledge and potential fields of research in NEC pathophysiology and therapeutic assessment.

Identifying the risk factors of ICU-acquired fungal infections: clinical evidence from using machine learning

BackgroundFungal infections are associated with high morbidity and mortality in the intensive care unit (ICU), but their diagnosis is difficult. In this study, machine learning was applied to design and define the predictive model of ICU-acquired fungi (ICU-AF) in the early stage of fungal infections using Random Forest.ObjectivesThis study aimed to provide evidence for the early warning and management of fungal infections.MethodsWe analyzed the data of patients with culture-positive fungi during their admission to seven ICUs of the First Affiliated Hospital of Chongqing Medical University from January 1, 2015, to December 31, 2019. Patients whose first culture was positive for fungi longer than 48 h after ICU admission were included in the ICU-AF cohort. A predictive model of ICU-AF was obtained using the Least Absolute Shrinkage and Selection Operator and machine learning, and the relationship between the features within the model and the disease severity and mortality of patients was analyzed. Finally, the relationships between the ICU-AF model, antifungal therapy and empirical antifungal therapy were analyzed.ResultsA total of 1,434 cases were included finally. We used lasso dimensionality reduction for all features and selected six features with importance ≥0.05 in the optimal model, namely, times of arterial catheter, enteral nutrition, corticosteroids, broadspectrum antibiotics, urinary catheter, and invasive mechanical ventilation. The area under the curve of the model for predicting ICU-AF was 0.981 in the test set, with a sensitivity of 0.960 and specificity of 0.990. The times of arterial catheter (p = 0.011, OR = 1.057, 95% CI = 1.053–1.104) and invasive mechanical ventilation (p = 0.007, OR = 1.056, 95%CI = 1.015–1.098) were independent risk factors for antifungal therapy in ICU-AF. The times of arterial catheter (p = 0.004, OR = 1.098, 95%CI = 0.855–0.970) were an independent risk factor for empirical antifungal therapy.ConclusionThe most important risk factors for ICU-AF are the six time-related features of clinical parameters (arterial catheter, enteral nutrition, corticosteroids, broadspectrum antibiotics, urinary catheter, and invasive mechanical ventilation), which provide early warning for the occurrence of fungal infection. Furthermore, this model can help ICU physicians to assess whether empiric antifungal therapy should be administered to ICU patients who are susceptible to fungal infections.

A Case of Lepromatous Leprosy (Lucio’s Phenomenon) Presenting as Periorbital Edema

Despite low prevalence of leprosy worldwide, new cases continue to present and require swift evaluation and diagnosis to prevent complications. Here, we describe a case of lepromatous leprosy with Lucio’s phenomenon initially presenting with facial and periorbital edema. A 38-year-old Brazilian woman presented to the emergency department with facial swelling and erythema, initially treated as cellulitis. Due to rapid worsening despite broad-spectrum antibiotics, she underwent soft tissue exploration and biopsy due to concern for necrotizing fasciitis. During her course, she also developed retiform purpura of bilateral upper and lower extremities. Periorbital and lower extremity pathological specimens ultimately revealed acid-fast bacilli consistent with Mycobacterium leprae, and the patient improved with multidrug therapy. This case illustrates the diagnostic difficulty of lepromatous leprosy with Lucio’s phenomenon, which can initially present with periorbital edema.

The impact of levofloxacin prophylaxis on empiric intravenous antibiotic use in pediatric hematopoietic stem cell transplant recipients.

Levofloxacin prophylaxis during periods of neutropenia in pediatric hematopoietic stem cell transplant (HSCT) may reduce the number of febrile episodes and use of empiric intravenous antibiotics (EIA); however, the literature is conflicting. This retrospective review compared EIA use before and after implementation of levofloxacin prophylaxis at a children's hospital. Levofloxacin prophylaxis was associated with reduced use of certain EIA; however, did not reduce the number of positive blood cultures or clinical deteriorations. Therefore, levofloxacin prophylaxis may have implications for the stewardship of broad-spectrum intravenous antibiotics used in pediatric HSCT.

Beta-lactam allergy risk stratification in a maternity population in Australia: Scope for allergy de-labelling.

Unconfirmed beta-lactam allergy in pregnant people has been associated with higher morbidity, unnecessary exposure to broad-spectrum antibiotics and prolonged hospitalisation. There are no published data on beta-lactam allergies in pregnant people in Australia. The aim was to describe patient-reported beta-lactam allergies and appropriateness for antibiotic allergy de-labelling in a maternity cohort in Australia. Maternity patients aged ≥18 years admitted to our institution between March 2021 and June 2021 with a beta-lactam allergy documented in their electronic medical record were interviewed for details of their allergy. The documented allergies were compared to the allergy history obtained from the interview. Severity of the allergy was rated, and appropriateness for allergy de-labelling was assessed using the Victorian Therapeutics Advisory Group beta-lactam antibiotic allergy assessment tool. One hundred and fifty-three beta-lactam allergies (182 reactions) were reported by 145 patients. Penicillin class antibiotics were the most frequently implicated, including unspecified penicillins (95/153, 62%), amoxicillin (19/153, 13%) and amoxicillin-clavulanate (8/153, 5%). Allergy documentation required amending in 52 of 145 patients (36%); 85 of 153 (56%) of the beta-lactam allergies were considered low risk and potentially appropriate for direct oral re-challenge. Beta-lactam allergies were inaccurately documented in more than one third of the maternity patients included in our study. As such, education of maternity care providers about the importance of accurate allergy history taking remains an urgent unmet need. Furthermore, allergy assessment and de-labelling during pregnancy should be considered in maternity patients to optimise antibiotic prescribing and to improve maternal and neonatal health outcomes.

Aging amplifies a gut microbiota immunogenic signature linked to heightened inflammation.

Aging is associated with low-grade inflammation that increases the risk of infection and disease, yet the underlying mechanisms remain unclear. Gut microbiota composition shifts with age, harboring microbes with varied immunogenic capacities. We hypothesized the gut microbiota acts as an active driver of low-grade inflammation during aging. Microbiome patterns in aged mice strongly associated with signs of bacterial-induced barrier disruption and immune infiltration, including marked increased levels of circulating lipopolysaccharide (LPS)-binding protein (LBP) and colonic calprotectin. Exvivo immunogenicity assays revealed that both colonic contents and mucosa of aged mice harbored increased capacity to activate toll-like receptor 4 (TLR4) whereas TLR5 signaling was unchanged. We found patterns of elevated innate inflammatory signaling (colonic Il6, Tnf, and Tlr4) and endotoxemia (circulating LBP) in young germ-free mice after 4 weeks of colonization with intestinal contents from aged mice compared with young counterparts, thus providing a direct link between aging-induced shifts in microbiota immunogenicity and host inflammation. Additionally, we discovered that the gut microbiota of aged mice exhibited unique responses to a broad-spectrum antibiotic challenge (Abx), with sustained elevation in Escherichia (Proteobacteria) and altered TLR5 immunogenicity 7 days post-Abx cessation. Together, these data indicate that old age results in a gut microbiota that differentially acts on TLR signaling pathways of the innate immune system. We found that these age-associated microbiota immunogenic signatures are less resilient to challenge and strongly linked to host inflammatory status. Gut microbiota immunogenic signatures should be thus considered as critical factors in mediating chronic inflammatory diseases disproportionally impacting older populations.

Intravenous cefuroxime as a first-line treatment for women hospitalized for pyelonephritis

Abstract Background Empirical treatment of pyelonephritis in the emergency ward includes broad-spectrum antibiotics. Such a strategy favours broad-spectrum antibiotic overuse. Local antibiotic stewardship teams can propose local recommendations to adapt empirical antibiotic treatment devoted to spare precious molecules that remain active on MDR bacteria, such as fluoroquinolones or other broad-spectrum antibiotics. Objectives We aimed to evaluate the incidence of urinary tract infection recurrence within 3 months after hospital discharge following empirical antibiotic therapy with cefuroxime in women with pyelonephritis in the emergency room. Patients and methods We conducted a retrospective, single-centre study. We identified 109 women treated for pyelonephritis, 95 with cefuroxime at any time, and 14 with only other antibiotics, and divided them into subgroups based on antibiotic switch to other molecules. We compared the incidence of urinary tract infection recurrence in the subgroups. Results In the group of patients treated with cefuroxime only, we identified five cases of recurrence (9.4%) in a total of 53 patients, but only 1 (1.9%) case of recurrence associated with the same uropathogen. No significant difference in clinical outcome, length of antibiotic treatment, or urinary tract infection recurrence was observed between the subgroups. Conclusions Our study supports that a strategy elaborated by an antibiotic stewardship team based on local ecology and aimed at proposing the narrowest-spectrum antibiotic upon treatment initiation in the emergency room is safe.

Prevention Strategies for the Crime of Adultery in the Light of Islamic Law

Adultery is a serious offense which is prohibited in Islam. Adultery may cause a lot of repercussions, among them sexually transmitted infections (STIs), also referred to as sexually transmitted diseases (STDs). These infections are sexually transmitted through vaginal, anal, and oral. The significance of the research emerged due to a large number of deaths emanating from HIV/AIDS and other infectious diseases caused by adultery; for example, statistically, about 374 million people living with STIs and more than 1 million sexually transmitted infections (STIs) are acquired every day worldwide. A qualitative data analysis has been deployed in this study that has been gathered from a variety of sources, they include books, journal articles, reports, conference papers, and websites. The information has been analyzed through an explanatory research approach by providing scholars’ opinions and their arguments on the subject matter. Most importantly, this research has established that Islam indeed has put in place some preventive measures to reduce the risk of multi-crimes occurring and their potential harmful effects on individuals and the society at large, and more so, in reference to our study including: self-accountability, lowering the gaze (by shifting away on what is illegal to look at), meet with a non-mahram woman in privacy, shaking hands with a non-mahram woman, tabarruj (make-up grooming), command women to stay at home, wear Hijab for modesty and chastity, indulge in marriage and accept polygamy, impose penalty for adulterous disobedient, among others. In this regard, it is therefore, recommended to implement the preventive strategies set by Islam for the crime of adultery to uphold societal mortality and preserve the wellbeing of the society at a broader spectrum.

Observations of coastal infragravity wave characteristics under swell-dominated conditions

This study analyzed the characteristics of infragravity (hereafter IG) waves under a microtidal and swell-dominated wave climate based on the field observations collected in the nearshore waters (water depth: ∼ 13 m) of southern Sri Lanka. The main focus is on the dependence of nearshore IG waves on the incident short wave parameters, with particular attention to the influence of the short wave spectral shape on the IG wave characteristics. The observation results indicate that IG waves are primarily locally excited by incident swell wave energy, and accurate prediction of the IG wave height can be achieved using the parameter HS2Tm−1,0, which represents the short wave energy flux. Bound IG wave energy is much smaller than the free IG wave under conventional sea states but becomes significant under high-energy swell sea states.Higher levels of IG wave energy are found to be forced under narrower spectral shapes and smaller directional spreading short wave conditions, and these conditions typically correspond to stronger coupling strengths in the bound IG wave theory. Compared to the single-peaked spectra wave condition, the forced IG wave energy decreases under the double-peaked spectra wave condition. This is likely mainly because the latter tends to have a broader spectrum and a larger directional spreading. On the other hand, under the narrow-banded spectral short wave conditions, IG wave energy is inclined to be distributed over a lower and smaller frequency range. This is noteworthy because lower-frequency IG waves tend to be more difficult to break. In addition, the bound IG wave energy was found to increase at low tide, but for the intermediate water depths in which the observation site is located in this study, the influence of the small tidal range in the study area on the IG wave energy was not significant.

A finely balanced order–disorder equilibrium sculpts the folding–binding landscape of an antibiotic sequestering protein

TipA, a MerR family transcription factor from Streptomyces lividans, promotes antibiotic resistance by sequestering broad-spectrum thiopeptide-based antibiotics, thus counteracting their inhibitory effect on ribosomes. TipAS, a minimal binding motif which is expressed as an isoform of TipA, harbors a partially disordered N-terminal subdomain that folds upon binding multiple antibiotics. The extent and nature of the underlying molecular heterogeneity in TipAS that shapes its promiscuous folding-function landscape is an open question and is critical for understanding antibiotic-sequestration mechanisms. Here, combining equilibrium and time-resolved experiments, statistical modeling, and simulations, we show that the TipAS native ensemble exhibits a pre-equilibrium between binding-incompetent and binding-competent substates, with the fully folded state appearing only as an excited state under physiological conditions. The binding-competent state characterized by a partially structured N-terminal subdomain loses structure progressively in the physiological range of temperatures, swells on temperature increase, and displays slow conformational exchange across multiple conformations. Binding to the bactericidal antibiotic thiostrepton follows a combination of induced-fit and conformational-selection-like mechanisms, via partial binding and concomitant stabilization of the binding-competent substate. These ensemble features are evolutionarily conserved across orthologs from select bacteria that infect humans, underscoring the functional role of partial disorder in the native ensemble of antibiotic-sequestering proteins belonging to the MerR family.

Gut microbiota affects mPXR agonist PCN-induced hepatomegaly by regulating PXR and YAP activation.

Pregnane X receptor (PXR) is essential in the regulation of liver homeostasis and the gut microbiota is closely linked to liver physiological and pathological status. We previously found that activation of PXR significantly promotes liver enlargement through interaction with yes-associated protein (YAP). However, whether gut microbiota is contributed to PXR-induced hepatomegaly and the involved mechanisms remain unclear. In this study, C57BL/6 mice were administered the mouse-specific agonist PCN for 5 days. Depletion of gut microbiota was achieved using broad-spectrum antibiotics (ABX) and fecal microbiota transplantation (FMT) was performed to restore the gut microbial. The composition of gut microbiota was analyzed by 16S rRNA sequencing, while the expression of PXR, YAP and their downstream target genes and proteins were assessed. The results indicated that PCN treatment altered the composition and abundance of specific bacterial taxa. Furthermore, depletion of gut microbiota using ABX significantly attenuated PCN-induced hepatomegaly. FMT experiment further demonstrated that the fecal microbiota from PCN-treated mice could induce liver enlargement. Mechanistic studies revealed that ABX treatment impeded the PXR and YAP activation induced by PCN, as evidenced by decreased expression of PXR, YAP, and their downstream targets. Moreover, alterations in PXR and YAP activation were likely contributing to hepatomegaly in recipient mice following FMT from PCN-treated mice. Collectively, the current study demonstrated that gut microbiota is involved in PCN-induced hepatomegaly via regulating PXR and YAP activation, providing potential novel insights into the involvement of gut microbiota in PXR-mediated hepatomegaly. Significance Statement This work describes that the composition of gut microbiota is altered in mPXR agonist PCN-induced hepatomegaly. The treatment with an antibiotic cocktail (ABX) depletes the intestinal microbiota, leading to the impairment of liver enlargement caused by PCN. Besides, fecal microbiota transplantation (FMT) from PCN-treated mice induces liver enlargement. Further study revealed that gut microbiota is involved in hepatomegaly via regulating PXR and YAP activation.

Prehospital management of sepsis with IV antibiotics: a UK literature review

Background: Sepsis mortality rates increase if prompt treatment is not administered. The Sepsis Six care bundle advocates the early administration of broad-spectrum intravenous antibiotics to reduce mortality and morbidity but this is not routinely practised nationally in UK prehospital settings, although UK ambulance services regularly attend septic patients. Aims: A literature review was conducted to investigate knowledge around paramedics' ability to recognise and treat prehospital sepsis with intravenous antibiotics in the UK and the impact of this on patient outcomes. Methods: A search was conducted and the three eligible studies included underwent a structured critical appraisal and thematic analysis. Findings: Three themes emerged: diagnostic accuracy; administration of prehospital antibiotics; and impact on patient outcomes. Conclusion: There is a significant gap in evidence in this field in the UK, and it was difficult to make generalised recommendations from the studies. Paramedics have the potential to be highly accurate in the recognition of sepsis and administer intravenous antibiotics when following a protocol. No major studies measure patient outcomes following prehospital intravenous antibiotics administration by paramedics in the UK and large empirical studies should be conducted to assess the effectiveness of this.

Ciprofloxacin affects nutrient removal in manganese ore-based constructed wetlands: Adaptive responses of macrophytes and microbes

Ciprofloxacin (CIP) has received considerable attention in recent decades due to its high ecological risk. However, little is known about the potential response of macrophytes and microbes to varying levels of CIP exposure in constructed wetlands. Therefore, lab-scale manganese ore-based tidal flow constructed wetlands (MO-TFCWs) were operated to evaluate the responses of macrophytes and microbes to CIP over the long term. The results indicated that total nitrogen removal improved from 79.93% to 87.06% as CIP rose from 0 to 4mgL-1. The chlorophyll content and antioxidant enzyme activities in macrophytes were enhanced under CIP exposure, but plant growth was not inhibited. Importantly, CIP exposure caused a marked evolution of the substrate microbial community, with increased microbial diversity, expanded niche breadth and enhanced cooperation among the top 50 genera, compared to the control (no CIP). Co-occurrence network also indicated that microorganisms may be more inclined to co-operate than compete. The abundance of the keystone bacterium (involved in nitrogen transformation) norank_f__A0839 increased from 0.746% to 3.405%. The null model revealed drift processes (83.33%) dominated the community assembly with no CIP and 4mgL-1 CIP. Functional predictions indicated that microbial carbon metabolism, electron transfer and ATP metabolism activities were enhanced under prolonged CIP exposure, which may contribute to nitrogen removal. This study provides valuable insights that will help achieve stable nitrogen removal from wastewater containing antibiotic in MO-TFCWs. Environmental ImplicationCiprofloxacin (CIP) is a broad-spectrum antibiotic that is widely to treat humans and livestock, and which has been reported to have potentially adverse effects on plants and microbes when treating CIP-containing wastewater in constructed wetlands (CWs), thereby posing challenges to treatment performance and stability. This study combined the dynamic response of plants and microbes, and ecological mechanisms to analyze nitrogen removal under different CIP concentration exposures. These results help to assess the effects of long-term exposure to CIP on nitrogen removal in manganese ore-based tidal flow CWs and provide a scientific basis for achieving stable and efficient nitrogen removal.

Triggered Release of Ampicillin from Metallic Implant Coatings for Combating Periprosthetic Infections.

Periprosthetic infections caused by Staphylococcus aureus (S. aureus) pose unique challenges in orthopedic surgeries, in part due to the bacterium's capacity to invade surrounding bone tissues besides forming recalcitrant biofilms on implant surfaces. We previously developed prophylactic implant coatings for the on-demand release of vancomycin, triggered by the cleavage of an oligonucleotide (Oligo) linker by micrococcal nuclease (MN) secreted by the Gram-positive bacterium, to eradicate S. aureus surrounding the implant in vitro and in vivo. Building upon this coating platform, here we explore the feasibility of extending the on-demand release to ampicillin, a broad-spectrum aminopenicillin β-lactam antibiotic that is more effective than vancomycin in killing Gram-negative bacteria that may accompany S. aureus infections. The amino group of ampicillin was successfully conjugated to the carboxyl end of an MN-sensitive Oligo covalently integrated in a polymethacrylate hydrogel coating applied to titanium alloy pins. The resultant Oligo-Ampicillin hydrogel coating released the β-lactam in the presence of S. aureus and successfully cleared nearby S. aureus in vitro. When the Oligo-Ampicillin-coated pin was delivered to a rat femoral canal inoculated with 1000 cfu S. aureus, it prevented periprosthetic infection with timely on-demand drug release. The clearance of the bacteria from the pin surface as well as surrounding tissue persisted over 3 months, with no local or systemic toxicity observed with the coating. The negatively charged Oligo fragment attached to ampicillin upon cleavage from the coating did diminish the antibiotic's potency against S. aureus and Escherichia coli (E. coli) to varying degrees, likely due to electrostatic repulsion by the anionic surfaces of the bacteria. Although the on-demand release of the β-lactam led to adequate killing of S. aureus but not E. coli in the presence of a mixture of the bacteria, strong inhibition of the colonization of the remaining E. coli on hydrogel coating was observed. These findings will inspire considerations of alternative broad-spectrum antibiotics, optimized drug conjugation, and Oligo linker engineering for more effective protection against polymicrobial periprosthetic infections.

Prevalence and predictors of multidrug-resistant bacteremia in liver cirrhosis.

Improved knowledge of local epidemiology and predicting risk factors of multidrug-resistant (MDR) bacteria are required to optimize the management of infections. This study examined local epidemiology and antibiotic resistance patterns of liver cirrhosis (LC) patients and evaluated the predictors of MDR bacteremia in Korea. This was a retrospective study including 140 LC patients diagnosed with bacteremia between January 2017 and December 2022. Local epidemiology and antibiotic resistance patterns and the determinants of MDR bacteremia were analyzed using logistic regression analysis. The most frequently isolated bacteria, from the bloodstream, were Escherichia coli (n = 45, 31.7%) and Klebsiella spp. (n = 35, 24.6%). Thirty-four isolates (23.9%) were MDR, and extended-spectrum beta-lactamase E. coli (52.9%) and methicillin-resistant Staphylococcus aureus (17.6%) were the most commonly isolated MDR bacteria. When Enterococcus spp. were cultured, the majority were MDR (MDR 83.3% vs. 16.7%, p = 0.003), particularly vancomycin-susceptible Enterococcus faecium. Antibiotics administration within 30 days and/or nosocomial infection was a significant predictor of MDR bacteremia (OR: 3.40, 95% CI: 1.24-9.27, p = 0.02). MDR bacteremia was not predicted by sepsis predictors, such as positive systemic inflammatory response syndrome (SIRS) or quick Sequential Organ Failure Assessment (qSOFA). More than 70% of strains that can be treated with a third-generation cephalosporin have been cultured. In cirrhotic patients, antibiotic administration within 30 days and/or nosocomial infection are predictors of MDR bacteremia; therefore, empirical administration of broad-spectrum antibiotics should be considered when these risk factors are present.

GORE-TEX SUTURE-ASSOCIATED ENDOPHTHALMITIS IN A SCLERAL-SUTURED INTRAOCULAR LENS.

To describe a unique case of Gore-Tex (Gore Medical, AZ) suture-associated delayed-onset endophthalmitis in a patient with a history of scleromalacia, pathologic myopia, multiple prior vitrectomies in the setting of a scleral-sutured intraocular lens (IOL). A 69-year-old man complained of blurry vision and eye pain 21 months after implantation of a scleral-sutured IOL and was found to have an exposed Gore-Tex suture with scleromalacia, vision loss to hand motion, a hypopyon, and vitritis. He was diagnosed with culture-positive endophthalmitis. He had a previous history of a rhegmatogenous retinal detachment repair and subsequent dislocated IOL in this eye treated with a scleral-sutured IOL. A vitreous tap and injection of broad-spectrum antibiotics and suture removal at the slit lamp were performed at the time of presentation. One week later, he underwent pars plana vitrectomy and removal of the IOL. After the tap and inject and subsequent lens removal, his vision has returned to his preoperative vision of 20/100 with refraction. Gore-Tex suture is a nonabsorbable and flexible option with great tensile strength that has emerged as a favored alternative to polypropylene for the use in transscleral fixated IOLs. Although endophthalmitis and suture erosion are known complications of this procedure, this report describes one of the first cases of Gore-Tex suture-associated endophthalmitis.

Anti-candidiasis functional material for women’s cotton undergarments

The escalating incidence of Candida spp. infections among individuals with compromised immune systems is attributed to various factors, including broad-spectrum antibiotic usage, common health issues, and inadequate undergarments, requiring novel preventive measures. While the pathogenic mechanisms of Candida spp. infections remain incompletely understood, their virulence attributes and opportunistic nature challenge host defenses. In response, this research study introduces an innovative nanobiotechnological approach employing L-cysteine to develop nontoxic anti- Candida spp. textile materials. Cotton, an ideal material for women’s underwear, was functionalized with L-cysteine through an exhaustion procedure following activation with 2,2,6,6-tetramethylpiperidinyl-1-oxy free radical. The results demonstrated increased energy dispersive X-ray peaks corresponding to sulfur atoms in the functionalized cotton fabric, confirming that L-cysteine remained attached to the cotton surface even after washing cycles. Moreover, the cotton containing L-cysteine displayed morphology and mechanical properties similar to the nonfunctionalized cotton, indicating that the incorporation of L-cysteine did not impact the cotton properties. In addition, cotton functionalized with L-cysteine exhibited a significant reduction in yeast growth – 87.04 ± 1.90% for Candida albicans and 65.28 ± 3.03% for Candida parapsilosis – highlighting its potential as a class I medical device, particularly for preventing candidiasis in women’s medical underwear.