Broad Spectrum Research Articles

Bacteriocins sourced from traditional fermented foods for ensuring food safety: the microbial guards.

Concerns about food safety have consistently driven the exploration of potent antimicrobials with probiotic origins. Identification of probiotic-derived bacteriocins as robust alternatives to antibiotics has gained traction following the COVID-19 pandemic. Additionally, the global market is witnessing an increasing preference for minimally processed food products free from chemical additives. Another contributing factor to the search for potent antimicrobials is the escalating number of infections caused by antibiotic-resistant bacteria and the need to mitigate the significant damage inflicted on the commensal human microbiota by broad-spectrum antibiotics. As an alternative bio-preservation strategy, there is substantial enthusiasm for the use of bacteriocins or starter cultures producing bacteriocins in preserving a variety of food items. This review specifically focuses on bacteriocins originating from lactic acid bacteria associated with fermented foods and explores their technological applications as nanobiotics. The food-grade antibiotic alternatives, whether utilized independently or in combination with other antimicrobials and administered directly or encapsulated, are anticipated to possess qualities of safety, stability and non-toxicity suitable for application in the food sector. © 2024 Society of Chemical Industry.

CLINICAL COMPLICATIONS OF MALIGNANT OTITIS EXTERNA AND SURGICAL TREATMENT

For clinical complications of malignant otitis externa and its surgical treatment, the introduction addresses a rare and serious condition, characterized by necrotizing infection of the external auditory canal, often associated with comorbidities such as decompensated diabetes mellitus. This condition requires rapid intervention due to the potential for spread to adjacent structures such as the skull and skull base, resulting in serious complications such as facial paralysis, osteomyelitis, and meningitis. Management includes broad-spectrum intravenous antibiotic therapy and, in many cases, surgical intervention to debride necrotic tissue and control infection. Objective: to synthesize recent evidence on the effectiveness of surgical treatments in malignant otitis externa, highlighting clinical outcomes and associated mortality. Methodology: it was structured according to the PRISMA checklist, using PubMed, Scielo and Web of Science databases to search for articles published in the last 10 years. Descriptors included "malignant otitis externa", "surgical treatment", "complications", "mortality" and "intervention". Inclusion criteria were clinical studies and systematic reviews that addressed surgical treatment and clinical outcomes. Exclusion criteria were studies focusing exclusively on non-surgical treatments, isolated case reports and studies with fewer than 10 participants. Results: highlighted the effectiveness of early surgical debridement in reducing mortality and serious neurological complications. The analysis revealed that adjuvant antibiotic therapy and intensive surveillance are crucial for successful management. Conclusion: the importance of a multidisciplinary approach and timely surgical intervention is emphasized to improve outcomes in patients with malignant otitis externa, highlighting the need for further studies to elucidate ideal therapeutic protocols and prevention strategies

Artificial intelligence-enabled antibiotic prescribing and clinical support in Nigerian health-care settings: Budgetary constraints, challenges, and prospect

Today, resistance developed by bacteria to common antibiotics that were otherwise regarded as effective is posing a serious challenge. It is believed that without any different efforts, this perennial problem will undermine all the ongoing efforts in antibiotic discovery and therapy development. In Nigeria, antibiotics are frequently prescribed in hospitals. However, issues like multidrug resistance (MDR) and inappropriate use and misuse of antibiotics, including incorrect dosages and use of broad-spectrum antibiotics for targeted infections, have precipitated the rise of MDR bacteria. Consequently, this leads to higher healthcare costs, mainly due to prolonged hospital stays and additional medications as well as increased patient mortality. The prospects of artificial intelligence (AI)-enabled antibiotic prescribing hold significant promise in transforming the current health-care practices. AI has the potential to enhance the precision and efficiency of antibiotic treatment through advanced algorithms and data analytics. This technology can contribute to improved diagnostic accuracy, providing real-time clinical support, optimizing dosage recommendations, personalized treatment plans, and streamlined antimicrobial stewardship, ultimately aiding the global fight against antibiotic resistance and optimizing patient outcomes. The integration of AI in antibiotic prescribing reflects a cutting-edge approach with the potential to revolutionize how antibiotics are prescribed to address challenges in antimicrobial stewardship, clinical decision-making, and combating antibiotic resistance. One of the key impediments to integrating AI into Nigeria’s health-care system is budgetary constraints. Addressing these constraints through strategic investments, improved budgetary allocation to research and development, and leveraging the opportunities presented by AI technologies can significantly enhance antibiotic prescribing and health-care practices, leading to improved public health outcomes.

Midurethral sling infectious complications: A systematic review

BackgroundThe French Health Authority (Haute Autorité de santé) and French scientific societies (Collège national des gynécologues et obstétriciens français) recommend the use of midurethral slings as the surgical treatment of choice for stress incontinence due to urethral hypermobility and failure of hygienic diet and pelvic rehabilitation. Within a year of implantation, almost 90% of patients no longer experience stress urinary incontinence. Despite their recognized efficacy, retropubic and/or trans-obturator midurethral sling can expose patients to potentially severe infectious complications. MethodsA comprehensive literature review using Pubmed, Medline, Embase and Cochrane: “stress urinary incontinence”, and/or the following keywords “complications”, “infections”, “abscess”, “prosthetic exposures”, “fistula”, “erosion”, “cellulitis”, “fasciitis” in association with the keywords “midurethral slings”, “suburethral sling”, “tension free vaginal tape” and “trans-obturator tape. In the 330 articles, 61 really dealt with infectious complications following the implantation of synthetic midurethral slings in women. ResultsPreoperative urinalysis and intraoperative antibiotic prophylaxis were rarely reported (n=1 and n=11, respectively). We recorded thirty-six cases of abscess, twenty-one cases of cellulitis, sixteen cases of fistula and forty-one cases of prosthetic exposure. In 95.5% of cases, patients were treated with broad-spectrum antibiotics. Total explantation of the prosthesis was performed in 56% of patients at the initial management, with two-stage explantation performed in 23% of cases, partial explantation was carried out in 12% of cases, and the prosthesis was left in place in 9% of cases. No deaths were recorded. ConclusionTo limit the risk of urinary tract infections and potential prosthetic infections, a prophylactic approach should be adopted by performing a preoperative urinalysis and administering intraoperative antibiotic prophylaxis should be discussed. In the event of prosthetic and/or surgical site infection, broad-spectrum probabilistic antibiotic therapy should be initiated as early as possible until targeted antibiotic therapy. Total explantation of the prosthesis appears to be the most appropriate surgical strategy.

Early stoppage of empirical antibiotic therapy at clinical improvement in paediatric leukaemia patients with high-risk febrile neutropenia (ESAT-HR-FN study): Study protocol of a single centre investigator initiated randomised open label non-inferiority trial

Background and rationaleFebrile neutropenia (FN) is one of the major causes of early mortality among children undergoing induction chemotherapy for haematological malignancies. FN occurs in up to 80 % of the children undergoing intensive chemotherapy and FN specific mortality is as high as 10 %. The management of high-risk FN (HR-FN) is by early initiation of broad-spectrum empirical antibiotic therapy (EAT) which is continued till blood count recovery. Adverse effects of prolonged EAT among children without proven infective focus have questioned the rationale behind the duration of EAT. The non inferiority of early stoppage of EAT in patients with low-risk FN (LR-FN) when afebrile for 48 h, irrespective of marrow recovery, is proven among adults and children. However, there is paucity of data regarding the same in children with HR-FN. This study aims to determine whether early discontinuation of EAT in children with HR-FN without proven infective focus who become afebrile and awaiting marrow recovery, would reduce antibiotic duration and their adverse effects without any negative consequences for patients. ObjectiveTo compare the rates of recurrent fever in paediatric patients (2–18 years) with HR-FN when EAT is continued till marrow recovery (control group) versus when stopped early at defervescence irrespective of marrow recovery (study group). MethodologyThis is the study protocol of a phase 3, single centre, randomized, open label, non-inferiority clinical trial. The primary outcome is the rate of fever recurrence among patients with HR-FN, when EAT is stopped early irrespective of marrow recovery (study group) and will be compared to the rate of fever recurrence on continuation of EAT till marrow recovery which is defined as an absolute neutrophil count (ANC) ≥ 500/mm3 (control group). Secondary outcomes include the comparison of duration of antibiotic use, mortality rates, hospital re-admission rates, requirement of multiple broad-spectrum antibiotics, therapeutic anti-fungal usage and need for organ support between the study and the control groups. A total of 280 children with acute leukaemia undergoing EAT for grade 3 or severe FN (ANC <500/μL) without clinico-laboratory evidence of infective foci are being randomized in the ratio of 1:1 between the study and the control group after defervescence for 48 h. The patients will be followed up for primary outcome (fever recurrence) till the end of induction period (day 35) or recovery of ANC ≥500/mm3 whichever is earlier. Expected outcomeESAT-HR FN study is the first large phase 3 randomised study to assess the impact of early stoppage of EAT irrespective of marrow recovery among a homogenous paediatric cohort of HR-FN in the setting of induction chemotherapy for acute leukaemia. This study will be seminal in addressing the duration of EAT in HR-FN among children without infective foci and if proven to be non-inferior this strategy will help to reduce the adverse effects from prolonged antibiotic use, the emergence of drug resistance, decrease hospital stay length and overall health care costs.

Clinical perspective and outcome of culture-negative microbial keratitis: A retrospective study.

To study the risk factors, clinical features, and treatment outcomes of patients with culture-negative keratitis (CNK). A retrospective data review of 933 patients with CNK was performed from January 2018 to December 2020. The variables such as the history of injury, visual acuity, slit-lamp findings with measurements of size and depth of ulcer, microbiological evaluation, duct patency, blood glucose levels, and treatment were considered, and clinical outcome was analyzed. Of the 933 patients with CNK, 763 (81.8%) were medically managed, with a mean treatment duration of 2.08 ± 1.7 weeks. Among them, 622 (66.7%) were both smear and culture-negative, and 311 (33.3%) showed only smear positivity. Smear-positive patients showed a positive correlation with the history of injury. A higher incidence of fungal growth on repeat culture was observed. Surgical interventions were done only in 18.2% of the patients; the rest were treated with topical medications alone. High clinical suspicion, differentiation of causative organisms based on clinical findings, and initiating empirical therapy with broad-spectrum antibiotics and antifungals improve the ultimate prognosis in patients with CNK, even though a standard protocol for empirical medical treatment may differ among institutions and surgeons based on their clinical experience and geographical variations.

Phytoremediation of diclofenac and sulfamethoxazole in Arabidopsis thaliana cells and seedlings

Diclofenac (DLF), a widely recognized non-steroidal anti-inflammatory drug (NSAID), and sulfamethoxazole (SMX), a broad-spectrum sulfonamide antibiotic, are commonly prescribed medications that have raised concerns as significant contributors to pharmaceutical pollution in natural ecosystems despite their clinical effectiveness. This study investigates the potential phytoremediation pathways for these two drugs in plant systems by tracking and quantifying the fate of the parent compounds and their metabolites in Arabidopsis thaliana using cell and seedling cultures. Results indicated significant differences in the dissipation of DLF according to the treatment and time interaction within the cell cultures. Viable plant cells showed complete dissipation of DLF from an initial concentration of 2,758 ng/mL in 96 h, whereas non-viable cells and blank solutions remained stable. The dissipation of SMX was comparable across viable, non-viable, and blanks, showing a minor decrease from 842 to 799 ng/mL over 120 hours following the treatment of viable cells. DLF metabolites including 4'-hydroxy-diclofenac, 5-hydroxy-diclofenac, acyl-glutamatyl-diclofenac, 1-(2,6-dichlorophenyl)-5-hydroxy-2-indolinone, 5-sulfooxy-diclofenac, 5-glucopyranosyloxy-diclofenac, 1-(2,6-dichloro-4-hydroxyphenyl)-2-indolinone, and 4'-glucopyranosyloxy-diclofenac were recognized, likely formed through acylation, glutamyl conjugation, hydroxylation, dehydration, cyclization, sulfonation, and glucosidation. While for SMX, metabolites including sulfamethoxazole-glucuronide, nitroso-sulfamethoxazole, N4-acetylsulfamethoxazole, and N4-acetyl-5-OH-sulfamethoxazole were identified, potentially produced through glucuronidation, nitrosation, acetylation, and hydroxylation. Phase I metabolite concentrations of DLF and SMX peaked earlier than those of phase II metabolites. Hydroponic A. thaliana demonstrated comparable efficiencies in the phytoremediation of DLF and SMX, with concentrations varying from 1 mg/L to 10 mg/L. Detectable levels of both parent compounds and their metabolites confirmed successful absorption and metabolism within the plant system. This study provides valuable insights into the potential of phytoremediation as a sustainable approach for reducing the environmental toxicity of DLF and SMX and suggests comparable metabolic efficiency. These findings contribute to the growing body of knowledge on phytoremediation and its application in addressing pollution from pharmaceuticals and personal care products.

The vehicle of administration, feed or water, and prandial state influence the oral bioavailability of amoxicillin in piglets.

Feed and water components may interact with drugs and affect their dissolution and bioavailability. The impact of the vehicle of administration (feed and water) and the prandial condition of weaner piglets on amoxicillin´s oral bioavailability was evaluated. First, amoxicillin's in vitro dissolution and stability in purified, soft, and hard water, as well as release kinetics from feed in simulated gastric and intestinal media were assessed. Then, pharmacokinetic parameters and bioavailability were determined in fasted and fed pigs using soft water, hard water, or feed as vehicles of administration following a balanced incomplete block design. Amoxicillin showed similar dissolution profiles in soft and hard water, distinct from the dissolution profile obtained with purified water. Complete dissolution was only achieved in purified water, and merely reached 50% in soft or hard water. Once dissolved, antibiotic concentrations decreased by around 20% after 24h in all solutions. Korsmeyer-Peppas model best described amoxicillin release from feed in simulated gastric and intestinal media. Feed considerably reduced antibiotic dissolution in both simulated media. In vivo, amoxicillin exhibited significantly higher bioavailability when delivered via water to fasted than to fed animals, while in-feed administration yielded the lowest values. All treatments showed a similar rate of drug absorption. In conclusion, we demonstrated that water and feed components, as well as feed present in gastrointestinal tract of piglets decrease amoxicillin´s oral bioavailability. Therefore, the use of oral amoxicillin as a broad-spectrum antibiotic to treat systemic infections in pigs should be thoroughly revised.

Biguanide-Vancomycin Conjugates are Effective Broad-Spectrum Antibiotics against Actively Growing and Biofilm-Associated Gram-Positive and Gram-Negative ESKAPE Pathogens and Mycobacteria.

Strategies to increase the efficacy and/or expand the spectrum of activity of existing antibiotics provide a potentially fast path to clinically address the growing crisis of antibiotic-resistant infections. Here, we report the synthesis, antibacterial efficacy, and mechanistic activity of an unprecedented class of biguanide-antibiotic conjugates. Our lead biguanide-vancomycin conjugate, V-C6-Bg-PhCl (5e), induces highly effective cell killing with up to a 2 orders-of-magnitude improvement over its parent compound, vancomycin (V), against vancomycin-resistant enterococcus. V-C6-Bg-PhCl (5e) also exhibits improved activity against mycobacteria and each of the ESKAPE pathogens, including the Gram-negative organisms. Furthermore, we uncover broad-spectrum killing activity against biofilm-associated Gram-positive and Gram-negative bacteria as well as mycobacteria not observed for clinically used antibiotics such as oritavancin. Mode-of-action studies reveal that vancomycin-like cell wall synthesis inhibition with improved efficacy attributed to enhanced engagement at vancomycin binding sites through biguanide association with relevant cell-surface anions for Gram-positive and Gram-negative bacteria. Due to its potency, remarkably broad activity, and lack of acute mammalian cell toxicity, V-C6-Bg-PhCl (5e) is a promising candidate for treating antibiotic-resistant infections and notoriously difficult-to-treat slowly growing and antibiotic-tolerant bacteria associated with chronic and often incurable infections. More generally, this study offers a new strategy (biguanidinylation) to enhance antibiotic activity and facilitate clinical entry.

Antibacterial and mechanism of action studies of boxazomycin A.

Boxazomycins A-C are potent broad-spectrum antibiotics isolated from Actinomycetes strain G495-1 in 1987. We now report that boxazomycin A inhibits bacterial growth by selectively inhibiting protein synthesis, its effect is bacteriostatic, and it is equally active against drug resistant bacterial strains. No cross-resistance to protein synthesis inhibitors was observed suggesting that its inhibition is distinct from clinical protein synthesis inhibitors. We also report in vivo efficacy in a Staphylococcus aureus murine infection model supported by corresponding pharmacokinetic studies.

Extraction, Phytochemistry &amp; Pharmacological Potential of Camellia sinensis: A Comprehensive Review

Abstract: Camellia sinensis (L.) is acknowledged globally as the second most consumed beverage after water. Researchers have dedicated substantial efforts to validate the claims surrounding this plant through rigorous pharmacological screening, aiming to substantiate its traditional applications in treating various ailments. This work extensively delves into aspects such as marketed formulations of green tea, extraction techniques, phytochemistry, pharmacology, interactions between drugs and green tea, and its distinctive characteristics. Key research unequivocally suggests that green tea holds substantial health benefits for individuals. Presently, a multitude of pharmacologically active constituents have been successfully isolated and identified from green tea, encompassing polyphenols, alkaloids, amino acids, polysaccharides, and volatile components. Recent investigations have illuminated the broad spectrum of pharmacological properties exhibited by green tea, encompassing antioxidant, anticancer, hypoglycemic, antibacterial, antiviral, and neuroprotective attributes. The review amalgamates current research findings to present a thorough understanding of the diverse bioactive compounds found in Camellia sinensis, such as polyphenols, catechins, and alkaloids, and their contributions to its health-promoting properties. The review further highlights the significance of extraction techniques in preserving and enhancing the bioactivity of these compounds. Overall, this comprehensive review serves as a valuable resource for researchers, practitioners, and enthusiasts, consolidating the current knowledge surrounding Camellia sinensis and its multifaceted role in promoting human health.

Use of antimicrobials in patients in Palliative Care admitted to the Intensive Care Unit: A retrospective study

Introduction: Palliative care (PC) improves the quality of life of patients and their families. The use of antimicrobials is controversial in PC patients, especially in those admitted to the intensive care unit (ICU). Objective: To evaluate the use of antimicrobials in PC patients admitted to the ICU. Methods: This is a retrospective study, performed from August 2019 to September 2020. Data on demographic profile, hospitalization, PC, and use of antimicrobials were collected from the Erasto Gaertner Hospital database, in Curitiba, Brazil. Results: 182 patients were studied, median age of 65 years and 52% men. The median length of stay in the ICU was 3 days; the median total length of stay in the hospital was 6 days and 89.5% of the patients died. The time in ICU of patients treated with antibiotics (14.8%) was significantly longer (p=0.033) than for patients who were not (85.2%). Using or not using antibiotics did not change the outcome. Among those who took antibiotics, death occurred in 81.5% of cases and among those who did not use, 74.8% died (p=0.627). Between the cases that used broad-spectrum antibiotics 17/19 (89.5%) died and the mean hospital stay was 16.2 days. Among cases that used narrow-spectrum 5/9 (62.5%) died and the mean hospital stay was 6.4 days (p=0.033). Conclusion: The administration and/or the spectrum of antibiotics in PC patients admitted to the ICU did not change the mortality rate. The administration of antibiotics increased the length of stay in the ICU.

Salvaging Vision: A Study of Non-Traumatic Optic Neuropathies

Background and Objectives: Various ear, nose, and throat (ENT) conditions can result in vision loss. The purpose of this study is to identify the etiologies, presentations, and radiological findings associated with impaired vision in the context of ENT. Additionally, this article discusses management protocols, including optic nerve decompression and orbital decompression.Methods: In a retrospective study, we examined the period from 2016 to 2022 at a tertiary care hospital in Mumbai, India. The analysis included 11 patients who presented with progressive diminution of vision. All patients received a regimen of broad-spectrum intravenous antibiotics and high-dose intravenous steroids. This was followed by either endoscopic optic nerve decompression or orbital decompression. Subsequent improvements in vision were documented, and any complications were evaluated.Results: A total of 11 patients were treated with medical management followed by successful surgery, with 10 patients demonstrating significant vision improvement.Conclusion: Identifying the etiology of vision loss and managing the condition can present challenges for otorhinolaryngologists. A thorough grasp of the underlying pathophysiology, combined with active surveillance of clinical and radiological indicators, can enable these clinicians to achieve effective and rewarding outcomes.

“In Silico” prediction of antibiotics biodegradation by Ganoderma lucidum GILCC 1 laccase

Antibiotics present a pressing environmental challenge as emerging pollutants due to their persistence and role in promoting antibiotic-resistant bacteria. To model the utilization of Ganoderma lucidum GlLCC1 laccase in degrading antibiotics, a 3D homology model of GILCC1, based on Lentinus tigrinus mushroom laccase, was utilized. Five broad-spectrum WHO-designated antibiotics with molecular weights between 100 and 500 Da were selected. Molecular dynamics simulations were conducted at pH 3.0 and 7.0 to evaluate the interactions between GILCC1 and antibiotics in a TIP3P water box, with system behaviour assessed at 300 °K using an NPT assembly. ABTS (2,2ʹ-Azino-bis (3-ethylbenzthiazoline-6-sulfonic Acid)) served as the comparison molecule. The binding free energy indicated a strong affinity between 3D GILCC1 and various ligands. At pH 3.0, GILCC1 exhibited significant Gibbs free energy (ΔG), indicating a high affinity for Levofloxacin (LVX; −8.2 kcal mol−1), Sulfisoxazole (SFX; −7.8 kcal mol−1), Cefuroxime (CXM; −7.5 kcal mol−1), Cephradine (CFD; −7. 5 kcal mol−1), ABTS (−7.6 kcal mol−1), and Tetracycline (TE; −7.5 kcal mol−1), attributed to pocket topology and interactions such as hydrogen bonds and van der Waals forces. Electron transfer in GILCC1 involved a chain of residues, including His395 and Phe239. Although the affinity decreased at pH 7.0, the potential of GILCC1 to degrade antibiotics remained plausible. This study accurately predicted the behaviour of the laccase-antibiotic system, providing atomic-level insights into molecular interactions and emphasizing the importance of experimental assays and assessments of antibiotic degradation in wastewater, considering various chemical compounds. The use of ABTS as a mediator was suggested to enhance molecule affinity.Graphical abstract

Navigating Diagnostic and Therapeutic Challenges in Suspected Neuromelioidosis: A Comprehensive Case-Report of a Post-natal Mother

Neuromelioidosis, a severe neurological form of melioidosis caused by Burkholderia pseudomallei, presents significant diagnostic and therapeutic challenges. This case report describes a 28-year-old post-natal woman with progressive right-sided weakness, facial palsy, and respiratory distress. MRI findings, including the tunnel sign, and cerebrospinal fluid (CSF) analysis were crucial for diagnosis. Despite initial broad-spectrum antibiotics, targeted treatment with meropenem, ceftazidime, and trimethoprim-sulfamethoxazole led to significant clinical improvement. This case highlights the importance of early recognition and appropriate management of neuromelioidosis to improve patient outcomes.

Tricalcium phosphate-loaded injectable hydrogel as a promising osteogenic and bactericidal teicoplanin-delivery system for osteomyelitis treatment: An in vitro and in vivo investigation

Osteomyelitis is an inflammation of bone tissue usually caused by pyogenic bacteria. The most recurrent clinical approach consists of bone debridement followed by parenteral administration of antibiotics. However, systemic antibiotic treatment has limitations regarding absorption rate and bioavailability over time. The main challenge of osteomyelitis treatment consists of coupling the persistent infection treatment with the regeneration of the bone debrided. In this work, we developed an injectable drug delivery system based on poloxamer 407 hydrogel containing undoped Mg, Zn-doped tricalcium phosphate (β-TCP), and teicoplanin, a broad-spectrum antibiotic. We evaluated how the addition of teicoplanin and β-TCP affected the micellization, gelation, particle size, and surface charge of the hydrogel. Later, we studied the hydrogel degradation and drug delivery kinetics. Finally, the bactericidal, biocompatibility, and osteogenic properties were evaluated through in vitro studies and confirmed by in vivo Wistar rat models. Teicoplanin was found to be encapsulated in the corona portions of the hydrogel micelles, yielding a bigger hydrodynamics radius. The encapsulated teicoplanin showed a sustained release over the evaluated period, enough to trigger antibacterial properties against Gram-positive bacteria. Besides, the formulations were biocompatible and showed bone healing ability and osteogenic properties. Finally, in vivo studies confirmed that the proposed locally injected formulations yielded osteomyelitis treatment with superior outcomes than parenteral administration while promoting bone regeneration. In conclusion, the presented formulations are promising drug delivery systems for osteomyelitis treatment and deserve further technological improvements.

Evaluating Antibiotic De-escalation for Autologous Stem Cell Transplant Patients With Febrile Neutropenia in a Real-World Clinical Setting

Febrile neutropenia (FN) is a complication in approximately 90% of autologous stem cell transplant (SCT) patients. Guidelines support early broad-spectrum antibiotics (BSA) to prevent morbidity and mortality. However, in patients who are clinically stable and deemed to have a fever of unknown origin, the optimal duration of BSA is unknown. Accumulating evidence suggests that de-escalation of BSA in select patients may decrease duration of BSA exposure without compromising clinical outcomes such as infection, recurrent fever, and readmission. With this, a de-escalation protocol was implemented at Vanderbilt University Medical Center (VUMC) to identify autologous SCT patients who may benefit from early de-escalation of BSA. The objectives of this study were to analyze the impact of early empiric antibiotic de-escalation on the duration of BSA as well as its impact on the incidence of recurrent fever and documented infection in autologous SCT patients. This was a single-center, retrospective study evaluating patients older than 18 years of age who underwent autologous SCT and experienced an episode of FN from January 2018 to December 2022 at VUMC (N = 195). The protocol was initiated on January 1, 2020, to de-escalate BSA back to prophylaxis in stable neutropenic patients determined to have a fever of unknown origin. The primary outcome was the number of BSA days within 30 days. Secondary clinical outcomes included recurrent fever, documented infection, readmission, 30-day mortality, and 90-day non-relapsed mortality (NRM). Outcomes were compared across pre- and post-protocol groups with a Wilcoxon rank sum test, Pearson chi-square test, or regression analysis as appropriate. The median BSA duration was 4.7 and 2.7 days in the pre- and post-protocol groups, respectively (p <0.001). Recurrent fever (14.2% vs. 16.0%, p = 0.726), documented infection (1.7% vs. 6.7%, p = 0.068), and readmission (13.3% vs. 22.7%, p = 0.091) within 30 days were not significantly different between the two groups. Neither 30-day mortality (0.8% vs. 1.3%, p = 0.736) nor 90-day NRM (0.8% vs. 1.3%, p = 0.736) differed. The implementation of an early de-escalation protocol for autologous SCT patients who develop FN was associated with a reduction in duration of BSA compared to the pre-protocol group without a significant difference in readmission, recurrent fevers, and documented infections. This study adds to existing evidence that early de-escalation of BSA in FN patients with a fever of unknown origin who are afebrile and clinically stable is safe and reduces unnecessary antibiotic use.

Outcome of Fournier's gangrene in relation to Fournier Gangrene Severity Index (FGSI) score.

Fournier's gangrene is a rapidly progressive necrotizing fasciitis, involving perineum mainly. The purpose of the study is to evaluate etiology, treatment, and outcome of Fournier's gangrene so that such type patient's management can be done by primary care physicians with best outcomes. This was a retrospective study including 156 patients, treated for Fournier's gangrene, between Jan 2012 and Dec 2018. The outcome and prognosis of Fournier's gangrene were reviewed. The mean age and mode among survival patients were 47.94 ± 14.9 and 60 years, and the mean age and mode in nonsurvival patients was 47.64 ± 15.9 and 65 years. The most common predisposing factor was diabetes mellitus (n = 49, 31.4%) having mortality rate was 9% (n = 14). Most common causative bacteria were E. coli. In the study, the survival rate was 100% in patients having Fournier Gangrene Severity Index (FGSI)≤3. As FGSI increased from 3, the mortality rate increased. Fournier gangrene is a surgical emergency. Early diagnosis, serial surgical debridement, and broad-spectrum antibiotics decrease the mortality and morbidity of patients. The sensitivity and specificity of FGSI determine the prognosis of Fournier's gangrene. FGSI is a simple method to know the severity and prognosis.

Is Prompt Hyperbaric Oxygen Adjunctive Therapy Able to Reduce Mortality and Amputation in Management of Necrotizing Soft-Tissue Infection?

Background: Necrotizing soft-tissue infection (NSTI) is a rare and serious disease with high morbidity and mortality. Standard therapeutic concepts have included urgent surgical intervention, broad-spectrum antibiotic treatment, and intensive care. Hyperbaric oxygen therapy (HBOT) is used as adjuvant therapy in some centers, but its benefits remain controversial. Methods: A retrospective analysis was conducted in which 98 patients with a clinical diagnosis of NSTI were treated with standard treatments plus HBOT. The clinical outcomes were wound healing, performance status, hospital length, complication rate, recurrence rate, morbidity (amputation rate), and mortality. Primary or secondary outcomes were compared between the time interval of HBOT and the clinical outcomes. Results: The average times from diagnosis of NSTI to initial HBO treatment and from initial surgery to initial HBO treatment were both significantly longer in dead patients than in surviving patients (P = 0.031; P = 0.020). These two time intervals were both significantly longer in amputated patients than in preserved patients (P = 0.031; P = 0.037). Conclusions: Using combined treatment with early surgical debridement combined with HBOT, it is possible to reduce hospital stay, intensive care unit stay, number of debridements, improve complete wound healing rate, and lower amputation and mortality rates among patients with NSTI. The early onset of HBOT soon after diagnosis, especially during critical conditions, is proved to be associated with higher survival and preservation rates.

Evaluating bentonite clay’s potential in protecting intestinal flora and alleviating pseudomembranous colitis following antibiotic usage

As the most commonly used drugs, antibiotics have several adverse effects. When intravenous broad-spectrum antibiotics are administered for infections outside the gut, they are also released into the gut, upsetting the natural balance of flora and potentially causing opportunistic infections there. Pseudomembranous colitis induced by the excessive growth of Clostridioides difficile following antibiotic administration and disruption of the normal gut flora is a main consequence of antibiotic therapy. Unfortunately, effective strategies to mitigate the damage caused by antibiotics to the microbiota remain elusive, with limited information available on the subject. Several studies have examined the effects of enzymatic inactivation of specific antibiotics, but non-enzymatic inactivation of antibiotics has been explored to a lesser extent, resulting in the introduction of only a restricted number of products. We believe that bentonite clay, an underutilized substance that exhibits promising features for counteracting the unfavorable effects of antibiotics has a high potential to circumvent the side effects of antibiotics. It is a cost-effective and safe and has garnered significant attention in the medical history, predominantly for its superior adsorption properties. Given the diverse characteristics of bentonite clay, capacity to protect the natural flora, antibacterial and anti-inflammatory traits, and its contribution to wound healing, it is plausible to assume that bentonite clay exhibits significant potential in mitigating the detrimental consequences of antibiotic on the natural gut microbiota and following pseudomembranous colitis. Further research is necessary to unravel the full extent of its therapeutic effects in combating this condition.