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 postprotocol 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 postprotocol groups, respectively (P < .001). Recurrent fever (14.2% versus 16.0%, P = .726), documented infection (1.7% versus 6.7%, P = .068), and readmission (13.3% versus 22.7%, P = .091) within 30 days were not significantly different between the two groups. Neither 30-day mortality (0.8% versus 1.3%, P = .736) nor 90-day NRM (0.8% versus 1.3%, P = .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 preprotocol 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.

The lung microbiota is a complex community of microorganisms that colonize the respiratory tract of individuals from, or even before, birth. Although the lungs were traditionally believed to be sterile, recent research has shown that there is a diversity of bacterial species in the respiratory system. Knowledge about the lung microbiota in newborns and its relationship with bacterial infections is of vital importance to understand the pathogenesis of respiratory diseases in neonatal patients undergoing mechanical ventilation. In this article, the current evidence on the composition of the lung microbiota in newborns will be reviewed, as well as the risks that an altered microbiota can impose on premature newborns. Although advances in neonatal intensive care units have significantly improved the survival rate of preterm infants, the diagnosis and treatment of ventilator-associated pneumonia has not progressed in recent decades. Avoiding dysbiosis caused by inappropriate use of antibiotics around birth, as well as avoiding intubation of patients or promoting early removal of endotracheal tubes, are among the most important preventive measures for ventilator-associated pneumonia. The potential benefit of probiotics and prebiotics in preventing infectious, allergic or metabolic complications in the short or long term is not clearly established and constitutes a very important field of research in perinatal medicine.

Hepatic encephalopathy (HE) is a formidable complication in patients with decompensated cirrhosis, often necessitating the administration of rifaximin (RFX) for effective management. RFX, is a gut-restricted, poorly-absorbable oral rifamycin derived antibiotic that can be used in addition to lactulose for the secondary prophylaxis of HE. It has shown notable reductions in infection, hospital readmission, duration of hospital stay, and mortality. However, limited data exist about the concurrent use of RFX with broad-spectrum antibiotics, because the patients are typically excluded from studies assessing RFX efficacy in HE. A pharmacist-driven quasi-experimental pilot study was done to address this gap. They argue against the necessity of RFX in HE during broad-spectrum antibiotic treatment, particularly in critically ill patients in intensive care unit (ICU). The potential for safe RFX discontinuation without adverse effects is clearly illuminated and valuable insight into the optimization of therapeutic strategies is offered. The findings also indicate that RFX discontinuation during broad-spectrum antibiotic therapy was not associated with higher rates of delirium or coma, and this result remained robust after adjustment in multivariate analysis. Furthermore, rates of other secondary clinical and safety outcomes, including ICU mortality and 48-hour changes in vasopressor requirements, were comparable. However, since the activity of RFX is mainly confined to the modulation of gut microbiota, its potential utility in patients undergoing extensive systemic antibiotic therapy is debatable, given the overlapping antibiotic activity. Further, this suggests that the action of RFX on HE is class-specific (related to its activity on gut microbiota), rather than drug-specific. A recent double-blind randomized controlled (ARiE) trial provided further evidence-based support for RFX withdrawal in critically ill cirrhotic ICU patients receiving broad-spectrum antibiotics. Both studies prompt further discussion about optimal therapeutic strategy for patients facing the dual challenge of HE and systemic infections. Despite these compelling results, both studies have limitations. A prospective, multi-center evaluation of a larger sample, with placebo control, and comprehensive neurologic evaluation of HE is warranted. It should include an exploration of longer-term outcome and the impact of this protocol in non-critically ill liver disease patients.

UNASSIGNED: During the COVID-19 Delta variant surge, the CLAIRE cross-sectional study sampled saliva from 120 hospitalized patients, 116 of whom had a positive COVID-19 PCR test. Patients received antibiotics upon admission due to possible secondary bacterial infections, with patients at risk of sepsis receiving broad-spectrum antibiotics (BSA).
UNASSIGNED: The saliva samples were analyzed with shotgun DNA metagenomics and respiratory RNA virome sequencing. Medical records for the period of hospitalization were obtained for all patients. Once hospitalization outcomes were known, patients were classified based on their COVID-19 disease severity and the antibiotics they received.
UNASSIGNED: Our study reveals that BSA regimens differentially impacted the human salivary microbiome and disease progression. 12 patients died and all of them received BSA. Significant associations were found between the composition of the COVID-19 saliva microbiome and BSA use, between SARS-CoV-2 genome coverage and severity of disease. We also found significant associations between the non-bacterial microbiome and severity of disease, with Candida albicans detected most frequently in critical patients. For patients who did not receive BSA before saliva sampling, our study suggests Staphylococcus aureus as a potential risk factor for sepsis.
UNASSIGNED: Our results indicate that the course of the infection may be explained by both monitoring antibiotic treatment and profiling a patient\'s salivary microbiome, establishing a compelling link between microbiome and the specific antibiotic type and timing of treatment. This approach can aid with emergency room triage and inpatient management but also requires a better understanding of and access to narrow-spectrum agents that target pathogenic bacteria.

Hematopoietic stem cells (HSCs) undergo self-renewal and differentiation in the bone marrow, which is tightly regulated by cues from the microenvironment. The gut microbiota, a dynamic community residing on the mucosal surface of vertebrates, plays a crucial role in maintaining host health. Recent evidence suggests that the gut microbiota influences HSCs differentiation by modulating the bone marrow microenvironment through microbial products. This paper comprehensively analyzes the impact of the gut microbiota on hematopoiesis and its effect on HSCs fate and differentiation by modifying the bone marrow microenvironment, including mechanical properties, inflammatory signals, bone marrow stromal cells, and metabolites. Furthermore, we discuss the involvement of the gut microbiota in the development of hematologic malignancies, such as leukemia, multiple myeloma, and lymphoma.

Information on the long-term effects of non-restrictive antimicrobial stewardship (AMS) strategies is scarce. We assessed the effect of a stepwise, multimodal, non-restrictive AMS programme on broad-spectrum antibiotic use in the intensive care unit (ICU) over an 8-year period. Components of the AMS were progressively implemented. Appropriateness of antibiotic prescribing was also assessed by monthly point-prevalence surveys from 2013 onwards. A Poisson regression model was fitted to evaluate trends in the reduction of antibiotic use and in the appropriateness of their prescription. From 2011 to 2019, a total of 12,466 patients were admitted to the ICU. Antibiotic use fell from 185.4 to 141.9 DDD per 100 PD [absolute difference, -43.5 (23%), 95% CI -100.73 to 13.73; p = 0.13] and broad-spectrum antibiotic fell from 41.2 to 36.5 [absolute difference, -4.7 (11%), 95% CI -19.58 to 10.18; p = 0.5]. Appropriateness of antibiotic prescribing rose by 11% per year [IRR: 0.89, 95% CI 0.80 to 1.00; p = 0.048], while broad-spectrum antibiotic use showed a dual trend, rising by 22% until 2015 and then falling by 10% per year since 2016 [IRR: 0.90, 95% CI 0.81 to 0.99; p = 0.03]. This stepwise, multimodal, non-restrictive AMS achieved a sustained reduction in broad-spectrum antibiotic use in the ICU and significantly improved appropriateness of antibiotic prescribing.

BACKGROUND: In recent years, new drugs for the treatment of various diseases, thereby the emergence of antimicrobial resistance tremendously increased because of the increased consumption rate of various drugs. However, the irrational use of antibiotics increases the microbial resistance along with that the frequency of mortality associated with infections is higher. Broad-spectrum antibiotics were effectively against various bacteria and the unrestricted application of antibiotics lead to the emergence of drug resistance. The present study was aimed to detect the antibacterial properties of lipopeptide novel drug producing Streptomyces parvulus.
METHODS: A lipopeptide-producing S. parvulus was isolated from the soil sample. The inhibitory effect of lipopeptide was detected against Gram-positive and Gram-negative bacteria. Bactericidal activity and minimum inhibitory concentration (MIC) were assayed. The IC50 value was analysed against ovarian and human melanoma cell lines. The experimental mouse model was infected withKlebsiella pneumoniae and treated with lipopeptide and bactericidal activity was determined.
RESULTS: The results indicated that the antibacterial activity of lipopeptide ranges from 13 ± 1 mm to 32 ± 2 mm against Gram-positive and Gram-negative strains. The lowest MIC value was noted as 1.5 ± 0.1 µg/mL against K. pneumoniae and the highest against E. aerogenes (7.5 ± 0.2 µg/mL). The IC50 value was considerably high for the ovarian cell lines and human melanoma cell lines (426 µg/mL and 503 µg/mL). At 25 µg/mL concentration of lipopeptide, only 16.4% inhibition was observed in the ovarian cell line whereas 20.2% inhibition was achieved at this concentration in the human melanoma cell line. Lipopeptide inhibited bacterial growth and was completely inhibited at a concentration of 20 µg/mL. Lipopeptide reduced bacterial load in experimental mice compared to control (p < 0.05).
CONCLUSIONS: Lipopeptide activity and its non-toxic nature reveal that it may serve as a lead molecule in the development of a novel drug.

The global challenge of antibiotic resistance necessitates the introduction of more effective antibiotics. Here we report a potentially general design strategy, exemplified with vancomycin, that improves and expands antibiotic performance. Vancomycin is one of the most important antibiotics in use today for the treatment of Gram-positive infections. However, it fails to eradicate difficult-to-treat biofilm populations. Vancomycin is also ineffective in killing Gram-negative bacteria due to its inability to breach the outer membrane. Inspired by our seminal studies on cell penetrating guanidinium-rich transporters (e.g., octaarginine), we recently introduced vancomycin conjugates that effectively eradicate Gram-positive biofilm bacteria, persister cells and vancomycin-resistant enterococci (with V-r8, vancomycin-octaarginine), and Gram-negative pathogens (with V-R, vancomycin-arginine). Having shown previously that the spatial array (linear versus dendrimeric) of multiple guanidinium groups affects cell permeation, we report here for the first time vancomycin conjugates with dendrimerically displayed guanidinium groups that exhibit superior efficacy and breadth, presenting the best activity of V-r8 and V-R in single broad-spectrum compounds active against ESKAPE pathogens. Mode-of-action studies reveal cell-surface activity and enhanced vancomycin-like killing. The vancomycin-polyguanidino dendrimer conjugates exhibit no acute mammalian cell toxicity or hemolytic activity. Our study introduces a new class of broad-spectrum vancomycin derivatives and a general strategy to improve or expand antibiotic performance through combined mode-of-action and function-oriented design studies.

There is scarce evidence to demonstrate the pattern of antibiotic use in children in China. We aimed to describe antibiotic prescribing practices among children in primary healthcare institutions (PHIs) in China. We described outpatient antibiotic prescriptions for children in PHIs from January 2017 to December 2019 at both the national and diagnostic levels, utilizing the antibiotic prescribing rate (APR), multi-antibiotic prescribing rate (MAPR), and broad-spectrum prescribing rate (BAPR). Generalized estimating equations were adopted to analyze the factors associated with antibiotic use. Among the total 155,262.2 weighted prescriptions for children, the APR, MAPR, and BAPR were 43.5%, 9.9%, and 84.8%. At the national level, J01DC second-generation cephalosporins were the most prescribed antibiotic category (21.0%, N = 15,313.0), followed by J01DD third-generation cephalosporins (17.4%, N = 12,695.8). Watch group antibiotics accounted for 55.0% of the total antibiotic prescriptions (N = 52,056.3). At the diagnostic level, respiratory tract infections accounted for 67.4% of antibiotic prescriptions, among which prescriptions with diagnoses classified as potentially bacterial RTIs occupied the highest APR (55.0%). For each diagnostic category, the MAPR and BAPR varied. Age, region, and diagnostic categories were associated with antibiotic use. Concerns were raised regarding the appropriateness of antibiotic use, especially for broad-spectrum antibiotics.

Cervical necrotizing fasciitis is an immensely progressive, difficult-to-diagnose soft tissue infection of the fascial planes, skin, and subcutaneous tissue. It has marked morbidity and mortality. In this case report, we analyzed the risk factors, laboratory indices, and treatment modalities that affect the outcome of this fatal disease. This is a retrospective case series of cases admitted within a short span of six months between January and June 23. The cases were followed up monthly for three months, and the diagnosis was made on a clinical, pathological, radiological, and histopathological basis. All the cases were managed with neck exploration and aggressive surgical debridement in an emergency department, dressing of the wound with hydrogen peroxide and betadine twice daily, triple broad-spectrum antibiotic therapy for polymicrobial infection, and tight glycemic control. There were no complications, and all the patients survived. We report our cases of cervical necrotizing fasciitis that had similar presentations but varied outcomes. Here, we would like to advocate the importance of immediate management in the form of neck exploration and debridement at the earliest after the diagnosis has been established. Hyperglycemia should be brought under control, and daily aseptic dressing with removal of the slough and source of infection would greatly affect the outcome of this deadly disease.