Administration Of Broad-spectrum Antibiotics Research Articles

Prophylactic application of antibiotics selects extended‐spectrum β‐lactamase and carbapenemases producing Gram‐negative bacteria in the oral cavity

Prophylactic administration of broad-spectrum antibiotics in surgery can change the oral microbiome and induce colonization of oral cavity with Gram-negative bacteria including multidrug (MDR) or extensively drug resistant (XDR) organisms which can lead to lower respiratory tract infections. The aim of the study was to analyse the Gram-negative isolates obtained from oral cavity of the mechanically ventilated patients in ICUs, after prophylactic application of antibiotics and their resistance mechanisms and to compare them with the isolates obtained from tracheal aspirates from the same patients. The antibiotic susceptibility was determined by broth dilution method. PCR was applied to detect genes encoding β-lactamases. Marked diversity of Gram-negative bacteria and resistance mechanisms was found. High resistance rates and high rate of blaCTX-M and carbapenemase encoding genes (blaVIM-1 , blaOXA-48 ) were found among Klebsiella pneumoniae. Pseudomonas aeruginosa was found to harbour blaVIM and in one strain blaPER-1 gene, whereas Acinetobacter baumannii produced OXA-23-like and OXA-24/40-like oxacillinases and was XDR in all except one case. All XDR isolates belong to international clonal lineage II (IC II). The main finding of the study is that the prophlylactic application of antibiotics in surgery intensive care units (ICUs) is associated with the colonization of oral cavity and lower respiratory tract with Gram-negative bacteria. The identity of Gram-negative bacteria in oral cavity reflected those found in endotracheal aspirates leading to conclusion that oral swab as non-invasive specimen can predict the colonization of lower respiratory tract with resistant Gram-negative organisms and the risk for development of ventilator-associated pneumonia.

Pyoderma gangrenosum after cesarean delivery

A 23-year-old primigravida underwent a low-transverse cesarean delivery at 28 weeks’ gestation for hemolysis, elevated liver enzymes, and low platelet count syndrome. On postoperative day (POD) 6 (Figure 1), the patient developed fevers with signs of wound infection and underwent debridement. On POD 10, despite administration of broad-spectrum antibiotics, worsening wound breakdown was noted (Figure 2) and thus a second debridement was performed. On POD 17, skin breakdown and erythema extended beyond the surgical margins (Figure 3) with violaceous, undermined borders.

Trends in bacterial bloodstream infections and resistance in immuno-compromised patients with febrile neutropenia: a retrospective analysis.

Bacterial infections remain a major cause of morbidity and mortality in immunocompromised children. From the onset of fever, an early administration of broad-spectrum antibiotics is begun; this strategy could induce emergence of multi-drug resistant bacteria (MDR). We describe the incidence and microbiological spectrum, including MDR bacteria of bacterial documented blood-stream infections (BSI) in immunocompromised children. A retrospective, descriptive study was conducted in a tertiary referral centre in France from January 2014 to December 2017. Our cohort included a large scale of patients with febrile neutropenia: haematological and oncological malignancies, haematopoietic stem cell transplantations, severe combined immunodeficiency syndromes. BSI were defined by positive blood culture samples associated with fever. Among 760 febrile neutropenia episodes in 7301 admitted patients, we identified 310 documented BSI with a mean of 7.4 BSI/1000 patient bed days. Only 2.9% BSIs were caused by MDR bacteria, none vancomycin resistant. Coagulase-negative staphylococci were identified in 49.7% BSI and Staphylococcus aureus caused 6.5% infections. Gram-negative bacilli accounted for 21.6% of isolated bacteria, Pseudomonas for 4.8%. The incidence of BSI annually decreased by 0.75% (p = 0.002).Conclusion: With a step-down strategy at 48h of initial broad-spectrum antibiotic therapy, we reported a low number of MDR bacteria, no deaths related to BSI. What is Known: • Bacterial bloodstream infections are a leading cause of morbidity and mortality in immunocompromised children • Multi-drug resistant bacteria are emerging worldwide. What is New: • Initial broad-spectrum antibiotic therapy with a step-down strategy at 48h: no deaths related to bloodstream infections with a low number of resistant bacteria. • Parental and nurse stewardship to decrease bloodstream infections incidence with a drop of staphylococcal infections.

22 Acute Kidney Injury in Burn Patients Following Combination Antibiotic Therapy: A Large Database Analysis

Abstract Introduction Burn patients are prone to infections, which often warrants broad-spectrum antibiotic coverage. Vancomycin is a common antibiotic used at burn centers and is administered alone, or in combination with other agents such as piperacillin-tazobactam (Pip/Tazo). A recent study showed that this combination therapy was associated with increased rates of acute kidney injury (AKI) in adult and pediatric burn patients when compared to vancomycin in combination with other antibiotics. However, other studies failed to demonstrate these findings. The degree of nephrotoxic effect of the combination therapy relative to its drug components has not been demonstrated in burn patients. Using a large national database encompassing 41 health care organizations, we sought to determine whether a combination of vancomycin and Pip/Tazo exacerbates AKI in burn patients. Methods Using the TriNetX Global Health Research Network, we identified the population of burn patients with ICD-10 codes T20-T25 and T30-T32 between 2000–2020. We then grouped this population into 4 cohorts based on the administration of broad-spectrum antibiotics they received after the burn incident: vancomycin, Pip/Tazo alone, combination, and neither vancomycin nor Pip/Tazo. All cohorts were balanced for age, gender, and race. We explored the distribution of these cohorts and conducted comparative outcome analysis to determine the relative risk of developing AKI using the ICD10 code N17. Results Comparative analysis showed burn patients who received vancomycin had a 4.81% increased associated risk with AKI compared to those who did not receive either vancomycin or Pip/Tazo (p< 0.0001, RR =3.35, 95%CI= 2.63–4.26). Patients who received Pip/Tazo monotherapy had a 5.1% increased association with AKI compared to those who did not receive either drug (p< 0.0001, RR =3.57, 95%CI: 2.33–5.45). The combination of vancomycin with Pip/Tazo increased the association with AKI by 9.49% compared to patients who did not receive either drug (p< 0.00001, RR=5.65, 95%CI: 4.40–7.26). Combination therapy also increased the risk of AKI when compared to the vancomycin monotherapy (5.01%, p< 0.00001, RR= 1.69, 95%CI: 1.42–2.00) and Pip/Tazo monotherapy (4.85%, p< 0.00002, RR= 1.62, 95%CI: 4.40–7.26). Conclusions The use of broad-spectrum antibiotics in burn patients is associated with a higher risk of AKI. The combination of these drugs affords an increased relative risk of AKI when compared to monotherapy with the respective component drugs. Whether this is associated with selection bias or drug-effect warrants further investigation.

A case report of iodine-125 seed placement during operation for the treatment of advanced gallbladder carcinoma with septic shock*

Abstract This case report describes a patient with advanced gallbladder cancer who developed septic shock associated with iodine-125 (125I) seed implantation. The treatment process is described to provide a clinical reference for similar cases. A 52-year-old woman with recurrence of advanced gallbladder cancer underwent 125I seed implantation and developed postoperative sepsis with septic shock. The blood culture suggested infection with Aeromonas caviae and Enterococcus faecalis. Vancomycin and imipenem were immediately administered according to the drug sensitivity results, along with immunoglobulin therapy and vasoactive drugs. The patient’s condition gradually stabilized after comprehensive treatment. Sepsis with septic shock is a rare but potentially fatal complication of 125I seed implantation. Timely administration of broad-spectrum antibiotics, immunoglobulin therapy, and vasoactive drugs is very important to stabilize the patient’s condition. Our treatment of this patient can serve as a reference for clinicians to manage this complication in similar cases.

Open-fracture dislocation of the talus

Purpose The aim was to evaluate the incidence of infection and functional outcome of these injuries. Patients and methods A total of 14 patients with open-talar fracture dislocations or total dislocations of the talus were managed and the functional results evaluated between November 2012 and December 2016. Eleven of these patients were males and three were females. The injuries were sustained between the 20- and 50-year age group . The right side was affected in 10 and the left side was injured in four patients. Road traffic accident was the cause in nine patients and fall from the height was the cause in five patients. The principles of management were debridement and minimal fixation of fractures. Results The mean follow-up period was 33 months (range: 16–50 months). Two of 14 cases (14.2%) developed infection. One patient had resolved clinically with antibiotics alone. One patient had persistent drainage 4 months after injury and required late ankle and subtalar arthrodesis. The functional outcome according to Boston Children’s Hospital ankle grading system was excellent in six (42.85%), good in five (35.71%), fair in two (14.28%), and failure in one (7.14%). There was no evidence of osteonecrosis or collapse of the talar dome. Conclusion In conclusion, patients with major open-fracture dislocation of the talus have a significant incidence of the best results with modern orthopedic techniques that dramatically decreased the rates of infection, avascular necrosis (AVN), and poor functional results although continued work is required to improve patient care and outcomes. Open-talar fractures should be managed as emergently including administration of broad-spectrum antibiotics, irrigation of the wound, operative debridement, reduction, and minimal fixation.

10351 Antibiotic Use for Respiratory Syncytial Virus in the Middle East: A Surveillance Study in Hospitalized Jordanian Children

ABSTRACT IMPACT: Antibiotic stewardship guidelines should consider the barriers clinicians in low- and middle-income countries face due to limited biomarkers for determining the etiologic pathogen for viral infections like respiratory syncytial virus (RSV) that have a similar presentation to bacterial infections. OBJECTIVES/GOALS: We aimed to evaluate antibiotic administration practices in children who were hospitalized at a government-run hospital in Amman, Jordan, where point-of-care testing is limited. We hypothesized those with RSV are more likely to be administered antibiotics during their hospitalization than children without RSV. METHODS/STUDY POPULATION: We conducted a cross-sectional cohort study in Jordanian children hospitalized with history of acute respiratory symptoms and/or fever from 2010 to 2013. Admitting diagnoses were dichotomized into suspected viral- (e.g., bronchiolitis) and bacterial-like infection (e.g., sepsis, pneumonia). Stratifying by sex, we performed a polytomous logistic regression adjusting for age, underlying medical condition, maternal education, and region of residence to estimate prevalence odds ratios (PORs) and 95% confidence intervals for macrolides, broad-, and narrow-spectrum antibiotics during hospitalization. Sensitivity and specificity of admission diagnoses and laboratory results were compared. RESULTS/ANTICIPATED RESULTS: Children with a suspected viral-like admission diagnosis, compared to those with suspected bacterial-like, were 89% less likely to be administered a narrow-spectrum antibiotic (POR: 0.11; p<0.001). There were slight differences by sex with males having a lower prevalence than females of narrow-spectrum or broad-spectrum antibiotic administration; but they had a higher prevalence of macrolide administration. Overall, children with RSV had a 30% probability (sensitivity) of being assigned to a suspected viral infection; whereas RSV-negative children had an 85% probability (specificity) of being assigned to a suspected bacterial infection. DISCUSSION/SIGNIFICANCE OF FINDINGS: Children with a suspected viral-like infection were less likely to receive an antibiotic; however, when evaluating the accuracy of admission diagnosis to RSV-laboratory results there were considerable misclassifications. These results highlight the need for developing antibiotic interventions for Jordan and the rest of the Middle East.

Ventilator Associated Pneumonia

This review discusses the prevention and identification of ventilator associated pneumonia. The ventilator associated pneumonia is a hospital acquired pneumonia and it spreads through bacteria like Steprtococcus pneumonia. The present review explains the transmission in to the lungs through the NG tubes and oxygen tube through the nasal cavity and through wind wipe. Once the infection spreads to the lungs it presents with signs and symptoms such as breathlessness restlessness low oxygen levels. The recommended investigations are sputum culture for bacterial identification and other confirmatory tests. Once the diagnosis of pneumonia is confirmed the focus is on the treatment which includes administration of broad spectrum antibiotics. Few strategies recommended for the prevention of ventilator associated pneumonia are hygiene of the self and patient cleaning of the used catheter and tubes vaccinating the attending staff against infection and updating the knowledge of the staff regarding ventilator associated pneumonia and educating the family regarding the hygiene during this conditionnbsp

Absceso del tegmento dorsolateral protuberancial por coinfección de E. coli y virus de la gripe A (H1N1)pdm09

Brain stem abscesses are rare entities that predominantly affect the pons. A wide variety of microorganisms may be implied, depending on the focus of dissemination. We present the case of a female patient with multiple comorbidities who developed multi-lobar pneumonia due to influenza A(H1N1)pdm09 virus during the postoperative period after an emergent cholecystectomy, requiring mechanical ventilation (MV). Following clinical improvement and withdrawal of MV, the patient did not recover consciousness. Forty-eight hours later, imaging exams showed an abscess in the left pontine dorsolateral tegmentum –a region recently associated with coma-. Despite the administration of broad-spectrum antibiotics, the patient died five days later. This case illustrates the importance of considering pontine abscesses as a cause of poor neurological course in critically ill patients, as well as the need for doing imaging exams to rule out intracranial lesions, particularly in coma-associated areas.

Characteristic of Bacterias And Antibiotic Sensitivity of Blood Culture in Sepsis

Introduction: Sepsis is a group of symptoms caused by infection, characterized byorgan dysfunction due to compromised hosts response to infection hence may leadto a life-threatening condition. One of the treatments for sepsis stated in one hour-bundle is the administration of broad-spectrum antibiotics before the culture resultsobtained. Improper use of antibiotics may lead to antibiotic resistance. The purposeof this study was to describe the microbes pattern and their sensitivity to antibioticsin patients with sepsis at Muhammad Hoesin Hospital, Palembang, to contribute toa useful treatment guideline and to provide a reference for further research.Methods: This study was a descriptive observational study with a cross-sectionaldesign using medical record of patients diagnosed with sepsis whose blood cultureresults were positive. This study was conducted at Muhammad Hoesin Hospital,Palembang, from January 2017 to December 2018. The data was processed andanalyzed by univariate analysis using the SPSS 21.0 computer program. Results:The study subjects were predominantly children with Gram-positive bacteria(24.6%) as the most common cause. The most common bacteria observed wereStaphylococcus epidermidis (35.7%), Staphylococcus aureus (27.3%), Staphylococcushaemolyticus (24%), and Staphylococcus hominis (21.4%). Linezolid (100%),nitrofurantoin (100%), and quinupristin/dalfopristin (100%) were found to besensitive to gram-positive bacteria. Conclusion: Gram-positive bacteria were themost common cause of sepsis in Muhammad Hoesin Hospital, Palembang. Thebacteria were sensitive to linezolid, nitrofurantoin, and quinupristin/ dalfopristin.

A case of retropharyngeal emphysema as a complication of pneumothorax.

Retropharyngeal emphysema is a rare condition, and it is important to determine whether the patient presents with complications including pneumomediastinum or other severe clinical presentations such as an upper airway obstruction. In such cases, patients should undergo urgent tracheostomy and surgical neck drainage with concurrent administration of broad‐spectrum antibiotics.

Antibiotic Therapy and Low Gut Microbiome Diversity Is Associated with Decreased Response and High Toxicity in BCP-ALL and DLBCL Patients after Treatment with CD19. CAR T-Cells

Viktoria Blumenberg and Maria-Luisa Schubert contributed equally. Introduction: The CD19 specific chimeric antigen receptor (CAR) T-cell products Axicabtagene-Ciloleucel and Tisagenlecleucel are approved for the treatment of refractory/relapsed B-cell precursor ALL (BCP-ALL) and Diffuse Large B-cell lymphoma (DLBCL). Despite high response rates, long term remission is only achieved in a subgroup if patients. In addition, CAR T cell therapy is accompanied by potentially severe immune related toxicities including cytokine release syndrome (CRS) or neurotoxicity (ICANS). Therefore, we need to identify biological mechanisms of treatment resistance and toxicity occurring in the host in addition to improve the CAR T product itself. The impact of the gut microbiome on T-cell based immunotherapies such as checkpoint inhibition or allogeneic hematopoietic stem cell transplant has been shown, but it´s role in mediating anti-tumor responses and the occurrence of immunotoxicities of CAR T-cell therapy has not yet been reported so far. Methods: Patients with r/r BCP-ALL and DLBCL were treated with the commercially available CD19 specific CAR T-cell products Axicabtagene-Ciloleucel or Tisagenlecleucel or in-house manufactured CD19-targeted CD28-4-1BB-CD3ζ CAR T-cells at both our institutions. Fecal biospecimens from 33 patients were collected sequentially before, during and after CAR T transfusion (specific time points: before lymphodepleting chemotherapy, day of CAR T-cell transfusion and in 7 day intervals up to day 28). 16S rRNA sequencing and shotgun metagenome sequencing has been performed on 137 stool samples. Sequencing results and clinical metadata are integrated into a patient-centered "hospitalome" including infections and immunotoxicities as well as concomitant anti-infective, immunosuppressive agents and treatment response. Patients having received any type of anti-infective medication exceeding prophylaxis on the day of CAR T cell transfusion or up to two weeks prior were distinguished from patients without prior anti-infective medication or only receiving anti-infective drugs from day 1 after CAR T-cell transfusion. Results: Patients receiving anti-infectives up to two weeks prior to CAR T-cell transfusion display a significantly lower response rate compared to patients, who have been treated with antibiotic and / or -mycotic treatment after day 0 (Tab. 1). Before CAR T-cell transfusion patients showed a heterogeneous, but largely diverse gut microbial taxa (Shannon index median: 4.2.). After CAR T-cell transfusion the alpha diversity (i.e. within-sample diversity) decreases with the nadir at day 14 (Shannon index, median 2.4), which depended significantly on broad-spectrum antibiotic administration (Fig. 1-2). Furthermore, loss of diversity correlated significantly with the occurrence of CRS (p<0.001, univariate GLM with Shannon diversity index vs. occurrence of CRS, irrespective of grade). Diversity loss was not associated with clinical response at day 90 or the development of ICANS. Age had no effect on microbiome changes and no inter-center effect was detected. Assessment of beta diversity (i.e. variation between samples) demonstrated compositional changes of the microbiome in CAR T-cell patients with approximately 25% of all samples displaying a mono-domination of the microbiome by Enterococcus spp. (i.e., rel. abundance > 30% per sample). The expansion of enterococci was again found in samples of patients, who received antibiotic treatment. Conclusion: The gut microbiome of CAR T-cell patients undergoes large and diverse compositional changes, whereas altered diversity is significantly associated with administration of anti-infectives prior to CAR T-cell transfusion and the occurrence of CRS. The assessment of the gut microbial taxa of CAR T-cell patients might serve as a predictive biomarker for immunotoxicity and, eventually, treatment response. Disclosures Blumenberg: Gilead: Consultancy, Research Funding; Novartis: Research Funding; Celgene: Research Funding. Schubert:Kite / Gilead: Consultancy; Takeda: Consultancy. Buecklein:Amgen: Consultancy; Pfizer: Consultancy; Celgene: Research Funding; Novartis: Research Funding; Gilead: Consultancy, Research Funding. Müller-Tidow:Pfizer: Research Funding, Speakers Bureau; Daiichi Sankyo: Research Funding; BiolineRx: Research Funding; Janssen-Cilag GmbH: Speakers Bureau. Dreger:Gilead: Consultancy, Speakers Bureau; AbbVie: Consultancy, Speakers Bureau; AstraZeneca: Consultancy; Roche: Consultancy, Speakers Bureau; Neovii: Research Funding; Riemser: Consultancy, Research Funding, Speakers Bureau; Janssen: Consultancy; Novartis: Consultancy, Speakers Bureau. Schmitt:Apogenix: Research Funding; Hexal: Other: Travel grants , Research Funding; Novartis: Other: educational activities and conferences, Research Funding; Kite: Other: Travel grants, educational activities and conferences; MSD: Membership on an entity's Board of Directors or advisory committees, Other: PI of clinical trials on letermovir; TolerogenixX Ltd: Other: Co-Founder and shareholder. Subklewe:Roche AG: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; AMGEN: Consultancy, Honoraria, Research Funding; Janssen: Consultancy; Pfizer: Consultancy, Honoraria; Gilead Sciences: Consultancy, Honoraria, Research Funding; Seattle Genetics: Research Funding; Morphosys: Research Funding; Celgene: Consultancy, Honoraria.

Pediatric infection and sepsis in five age subgroups: single-center registry

SummaryBackgroundSepsis is, worldwide, one of the leading causes of death among infants and children. Over the past two decades, mortality rates have declined due to advanced treatment options; however, the incidence of sepsis and septic shock is still on the rise in many hospital settings. The objective of this study was to evaluate the course of this disease in pediatric intensive care patients.MethodsAn evaluation of pediatric patients in the intensive care unit diagnosed with infections or sepsis between 2005 and 2015 was performed via a retrospective exploratory data analysis.ResultsDuring the observational period, 201 patients were diagnosed with infection or sepsis. The study population was divided into five age subgroups. The majority of patients were newborns, infants, and toddlers. Forty percent had sepsis; 6% had septic shock. Viral infection was the most prevalent (59%). The overall survival rate was 83%; newborns and adolescents had the lowest survival rates.ConclusionWith this registry, children divided into five age subgroups with infection or sepsis were evaluated and treatment strategies were examined. We have shown that our findings on children treated in our pediatric intensive care unit conform with current literature about pediatric sepsis. In addition to maintaining strict hygiene standards, optimal aspects of sepsis care should be stringently observed, such as the quick administration of empirical broad-spectrum antibiotics, initial adequate fluid resuscitation, and a reliable and frequent routine of source control.

Adjuvant chemotherapy-associated febrile neutropenia in a patient with breast malignancy: A case report

Adjuvant chemotherapy has been widely applied in patients with breast malignancy after surgery to prevent its recurrence and to improve survival comprehensively. Febrile neutropenia is one of the most life-threatening chemotherapy-associated toxicities. A 66 years old woman came to an emergency department of a secondary healthcare facility one week after her final chemotherapy with dose regimen of docetaxel and epirubicin, followed by having nausea, vomitus, and general fatigue with a fever of 38.2°C. Based on her medical record, she had experienced breast malignancy for almost two years and had already conducted mastectomy three months after her diagnosis. Her leukocyte number was only 300 cells per mm3, with 23% neutrophil, hypoalbuminemia, and hypokalaemia. She was then treated in an internal ward and was given intravenous ceftazidime, fluid, granulocyte colony-stimulating factor, albumin transfusion, intravenous potassium replacement, and symptomatic medication. After two days of inpatient care, she was referred to an oncology team in a tertiary healthcare facility. Febrile neutropenia is considered as a fever with a low neutrophil number as a result of bone marrow suppression. The neutrophil plays an essential role as the body’s first line of defence. This condition could make the patient more vulnerable to infections. The Patient was given broad-spectrum antibiotics and typically hospitalized to allow close monitoring until the neutropenia was resolved. Febrile neutropenia possesses a serious threat to patients with breast malignancy who are on cytotoxic chemotherapy. Urgent full blood count and immediate broad-spectrum antibiotic administration are significant to reduce morbidity and mortality.

Epidural-related Maternal Fever: Still a Hot Topic, But What Are the Burning Issues?

(Anesth Analg. 2020;130:318–320) A number of studies controlling for predisposing obstetric and neonatal variables have confirmed the phenomenon of epidural-related maternal fever (ERMF), which is associated with an increased risk of neonatal mortality and morbidity. ERMF is thought to be a sterile inflammatory process, as it is not reduced by broad-spectrum antibiotic or acetaminophen administration. Placental inflammation is a common feature in ERMF, though no pathogenic bacteria are found.

Evaluation of Aminoglycosides Consumption in Open Heart Surgery Based on the Defined Daily Dose Index

Background: Resistance to antibiotics, including aminoglycosides (AMG) is one of the problems associated with inappropriate administration of broad-spectrum antibiotics. Objectives: This study aimed to assess the clinical features of aminoglycosides consumption based on the Defined Daily Dose (DDD) index in open heart surgery.
 Methods: This study was done on 268 patients who underwent heart surgery during 2015 and 2016. Clinical and demographic characteristics, laboratory data, and aminoglycoside-related data such as dose and the total duration of administration were collected through a questionnaire designed by the authors. The patients’ DDD/100 bed-days were calculated, too.
 Results: Out of 268 patients, 170 patients (63.4%) were male. The Mean±SD age of the patients was 60.65±10.71 years and the Mean±SD duration of hospitalization was 12.19±7.02 days. Ischemic heart disease was the most prevalent cause of hospitalization. The Mean duration of receiving aminoglycosides was 3.61 days. In 134 patients (50%), creatinine clearance was less than 60 mL/min during aminoglycosides administration. In 25 patients (9.32%), a 50% increase in serum creatinine during receiving aminoglycosides was observed. Creatinine clearance had not been calculated for any patient.
 Conclusion: In this study, monitoring the side effects of aminoglycosides and the serum concentration was not routinely performed. Dose adjustment of aminoglycosides based on renal function test was not considered in a large number of patients and as a result, the dose was inappropriate in many patients. Therefore, it is recommended that the guidelines of drug usage were followed and the patients were monitored more closely for side effects.

Broad-spectrum antibiotics alter the microbiome, increase intestinal fxr, and decrease hepatic steatosis in zebrafish short bowel syndrome.

Short bowel syndrome (SBS) is associated with changes in the intestinal microbiome and marked local and systemic inflammation. There is also a late complication of SBS, intestinal failure associated liver disease (IFALD) in which hepatic steatosis progresses to cirrhosis. Most patients with SBS arrive at massive intestinal resection after a contaminating intraabdominal catastrophe and have a history of exposure to broad-spectrum antibiotics. We therefore investigated whether the administration of broad-spectrum antibiotics in conjunction with SBS in zebrafish (ZF) would replicate these systemic effects observed in humans to identify potentially druggable targets to aid in the management of SBS and resulting IFALD. In zebrafish with SBS, broad-spectrum antibiotics altered the microbiome, decreased inflammation, and reduced the development of hepatic steatosis. After two weeks of broad-spectrum antibiotics, these fish exhibited decreased alpha diversity, with less variation in microbial community composition between SBS and sham fish. Additionally, administration of broad-spectrum antibiotics was associated with decreased expression of intestinal toll-like receptor 4 (tlr4), increased expression of the intestinal gene encoding the Farnesoid X receptor (fxr), decreased expression of downstream hepatic cyp7a1, and decreased development of hepatic steatosis. SBS in zebrafish reproducibly results in increased epithelial surface area as occurs in human patients who demonstrate intestinal adaptation, but antibiotic administration in zebrafish with SBS reduced these gains with increased cell death in the intervillus pocket that contains stem/progenitor cells. These alternate states in SBS zebrafish might direct the development of future human therapies.NEW & NOTEWORTHY In a zebrafish model that replicates a common clinical scenario, systemic effects of the administration of broad-spectrum antibiotics in a zebrafish model of SBS identified two alternate states that led to the establishment of fat accumulation in the liver or its absence. Broad-spectrum antibiotics given to zebrafish with SBS over 2 wk altered the intestinal microbiome, decreased intestinal and hepatic inflammation, and decreased hepatic steatosis.

Colonization Potential to Reconstitute a Microbe Community in Pseudo Germ-Free Mice After Fecal Microbe Transplant From Equol Producer.

Human intestinal microbiota plays a crucial role in the conversion of isoflavones into equol. Usually, human microbiota-associated (HMA) animal models are used, since it is difficult to establish the mechanism and causal relationship between equol and microbiota in human studies. Currently, several groups have successfully established HMA animal models that produce equol through germ-free mice or rats; however, the HMA model of producing equol through pseudo germ-free mice has not been established. The objective of this study is to establish an HMA mice model for equol production through pseudo germ-free mice, mimicking the gut microbiota of an adult human equol producer. First, a higher female equol producer was screened as a donor from 15 volunteers. Then, mice were exposed to vancomycin, neomycin sulfate, metronidazole, and ampicillin for 3 weeks to obtain pseudo germ-free mice. Finally, pseudo germ-free mice were inoculated with fecal microbiota of the equol producer for 3 weeks to establish HMA mice of producing equol. The results showed that (i) the ability to produce equol was partially transferred from the donor to the HMA mice. (ii) Most of the original intestinal microbiota of mice were eliminated after broad-spectrum antibiotic administration. (iii) The taxonomy data from HMA mice revealed similar taxa to the donor sample, and the species richness returned to the level close to the donor. (iv) The family Coriobacteriaceae and genera Collinsella were successfully transferred from the donor to HMA mice. In conclusion, the HMA mice model for equol production, based on pseudo germ-free mice, can replace the model established by germ-free mice. The model also provides a basis for studying microbiota during the conversion from isoflavones into equol.

Diabetes mellitus and necrotizing fasciitis – a deadly combination; case report

Necrotizing fasciitis is a rapidly destructive affliction of soft tissues, with a mortality rate that may reach 73% of the cases. It is characterized by a progressive inflammation and extended necrosis of the subcutaneous tissue and the fascia. Necrotizing fasciitis was first described in 1848, and later in 1920 Meleney identified 20 patients in China in which the infection was presumably triggered by hemolytic streptococcus, linking pathological bacteria to the condition. In 1952, Wilson coined the term necrotizing fasciitis although without successfully identifying the specific pathological bacteria involved. In most cases, both risk and aggravating factors are present, the main risk factors being diabetes mellitus, liver cirrhosis, renal failure, and immunosuppressant states. Location may vary, but most frequently the disease occurs in the limbs, the trunk, and the perineum. Treatment depends on the location and the time of diagnosis and may range from large incisions with extensive debridement to organ amputations such as those of the limbs or breasts. Treatment is complex and expensive, and besides surgery, includes the administration of broad-spectrum antibiotics, anti-inflammatory drugs, intensive therapy support, and long-term hospitalizations. The prognosis is guarded. The present case entails a 56-year old female patient who presented with many risk factors favoring the occurrence of necrotizing fasciitis, namely diabetes mellitus, liver cirrhosis (decompensated with ascites and portal encephalopathy phenomena), untreated hepatitis B infection, chronic renal failure with diabetic nephrotic syndrome, and obesity.

Anaerobic Necrotizing Pneumonia: Another Potential Life-threatening Complication of Vaping?

An adolescent girl with a history of frequent electronic cigarette use of nicotine was hospitalized with severe necrotizing pneumonia. Blood cultures obtained before the administration of empirical broad-spectrum intravenous antibiotics had positive results for the growth of Fusobacterium necrophorum The pathogen is an uncommon but well-known cause of anaerobic pneumonia with unique features that are collectively referred to as Lemierre syndrome or postanginal sepsis. The syndrome begins as a pharyngeal infection. Untreated, the infection progresses to involve the ipsilateral internal jugular vein, resulting in septic thrombophlebitis with direct spread from the neck to the lungs causing multifocal necrotizing pneumonia. The teenager we present in this report had neither a preceding pharyngeal infection nor Doppler ultrasonographic evidence for the presence of deep neck vein thrombi, leading us to explore alternative mechanisms for her pneumonia. We propose the possibility that her behavior of frequent vaping led to sufficient pharyngeal irritation such that F necrophorum colonizing her oropharynx was inhaled directly into her lungs during electronic cigarette use. Preexisting, but not yet recognized, vaping-related lung injury may have also contributed to her risk of developing the infection. The patient was hospitalized for 10 days. At follow-up one month later, she still became short of breath with minimal exertion.