Broad-spectrum Antibiotic Treatment Research Articles

Host response during unresolved urinary tract infection alters female mammary tissue homeostasis through collagen deposition and TIMP1.

Exposure to pathogens throughout a lifetime influences immunity and organ function. Here, we explore how the systemic host-response to bacterial urinary tract infection (UTI) induces tissue-specific alterations to the mammary gland. Utilizing a combination of histological tissue analysis, single cell transcriptomics, and flow cytometry, we identify that mammary tissue from UTI-bearing mice displays collagen deposition, enlarged ductal structures, ductal hyperplasia with atypical epithelial transcriptomes and altered immune composition. Bacterial cells are absent in the mammary tissue and blood of UTI-bearing mice, therefore, alterations to the distal mammary tissue are mediated by the systemic host response to local infection. Furthermore, broad spectrum antibiotic treatment resolves the infection and restores mammary cellular and tissue homeostasis. Systemically, unresolved UTI correlates with increased plasma levels of the metalloproteinase inhibitor, TIMP1, which controls extracellular matrix remodeling and neutrophil function. Treatment of nulliparous and post-lactation UTI-bearing female mice with a TIMP1 neutralizing antibody, restores mammary tissue normal homeostasis, thus providing evidence for a link between the systemic host response during UTI and mammary glandalterations.

Good Performance of Revised Scoring Systems in Predicting Clinical Outcomes of Aeromonas Bacteremia in the Emergency Department: A Retrospective Observational Study.

Aeromonas species, Gram-negative, non-sporulating, facultative, and anaerobic bacilli, widely distributed in aquatic environments, derive various infections, including bacteremia. Most of these infections were opportunistic and found in patients with predisposing conditions. Among the infections, bacteremia remains with notable mortality, reported from 15% to 45%. However, predicting systems for assessing the mortality risk of this disease have yet to be investigated. We aimed to validate the performance of specific predictive scoring systems to assess the clinical outcomes of Aeromonas bacteremia and applied the revised systems to predict mortality risk. A retrospective observational study reviewed patients with bacteremia caused by Aeromonas spp. based on at least one positive blood culture sample collected in the emergency department from January 2012 to December 2020. The outcome was in-hospital mortality. We used seven predictive scoring systems to predict the clinical outcome. According to the effectiveness in predicting mortality, we revised three of the seven predictive scoring systems by specific characteristics to refine their risk-predicting performances. We enrolled 165 patients with bacteremia caused by Aeromonas spp., including 121 males (73.3%) and 44 females (26.7%), with a mean age of 66.1 ± 14.9 years and an average length of hospital stay of 12.4 ± 10.9 days. The overall mortality rate was 32.7% (54/165). The non-survivors had significantly higher scores in MEDS (6.7 ± 4.2 vs. 12.2 ± 3.3, p < 0.001), NEWS (4.0 ± 2.8 vs. 5.3 ± 3.0, p = 0.008), and qSOFA (0.3 ± 0.6 vs. 0.6 ± 0.7, p = 0.007). Regarding mortality risk prediction, the MEDS demonstrated the best predictive power with AUC of ROC measured up to 0.834, followed by NEWS (0.626) and qSOFA (0.608). We revised the MEDS, NEWS, and qSOFA by hemoglobin and lactate. We found that the revised scores had better powerful performance, including 0.859, 0.767, and 0.691 of the AUC of ROC, if the revised MEDS ≥10, revised NEWS ≥8, and revised qSOFA ≥2, respectively. MEDS, NEWS, and qSOFA were good tools for predicting outcomes in patients with Aeromonas spp. bacteremia. The revised MEDS, NEWS, and qSOFA demonstrated more powerful predicting performance than the original scoring systems. We suggested that patients with higher scores in revised MEDS (≥10), revised NEWS (≥8), and revised qSOFA (≥2) received early goal-directed therapy and appropriate broad-spectrum antibiotic treatment as early as possible to reduce mortality.

2724. Community-acquired Pneumonia in Immunocompromised Patients: Predictors and Outcomes Associated with Empiric Broad-spectrum Antibiotic Treatment

Abstract Background Immunocompromised patients (ICP) are at higher risk of infection, but are often excluded from trials for community-acquired pneumonia (CAP). Due to limited data on CAP treatment in ICP, the IDSA/ATS CAP guideline omits recommendations for ICP. We aimed to assess predictors and outcomes associated with empiric broad-spectrum antibiotic (BSA) use versus standard CAP treatment in ICP hospitalized with CAP without IDSA risk factors for drug-resistant organisms (DRO). Methods We collected data from non-ICU adult ICP hospitalized with CAP [Table 1] between 1/2017 to 12/2022 at 69 Michigan hospitals who received either BSA on hospital day 1 or 2 or a standard CAP regimen. BSA included anti-MRSA and anti-Pseudomonal antibiotics. We excluded patients with moderate/severe COPD, structural lung disease, pulmonary complications, and IDSA risk factors for DRO. Collected data included patient characteristics, laboratory results, antibiotic data, and 30-day outcomes via phone follow up. Logistic regression was used to assess predictors of empiric BSA accounting for hospital-level clustering. We assessed the association of empiric BSA vs. empiric standard CAP treatment with 30-day outcomes using regression models adjusted for variables associated with probability of treatment and known predictors of each outcome. Results Of 40,882 patients with CAP, 2719 were ICP. Of 2719 ICP with CAP, 41% (N=1115) received standard empiric CAP coverage. Compared to ICP who received standard empiric CAP coverage, those who received empiric BSA had a higher incidence of severe sepsis, higher Pneumonia Severity Index, and hospitalization or IV antibiotics in prior 90 days [Table 2]. The most common CAP pathogen identified was Pseudomonas (2.0% (22/1115) standard CAP vs 2.5% (40/1604) BSA) [Table 3]. Of ICP started on BSA, median duration of BSA was 4.4 days [SD 3.4]. After adjustments, receipt of empiric BSA was associated with increased readmission, transfer to ICU and longer hospitalization compared to standard empiric CAP coverage [Table 4]. Conclusion ICP hospitalized with CAP often received empiric BSA but few had identified DRO. Empiric BSA use for CAP in ICP without IDSA risk factors for DRO was associated with worse patient outcomes compared to standard empiric CAP coverage. Disclosures Elizabeth McLaughlin, MS, RN, Blue Cross Blue Shield of Michigan: Support provided through the Value Partnership Program

Interplay of gut microbiota and host epithelial mitochondrial dysfunction is necessary for the development of spontaneous intestinal inflammation in mice

BackgroundIntestinal epithelial cell (IEC) mitochondrial dysfunction involvement in inflammatory bowel diseases (IBD), including Crohn’s disease affecting the small intestine, is emerging in recent studies. As the interface between the self and the gut microbiota, IECs serve as hubs of bidirectional cross-talk between host and luminal microbiota. However, the role of mitochondrial-microbiota interaction in the ileum is largely unexplored. Prohibitin 1 (PHB1), a chaperone protein of the inner mitochondrial membrane required for optimal electron transport chain function, is decreased during IBD. We previously demonstrated that mice deficient in PHB1 specifically in IECs (Phb1i∆IEC) exhibited mitochondrial impairment, Paneth cell defects, gut microbiota dysbiosis, and spontaneous inflammation in the ileum (ileitis). Mice deficient in PHB1 in Paneth cells (epithelial secretory cells of the small intestine; Phb1∆PC) also exhibited mitochondrial impairment, Paneth cell defects, and spontaneous ileitis. Here, we determined whether this phenotype is driven by Phb1 deficiency-associated ileal microbiota alterations or direct effects of loss of PHB1 in host IECs.ResultsDepletion of gut microbiota by broad-spectrum antibiotic treatment in Phb1∆PC or Phb1i∆IEC mice revealed a necessary role of microbiota to cause ileitis. Using germ-free mice colonized with ileal microbiota from Phb1-deficient mice, we show that this microbiota could not independently induce ileitis without host mitochondrial dysfunction. The luminal microbiota phenotype of Phb1i∆IEC mice included a loss of the short-chain fatty acid butyrate. Supplementation of butyrate in Phb1-deficient mice ameliorated Paneth cell abnormalities and ileitis. Phb1-deficient ileal enteroid models suggest deleterious epithelial-intrinsic responses to ileal microbiota that were protected by butyrate.ConclusionsThese results suggest a mutual and essential reinforcing interplay of gut microbiota and host IEC, including Paneth cell, mitochondrial health in influencing ileitis. Restoration of butyrate is a potential therapeutic option in Crohn’s disease patients harboring epithelial cell mitochondrial dysfunction.BykqUrdWkjvtZT9W9KFZmHVideo

Microbiota do not restrict rotavirus infection of colon.

Alterations of the gut microbiome can have significant effects on gastrointestinal homeostasis leading to various diseases and symptoms. Increased understanding of rotavirus infection in relation to the microbiota can provide better understanding on how microbiota can be used for clinical prevention as well as treatment strategies. Our volumetric 3D imaging data show that antibiotic treatment and its consequent reduction of the microbial load does not alter the extent of rotavirus infection of enterocytes in the small intestine and that restriction factors other than bacteria limit the infection of colonocytes.

An international consensus based on the Delphi method to define failure of medical treatment in pyogenic spinal infections

Background contextPyogenic spinal infections (PSIs) are severe conditions with high morbidity and mortality. If medical treatment fails, patients may require surgery, but there is no consensus regarding the definition of medical treatment failure. PurposeTo determine criteria for defining failure of medical treatment in PSI through an international consensus of experts. Study designA two-round basic Delphi method study. SampleOne hundred and fifty experts from 22 countries (authors or co-authors of clinical guidelines or indexed publications on the topic) were invited to participate; 33 answered both rounds defining the criteria. Outcome measuresA scale of 1 to 9 (1: no relevance; 9: highly relevant) applied to each criterion. MethodsWe created an online survey with 10 criteria reported in the literature to define the failure of medical treatment in PSIs. We sent this survey via email to the experts. Agreement among the participants on relevant criteria (score ≥7) was determined. One month later, the second round of evaluations was sent. An extra criterion suggested by six responders in the first round was incorporated. The final version was reached with the criteria considered relevant and with high agreement. ResultsThe consensus definition is: (1) There is an uncontrolled sepsis despite broad spectrum antibiotic treatment, and (2) There is an infection relapse, following a six-week period of antibiotics with clinical and laboratory improvement. ConclusionsOur definition of failure following nonsurgical treatment of PSI can offer a standardized approach to guide clinical decision-making. Furthermore, it has the potential to enhance scientific reporting within this field.

Uncovering Predictive Factors and Interventions for Restoring Microecological Diversity after Antibiotic Disturbance.

Antibiotic treatment can lead to a loss of diversity of gut microbiota and may adversely affect gut microbiota composition and host health. Previous studies have indicated that the recovery of gut microbes from antibiotic-induced disruption may be guided by specific microbial species. We expect to predict recovery or non-recovery using these crucial species or other indices after antibiotic treatment only when the gut microbiota changes. This study focused on this prediction problem using a novel ensemble learning framework to identify a set of common and reasonably predictive recovery-associated bacterial species (p-RABs), enabling us to predict the host microbiome recovery status under broad-spectrum antibiotic treatment. Our findings also propose other predictive indicators, suggesting that higher taxonomic and functional diversity may correlate with an increased likelihood of successful recovery. Furthermore, to explore the validity of p-RABs, we performed a metabolic support analysis and identified Akkermansia muciniphila and Bacteroides uniformis as potential key supporting species for reconstruction interventions. Experimental results from a C57BL/6J male mouse model demonstrated the effectiveness of p-RABs in facilitating intestinal microbial reconstitution. Thus, we proved the reliability of the new p-RABs and validated a practical intervention scheme for gut microbiota reconstruction under antibiotic disturbance.

Septic arthritis of the temporomandibular joint: a systematic review

Introduction: This study aimed to describe the history, clinical presentation, laboratory examination, treatment, and long-term functional characteristics of patients with septic arthritis of the temporomandibular joint (SATMJ). Methods: All articles in the English literature on SATMJ were queried using PubMed, Science Direct, and Google Scholar (2013 to 8 March 2023), and the keywords "temporomandibular OR TMJ AND septic arthritis". Articles are included if related to the SATMJ in patients of all ages, using case reports, case series, and cohort studies. The Newcastle-Ottawa Scale was applied to all included investigations. Article selection followed PRISMA’s guidelines for measuring the quality of systematic reviews. Results: A preliminary literature search yielded 220 results, of which 25 matched the inclusion requirements, and one more came via reference checking. There were 25 cases with a mean age of 26.7 years (0.1 to 85). Symptoms mainly consisted of TMJ/preauricular pain (n=17, 42.5%), trismus (n=20, 50%), and facial/preauricular swelling (n=24, 60%). Most patients had no systemic symptoms (n=16, 40%). The average mouth opening measured 16.3 mm (5 to 36). The diagnosis was made using the following imaging techniques: X-ray (n=6, 15%), CT scan (n=33, 82.5%), MRI (n=16, 40%), and ultrasound (n=1, 2.5%). Staphylococcus aureus (n = 10, 25%) was the most frequently isolated. Approximately 40 patients (100%) received antibiotics, 26 (65%) patients underwent surgery (e.g., joint aspiration, arthroscopy, etc.), of which two patients (5%) required further surgical intervention. In general, long-term results were positive. In 10 of the 40 patients (25%) who had documented follow-up, sequelae occurred. Conclusion: In the event of trismus, jaw pain, or preauricular edema, SATMJ should be considered. Quick examination and broad-spectrum antibiotic treatment are part of management. Although surgery is not always necessary, it can be life-saving in serious circumstances.

Early Antibiotic Deescalation and Discontinuation in Patients with Febrile Neutropenia after Cellular Therapy: A Single-Center Prospective Unblinded Randomized Trial

The optimal duration of empiric antimicrobial therapy of febrile neutropenia in patients after cellular therapy is unclear. Early deescalation has been suggested by some authorities; however, data are lacking for cellular therapy recipients. We performed a randomized controlled study of cellular therapy recipients with febrile neutropenia to evaluate the safety and noninferiority of an early deescalation and discontinuation antibiotic strategy (EDD arm) versus standard broad-spectrum antibiotic treatment until recovery of neutropenia (standard duration arm). The primary outcome was the fraction of antibiotic-free neutropenia days. We randomized 110 patients to the standard duration arm (n=51) or EDD arm (n=59). The fraction of antibiotic-free neutropenia days was higher in the EDD arm compared to the standard duration arm (median, .8 [interquartile range (IQR), .62 to .86] versus .51 [IQR, .17 to .86]; P=.016). This was true for the per-protocol, allogeneic hematopoietic cell transplantation (HCT), autologous HCT, and anti-CD19 chimeric antigen receptor T cell therapy subgroups. Treatment success rate, subsequent fever, death within 30 days, and other common cellular therapy-related toxicities were all similar between the 2 study arms. An EDD antibiotic strategy in patients after cellular therapy was safe and associated with a substantial reduction in broad-spectrum antibiotic utilization without compromising cellular therapy outcomes.

The dose-response relationship between smoking and the risk factor for invasive pulmonary aspergillosis in patients with severe fever with thrombocytopenia syndrome.

Invasive pulmonary aspergillosis (IPA) is common in immuno-compromised people, and a high incidence of IPA has been found in patients with severe fever with thrombocytopenia syndrome (SFTS). Our study aimed to determine the independent risk factors for IPA and the relationship between smoking status and the risk of IPA in SFTS patients. A retrospective analysis of SFTS patients in the First Affiliated Hospital of Nanjing Medical University from May 2011 to December 2021 was reviewed. The patients were divided into two groups: IPA and non-IPA groups. We compared demographic characteristics, clinical manifestation, laboratory parameters, treatment, and prognosis, and explored the risk factors of IPA using logistic regression and ROC curve. The dose-dependent effect of smoking on the risk of IPA was further estimated, including the age of smoking initiation, daily smoking amount, smoking duration, and pack-years of smoking. In total, 189 individuals were included. Compared with the non-IPA group, the IPA group had higher levels of smoking, drinking, cough, dyspnea, aCCI scores, Dabie bandavirus (DBV) RNA load, ferritin, PCT, IL-6, APTT, LDH, BUN, creatinine, and lower levels of FT4 and TSH. The incidences of MODS, admission to ICU, ventilation, and broad-spectrum antibiotic treatment were significantly higher in the IPA group than in the non-IPA group. Multivariable logistic analysis showed that smoking history, cough, creatinine, admission to ICU, broad-spectrum, and corticosteroid therapies were the independent risk factors for IPA in SFTS patients. We further confirmed that the age of smoking initiation <30 years, smoking at least one pack per day, smoking for at least 40 years, and having at least 40 pack-years of smoking exposure were the independent risk factors for IPA among smokers. The prognosis of SFTS patients in the IPA group is worse than that of the non-IPA group. Attention should be paid to SFTS patients with a smoking history, cough, creatinine, admission to ICU, and broad-spectrum and corticosteroid therapies. There is a strong dose-dependent association between smoking and IPA development in SFTS patients. Prophylactic antifungal therapy should be considered for SFTS patients with these risk factors, but further studies are necessary to determine if it is beneficial for the prognosis of these patients.

Mild magnetic hyperthermia is synergistic with an antibiotic treatment against dual species biofilms consisting of S. aureus and P. aeruginosa by enhancing metabolic activity

Objective The wound biofilm infections that develop tolerance to standard-of-care antimicrobial treatment has been increasing. The objective of this study was to demonstrate a proof-of-concept of mild magnetic nanoparticle (MNP)/alternating magnetic field (AMF) hyperthermia as an anti-biofilm therapy against multispecies biofilm infections. Methods Using both an in vitro cell culture and in vivo murine model of wound infection, we investigated whether MNP/AMF hyperthermia applied at a mild thermal dosage would be synergistically effective against dual species biofilm infection consisting of S. aureus and P. aeruginosa when combined with a broad-spectrum antibiotic, ciprofloxacin (CIP). Results The combined treatment of MNP/AMF hyperthermia and CIP to the wounds of diabetic mice (db/db mice) significantly reduced the CFU number of S. aureus and P. aeruginosa by 2-log and 3-log, respectively, compared to the untreated control group, whereas either mild MNP/AMF hyperthermia or CIP treatment alone had little effect on the eradication of both bacteria. Our gene microarray data obtained from the culture of S. aureus biofilm suggest that mild MNP/AMF could shift the expression of genes for cellular respiration from anaerobic fermentation to an aerobic glycolytic/tricarboxylic acid cycle (TCA) pathway, implicating that the beneficial effect of mild MNP/AMF hyperthermia on the increased susceptibility of biofilm bacteria to an antibiotic treatment is associated with an increased metabolic activity. Conclusion Our results support the translational potential of mild MNP/AMF as an adjunctive therapy that can be combined with a broad-spectrum antibiotic treatment for the management of wound biofilm infections associated with multispecies bacteria.

Risk Factors and outcomes associated with inappropriate empiric broad-spectrum antibiotic use in hospitalized patients with community-acquired pneumonia

Background: Inappropriate broad-spectrum antibiotic use targeting methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa can result in increased adverse events, antibiotic resistance, and Clostridioides difficile infection. In 2019, revised ATS/IDSA community-acquired pneumonia (CAP) guidelines removed healthcare-associated pneumonia (HCAP) as a clinical entity and modified patient factors warranting empiric broad-spectrum antibiotic (BSA) use. As a result, most patients hospitalized with CAP should receive empiric antibiotics targeting standard CAP pathogens. Based on revised guidelines, we evaluated predictors and outcomes associated with inappropriate BSA use among hospitalized patients with CAP. Methods: Between November 2019 and July 2022, trained abstractors collected data on non-ICU adult medical patients admitted with CAP at 67 Michigan hospitals who received either an inappropriate empiric BSA on hospital day 1 or 2 or a standard CAP regimen. Inappropriate empiric BSA use was defined as use of an anti-MRSA or anti-pseudomonal antibiotic in a patient eligible for standard CAP coverage per IDSA guidelines. Patients with immune compromise, moderate or severe chronic obstructive pulmonary disease (COPD), pulmonary complication, or guideline-concordant treatment with BSA were excluded. Data collected included comorbidities, antibiotic use and hospitalizations in the preceding 90 days, cultures in the preceding year, signs or symptoms of pneumonia, hospital characteristics, and 30-day postdischarge patient outcomes. Data were collected through chart review and patient phone calls. Predictors of inappropriate empiric BSA were evaluated using logistic general estimating equation (GEE) models, accounting for hospital-level clustering. We assessed the effect of inappropriate empiric BSA (vs standard CAP therapy) on 30-day patient outcomes using logistic GEE models controlling for predictors associated with the outcome and probability of treatment. Results: Of 8,286 included patients with CAP, 2,215 (26.7%) were empirically treated with inappropriate BSA. The median BSA treatment was 3 days (IQR, 2.5). After adjustments, factors associated with inappropriate empiric BSA treatment included hospitalization or treatment with high-risk antibiotics in preceding 90 days, transfer from a postacute care facility, hemodialysis, support with ≥3 L supplemental oxygen, severe sepsis, leukocytosis, and higher pneumonia severity index (Fig. 1). After adjustments, patients with inappropriate empiric BSA treatment had higher readmissions 30 days after discharge, more transfers to the intensive care unit, more antibiotic-associated adverse events, and longer hospitalizations (Fig. 2). Conclusions: Patients hospitalized with CAP often received inappropriate BSA as empiric coverage, and this inappropriate antibiotic selection was associated with worse patient outcomes. To improve patient outcomes, stewardship efforts should focus on reducing inappropriate BSA use in patients hospitalized for CAP with historic HCAP risk factors or severe CAP without other guideline-directed indications for BSA.Financial support. H.M.S. initiative is underwritten by Blue Cross and Blue Shield of Michigan.Disclosures: None

714 Actinomyces Necrotizing Soft Tissue Infections: A Case Series from a Single Institution

Abstract Introduction Necrotizing soft tissue infections (NSTI) are rare, severe infections that can lead to septic shock. NSTI have a mortality rate of 20-50% in patients who require intensive care. Management includes surgical debridement and broad-spectrum antibiotics until definitive culture results. Actinomyces is a slow-growing bacterium found in the mouth, skin, genitourinary, and gastrointestinal tracts, with several case reports of actinomyces related NSTI. At this single institution, NSTI are managed by burn surgeons. The goal of this study is to quantify patients with actinomyces-related infections, identify modifiable risk factors, and demonstrate the pharmacology of effective antibiotic treatment. Methods All patients with actinomyces-related infections admitted to a single institution’s burn center from January 2020 to September 2022 were included. Patients were identified via the institution’s data warehouse. Patient demographics, infection location, associated injuries or illnesses, antibiotic exposure, and treatments required were obtained. Results were recorded and compared using descriptive statistical analysis. Results A total of 22 patients with actinomyces infections were identified, 18 with NSTI and 4 with non-NSTI infections (1 hidradenitis suppurativa, 1 Job’s syndrome, and 2 burn-related). Average age was 50.3 years old, and 68% of patients were male. Seventy-four percent of patients were obese, and average BMI for obese patients was 40.3 kg/m2. Fourteen NSTI patients had diabetes or pre-diabetes (mean A1c 9.4%), and two were taking a sodium-glucose co-transporter 2 inhibitor. All NSTI patients underwent surgical debridement and broad-spectrum antibiotic treatment. The groin was the most common site of infection. Time from collection of sample to culture resulting with Actinomyces was 44 to 185 hours (mean 111 hours). Species isolated were A. europaeus, A. radingae, A. turicensis, A. odontolyticus, and A. funkei. Three of the NSTI patients died. Among NSTI survivors, average length of stay was 34 days, duration of antibiotics was 10.7 days (6 to 16 days), and 50% of patients were de-escalated to either ampicillin/sulbactam, or ertapenem. Conclusions To our knowledge this is the largest single institutional series to date for patients affected by Actinomyces related NSTI. The high percentage of patients with diabetes, 73% of NSTI patients, suggests an increased susceptibility to infection for these patients. A variety of Actinomyces isolates are present in NSTI. The mortality rate (17%) of these ICU admitted NSTI patients agrees with prior studies. Applicability of Research to Practice Novel findings of actinomyces infection in NSTI patients

The metabolic role of gut dysbiosis in altered T cell responses to influenza virus infection

Abstract Commensal gut microbiota modulates protective immune responses to viral infections at extra-intestinal sites, including the lungs. Gut dysbiosis induced by broad-spectrum antibiotic treatment appears to alter adaptive immunity to influenza infection (IAV/PR8). However, the mechanism by which microbial metabolism influences immune responses across the gut-lung axis remains unclear. Here, we used flow cytometric analysis to investigate T cell responses to IAV in specific pathogen free (SPF), Altered Schaedler flora (ASF) and germ-free mice models. We show that, compared to SPF mice, ASF and germ-free mice have significantly reduced levels of regulatory T cells (Tregs) and virus specific cytotoxic CD4 and CD8 T cells at 10 days post infection. Further analysis of microbial mediators in the peripheral blood of these mice revealed significantly increased levels of L-arginine in the serum of ASF and germ-free mice compared to SPF mice. We noted that, germ-free and ASF mice lack bacteria that metabolize dietary amino acids, including L-arginine, regulating its increased availability in the peripheral blood of these mice. To investigate the role of L-arginine as a microbial mediator of reduced T cell responses to IAV, we supplemented L-arginine or administered neomycin (to induce selective disruption of arginine metabolizing bacteria) to separate cohorts of SPF mice. We observed altered cytotoxic and effector T cell responses at 10 days post infection in the experimental groups, however, Tregs were not significantly affected. Our data suggests that selective dysbiosis may increase L-arginine levels in the serum of SPF mice which may directly affect virus specific effector T cell responses in the lung mucosa.

Protective Effects of Female Gut Microbiota Transplantation on Hypertension and Renal Damage in Male Dahl Salt-Sensitive Rats

We have previously demonstrated through microbiota transplantation studies that the gut microbiota importantly contributes to the development of hypertension, renal damage, and renal inflammation in the Dahl Salt-Sensitive (SS) rat fed a 4.0% NaCl high salt diet (HS). We also know that female SS rats are significantly protected from salt-induced hypertension, renal injury, and renal immune cell infiltration compared to males. One potential explanation for this sex difference is the substantial divergence we have observed in gut microbiota composition between male and female SS rats. Therefore, we hypothesized that gut microbiota transplantation between males and females would modulate the observed sex differences in salt-sensitivity. At 8 weeks of age, we first suppressed the native gut microbiota of male SS rat recipients via broad-spectrum antibiotics treatment (bacitracin and streptomycin, 2 g each/L, p.o.) for 3 days, followed by inoculation with either male or female donor cecal contents (oral gavage, 1 mL) for 7 consecutive days. Thus, our experimental groups are 1) male recipient rats repopulated with male donor microbiota (M+M, n=4) and 2) male recipient rats repopulated with female donor microbiota (M+F, n=3). Donor rats were maintained on the 0.4% NaCl low salt diet (LS) to more closely mimic the intrinsic microbiota of each sex. Telemeters were implanted at 10 weeks to allow for the continuous monitoring of blood pressure, followed by 3 weeks of HS challenge. At baseline, there were no differences in mean arterial pressure (MAP) between groups (123.4±1.3 vs 124.5±3.6 mmHg, M+M vs M+F on HS day 0, p=0.765). However, during the last week of HS challenge, males receiving female cecal microbiota transplantation had significantly reduced MAP compared to controls (153.6±3.4 vs 144.1±4.8 mmHg, M+M versus M+F on HS day 19, p=0.013). At the conclusion of the study, this reduction in blood pressure also coincided with a protection from renal damage, indicated by reduced urinary albumin excretion (209.0±37.1 vs 143.7±19.2 mg/day, M+M vs M+F, p=0.035), and an improvement in renal function, indicated by an increase in creatinine clearance (0.36±0.02 vs 0.48±0.01 ml/min/g kidney, M+M vs M+F, p=0.002). However, there appeared to be no effects on renal inflammation, with no changes to either the circulating or renal immune cell profile between rats receiving male or female microbiota. Furthermore, in female SS rat recipients that were subsequently transplanted with either male or female donor cecal contents, we observed no significant effects related to sex of donor microbiota in terms of blood pressure, renal damage, or renal inflammation. Together, these data demonstrate the anti-hypertensive and renoprotective effects of the female gut microbiota to recipient male SS rats. Moreover, there are additional factors within the female host that appear to be protective against the male microbiota. 19CDA34660184, HL161231 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Impact of guidelines implementation on empiric antibiotic treatment for pediatric uncomplicated osteomyelitis and septic arthritis over a ten-year period: Results of the ELECTRIC study (ostEomyeLitis and sEptiC arThritis tReatment in children).

Due to the growing evidence of the efficacy of intravenous (IV) cefazolin with an early switch to oral cefalexin in uncomplicated pediatric osteomyelitis (OM) and septic arthritis (SA) in children, we changed our guidelines for empiric antibiotic therapy in these conditions. This study aims at evaluating the impact of the guidelines' implementation in reducing broad-spectrum antibiotic prescriptions, duration of IV antibiotic treatment and hospital stay, treatment failure and recurrence. This is a retrospective, observational, quasi-experimental study. The four years pre-intervention were compared to the six years, ten months post-intervention (January 2012, through December 2015; January 2016, through October 31st, 2022). All patients aged 3 months to 18 years with OM or SA were evaluated for inclusion. Each population was divided into three groups: pre-intervention, post-intervention not following the guidelines, and post-intervention following the guidelines. Differences in antibiotic prescriptions such as Days of Therapy (DOT), activity spectrum and Length of Therapy (LOT), length of hospital stay (LOS), broad-spectrum antibiotics duration (bsDOT), treatment failure and relapse at six months were analyzed as outcomes. Of 87 included patients, 48 were diagnosed with OM (8 pre-intervention, 9 post-intervention not following the guidelines and 31 post-intervention following the guidelines) and 39 with SA (9 pre-intervention, 12 post-intervention not following the guidelines and 18 post-intervention following the guidelines). In OM patients, IV DOT, DOT/LOT ratio, and bsDOT were significantly lower in the guidelines group, with also the lowest proportion of patients discharged on IV treatment. Notably, significantly fewer cases required surgery in the post-intervention groups. Considering SA, LOS, IV DOT, DOT/LOT ratio, and bsDOT were significantly lower in the guidelines group. The treatment failure rate was comparable among all groups for both OM and SA. There were no relapse cases. The overall adherence was between 72 and 100%. The implementation of guidelines was effective in decreasing the extensive use of broad-spectrum antibiotics and combination therapy for both OM and SA. Our results show the applicability, safety, and efficacy of a narrow-spectrum IV empirical antibiotic regimen with cefazolin, followed by oral monotherapy with first/second-generation cephalosporins, which was non-inferior to broad-spectrum regimens.

Idiopathic Fournier’s Gangrene: Report of 2 Cases

Fournier's gangrene is a rare, life-threatening soft tissue infection that, if not treated promptly, can immediately develop into systemic toxicity. One of the deadliest surgical emergencies observed worldwide is Fournier's gangrene, FG predominantly affects men but can be seen in women. The condition's mortality and morbidity, have greatly decreased over time as a result of recent advancements in critical care medicine and surgical methods. Early diagnosis, examination of the risk and etiological variables, metabolic and physiological parameters, timely resuscitation, forceful surgical debridement, broad-spectrum antibiotic treatment, and ongoing monitoring of these parameters are necessary for a favorable outcome. This will reduce the condition's high death and morbidity rates. Two distinct examples of Fournier gangrene are described in this study. In this section, we have 2 FG cases. A young adult with FG who had no accompanying comorbidities was our first instance. He had necrotizing fasciitis, which starts in the perineum and spreads to the belly and chest, and it took him longer to heal. Despite this, he made a full recovery without suffering any serious post-operative morbidity. An elderly man patient who had no concomitant conditions was our second example. Our observations show that He made a full recovery without experiencing any significant post-operative morbidity.

Conservative management of scrotal pyoceles – A case series and literature review

Study objectiveWe describe the common presenting signs and symptoms, treatment modalities, and outcomes of acutely presenting scrotal pyoceles. MethodsWe conducted a retrospective chart review of all adult patients treated for ultrasound-confirmed scrotal pyoceles between 2010 and 2020 at two sites within the [redacted]. Vitals at presentation, microbiology, and inpatient courses including antibiotic treatment and surgical procedures were collected. ResultsA total of 360 scrotal ultrasounds were reviewed identifying 15 patients with pyoceles, 11 patients presenting to the emergency department and 4 hospitalized patients. The most common chief complaint was testicular pain (67%). Only seven patients (47%) met SIRS criteria upon presentation. All patients were initially treated with broad-spectrum antibiotics and observation; 11 (73%) responded to this management alone, while four patients (27%) required surgical drainage due to persistent infection. No patients contracted Fournier's gangrene. ConclusionThis study reports the largest published database of scrotal pyoceles to date and describes our clinical approach to management. While pyoceles have traditionally been treated aggressively with surgical drainage, this case series suggests that most patients improve with broad-spectrum antibiotic treatment and observation alone, requiring surgical drainage if infection persists. Future investigations including multi-institutional data will be necessary to validate our institution's approach.

Extraintestinal Clostridioides difficile Infection (CDI): A Recurrent Battle with Resilient Abdominal Wall Abscess.

Risk factors for extraintestinal CDI include prior hospital stay, prolonged antibiotic therapy, proton pump inhibitor (PPI) use, relative state of immunodeficiency such as malnutrition and diabetes mellitus, previous abdominal surgery especially following perforation and leak of intestinal content.Presentation can be late following surgery with mesh repair (foreign body implantation) for intestinal perforation as they have high risk of colonisation, which later leads to infection.For extraintestinal CDI in the presence of a foreign body, removal is the desired course of action. But it is not always possible given the presence of comorbidities in this population, thus resulting in a prolonged course of antibiotics.

Emergence of Raoultella ornithinolytica Producing Beta Lactamase Enzyme in Different Clinical Specimens in Erbil City

Background: Raoultella ornithinolytica should never be regarded as merely a saprophytic bacterium that occasionally contaminates bronchial lavage or other deep respiratory samples or surgical sites is an underreported, emerging hospital-acquired infection and is particularly related with invasive operations.R. ornithinolytica isolates have significant antimicrobial resistance rates, and physicians should be aware of this so that, before accurate microbiological data are received, an immediate broad-spectrum antibiotic treatment can be instituted..&#x0D; Objectives: The goal of our study was to retrospectively examine R. ornithinolytica, which was isolated from a variety of clinical samples in Erbil, and to examine its epidemiology, antibiotic sensitivity patterns, and ability to produce the enzyme extend spectrum beta lactamase.&#x0D; Methods: A total of 2350 samples were collected from three different sources(Urine ,High vaginal swab and wound), collected from female and male from patient attending Rizgary hospital and Central lab in Erbil city during the July 2017 to Februry 2018 . Only 10 cases had been identified as R. ornithinolytica and all isolates isolated and identified by using microscopical, morphological , biochemical tests and Vitek 2 compact system . Also antibiotics susceptibility testing was performed by using Vitec 2 compact system according to the standard protocol against 13 antibiotics which are (Ampicillin /Sulbactam , Piperacillin/ Tazobactam, Cefazolin, Ceftazidim , Ceftriaxon , Cefepime, Levofloxacin , Trimethoprim/ Sulfamethoxazol, Gentamycin, Tobramycin, Ertapenem, Imipenem, Ciprofloxacin).&#x0D; Results: Only ten R. ornithinolytica isolates isolated from 2350 distribution according to their source of isolation High vaginal swab 6(0.23%) appeared to be the most dominant specimen than other specimens followed by urine sample 3(0.13%) then wound 1(0.04%).The highest percentage of R. ornithinolytica. isolated from female .Most isolates from high vaginal swab sample 6(0.26%) followed by urine 3 (0.13%) then wound 1(0.04), when performing of antibiotic susceptibility the highest resistances rate were to Cefazolin and Trimethoprim / Sulfamethoxazol 10 (100%) followed by Ampicillin / Sulbactam , Piperacillin / Tazobactam, Ceftriaxon , Gentamycin , Tobramycin and Ciprofloxacin 7(70%) for each, 6(60%)isolates ESBL producer, all isolated R. ornithinolytica were resistance to more than 8 antibiotics and two isolates completely resistance to all thirteen antibiotics.&#x0D; Conclusion: The overall prevalence of R. ornithinolytica isolates was low in Erbil city and we can be observed and isolated from varies clinical samples and causes serious infections and susceptibility to some antibiotics are low and also most isolates multiresistance and ESBL producers and These findings offer a reliable measure of the prevalence of Raoultella ornithinolytica in our region and provide a baseline for future studies that will enable the monitoring of trends over time. If current resistance trends continue, high societal and economic costs can be anticipated; better management of infections caused by resistanceR.ornithinolytica is becoming essential.