Broad Antibiotics Research Articles

Patterns, Predictors, and Outcomes of Bacterial Growth and Infectious Complications after Pancreatic Resection.

Infectious complications after pancreatic resections are common, but perioperative factors linked to postoperative bacterial growth are not well-studied. This retrospective study analyzed bacterial cultures from patients undergoing pancreatic resection (November 2008 to October 2022), assessing predictors for positive cultures and characterizing bacteria. Complications and outcomes of patients with positive cultures were also examined. Among 620 patients, bile samples were collected in 95 (95/620; 15.3%), with 60 (60/95; 63.1%) testing positive, 58 of them underwent pancreaticoduodenectomy. Of these, in 50 (50/58; 86.2%) the culture yielded polymicrobial growth but specific types of bacteria were not identified. Multivariate analysis identified preoperative bile duct stenting as a significant predictor of positive bile cultures (OR: 3.54; 95% CI: 1.95-6.42; p < 0.001), and positive cultures were linked to higher reoperation rates (OR: 2.40; 95% CI:1.18-4.90; p < 0.001. Positive drain cultures within 30 days from surgery were associated with higher rates of clinically significant pancreatic fistula (OR: 2.24; 95% CI: 1.00-5.11; p = 0.05), and reoperations) OR: 4.37; 95% CI: 1.62-11.79; p = 0.03). Patients with pancreatic adenocarcinoma and positive bile cultures had shorter disease-free survival with a median of 13 months (95% CI: 8-17) versus 18 months (95% CI: 8-29; p = 0.04). Bile sampling is recommended in all pancreaticoduodenectomies. Managing polymicrobial growth with broad and prolonged antibiotics may reduce postoperative infections.

Establishing Medical Intelligence-Leveraging Fast Healthcare Interoperability Resources to Improve Clinical Management: Retrospective Cohort and Clinical Implementation Study.

FHIR (Fast Healthcare Interoperability Resources) has been proposed to enable health data interoperability. So far, its applicability has been demonstrated for selected research projects with limited data. This study aimed to design and implement a conceptual medical intelligence framework to leverage real-world care data for clinical decision-making. A Python package for the use of multimodal FHIR data (FHIRPACK [FHIR Python Analysis Conversion Kit]) was developed and pioneered in 5 real-world clinical use cases, that is, myocardial infarction, stroke, diabetes, sepsis, and prostate cancer. Patients were identified based on the ICD-10 (International Classification of Diseases, Tenth Revision) codes, and outcomes were derived from laboratory tests, prescriptions, procedures, and diagnostic reports. Results were provided as browser-based dashboards. For 2022, a total of 1,302,988 patient encounters were analyzed. (1) Myocardial infarction: in 72.7% (261/359) of cases, medication regimens fulfilled guideline recommendations. (2) Stroke: out of 1277 patients, 165 received thrombolysis and 108 thrombectomy. (3) Diabetes: in 443,866 serum glucose and 16,180 glycated hemoglobin A1c measurements from 35,494 unique patients, the prevalence of dysglycemic findings was 39% (13,887/35,494). Among those with dysglycemia, diagnosis was coded in 44.2% (6138/13,887) of the patients. (4) Sepsis: In 1803 patients, Staphylococcus epidermidis was the primarily isolated pathogen (773/2672, 28.9%) and piperacillin and tazobactam was the primarily prescribed antibiotic (593/1593, 37.2%). (5) PC: out of 54, three patients who received radical prostatectomy were identified as cases with prostate-specific antigen persistence or biochemical recurrence. Leveraging FHIR data through large-scale analytics can enhance health care quality and improve patient outcomes across 5 clinical specialties. We identified (1) patients with sepsis requiring less broad antibiotic therapy, (2) patients with myocardial infarction who could benefit from statin and antiplatelet therapy, (3) patients who had a stroke with longer than recommended times to intervention, (4) patients with hyperglycemia who could benefit from specialist referral, and (5) patients with PC with early increases in cancer markers.

The straight and narrow: A game theory model of broad- and narrow-spectrum empiric antibiotic therapy

Physicians prescribe empiric antibiotic treatment when definitive knowledge of the pathogen causing an infection is lacking. The options of empiric treatment can be largely divided into broad- and narrow-spectrum antibiotics. Prescribing a broad-spectrum antibiotic increases the chances of covering the causative pathogen, and hence benefits the current patient’s recovery. However, prescription of broad-spectrum antibiotics also accelerates the expansion of antibiotic resistance, potentially harming future patients. We analyse the social dilemma using game theory. In our game model, physicians choose between prescribing broad and narrow-spectrum antibiotics to their patients. Their decisions rely on the probability of an infection by a resistant pathogen before definitive laboratory results are available. We prove that whenever the equilibrium strategies differ from the socially optimal policy, the deviation is always towards a more excessive use of the broad-spectrum antibiotic. We further show that if prescribing broad-spectrum antibiotics only to patients with a high probability of resistant infection is the socially optimal policy, then decentralization of the decision making may make this policy individually irrational, and thus sabotage its implementation. We discuss the importance of improving the probabilistic information available to the physician and promoting centralized decision making.

Utility of bronchoalveolar lavage for COVID-19: a perspective from the Dragon consortium.

Diagnosing COVID-19 and treating its complications remains a challenge. This review reflects the perspective of some of the Dragon (IMI 2-call 21, #101005122) research consortium collaborators on the utility of bronchoalveolar lavage (BAL) in COVID-19. BAL has been proposed as a potentially useful diagnostic tool to increase COVID-19 diagnosis sensitivity. In both critically ill and non-critically ill COVID-19 patients, BAL has a relevant role in detecting other infections or supporting alternative diagnoses and can change management decisions in up to two-thirds of patients. BAL is used to guide steroid and immunosuppressive treatment and to narrow or discontinue antibiotic treatment, reducing the use of unnecessary broad antibiotics. Moreover, cellular analysis and novel multi-omics techniques on BAL are of critical importance for understanding the microenvironment and interaction between epithelial cells and immunity, revealing novel potential prognostic and therapeutic targets. The BAL technique has been described as safe for both patients and healthcare workers in more than a thousand procedures reported to date in the literature. Based on these preliminary studies, we recognize that BAL is a feasible procedure in COVID-19 known or suspected cases, useful to properly guide patient management, and has great potential for research.

Microemulgel Delivery of Ciprofloxacin Hydrochloride

Background: Ciprofloxacin hydrochloride is broad spectrum carboxyfluoroquinolone antibiotic from biopharmaceutics classification system (BCS) class IV. The oral dosage form exhibits gastric irritation whereas the topical cream has demonstrated poor penetration and low bioavailability. Objective: To optimize microemulsion-based gel of ciprofloxacin hydrochloride to increase its solubility and permeability through the cutaneous layer for targeting bacterial skin infections. Methods: To develop microemulsion, oil (soya oil, castor oil, oleic acid, isopropyl myristate and vegetable oil), surfactant (cremophore, span 80, tween 80) and cosurfactant (PEG 600 and PEG 400, propylene glycol) were evaluated. To depict the microemulsion formulation pseudo ternary phase diagram was employed. %Transmittance, zeta potential, dissolution study and size analysis were carried out for evaluation of microemulsion. 32 factorial design was used. Two variables i.e concentration of Sepineo P600 and Carbopol 934 effect on microemulgel was evaluated. Evaluation of gel was carried for physical parameters, antimicrobial, in-vitro and ex-vivo release study. Results: Solubility analysis suggested tween 80, oleic acid and propylene glycol for the formulation of microemulsion. Zeta potential for microemulsion batch F1 was -11.3 mV. This indicated good stability. In-vitro release study showed 91.98% percentage cumulative drug release for batch F1 at 8 hours. Microemulsion-based gel (F1) showed 22.96% inhibition against bacteria which proved its antibacterial activity. Conclusion: The obtained results exhibited that the permeability and bioavailability of the drug was increased when given through a topical route.

The potential to produce tropodithietic acid by Phaeobacter inhibens affects the assembly of microbial biofilm communities in natural seawater

Microbial secondary metabolites play important roles in biotic interactions in microbial communities and yet, we do not understand how these compounds impact the assembly and development of microbial communities. To address the implications of microbial secondary metabolite production on biotic interactions in the assembly of natural seawater microbiomes, we constructed a model system where the assembly of a natural seawater biofilm community was influenced by the addition of the marine biofilm forming Phaeobacter inhibens that can produce the antibiotic secondary metabolite tropodithietic acid (TDA), or a mutant incapable of TDA production. Because of the broad antibiotic activity of TDA, we hypothesized that the potential of P. inhibens to produce TDA would strongly affect both biofilm and planktonic community assembly patterns. We show that 1.9 % of the microbial composition variance across both environments could be attributed to the presence of WT P. inhibens, and especially genera of the Bacteriodetes were increased by the presence of the TDA producer. Moreover, network analysis with inferred putative microbial interactions revealed that P. inhibens mainly displayed strong positive associations with genera of the Flavobacteriaceae and Alteromonadaceae, and that P. inhibens acts as a keystone OTU in the biofilm exclusively due to its potential to produce TDA. Our results demonstrate the potential impact of microbial secondary metabolites on microbial interactions and assembly dynamics of complex microbial communities.

Is conservative management safe in patients with acute ureterolithiasis and perirenal stranding?

In patients presenting with ureterolithiasis, perirenal stranding is frequently observed in non-contrast computed tomography. Because perirenal stranding may be caused by tears in the collecting system, previous studies have described an increased risk of infectious complications and suggested broad empiric antibiotic therapy and immediate decompressing of the upper urinary tract. We hypothesized that these patients can also be managed conservatively. Therefore, we retrospectively identified patients with ureterolithiasis and perirenal stranding and compared diagnostic and treatment characteristics as well as treatment outcomes between patients undergoing conservative versus interventional management by ureteral stenting, percutaneous drainage or primary ureteroscopic stone removal. We classified perirenal stranding as mild, moderate or severe based on its radiological extent. Of 211 patients, 98 were managed conservatively. Patients in the interventional group had larger ureteral stones, more proximal ureteral stone location, more severe perirenal stranding, higher systemic and urinary infectious parameters, higher creatinine levels, and received more frequent antibiotic therapy. The conservatively managed group experienced a spontaneous stone passage rate of 77%, while 23% required delayed intervention. In the interventional and conservative groups, 4% and 2% of patients, respectively, developed sepsis. None of the patients in either group developed a perirenal abscess. Comparison of perirenal stranding grade between mild, moderate and severe in the conservatively treated group showed no difference in the spontaneous stone passage and infectious complications. In conclusion, conservative management without prophylactic antibiotics for ureterolithiasis and perirenal stranding is a valid treatment option as long as no clinical or laboratory signs of renal failure or infections are observed.

Industry update, December 2022.

Industry update, December 2022.

562. Multipronged Approach to Recruitment of Pediatric Patients with Beta-Lactam Allergies for Evaluation and De-labeling

Abstract Background Penicillin allergy is the most commonly reported drug allergy in the pediatric population. However, most reports do not represent true IgE-mediated or late-onset severe hypersensitivity reactions. False allergy labels can lead to unnecessarily broad and/or non-first line antibiotic utilization, the development of antibiotic resistance, adverse drug side effects, and have implications for the use of antimicrobials in adulthood. In an effort to decrease inappropriate allergy labeling, we have implemented a multipronged approach for the evaluation of documented beta-lactam allergies in pediatric patients and potential “de-labeling” of inaccurate or outdated allergies. Methods We performed retrospective chart review of pediatric patients (0-18 years) with a documented beta-lactam allergy who were seen in clinic at a single tertiary medical center between 2014-2019. Prospective telephone screening then began to further characterize reaction symptoms and timing to determine patient candidacy for allergy testing (Fig. 1). Inpatient screening began in April 2022. If amenable to referral, eligible patients are then referred for outpatient Allergy and Immunology (A/I) assessment. Figure 1Process map for pediatric beta-lactam allergy risk-stratifying algorithm. Results A total of 1160 eligible pediatric patients were identified, and initial results are summarized (Fig. 2). Of those screened, 48 (57%) patients were referred. 5 (6%) patients were de-labeled via screening, of which 3 had received and tolerated repeat dosing. 11 (33%) patients have attended allergy appointments; 4 (36%) were tested and all were de-labeled (ages 6-11 years) from mostly non-IgE-mediated reactions. Additionally, 16 patients have upcoming appointments, and recruitment efforts are ongoing to include increased inpatient recruitment. Conclusion Use of an inpatient and outpatient algorithm can help identify pediatric patients less likely to have a true or persistent beta-lactam allergy (delayed-onset mild symptoms, or IgE-mediated reaction &amp;gt;5 years ago) and who could benefit from formal allergy testing to potentially remove their allergy label. In the future, algorithm implementation within the electronic medical record may assist clinicians in thorough documentation of beta-lactam allergies and expeditious referral for allergy testing when appropriate. Disclosures All Authors: No reported disclosures.

The Review on Azithromycin

Azithromycin is broad spectrum macrolide antibiotic with long half life and excellent tissue penetration. Azithromycin is an azalide antimicrobial agent active in vitro major pathogens responsible for infectious of the respiratory tract, skin and soft tissue in children. In children azithromycin is usually given as either a 3- day course of 10 mg/kg/day on the first day,followed by 5 mg/kg/day for a further 4 days. Azithromycin is a subclass of microlide antibiotics. It is derived from erythromycin with a methyl–substituted nitrogen atom incorporated in lactone ring, thus making the lacctone ring 15-membered. Pathogen that are generally susceptible to azithromycin include Haemophilus influenzae (including ampicillin-resistant strains), Moraxella catarrhalis, Chalmydia pneumoniae, Chlamydia trachomatis, Mycoplasma pneumoniae Streptococcus pyogens and streptococcus agalactiae. Azithromycin is administerd once daily achieves clinically relevent concentration at sites of infection, is slowly eliminated from the body and has few drug interaction.A five day treatment administration (500 mg on day 1 followed by 250 mg on days 2-5 ) or a three day regimen (500 mg daily for three days).

Overview of heteroresistance, persistence and optimized strategies to control them

Antibiotic-resistant bacteria have become much more prevalent, posing a significant concern to universal care. In basic concepts, the phenomenon of heteroresistance is typified as antibiotic resistance displayed by a subgroup of the entire bacterial community which is typically thought to be sensitive to these antibiotics based on standard in-vitro sensitivity assays. Although this small subgroup is temporarily dormant nondividing state displays enhanced resistance to broad antibiotics ranges. Persistence is a subpopulation of a sensitive bacterial isolate that can tolerate the bactericidal antibiotics because of its dormant physiological state. Until recent times, the occurrence of heteroresistance and persistence phenomena are often misunderstood and perhaps neglected. Here, we review the outline literature about bacterial heteroresistance, their detection methods, their associated mechanisms, the objectives of some bacterial species to develop heteroresistance. Bacterial persistence, some of their features, their main mechanisms, and their clinical importance are also described. Furthermore, this study provides optimized strategies to combat both phenomena.

THE NONCOMPLIANT PATIENT WITH THE BROKEN STENT

THE NONCOMPLIANT PATIENT WITH THE BROKEN STENT

Assessment of antimicrobial prescribing practice, knowledge, and culture in three teaching hospitals.

Antimicrobial resistance (AR) is one of the most critical threats to global health. One of its root causes, misuse of antibiotics, can stem from prescribers' preconceived ideas, differing attitudes, and lack of knowledge. Canadian data on this subject are scarce. This study aimed to understand the culture and knowledge of antimicrobial prescribing to optimize strategies targeting prescribers in the local antimicrobial stewardship program (ASP). An anonymous online survey was developed and distributed to antimicrobials prescribers at three acute-care teaching hospitals. The questionnaire surveyed perception of AR and ASPs. A total of 440 respondents completed the entire survey. All agreed that AR is a significant challenge in Canada. The vast majority (86%) of respondents believed that AR is a significant problem at their working hospital. However, only 36% of respondents believed that antibiotics are misused locally. Most (92%) agreed that ASPs can decrease AR. Several knowledge gaps were identified through clinical questions. For example, respondents failed to identify treatment indications for asymptomatic bacteriuria 15% of the time and 59% chose an unnecessarily broad antibiotic when presented a microbiology report with susceptibility results associated with a common clinical syndrome. Prescribers' self-reported confidence did not correlate with their knowledge score. Respondents recognized AR as a critical issue but awareness and knowledge on antibiotic misuse were lacking. As shown in previous studies, respondents see the threat of AR in a more theoretical way. This study provided a better understanding of antimicrobial prescribing practices and ways to optimize them within three teaching hospitals in Montréal. Barriers to optimal antimicrobial prescribing were identified and strategies for improving the effectiveness of the ASP will be developed accordingly.

Clinical Characteristics and Outcome of Bleb-Related Infection in Glaucoma Patients

Objective: To study the clinical characteristics, causative organism, treatment, and clinical outcomes of bleb-related infection.Materials and Methods: The medical charts of patients who were diagnosed with bleb-related infection, including blebitis and bleb-related endophthalmitis (BRE), from September 2001 to December 2019 at Siriraj Hospital were reviewed. The patients’ demographic data, clinical characteristics, microorganisms found, treatment, and clinical outcomes were explored.Results: We found a total of 42 eyes from 41 patients had been diagnosed with blebitis (11 eyes) and BRE (31 eyes) over the 18-year study period. More than 80% of the patients had experienced pain and redness as the presenting symptoms. The most common bleb characteristic in BRE was purulent bleb (74.2%), while in blebitis it was bleb injection (45.5%). Bleb leakage was documented in 27.3% and 22.6% of patients with blebitis and BRE, respectively. Among the 41 patients, 10 had a history of minor trauma before the onset of infection, such as a rubbed eye, foreign body entering into the eye, water splashed into the eyes, or the eyes had been washed with soap. The yield of vitreous culture in bleb-related endophthalmitis was 48.3%. The most common microorganisms were Streptococcus spp., Enterococcus spp., and Haemophilus Influenzae. Generally, the treatment for blebitis at our institute is broad spectrum topical and systemic antibiotics, while intravitreal broad spectrum antibiotics are added to the treatment regimen for BRE patients. For BRE in our cohort, 11 eyes required vitrectomy and 7 eyes had undergone bleb excision. Treatment for blebitis tended to have a good visual outcome, with a stable visual prognosis for 9 out of the 11 eyes diagnosed with blebitis. However, most of the BRE eyes had a worsened visual outcome. Enterococcus spp. and Haemophilus Influenzae resulted in poor visual outcomes.Conclusion: The clinical characteristics of bleb-related infection in our patients were pain and redness. One fourth of patients had a history of minor trauma to the eye. To prevent bleb-related infection, the importance of patient education after trabeculectomy should be highlighted. Patients with presenting symptoms and unwanted behavior that could result in bleb infection should be identified and receive treatment alongside education.

Ceftriaxone resistance and adequacy of initial antibiotic therapy in community onset bacterial pneumonia.

Much remains unknown about the impact of initial antibiotic adequacy on mortality in community onset bacterial pneumonia (COBP). Therefore, we performed a study to determine how the adequacy of initial antibiotic therapy affects in-hospital mortality for patients with COBP.We carried out a retrospective cohort study among the 11 BJC Healthcare community and academic hospitals in Missouri and Illinois. The electronic medical records for BJC Healthcare were queried to obtain a set of patient admissions with culture positive (respiratory or blood) COBP admitted from January 1, 2016 through December 31, 2019. Patients with COBP required an International Classification of Diseases (ICD)-10 diagnostic code for pneumonia, admission to the hospital through an emergency department, a chest radiograph with an infiltrate, an abnormal white blood cell count or temperature, an order for 1 or more new antibiotics, and a positive respiratory or blood culture. Antibiotic selection was deemed adequate if the patient had organisms susceptible to at least one of the antibiotics received according to in vitro testing using standard laboratory breakpoints.Among 36,645 screened pneumonia admissions, 1843 met criteria for culture positive COBP. Eight hundred nineteen (44.4%) had ceftriaxone-resistant (CTX-R) organisms and 1024 had ceftriaxone-sensitive (CTX-S) organisms. The most common CTX-R pathogens were methicillin resistant Staphylococcus aureus (46.9%), Pseudomonas species (38.4%), and Escherichia coli (4.5%). On the day of admission 71% of all patients were given adequate antibiotic treatment (62.2% of CTX-R and 77.9% of CTX-S). Unnecessarily broad initial treatment was administered to 57.1% of CTX-S patients. In a logistic regression model accounting for comorbidities and severity of illness, inadequate therapy on the day of admission was associated with higher in-hospital mortality (P = .005). Among CTX-S patients who were adequately treated, initial use of unnecessarily broad antibiotics was associated with increased in-hospital mortality (P = .003).Ceftriaxone resistance was common in this cohort of culture positive COBP patients. Inappropriate coverage on day of admission was associated with greater likelihood of in-hospital mortality.

A retrospective longitudinal observational study of natural history of ESBL/MDR gram negative organisms in patients hospitalized in a tertiary hospital

Background: The IDSA recommends that when determining empiric treatment for a given patient, clinicians should consider previous organisms and associated antibiotic susceptibility data in the prior 6 months when multidrug-resistant/extended-spectrum β-lactamase gram-negative rods (MDR /ESBL GNR) is suspected. The presence of MDR GN in cultures on previous hospitalization or in surveillance cultures leads to use of broader-spectrum empiric antibiotic in subsequent admissions. We sought to determine whether the presence of an MDRO in 1 hospital admission dictates the need for broader-spectrum antibiotic use in subsequent hospitalizations when a different site is considered the source of infection. Methods: The study was conducted at a 700-bed tertiary-care level I trauma center. Infection control records were reviewed for patients aged 21–99 years admitted between July 1, 2013, through January 31, 2014, who had any ESBL or MDR GNR at any site including surveillance culture. The charts were surveyed until January 31, 2016, for ESBL or MDR gram-negative organisms at any site during subsequent hospitalizations. The CDC definition of MDR/ESBL was applied. Results: Of the 50 people followed, 34 patients (68%) had ESBL/MDR recovered at a single sentinel site, 6 patients (12%) had ESBL/MDR in multiple sites, and in 10 patients (20%) had ESBL/MDR only in surveillance cultures during their primary hospitalization. In 34 patients with a single sentinel site MDRO/ESBL in their primary hospitalization, 16 (47%) were identified in urine, 13 (38%) were identified by bronchoalveolar lavage (lung), 4 (12%) were identified on skin or MS, and 1 (3%) was identified at another site. When lung and urine were the sole sites of recovery of MDRO/ESBL in primary hospitalization, respectively, 3 patients (23%) and 2 patients (12.5%) subsequently developed MDROs in a secondary site on subsequent admissions. Overall, 10 bacteremia episodes occurred in 8 patients among 189 total admissions. MDRO/ESBL Klebsiella spp were identified in the cultures of 5 patients (50%), MDRO Acinetobacter spp were identified in the cultures of 3 patients (30%), and ESBL E. coli was identified in the cultures of 2 patients (20%). The organism causing bacteremia was present at a different sites during the same admission in only 3 (30%) of these cases: 2 were cultured from urine and 1 was cultured from a pulmonary source. Conclusions: The presence of MDRO at 1 site in a previous hospitalization may not be sufficient evidence to justify very broad antibiotics for patients during subsequent admissions, especially when another site is considered the source of infection. More studies are needed on natural history of MDRO in different patient populations with different risk factors.Funding: NoneDisclosures: None

A Case of Ketoacidosis Decompensation Revealing a Fournier’s Gangrene at the Early Stage

A 81-year-old man with a 5-year history of diabetes mellituswas admitted for ketotic decompensation. On admission, the patient was found to be asthenic, drowsy, dehydrated and ketotic. The scrotum was grossly swollen with early patches of gangrene. On the biological assessment: C-reactive protein 264 mg/dl, serum potassium was low at 2.8 mmol/l. A scrotal ultrasound revealed a low abundance right hydrocele with edematous infiltration of scrotal envelopes. The patient was put on: intravenous insulin, fluids, potassium, and a broad empirical antibiotic therapy without any need for surgery with a good clinical and biological evolution.

Management of Severe Non-Infectious Acute Respiratory Failure in Lung Transplant Recipients

<h3>Purpose</h3> Acute respiratory failure (ARF) necessitating mechanical ventilation (MV) is the leading cause of ICU readmission after lung transplantation and is associated with a 6-month survival of <50%. Management strategies for patients with non-infectious causes of severe ARF are under-reported. We hypothesized that aggressive, early treatment of non-infectious ARF with awake venovenous extracorporeal membrane oxygenation (VV-ECMO) and augmented immunosuppression would improve outcomes. <h3>Methods</h3> This is a retrospective, single-center case series between 1/1/2018-12/1/2020. Lung transplant recipients (LTRs) with severe ARF with diffuse allograft infiltrates on chest X-ray and PaO2/FiO2 <150 were considered for VV-ECMO. All LTRs received empiric broad antibiotics. If initial cultures were negative, augmented immunosuppression with a combination of high-dose steroids, plasma exchange, intravenous immunoglobulin, rituximab, antithymocyte globulin or alemtuzumab was initiated. VV-ECMO support was via a bicaval, dual lumen single cannula. <h3>Results</h3> Ninety-nine LTRs were re-admitted to an ICU during the study period, with 5 meeting criteria for non-infectious severe ARF. Median duration of ECMO was 21 days (IQR 7-28). Four of the five patients received antibody and/or augmented T-cell depleting therapies, and 12-month survival was 80%. (Fig 1). Lung function stabilized following the ARF insult in survivors (Fig 2). <h3>Conclusion</h3> Treatment with awake VV-ECMO and augmented immunosuppression in LTRs with severe non-infectious ARF is associated with excellent 12-month outcomes that are better than previously reported with MV.

Vital Necessity of Total Pacemaker Lead Extraction Following Heart Transplantation

Introduction A 53-year-old patient was admitted through our emergency room presenting high fever and sudden fatigue six months after a high-risk heart transplantation (HTx) due to dilated cardiomyopathy and valvular heart disease. Several pacemaker leads and a CRT(D) device were initially abandoned intracorporeally due to extensive thrombosis surrounding the leads. Hemodialysis was initially necessary through an implanted Demers atrial catheter due to postoperative acute kidney injury (AKI) for a total of six months. Case Report The patient was urgently transferred to our ICU with advancing sepsis for immediate broad antibiotic therapy as well as catecholamine-assisted stabilization of hemodynamics. Following total renal recovery, the Demers catheter was successfully removed. Blood cultures revealed a colonization with staphylococcus aureus (MSSA) and candida glabrata, which led to additional antimycotic therapy. Transesophageal echocardiograms excluded an endocardial infestation twice. After achieving stable status, a decision for a high-risk transvenous lead extraction as most-probable focus of infection was made. The CRT-D-device was removed through a left pectoral incision. After lead stabilization with a Lasso Snare and Liberator Lead Locking Device through a femoral, venous sheath, an excimer-laser was implemented to release and extract the right-atrial and right-ventricular leads. Next, the four remaining leads were uncovered through a right pectoral incision and stabilized using a Liberator Lead Locking Device. These were then extracted using a mechanical extraction sheath (Cook Evolution RL). Chest X-rays excluded remaining foreign material. Following surgical removal of all remaining leads and antimicrobial therapy for six weeks, the patient was discharged with normal inflammation parameters and fully recovered. Summary Due to the necessary immunosuppression, patients following HTx show an elevated risk for major infection and rapid development to sepsis, when foreign material is abandoned intracorporeally. Based on this study case, we strongly recommend total extraction of remaining pacemaker leads as soon as possible to avoid severe infection-related complications after HTx. A two-stage transvenous lead extraction with an excimer-laser seems to enable the safest path for extraction of heavily thrombosed pacemaker leads. A 53-year-old patient was admitted through our emergency room presenting high fever and sudden fatigue six months after a high-risk heart transplantation (HTx) due to dilated cardiomyopathy and valvular heart disease. Several pacemaker leads and a CRT(D) device were initially abandoned intracorporeally due to extensive thrombosis surrounding the leads. Hemodialysis was initially necessary through an implanted Demers atrial catheter due to postoperative acute kidney injury (AKI) for a total of six months. The patient was urgently transferred to our ICU with advancing sepsis for immediate broad antibiotic therapy as well as catecholamine-assisted stabilization of hemodynamics. Following total renal recovery, the Demers catheter was successfully removed. Blood cultures revealed a colonization with staphylococcus aureus (MSSA) and candida glabrata, which led to additional antimycotic therapy. Transesophageal echocardiograms excluded an endocardial infestation twice. After achieving stable status, a decision for a high-risk transvenous lead extraction as most-probable focus of infection was made. The CRT-D-device was removed through a left pectoral incision. After lead stabilization with a Lasso Snare and Liberator Lead Locking Device through a femoral, venous sheath, an excimer-laser was implemented to release and extract the right-atrial and right-ventricular leads. Next, the four remaining leads were uncovered through a right pectoral incision and stabilized using a Liberator Lead Locking Device. These were then extracted using a mechanical extraction sheath (Cook Evolution RL). Chest X-rays excluded remaining foreign material. Following surgical removal of all remaining leads and antimicrobial therapy for six weeks, the patient was discharged with normal inflammation parameters and fully recovered. Due to the necessary immunosuppression, patients following HTx show an elevated risk for major infection and rapid development to sepsis, when foreign material is abandoned intracorporeally. Based on this study case, we strongly recommend total extraction of remaining pacemaker leads as soon as possible to avoid severe infection-related complications after HTx. A two-stage transvenous lead extraction with an excimer-laser seems to enable the safest path for extraction of heavily thrombosed pacemaker leads.

Sodium dehydroacetate confers broad antibiotic tolerance by remodeling bacterial metabolism

Antibiotic tolerance has been a growing crisis that is seriously threatening global public health. However, little is known about the exogenous factors capable of triggering the development of antibiotic tolerance, particularly in vivo. Here we uncovered that an previously approved food additive termed sodium dehydroacetate (DHA-S) supplementation remarkably impaired the activity of bactericidal antibiotics against various bacterial pathogens. Mechanistic studies indicated that DHA-S induced glyoxylate shunt and reduced bacterial cellular respiration by inhibiting the enzymatic activity of α-ketoglutarate dehydrogenase (α-KGDH). Furthermore, DHA-S mitigated oxidative stress imposed by bactericidal antibiotics and enhanced the function of multidrug efflux pumps. These actions worked together to induce bacterial tolerance to antibiotic killing. Interestingly, the addition of five exogenous amino acids, particularly cysteine and proline, effectively reversed antibiotic tolerance elicited by DHA-S both in vitro and in mouse models of infection. Taken together, these findings advance our understanding of the potential risks of DHA-S in the treatment of bacterial infections, and shed new insights into the relationships between antibiotic tolerance and bacterial metabolism.