Prognostic implications of ultra-short heart rate variability indices in hospitalized patients with infective endocarditis.

BACKGROUND: Infective endocarditis (IE) is a disease that poses a serious health risk. It is important to identify high-risk patients early in the course of their treatment. In the current study, we evaluated the prognostic value of ultra-short heart-rate variability (HRV), an index of vagal nerve activity, in IE. METHODS: Retrospective analysis was performed on adult patients admitted to a tertiary hospital due to IE. A logistic regression (LR) was used to determine whether clinical, laboratory, and HRV parameters were predictive of specific clinical features (valve type, staphylococcal infection) or severe short-term complications (cardiac, metastatic infection, and death). The accuracy of the model was evaluated through the measurement of the area under the curve (AUC) of the receiver operating characteristic curve (ROC). An analysis of survival was conducted using Cox regression. A number of HRV indices were calculated, including the standard deviation of normal heart-beat intervals (SDNN) and the root mean square of successive differences (RMSSD). RESULTS: 75 patients, aged 60.3(±18.6) years old, were examined. When compared with published age- and gender-adjusted HRV norms, SDNN and RMSSD were found to be relatively low in our cohort (75%-76% lower than the median; 33%-41% lower than the 2nd percentile). 26(34.6%) patients developed a metastatic infection, with RMSSD<7.03ms (adjusted odds ratio (aOR) 9.340, p = 0.002), incorporated in a multivariate LR model (AUC 0.833). Furthermore, 27(36.0%) patients were diagnosed with Staphylococcus IE, with SDNN<4.92ms (aOR 5.235, p = 0.004), a major component of the multivariate LR model (AUC 0.741). Multivariate Cox regression survival model, included RMSSD (HR 1.008, p = 0.012). CONCLUSION: SDNN, and particularly RMSSD, derived from ultra-short ECG recordings, may provide prognostic information about patients presenting with IE.

NETosis induction reflects COVID-19 severity and long COVID: insights from a 2-center patient cohort study in Israel.

BACKGROUND: COVID-19 severity and its late complications continue to be poorly understood. Neutrophil extracellular traps (NETs) form in acute COVID-19, likely contributing to morbidity and mortality. OBJECTIVES: This study evaluated immunothrombosis markers in a comprehensive cohort of acute and recovered COVID-19 patients, including the association of NETs with long COVID. METHODS: One-hundred-seventy-seven patients were recruited from clinical cohorts at 2 Israeli centers: acute COVID-19 (mild/moderate, severe/critical), convalescent COVID-19 (recovered and long COVID), along with 54 non-COVID controls. Plasma was examined for markers of platelet activation, coagulation, and NETs. Ex vivo NETosis induction capability was evaluated after neutrophil incubation with patient plasma. RESULTS: Soluble P-selectin, factor VIII, von Willebrand factor, and platelet factor 4 were significantly elevated in patients with COVID-19 versus controls. Myeloperoxidase (MPO)-DNA complex levels were increased only in severe COVID-19 and did not differentiate between COVID-19 severities or correlate with thrombotic markers. NETosis induction levels strongly correlated with illness severity/duration, platelet activation markers, and coagulation factors, and were significantly reduced upon dexamethasone treatment and recovery. Patients with long COVID maintained higher NETosis induction, but not NET fragments, compared to recovered convalescent patients. CONCLUSIONS: Increased NETosis induction can be detected in patients with long COVID. NETosis induction appears to be a more sensitive NET measurement than MPO-DNA levels in COVID-19, differentiating between disease severity and patients with long COVID. Ongoing NETosis induction capability in long COVID may provide insights into pathogenesis and serve as a surrogate marker for persistent pathology. This study emphasizes the need to explore neutrophil-targeted therapies in acute and chronic COVID-19.

A point-of-need platform for rapid measurement of a host-protein score that differentiates bacterial from viral infection: Analytical evaluation.

The objective was to evaluate the analytical performance of a new point-of-need platform for rapid and accurate measurement of a host-protein score that differentiates between bacterial and viral infection. The system comprises a dedicated test cartridge (MeMed BV®) and an analyzer (MeMed Key®). In each run, three host proteins (TRAIL, IP-10 and CRP) are measured quantitatively and a combinational score (0-100) computed that indicates the likelihood of Bacterial versus Viral infection (BV score). Serum samples collected from patients with acute infection representing viral (0 ≤ score < 35), equivocal (35 ≤ score ≤ 65), or bacterial (65 < score ≤ 100) scores based on pre-defined score cutoffs were employed for the analytical evaluation studies as well as samples from healthy individuals. To assess reproducibility, triplicate runs were conducted at 3 different sites, on 2 analyzers per site over 5 non-consecutive days. Lower limit of quantitation (LLoQ) and analytical measurement range were established utilizing recombinant proteins. Sample stability was evaluated using patient samples representative of BV score range (0-100). MeMed Key® and MeMed BV® passed the acceptance criteria for each study. In the reproducibility study, TRAIL, IP-10 and CRP measurements ranged with coefficient of variation from 9.7 to 12.7%, 4.6 to 6.2% and 5.0 to 11.6%, respectively. LLoQ concentrations were established as 15 pg/mL, 100 pg/mL and 1 mg/L for TRAIL, IP-10 and CRP, respectively. In summary, the analytical performance reported here, along with diagnostic accuracy established in the Apollo clinical validation study (NCT04690569), supports that MeMed BV® run on MeMed Key® can serve as a tool to assist clinicians in differentiating between bacterial and viral infection.

Ultrashort Heart Rate Variability for Early Risk Stratification in Pneumonia Patients: Preliminary Analysis.

BACKGROUND: Pneumonia patients are susceptible to autonomic nervous system changes. Ultrashort HRV (usHRV) is the measurement of cyclic changes in heart rate over a period < 5 minutes. OBJECTIVES: To describe usHRV in patients with pneumonia and assess the correlation with mortality. METHODS: We conducted a retrospective analysis, which included patients diagnosed with pneumonia in the emergency department (ED). UsHRV indices were calculated from a 10-second ED electrocardiogram and correlated with mortality utilizing logistic and Cox regressions. RESULTS: The study comprised 240 patients. Mortality rates over 30, 90, and 365 days were 13%, 18%, and 30%, respectively. usHRV frequency-domain parameters had significant univariate correlations with mortality. Normalized low frequency (LF) and high frequency (HF) were correlated with 30-, 90-, and 365-day mortality in an opposite direction (odds ratio [OR] 0.094, P = 0.028 vs. OR 4.589, P =0.064; OR 0.052, P = 0.002 vs. OR 6.975, P =0.008; OR 0.055, P < 0.001 vs. OR 7.931, P < 0.001; respectively). Survival analysis was conducted for a follow-up median period of 5.86 years (interquartile range 0.65-9.77 years). Univariate Cox proportional hazard regression revealed time-domain indices with significant correlation with survival (SDNN and RMSSD; hazard ratio [HR] 1.005, 1.005; P = 0.032, P = 0.005; respectively) as well as frequency-domain parameters (normalized LF, HF, LF/HF ratio, and total power; HR 0.102, 5.002, 0.683, 0.997, respectively; P < 0.001). CONCLUSIONS: usHRV may predict mortality in pneumonia patients and serve as a novel risk stratification tool.

A common presentation - turning out as an uncommon diagnosis: From hip pain to Langerhans cell histiocytosis.

Langerhans cell histiocytosis (LCH) is an uncommon clonal proliferation of myeloid progenitor cells, it is especially rare in adults. We present a case of multi-system LCH in a 53-year-old woman, the sole symptom of which was prolonged, non-resolving hip pain for 18 months prior to the diagnosis. Initial evaluation included imaging studies aimed at identifying a presumed local etiology. X-ray demonstrated non-specific arthritic changes on the left femur. Computed tomography (CT) and magnetic resonance imaging (MRI) scans identified a lytic lesion at the same location, warranting a systemic workup. After non-invasive investigations failed to reveal the underlying etiology, a biopsy was performed, revealing cores of Langerhans cells that stained positive for both CD1a and langerin. These findings verified the surprising, uncommon diagnosis of LCH. A comprehensive workup was conducted in order to determine the extent of the disease and its molecular nature - revealing a BRAFV600E-positive, high-risk, multi-system LCH with skeletal, lung and liver involvement.

Mechanical ventilation for older medical patients in a large tertiary medical care center.

BACKGROUND: The development of technologies for the prolongation of life has resulted in an increase in the number of older ventilated patients in internal medicine and chronic care wards. Our study aimed to determine the factors influencing the outcomes of older ventilated medical patients in a large tertiary medical center. METHODS: We performed a prospective observational cohort study including all newly ventilated medical patients aged 65 years and older over a period of 18 months. Data were acquired from computerized medical records and from an interview of the medical personnel initiating mechanical ventilation. RESULTS: A total of 554 patients underwent mechanical ventilation for the first time during the study period. The average age was 79 years, and 80% resided at home. Following mechanical ventilation, 8% died in the emergency room, and the majority of patients (351; 63%) were hospitalized in internal medicine wards. In-hospital mortality was 64.1%, with 48% dying during the first week of hospitalization. Overall 6-months survival was 26%. We found that a combination of age 85 years and older, functional status prior to ventilation, and associated morbidity (diabetes with target organ injury and/or oncological solid organ disease) were the strongest negative predictors of survival after discharge from the hospital. CONCLUSION: Mechanical ventilation at older age is associated with poor survival and it is possible to identify factors predicting survival. In the midst of the COVID-19 pandemic, the findings of this study may help in the decision-making process regarding mechanical ventilation for older people.

Ultra Short Heart Rate Variability Predicts Clinical Outcomes in Patients with a Clinical Presentation Consistent with Myocarditis: A Derivation Cohort Analysis.

Myocarditis prognosis varies substantially, hence identification of novel prognostic factors is crucial. The prognostic role of ultra-short heart-rate variability (HRV) in myocarditis remains unknown. In a retrospective study, adult patients admitted to a tertiary hospital due to clinically suspected myocarditis were included. Clinical, laboratory and HRV parameters were assessed as predictors of severe short term complications (heart failure (HF), dilated cardiomyopathy­DCM, ventricular arrhythmia­VA and death), utilizing logistic regression (LR). Accuracy was evaluated with receiver operating characteristic (ROC) curve area under the curve (AUC). HRV indices included standard deviation of normal beat intervals (SDNN) and root mean square of successive differences (RMSSD). 115 patients, aged 34 (±13) years old, were examined. Six patients (5%) developed severe HFrEF. RMSSD was included in a multivariate LR model (RMSSD < 10.72 ms adjusted odds ratio (AOR) 14.056, p-value 0.024). Model classification accuracy was very good, with an AUC of 86%. Eight patients (7%) developed DCM. RMSSD < 10.72 ms was included in a multivariate classification model (AOR 8.826, p-value 0.013); model classification AUC of 82%. HRV did not predict development of VA or death. SDNN and especially RMSSD may be prognostic indicators in myocarditis.

Implantable cardioverter defibrillator related Actinomyces Odontolyticus endocarditis and bacteremia-First reported case.

Actinomyces Odontolyticus is a gram-positive bacillus, usually found in the oropharynx, gastrointestinal and urogenital tracts, as commensal flora. Infections caused by this organism are rare but may occur, more commonly in immunocompromised patients. We report a case of a 54-year-old man, who presented to the emergency department (ED), with fever and chills. The patient had undergone an implantable cardioverter defibrillator (ICD) insertion, 5 months prior to his arrival, and was diagnosed with Actinomyces Odontolyticus bacteremia, during the hospitalization. Transesophageal echocardiogram (TEE) revealed vegetations on the tricuspid valve and the ICD electrode. This is the first reported case of ICD related Actinomyces endocarditis and bacteremia based on our literature review. This case emphasizes the importance of probing for the source of actinomyces infection, while considering the indolent properties of the disease.

[TEACHING INTERNAL MEDICINE IN THE SHADOW OF THE COVID-19 OUTBREAK - THE EXPERIENCE OF THE TECHNION FACULTY OF MEDICINE].

INTRODUCTION: The clerkship of internal medicine is pursued in the 2nd semester of the 4th year at the Technion Medical School. Following the COVID-19 outbreak, frontal and bedside teaching was interrupted. Therefore, we decided to provide distant teaching until having the opportunity to resume clinical bedside teaching. A team of tutors composed a course of weekly units, each week assigned to a different subject in internal medicine. A total of 120 students were divided into 15 groups of 8 students, each group guided by a personal tutor. The format of each unit included online pretest, clinical virtual cases and two separate 2 hour ZOOM sessions with the tutor. The pretest was based on 1-3 chapters from Harrison's Internal Medicine textbook, 20th edition, and consisted of both clinical reasoning and knowledge questions. During ZOOM sessions with the tutor, the students practiced clinical problem solving. In addition, all the students were granted free access to the commercial "Aquifer" case-based virtual course for more practice. The students' feedback at the end of the learning period revealed that, although frustrated in being away from the clinics, the overall level of satisfaction from the course was good (rated 5 or 4/5 by 65% of responders) and the time was used efficiently. In conclusion, the students received a positive proactive learning experience of both theoretical aspects and clinical reasoning skills in internal medicine. There is no doubt that bedside teaching in medicine is invaluable and can't be replaced by any other means, however, given the circumstances, our format provided a reasonable temporary alternative.

[HEART RATE VARIABILITY: THE AGE-OLD TOOL STILL REMAINS CURRENT].

INTRODUCTION: Heart rate variability (HRV), the fluctuation in the time intervals between adjacent heartbeats, is generated by heart-brain interactions and dynamic autonomic nervous system processes. The study of HRV originated in the 18th century and served Einthoven in the development of the electrocardiogram (ECG), the basis for modern ECG technology. HRV reflects the regulation of autonomic balance, blood pressure, gas exchange, heart, and vascular tone. While 24-hour recording remains the gold standard for HRV assessment, short (5 minutes) and ultra-short (less than 5 minutes) HRV documentation is accurate and considered a more practical means of HRV measurement. HRV metrics include: time-domain indices (e.g. Standard Deviation of NN intervals (SDNN) - correlates with morbidity and mortality of patients after an acute coronary event); frequency-domain measurements (e.g. High Frequency - influenced by breathing and reflects parasympathetic activity); and non-linear analysis, which enables quantification of the unpredictability of a time series. While ECG is the cornerstone of chest pain triage, HRV may assist in the diagnosis of future cardiac disease, including heart failure and atrial fibrillation. In addition, HRV has been extensively studied as a means for risk stratification. Reduced SDNN following an acute coronary event, has been correlated with mortality. Lower SDNN levels were also associated with ventricular arrhythmia in pediatrics patients with acute myocarditis. Higher non-linear indices after an acute coronary event have been related to all-cause mortality.

Teaching During the COVID-19 Pandemic: The Experience of the Faculty of Medicine at the Technion-Israel Institute of Technology.

BACKGROUND: The coronavirus disease-2019 (COVID-19) pandemic forced drastic changes in all layers of life. Social distancing and lockdown drove the educational system to uncharted territories at an accelerated pace, leaving educators little time to adjust. OBJECTIVES: To describe changes in teaching during the first phase of the COVID-19 pandemic. METHODS: We described the steps implemented at the Technion-Israel Institute of Technology Faculty of Medicine during the initial 4 months of the COVID-19 pandemic to preserve teaching and the academic ecosystem. RESULTS: Several established methodologies, such as the flipped classroom and active learning, demonstrated effectiveness. In addition, we used creative methods to teach clinical medicine during the ban on bedside teaching and modified community engagement activities to meet COVID-19 induced community needs. CONCLUSIONS: The challenges and the lessons learned from teaching during the COVID-19 pandemic prompted us to adjust our teaching methods and curriculum using multiple online teaching methods and promoting self-learning. It also provided invaluable insights on our pedagogy and the teaching of medicine in the future with emphasis on students and faculty being part of the changes and adjustments in curriculum and teaching methods. However, personal interactions are essential to medical school education, as are laboratories, group simulations, and bedside teaching.

COVID-19-Associated Suspected Myocarditis as the Etiology for Recurrent and Protracted Fever in an Otherwise Healthy Adult.

Current reports concerning cardiac involvement in the novel corona virus disease (COVID-19) mostly document acute myocardial injury at presentation. Here, we present a healthy young male, with presumed acute myocarditis, presenting 20 days after initial diagnosis of COVID-19 - and after a clinical, and apparent laboratory, resolution of the original episode. His sole substantial clinical finding upon admission was fever, which was followed by a witnessed elevation in troponin-I.

Placenta-Derived Cell Therapy to Treat Patients With Respiratory Failure Due to Coronavirus Disease 2019.

OBJECTIVES: To determine whether placental cell therapy PLacental eXpanded (PLX)-PAD (Pluristem Therapeutics, Haifa, Israel) may be beneficial to treating critically ill patients suffering from acute respiratory distress syndrome due to coronavirus disease 2019. DESIGN: Retrospective case report of critically ill coronavirus disease 2019 patients treated with PLacental eXpanded (PLX)-PAD from March 26, 2020, to April 4, 2020, with follow-up through May 2, 2020. SETTING: Four hospitals in Israel (Rambam Health Care Campus, Bnai Zion Medical Center, and Samson Assuta Ashdod University Hospital), and Holy Name Medical Center in New Jersey. PATIENTS: Eight critically ill patients on invasive mechanical ventilation, suffering from acute respiratory distress syndrome due to coronavirus disease 2019. INTERVENTIONS: Intramuscular injection of PLacental eXpanded (PLX)-PAD (300 × 106 cells) given as one to two treatments. MEASUREMENTS AND MAIN RESULTS: Mortality, time to discharge, and changes in blood and respiratory variables were monitored during hospitalization to day 17 posttreatment. Of the eight patients treated (median age 55 yr, seven males and one female), five were discharged, two remained hospitalized, and one died. By day 3 postinjection, mean C-reactive protein fell 45% (240.3-131.3 mg/L; p = 0.0019) and fell to 77% by day 5 (56.0 mg/L; p < 0.0001). Pao2/Fio2 improved in 5:8 patients after 24-hour posttreatment, with similar effects 48-hour posttreatment. A decrease in positive end-expiratory pressure and increase in pH were statistically significant between days 0 and 14 (p = 0.0032 and p = 0.00072, respectively). A decrease in hemoglobin was statistically significant for days 0-5 and 0-14 (p = 0.015 and p = 0.0028, respectively), whereas for creatinine, it was statistically significant between days 0 and 14 (p = 0.032). CONCLUSIONS: Improvement in several variables such as C-reactive protein, positive end-expiratory pressure, and Pao2/Fio2 was observed following PLacental eXpanded (PLX)-PAD treatment, suggesting possible therapeutic effect. However, interpretation of the data is limited due to the small sample size, use of concomitant investigational therapies, and the uncontrolled study design. The efficacy of PLacental eXpanded (PLX)-PAD in coronavirus disease 2019 should be further evaluated in a controlled clinical trial.

Cannabis treatment in hospitalized patients using the SYQE inhaler: Results of a pilot open-label study.

OBJECTIVE: The objectives were to evaluate the, usability, feasibility of use, satisfaction, and safety of the Syqe Inhaler Exo (Syqe Inhaler), a metered dose, Pharmacokinetics-validated, cannabis inhaler device in a cohort of hospitalized patients that were using medical cannabis under license as a part of their ongoing medical treatment. METHOD: Before and after inhaling from the Syqe Inhaler, participants were asked to fill a questionnaire regarding pain reduction on a visual analog scale from 0 to 10 and, if relevant, reduction in chemotherapy-induced nausea and vomiting and/or spasticity. A patient satisfaction questionnaire and a usability questionnaire were filled in following the last use. Prescribed treatment included 4 daily doses of 500 µg tetrahydrocannabinol each delivered from 16 mg cannabis flos per inhalation plus up to an additional four SOS (distress code for more doses of cannabis) doses. RESULT: Daily cannabis dose consumed during hospitalization with the Syqe Inhaler was 51 mg (20-96) versus 1,000 mg (660-3,300) consumed prehospitalization. Patients were easily trained and continued to use Syqe Inhaler for the duration of their hospitalization (5 [3-7] days). Pain intensity 30-60 minutes following inhalations was reported to be significantly lower than preinhalation 4 [1-5] versus 7 [2-9]). Participants ranked their satisfaction with Syqe Inhaler as 6 (5-7). Three participants reported mild cough, which resolved spontaneously. SIGNIFICANCE OF RESULTS: Cannabis inhalation by combustion is not feasible for hospitalized patients. The use of Syqe Inhaler during hospitalization yielded high levels of patients and staff satisfaction with no complications.

Massive Gastrointestinal Bleeding from a Jejunal Dieulafoy Lesion: An Extraordinary Presentation.

We present an atypical and rare case of a previously healthy 27-year-old male who presented with acute onset of abdominal pain, bloody diarrhea, and syncope. At the Emergency Department, vital signs were stable with no signs of shock. Physical examination revealed diffuse tenderness of the abdomen and cherry red blood was noted upon rectal examination. Blood tests showed marked leukocytosis without anemia. Sigmoidoscopy was performed which revealed hematochezia with no obvious site of bleeding. The patient was admitted to the hospital with a working diagnosis of dysentery and received supportive care. During the following days, blood tests revealed an ongoing decline of hemoglobin levels which necessitated a new workup of gastrointestinal bleeding. Investigation modalities including upper and lower endoscopies as well as angiography failed to demonstrate a bleeding site. Scintigraphy, which was performed next, demonstrated an increased radiotracer activity in the right abdomen consistent with small bowel bleeding. Following these results, the patient underwent urgent laparotomy and surgical resection was performed. The histopathological findings were consistent with a Dieulafoy lesion. This case illustrates the importance of the complementary role of various modalities in locating the bleeding site along the gastrointestinal tract.

Trimethoprim-sulfamethoxazole vs. colistin or ampicillin-sulbactam for the treatment of carbapenem-resistant Acinetobacter baumannii: A retrospective matched cohort study.

OBJECTIVES: This study aimed to assess the effectiveness of trimethoprim-sulfamethoxazole (TMP/SMX) as monotherapy for the treatment of carbapenem-resistant Acinobacter baumannii (A. baumannii) (CRAB) infections. METHODS: This retrospective cohort study included patients receiving TMP/SMX as the main treatment for severe infections caused by CRAB, who were matched with patients treated with colistin or ampicillin-sulbactam (AMP/SUL) by age, Charlson score, department, and source of infection. Outcomes were compared among all patients and in a subgroup of propensity-score (PS) matched patients. The PS matching was performed using a match tolerance of 0.15 with replacement. RESULTS: Fifty-three patients treated with TMP/SMX and 83 matched patients treated with colistin or AMP/SUL were included. Variables that were independently significantly associated with TMP/SMX treatment included admission for infection and septic shock, while abnormal cognition on admission and intensive care unit admission were associated with colistin or AMP/SUL treatment. All-cause 30-day mortality was lower with TMP/SMX compared with the comparator antibiotics among all patients (24.5%, 13 of 53 vs. 38.6%, 32 of 83, P=0.09) and in the PS-matched subgroup (29%, 9 of 31 vs. 55.2% 16 of 29, P=0.04). Treatment failure rates were not significantly different overall (34%, 18 of 53 vs. 42.4%, 35 of 83, P=0.339) and in the PS-matched subgroup (35.5%, 11 of 31 vs. 44.8%, 13 of 29, P=0.46). Time to clinical stability and hospitalization duration were significantly shorter with TMP/SMX. Patients treated with TMP/SMX probably had less severe infections than those treated with other antibiotics, even after matching. CONCLUSIONS: TMP/SMX might be a valuable treatment option for TMP/SMX-susceptible CRAB infections. Given the very limited available treatment options, further studies assessing its effectiveness and safety are necessary.

[REDUCTION OF ANTIBIOTIC CONSUMPTION IN RAMBAM HEALTH CARE CAMPUS - THE ROLE OF AN ANTIBIOTIC STEWARDSHIP PROGRAM].

INTRODUCTION: Antibiotic stewardship programs (ASP) are designed to optimize antibiotic use in hospitals. Antibiotic consumption is one of the measures assessing the effects of ASPs. AIMS: To evaluate the effect of an ASP on antibiotic consumption in our hospital and compare it to hospitals in Israel and worldwide. METHODS: Between October 2012 and March 2013 an ASP was implemented in Rambam Hospital. The program included educational activities, publication of local guidelines for empirical antibiotic treatment, structured infectious diseases consultations, pre-authorization antibiotic restrictions and stop orders. We compared antibacterial antibiotic consumption in defined daily doses (DDD)/100 hospital days (HD) between the periods before (1/2010-3/2013) and after (4/2013-9/2014) implementing the ASP. The study was conducted in the medical departments, hematology, the intensive care unit (ICU) and all pediatric wards. RESULTS: Total antibiotic consumption before implementing the ASP was 96±11.2 DDD/100 HD in medical departments, 186.4±42.8 in the ICU and 185.5±59 in hematology; all values were higher than the worldwide-reported averages for these departments. Following the ASP, total antibiotic consumption decreased by 12% (p=0.008) in the medical departments and by 26% (p=0.002) in hematology, mostly due to reductions in non-restricted antibiotics. No significant changes were observed overall in the ICU and in pediatric wards. There was a significant reduction in consumption of vancomycin and carbapenems in all settings, the latter was reduced to nearly half. Amikacin use quadrupled in the medical departments. CONCLUSIONS: Implementation of an ASP lead to a reduction in non-restricted and restricted antibiotic consumption, especially carbapenems.

Campylobacter bacteraemia: 16 years of experience in a single centre.

BACKGROUND: Campylobacter bacteraemia (CB) is rare and usually occurs in immune-compromised patients. In this study we examined the incidence and epidemiology of CB in one institution over 15.5 years. METHODS: The medical records of all the consecutive patients with CB admitted to our hospital from 2000 to 2015 were retrospectively reviewed. Clinical characteristics, microbiologic and outcome data were collected. RESULTS: During the study period, 65 patients with CB were identified. The majority of the patients were middle aged and immune-compromised. Campylobacter jejuni was the most commonly identified species (33/47, 70%). The main underlying conditions were haematological malignancies (43%) and chronic liver disease (14%). Fifty-seven percent of the patients were receiving immunosuppressive therapy at the time of bacteraemia. The most common presenting symptoms were fever (85%), diarrhoea (40%), abdominal pain (40%), and nausea and vomiting (40%). Of the isolates tested, 97% were susceptible to macrolides, and only 35% were susceptible to quinolones. Susceptibility to quinolones decreased over the years. Most patients did not receive adequate empiric antibiotic treatment (81.5%) and about 20% never received directed therapy. Mortality and relapse rates were low (5% each). There was no association between adequate empirical or definitive antibiotic therapy and adverse outcomes. CONCLUSION: The main predisposing factor for Campylobacter bacteraemia in our cohort was immunosuppression. Prognosis was generally favourable regardless of appropriateness of antibiotic therapy.

Polymicrobial pulmonary infection in patients with hematological malignancies: prevalence, co-pathogens, course and outcome.

PURPOSE: The frequency and clinical significance of polymicrobial pneumonia in patients with hematological malignancies (HM) are poorly understood. The aim of the present study is to describe the prevalence, risk factors, clinical characteristics, and outcome of patients with HM and polymicrobial pneumonia. METHODS: Over a 5 year period, 436 consecutive adult patients with HM and pulmonary infiltrates underwent diagnostic fiberoptic bronchoscopy with bronchoalveolar lavage. For 219 patients an infectious etiology was diagnosed, of them 45 (20.5 %) had polymicrobial etiology. Risk factors, clinical course and outcome of polymicrobial pulmonary infection in patients with HM were established. RESULTS: 45 patients with HM were identified with polymicrobial pulmonary infection, 39 of them with two pathogens, and 6 with three. The most common co-pathogen identified was Aspergillus sp. (87 %). Allogeneic hematopoietic stem cell transplantation (HSCT) and graft versus host disease (GVHD) were predictors of polymicrobial infection. Compared to patients with monomicrobial pneumonia, patients with polymicrobialpulmonary infection had a more severe clinical course with more dyspnea (69 vs. 49 %, P = 0.016), hemoptysis (16 vs. 7 %, P = 0.065) and more required respiratory support (27 vs. 17 %, P = 0.125). In-hospital mortality was significantly higher in patients with polymicrobial pulmonary infection than in patients with monomicrobial pulmonary infection (49 vs. 19 %, P < 0.001). CONCLUSIONS: Polymicrobial pulmonary infection occurs quite frequently in patients with HM, especially in allogeneic HSCT recipients and in patients with GVHD. The clinical course of polymicrobial pulmonary infection is severe and mortality approaches 50 %. The clinician taking care of these patients should always look for additional copathogens in profoundly immunosuppressed patients with pneumonia.

Treatment of Carbapenem-Resistant Acinetobacter baumannii Ventilator-Associated Pneumonia: Retrospective Comparison Between Intravenous Colistin and Intravenous Ampicillin-Sulbactam.

Carbapenem-resistant Acinetobacter baumannii has been increasingly reported as the causative agent of ventilator-associated pneumonia (VAP) among patients in the intensive care units. However, there are insufficient data to guide the appropriate treatment for such infection. Our aim was to compare the outcome of carbapenem-resistant A. baumannii VAP treated with colistin or with ampicillin-sulbactam. We conducted a retrospective study of patients diagnosed with carbapenem-resistant A. baumannii VAP during 2008 and 2009. Clinical and microbiologic cure rates, 30-day mortality, and change in renal function were compared between patients treated with colistin versus those treated with ampicillin-sulbactam. The association between treatment and mortality was examined through multivariable logistic regression analysis. Of the 98 patients diagnosed with carbapenem-resistant A. baumannii VAP, 66 were treated with colistin and 32 with ampicillin-sulbactam. Baseline characteristics of patients were similar, except for a longer intensive care unit stay and lower creatinine clearance test before VAP diagnosis among patients treated with colistin. Clinical cure rates were similar in the 2 groups. In the colistin group, microbiologic failure rates were higher at 7 days [16/33 (48%) vs. 3/17 (18%); P = 0.03]; patients had a more significant elevation in creatinine (+0.2 ± 1.0 mg/dL vs. -0.3 ± 1.1 mg/dL; P = 0.021), and treatment was associated with an increased 30-day mortality (adjusted-odds ratio, 6.5; 95% confidence interval, 1.348-31.342; P = 0.02). In conclusion, patients treated with colistin or ampicillin-sulbactam had similar clinical cure rates. However, colistin was associated with higher rates of microbiologic failure, reduction in renal function, and an increased 30-day mortality. A prospective study comparing high-dose colistin and ampicillin-sulbactam for the treatment of carbapenem-resistant A. baumannii VAP is warranted.