Obesity Paradox in Patients Hospitalized with Community Acquired Sepsis: Does Age Make a Difference?

BACKGROUND: Higher body mass index (BMI) has been shown to be a protective factor from mortality in sepsis patients. Yet, whether this effect is different in the very elderly is currently unknown. OBJECTIVES: To investigate the relationship between BMI and sepsis outcomes in patients older and younger than 80 years of age. METHODS: A retrospective analysis of consecutive patients admitted with sepsis to Shamir Medical Center, Israel, was conducted. We compared patients older than and younger than 80 years of age with a BMI higher and lower than 25 kg/m² for hospitalization outcomes. RESULTS: Patients older than 80 years presented with multiple co-morbidities compared to younger patients, but with no difference between BMI groups. Similarly, hospitalization outcomes of functional deterioration, discharge to long-term care facilities, and readmission were not significantly different between BMI groups in the same age category. Mortality was significantly different between BMI groups in patients older than 80 years of age, with higher mortality in BMI < 25 kg/m²: in-hospital mortality (23.4% vs. 14.9%, P < 0.001), 30-day mortality (27.6% vs. 17.9%, P < 0.001), and 90-day mortality (43.4% vs. 28.9%, P < 0.001). This difference was not significant between the groups younger than 80 years old. On logistic regression, BMI over 25 kg/m² was protective in all mortality categories. Nevertheless, there was no significant interaction between age over 80 years to BMI over 25 kg/m² in all mortality outcomes. CONCLUSIONS: Among patients hospitalized with sepsis, higher BMI is a protective factor against mortality in both elderly and younger patients.

[THE EPIDEMIOLOGY OF CLOSTRIDIUM DIFFICILE INFECTIONS AND ASPECTS PERTAINING TO TREATMENT WITH VANCOMYCIN AT ASSAF HAROFEH MEDICAL CENTER].

BACKGROUND: The epidemiology of Clostridium difficile infections (CDI) have evolved dramatically in the past decade. Vancomycin is the treatment of choice for moderate to severe CDI. However, controlled comparative data pertaining to mild CDI is lacking. Furthermore, the potential impact of vancomycin treatment on subsequent vancomycin-resistant Enterococcus (VRE) isolation remains unknown. METHODS: A retrospective cohort analysis was executed at the Assaf Harofeh Medical Center, from 2013 to 2015. Adult patients (>18 years) with a first episode of acute CDI, determined per pre-established criteria, were enrolled. The efficacy of vancomycin vs. metronidazole among patients with mild CDI, and the independent association of oral vancomycin treatment during the acute CDI and later (up to 18 months) VRE isolation, was analyzed by logistic regression. RESULTS: A total of 260 patients with CDI were enrolled. The majority were elderly (75%), and 56% had moderate to severe disease. Among 75 patients with mild disease, no differences were observed in terms of clinical outcomes between vancomycin or metronidazole treatment. Metronidazole remained non-inferior even after incorporating a prediction score to control for confounders associated with being a "vancomycin case". In multivariable analysis, oral vancomycin treatment during the acute CDI was the strongest independent predictor for later isolation of VRE (aOR=74, p=0.004). CONCLUSIONS: Our study suggests that metronidazole should remain the recommended treatment of choice for mild CDI, due to clinical non-inferiority and an apparent association between vancomycin therapy and subsequent VRE isolation on an individual patient level analysis.

Clinical and Epidemiological Significance of Carbapenem Resistance in Acinetobacter baumannii Infections.

Carbapenems are considered the treatment of choice for Acinetobacter baumannii infections. Many facilities implement preventive measures toward only carbapenem-resistant A. baumannii (CRAB). However, the independent role of the carbapenem resistance determinant on patient outcomes remains controversial. In a 6-year analysis of adults with A. baumannii bloodstream infection (BSI), the outcomes of 149 CRAB isolates were compared to those of 91 patients with carbapenem-susceptible A. baumannii In bivariable analyses, CRAB BSIs were significantly associated with worse outcomes and with a delay in the initiation of appropriate antimicrobial therapy (DAAT). However, in multivariable analyses, carbapenem resistance status was no longer associated with poor outcomes, while DAAT remained an independent predictor. The epidemiological significance of A. baumannii should not be determined by its resistance to carbapenems.

Diabetic foot infection in hospitalized adults.

BACKGROUND: Acute infections of the diabetic foot (DFI) are a common and complex condition. Patients are generally managed in the ambulatory setting and epidemiological data pertaining to hospitalized patients is lacking. The aim of this study was to analyze the epidemiology, microbiology and outcomes of hospitalized patients with DFI, who are managed at a referral center equipped with hyperbaric oxygen (HBO) therapy. METHODS: A retrospective cohort study of adult patients admitted to a tertiary referral center with DFI over a six-month period in 2013 was undertaken. Predictors of clinical outcomes and efficacy of treatment modalities were analyzed by Cox regression. RESULTS: Sixty-one patients with DFI were identified. Most patients were elderly (67 ± 13 years), with long-standing (17 ± 9 years), poorly controlled (HbA1c 9 ± 3%) diabetes. Most patients had polymicrobial infection (80%); specifically, anaerobic (39%) and multi or extensively-drug resistant organisms (61%). Administration of appropriate antimicrobials was delayed for >48 h in 83%. Advanced age was associated with worse outcomes. Sicker patients with severe peripheral vascular disease were managed with HBO. The use of HBO was associated with higher costs and increased functional deterioration, and did not prevent future limb amputation. CONCLUSIONS: Our study illustrates the descriptive epidemiology of hospitalized adults with DFI predominantly of polymicrobial etiology. MDROs and anaerobic organisms are common causative pathogens, and appropriate antibiotics were frequently delayed. HBO treatment may delay the need for limb amputation, but not obviate this eventual outcome.

Simple bedside score to optimize the time and the decision to initiate appropriate therapy for carbapenem-resistant Enterobacteriaceae.

BACKGROUND: Epidemiological characteristics of patients with bloodstream infections (BSI) due to extended-spectrum ß-lactamase producing (ESBL) and carbapenem-resistant (CRE) strains are often similar. Mortality rates for CRE BSI are 70%, and mean time to initiation of appropriate therapy is ~5 days. A bedside score was developed to differentiate CRE-BSIs from ESBL-BSIs, in order to help decrease the time to initiation of appropriate therapy for CRE and mortality rates. FINDINGS: Score was developed based of data (2007-2010) abstracted from charts of adult patients from Assaf Harofeh Medical Center (AHMC, Zeriffin, Israel), and validated on a cohort of patients from Detroit Medical Center (DMC, MI, USA). A multivariate model for presence of CRE was generated. A clinical prediction score and ROC curve was derived. 451 patients with ESBL BSIs (285 from AHMC and 166 from DMC) and 74 patients with CRE BSIs (58 from AHMC and 16 from DMC) were included. The prediction score included chemotherapy in the past 3 months (19 points), presence of foreign invasive devices (10 points), no peripheral vascular disease (10 points), reduced consciousness or cognition at time of acute illness (9 points), time in hospital prior to BSI ≥ 3 days (7 points), and age younger than 65 years (6 points). A score of ≥32 to define "high CRE risk" had sensitivity of 59%, specificity of 76%, PPV of 34% and NPV of 90%. CONCLUSIONS: The score's 90% NPV implies it could reduce un-necessary (and toxic) empiric use of anti-CRE therapeutics, but this should be studied prospectively and on broader populations in order to test its potential role in reducing mortality.

Campylobacter coli infection causing second trimester intrauterine growth restriction (IUGR): a case report and review of the literature.

Campylobacter is a gram-negative, microaerophilic, curved rod and a normal resident of the gastrointestinal flora and may be the cause of disease in animals. Transmission to humans occurs by ingestion of contaminated food or by direct contact with infected animals. In the past few decades, an increasing number of reports have implicated the presence of this organism in human abortions as well. An infectious mechanism due to primary placental inflammatory damage followed by secondary damage to the fetus following placental insufficiency and ischemia was suggested. The most common species of Campylobacter are Campylobacter jejuni and Campylobacter coli, which are classically associated with enteritis in humans. We present a rare case of mid-gestation intrauterine growth restriction (IUGR) associated with maternal bacteremia caused by C. coli infection. Our literature review focuses on Campylobacter infections occurring in the second and third trimesters of pregnancy. In all cases, mild maternal symptoms consisting of fever and weakness were presented. However, associated adverse fetal outcome, including abortions, IUGR or preterm labor may occur more frequently than anticipated. Our report strengthens the importance of awareness to this finding and focuses the need to consume properly cooked meat during pregnancy.

Does the "Obesity Paradox" Have an Expiration Date? A Retrospective Cohort Study.

(1) Background: The "obesity paradox" refers to a protective effect of higher body mass index (BMI) on mortality in acute infectious disease patients. However, the long-term impact of this paradox remains uncertain. (2) Methods: A retrospective study of patients diagnosed with community-acquired acute infectious diseases at Shamir Medical Center, Israel (2010-2020) was conducted. Patients were grouped by BMI: underweight, normal weight, overweight, and obesity classes I-III. Short- and long-term mortality rates were compared across these groups. (3) Results: Of the 25,226 patients, diverse demographics and comorbidities were observed across BMI categories. Short-term (90-day) and long-term (one-year) mortality rates were notably higher in underweight and normal-weight groups compared to others. Specifically, 90-day mortality was 22% and 13.2% for underweight and normal weight respectively, versus 7-9% for others (p < 0.001). Multivariate time series analysis revealed underweight individuals had a significantly higher 5-year mortality risk (HR 1.41 (95% CI 1.27-1.58, p < 0.001)), while overweight and obese categories had a reduced risk (overweight-HR 0.76 (95% CI 0.72-0.80, p < 0.001), obesity class I-HR 0.71 (95% CI 0.66-0.76, p < 0.001), obesity class II-HR 0.77 (95% CI 0.70-0.85, p < 0.001), and obesity class III-HR 0.79 (95% CI 0.67-0.92, p = 0.003)). (4) Conclusions: In this comprehensive study, obesity was independently associated with decreased short- and long-term mortality. These unexpected results prompt further exploration of this counterintuitive phenomenon.

The role of readily available clinical, laboratory and radiologic findings in distinguishing a/H1N1/2009 influenza from other causes of acute febrile respiratory illness under pandemic conditions.

BACKGROUND: During an influenza pandemic, clinicians need easily available clinical and laboratory criteria to distinguish influenza from similar respiratory illnesses. We compared A/H1N1/2009-polymerase chain reaction (PCR)-positive and matched PCR-negative hospitalized patients with suspected H1N1 influenza to identify factors that could assist physicians at patient admission. OBJECTIVES: To identify factors significantly associated with A/ H1N1/2009 infection. METHODS: A group of 145 patients with PCR-confirmed A/H1N1 2009 influenza admitted between 27 May 2009 and 3 December 2009 was matched with 145 PCR-negative patients by age, epidemiological week and pregnancy status. Epidemiological and clinical parameters and radiological findings on initial chest X-ray were compared between the two groups. RESULTS: Asthma (PCR+ 26%, PCR- 12%, P = 0.006) and military service (PCR+ 13%, PCR- 4%, P = 0.15) were associated with PCR-positive status in non-pregnant patients. At presentation, fever, cough, myalgia and fulfilling the pandemic influenza case definition were significantly more frequent in nonpregnant PCR+ patients (62/90/43/59% in PCR+ versus 38/69/30/35% in PCR-). In pregnant patients, fever and fulfilling the case definition were significantly associated with PCR-positive status. Mean leukocyte and absolute lymphocyte counts were significantly lower in both pregnant and nonpregnant PCR-positive patients. Significantly more PCR-negative non-pregnant patients (43% vs. 22% PCR+, P = 0.004) had abnormal chest X-ray (CXR) findings on presentation. In PCR-positive patients, patchy consolidation and interstitial infiltrates were the most common abnormalities. CONCLUSIONS: Under the conditions generated by the A/ H1 1/2009 pandemic, radiological findings did not distinguish reliably between influenza and other febrile respiratory illnesses. Asthma, military service, the pandemic case definition (particularly fever, cough and myalgia)

Morbidity among Israeli backpack travelers to tropical areas.

BACKGROUND: Travelers to tropical areas may be susceptible to illness or injuries. This study aims to assess morbidity among travelers during their travel and compare those who became ill or were injured with those who did not. METHODS: This prospective study included 400 travelers who were counselled by a physician in pre-travel clinics in central Israel between 2017 and 2018. Participants were interviewed within a month after their return regarding morbidity during travel, including health problems that started one week following their return. RESULTS: Most travelers (N = 320, 80%) reported at least one illness or injury. Illnesses/injuries were more common among females than males (84.9% vs. 75.1%, p = 0.01), travel periods longer than 30 days (87.7% vs. 77.2%, p = 0.03), and travelers accompanied by their friends or solo travelers compared with those who traveled with their family/partner (83.8% and 70.0%, respectively, p = 0.002). The most common complaint was diarrhea (N = 159, 49.6%), followed by high-altitude sickness (N = 118, 36.9%) and fever (N = 100, 31.2%). Altitude sickness symptoms were more common in females than in males (58.9% vs. 41.0%, p = 0.006) and in those who ascended rapidly in comparison to those who ascended gradually (58.7% vs. 44.6%, p = 0.04). Animal injury was reported by 30 (7.5%) participants yet only eight (27.0%) received medical care, seven of whom (23.3%) were vaccinated against rabies. CONCLUSIONS: Being a female, traveling with friends or alone and longer travel periods were associated with illness/injury. Practitioners at pre-travel clinics should inform travelers of the possible risks including the potential severe consequences of rabies and altitude sickness.

The association of diabetes and hyperglycemia with sepsis outcomes: a population-based cohort analysis.

The independent association of diabetes and hyperglycemia on the outcomes of sepsis remains unclear. We conducted retrospective cohort analyses of outcomes among patients with community-onset sepsis admitted to Shamir Medical Center, Israel (08-12/2016). Statistical associations were queried by Cox and logistic regressions, controlled for by matched propensity score analyses. Among 1527 patients with community-onset sepsis, 469 (30.7%) were diabetic. Diabetic patients were significantly older, with advanced complexity of comorbidities, and were more often exposed to healthcare environments. Despite statistically significant univariable associations with in-hospital and 90-day mortality, the adjusted Hazard Ratios (aHR) were 1.21 95% CI 0.8-1.71, p = 0.29 and 1.13 95% CI 0.86-1.49, p = 0.37, respectively. However, hyperglycemia at admission (i.e., above 200 mg/dl (was independently associated with: increased in-hospital mortality, aHR 1.48 95% CI 1.02-2.16, p = 0.037, 30-day mortality, aHR 1.8 95% CI 1.12-2.58, p = 0.001), and 90-day mortality, aHR 1.68 95% CI 1.24-2.27, p = 0.001. This association was more robust among diabetic patients than those without diabetes. In this study, diabetes was not associated with worse clinical outcomes in community-onset sepsis. However, high glucose levels at sepsis onset are independently associated with a worse prognosis, particularly among diabetic patients. Future trials should explore whether glycemic control could impact the outcomes and should be part of the management of sepsis, among the general adult septic population.

Patient-Reported Outcome Measures After Hospitalization During the COVID-19 Pandemic: A Survey Among COVID-19 and Non-COVID-19 Patients.

BACKGROUND: Many people recovering from COVID-19 suffer from long-term sequelae. The objective of this study was to assess health-related quality of life (HRQoL) in COVID-19 patients several months after discharge. METHODS: We conducted a retrospective cross-sectional case-control study on COVID-19 and non-COVID-19 pneumonia patients admitted to Shamir Medical Center, Israel (03-07/2020). In the months following discharge, patients were invited to participate in a survey and fill the RAND-36 questionnaire. Patients' characteristics and comorbidities were extracted from electronic charts. RESULTS: Among 66 COVID-19 participants, the median age was 58.5 (IQR 49.8-68.3), 56.1% were female, and 36.4% were obese. The median length of stay was 7 days (IQR 4-10). Patient-reported outcome measures were reported at a median follow-up of 9-months (IQR 6-9). Pain, general health, vitality, and health change had the lowest scores (67.5, 60, 57.5, and 25, respectively). Matching to patients hospitalized with pneumonia due to other pathogens was performed on 42 of the COVID-19 patients. Non-COVID-19 patients were more frequently current or past smokers (50% vs 11.9%, p < 0.01) and suffered more often from chronic lung disease (38.1% vs 9.5%, p = 0.01). The score for health change was significantly lower in the COVID-19 group (25 vs 50, p < 0.01). CONCLUSION: Post COVID-19 patients continue to suffer from an assortment of symptoms and perceive a deterioration in their health many months after hospitalization. This emphasizes the importance of prolonged medical follow-up in this population, and the need for additional research to better understand this novel disease's long-term effects.

The epidemiology of carbapenem resistant Enterobacter spp: A case-case-control matched analysis.

A case-case-control investigation (216 patients) examined the risk factors and outcomes of carbapenem-resistant Enterobacter (CR-En) acquisition. Recent exposure to fluoroquinolones, intensive care unit (ICU) stay, and rapidly fatal McCabe condition were independent predictors for acquisition. Acquiring CR-En was independently associated with discharge to a long-term care facility after being admitted from home.

Adherence to antimalarial chemoprophylaxis among Israeli travelers visiting malaria-endemic areas.

BACKGROUND: Travelers are recommended to take antimalarial chemoprophylaxis (AMC) when traveling to endemic areas. METHODS: This prospective comparative cohort study included 400 Israeli travelers to malaria-endemic areas, recruited in pre-travel clinics. They were contacted within one month following their return and asked about their actual adherence and the reasons for non-adherence. RESULTS: Of 400 travelers with a mean age of 24.6 [SD = 4] years, 201 (50.2%) were men and 328 (82%) were singles. The majority (N = 185, 46.3%) traveled with friends, and the most common travel destination was southeast Asia (N = 267, 66.8%). Most travelers (N = 340, 85%) did not adhere to the AMC. In the multivariate analysis, non-adherence was found to be significantly associated with traveling solo or with friends, traveling to southeast Asia and longer travel duration. The most common reason for non-adherence among travelers was the perception that the risk of contracting malaria is low (N = 251, 73.8%). CONCLUSION: In this study, 85% of the Israeli travelers did not adhere to the AMC, especially those traveling solo or with friends, visiting southeast Asia and for a long period. Counselors at the pre-travel clinics should stress the importance of AMC in highly endemic countries and consider alternative treatment strategies, especially in low risk areas or long duration travel, such as short-term schedule or reserve AMC for field trips.

Antimicrobial use for asymptomatic bacteriuria-First, do no harm.

OBJECTIVE: Administration of antimicrobials to patients with asymptomatic bacteriuria (ASB) is a common error that can lead to worse outcomes. However, controlled analyses quantifying the commonality and impact of this practice are lacking. We analyzed the independent predictors for antimicrobials misuse in ASB and quantified the impact of this practice on clinical outcomes. DESIGN: Retrospective case-control and cohort analyses for calendar year 2017. SETTING: Tertiary-care, university-affiliated medical center. PATIENTS: The study included adult (>18 years) patients with positive urine culture. Pregnant women, renal transplant recipients, and patients who underwent urologic procedures were excluded. METHODS: ASB was determined according to US Centers for Disease Control and Prevention (CDC) criteria. Multivariable logistic regression models were constructed to analyze predictors and outcomes associated with antimicrobial use for patients with ASB. RESULTS: The study included 1,530 patient-unique positive urine cultures. Among these patients, 610 patients (40%) were determined to have ASB. Of the 696 isolates, 219 (36%) were multidrug-resistant organisms (MDROs). Also, 178 (29%) patients received antimicrobials specifically due to the ASB. Independent predictors for improper administration of antimicrobials were dependent functional status (adjusted odds ratio [aOR], 2.3; 95% CI, 1.4-3.6) and male sex (aOR, 2; 95% CI, 1.25-2.6). Use of antimicrobials was independently associated with re-hospitalizations (aOR, 1.7; 95% CI, 1.1-2.6) and later, acute Clostridioides difficile infections (CDI) in the following 90 days (aOR, 4.5; 95% CI, 2-10.6). CONCLUSIONS: ASB is a common condition, frequently resulting from an MDRO. Male sex and poor functional status were independent predictors for mistreatment, and this practice was independently associated with rehospitalizations and CDI in the following 90 days.

The Clinical and Molecular Epidemiology of Noncarbapenemase-Producing Carbapenem-Resistant Enterobacteriaceae: A Case-Case-Control Matched Analysis.

BACKGROUND: Risk factors and outcomes associated with carbapenem-resistant Enterobacteriaceae (CRE) acquisitions are derived primarily from cohorts consisting of carbapenemase-producing (CP) strains. Worldwide epidemiology of non-CP-CRE is evolving, but controlled epidemiological analyses are lacking. METHODS: A matched case-case-control investigation was conducted at Shamir (Assaf Harofeh) Medical Center, Israel, on November 2014-December 2016. Noncarbapenemase-producing CRE (as defined by the US Clinical and Laboratory Standards Institute Standards) carriers were matched to patients with non-CRE Enterobacterales and to uninfected controls (1:1:1 ratio). Matched and nonmatched multivariable regression models were constructed to analyze predictors for acquisition and the independent impact of carriage on multiple outcomes, respectively. Representative isolates were whole genome sequenced and analyzed for resistome and phylogeny. RESULTS: Noncarbapenemase-producing CRE carriers (n = 109) were matched to the 2 comparative groups (overall n = 327). Recent exposure to antibiotics (but not specifically to carbapenems), prior intensive care unit admission, and chronic skin ulcers were all independent predictors for non-CP-CRE acquisition. Acquisitions were almost exclusively associated with asymptomatic carriage (n = 104), and despite strong associations per univariable analyses, none were independently associated with worse outcomes. Genomic analyses of 13 representative isolates revealed polyclonality, confirmed the absence of carbapenemases, but confirmed the coexistence of multiple other genes contributing to carbapenem-resistance phenotype (multiple beta-lactamases and efflux pumps). CONCLUSIONS: Noncarbapenemase-producing CRE acquisitions are primarily associated with asymptomatic carriage, specifically among prone populations with extensive recent exposures to antibiotics. The prevalent mode of acquisition is "emergence of resistance" (not "patient-to-patient transmission"), and therefore the role of stewardship interventions in reducing the spread of these therapeutically challenging pathogens should be further explored.

The impact of improper empirical usage of antipseudomonals on admission to an acute care hospital.

BACKGROUND: Many septic patients are receiving empirical antipseudomonal (or Gram-negative non-glucose fermenting [GNNGF]) coverage on admission to acute care hospitals, despite the fact that the indications are not scientifically established. Overuse of antipseudomonals might contribute to the burden of resistance. MATERIALS AND METHODS: Retrospective observational analyses of the characteristics of septic adult patients who received empirical antipseudomonals, along with its impact on outcomes, were executed at Shamir Medical Center, Zerifin, Israel (08-12/2016). Proper empirical antipseudomonal usage was defined by the following: (1) if the patient received the agents as per Infectious Disease Society of America (IDSA) guidelines; (2) if the patient had a positive multidrug-resistant organism (MDRO) test on his or her admission score (https://assafharofe.azurewebsites.net); or (3) if a GNNGF was the eventual causative pathogen. Risk factors and outcomes were queried by logistic and Cox regression. RESULTS: GNNGF was the causative pathogen in only 57 (3.7%) of 1536 patients with acute sepsis. There were 192 (13%) who received empirical antipseudomonals, of whom 161 (84%) were defined as proper. Patients who received empirical antipseudomonals were significantly older (P < 0.001), with higher indices of chronic and acute conditions, and higher rates of past MDRO carriage; 24 patients received empirical antipseudomonals only because of IDSA guidelines (15%), and that was an independent predictor for later acquisition (up to 90 days) of carbapenem-resistant A. baumannii (CRAB; odds ratio [aOR] = 7.1; P = 0.03). CONCLUSIONS: Improper empirical usage of antipseudomonals in acute care hospitals is common. Instituting empirical antipseudomonals solely due to IDSA guidelines was independently associated with later acquisition of CRAB. Empirical antipseudomonal usage should be based on scientifically established prediction tools and not on IDSA guidelines.