The Impact of Thrombocytopenia and Lymphopenia on Mortality in Patients Infected with Influenza Virus: A Retrospective Cohort Study.

INTRODUCTION: Influenza virus causes significant global annual morbidity and mortality. Thrombocytopenia is recognized as a poor prognostic factor in sepsis and is associated with mortality, while lymphopenia has been established as a poor prognostic factor in other viral infections. We aimed to assess the incidence of thrombocytopenia and lymphopenia in seasonal influenza and their effect on clinical outcomes. METHODS: This single-center, retrospective, cohort study included consecutive adult patients, hospitalized in Rabin Medical Center between October 2017 and April 2018, with laboratory-confirmed influenza. Patients were grouped according to blood counts on admission: (1) thrombocytopenia (<150 K/mL), (2) lymphopenia (<0.5 K/mL), and (3) both thrombocytopenia and lymphopenia. Patients without thrombocytopenia and lymphopenia were designated as controls. The primary outcome was 30-day all-cause mortality. Risk factors were identified by univariable and multivariable analyses, using logistic regression and reported as odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: A total of 625 patients were included, 112 (18%) had thrombocytopenia, 98 (15.6%) had lymphopenia, and 107 (17%) had both. The crude 30-day all-cause mortality was 7.6% (48/625). Mortality rates were 7.1% (8/112) for the thrombocytopenia group, 11.2% (11/98) for the lymphopenia group, and 14.9% (16/107) for patients with both versus 4.2% (13/308) in the control (p = 0.000 for all). In a multivariable regression model, significant thrombocytopenia (<100 K/µL) [OR 5.07 (95% CI 1.5-16.2)], age [OR 1.07 (95% CI 1.02-1.11)], time to oseltamivir [OR 1.006 (95% CI 1.002-1.11)], and significant respiratory support [OR 8.85 (3.4-22.6)] were associated with 30-day all-cause mortality. CONCLUSION: Patients hospitalized with seasonal influenza and thrombocytopenia <100 K/mL on admission, have an increased 30-day all-cause mortality.

Community versus health care-associated Clostridioides difficile infection: A comparison between clinical characteristics and outcomes in hospitalized patients.

BACKGROUND: Clostridioides difficile infection (CDI) can be divided according to its acquisition site, health care (HC) or community (CA) associated CDI. Studies showed severe disease, higher recurrence, and mortality among HC-CDI patients, while others reported the opposite. We aimed to compare the outcomes according to the CDI acquisition site. METHODS: The study analyzed medical records and laboratory computerized system data to identify patients (≥18 years old) who were hospitalized with the first CDI from January 2013 to March 2021. Patients were divided into HC-CDI and CA-CDI groups. The primary outcome was 30-day mortality. Other outcomes: CDI severity, colectomy, intensive care unit (ICU) admission, length of hospitalization, 30 and 90-day recurrence, and 90 days all-cause mortality. RESULTS: Of 867 patients, 375 were defined as CA-CDI and 492 as HC-CDI. CA-CDI patients had more underlying malignancy (26% vs 21% P = .04) and inflammatory bowel disease (7% vs 1%, P < .001). The 30 days mortality was similar (10% CA-CDI and 12% HC-CDI, P = .5), and the acquisition site was not found to be a risk factor. There was no difference in severity nor in complications, but the recurrence rate was higher among those with CA-CDI (4% vs 2%, P = .055). CONCLUSIONS: There were no differences between the CA-CDI and HC-CDI groups regarding rates, in-hospital complications, short-term mortality, and 90-day recurrence rates. However, the CA-CDI patients had a higher recurrence rate at 30 days.

Risk factors for functional decline among survivors of Gram-negative bloodstream infection: A prospective cohort study.

OBJECTIVE: To identify risk factors for functional decline after hospitalization for Gram-negative bacteremia. PATIENTS AND METHODS: A prospective cohort study based on a randomized controlled trial conducted between January 1, 2013 and August 31, 2017 in Israel and Italy. Hospitalized patients with Gram-negative bacteremia who survived until day 90 and were not bedridden at baseline were included. The primary end point was functional decline at 90 days. RESULTS: Five hundred and nine patients were included. The median age of the cohort was 71 years (interquartile range [IQR], 60-80 years), 46.4% (236/509) were male and 352 of 509 (69%) patients were independent at baseline. Functional decline at 90 days occurred in 24.4% of patients (124/509). In multivariable analysis; older age (odds ratio [OR], 1.03; for an one-year increment, 95% confidence interval [CI] 1.01-1.05), functional dependence in instrumental activities of daily living at baseline (OR, 4.64; 95% CI 2.5-8.6), low Norton score (OR, 0.87; 95% CI 0.79-0.96) and underlying comorbidities: cancer (OR, 2.01; 95% CI 1.14-3.55) and chronic pulmonary disease (OR, 2.23 95% CI 1.12-4.42) and longer length of hospital stay (OR 1.09; for one-day increment, 95% CI 1.04-1.15) were associated with functional decline. Appropriate empirical antibiotic treatment was associated with lower rates of functional decline within 90 days (OR, 0.4; 95% CI 0.21-0.78). CONCLUSIONS: Patients surviving bloodstream infections have poor long term trajectories after clinical recovery and hospital discharge. This has vast implications for patients, their family members and health policy makers.

Polymicrobial and monomicrobial necrotizing soft tissue infections: comparison of clinical, laboratory, radiological, and pathological hallmarks and prognosis. A retrospective analysis.

BACKGROUND: Necrotizing soft tissue infection (NSTI) is a life-threatening infection associated with high morbidity and mortality. Treatment consists of surgery and antibiotics. Many studies have addressed NSTI and its subtypes, but few have reviewed the clinical, radiological, and pathological differences between the polymicrobial and monomicrobial diseases. The objective of our study was to evaluate the clinical, radiological, and pathological features of patients with polymicrobial (NSTI I) and monomicrobial (NSTI II) infections and their association with outcome. METHODS: The cohort consisted of patients hospitalized with NSTI at a tertiary medical center in 2002-2019. The medical charts were reviewed for clinical, radiological, and pathological features. Findings were compared between patients in whom blood/tissue bacterial cultures yielded one or more than one pathological isolate. The primary clinical outcome measure of the study was all-cause mortality at 90 days. Secondary outcomes were duration of hospitalization, intensive care unit (ICU) admission, score on the LRINEC (Laboratory Risk Indicator for Necrotizing Fasciitis), and need for vasopressor treatment. RESULTS: A total of 81 patients met the inclusion criteria: 54 (66.6%) with monomicrobial NSTI and 27 (33.3%) with polymicrobial NSTI. There were no significant between-group differences in in-hospital and 90-day mortality. On multivariate analysis, the monomicrobial disease group had a significantly higher 90-day mortality rate in addition to higher rates of in-hospital mortality, ICU admission, and vasopressor use than the polymicrobial disease group. CONCLUSION: Our study is the first to compare the clinical, radiological, and pathological differences between the two most common types of NSTI. The results demonstrate better prognosis for polymicrobial NSTI, with minimal ICU stay, lower mortality, and lower use of vasopressors. LEVEL OF EVIDENCE: Prognostic and epidemiological, level III.

The Importance of Abnormal Platelet Count in Patients with Clostridioides difficile Infection.

BACKGROUND: Clostridium difficile infection (CDI) causes morbidity and mortality. Platelets have been increasingly recognized as an important component of innate and adaptive immunity. We aimed to assess the incidence of thrombocytopenia and thrombocytosis in CDI and the effect of an abnormal platelet count on clinical outcomes. METHODS: This single-center, retrospective cohort study consisted of all adult patients hospitalized in Rabin Medical Center between 1 January 2013 and 31 December 2018 with laboratory confirmed CDI. The primary outcome was 30-day all-cause mortality. Risk factors for 30-day all-cause mortality were identified by univariable and multivariable analyses, using logistic regression. RESULTS: A total of 527 patients with CDI were included. Among them 179 (34%) had an abnormal platelet count: 118 (22%) had thrombocytopenia and 61 (11.5%) had thrombocytosis. Patients with thrombocytosis were similar to control patients other than having a significantly higher white blood cell count at admission. Patients with thrombocytopenia were younger than control patients and were more likely to suffer from malignancies, immunosuppression, and hematological conditions. In a multivariable analysis, both thrombocytosis (OR 1.89, 95% CI 1.01-3.52) and thrombocytopenia (OR 1.70, 95% CI 1.01-2.89) were associated with 30-days mortality, as well as age, hypoalbuminemia, acute kidney injury, and dependency on activities of daily living. A sensitivity analysis restricted for patients without hematological malignancy or receiving chemotherapy revealed increased mortality with thrombocytosis but not with thrombocytopenia. CONCLUSIONS: In this retrospective study of hospitalized patients with CDI, we observed an association between thrombocytosis on admission and all-cause mortality, which might represent a marker for disease severity. Patients with CDI and thrombocytopenia also exhibited increased mortality, which might reflect their background conditions and not the severity of the CDI. Future studies should assess thrombocytosis as a severity marker with or without the inclusion of the WBC count.

The Role of 18-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography (FDG-PET/CT) in Management of Nocardiosis: A Retrospective Study and Review of the Literature.

INTRODUCTION: 18-Fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) is a well-established tool for managing metastatic infections. Nocardiosis, a primarily pulmonary infection, disseminates at high rates. Routine imaging includes chest CT and brain imaging. We examined the use of FDG-PET/CT in nocardiosis and assessed its contribution to diagnosis and management. METHODS: A retrospective study in two tertiary medical centers during 2011-2020. Individuals with nocardiosis for whom FDG-PET/CT was implemented for any reason were included and their medical records were reviewed. A board-certified nuclear medicine physician independently reviewed all scans. Additionally, a systematic review was conducted according to the PRISMA guidelines, to extract data from publications reporting FDG-PET/CT use for the management of nocardiosis. RESULTS: FDG-PET/CT contributed to the management of all seven patients who met inclusion criteria. It assisted in ruling out an underlying malignancy (29%, 2/7); establishing a wide infection extent (57%, 4/7); and affecting decisions regarding treatment (57%, 4/7), including drug regimen, oral step-down, and duration of therapy. We identified 20 published case reports on this topic. In 80% (16/20), FDG-PET/CT contributed to the management of nocardiosis similar to our study. In addition, in most of the literature cases, FDG-PET/CT guided the diagnostic biopsy. CONCLUSION: FDG-PET/CT is valuable in the diagnosis and management of individuals with nocardiosis. The contribution of incorporating FDG-PET/CT to the management of individuals with nocardiosis and its role in monitoring treatment response and shortening treatment duration should be evaluated in prospective studies.

Evaluation of Seropositivity Following BNT162b2 Messenger RNA Vaccination for SARS-CoV-2 in Patients Undergoing Treatment for Cancer.

Importance: Patients with cancer undergoing treatment are at high risk of COVID-19 following SARS-CoV-2 infection; however, their ability to produce an adequate antibody response to messenger RNA SARS-CoV-2 vaccines is unclear. Objective: To evaluate rates of antispike (anti-S) antibody response to a BNT162b2 vaccine in patients with cancer who are undergoing systemic treatment vs healthy controls. Design, Setting, and Participants: This prospective cohort study included 102 adult patients with solid tumors undergoing active intravenous anticancer treatment and 78 controls who received the second dose of the BNT162b2 vaccine at least 12 days before enrollment. The controls were taken from a convenience sample of the patients' family/caregivers who accompanied them to treatment. The study was conducted between February 22, 2021, and March 15, 2021 at Davidoff Cancer Center at Beilinson Hospital (Petah Tikva, Israel). Interventions: Blood samples were drawn from the study participants. Serum samples were analyzed and the titers of the IgG antibodies against SARS-CoV-2 spike receptor-binding domain were determined using a commercially available immunoassay. Seropositivity was defined as 50 or greater AU/mL. Main Outcomes and Measures: The primary outcome was the rate of seropositivity. Secondary outcomes included comparisons of IgG titers and identifying factors that were associated with seropositivity using univariate/multivariable analyses. Results: The analysis included 180 participants, which comprised 102 patients with cancer (median [interquartile range (IQR)] age, 66 [56-72] years; 58 men [57%]) and 78 healthy controls (median [IQR] age, 62 [49-70] years; 25 men [32%]). The most common tumor type was gastrointestinal (29 [28%]). In the patient group, 92 (90%) were seropositive for SARS-CoV 2 antispike IgG antibodies after the second vaccine dose, whereas in the control group, all were seropositive. The median IgG titer in the patients with cancer was significantly lower than that in the controls (1931 [IQR, 509-4386] AU/mL vs 7160 [IQR, 3129-11 241] AU/mL; P < .001). In a multivariable analysis, the only variable that was significantly associated with lower IgG titers was treatment with chemotherapy plus immunotherapy (ß, -3.5; 95% CI, -5.6 to -1.5). Conclusions and Relevance: In this cohort study of patients with cancer who were receiving active systemic therapy, 90% of patients exhibited adequate antibody response to the BNT162b2 vaccine, although their antibody titers were significantly lower than those of healthy controls. Further research into the clinical relevance of lower titers and their durability is required. Nonetheless, the data support vaccinating patients with cancer as a high priority, even during therapy.

Cat Scratch Disease Presenting as Fever of Unknown Origin Is a Unique Clinical Syndrome.

BACKGROUND: Fever of unknown origin (FUO) is a rare manifestation of cat scratch disease (CSD). Data regarding CSD-associated FUO (CSD-FUO), particularly in adults, are limited. We aimed to study disease manifestations and long-term clinical outcome. METHODS: A national CSD surveillance study has been conducted in Israel since 1991. Data are obtained using questionnaires, review of medical records, and telephone interviews. FUO was defined as fever of ≥14 days without an identifiable cause. CSD-FUO patients were identified in the 2004-2017 CSD national registry. Follow-up included outpatient clinic visits and telephone/e-mail surveys. RESULTS: The study included 66 CSD-FUO patients. Median age was 35.5 years (range, 3-88). Median fever duration was 4 weeks (range, 2-9). Relapsing fever pattern was reported in 52% of patients, weight loss in 57%, and night sweats in 48%. Involvement of ≥1 organs occurred in 59% of patients; hepatosplenic space-occupying lesions (35%), abdominal/mediastinal lymphadenopathy (20%), ocular disease (18%), and multifocal osteomyelitis (6%) were the most common. Malignancy, particularly lymphoma, was the initial radiological interpretation in 21% of patients; 32% underwent invasive diagnostic procedures. Of the 59 patients available for follow-up (median duration, 31 weeks; range, 4-445), 95% had complete recovery; 3 patients remained with ocular sequelae. CONCLUSION: This is the first attempt to characterize CSD-FUO as a unique syndrome that may be severe and debilitating and often mimics malignancy. Relapsing fever is a common clinical phenotype. Multiorgan involvement is common. Recovery was complete in all patients except in those with ocular disease.

Chronic use of oral iron supplements is associated with poor clinical outcomes in patients with gram-negative bacteremia.

An unabsorbed dietary iron supplementation can modify the colonic microbiota equilibrium and favor the growth of pathogenic strains over barrier strains. Nevertheless, the impact of oral iron supplements (OIS) use on the clinical outcomes of patients with gram-negative bacteremia (GNB) has not been evaluated. To explore the impact of OIS on the outcomes of patients with GNB. A retrospective study conducted in a tertiary hospital including patients with GNB during 2011-2016. The entire cohort was divided into chronic OIS users (study group) and nonusers (control group). The two groups were compared for the study outcomes, septic shock at presentation, length of hospital stay (LOS), and short-term mortality. The study cohort included 232 patients; 44 patients in the study group and 188 in the control one. There was no any significant difference in demographic and comorbidities characteristics between the two groups. Escherichia coli comprised the majority of bacteria (69%), while the urinary tract was the main source of the bacteremia. OIS alone and after adjustment was significantly associated with septic shock at presentation (OR = 2, CI95% [1.03-5], p = 0.04 and OR = 5, CI95% [1.4-15], p = 0.01, respectively). By multivariate analysis, OIS was significantly associated with 30-day mortality (OR = 3, CI95% [1.05-7], p = 0.04), but had no impact on LOS (16 + 23 vs. 12 + 15, p = 0.9). There is a significant association between chronic OIS exposure and increased adverse outcomes in patients with GNB. These findings might have important clinical implications.

Molecular-based diagnosis of Clostridium difficile infection is associated with reduced mortality.

Polymerase chain reaction (PCR) for the diagnosis of Clostridium difficile infection (CDI) might result in overdiagnosis. The clinical outcomes of symptomatic CDI patients diagnosed by PCR remain uncertain. We aimed to determine whether patients whose diagnosis of CDI was based on PCR had different characteristics and clinical outcomes than those diagnosed by toxin immunoassay. Consecutive CDI patients, hospitalized at Rabin Medical Center, Beilinson Hospital, Petah Tikva, Israel, between January 2013 and January 2016, were identified retrospectively and included in the study. Diagnosis of CDI was based on PCR or diagnosis by immunoassay for C. difficile toxin. The main outcome was 30- and 90-day all-cause mortality. The PCR group included 165 patients and the immunoassay group included 157 patients. In comparison to the immunoassay group, patients in the PCR group were more likely to be younger, to be independent, to undergo previous abdominal surgery, and to use laxatives. The 30-day mortality rate in the PCR group was significantly lower than that in the immunoassay group, 29/165 (18%) vs 49/157 (31%), respectively; p = 0.028. On multivariate analysis, PCR diagnosis was associated with reduced mortality, OR 0.48 (95% CI 0.26-0.88). PCR-based diagnosis of CDI is associated with reduced all-cause mortality rates. Further studies are needed to determine the management of patients with discrepant immunoassay and PCR diagnosis of CDI.

Epidemiology, microbiology, clinical characteristics, and outcomes of candidemia in internal medicine wards-a retrospective study.

BACKGROUND: The clinical characteristics of internal medicine ward (IMW) patients with candidemia are unclear. The aim of this study was to define the clinical characteristics of candidemic IMW patients and to study the incidence, species distribution, and outcomes of these patients compared to surgical and intensive care unit (ICU) candidemic patients. METHODS: A retrospective cohort of candidemic patients in IMWs, general surgery wards, and an ICU at Beilinson Hospital during the period 2007-2014 was analyzed. RESULTS: A total of 118 patients with candidemia were identified in six IMWs, two general surgery wards, and one ICU in the hospital. Candida albicans was the leading causative agent (41.1%). Higher proportions of Candida parapsilosis and Candida tropicalis isolates were observed in the IMW patients. IMW patients were significantly older, with poorer functional capacity, and had more frequently been exposed to antibiotic therapy within 90 days, in particular ß-lactam-ß-lactamase inhibitor combinations and cephalosporins. At onset of candidemia, a significantly lower number of IMW patients were mechanically ventilated (p<0.01); these patients did not have central line catheters comparable to ICU and surgical patients (p<0.001). They were less likely to receive adequate antifungal therapy within 48h, and this was the only significant predictor of survival in these patients (p=0.028): hazard ratio 3.7 (95% confidence interval 1.14-12.5) for therapy delayed to >48h. CONCLUSIONS: IMW candidemic patients account for a substantial proportion of candidemia cases and have unique characteristics and high mortality rates.

Evaluation of a new immunochromatography test for rapid and simultaneous detection of Clostridium difficile antigen and toxins.

BACKGROUND: Clostridium difficile infection is considered the most common cause of nosocomial infectious diarrhea among adults in the developed world. It is responsible for virtually all cases of pseudomembranous colitis. The Tox A/B enzyme immunoassay (EIA) is the most widely used test for the detection of C. difficile toxins A and B. However, it is associated with poor sensitivity and an unacceptable high rate of false-negative results. OBJECTIVES: To evaluate the performance of the C. DIFF QUIK CHEK COMPLETE assay, designed to simultaneously detect C. difficile-produced glutamate dehydrogenase (GDH) and toxins A and B. METHODS: Using the C. DIFF QUIK CHEK COMPLETE assay, the Tox A/B EIA, and polymerase chain reaction (PCR), we tested 223 stool specimens from hospitalized patients with antibiotics-associated diarrhea. Sensitivity and specificity, and positive and negative predictive values (PPV, NPV) were calculated for the C. DIFF QUIK CHEK COMPLETE test and the Tox A/B EIA against PCR RESULTS: The C. DIFF QUIK CHEK COMPLETE test had a sensitivity of 83.5% and specificity of 94.3% compared to PCR for Tox A/B, with 93.7% correlation (PPV 98.5%, NPV 91.7%). The Tox A/B EIA yielded corresponding values of 72.1% and 93.1%, with 85.6% correlation (PPV 85.1%, NPV 85.8%). CONCLUSIONS: Given the importance of an early and appropriate diagnosis of Clostridium difficile-associated infection, the C. DIFF QUIK CHEK COMPLETE test may be of huge benefit to practitioners.

Obesity as a risk factor for Clostridium difficile infection.

BACKGROUND: Obesity and Clostridium difficile infection (CDI) are both related to an increased Firmicutes/Bacteroidetes ratio in the intestinal microbiota. However, an association between obesity and CDI is unknown. We aimed to assess the association between obesity and CDI in hospitalized patients. METHODS: We conducted a retrospective case-control study. From January to December 2011, all consecutive patients hospitalized with CDI, in 2 internal medical departments in 2 hospitals, were included. Patients with CDI were compared to hospitalized patients without diarrhea, during the same period and in the same departments, and matched by age, sex, Charlson score, length of hospitalization, and antibiotic use during the last 3 months. RESULTS: Of the 6300 patients hospitalized, 178 were diagnosed with CDI. CDI prevalence was 2.8% (178/6300). Thirty patients were excluded from the study. The 148 cases with CDI were compared to 148 hospitalized controls. Mean body mass index (BMI) in the CDI group was 33.6 (SD, 4.3) versus 28.9 (SD, 5.4) in the control group (P = .001). The multivariable model of conditional logistic regression for matched pairs showed that a history of intra-abdominal surgery (odds ratio [OR] = 2.865; 95% confidence interval [CI], 1.26-6.52) and a high BMI value (OR = 1.196 per 1-unit increase in the BMI scale; 95% CI, 1.12-1.27) were the only variables found to be significantly associated with CDI. CONCLUSIONS: Our findings suggest that obesity is associated with the risk of CDI. Further studies are needed to reveal the exact mechanisms underlying this association.

Do statins protect against the development of Clostridium difficile-associated diarrhoea?

OBJECTIVES: To assess whether prior statin use protects against the development of Clostridium difficile-associated diarrhoea (CDAD) in hospitalized patients. PATIENTS AND METHODS: A retrospective case-control study conducted in three hospitals included all hospitalized patients diagnosed with CDAD in the Internal Medicine Departments (IMDs) during a 1 year period. Subjects were determined to have CDAD if their stool sample was positive for C. difficile toxin in the context of diarrhoea at the time of diagnosis. Patients with CDAD were compared with patients without CDAD, hospitalized during the same period and in the same departments, matched for age, gender, comorbidities (Charlson score), length of hospitalization and antibiotic use during the last 3 months. RESULTS: Prevalence of CDAD was 2.87% (197/6850 patients hospitalized in the IMDs). The 197 cases with CDAD were compared with 169 hospitalized patient controls. Sixty-four out of 197 (32.5%) patients in the CDAD group were statin users versus 87/169 (51.5%) of the controls (P = 0.02). Multivariate analysis showed that a Charlson score >3 [OR = 2.2 (95% CI 1.8-2.8), P = 0.024], chemotherapy during the last 6 months [OR = 3.09 (95% CI 1.95-3.91), P = 0.002], a history of intra-abdominal surgery [OR = 2.99 (95% CI 2.58-3.24), P = 0.003] and no statin use [OR = 2.2 (95% CI 1.82-2.73), P = 0.034] were associated with CDAD. CONCLUSIONS: Prior statin use may provide protection against CDAD. Further studies are warranted to evaluate this association.

A nationwide surveillance of invasive pneumococcal disease in adults in Israel before an expected effect of PCV7.

Pneumococcal infections in adults vary in severity and incidence is affected by childhood vaccination policy. Here, we try to define the host determinants and the interaction with specific serotypes that result in invasive pneumococcal disease (IPD) before an expected effect of pneumococcal conjugate vaccines. A nationwide active surveillance was initiated on July 2009, at the time of national implementation of PCV7 in Israel. The surveillance included all 27 laboratories and medical centers performing blood cultures in Israel, providing all blood and CSF pneumococcal isolates from persons ≥18y. Capture-recapture method assured that >95% of all cases were reported. IPD outcome and medical history were recorded and isolates were serotyped. Four hundred and sixty IPD cases were reported (annual incidence [/100,000] of 9.25). Incidence increased with age, from 2.6 among 18-34y to 66.8 among ≥85y. The most common diagnosis was pneumonia (72.4%), followed by bacteremia with no apparent focus (20.2%). Case fatality rate increased with age and number of comorbidities (34.5% for ≥75y or those with ≥3 comorbidities vs. 9.2-11.2% among <65y or those with no comorbidities; p=0.015). Variables independently associated with mortality were: age ≥75, chronic renal failure, malignancy, neurosurgery, alcohol abuse, multi-lobar pneumonia and sepsis with no apparent focus. The predominant serotypes in patients 18-49y were 1, 5, 8, 7F and 9V (constituting 56.3% in this age-group vs. 11.9% in ≥75y; p<0.01). The predominant serotypes among patients ≥75y were 3, 19A, 23F and 14 (40.3% of this age-group vs. 12.9% of 18-49y; p<0.01). Overall, PCV7 and PCV13 covered 25.6% and 63.7% of isolates, respectively, and 30.9% and 67.9% of isolates in mortality cases respectively. This nationwide active surveillance provides the baseline incidence, mortality rates and risk group distributions of IPD in adults before expected PCV effect.

The impact of fluoroquinolone resistance of Gram-negative bacteria in respiratory secretions on the outcome of lung transplant (non-cystic fibrosis) recipients.

Bacterial airway colonization is frequent among lung transplant recipients. These patients are often treated with antibiotics, which may lead to selection of resistant bacteria. The purpose of this study was to assess whether antibiotic treatment causes acquisition of quinolone-resistant Gram-negative bacteria (QR-GNB), and the effect of such colonization on mortality and on lung rejection. We retrospectively examined data from non-cystic fibrosis, non-bronchiectases lung transplant recipients for antibiotic treatment, GNB in respiratory secretions, bronchiolitis obliterans syndrome (BOS), and mortality. Of 126 patients included, 86 patients had QR-GNB, 22 had quinolone-sensitive bacteria (QS-GNB), and 17 had no growth. Median antibiotic exposure, defined as the fraction of days with antibiotic treatment, was 2.8% in patients without growth, 11.1% in patients with QS-GNB (p=0.012), and 26% in patients with QR-GNB (p<0.0001). Age-adjusted mortality hazard ratio was 9.2 (95% CI 1.272-78.9) for patients with QR-GNB compared with QS-GNB. Age-adjusted hazard ratios for BOS was 3.7 (95% CI 1.33-10.3) for QR-GNB compared with QS-GNB. We found a positive correlation between antibiotic treatment and emergence of QR-GNB. Airway colonization with QR-GNB was significantly associated with mortality and with BOS. Further research is needed to determine whether a change in antibiotic subscription policy is required.

Fungal malignant external otitis.

OBJECTIVE: To investigate the clinical characteristics and outcome of fungal malignant external otitis (MEO). METHODS: The files of 60 patients treated for MEO in 1990-2008 at a tertiary medical center were reviewed for clinical characteristics and outcome, and findings were compared between patients with fungal and nonfungal infection. RESULTS: Mean duration of follow-up was 4 years. Nine patients (15%) had fungal disease; the main pathogen was Candida spp. Compared with the nonfungal MEO group, patients with a fungal infection were younger at diagnosis (average 68 vs. 74 years, p = 0.01) and had more facial nerve palsies (55% vs. 14%, p = 0.01), fewer positive bacterial cultures at presentation (33% vs. 75%, p = 0.02), and higher rates of surgery (78% vs. 18%, p = 0.0008) and hyperbaric treatment (78% vs. 4%, p = 0.0001). Eighty-nine percent had persistent infection (>2 courses of systemic antibiotics before antifungal treatment) compared with 12% in the nonfungal group (p = 0.0001). Fungal disease was associated with more persistently positive imaging findings (87.5% vs. 25%, p = 0.0001). There was no significant between-group difference in survival. CONCLUSION: Fungal MEO probably occurs secondary to prolonged antibiotic treatment for bacterial MEO. The fungal disease is more invasive than the bacterial disease, although survival is the same. Treatment should be aggressive and hyperbaric oxygen therapy should be considered.

Duration of antibiotic prophylaxis for cardiac surgery: prospective observational study.

OBJECTIVES: To assess the effect of prolonging antibiotic prophylaxis in cardiac surgery. METHODS: Prospective before-after cohort study. In 2004, cefazolin was given pre- and intraoperatively at 1g doses while in 2007 it was continued after surgery for 24h. All consecutive adult patients undergoing coronary artery bypass graft, valve, and/or aortic operations during the study periods were included. The primary outcomes were deep sternal wound infection (DSWI) and mortality. Univariate and multivariate analyses were conducted to assess risk factors for DSWI. RESULTS: 954 patients between 1/2004 and 12/2004 were compared to 424 patients between 1/2007 and 6/2007. In 2007, there were significantly more patients >60yrs., emergency and combined operations and the mean logistic EuroSCORE was higher compared to 2004 (8.53% vs. 6.92%, p=0.006). The rate of DSWI decreased non-significantly from 3.8% (36/954) in 2004 to 2.6% (11/424) in 2007, p=0.27. The adjusted odds ratio of the study period for DSWI was 0.89 (95% confidence interval 0.70-1.13). There was no difference in 30-day (5.2% vs. 5.4%) or 6-month mortality (9.2% in both periods), despite increasing patients' risk. CONCLUSIONS: Increasing the duration of antibiotic prophylaxis did not result in a significant decrease in DSWI. The value of prolonging antibiotic prophylaxis after cardiac operations should be further evaluated.

Soluble triggering receptor expressed on myeloid cells-1 for diagnosing empyema.

BACKGROUND: Studies have shown that soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) is upregulated by microbial products in the bronchoalveolar lavage fluid, and cerebrospinal fluid of patients with pneumonia and bacterial meningitis, respectively. Our goal was to evaluate whether sTREM-1 in pleural fluid can distinguish pleural empyema from postthoracotomy-related pleural effusion and effusions of other etiologies. METHODS: Patients who presented with pleural effusion were identified through laboratory records. In addition to routine biochemical markers, differential white blood cells, cytology, Gram stain, and pleural fluid culture, pleural fluid sTREM-1 was measured by enzyme-linked immunosorbent assay using a commercial kit (R&D Systems, Minneapolis, MN). RESULTS: Eighty-nine patients were included in the study: 17 with empyema, 7 simple parapneumonic effusion, 18 transudate, 12 postthoracotomy pleural effusion, 22 malignancy, 1 connective tissue disease, and 12 with undetermined effusion. Mean levels of sTREM-1 were significantly higher in empyema than in postthoracotomy pleural effusion (687 +/- 479 pg/mL vs 34 +/- 81 pg/mL, p < 0.0001, respectively) and in effusions of other etiologies (15 +/- 54 pg/mL, p < 0.0001). A cutoff value of 114 pg/mL for pleural sTREM-1 achieved a sensitivity of 94% and a specificity of 93% in differentiating empyema from pleural effusions of other etiologies. The area under the receiver operating characteristic curve for pleural effusion sTREM-1 as a predictor for empyema was 0.966. CONCLUSIONS: Our findings suggest that sTREM-1 in the pleural fluid can potentially assist clinicians in the differentiation of bacterial from nonbacterial pleural effusion, particularly in postthoracotomy pleural effusion.

Selective low-dose valganciclovir for prevention of cytomegalovirus disease following kidney transplantation.

OBJECTIVES: To assess the safety of a cytomegalovirus prophylaxis regimen using selective low-dose valganciclovir. METHODS: Retrospective before-after comparison, including consecutive kidney transplant recipients between 2002 and 2004. Excluded were deaths or graft loss within one month after transplantation. During the first period, universal prophylaxis with oral ganciclovir was used. During the second period, selective prophylaxis with low-dose valganciclovir (450 mg/day) was given to patients at high-risk for CMV disease (D+/R- recipients and patients treated with anti-lymphocyte antibodies) and oral acyclovir to all other patients. We compared the incidence of CMV disease between the two periods. RESULTS: Two hundred and sixty-four patients underwent kidney transplantation of which 221 were included. The incidence of CMV disease was higher with selective low-dose valganciclovir compared to universal ganciclovir without statistical significance, by intention to treat (4.7% vs. 8.5%, respectively, OR 1.88, 95% CI 0.63-5.60) and among patients adhering to the prophylaxis protocol (3.1% vs. 6.8% respectively, OR 2.85, 95% CI 0.65-12.38). Only late-onset CMV was observed for compliant patients. On multivariate analysis, only recipients' serostatus remained significantly associated with CMV disease (OR 0.22, 95% CI 0.07-0.70). CONCLUSIONS: Selective low-dose valganciclovir may provide similar protection against CMV when compared to universal oral ganciclovir. Prolongation of prophylaxis beyond 100 days should be explored.