Daptomycin Exposure Prediction With a Limited Sampling Strategy.

BACKGROUND: Daptomycin is a cyclic lipopeptide antibiotic used to treat serious infectious endocarditis caused by Staphylococcus aureus . The pharmacodynamic parameter correlating best with efficacy is the ratio of the estimated area under the concentration (AUC 0-24 )-time curve to the minimum inhibitory concentration. The aim of the study is to develop a limited sampling strategy to estimate AUC 0-24 using a reduced number of samples. METHODS: Sixty-eight daptomycin AUC 0-24 values were calculated for 50 White patients who underwent treatment for at least 5 consecutive days. Plasma concentrations were detected using a validated high-performance liquid chromatography-tandem mass spectrometry analytical method, with daptomycin-d5 as an internal standard. Multiple regression was used to evaluate the ability of 2 concentration-time points to predict the AUC 0-24 calculated from the entire pharmacokinetic profile. Prediction bias was calculated as the mean prediction error, whereas prediction precision was estimated as the mean absolute prediction error. The development and validation datasets comprised 40 and 10 randomly selected patients, respectively. RESULTS: The AUC 0-24 (mg*h/L) was best estimated using the daptomycin trough concentration and plasma concentrations detected 2 hours after dosing. We calculated a mean prediction error of 1.6 (95% confidence interval, -10.7 to 10.9) and a mean absolute prediction error of 11.8 (95% confidence interval, 5.3-18.3), with 73% of prediction errors within ±15%. CONCLUSIONS: An equation was developed to estimate daptomycin exposure (AUC 0-24 ), offering clinical applicability and utility in generating personalized dosing regimens, especially for individuals at high risk of treatment failure or delayed response.

Efficacy of ceftazidime-avibactam in solid organ transplant recipients with bloodstream infections caused by carbapenemase-producing Klebsiella pneumoniae.

We aimed to compare the efficacy of ceftazidime-avibactam (CAZ-AVI) versus the best available therapy (BAT) in solid organ transplant (SOT) recipients with bloodstream infection caused by carbapenemase-producing Klebsiella pneumoniae (CPKP-BSI). A retrospective (2016-2021) observational cohort study was performed in 14 INCREMENT-SOT centers (ClinicalTrials.gov identifier: NCT02852902; Impact of Specific Antimicrobials and MIC Values on the Outcome of Bloodstream Infections Due to ESBL- or Carbapenemase-producing Enterobacterales in Solid Organ Transplantation: an Observational Multinational Study). Outcomes were 14-day and 30-day clinical success (complete resolution of attributable manifestations, adequate source control, and negative follow-up blood cultures) and 30-day all-cause mortality. Multivariable logistic and Cox regression analyses adjusted for the propensity score to receive CAZ-AVI were constructed. Among 210 SOT recipients with CPKP-BSI, 149 received active primary therapy with CAZ-AVI (66/149) or BAT (83/149). Patients treated with CAZ-AVI had higher 14-day (80.7% vs 60.6%, P = .011) and 30-day (83.1% vs 60.6%, P = .004) clinical success and lower 30-day mortality (13.25% vs 27.3%, P = .053) than those receiving BAT. In the adjusted analysis, CAZ-AVI increased the probability of 14-day (adjusted odds ratio [aOR], 2.65; 95% confidence interval [CI], 1.03-6.84; P = .044) and 30-day clinical success (aOR, 3.14; 95% CI, 1.17-8.40; P = .023). In contrast, CAZ-AVI therapy was not independently associated with 30-day mortality. In the CAZ-AVI group, combination therapy was not associated with better outcomes. In conclusion, CAZ-AVI may be considered a first-line treatment in SOT recipients with CPKP-BSI.

A worldwide survey on perioperative antimicrobial prophylaxis for heart transplantation: From theory to clinical practice.

BACKGROUND: The aim of our survey was to analyze the current attitudes toward antimicrobial prophylaxis in heart transplanting centers worldwide. METHODS: The survey was composed of a total of 50 questions, it consisted of four different sections as follows. The first section collected physicians' personal data and centers' general characteristics, second assessed the approach to patients colonized with multidrug-resistant organisms (MDROs), while the third consisted of the infection risk related to cardiovascular devices, and antimicrobial treatment data, the last focused on donor's colonization. RESULTS: A total of 56 answers from 26 different countries were collected, mostly from Europe (n = 30) and the USA (n = 16). A first-generation cephalosporin (58.9%) or a combination therapy with vancomycin (10.7%) were the most frequently prescribed antimicrobial prophylaxis. Roughly 30% of the centers used different antimicrobial prophylaxis,mostly including Gram negative bacteria coverage. The frequency of screening for multidrug resistant Gram-negative bacteria was higher in Europe, where the percentage of centers providing screening for extended spectrum beta-lactamase (46.7%) and carbapenem-resistant Enterobacteriaceae (CRE) (53.3%) was higher than in other geographic area (p = .019; p = .013, respectively). CONCLUSION: This survey highlights a heterogeneity of clinical practice concerning antimicrobial prophylaxis at transplant. The concern for potential Gram-negative bacteria infection was responsible for broader antimicrobial coverage in 30% of centers.

Adoptive Transfer of JC Virus-Specific T Lymphocytes for the Treatment of Progressive Multifocal Leukoencephalopathy.

OBJECTIVE: Progressive multifocal leukoencephalopathy (PML) is still burdened by high mortality in a subset of patients, such as those affected by hematological malignancies. The aim of this study was to analyze the safety and carry out preliminary evaluation of the efficacy of polyomavirus JC (JCPyV)-specific T cell therapy in a cohort of hematological patients with PML. METHODS: Between 2014 and 2019, 9 patients with a diagnosis of "definite PML" according to the 2013 consensus who were showing progressive clinical deterioration received JCPyV-specific T cells. Cell lines were expanded from autologous or allogenic peripheral blood mononuclear cells by stimulation with JCPyV antigen-derived peptides. RESULTS: None of the patients experienced treatment-related adverse events. In the evaluable patients, an increase in the frequency of circulating JCPyV-specific lymphocytes was observed, with a decrease or clearance of JCPyV viral load in cerebrospinal fluid. In responsive patients, transient appearance of punctate areas of contrast enhancement within, or close to, PML lesions was observed, which was interpreted as a sign of immune control and which regressed spontaneously without the need for steroid treatment. Six of 9 patients achieved PML control, with 5 alive and in good clinical condition at their last follow-up. INTERPRETATION: Among other novel treatments, T cell therapy is emerging as a viable treatment option in patients with PML, particularly for those not amenable to restoration of specific immunity. Neurologists should be encouraged to refer PML patients to specialized centers to allow access to this treatment strategy. ANN NEUROL 2021;89:769-779.

Sars-Cov 2 versus Flu: ECMO-associated bloodstream infections.

SARS-CoV-2 and flu may lead to severe acute respiratory distress syndrome (ARDS) requiring extracorporeal membrane oxygenation (ECMO). The aim of the present study is to compare the incidence of bloodstream infections (BSIs) and outcome in patients with flu and SARS-CoV-2 infection hospitalized in ICU and undergoing ECMO. This study is a retrospective analysis of the San Matteo COVID-19 Registry (SMACORE) cohort. The study was conducted from January 2018 to April 2020. Demographic data and microbiological data were recorded during hospitalization. BSIs occurring during ECMO were analyzed. Eighteen patients treated with ECMO, 22 subjects with SARS-CoV-2 infection and 7 with flu, median age 61years for SARS-CoV-2 and 50 for flu (p=NS). Median ECMO duration was similar in the two pathologies. Median time to bloodstream infection from ECMO initiation was similar. Bloodstream infection incidence rate was 2.65 per 100 patients/days for flu and 2.2 per 100 patients/days for SARS-CoV-2. Global infection rate was 5 per 100 patients/days for SARS-CoV-2 patients and 5.3 per 100 patients/days for flu. Mortality during ECMO was 40.9% (5 out of 22 patients) for SARS-CoV-2 infection while none died among flu patients. ECMO-associated mortality was higher in SARS-CoV-2 infection compared with flu infection.

Propensity Score and Desirability of Outcome Ranking Analysis of Ertapenem for Treatment of Nonsevere Bacteremic Urinary Tract Infections Due to Extended-Spectrum-Beta-Lactamase-Producing Enterobacterales in Kidney Transplant Recipients.

There are scarce data on the efficacy of ertapenem in the treatment of bacteremia due to extended-spectrum-beta-lactamase (ESBL)-producing Enterobacterales (ESBL-E) in kidney transplant (KT) recipients. We evaluated the association between treatment with ertapenem or meropenem and clinical cure in KT recipients with nonsevere bacteremic urinary tract infections (B-UTI) caused by ESBL-E. We performed a registered, retrospective, international (29 centers in 14 countries) cohort study (INCREMENT-SOT, NCT02852902). The association between targeted therapy with ertapenem versus meropenem and clinical cure at day 14 (the principal outcome) was studied by logistic regression. Propensity score matching and desirability of outcome ranking (DOOR) analyses were also performed. A total of 201 patients were included; only 1 patient (treated with meropenem) in the cohort died. Clinical cure at day 14 was reached in 45/100 (45%) and 51/101 (50.5%) of patients treated with ertapenem and meropenem, respectively (adjusted OR 1.29; 95% CI 0.51 to 3.22; P = 0.76); the propensity score-matched cohort included 55 pairs (adjusted OR for clinical cure at day 14, 1.18; 95% CI 0.43 to 3.29; P = 0.74). In this cohort, the proportion of cases treated with ertapenem with better DOOR than with meropenem was 49.7% (95% CI, 40.4 to 59.1%) when hospital stay was considered. It ranged from 59 to 67% in different scenarios of a modified (weights-based) DOOR sensitivity analysis when potential ecological advantage or cost was considered in addition to outcome. In conclusion, targeted therapy with ertapenem appears as effective as meropenem to treat nonsevere B-UTI due to ESBL-E in KT recipients and may have some advantages.

Efficacy of ß-lactam/ß-lactamase inhibitors to treat extended-spectrum beta-lactamase-producing Enterobacterales bacteremia secondary to urinary tract infection in kidney transplant recipients (INCREMENT-SOT Project).

BACKGROUND: Whether active therapy with ß-lactam/ß-lactamase inhibitors (BLBLI) is as affective as carbapenems for extended-spectrum ß-lactamase-producing Enterobacterales (ESBL-E) bloodstream infection (BSI) secondary to urinary tract infection (UTI) in kidney transplant recipients (KTRs) remains unclear. METHODS: We retrospectively evaluated 306 KTR admitted to 30 centers from January 2014 to October 2016. Therapeutic failure (lack of cure or clinical improvement and/or death from any cause) at days 7 and 30 from ESBL-E BSI onset was the primary and secondary study outcomes, respectively. RESULTS: Therapeutic failure at days 7 and 30 occurred in 8.2% (25/306) and 13.4% (41/306) of patients. Hospital-acquired BSI (adjusted OR [aOR]: 4.10; 95% confidence interval [CI]: 1.50-11.20) and Pitt score (aOR: 1.47; 95% CI: 1.21-1.77) were independently associated with therapeutic failure at day 7. Age-adjusted Charlson Index (aOR: 1.25; 95% CI: 1.05-1.48), Pitt score (aOR: 1.72; 95% CI: 1.35-2.17), and lymphocyte count ≤500 cells/µL at presentation (aOR: 3.16; 95% CI: 1.42-7.06) predicted therapeutic failure at day 30. Carbapenem monotherapy (68.6%, primarily meropenem) was the most frequent active therapy, followed by BLBLI monotherapy (10.8%, mostly piperacillin-tazobactam). Propensity score (PS)-adjusted models revealed no significant impact of the choice of active therapy (carbapenem-containing vs any other regimen, BLBLI- vs carbapenem-based monotherapy) within the first 72 hours on any of the study outcomes. CONCLUSIONS: Our data suggest that active therapy based on BLBLI may be as effective as carbapenem-containing regimens for ESBL-E BSI secondary to UTI in the specific population of KTR. Potential residual confounding and unpowered sample size cannot be excluded (ClinicalTrials.gov identifier: NCT02852902).

Minimally invasive procedure for removal of infected ventriculoatrial shunts.

BACKGROUND: Ventriculoatrial shunts were one of the most common treatments of hydrocephalus in pediatric and adult patients up to about 40 years ago. Thereafter, due to the widespread recognition of the severe cardiac and renal complications associated with ventriculoatrial shunts, they are almost exclusively implanted when other techniques fail. However, late infection or atrial thrombi of previously implanted shunts require removal of the atrial catheter several decades after implantation. Techniques derived from management of central venous access catheters can avoid cardiothoracic surgery in such instances. METHODS: We retrospectively investigated all the patients requiring removal of a VA shunt for complications treated in the last 5 years in our institution. RESULTS: We identified two patients that were implanted 28 and 40 years earlier. Both developed endocarditis with a large atrial thrombus and were successfully treated endovascularly. The successful percutaneous removal was achieved by applying, for the first time in this setting, the endoluminal dilation technique as proposed by Hong. After ventriculoatrial shunt removal and its substitution with an external drainage, both patients where successfully weaned from the need for a shunt and their infection resolved. CONCLUSION: Patients carrying a ventriculoatrial shunt are now rarely seen and awareness of long-term ventriculoatrial shunt complications is decreasing. However, these complications must be recognized and treated by shunt removal. Endovascular techniques are appropriate even in the presence of overt endocarditis, atrial thrombi, and tight adherence to the endocardial wall. Moreover, weaning from shunt dependence is possible even decades after shunting.

An eight-year experience of Nocardia infection in Italy: does immunosuppression matter?

Nocardia has always been considered a pathogen of the immunocompromised host, but recent evidence has also highlighted its role as a pathogen in the immunocompetent. We aim to assess the role of immunosuppression in the disease. We reviewed all the cases of infections due to Nocardia spp. in our center that occurred from 1 January 2012 to 30 September 2019. Patients were divided into three groups: typical immunocompromised (PLWHIV, solid organ or hematopoietic cell transplant recipients, individuals under immunosuppressive drugs), atypical immunocompromised (ongoing chronic diseases involving the lung, kidney, liver and diabetes) and immunocompetent. We identified 53 patients with an infection by Nocardia spp. Thirty-four (60.4%) of them were immunocompromised, 22 (64.7%) typical and 12 (35.3%) atypical immunocompromised. Nineteen (35.8%) were immunocompetent. The two conditions most frequently associated with infection were chronic lung disease (41.5%) and ongoing treatment with immunosuppressive drugs (33.9%). In our cohort a remarkable prevalence of nocardiosis in immunocompetent and atypical immunosuppressed patients was observed.

SARS Cov-2 infection in a renal-transplanted patient: A case report.

The clinical manifestation of COVID-19 can vary from an asymptomatic course to ARDS requiring invasive mechanical ventilation and extracorporeal membrane oxygenation. A kidney transplanted patient infected with SARS CoV-2 infection showed a mild disease despite immune suppression. It is possible that Immunosuppression can "be protective" as the cytokine storm is an important factor in the disease story. Despite the good outcome reported in the present case report, is remains of vital importance the solid organ transplant patients use precautions in order to avoid the infection.

Mortality reduction in 46 severe Covid-19 patients treated with hyperimmune plasma. A proof of concept single arm multicenter trial.

Hyperimmune plasma from Covid-19 convalescent is a potential treatment for severe Covid-19. We conducted a multicenter one arm proof of concept interventional study. Patients with Covid-19 disease with moderate-to-severe Acute Respiratory Distress Syndrome, elevated C-reactive Protein and need for mechanical ventilation and/or CPAP were enrolled. One to three 250-300 ml unit of hyperimmune plasma (neutralizing antibodies titer ≥1:160) were administered. Primary outcome was 7-days hospital mortality. Secondary outcomes were PaO2/FiO2, laboratory and radiologic changes, as well as weaning from mechanical ventilation and safety. The study observed 46 patients from March, 25 to April, 21 2020. Patients were aged 63, 61% male, of them, 30 were on CPAP and 7 intubated. PaO2/FiO2 was 128 (SD 47). Bilateral infiltrates on chest X-ray was present in 36 patients (84%). Symptoms and ARDS duration were 14 (SD 7) and 6 days (SD 3). Three patients (6.5%) died within 7 days as compared to an expected 15% from the National Statistics and 30% from a small concurrent cohort of 23 patients. The upper one-sided 90%CI was 13.9%, allowing to reject the null hypothesis of a 15% mortality. PaO2/FiO2 increased by 112 units (95%CI 82 to142) in survivors, the chest radiogram severity decreased in 23% (95%CI 5% to 42%); CRP, Ferritin and LDH decreased by 60, 36 and 20% respectively. Weaning from CPAP was obtained in 26/30 patients and 3/7 were extubated. Five serious adverse events occurred in 4 patients (2 likely, 2 possible treatment related). In conclusion, Hyperimmune plasma in Covid-19 shows promising benefits, to be confirmed in a randomized controlled trial. This proof of concept study could open to future developments including hyperimmune plasma banking, development of standardized pharmaceutical products and monoclonal antibodies.

Running out of bullets: The challenging management of acute hepatitis and SARS-COV-2 from the SMatteo COvid19 Registry (SMACORE).

Liver impairment is frequent in patients with novel coronavirus disease (COVID-19) and direct viral tropism for the liver has been proven. Since several of the currently administered drugs against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are possibly hepatotoxic, the management of patients with COVID-19 and liver failure is still an almost unexplored field. Taking this challenging case of acute HBV with persistent hyperbilirubinemia and SARS-COV-2 infection with respiratory distress as a starting point, we here loop through this condition. Where the available therapeutic options are scarce, we here propose hemoperfusion (HP) as an attractive alternative to both delay any late-stage progression of hyper inflammation process in COVID-19 and remove the toxins involved in acute liver failure.

Migrations do not modify Mycobacterium tuberculosis resistance rates: a 20-year retrospective study.

Tuberculosis (TB) caused by resistant strains is becoming a public health concern also in high-income countries. In Pavia province, Northern Italy, the prevalence of foreign-born has increased in recent years. Nevertheless, it is unclear if this has modified epidemiology and resistance patterns of Mycobacterium tuberculosis. We retrospectively collected data on all the Mycobacterium tuberculosis strains isolated by culture in the microbiology reference laboratory of the province of Pavia from 01/01/1998 to 31/12/2017. Overall, 919 patients were identified, 320 were foreign-born (34.8%). The proportion of cases due to foreign-born patients increased during the study period as did resistance to isoniazid (INH) (p = 0.01), while resistance to rifampicin (RIF) did not (p = 0.8). INH and RIF resistance were comparable among Italian and foreign-born patients (7.9% vs 9.7% for INH and 4% vs 5% for RIF, respectively). Twenty-height (3.05%) patients harboured MDR strains. Prevalence of MDR strains was not different between Italians and foreign-born patients (2.8% vs 3.4%, p = 0.6). During the study period the proportion of TB cases due to foreign-born patients and INH resistance increased. This increase was equal among Italian and foreign-born patients. Migrants in our area are not a driver of resistance to anti-mycobacterial drugs.

The obesity paradox: Analysis from the SMAtteo COvid-19 REgistry (SMACORE) cohort.

BACKGROUND AND AIMS: Obesity has been suggested as a possible risk factor for a more severe course of COVID-19; however, conclusive evidence is lacking and few studies have investigated the role of BMI as a risk factor for admission to intensive care unit (ICU) and mortality. We retrospectively analyzed a COVID-19 cohort recruited during the first 40 days of the epidemic in Italy. We examined the association between obesity and 30-day mortality, admission to ICU, mortality and length of hospital stay in patients with COVID-19. METHODS AND RESULTS: Demographic, clinical and outcome data were retrospectively analyzed in 331 patients with COVID-19 admitted to hospital between 21 February and 31 March 2020. The predictive effect of obesity on mortality was assessed using a Cox proportional-hazard regression model, its effect on ICU admission and mortality in the ICU using logistic regressions, and its effect on length of hospital stay using a linear regression. Seventy-four of 331 patients had a BMI ≥30 kg/m2. Among obese patients, 21 (28.4%) required admission in ICU and 25 died (33.8%). After controlling for sex, age, comorbidities and clinical data, obesity was not significantly associated with mortality, mortality in ICU and length of hospital stay. The effect of obesity on ICU admission remained significant after controlling for sex, age, interstitial lung disease, heart disease and serum C-reactive protein. CONCLUSIONS: Obese patients with COVID-19 were more likely to be admitted to ICU than non-obese patients. However, there were no significant differences in mortality between the two groups.

Clinical characteristics of coronavirus disease (COVID-19) early findings from a teaching hospital in Pavia, North Italy, 21 to 28 February 2020.

We describe clinical characteristics, treatments and outcomes of 44 Caucasian patients with coronavirus disease (COVID-19) at a single hospital in Pavia, Italy, from 21-28 February 2020, at the beginning of the outbreak in Europe. Seventeen patients developed severe disease, two died. After a median of 6 days, 14 patients were discharged from hospital. Predictors of lower odds of discharge were age > 65 years, antiviral treatment and for severe disease, lactate dehydrogenase > 300 mg/dL.

Extended Infusion of ß-Lactams for Bloodstream Infection in Patients With Liver Cirrhosis: An Observational Multicenter Study.

BACKGROUND: We analyzed the impact of continuous/extended infusion (C/EI) vs intermittent infusion of piperacillin-tazobactam (TZP) and carbapenems on 30-day mortality of patients with liver cirrhosis and bloodstream infection (BSI). METHODS: The BICRHOME study was a prospective, multicenter study that enrolled 312 cirrhotic patients with BSI. In this secondary analysis, we selected patients receiving TZP or carbapenems as adequate empirical treatment. The 30-day mortality of patients receiving C/EI or intermittent infusion of TZP or carbapenems was assessed with Kaplan-Meier curves, Cox-regression model, and estimation of the average treatment effect (ATE) using propensity score matching. RESULTS: Overall, 119 patients received TZP or carbapenems as empirical treatment. Patients who received C/EI had a significantly lower mortality rate (16% vs 36%, P = .047). In a Cox-regression model, the administration of C/EI was associated with a significantly lower mortality (hazard ratio [HR], 0.41; 95% confidence interval [CI], 0.11-0.936; P = .04) when adjusted for severity of illness and an ATE of 25.6% reduction in 30-day mortality risk (95% CI, 18.9-32.3; P < .0001) estimated with propensity score matching. A significant reduction in 30-day mortality was also observed in the subgroups of patients with sepsis (HR, 0.21; 95% CI, 0.06-0.74), acute-on-chronic liver failure (HR, 0.29; 95% CI, 0.03-0.99), and a model for end-stage liver disease score ≥25 (HR, 0.26; 95% CI, 0.08-0.92). At competing risk analysis, C/EI of beta-lactams was associated with significantly higher rates of hospital discharge (subdistribution hazard [95% CI], 1.62 [1.06-2.47]). CONCLUSIONS: C/EI of beta-lactams in cirrhotic patients with BSI may improve outcomes and facilitate earlier discharge.

Epidemiology of Mycobacterium tuberculosis infection in Pavia province, Lombardy, Northern Italy, 1998-2013.

This study investigated the epidemiology of tuberculosis in the last 16 years in the province of Pavia, Lombardy, Northern Italy. The objective was to evaluate the clinical pattern of tuberculosis in immigrant groups compared with Italians in an observational retrospective study conducted from 1998 to 2013. In all, 615 tuberculosis cases were admitted, 354 males (57.3%), median age 47-years, 425 (69.1%) Italian-born patients, 190 (30.9%) immigrants. The ratio between the immigrant group and the Italian-born group of patients increased from 1.7% to 54.5% in the study period (p=0.001). HIV was the most common comorbidity, affecting 48 patients (7.8%), followed by diabetes in 35 (5.7%) and COPD in 30 (4.9%). The overall admission-associated mortality was 5.5%. Italian-born patients were older than non-Italian born subjects and had at least one comorbidity, 162 (38.1%) and 22 (11.6%), respectively (p<0,0001). Mortality was increased among Italian-born compared with non-Italian-born patients (7.3% versus 1.6%, p=0.004). No significant variation in extra-pulmonary tuberculosis (EPTB) prevalence occurred. Considering specific form of EPTB, HIV infection was associated with an increased risk of EPTB (RR 2.02, 95%CI 1.09-3.74, p=0.026). There was a high risk of tuberculosis among immigrants, whereas a decreasing trend was consistently observed among Italian-born patients. Italian-born patients show a higher tuberculosis-associated mortality risk due to older age and comorbidities.

Epidemiological characteristics of bloodstream infections in patients with different degrees of liver disease.

Observational retrospective study to evaluate the etiology, the outcome and the risk factors of bloodstream infections (BSIs) in patients with liver disease. One hundred and forty-eight BSIs were diagnosed (infection rate: 0.60 per 100 days of hospital stay), 62 BSIs (41.9 %) were associated with Gram-positive bacteria (infection rate: 0.25 per 100 days of hospital stay) and 80 (54.4 %) with Gram-negative bacteria (infection rate: 0.32 per 100 days of hospital stay). Admission-associated mortality was higher in patients with BSI than in those without BSI (20.6 versus 5.0 %, p < 0.001). Patients with cirrhosis had an increased risk to develop a BSI compared with patients with chronic hepatitis, specifically for Gram-positive (and Staphylococcus spp)-related BSI.

Post-exposure rate of tuberculosis infection among health care workers measured with tuberculin skin test conversion after unprotected exposure to patients with pulmonary tuberculosis: 6-year experience in an Italian teaching hospital.

BACKGROUND: This study assesses the risk of LTBI at our Hospital among HCWs who have been exposed to TB patients with a delayed diagnosis and respiratory protection measures were not implemented. METHODS: All HCWs exposed to a patient with cultural confirmed pulmonary TB and respiratory protection measures were not implemented were included. Data on TST results performed in the past (defined as T0) were recorded. TST was performed twice: first, immediately after exposure to an index patient (T1) and three months later (T2). The period of time between T0 and T1 was used to calculate he annual rate of tuberculosis infection (ARTI), while le period of time between T1 and T2 was used to calculate the post exposure annual rate of tuberculosis infection (PEARTI). RESULTS: Fourteen index patients were admitted; sputum smear was positive in 7 (58.3%), 4 (28.6%) were non-Italian born patients. 388 HCWs were exposed to index patients, a median of 27 (12-39) HCW per each index patient. One hundred eighty (46.4%) HCWs received BCG in the past. One hundred twenty two HCWs (31%) were TST positive at a previous routine screening and not evaluated in this subset. Among the remaining 255 HCWs with negative TST test in the past, TST at T1 was positive in 11 (4.3%). ARTI was 1.6 (95% CI 0.9-2.9) per 100 PY. TST at T2 was positive in 9 (3.7%) HCWs, that were TST negative at T1. PEARTI was 26 (95% CI 13.6-50) per 100 PY. At univariate analysis, older age was associated with post exposure latent tuberculosis infection (HR 1.12; 95% CI 1.03-1.22, p=0.01). CONCLUSIONS: PEARTI was considerably higher among HCWs exposed to index patients than ARTI. These data underscore the overwhelming importance of performing a rapid diagnosis, as well as implementing adequate respiratory protection measures when TB is suspected.