De-Escalation and Discontinuation of Empirical Antibiotic Treatment in a Cohort of Allogeneic Hematopoietic Stem Cell Transplantation Recipients during the Pre-Engraftment Period

To investigate rates and outcomes of antibiotic de-escalation during pre-engraftment neutropenia in allogeneic hematopoietic stem cell transplantation (HSCT) recipients. 110 consecutive HSCTs performed between January 2013 and March 2014 were analyzed. De-escalation was defined as narrowing the spectrum of antibiotic treatment either within (early) or after 96 hours (late) from starting antibiotics. Discontinuation, considered a form of de-escalation, was defined as stopping antibiotics before engraftment. De-escalation failure was defined as restarting/escalating antibiotics within 96 hours after de-escalation. Predictors of de-escalation were analyzed. Among 102 patients who started antibiotics and were included, 68 (67%) received monotherapy (mainly piperacillin-tazobactam, n = 58), whereas 34 (33%) received combination therapy (mainly meropenem plus glycopeptide, n = 24). Median duration of neutropenia was 17 days. Bloodstream infections (BSIs) were diagnosed in 28 patients (20%). Early de-escalation rate was 25.5% (n = 26) and mostly consisted of reducing the spectrum of \u3b2-lactams (n = 11, 42%). In comparison with theoretical scenario of continuing therapy until engraftment, the median savings in terms of antibiotic days were 10 for meropenem, 8 for piperacillin-tazobactam, and 7 for vancomycin. Failure rate of early de-escalation was 15% (4/26). Late de-escalation rate was 30.4% (n = 31) and failure rate 19% (6/31). The rate of de-escalation any time before engraftment was 55.9% (n = 57), including discontinuation in 33 patients (32%). Death at day 60 after HSCT occurred in 3 patients who never underwent de-escalation. Acute myeloid disease and BSIs were independent predictors of early de-escalation. De-escalation, including discontinuation, is feasible and safe in pre-engraftment neutropenia after allogeneic HSCT

Blood Stream Infections in Allogeneic Hematopoietic Stem Cell Transplant Recipients: Reemergence of Gram-Negative Rods and Increasing Antibiotic Resistance

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Risk factors for infections due to carbapenem-resistant Klebsiella pneumoniae after open heart surgery

OBJECTIVES Patients undergoing major surgery are at increased risk of developing infections due to resistant organisms, including carbapenem-resistant Klebsiella pneumoniae (CR-Kp). In this study, we assessed risk factors for CR-Kp infections after open heart surgery in a teaching hospital in northern Italy. METHODS A retrospective study was conducted from January to December 2014. The primary outcome measure was postoperative CR-Kp infection, defined as a time-to-event end-point. The effect of potentially related variables was assessed by univariable and multivariable analyses. Secondary end-points were in-hospital mortality and 180-day postoperative mortality. RESULTS Among 553 patients undergoing open heart surgery, 32 developed CR-Kp infections (6%). In the final multivariable model, CR-Kp colonization [hazard ratio (HR) 227.45, 95% confidence intervals (CI) 67.13-1225.20, P < 0.001], cardiopulmonary bypass time in minutes (HR 1.01, 95% CI 1.01-1.02, P < 0.001), chronic obstructive pulmonary disease (HR 3.99, 95% CI 1.61-9.45, P = 0.004), SOFA score (HR 1.29, 95% CI 1.08-1.53, P = 0.007), preoperative mechanical ventilation (HR 8.10, 95% CI 1.31-48.57, P = 0.026), prolonged mechanical ventilation (HR 2.48, 95% CI 1.08-6.15, P = 0.032) and female sex (HR 2.08, 95% CI 1.00-4.36, P = 0.049) were associated with the development of CR-Kp infection. Increased in-hospital mortality and 180-day mortality were observed in patients who developed CR-Kp infections in comparison with those who did not. CONCLUSIONS In our cohort, CR-Kp colonization was an important predictor of CR-Kp infection after open heart surgery. CR-Kp infection after surgery significantly affected survival. Preventing colonization is conceivably the most effective current strategy to reduce the impact of CR-Kp

Population pharmacokinetics and probability of target attainment of meropenem in critically ill patients

Purpose: Patients admitted to intensive care unit (ICU) with Klebsiella pneumoniae infections are characterized by high mortality. The aims of the present study were to investigate the population pharmacokinetics parameters and to assess the probability of target attainment of meropenem in critically ill patients to provide information for more effective regimens. Methods: Twenty-seven consecutive patients were included in the study. Meropenem was administered as 3-h intravenous (i.v.) infusions at doses of 1\u20132 g every 8 or 12 h. Meropenem plasma concentrations were measured by a high-performance liquid chromatography (HPLC) method, and a population pharmacokinetics analysis was performed using NONMEM software. Meropenem plasma disposition was simulated for extended (3 h; 5 h) or continuous i.v. infusions, and the following parameters were calculated: time during which free drug concentrations were above minimum inhibitory concentration (MIC) (fT > MIC), free minimum plasma concentrations above 4 7 MIC (fCmin > 4 7 MIC), probability of target attainment (PTA), and cumulative fraction of response (CFR). Results: Gender and severity of sepsis affected meropenem clearance, whose typical population values ranged from 6.22 up to 12.04 L/h (mean \ub1 standard deviation (SD) value, 9.38 \ub1 4.47 L/h). Mean Cmin value was 7.90 \ub1 7.91 mg/L, suggesting a high interindividual variability. The simulation confirmed that 88 and 97.5 % of patients achieved effective Cmin > 4 7 MIC values after 3- and 5-h i.v. infusions of meropenem 2 g  7 3/day, respectively. On the contrary, the same total daily doses reached the target Cmin > 4 7 MIC values in 100 % of patients when administered as continuous i.v. infusions. Conclusions: Several factors may influence meropenem pharmacokinetics in ICU patients. Continuous i.v. infusions of meropenem seem to be more effective than standard regimens to achieve optimal therapeutic targets

Epidemiology, management, and outcome of carbapenem-resistant Klebsiella pneumoniae bloodstream infections in hospitals within the same endemic metropolitan area

In the last decade, carbapenem-resistant Klebsiella pneumoniae (CR-Kp) has become endemic in several countries, including Italy. In the present study, we assessed the differences in epidemiology, management, and mortality of CR-Kp bloodstream infection (BSI) in the three main adult acute-care hospitals of the metropolitan area of Genoa, Italy.From January 2013 to December 2014, all patients with CR-Kp BSI were identified through the computerized microbiology laboratory databases of the three hospitals. The primary endpoints of the study were incidence and characteristics of CR-Kp BSI in hospitals within the same endemic metropolitan area. Secondary endpoints were characteristics of CR-Kp BSI in hospitals with and without internal infectious diseases consultants (IDCs) and 15-day mortality.During the study period, the incidence of healthcare-associated CR-Kp BSI in the entire study population was 1.35 episodes per 10,000 patient-days, with substantial differences between the three hospitals. Patients admitted to the two hospital with internal IDCs were more likely to receive post-susceptibility test combined therapy including carbapenems (77% vs. 26%, p <. 0.001), adequate post-susceptibility test therapies (86% vs. 52%, p <. 0.001), and post-susceptibility therapies prescribed by an infectious diseases specialist (84% vs. 14%, p <. 0.001). Overall, the crude 15-days mortality was 26%. In the final multivariable model, only septic shock at BSI presentation was unfavorably and independently associated with 15-days mortality (odds ratio [OR] 6.7, 95% confidence intervals [CI] 2.6-17.6, p <. 0.001), while a protective effect was observed for post-susceptibility test combined therapies including a carbapenem (OR 0.11, 95% CI 0.03-0.43, p = 0.002).Mortality of CR-Kp remains high. Differences in the incidence of CR-Kp BSI were detected between acute-care centers within the same endemic metropolitan area. Efforts should be made to improve the collaboration and coordination between centers, to prevent further diffusion of CR-Kp

Tigecycline use in serious nosocomial infections: a drug use evaluation

<p>Abstract</p> <p>Background</p> <p>Tigecycline is a novel antibiotic with activity against multidrug resistant bacteria. The aim of this study was to assess the efficacy of tigecycline use in serious hospital-acquired infections (HAI)</p> <p>Case presentation</p> <p>Prospective observational study of tigecycline use was conducted in a 1500 beds university hospital. From January 1, 2007 and January 31, 2010, 207 pts were treated with tigecycline for the following indications: intra-abdominal, pneumonia, bloodstream and complicated skin and soft tissue infections and febrile neutropenia. The therapy was targeted in 130/207 (63%) and empirical in 77/207 (37%) patients. All bacteria treated were susceptible to tigecycline. Median duration of tigecycline therapy was 13 days (range, 6-28). Clinical success was obtained in 151/207 (73%) cases, with the highest success rate recorded in intra-abdominal infections [81/99 (82%)]. Microbiological success was achieved in 100/129 (78%) treated patients. Adverse clinical events were seen in 16/207 patients (7.7%):</p> <p>Conclusions</p> <p>Considering the lack of data on tigecycline for critically ill patients, we think that the reported data of our clinical experience despite some limitations can be useful for clinicians.</p

Hypoalbuminemia as a predictor of acute kidney injury during colistin treatment

This study aimed to assess the predictors of acute kidney injury (AKI) during colistin therapy in a cohort of patients with bloodstream infections (BSI) due to colistin-susceptible Gram-negative bacteria, focusing on the role of serum albumin levels. The study consisted of two parts: (1) a multicentre retrospective clinical study to assess the predictors of AKI during colistin therapy, defined according to the Kidney Disease: Improving Global Outcomes (KDIGO) criteria; and (2) bioinformatic and biochemical characterization of the possible interaction between human serum albumin and colistin. Among the 170 patients included in the study, 71 (42%), 35 (21%), and 11 (6%) developed KDIGO stage 1 (K1-AKI), KDIGO stage 2 (K2-AKI), and KDIGO stage 3 (K3-AKI), respectively. In multivariable analyses, serum albumin &lt;2.5 g/dL was independently associated with K1-AKI (subdistribution hazard ratio [sHR] 1.85, 95% confidence interval [CI] 1.17\u20132.93, p = 0.009) and K2-AKI (sHR 2.37, 95% CI 1.15\u20134.87, p = 0.019). Bioinformatic and biochemical analyses provided additional information nurturing the discussion on how hypoalbuminemia favors development of AKI during colistin therapy. In conclusion, severe hypoalbuminemia independently predicted AKI during colistin therapy in a large cohort of patients with BSI due to colistin-susceptible Gram-negative bacteria. Further study is needed to clarify the underlying causal pathways

Combined use of serum (1,3)-\u3b2-D-glucan and procalcitonin for the early differential diagnosis between candidaemia and bacteraemia in intensive care units

BACKGROUND: This study aimed to assess the combined performance of serum (1,3)-\u3b2-D-glucan (BDG) and procalcitonin (PCT) for the differential diagnosis between candidaemia and bacteraemia in three intensive care units (ICUs) in two large teaching hospitals in Italy. METHODS: From June 2014 to December 2015, all adult patients admitted to the ICU who had a culture-proven candidaemia or bacteraemia, as well as BDG and PCT measured closely to the time of the index culture, were included in the study. The diagnostic performance of BDG and PCT, used either separately or in combination, was assessed by calculating the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and positive and negative likelihood ratios (LR+ and LR-). Changes from pre-test probabilities to post-test probabilities of candidaemia and bacteraemia were inferred from Fagan's nomograms. RESULTS: One hundred and sixty-six patients were included, 73 with candidaemia (44%) and 93 with bacteraemia (56%). When both markers indicated candidaemia (BDG 6580 pg/ml and PCT &lt;2 ng/ml) they showed higher PPV (96%) compared to 79% and 66% for BDG or PCT alone, respectively. When both markers indicated bacteraemia (BDG &lt;80 pg/ml and PCT 652 ng/ml), their NPV for candidaemia was similar to that of BDG used alone (95% vs. 93%). Discordant BDG and PCT results (i.e. one indicating candidaemia and the other bacteraemia) only slightly altered the pre-test probabilities of the two diseases. CONCLUSIONS: The combined use of PCT and BDG could be helpful in the diagnostic workflow for critically ill patients with suspected candidaemia