Ventilator-associated pneumonia (VAP) is the most frequent life-threatening nosocomial infection in intensive care units. The diagnostic is difficult because radiological and clinical signs are ...inaccurate and could be associated with various respiratory diseases. The concept of infection-related ventilator-associated complication has been proposed as a surrogate of VAP to be used as a benchmark indicator of quality of care. Indeed, bundles of prevention measures are effective in decreasing the VAP rate. In case of VAP suspicion, respiratory secretions must be collected for bacteriological secretions before any new antimicrobials. Quantitative distal bacteriological exams may be preferable for a more reliable diagnosis and therefore a more appropriate use antimicrobials. To improve the prognosis, the treatment should be adequate as soon as possible but should avoid unnecessary broad-spectrum antimicrobials to limit antibiotic selection pressure. For empiric treatments, the selection of antimicrobials should consider the local prevalence of microorganisms along with their associated susceptibility profiles. Critically ill patients require high dosages of antimicrobials and more specifically continuous or prolonged infusions for beta-lactams. After patient stabilization, antimicrobials should be maintained for 7-8 days. The evaluation of VAP treatment based on 28-day mortality is being challenged by regulatory agencies, which are working on alternative surrogate endpoints and on trial design optimization.
Summary Background Reduced duration of antibiotic treatment might contain the emergence of multidrug-resistant bacteria in intensive care units. We aimed to establish the effectiveness of an ...algorithm based on the biomarker procalcitonin to reduce antibiotic exposure in this setting. Methods In this multicentre, prospective, parallel-group, open-label trial, we used an independent, computer-generated randomisation sequence to randomly assign patients in a 1:1 ratio to procalcitonin (n=311 patients) or control (n=319) groups; investigators were masked to assignment before, but not after, randomisation. For the procalcitonin group, antibiotics were started or stopped based on predefined cut-off ranges of procalcitonin concentrations; the control group received antibiotics according to present guidelines. Drug selection and the final decision to start or stop antibiotics were at the discretion of the physician. Patients were expected to stay in the intensive care unit for more than 3 days, had suspected bacterial infections, and were aged 18 years or older. Primary endpoints were mortality at days 28 and 60 (non-inferiority analysis), and number of days without antibiotics by day 28 (superiority analysis). Analyses were by intention to treat. The margin of non-inferiority was 10%. This trial is registered with ClinicalTrials.gov , number NCT00472667. Findings Nine patients were excluded from the study; 307 patients in the procalcitonin group and 314 in the control group were included in analyses. Mortality of patients in the procalcitonin group seemed to be non-inferior to those in the control group at day 28 (21·2% 65/307 vs 20·4% 64/314; absolute difference 0·8%, 90% CI −4·6 to 6·2) and day 60 (30·0% 92/307 vs 26·1% 82/314; 3·8%, −2·1 to 9·7). Patients in the procalcitonin group had significantly more days without antibiotics than did those in the control group (14·3 days SD 9·1 vs 11·6 days SD 8·2; absolute difference 2·7 days, 95% CI 1·4 to 4·1, p<0·0001). Interpretation A procalcitonin-guided strategy to treat suspected bacterial infections in non-surgical patients in intensive care units could reduce antibiotic exposure and selective pressure with no apparent adverse outcomes. Funding Assistance Publique-Hôpitaux de Paris, France, and Brahms, Germany.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Acute respiratory infections (ARIs) comprise a large and heterogeneous group of infections including bacterial, viral and other aetiologies. In recent years, procalcitonin - the prohormone of ...calcitonin - has emerged as a promising marker for the diagnosis of bacterial infections and for improving decisions about antibiotic therapy. Several randomised controlled trials (RCTs) have demonstrated the feasibility of using procalcitonin for starting and stopping antibiotics in different patient populations with acute respiratory infections and different settings ranging from primary care to emergency departments (EDs), hospital wards and intensive care units (ICUs).
The aim of this systematic review based on individual patient data was to assess the safety and efficacy of using procalcitonin for starting or stopping antibiotics over a large range of patients with varying severity of ARIs and from different clinical settings.
We searched the Cochrane Central Register of Controlled Trials (CENTRAL 2011, Issue 2) which contains the Acute Respiratory Infections Group's Specialised Register, MEDLINE (1966 to May 2011) and EMBASE (1974 to May 2011) to identify suitable trials.
We included RCTs of adult participants with ARIs who received an antibiotic treatment either based on a procalcitonin algorithm or usual care/guidelines. Trials were excluded if they exclusively focused on paediatric patients or if they used procalcitonin for another purpose than to guide initiation and duration of antibiotic treatment.
Two teams of review authors independently evaluated the methodology and extracted data from primary studies. The primary endpoints were all-cause mortality and treatment failure at 30 days. For the primary care setting, treatment failure was defined as death, hospitalisation, ARI-specific complications, recurrent or worsening infection, and patients reporting any symptoms of an ongoing respiratory infection at follow-up. For the ED setting, treatment failure was defined as death, ICU admission, re-hospitalisation after index hospital discharge, ARI-associated complications, and recurrent or worsening infection within 30 days of follow-up. For the ICU setting, treatment failure was defined as death within 30 days of follow-up. Secondary endpoints were antibiotic use (initiation of antibiotics, duration of antibiotics and total exposure to antibiotics (total amount of antibiotic days divided by total number of patients)), length of hospital stay for hospitalised patients, length of ICU stay for critically ill patients, and number of days with restricted activities within 14 days after randomisation for primary care patients.For the two co-primary endpoints of all-cause mortality and treatment failure, we calculated odds ratios (ORs) and 95% confidence intervals (CIs) using multivariable hierarchical logistic regression. The hierarchical regression model was adjusted for age and clinical diagnosis as fixed-effect. The different trials were added as random-effects into the model. We fitted corresponding linear regression models for antibiotic use. We conducted sensitivity analyses stratified by clinical setting and ARI diagnosis to assess the consistency of our results.
We included 14 trials with 4221 participants. There were 118 deaths in 2085 patients (5.7%) assigned to procalcitonin groups compared to 134 deaths in 2126 control patients (6.3%) (adjusted OR 0.94, 95% CI 0.71 to 1.23). Treatment failure occurred in 398 procalcitonin group patients (19.1%) and in 466 control patients (21.9%). Procalcitonin guidance was not associated with increased mortality or treatment failure in any clinical setting, or ARI diagnosis. These results proved robust in various sensitivity analyses. Total antibiotic exposure was significantly reduced overall (median (interquartile range) from 8 (5 to 12) to 4 (0 to 8) days; adjusted difference in days, -3.47, 95% CI -3.78 to -3.17, and across all the different clinical settings and diagnoses.
Use of procalcitonin to guide initiation and duration of antibiotic treatment in patients with ARI was not associated with higher mortality rates or treatment failure. Antibiotic consumption was significantly reduced across different clinical settings and ARI diagnoses. Further high-quality research is needed to confirm the safety of this approach for non-European countries and patients in intensive care. Moreover, future studies should also establish cost-effectiveness by considering country-specific costs of procalcitonin measurement and potential savings in consumption of antibiotics and other healthcare resources, as well as secondary cost savings due to lower risk of side effects and reduced antimicrobial resistance.
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NUK, OILJ, UL, UM, UPUK, VSZLJ
The widespread use of combination antiretroviral therapies (cART) has converted the prognosis of HIV infection from a rapidly progressive and ultimately fatal disease to a chronic condition with ...limited impact on life expectancy. Yet, HIV-infected patients remain at high risk for critical illness due to the occurrence of severe opportunistic infections in those with advanced immunosuppression (i.e., inaugural admissions or limited access to cART), a pronounced susceptibility to bacterial sepsis and tuberculosis at every stage of HIV infection, and a rising prevalence of underlying comorbidities such as chronic obstructive pulmonary diseases, atherosclerosis or non-AIDS-defining neoplasms in cART-treated patients aging with controlled viral replication. Several patterns of intensive care have markedly evolved in this patient population over the late cART era, including a steady decline in AIDS-related admissions, an opposite trend in admissions for exacerbated comorbidities, the emergence of additional drivers of immunosuppression (e.g., anti-neoplastic chemotherapy or solid organ transplantation), the management of cART in the acute phase of critical illness, and a dramatic progress in short-term survival that mainly results from general advances in intensive care practices. Besides, there is a lack of data regarding other features of ICU and post-ICU care in these patients, especially on the impact of sociological factors on clinical presentation and prognosis, the optimal timing of cART introduction in AIDS-related admissions, determinants of end-of-life decisions, long-term survival, and functional outcomes. In this narrative review, we sought to depict the current evidence regarding the management of HIV-infected patients admitted to the intensive care unit.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Data in the literature about HSV reactivation in COVID-19 patients are scarce, and the association between HSV-1 reactivation and mortality remains to be determined. Our objectives were to evaluate ...the impact of Herpes simplex virus (HSV) reactivation in patients with severe SARS-CoV-2 infections primarily on mortality, and secondarily on hospital-acquired pneumonia/ventilator-associated pneumonia (HAP/VAP) and intensive care unit-bloodstream infection (ICU-BSI).
We conducted an observational study using prospectively collected data and HSV-1 blood and respiratory samples from all critically ill COVID-19 patients in a large reference center who underwent HSV tests. Using multivariable Cox and cause-specific (cs) models, we investigated the association between HSV reactivation and mortality or healthcare-associated infections.
Of the 153 COVID-19 patients admitted for ≥ 48 h from Feb-2020 to Feb-2021, 40/153 (26.1%) patients had confirmed HSV-1 reactivation (19/61 (31.1%) with HSV-positive respiratory samples, and 36/146 (24.7%) with HSV-positive blood samples. Day-60 mortality was higher in patients with HSV-1 reactivation (57.5%) versus without (33.6%, p = 0.001). After adjustment for mortality risk factors, HSV-1 reactivation was associated with an increased mortality risk (hazard risk HR 2.05; 95% CI 1.16-3.62; p = 0.01). HAP/VAP occurred in 67/153 (43.8%) and ICU-BSI in 42/153 (27.5%) patients. In patients with HSV-1 reactivation, multivariable cause-specific models showed an increased risk of HAP/VAP (csHR 2.38, 95% CI 1.06-5.39, p = 0.037), but not of ICU-BSI.
HSV-1 reactivation in critically ill COVID-19 patients was associated with an increased risk of day-60 mortality and HAP/VAP.
Background. Procalcitonin algorithms may reduce antibiotic use for acute respiratory tract infections (ARIs). We undertook an individual patient data meta-analysis to assess safety of this approach ...in different ARI diagnoses and different clinical settings. Methods. We identified clinical trials in which patients with ARI were assigned to receive antibiotics based on a procalcitonin algorithm or usual care by searching the Cochrane Register, MEDLINE, and EMBASE. Individual patient data from 4221 adults with ARIs in 14 trials were verified and reanalyzed to assess risk of mortality and treatment failure—overall and within different clinical settings and types of ARIs. Results. Overall, there were 118 deaths in 2085 patients (5.7%) assigned to procalcitonin groups compared with 134 deaths in 2126 control patients (6.3%; adjusted odds ratio, 0.94; 95% confidence interval CI, .71–1.23). Treatment failure occurred in 398 procalcitonin group patients (19.1%) and in 466 control patients (21.9%; adjusted odds ratio, 0.82; 95% CI, .71–.97). Procalcitonin guidance was not associated with increased mortality or treatment failure in any clinical setting or ARI diagnosis. Total antibiotic exposure per patient was significantly reduced overall (median interquartile range, from 8 5–12 to 4 0–8 days; adjusted difference in days, −3.47 95% CI, −3.78 to −3.17) and across all clinical settings and ARI diagnoses. Conclusions. Use of procalcitonin to guide initiation and duration of antibiotic treatment in patients with ARIs was effective in reducing antibiotic exposure across settings without an increase in the risk of mortality or treatment failure. Further high-quality trials are needed in critical-care patients.
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BFBNIB, NUK, PNG, UL, UM, UPUK
To analyze the impact of chronic kidney disease (CKD) on major clinical outcome in SLE by using a nationwide database.
Characteristics of all admitted SLE patients experiencing CKD (eGFR ...<60 mL/min/1.73 m2) in France from 2009 to 2015 were analyzed through the French medico- administrative database. Factors associated with CKD and major clinical outcomes such as end-stage renal disease (ESRD), cardiovascular event (CVE), septic shock and death were assessed. We used a multivariate Cox proportional hazard model and subdistribution hazard models to analyze survival without major clinical events according to the presence of CKD.
From 2009 to 2015, 26,320 SLE patients were hospitalized in France. Among them, 6439 (86.5% women; mean age 45.7 16.5 years old) had a baseline stay in 2009 during which CKD was reported in 428 (6.7%) cases. Multivariate analysis showed that lupus nephritis (OR 6.6 5.2–8.4), high blood pressure (OR 3.5 2.8–4.5), septic shock (OR 3.2 1.7–6.0) and past cardiovascular history (OR 1.4 1.0–2.0) were associated with CKD status. From 2009 to 2015, ESRD, CVE, septic shock, and death occurred in 4.0%, 14.4%, 6.3% and 9.6% of the 6439 SLE patients. CKD at baseline was independently and strongly associated with the occurrence of ESRD (sdHR 15.9 11.6–21.9), CVE (sdHR 1.7 1.4–2.2), septic shock (sdHR 2.1 1.5–2.8) and death (HR 1.7 1.3–2.2) during the follow up.
CKD is a major risk factor for overall morbidity and mortality in SLE patients, highlighting the need for early pre-CKD lupus nephritis diagnosis and treatment.
•Nationwide database analysis of major outcomes in SLE was performed.•CKD is a major risk factor for overall morbidity and mortality in SLE.•Early pre-CKD lupus nephritis diagnosis and treatment is mandatory.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background
Sepsis is one of the leading causes of death worldwide. The associated incidence, mortality and trends do not differ greatly between documented reports. The purpose of this study was to ...provide an in-depth description of patients with sepsis and septic shock hospitalized in France from 2010 to 2015 and to explore the temporal trends of their clinical characteristics, costs and outcomes.
Methods
Retrospective cohort study of the French hospital administrative database in which organ failure therapies and severity scores are systematically registered. All patients admitted between 2010 and 2015 for sepsis and septic shock as defined by an ICD-10 code for infection, and for organ failure or the use of organ failure supplementation were included. Incidence, outcomes and trends were analyzed. Subgroup analyses based on several coding strategies and adjusted for severity scores were performed.
Results
A total of 737,147 patients with sepsis and 492,902 patients with septic shock were included. From 2010 to 2015, the incidence of sepsis and septic shock increased, respectively, from 206 to 243 and from 135 to 171 cases per 100,000 population. Case fatality remained at 34% for sepsis, but decreased from 46 to 44% for septic shock.
Median hospital stay costs amounted to €11,400 (IQR: 5036; 24,364) for patients with sepsis and €16,439 (IQR: 7339; 29,360) for patients with septic shock.
After adjustment for case-mix and illness severity, the risk of death was stable for sepsis (0.08% − 0.04; 0.20 per year), but decreased for sepsis patients admitted to the intensive care unit and for cases of septic shock (− 0.33% − 0.40; − 0.27 per year).
Conclusions
Sepsis is common, frequently fatal and expensive to treat. Its incidence has increased. Case fatality has decreased in most severely affected patients, owing partly to general improvements in care.
Increasing experimental evidence suggests that acute respiratory distress syndrome (ARDS) may promote AKI. The primary objective of this study was to assess ARDS as a risk factor for AKI in ...critically ill patients.
This was an observational study on a prospective database fed by 18 intensive care units (ICUs). Patients with ICU stays >24 hours were enrolled over a 14-year period. ARDS was defined using the Berlin criteria and AKI was defined using the Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease criteria. Patients with AKI before ARDS onset were excluded.
This study enrolled 8029 patients, including 1879 patients with ARDS. AKI occurred in 31.3% of patients and was more common in patients with ARDS (44.3% versus 27.4% in patients without ARDS; P<0.001). After adjustment for confounders, both mechanical ventilation without ARDS (odds ratio OR, 4.34; 95% confidence interval 95% CI, 3.71 to 5.10) and ARDS (OR, 11.01; 95% CI, 6.83 to 17.73) were independently associated with AKI. Hospital mortality was 14.2% (n=1140) and was higher in patients with ARDS (27.9% versus 10.0% in patients without ARDS; P<0.001) and in patients with AKI (27.6% versus 8.1% in those without AKI; P<0.001). AKI was associated with higher mortality in patients with ARDS (42.3% versus 20.2%; P<0.001).
ARDS was independently associated with AKI. This study suggests that ARDS should be considered as a risk factor for AKI in critically ill patients.
Purpose
Noninvasive ventilation (NIV) had proven benefits in clinical trials that included selected patients admitted to highly skilled centers. Whether these benefits apply to every patient and in ...everyday practice deserves appraisal. The aim of the study was to assess the use and outcomes of NIV over the last 15 years.
Methods
Multicenter database study of critically ill patients who required ventilatory support for acute respiratory failure between 1997 and 2011. The impact of first-line NIV on 60-day mortality was evaluated using a marginal structural model. Follow-up was censored on day 60.
Results
Of 3,163 patients, 1,232 (39 %) received NIV. Over the study period, first-line NIV increased from 29 to 42 %, and NIV success rates increased from 69 to 84 %. NIV decreased 60-day mortality adjusted hazard ratio (aHR), 0.75; 95 % confidence interval (95 % CI), 0.68–0.83;
P
< 0.0001. This protective effect was observed in patients with acute-on-chronic respiratory failure (aHR, 0.71; 95 % CI, 0.57–0.90;
P
= 0.004), but not in patients with cardiogenic pulmonary edema (aHR, 0.85; 95 % CI, 0.70–1.03;
P
= 0.10) or in patients with hypoxemic ARF, either immunocompetent (aHR, 1.18; 95 % CI, 0.87–1.59;
P
= 0.30) or immunocompromised (aHR, 0.89; 95 % CI, 0.70–1.13;
P
= 0.35). NIV failure was an independent time-dependent risk factor for mortality (aHR, 4.2; 95 % CI, 2.8–6.2;
P
< 0.0001).
Conclusions
The use of NIV increased steadily over the study period. First-line NIV was associated with better 60-day survival and fewer ICU-acquired infections compared to first-line intubation. Survival benefits from NIV occurred only in patients with acute-on-chronic respiratory failure and immunocompromised patients.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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