Long-Term Effects of a Stepwise, Multimodal, Non-Restrictive Antimicrobial Stewardship Programme for Reducing Broad-Spectrum Antibiotic Use in the ICU.

Information on the long-term effects of non-restrictive antimicrobial stewardship (AMS) strategies is scarce. We assessed the effect of a stepwise, multimodal, non-restrictive AMS programme on broad-spectrum antibiotic use in the intensive care unit (ICU) over an 8-year period. Components of the AMS were progressively implemented. Appropriateness of antibiotic prescribing was also assessed by monthly point-prevalence surveys from 2013 onwards. A Poisson regression model was fitted to evaluate trends in the reduction of antibiotic use and in the appropriateness of their prescription. From 2011 to 2019, a total of 12,466 patients were admitted to the ICU. Antibiotic use fell from 185.4 to 141.9 DDD per 100 PD [absolute difference, -43.5 (23%), 95% CI -100.73 to 13.73; p = 0.13] and broad-spectrum antibiotic fell from 41.2 to 36.5 [absolute difference, -4.7 (11%), 95% CI -19.58 to 10.18; p = 0.5]. Appropriateness of antibiotic prescribing rose by 11% per year [IRR: 0.89, 95% CI 0.80 to 1.00; p = 0.048], while broad-spectrum antibiotic use showed a dual trend, rising by 22% until 2015 and then falling by 10% per year since 2016 [IRR: 0.90, 95% CI 0.81 to 0.99; p = 0.03]. This stepwise, multimodal, non-restrictive AMS achieved a sustained reduction in broad-spectrum antibiotic use in the ICU and significantly improved appropriateness of antibiotic prescribing.

Development and validation of a measurement procedure based on ultra-high performance liquid chromatography-tandem mass spectrometry for simultaneous measurement of ß-lactam antibiotic concentration in human plasma.

BACKGROUND: The administration of ß-lactam antibiotics in continuous infusion could let optimize the pharmacokinetic/pharmacodynamic parameters, especially in the treatment of serious bacterial infections. In this context, and also due to variability in their plasmatic concentrations, therapeutic drug monitoring (TDM) may be useful to optimize dosing and, therefore, be useful for the clinicians. MATERIAL AND METHODS: We developed and validated a measurement procedure based on ultra-high performance liquid chromatography-tandem mass spectrometry for simultaneous measurement of amoxicillin, ampicillin, cloxacillin, piperacillin, cefepime, ceftazidime, cefuroxime, aztreonam and meropenem concentrations in plasma. The chromatographic separation was achieved using an Acquity®-UPLC® BEH™ (2.1×100mm id, 1.7µm) reverse-phase C18 column, with a water/acetonitrile linear gradient containing 0.1% formic acid at a 0.4mL/min flow rate. ß-Lactam antibiotics and their internal standards were detected by electrospray ionization mass spectrometry in multiple reaction monitoring mode. RESULTS: Chromatography run time was 7.0min and ß-lactam antibiotics eluted at retention times ranging between 1.08 and 1.91min. The lower limits of quantification were between 0.50 and 1.00mg/L. Coefficients of variation and relative bias absolute values were <13.3% and 14.7%, respectively. Recovery values ranged from 55.7% to 84.8%. Evaluation of the matrix effect showed ion enhancement for all antibiotics. No interferences or carry-over were observed. CONCLUSIONS: Our measurement procedure could be applied to daily clinical laboratory practice to measure the concentration of ß-lactam antibiotics in plasma, for instance in patients with bone and joint infections and critically ill patients.

Control of endemic extensively drug-resistant Acinetobacter baumannii with a cohorting policy and cleaning procedures based on the 1 room, 1 wipe approach.

BACKGROUND: Our institution experienced an endemic situation with extensively drug-resistant (XDR) Acinetobacter baumannii in the intensive care units (ICUs). Here, we describe the long-term results of the implementation of a screening and cohorting policy and new cleaning techniques based on a procedure that we call the 1 room, 1 wipe approach. METHODS: We conducted a 4-year quasi-experimental study in the ICUs of an 800-bed teaching hospital. The main actions implemented were active surveillance of XDR A baumannii and cohorting of carriers and introducing new cleaning techniques intended to avoid sharing wipes between rooms. RESULTS: XDR A baumannii significantly decreased from 132 cases in 2011 to 8 cases in 2014 and from 10.78 cases per 1,000 patient days in 2011 to 0.69 cases per 1,000 patient days in 2014. Segmented regression analysis showed that after implementing the measures, the monthly rates presented a sustained negative slope, with a significant change of -0.623 (P = .002). CONCLUSIONS: The prompt identification and isolation of patients and adequate environmental cleaning are effective measures for reducing XDR A baumannii in ICUs. The 1 wipe, 1 room approach should be considered a standard measure for cleaning hospital facilities to avoid cross-transmission as a result of reusable cleaning wipes.

Epidemiology, clinical features, and prognosis of elderly adults with severe forms of influenza A (H1N1.

OBJECTIVES: To examine epidemiological and clinical data of individuals aged 65 and older with influenza virus A (H1N1) admitted to the intensive care unit (ICU) and to identify independent predictors of ICU mortality. DESIGN: Prospective, observational, multicenter study to determine prognostic factors in individuals infected with influenza A (H1N1) admitted to the ICU. SETTING: One hundred forty-eight Spanish ICUs. PARTICIPANTS: Individuals with influenza A (H1N1) confirmed using real-time polymerase chain reaction from April 2009 to July 2011. MEASUREMENTS: Individuals aged 65 and older were compared with younger individuals. A multivariate analysis was conducted to determine independent predictors of mortality in this population. RESULTS: One thousand one hundred twenty individuals (129 (11.5%) aged 65) were included. Prevalence of chronic diseases was more common in older individuals. Viral pneumonitis was more frequent in individuals younger than 65 (70.5% vs 54.3%, P < .001). In older individuals, Acute Physiology and Chronic Health Evaluation II score (odds ratio (OR) = 1.11, 95% confidence interval (CI) = 1.11­1.20, P = .002), immunosuppression (OR = 3.66, 95% CI, 1.33­10.03, P = .01) and oseltamivir therapy initiated after 48 hours (OR = 3.32, 95% CI = 1.02­10.8, P = .04) were identified as independent variables associated with mortality. Corticosteroid use was associated with a trend toward greater mortality (OR = 2.39, 95% CI = 0.98­5.91, P = .06). CONCLUSION: Individuals aged 65 and older with influenza A (H1N1) admitted to the ICU have a higher incidence of underlying diseases than younger individuals and differences in clinical presentation. Early oseltamivir therapy is associated with better outcomes in elderly adults.

Ventilatory support in critically ill hematology patients with respiratory failure.

INTRODUCTION: Hematology patients admitted to the ICU frequently experience respiratory failure and require mechanical ventilation. Noninvasive mechanical ventilation (NIMV) may decrease the risk of intubation, but NIMV failure poses its own risks. METHODS: To establish the impact of ventilatory management and NIMV failure on outcome, data from a prospective, multicenter, observational study were analyzed. All hematology patients admitted to one of the 34 participating ICUs in a 17-month period were followed up. Data on demographics, diagnosis, severity, organ failure, and supportive therapies were recorded. A logistic regression analysis was done to evaluate the risk factors associated with death and NIVM failure. RESULTS: Of 450 patients, 300 required ventilatory support. A diagnosis of congestive heart failure and the initial use of NIMV significantly improved survival, whereas APACHE II score, allogeneic transplantation, and NIMV failure increased the risk of death. The risk factors associated with NIMV success were age, congestive heart failure, and bacteremia. Patients with NIMV failure experienced a more severe respiratory impairment than did those electively intubated. CONCLUSIONS: NIMV improves the outcome of hematology patients with respiratory insufficiency, but NIMV failure may have the opposite effect. A careful selection of patients with rapidly reversible causes of respiratory failure may increase NIMV success.

Pandemic and post-pandemic influenza A (H1N1) infection in critically ill patients.

BACKGROUND: There is a vast amount of information published regarding the impact of 2009 pandemic Influenza A (pH1N1) virus infection. However, a comparison of risk factors and outcome during the 2010-2011 post-pandemic period has not been described. METHODS: A prospective, observational, multi-center study was carried out to evaluate the clinical characteristics and demographics of patients with positive RT-PCR for H1N1 admitted to 148 Spanish intensive care units (ICUs). Data were obtained from the 2009 pandemic and compared to the 2010-2011 post-pandemic period. RESULTS: Nine hundred and ninety-seven patients with confirmed An/H1N1 infection were included. Six hundred and forty-eight patients affected by 2009 (pH1N1) virus infection and 349 patients affected by the post-pandemic Influenza (H1N1)v infection period were analyzed. Patients during the post-pandemic period were older, had more chronic comorbid conditions and presented with higher severity scores (Acute Physiology And Chronic Health Evaluation II (APACHE II) and Sequential Organ Failure Assessment (SOFA)) on ICU admission. Patients from the post-pandemic Influenza (H1N1)v infection period received empiric antiviral treatment less frequently and with delayed administration. Mortality was significantly higher in the post-pandemic period. Multivariate analysis confirmed that haematological disease, invasive mechanical ventilation and continuous renal replacement therapy were factors independently associated with worse outcome in the two periods. HIV was the only new variable independently associated with higher ICU mortality during the post-pandemic Influenza (H1N1)v infection period. CONCLUSION: Patients from the post-pandemic Influenza (H1N1)v infection period had an unexpectedly higher mortality rate and showed a trend towards affecting a more vulnerable population, in keeping with more typical seasonal viral infection.

Acute kidney injury in critical ill patients affected by influenza A (H1N1) virus infection.

INTRODUCTION: Little information exists about the impact of acute kidney injury (AKI) in critically ill patients with the pandemic 2009 influenza A (H1N1) virus infection. METHODS: We conducted a prospective, observational, multicenter study in 148 Spanish intensive care units (ICUs). Patients with chronic renal failure were excluded. AKI was defined according to Acute Kidney Injury Network (AKIN) criteria. RESULTS: A total of 661 patients were analyzed. One hundred eighteen (17.7%) patients developed AKI; of these, 37 (31.4%) of the patients with AKI were classified as AKI I, 15 (12.7%) were classified as AKI II and 66 (55.9%) were classified as AKI III, among the latter of whom 50 (75.7%) required continuous renal replacement therapy. Patients with AKI had a higher Acute Physiology and Chronic Health Evaluation II score (19.2 ± 8.3 versus 12.6 ± 5.9; P < 0.001), a higher Sequential Organ Failure Assessment score (8.7 ± 4.2 versus 4.8 ± 2.9; P < 0.001), more need for mechanical ventilation (MV) (87.3% versus 56.2%; P < 0.01, odds ratio (OR) 5.3, 95% confidence interval (CI) 3.0 to 9.4), a greater incidence of shock (75.4% versus 38.3%; P < 0.01, OR 4.9, 95% CI, 3.1 to 7.7), a greater incidence of multiorgan dysfunction syndrome (92.4% versus 54.7%; P < 0.01, OR 10.0, 95% CI, 4.9 to 20.21) and a greater incidence of coinfection (23.7% versus 14.4%; P < 0.01, OR 1.8, 95% CI, 1.1 to 3.0). In survivors, patients with AKI remained on MV longer and ICU and hospital length of stay were longer than in patients without AKI. The overall mortality was 18.8% and was significantly higher for AKI patients (44.1% versus 13.3%; P < 0.01, OR 5.1, 95% CI, 3.3 to 7.9). Logistic regression analysis was performed with AKIN criteria, and it demonstrated that among patients with AKI, only AKI III was independently associated with higher ICU mortality (P < 0.001, OR 4.81, 95% CI 2.17 to 10.62). CONCLUSIONS: In our cohort of patients with H1N1 virus infection, only those cases in the AKI III category were independently associated with mortality.

Community-acquired respiratory coinfection in critically ill patients with pandemic 2009 influenza A(H1N1) virus.

BACKGROUND: Little is known about the impact of community-acquired respiratory coinfection in patients with pandemic 2009 influenza A(H1N1) virus infection. METHODS: This was a prospective, observational, multicenter study conducted in 148 Spanish ICUs. RESULTS: Severe respiratory syndrome was present in 645 ICU patients. Coinfection occurred in 113 (17.5%) of patients. Streptococcus pneumoniae (in 62 patients [54.8%]) was identified as the most prevalent bacteria. Patients with coinfection at ICU admission were older (47.5±15.7 vs 43.8±14.2 years, P<.05) and presented a higher APACHE (Acute Physiology and Chronic Health Evaluation) II score (16.1±7.3 vs 13.3±7.1, P<.05) and Sequential Organ Failure Assessment (SOFA) score (7.0±3.8 vs 5.2±3.5, P<.05). No differences in comorbidities were observed. Patients who had coinfection required vasopressors (63.7% vs 39.3%, P<.05) and invasive mechanical ventilation (69% vs 58.5%, P<.05) more frequently. ICU length of stay was 3 days longer in patients who had coinfection than in patients who did not (11 [interquartile range, 5-23] vs 8 [interquartile range 4-17], P=.01). Coinfection was associated with increased ICU mortality (26.2% vs 15.5%; OR, 1.94; 95% CI, 1.21-3.09), but Cox regression analysis adjusted by potential confounders did not confirm a significant association between coinfection and ICU mortality. CONCLUSIONS: During the 2009 pandemics, the role played by bacterial coinfection in bringing patients to the ICU was not clear, S pneumoniae being the most common pathogen. This work provides clear evidence that bacterial coinfection is a contributor to increased consumption of health resources by critical patients infected with the virus and is the virus that causes critical illness in the vast majority of cases.

Intensive care adult patients with severe respiratory failure caused by Influenza A (H1N1)v in Spain.

INTRODUCTION: Patients with influenza A (H1N1)v infection have developed rapidly progressive lower respiratory tract disease resulting in respiratory failure. We describe the clinical and epidemiologic characteristics of the first 32 persons reported to be admitted to the intensive care unit (ICU) due to influenza A (H1N1)v infection in Spain. METHODS: We used medical chart reviews to collect data on ICU adult patients reported in a standardized form. Influenza A (H1N1)v infection was confirmed in specimens using real-time reverse transcriptase-polymerase-chain-reaction (RT PCR) assay. RESULTS: Illness onset of the 32 patients occurred between 23 June and 31 July, 2009. The median age was 36 years (IQR = 31 - 52). Ten (31.2%) were obese, 2 (6.3%) pregnant and 16 (50%) had pre-existing medical complications. Twenty-nine (90.6%) had primary viral pneumonitis, 2 (6.3%) exacerbation of structural respiratory disease and 1 (3.1%) secondary bacterial pneumonia. Twenty-four patients (75.0%) developed multiorgan dysfunction, 7 (21.9%) received renal replacement techniques and 24 (75.0%) required mechanical ventilation. Six patients died within 28 days, with two additional late deaths. Oseltamivir administration delay ranged from 2 to 8 days after illness onset, 31.2% received high-dose (300 mg/day), and treatment duration ranged from 5 to 10 days (mean 8.0 +/- 3.3). CONCLUSIONS: Over a 5-week period, influenza A (H1N1)v infection led to ICU admission in 32 adult patients, with frequently observed severe hypoxemia and a relatively high case-fatality rate. Clinicians should be aware of pulmonary complications of influenza A (H1N1)v infection, particularly in pregnant and young obese but previously healthy persons.