Impact of antimicrobial stewardship in organisms causing nosocomial infection among COVID-19 critically ill adults.

OBJECTIVE: To evaluate the implementation of an antibiotic stewardship program in critically ill COVID-19 patients and to establish risk factors for coinfection. Secondary objective was to analyze the evolution of the etiology of respiratory nosocomial infections. METHODS: Single-center observational cohort study of consecutive patients admitted to ICU due to COVID-19 pneumonia from March 2020 to October 2022. An antibiotic stewardship program was implemented at the end of the second wave. RESULTS: A total of 878 patients were included during 6 pandemic waves. Empirical antibiotic consumption decreased from the 96% of the patients during the first pandemic wave, mainly in combination (90%) to the 30% of the patients in the 6th pandemic wave most in monotherapy (90%). There were not differences in ICU and Hospital mortality between the different pandemic periods. In multivariate analysis, SOFA at admission was the only independent risk factor for coinfection in critically ill COVID-19 patients (OR 1,23 95%CI 1,14 to 1,35). Differences in bacterial etiology of first nosocomial respiratory infection were observed. There was a progressive reduction in Enterobacteriaceae and non- fermentative Gram Negative Bacilli as responsible pathogens, while methicillin-sensitive Staphylococcus aureus increased during pandemic waves. In the last wave, however, a trend to increase of potentially resistant pathogens was observed. CONCLUSIONS: Implementation of an antibiotic stewardship program was safe and not associated with worse clinical outcomes, being severity at admission the main risk factor for bacterial coinfection in covid-19 patients. A decline in potentially resistant pathogens was documented throughout the pandemic.

Lung microbiome on admission in critically ill patients with acute bacterial and viral pneumonia.

Composition of pulmonary microbiome of patients with severe pneumonia is poorly known. The aim of this work was to analyse the lung microbiome of patients admitted to the intensive care unit  (ICU) with severe community acquired pneumonia (CAP) between 2019 and 2021 in comparison with a control group of 6 patients undergoing digestive surgery. As a second objective, the diagnostic capabilities of metagenomics was also studied in a small group of selected patients. The lung microbiome of patients with viral (5 with Influenza A and 8 with SARS-CoV-2) pneumonia at admission showed a similar diversity as the control group (p = 0.140 and p = 0.213 respectively). Contrarily, the group of 12 patients with pneumococcal pneumonia showed a significant lower Simpson´s index (p = 0.002). In the control group (n = 6) Proteobacteria (36.6%), Firmicutes (24.2%) and Actinobacteria (23.0%) were the predominant phyla. In SARS-CoV-2 patients (n = 8), there was a predominance of Proteobacteria (mean 41.6%) (Moraxella and Pelomonas at the genus level), Actinobacteria (24.6%) (Microbacterium) and Firmicutes (22.8%) mainly Streptococcus, Staphylococcus and Veillonella. In patients with Influenza A pneumonia (n = 5) there was a predominance of Firmicutes (35.1%) mainly Streptococcus followed by Proteobacteria (29.2%) (Moraxella, Acinetobacter and Pelomonas). In the group of pneumococcal pneumonia (n = 12) two phyla predominated: Firmicutes (53.1%) (Streptococcus) and Proteobacteria (36.5%) (Haemophilus). In the 7 patients with non-pneumococcal bacterial pneumonia Haemophilus influenzae (n = 2), Legionella pneumophila (n = 2), Klebsiella pneumoniae, Streptococcus pyogenes and Leptospira were detected by metagenomics, confirming the diagnosis done using conventional microbiological techniques. The diversity of the respiratory microbiome in patients with severe viral pneumonia at ICU admission was similar to that of the control group. Contrarily, patients with pneumococcal pneumonia showed a lower grade of diversity. At initial stages of SARS-CoV-2 infection, no important alterations in the pulmonary microbiome were observed. The analysis of bacterial microbiome showed promising results as a diagnostic tool.

Effectiveness of prolonged versus standard-course of oseltamivir in critically ill patients with severe influenza infection: A multicentre cohort study.

The aim of this study is to investigate the effectiveness of prolonged versus standard course oseltamivir treatment among critically ill patients with severe influenza. A retrospective study of a prospectively collected database including adults with influenza infection admitted to 184 intensive care units (ICUs) in Spain from 2009 to 2018. Prolonged oseltamivir was defined if patients received the treatment beyond 5 days, whereas the standard-course group received oseltamivir for 5 days. The primary outcome was all-cause ICU mortality. Propensity score matching (PSM) was constructed, and the outcome was investigated through Cox regression and RCSs. Two thousand three hundred and ninety-seven subjects were included, of whom 1943 (81.1%) received prolonged oseltamivir and 454 (18.9%) received standard treatment. An optimal full matching algorithm was performed by matching 2171 patients, 1750 treated in the prolonged oseltamivir group and 421 controls in the standard oseltamivir group. After PSM, 387 (22.1%) patients in the prolonged oseltamivir and 119 (28.3%) patients in the standard group died (p = 0.009). After adjusting confounding factors, prolonged oseltamivir significantly reduced ICU mortality (odds ratio [OR]: 0.53, 95% confidence interval [CI]: 0.40-0.69). Prolonged oseltamivir may have protective effects on survival at Day 10 compared with a standard treatment course. Sensitivity analysis confirmed these findings. Compared with standard treatment, prolonged oseltamivir was associated with reduced ICU mortality in critically ill patients with severe influenza. Clinicians should consider extending the oseltamivir treatment duration to 10 days, particularly in higher-risk groups of prolonged viral shedding. Further randomized controlled trials are warranted to confirm these findings.

Early oseltamivir treatment improves survival in critically ill patients with influenza pneumonia.

BACKGROUND: The relationship between early oseltamivir treatment (within 48 h of symptom onset) and mortality in patients admitted to intensive care units (ICUs) with severe influenza is disputed. This study aimed to investigate the association between early oseltamivir treatment and ICU mortality in critically ill patients with influenza pneumonia. METHODS: This was an observational study of patients with influenza pneumonia admitted to 184 ICUs in Spain during 2009-2018. The primary outcome was to evaluate the association between early oseltamivir treatment and ICU mortality compared with later treatment. Secondary outcomes were to compare the duration of mechanical ventilation and ICU length of stay between the early and later oseltamivir treatment groups. To reduce biases related to observational studies, propensity score matching and a competing risk analysis were performed. RESULTS: During the study period, 2124 patients met the inclusion criteria. All patients had influenza pneumonia and received oseltamivir before ICU admission. Of these, 529 (24.9%) received early oseltamivir treatment. In the multivariate analysis, early treatment was associated with reduced ICU mortality (OR 0.69, 95% CI 0.51-0.95). After propensity score matching, early oseltamivir treatment was associated with improved survival rates in the Cox regression (hazard ratio 0.77, 95% CI 0.61-0.99) and competing risk (subdistribution hazard ratio 0.67, 95% CI 0.53-0.85) analyses. The ICU length of stay and duration of mechanical ventilation were shorter in patients receiving early treatment. CONCLUSIONS: Early oseltamivir treatment is associated with improved survival rates in critically ill patients with influenza pneumonia, and may decrease ICU length of stay and mechanical ventilation duration.

Human metapneumovirus as cause of severe community-acquired pneumonia in adults: insights from a ten-year molecular and epidemiological analysis.

BACKGROUND: Information on the clinical, epidemiological and molecular characterization of human metapneumovirus in critically ill adult patients with severe community-acquired pneumonia (CAP) and the role of biomarkers identifying bacterial coinfection is scarce. METHODS: This is a retrospective epidemiological study of adult patients with hMPV severe CAP admitted to ICU during a ten-year period with admission PSI score ≥ 3. RESULTS: The 92.8% of the 28 patients with severe CAP due to human metapneumovirus were detected during the first half of the year. Median age was 62 years and 60.7% were male. The genotyping of isolated human metapneumovirus showed group B predominance (60.7%). All patients had acute respiratory failure. Median APACHE II and SOFA score were 13 and 6.55, respectively. The 25% were coinfected with Streptococcus pneumoniae. 60.7% of the patients had shock at admission and 50% underwent mechanical ventilation. Seven patients developed ARDS, three of them younger than 60 years and without comorbidities. Mortality in ICU was 14.3%. Among survivors, ICU and hospital stay were 6.5 and 14 days, respectively. Plasma levels of procalcitonin were higher in patients with bacterial coinfection (18.2 vs 0.54; p < 0.05). The levels of C-reactive protein, however, were similar. CONCLUSION: Human metapneumovirus was associated with severe CAP requiring ICU admission among elderly patients or patients with comorbidities, but also in healthy young subjects. These patients often underwent mechanical ventilation with elevated health resource consumption. While one out of four patients showed pneumococcal coinfection, plasma procalcitonin helped to implement antimicrobial stewardship.

Factors associated with ventilator-associated events: an international multicenter prospective cohort study.

A secondary analysis of a prospective multicenter cohort was performed in six intensive care units (ICU) in four European countries (France, Greece, Spain and Turkey). The main objective was to identify factors associated with ventilator-associated events (VAEs) in adults who underwent mechanical ventilation (MV) ≥ 48 h. Secondary objectives were to identify: variables influencing VAE in the subpopulation with endotracheal intubation and in those subjects who were ventilated > 7 days. Subjects who had undergone MV ≥ 48 h were included. In subjects with multiple episodes of MV, only the first one was eligible. The adult definitions for VAEs were adjusted to the 2015 update of the CDC's 2013 National Healthcare Safety Network Association. Factors associated with VAE were estimated through multivariate Cox proportional hazards analysis. Among 163 adults (42 tracheostomies), 76 VAEs (34.9 VAEs/1,000 ventilator-days) were documented: 9 were Ventilator-Associated Conditions (VAC) and 67 Infection-related Ventilator-Associated Complications (IVAC)-plus (9 only IVAC and 58 Possible Ventilator-Associated Pneumonia). VAEs developed after a median of 6 days (interquartile range: 4-9). VAEs were independently associated with long-acting sedative/analgesic drugs (Hazard Ratio [HR]: 4.30), selective digestive decontamination (SDD) (HR: 0.38), and surgical/trauma admission (HR: 2.30). Among 116 subjects with endotracheal tube, SDD (HR: 0.21) and surgical/trauma admission (HR: 3.11) remained associated with VAE. Among 102 subjects ventilated >7 days, only long-acting sedative/analgesic agents (HR: 8.69) remained independently associated with VAE. In summary, SDD implementation and long-acting analgesic/sedative agents restriction prescription may prevent early and late VAEs, respectively. Bundles developed to prevent VAEs should include these two interventions.

Clinical characteristics, evolution, and treatment-related risk factors for mortality among immunosuppressed patients with influenza A (H1N1) virus admitted to the intensive care unit.

PURPOSE: Information about immunocompromised patients infected with influenza A (H1N1) virus and requiring admission to the ICU is lacking. Our objective was to know the clinical characteristics of these patients and to identify treatment-related variables associated with mortality. MATERIAL AND METHODS: A prospective multicenter observational cohort study was based on data from a Spanish registry (2009-2015) collected by 148 Spanish ICUs. All patients admitted to the ICU with the diagnosis of influenza A (H1N1) virus infection were included. Immunosuppression was clearly defined. Factors associated with mortality in immunocompromised patients were assessed by conventional logistic regression analysis and by a propensity score (PS) adjusted-multivariable analysis. RESULTS: Of 1899 patients with influenza A (H1N1) infection, 238 (12.5%) were classified as immunocompromised. Mortality was significantly higher in immunosuppressed patients. Four variables independently associated with mortality were identified: SOFA score, need of vasopressor, use of corticosteroids, and acute renal failure, AKIN 3 stage. In the PS-adjusted model, corticosteroid therapy remained as an independent factor associated with increased mortality (OR 2.25;95%CI, 1.15-4.38;p = 0.017). In the subgroup of hematological patients (n = 141), corticosteroid therapy was also associated with increased mortality (OR 3.12; 95%CI, 1.32-7.41; p = 0.010). CONCLUSION: Immunocompromised individuals with influenza A (H1N1) admitted to the ICU have a poor outcome. In this population, the use of corticosteroids is strongly discouraged.

Procalcitonin (PCT) levels for ruling-out bacterial coinfection in ICU patients with influenza: A CHAID decision-tree analysis.

OBJECTIVES: To define which variables upon ICU admission could be related to the presence of coinfection using CHAID (Chi-squared Automatic Interaction Detection) analysis. METHODS: A secondary analysis from a prospective, multicentre, observational study (2009-2014) in ICU patients with confirmed A(H1N1)pdm09 infection. We assessed the potential of biomarkers and clinical variables upon admission to the ICU for coinfection diagnosis using CHAID analysis. Performance of cut-off points obtained was determined on the basis of the binominal distributions of the true (+) and true (-) results. RESULTS: Of the 972 patients included, 196 (20.3%) had coinfection. Procalcitonin (PCT; ng/mL 2.4 vs. 0.5, p < 0.001), but not C-reactive protein (CRP; mg/dL 25 vs. 38.5; p = 0.62) was higher in patients with coinfection. In CHAID analyses, PCT was the most important variable for coinfection. PCT <0.29 ng/mL showed high sensitivity (Se = 88.2%), low Sp (33.2%) and high negative predictive value (NPV = 91.9%). The absence of shock improved classification capacity. Thus, for PCT <0.29 ng/mL, the Se was 84%, the Sp 43% and an NPV of 94% with a post-test probability of coinfection of only 6%. CONCLUSION: PCT has a high negative predictive value (94%) and lower PCT levels seems to be a good tool for excluding coinfection, particularly for patients without shock.

Improvement of antibiotic therapy and ICU survival in severe non-pneumococcal community-acquired pneumonia: a matched case-control study.

INTRODUCTION: We aimed to compare intensive care unit mortality due to non-pneumococcal severe community-acquired pneumonia between the periods 2000-2002 and 2008-2014, and the impact of the improvement in antibiotic strategies on outcomes. METHODS: This was a matched case-control study enrolling 144 patients with non-pneumococcal severe pneumonia: 72 patients from the 2000-2002 database (CAPUCI I group) were paired with 72 from the 2008-2014 period (CAPUCI II group), matched by the following variables: microorganism, shock at admission, invasive mechanical ventilation, immunocompromise, chronic obstructive pulmonary disease, and age over 65 years. RESULTS: The most frequent microorganism was methicillin-susceptible Staphylococcus aureus (22.1%) followed by Legionella pneumophila and Haemophilus influenzae (each 20.7%); prevalence of shock was 59.7%, while 73.6% of patients needed invasive mechanical ventilation. Intensive care unit mortality was significantly lower in the CAPUCI II group (34.7% versus 16.7%; odds ratio (OR) 0.78, 95% confidence interval (CI) 0.64-0.95; p = 0.02). Appropriate therapy according to microorganism was 91.5% in CAPUCI I and 92.7% in CAPUCI II, while combined therapy and early antibiotic treatment were significantly higher in CAPUCI II (76.4 versus 90.3% and 37.5 versus 63.9%; p < 0.05). In the multivariate analysis, combined antibiotic therapy (OR 0.23, 95% CI 0.07-0.74) and early antibiotic treatment (OR 0.07, 95% CI 0.02-0.22) were independently associated with decreased intensive care unit mortality. CONCLUSIONS: In non-pneumococcal severe community-acquired pneumonia , early antibiotic administration and use of combined antibiotic therapy were both associated with increased intensive care unit survival during the study period.

Decrease in mortality in severe community-acquired pneumococcal pneumonia: impact of improving antibiotic strategies (2000-2013).

OBJECTIVE: The objective of the present study was to compare antibiotic prescribing practices and survival in the ICU for patients with pneumococcal severe community-acquired pneumonia (SCAP) between 2000 and 2013. METHODS: This was a matched case-control study of two prospectively recorded cohorts in Europe. Eighty patients from the Community-Acquired Pneumonia en la Unidad de Cuidados Intensivos (CAPUCI) II study (case group) were matched with 80 patients from CAPUCI I (control group) based on the following: shock at admission, need of mechanical ventilation, COPD, immunosuppression, and age. RESULTS: Demographic data were comparable in the two groups. Combined antibiotic therapy increased from 66.2% to 87.5% (P < .01), and the percentage of patients receiving the first dose of antibiotic within 3 h increased from 27.5% to 70.0% (P < .01). ICU mortality was significantly lower (OR, 0.82; 95% CI, 0.68-0.98) in cases, both in the whole population and in the subgroups of patients with shock (OR, 0.67; 95% CI, 0.50-0.89) or receiving mechanical ventilation (OR, 0.73; 95% CI, 0.55-0.96). In the multivariate analysis, ICU mortality increased in patients requiring mechanical ventilation (OR, 5.23; 95% CI, 1.60-17.17) and decreased in patients receiving early antibiotic treatment (OR, 0.36; 95% CI, 0.15-0.87) and combined therapy (OR, 0.19; 95% CI, 0.07-0.51). CONCLUSIONS: In pneumococcal SCAP, early antibiotic prescription and use of combination therapy increased. Both were associated with improved survival.

Elevation of creatine kinase is associated with worse outcomes in 2009 pH1N1 influenza A infection.

BACKGROUND: Current medical knowledge lacks specific information regarding creatine kinase (CK) elevation in influenza A pH1N1 (2009) infection. OBJECTIVES: Primary endpoints were correlation between CK at intensive care unit (ICU) admission and ICU mortality. Secondary endpoints were ICU length of stay (LOS), mechanical ventilation (MV), and requirement of renal replacement techniques (RRT). MATERIALS AND METHODS: A prospective multicenter register included all adults admitted for severe acute respiratory insufficiency (SARI) with confirmed pH1N1 in 148 ICUs. Clinical data including demographics, comorbidities, laboratory information, organ involvement, and prognostic data were registered. Post hoc classification of subjects was determined according to CK level. Data are expressed as median (interquartile range). RESULTS: Five hundred and five (505) patients were evaluable. Global ICU mortality was 17.8 % without documented differences between breakpoints. CK ≥500 UI/L was documented in 23.8 % of ICU admissions, being associated with greater renal dysfunction: acute kidney injury (AKI) was more frequent (26.1 versus 17.1 %, p < 0.05) and twofold requirement of RRT [11 versus 5.6 %, p < 0.05; odds ratio (OR) = 2.09 (95 % confidence interval [CI] 1.01-4.32)]. Increase of CK ≥1,000 UI/L was associated with two or more quadrant involvement on chest X-ray (63.2 versus 40.2 %, p < 0.01) and increased intubation risk (73.9 versus 56.7 %, p = 0.07) and duration of mechanical ventilation (median 15 days versus 11 days, p < 0.01). As a result, CK ≥1,000 UI/L was associated with 5 extra days of ICU and hospital LOS. CONCLUSIONS: CK is a biomarker of severity in pH1N1 infection. Elevation of CK was associated with more complications and increased ICU LOS and healthcare resources.

Corticosteroid therapy in patients with primary viral pneumonia due to pandemic (H1N1) 2009 influenza.

OBJECTIVE: During the first pandemic, some patients with pandemic (H1N1) 2009 influenza were treated with corticosteroids. The objective of this study was to assess the effect on survival of corticosteroid therapy in patients with pandemic (H1N1) 2009 influenza. METHODS: Prospective, observational, multicenter study performed in 148 ICU. Data were recorded in the GTEI/SEMICYUC registry. Adult patients with pandemic (H1N1) 2009 influenza confirmed by rt-PCR were included in the analysis. Database records specified corticosteroid type and reason for corticosteroid treatment. RESULTS: 372 patients with the diagnosis of primary viral pneumonia and completed outcomes treated in an ICU were included in the database. Mechanical ventilation was used in 70.2% of the patients. 136 (36.6%) patients received corticosteroids after a diagnosis of primary viral pneumonia. Obesity (35.6% vs 47.8% p = 0.021) and asthma (7.6% vs 15.4% p = 0.018), were more frequent in the group treated with corticosteroids. A Cox regression analysis adjusted for severity and potential confounding factors found that the use of corticosteroid therapy was not significantly associated with mortality (HR = 1.06, 95% CI 0.626-1.801; p = 0.825). CONCLUSIONS: Corticosteroid therapy in a selected group of patients with primary viral pneumonia due to pandemic (H1N1) 2009 influenza does not improve survival.

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.

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.

Ventilator-associated pneumonia: impact of organisms on clinical resolution and medical resources utilization.

BACKGROUND: Clinical resolution of ventilator-associated pneumonia (VAP) determines the duration of treatment and mechanical ventilation. The aim of this study was to evaluate the influence of organisms and their susceptibility to treatment on outcomes. METHODS: Prospective observational study in three teaching ICUs. Sixty episodes of VAP with appropriate therapy (Haemophilus influenzae, 15 episodes; methicillin-sensitive Staphylococcus aureus [MSSA], 15 episodes; Pseudomonas aeruginosa, 15 episodes; and methicillin-resistant S aureus [MRSA], 15 episodes), and 30 episodes with initial inappropriate therapy, all due to P aeruginosa, were compared. The main outcome measures were clinical resolution variables and, in survivors, length of mechanical ventilation after VAP onset. RESULTS: A significant delay in the resolution of hypoxemia was observed in VAP episodes due to MRSA and P aeruginosa with inappropriate antibiotic therapy (IAT) (median time to resolution, 10 and 8 days, respectively) when compared with the remaining pathogens (median time to resolution, 2 days). A multiple regression model, adjusted for disease severity, confirmed the delayed clinical resolution for MRSA and P aeruginosa with IAT. Similar associations were documented for defervescence. Among survivors, the median duration of mechanical ventilation after VAP onset was significantly longer for MRSA (17 days) and P aeruginosa IAT (11 days) when compared with episodes due to H influenzae or MSSA (6 days). Multiple regression analysis, adjusted for disease severity, confirmed that MRSA required significantly (R(2) = 0.132; p < 0.01) longer respiratory support than other organisms. CONCLUSIONS: When treated promptly, the resolution of VAP due to MSSA, H influenzae, and P aeruginosa was comparable. The resolution of MRSA VAP, regardless of the appropriateness of initial antibiotic therapy, was associated with longer respiratory support.

Risk factors for ventilator-associated pneumonia by Pseudomonas aeruginosa in presence of recent antibiotic exposure.

BACKGROUND: To facilitate the decision-making process for therapy and prevention of ventilator-associated pneumonia (VAP) in patients undergoing recent antibiotic exposure, this study investigated whether the development of VAP episodes caused by Pseudomonas aeruginosa or other pathogens are related to different risk factors, thereby distinguishing two risk population for this serious complication. METHODS: A 5-year retrospective case-control observational study was conducted. Cases of VAP caused by P. aeruginosa were compared with those caused by other pathogens. Univariate and multivariate analysis was performed using SPSS 11.0 software (SPSS Inc., Chicago, IL). RESULTS: Two groups were identified: P. aeruginosa (group P) was isolated in 58 (63.7%) episodes, and 33 episodes served as controls (group C), after a median of 12 days (interquartile range, 4-28 days) and 9 days (interquartile range, 3-12.5 days) of mechanical ventilation, respectively. P. aeruginosa was identified in 34.7% of episodes with early-onset pneumonia and in 73.5% with late-onset pneumonia. In a logistic regression analysis, P. aeruginosa was independently associated with duration of stay of 5 days or longer (relative risk = 3.59; 95% confidence interval, 1.04-12.35) and absence of coma (relative risk = 8.36; 95% confidence interval, 2.68-26.09). Risk for pathogens different from P. aeruginosa (group C) in early-onset pneumonia associated with coma was estimated to be 87.5%. CONCLUSIONS: Risk factors in episodes under recent antibiotic treatment caused by P. aeruginosa or other microorganism are not the same, a fact that could have implications for preventive and therapeutic approaches for this infection.

Colonization of the medial lumen is a risk factor for catheter-related bloodstream infection.

OBJECTIVE: To analyze the colonization of each lumen and the risk factors for triple-lumen central venous catheter-related bloodstream infection (CRBI). DESIGN AND SETTING: Prospective, observational study in the medical-surgical intensive care unit (ICU) of a teaching hospital. PATIENTS: A total of 120 patients requiring the insertion of a triple-lumen catheter. INTERVENTIONS: Cultures of the catheter. MEASUREMENTS AND RESULTS: The catheters were removed when CRBI was suspected or at discharge from ICU. At the removal time, blood cultures, a swab of the insertion site and a culture of the catheter tip were performed. Furthermore, we made quantitative cultures of the proximal, medial and distal lumen. We diagnosed CRBI in six patients (3.35 CRBI/1,000 days at risk), and we observed that in these patients colonization of the medial lumen was more frequent (5/6) than in patients without CRBI (9/114; p = 0.0001). The logistic regression analysis showed that colonization of the medial lumen was an independent risk factor for CRBI (OR 28.1, 95% CI 2.2-364.9). CONCLUSIONS: Colonization of the medial lumen is an independent risk factor for triple-lumen catheter-related bloodstream infection, possibly due to the absence of use of this lumen.

Impact of diversity of antibiotic use on the development of antimicrobial resistance.

OBJECTIVES: To evaluate the impact of different antibiotic strategies on acquisition of resistant microorganisms. METHODS: A prospective study was conducted over a 44 month period in a single ICU. Four empirical antibiotic strategies for ventilator-associated pneumonia (VAP) were sequentially implemented. Over the initial 10 months, patient-specific antibiotic therapy was prescribed; then, 4 month periods of prioritization or restriction rotation cycles of various antimicrobial agents were implemented for a total of 24 months; and, finally, during the last 10 months (mixing period) the first-line antibiotic for VAP was changed following a pre-established schedule to ensure maximum heterogeneity. Antibiotic consumption was closely monitored every month, and antimicrobial resistance patterns were regularly assessed. Antimicrobial heterogeneity was estimated using a modified Peterson index (AHI) measuring the ratios for the five most used antibiotics. Colonization by targeted microorganisms and susceptibility patterns were compared with the patient-specific period. RESULTS: Higher diversity of antibiotic prescription was obtained during patient-specific therapy (AHI = 0.93) or mixing periods (AHI = 0.95) than during prioritization (AHI = 0.70) or restriction periods (AHI = 0.68). High homogeneity was associated with increases in carbapenem-resistant Acinetobacter baumannii (CR-Ab) [relative risk (RR) 15.5; 95%CI 5.5-42.8], extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae (RR 4.2; 95%CI 1.9-9.3) and Enterococcus faecalis (RR 1.7; 95%CI 1.1-2.9). During the restriction period, incidence of ESBL-producing Enterobacteriaceae and E. faecalis returned to patient-specific rates but CR-Ab remained higher. CONCLUSIONS: Antibiotic prescription patterns balancing the use of different antimicrobials should be promoted to reduce the selection pressure that aids the development of resistance.

Clinical approach to the patient with suspected ventilator-associated pneumonia.

Management of ventilator-associated pneumonia needs to balance the avoidance of unnecessary antibiotic overuse with the provision of adequate initial empiric therapy. A clinical diagnosis based on new pulmonary opacity and purulent respiratory secretions plus other signs of inflammation is valuable in screening for patients with suspected ventilator-associated pneumonia. A rational strategy starts with immediate initiation of adequate antibiotics and collection of respiratory secretions to evaluate the causative organism. As a minimum, an endotracheal aspirate with direct staining and quantitative cultures should be obtained. Overall, the need to choose adequate antibiotics correctly and expeditiously calls for the use of broad-spectrum antibiotics, but the choice should be narrowed quickly in the light of microbiologic information. However, some patients (those who develop an infection within 5 days of hospitalization, those without recent antibiotic exposure, and those without hospitalization in the past 3 months) are at low risk of infection by resistant organisms. In that subset, adequate initial selection could be a non-pseudomonal third-generation cephalosporin, since antibiotics should target usual community-acquired organisms in addition to some Enterobacteriaceae and Staphylococcus aureus. Coverage of methicillin-resistant S. aureus should be limited only to intensive care units with concomitant index cases and to patients under antibiotic exposure. Patients at risk of Pseudomonas aeruginosa (e.g., 1 week of prior hospitalization or chronic obstructive pulmonary disease) require initial use of a combination of piperacilin/tazobactam and ciprofloxacin, or amikacin plus imipenem, meropenem, or an antipseudomonal cephalosporin. If risk of Acinetobacter baumannii exists, one of these agents should be a carbapenem. After 48 hours of therapy, each patient should be re-evaluated based mainly on resolution of hypoxemia and fever plus the initial microbiologic information. Whereas broad-spectrum therapy is initially warranted in many patients, this treatment may be narrowed considerably as culture results identify the causative organism and its sensitivity. Recent data suggest that reducing overall treatment duration to a maximum of 1 week is safe, effective and is less likely to promote the growth of resistant organisms in patients who are clinically improving. Optimal management should be based on a strategy combining early high doses of an effective agent for a short period of time, which is then simplified in the light of microbiologic information.