Intra-abdominal infections survival guide: a position statement by the Global Alliance For Infections In Surgery.

Intra-abdominal infections (IAIs) are an important cause of morbidity and mortality in hospital settings worldwide. The cornerstones of IAI management include rapid, accurate diagnostics; timely, adequate source control; appropriate, short-duration antimicrobial therapy administered according to the principles of pharmacokinetics/pharmacodynamics and antimicrobial stewardship; and hemodynamic and organ functional support with intravenous fluid and adjunctive vasopressor agents for critical illness (sepsis/organ dysfunction or septic shock after correction of hypovolemia). In patients with IAIs, a personalized approach is crucial to optimize outcomes and should be based on multiple aspects that require careful clinical assessment. The anatomic extent of infection, the presumed pathogens involved and risk factors for antimicrobial resistance, the origin and extent of the infection, the patient's clinical condition, and the host's immune status should be assessed continuously to optimize the management of patients with complicated IAIs.

Risk factors for surgical site infection following cardiac surgery in a region endemic for multidrug resistant organisms.

OBJECTIVES: To identify risk factors for surgical site infections following cardiosurgery in an area endemic for multidrug resistant organisms. DESIGN: Single-center, historical cohort study including patients who underwent cardiosurgery during a 6-year period (2014-2020). SETTING: Joint Commission International accredited, multiorgan transplant center in Palermo, Italy. MAIN OUTCOME MEASURES: Surgical site infection was the main outcome. RESULTS: On a total of 3609 cardiosurgery patients, 184 developed surgical site infection (5.1 %). Intestinal colonization with multidrug resistant organisms was more frequent in patients with surgical site infections (69.6 % vs. 33.3 %; p < 0.001). About half of surgical site infections were caused by Gram-negative bacteria (n = 97; 52.7 %). Fifty surgical site infections were caused by multidrug resistant organisms (27.1 %), with extended-spectrum Beta-lactamase-producing Enterobacterales (n = 16; 8.7 %) and carbapenem-resistant Enterobacterales (n = 26; 14.1 %) being the predominant resistance problem. However, in only 24 of surgical site infections caused by multidrug resistant organisms (48 %), mostly carbapenem-resistant Enterobacterales (n = 22), a pathogen match between the rectal surveillance culture and surgical site infections clinical culture was demonstrated. Nevertheless, multivariate logistic regression analysis identified a rectal swab culture positive for multidrug resistant organisms as an independent risk factor for SSI (odds ratio 3.95, 95 % confidence interval 2.79-5.60). Other independent risk factors were female sex, chronic dialysis, diabetes mellitus, previous cardiosurgery, previous myocardial infarction, being overweight/obese, and longer intubation time. CONCLUSION: In an area endemic for carbapenem-resistant Enterobacterales, intestinal colonization with multidrug resistant organisms was recognized as independent risk factor for surgical site infections. IMPLICATIONS FOR CLINICAL PRACTICE: No causal relationship between colonization with resistant pathogens and subsequent infection could be demonstrated. However, from a broader epidemiological perspective, having a positive multidrug resistant organisms colonization status appeared a risk factor for surgical site infections. Therefore, strict infection control measures to prevent cross-transmission remain pivotal (e.g., nasal decolonization, hand hygiene, and skin antisepsis).

The effect of late-onset sepsis on mortality across different gestational ages in a neonatal intensive care unit: A historical study.

OBJECTIVES: Late-onset sepsis is a frequent complication in neonatal intensive care units. This study aims to understand the effect of late-onset sepsis on mortality in hospitalised neonatal patients across different gestational ages. DESIGN: This is a single-centre, historical cohort study including neonates admitted to hospital during a 10-year period (2002 - 2011). Neonates were stratified by gestational age: extremely preterm (<28 weeks), very preterm (28 to 32 weeks), late preterm (33 to 36 weeks), full term (>37 weeks). SETTING: Tertiary NICU in Ghent, Belgium. MAIN OUTCOME MEASURES: Logistic regression analysis was used to assess adjusted relationships between late-onset sepsis and mortality, reported as odds ratio (OR) and 95% confidence interval (CI). RESULTS: A total of 4928 neonates were included, of which 2071 were term (42.0%), 1425 were late preterm (28.9%), 1165 very preterm (23.6%) and 264 were extremely preterm neonates (5.4%). 40 neonates developed late-onset sepsis (8.2 episodes/1000 patient days). Overall, in-hospital mortality was 5.4%. Late-onset sepsis was an independent risk factor for mortality in the total cohort (OR = 2.41; 95% CI = 1.46-3.96). However, when gestational age groups were considered separately, late-onset sepsis was associated with mortality in very preterm neonates (OR = 2.45; 95% CI = 1.03-5.84) and in the late preterm neonates (OR = 3.92; 95% CI = 1.41-10.87), but not in other neonates. Comorbidities burdening neonatal hospital survival include acute lung disease, brain damage, periventricular leukomalacia, surgery, and broncho-pulmonary dysplasia. CONCLUSION: Late-onset sepsis is an independent risk factor for mortality in very preterm and late preterm neonates. Understanding how late-onset sepsis among other factors impact mortality enables a patient and family-centred approach to nursing care including the anticipation of realistic milestones. IMPLICATIONS FOR CLINICAL PRACTICE: Late-onset sepsis is especially detrimental to preterm neonates and this could be taken into consideration by nurses when communicating with families in the perinatal period.

Heterogeneity hampers the identification of general pressure injury risk factors in intensive care populations: A predictive modelling analysis.

OBJECTIVE: To determine risk factors for pressure injury in distinct intensive care subpopulations according to admission type (Medical; Surgical elective; Surgery emergency; Trauma/Burns). METHODOLOGY/DESIGN: Predictive modelling using generalised linear mixed models with backward elimination on prospectively gathered data of 13 044 adult intensive care patients. SETTINGS: 1110 intensive care units, 89 countries worldwide. MAIN OUTCOME MEASURES: Pressure injury risk factors. RESULTS: A generalised linear mixed model including admission type outperformed a model without admission type (p = 0.004). Admission type Trauma/Burns was not withheld in the model and excluded from further analyses. For the other three admission types (Medical, Surgical elective, and Surgical emergency), backward elimination resulted in distinct prediction models with 23, 17, and 16 predictors, respectively, and five common predictors only. The Area Under the Receiver Operating Curve was 0.79 for Medical admissions; and 0.88 for both the Surgical elective and Surgical emergency models. CONCLUSIONS: Risk factors for pressure injury differ according to whether intensive care patients have been admitted for medical reasons, or elective or emergency surgery. Prediction models for pressure injury should target distinct subpopulations with differing pressure injury risk profiles. Type of intensive care admission is a simple and easily retrievable parameter to distinguish between such subgroups.

Invasive pulmonary aspergillosis in solid-organ transplant patients in the intensive care unit.

INTRODUCTION: Solid-organ transplantation (SOT) is a well-known risk factor for invasive pulmonary aspergillosis (IPA). We report on the epidemiology and outcome of SOT patients with IPA in an intensive care unit (ICU) setting. METHODS: This is a secondary study based on a subset of SOT patients from a prospective observational multicenter cohort (the AspICU project) including ICU patients with at least one Aspergillus spp. positive culture. Cases were classified as proven, probable, or putative IPA, or as Aspergillus-colonized. Mortality was reported at 12 weeks. RESULTS: The study included 52 SOT patients (of which 18 lung, 17 liver, 12 kidney, and five heart transplants). Sixteen patients had proven IPA, 28 were categorized as putative IPA (of which only five reached a probable IPA diagnosis according to the European Organization for Research and Treatment of Cancer/Mycosis Study Group and Research Consortium criteria), and eight as Aspergillus-colonization. Among patients with IPA, 20 (45.5%) developed IPA during their ICU stay following transplantation whereas 24 patients (54.5%) had a medical ICU admission. Regarding medical imaging, nearly all IPA cases presented with non-specific findings as only nine demonstrated robust findings suggestive for invasive fungal disease. Overall, severity of the disease was reflected by a high prevalence of underlying conditions and acute organ derangements. Mortality among patients with IPA was 68%. Lung transplantation was associated with better survival (50%). CONCLUSION: IPA in SOT patients in the ICU develops in the presence of overall high severity of the disease. It rarely presents with suggestive medical imaging thereby hampering diagnosis. IPA in ICU patients with SOT carries a grim prognosis.

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study.

PURPOSE: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. METHODS: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. RESULTS: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9-27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6-16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score < 19, ICU stay > 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2-1.8), stage II (OR 1.6; 95% CI 1.4-1.9), and stage III or worse (OR 2.8; 95% CI 2.3-3.3). CONCLUSION: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat.

Invasive Pulmonary Aspergillosis in Chronic Obstructive Pulmonary Disease Exacerbations.

Nowadays, reports in the literature support that patients with severe chronic obstructive pulmonary disease (COPD) are at higher risk to develop invasive pulmonary aspergillosis (IPA). However, the interpretation of Aspergillus-positive cultures from the airways in critically ill COPD is still a challenge. Indeed, as the patient could be merely colonized, tissue samples are required to ascertain IPA diagnosis but they are rarely obtained before death. Consequently, diagnosis is often only suspected on the basis of a combination of three elements: clinical characteristics, radiological images (mostly thoracic CT scan), and microbiological, and occasionally serological, results. To facilitate the analysis of these data, several algorithms have been developed, and the best effectiveness has been demonstrated by the Clinical algorithm. This is of importance as IPA prognosis in these patients remains presently very poor and using such an algorithm could promote prompter diagnosis, early initiation of treatment, and subsequently improved outcome.While the most classical presentation of IPA in critically ill COPD patients features a combination of obstructive respiratory failure, antibiotic-resistant pneumonia, recent or chronic corticosteroid therapy, and positive Aspergillus cultures from the lower respiratory tract, the present article will also address less typical presentations and discuss the most appropriate treatments which could alter prognosis.

Diagnosing invasive pulmonary aspergillosis in ICU patients: putting the puzzle together.

PURPOSE OF REVIEW: The approach to diagnose invasive pulmonary aspergillosis in the absence of lung biopsy in ICU patients is reviewed. This approach should be based on four pillars: mycology, medical imaging, underlying conditions, and acute disease expression. RECENT FINDINGS: Diagnosing invasive pulmonary aspergillosis in the absence of histopathologic evidence is a matter of probability weighting. Initiating antifungal therapy in an early phase and with a lower likelihood of disease might outweigh further diagnostic workout with further delay in appropriate treatment. However, in ICU patients, a preemptive antifungal strategy has not been established yet. SUMMARY: For mycology, a positive galactomannan test on serum or broncho-alveolar lavage fluid is highly indicative of invasive pulmonary aspergillosis. The meaning of positive culture results, lateral-flow device test, or PCR-assay is ambiguous. A negative galactomannan or PCR test has high negative predictive value. Clinical features suggestive for invasive fungal disease on CT-scan are highly indicative but rare in ventilated patients. An immunocompromised status indicates high-risk. chronic obstructive pulmonary disease, hepatic cirrhosis, and AIDS indicate moderate risk. Invasive pulmonary aspergillosis in the absence of underlying conditions is rare. Acute diseases frequently associated with invasive pulmonary aspergillosis include sepsis and/or respiratory insufficiency because of influenza, acute respiratory distress syndrome, or pneumonia.

Nebulization of Antiinfective Agents in Invasively Mechanically Ventilated Adults: A Systematic Review and Meta-analysis.

BACKGROUND: Nebulization of antiinfective agents is a common but unstandardized practice in critically ill patients. METHODS: A systematic review of 1,435 studies was performed in adults receiving invasive mechanical ventilation. Two different administration strategies (adjunctive and substitute) were considered clinically relevant. Inclusion was restricted to studies using jet, ultrasonic, and vibrating-mesh nebulizers. Studies involving children, colonized-but-not-infected adults, and cystic fibrosis patients were excluded. RESULTS: Five of the 11 studies included had a small sample size (fewer than 50 patients), and only 6 were randomized. Diversity of case-mix, dosage, and devices are sources of bias. Only a few patients had severe hypoxemia. Aminoglycosides and colistin were the most common antibiotics, being safe regarding nephrotoxicity and neurotoxicity, but increased respiratory complications in 9% (95% CI, 0.01 to 0.18; I = 52%), particularly when administered to hypoxemic patients. For tracheobronchitis, a significant decrease in emergence of resistance was evidenced (risk ratio, 0.18; 95% CI, 0.05 to 0.64; I = 0%). Similar findings were observed in pneumonia by susceptible pathogens, without improvement in mortality or ventilation duration. In pneumonia caused by resistant pathogens, higher clinical resolution (odds ratio, 1.96; 95% CI, 1.30 to 2.96; I = 0%) was evidenced. These findings were not consistently evidenced in the assessment of efficacy against pneumonia caused by susceptible pathogens. CONCLUSIONS: Performance of randomized trials evaluating the impact of nebulized antibiotics with more homogeneous populations, standardized drug delivery, predetermined clinical efficacy, and safety outcomes is urgently required. Infections by resistant pathogens might potentially have higher benefit from nebulized antiinfective agents. Nebulization, without concomitant systemic administration of the drug, may reduce nephrotoxicity but may also be associated with higher risk of respiratory complications.

The value of polyurethane-cuffed endotracheal tubes to reduce microaspiration and intubation-related pneumonia: a systematic review of laboratory and clinical studies.

BACKGROUND: When conventional high-volume, low-pressure cuffs of endotracheal tubes (ETTs) are inflated, channel formation due to folds in the cuff wall can occur. These channels facilitate microaspiration of subglottic secretions, which is the main pathogenic mechanism leading to intubation-related pneumonia. Ultrathin polyurethane (PU)-cuffed ETTs are developed to minimize channel formation in the cuff wall and therefore the risk of microaspiration and respiratory infections. METHODS: We systematically reviewed the available literature for laboratory and clinical studies comparing fluid leakage or microaspiration and/or rates of respiratory infections between ETTs with polyvinyl chloride (PVC) cuffs and ETTs with PU cuffs. RESULTS: The literature search revealed nine in vitro experiments, one in vivo (animal) experiment, and five clinical studies. Among the 9 in vitro studies, 10 types of PU-cuffed ETTs were compared with 17 types of PVC-cuffed tubes, accounting for 67 vs. 108 experiments with 36 PU-cuffed tubes and 42 PVC-cuffed tubes, respectively. Among the clinical studies, three randomized controlled trials (RCTs) were identified that involved 708 patients. In this review, we provide evidence that PU cuffs protect more efficiently than PVC cuffs against fluid leakage or microaspiration. All studies with leakage and/or microaspiration as the primary outcome demonstrated significantly less leakage (eight in vitro and two clinical studies) or at least a tendency toward more efficient sealing (one in vivo animal experiment). In particular, high-risk patients intubated for shorter periods may benefit from the more effective sealing capacity afforded by PU cuffs. For example, cardiac surgery patients experienced a lower risk of early postoperative pneumonia in one RCT. The evidence that PU-cuffed tubes prevent ventilator-associated pneumonia (VAP) is less robust, probably because microaspiration is postponed rather than eliminated. One RCT demonstrated no difference in VAP risk between patients intubated with either PU-cuffed or PVC-cuffed tubes, and one before-after trial demonstrated a favorable reduction in VAP rates following the introduction of PU-cuffed tubes. CONCLUSIONS: Current evidence can support the use of PU-cuffed ETTs in high-risk surgical patients, while there is only very limited evidence that PU cuffs prevent pneumonia in patients ventilated for prolonged periods.

Chronic pulmonary aspergillosis: rationale and clinical guidelines for diagnosis and management.

Chronic pulmonary aspergillosis (CPA) is an uncommon and problematic pulmonary disease, complicating many other respiratory disorders, thought to affect ~240 000 people in Europe. The most common form of CPA is chronic cavitary pulmonary aspergillosis (CCPA), which untreated may progress to chronic fibrosing pulmonary aspergillosis. Less common manifestations include: Aspergillus nodule and single aspergilloma. All these entities are found in non-immunocompromised patients with prior or current lung disease. Subacute invasive pulmonary aspergillosis (formerly called chronic necrotising pulmonary aspergillosis) is a more rapidly progressive infection (<3 months) usually found in moderately immunocompromised patients, which should be managed as invasive aspergillosis. Few clinical guidelines have been previously proposed for either diagnosis or management of CPA. A group of experts convened to develop clinical, radiological and microbiological guidelines. The diagnosis of CPA requires a combination of characteristics: one or more cavities with or without a fungal ball present or nodules on thoracic imaging, direct evidence of Aspergillus infection (microscopy or culture from biopsy) or an immunological response to Aspergillus spp. and exclusion of alternative diagnoses, all present for at least 3 months. Aspergillus antibody (precipitins) is elevated in over 90% of patients. Surgical excision of simple aspergilloma is recommended, if technically possible, and preferably via video-assisted thoracic surgery technique. Long-term oral antifungal therapy is recommended for CCPA to improve overall health status and respiratory symptoms, arrest haemoptysis and prevent progression. Careful monitoring of azole serum concentrations, drug interactions and possible toxicities is recommended. Haemoptysis may be controlled with tranexamic acid and bronchial artery embolisation, rarely surgical resection, and may be a sign of therapeutic failure and/or antifungal resistance. Patients with single Aspergillus nodules only need antifungal therapy if not fully resected, but if multiple they may benefit from antifungal treatment, and require careful follow-up.

Risk Factors for Health Care-Associated Sepsis in Critically Ill Neonates Stratified by Birth Weight.

BACKGROUND: Health care-associated bloodstream infection (HABSI) is a frequent complication in neonatal intensive care. Research on risk factors stratified by birth weight and adjusted for severity of illness and comorbidities is limited. Our objective is to describe independent risk factors for HABSI in critically ill neonates with emphasis on risk variation between birth weight groups. METHODS: We performed a single-center historical cohort study in a tertiary referral center. A neonatal intensive care-audit system was used to identify eligible neonates admitted for ≥72 hours (2002-2011). HABSI is defined according to National Institute of Child Health and Human Development criteria. Risk factors for HABSI were assessed by univariate and logistic regression analysis for the total cohort and for birth weight subgroups, that is, neonates ≤1500 g and >1500 g. RESULTS: A total of 342 neonates developed HABSI in 5134 admissions of ≥72 hours (6.7%). Very low birth weight, total parenteral nutrition (TPN), mechanical ventilation, gastrointestinal disease, surgery (cardiac and other type), and renal insufficiency are independent risk factors for the total cohort. Gastrointestinal disease and cardiac surgery are independent risk factors in both birth weight groups; mechanical ventilation (odds ratio [OR]: 2.6; confidence interval [CI]: 1.6-4.0) and other type of surgery (OR: 4.3; CI: 2.1-8.8) are solely independent risk factors in the ≤1500-g cohort; TPN is exclusively an independent risk factor (OR: 7.9; CI: 3.9-16.2) in the >1500-g cohort. CONCLUSIONS: In our neonatal intensive care unit, risk stratification by birth weight revealed some difference. Special attention concerning infection control practices is for neonates receiving TPN, mechanical ventilation, cardiac surgery, and with a gastrointestinal disease.

Epidemiology of invasive aspergillosis in critically ill patients: clinical presentation, underlying conditions, and outcomes.

INTRODUCTION: Invasive aspergillosis (IA) is a fungal infection that particularly affects immunocompromised hosts. Recently, several studies have indicated a high incidence of IA in intensive care unit (ICU) patients. However, few data are available on the epidemiology and outcome of patients with IA in this setting. METHODS: An observational study including all patients with a positive Aspergillus culture during ICU stay was performed in 30 ICUs in 8 countries. Cases were classified as proven IA, putative IA or Aspergillus colonization according to recently validated criteria. Demographic, microbiologic and diagnostic data were collected. Outcome was recorded 12 weeks after Aspergillus isolation. RESULTS: A total of 563 patients were included, of whom 266 were colonized (47%), 203 had putative IA (36%) and 94 had proven IA (17%). The lung was the most frequent site of infection (94%), and Aspergillus fumigatus the most commonly isolated species (92%). Patients with IA had higher incidences of cancer and organ transplantation than those with colonization. Compared with other patients, they were more frequently diagnosed with sepsis on ICU admission and more frequently received vasopressors and renal replacement therapy (RRT) during the ICU stay. Mortality was 38% among colonized patients, 67% in those with putative IA and 79% in those with proven IA (P < 0.001). Independent risk factors for death among patients with IA included older age, history of bone marrow transplantation, and mechanical ventilation, RRT and higher Sequential Organ Failure Assessment score at diagnosis. CONCLUSIONS: IA among critically ill patients is associated with high mortality. Patients diagnosed with proven or putative IA had greater severity of illness and more frequently needed organ support than those with Aspergillus spp colonization.

Association among duration of mechanical ventilation, cuff material of endotracheal tube, and postoperative nosocomial pneumonia in cardiac surgical patients: a prospective study.

OBJECTIVES: Postoperative pulmonary complications are a burden for high-risk surgical patients with a risk of aspiration of subglottic secretions along the polyvinyl chloride cuff. The introduction of a polyurethane cuff diminishes secretion leakage with a decreased rate of pneumonia. The aim of the current analysis was to determine the time at which a polyurethane cuffed endotracheal tube might be advantageous to prevent aspiration in a setting of high-risk surgical patients. METHODS: The present investigation is based on published data obtained in postoperative cardiac surgical patients undergoing operation from 2006 to 2007. Cuff pressure was kept between 20 and 26 cmH2O intraoperatively and in the intensive care unit. The current post hoc analysis determines (1) the discriminatory cutoff value of intubation duration for predicting postoperative pneumonia and (2) the potential factors associated with prolonged intubation. RESULTS: Forty-three patients (32%) were diagnosed with early postoperative pneumonia. Receiver operating characteristics analysis revealed a cutoff value of 16.6 hours for the duration of mechanical ventilation to discriminate patients with postoperative pneumonia. A stepwise binary logistic regression analysis revealed that a polyvinyl chloride cuff was associated with a 10-fold increased risk for prolonged intubation. CONCLUSIONS: The current analyses provide evidence that among cardiac surgical patients, mechanical ventilation more than 16.6 hours is associated with an increased likelihood of postoperative pneumonia.

Cerebral aspergillosis in adult critically ill patients: a descriptive report of 10 patients from the AspICU cohort.

An unexpectedly high incidence of invasive pulmonary aspergillosis (IPA) has been reported in non-neutropenic intensive care unit (ICU) patients. After the respiratory tract, the brain is most often affected by invasive aspergillosis. However, little is known about brain involvement by Aspergillus in critically ill patients. In this study, demographics, risk profile, diagnosis, treatment and outcome of proven cases of invasive cerebral aspergillosis (ICA) taken from a cohort of 563 adult patients with evidenced Aspergillus involvement during their ICU stay were reviewed. Ten patients with central nervous system aspergillosis were identified. All had one or more host factors predisposing for invasive aspergillosis. The clinical and radiological presentation was non-specific and exclusively pulmonary-related. All but one patient had proven or probable/putative IPA. On cerebral computed tomography, lesions appeared as either solitary and hyperdense or were multiple and randomly distributed throughout the brain. One patient presented with sole meningeal infestation. Aspergillus infection was confirmed by brain biopsy in three subjects. Voriconazole was used as primary treatment in only one-half of the patients. Mortality was 90%. ICA is not frequently observed in adult ICU patients. Diagnosis must be considered in patients at risk presenting with proven or probable/putative IPA in association with suggestive neuroradiological findings. The brain is most likely affected through haematogenous dissemination from the lungs. Current treatment recommendations are not always applied and outcome remains dismal.

A clinical algorithm to diagnose invasive pulmonary aspergillosis in critically ill patients.

RATIONALE: The clinical relevance of Aspergillus-positive endotracheal aspirates in critically ill patients is difficult to assess. OBJECTIVES: We externally validate a clinical algorithm to discriminate Aspergillus colonization from putative invasive pulmonary aspergillosis in this patient group. METHODS: We performed a multicenter (n = 30) observational study including critically ill patients with one or more Aspergillus-positive endotracheal aspirate cultures (n = 524). The diagnostic accuracy of this algorithm was evaluated using 115 patients with histopathologic data, considered the gold standard. Subsequently, the diagnostic workout of the algorithm was compared on the total cohort (n = 524), with the categorization based on the diagnostic criteria of the European Organization for the Research and Treatment of Cancer/Mycoses Study Group. MEASUREMENTS AND MAIN RESULTS: Among 115 histopathology-controlled patients, 79 had proven aspergillosis. The algorithm judged 86 of 115 cases to have putative aspergillosis. This diagnosis was confirmed in 72 and rejected in 14 patients. The algorithm judged 29 patients to have Aspergillus colonization. This was confirmed in 22 and rejected in 7 patients. The algorithm had a specificity of 61% and a sensitivity of 92%. The positive and negative predictive values were 61 and 92%, respectively. In the total cohort (n = 524), 79 patients had proven invasive pulmonary aspergillosis (15.1%). According to the European Organization for the Research and Treatment of Cancer/Mycoses Study Group criteria, 32 patients had probable aspergillosis (6.1%) and 413 patients were not classifiable (78.8%). The algorithm judged 199 patients to have putative aspergillosis (38.0%) and 246 to have Aspergillus colonization (46.9%). CONCLUSIONS: The algorithm demonstrated favorable operating characteristics to discriminate Aspergillus respiratory tract colonization from invasive pulmonary aspergillosis in critically ill patients.

Oral bioavailability of moxifloxacin after Roux-en-Y gastric bypass surgery.

OBJECTIVES: Roux-en-Y gastric bypass surgery is the most commonly performed procedure for the treatment of morbid obesity. This anatomical alteration may affect the absorption and consequently the bioavailability of oral drugs. This study aims to investigate the oral bioavailability of moxifloxacin in 12 healthy volunteers who underwent gastric bypass surgery. PATIENTS AND METHODS: In this randomized crossover study, each subject received two single standard doses of 400 mg of moxifloxacin orally or intravenously administered on two occasions separated by a washout period of 1 week. Serial venous blood samples were drawn up to 72 h after dosing and moxifloxacin plasma levels were measured by a validated HPLC method with fluorescence detection. [clinicaltrials.gov database (identifier: NCT01130922).] RESULTS: After oral dosing, moxifloxacin plasma concentrations reached a maximum (C(max)) of 3.38 ± 1.41 mg/L after 1.75 h (0.75-4.00). After intravenous dosing, C(max) and T(max) were 4.53 ± 1.43 mg/L and 1.03 h (0.75-2.50), respectively. The mean areas under the plasma concentration time curve extrapolated to infinity (AUC(∞)) were 46.2 ± 1.4 mg ·â€Šh/L after oral dosing and 52.3 ± 1.3 mg ·â€Šh/L after intravenous dosing, resulting in a mean oral bioavailability of 88.32% [90% confidence interval (CI) 85.64%-91.08%]. CONCLUSIONS: This study confirms that exposure to moxifloxacin is equivalent for oral and intravenous administration of 400 mg dosages in healthy volunteers who underwent gastric bypass surgery. But these exposures were more than 50% higher than those described for subjects without gastric bypass. This may suggest a higher enterohepatic recirculation of moxifloxacin after gastric bypass.

Epidemiology of infection in critically ill patients with acute renal failure.

OBJECTIVES: Critically ill patients with infection are at increased risk for developing acute renal failure (ARF), and ARF is associated with an increased risk for infection. Both conditions are associated with prolonged length of stay (LOS) and worse outcome; however, little data exist on the epidemiology of infection in this specific cohort. Therefore, we investigated the occurrence of infection in a cohort of critically ill patients with ARF treated with renal replacement therapy (RRT). In addition, we assessed whether this infection worsened outcome. DESIGN: Retrospective cohort study. SETTING: General intensive care unit (ICU) in an academic tertiary care center comprising a 22-bed surgical ICU, eight-bed cardiac surgery ICU, 14-bed medical ICU, and six-bed burn center. PATIENTS: Six hundred forty-seven consecutive critically ill patients with ARF treated with RRT, admitted between 2000 and 2004. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: total of 519 (80.2%), 193 (29.8%), 66 (10.2%), and ten (1.5%) patients developed one, two, three, and four episodes of infection, respectively. Of 788 episodes of infection observed, 364 (46.2%) occurred before, 318 (40.3%) during, and 106 (13.4%) after discontinuation of RRT. Pneumonia (54.3%) was most frequent, followed by intra-abdominal (11.9%) and urinary tract infections (9.7%). Infections were caused by Gram-negative organisms in 33.7%, Gram-positive organisms in 21.6%, and yeasts in 9.8%. Patients with infection had higher mortality (p = 0.04) and longer ICU and hospital LOS. They needed more vasoactive therapy and spent more time on mechanical ventilation and RRT (all p < 0.001) than patients without infection. After adjustment for potential confounders, Acute Physiology and Chronic Health Evaluation II score, age, mechanical ventilation, and vasoactive therapy were associated with worse outcome, but infection was not. CONCLUSIONS: Infection occurred in four fifths of critically ill patients with ARF treated with RRT and was in an unadjusted analysis associated with longer LOS and higher mortality. After correction for other covariates, infection was no longer associated with in-hospital mortality.

Polyurethane cuffed endotracheal tubes to prevent early postoperative pneumonia after cardiac surgery: a pilot study.

OBJECTIVE: Patients receiving mechanical ventilation through an endotracheal tube are at increased risk for pneumonia. Because microaspiration of contaminated supraglottic secretions past the endotracheal tube cuff is considered to be central in the pathogenesis of ventilator-associated and postoperative pneumonia, better sealing of the upper trachea by the endotracheal tube cuff could possibly reduce this risk. We therefore postulated that use of a polyurethane cuffed tube would prevent early postoperative pneumonia through this mechanism in a population of cardiac surgical patients. METHODS: In a prospective, single-blind, randomized study, patients scheduled for cardiac surgery were allocated to intubation with a polyurethane cuffed endotracheal tube or the routinely used polyvinyl chloride cuffed endotracheal tube. Patients were scheduled for routine or emergency cardiac surgery and admitted to an 8-bed cardiac surgical intensive care unit of a tertiary care hospital. RESULTS: A total of 134 patients were available for analysis (67 in each group). Whereas mortality was not different between the groups, the incidence of early postoperative pneumonia and empirical prescription of antibiotic therapy were significantly lower in the polyurethane group than in the polyvinyl chloride group (23% vs 42%, P < .03). Intensive care unit and hospital stays were not significantly different between the two study subsets (3 +/- 5 days vs 3 +/- 4 days and 16 +/- 9 vs 17+/-11 days, respectively). In a multivariate regression analysis, preoperative serum creatinine levels (odds ratio 1.85, confidence interval 1.02-3.37, P = .04) and perioperative transfusion (odds ratio 1.50, confidence interval 1.08-3.37, P = .015) were independently associated with increased risk of early postoperative pneumonia, whereas use of a polyurethane endotracheal tube was protective (odds ratio 0.31, confidence interval 0.13-0.77, P = .01). CONCLUSION: Polyurethane cuffed endotracheal tubes can reduce the frequency of early postoperative pneumonia in cardiac surgical patients.