IntroductionTwo small randomized controlled trials have suggested beneficial effects of antibiotic treatment in patients with ventilator-associated tracheobronchitis (VAT). The primary aim of this study is to determine the impact of appropriate antibiotic treatment on transition from VAT to ventilator-associated pneumonia (VAP) in critically ill patients. The secondary objective was to determine the incidence of VAP in patients with VAT.MethodsThis was a prospective observational multicenter study. All patients with a first episode of VAT were eligible. Patients with tracheostomy at intensive care unit (ICU) admission, and those with VAP prior to VAT were excluded. VAT was defined using all the following criteria: fever > 38°C with no other cause, purulent tracheal secretions, positive tracheal aspirate (≥105 cfu/mL), and absence of new infiltrate on chest X ray. Only VAP episodes diagnosed during the 96 h following VAT, and caused by the same bacteria, were taken into account. Antibiotic treatment was at the discretion of attending physicians. Risk factors for transition from VAT to VAP were determined using univariate and multivariate analysis. All variables from univariate analysis with P values <0.1 were incorporated in the multivariate logistic regression analysis.ResultsOne thousand seven hundred and ten patients were screened for this study. Eighty-six, and 123 patients were excluded for tracheostomy at ICU admission, and VAP prior to VAT; respectively. One hundred and twenty two (7.1%) patients were included. 17 (13.9%) patients developed a subsequent VAP. The most common microorganisms in VAT patients were Pseudomonas aeruginosa (30%), Staphylococcus aureus (18%), and Acinetobacter baumannii (10%). Seventy-four (60%) patients received antimicrobial treatment, including 58 (47.5%) patients who received appropriate antimicrobial treatment. Appropriate antibiotic treatment was the only factor independently associated with reduced risk for transition from VAT to VAP (OR [95% CI] 0.12[0.02-0.59], P = 0.009). The number of patients with VAT needed to treat to prevent one episode of VAP, or one episode of VAP related to P. aeruginosa was 5, and 34; respectively.ConclusionsAppropriate antibiotic treatment is independently associated with reduced risk for transition from VAT to VAP.

bColistin pharmacokinetics were prospectively studied after intravenous administration of colistin methanesulphonate in critically ill patients without central nervous system infection (controls, n ‫؍‬ 5) and in patients with external ventricular drain-associated ventriculitis after intravenous administration (EVDViv, n ‫؍‬ 3) or combined intravenous/intraventricular administration (EVDVcomb, n ‫؍‬ 4). Cerebrospinal fluid (CSF)/serum colistin concentration ratios were higher in EVDViv than in control patients (11% versus 7%, P < 0.05) and in EVDVcomb compared to all other patients (P < 0.0001). CSF colistin concentrations above the MIC of 0.5 g/ml were achieved only in EVDVcomb patients. Previous studies have suggested that the level of antibiotics in the ventricular cerebrospinal fluid (CSF) is important for the outcome of external ventricular drainage (EVD)-related ventriculitis (1-3). The presence of multiresistant bacteria and the poor penetration of many drugs through the blood-brain barrier have imposed the use of intrathecal therapies (4).Today, colistin, administered as its prodrug colistin methanesulphonate (CMS), is one of the few antibiotics available for treatment of infections by multidrug-resistant Gram-negative organisms. However, intravenous (i.v.) administration is reported to have a relatively poor CSF distribution and clinical outcomes vary (5-7). Data with respect to the efficacy of intraventricular polymyxins, as an add-on therapy, combined with systemic antibiotics are sparse and mainly observational (5, 8).We aimed to determine the effect of intravenous and combined intravenous/intraventricular CMS administration on colistin concentrations in the CSF and serum in critically ill patients with or without central nervous system (CNS) infection.This prospective case-controlled randomized study was conducted in a tertiary hospital, during a 12-month period between 2011 and 2012. Inclusion criteria were as follows: age Ͼ 18 years, diagnosis of EVD-related ventriculitis caused by Gram-negative bacteria, controlled intracranial pressure (Ͻ20 mm Hg) for 24 h prior to the study, no renal failure, and no allergy to colistin. Patients with EVD on i.v. CMS treatment for infections by Gramnegative bacteria other than CNS infections were included in the study as controls. The study was approved by the Hospital Ethics and Research Committee and performed in accordance with good clinical practice guidelines.Control patients received 3,000,000 IU (240 mg) CMS (approximately 90 mg colistin base activity [CBA]) i.v. every 8 h. Patients with EVD-associated ventriculitis caused by Gram-negative bacteria (diagnosed on the basis of clinical grounds plus positive CSF cultures or CSF inflammation, including pleocytosis and a reduced CSF/serum glucose ratio) were randomized to receive the same i.v. dose (EVDViv group), or the i.v. dose combined with 125,000 IU (10 mg) CMS (ϳ3.75 CBA) administered intraventricularly, once daily (EVDVcomb). A 2-ml volume of 0.9% NaCl (volume of catheter lumen) was instilled via the ca...

The implementation of a bundle of measures for external cerebral ventricular drainage-associated ventriculitis control was associated with significantly decreased postintervention prevalence of the infection.

VAT is a nosocomial infection that might be associated with prolonged stay in the ICU, especially in neurocritical patients. VAT was not associated with increased mortality in our study.

Objective. To identify risk factors for the first episode of Klebsiella Pneumonia resistant to carbapenems (KPRC) infection in critically ill patients. Design, Setting, and Methods. This prospective cohort study was conducted in a 12-bed general Intensive Care Unit (ICU) in a University Hospital on ICU patients who required mechanical ventilation (MV) for >48 hours during a 12-month period. Clinical and microbiologic data were studied. Characteristics of KPRC patients were compared with those of critically ill patients who presented nonmultidrug resistant (MDR) bacterial infections or no documented infection at all. Results. Twenty-five patients presented KPRC infection, 18 presented non-MDR bacterial infection, and 39 patients presented no infection. Compared to patients without documented infection or infected by non MDR bacteria, patients with KPRC infection had received more frequently or for longer duration antibiotics against Gram-negative bacteria (carbapenems, colistin P < 0.05). Duration of colistin administration prior to KPRC isolation was independently associated with increased frequency of KPRC infection (odds ratio, 1.156 per day; 95% confidence interval, 1.010 to 1.312; P = 0.025). KPRC patients stayed longer in the ICU and received mechanical ventilation and sedation for longer periods and presented increased mortality (P < 0.05). Conclusion. KPRC infection is an emerging problem which might be more common in patients with previous use of antibiotics and especially colistin.

We evaluated whether prophylactic nebulised colistin could reduce ventilator-associated pneumonia (VAP) rates in an intensive care unit (ICU) setting with prevalent multidrug-resistant (MDR) bacteria.We used a single-centre, two-arm, randomised, open-label, controlled trial in a 12-bed ICU in the University Hospital of Larissa, Greece. Patient inclusion criteria included mechanical ventilation of >48 h. The two arms consisted of prophylaxis with 500 000 U colistin (Col group) or normal saline (NS group), thrice daily, for the first 10 ICU days or until extubation. The primary outcome of the study was the 30-day VAP incidence.In total, 168 patients entered the study. VAP incidence was not different between Col and NS group patients (14 (16.7%) versus 25 (29.8%), respectively, p=0.07). Regarding the secondary outcomes, the intervention resulted in a lower VAP incidence density rate (11.4 versus 25.6, respectively, p<0.01), and less Gram-negative bacteria-VAP ( p=0.03) and MDR-VAP ( p=0.04). Among VAP patients (n=39), prophylaxis with inhaled colistin improved ICU survival ( p=0.016). There was no evidence of increased resistance to colistin or multidrug resistance.Our findings suggest that nebulised colistin had no significant effect on VAP incidence. @ERSpublications In a RCT, nebulised colistin prophylaxis did not decrease ventilator-associated pneumonia incidence

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Ventriculitis or post-neurosurgical meningitis or healthcare-associated ventriculitis and meningitis (VM) is a severe infection that complicates central nervous system operations or is related to the use of neurosurgical devices or drainage catheters. It can further deteriorate patients who have already presented significant neurologic injury and is associated with high morbidity, mortality, and poor functional outcome. VM can be difficult to distinguish from aseptic meningitis, inflammation that follows hemorrhagic strokes and neurosurgical operations. The associated microorganisms can be either skin flora or nosocomial pathogens, most commonly, Gram-negative bacteria. Classical microbiology can fail to isolate the culprit pathogen. Novel cerebrospinal fluid (CSF) biomarkers and molecular microbiology can fill the diagnostic gap and expedite pathogen identification and treatment. The pathogens may demonstrate significant resistant patterns and their antibiotic treatment can be difficult, as many important drug classes, including the beta-lactams and the glycopeptides, hardly penetrate to the CSF, and do not achieve therapeutic levels at the site of the infection. Treatment modifications, such as higher daily dose and prolonged or continuous administration, might increase antibiotic levels in the site of infection and facilitate pathogens clearance. However, in the case of therapeutic failure or infection due to difficultto-treat bacteria, the direct antibiotic instillation into the CSF, in addition to the intravenous antibiotic delivery, may help in the resolution of infection. However, intraventricular antibiotic therapy may result in aseptic meningitis and seizures, concerning the administration of aminoglycosides, polymyxins, and vancomycin. Meanwhile, bacteria form biofilms on the catheter or the device that should routinely be removed. Novel neurosurgical treatment modalities comprise endoscopic evacuation of debris and irrigation of the ventricles. VM prevention includes perioperative antibiotics, antimicrobial impregnated catheters, and the implementation of standardized protocols, regarding catheter insertion and manipulation.