Marios Karvouniaris

Combined Intravenous and Intraventricular Administration of Colistin Methanesulfonate in Critically Ill Patients with Central Nervous System Infection

ABSTRACT Colistin 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 μg/ml were achieved only in EVDVcomb patients.

Bundle of Measures for External Cerebral Ventricular Drainage-associated Ventriculitis*

Objective:To assess the prevalence and outcome of external cerebral ventricular drainage-associated ventriculitis in neurocritical patients before and after the implementation of a bundle of external cerebral ventricular drainage-associated ventriculitis control measures. Design:Clinical prospective case series. Setting:University Hospital of Larissa, Greece. Patients:Consecutive patients were recruited from the ICU of the hospital. Patient inclusion criteria included presence of external ventricular drainage and ICU stay more than 48 hours. Intervention:The bundle of external cerebral ventricular drainage-associated ventriculitis control measures included 1) reeducation of ICU personnel on issues of infection control related to external cerebral ventricular drainage, 2) meticulous intraventricular catheter handling, 3) cerebrospinal fluid sampling only when clinically necessary, and 4) routine replacement of the drainage catheter on the seventh drainage day if the catheter was still necessary. The bundle was applied after an initial period (preintervention) where standard policy for external cerebral ventricular drainage-associated ventriculitis was established. Measurements:External cerebral ventricular drainage-associated ventriculitis prevalence, external cerebral ventricular drainage-associated ventriculitis events per 1,000 drainage days (drain-associated infection rate), length of ICU stay, Glasgow Outcome Scale at 6 months, and risk factors for external cerebral ventricular drainage-associated ventriculitis. Main Results:Eighty-two patients entered the study in the preintervention period and 57 patients during the intervention period. During the preintervention and intervention period, external cerebral ventricular drainage-associated ventriculitis prevalence was 28% and 10.5% (p = 0.02) and drain-associated infection rate was 18 and 7.1, respectively (p = 0.0001); mean (95% CI) length of ICU stay in patients who presented external cerebral ventricular drainage-associated ventriculitis was 44.4 days (36.4–52.4 d), whereas mean (95% CI) length of ICU stay in patients who did not was 20 days (16.9–23.2 d) (p < 0.001). Furthermore, the length of ICU stay was associated with length of drainage (p = 0.0001). Therefore, the presence of external cerebral ventricular drainage-associated ventriculitis and the length of drainage were the only variables associated with a prolonged ICU stay. Unfavorable outcome in Glasgow Outcome Scale at 6 months was not associated with the presence of external cerebral ventricular drainage-associated ventriculitis (p = 0.5). No significant differences were found when Glasgow Outcome Scale was analyzed according to the two study periods. Conclusions: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.

Sepsis-associated takotsubo cardiomyopathy can be reversed with levosimendan.

Sepsis is a stressful physical condition, and at the acute phase, overstimulation of the sympathetic nervous system may occur; these events have the potential to induce cardiomyopathy. Takotsubo cardiomyopathy (TTC) is a form of catecholamine-induced cardiomyopathy, which occurs very rarely in sepsis. However, TTC management in critically ill patients with sepsis may be challenging because the use of exogenous catecholamines for circulatory support might augment further TTC. Herein, we report a rare case of TTC after urosepsis; and we point out that cardiac function may improve after catecholamine withdrawal and the application of calcium channel sensitizer levosimendan.

Nebulised colistin for ventilator-associated pneumonia prevention.

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. In a RCT, nebulised colistin prophylaxis did not decrease ventilator-associated pneumonia incidence http://ow.ly/R8FOE

Ventilator-Associated Tracheobronchitis Increases the Length of Intensive Care Unit Stay

OBJECTIVE To investigate prospectively the clinical course and risk factors for ventilator-associated tracheobronchitis (VAT) and the impact of VAT on intensive care unit (ICU) morbidity and mortality. DESIGN Prospective cohort study. SETTING University Hospital Larissa, Larissa, Greece. PATIENTS Critical care patients who received mechanical ventilation for more than 48 hours were prospectively studied between 2009 and 2011. METHODS The modified Clinical Pulmonary Infection Score, white blood cell count, and C-reactive protein level were systematically assessed every 2 days for the first 2 weeks of ICU stay. Bronchial secretions were assessed daily. Quantitative cultures of endotracheal secretions were performed on the first ICU day for every patient and every 2 days thereafter for the first 2 weeks or more at the discretion of the attending physicians. Definition of VAT was based on previously published criteria. RESULTS A total of 236 patients were observed; 42 patients (18%) presented with VAT. Gram-negative pathogens, which were usually multidrug resistant, were responsible for 92.9% of cases. Patients with a neurosurgical admission presented with VAT significantly more often than did other ICU patients (28.5% vs 14.1%; . The occurrence P=.02) of VAT was a significant risk factor for increased duration of ICU stay (OR [95% CI], 3.04 [1.35–6.85]; P=.01). Age (OR [95% CI], 1.04 [1.015–1.06]; P=.02), Acute Physiology and Chronic Health Evaluation II score (OR [95% CI], 1.08 [1.015–1.16]; P=.02), and C-reactive protein level at admission (OR [95% CI], 1.05 [1.01–1.1]; P=.02) were independent factors for ICU mortality. CONCLUSIONS 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.

Risk Factors for the First Episode of Klebsiella pneumoniae Resistant to Carbapenems Infection in Critically Ill Patients: A Prospective 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.

Inhaled Antibiotics for Nosocomial Pneumonia

Pneumonia, especially the more severe forms, is associated with considerable morbidity and mortality. Systemic use of antibiotics is the cornerstone of the management of pneumonia in all patients, including critical care patients. Several adjunctive strategies have been suggested to improve management. Notably, localized treatment in the lungs via the instillation or inhalation or nebulization of antibiotics may offer the theoretical advantage of a therapy which targets the lung while it has no systematic effects. However, the use of inhaled antibiotics is controversial. Methods of antibiotic delivery and microbiology vary between available studies and despite the favorable profile of this strategy, concerns have been raised by early data that this therapeutic approach may increase the appearance of resistant bacteria. In this report, we reviewed available evidence from animal and human clinical studies in respect of the role of inhaled antibiotic therapy in pneumonia. In most studies, pneumonia cure rates were found to be comparable to that of systemic antibiotic only therapy and occasionally better. Inhaled antibiotic therapy was found to have an acceptable safety profile by avoiding systemic toxicity; despite previous concerns regarding the emergence of antimicrobial resistance, recent studies did not support such concerns. However, in respect of the sparity of data larger randomized trial are needed to shed more light in this promising form of treatment.

Nosocomial MRSA Pneumonia: Data from Recent Clinical Trials

MRSA infections, especially pneumonia have been associated with considerable morbidity and mortality and the management of MRSA infections is considered as an issue of high priority for scientific societies. Many studies which have been published during the last 10 years have provided evidence for MRSA pneumonia epidemiology, diagnosis and treatment. The main regime of antibiotic treatment recommended for MRSA pneumonia is either vancomycin or linezolid. Despite its pK/pD superiority over vancomycin, linezolid has to date failed to show clear advantage over vancomycin in recent clinical trials.

Adjunctive therapies in severe pneumonia in critical care patients.

AIM To review available evidence for the role of adjunctive therapies in severe pneumonia. METHODS We focused on therapies that have attracted recently interest such as glucocorticosteroids (GCs), statins and recombinant activated protein-C. RESULTS Experimental animal and human studies showed that GCs are able to modulate the inflammatory response and may offer a benefit in patients with severe sepsis. Randomized trials in pneumonia are few, mostly limited in septic shock and ARDS patients. Recombinant activated protein C is a potent anticoagulant and profibrinolytic enzyme which can inhibit the systemic inflammatory response. Available data, although limited, showed that activated protein C can reduce mortality in severe sepsis, especially in severe pneumonia due to S. Pneumoniae. Statins have pleiotropic properties which can affect the inflammatory cascade. The use of statins has been found to be associated with decreased mortality in some studies with pneumina whereas the use of statins was associated with increased risk of death in others. However, data come from observational or retrospective studies. CONCLUSION Treatment with GCs may modulate the inflammatory response in critically ill patients with pneumonia but a clear effect of steroids on survival is debatable. The administration of GCs should be considered in patients with severe pneumonia when vasopressor dependent septic shock. Activated protein-C may be considered in patients with severe CAP or HAP and sepsis or organ failure. The role of statins in the management of severe pneumonia remains controversial until data from clinical trails will be available.

The Role of Intraventricular Antibiotics in the Treatment of Nosocomial Ventriculitis/Meningitis from Gram-Negative Pathogens: A Systematic Review and Meta-Analysis

BACKGROUND The emergence of multidrug-resistant pathogens has resulted in difficult-to-treat ventriculitis/meningitis (VM). We used a meta-analysis to study the role of intraventricular (IVT) antibiotic administration as an adjunct (IVT plus intravenous [IV]) to the classic intravenous antimicrobial therapy (IV-only) in the management of VM in terms of infection control, functional outcome, microbial eradication, complications, cost-benefit analysis, infectious mortality, and overall mortality. METHODS The electronic search focused on adult neurosurgical cases complicated by gram-negative VM and was limited to studies comparing IVT plus IV and IV-only. The quality of the overall body of evidence was assessed according to GRADE (Grading of Recommendations Assessment, Development, and Evaluation). The pooled estimates for each question were summarized as odds ratios (ORs) and visualized using forest plots. Every outcome was stratified according to carbapenem resistance. RESULTS Eleven studies with 348 patients fulfilled the eligibility criteria. No evidence was found for infection control, functional outcome, or complications. For the remaining items evaluated, the overall quality of the best available evidence was low. IVT plus IV treatment was statistically superior to IV-only therapy in eradication (OR, 10.06; 95% confidence interval [CI], 2.62-38.65), infectious mortality (OR, 0.1; 95% CI, 0.03-0.36), and overall mortality (OR, 0.22; 95% CI, 0.08-0.60) in the management of carbapenem-resistant pathogens only. CONCLUSIONS Combined IVT plus IV treatment did not prove superior to standard IV-only treatment in the management of VM. Nevertheless, weak evidence showed that IVT treatment might serve as an adjunct in the management of carbapenem-resistant pathogens.