Nikolaos Markou

Intravenous colistin in the treatment of sepsis from multiresistant Gram-negative bacilli in critically ill patients

IntroductionThe increasing prevalence of multiresistant Gram-negative strains in intensive care units (ICUs) has recently rekindled interest in colistin, a bactericidal antibiotic that was used in the 1960s for treatment of infections caused by Gram-negative bacilli. We conducted the present observational study to evaluate the efficacy of intravenous colistin in the treatment of critically ill patients with sepsis caused by Gram-negative bacilli resistant to all other antibiotics.Patients and methodCritically ill patients with sepsis caused by Gram-negative bacilli resistant to all antibiotics with the exception of colistin were treated in the six-bed ICU of a trauma hospital. Diagnosis of infection was based on clinical data and isolation of bacteria, and the bacteria were tested with respect to their susceptibility to colistin. Clinical response to colistin was evaluated.ResultsTwenty-four patients (mean age 44.3 years, mean Acute Physiology and Chronic Health Evaluation II score 20.6) received 26 courses of colistin. Clinical response was observed for 73% of the treatments. Survival at 30 days was 57.7%. Deterioration in renal function was observed in 14.3% of 21 patients who were not already receiving renal replacement therapy, but in only one case did this deterioration have serious clinical consequences.ConclusionThe lack of a control group in the present study does not allow any definite conclusions to be drawn regarding the clinical effectiveness of colistin. On the other hand, this drug has an acceptable safety profile and its use should be considered in severe infections with multiresistant Gram-negative bacilli.

Colistin serum concentrations after intravenous administration in critically ill patients with serious multidrug-resistant, gram-negative bacilli infections: a prospective, open-label, uncontrolled study.

BACKGROUND The emergence of multidrug-resistant nosocomial pathogens, such as Pseudomonas aeruginosa and Acinetobacter baumannii, has led to the revival of the systemic use of antimicrobial agent colistin in critically ill patients, but only limited data are available to define its pharmacokinetic profile in these patients. OBJECTIVE The aim of this study was to assess steady-state serum concentrations of colistin after i.v. administration of colistin methanesulfonate (CMS) in critically ill patients with stable kidney function. METHODS This prospective, open-label, uncontrolled study was conducted at 2 intensive care units in the Athens Trauma Hospital, KAT, Athens, Greece. Adult patients were nonconsecutively enrolled if they were critically ill and had stable kidney function (<0.5 mg/dL change in serum creatinine prior to and until the day of sample collection) and had been receiving CMS as part of a treatment regimen for sepsis irrespective of site of infection with multidrug-resistant, gram-negative bacilli. After i.v. administration of 225-mg CMS (with the exception of 1 patient who received 150 mg) every 8 or 12 hours for at least 2 days, blood samples were collected just before and at 10 minutes and 1, 2, 4, 6, and 8 hours after i.v. infusion (duration, 30 minutes) of the colistin dose on the sampling day. RESULTS Fourteen nonconsecutive patients were enrolled in the study (13 male, 1 female; mean [SD] age, 62.0 [19.2] years; mean [SD] estimated weight, 72.5 [8.5] kg; mean [SD] Acute Physiology And Chronic Health Evaluation II score on admission, 17.1 [6.0]). At steady state, mean (SD) colistin maximum and minimum concentrations were 2.93 (1.24) and 1.03 (0.44) mg/L, respectively, while mean (SD) apparent total body clearance, apparent volume of distribution, and t(1/2) were 13.6 (5.8) L/h, 139.9 (60.3) L, and 7.4 (1.7) hours, respectively. Colistin-related nephrotoxicity was not observed in the study patients. CONCLUSION CMS dosage regimens administered to these critically ill adult patients were associated with suboptimal Cmax/MIC ratios for many strains of gram-negative bacilli currently reported as sensitive (MIC, < or = 2 microg/mL).

Sleep-Disordered Breathing in Nondialyzed Patients with Chronic Renal Failure

The prevalence and significance of sleep-disordered breathing (SDB) in dialysis-independent chronic renal failure (CRF) remains unknown. We studied the presence of SDB in nondialyzed CRF patients. Diagnostic polysomnography was performed in consecutive stable nondialyzed CRF patients. Inclusion criteria were age ≤70 years, absence of systolic dysfunction or history of pulmonary edema, FEV1 > 70% pr, absence of neurologic disease or hypothyroidism, and calculated creatinine clearance <40 ml/min. Thirty-five patients (19 male, 16 female) were studied. An apnea–hypopnea index (AHI) ≥5/h was present in 54.3% (almost exclusively obstructive events). AHI correlated with urea (r = 0.35, p = 0.037), age (r = 0.379, p = 0.025), and body mass index (BMI) (r = 0.351, p = 0.038), but not with creatinine clearance. AHI or SDB were unrelated to gender. In nondiabetics (n = 25), AHI correlated with urea (r = 0.608, p = 0.001) and creatinine clearance (r = −0.50, p = 0.012). Nondiabetics with severe CRF (calculated GFR < 15 ml/min/1.73 m2) had a significantly higher AHI compared with less severe CRF. Restless legs syndrome (RLS) was present in 37.1% and periodic limb movements in 28.6%. Daytime sleepiness was not associated with respiratory events, but was more common in patients with RLS. The prevalence of SDB and RLS is high in dialysis-independent CRF. SDB weakly correlates with indices of kidney function and this association becomes stronger in nondiabetics.

Colistin pharmacokinetics in intensive care unit patients on continuous venovenous haemodiafiltration: an observational study

OBJECTIVES Available data on colistin pharmacokinetics in patients undergoing continuous renal replacement therapy (CRRT) are limited. Our aim was to study colistin pharmacokinetics in critically ill patients treated with colistin methane sulphonate for Gram-negative sepsis and undergoing continuous venovenous haemodiafiltration for acute renal failure. PATIENTS AND METHODS Three patients were studied. The colistin methane sulphonate dose administered was at the discretion of the attending physician and was in all cases lower than that recommended for individuals with intact renal function. Colistin methane sulphonate was administered intravenously over 30 min, and blood samples were collected from each patient pre- and post-filter for the HPLC determination of colistin levels in serum before infusion, at 10, 60, 120, 240, 360, 480 and 600 min from the end of infusion, and immediately before the next dose. Concurrently, spot samples of effluent from the haemofilter were also collected and analysed. Both colistin total extracorporeal clearance and clearance in the effluent were calculated. RESULTS Extracorporeal clearance resulted in substantial removal of colistin (43%-59% of total colistin clearance). Total colistin clearance was found to be reduced (varying between 3.3 and 4.5 L/h), compared with patients with normal renal function. Colistin methane sulphonate dosage resulted in clearly suboptimal colistin steady-state concentrations. CONCLUSIONS In spite of substantial extracorporeal clearance, total colistin clearance was reduced, compared with patients with normal renal function. Colistin adsorption by the haemofilter contributed to its extracorporeal clearance to a large extent. Studies on other patients receiving colistin methane sulphonate and undergoing CRRT are required before more appropriate dosage regimens can be recommended.

Severity of illness and outcome in adult patients with Primary Varicella pneumonia

Background: Varicella pneumonia is a serious complication of primary varicella infection in adults that often results in respiratory failure and death. Objective: To analyze the clinical and laboratory manifestations of primary varicella pneumonia in patients admitted to our intensive care unit (ICU). Methods: Retrospective study on patients treated in our ICU with a diagnosis of primary varicella pneumonia during a period of 15 years. We recorded age, gender, smoking habits, clinical and laboratory findings, arterial blood gases, chest radiograph, illness severity (SAPS II), length of stay, necessity for mechanical ventilation, complications, therapy and survival. We examined the influence of the duration of respiratory symptoms and rash prior to admission, and the influence of illness severity on outcome. Results: There was a statistically significant difference in duration of respiratory symptoms, duration of rash and SAPS II on admission between: (a) mechanically ventilated patients vs. spontaneously breathing patients (p < 0.007, p < 0.00, p < 0.00), (b) patients who survived vs. patients with poor outcome (p < 0.001, p < 0.000, p < 0.000), and (c) mechanically ventilated patients with poor outcome vs. mechanically ventilated patients who survived (p < 0.001, p < 0.00, p < 0.000). Overall mortality was 13.6%; death occurred only in mechanically ventilated patients (mortality 33.3%). Conclusions: Primary varicella pneumonia remains a critical problem with significant mortality. When recognized before respiratory failure ensues and mechanical ventilation becomes mandatory, patients could have an excellent outcome. Adult patients who delay asking for medical support, the disease may lead to the need for mechanical ventilation and severe complications with a fatal outcome.

Increased blood troponin levels in ICU patients.

Purpose of reviewCardiac troponins in serum have become the biomarkers of choice for the diagnosis of myocardial infarction. Yet, troponin can also be elevated by a multitude of causes in the absence of overt myocardial ischemia. Such nonspecific elevations are particularly common in the critically ill. This article aims to provide information on the significance of troponin elevations in unselected critically ill patients and in patients with sepsis or septic shock. Recent findingsRecent studies reconsider the possible association of troponin elevations with myocardial infarction in unselected critically ill patients. There are also more data on the prognostic significance of troponin in this population. In patients with sepsis, recent studies suggest that troponin may be a reliable index of sepsis-induced myocardial dysfunction, although the implications of this finding in the management of sepsis remain unclear for the time being. Troponin also appears to be a predictor of short and possibly also long-term outcome in septic patients. The advent of newer assays with even higher sensitivity, may lead to further redefinition of the role of troponin in the ICU. SummaryTroponin is frequently elevated in critically ill patients. More research is needed on the diagnostic and prognostic significance and possible clinical applications of troponin measurements in patients with sepsis and critical illness.

Rare roentgenologic manifestations of pulmonary edema.

Purpose of reviewUnilateral pulmonary edema (UPE) is an unusual manifestation of pulmonary edema that is frequently confused with other causes of unilateral alveolar and interstitial infiltrates. Until now limited data existed regarding the prevalence, cause, and outcome of patients presenting with cardiogenic UPE. The purpose of this review is to give insights into this rare entity. Recent findingsIn a recent retrospective study, the prevalence of UPE was 2.1% of all cases of cardiogenic pulmonary edema. UPE was right-sided in 89%. All patients with UPE had severe mitral regurgitation. In patients with UPE, blood pressure was significantly lower, whereas noninvasive or invasive ventilation and catecholamines were used more frequently compared with patients with bilateral pulmonary edema. In-hospital mortality was higher for patients with UPE (39 vs. 8% for bilateral pulmonary edema) and UPE was independently related to death (a 6.5-fold higher risk of death). Delayed treatment of UPE could be one of the explanations for this increased mortality. SummaryUPE is not that rare as considered to be and is mostly related to severe organic or functional mitral regurgitation. Probably because of initial misdiagnosis and delayed appropriate treatment, UPE is related to increased mortality. History, absence of signs of infection, and elevated serum cardiac markers such as B-natriuretic peptide may help to differentiate UPE from other diagnoses. The key examination remains bedside transthoracic echocardiography, although transesophageal echocardiography can also provide additional information regarding the severity and mechanism of mitral regurgitation and documentation of the differential pressure between the right and left pulmonary veins.

A Case of Drug-Induced Pneumonitis Caused by Carvedilol

We present a case of drug- induced pneumonitis caused by carvedilol. Forty days after drug cessation, there was almost complete resolution of pulmonary infiltrates. This is the first report of pneumonitis caused by carvedilol.

Primary thoracic muscle tuberculosis: two case reports

BackgroundThe aim of this case report is to present our experience with two very rare cases of thoracic muscle tuberculosis. Muscle tuberculosis, as a primary disease, can only be detected in cases in which mycobacteria have been transplanted to a muscle through an infected needle.Case presentationsCase 1 is a 38-year-old immigrant man and Case 2 is a 24-year-old immigrant man, both originating from Sub-Saharan African Countries; they presented in the past two years to our hospital with swellings at the base of the hemithorax and were diagnosed as having muscle tuberculosis. Administration of anti-tuberculosis chemotherapy caused: (a) diminution of inflammation, (b) diminution of the size of local fusiform injury, and (c) clinical improvement.ConclusionsThoracic muscle tuberculosis should be considered to be one of the etiologies of muscular disease in European countries with a high incidence of immigrants originating from endemic geographical areas.

Organization of Ventilatory Support

Mechanical ventilation constitutes one of the therapeutic cornerstones in the treatment of the critically ill. Depending on the indication for mechanical ventilation, the severity of the patient and the resources available, mechanical ventilation can be applied nowadays at a variety of locations and under different organizational settings. As a rule, the requirements are much more demanding for invasive mechanical ventilation and for the acutely ill patient, especially with increasing patient severity.