George Samonis

Real-time ultrasound-guided catheterisation of the internal jugular vein: a prospective comparison with the landmark technique in critical care patients

IntroductionCentral venous cannulation is crucial in the management of the critical care patient. This study was designed to evaluate whether real-time ultrasound-guided cannulation of the internal jugular vein is superior to the standard landmark method.MethodsIn this randomised study, 450 critical care patients who underwent real-time ultrasound-guided cannulation of the internal jugular vein were prospectively compared with 450 critical care patients in whom the landmark technique was used. Randomisation was performed by means of a computer-generated random-numbers table, and patients were stratified with regard to age, gender, and body mass index.ResultsThere were no significant differences in gender, age, body mass index, or side of cannulation (left or right) or in the presence of risk factors for difficult venous cannulation such as prior catheterisation, limited sites for access attempts, previous difficulties during catheterisation, previous mechanical complication, known vascular abnormality, untreated coagulopathy, skeletal deformity, and cannulation during cardiac arrest between the two groups of patients. Furthermore, the physicians who performed the procedures had comparable experience in the placement of central venous catheters (p = non-significant). Cannulation of the internal jugular vein was achieved in all patients by using ultrasound and in 425 of the patients (94.4%) by using the landmark technique (p < 0.001). Average access time (skin to vein) and number of attempts were significantly reduced in the ultrasound group of patients compared with the landmark group (p < 0.001). In the landmark group, puncture of the carotid artery occurred in 10.6% of patients, haematoma in 8.4%, haemothorax in 1.7%, pneumothorax in 2.4%, and central venous catheter-associated blood stream infection in 16%, which were all significantly increased compared with the ultrasound group (p < 0.001).ConclusionThe present data suggest that ultrasound-guided catheterisation of the internal jugular vein in critical care patients is superior to the landmark technique and therefore should be the method of choice in these patients.

Fungal Infections Complicating Tumor Necrosis Factor α Blockade Therapy

Tumor necrosis factor α (TNF-α) blockade has emerged as a useful therapy for collagen vascular diseases or graft-vs-host disease. Fungal infections complicating such therapy have been reported sporadically. MEDLINE and PubMed databases (from January 1, 1966, to June 1, 2007) were searched for reports of invasive fungal infections (IFIs) associated with the 3 available anti-TNF-α agents, ie, infliximab, etanercept, and adalimumab. Of the 281 cases of IFI associated with TNF-α inhibition, 226 (80%) were associated with infliximab, 44 (16%) with etanercept, and 11 (4%) with adalimumab. Fungal infections associated with infliximab occurred a median of 55 days (interquartile range [IQR], 15-140 days) after initiation of therapy and 3 infusions of the medication (IQR, 2-5), whereas those associated with etanercept occurred a median of 144 days (IQR, 46-240 days) after initiation of therapy. The median age of patients was 58 years (IQR, 44-68 years), and 62% were male. Use of at least 1 other immunosuppressant medication, typically a systemic corticosteroid, was reported during the course of the fungal infection in 102 (98%) of the 104 patients for whom data were available. The most prevalent IFIs were histoplasmosis (n=84 [30%]), candidiasis (n=64 [23%]), and aspergillosis (n=64 [23%]). Pneumonia was the most common pattern of infection. Of the 90 (32%) of 281 cases for which outcome information was available, 29 fatalities (32%) were recorded. Tumor necrosis factor α blockade is associated with IFI across a range of host groups. A high index of suspicion in patients treated with TNF-α antagonists is recommended because the course of such infections can be serious or fulminant, and rapid access to health care should be provided. Surveillance of IFIs complicating TNF-α blockade and other biologic therapies is warranted through well-organized prospective patient registries.

A multicenter phase III trial comparing irinotecan-gemcitabine (IG) with gemcitabine (G) monotherapy as first-line treatment in patients with locally advanced or metastatic pancreatic cancer

Our purpose was to determine the response rate and median and overall survival of gemcitabine as monotherapy versus gemcitabine plus irinotecan in advanced or metastatic pancreatic cancer. Patients with histologically or cytologically confirmed adenocarcinoma who were chemotherapy and radiotherapy naive were enrolled. Patients were centrally randomised at a one-to-one ratio to receive either gemcitabine monotherapy (900 mg m−2 on days 1, 8 and 15 every 4 weeks (arm G), or gemcitabine (days 1 and 8) plus irinotecan (300 mg m−2 on day 8) (arm IG), repeated every 3 weeks. The total number of cycles administered was 255 in the IG arm and 245 in the G arm; the median number of cycles was 3. In all, 145 patients (71 in arm IG and 74 in arm G) were enrolled; 60 and 70 patients from arms IG and G, respectively, were evaluable. A complete clinical response was achieved in three (4.3%) arm G patients; nine (15%) patients in arm IG and four (5.7%) in arm G achieved a partial response. The overall response rate was: arm IG 15% and arm G 10% (95% CI 5.96–24.04 and 95% CI 2.97–17.03, respectively; P=0.387). The median time to tumour progression was 2.8 months and 2.9 months and median survival time was 6.4 and 6.5 months for the IG and G arms, respectively. One-year survival was 24.3% for the IG arm and 21.8% for the G arm. No statistically significant difference was observed comparing gemcitabine monotherapy versus gemcitabine plus irinotecan in the treatment of advanced pancreatic cancer, with respect to overall and 1-year survival.

Effect of Aminoglycoside and β-Lactam Combination Therapy versus β-Lactam Monotherapy on the Emergence of Antimicrobial Resistance: A Meta-analysis of Randomized, Controlled Trials

BACKGROUND The addition of an aminoglycoside to a beta -lactam therapy regimen has been suggested to have a beneficial effect in delaying or preventing the development of antimicrobial resistance. We studied the effect of aminoglycoside/ beta -lactam combination therapy versus beta-lactam monotherapy on the emergence of resistance. METHODS We performed a meta-analysis of randomized, controlled trials (RCTs) that compared aminoglycoside/ beta-lactam combination therapy with beta-lactam monotherapy and that reported data regarding the emergence of resistance (primary outcome) and/or development of superinfection, treatment failure, treatment failure attributable to emergence of resistance, treatment failure attributable to superinfection, all-cause mortality during treatment, and mortality due to infection. Data for this meta-analysis were identified from the PubMed database, Current Contents database, Cochrane central register of controlled trials, and references in relevant articles. RESULTS A total of 8 RCTs were included in the analysis. Beta -lactam monotherapy was not associated with a greater emergence of resistance than was the aminoglycoside/ beta-lactam combination (odds ratio [OR], 0.90; 95% confidence interval [CI], 0.56-1.47). Actually, beta -lactam monotherapy was associated with fewer superinfections (OR, 0.62; 95% CI, 0.42-0.93) and fewer treatment failures (OR, 0.62; 95% CI, 0.38-1.01). Rates of treatment failure attributable to emergence of resistance (OR, 3.09; 95% CI, 0.75-12.82), treatment failure attributable to superinfection (OR, 0.60; 95% CI, 0.33-1.10), all-cause mortality during treatment (OR, 0.70; 95% CI, 0.40-1.25), and mortality due to infection (OR, 0.74; 95% CI, 0.46-1.21) did not differ significantly between the 2 regimens. CONCLUSIONS Compared with beta-lactam monotherapy, the aminoglycoside/ beta-lactam combination was not associated with a beneficial effect on the development of antimicrobial resistance among initially antimicrobial-susceptible isolates.

Outcome of infections due to pandrug-resistant (PDR) Gram-negative bacteria

BackgroundThe increasing problem of infections due to multidrug-resistant Gram-negative bacteria has led to re-use of polymyxins in several countries. However, there are already clinical isolates of Gram-negative bacteria that are resistant to all available antibiotics, including polymyxins.MethodsWe present a case series of patients with infections due to pathogens resistant to all antimicrobial agents tested, including polymyxins. An isolate was defined as pandrug-resistant (PDR) if it exhibited resistance to all 7 anti-pseudomonal antimicrobial agents, i.e. antipseudomonal penicillins, cephalosporins, carbapenems, monobactams, quinolones, aminoglycosides, and polymyxins.ResultsClinical cure of the infection due to pandrug-resistant (PDR) Gram-negative bacteria, namely Pseudomonas aeruginosa or Klebsiella pneumoniae was observed in 4 out of 6 patients with combination of colistin and beta lactam antibiotics.ConclusionColistin, in combination with beta lactam antibiotics, may be a useful agent for the management of pandrug-resistant Gram-negative bacterial infections. The re-use of polymyxins, an old class of antibiotics, should be done with caution in an attempt to delay the rate of development of pandrug-resistant Gram-negative bacterial infections.

Vinorelbine Plus Cisplatin Versus Docetaxel Plus Gemcitabine in Advanced Non-Small-Cell Lung Cancer: A Phase III Randomized Trial

PURPOSE To compare the activity and tolerability of docetaxel/gemcitabine (DG) and vinorelbine/cisplatin (VC) combinations in chemotherapy-naive non-small-cell lung cancer (NSCLC) patients. PATIENTS AND METHODS Patients with advanced NSCLC were randomly assigned to receive either DG (gemcitabine 1,000 mg/m(2) [days 1 and 8] plus docetaxel 100 mg/m(2) [day 8]) or VC (vinorelbine 30 mg/m(2) [days 1 and 8] plus cisplatin 80 mg/m(2) [day 8]) and prophylactic recombinant human granulocyte colony-stimulating factor (150 microg/m(2) subcutaneously [day 9 through 15]) every 3 weeks. Results A total of 413 randomly assigned patients were analyzed for response and toxicity (DG, n = 197; VC, n = 192). Median survival was 9.0 and 9.7 months (P = .965) for DG and VC arms, respectively; the corresponding 1-year survival rates were 34.3% and 40.8%, respectively. Overall response rate was 30% (95% CI, 23.9% to 36.3%) and 39.2% (95% CI, 32.5% to 45.9%; P = .053) for DG and VC, respectively. Toxicity was as follows (DG v VC): grade 2 to 4 anemia, 34% v 55% (P = .0001); grade 3 to 4 neutropenia, 16% v 37% (P = .0001); febrile neutropenia, 6% v 11% (P = .009); and grade 3 to 4 nausea and vomiting, 1% v 15% (P = .003). Nephrotoxicity occurred in 8% and ototoxicity in 2% of VC-treated patients. There were five and six treatment-related deaths in the DG and VC arms, respectively. Quality of life was improved in DG but not in VC patients. CONCLUSION Although the two regimens produced comparable overall survival, the DG regimen had a better toxicity profile. Therefore, DG could be used in the first-line setting of advanced NSCLC, especially for patients who cannot tolerate cisplatin.

Combination Therapy with Intravenous Colistin for Management of Infections Due to Multidrug-Resistant Gram-Negative Bacteria in Patients without Cystic Fibrosis

ABSTRACT Colistin, an antibiotic almost abandoned for intravenous administration for many years due to its reported toxicity, has been recently reintroduced in clinical practice due to the emergence of multidrug-resistant gram-negative bacteria and the lack of development of new antibiotics to combat them. To assess the safety and effectiveness of intravenous colistin, in combination with other antimicrobial agents, in the treatment of serious infections in patients without cystic fibrosis, a retrospective cohort study in a 450-bed tertiary-care hospital in Athens, Greece, was performed. Patients who were hospitalized from 1 October 2000 to 31 January 2004 and received intravenous colistin for more than 72 h were further analyzed. The primary outcome measure was the in-hospital mortality; secondary end points were the clinical outcome of the infections and the occurrence of colistin toxicity. Fifty patients received intravenous colistin with a median (mean) daily dose of 3 (4.5) million IU for 16.5 (21.3) days for the management of 54 episodes of infections due to multidrug-resistant gram-negative bacteria. The predominant infections were pneumonia (33.3%), bacteremia (27.8%), urinary tract infection (11.1%), and intra-abdominal infection (11.1%). The responsible pathogens were Acinetobacter baumannii (51.9%), Pseudomonas aeruginosa (42.6%), and Klebsiella pneumoniae (3.7%) strains (no pathogen was isolated from one case). In-hospital mortality was 24% (12/50 patients). Clinical response (cure or improvement) of the infection was observed in 66.7% of episodes (36/54). In the studied group, serum creatinine levels were decreased, at the end of colistin treatment, by an average of 0.2 ± 1.3 mg/dl compared to baseline levels. Deterioration of renal function during colistin therapy was observed in 4/50 patients (8%). Coadministration of other antimicrobial agents with spectrum against gram-negative microorganisms and the absence of a control group constitute the major limitations of this study. The use of intravenous colistin for the treatment of infections due to multidrug-resistant gram-negative bacteria appears to be safe and effective.

Aerosolized plus Intravenous Colistin versus Intravenous Colistin Alone for the Treatment of Ventilator-Associated Pneumonia: A Matched Case-Control Study

OBJECTIVES The incidence of ventilator-associated pneumonia (VAP) due to multidrug-resistant (MDR) organisms is increasing. Intravenous (IV) colistin or aerosolized (AS) plus IV colistin have been recently used to treat these life-threatening infections. The purpose of this study was to compare the efficacy and safety of AS plus IV colistin versus IV colistin alone for patients with MDR VAP due to gram-negative bacteria. METHODS A retrospective matched case-control study was performed at the Intensive Care Unit of the University Hospital of Heraklion, Greece, from January 2005 through December 2008. Forty-three patients with VAP due gram-negative MDR pathogens received AS plus IV colistin and were matched on the basis of age and Acute Physiology and Chronic Health Evaluation II score with 43 control patients who had received IV colistin alone. RESULTS Demographic characteristics, clinical status, and gram-negative isolated pathogens were similar between the 2 treatment groups. Acinetobacter baumannii (66 cases [77%]) was the most common pathogen, followed by Klebsiella pneumoniae (12 cases [14%]) and Pseudomonas aeruginosa (8 cases [9.3%]). No colistin-resistant strains were isolated from patients in either group. No significant differences between the 2 groups were observed regarding eradication of pathogens (P = .679), clinical cure (P = .10), and mortality (P = .289). Eight patients (19%) in each treatment group developed reversible renal dysfunction. No AS colistin-related adverse events were recorded. CONCLUSIONS Addition of AS colistin to IV colistin did not provide additional therapeutic benefit to patients with MDR VAP due to gram-negative bacteria.

Treatment failure and recurrence of Clostridium difficile infection following treatment with vancomycin or metronidazole: a systematic review of the evidence.

The objective of this review was to evaluate the frequency of treatment failure and recurrence of Clostridium difficile infection (CDI) following treatment with vancomycin or metronidazole in recently performed studies (last 10 years). Searches in PubMed and Scopus were performed by two reviewers independently. Data regarding treatment failure and recurrence following metronidazole and vancomycin treatment were extracted and analysed. In total, 39 articles (7005 patients) were selected for inclusion in the systematic review. The reported treatment failure was 22.4% with metronidazole (16 studies) and 14.2% with vancomycin (8 studies). Recurrence of CDI occurred in 27.1% of patients following metronidazole treatment (18 studies) and 24.0% of patients following vancomycin treatment (8 studies). Mean treatment failure and recurrence in the selected studies was 22.3% (24 studies) and 22.1% (37 studies). The reported outcomes depended on the study design (higher in prospective and retrospective cohort studies than in randomised controlled trials), geographic location of the study (higher in North America than in Europe and Asia), funding (higher in studies funded by non-profit organisations than pharmaceutical companies), mean age of the studied population (higher in older patients) and duration of follow-up (higher in studies with follow-up >1 month). In conclusion, infection with C. difficile is associated with 22.4% and 14.2% treatment failure and 27.1% and 24.0% recurrence after treatment with metronidazole and vancomycin, respectively. The variation in the reported outcomes amongst studies depends on the study design, location, funding, age and follow-up period.

Risk factors associated with the isolation of colistin-resistant gram-negative bacteria: a matched case-control study.

Objective:The emergence of multidrug-resistant Gram-negative bacteria has led to the re-use of colistin, but resistance to this agent has already been reported. We aimed to investigate the potential risk factors for the isolation of colistin-resistant Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa from hospitalized patients. Design:Matched case-control study. Setting:Tertiary care hospital in Athens, Greece. Patients:Case patients were those who had provided a clinical specimen from which a colistin-resistant K. pneumoniae, A. baumannii, or P. aeruginosa was isolated. Controls were selected from a pool of patients who had susceptible to colistin isolates and were matched (1:1) to cases for species of microorganism and site of isolation. Susceptibility to colistin was determined with the Etest. Interventions:None. Measurements and Main Results:Data regarding patient demographics, comorbidities, admission to the intensive care unit, prior antibiotic use, and invasive procedures performed were analyzed as risk factors in a matched bivariable model. Variables significantly associated with colistin-resistant isolates (p < .05) were entered in a backward multivariable logistic regression model. Forty-one colistin-resistant unique patient isolates were identified from January 1, 2006, until March 31, 2007. These isolates represented infection in 35 of 41 patients. Risk factors significantly associated with the isolation of colistin-resistant isolates were age, duration of intensive care unit stay, duration of mechanical ventilation, surgical procedures, use of colistin, use of monobactams, and duration of use of third-generation cephalosporins. In the multivariable model, use of colistin was identified as the only independent risk factor (adjusted odds ratio = 7.78, p = .002). Conclusions:Colistin-resistant K. pneumoniae, A. baumannii, and P. aeruginosa pathogens may be encountered in clinical practice, in association with inappropriate colistin use. To prevent this phenomenon, colistin should be used judiciously, given that treatment options for colistin-resistant Gram-negative bacteria are limited.