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Michalopoulos A.,ICU | Falagas M.E.,Alfa Institute of Biomedical science AIBS
Expert Opinion on Pharmacotherapy | Year: 2010

Importance of the field: Acinetobacter baumannii has emerged as a major cause of healthcare-associated infections. It commonly presents resistance to multiple antimicrobial agents, occasionally including carbapenems and polymyxins, and hence, it is considered the paradigm of multidrug-resistant (MDR) or pandrug-resistant (PDR) bacterium. MDR A. baumannii is a rapidly emerging pathogen, especially in the intensive care setting, causing infections including bacteremia, pneumonia/ventilator-associated pneumonia (VAP), meningitis, urinary tract infection, central venous catheter-related infection, and wound infection. Areas covered in this review: All potential antimicrobial agents that are available for the treatment of Acinetobacter infections are presented. Emphasis was given to the management of nosocomial infections due to MDR A. baumannii and its close relatives, spp. 3 and 13TU. Areas covered include bloodstream infections, pneumonia or VAP, meningitis, urinary tract infection, skin and soft-tissue or wound infections due to Acinetobacter. What the reader will gain: The antibiotics that are usually effective against A. baumannii infections include carbapenems, polymyxins E and B, sulbactam, piperacillin/tazobactam, tigecycline and aminoglycosides. Carbapenems (imipenem, meropenem, doripenem) are the mainstay of treatment for A. baumannii, though carbapenem-resistant Acinetobacter strains have increasingly been reported worldwide in recent years. However, although well-designed trials of new therapeutic approaches are certainly required, the most important factor necessary to guide clinicians in their choice of empirical or targeted therapy should be knowledge of the susceptibility patterns of strains present in their own geographical area. Take home message: Pooled data suggest that infections caused by A. baumannii, especially those with inappropriate treatment, are associated with considerable attributable mortality. The optimal treatment for A. baumannii nosocomial infections has not been established, especially for MDR strains. Therefore, well-designed clinical studies are necessary to guide clinicians on decisions regarding the best therapeutic approach for patients with MDR A. baumannii infections. In addition, new experimental studies are warranted to evaluate the activity and safety of peptides and other novel antibacterial agents for A. baumannii infections. © 2010 Informa UK Ltd. Source

Mavros M.N.,Johns Hopkins University | Mavros M.N.,Alfa Institute of Biomedical science AIBS | Mayo S.C.,Johns Hopkins University | Hyder O.,Johns Hopkins University | Pawlik T.M.,Johns Hopkins University
Journal of the American College of Surgeons | Year: 2012

Background: Fibrolamellar hepatocellular carcinoma (FLC) is a rare primary liver tumor presenting earlier in life than nonfibrolamellar hepatocellular carcinoma (NFL-HCC), with distinct epidemiologic and clinical characteristics. Although FLC is believed to have a better prognosis than NFL-HCC, data on treatment and prognosis are scarce. We performed a systematic review to investigate treatment options and clinical outcomes of patients with FLC. Study Design: The study is a systematic review of the literature and pooled analysis of individual patient data. Results: A total of 35 series were analyzed, reporting on 575 patients (52% female, elevated alpha-fetoprotein in 10%, cirrhosis in 3%, hepatitis B in 2%), most of whom were treated with partial hepatectomy (55%) or orthotopic liver transplantation (23%). Nineteen studies provided data on 206 individual patients with a median age of 21 years and tumor size of 12 cm. Median overall survival (OS) was 39 months; 1-year, 3-year, and 5-year OS rates were 85%, 53%, and 44%, respectively. For patients treated with liver resection, median OS was 18.5 years and 1-year, 3-year, and 5-year OS were 93%, 80%, and 70%, respectively. Based on data from 15 studies, FLC appeared to follow a relatively indolent course compared with NFL-HCC. Conclusions: Patients with FLC treated with partial hepatectomy have excellent long-term survival, with 5-year overall survival reaching 70%. Patients fared worse with the use of other therapeutic options including chemotherapy, intra-arterial therapy, and transplantation, although data directly comparing resection vs transplantation were limited. © 2012 American College of Surgeons. Source

Michalopoulos A.S.,Intensive Care Unit | Falagas M.E.,Alfa Institute of Biomedical science AIBS | Falagas M.E.,Tufts University
Minerva Anestesiologica | Year: 2014

During the last decade, inhaled antibiotics, especially colistin, has been widely used worldwide as a therapeutic option, supplementary to conventional intravenous antibiotics, for the treatment of multidrug-resistant (MDR) Gram-negative nosocomial and ventilator-associated pneumonia (VAP). Antimicrobial aerosols are commonly used in mechanically ventilated patients with VAP, although information regarding their efficacy and optimal technique of administration has been limited. Recent studies showed that the administration of inhaled antibiotics in addition to systemic antibiotics provided encouraging results associated with low toxicity for the management of VAP mainly due to MDR Gram negative bacteria. Although the theory behind aerosolized administration of antibiotics seems to be sound, there are limited data available to support the routine use of this modality since very few randomized controlled trials (RCTs) have still examined the efficacy of this approach in patients with VAP. Additionally, this route of antibiotic delivery has not been approved until now neither by the FDA nor by the European Medicines Agency (EMEA) in patients with VAP. However, since the problem of VAP due to MDR bacteria has been increased worldwide RCTs are urgently needed in order to prove the safety, efficiency and efficacy of inhaled antimicrobial agents administered alone or in conjunction with parenteral antibiotics for the management of VAP in critically ill patients. Indeed, more data are needed to establish the appropriate role of inhaled antibiotics for the treatment of VAP. (Minerva Anestesiol 2014;80:236-44). Source

Polyzos K.A.,Alfa Institute of Biomedical science AIBS | Polyzos K.A.,Atherosclerosis Research Unit | Konstantelias A.A.,Alfa Institute of Biomedical science AIBS | Falagas M.E.,Alfa Institute of Biomedical science AIBS | Falagas M.E.,Tufts University
Europace | Year: 2015

Infectious complications after cardiac implantable electronic device (CIED) implantation are increasing over time and are associated with substantial mortality and healthcare costs. The aim of this study was to systematically summarize the literature on risk factors for infection after pacemaker, implantable cardioverter-defibrillator, and cardiac resynchronization therapy device implantation. Electronic searches (up to January 2014) were performed in PubMed, Scopus, and Web of Science databases. Sixty studies (21 prospective, 9 case-control, and 30 retrospective cohort studies) met the inclusion criteria. The average device infection rate was 1-1.3%. In the meta-analysis, significant host-related risk factors for infection included diabetes mellitus (odds ratio (OR) [95% confidence interval] = 2.08 [1.62-2.67]), end-stage renal disease (OR = 8.73 [3.42-22.31]), chronic obstructive pulmonary disease (OR = 2.95 [1.78-4.90]), corticosteroid use (OR = 3.44 [1.62-7.32]), history of the previous device infection (OR = 7.84 [1.94-31.60]), renal insufficiency (OR = 3.02 [1.38-6.64]), malignancy (OR = 2.23 [1.26-3.95]), heart failure (OR = 1.65 [1.14-2.39]), pre-procedural fever (OR = 4.27 [1.13-16.12]), anticoagulant drug use (OR = 1.59 [1.01-2.48]), and skin disorders (OR = 2.46 [1.04-5.80]). Regarding procedure-related factors, post-operative haematoma (OR = 8.46 [4.01-17.86]), reintervention for lead dislodgement (OR = 6.37 [2.93-13.82]), device replacement/revision (OR = 1.98 [1.46-2.70]), lack of antibiotic prophylaxis (OR = 0.32 [0.18-0.55]), temporary pacing (OR = 2.31 [1.36-3.92]), inexperienced operator (OR = 2.85 [1.23-6.58]), and procedure duration (weighted mean difference = 9.89 [0.52-19.25]) were all predictors of CIED infection. Among device-related characteristics, abdominal pocket (OR = 4.01 [2.48-6.49]), epicardial leads (OR = 8.09 [3.46-18.92]), positioning of two or more leads (OR = 2.02 [1.11-3.69]), and dual-chamber systems (OR = 1.45 [1.02-2.05]) predisposed to device infection. This systematic review on risk factors for CIED infection may contribute to developing better infection control strategies for high-risk patients and can also help risk assessment in the management of device revisions. © The Author 2015. Source

Mavros M.N.,Alfa Institute of Biomedical science AIBS | Velmahos G.C.,Harvard University | Falagas M.E.,Alfa Institute of Biomedical science AIBS | Falagas M.E.,Tufts University
Chest | Year: 2011

Background: Atelectasis is considered to be the most common cause of early postoperative fever (EPF) but the existing evidence is contradictory. We sought to determine if atelectasis is associated with EPF by analyzing the relevant published evidence. Methods: We performed a systematic search in PubMed and Scopus databases to identify studies examining the association between atelectasis and EPF. Results: A total of eight studies, including 998 cardiac, abdominal, and maxillofacial surgery patients, were eligible for analysis. Only two studies specifically examined our question, and six additional articles reported sufficient data to be included. Only one study reported a significant association between postoperative atelectasis and fever, whereas the remaining studies indicated no such association. The performance of EPF as a diagnostic test for atelectasis was also assessed, and EPF performed poorly (pooled diagnostic OR, 1.40; 95% CI, 0.92-2.12). The significant heterogeneity among the studies precluded a formal metaanalysis. Conclusion: The available evidence regarding the association of atelectasis and fever is scarce. We found no clinical evidence supporting the concept that atelectasis is associated with EPF. More so, there is no clear evidence that atelectasis causes fever at all. Large studies are needed to precisely evaluate the contribution of atelectasis in EPF. © 2011 American College of Chest Physicians. Source

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