Archive for November, 2015

Bloodstream infections in intensive care unit patients: distribution and antibiotic resistance of bacteria.

Infect Drug Resist. 2015 Aug 10;8:287-96.

Russotto V1, Cortegiani A1, Graziano G2, Saporito L2, Raineri SM1, Mammina C2, Giarratano A1.

Author information

1Department of Biopathology and Medical Biotechnologies (DIBIMED), Section of Anaesthesia, Analgesia, Intensive Care and Emergency, Paolo Giaccone University Hospital, University of Palermo, Palermo, Italy.

2Department of Sciences for Health Promotion and Mother-Child Care, University of Palermo, Palermo, Italy.


Bloodstream infections (BSIs) are among the leading infections in critically ill patients. The case-fatality rate associated with BSIs in patients admitted to intensive care units (ICUs) reaches 35%-50%.

The emergence and diffusion of bacteria with resistance to antibiotics is a global health problem. Multidrug-resistant bacteria were detected in 50.7% of patients with BSIs in a recently published international observational study, with methicillin resistance detected in 48% of Staphylococcus aureus strains, carbapenem resistance detected in 69% of Acinetobacter spp., in 38% of Klebsiella pneumoniae, and in 37% of Pseudomonas spp.

Prior hospitalization and antibiotic exposure have been identified as risk factors for infections caused by resistant bacteria in different studies.

Patients with BSIs caused by resistant strains showed an increased risk of mortality, which may be explained by a higher incidence of inappropriate empirical therapy in different studies.

The molecular genetic characterization of resistant bacteria allows the understanding of the most common mechanisms underlying their resistance and the adoption of surveillance measures.

Knowledge of epidemiology, risk factors, mechanisms of resistance, and outcomes of BSIs caused by resistant bacteria may have a major influence on global management of ICU patients.

The aim of this review is to provide the clinician an update on BSIs caused by resistant bacteria in ICU patients.


November 26, 2015 at 7:43 pm

Ceftobiprole for the treatment of pneumonia: a European perspective.

Drug Des Devel Ther. 2015 Aug 18;9:4565-72.

Liapikou A1, Cillóniz C2, Torres A2.

Author information

16th Respiratory Department, Sotiria Chest Diseases Hospital, Athens, Greece.

2Pulmonology Department, Clinic Institute of Thorax (ICT), Hospital Clinic of Barcelona, Spain Insitut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.


Ceftobiprole, a new broad spectrum, parenteral cephalosporin, exhibits potent in vitro activity against a number of Gram-positive pathogens, including methicillin-resistant Staphylococcus aureus and penicillin-resistant Streptococcus pneumoniae, and Gram-negative pathogens associated with hospital-acquired pneumonia (HAP) and community-acquired pneumonia (CAP). Ceftobiprole has demonstrated noninferiority in two large-scale pivotal studies comparing it to ceftriaxone with or without linezolid in CAP, with clinical cure rates 86.6% versus 87.4%, or ceftazidime in HAP, with clinical cure rates of 77% versus 76%, respectively. However, ceftobiprole was inferior in the subgroup of patients undergoing mechanical ventilation. Ceftobiprole has so far demonstrated a good safety profile in preliminary studies, with similar tolerability to comparators. The most commonly observed adverse events of ceftobiprole included headache and gastrointestinal upset. It is the first cephalosporin monotherapy approved in the EU for the treatment of both CAP and HAP (excluding ventilator-associated pneumonia).


November 26, 2015 at 7:40 pm

Dalbavancin: A Novel Lipoglycopeptide Antibiotic with Extended Activity Against Gram-Positive Infections.

Infect Dis Ther. 2015 Sep;4(3):245-58.

Smith JR1, Roberts KD2, Rybak MJ3.

Author information

1High Point University School of Pharmacy, 833 Montlieu Avenue, High Point, NC, 27265, USA.

2St. Vincent Indianapolis, 2001 W. 86th Street, Indianapolis, IN, 46260, USA.

3Anti-Infective Research Laboratory, Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences, 259 Mack Avenue, Detroit, MI, 48201, USA.


Dalbavancin is a lipoglycopeptide antibiotic recently approved by the United States Food and Drug Administration (FDA) for acute bacterial skin and skin structure infections (ABSSSIs). It is active against gram-positive pathogens, including methicillin-resistant Staphylococcus aureus (MRSA), and minimum inhibitory concentrations (MICs) are consistently <0.125 µg/ml, much lower than most other anti-MRSA agents. Dalbavancin possesses an extended half-life of over 1 week, allowing an initial dose of 1000 mg followed by 500 mg 1 week later to complete a course of therapy for ABSSSI. It is approximately 95% protein bound and is widely distributed throughout the body, achieving concentrations similar to plasma levels in numerous tissues. Against MRSA, dalbavancin is 4-8 times more potent than vancomycin in vitro, and limited data suggest it possesses activity against MRSA with reduced susceptibility to vancomycin such as hVISA and VISA. Dalbavancin also possesses in vitro activity against streptococci and enterococci, although activity against vancomycin-resistant enterococci is lacking. In phase 3 ABSSSI studies, dalbavancin demonstrated similar activity to vancomycin and provides a more convenient dosing regimen. Limited phase 2 data suggest dalbavancin also possesses activity in catheter-related bloodstream infections. Potential further therapeutic uses include conditions that require long-term treatment such as osteomyelitis and infective endocarditis, although data are currently lacking. The extended half-life of dalbavancin, along with its in vitro activity against gram-positive organisms with reduced susceptibility to other anti-MRSA antibiotics, suggest it could have an exciting clinical role going forward.


November 26, 2015 at 7:38 pm

Predictive factors for metastatic infection in patients with bacteremia caused by methicillin-sensitive Staphylococcus aureus.

Am J Med Sci. 2015 Jan;349(1):24-8.

Horino T1, Sato F, Hosaka Y, Hoshina T, Tamura K, Nakaharai K, Kato T, Nakazawa Y, Yoshida M, Hori S.

Author information

1Department of Infectious Diseases and Infection Control, Jikei University School of Medicine, Tokyo, Japan.



Metastatic infections such as infective endocarditis and psoas abscess are serious complications of Staphylococcus aureus bacteremia because failure to identify these infections may result in bacteremia relapse or poor prognosis. In the present study, we determined the predictive factors for metastatic infection due to methicillin-sensitive S. aureus bacteremia.


A retrospective cohort study was conducted among patients with methicillin-sensitive S. aureus bacteremia at the Jikei University Hospital between January 2008 and December 2012. Factors analyzed included the underlying disease, initial antimicrobial treatment and primary site of infection.


During the 5-year study period, 73 patients met the inclusion criteria and were assessed. The most common primary site of bacteremia was catheter-related bloodstream infection (25/73 [34.2%]). Metastatic infection occurred in 14 of 73 patients (19.2%) (infective endocarditis [3], septic pulmonary abscess [3], spondylitis [4], psoas abscess [4], epidural abscess [3] and septic arthritis [1]). Six patients had multiple metastatic infections. Multivariate analysis revealed that the predictive factors associated with the development of metastatic infection were a delay in appropriate antimicrobial treatment of >48 hours, persistent fever for >72 hours after starting antibiotic treatment and lowest C-reactive protein levels of >3 mg/dL during 2 weeks after the onset of bacteremia.


This study demonstrated that additional diagnostic tests should be conducted to identify metastatic infection, particularly in patients with delayed antimicrobial treatment, persistent fever and persistently high C-reactive protein levels.


November 25, 2015 at 10:20 pm

Treatment of Tuberculosis

N Engl J of Med NOV.26,  2015  V.373 P.2149-2160


C.R. Horsburgh, Jr., C.E. Barry III, and C. Lange

From the Departments of Epidemiology, Biostatistics, and Medicine and the Center for Global Health and Development, Boston University, Boston (C.R.H.); the Tuberculosis Research Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, and the Institute for Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa (C.E.B.); and the Division of Clinical Infectious Diseases, German Center for Infection Research (DZIF) Tuberculosis Unit, Research Center Borstel, Borstel, and International Health/Infectious Diseases, University of Lübeck, Lübeck — both in Germany (C.L.). Address reprint requests to Dr. Horsburgh at the Department of Epidemiology, Boston University School of Public Health, 715 Albany St., T3E, Boston MA 02118, or at

Tuberculosis, a scourge since prehistoric times, affects more than 9 million people and causes the death of 1.5 million people each year. Effective treatment has been available for 60 years, but such treatment takes at least 6 months, and resistance to the drugs, which is increasing throughout the world, threatens the effectiveness of treatment.1 This review summarizes the theoretical principles of tuberculosis treatment, current therapeutic approaches, areas of uncertainty, and persistent challenges ….


November 25, 2015 at 10:17 pm

Improving hospital hygiene to reduce the impact of multidrug-resistant organisms in health care-a prospective controlled multicenter study.

BMC Infect Dis. 2015 Oct 22;15:441.

Gerlich MG1, Piegsa J2, Schäfer C3, Hübner NO4, Wilke F5, Reuter S6, Engel G7, Ewert R8, Claus F9, Hübner C10, Ried W11, Flessa S12, Kramer A13, Hoffmann W14.

Author information

1Institut für Community Medicine, Ernst-Moritz-Arndt-Universität, Ellernholzstraße 1-2, 17487, Greifswald, Germany.

2Institut für Community Medicine, Ernst-Moritz-Arndt-Universität, Ellernholzstraße 1-2, 17487, Greifswald, Germany.

3Institut für Community Medicine, Ernst-Moritz-Arndt-Universität, Ellernholzstraße 1-2, 17487, Greifswald, Germany.

4Institut für Hygiene und Umweltmedizin, Ernst-Moritz-Arndt-Universität, Walter-Rathenau-Straße 49a, 17475, Greifswald, Germany.

5Institut für Hygiene und Umweltmedizin, Ernst-Moritz-Arndt-Universität, Walter-Rathenau-Straße 49a, 17475, Greifswald, Germany.

6Universitätsapotheke, Ernst-Moritz-Arndt-Universität, Friedrich-Ludwig-Jahn-Straße 20, 17475, Greifswald, Germany.

7Universitätsapotheke, Ernst-Moritz-Arndt-Universität, Friedrich-Ludwig-Jahn-Straße 20, 17475, Greifswald, Germany.

8Zentrum für Innere Medizin, Klinik und Poliklinik für Innere Medizin B, Ernst-Moritz-Arndt-Universität, Ferdinand-Sauerbruch-Straße, 17475, Greifswald, Germany.

9Lehrstuhl für Allgemeine Volkswirtschaftslehre und Finanzwissenschaft, Ernst-Moritz-Arndt-Universität, Friedrich-Loeffler-Straße 70, 17487, Greifswald, Germany.

10Lehrstuhl für Allgemeine Betriebswirtschaftslehre und Gesundheitsmanagement, Ernst-Moritz-Arndt-Universität, Friedrich-Loeffler-Straße 70, 17487, Greifswald, Germany.

11Lehrstuhl für Allgemeine Volkswirtschaftslehre und Finanzwissenschaft, Ernst-Moritz-Arndt-Universität, Friedrich-Loeffler-Straße 70, 17487, Greifswald, Germany.

12Lehrstuhl für Allgemeine Betriebswirtschaftslehre und Gesundheitsmanagement, Ernst-Moritz-Arndt-Universität, Friedrich-Loeffler-Straße 70, 17487, Greifswald, Germany.

13Institut für Hygiene und Umweltmedizin, Ernst-Moritz-Arndt-Universität, Walter-Rathenau-Straße 49a, 17475, Greifswald, Germany.

14Institut für Community Medicine, Ernst-Moritz-Arndt-Universität, Ellernholzstraße 1-2, 17487, Greifswald, Germany.



Nosocomial infections are the most common complication during inpatient hospital care. An increasing proportion of these infections are caused by multidrug-resistant organisms (MDROs). This report describes an intervention study which was designed to address the practical problems encountered in trying to avoid and treat infections caused by MDROs. The aim of the HARMONIC (Harmonized Approach to avert Multidrug-resistant Organisms and Nosocomial Infections) study is to provide comprehensive support to hospitals in a defined study area in north-east Germany, to meet statutory requirements. To this end, a multimodal system of hygiene management was implemented in the participating hospitals.


HARMONIC is a controlled intervention study conducted in eight acute care hospitals in the ‘Health Region Baltic Sea Coast’ in Germany. The intervention measures include the provision of written recommendations on methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococci (VRE) and multi-resistant Gram-negative bacteria (MRGN), supplemented by regional recommendations for antibiotic prescriptions. In addition, there is theoretical and practical training of health care workers (HCWs) in the prevention and handling of MDROs, as well as targeted and critically gauged applications of antibiotics. The main outcomes of the implementation and analysis of the HARMONIC study are: (i) screening rates for MRSA, VRE and MRGN in high-risk patients, (ii) the frequency of MRSA decolonization, (iii) the level of knowledge of HCWs concerning MDROs, and (iv) specific types and amounts of antibiotics used. The data are predominantly obtained by paper-based questionnaires and documentation sheets. A computer-assisted workflow-based documentation system was developed in order to provide support to the participating facilities. The investigation includes three nested studies on risk profiles of MDROs, health-related quality of life, and cost analysis. A six-month follow-up study investigates the quality of life after discharge, the long-term costs of the treatment of infections caused by MDROs, and the sustainability of MRSA eradication.


The aim of this study is to implement and evaluate an area-wide harmonized hygiene program to control the nosocomial spreading of MDROs. Comparability between the intervention and control group is ensured by matching the hospitals according to size (number of discharges per year / number of beds) and level of care (standard or maximum). The results of the study may provide important indications for the implementation of regional MDRO management programs.


November 25, 2015 at 3:43 pm

Colonization with resistant microorganisms in patients transferred from abroad: who needs to be screened?

Antimicrob Resist Infect Control. 2015 Jul 25;4:31.

Kaspar T1, Schweiger A2, Droz S3, Marschall J1.

Author information

1Department of Infectious Diseases and Prevention, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.

2Department of Internal Medicine, University Hospital Basel, Basel, Switzerland.

3Institute for Infectious Diseases, University of Bern, Bern, Switzerland.



While multi-drug resistant organisms (MDRO) are a global phenomenon, there are significant regional differences in terms of prevalence. Traveling to countries with a high MDRO prevalence increases the risk of acquiring such an organism. In this study we determined risk factors for MDRO colonization among patients who returned from a healthcare system in a high-prevalence area (so-called transfer patients). Factors predicting colonization could serve as screening criteria to better target those at highest risk.


This screening study included adult patients who had been exposed to a healthcare system abroad or in a high-prevalence region in Switzerland over the past six months and presented to our 950-bed tertiary care hospital between January 1, 2012 and December 31, 2013, a 24-month period. Laboratory screening tests focused on Gram-negative MDROs and methicillin-resistant Staphylococcus aureus (MRSA).


A total of 235 transfer patients were screened and analyzed, of which 43 (18 %) were positive for an MDRO. Most of them yielded Gram-negative bacteria (42; 98 %), with only a single screening revealing MRSA (2 %); three screenings showed a combination of Gram-negative bacteria and MRSA. For the risk factor analysis we focused on the 42 Gram-negative MDROs. Most of them were ESBL-producing Escherichia coli and Klebsiella pneumoniae while only two were carbapenemase producers. In univariate analysis, factors associated with screening positivity were hospitalization outside of Europe (p<0.001), surgical procedure in a hospital abroad (p=0.007), and – on admission to our hospital – active infection (p=0.002), antibiotic treatment (p=0.014) and presence of skin lesions (p=0.001). Only hospitalization outside of Europe (Odds Ratio, OR 3.2 (95 % CI 1.5- 6.8)) and active infection on admission (OR 2.7 (95 % CI 1.07- 6.6)) remained as independent predictors of Gram-negative MDRO colonization.


Our data suggest that a large proportion of patients (i.e., 82 %) transferred to Switzerland from hospitals in high MDRO prevalence areas are unnecessarily screened for MDRO colonization. Basing our screening strategy on certain criteria (such as presence of skin lesions, active infection, antibiotic treatment, history of a surgical procedure abroad and hospitalization outside of Europe) promises to be a better targeted and more cost-effective strategy.


November 25, 2015 at 3:40 pm

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