Posts filed under ‘Bacteriemias’

Adjunctive rifampicin for Staphylococcus aureus bacteraemia (ARREST): a multicentre, randomised, double-blind, placebo-controlled trial.

Lancet. 2017 Dec 14. pii: S0140-6736(17)32456-X. [Epub ahead of print]

Thwaites GE1, Scarborough M2, Szubert A3, Nsutebu E4, Tilley R5, Greig J6, Wyllie SA7, Wilson P8, Auckland C9, Cairns J3, Ward D3, Lal P10, Guleri A11, Jenkins N12, Sutton J13, Wiselka M14, Armando GR15, Graham C16, Chadwick PR17, Barlow G18, Gordon NC2, Young B2, Meisner S19, McWhinney P20, Price DA21, Harvey D22, Nayar D23, Jeyaratnam D24, Planche T25, Minton J26, Hudson F3, Hopkins S27, Williams J28, Török ME29, Llewelyn MJ30, Edgeworth JD31, Walker AS32; United Kingdom Clinical Infection Research Group (UKCIRG).

Collaborators (452)

Author information



Staphylococcus aureus bacteraemia is a common cause of severe community-acquired and hospital-acquired infection worldwide. We tested the hypothesis that adjunctive rifampicin would reduce bacteriologically confirmed treatment failure or disease recurrence, or death, by enhancing early S aureus killing, sterilising infected foci and blood faster, and reducing risks of dissemination and metastatic infection.


In this multicentre, randomised, double-blind, placebo-controlled trial, adults (≥18 years) with S aureus bacteraemia who had received ≤96 h of active antibiotic therapy were recruited from 29 UK hospitals. Patients were randomly assigned (1:1) via a computer-generated sequential randomisation list to receive 2 weeks of adjunctive rifampicin (600 mg or 900 mg per day according to weight, oral or intravenous) versus identical placebo, together with standard antibiotic therapy. Randomisation was stratified by centre. Patients, investigators, and those caring for the patients were masked to group allocation. The primary outcome was time to bacteriologically confirmed treatment failure or disease recurrence, or death (all-cause), from randomisation to 12 weeks, adjudicated by an independent review committee masked to the treatment. Analysis was intention to treat. This trial was registered, number ISRCTN37666216, and is closed to new participants.


Between Dec 10, 2012, and Oct 25, 2016, 758 eligible participants were randomly assigned: 370 to rifampicin and 388 to placebo. 485 (64%) participants had community-acquired S aureus infections, and 132 (17%) had nosocomial S aureus infections. 47 (6%) had meticillin-resistant infections. 301 (40%) participants had an initial deep infection focus. Standard antibiotics were given for 29 (IQR 18-45) days; 619 (82%) participants received flucloxacillin. By week 12, 62 (17%) of participants who received rifampicin versus 71 (18%) who received placebo experienced treatment failure or disease recurrence, or died (absolute risk difference -1·4%, 95% CI -7·0 to 4·3; hazard ratio 0·96, 0·68-1·35, p=0·81). From randomisation to 12 weeks, no evidence of differences in serious (p=0·17) or grade 3-4 (p=0·36) adverse events were observed; however, 63 (17%) participants in the rifampicin group versus 39 (10%) in the placebo group had antibiotic or trial drug-modifying adverse events (p=0·004), and 24 (6%) versus six (2%) had drug interactions (p=0·0005).


Adjunctive rifampicin provided no overall benefit over standard antibiotic therapy in adults with S aureus bacteraemia.


UK National Institute for Health Research Health Technology Assessment.




January 16, 2018 at 11:05 am

2017 Infectious Diseases Society of America Clinical Practice Guidelines for the Diagnosis and Management of Infectious Diarrhea

Clinical Infectious Diseases November, 29  2017  V.65  N.12 P.1963–1973


Andi L Shane; Rajal K Mody; John A Crump; Phillip I Tarr; Theodore S Steiner …

These guidelines are intended for use by healthcare professionals who care for children and adults with suspected or confirmed infectious diarrhea. They are not intended to replace physician judgement regarding specific patients or clinical or public health situations. This document does not provide detailed recommendations on infection prevention and control aspects related to infectious diarrhea.


PDF (hacer CLIC en PDF)

January 9, 2018 at 7:59 am

Extensive colonization with carbapenemase-producing microorganisms in Romanian burn patients: infectious consequences from the Colectiv fire disaster

European Journal of Clinical Microbiology & Infectious Diseases January 2018 V.37 N.1 P.175–183

E. Pirii, A. W. Friedrich, J. W.A. Rossen, W. Vogels, G. I. J. M. Beerthuizen, M. K. Nieuwenhuis, A. M. D. Kooistra-Smid & E. Bathoorn

Health care of severe burn patients is highly specialized and may require international patient transfer. Burn patients have an increased risk of developing infections. Patients that have been hospitalized in countries where carbapenemase-producing microorganisms (CPMO) are endemic may develop infections that are difficult to treat. In addition, there is a risk on outbreaks with CPMOs in burn centers.

This study underlines that burn patients may extensively be colonized with CPMOs, and it provides best practice recommendations regarding clinical microbiology and infection control.

We evaluated CPMO-carriage and wound colonization in a burn patient initially treated in Romania, and transported to the Netherlands.

The sequence types and acquired beta-lactamase genes of highly-resistant microorganisms were derived from next generation sequencing data.

Next, we searched literature for reports on CPMOs in burn patients.

Five different carbapenemase-producing isolates were cultured: two unrelated OXA-48-producing Klebsiella pneumoniae isolates, OXA-23-producing Acinetobacter baumanii, OXA-48-producing Enterobacter cloacae, and NDM-1-producing Providencia stuartii.

Also, multi-drug resistant Pseudomonas aeruginosa isolates were detected. Among the sampling sites, there was high variety in CPMOs. We found 46 reports on CPMOs in burn patients.

We listed the epidemiology of CPMOs by country of initial treatment, and summarized recommendations for care of these patients based on these reports and our study.




January 7, 2018 at 10:12 am

Dental procedures, antibiotic prophylaxis, and endocarditis among people with prosthetic heart valves: Nationwide population based cohort and a case crossover study

BMJ September 7, 2017 V.358 

Sarah Tubiana, epidemiologist12, Pierre-Olivier Blotière, statistician2, Bruno Hoen, professor3, Philippe Lesclous, professor4, Sarah Millot, associate professor5, Jérémie Rudant, epidemiologist2 , Alain Weill, epidemiologist2, Joel Coste, professor2, François Alla, professor2, Xavier Duval, professor1

1INSERM, IAME, UMR 1137, Paris, France; Université Paris Diderot, IAME, UMR 1137, Sorbonne Paris Cité, Paris, France; INSERM CIC-1425, Assistance Publique-Hôpitaux de Paris, Hôpital Bichat Claude Bernard, Paris, France

2Department of Studies in Public Health, French National Health Insurance, Paris Cedex 20, France

3Service de Maladies Infectieuses et Tropicales et Inserm-CIC 1424, Centre Hospitalier Universitaire de Pointe-à-Pitre, Pointe-à-Pitre, France; Université des Antilles et de la Guyane, Faculté de Médecine Hyacinthe Bastaraud, Pointe-à-Pitre, Guadeloupe, France

4INSERM, U 1229, RMeS, Nantes, France, UFR d’Odontologie, Université de Nantes, Nantes, France, CHU Hôtel Dieu, Nantes, France

5Department of Odontology, CHRU Université de Montpellier, France; UMR 1149 INSERM, CRI. Université Paris Diderot, France



To assess the relation between invasive dental procedures and infective endocarditis associated with oral streptococci among people with prosthetic heart valves.


Nationwide population based cohort and a case crossover study.


French national health insurance administrative data linked with the national hospital discharge database.


All adults aged more than 18 years, living in France, with medical procedure codes for positioning or replacement of prosthetic heart valves between July 2008 and July 2014.

Main outcome measures

Oral streptococcal infective endocarditis was identified using primary discharge diagnosis codes. In the cohort study, Poisson regression models were performed to estimate the rate of oral streptococcal infective endocarditis during the three month period after invasive dental procedures compared with non-exposure periods. In the case crossover study, conditional logistic regression models calculated the odds ratio and 95% confidence intervals comparing exposure to invasive dental procedures during the three month period preceding oral streptococcal infective endocarditis (case period) with three earlier control periods.


The cohort included 138 876 adults with prosthetic heart valves (285 034 person years); 69 303 (49.9%) underwent at least one dental procedure. Among the 396 615 dental procedures performed, 103 463 (26.0%) were invasive and therefore presented an indication for antibiotic prophylaxis, which was performed in 52 280 (50.1%). With a median follow-up of 1.7 years, 267 people developed infective endocarditis associated with oral streptococci (incidence rate 93.7 per 100 000 person years, 95% confidence interval 82.4 to 104.9). Compared with non-exposure periods, no statistically significant increased rate of oral streptococcal infective endocarditis was observed during the three months after an invasive dental procedure (relative rate 1.25, 95% confidence interval 0.82 to 1.82; P=0.26) and after an invasive dental procedure without antibiotic prophylaxis (1.57, 0.90 to 2.53; P=0.08). In the case crossover analysis, exposure to invasive dental procedures was more frequent during case periods than during matched control periods (5.1% v 3.2%; odds ratio 1.66, 95% confidence interval 1.05 to 2.63; P=0.03).


Invasive dental procedures may contribute to the development of infective endocarditis in adults with prosthetic heart valves.



January 6, 2018 at 12:11 pm

Clindamycin affects group A streptococcus virulence factors and improves clinical outcome.

J Infect Dis 2017 Jan 15; 215:269.

Federica Andreoni  Claudia Zürcher  Andrea Tarnutzer  Katrin Schilcher  Andrina Neff Nadia Keller  Ewerton Marques Maggio  Claire Poyart  Reto A. Schuepbach Annelies S. Zinkernagel


Group A Streptococcus (GAS) has acquired an arsenal of virulence factors, promoting life-threatening invasive infections such as necrotizing fasciitis. Current therapeutic regimens for necrotizing fasciitis include surgical debridement and treatment with cell wall–active antibiotics. Addition of clindamycin (CLI) is recommended, although clinical evidence is lacking. Reflecting the current clinical dilemma, an observational study showed that only 63% of the patients with severe invasive GAS infection received CLI. This work thus aimed to address whether CLI improves necrotizing fasciitis outcome by modulating virulence factors of CLI-susceptible and CLI-resistant GAS in vitro and in vivo. Treatment with CLI reduced extracellular DNase Sda1 and streptolysin O (SLO) activity in vivo, whereas subinhibitory CLI concentrations induced expression and activity of SLO, DNase, and Streptococcus pyogenes cell envelope protease in vitro. Our in vivo results suggest that CLI should be administered as soon as possible to patients with necrotizing fasciitis, while our in vitro studies emphasize that a high dosage of CLI is essential.



January 6, 2018 at 12:09 pm

Trends in Antibiotic Susceptibility in Staphylococcus aureus in Boston, Massachusetts, from 2000 to 2014

Journal of Clinical Microbiology January 2018 V.56 N.1


Sanjat Kanjilal, Mohamad R. Abdul Sater, Maile Thayer, Georgia K. Lagoudas, Soohong Kim, Paul C. Blainey and Yonatan H. Grad

aDivision of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts, USA

bHarvard Medical School, Boston, Massachusetts, USA

cDepartment of Immunology & Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA

dMIT Department of Biological Engineering, Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA

eDivision of Infectious Diseases, Brigham and Women’s Hospital, Boston, Massachusetts, USA

The rate of infection by methicillin-resistant Staphylococcus aureus (MRSA) has declined over the past decade, but it is unclear whether this represents a decline in S. aureus infections overall. To evaluate the trends in the annual rates of infection by S. aureus subtypes and mean antibiotic resistance, we conducted a 15-year retrospective observational study at two tertiary care institutions in Boston, MA, of 31,753 adult inpatients with S. aureus isolated from clinical specimens. We inferred the gain and loss of methicillin resistance through genome sequencing of 180 isolates from 2016. The annual rates of infection by S. aureus declined from 2003 to 2014 by 4.2% (2.7% to 5.6%), attributable to an annual decline in MRSA of 10.9% (9.3% to 12.6%). Penicillin-susceptible S. aureus (PSSA) increased by 6.1% (4.2% to 8.1%) annually, and rates of methicillin-susceptible penicillin-resistant S. aureus (MSSA) did not change. Resistance in S. aureus decreased from 2000 to 2014 by 0.8 antibiotics (0.7 to 0.8). Within common MRSA clonal complexes, 3/14 MSSA and 2/21 PSSA isolates arose from the loss of resistance-conferring genes. Overall, in two tertiary care institutions in Boston, MA, a decline in S. aureus infections has been accompanied by a shift toward increased antibiotic susceptibility. The rise in PSSA makes penicillin an increasingly viable treatment option.


January 5, 2018 at 8:21 am

lytA Quantitative PCR on Sputum and Nasopharyngeal Swab Samples for Detection of Pneumococcal Pneumonia among the Elderly

Journal of Clinical Microbiology January 2018 V.56 N.1

Annika Saukkoriipi, Arto A. Palmu, Thierry Pascal, Vincent Verlant, William P. Hausdorff and Jukka Jokinen

aDepartment of Public Health Solutions, National Institute for Health and Welfare, Oulu, Finland

bDepartment of Public Health Solutions, National Institute for Health and Welfare, Tampere, Finland

cGSK, Wavre, Belgium

dDepartment of Public Health Solutions, National Institute for Health and Welfare, Helsinki, Finland

Real-time quantitative PCR (qPCR) assay of sputum or nasopharyngeal specimens has shown promising results in the detection of pneumococcal community-acquired pneumonia (PncCAP). We applied qPCR for the autolysin gene (lytA) and compared sputum and nasopharyngeal swab (NPS) pneumococcal loads in elderly patients with community-acquired pneumonia (CAP), and specifically in patients with PncCAP, to those in patient groups with other respiratory diseases. We studied patients aged ≥65 years with radiologically confirmed CAP, clinical CAP not retrospectively radiologically confirmed, other acute respiratory infections, or stable chronic lung disease. Pneumococcal etiology of CAP was ascertained by using a combination of multiple diagnostic methods. We analyzed sputum and NPS specimens by lytA qPCR with 104 pneumococcal genome equivalents (GE)/ml as a cutoff for positivity. Among PncCAP patients, lytA qPCR detected pneumococci in 94% of the sputum samples and in large quantities (mean, 6.82 ± 1.02 log10 GE/ml) but less frequently in NPS (44%) and in smaller quantities (5.55 ± 0.92 log10 GE/ml). In all other patient groups, ≤10% of the sputum samples and <5% of the NPS samples were lytA qPCR positive; but when they were positive, the sputum pneumococcal loads were similar to those in the PncCAP patients, suggesting a pneumococcal etiology in these patients. This was supported by other pneumococcal assay results. Overall, sputum lytA qPCR positivity was more common in PncCAP patients than in the other patient groups, but the quantitative results were mainly similar. NPS lytA qPCR was less sensitive than sputum lytA qPCR in detecting PncCAP.


January 5, 2018 at 8:20 am

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