#Age-Dependent Increase in #Incidence of #Staphylococcus aureus #Bacteremia, #Denmark, 2008–2015 (Emerg Infect Dis., abstract)

[Source: US Centers for Disease Control and Prevention (CDC), Emerging Infectious Diseases Journal, full page: (LINK). Abstract, edited.]

Volume 25, Number 5—May 2019 / CME ACTIVITY – Research

Age-Dependent Increase in Incidence of Staphylococcus aureus Bacteremia, Denmark, 2008–2015

Louise Thorlacius-Ussing  , Haakon Sandholdt, Anders Rhod Larsen, Andreas Petersen, and Thomas Benfield

Author affiliations: Hvidovre Hospital, University of Copenhagen, Copenhagen, Denmark (L. Thorlacius-Ussing, H. Sandholdt, T. Benfield); Statens Serum Institut, Copenhagen (A. Larsen, A. Petersen)



Staphylococcus aureus bacteremia (SAB) is a major cause of illness and death worldwide. We analyzed temporal trends of SAB incidence and death in Denmark during 2008–2015. SAB incidence increased 48%, from 20.76 to 30.37 per 100,000 person-years, during this period (p<0.001). The largest change in incidence was observed for persons >80 years of age: a 90% increase in the SAB rate (p<0.001). After adjusting for demographic changes, annual rates increased 4.0% (95% CI 3.0–5.0) for persons <80 years of age, 8.4% (95% CI 7.0–11.0) for persons 80–89 years of age, and 13.0% (95% CI 9.0–17.5) for persons >90 years of age. The 30-day case-fatality rate remained stable at 24%; crude population death rates increased by 53% during 2008–2015 (p<0.001). Specific causes and mechanisms for this rapid increase in SAB incidence among the elderly population remain to be clarified.

Keywords: Staphylococcus aureus; Bacteremia; Denmark.



#Chlorhexidine versus routine #bathing to prevent #MDR organisms and all-cause #bloodstream #infections in general medical and surgical units (#ABATE Infection trial)… (Lancet, abstract)

[Source: The Lancet, full page: (LINK). Abstract, edited.]

Chlorhexidine versus routine bathing to prevent multidrug-resistant organisms and all-cause bloodstream infections in general medical and surgical units (ABATE Infection trial): a cluster-randomised trial

Prof Susan S Huang, MD,  Prof Edward Septimus, MD, Ken Kleinman, ScD, Julia Moody, MS, Jason Hickok, MBA, Lauren Heim, MPH, Adrijana Gombosev, MS, Taliser R Avery, MS, Katherine Haffenreffer, BS, Lauren Shimelman, BA, Prof Mary K Hayden, MD, Prof Robert A Weinstein, MD, Caren Spencer-Smith, MIS, Rebecca E Kaganov, BA, Michael V Murphy, BA, Tyler Forehand, MBA, Julie Lankiewicz, MPH, Micaela H Coady, MS, Lena Portillo, BS, Jalpa Sarup-Patel, BS, John A Jernigan, MD, Jonathan B Perlin, MD, Prof Richard Platt, MD, for theABATE Infection trial team

Published: March 05, 2019 / DOI: https://doi.org/10.1016/S0140-6736(18)32593-5




Universal skin and nasal decolonisation reduces multidrug-resistant pathogens and bloodstream infections in intensive care units. The effect of universal decolonisation on pathogens and infections in non-critical-care units is unknown. The aim of the ABATE Infection trial was to evaluate the use of chlorhexidine bathing in non-critical-care units, with an intervention similar to one that was found to reduce multidrug-resistant organisms and bacteraemia in intensive care units.


The ABATE Infection (active bathing to eliminate infection) trial was a cluster-randomised trial of 53 hospitals comparing routine bathing to decolonisation with universal chlorhexidine and targeted nasal mupirocin in non-critical-care units. The trial was done in hospitals affiliated with HCA Healthcare and consisted of a 12-month baseline period from March 1, 2013, to Feb 28, 2014, a 2-month phase-in period from April 1, 2014, to May 31, 2014, and a 21-month intervention period from June 1, 2014, to Feb 29, 2016. Hospitals were randomised and their participating non-critical-care units assigned to either routine care or daily chlorhexidine bathing for all patients plus mupirocin for known methicillin-resistantStaphylococcus aureus (MRSA) carriers. The primary outcome was MRSA or vancomycin-resistant enterococcus clinical cultures attributed to participating units, measured in the unadjusted, intention-to-treat population as the HR for the intervention period versus the baseline period in the decolonisation group versus the HR in the routine care group. Proportional hazards models assessed differences in outcome reductions across groups, accounting for clustering within hospitals. This trial is registered withClinicalTrials.gov, number NCT02063867.


There were 189 081 patients in the baseline period and 339 902 patients (156 889 patients in the routine care group and 183 013 patients in the decolonisation group) in the intervention period across 194 non-critical-care units in 53 hospitals. For the primary outcome of unit-attributable MRSA-positive or VRE-positive clinical cultures ( figure 2), the HR for the intervention period versus the baseline period was 0·79 (0·73–0·87) in the decolonisation group versus 0·87 (95% CI 0·79–0·95) in the routine care group. No difference was seen in the relative HRs (p=0·17). There were 25 (<1%) adverse events, all involving chlorhexidine, among 183 013 patients in units assigned to chlorhexidine, and none were reported for mupirocin.


Decolonisation with universal chlorhexidine bathing and targeted mupirocin for MRSA carriers did not significantly reduce multidrug-resistant organisms in non-critical-care patients.


National Institutes of Health.

Keywords: Antibiotics; Drugs Resistance; Chlorhexidine; Mupirocin; MRSA; Bacteremia.


Dynamics of #resistance #plasmids in #ESBL-producing #Enterobacteriaceae during post-infection #colonization (Antimicrob Agents Chemother., abstract)

[Source: Antimicrobial Agents and Chemotherapy, full page: (LINK). Abstract, edited.]

Dynamics of resistance plasmids in extended spectrum β-lactamase-producing Enterobacteriaceae during post-infection colonization

Alma Brolund, Fredrika Rajer, Christian G Giske, Öjar Melefors, Emilia Titelman, Linus Sandegren

DOI: 10.1128/AAC.02201-18



Extended spectrum β-lactamase-producing Enterobacteriaceae (EPE) are a major cause of bloodstream infections and the colonization rate of EPE in the gut microbiota of individuals lacking prior hospitalization or comorbidities is increasing. In this study we performed an in-depth investigation of the temporal dynamics of EPE and their plasmids during one year by collecting fecal samples from three patients initially seeking medical care for urinary tract infections. In two of the patients the same strain that caused the UTI was found at all consecutive samplings from the gut microbiota and no other EPEs were detected, while in the third patient the UTI strain was only found in the initial UTI sample. Instead, this patient presented a complex situation where a mixed microbiota of different EPE strain types, including three different E. coli ST131 variants, as well as different bacterial species was identified over the course of the study. Different plasmid dynamics were displayed in each of the patients including spread of plasmids between different strain types over time, transposition of blaCTX-M-15 from the chromosome to a plasmid followed by subsequent loss through homologous recombination. Small cryptic plasmids were found in all isolates from all patients and they appear to move frequently between different strains in the microbiota. In conclusion, we could demonstrate an extensive variation of EPE strain types, plasmid composition, rearrangements and horizontal gene transfer of genetic material illustrating the high dynamics nature and interactive environment of the gut microbiota during post UTI carriage.

Copyright © 2019 American Society for Microbiology. All Rights Reserved.

Keywords: Antibiotics; Drugs Resistance; Beta-lactams; E. Coli; Enterobacteriaceae; Bacteremia.


The Anti-Staphylococcal #Lysin, CF-301, Activates Key Host Factors in #Human #Blood to Potentiate #MRSA #Bacteriolysis (Antimicrob Agents Chemother., abstract)

[Source: Antimicrobial Agents and Chemotherapy, full page: (LINK). Abstract, edited.]

The Anti-Staphylococcal Lysin, CF-301, Activates Key Host Factors in Human Blood to Potentiate MRSA Bacteriolysis

Chiara Indiani, Karen Sauve, Assaf Raz, Wessam Abdelhady, Yan Q. Xiong, Cara Cassino, Arnold S. Bayer, Raymond Schuch

DOI: 10.1128/AAC.02291-18



Bacteriophage-derived lysins are cell wall hydrolytic enzymes which represent a potential new class of antibacterial therapeutics in development to address burgeoning antimicrobial resistance. CF-301, the lead compound in this class, is in clinical development as an adjunctive treatment to potentially improve clinical cure rates of Staphylococcus aureus bacteremia and infective endocarditis (IE) when used in addition to antibiotics. In order to profile CF-301’s activity in a clinically relevant milieu, we assessed its in vitro activity in human blood vs. in a conventional testing medium (cation-adjusted Mueller Hinton Broth [caMHB]). CF-301 exhibited substantially greater potency (32-≥100-fold) in human blood vs. caMHB in three standard microbiologic testing formats (e.g. broth dilution MICs, checkerboard synergy and time-kill assays). We demonstrated that CF-301 acted synergistically with two key human blood factors, human serum lysozyme (HuLYZ) and albumin (HSA), which normally have no nascent antistaphylococcal activity, against a prototypic MRSA strain (MW2). Similar in vitroenhancement of CF-301 activity was also observed in rabbit, horse and dog (but not rat or mouse) blood. Two well-established MRSA IE models in rabbit and rat were used to validate these findings in vivo by demonstrating comparable synergistic efficacy with standard-of-care anti-MRSA antibiotics, at > 100-fold lower lysin doses in the rabbit vs the rat model. The unique properties of CF-301 which enable bactericidal potentiation of antimicrobial activity via activation of ‘latent’ host factors in human blood may have important therapeutic implications for the durable improvements in clinical outcomes of serious, antibiotic-resistant staphylococcal infections.

Copyright © 2019 American Society for Microbiology. All Rights Reserved.

Keywords: Antibiotics; Drugs Resistance; Bacteriophages; Bacteremia; Endocarditis; MRSA; Staphylococcus aureus.


#Bartonella spp. #Bloodstream #Infection in a #Canadian Family (Vector Borne Zoo Dis., abstract)

[Source: Vector Borne and Zoonotic Diseases, full page: (LINK). Abstract, edited.]

Bartonella spp. Bloodstream Infection in a Canadian Family

Edward B. Breitschwerdt, Ricardo G. Maggi, Caroline Quach, and Julie M. Bradley

Published Online: 27 Dec 2018 / DOI: https://doi.org/10.1089/vbz.2018.2353



Historically, Bartonella spp. have been associated with febrile illness (Oroya fever, trench fever, and cat scratch disease), endocarditis (numerous Bartonella spp.), and vasoproliferative lesions (Bartonella bacilliformis, Bartonella quintana, Bartonella henselae, and Bartonella vinsonii subsp. berkhoffii), occurring most often but not exclusively in immunocompromised patients. Recently, bloodstream infections with various Bartonella spp. have been documented in nonimmunocompromised individuals in association with a spectrum of cardiovascular, neurologic, and rheumatologic symptoms. As documented in this family, symptoms for which the medical implications remain unclear can occur in multiple family members infected with one or more Bartonella spp. Serial serologic and molecular microbiological findings supported exposure to or infection with Bartonella spp. in all seven family members. Either antibiotics failed to eliminate bacteremic infection, resulted in partial resolution of symptoms, or potentially reinfection occurred during the 19-month study period. There is a substantial need for clinical research to clarify the extent to which Bartonella spp. bacteremia induces nonspecific cardiovascular, neurologic, or rheumatologic symptoms for ongoing improvement in the sensitivity and specificity of diagnostic testing, and clarification as to if, when, and how to treat patients with documented Bartonella spp. bacteremia.

Keywords: Bartonella spp.; Bacteremia; Canada.


Effects of the #Australian National #Hand #Hygiene Initiative after 8 years on #infection control practices, #HCW #education, and clinical outcomes: a longitudinal study (Lancet Infect Dis., abstract)

[Source: The Lancet Infectious Diseases, full page: (LINK). Abstract, edited.]

Effects of the Australian National Hand Hygiene Initiative after 8 years on infection control practices, health-care worker education, and clinical outcomes: a longitudinal study

Prof M Lindsay Grayson, FRACP, Andrew J Stewardson, FRACP, Philip L Russo, MClinEpid, Kate E Ryan, MPhysio (Cardio), Karen L Olsen, BSc, Sally M Havers, MPH, Susan Greig, RN, Marilyn Cruickshank, PhD on behalf ofHand Hygiene Australia and the National Hand Hygiene Initiative

Published: September 28, 2018 / DOI: https://doi.org/10.1016/S1473-3099(18)30491-2




The National Hand Hygiene Initiative (NHHI) is a standardised culture-change programme based on the WHO My 5 Moments for Hand Hygiene approach to improve hand hygiene compliance among Australian health-care workers and reduce the risk of health-care-associated infections. We analysed its effectiveness.


In this longitudinal study, we assessed outcomes of the NHHI for the 8 years after implementation (between Jan 1, 2009, and June 30, 2017), including hospital participation, hand hygiene compliance (measured as the proportion of observed Moments) three times per year, educational engagement, cost, and association with the incidence of health-care-associated Staphylococcus aureus bacteraemia (HA-SAB).


Between 2009 and 2017, increases were observed in national health-care facility participation (105 hospitals [103 public and two private] in 2009 vs 937 hospitals [598 public and 339 private] in 2017) and overall hand hygiene compliance (36 213 [63·6%] of 56 978 Moments [95% CI 63·2–63·9] in 2009 vs 494 673 [84·3%] of 586 559 Moments [84·2–84·4] in 2017; p<0·0001). Compliance also increased for each Moment type and for each health-care worker occupational group, including for medical staff (4377 [50·5%] of 8669 Moments [95% CI 49·4–51·5] in 2009 vs 53 620 [71·7%] of 74 788 Moments [71·4–72·0]; p<0·0001). 1 989 713 NHHI online learning credential programmes were completed. The 2016 NHHI budget was equivalent to AUD$0·06 per inpatient admission nationally. Among Australia’s major public hospitals (n=132), improved hand hygiene compliance was associated with declines in the incidence of HA-SAB (incidence rate ratio 0·85; 95% CI 0·79–0·93; p≤0·0001): for every 10% increase in hand hygiene compliance, the incidence of HA-SAB decreased by 15%.


The NHHI has been associated with significant sustained improvement in hand hygiene compliance and a decline in the incidence of HA-SAB. Key features include sustained central coordination of a standardised approach and incorporation into hospital accreditation standards. The NHHI could be emulated in other national culture-change programmes.


Australian Commission on Safety and Quality in Health Care

Keywords: Nosocomial Outbreaks; Staphylococcus Aureus; Bacteremia; Hand hygiene; Health Care Workers; Australia.


Effect of #Piperacillin – #Tazobactam vs #Meropenem on 30-Day #Mortality for Patients With #Ecoli or #Klebsiella pneumoniae #Bloodstream Infection and Ceftriaxone Resistance – A RCT (JAMA, abstract)

[Source: JAMA, full page: (LINK). Abstract, edited.]

Original Investigation / September 11, 2018

Effect of Piperacillin-Tazobactam vs Meropenem on 30-Day Mortality for Patients With E coli or Klebsiella pneumoniae Bloodstream Infection and Ceftriaxone ResistanceA Randomized Clinical Trial

Patrick N. A. Harris, MBBS1,2,3; Paul A. Tambyah, MD4; David C. Lye, MBBS5,6,7; et al Yin Mo, MBBS4; Tau H. Lee, MBBS5,6,7; Mesut Yilmaz, MD8; Thamer H. Alenazi, MD9; Yaseen Arabi, MD9; Marco Falcone, MD10; Matteo Bassetti, MD, PhD11; Elda Righi, MD, PhD11; Benjamin A. Rogers, MBBS, PhD12,13; Souha Kanj, MD14; Hasan Bhally, MBBS15; Jon Iredell, MBBS, PhD16,17; Marc Mendelson, MBBS, PhD18; Tom H. Boyles, MD18; David Looke, MBBS3,19; Spiros Miyakis, MD, PhD20,21,22; Genevieve Walls, MB, ChB23; Mohammed Al Khamis, MD24; Ahmed Zikri, PharmD24; Amy Crowe, MBBS25,26; Paul Ingram, MBBS27,28,29; Nick Daneman, MD30; Paul Griffin, MBBS19,31,32; Eugene Athan, MBBS, MPH, PhD33; Penelope Lorenc, RN1; Peter Baker, PhD34; Leah Roberts, BSc35; Scott A. Beatson, PhD35; Anton Y. Peleg, MBBS, PhD36,37,38; Tiffany Harris-Brown, RN, MPH1; David L. Paterson, MBBS, PhD1,39; for the MERINO Trial Investigators and the Australasian Society for Infectious Disease Clinical Research Network (ASID-CRN)

Author Affiliations: 1 University of Queensland, UQ Centre for Clinical Research, Brisbane, Queensland, Australia; 2 Department of Microbiology, Pathology Queensland, Royal Brisbane and Women’s Hospital, Brisbane, Queensland, Australia; 3 Infection Management Services, Princess Alexandra Hospital, Brisbane, Queensland, Australia; 4 Department of Infectious Diseases, National University Hospital, Singapore; 5 Yong Loo Lin School of Medicine, National University of Singapore, Singapore; 6 Department of Infectious Diseases, Institute of Infectious Diseases and Epidemiology, Tan Tock Seng Hospital, Singapore; 7 Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore; 8 Department of Infectious Diseases and Clinical Microbiology, School of Medicine, Istanbul Medipol University, Istanbul, Turkey; 9 King Saud Bin Abdulaziz University for Health Sciences and King Abdullah International Medical Research Center, Riyadh, Saudi Arabia; 10 Department of Public Health and Infectious Diseases, “Sapienza” University of Rome, Italy; 11 Infectious Diseases Clinic, Department of Medicine University of Udine and Santa Maria Misericordia Hospital, Udine, Italy; 12 Monash University, Centre for Inflammatory Diseases, Melbourne, Victoria, Australia; 13 Monash Infectious Diseases, Monash Health, Melbourne, Victoria, Australia; 14 Division of Infectious Diseases, Department of Internal Medicine, American University of Beirut Medical Center, Beirut, Lebanon; 15 Department of Medicine and Infectious Diseases, North Shore Hospital, Auckland, New Zealand; 16 Marie Bashir Institute for Infectious Disease and Biosecurity, University of Sydney, Sydney, New South Wales, Australia; 17 Centre for Infectious Diseases and Microbiology, Westmead Hospital, Westmead, New South Wales, Australia; 18 Division of Infectious Diseases & HIV Medicine, Department of Medicine, Groote Schuur Hospital, University of Cape Town, Cape Town, South Africa; 19 University of Queensland, Brisbane, Queensland, Australia; 20 School of Medicine, University of Wollongong, Wollongong, New South Wales, Australia; 21 Illawarra Health and Medical Research Institute, Wollongong, New South Wales, Australia; 22 Department of Infectious Diseases, Wollongong Hospital, Wollongong, New South Wales, Australia; 23 Department of Infectious Diseases, Middlemore Hospital, Auckland, New Zealand; 24 King Fahad Specialist Hospital, Dammam, Saudi Arabia; 25 Department of Infectious Diseases, St Vincent’s Hospital, Melbourne, Victoria, Australia; 26 Department of Microbiology, St Vincent’s Hospital, Melbourne, Victoria, Australia; 27 School of Pathology and Laboratory Medicine, The University of Western Australia, Crawley, Australia; 28 Department of Infectious Diseases, Fiona Stanley Hospital, Murdoch, Australia; 29 Department of Microbiology, PathWest Laboratory Medicine, Perth, Western Australia; 30 Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada; 31 Department of Medicine and Infectious Diseases, Mater Hospital and Mater Medical Research Institute, Brisbane, Queensland, Australia; 32 QIMR Berghofer, Brisbane, Queensland, Australia; 33 Department of Infectious Diseases, Barwon Health and Deakin University, Geelong, Victoria, Australia; 34 School of Public Health, University of Queensland, Brisbane, Queensland, Australia; 35 Australian Centre for Ecogenomics, School of Chemistry and Molecular Biosciences, The University of Queensland, Queensland, Australia; 36 Infection & Immunity Program, Biomedicine Discovery Institute, Monash University, Clayton, Australia; 37 Department of Microbiology, Monash University, Clayton, Australia; 38 Department of Infectious Diseases, Alfred Hospital and Central Clinical School, Monash University, Melbourne, Victoria, Australia; 39 Department of Infectious Diseases, Royal Brisbane and Women’s Hospital, Brisbane, Queensland, Australia

JAMA. 2018;320(10):984-994. doi:10.1001/jama.2018.12163


Key Points

  • Question  – Can piperacillin-tazobactam be used as carbapenem-sparing therapy in patients with bloodstream infections caused by ceftriaxone-resistant Escherichia coli or Klebsiella pneumoniae?
  • Findings   – In this noninferiority randomized clinical trial that included 391 patients with E coli or K pneumoniae bloodstream infection and ceftriaxone resistance, the 30-day mortality rate for patients treated with piperacillin-tazobactam compared with meropenem was 12.3% vs 3.7%, respectively. The difference did not meet the noninferiority margin of 5%.
  • Meaning  – These findings do not support piperacillin-tazobactam compared with meropenem for these infections.




Extended-spectrum β-lactamases mediate resistance to third-generation cephalosporins (eg, ceftriaxone) in Escherichia coli and Klebsiella pneumoniae. Significant infections caused by these strains are usually treated with carbapenems, potentially selecting for carbapenem resistance. Piperacillin-tazobactam may be an effective “carbapenem-sparing” option to treat extended-spectrum β-lactamase producers.


To determine whether definitive therapy with piperacillin-tazobactam is noninferior to meropenem (a carbapenem) in patients with bloodstream infection caused by ceftriaxone-nonsusceptible E coli or K pneumoniae.

Design, Setting, and Participants 

Noninferiority, parallel group, randomized clinical trial included hospitalized patients enrolled from 26 sites in 9 countries from February 2014 to July 2017. Adult patients were eligible if they had at least 1 positive blood culture with E coli or Klebsiella spp testing nonsusceptible to ceftriaxone but susceptible to piperacillin-tazobactam. Of 1646 patients screened, 391 were included in the study.


Patients were randomly assigned 1:1 to intravenous piperacillin-tazobactam, 4.5 g, every 6 hours (n = 188 participants) or meropenem, 1 g, every 8 hours (n = 191 participants) for a minimum of 4 days, up to a maximum of 14 days, with the total duration determined by the treating clinician.

Main Outcomes and Measures 

The primary outcome was all-cause mortality at 30 days after randomization. A noninferiority margin of 5% was used.


Among 379 patients (mean age, 66.5 years; 47.8% women) who were randomized appropriately, received at least 1 dose of study drug, and were included in the primary analysis population, 378 (99.7%) completed the trial and were assessed for the primary outcome. A total of 23 of 187 patients (12.3%) randomized to piperacillin-tazobactam met the primary outcome of mortality at 30 days compared with 7 of 191 (3.7%) randomized to meropenem (risk difference, 8.6% [1-sided 97.5% CI, −∞ to 14.5%]; P = .90 for noninferiority). Effects were consistent in an analysis of the per-protocol population. Nonfatal serious adverse events occurred in 5 of 188 patients (2.7%) in the piperacillin-tazobactam group and 3 of 191 (1.6%) in the meropenem group.

Conclusions and relevance 

Among patients with E coli or K pneumoniae bloodstream infection and ceftriaxone resistance, definitive treatment with piperacillin-tazobactam compared with meropenem did not result in a noninferior 30-day mortality. These findings do not support use of piperacillin-tazobactam in this setting.

Trial Registration  anzctr.org.au Identifiers: ACTRN12613000532707 and ACTRN12615000403538 and ClinicalTrials.gov Identifier: NCT02176122

Keywords: Antibiotics; Drugs Resistance; Beta-lactams; Ceftriaxone; Piperacillin; Tazobactam; E. Coli; K. Pneumoniae; Bacteremia.