Effect of #Treating #Parents Colonized With #Staphylococcus aureus on #Transmission to #Neonates in the #ICU – A #RCT (JAMA, abstract)

[Source: Journal of American Medical Association, full page: (LINK). Abstract, edited.]

Preliminary Communication / December 30, 2019

Effect of Treating Parents Colonized With Staphylococcus aureus on Transmission to Neonates in the Intensive Care Unit – A Randomized Clinical Trial

Aaron M. Milstone, MD, MHS1,2,3; Annie Voskertchian, MPH1; Danielle W. Koontz, MAA1; et al. Dina F. Khamash, MD1,4; Tracy Ross, BS5; Susan W. Aucott, MD6; Maureen M. Gilmore, MD6; Sara E. Cosgrove, MD, MS2,7; Karen C. Carroll, MD8; Elizabeth Colantuoni, PhD9

Author Affiliations: 1 Division of Infectious Diseases, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland; 2 Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland; 3 Department of Hospital Epidemiology and Infection Control, The Johns Hopkins Hospital, Baltimore, Maryland; 4 Department of Pediatrics, Cooper University Health Care, Camden, New Jersey; 5 Division of Medical Microbiology, Department of Pathology, The Johns Hopkins Hospital, Baltimore, Maryland; 6 Division of Neonatology, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland; 7 Division of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland; 8 Division of Medical Microbiology, Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland; 9 Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland

JAMA. Published online December 30, 2019. doi: https://doi.org/10.1001/jama.2019.20785

 

Key Points

  • Question  – Does treating parents with short-course intranasal mupirocin and topical chlorhexidine bathing compared with placebo reduce acquisition of Staphylococcus aureus colonization in neonates?
  • Findings  – In this randomized clinical trial that included 190 neonates with parents colonized with S aureus, treating parents with intranasal mupirocin and chlorhexidine-impregnated cloths compared with placebo significantly reduced the hazard of acquiring colonization with a parental S aureus strain (hazard ratio, 0.43).
  • Meaning  – Treating colonized parents may reduce risk of S aureus transmission to neonates, but these findings are preliminary and require further research for replication and to assess generalizability.

 

Abstract

Importance  

Staphylococcus aureus is a leading cause of health care–associated infections in the neonatal intensive care unit (NICU). Parents may expose neonates to S aureus colonization, a well-established predisposing factor to invasive S aureus disease.

Objective  

To test whether treating parents with intranasal mupirocin and topical chlorhexidine compared with placebo would reduce transmission of S aureus from parents to neonates.

Design, Setting, and Participants  

Double-blinded randomized clinical trial in 2 tertiary NICUs in Baltimore, Maryland. Neonates (n = 236) with S aureus–colonized parent(s) were enrolled. The study period was November 7, 2014, through December 13, 2018.

Interventions  

Parents were assigned to intranasal mupirocin and 2% chlorhexidine–impregnated cloths (active treatment, n = 117) or petrolatum intranasal ointment and nonmedicated soap cloths (placebo, n = 119) for 5 days.

Main Outcomes and Measures  

The primary end point was concordant S aureus colonization by 90 days, defined as neonatal acquisition of an S aureus strain that was the same strain as a parental strain at time of screening. Secondary outcomes included neonatal acquisition of any S aureus strain and neonatal S aureus infections.

Results  

Among 236 randomized neonates, 208 were included in the analytic sample (55% male; 76% singleton births; mean birth weight, 1985 g [SD, 958 g]; 76% vaginal birth; mean parent age, 31 [SD, 7] years), of whom 18 were lost to follow-up. Among 190 neonates included in the analysis, 74 (38.9%) acquired S aureus colonization by 90 days, of which 42 (56.8%) had a strain concordant with a parental baseline strain. In the intervention and placebo groups, 13 of 89 neonates (14.6%) and 29 of 101 neonates (28.7%), respectively, acquired concordant S aureus colonization (risk difference, –14.1% [95% CI, –30.8% to –3.9%]; hazard ratio [HR], 0.43 [95.2% CI, 0.16 to 0.79]). A total of 28 of 89 neonates (31.4%) in the intervention group and 46 of 101 (45.5%) in the control group acquired any S aureus strain (HR, 0.57 [95% CI, 0.31 to 0.88]), and 1 neonate (1.1%) in the intervention group and 1 neonate (1.0%) in the control group developed an S aureus infection before colonization. Skin reactions in parents were common (4.8% intervention, 6.2% placebo).

Conclusions and Relevance  

In this preliminary trial of parents colonized with S aureus, treatment with intranasal mupirocin and chlorhexidine-impregnated cloths compared with placebo significantly reduced neonatal colonization with an S aureus strain concordant with a parental baseline strain. However, further research is needed to replicate these findings and to assess their generalizability.

Trial Registration  ClinicalTrials.gov Identifier: NCT02223520

Keywords: Intensive Care; Staphylococcus aureus; Pediatrics; Antibiotics; Mupirocin; Chlorhexidine.

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#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

 

Summary

Background

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.

Methods

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.

Findings

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.

Interpretation

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

Funding

National Institutes of Health.

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

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Sequential #evolution of #virulence and #resistance during clonal spread of community-acquired #MRSA (Proc Natl Acad Sci USA, abstract)

[Source: Proceedings of the National Academy of Sciences of the United States of America, full page: (LINK). Abstract, edited.]

Sequential evolution of virulence and resistance during clonal spread of community-acquired methicillin-resistant Staphylococcus aureus

Richard Copin, William E. Sause, Yi Fulmer, Divya Balasubramanian, Sophie Dyzenhaus, Jamil M. Ahmed, Krishan Kumar, John Lees, Anna Stachel, Jason C. Fisher, Karl Drlica, Michael Phillips, Jeffrey N. Weiser, Paul J. Planet, Anne-Catrin Uhlemann, Deena R. Altman, Robert Sebra, Harm van Bakel, Jennifer Lighter, Victor J. Torres, and Bo Shopsin

PNAS published ahead of print January 11, 2019 / DOI: https://doi.org/10.1073/pnas.1814265116

Edited by Emil C. Gotschlich, The Rockefeller University, New York, NY, and approved December 6, 2018 (received for review August 17, 2018)

 

Significance

Epidemics of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) are of growing medical concern. To understand the emergence of virulence and antimicrobial resistance, both of which promote CA-MRSA spread, we examined an on-going disease cluster within an enclosed community by analyzing the genome sequences of CA-MRSA clones characterized by high prevalence and a profound persistence. Metabolic adaptation and a phage primed the clone for success, and then a fully optimized variant was created by selection of plasmid-mediated biocide resistance. The data provide mechanistic insight and indicate that high-risk populations are incubators for evolution of consequential phenotypes. Immediate interruption of this evolutionary pattern is essential for forestalling dissemination of resistance from high-risk communities to hospitals and the general population.

 

Abstract

The past two decades have witnessed an alarming expansion of staphylococcal disease caused by community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA). The factors underlying the epidemic expansion of CA-MRSA lineages such as USA300, the predominant CA-MRSA clone in the United States, are largely unknown. Previously described virulence and antimicrobial resistance genes that promote the dissemination of CA-MRSA are carried by mobile genetic elements, including phages and plasmids. Here, we used high-resolution genomics and experimental infections to characterize the evolution of a USA300 variant plaguing a patient population at increased risk of infection to understand the mechanisms underlying the emergence of genetic elements that facilitate clonal spread of the pathogen. Genetic analyses provided conclusive evidence that fitness (manifest as emergence of a dominant clone) changed coincidently with the stepwise emergence of (i) a unique prophage and mutation of the regulator of the pyrimidine nucleotide biosynthetic operon that promoted abscess formation and colonization, respectively, thereby priming the clone for success; and (ii) a unique plasmid that conferred resistance to two topical microbiocides, mupirocin and chlorhexidine, frequently used for decolonization and infection prevention. The resistance plasmid evolved through successive incorporation of DNA elements from non-S. aureus spp. into an indigenous cryptic plasmid, suggesting a mechanism for interspecies genetic exchange that promotes antimicrobial resistance. Collectively, the data suggest that clonal spread in a vulnerable population resulted from extensive clinical intervention and intense selection pressure toward a pathogen lifestyle that involved the evolution of consequential mutations and mobile genetic elements.

MRSA – evolution – antimicrobial resistance – virulence

 

Footnotes

1 R.C. and W.E.S. contributed equally to this work.

2 To whom correspondence may be addressed. Email: Bo.Shopsin@nyumc.org, Victor.Torres@nyumc.org, or Jennifer.Lighter@nyumc.org.

Author contributions: R.C., W.E.S., J. Lighter, V.J.T., and B.S. designed research; R.C., W.E.S., Y.F., D.B., S.D., J.M.A., K.K., A.S., J.C.F., M.P., and D.R.A. performed research; R.C., J. Lees, P.J.P., A.-C.U., R.S., and H.v.B. contributed new reagents/analytic tools; R.C., W.E.S., D.B., and S.D. analyzed data; and R.C., W.E.S., K.D., J.N.W., V.J.T., and B.S. wrote the paper.

The authors declare no conflict of interest.

This article is a PNAS Direct Submission.

Data deposition: All genomic data reported in this paper have been deposited in the National Center for Biotechnology Information BioProject database (accession no. PRJNA497094).

This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1814265116/-/DCSupplemental.

Published under the PNAS license.

Keywords: Antibiotics; Drugs Resistance; Mupirocin; Chlorhexidine; MRSA; CA-MRSA; Staphylococcus aureus.

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Intracellular activity of #antimicrobial compounds used for #Staphylococcus aureus #nasal #decolonization (J Antimicrob Chemother., abstract)

[Source: Journal of Antimicrobial Chemotherapy, full page: (LINK). Abstract, edited.]

Intracellular activity of antimicrobial compounds used for Staphylococcus aureus nasal decolonization

J Rigaill, M F Morgene, M Gavid, Y Lelonge, Z He, A Carricajo, F Grattard, B Pozzetto, P Berthelot, E Botelho-Nevers, P O Verhoeven

Journal of Antimicrobial Chemotherapy, dky318, https://doi.org/10.1093/jac/dky318

Published: 16 August 2018

 

Abstract

Background

Staphylococcus aureus is able to invade mammalian cells during infection and was recently observed inside nasal mucosa of healthy carriers.

Objectives

To determine the intracellular activity of antimicrobial compounds used for decolonization procedures using a cell model mimicking S. aureus nasal epithelium invasion.

Patients and methods

HaCaT cells and human nasal epithelial cells (HNECs) recovered from nasal swabs of S. aureus carriers were visualized by confocal laser scanning microscopy to detect intracellular S. aureus cells. An HaCaT cell model, mimicking S. aureus internalization observed ex vivo in HNECs, was used to assess the intracellular activity against S. aureus of 21 antimicrobial compounds used for nasal decolonization, including mupirocin and chlorhexidine.

Results

HaCaT cells and HNECs were found to internalize S. aureus with the same focal pattern. Most antimicrobial compounds tested on HaCaT cells were shown to have weak activity against intracellular S. aureus. Some systemic antimicrobials, including fusidic acid, clindamycin, linezolid, minocycline, ciprofloxacin, moxifloxacin, rifampicin and levofloxacin, reduced S. aureus intracellular loads by 0.43–1.66 log cfu/106 cells compared with the control (P < 0.001). By contrast, mupirocin and chlorhexidine reduced the S. aureus intracellular load by 0.19 and 0.23 log cfu/106 cells, respectively.

Conclusions

These data indicate that most of the antimicrobial compounds used for nasal decolonization, including mupirocin and chlorhexidine, exhibit weak activity against intracellular S. aureus using the HaCaT cell model. This work emphasizes the need to better understand the role of the S. aureus intracellular reservoir during nasal colonization in order to improve decolonization procedures.

Issue Section: ORIGINAL RESEARCH

© The Author(s) 2018. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.

This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/about_us/legal/notices)

Keywords: Antibiotics; Staphylococcus aureus; Mupirocin; Chlorhexidine.

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In vitro susceptibility of #Neisseria gonorrhoeae strains to #mupirocin. An #antibiotic reformulated to parenteral nano-liposomal antibiotic (Antimicrob Agents Chemother., abstract)

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

In vitro susceptibility of Neisseria gonorrhoeae strains to mupirocin. An antibiotic reformulated to parenteral nano-liposomal antibiotic

Ahuva Cern a, Kristie L. Connolly b, Ann E. Jerse b and Yechezkel Barenholz a

Author Affiliations: a Laboratory of Membrane and Liposome Research, Department of Biochemistry, IMRIC, The Hebrew University – Hadassah Medical School, Jerusalem, Israel; b Department of Microbiology and Immunology, F. Edward Hèbert School of Medicine, Uniformed Services University, Bethesda, Maryland, USA

 

ABSTRACT

Neisseria gonorrhoeae is an urgent antibiotic-resistant threat. This study determined the minimum inhibitory concentrations (MIC) of mupirocin to be 0.0039-0.0625 μg/ml for 94 N. gonorrhoeae strains. Cross-resistance with other antibiotics was not detected.

Mupirocin, currently limited to topical administration, demonstrated activity by injection when delivered in nano-liposomes. The nano-liposomal formulation of mupirocin is a potential treatment for drug-resistant N. gonorrhoeae.

Copyright © 2018 American Society for Microbiology. All Rights Reserved.

Keywords: Antibiotics; Drugs Resistance; N. Gonorrhoeae.

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#Prevention of #surgical site #infections: #decontamination with #mupirocin based on pre-operative screening for #Staphylococcus aureus carriers or universal decontamination? (Clin Infect Dis., abstract)

[Source: Clinical Infectious Diseases Journal, full page: (LINK). Abstract, edited.]

Prevention of surgical site infections: decontamination with mupirocin based on pre-operative screening for Staphylococcus aureus carriers or universal decontamination? [      ]

David J. Hetem 1, Martin C.J. Bootsma 2,3, and Marc J.M. Bonten 1,2

Author Affiliations: 1Department of Clinical Microbiology, University Medical Center Utrecht, Utrecht, the Netherlands 2Julius Center for Health Sciences and Primary Care, University Medical Center, Utrecht 3Department of Mathematics, Utrecht University, Utrecht, the Netherlands

Corresponding author: M.J.M. Bonten, MD, Phd. University Medical Center Utrecht, Department of Clinical Microbiology, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands, m.j.m.bonten@umcutrecht.nl

 

Abstract

Peri-operative decolonization of Staphylococcus aureus nasal carriers with mupirocin together with chlorhexidine body washing reduces the incidence of S. aureus surgical site infection (SSI). A targeted strategy, applied in S. aureus carriers only, is costly and implementation may reduce effectiveness. Universal decolonization is more cost-effective, but increases exposure of non-carriers to mupirocin, and the risk of resistance to mupirocin in staphylococci. High-level mupirocin resistance in S. aureus can emerge through horizontal gene transfer originating from coagulase-negative staphylococci (CoNS) and through clonal transmission. The current evidence on the occurrence of high-level mupirocin resistance in S. aureus and CoNS, in combination with the results of mathematical modelling, strongly suggest that the increased selection of high-level mupirocin resistance in CoNS does not constitute an important risk for high-level mupirocin resistance in S. aureus.

As compared to a targeted strategy, universal decolonization seems associated with an equally low risk of mupirocin resistance in S. aureus.

10.1093/cid/civ99210.1093/cid/civ901

© The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Keywords: Research; Abstracts; Antibiotics; Drugs Resistance; Staphylococcus Aureus; Mupirocin.

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