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.

——

Evaluation of the activity of a combination of three #bacteriophages alone or in association with #antibiotics on #Staphylococcus aureus embedded in #biofilm or internalised in #osteoblasts (Antimicrob Agents Chemother., abstract)

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

Evaluation of the activity of a combination of three bacteriophages alone or in association with antibiotics on Staphylococcus aureus embedded in biofilm or internalised in osteoblasts

Camille Kolenda, Jérôme Josse, Mathieu Medina, Cindy Fevre, Sébastien Lustig, Tristan Ferry, Frédéric Laurent

DOI: 10.1128/AAC.02231-19

 

ABSTRACT

Background:

Staphylococcus aureus is responsible for difficult-to-treat bone and joint infections (BJIs). This is related to its ability to form biofilm, and to be internalised and persist inside osteoblasts. Recently, bacteriophage therapy has emerged as a promising option to improve treatment of such infections but data on its activity against the specific bacterial lifestyles presented above remain scarce.

Methods:

We evaluated the activity of a combination of three bacteriophages, recently used for compassionate treatment in France, against S. aureus HG001 in a model of staphylococcal biofilm and a model of osteoblasts infection, alone or in association with vancomycin or rifampicin.

Results:

The activity of bacteriophages against biofilm-embedded S. aureus was dose-dependent. In addition, synergistic effects were observed when bacteriophages were combined with antibiotics used at the lowest concentrations. Phage penetration into osteoblasts was observed only when the cells were infected, suggesting a S. aureus-dependent Trojan horse mechanism for internalisation. The intracellular bacterial count of bacteria in infected osteoblasts treated with bacteriophages, as well as with vancomycin, was significantly higher than in cells treated with lysostaphin, used as control condition, owing to the absence of intracellular activity, and the rapid killing of bacteria released after death of infected cells. These results suggest that bacteriophages are both inactive in the intracellular compartment after being internalised in infected osteoblasts, and present a delayed killing effect on bacteria released after cell lysis into the extracellular compartment which avoid to prevent them from infecting other osteoblasts.

Conclusion:

The combination of bacteriophages tested was highly active against S. aureus embedded in biofilm but showed no activity against intracellular bacteria in the cell model used.

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

Keywords: Antibiotics; Drugs Resistance; Staphylococcus aureus; Bacteriophages.

——-

Protective Efficacy of #Monoclonal #Antibodies Neutralizing Alpha-Hemolysin and Bicomponent Leukocidins in Rabbit Model of #Staphylococcus aureus Necrotizing #Pneumonia (Antimicrob Agents Chemother., abstract)

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

Protective Efficacy of Monoclonal Antibodies Neutralizing Alpha-Hemolysin and Bicomponent Leukocidins in Rabbit Model of Staphylococcus aureus Necrotizing Pneumonia

Trang T. T. Vu, Nhu T.Q. Nguyen, Vuvi G. Tran, Emmanuelle Gras, Yanjie Mao, David H. Jung, Christine Tkaczyk, Bret R. Sellman, Binh An Diep

DOI: 10.1128/AAC.02220-19

 

ABSTRACT

Staphylococcus aureus is a major human pathogen, causing a wide range of infections by producing an arsenal of cytotoxins. We found that passive immunization with either a monoclonal antibody (mAb) neutralizing alpha-hemolysin or a broadly cross-reactive mAb that neutralize Panton-Valentine leukocidin, leukocidin ED and gamma-hemolysins HlgAB/HlgCB only conferred partial protection, whereas the combination of those two mAbs conferred significant protection in a rabbit model of necrotizing pneumonia caused by the USA300 MRSA epidemic clone.

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

Keywords: Staphylococcus aureus; Monoclonal antibodies; Animal models.

——

#Genome #investigations show host #adaptation and #transmission of LA- #MRSA CC398 from #pigs into #Danish #healthcare #institutions (Sci Rep., abstract)

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

Genome investigations show host adaptation and transmission of LA-MRSA CC398 from pigs into Danish healthcare institutions

Raphael Niklaus Sieber, Anders Rhod Larsen, Tinna Ravnholt Urth, Søren Iversen, Camilla Holten Møller, Robert Leo Skov, Jesper Larsen & Marc Stegger

Scientific Reports, volume 9, Article number: 18655 (2019)

 

Abstract

Over the last decade, an increasing number of infections with livestock-associated methicillin-resistant Staphylococcus aureus of clonal complex 398 (LA-MRSA CC398) in persons without contact to livestock has been registered in Denmark. These infections have been suggested to be the result of repeated spillover of random isolates from livestock into the community. However, other studies also found emerging sub-lineages spreading among humans. Based on genome-wide SNPs and genome-wide association studies (GWAS), we assessed the population structure and genomic content of Danish LA-MRSA CC398 isolates from healthcare-associated infections from 2014 to 2016 (n = 73) and compared these to isolates from pigs in Denmark from 2014 (n = 183). Phylogenetic analyses showed that most human isolates were closely related to and scattered among pig isolates showing that the majority of healthcare-associated infections are the result of repeated spillover from pig farms, even though cases of human-to-human transmission also were identified. GWAS revealed frequent loss of antimicrobial resistance genes and acquisition of human-specific virulence genes in the human isolates showing adaptation in response to changes in selective pressures in different host environments, which over time could lead to the emergence of LA-MRSA CC398 lineages more adapted to human colonization and transmission.

Keywords: Antibiotics; Drugs Resistance; Staphylococcus aureus; MRSA; Pigs; Human; Nosocomial outbreaks; Denmark.

——

Molecular Characterization of #MRSA in a Tertiary Care #hospital in #Kuwait (Sci Rep., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Sci Rep. 2019 Dec 6;9(1):18527. doi: 10.1038/s41598-019-54794-8.

Molecular Characterization of Methicillin- Resistant Staphylococcus aureus in a Tertiary Care hospital in Kuwait.

Alfouzan W1,2, Udo EE3, Modhaffer A1, Alosaimi A1.

Author information: 1 Microbiology Unit, Department of Laboratory Medicine, Farwaniya hospital, Ministry of Health, Sabah Al Nasser, Kuwait. 2 Department of Microbiology, Faculty of Medicine, Kuwait University, Jabriya, Kuwait. 3 Department of Microbiology, Faculty of Medicine, Kuwait University, Jabriya, Kuwait. EDET@hsc.edu.kw.

 

Abstract

Methicillin-resistant Staphylococcus aureus (MRSA) are a major cause of healthcare and community- associated infections due to their ability to express a variety of virulence factors. We investigated 209 MRSA isolates obtained from 1 January to 31 December 2016 using a combination of phenotypic and genotypic methods to understand the genetic backgrounds of MRSA strains obtained in a General hospital in Kuwait. Antibiotics susceptibility was performed with disk diffusion, and MIC was measured with Etest strips. Molecular typing was performed using SCCmec typing, spa typing, and DNA microarray for antibiotic resistance and virulence genes. The isolates were susceptible to vancomycin, teicoplanin, rifampicin, ceftaroline, and linezolid but were resistant to gentamicin, tetracycline, erythromycin, fusidic acid, chloramphenicol and ciprofloxacin. Molecular typing revealed six SCCmec types, 56 spa types and 16 clonal complexes (CC). The common SCCmec types were type IV (39.5%), type III (34.4%), type V (25.8%) and type VI (3.8%). The dominant spa types were t860 (23.9%), t945 (8.6%), t127 (6.7%), t688 (6.7%), t304 (6.2) and t044 (5.7%). The other spa types occurred sporadically. Genes for PVL was detected in 59 (28.2%) of the isolates. CC8-ST239-MRSA-III + SCCmer (23.3%) was the most prevalent clone, followed by CC6-MRSA-IV (8.3%), CC80-MRSA-IV [PVL+] (5.8%), CC5-MRSA-VI + SCCfus (5.0%), CC30-MRSA-IV[PVL+] (4.1%), CC1-MRSA-V + SCCfus [PVL+] (4.1%), CC5-MRSA-V + SCCfus (4.1%) and CC22-MRSA-IV[PVL+] (4.1%). The study revealed that despite the emergence of MRSA with diverse genetic backgrounds over the years, ST239-MRSA-III remained the dominant clone in the hospital. This warrants reassessment of infection prevention and control procedures at this hospital.

PMID: 31811246 DOI: 10.1038/s41598-019-54794-8

Keywords: Antibiotics; Drugs Resistance; MRSA; Staphylcoccus aureus; Nosocomial outbreaks; Kuwait.

—–

#Monoclonal #antibody anti-PBP2a protects mice against #MRSA (methicillin-resistant #Staphylococcus aureus) infections (PLOS One, abstract)

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

OPEN ACCESS /  PEER-REVIEWED / RESEARCH ARTICLE

Monoclonal antibody anti-PBP2a protects mice against MRSA (methicillin-resistant Staphylococcus aureus) infections

Felipe Betoni Saraiva, Ana Caroline Cavalcante de Araújo, Anna Érika Vieira de Araújo, José Procópio Moreno Senna

___

Published: November 27, 2019 / DOI: https://doi.org/10.1371/journal.pone.0225752

 

Abstract

Methicillin-resistant Staphylococcus aureus (MRSA) is a multidrug-resistant bacterium responsible for serious nosocomial and community-acquired infections worldwide. Since few antibiotics are effective for treating MRSA infections, the development of new therapies is of great importance. Previous studies demonstrated that PBP2a is a target that generates protective antibodies against MRSA. A murine monoclonal antibody (MAb) that recognizes PBP2a from MRSA strains was previously isolated and characterized. In this report, we evaluated the biodistribution of this MAb in blood and tissues, as well as the extent of protection conferred using prophylactic and therapeutic assays compared to vancomycin treatment. Biodistribution was evaluated 12–96 h after MAb administration. It predominantly remained in the serum, but it was also detectable in the kidneys, lungs, and spleen at low concentrations (about 4.5% in the kidneys, 1.9% in the lungs, and 0.7% the spleen) at all observed timepoints. Prophylactic studies in a murine model demonstrated a significant bacterial load reduction in the kidneys of the groups treated with either with IgG (greater than 3 logs) or F(ab’)2 (98%) when compared to that of the control groups (untreated). Mice were challenged with a lethal dose, and the survival rate was higher in the treated mice. Treatment with the MAb resulted in a bacterial load reduction in the kidneys similar to that of mice treated with vancomycin, and a MAb/vancomycin combination therapy was also effective. These results demonstrate that an anti-PBP2a MAb may be a promising therapeutic for treating MRSA infections.

___

Citation: Saraiva FB, de Araújo ACC, de Araújo AÉV, Senna JPM (2019) Monoclonal antibody anti-PBP2a protects mice against MRSA (methicillin-resistant Staphylococcus aureus) infections. PLoS ONE 14(11): e0225752. https://doi.org/10.1371/journal.pone.0225752

Editor: Paulo Lee Ho, Instituto Butantan, BRAZIL

Received: April 30, 2019; Accepted: October 29, 2019; Published: November 27, 2019

Copyright: © 2019 Saraiva et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: All relevant data are within the manuscript and its Supporting Information files.

Funding: This work was supported by Instituto de Tecnologia em Imunobiológicos Bio-Manguinhos (Fiocruz).

Competing interests: The authors have declared that no competing interests exist.

Keywords: Antibiotics; Drugs Resistance; Staphylococcus aureus; MRSA; Monoclonal antibodies.

——

#Evolution and #Global #Transmission of a #MDR, CA #MRSA #Lineage from the #Indian Subcontinent (MBio, abstract)

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

Evolution and Global Transmission of a Multidrug-Resistant, Community-Associated Methicillin-Resistant Staphylococcus aureus Lineage from the Indian Subcontinent

Eike J. Steinig, Sebastian Duchene, D. Ashley Robinson, Stefan Monecke, Maho Yokoyama, Maisem Laabei, Peter Slickers, Patiyan Andersson, Deborah Williamson, Angela Kearns, Richard V. Goering, Elizabeth Dickson, Ralf Ehricht, Margaret Ip, Matthew V. N. O’Sullivan, Geoffrey W. Coombs, Andreas Petersen, Grainne Brennan, Anna C. Shore, David C. Coleman, Annalisa Pantosti, Herminia de Lencastre, Henrik Westh, Nobumichi Kobayashi, Helen Heffernan, Birgit Strommenger, Franziska Layer, Stefan Weber, Hege Vangstein Aamot, Leila Skakni, Sharon J. Peacock, Derek Sarovich, Simon Harris, Julian Parkhill, Ruth C. Massey, Mathew T. G. Holden, Stephen D. Bentley, Steven Y. C. Tong

Paul J. Planet, Invited Editor, Victor J. Torres, Editor

DOI: 10.1128/mBio.01105-19

 

ABSTRACT

The evolution and global transmission of antimicrobial resistance have been well documented for Gram-negative bacteria and health care-associated epidemic pathogens, often emerging from regions with heavy antimicrobial use. However, the degree to which similar processes occur with Gram-positive bacteria in the community setting is less well understood. In this study, we traced the recent origins and global spread of a multidrug-resistant, community-associated Staphylococcus aureus lineage from the Indian subcontinent, the Bengal Bay clone (ST772). We generated whole-genome sequence data of 340 isolates from 14 countries, including the first isolates from Bangladesh and India, to reconstruct the evolutionary history and genomic epidemiology of the lineage. Our data show that the clone emerged on the Indian subcontinent in the early 1960s and disseminated rapidly in the 1990s. Short-term outbreaks in community and health care settings occurred following intercontinental transmission, typically associated with travel and family contacts on the subcontinent, but ongoing endemic transmission was uncommon. Acquisition of a multidrug resistance integrated plasmid was instrumental in the emergence of a single dominant and globally disseminated clade in the early 1990s. Phenotypic data on biofilm, growth, and toxicity point to antimicrobial resistance as the driving force in the evolution of ST772. The Bengal Bay clone therefore combines the multidrug resistance of traditional health care-associated clones with the epidemiological transmission of community-associated methicillin-resistant S. aureus (MRSA). Our study demonstrates the importance of whole-genome sequencing for tracking the evolution of emerging and resistant pathogens. It provides a critical framework for ongoing surveillance of the clone on the Indian subcontinent and elsewhere.

 

IMPORTANCE

The Bengal Bay clone (ST772) is a community-associated and multidrug-resistant Staphylococcus aureus lineage first isolated from Bangladesh and India in 2004. In this study, we showed that the Bengal Bay clone emerged from a virulent progenitor circulating on the Indian subcontinent. Its subsequent global transmission was associated with travel or family contact in the region. ST772 progressively acquired specific resistance elements at limited cost to its fitness and continues to be exported globally, resulting in small-scale community and health care outbreaks. The Bengal Bay clone therefore combines the virulence potential and epidemiology of community-associated clones with the multidrug resistance of health care-associated S. aureus lineages. This study demonstrates the importance of whole-genome sequencing for the surveillance of highly antibiotic-resistant pathogens, which may emerge in the community setting of regions with poor antibiotic stewardship and rapidly spread into hospitals and communities across the world.

Keywords: Antibiotics; Drugs Resistance; Staphylococcus aureus; MRSA; CA-MRSA; India; Bangladesh.

——