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The Journal of Allergy and Clinical... Jan 2019As an interface with the environment, the skin is a complex ecosystem colonized by many microorganisms that coexist in an established balance. The cutaneous microbiome... (Review)
Review
As an interface with the environment, the skin is a complex ecosystem colonized by many microorganisms that coexist in an established balance. The cutaneous microbiome inhibits colonization with pathogens, such as Staphylococcus aureus, and is a crucial component for function of the epidermal barrier. Moreover, crosstalk between commensals and the immune system is now recognized because microorganisms can modulate both innate and adaptive immune responses. Host-commensal interactions also have an effect on the developing immune system in infants and, subsequently, the occurrence of diseases, such as asthma and atopic dermatitis (AD). Later in life, the cutaneous microbiome contributes to the development and course of skin disease. Accordingly, in patients with AD, a decrease in microbiome diversity correlates with disease severity and increased colonization with pathogenic bacteria, such as S aureus. Early clinical studies suggest that topical application of commensal organisms (eg, Staphylococcus hominis or Roseomonas mucosa) reduces AD severity, which supports an important role for commensals in decreasing S aureus colonization in patients with AD. Advancing knowledge of the cutaneous microbiome and its function in modulating the course of skin disorders, such as AD, might result in novel therapeutic strategies.
Topics: Adaptive Immunity; Dermatitis, Atopic; Female; Humans; Immunity, Innate; Male; Microbiota; Skin; Staphylococcal Skin Infections; Staphylococcus aureus
PubMed: 30476499
DOI: 10.1016/j.jaci.2018.11.015 -
Science Translational Medicine Feb 2017The microbiome can promote or disrupt human health by influencing both adaptive and innate immune functions. We tested whether bacteria that normally reside on human... (Clinical Trial)
Clinical Trial
The microbiome can promote or disrupt human health by influencing both adaptive and innate immune functions. We tested whether bacteria that normally reside on human skin participate in host defense by killing , a pathogen commonly found in patients with atopic dermatitis (AD) and an important factor that exacerbates this disease. High-throughput screening for antimicrobial activity against was performed on isolates of coagulase-negative (CoNS) collected from the skin of healthy and AD subjects. CoNS strains with antimicrobial activity were common on the normal population but rare on AD subjects. A low frequency of strains with antimicrobial activity correlated with colonization by The antimicrobial activity was identified as previously unknown antimicrobial peptides (AMPs) produced by CoNS species including and These AMPs were strain-specific, highly potent, selectively killed , and synergized with the human AMP LL-37. Application of these CoNS strains to mice confirmed their defense function in vivo relative to application of nonactive strains. Strikingly, reintroduction of antimicrobial CoNS strains to human subjects with AD decreased colonization by These findings show how commensal skin bacteria protect against pathogens and demonstrate how dysbiosis of the skin microbiome can lead to disease.
Topics: Amino Acid Sequence; Animals; Anti-Infective Agents; Antimicrobial Cationic Peptides; Bacteria; Coagulase; Colony Count, Microbial; Dermatitis, Atopic; Dysbiosis; Humans; Mice; Microbiota; Skin; Staphylococcus aureus; Sus scrofa
PubMed: 28228596
DOI: 10.1126/scitranslmed.aah4680 -
PloS One 2020A large proportion of neonates are treated for presumed bacterial sepsis with broad spectrum antibiotics even though their blood cultures subsequently show no growth....
BACKGROUND
A large proportion of neonates are treated for presumed bacterial sepsis with broad spectrum antibiotics even though their blood cultures subsequently show no growth. This study aimed to investigate PCR-based methods to identify pathogens not detected by conventional culture.
METHODS
Whole blood samples of 208 neonates with suspected early onset sepsis were tested using a panel of multiplexed bacterial PCRs targeting Streptococcus pneumoniae, Streptococcus agalactiae (GBS), Staphylococcus aureus, Streptococcus pyogenes (GAS), Enterobacteriaceae, Enterococcus faecalis, Enterococcus faecium, Ureaplasma parvum, Ureaplasma urealyticum, Mycoplasma hominis and Mycoplasma genitalium, a 16S rRNA gene broad-range PCR and a multiplexed PCR for Candida spp.
RESULTS
Two-hundred and eight samples were processed. In five of those samples, organisms were detected by conventional culture; all of those were also identified by PCR. PCR detected bacteria in 91 (45%) of the 203 samples that did not show bacterial growth in culture. S. aureus, Enterobacteriaceae and S. pneumoniae were the most frequently detected pathogens. A higher bacterial load detected by PCR was correlated positively with the number of clinical signs at presentation.
CONCLUSION
Real-time PCR has the potential to be a valuable additional tool for the diagnosis of neonatal sepsis.
Topics: Age of Onset; Bacteria; Bacterial Infections; Candida; Candidiasis; DNA, Ribosomal; Early Diagnosis; Enterobacteriaceae; Enterococcus; Humans; Infant, Extremely Premature; Infant, Newborn; Infant, Premature; Multiplex Polymerase Chain Reaction; Mycoplasma; Neonatal Sepsis; RNA, Ribosomal, 16S; Real-Time Polymerase Chain Reaction; Sensitivity and Specificity; Staphylococcus aureus; Streptococcus; Ureaplasma
PubMed: 31978082
DOI: 10.1371/journal.pone.0226817 -
Drug Safety - Case Reports Nov 2017Our case describes a 77-year-old, African American male who was experiencing recurrent hypoglycemic episodes, which resulted in two emergency department (ED) visits and...
Our case describes a 77-year-old, African American male who was experiencing recurrent hypoglycemic episodes, which resulted in two emergency department (ED) visits and a subsequent inpatient admission during his second ED visit. He was prescribed linezolid 600 mg twice daily for 14 days for the treatment of a Staphylococcus hominis urinary tract infection. Nine and a half days into therapy, the patient began having recurrent hypoglycemic episodes. These episodes persisted despite repeated intravenous dextrose boluses. The patient's linezolid was discontinued during the second day of his inpatient admission. After a brief lag period after the final linezolid administration, the patient's blood glucose level stabilized within normal limits. He was later discharged home. The Naranjo scale scores the causality of this reaction between 4 and 8, indicating possible to probable causality. The patient had a follow-up appointment with his primary care physician 2 weeks after discharge, with no noted blood glucose complications. Two months after discharge, he entered hospice care for his advancing heart failure and later expired due to causes unrelated to blood glucose complications.
PubMed: 29124464
DOI: 10.1007/s40800-017-0061-0 -
Nature Medicine Apr 2021Staphylococcus aureus colonizes patients with atopic dermatitis (AD) and exacerbates disease by promoting inflammation. The present study investigated the safety and... (Randomized Controlled Trial)
Randomized Controlled Trial
Staphylococcus aureus colonizes patients with atopic dermatitis (AD) and exacerbates disease by promoting inflammation. The present study investigated the safety and mechanisms of action of Staphylococcus hominis A9 (ShA9), a bacterium isolated from healthy human skin, as a topical therapy for AD. ShA9 killed S. aureus on the skin of mice and inhibited expression of a toxin from S. aureus (psmα) that promotes inflammation. A first-in-human, phase 1, double-blinded, randomized 1-week trial of topical ShA9 or vehicle on the forearm skin of 54 adults with S. aureus-positive AD (NCT03151148) met its primary endpoint of safety, and participants receiving ShA9 had fewer adverse events associated with AD. Eczema severity was not significantly different when evaluated in all participants treated with ShA9 but a significant decrease in S. aureus and increased ShA9 DNA were seen and met secondary endpoints. Some S. aureus strains on participants were not directly killed by ShA9, but expression of mRNA for psmα was inhibited in all strains. Improvement in local eczema severity was suggested by post-hoc analysis of participants with S. aureus directly killed by ShA9. These observations demonstrate the safety and potential benefits of bacteriotherapy for AD.
Topics: Administration, Topical; Adolescent; Adult; Aged; Aged, 80 and over; Animals; Bacterial Proteins; Bacteriocins; Colony Count, Microbial; Dermatitis, Atopic; Humans; Inflammation; Mice, Inbred BALB C; Microbial Sensitivity Tests; Microbial Viability; Middle Aged; Peptides, Cyclic; Reproducibility of Results; Skin; Staphylococcal Infections; Staphylococcus aureus; Staphylococcus hominis; Transcription, Genetic; Treatment Outcome; Virulence Factors; Young Adult; Mice
PubMed: 33619370
DOI: 10.1038/s41591-021-01256-2 -
Microbiology Spectrum Dec 2022To evaluate the activities of eravacycline, tedizolid, nemonoxacin, norvancomycin, and ceftaroline against Staphylococcus and species isolates were collected as part...
Activities of Eravacycline, Tedizolid, Norvancomycin, Nemonoxacin, Ceftaroline, and Comparators against 1,871 and 1,068 Species Isolates from China: Updated Report of the CHINET Study 2019.
To evaluate the activities of eravacycline, tedizolid, nemonoxacin, norvancomycin, and ceftaroline against Staphylococcus and species isolates were collected as part of the China Antimicrobial Surveillance Network (CHINET) in 2019 to provide susceptibility data for Staphylococcus spp. and spp. for their future development and application in clinical practice. Antimicrobial susceptibility testing was performed using the CLSI broth microdilution reference method. Eravacycline was highly active against Staphylococcus and species isolates, proved by the MIC: 0.06/0.125, 0.06/0.25, 0.06/0.25, 0.06/0.25, 0.125/0.5, 0.125/0.25, and 0.03/0.06 mg/L for Staphylococcus aureus, methicillin-resistant S. aureus (MRSA), S. epidermidis, S. hominis, S. haemolyticus, Enterococcus faecalis, and E. faecium, respectively. S. aureus isolates tested were fully susceptible to tedizolid. Still, nonsusceptible isolates were found for E. faecalis (72/567 [12.7%]) and E. faecium (12/501 [2.4%]). Norvancomycin at 2 mg/L could inhibit 100% of Staphylococcus spp., while 1 mg/L of ceftaroline could inhibit 78.9% of MRSA and 99.9% of methicillin-susceptible S. aureus (MSSA) isolates. Additionally, nemonoxacin was also active against Staphylococcus and species isolates tested (shown by the following MICs and ranges, in milligrams per liter: 2 and ≤0.015 to 8 for MRSA, 0.25 and ≤0.015 to 4 for MSSA, 0.5 and ≤0.015 to 8 for S. epidermidis, and 4 and ≤0.015 to >32 for E. faecalis). In conclusion, both eravacycline and tedizolid were highly active against clinical isolates of Staphylococcus spp. and spp. recently collected across China. Nemonoxacin showed potent activity against Staphylococcus spp. and E. faecalis but limited activity against E. faecium. Norvancomycin and ceftaroline displayed highly potent activity against Staphylococcus spp. Antimicrobial resistance has become a severe threat to global public health. According to statistics, nearly 700,000 people die from bacterial infections worldwide (J. O'Neill, , 2014; C. Y. Chin, K. A. Tipton, M. Farokhyfar, E. M. Burd, et al., Nat Microbiol 3:563-569, 2018, https://doi.org/10.1038/s41564-018-0151-5). The number of bacterial infections is expected to climb to 10 million by 2050, showing that bacterial resistance has become a significant problem that cannot be ignored. It is crucial to develop new antimicrobial agents to combat antimicrobial-resistant bacteria. In this study, we evaluated the activities of eravacycline, tedizolid, nemonoxacin, norvancomycin, and ceftaroline against Staphylococcus spp. and species isolates which were collected as part of CHINET in 2019. We believe that this study can provide susceptibility data for Staphylococcus spp. and spp. for their future development and application in clinical practice.
Topics: Humans; Enterococcus; Anti-Bacterial Agents; Staphylococcus; Staphylococcus aureus; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Ceftaroline
PubMed: 36326536
DOI: 10.1128/spectrum.01715-22 -
IDCases 2022and are the most common pathogens causing skin and soft tissue infections (SSTI). Guideline-recommended empiric antibiotics targeting these organisms would also treat...
and are the most common pathogens causing skin and soft tissue infections (SSTI). Guideline-recommended empiric antibiotics targeting these organisms would also treat coagulase negative Staphylococci, which are not typically considered skin and soft tissue pathogens. Coagulase negative Staphylococci are, however, well known for their propensity to cause indolent infections in the setting of prosthetic material. Here, we present a case of a patient with surgical clips from a femoral artery surgical repair one year prior, presenting with cellulitis at the prior surgical site, complicated by high-grade bacteremia. Signs of infection persisted after 4 days of appropriate antibiotic therapy and resolved rapidly upon non-steroidal anti-inflammatory administration. This case highlights the importance of recognizing coagulase negative Staphylococci as a possible etiology of cellulitis in patients with prosthetic material, and of considering anti-inflammatory medications as a supplement to antibiotic therapy to hasten resolution of cellulitis in appropriate patients.
PubMed: 35145866
DOI: 10.1016/j.idcr.2022.e01436 -
Case Reports in Infectious Diseases 2022(. ) is a Gram-positive, coagulase-negative bacteria that occurs as a normal commensal organism on the skin and may rarely cause native valve endocarditis (NVE). We...
(. ) is a Gram-positive, coagulase-negative bacteria that occurs as a normal commensal organism on the skin and may rarely cause native valve endocarditis (NVE). We present a 62-year-old male with type 2 diabetes mellitus, coronary artery disease, and hypertension presenting with fever and abdominal pain. CT (computerized tomography) of the abdomen revealed splenic and renal infarcts; further imaging with MRI (magnetic resonance imaging) revealed enhancements consistent with discitis in T5-6 and L1-2. Three sets of blood cultures were positive for . sensitive to methicillin on antimicrobial susceptibility tests, and echocardiogram showed posterior mitral valve vegetation. The patient was initially treated with 10 weeks of nafcillin IV (intravenous) 2 g q4 hours. He had recurrent bouts of S. bacteremia that was treated with IV vancomycin. His clinical course was complicated by new-onset atrial fibrillation with rapid ventricular response and congestive heart failure. Once bacteremia was cleared, his infective endocarditis was successfully definitively treated with mitral valve replacement and tricuspid repair.
PubMed: 35607353
DOI: 10.1155/2022/7183049 -
The Ubiquitous Human Skin Commensal Staphylococcus hominis Protects against Opportunistic Pathogens.MBio Jun 2022Staphylococcus hominis is frequently isolated from human skin, and we hypothesize that it may protect the cutaneous barrier from opportunistic pathogens. We determined...
Staphylococcus hominis is frequently isolated from human skin, and we hypothesize that it may protect the cutaneous barrier from opportunistic pathogens. We determined that S. hominis makes six unique autoinducing peptide (AIP) signals that inhibit the major virulence factor accessory gene regulator () quorum sensing system of Staphylococcus aureus. We solved and confirmed the structures of three novel AIP signals in conditioned medium by mass spectrometry and then validated synthetic AIP activity against all S. aureus classes. Synthetic AIPs also inhibited the conserved system in a related species, Staphylococcus epidermidis. We determined the distribution of S. hominis types on healthy human skin and found S. hominis -I and -II were highly represented across subjects. Further, synthetic AIP-II was protective against S. aureus-associated dermonecrotic or epicutaneous injury. Together, these findings demonstrate that a ubiquitous colonizer of human skin has a fundamentally protective role against opportunistic damage. Human skin is home to a variety of commensal bacteria, including many species of coagulase-negative staphylococci (CoNS). While it is well established that the microbiota as a whole maintains skin homeostasis and excludes pathogens (i.e., colonization resistance), relatively little is known about the unique contributions of individual CoNS species to these interactions. Staphylococcus hominis is the second most frequently isolated CoNS from healthy skin, and there is emerging evidence to suggest that it may play an important role in excluding pathogens, including Staphylococcus aureus, from colonizing or infecting the skin. Here, we identified that S. hominis makes 6 unique peptide inhibitors of the S. aureus global virulence factor regulation system (). Additionally, we found that one of these peptides can prevent topical or necrotic S. aureus skin injury in a mouse model. Our results demonstrate a specific and broadly protective role for this ubiquitous, yet underappreciated skin commensal.
Topics: Animals; Bacterial Proteins; Humans; Mice; Peptides; Staphylococcal Infections; Staphylococcus; Staphylococcus aureus; Staphylococcus epidermidis; Staphylococcus hominis; Virulence Factors
PubMed: 35608301
DOI: 10.1128/mbio.00930-22 -
Arquivos Brasileiros de Oftalmologia 2023Staphylococcus hominis (S. hominis) is a coagulase-negative Staphylococci and an infrequent cause of endophthalmitis. Due to its ability to produce biofilm, especially...
Staphylococcus hominis (S. hominis) is a coagulase-negative Staphylococci and an infrequent cause of endophthalmitis. Due to its ability to produce biofilm, especially in diabetic patients, strains may acquire antibiotic resistance. We present two cases of S. hominis endophthalmitis, one with acute endophthalmitis after intravitreal bevacizumab injection and one with chronic endophthalmitis following undiagnosed penetrating ocular trauma. Although there are only four published S. hominis endophthalmitis cases in the literature, to the best of our knowledge, there has been no previously published case after intravitreal bevacizumab.
Topics: Humans; Bevacizumab; Staphylococcus hominis; Endophthalmitis; Intravitreal Injections; Retrospective Studies; Anti-Bacterial Agents; Eye Infections, Bacterial; Angiogenesis Inhibitors
PubMed: 35319646
DOI: 10.5935/0004-2749.20230035