• Antibiotic use
• Antimicrobial resistance
• CRE
• ESBL
• Infection prevention
• MDRO
• MRSA

• Humans
• Critical Care/methods
• Cross Infection/prevention & control
• Cross Infection/transmission
• Infection Control/methods
• Intensive Care Units
• Drug Resistance, Multiple

• Antibiotic resistance
• Multidrug resistant gram-negative bacteria
• aztreonam-avibactam
• complicated intra-abdominal infections
• β-lactam-β-lactamase inhibitors

• Humans
• Intraabdominal Infections/drug therapy
• Intraabdominal Infections/microbiology
• Aztreonam/therapeutic use
• Anti-Bacterial Agents/therapeutic use
• Anti-Bacterial Agents/pharmacology
• Anti-Bacterial Agents/adverse effects
• Anti-Bacterial Agents/pharmacokinetics
• Drug Combinations
• Azabicyclo Compounds/therapeutic use
• Azabicyclo Compounds/pharmacology
• Azabicyclo Compounds/pharmacokinetics
• Gram-Negative Bacterial Infections/drug therapy
• Gram-Negative Bacterial Infections/microbiology
• beta-Lactamase Inhibitors/therapeutic use
• beta-Lactamase Inhibitors/pharmacology
• Gram-Negative Bacteria/drug effects
• Animals

• ARGs
• ICU
• Staphylococcus aureus
• VFGs
• genomic sequence

• Humans
• Staphylococcal Infections/microbiology
• Staphylococcal Infections/epidemiology
• Intensive Care Units
• Tertiary Care Centers
• Virulence Factors/genetics
• Methicillin-Resistant Staphylococcus aureus/genetics
• Methicillin-Resistant Staphylococcus aureus/isolation & purification
• Methicillin-Resistant Staphylococcus aureus/pathogenicity
• Carrier State/microbiology
• Carrier State/epidemiology
• Staphylococcus aureus/genetics
• Staphylococcus aureus/isolation & purification
• Staphylococcus aureus/pathogenicity
• Cross Infection/microbiology
• Cross Infection/epidemiology
• Whole Genome Sequencing
• Male
• Molecular Epidemiology
• Nose/microbiology
• Female
• Virulence/genetics
• Community-Acquired Infections/microbiology
• Community-Acquired Infections/epidemiology
• Aged
• Middle Aged
• Genome, Bacterial
• Genotype

• JP19K18326 MEXT | Japan Society for the Promotion of Science (JSPS)
• 21fk0108604j0001, 22fk0108604j0002, 23fk0108604j0003 Japan Agency for Medical Research and Development (AMED)

• Drug-resistant organism
• Early effective therapy
• Novel diagnostics
• Window

• Pseudomonas aeruginosa
• antimicrobial stewardship
• critically ill
• methicillin-resistant Staphylococcus aureus
• pneumonia
• procalcitonin

• Meta-analysis
• Methicillin-resistant Staphylococcus aureus
• Pregnant women
• Systematic review
• Worldwide prevalence

• Bloodstream infection
• Community-onset MRSA
• Immunocompetent adult
• Osteomyelitis
• Pectoral abscess
• ST5/SCCmec type IVc
• Toxic shock syndrome toxin

Colonisation of humans by Staphylococcus aureus is a major risk factor for infection, yet the bacterial and host factors involved are not fully understood. The first step during skin colonisation is adhesion of the bacteria to corneocytes in the stratum corneum where the cornified envelope protein loricrin is the main ligand for S. aureus. Here we report a novel loricrin-binding protein of S. aureus, the cell wall-anchored fibronectin binding protein B (FnBPB). Single-molecule force spectroscopy revealed both weak and ultra-strong (2 nN) binding of FnBPB to loricrin and that mechanical stress enhanced the strength of these bonds. Treatment with a peptide derived from fibrinogen decreased the frequency of strong interactions, suggesting that both ligands bind to overlapping sites within FnBPB. Finally, we show that FnBPB promotes adhesion to human corneocytes by binding strongly to loricrin, highlighting the relevance of this interaction to skin colonisation.

The first step during skin colonization by is its adhesion to corneocytes. Da Costa et al. show that the cell wall-anchored fibronectin binding protein B (FnBPB) of S. aureus binds to loricrin. Applying single cell force spectroscopy, they demonstrate that this interaction promotes adhesion of S. aureus to human corneocytes.

Treatment of pulmonary infections in the intensive care unit (ICU) represents a great challenge, especially infections caused by antibiotic resistance pathogens. A thorough and up-to-date knowledge of the local spectrum of antibiotic resistant bacteria can improve the antibiotic treatment efficiency. In this study, we aimed to reveal the profile of bacteria with antibiotic resistance genes (ARGs) in real-world samples from ICU admission patients with pulmonary infection in Mainland, China, by metagenomic next-generation sequencing (mNGS).

A total of 504 different types of clinical samples from 452 ICU admission patients with pulmonary infection were detected by mNGS analysis.

A total of 485 samples from 434 patients got successful mNGS results. Among 434 patients, one or more bacteria with ARGs were detected in 192 patients (44.24%, 192/434), and ≥2 bacteria with ARGs were detected in 85 (19.59%, 85/434) patients. The predominant detected bacteria were Corynebacterium striatum (C. striatum) (11.76%, 51/434), Acinetobacter baumannii (A. baumannii) (11.52%, 50/434) and Enterococcus faecium (E. faecium) (8.99%, 39/434). ermX conferred resistance to MSL_B and cmx to phenicol were the only two ARGs detected in C. striatum; in A. baumannii, most of ARGs were resistance-nodulation-division (RND)-type efflux pumps genes, which conferred resistance to multi-drug; ermB conferred resistance to MSL_B and efmA to multi-drug were the predominant ARGs in E. faecium. Bacteria with ARGs were detected in 50% (140/280) bronchoalveolar lavage fluid (BALF) and 50.5% (48/95) sputum samples, which were significantly higher than in blood and cerebrospinal fluid (CSF) samples.

High level of bacteria with ARGs was observed in clinical samples, especially BALF and sputum samples from ICU admission patients with pulmonary infection in Mainland, China. And C. striatum resistant to MSL_B and/or phenicol, multi-drug resistance A. baumannii and E. faecium were the lead bacteria.

• antibiotic resistance genes
• antibiotic resistant bacteria
• intensive care units
• pulmonary infection

Antimicrobial resistance is an increasingly serious problem in public health globally. Monitoring resistance levels within healthcare and community settings is critical to combat its ongoing increase. This study aimed to describe the rates and molecular mechanisms of mupirocin resistance in clinical Staphylococcus aureus isolates from Tygerberg Hospital, and to describe its association with strain types.

We retrospectively selected 212 S. aureus isolates which were identified from blood samples and pus swabs during the years 2009–2011 and 2015–2017. The isolates were identified using conventional microbiological methods and genotyping was done using spa typing. Cefoxitin (30 μg) disc diffusion and the two disc strategy (5 μg and 200 μg) were used to determine susceptibility to methicillin and mupirocin, respectively. Isolates with high-level resistance were screened for the plasmid mediated genes mupA and mupB by PCR, and sequencing of the ileS gene was done for all isolates exhibiting low-level resistance to describe the mutations associated with this phenotype. Chi-square test was used to assess the associations between mupirocin resistance and S. aureus genotypes.

Of 212 S. aureus isolates, 12% (n = 25) were resistant to mupirocin, and 44% (n = 93) were methicillin resistant. Strain typing identified 73 spa types with spa t045 being the most predominant constituting 11% of the isolates. High-level mupirocin resistance was observed in 2% (n = 5), and low-level resistance in 9% (n = 20) of the isolates. The prevalence of high-level mupirocin resistance amongst MRSA and MSSA was 4 and 1% respectively, while the prevalence of low-level mupirocin resistance was significantly higher in MRSA (18%) compared to MSSA (3%), (p = 0.032). mupA was the only resistance determinant for high-level resistance, and the IleS mutation V588F was identified in 95% of the isolates which showed low-level resistance. A significant association was observed between spa type t032 and high-level mupirocin resistance, and types t037 and t012 and low-level resistance (p <  0.0001).

The study reported higher rates of low-level mupirocin resistance compared to high-level resistance, and in our setting, mupirocin resistance was driven by certain genotypes. Our study advocates for the continuous screening for mupirocin resistance in S. aureus in clinical settings to better guide treatment and prescribing practices.

• Antimicrobial resistance
• MRSA
• Mupirocin
• South Africa
• Staphylococcus aureus
• spa-typing

• Colonization
• Intensive care unit
• Nose
• Rectum
• Staphylococcal infections
• Staphylococcus aureus

• Adult
• Aged
• Aged, 80 and over
• Carrier State/epidemiology
• Critical Illness
• Female
• Genotype
• Humans
• Incidence
• Intensive Care Units
• Male
• Middle Aged
• Molecular Typing
• Nasal Mucosa/microbiology
• Prospective Studies
• Rectum/microbiology
• Staphylococcal Infections/epidemiology
• Staphylococcus aureus/classification
• Staphylococcus aureus/genetics
• Staphylococcus aureus/isolation & purification

• 2012-A01182-41 Centre Hospitalier Universitaire de Saint-Etienne

• Diabetes
• Diabetic patients
• MRSA
• Meta-analysis
• Methicillin-resistant Staphylococcus aureus
• Prevalence
• Resistance

• Diabetic Foot/epidemiology
• Diabetic Foot/microbiology
• Female
• Humans
• Methicillin-Resistant Staphylococcus aureus/pathogenicity
• Prevalence
• Staphylococcal Infections/epidemiology
• Staphylococcal Infections/microbiology

• Acquisition
• Burns
• Colonization
• MRSA

• HIV
• MRSA
• Meta-analysis
• Prevalence
• Risk factor

• Antibiotic stewardship
• Antimicrobial resistance
• Carbapenem
• Critical illness
• Empirical therapy
• Outcome
• Sepsis

• Anti-Infective Agents/adverse effects
• Anti-Infective Agents/therapeutic use
• Antimicrobial Stewardship/methods
• Humans
• Intensive Care Units/organization & administration
• Medical Overuse/prevention & control
• Rationalization
• Risk Factors

• Africa
• Meta-analysis
• Mupirocin
• Prevalence
• Staphylococcus aureus
• Systematic review

• Africa
• Animals
• Anti-Bacterial Agents/pharmacology
• Bacterial Proteins/genetics
• Bacterial Proteins/metabolism
• Cattle
• Cattle Diseases/drug therapy
• Cattle Diseases/microbiology
• Databases, Bibliographic
• Drug Resistance, Bacterial
• Humans
• Mupirocin/pharmacology
• Sheep
• Sheep Diseases/drug therapy
• Sheep Diseases/microbiology
• Staphylococcal Infections/drug therapy
• Staphylococcal Infections/microbiology
• Staphylococcal Infections/veterinary
• Staphylococcus aureus/classification
• Staphylococcus aureus/drug effects
• Staphylococcus aureus/genetics
• Staphylococcus aureus/isolation & purification

• Wellcome Trust
• R01 HD093578 NICHD NIH HHS
• 102429/Z/13/Z Wellcome Trust
• CIHR
• German Academic Exchange Service

Nosocomial infection (NI) control is an important issue in neurocritical care due to secondary brain damage and the increased morbidity and mortality of primary acute neurocritical care patients. The primary aim of this study was to determine incidence of nosocomial infections and multidrug-resistant bacteria and seek predictors of nosocomial infections in a preventive multimodal nosocomial infection protocol in the neurointensive care unit (NICU). The secondary aim focused on their impact on stay, mortality and cost in the NICU.

A10-year, single-centre prospective observational cohort study was conducted on 3464 acute brain disease patients. There were 198 (5.7%) patients with nosocomial infection (wound 2.1%, respiratory 1.8%, urinary 1.0%, bloodstream 0.7% and other 0.1%); 67 (1.9%) with Extended spectrum beta-lactamase (ESBL); 52 (1.5%) with Methicillin-resistant Staphylococcus aureus (MRSA), nobody with Vancomycin-resistant enterococcus (VRE). The protocol included hygienic, epidemiological status and antibiotic policy. Univariate and multivarite logistic regression analysis was used for identifying predictors of nosocomial infection.

From 198 NI patients, 153 had onset of NI during their NICU stay (4.4%; wound 1.0%, respiratory 1.7%, urinary 0.9%, bloodstream 0.6%, other 0.1%); ESBL in 31 (0.9%) patients, MRSA in 30 (0.9%) patients. Antibiotics in prophylaxis was given to 63.0% patients (59.2 % for operations), in therapy to 9.7% patients. Predictors of NI in multivariate logistic regression analysis were airways (OR 2.69, 95% CI 1.81-3.99, p<0.001), urine catheters (OR 2.77, 95% CI 1.00-7.70, p=0.050), NICU stay (OR 1.14, 95% CI 1.12-1.16, p<0.001), transfusions (OR 1.79, 95% CI 1.07-2.97, p=0.025) antibiotic prophylaxis (OR 0.50, 95% CI 0.34-0.74, p<0.001), wound complications (OR 2.30, 95% CI 1.33-3.97, p=0.003). NI patients had longer stay (p<0.001), higher mortality (p<0.001) and higher TISS sums (p<0.001) in the NICU.

The presented preventive multimodal nosocomial infection control management was efficient; it gave low rates of nosocomial infections (4.2%) and multidrug-resistant bacteria (ESBL 0.9%, MRSA 0.9% and no VRE). Strong predictors for onset of nosocomial infection were accesses such as airways and urine catheters, NICU stay, antibiotic prophylaxis, wound complications and transfusion. This study confirmed nosocomial infection is associated with worse outcome, higher cost and longer NICU stay.

• Multidrug-resistant bacteria
• Neurocritical care
• Nosocomial infections
• Outcome
• Preventive protocol

• MRSA
• anti-microbial resistance
• biofilms
• nanomedicine

Colonization with Staphylococcus aureus is a well-defined risk factor for disease in hospitals, which can range from minor skin infections to severe, systemic diseases. However, the generalizability of this finding has not been thoroughly investigated outside of the hospital environment. We aimed to assess the role of S. aureus colonization as a risk factor for disease in the community.

We performed a meta-analysis of observational studies and searched PubMed for articles published between December 1979 and May 23, 2016. We included cohort, cross-sectional, and case-control studies that reported quantitative estimates of both S. aureus colonization and disease statuses of all study subjects. We excluded studies on recently hospitalized subjects, long-term care facilities, surgery patients, dialysis patients, hospital staff, S. aureus outbreaks, and livestock-associated infections. Our meta-analysis was performed using random-effects analysis to obtain pooled odds ratios (ORs) to compare the odds of S. aureus disease with respect to S. aureus colonization status.

We identified 3477 citations, of which 12 articles on 6998 subjects met the eligibility criteria. Overall, subjects colonized with S. aureus were more likely to progress to disease than those who were non-colonized: (OR 1.87, 95% CI 1.21–2.88, n = 7 studies). We observed a larger effect with methicillin-resistant S. aureus colonization (7.06, 4.60–10.84, n = 7 studies). However, the methicillin-sensitive S. aureus colonization was not associated with greater odds of disease (1.20, 0.69–2.06, n = 4 studies). Heterogeneity was present across studies in all of the subgroups: S. aureus (I² = 95.0%, χ² = 120.3, p < 0.001), MRSA (I² = 92.8%, χ² = 82.8, p = p < 0.001), and MSSA (I² = 86.3%, χ² = 21.8, p < 0.001).

While the majority of papers individually support the assumption that colonization is a risk factor for S. aureus disease in the general population, there is marked heterogeneity between studies and further investigation is needed to identify the major sources of this variance. There is a shortage of literature addressing this topic in the community setting and a need for further research on colonization as a focus for disease prevention.

The online version of this article (10.1186/s12879-018-2990-3) contains supplementary material, which is available to authorized users.

• Colonization
• Community-associated
• Infection
• Staphylococcus aureus

• MRSA
• VRE
• discrete event simulation
• infection control
• patient flow

• Anti-Bacterial Agents/therapeutic use
• Cross Infection/prevention & control
• Enterococcus/drug effects
• Female
• Hospitals, General
• Humans
• Infection Control
• Male
• Methicillin/therapeutic use
• Methicillin-Resistant Staphylococcus aureus
• Models, Theoretical
• Organizational Policy
• Patient Transfer
• Vancomycin/therapeutic use

• K01 AI110524 NIAID NIH HHS
• UL1 TR001102 NCATS NIH HHS

• Animals
• Antibodies, Monoclonal/immunology
• Antibodies, Monoclonal/therapeutic use
• Bacteremia/immunology
• Bacteremia/prevention & control
• Humans
• Immunoglobulin G
• Mice
• Staphylococcal Infections/immunology
• Staphylococcal Infections/prevention & control
• Staphylococcal Protein A/immunology

• Clostridium difficile
• closure of ileostomy
• reversal of ileostomy

• ICU pneumonia
• P. aeruginosa
• S. aureus
• Vap

• Iran
• MRSA
• Meta-analysis
• Systematic review

Methicillin-resistant Staphylococcus aureus (MRSA) is a major pathogen responsible for hospital and community acquired infection. Colonization with MRSA is associated with a high risk of developing infection. This study aimed to determine the rate of MRSA carriage on admission and the associated risk factors among patients attending regional hospitals, in Dar es Salaam, Tanzania.

A total of 258 patients were included in this study. Nasal swabs were collected on admission to the hospital and after 48 h of hospital stay for detection of MRSA. Of 258 patients enrolled, 89 (34.5%) were colonized with S. aureus and out them 22 (24.7%) were carriers of MRSA, giving an overall MRSA nasal carriage rate of 8.5% (22/258). One patient acquired MRSA while admitted in the hospital. Most of the S. aureus isolates 85 (95.5%) were resistant to penicillin. Resistance to gentamycin, ciprofloxacin, kanamycin, linezolid and mupirocin were 14.6, 11.2, 11.2, 3.4 and 1.1%, respectively. The prevalence of inducible clindamycin resistance, constitutive clindamycin resistance, MS phenotype (resistance to erythromycin alone), and multidrug resistance was 21.3, 3.4, 12.4, and 16.9%, respectively. We observed a statistically significant association between MRSA and multiple drugs resistance among S. aureus isolates (p = 0.001). Of the risk factors investigated none were statistically significant associated with MRSA.

There is a high prevalence of MRSA among patients on admission at the two municipal hospitals in Dar es Salaam. The high prevalence of MRSA and the increased rates of resistance to commonly used antimicrobials among MRSA isolates call for attention to the importance of including the screening of MRSA in our hospitals setting in order to prevent further spread of MRSA strains to other patients and to the communities. Control and prevention strategies should be emphasized including decolonization.

• Antibiotic resistance
• Infection
• MRSA nasal carriage

• Cost-effectiveness
• Infection control
• Isolation
• Surveillance

• Bacteriological Techniques/economics
• Bacteriological Techniques/methods
• Carrier State/diagnosis
• Carrier State/microbiology
• Costs and Cost Analysis
• Epidemiological Monitoring
• Humans
• Infection Control/methods
• Intensive Care Units
• Mass Screening/economics
• Mass Screening/methods
• Methicillin-Resistant Staphylococcus aureus/isolation & purification
• Patient Isolation/methods
• Staphylococcal Infections/diagnosis
• Staphylococcal Infections/microbiology

• MRSA
• Staphylococcus aureus
• methicillin-resistant Staphylococcus aureus
• nasal swab
• pediatric neck abscess

• Consensus statement
• Delphi method
• Rib fractures
• Rib plating
• Surgical stabilization of rib fractures

• Contamination
• Environment
• Meta-analysis
• Methicillin-resistant Staphylococcus aureus
• Staphylococcus aureus

• Drug Resistance, Microbial
• Environmental Monitoring
• Environmental Pollutants/isolation & purification
• Staphylococcus aureus/genetics
• Staphylococcus aureus/isolation & purification

• MRSA
• athletes
• metaanalysis
• methicillin-resistant S. aureus
• risk for infection

Much of the morbidity and mortality associated with influenza virus respiratory infection is due to bacterial coinfection with pathogens that colonize the upper respiratory tract such as methicillin-resistant Staphylococcus aureus (MRSA) and Streptococcus pneumoniae. A major component of the immune response to influenza virus is the production of type I and III interferons. Here we show that the immune response to infection with influenza virus causes an increase and restructuring of the upper respiratory microbiota in wild-type (WT) mice but not in Il28r^−/− mutant mice lacking the receptor for type III interferon. Mice lacking the IL-28 receptor fail to induce STAT1 phosphorylation and expression of its regulator, SOCS1. Il28r^−/− mutant mice have increased expression of interleukin-22 (IL-22), as well as Ngal and RegIIIγ, in the nasal cavity, the source of organisms that would be aspirated to cause pneumonia. Proteomic analysis reveals changes in several cytoskeletal proteins that contribute to barrier function in the nasal epithelium that may contribute to the effects of IL-28 signaling on the microbiota. The importance of the effects of IL-28 signaling in the pathogenesis of MRSA pneumonia after influenza virus infection was confirmed by showing that WT mice nasally colonized before or after influenza virus infection had significantly higher levels of infection in the upper airways, as well as significantly greater susceptibility to MRSA pneumonia than Il28r^−/− mutant mice did. Our results suggest that activation of the type III interferon in response to influenza virus infection has a major effect in expanding the upper airway microbiome and increasing susceptibility to lower respiratory tract infection.

S. aureus and influenza virus are important respiratory pathogens, and coinfection with these organisms is associated with significant morbidity and mortality. The ability of influenza virus to increase susceptibility to S. aureus infection is less well understood. We show here that influenza virus leads to a change in the upper airway microbiome in a type III interferon-dependent manner. Mice lacking the type III interferon receptor have altered STAT1 and IL-22 signaling. In coinfection studies, mice without the type III interferon receptor had significantly less nasal S. aureus colonization and subsequent pneumonia than infected WT mice did. This work demonstrates that type III interferons induced by influenza virus contribute to nasal colonization and pneumonia due to S. aureus superinfection.

The I100V isoform of toluene-4-monooxygenase was used to catalyze the oxidative polymerization of anthranil and various indoles under mildly acidic conditions, favoring the production of trimers. Compounds produced in sufficient yield were purified and tested for their ability to inhibit the growth of B. anthracis, E. faecalis, L. monocytogenes, S. aureus, and in some cases, F. tularensis. 15 of the compounds displayed promising antibacterial activity (MIC < 5 µg/ml) against one or more of the strains tested, with the best MIC values being <0.8 µg/ml. All of these compounds had good selectivity, showing minimal cytotoxicity towards HepG2 cells. The structure was solved for six of the compounds that could be crystallized, revealing that minimally two classes of indole based trimers were produced. One compound class produced was a group of substituted derivatives of the natural product 2,2-bis(3-indolyl) indoxyl. The other group of compounds identified was classified as tryptanthrin-like compounds, all having multi-ring pendant groups attached at position 11 of tryptanthrin. One compound of particular interest, SAB-J85, had a structure that suggests that any compound, with a ring structure that can be activated by an oxygenase, might serve as a substrate for combinatorial biocatalysis.

• Cross Infection/prevention & control
• Cross Infection/transmission
• Female
• Gloves, Protective
• Humans
• Masks
• Methicillin-Resistant Staphylococcus aureus
• Protective Clothing
• Staphylococcal Infections/prevention & control
• Staphylococcal Infections/transmission

Persisters are a subpopulation of normal bacterial cells that show tolerance to conventional antibiotics. Persister cells are responsible for recalcitrant chronic infections and new antibiotics effective against persisters would be a major development in the treatment of these infections. Using the reporter dye SYTOX Green that only stains cells with permeabilized membranes, we developed a fluorescence-based screening assay in a 384-well format for identifying compounds that can kill methicillin-resistant Staphylococcus aureus (MRSA) persisters. The assay proved robust and suitable for high throughput screening (Z`-factor: >0.7). In screening a library of hits from a previous screen, which identified compounds that had the ability to block killing of the nematode Caenorhabditis by MRSA, we discovered that the low molecular weight compound NH125, a bacterial histidine kinase inhibitor, kills MRSA persisters by causing cell membrane permeabilization, and that 5 μg/mL of the compound can kill all cells to the limit of detection in a 10⁸ CFU/mL culture of MRSA persisters within 3h. Furthermore, NH125 disrupts 50% of established MRSA biofilms at 20 μg/mL and completely eradicates biofilms at 160 μg/mL. Our results suggest that the SYTOX Green screening assay is suitable for large-scale projects to identify small molecules effective against MRSA persisters and should be easily adaptable to a broad range of pathogens that form persisters. Since NH125 has strong bactericidal properties against MRSA persisters and high selectivity to bacteria, we believe NH125 is a good anti-MRSA candidate drug that should be further evaluated.

• Animals
• Anti-Bacterial Agents/chemistry
• Anti-Bacterial Agents/pharmacokinetics
• Biofilms/drug effects
• Caenorhabditis elegans/microbiology
• Drug Evaluation, Preclinical
• Fluorescence
• Methicillin-Resistant Staphylococcus aureus/physiology
• Organic Chemicals/chemistry
• Staphylococcal Infections/drug therapy

• P01 AI083214 NIAID NIH HHS
• U54 AI057159 NIAID NIH HHS

Staphylococcus aureus (SA) infections remain a major cause of morbidity and mortality despite the availability of numerous effective anti-staphylococcal antibiotics. This organism is responsible for both nosocomial and community-acquired infections ranging from relatively minor skin and soft tissue infections to life-threatening systemic infections. The increasing incidence of methicillin-resistant strains has granted an increasing use of vancomycin causing a covert progressive increase of its minimum inhibitory concentration (MIC) (dubbed the MIC “creep”). In this way, the emergence of vancomycin-intermediate SA (VISA) strains and heteroresistant-VISA has raised concern for the scarcity of alternative treatment options. Equally alarming, though fortunately less frequent, is the emergence of vancomycin-resistant SA. These strains show different mechanisms of resistance but have similar problems in terms of therapeutic approach. Ultimately, various debate issues have arisen regarding the emergence of SA strains with a minimum inhibitory concentration sitting on the superior limit of the sensitivity range (i.e., MIC = 2 μg/mL). These strains have shown certain resilience to vancomycin and a different clinical behaviour regardless of vancomycin use, both in methicillin-resistant SA and in methicillin-sensitive SA. The aim of this text is to revise the clinical impact and consequences of the emergence of reduced vancomycin susceptibility SA strains, and the different optimal treatment options known.

• Staphylococcus aureus
• Minimum inhibitory concentration
• Methicillin-resistant Staphylococcus aureus
• Vancomycin-intermediate Staphylococcus aureus
• Heteroresistant-vancomycin-intermediate Staphylococcus aureus
• Vancomycin resistant Staphylococcus aureus

The impact of Clostridium difficile colonization in C. difficile infection (CDI) is inadequately explored. As a result, asymptomatic carriage is not considered in the development of infection control policies and the burden of carrier state in long-term care facilities (LTCFs) is unknown.

To explore the epidemiology of C. difficile colonization in LTCFs, identify predisposing factors and describe its impact on healthcare management.

PubMed, Embase and Web of Science (up to June 2014) without language restriction, complemented by reference lists of eligible studies.

All studies providing extractable data on the prevalence of toxigenic C. difficile colonization among asymptomatic residents in LTCFs.

Two authors extracted data independently.

The pooled colonization estimates were calculated using the double arcsine methodology and reported along with their 95% random-effects confidence intervals (CIs), using DerSimonian-Laird weights. We assessed the impact of patient-level covariates on the risk of colonization and effects were reported as odds ratios (OR, 95% CI). We used the colonization estimates to simulate the effective reproduction number R through a Monte Carlo technique.

Based on data from 9 eligible studies that met the specified criteria and included 1,371 subjects, we found that 14.8% (95%CI 7.6%-24.0%) of LTCF residents are asymptomatic carriers of toxigenic C. difficile. Colonization estimates were significantly higher in facilities with prior CDI outbreak (30.1% vs. 6.5%, p = 0.01). Patient history of CDI (OR 6.07; 95% CI 2.06–17.88; effect derived from 3 studies), prior hospitalization (OR 2.11; 95% CI 1.08–4.13; derived from 3 studies) and antimicrobial use within previous 3 months (OR 3.68; 95% CI 2.04–6.62; derived from 4 studies) were associated with colonization. The predicted colonization rate at admission was 8.9%.

Asymptomatic carriage of toxigenic C. difficile represents a significant burden in LTCFs and is associated with prior CDI outbreaks in the facility, a history of CDI, prior hospitalization and antimicrobial use. These findings can impact infection control measures at LTCFs.

• Carrier State/epidemiology
• Clostridioides difficile
• Databases, Factual
• Enterocolitis, Pseudomembranous/epidemiology
• Enterocolitis, Pseudomembranous/transmission
• Humans
• Infection Control
• Long-Term Care
• Prevalence
• Risk Factors

• Merck V710 vaccine
• Staphylococcus aureus
• cardiac surgery
• postoperative infection

• Critical Care/methods
• Cross Infection/prevention & control
• Humans
• Infection Control/methods
• Pneumonia, Ventilator-Associated/prevention & control
• Sepsis/prevention & control