Dataset Information

Diagnostic Stewardship: A Clinical Decision Rule for Blood Cultures in Community-Onset Methicillin-Resistant Staphylococcus aureus (MRSA) Skin and Soft Tissue Infections.

ABSTRACT: INTRODUCTION:The emergence, spread and persistence of methicillin-resistant Staphylococcus aureus (MRSA) as a causative pathogen in community-onset (CO) skin and soft tissue infections (SSTIs) have resulted in substantial changes in the management of these infections. The indications for obtaining blood cultures in patients with CO-MRSA SSTIs remain poorly defined. The objectives of this study were to derive and validate a clinical decision rule that predicts the probability of MRSA bacteremia in CO-MRSA SSTIs and to identify a low-risk population for whom blood cultures may be safely omitted. METHODS:This was a retrospective, case-control study with an internal temporal validation cohort conducted at two large urban academic medical centers. Hospitalized adults with CO-MRSA SSTI between 2010 and 2018 were included. Independent predictors of MRSA bacteremia were identified through multivariable logistic regression. A decision rule was derived using weighted coefficient-based scoring. The decision rule was validated in an internal temporal validation cohort. RESULTS:A total of 307 patients (155 cases and 152 controls) were included in the derivation cohort. A decision rule was created with a "major criterion" defined as purulent cellulitis and "minor criteria" defined as abnormal temperature, intravenous drug use, leukocytosis, tachycardia, body mass index < 25 kg/m2 and non-upper extremity infection site. A blood culture is indicated by this rule for patients with one major or at least two minor criteria. Otherwise patients are classified as low risk, and blood cultures may be omitted. The sensitivity of the decision rule in the derivation and validation cohorts was 98.71% (95% CI 95.42%, 99.84%) and 95.65% (78.05%, 99.89%), respectively. The specificity was 23.03% (95% CI 16.59%, 30.54%) and 30.77% (95% CI 24.15%, 38.02%), respectively. CONCLUSION:The decision rule developed and validated in this study provides a standardized, evidenced-based approach to determine the need for blood cultures based on bacteremia risk.

SUBMITTER: Jorgensen SCJ

PROVIDER: S-EPMC6522577 | biostudies-other | 2019 Jun

REPOSITORIES: biostudies-other

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Diagnostic Stewardship: A Clinical Decision Rule for Blood Cultures in Community-Onset Methicillin-Resistant Staphylococcus aureus (MRSA) Skin and Soft Tissue Infections.

Jorgensen Sarah C J SCJ Lagnf Abdalhamid M AM Bhatia Sahil S Singh Nivedita B NB Shammout Laila K LK Davis Susan L SL Rybak Michael J MJ

Infectious diseases and therapy 20190219 2

<h4>Introduction</h4>The emergence, spread and persistence of methicillin-resistant Staphylococcus aureus (MRSA) as a causative pathogen in community-onset (CO) skin and soft tissue infections (SSTIs) have resulted in substantial changes in the management of these infections. The indications for obtaining blood cultures in patients with CO-MRSA SSTIs remain poorly defined. The objectives of this study were to derive and validate a clinical decision rule that predicts the probability of MRSA bact ...[more]

PMID: 30783995

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Project description:The herbal products proved to be more promising antimicrobials even though their antimicrobial activity is milder than commercially available antibiotics. Moreover, herbal drugs may act synergistically with antibiotics to kill microbes. In this study, we aimed to enhance the activity of penicillin against MRSA through combination with the active saponin fraction isolated from the Zygophyllum album plant. Three different types of metabolites (saponins, sterols, and phenolics) have been extracted from Zygophyllum album with ethanol and purified using different chromatographic techniques. The antibacterial activity of crude extract and the separated metabolites were checked against MRSA isolates, Saponin fraction (ZA-S) was only the active one followed by the crude extract. Therefore, the compounds in this fraction were identified using ultra-high-performance liquid chromatography connected to quadrupole time-of-flight mass spectrometry (UHPLC/QTOF-MS) operated in positive and negative ionization modes. UHPLC/QTOF-MS revealed the presence of major six ursane-type tritepenoidal saponins (Quinovic acid, Quinovic acid 3β-O-β-D-quinovopyranoside, Zygophylloside C, Zygophylloside G, Zygophylloside K and Ursolic acid), in addition to Oleanolic acid. Interaction studies between saponin fraction and penicillin against MRSA were performed through the checkerboard method and time-kill assay. According to checkerboard results, only three combinations showed a fractional inhibitory concentration index less than 0.5 at concentrations of (62.5 + 312.5, 62.5 + 156.25, and 62.5 + 78.125 of penicillin and ZA-S, respectively). Time kill assay results showed that the highest reduction in log10 colony-forming unit (CFU)/ml of initial inoculum of MRSA after 24 h occurred by 3.7 at concentrations of 62.5 + 312.5 (µg/µg)/ml of penicillin and ZA-S, respectively. Thus, the combination between saponin fraction of Zygophyllum album and penicillin with these concentrations could be a potential agent against MRSA that can serve as possible model for new antibacterial drug.

Project description:Methicillin-resistant Staphylococcus aureus (MRSA) is a leading cause of health care-associated (HA) and community-associated (CA) infections. USA300 strains are historically CA-MRSA, while USA100 strains are HA-MRSA. Here, we update an antibiotic prediction rule to distinguish these two genotypes based on antibiotic resistance phenotype using whole-genome sequencing (WGS), a more discriminatory methodology than pulsed-field gel electrophoresis (PFGE). MRSA clinical isolates collected from 2007 to 2017 underwent WGS; associated epidemiologic data were ascertained. In developing the rule, we examined MRSA isolates that included a population with a history of incarceration. Performance characteristics of antibiotic susceptibility for predicting USA300 compared to USA100, as defined by WGS, were examined. Phylogenetic analysis was performed to examine resistant USA300 clades. We identified 275 isolates (221 USA300, 54 USA100). Combination susceptibility to clindamycin or levofloxacin performed the best overall (sensitivity 80.7%, specificity 75.9%) to identify USA300. The average number of antibiotic classes with resistance was higher for USA100 (3 versus 2, P < 0.001). Resistance to ≤2 classes was predictive for USA300 (area under the curve (AUC) 0.84, 95% confidence interval 0.78 to 0.90). Phylogenetic analysis identified a cluster of USA300 strains characterized by increased resistance among incarcerated individuals. Using a combination of clindamycin or levofloxacin susceptibility, or resistance to ≤2 antibiotic classes, was predictive of USA300 as defined by WGS. Increased resistance was observed among individuals with incarceration exposure, suggesting circulation of a more resistant USA300 clade among at-risk community networks. Our phenotypic prediction rule could be used as an epidemiologic tool to describe community and nosocomial shifts in USA300 MRSA and quickly identify emergence of lineages with increased resistance. IMPORTANCE Methicillin-resistant Staphylococcus aureus (MRSA) is an important cause of health care-associated (HA) and community-associated (CA) infections, but the epidemiology of these strains (USA100 and USA300, respectively) now overlaps in health care settings. Although sequencing technology has become more available, many health care facilities still lack the capabilities to perform these analyses. In this study, we update a simple prediction rule based on antibiotic resistance phenotype with integration of whole-genome sequencing (WGS) to predict strain type based on antibiotic resistance profiles that can be used in settings without access to molecular strain typing methods. This prediction rule has many potential epidemiologic applications, such as analysis of retrospective data sets, regional monitoring, and ongoing surveillance of CA-MRSA infection trends. We demonstrate application of this rule to identify an emerging USA300 strain with increased antibiotic resistance among incarcerated individuals that deviates from the rule.

Project description:Patients with community-onset (CO) methicillin-resistant Staphylococcus aureus (MRSA) infections contribute to MRSA contamination of the home environment and may be reexposed to MRSA strains from this reservoir. This study evaluates One Health risk factors, which focus on the relationship between humans, animals, and the environment, for the increased prevalence of multiple antimicrobial-resistant MRSA isolates in the home environment. During a trial of patients with CO-MRSA infection, MRSA was isolated from the household environment at the baseline and 3 months later, following randomization of patients and household members to mupirocin-based decolonization therapy or an education control group. Up to two environmental MRSA isolates collected at each visit were tested. MRSA isolates were identified in 68% (65/95) of homes at the baseline (n = 104 isolates) and 51% (33/65) of homes 3 months later (n = 56 isolates). The rates of multidrug resistance (MDR) were 61% among isolates collected at the baseline and 55% among isolates collected at the visit 3 months later. At the baseline, 100% (14/14) of MRSA isolates from rural homes were MDR. While antimicrobial use by humans or pets was associated with an increased risk for the isolation of MDR MRSA from the environment, clindamycin use was not associated with an increased risk for the isolation of MDR MRSA. Incident low-level mupirocin-resistant MRSA strains were isolated at 3 months from 2 (5%) of 39 homes that were randomized to mupirocin treatment but none of the control homes. Among patients recently treated for a CO-MRSA infection, MRSA and MDR MRSA were common contaminants in the home environment. This study contributes to evidence that occupant use of antimicrobial drugs, except for clindamycin, is associated with MDR MRSA in the home environmental reservoir. (This study has been registered at ClinicalTrials.gov under registration no. NCT00966446.)IMPORTANCE MRSA is a common bacterial agent implicated in skin and soft tissue infections (SSTIs) in both community and health care settings. Patients with CO-MRSA infections contribute to environmental MRSA contamination in these settings and may be reexposed to MRSA strains from these reservoirs. People interact with natural and built environments; therefore, understanding the relationships between humans and animals as well as the characteristics of environmental reservoirs is important to advance strategies to combat antimicrobial resistance. Household interactions may influence the frequency and duration of exposure, which in turn may impact the duration of MRSA colonization or the probability for recurrent colonization and infection. Therefore, MRSA contamination of the home environment may contribute to human and animal recolonization and decolonization treatment failure. The aim of this study was to evaluate One Health risk factors that may be amenable to intervention and may influence the recovery of MDR and mupirocin resistance in CO-MRSA isolates.

Project description:BackgroundMethicillin-resistant Staphylococcus aureus (MRSA) is a major nosocomial pathogen subdivided into lineages termed sequence types (STs). Since the 1950s, successive waves of STs have appeared and replaced previously dominant lineages. One such event has been occurring in China since 2013, with community-associated (CA-MRSA) strains including ST59 largely replacing the previously dominant healthcare-associated (HA-MRSA) ST239. We previously showed that ST59 isolates tend to have a competitive advantage in growth experiments against ST239. However, the underlying genomic and phenotypic drivers of this replacement event are unclear.MethodsHere, we investigated the replacement of ST239 using whole-genome sequencing data from 204 ST239 and ST59 isolates collected in Chinese hospitals between 1994 and 2016. We reconstructed the evolutionary history of each ST and considered two non-mutually exclusive hypotheses for ST59 replacing ST239: antimicrobial resistance (AMR) profile and/or ability to colonise and persist in the environment through biofilm formation. We also investigated the differences in cytolytic activity, linked to higher virulence, between STs. We performed an association study using the presence and absence of accessory virulence genes.ResultsST59 isolates carried fewer AMR genes than ST239 and showed no evidence of evolving towards higher AMR. Biofilm production was marginally higher in ST59 overall, though this effect was not consistent across sub-lineages so is unlikely to be a sole driver of replacement. Consistent with previous observations of higher virulence in CA-MRSA STs, we observed that ST59 isolates exhibit significantly higher cytolytic activity than ST239 isolates, despite carrying on average fewer putative virulence genes. Our association study identified the chemotaxis inhibitory protein (chp) as a strong candidate for involvement in the increased virulence potential of ST59. We experimentally validated the role of chp in increasing the virulence potential of ST59 by creating Δchp knockout mutants, confirming that ST59 can carry chp without a measurable impact on fitness.ConclusionsOur results suggest that the ongoing replacement of ST239 by ST59 in China is not associated to higher AMR carriage or biofilm production. However, the increase in ST59 prevalence is concerning since it is linked to a higher potential for virulence, aided by the carriage of the chp gene.

Dataset Information

Diagnostic Stewardship: A Clinical Decision Rule for Blood Cultures in Community-Onset Methicillin-Resistant Staphylococcus aureus (MRSA) Skin and Soft Tissue Infections.

Publications

Diagnostic Stewardship: A Clinical Decision Rule for Blood Cultures in Community-Onset Methicillin-Resistant Staphylococcus aureus (MRSA) Skin and Soft Tissue Infections.

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