Role of Berberine in the Treatment of Methicillin-Resistant Staphylococcus aureus Infections.
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ABSTRACT:
SUBMITTER: Chu M
PROVIDER: S-EPMC4840435 | biostudies-other | 2016 Apr
REPOSITORIES: biostudies-other
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Project description:To evaluate the clinical outcomes associated with anti-methicillin-resistant Staphylococcus aureus (MRSA) antimicrobials.We reviewed a prospective database of 247 consecutive patients with clinically and microbiologically confirmed MRSA infections, hospitalized in 7 Japanese hospitals between April 2014 and March 2015, and treated with anti-MRSA pharmaceuticals. Survival was measured at 30 days. We examined the relationships between initial antimicrobial administered and survival and organ toxicity. HR and 95% CIs were calculated.Overall 30-day mortality was 12%. The lungs were infected in 105 (41%), skin and soft tissue in 73 (30%), and bones and joints in 21 (9%) patients. Bacteremia complicated the illness in 69 patients (28%). Among 5 pharmaceuticals, vancomycin was prescribed to 174 (71%), linezolid to 38 (16%), teicoplanin to 22 (9%), and daptomycin to 11 (5%) patients. Vancomycin tended to be associated with the lowest survival (HR=2.47; 95% CI=0.93-6.51; P=0.067), particularly in the lung-infected subgroup (HR=4.85; 95% CI=1.12-20.94; P=0.034) after adjustments for baseline illness severity. The incidence of renal dysfunction tended to be higher in patients with trough serum concentrations of vancomycin >15 mg/dL.In this observational study reflecting real-world conditions, vancomycin was associated with higher 30-day mortality and incidence of kidney dysfunction than other anti-MRSA agents. The significance of the differences observed among antimicrobials other than vancomycin is uncertain.
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Project description:Methicillin-resistant Staphylococcus aureus (MRSA) is a significant cause of health care-associated infections. Vancomycin remains an acceptable treatment option. There has been a welcome increase in the number of agents available for the treatment of MRSA infection. These drugs have certain differentiating attributes and may offer some advantages over vancomycin, but they also have significant limitations. These agents provide some alternative when no other options are available.
| S-EPMC5204005 | biostudies-other
Project description:To investigate the efficacy and safety of Vancomycin Ophthalmic Ointment 1% (Toa Pharmaceutical Co., Ltd, Toyama, Japan) in patients with external ocular infections caused by methicillin-resistant Staphylococcus aureus (MRSA) or methicillin-resistant Staphylococcus epidermidis (MRSE). A case series. This study was a multicentre, open-label, uncontrolled study in Japan approved as orphan drug status. Patients with MRSA or MRSE external ocular infections unresponsive to the treatment of fluoroquinolone eye drops. Vancomycin Ophthalmic Ointment 1% was administered four times daily. The subjective and objective clinical scores and bacterial cultures were collected at days 0 (baseline), 3, 7 and 14. The primary outcome was clinical response evaluation (efficacy rate) determined as complete response, partial response, no response and worsening. Secondary outcome was the eradication of the bacteria. Safety was assessed by adverse events including cases in which neither MRSA nor MRSE was detected. Twenty-five cases with MRSA (20) or MRSE (5) infections were enrolled. Of these 25 cases, 4 discontinued the treatment due to the negative results for bacterial culture during screening or at baseline. Of the 21 cases with conjunctivitis (14), blepharitis (3), meibomitis (1), dacryocystitis (2) or keratitis (1), 14 (66.7%) cases were evaluated as being excellently (complete response, 2 cases) or well (partial response, 12 cases) treated. The eradication rates were 68.4% in MRSA (13 of 19 cases) and 100% in MRSE (2 of 2 cases). Ten adverse events occurred in 7 (28.0%) of 25 cases at the local administration site. Vancomycin Ophthalmic Ointment 1% was considered to be useful for the treatment of intractable ocular MRSA/MRSE infections.
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Project description:BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is a major pathogen that causes severe morbidity and mortality in hospitalized patients. It is unclear whether repeated MRSA infections in pediatric patients are caused by relapse of previous infecting strains or by acquiring new strains from extrinsic sources. The study aimed to define the genetic relatedness of MRSA isolates from children with repeated infections. METHODOLOGY/PRINCIPAL FINDINGS: Children with multiple MRSA infections during 2004-2006 were identified in a teaching hospital. Repeated infections were confirmed by chart review and the responsible isolates were genotyped and screened for Panton-Valentine leukocidin (PVL) genes. Two consecutive episodes comprised an infection pair, and strain relatedness was defined for each pair as indistinguishable, highly related, or distinct if the isolates were of the same subtype, the same genotype, or different genotype, respectively. A total of 114 episodes comprising 66 infection pairs were identified in 48 children. The interval of infection pairs ranged from 15 days to 346 days, with a median duration of 57.5 days. Genotypings classified all isolates into 7 genotypes and 31 subtypes. Of 66 pairs, 46 (69.7%), 13 (19.7%) and 7 (10.6%) pairs were caused by indistinguishable, highly related and distinct strains, respectively. Subsequent infections caused by indistinguishable strains were more common for PVL-positive strains (17/18, 94.4%) than for PVL-negative strains (29/48, 60.4%, P = 0.007). The strain relatedness was not affected by the durations of interval between infections. CONCLUSIONS/SIGNIFICANCE: Most repeated MRSA infections in children are caused by indistinguishable strains even after a long period of interval, suggesting that persistent carriage and relapse of initial infecting strains were responsible for the majority of recurrent MRSA infections.
| S-EPMC3010989 | biostudies-other
Project description:Background:Despite substantial attention to the individual topics, little is known about the relationship between racial disparities and antimicrobial-resistant and/or healthcare-associated infection trends, such as for methicillin-resistant Staphylococcus aureus (MRSA). Methods:We analyzed Emerging Infections Program 2005-2014 surveillance data (9 US states) to determine whether reductions in invasive MRSA incidence (isolated from normally sterile body sites) affected racial disparities in rates. Case classification included hospital-onset (HO, culture >3 days after admission), healthcare-associated community onset (HACO, culture ?3 days after admission and dialysis, hospitalization, surgery, or long-term care residence within 1 year prior), or community-associated (CA, all others). Negative binomial regression models were used to evaluate the adjusted rate ratio (aRR) of MRSA in black patients (vs in white patients) controlling for age, sex, and temporal trends. Results:During 2005-2014, invasive HO and HACO (but not CA) MRSA rates decreased. Despite this, blacks had higher rates for HO (aRR, 3.20; 95% confidence interval [CI], 2.35-4.35), HACO (aRR, 3.84; 95% CI, 2.94-5.01), and CA (aRR, 2.78; 95% CI, 2.30-3.37) MRSA. Limiting the analysis to chronic dialysis patients reduced, but did not eliminate, the higher HACO MRSA rates among blacks (aRR, 1.83; 95% CI, 1.72-1.96), even though invasive MRSA rates among dialysis patients decreased during 2005-2014. These racial differences did not change over time. Conclusions:Previous reductions in healthcare-associated MRSA infections have not affected racial disparities in MRSA rates. Improved understanding of the underlying causes of these differences is needed to develop effective prevention interventions that reduce racial disparities in MRSA infections.
| S-EPMC6232852 | biostudies-literature
Project description:Immunoblotting sera from 26 patients with septicemia due to an epidemic strain of methicillin-resistant Staphylococcus aureus (EMRSA-15), 6 of whom died, revealed an immunodominant EMRSA-15 antigen at 61 kDa. There was a statistically significant correlate (P < 0.001) between survival and immunoglobulin G to the 61-kDa band. The antigen was identified by sequencing positive clones obtained by screening a genomic expression library of EMRSA-15 with pooled sera from patients taken after the septicemic episode. Eluted antibody reacted with the 61-kDa antigen on immunoblots. The amino terminus was obtained by searching the S. aureus NCTC 8325 and MRSA strain COL databases, and the whole protein was expressed in Escherichia coli TOP 10F'. The derived amino acid sequence showed homology with ABC transporters, with paired Walker A and Walker B motifs and 73% homology to YkpA from Bacillus subtilis. Epitope mapping of the derived amino acid sequence with sera from patients who had recovered from EMRSA-15 septicemia delineated seven epitopes. Three of these epitopes, represented by peptides 1 (KIKVYVGNYDFWYQS), 2 (TVIVVSHDRHFLYNNV), and 3 (TETFLRGFLGRMLFS), were synthesized and used to isolate human recombinant antibodies from a phage antibody display library. Recombinant antibodies against peptides 1 and 2 gave logarithmic reductions in organ colony counts, compared with control groups, in a mouse model of the infection. This study suggests the potential role of an ABC transporter as a target for immunotherapy.
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Project description:BackgroundLivestock-associated methicillin-resistant Staphylococcus aureus clonal complex 398 (LA-MRSA CC398) is causing an increasing number of skin and soft tissue infections (SSTIs) in Denmark and other European countries with industrial pig production. Yet, its impact on MRSA bloodstream infections (BSIs) has not been well studied.MethodsWe investigated the clinical epidemiology of all human cases of LA-MRSA CC398 BSI during 2010-2015. Cases of LA-MRSA CC398 BSI were compared to cases of BSI caused by other types of MRSA and cases of SSTI caused by LA-MRSA CC398. Whole-genome sequence analysis was used to assess the phylogenetic relationship among LA-MRSA CC398 isolates from Danish pigs and cases of BSI and SSTI.ResultsThe number of LA-MRSA CC398 BSIs and SSTIs increased over the years, peaking in 2014, when LA-MRSA CC398 accounted for 16% (7/44) and 21% (211/985) of all MRSA BSIs and SSTIs, corresponding to 1.2 and 37.4 cases of BSI and SSTI per 1000000 person-years, respectively. Most patients with LA-MRSA CC398 BSI had no contact to livestock, although they tended to live in rural areas. LA-MRSA CC398 caused 24.3 BSIs per 1000 SSTIs among people with no livestock contact, which is similar to the ratio observed for other types of MRSA. Whole-genome sequence analysis showed that most of the BSI and SSTI isolates were closely related to Danish pig isolates.ConclusionsThis study demonstrates that the increasing number of LA-MRSA CC398 BSIs occurred in parallel with a much larger wave of LA-MRSA CC398 SSTIs and an expanding pig reservoir.
| S-EPMC5850567 | biostudies-literature
Project description:BackgroundBloodstream infections due to Staphylococcus aureus cause significant patient morbidity and mortality worldwide. Of major concern is the emergence and spread of methicillin-resistant S. aureus (MRSA) in bloodstream infections, which are associated with therapeutic failure and increased mortality.MethodsWe generated high quality draft genomes from 323 S. aureus blood culture isolates from patients diagnosed with bloodstream infection at the Dartmouth-Hitchcock Medical Center, New Hampshire, USA in 2010-2018.ResultsIn silico detection of antimicrobial resistance genes revealed that 133/323 isolates (41.18%) carry horizontally acquired genes conferring resistance to at least three antimicrobial classes, with resistance determinants for aminoglycosides, beta-lactams and macrolides being the most prevalent. The most common resistance genes were blaZ and mecA, which were found in 262/323 (81.11%) and 104/323 (32.20%) isolates, respectively. Majority of the MRSA (102/105 isolates or 97.14%) identified using in vitro screening were related to two clonal complexes (CC) 5 and 8. The two CCs emerged in the New Hampshire population at separate times. We estimated that the time to the most recent common ancestor of CC5 was 1973 (95% highest posterior density (HPD) intervals: 1966-1979) and 1946 for CC8 (95% HPD intervals: 1924-1959). The effective population size of CC8 increased until the late 1960s when it started to level off until late 2000s. The levelling off of CC8 in 1968 coincided with the acquisition of SCCmec Type IV in majority of the strains. The plateau in CC8 also coincided with the acceleration in the population growth of CC5 carrying SCCmec Type II in the early 1970s, which eventually leveled off in the early 1990s. Lastly, we found evidence for frequent recombination in the two clones during their recent clonal expansion, which has likely contributed to their success in the population.ConclusionsWe conclude that the S. aureus population was shaped mainly by the clonal expansion, recombination and co-dominance of two major MRSA clones in the last five decades in New Hampshire, USA. These results have important implications on the development of effective and robust strategies for intervention, control and treatment of life-threatening bloodstream infections.
| S-EPMC8215799 | biostudies-literature
Project description:ImportanceEstimating the US burden of methicillin-resistant Staphylococcus aureus (MRSA) infections is important for planning and tracking success of prevention strategies.ObjectiveTo describe updated national estimates and characteristics of health care- and community-associated invasive methicillin-resistant Staphylococcus aureus (MRSA) infections in 2011.Design, setting, and participantsActive laboratory-based case finding identified MRSA cultures in 9 US metropolitan areas from 2005 through 2011. Invasive infections (MRSA cultured from normally sterile body sites) were classified as health care-associated community-onset (HACO) infections (cultured ≤ 3 days after admission and/or prior year dialysis, hospitalization, surgery, long-term care residence, or central vascular catheter presence ≤ 2 days before culture); hospital-onset infections (cultured >3 days after admission); or community-associated infections if no other criteria were met. National estimates were adjusted using US census and US Renal Data System data.Main outcomes and measuresNational estimates of invasive HACO, hospital-onset, and community-associated MRSA infections using US census and US Renal Data System data as the denominator.ResultsAn estimated 80,461 (95% CI, 69,515-93,914) invasive MRSA infections occurred nationally in 2011. Of these, 48,353 (95% CI, 40,195-58,642) were HACO infections; 14,156 (95% CI, 10,096-20,440) were hospital-onset infections; and 16,560 (95% CI, 12,806-21,811) were community-associated infections. Since 2005, adjusted national estimated incidence rates decreased among HACO infections by 27.7% and hospital-onset infections decreased by 54.2%; community-associated infections decreased by only 5.0%. Among recently hospitalized community-onset (nondialysis) infections, 64% occurred 3 months or less after discharge, and 32% of these were admitted from long-term care facilities.Conclusions and relevanceAn estimated 30,800 fewer invasive MRSA infections occurred in the United States in 2011 compared with 2005; in 2011 fewer infections occurred among patients during hospitalization than among persons in the community without recent health care exposures. Effective strategies for preventing infections outside acute care settings will have the greatest impact on further reducing invasive MRSA infections nationally.
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Project description:In this work, we investigate the role of environmental contamination on the clinical epidemiology of antibiotic-resistant bacteria in hospitals. Methicillin-resistant Staphylococcus aureus (MRSA) is a bacterium that causes infections in different parts of the body. It is tougher to treat than most strains of Staphylococcus aureus or staph, because it is resistant to some commonly used antibiotics. Both deterministic and stochastic models are constructed to describe the transmission characteristics of MRSA in hospital setting. The deterministic epidemic model includes five compartments: colonized and uncolonized patients, contaminated and uncontaminated health care workers (HCWs), and bacterial load in environment. The basic reproduction number R 0 is calculated, and its numerical and sensitivity analysis has been performed to study the asymptotic behavior of the model, and to help identify factors responsible for observed patterns of infections. A stochastic epidemic model with stochastic simulations is also presented to supply a comprehensive analysis of its behavior. Data collected from Beijing Tongren Hospital will be used in the numerical simulations of our model. The results can be used to provide theoretical guidance for designing efficient control measures, such as increasing the hand hygiene compliance of HCWs and disinfection rate of environment, and decreasing the transmission rate between environment and patients and HCWs.
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