Eradication Of Methicillin-resistant Staphylococcus Aureus Research Articles

Eradication of methicillin resistant Staphylococcus aureus detected for the first time in cystic fibrosis: A single center observational study.

To retrospectively identify CF patients with methicillin resistant Staphylococcus aureus (MRSA) and to assess the long-term success of an eradication scheme introduced in 2002 for all newly colonized patients. All microbiological results from all 505 CF patients followed between 2002 and 2012 were analyzed focusing on the detection of MRSA. Retrospective patient record analysis of MRSA positive CF patients regarding eradication and clinical outcome. We identified 57 patients with MRSA, mean age 15.3 years (range: 0.6-36.9, incidence 0.9%/year). Of these, nine patients were lost to follow-up; seven chronically colonized patients were excluded from the intervention. Eradication was suggested to all patients, 37/41 gave their consent to the following two-step approach: (i) dual iv antibiotic treatment over 3 weeks, accompanied by hygienic directives and topical therapy for 5 days followed by a 6-week period with dual oral antibiotic therapy and inhalation with vancomycin. (ii) Each new MRSA detection was treated with 6 weeks inhalation of vancomycin and topical therapy for 5 days. Long-term eradication was rated by the microbiological status in the third year after first detection. MRSA was eradicated in 31 of 37 patients (84%) whose clinical course was stable (mean FEV1 one year before MRSA 80.4%, 3 years after MRSA 81.0%). MRSA colonization mandates complex and expensive hygienic measures which are not well accepted by patients. Therefore, MRSA eradication is desirable. Intensive therapy regimens may be successful in patients with CF and might help to maintain a stable clinical course. Pediatr Pulmonol. 2016;51:1010-1019. © 2016 Wiley Periodicals, Inc.

Diagnostics and Eradication Therapy for MRSA Carriers in the Outpatient Sector: an Analysis of the Reimbursement Situation in the Light of Current Reimbursement Changes

Infection with methicillin-resistant Staphylococcus aureus (MRSA) occurs in both the inpatient and outpatient sector. The reimbursement for diagnostic services and eradication therapy in the outpatient sector was regulated for the first time on 01.04.2012 and after a 2-year test period, has been adopted into the standard range of care services. The aim of this retrospective study was to give an overview of the current situation in services and reimbursement in Germany and describe MRSA patients and their treatment in the outpatient sector. Secondary data, namely reimbursement data of the National Association of Statutory Health Insurance Physicians (KBV) und the Physicians' Association (KV) Mecklenburg-West Pomerania for the period 01/04/2012-31/03/2014 were analyzed. Results show that on the federal level, MRSA services amounting to € 3,235,870.18 have been reimbursed and that diagnostic costs exceed treatment costs. In Germany, 5,627 doctors invoiced services related to MRSA; 51,56% of these were general practitioners and 21,25% specialists in internal medicine working in general practice. In the KV Mecklenburg-Western Pomerania, patients were elderly (average age 69,13), cost for services were on average 27,76 €, and 76,85% of the patients were treated within one quarter. On the whole, there were regional differences in the identification and eradication of MRSA in the outpatient setting. In order to provide an extended base for a more efficient resource allocation in the health care sector, in addition to analysis of MRSA eradication from the medical point of view, attention needs to be paid to patient flow between the out- and inpatient sectors, as well as economic aspects.

MRSA eradication of newly acquired lower respiratory tract infection in cystic fibrosis.

UK cystic fibrosis (CF) guidelines recommend eradication of methicillin-resistant Staphylococcus aureus (MRSA) when cultured from respiratory samples. As there is no clear consensus as to which eradication regimen is most effective, we determined the efficacy of eradication regimens used in our CF centre and long-term clinical outcome.All new MRSA positive sputum cultures (n=37) that occurred between 2000 and 2014 were reviewed. Eradication regimen characteristics and clinical, microbiological and long-term outcome data were collected.Rifampicin plus fusidic acid was the most frequently used regimen (24 (65%) out of 37 patients), with an overall success rate of 79% (19 out of 24 patients). Eradication failure was more likely in patients with an additional MRSA-positive peripheral screening swab (p=0.03) and was associated with worse survival (p=0.04).Our results demonstrate the feasibility and clinical benefits of MRSA eradication. As peripheral colonisation was associated with lower eradication success, strategies combining systemic and topical treatments should be considered to optimise outcomes in CF patients.

Vancomycin AUC24 /MIC Ratio in Patients with Methicillin-Resistant Staphylococcus aureus Pneumonia.

Vancomycin is the treatment of choice for serious methicillin-resistant Staphylococcus aureus (MRSA) infections. The area under the concentration-time curve from 0 to 24 hr (AUC24 )/minimum inhibitory concentration (MIC) ratio was recently introduced as a parameter for assessing clinical outcome by S. aureus. This study was purposed to apply the vancomycin AUC24 /MIC in patients with MRSA pneumonia. Forty-seven patients with confirmed lower respiratory infection caused by MRSA during 2011 were enrolled. All patients were treated with vancomycin. Clinical characteristics and laboratory data were collected. AUC24 /MIC values were calculated as previously reported and patients were divided into two groups based on the bacteriologic response, which was eradicated or not, and an AUC24 /MIC value (above or below 400). MRSA infections were eradicated in 39 patients but 8 patients had persistent MSRA infection in the following cultures. The mean AUC24 /MIC values and vancomycin concentrations were not statistically different between patients with and without MRSA eradication. All 13 patients with a vancomycin MIC of 2 mg/L had an AUC24 /MIC below 400. AUC24 /MIC might not be a reliable indicator for assessing treatment response of vancomycin in MRSA pneumonia. Relationship between vancomycin AUC24 /MIC and therapeutic outcome needs to undergo further studies, including sufficiently large sample size.

102 MRSA eradication in CF patients with lower respiratory tract infection

Objectives Lower respiratory tract infection with methicillin-resistant Staphylococcus aureus (MRSA) is associated with increased morbidity and mortality in CF. Although attempting eradication is recommended, an optimal strategy has yet to be defined. The aim of this study was to determine the success rate of MRSA eradication regimens used in the Belfast Adult CF Centre. Methods Medical notes from adult CF patients who acquired a new MRSA respiratory infection (n = 35) between 1 January 2000 and 31 December 2014 were reviewed. A new MRSA episode was defined as no previous history of MRSA or a successful eradication. Successful eradication was defined as ≥2 negative respiratory cultures for MRSA in a period of ≥6 months following eradication. Results In total, 36 MRSA episodes were identified. Two patients spontaneously cleared MRSA without specific treatment conferring an overall eradication success rate of 73.5% (25/34). The table details the eradication protocols used and their efficacy. Interestingly, a few patients achieved eradication with a shorter course of rifampicin & fusidic acid or doxycycline (3 weeks rather than 6). Only 2 patients had established chronic MRSA infection (≥6 months) before eradication was attempted (successful). TableEradication protocols and efficacyProtocolDuration (days)Episodes (n)Success (%)Rifampicin/fusidic acid422268.1213100Doxycycline423100211100TMP-SMX4210Linezolid4210Minocycline/fusidic acid421100Rifampicin/TMP-SMX421100Teicoplanin111100 Conclusion Rifampicin & fusidic acid for 6 weeks is the most frequent protocol used with a 68% success rate. Promising efficacy of a 3 week eradication course warrants further investigation.

Nasal methicillin-resistant Staphylococcus aureus colonization is associated with increased wound occurrence after major lower extremity amputation

Wound occurrence (WO) after major lower extremity amputation (MLEA) can be due to wound infection or sterile dehiscence. We sought to determine the association of nasal methicillin-resistant Staphylococcus aureus (MRSA) colonization and other patient factors with overall WO, WO due to wound infection, and WO due to sterile dehiscence. The medical records of all patients undergoing MLEA from August 1, 2011, to November 1, 2013, were reviewed. Demographic data, hemoglobin A1c level, albumin concentration, dialysis dependence, peripheral vascular disease (PVD), nasal MRSA colonization, and diabetes mellitus (DM) were examined as variables. The overall WO rate was determined, and the cause of WO was categorized as either a sterile dehiscence or a wound infection. Eighty-three patients underwent 96 MLEAs during a 27-month period. The rates of overall WO, WO due to infection, and WO due to sterile dehiscence were 39%, 19%, and 19%, respectively (1% developed a traumatic wound). On univariate analysis, PVD, MRSA colonization, DM, and dialysis dependence were all associated with higher rates of overall WO (P < .05). On multivariate analysis, MRSA colonization was associated with higher rates of overall WO (P = .03) and WO due to wound infection (11% vs 45%; P < .01). DM and PVD were associated with higher rates of overall WO and WO due to sterile dehiscence on both univariate and multivariate analysis (P < .05). Nasal MRSA colonization is associated with higher rates of overall WO and WO due to wound infection. DM and PVD are associated with higher rates of overall WO and WO due to sterile dehiscence but are not associated with WO due to wound infection. Further studies addressing the effect of nasal MRSA eradication on postoperative wound outcomes after MLEA are warranted.

Transmission and microevolution of USA300 MRSA in U.S. households: evidence from whole-genome sequencing.

ABSTRACTMethicillin-resistant Staphylococcus aureus (MRSA) USA300 is a successful S. aureus clone in the United States and a common cause of skin and soft tissue infections (SSTIs). We performed whole-genome sequencing (WGS) of 146 USA300 MRSA isolates from SSTIs and colonization cultures obtained from an investigation conducted from 2008 to 2010 in Chicago and Los Angeles households that included an index case with an S. aureus SSTI. Identifying unique single nucleotide polymorphisms (SNPs) and analyzing whole-genome phylogeny, we characterized isolates to understand transmission dynamics, genetic relatedness, and microevolution of USA300 MRSA within the households. We also compared the 146 USA300 MRSA isolates from our study with the previously published genome sequences of the USA300 MRSA isolates from San Diego (n = 35) and New York City (n = 277). We found little genetic variation within the USA300 MRSA household isolates from Los Angeles (mean number of SNPs ± standard deviation, 17.6 ± 35; π nucleotide diversity, 3.1 × 10−5) or from Chicago (mean number of SNPs ± standard deviation, 12 ± 19; π nucleotide diversity, 3.1 × 10−5). The isolates within a household clustered into closely related monophyletic groups, suggesting the introduction into and transmission within each household of a single common USA300 ancestral strain. From a Bayesian evolutionary reconstruction, we inferred that USA300 persisted within households for 2.33 to 8.35 years prior to sampling. We also noted that fluoroquinolone-resistant USA300 clones emerged around 1995 and were more widespread in Los Angeles and New York City than in Chicago. Our findings strongly suggest that unique USA300 MRSA isolates are transmitted within households that contain an individual with an SSTI. Decolonization of household members may be a critical component of prevention programs to control USA300 MRSA spread in the United States.

Linezolid versus vancomycin for the treatment of suspected methicillin-resistant Staphylococcus aureus nosocomial pneumonia: a systematic review employing meta-analysis.

The optimal therapy involving linezolid or vancomycin for suspected methicillin-resistant Staphylococcus aureus (MRSA) nosocomial pneumonia (NP) remains controversial. This study compared the efficacy and safety of linezolid and vancomycin therapies in patients with NP. A systematic review of randomized controlled trials with meta-analyses performed by searching PubMed, EMBASE, MEDLINE, and the Cochrane Central Register of Controlled Trials. We screened for relevant randomized controlled studies in which patients with NP were enrolled and linezolid and vancomycin therapies were compared. Nine trials involving 2618 pneumonia patients were reviewed. Linezolid was not found to be superior to vancomycin for clinical cure when categories of pathogen were not considered and in a subgroup of NP patients with MRSA infection [relative risk (RR)=1.16, 95 % confidence interval (CI)=0.95-1.43, P=0.15]. Compared with vancomycin, linezolid has no difference in the overall microbiological eradication rate (RR=1.12, 95 % CI=0.96-1.30, P=0.15) and specific MRSA eradication rate (RR=1.16, 95 % CI=0.93-1.45, P=0.19) in NP patients. In addition, nephrotoxicity was more frequent with vancomycin (RR=0.50, 95 % CI=0.31-0.81, P=0.005), but no differences between the treatments were found for all-cause mortality, thrombocytopenia, gastrointestinal effects, and drug discontinuation due to adverse events. These results suggest that linezolid is not superior to vancomycin with respect to both clinical and microbiological cure rates in patients with MRSA NP.

Increase in ventilated air spaces after eradication of chronic methicillin-resistant Staphylococcus aureus infection in cystic fibrosis patients

Effective microbiogical eradication of methicillin-resistant Staphylococcus aureus (MRSA) in patients with cystic fibrosis (CF) can be obtained, but its effect is not always clear-cut in terms of spirometric indices. The aim of this observational prospective cohort study was to study the potential effect of eradication of chronic MRSA infection on lung function including ventilation distribution. Six CF patients, chronically colonized with MRSA (median age: 21 years (range 14–46); median FEV1: 76 (95%CI 58–98)%pred) were successfully eradicated using oral rifampicin and fusidic acid in combination with topical decolonization measures. Lung function and multiple breath washout test were performed at the start and at the end of the eradication protocol and after an average follow-up period of 7·5±1·5(SD) months. One patient cultured MRSA again 4 months after successful eradication. All patients reported reduced sputum production and viscosity. By the end of the follow-up period, there was an increase in ventilated FRCMBW and no change in plethysmographic FRCPL. This resulted in a significant decrease of trapped air by half a litre (from 579 to 40 ml; P = 0·013). Lung clearance index (LCI) also showed a small but significant decrease (from 7·2 to 6·7; P = 0·014) after eradication of MRSA. We conclude that MRSA eradication can be successful, also in terms of recruitment of previously unventilated air spaces, potentially due to reduced sputum production and/or viscosity.

Investigation of the antibacterial activity and efflux pump inhibitory effect of co-loaded piperine and gentamicin nanoliposomes in methicillin-resistant Staphylococcus aureus

Objective: Antibiotic resistance has stimulated the research for developing novel strategies that can prevent bacterial growth. Methicillin-resistant Staphylococcus aureus (MRSA), regarded as one of the most serious antibiotic-resistant bacteria which has been conventionally recognized as a nosocomial pathogen.Materials and methods: Nanoliposomal formulations of piperine and gentamicin were prepared by dehydration-rehydration (DRV) method and characterized for size, zeta potential and encapsulation efficiency. Antibactericidal activities of liposomal and free forms were evaluated against MRSA ATCC 43300 by the determination of minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC) and fractional inhibitory concentration index (FICI). The time-kill studies were carried out to evaluate the potency of antibacterial agents. The effect of piperine on bacterial efflux pumps was also investigated.Results: MIC values of gentamicin and piperine were 32 and 100 µg/mL, respectively. Synergetic effects were observed by the combination of gentamicin and piperine and FICI was determined to be 0.5. Following incorporation of gentamicin into liposomal gentamicin and liposomal combination, the MIC values were reduced 16- and 32-fold, respectively. MBC values of gentamicin reduced 4 and 8 times following incorporation into gentamicin and combination liposomes, respectively. In comparison with vancomycin, liposomal combination was more effective in bacterial inhibition and killing. Liposomal combination was the most effective preparations in time-kill study. Our findings indicated that liposomal piperine was able to inhibit the efflux pump sufficiently.Conclusion: The results of this study revealed that liposomal combination is a powerful nano-antibacterial agent to eradicate MRSA infection. This dual-loaded formulation was an effective approach for eradication of MRSA.

Airborne methicillin-resistant Staphylococcus aureus in the indoor environment of King Abdullah University Hospital, Jordan

Methicillin-resistant Staphylococcus aureus (MRSA) is seen with increasing frequency in hospitals and is considered as a major cause of hospital-acquired infection. The objectives of this study were to isolate and characterize the airborne MRSA in different wards of a referral university hospital. Thirty-four air samples of 100 litres volume/min were collected by a microbiological air sampler, then impacted on trypticase soy agar (TSA) and incubated at 37℃ for 48 h. Recovered colonies were identified by standard methods. From all S. aureus, 9.3% was identified as MRSA which comprised 4.2%, 3.1% and 2% in the adult and nursery intensive care units, and operating theatres (ICU, NICU and OT, respectively). MRSA isolates were remarkably susceptible (87.1%) to each of amikacin, chloramphenicol, imipenem and rifampin. MRSA isolates were shown in all units with minimum inhibitory concentration value of &gt;256, 32 and 6 µg/l in ICU, OT and NICU, respectively. Polymerase chain reaction analysis of all MRSA isolates indicated the amplification of the mec A gene. It is concluded that MRSA was isolated from all units making eradication of MRSA a target hard to achieve. However, the antibiotic resistance profile of the MRSA isolates looks promising leaving a room to combat nosocomial infections.

Antibiotic therapy for the treatment of methicillin-resistant Staphylococcus aureus (MRSA) in non surgical wounds.

Non surgical wounds include chronic ulcers (pressure or decubitus ulcers, venous ulcers, diabetic ulcers, ischaemic ulcers), burns and traumatic wounds. The prevalence of methicillin-resistant Staphylococcus aureus (MRSA) colonisation (i.e. presence of MRSA in the absence of clinical features of infection such as redness or pus discharge) or infection in chronic ulcers varies between 7% and 30%. MRSA colonisation or infection of non surgical wounds can result in MRSA bacteraemia (infection of the blood) which is associated with a 30-day mortality of about 28% to 38% and a one-year mortality of about 55%. People with non surgical wounds colonised or infected with MRSA may be reservoirs of MRSA, so it is important to treat them, however, we do not know the optimal antibiotic regimen to use in these cases. To compare the benefits (such as decreased mortality and improved quality of life) and harms (such as adverse events related to antibiotic use) of all antibiotic treatments in people with non surgical wounds with established colonisation or infection caused by MRSA. We searched the following databases: The Cochrane Wounds Group Specialised Register (searched 13 March 2013); The Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 2); Database of Abstracts of Reviews of Effects (2013, Issue 2); NHS Economic Evaluation Database (2013, Issue 2); Ovid MEDLINE (1946 to February Week 4 2013); Ovid MEDLINE (In-Process & Other Non-Indexed Citations, March 12, 2013); Ovid EMBASE (1974 to 2013 Week 10); EBSCO CINAHL (1982 to 8 March 2013). We included only randomised controlled trials (RCTs) comparing antibiotic treatment with no antibiotic treatment or with another antibiotic regimen for the treatment of MRSA-infected non surgical wounds. We included all relevant RCTs in the analysis, irrespective of language, publication status, publication year, or sample size. Two review authors independently identified the trials, and extracted data from the trial reports. We calculated the risk ratio (RR) with 95% confidence intervals (CI) for comparing the binary outcomes between the groups and planned to calculate the mean difference (MD) with 95% CI for comparing the continuous outcomes. We planned to perform the meta-analysis using both fixed-effect and random-effects models. We performed intention-to-treat analysis whenever possible. We identified three trials that met the inclusion criteria for this review. In these, a total of 47 people with MRSA-positive diabetic foot infections were randomised to six different antibiotic regimens. While these trials included 925 people with multiple pathogens, they reported the information on outcomes for people with MRSA infections separately (MRSA prevalence: 5.1%). The only outcome reported for people with MRSA infection in these trials was the eradication of MRSA. The three trials did not report the review's primary outcomes (death and quality of life) and secondary outcomes (length of hospital stay, use of healthcare resources and time to complete wound healing). Two trials reported serious adverse events in people with infection due to any type of bacteria (i.e. not just MRSA infections), so the proportion of patients with serious adverse events was not available for MRSA-infected wounds. Overall, MRSA was eradicated in 31/47 (66%) of the people included in the three trials, but there were no significant differences in the proportion of people in whom MRSA was eradicated in any of the comparisons, as shown below.1. Daptomycin compared with vancomycin or semisynthetic penicillin: RR of MRSA eradication 1.13; 95% CI 0.56 to 2.25 (14 people).2. Ertapenem compared with piperacillin/tazobactam: RR of MRSA eradication 0.71; 95% CI 0.06 to 9.10 (10 people).3. Moxifloxacin compared with piperacillin/tazobactam followed by amoxycillin/clavulanate: RR of MRSA eradication 0.87; 95% CI 0.56 to 1.36 (23 people). We found no trials comparing the use of antibiotics with no antibiotic for treating MRSA-colonised non-surgical wounds and therefore can draw no conclusions for this population. In the trials that compared different antibiotics for treating MRSA-infected non surgical wounds, there was no evidence that any one antibiotic was better than the others. Further well-designed RCTs are necessary.

β-Lactams Enhance Vancomycin Activity against Methicillin-Resistant Staphylococcus aureus Bacteremia Compared to Vancomycin Alone

Vancomycin (VAN) is often used to treat methicillin-resistant Staphylococcus aureus (MRSA) bacteremia despite a high incidence of microbiological failure. Recent in vitro analyses of β-lactams in combination with VAN demonstrated synergistic activity against MRSA. The goal of this study was to examine the impact of combination therapy with VAN and a β-lactam (Combo) on the microbiological eradication of MRSA bacteremia compared to VAN alone. This was a retrospective cohort study of patients with MRSA bacteremia who received Combo therapy or VAN alone. Microbiological eradication of MRSA, defined as a negative blood culture obtained after initiation of therapy, was used to evaluate the efficacy of each regimen. A total of 80 patients were included: 50 patients in the Combo group and 30 patients in the VAN-alone group. Microbiological eradication was achieved in 48 patients (96%) in the Combo group compared to 24 patients (80%) in the VAN-alone group (P = 0.021). In a multivariable model, the Combo treatment had a higher likelihood of achieving microbiological eradication (adjusted odds ratio, 11.24; 95% confidence interval, 1.7 to 144.3; P = 0.01). In patients with infective endocarditis (n = 22), 11/11 (100%) who received Combo therapy achieved microbiological eradication compared to 9/11 (81.8%) treated with VAN alone, but the difference was not statistically significant (P = 0.20). Patients with MRSA bacteremia who received Combo therapy were more likely to experience microbiological eradication of MRSA than patients who received VAN alone.

Antibiotic therapy for the treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections in surgical wounds.

Methicillin-resistant Staphylococcus aureus (MRSA) infection after surgery is usually rare, but incidence can be up to 33% in certain types of surgery. Postoperative MRSA infection can occur as surgical site infections (SSI), chest infections, or bloodstream infections (bacteraemia). The incidence of MRSA SSIs varies from 1% to 33% depending upon the type of surgery performed and the carrier status of the individuals concerned. The optimal antibiotic regimen for the treatment of MRSA in surgical wounds is not known. To compare the benefits and harms of various antibiotic treatments in people with established surgical site infections (SSIs) caused by MRSA . In February 2013 we searched the following databases: The Cochrane Wounds Group Specialised Register; The Cochrane Central Register of Controlled Trials (CENTRAL); Database of Abstracts of Reviews of Effects (DARE); NHS Economic Evaluation Database; Health Technology Assessment (HTA) Database; Ovid MEDLINE; Ovid MEDLINE (In-Process & Other Non-Indexed Citations); Ovid EMBASE; and EBSCO CINAHL. We included only randomised controlled trials (RCTs) comparing one antibiotic regimen with another antibiotic regimen for the treatment of SSIs due to MRSA. All RCTs irrespective of language, publication status, publication year, or sample size were included in the analysis. Two review authors independently decided on inclusion and exclusion of trials, and extracted data. We planned to calculate the risk ratio (RR) with 95% confidence intervals (CI) for comparing the binary outcomes between the groups and mean difference (MD) with 95% CI for comparing the continuous outcomes. We planned to perform the meta-analysis using both a fixed-effect and a random-effects model. We performed intention-to-treat analysis whenever possible. We included one trial involving 59 people hospitalised because of MRSA SSIs. Thirty participants were randomised to linezolid (600 mg either intravenously or orally every 12 hours for seven to 14 days) and 29 to vancomycin (1 g intravenously every 12 hours for seven to 14 days). The type of surgical procedures that were performed were not reported. The trial reported one outcome, which was the eradication of MRSA. The proportion of people in whom MRSA was eradicated was statistically significantly higher in the linezolid group than in the vancomycin group (RR 1.80; 95% CI 1.20 to 2.68). There is currently no evidence to recommend any specific antibiotic in the treatment of MRSA SSIs. Linezolid is superior to vancomycin in the eradication of MRSA SSIs on the basis of evidence from one small trial that was at high risk of bias, but the overall clinical implications of using linezolid instead of vancomycin are not known. Further well-designed randomised clinical trials are necessary in this area.

Effect of the methanol extracts of Salvia libanotica, Rosmarinus officinalis, Capparis spinosa and Achillea fragrantissima against two strains of Staphylococcus aureus

Control of Staphylococcal infections is difficult, especially decreasing the incidence of methicillinresistant Staphylococcus aureus (MRSA) among hospitalized patients. Meanwhile, medicinal plants have many traditional claims including the treatment of ailments of infectious origin. Four Jordanian medicinal plants, Salvia libanotica, Rosmarinus officinalis, Capparis spinosa, and Achillea fragrantissima used by traditional medical practitioners were investigated for in vitro anti-MRSA activity. The objective of the study was to determine the presence of anti-MRSA activity in the crude extracts of some of the commonly used medicinal plants in Jordan; S. libanotica, R. officinalis, C. spinosa, and A. fragrantissima. Fresh plant materials were collected from the local market and from the Hashemite University Herbarium. Methanol extracts of the pulverized plants’ leaves were obtained by maceration. Bacterial culture used was a strain of MRSA isolated from a Jordanian hospital, identified by biochemical and coagulase tests and examined for antibiotic susceptibility patterns by disc diffusion method. Staphylococcus aureus ATCC (25923) was used as a standard strain. Susceptibility testing of the plant extracts was performed by the agar diffusion method. Minimum inhibitory concentration was determined only for S. libanotica and R. officinalis. Methanol extracts of S. libanotica and R. officinalis were affective against MRSA. However, C. spinosa, and A. fragrantissima were ineffective in MRSA eradication. This finding forms a basis for further studies on screening of local medicinal plant extracts for antibacterial properties and may help in control of MRSA infections especially in case of chemotherapy failure.

Predictors of clinical and microbiological treatment failure in patients with methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia: a retrospective cohort study in a region with low MRSA prevalence

Invasive infections with methicillin-resistant Staphylococcus aureus (MRSA) have been associated with increased morbidity and mortality. The aim of the present study was to identify independent predictors of early mortality and treatment failure in patients with MRSA bacteraemia. A total of 132 adult patients who developed MRSA bacteraemia during hospitalization in the University Hospital of Vienna between 2000 and 2011 were screened and 124 were included in a retrospective cohort study. Patient demographics, source of bacteraemia, antimicrobial treatment and microbiological characteristics were evaluated. The 28-day crude mortality was 30.6%. Predictors of early mortality identified in multivariate Cox regression analysis included higher patientage (adjusted hazard ratio (aHR) 1.03, 95% CI 1.01–1.06, p 0.006), pneumonia (aHR 3.86, 95% CI 1.83–8.12, p <0.001) and failure to use MRSA active treatment (aHR 8.77, 95% CI 3.50–21.93, p <0.001). Ninety-one (73.4%) patients received glycopeptides as specific MRSA treatment. Of 63 patients treated with vancomycin, only 14 (22.6%) patients had aimed trough levels of 15–20 mg/L. Vancomycin MIC ≥ 2 mg/L was detected in 28.2% and was associated with glycopeptide pretreatment (p 0.001). All MRSA isolates were susceptible to linezolid and tigecycline. Persistent bacteraemia ≥ 7 days was documented in 25 (20.2%) patients. Independent determinants for microbiological eradication failure in patients with MRSA bacteraemia included endocarditis (p <0.001) and vancomycin trough levels (p 0.014), but not vancomycin MIC. Failure of clinical and microbiological eradication of MRSA among patients with MRSA bacteraemia was associated with clinical entity rather than with bacterial traits. Pharmacokinetic parameters seem to be decisive on microbiological and clinical success.

Evaluation of Linezolid and Vancomycin in the treatment of Methicillin-Resistant Staphylococcus aureus(MRSA) in Cystic Fibrosis Patients

Background: Cystic fibrosis (CF) patients often have pulmonary colonization with multiple organisms, including methicillin-resistant Staphylococcus aureus (MRSA), resulting in frequent hospitalizations and decreased quality of life. The pupose of this study was to evaluate the effectiveness of linezolid (LZD) and vancomycin (VAN) in the treatment of MRSA in the CF population. Methods: A prospective, pilot study was conducted in CF patients with pulmonary exacerbation and sputum culture positive for MRSA randomized to receive intravenous LZD or VAN. The primary endpoint was microbiological eradication of MRSA and secondary endpoints included Kanga Clinical Score and change in quality of life questionaire (CF QOL) score. Patients were followed for 6 months post treatment. The ability to conduct a comprehensive outcome protocol in this population at a children's hospital was also evaluated. Results: Eight subjects were randomized to receive LZD (n=5) or VAN (n=3), with average duration of therapy of 19.8 and 21 days, respectively. The primary endpoint of microbiological eradication at end of treatment (EOT) was achieved in 3 patients treated with LZD and 2 with VAN. Kanga Clinical Scores calculated at baseline and EOT showed a significant decrease in all subjects from a median of 26/50 to 16/50. Six patients or caregivers completed the CF QOL questionnaire. Five patients (2 treated with LZD, 3 with VAN) had improvements in CFQOL scores at EOT. No clinically significant adverse events were noted. Conclusions: VAN and LZD were clinically effective and well tolerated in the treatment of MRSA in our CF population. Eradication of MRSA was less likely in patients with long-standing infection. Comprehensive study protocols such as this may be utilized in a large, randomized controlled trial to determine standardized treatment for newly acquired MRSA in CF patients.

Eradication of chronic methicillin-resistant Staphylococcus aureus infection in cystic fibrosis patients. An observational prospective cohort study of 11 patients

Chronic airway infection with methicillin-resistant Staphylococcus aureus (MRSA) in patients with cystic fibrosis (CF) is an increasing clinical problem, and therapeutic options are limited. Because chronic infection with MRSA can be associated with accelerated decline in lung function, eradication of MRSA is attempted in most CF centres today. The aim of this observational prospective cohort study was to determine whether it is possible to eradicate MRSA from airways of CF patients using prolonged oral antibiotic combination therapy together with topical decolonization measures. Eleven CF patients, (median age: 9 years (range 1-43); median FEV1: 91%pred (95%CI 74%-100%pred)) who were chronically infected with MRSA, were treated daily for six months with rifampicin and fusidic acid orally. This study did not include a patient control group. Two patients had to switch to an alternative schedule, using rifampicin and clindamycin, due to the resistance pattern of MRSA. Topical decolonization measures were applied to all patients and included mupirocin-containing nasal ointment in both nostrils three times daily for five days and chlorhexidine hair and body wash once daily for five days. Microbiological eradication was achieved in all patients at the end of the six-month eradication protocol, even when significant time (range 18 months to 9 years) had elapsed since initial isolation. In only one patient MRSA reappeared in the six-month follow-up period after the initial study period. Side-effects, like nausea, vomiting and diarrhoea were seen in five out of eleven patients, but did not lead to therapy cessation. Chronic MRSA infection can be eradicated from respiratory tract samples using a six month dual antibiotic regimen and topical MRSA decolonization measures.

The Development of Appropriate Dosage of Anti-bacterial and Anti-fungal Agents Based on Pharmacokinetics and Pharmacodynamics

An initial loading procedure has been recommended to enable teicoplanin to promptly reach an effective serum concentration for the treatment of methicillin-resistant Staphylococcus aureus (MRSA). The mean trough concentrations were 13.2 mg/L for patients with eradication of MRSA. I showed that the administration of ≥36 mg/kg during the first 3 days was effective in promptly obtaining a trough concentration target of ≥13 mg/L for the initial treatment of MRSA infections. The major adverse effect associated with linezolid treatment is reversible myelosuppression, primarily thrombocytopenia. I demonstrated that the incidence of linezolid-induced thrombocytopenia was higher among patients with renal failure than in patients with normal renal function. A statistically significant (p<0.01) and strong correlation (r=0.933) was observed between linezolid and creatinine clearance. A negative correlation (r=-0.567) was also shown between linezolid clearance and blood urea nitrogen. Voriconazole trough plasma concentration has been reported to correlate with hepatotoxicity. Logistic regression analysis revealed that the therapeutic range for the voriconazole trough concentration should be 2-4 mg/L. Nonlinear pharmacokinetic analysis suggested that voriconazole therapy should be initiated with a dose of 7.2-8.9 mg/kg/day for CYP2C19 wild type and 4.4-6.5 mg/kg/day for the non-wild type in patients. Anaemia and thrombocytopenia are major side effects of liposomal amphotericin B. I demonstrated that the doses of liposomal amphotericin B estimated to cause side effects of a low red blood cell count, anaemia and thrombocytopenia with 50% probability are 4.0, 3.3 and 3.0 mg/kg/day, respectively.

Decolonization with Mupirocin and Subsequent Risk of Methicillin-Resistant Staphylococcus aureus Carriage in Veterans Affairs Hospitals

IntroductionHospital-acquired methicillin-resistant Staphylococcus aureus (MRSA) infections remain one of the leading causes of preventable patient mortality in the US. Eradication of MRSA through decolonization could prevent both MRSA infections and transmission; however, there is currently no consensus within the infectious disease community on the proper role of decolonization in the prevention of infections. The purpose of this study was to assess the impact of decolonization with mupirocin on subsequent MRSA carriage.MethodsPatients included in this study were those with an inpatient admission to a Department of Veterans Affairs (VA) hospital between January 1, 2008 and December 31, 2009 who had a positive MRSA screen on admission and a subsequent re-admission during the same time period. Exposure to mupirocin on the initial hospital admission was measured using Barcode Medication Administration data and MRSA carriage was measured using microbiology text reports and lab data containing results from surveillance swabs collected from the nares. Chi-square tests were used to test for differences in re-admission MRSA carriage rates between mupirocin-receiving and non-mupirocin-receiving patients.ResultsOf the 25,282 MRSA-positive patients with a subsequent re-admission included in the present study cohort, 1,183 (4.7%) received mupirocin during their initial hospitalization. Among the patients in the present study cohort who were re-admitted within 30 days, those who received mupirocin were less likely to test positive for MRSA carriage than those who did not receive mupirocin (27.2% vs. 55.1%, P < 0.001). The proportion of those who tested positive for MRSA during re-admissions that occurred 30–60 days, 60–120 days, and >120 days were 33.9, 37.3, and 41.0%, respectively, among mupirocin patients and 52.7%, 53.0%, and 51.9%, respectively, for patients who did not receive mupirocin (P < 0.001 at each time point).ConclusionPatients decolonized with mupirocin in VA hospitals were less likely to be colonized with MRSA on re-admission as long as 4 months after decolonization.