Vancomycin-resistant Enterococcus faecium pneumonia in a uremic patient on hemodialysis: a case report and review of the literature.

BACKGROUND: Even though enterococci can cause serious infections in multiple sites, they are a rare cause of pneumonia. We reported a uremic patient with vancomycin-resistant E. faecium (VRE-fm) pneumonia, possibly related to epileptic seizures. CASE PRESENTATION: A 57-year old man with uremia on hemodialysis was admitted to the hospital with complaint of recurrent epileptic seizures, followed by a two-week history of recurrent fever and cough with purulent sputum. Chest CT demonstrated multiple exudation of both lungs. He was diagnosed as community acquired pneumonia. Despite antibiotic combination therapy, abnormal chest shadows aggravated. Sputum and blood cultures were initially negative, but later blood culture grew VRE-fm. We suspected aspiration of gastrointestinal content induced by epilepsy as the most likely mechanism. The patient was successfully treated with a four-week course of linezolid according to the antibiotic susceptibility testing. CONCLUSIONS: Physicians should consider multi-drug resistant organisms such as VRE in uremic patients with pneumonia that fails to resolve with broad-spectrum antibiotics, especially in the cases with aspiration induced by epilepsy, immunocompromised conditions, and repeated or prolonged hospitalizations.

Genomic insights on heterogeneous resistance to vancomycin and teicoplanin in Methicillin-resistant Staphylococcus aureus: A first report from South India.

Methicillin-resistant Staphylococcus aureus (MRSA) infection is an important clinical concern in patients, and is often associated with significant disease burden and metastatic infections. There is an increasing evidence of heterogeneous vancomycin-intermediate S. aureus (hVISA) associated treatment failure. In this study, we aim to understand the molecular mechanism of teicoplanin resistant MRSA (TR-MRSA) and hVISA. A total of 482 MRSA isolates were investigated for these phenotypes. Of the tested isolates, 1% were identified as TR-MRSA, and 12% identified as hVISA. A highly diverse amino acid substitution was observed in tcaRAB, vraSR, and graSR genes in TR-MRSA and hVISA strains. Interestingly, 65% of hVISA strains had a D148Q mutation in the graR gene. However, none of the markers were reliable in differentiating hVISA from TR-MRSA. Significant pbp2 upregulation was noted in three TR-MRSA strains, which had teicoplanin MICs of 16 or 32 µg/ml, whilst significant pbp4 downregulation was not noted in these strains. In our study, multiple mutations were identified in the candidate genes, suggesting a complex evolutionary pathway involved in the development of TR-MRSA and hVISA strains.

Risk factors of treatment failure and 30-day mortality in patients with bacteremia due to MRSA with reduced vancomycin susceptibility.

Bacteremia caused by MRSA with reduced vancomycin susceptibility (MRSA-RVS) frequently resulted in treatment failure and mortality. The relation of bacterial factors and unfavorable outcomes remains controversial. We retrospectively reviewed clinical data of patients with bacteremia caused by MRSA with vancomycin MIC = 2 mg/L from 2009 to 2012. The significance of bacterial genotypes, agr function and heterogeneous vancomycin-intermediate S. aureus (hIVSA) phenotype in predicting outcomes were determined after clinical covariates adjustment with multivariate analysis. A total of 147 patients with mean age of 63.5 (±18.1) years were included. Seventy-nine (53.7%) patients failed treatment. Forty-seven (31.9%) patients died within 30 days of onset of MRSA bacteremia. The Charlson index, Pitt bacteremia score and definitive antibiotic regimen were independent factors significantly associated with either treatment failure or mortality. The hVISA phenotype was a potential risk factor predicting treatment failure (adjusted odds ratio 2.420, 95% confidence interval 0.946-6.191, P = 0.0652). No bacterial factors were significantly associated with 30-day mortality. In conclusion, the comorbidities, disease severity and antibiotic regimen remained the most relevant factors predicting treatment failure and 30-day mortality in patients with MRSA-RVS bacteremia. hIVSA phenotype was the only bacterial factor potentially associated with unfavorable outcome in this cohort.

The role of Enterococcus spp. and multidrug-resistant bacteria causing pyogenic liver abscesses.

BACKGROUND: Pyogenic liver abscesses (PLA) remain a significant clinical problem. Unfortunately, little is known about current bacterial susceptibility profiles and the incidence of multidrug resistant organisms (MDROs) causing PLA in Western countries. Yet, this crucial information is pivotal to guide empirical antibiotic therapy. Aim of this study was to provide detailed characteristics of PLA with a special focus on underlying bacterial pathogens and their susceptibility to antibiotics. METHODS: A retrospective study of patients diagnosed with PLA from 2009 to 2015 in a large tertiary reference center in Germany was performed in order to characterize PLA and antimicrobial susceptibility profiles of causative bacterial species. RESULTS: Overall, 86 patients were included. The most common causes of PLA were bile duct stenosis/obstruction (31.4%) and leakage of biliary anastomosis (15.1%). Frequent predisposing diseases were malignancies (34.9%), diabetes (24.4%) and the presence of liver cirrhosis (16.3%). Of note, Enterococcus spp. were the most frequently cultured bacterial isolates (28.9%), and in 1/3 of cases vancomycin resistance was observed. In addition, a relevant frequency of gram-negative MDROs was identified. In particular, an alarming 10% and 20% of gram-negative bacteria were resistant to carbapenems and tigecycline, respectively. Of note, MDRO status did not predict ICU stay or survival in multivariate regression analysis. The mortality rate in our series was 16.3%. CONCLUSION: Our study demonstrates an as yet underreported role of Enterococcus spp., often associated with vancomycin resistance, as well as of gram-negative MDROs causing PLA.

Streptomyces sp. AT37 isolated from a Saharan soil produces a furanone derivative active against multidrug-resistant Staphylococcus aureus.

A novel actinobacterium strain, named AT37, showed a strong activity against some multidrug-resistant Staphylococcus aureus, including methicillin-resistant S. aureus MRSA ATCC 43300, other clinical isolates of MRSA and vancomycin resistant S. aureus VRSA S1. The strain AT37 was isolated from a Saharan soil by a dilution agar plating method using chitin-vitamin agar medium supplemented with rifampicin. The morphological and chemical studies indicated that this strain belonged to the genus Streptomyces. Its 16S rRNA gene sequence was determined and a database search indicated that it was closely associated with the type strain of Streptomyces novaecaesareae NBRC 13368T with 99.6% of similarity. However, the comparison of the morphological and the physiological characteristics of the strain with those of the nearest species showed significant differences. The strain AT37 secreted the antibiotic optimally during mid-stationary phase of growth. One active compound (AT37-1) was extracted from the culture broth with dichloromethane, separated on silica gel plates and purified by HPLC. Based on spectroscopic analysis of UV-Visible, infrared, and 1H and 13C NMR spectra and spectrometric analysis, the chemical structure of the compound AT37-1 was identified as 5-[(5E,7E,11E)-2,10-dihydroxy-9,11-dimethyl-5,7,11-tridecatrien-1-yl]-2-hydroxy-2-(1-hydroxyethyl)-4-methyl-3(2H)-furanone. Minimum inhibitory concentrations and minimum biofilm inhibitory concentration (MBIC50) of this compound showed significant activity against multidrug-resistant S. aureus with 15-30 and 10-15 µg/mL, respectively.

Antimicrobial peptide isolated from Bacillus amyloliquefaciens K14 revitalizes its use in combinatorial drug therapy.

The present study was performed to evaluate the antibacterial activities of an antimicrobial peptide (CSpK14) and the synergies thereof with ß-lactams against vancomycin-resistant Staphylococcus aureus (VRSA) and Enterococci (VRE). Our strain was isolated from fermented food (kimchi), which is 99.79 % homologous with Bacillus amyloliquefaciens subsp. plantarum FZB42(T). CSpK14 was purified to homogeneity by diammonium sulfate precipitation, concentration, dialysis, and followed by two-stage chromatographic separation, i.e., Sepharose Cl-6B and Sephadex G-25 chromatography, and had a molar mass of ~4.6 kDa via Tricine SDS-PAGE and in situ examination. It was stable at pH 6.0-11.5 and temperature up to 80 °C. In addition, it was also stable with various metal ions, solvents, and proteases. The N-terminal amino acid sequence was H-Y-D-P-G-D-D-S-G-N-T-G and did not show any significant homology with reported peptides. However, it shows some degrees of identity with alpha-2-macroglobulin and ligand-gated channel protein from different microorganisms. CSpK14 significantly reduced the minimum inhibitory concentrations (MICs) of ß-lactams and had no effect on non-ß-lactams against VRSA and VRE. MICs of CSpK14/oxacillin and CSpK14/ampicillin were reduced by 8- to 64-fold and 2- to 16-fold, respectively. The time killing assay between CSpK14/oxacillin (2.29-2.37 Δlog10CFU/mL at 24 h) and CSpK14/ampicillin (2.30-2.38 Δlog10CFU/mL at 24 h) being >2-fold and fractional inhibitory concentration index ˂0.5 revealed synergy. Furthermore, the biofilms formed by VRSA and VRE were reduced completely. CSpK14 was simple to purify, had low molecular mass, was stable over a wide pH range or tested chemicals, had broad inhibitory spectrum, and possessed potent synergistic antimicrobial-antibiofilm properties. CSpK14 synergistically enhanced the efficacy of ß-lactams and is therefore suitable for combination therapy.

Vancomycin-resistant Enterococcal Bloodstream Infections in Hematopoietic Stem Cell Transplant Recipients and Patients with Hematologic Malignancies: Impact of Daptomycin MICs of 3 to 4 mg/L.

PURPOSE: Case reports of treatment failure with standard-dose daptomycin (6 mg/kg) have recently surfaced in vancomycin-resistant Enterococcus (VRE) bloodstream infection (BSI) episodes with daptomycin MICs of 3 to 4 mg/L. The clinical implications of daptomycin MICs of 3 to 4 mg/L in VRE BSIs have not been elucidated. METHODS: We performed a single institutional retrospective analysis of adult stem cell transplant recipients and patients with hematologic malignancies diagnosed with VRE BSI from 2006 to 2014 and compared outcomes between those with daptomycin MICs of 3 to 4 mg/L those with 2 mg/L, as determined by Etest. FINDINGS: Forty-two daptomycin-treated VRE BSI episodes, all due to Enterococcus faecium were identified; 19 episodes with daptomycin MICs of 3 to 4 mg/L and 23 episodes with a daptomycin MIC of 2 mg/L. Patients in the higher daptomycin MIC group were more likely to be male, to be stem cell transplant recipients, and to have received high-dose daptomycin treatment (>6 mg/kg). In unadjusted analyses, microbiological failure in the daptomycin MICs 3 to 4 mg/L versus 2 mg/L groups (odds ratio = 1.79, 95% CI, 0.52-6.11; P = 0.35), the median duration of bacteremia (4 days in daptomycin MICs 3-4 mg/L vs 3 days in daptomycin MIC 2 mg/L; P = 0.18) and all-cause 30-day mortality (21% in daptomycin MICs 3-4 mg/L vs 35% in daptomycin MIC 2 mg/L group; P = 0.49) were not different. In adjusted analyses, the association between higher Pitt bacteremia scores and all-cause 30-day mortality was statistically significant (P = 0.0006), whereas the association between daptomycin MICs of 3 to 4 mg/L and all-cause 30-day mortality approached statistical significance (P = 0.06). IMPLICATIONS: Duration of bacteremia and microbiological failure rates did not differ by daptomycin MICs in VRE BSI episodes in our patients, composed of adult stem cell transplant recipients and patients with hematologic malignancies. There was a nonsignificant trend in multivariable analysis suggesting that all-cause 30-day mortality was lower in patients whose VRE bloodstream isolates were with daptomycin MICs of 3 to 4 mg/L.

Glycyrrhizic Acid Decreases Gentamicin-Resistance in Vancomycin-Resistant Enterococci.

The resistance of commensal bacteria against first and second line antibiotics has reached an alarming level in many parts of the world and endangers the effective treatment of infectious diseases. Particularly vancomycin-resistant Enterococcus faecium represents an increasing clinical problem in the treatment of infectious diseases and hinders adequate antibiotic stewardship. In consideration of the lack of novel antibiotic compounds, the development of resistance-modifying agents, however, can mitigate the spread of bacterial drug resistance and might possibly extend the useful application indices of an existing licensed antibiotic. Given that saponins modify the local chemical environment at cell membranes and might modify the uptake or mode of action of antibiotics in bacteria, we investigated the influence of the triterpenoid saponin glycyrrhizic acid of Glycyrrhiza glabra on the susceptibility of vancomycin-resistant enterococci against the aminoglycoside antibiotic gentamicin in 47 clinical isolates by applying the checkerboard method. The fractional inhibitory concentration indices values were determined between 0.016 and ≤ 0.5 (synergy is accepted with values ≤ 0.5). Glycyrrhizic acid at the subinhibitory concentration of 2.4 mM was found to reduce the minimal inhibitory concentration of gentamicin in intrinsically resistant E. faecium strains down to 6.25 % of the minimal inhibitory concentration of gentamicin alone, whereas relatively low concentrations of glycyrrhizic acid (18 µM) resulted in increased susceptibilities for some E. faecium isolates to gentamicin. In conclusion, our study points towards a therapeutic potential of glycyrrhizic acid in co-application with gentamicin for defined local bacterial infections caused by vancomycin resistant Enterococcus strains.

Endophthalmitis caused by Gram-positive organisms with reduced vancomycin susceptibility: literature review and options for treatment.

BACKGROUND: Endophthalmitis caused by Gram-positive organisms with reduced vancomycin susceptibility and/or resistance is an important clinical issue worldwide. PURPOSE: To review the published literature on endophthalmitis caused by Gram-positive organisms with reduced vancomycin susceptibility and/or vancomycin resistance. METHODS: The data were analysed from a PubMed search of endophthalmitis cases caused by Gram-positive organisms with reported reduced vancomycin susceptibility and/or vancomycin resistance from 1990 to 2015. RESULTS: From 18 publications identified, a total of 27 endophthalmitis cases caused by Gram-positive organisms with reduced vancomycin susceptibility and/or vancomycin resistance were identified. The aetiologies of endophthalmitis were exogenous in 19/27 cases (11 post-cataract surgery, 2 post-penetrating keratoplasty, 1 post-glaucoma surgery, 4 post-open globe injury, 1 post-intravitreal injection of ranibizumab), and endogenous in 4/24 cases; no details were available about the four remaining patients. The causative organisms included Enterococcus species (7/27), coagulase-negative staphylococci (4/27), Staphylococcus aureus (4/27), Bacillus species (4/27), Streptococcus species (3/27), Leuconostoc species (3/27), Staphylococcus hominis (1/27), and unidentified Gram-positive cocci (1/27). Visual acuity of 20/400 or better at the final follow-up was recorded in 10/26 patients (38.5%; data were not available for one patient). Treatment options include fluoroquinolones, penicillin, cephalosporins, tetracyclines, and oxazolidinones. CONCLUSIONS: In the current study, visual acuity outcomes were generally poor. Enterococcus and Staphylococcus species were the most common organisms reported and postoperative endophthalmitis after cataract surgery was the most common clinical setting.

Outcomes of Aminopenicillin Therapy for Vancomycin-Resistant Enterococcal Urinary Tract Infections.

Vancomycin-resistant urinary tract infections are often challenging to treat. This retrospective cohort study compared outcomes between patients treated for vancomycin-resistant enterococcal urinary tract infection with an aminopenicillin and those treated with a non-ß-lactam antibiotic. Inpatients treated with an enterococcus-active agent for their first symptomatic vancomycin-resistant enterococcal urinary tract infection between 1 January 2012 and 31 December 2013 were considered for inclusion. Patients with colonization, on hospice, or receiving comfort care only were excluded. The primary endpoint of clinical cure was defined as resolution of clinical symptoms, or symptom improvement to the extent that no additional antibacterial drug therapy was necessary, and lack of microbiologic persistence. Secondary endpoints of 30-day readmission or retreatment and 30-day all-cause mortality were also compared. A total of 316 urinary isolates were screened, and 61 patients with symptomatic urinary tract infection were included. Twenty (35%) of the 57 isolates tested were ampicillin susceptible. Thirty-one patients received an aminopenicillin, and 30 received a non-ß-lactam. Rates of clinical cure for aminopenicillin versus non-ß-lactam treatment were 26/31 (83.9%) and 22/30 (73.3%) (P = 0.315), respectively. Rates of 30-day readmission (6/31, or 19.4%, versus 9/30, or 30%, respectively; P = 0.334), 30-day retreatment (4/31, or 12.9%, versus 4/30, 13.3%, respectively; P = 0.960), and 30-day all-cause mortality (2/31, or 6.5%, versus 1/30, or 3.3%, respectively; P = 0.573) were also not significantly different between groups. Aminopenicillins may be a viable option for treating vancomycin-resistant urinary tract infection regardless of the organism's ampicillin susceptibility. Prospective validation with larger cohorts of patients should be considered.

A new approach to the analysis of antibiotic resistance data from hospitals.

We aimed to develop a new approach to the analysis of antimicrobial resistance data from the hospitals, which allows simultaneous analysis of both individual- and population-level determinants of bacterial resistance. This was a retrospective cohort study that included adult patients who stayed in the hospital >2 days. We analyzed data using shared frailty Cox models and tested our approach using a priori hypotheses based on biology and epidemiology of antibiotic resistance. For gram-negative bacteria, the use of the major selecting antibiotic by an individual was the main risk factor for acquiring resistant species. Hazard ratios (HRs) were strikingly high for ceftazidime-resistant Enterobacter species (HR=11.17; 95% confidence interval [CI]: 5.67-22.02), ciprofloxacin-resistant Pseudomonas aeruginosa (HR=4.41; 95% CI: 2.14-9.08), and imipenem-resistant P. aeruginosa (HR=7.92; 95% CI: 4.35-14.43). Ward-level use was significant for vancomycin-resistant enterococci (VRE) (HR=1.40; 95% CI: 1.07-1.83) and for imipenem-resistant P. aeruginosa (HR=1.40; 95% CI: 1.08-1.83). Previous incidence of infection in the same ward increased the risk of acquiring methicillin-resistant Staphylococcus aureus (HR=1.22; 95% CI: 1.15-1.30) and VRE (HR=1.53; 95% CI: 1.38-1.70). Our results were consistent with our hypotheses and showed that combining population- and individual-level data is crucial for the exploration of antimicrobial resistance development.

Impact of different antimicrobial therapies on clinical and fiscal outcomes of patients with bacteremia due to vancomycin-resistant enterococci.

Vancomycin-resistant enterococci (VRE) are a growing health problem, and uncertainties exist regarding the optimal therapy for bloodstream infection due to VRE. We conducted systematic comparative evaluations of the impact of different antimicrobial therapies on the outcomes of patients with bloodstream infections due to VRE. A retrospective study from January 2008 to October 2010 was conducted at Detroit Medical Center. Unique patients with blood cultures due to VRE were included and reviewed. Three major therapeutic classes were analyzed: daptomycin, linezolid, and ß-lactams. Three multivariate models were conducted for each outcome, matching for a propensity score predicting the likelihood of receipt of one of the therapeutic classes. A total of 225 cases of bacteremia due to VRE were included, including 86 (38.2%) cases of VR Enterococcus faecalis and 139 (61.8%) of VR Enterococcus faecium. Bacteremia due to VR E. faecalis was more frequent among subjects treated with ß-lactams than among those treated with daptomycin or linezolid. The median dose of daptomycin was 6 mg/kg of body weight (range, 6 to 12 mg/kg). After controlling for propensity score and bacteremia due to VR E. faecalis, differences in mortality were nonsignificant among the treatment groups. Therapy with daptomycin was associated with higher median variable direct cost per day than that for linezolid. This large study revealed the three therapeutic classes (daptomycin, linezolid, and ß-lactams) are similarly efficacious in the treatment of bacteremia due to susceptible strains of VRE.

Frequency and antibiogram of vancomycin resistant enterococcus in a tertiary care hospital.

OBJECTIVE: To determine the frequency of Vancomycin Resistant Enterococcus (VRE) in a tertiary care hospital of Rawalpindi, Pakistan. STUDY DESIGN: Observational, cross-sectional study. PLACE AND DURATION OF STUDY: Department of Microbiology, Army Medical College, Rawalpindi, from May 2011 to May 2012. METHODOLOGY: Vancomycin resistant Enterococcus isolated from the clinical specimens including blood, pus, double lumen tip, ascitic fluid, tracheal aspirate, non-directed bronchial lavage (NBL), cerebrospinal fluid (CSF), high vaginal swab (HVS) and catheter tips were cultured on blood agar and MacConkey agar, while the urine samples were grown on cystine lactose electrolyte deficient agar. Later the antimicrobial susceptibility testing of the isolates was carried out using the modified Kirby-Bauer disc diffusion method on Mueller Hinton agar. RESULTS: A total of 190 enterococci were isolated. Of these, 22 (11.57%) were found to be resistant to vancomycin. The antimicrobial sensitivity pattern revealed maximum resistance against ampicillin (86.36%) followed by erythromycin (81.81%) and gentamicin (68.18%) while all the isolates were 100% susceptible to chloramphenicol and linezolid. CONCLUSION: The frequency of VRE was 11.57% with the highest susceptibility to linezolid and chloramphenicol.

Detection of vancomycin-resistant enterococci (VRE) at four U.S. wastewater treatment plants that provide effluent for reuse.

Vancomycin-resistant enterococci (VRE), a leading cause of hospital-acquired infections, can occur in wastewater. However, to date, no previous studies have evaluated the occurrence of VRE at wastewater treatment plants (WWTPs) that send their treated effluent to reuse sites. We evaluated the occurrence, concentration, and antimicrobial resistance patterns of VRE at U.S. WWTPs associated with reuse sites. We collected 44 wastewater samples, representing treatment steps from influent to effluent, from two Mid-Atlantic and two Midwest WWTPs between October 2009 and October 2010. Samples were analyzed for total enterococci and VRE using membrane filtration. Isolates were confirmed using biochemical tests and PCR. Antimicrobial susceptibility testing was performed by Sensititre microbroth dilution. Data were analyzed by two-sample proportion tests and analysis of variance. We detected VRE in 27% (12/44) of all wastewater samples collected and VRE represented 3% of total enterococci detected at all WWTPs. More samples were VRE-positive from the Mid-Atlantic compared to the Midwest WWTPs (p=0.008). VRE concentrations decreased as treatment progressed at all WWTPs, except at Mid-Atlantic WWTP1 where there was an increase in VRE concentrations in activated sludge reactor samples. VRE were not detected in chlorinated effluent, but were detected in one un-chlorinated effluent sample. All unique VRE isolates were multidrug resistant. Fifty-five percent (12/22) of the isolates displayed high-level aminoglycoside resistance. Our findings show that chlorination reduces the occurrence of VRE in wastewater. However, WWTP workers could be exposed to VRE during wastewater treatment. Our data also raise potential concerns about VRE exposure among individuals who come into contact with un-chlorinated reclaimed water.

Reduced vancomycin susceptibility in an in vitro catheter-related biofilm model correlates with poor therapeutic outcomes in experimental endocarditis due to methicillin-resistant Staphylococcus aureus.

Staphylococcus aureus is the most common cause of endovascular infections, including catheter sepsis and infective endocarditis (IE). Vancomycin (VAN) is the primary choice for treatment of methicillin-resistant S. aureus (MRSA) infections. However, high rates of VAN treatment failure in MRSA infections caused by VAN-susceptible strains have been increasingly reported. Biofilm-associated MRSA infections are especially prone to clinical antibiotic failure. The present studies examined potential relationships between MRSA susceptibility to VAN in biofilms in vitro and nonsusceptibility to VAN in endovascular infection in vivo. Using 10 "VAN-susceptible" MRSA bloodstream isolates previously investigated for VAN responsiveness in experimental IE, we studied the mechanism(s) of such in vivo VAN resistance, including: (i) VAN binding to MRSA organisms; (ii) the impact of VAN on biofilm formation and biofilm composition; (iii) VAN efficacy in an in vitro catheter-related biofilm model; (iv) effects on cell wall thickness. As a group, the five strains previously categorized as VAN nonresponders (non-Rsp) in the experimental IE model differed from the five responders (Rsp) in terms of lower VAN binding, increased biofilm formation, higher survival in the presence of VAN within biofilms in the presence or absence of catheters, and greater biofilm reduction upon proteinase K treatment. Interestingly, sub-MICs of VAN significantly promoted biofilm formation only in the non-Rsp isolates. Cell wall thickness was similar among all MRSA strains. These results suggest that sublethal VAN levels that induce biofilm formation and reduce efficacy of VAN in the in vitro catheter-associated biofilms may contribute to suboptimal treatment outcomes for endovascular infections caused by "VAN-susceptible" MRSA strains.

High vancomycin minimum inhibitory concentration and clinical outcomes in adults with methicillin-resistant Staphylococcus aureus infections: a meta-analysis.

BACKGROUND: Patients with methicillin-resistant Staphylococcus aureus (MRSA) infections caused by isolates with a high but 'susceptible' minimum inhibitory concentration (MIC) to vancomycin may suffer poor outcomes. The aim of this study was to determine the association of high compared to low vancomycin MICs and clinical outcomes (treatment failure and mortality) in patients with MRSA infections. METHODS: PubMed, the Cochrane Library, and electronic abstracts from meetings were queried from January 2000 to July 2010. Two reviewers independently screened titles and abstracts of studies evaluating outcomes of patients with MRSA infections, using broth microdilution (BMD) or the Etest to determine MIC, for full-text review. Patients participating in included studies were classified into two mutually exclusive groups: high MIC or low MIC. High MIC was defined as MIC ≥1mg/l by BMD or ≥1.5mg/l by Etest. Study-defined failure and mortality were assessed in each group. RESULTS: Fourteen publications and six electronic abstracts met the inclusion criteria, with 2439 patients (1492 high MIC and 947 low MIC). There was no evidence of publication bias or heterogeneity. An increased risk of failure was observed in the high MIC group compared to the low MIC group (summary risk ratio (RR) 1.40, 95% confidence interval (CI) 1.15-1.71). The overall mortality risk was greater in the high MIC group than in the low MIC group (summary RR 1.42, 95% CI 1.08-1.87). Sensitivity analyses showed similar findings for failure (summary RR 1.37, 95% CI 1.09-1.73) and mortality (summary RR 1.46, 95% CI 1.06-2.01) for patients with bacteremia. The study quality was poor-to-moderate, and study-defined endpoints were variable. CONCLUSIONS: A susceptible but high MIC to vancomycin is associated with increased mortality and treatment failure among patients with MRSA infections.

Achyrofuran is an antibacterial agent capable of killing methicillin-resistant vancomycin-intermediate Staphylococcus aureus in the nanomolar range.

Currently, there is a pressing need for novel antibacterial agents against drug-resistant bacteria, especially those which have been common in our communities and hospitals, such as methicillin-resistant Staphylococcus aureus (MRSA). The South American plant Achyrocline satureioides ("Marcela") has been widely used in traditional medicine for a number of diseases, including infections. Several crude extracts from this plant have shown good antimicrobial activities in vitro. In the search for the active principle(s) that confers these antimicrobial activities, we have processed the dichloromethane extract from the aerial parts of the plant. One of the isolated compounds showed extraordinary antibacterial activities against a set of clinically relevant Gram-positive strains that widely differ in their antibiogram profiles. This compound was identified as achyrofuran on the basis of its spectroscopic and physical data. We determined the MIC to be around 0.1 µM (0.07 µg/ml) for the reference methicillin-resistant and vancomycin-intermediate S. aureus strain NRS402. Moreover, nanomolar concentrations of achyrofuran killed 10(6) bacteria within 12 h. Based on the presence of the 2,2'-biphenol core, we further studied whether achyrofuran killed bacteria through a mechanism of action similar to that reported for the naturally occurring antibiotic MC21-A. Indeed, we found that achyrofuran was not bacteriolytic by itself although it greatly compromised membrane impermeability as determined by increased SYTOX Green uptake.

Antimicrobial and anti-biofilm properties of new taxodione derivative from hairy roots of Salvia austriaca.

The aim of the present report was to evaluate antimicrobial/anti-biofilm activity of 7-(2-oxohexyl)-taxodione, a novel taxodione derivative isolated from n-hexane extract of Salvia austriaca hairy roots. Antimicrobial assays showed that 7-(2-oxohexyl)-taxodione was at least 4 times more active than taxodione against methicillin-susceptible as well against methicillin-resistant staphylococci with MIC of 1.25-2.5 µgml(-1). This compound was less active against vancomycin-resistant enterococci (VRE), on the same level as taxodione (MIC ranged 10.0-20.0 µgml(-1)). The presence of 7-(2-oxohexyl)-taxodione in the culture medium (at MIC, ½ MIC or » MIC) decreased adhesion of staphylococci to abiotic surfaces, which in turn caused a reduction in biofilm formation during 24h, by approximately 25-30%. Also, the extent of established biofilm eradication was found to be significant, although it required an increased concentration of the compound. This is the first report on the antimicrobial activity of this, up to now not known compound, isolated from transformed roots of S. austriaca.

Bactericidal activity of soymilk fermentation broth by in vitro and animal models.

Soybean fermentation broth (SFB) exhibits potent antibacterial activity against different species of bacteria in in vitro assays and animal models. Four isoflavone compounds-daidzin, genistin, genistein, and daidzein-of SFB were analyzed and quantified by high-performance liquid chromatography. In the in vitro test, daidzin and daidzein had more potent antibacterial activity than genistin. The minimum inhibition concentration values for these bacteria of SFB ranged from 1.25% to 5%, and the minimum bactericidal concentration values of strains ranged from 2.5% to 10%, depending on the species or strain. Vancomycin-resistant Entercoccus faecalis (VRE) strains were also tested for susceptibility to SFB in two species of animal model: the Sprague-Dawley rat and the BALB/c mouse. SFB-fed Sprague-Dawley rats showed excellent elimination efficiency against VRE, close to 99% compared with the phosphate-buffered saline-fed control group. In the BALB/c mouse model, SFB antibacterial activity was 65-80% against VRE compared with the control. In conclusion, SFB contains natural antibacterial substances such as daidzin, genistin, and daidzein that inhibit bacterial growth.

Synergistic properties of the terpenoids aromadendrene and 1,8-cineole from the essential oil of Eucalyptus globulus against antibiotic-susceptible and antibiotic-resistant pathogens.

The aim of the present study was to investigate the chemical composition of the essential oil of the fruits of Eucalyptus globulus and to examine the potential application of the fruit oil against multidrug-resistant bacteria. GLC/MS analysis in the fruit oil showed that aromadendrene was the main compound followed by 1,8-cineole and globulol. The three most abundant components of the fruit oil were also tested individually against microorganisms. In addition, the synergistic effects of combinations of the major constituents (aromadendrene and 1,8-cineole) of the fruit oil were also investigated. All Gram-positive bacteria were susceptible to the fruit oil with different degrees of susceptibility as determined by microdilution method. The oil exerted a marked inhibition against multidrug-resistant bacteria such as methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE) Enterococcus faecalis. The results indicated that aromadendrene might be responsible for the antimicrobial properties, whereas 1,8-cineole and globulol exhibited low activities. The checkerboard assay demonstrated that combinations of 1,8-cineole and aromadendrene reduce the MIC in most cases in an additive way, whereas the time-kill assay indicates a synergistic effect.