Design, expression, and characterization of a novel targeted plectasin against methicillin-resistant Staphylococcus aureus.

Oct 2012

Mao R, Teng D, Wang X, Xi D, Zhang Y, Hu X, Yang Y, Wang J.

Source

Key Laboratory of Feed Biotechnology, Ministry of Agriculture, Beijing, 100081, China.

Abstract

A novel specifically targeted antimicrobial peptide (STAMP) that was especially effective against methicillin-resistant Staphylococcus aureus (MRSA) was designed by fusing the AgrD1 pheromone to the N-terminal end of plectasin. This STAMP was named Agplectasin, and its gene was synthesized and expressed in Pichia pastoris X-33 via pPICZαA. The highest amount of total secreted protein reached 1,285.5 mg/l at 108 h during the 120-h induction. The recombinant Agplectasin (rAgP) was purified by cation exchange chromatography and hydrophobic exchange chromatography; its yield reached 150 mg/l with 94 % purity. The rAgP exhibited strong bactericidal activity against S. aureus but not Staphylococcusepidermidis or other types of tested bacteria. A bactericidal kinetics assay showed that the rAgP killed over 99.9 % of tested S. aureus (ATCC 25923 and ATCC 43300) in both Mueller-Hinton medium and human blood within 10 h when treated with 4× minimal inhibitory concentration. The rAgP caused only approximately 1 % hemolysis of human blood cells, even when the concentration reached 512 μg/ml, making it potentially feasible as a clinical injection agent. In addition, it maintained a high activity over a wide range of pH values (2.0-10.0) and demonstrated a high thermal stability at 100 °C for 1 h. These results suggested that this STAMP has the potential to eliminate MRSA strains without disrupting the normal flora.

PubMed

Nursing home characteristics associated with methicillin-resistant Staphylococcus aureus (MRSA) Burden and Transmission.

Oct 2012

Murphy CR, Quan V, Kim D, Peterson E, Whealon M, Tan G, Evans K, Meyers H, Cheung M, Lee BY, Mukamel DB, Huang SS.

Abstract

BACKGROUND: MRSA prevalence in nursing homes often exceeds that in hospitals, but reasons for this are not well understood. We sought to measure MRSA burden in a large number of nursing homes and identify facility characteristics associated with high MRSA burden.

METHODS:

We performed nasal swabs of residents from 26 nursing homes to measure MRSA importation and point prevalence, and estimate transmission. Using nursing home administrative data, we identified facility characteristics associated with MRSA point prevalence and estimated transmission risk in multivariate models.

RESULTS:

We obtained 1,649 admission and 2,111 point prevalence swabs. Mean MRSA point prevalence was 24%, significantly higher than mean MRSA admission prevalence, 16%, with a mean estimated MRSAtransmission risk of 16%.In multivariate models, higher MRSA point prevalence was associated with higher admission prevalence and higher proportions of residents with indwelling devices . Higher estimated MRSAtransmission risk was associated with higher proportions of residents with diabetes  and lower levels of social engagement .

CONCLUSIONS:

MRSA importation was a strong predictor of MRSA prevalence, but MRSA burden and transmission were also associated with nursing homes caring for more residents with chronic illnesses or indwelling devices. Frequent social interaction among residents appeared to be protective of MRSA transmission, suggesting that residents healthy enough to engage in group activities do not incur substantial risks of MRSA from social contact. Identifying characteristics of nursing homes at risk for high MRSA burden and transmission may allow facilities to tailor infection control policies and interventions to mitigate MRSA spread.

PubMed

Hand hygiene, not isolation, reduces MRSA

October 25, 2012 | By Karen Cheung-Larivee

Proper hand hygiene can reduce methicillin-resistant Staphylococcus aureus (MRSA) infections by as much as 95 percent, according to Virginia Commonwealth University researchers. In a nine-year study, researchers found horizontal infection-prevention strategies that encourage hand washing to prevent MRSA and other infections that are transmitted via contact could be more effective than the traditional vertical approach of simply isolating MRSA patients. Isolating patients not only causes feelings of anxiety and depression, but also results in fewer visits by providers and increases the chances of bed sores and falls, lead investigator Michael B. Edmond, chair of infectious diseases at the VCU School of Medicine, said in a statement yesterday. "Patient safety is the key benefit to this approach. We found that it not only prevents MRSA, but other infections that are transmitted via contact. It can also save hospitals a lot of money," Edmond said.

Read more: Hand hygiene, not isolation, reduces MRSA - FierceHealthcare http://www.fiercehealthcare.com/story/hand-hygiene-not-isolation-reduces-mrsa/2012-10-25#ixzz2APOmHfVR
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In vitro activities of antibiotics and antimicrobial cationic peptides alone and in combination against methicillin resistance Staphylococcus aureus biofilms.

Oct 2012

Mataraci E, Dosler S.

Source

Department of Pharmaceutical Microbiology Faculty of Pharmacy, Istanbul University, 34116, Beyazit-Istanbul, Turkiye.

Abstract

Methicillin-resistant Staphylococcus aureus (MRSA) strains are most often found in hospital and community-acquired infections. The danger of MRSA infections results from not only the emergence of multi-drug resistance but also the occurrence of strong biofilm forming bacteria. We investigated the in-vitro activities of antibiotics (daptomycin, linezolid, teichoplanine, azithromycin and ciprofloxacin) and antimicrobial cationic peptides (AMPs; indolicidin, CAMA: cecropin (1-7)-melittin A (2-9) amide, and nisin) alone or in combination against MRSA ATCC 43300 biofilms. The minimum inhibitory concentrations (MIC) and minimum biofilm eradication concentrations (MBEC) were determined by microbroth dilution technique. Antibiotic and AMP combinations were assessed using the chequerboard technique. For MRSA planktonic cells, MICs of antibiotics and AMPs were ranged between 0.125-512 and 8-16 mg/L, and the MBEC values of them were 512-5120 and 640 mg/L, respectively. With a fractional inhibitory concentration of ≤ 0.5 as borderline, synergistic interactions againstMRSA biofilms were frequent with almost all antibiotic-antibiotic and antibiotic-AMP combinations. Against planktonic cells, they generally had an additive effect. No antagonism was observed. All of the antibiotics, AMPs, and their combinations were able to inhibit the attachment of bacteria at the 1/10xMIC and biofilm formation at 1xMIC. Biofilm-associated MRSA was not affected by therapeutically achievable concentrations of antimicrobial agents. Using a combination of antimicrobial agents can provide a synergistic effect, which rapidly enhances anti-biofilm activity and may help prevent or delay the emergence of resistance. AMPs seem to be a good candidate for further investigations in the treatment of MRSA biofilms, alone or in combination with antibiotics.

American Society for Microbiology

Impact of vancomycin minimum inhibitory concentration on clinical outcomes of patients with vancomycin-susceptible Staphylococcus aureus infections: a meta-analysis and meta-regression.

Oct 2012

Mavros MN, Tansarli GS, Vardakas KZ, Rafailidis PI, Karageorgopoulos DE, Falagas ME.

Source

Alfa Institute of Biomedical Sciences (AIBS), Athens, Greece; Department of Surgery, Massachusetts General Hospital & Harvard Medical School, Boston, MA, USA.

Abstract

Although the vancomycin minimum inhibitory concentration (VMIC) susceptibility breakpoint for Staphylococcus aureus was recently lowered to ≤2mg/L, it is argued that isolates in the higher levels of the susceptible range may bear adverse clinical outcomes. Clinical outcomes (all-cause mortality and treatment failure) of patients with S. aureus infections by 'high-VMIC' (conventionally defined as VMIC >1mg/L but ≤2mg/L) and 'low-VMIC' (VMIC≤1mg/L) isolates were compared by performing a systematic review and meta-analysis. The effect of potential confounders was assessed by univariate meta-regression analyses. In total, 33 studies (6210 patients) were included. Most studies were retrospective (28/33), used the Etest (22/33) and referred to meticillin-resistant S. aureus (MRSA) infections (26/33) and bacteraemia (23/33). Irrespective of VMIC testing method, meticillin resistance and site of infection, the high-VMIC group had higher mortality [relative risk (RR)=1.21 (95% confidence interval 1.03-1.43); 4612 patients] and more treatment failures [RR=1.67 (1.26-2.21); 2049 patients] than the low-VMIC group. The results were not affected by the potential confounders and were reproduced in the subset of patients withMRSA infections [mortality, RR=1.19 (1.02-1.40), 2956 patients; treatment failure, RR=1.69 (1.26-2.25), 1793 patients]. In conclusion, infection by vancomycin-susceptible S. aureus with VMIC>1mg/L appears to be associated with higher mortality than VMIC≤1mg/L. Further research is warranted to verify these results and to assess the impact of VMIC on meticillin-susceptible S. aureus infections. Evaluation of alternative antimicrobial agents also appears justified.

Elsevier