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Link: Journal of Biological Chemistry.
Emergence of methicillin-resistant Staphylococcus aureus (MRSA) has created challenges in treatment of nosocomial infections. The recent clinical emergence of vancomycin-resistant MRSA is a new disconcerting chapter in the evolution of these strains. S. aureus normally produces four PBPs, which are susceptible to modification bybeta-lactam antibiotics, an event that leads to bacterial death. The gene product of mecA from MRSA is a penicillin-binding protein (PBP) designated PBP 2a. PBP 2a is refractory to the action of all commercially available beta-lactam antibiotics. Furthermore, PBP 2a is capable of taking over the functions of the other PBPs of S. aureus in the face of the challenge by beta-lactam antibiotics. Three cephalosporins (compounds 1–3) have been studied herein, which show antibacterial activities against MRSA, including the clinically important vancomycin-resistant strains. These cephalosporins exhibit substantially smaller dissociation constants for the preacylation complex compared with the case of typical cephalosporins, but their pseudo-second-order rate constants for encounter with PBP 2a (k2/Ks) are not very large (≤200 M–1 s–1). It is documented herein that these cephalosporins facilitate a conformational change in PBP 2a, a process that is enhanced in the presence of a synthetic surrogate for cell wall, resulting in increases in the k2/Ks parameter and in more facile enzyme inhibition. These findings argue that the novel cephalosporins are able to co-opt interactions between PBP 2a and the cell wall in gaining access to the active site in the inhibition process, a set of events that leads to effective inhibition of PBP 2a and the attendant killing of the MRSA strains.
Link: Journal of Medical Microbiology.
A bromotyrosine alkaloid family of antimicrobial agents was synthesized using the known structure of a natural inhibitor of the mycobacterial mycothiol S-conjugate amidase (MCA) as a template. This series of compounds represents a novel class of anti-infective agents against Gram-positive pathogens, including mycobacteria and meticillin- and vancomycin-resistant Staphylococcus aureus. The fact that these compounds are active against mycobacterial strains in which the MCA gene is deleted and against Gram-positive bacteria lacking mycothiol suggests the existence of an alternative target for these compounds. One member of this family, EXEG1706, was identified as the lead compound possessing low MICs (2�5–25 �g ml–1) for several clinical isolates, whilst having low toxicity for THP-1 monocytes and macrophages.
Link: Antimicrobial Agents and Chemotherapy.
We present here findings of a strong positive correlation between reduced daptomycin susceptibility and vancomycin resistance in vancomycin-intermediate Staphylococcus aureus (VISA). This correlation is related to cell wall thickening, suggesting that, similar to the case with vancomycin resistance in VISA, the physical barrier of a thickened cell wall may contribute to daptomycin resistance in S. aureus.
Link: Characterisation
Vancomycin has been the drug of choice for 30 years for the treatment of methicillin-resistant Staphylococcus aureus (MRSA). Emergence of decreased vancomycin susceptibility in MRSA strains presents a significant clinical problem with few therapeutic options. This study was performed to generate and characterise S. aureus strains with reduced susceptibility to vancomycin. Eighteen S. aureus strains were subjected to serial passaging on vancomycin to generate vancomycin intermediate resistant S. aureus (VISA) strains. Minimum inhibitory concentration (MIC) determination was performed for the parent and the passaged cultures with 13 different antibiotics. The strains were tested by the following five methods: simplified population analysis; CDC method; modified vancomycin agar screen; population analysis profile (PAP); and modified population analysis (PAP-area under the curve (AUC) ratio). Phenotypic changes such as doubling time, synergy with beta-lactam antibiotics and effect on norA efflux pumps were also studied for these strains. The result indicated that 8 VISA mutants (vancomycin MICs, 8-16mug/mL) were generated in vitro from the 18 S. aureus strains. The CDC and modified agar methods proved to be the most sensitive and specific methods for detection of VISA strains. The PAP for all the VISA strains ranged from 12mug/mL to >16mug/mL, with a PAP-AUC ratio of >1.3. All mutants showed increased doubling time compared with their parent isolate. Synergism of the vancomycin and beta-lactam combinations was observed for all methicillin-resistant mutants. Upon acquisition of vancomycin resistance, a few mutants showed decreased oxacillin resistance. Two VISA strains were chosen for molecular characterisation of the mecA gene and one mutant showed genotypic changes with deletion of mecA. Loss of norA efflux pumps leading to fluoroquinolone sensitivity was also observed in four mutants.
Link: News - Spalding Today
"I think that over the period I was sedated it must have got into my head what had happened as when I woke up I didn't notice that my legs had been amputated." Sue said that Alan seemed to recover within five days but then he contracted VRSA (Vancomycin Resistant Straphy-lococccus Aureus), a more dangerous form of MRSA. But high doses of antibiotics led to Alan developing bacterial virus Clostridium. He was again treated with antibiotics but insisted on being released early to spend New Year's Eve with his wife. Alan threw himself into rehabilitation, which started in spring 2004, and was inspired by other people at the clinic.
Link: HighWire Press -- Medline Abstract.
The danger here is that VRE will combine with MRSA to cause VRSA and therefore cause the treatment community to lose a key drug. This article notes that nearly 3% of patients had colonies of both but that only deliberate testing revealed this.
We assessed the prevalence, risk factors, and clinical outcomes of patients co-colonized with vancomycin-resistant enterococci (VRE) and methicillin-resistant Staphylococcus aureus (MRSA) upon admission to the medical and surgical intensive care units (ICUs) of a tertiary-care facility between January 1, 2002, and December 31, 2003. Co-colonization was defined as a VRE-positive perirectal surveillance culture with an MRSA-positive anterior nares surveillance culture collected concurrently. Among 2,440 patients, 65 (2.7%) were co-colonized. Independent risk factors included age (odds ratio [OR] 1.03, 95% confidence interval [CI] 1.01-1.05), admission to the medical ICU (OR 4.38, 95% CI 2.46-7.81), male sex (OR 1.93, 95% CI 1.14-3.30), and receiving antimicrobial drugs on a previous admission within 1 year (OR 3.06, 95% CI 1.85-5.07). None of the co-colonized patients would have been identified with clinical cultures alone. We report a high prevalence of VRE/MRSA co-colonization upon admission to ICUs at a tertiary-care hospital.
Link: Investigation of beta-lactam antibiotic-induced vancomycin-resistant MRSA (BIVR)..
We could not detect hetero-vancomycin-intermediate resistant Staphylococcus aureus (hetero-VISA), according to the definition of hetero-VISA, from the clinical isolates of 140 methicillin-resistant S. aureus (MRSA) strains. However, 15 beta-lactam antibiotic-induced vancomycin-resistant MRSA (BIVR) strains were detected from the same strains. We screened 1882 MRSA clinical isolates obtained in 2002 from 21 institutes throughout Japan. The detection rate of blood-isolated BIVR was 12.6% (19/151), and that of nonblood-isolated BIVR was 4.9% (85/1731; P < 0.001; chi2 test). Uridine-diphosphate-N-acetylmuramyl-L: -alanyl-D: -isoglutamyl-L: -lysine, used as the peptidoglycan material of S. aureus, showed the same results as beta-lactam antibiotics in BIVR.
The in vitro combination effects of pazufloxacin (PZFX) with an anti-MRSA drug such as vancomycin (VCM), teicoplanin (TEIC), arbekacin (ABK), minocycline (MINO), rifampicin (RFP) and sulfamethoxazole-trimethoprim (ST) were investigated against 26 strains of beta-lactam antibiotic induced vancomycin-resistant MRSA (BIVR) by the checkerboard method. The additive and synergistic effects were observed with the combination of PZFX and VCM (50%, 13/26 strains), PZFX and TEIC (96%, 25/26 strains), PZFX and ABK (65%, 17/26 strains), PZFX and MINO (46%, 12/26 strains), PZFX and ST (54%, 14/26 strains). The synergistic effects were observed with the combination of PZFX and TEIC (4%, 1/26 strains), PZFX and ABK or MINO (15%, 4/26 strains). The antagonistic effects were observed with only PZFX and MINO (12%, 3/26 strains), others were all indifference.
Reduced susceptibility or resistance to vancomycin has been reported among clinical isolates of staphylococci in previous studies. In the present study we report on the isolation of four vancomycin-resistant staphylococcal strains from healthy carriers inside and outside the hospital environment. These carriers did not receive treatment with any antibiotic.
Link: Journal of Biological Chemistry.
The non-pathogenic, non-glycopeptide-producing actinomycete Streptomyces coelicolor carries a cluster of seven genes (vanSRJKHAX) that confers inducible, high-level resistance to vancomycin.
(Very technical but of interest to VRSA researchers)
Link: HighWire Press -- Medline Abstract.
Individuals undergoing hemodialysis may be at increased risk for emerging antimicrobial resistance from vancomycin-intermediate Staphylococcus aureus (VISA) and vancomycin-resistant S. aureus (VRSA). The laboratory detection of VISA and VRSA is challenging and requires the use of well-thought-out algorithms.
Link: HighWire Press -- Medline Abstract.
Antimicrobial susceptibilities and genetic relatedness of the vancomycin-resistant Staphylococcus aureus strain (VRSA) isolated at Hershey, Pa. (VRSA Hershey), and its vancomycin-susceptible and high-level-resistant derivatives were studied and compared to 32 methicillin-resistant S. aureus strains (MRSA) isolated from patients and medical staff in contact with the VRSA patient.
Link: Antimicrobial Agents and Chemotherapy.
To investigate the prevalence of Staphylococcus aureus with reduced susceptibility to vancomycin among methicillin-resistant S. aureus (MRSA) strains in Asian countries, a total of 1,357 clinical isolates of MRSA collected from 12 Asian countries were screened by using brain heart infusion agar plates containing 4 mg of vancomycin per liter. The presence of strains that were heterointermediately resistant to vancomycin (hVISA) was confirmed by population analysis. Of 347 (25.6%) MRSA isolates that grew on the screening agar plates, 58 isolates (4.3%) were hVISA.
JAMA
Additional testing at CDC indicated that Microscan® and Vitek® (bioMerieux, Hazelwood, Missouri) testing panels and cards available in the United States did not detect vancomycin resistance in this VRSA isolate. Consequently, additional VRSA infections might have occurred but were undetected by laboratories using automated methods
Resistant Microbes, Antibiotic Abuse, and the Threat to Public Health
The reason why we are so concerned with vancomycin-resistant enterococcus (VRE), is because VRE + MRSA could lead to VRSA--a vancomycin-resistant S. aureus or "Catastrostaph," as I call it. In 1991 a scientist named Nobel was able to show in the laboratory that VRE could transmit its highly resistant gene to S. aureus and cause the proliferation of this super bug. Nobel was so concerned about it that he destroyed his isolates.
Medscape
Very technical item about MRSA strains and resistance to Vancomycin. Not good news but worth reading
Scientific American
But some bacteria that are closely related to S. aureus--which often causes life-threatening infections in hospital settings--can fend off vancomycin, prompting concerns that soon S. aureus will, too. Scientists describe one instance of a vancomycin-resistant strain of the ubiquitous bug in the current issue of the journal Science and show that the gene responsible for its invulnerability jumped from another bacteria.
sundaymail
A NEW superbug at least as deadly as MRSA is sweeping Scottish hospitals.
Known victims of VRE (Vancomycin Resistant Enterococci) have soared by nearly 50 per cent but doctors believe many cases go unreported.
Business Week
This is an article that extols the the possibility of a particular drug cure. But it's challenging reading nevertheless
Medscape
The VRSA problem is linked to co-infection from VRE, where resistant organisms corrupt MRSA to create VRSA. (Two diseases mate in laymans terms!). This article also notes that automated tests may be missing VRSA and that other methods may be needed to ensure that it is monitored properly
Bangkok's Independent Newspaper
VRSA colonised people are beggining to be identified within the Thai hospital system
ic Southlondon
VISA, the next step after MRSA and the forerunner of the fully fledged VRSA has come to Britian
Dr. Koop All 5 MRSA strains are now thought to be resistant to vancomycin, up till now a key treatment for the bug.
this is bristol
This widely reported item suggest that VRSA is on the rise but also mentions a new spray for use in hygiene responses to MRSA. Doctors fear the bug will continue to mutate
MRSA - Here to stay?
This a helpful overview of the issues surrounding the medical nature of MRSA. It also highlights the emergence of VRSA - strains of the virus that are resitant to the vaccine vancomycin used to treat MRSA. This a thorough and useful introduction to the subject
A short introduction from Dave Roberts
This 12 minute introduction will help you grasp the key facts and the key issues surrounding drug resistant staph aureus (mersa, mursa)
