MRSA (Mersa) Questions

Concern that VRSA could spread into community

Link: HighWire Press -- Medline Abstract.

To gain a better understanding of epidemiology of resistance in Staphylococcus aureus, we describe the molecular epidemiology of methicillin-resistant Staphylococcus aureus bloodstream isolates in Urban Detroit. Bloodstream isolates from July 2005 to February 2007 were characterized. Two hundred and ten bloodstream isolates from 201 patients were evaluated. Patient characteristics were: median age 54 years, 56% male, 71% African-American. Seventy-six percent of infections were health care-associated, with 55% community onset and 21% hospital acquired, and 24% were community-associated. The most common sources were skin/wound (25%), central venous catheters (24%), unknown source (20%) and endocarditis (9%). Ninety percent and 5 % of isolates had MIC to vancomycin of /=1.5 mg/L. Results of PFGE showed seventeen strain types. The predominant strains were USA100 (104 isolates) and USA300 (74 isolates). Forty-nine percent of the isolates were SCCmec II and 56% were agr II. All USA300 isolates were positive for the PVL toxin genes and agr I. Forty-seven percent of USA300 bloodstream infections were health care-associated (35% community onset and 12% hospital onset). USA300 strains were more common in injection drug users with skin/wound as the predominant source of infection. Thirty percent of the USA100 strains were closely related to vancomycin-resistant Staphylococcus aureus isolates. The results of this study show that vancomycin MICs using automated dilution testing with Vitek-2 and E-test is highly discordant. Most MRSA causing bacteremia are health care-associated, commonly have MICs to vancomycin that are high within the susceptible range, and are not detected by routine automated dilution testing and have significant diversity of molecular characteristics. USA100 strains that are closely related to VRSA isolates and USA300 strains are common as causes of both hospital and community onset infection. Infection control measures should focus not only on prevention of spread of community strains in the hospital but also prevention of spread of hospital strains associated with VRSA into the community.

VRSA emerges in Detroit

Link: Mich. doctors fear new germ could spread easily | Freep.com | Detroit Free Press.

Seven of nine confirmed cases of a new and potentially deadly bacteria have emerged in metro Detroit, and experts fear the drug-resistant germ may develop the ability to spread easily. Advertisement "Doctors are more than concerned. We are alarmed," said Dr. Marcus Zervos, head of infectious diseases for the Henry Ford Health System. "We don't want this bacteria to become more communicable. We know that would be a nightmare." The bacteria, which often causes skin boils, is called Vancomycin-resistant Staphylococcus aureus, or VRSA. It's a close cousin of MRSA, or Methicillin-resistant Staphylococcus aureus. That's the antibiotic-resistant infection that killed a Virginia teenager last spring. The incident prompted scores of schools across the country, including about a half-dozen in the Detroit area, to temporarily close and disinfect. No one has died of the VRSA bacteria, which so far has infected only people with chronic health problems, such as diabetes or kidney failure. Those diseases affect more than 500,000 Michiganders and often come with open sores or catheter wounds where VRSA can breed.

VRSA case in India

Link: Identification and characterization of a vancomycin-resistant Staphylococcus aureus isolated from Kolkata (South Asia) -- Saha et al. 57 (1): 72 -- Journal of Medical Microbiology.

A pathogenic vancomycin-resistant Staphylococcus aureus (VRSA) isolate (MIC ≥64 �g ml–1) was obtained from a Kolkata hospital in June 2005. Species identification was confirmed by Gram staining, standard biochemical tests and PCR amplification of the nuc gene, which encodes the thermostable nuclease that is highly specific for S. aureus. The VRSA isolate was also resistant to beta-lactams (amoxicillin, ampicillin, cefepime, cefotaxime, cefuroxime, cephalexin and meticillin), chloramphenicol, streptomycin, macrolides (erythromycin and roxithromycin), clindamycin, rifampicin and trimethoprim-sulfamethoxazole. However, the isolate was susceptible to gentamicin (an aminoglycoside) and ciprofloxacin (a fluoroquinolone). The resistance to vancomycin was inducible in vitro, because the MIC of vancomycin increased from 64 �g ml–1 initially to 1024 �g ml–1 during culture of this VRSA strain in the presence of vancomycin. The VRSA isolate contained a large plasmid (~53.4 kb) and four small plasmids of ~6, 5.5, 5.1 and 1.5 kb. The large plasmid of ~53.4 kb harboured the vancomycin-resistance genes vanHAX, which was confirmed by PCR amplification using the same plasmid as template and, separately, primers specific for the 2.61 kb vanHAX gene cluster, vanH (969 bp), vanA (1032 bp) and vanX (609 bp). The VRSA isolate was also positive for mecA. Vancomycin resistance was successfully transferred from this VRSA donor to a vancomycin-sensitive recipient S. aureus clinical isolate by a broth mating procedure. The MIC of vancomycin for the transconjugant was 32 �g ml–1, as against 2 �g ml–1 for the parent strain. Nucleotide sequencing of the PCR product showed partial homology with van genes of an enterococcal transposon Tn1546-like element. This is believed to be the first Indian S. aureus isolate that has been shown to be phenotypically vancomycin-resistant, presumably due to a vanHAX analogue.

Vancomycin Resistance Emerging

Link: HighWire Press -- Medline Abstract.

RESULTS: A total of 20 out of 209 MRSA bacteraemia patients were treated with vancomycin for at least 5 days with adequate trough levels, and fulfilled the study's inclusion and exclusion criteria. Twenty-two S. aureus isolates from these patients' blood cultures were identified as MRSA, including two hetero-VISA from separate patients and two VISA with vancomycin MIC of 4 mg/L from one patient. Between patients who showed 'good' vancomycin response and patients who did not, there was a significant difference (p < 0.01) in their corresponding MRSAs' vancomycin susceptibility expressed by 'area under curve' (AUC) of population analysis. Significant correlations were found between AUC and initial vancomycin therapeutic response parameters of 'days till afebrile' (r = 0.828, p < 0.01) and 'days till CRP <= 30% of maximum' (r = 0.627, p < 0.01) CONCLUSIONS: Our study results caution healthcare personnel that early consideration should be given to cases with a poor vancomycin treatment response that could signify the involvement of MRSA with reduced susceptibility to vancomycin.

Action of New Cephalosporin Antibiotics Effective Against MRSA & VRSA

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.

VRSA drug identified?

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.

VISA a sign of resistance to other drugs

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.

Characterisation of laboratory-generated vancomycin intermediate resistant Staphylococcus aureus strains.

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.

VRSA sufferer struggling back to normality

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.

3% colnised with VRE and MRSA?

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.