More Antibiotic Resistance Problems

A hospital in the UK has reported an outbreak of nasty MRSA infections.
 This time, the organisms are the PVL-producing MRSA.

MRSA stands for Methicillin-resistant Staphylococcus aureus.
 PVL stands for Panton-Valentine leukocidin.  PVL is
a toxin produced by the bacteria.  As the name suggests, it
kills white blood cells.  

New strain of superbug targets the young, and its latest victim is an
NHS nurse

By Jeremy Laurance, Health Editor

Published: 18 December 2006

A nurse and a patient have died from a deadly new
strain of MRSA after a superbug outbreak at a hospital.

The Health Protection Agency said three other nurses in the West
Midlands hospital were among eight people who contracted the new, more
lethal strain of MRSA, four of whom have infections including boils and
abscesses. Two have died.

It is the first time that the toxic strain of the superbug, known as
PVL-producing MRSA, has caused infection and deaths in a hospital, the
agency said. The outbreak has alarmed public health officials who say
it could pose risks for staff as well as patients...

Just how nasty is this bug?

Richard Campbell-Smith was just four weeks from
completing his training as a Royal Marine when he scratched himself on
a gorse bush during a week-long training exercise in October 2004.

The 18-year-old recruit, described as "super-fit", contracted the
common bacterial bug staphylococcus, which usually produces a small
amount of pus in a graze.

But he was soon finding it hard to walk and was admitted to the medical
centre in Lympstone, Devon. Two days later he collapsed by his bed and
was taken to hospital. He died there from what doctors said was heart
and respiratory failure...

I don't know the particulars of this case, but it seems likely that he
must have had some particular susceptibility, combined with the high
virulence of the organism, to have such a dramatic outcome.  

It is not clear what role the PVL toxin plays.  It seems
plausible that a toxin that kills white blood cells would increase the
lethality of an infectious organism, but that may not be the case,
according to researchers at the University of Chicago:

Panton-Valentine Leukocidin the Major Virulence Determinant in
Community-Associated Methicillin-Resistant Staphylococcus aureus

The Journal of Infectious Diseases, volume 194 (2006),
pages 1761–1770

DOI: 10.1086/509506

PubMed ID: 17109350

    Methicillin-resistant Staphylococcus
aureus (MRSA) remains a major problem in hospitals, and it is now
spreading in the community. A single toxin, Panton-Valentine leukocidin
(PVL), has been linked by epidemiological studies to
community-associated MRSA (CA-MRSA) disease. However, the role that PVL
plays in the pathogenesis of CA-MRSA has not been tested directly. To
that end, we used mouse infection models to compare the virulence of
PVL-positive with that of PVL-negative CA-MRSA representing the leading
disease-causing strains. Unexpectedly, strains lacking PVL were as
virulent in mouse sepsis and abscess models as those containing the
leukotoxin. Isogenic PVL-negative (lukS/F-PV knockout) strains of
USA300 and USA400 were as lethal as wild-type strains in a sepsis
model, and they caused comparable skin disease. Moreover, lysis of
human neutrophils and pathogen survival after phagocytosis were similar
between wild-type and mutant strains. Although the toxin may be a
highly linked epidemiological marker for CA-MRSA strains, we conclude
that PVL is not the major virulence determinant of CA-MRSA.

This underscores the importance of not making assumptions, no matter
how plausible they may seem.  You have to do the study to
check your assumptions.  It the case of PVL-producing MRSA, it
may be that the antibiotic resistance is the more important factor.
 More studies are needed, obviously.  If we can
figure out what it is about this organism that makes it so virulent, we
might be able to figure out how to stop it.  More importantly,
if it teaches us something we do not currently know about the
pathophysiology of infection, we might be able to generalize what we
learn from this, and apply it to other kinds of infections.


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