Transcript lynfield_part2

Regulation of erm Methylase
Constitutive
ermC
Inducible
ermI
Methylase
Methylase
Macrolides
Inducible Macrolide-LincosamideStreptogramin B (MLSB) Phenotype
E
C
E
C
Blunted Zone
Zone of Inhibition
Clinical Implications
Constitutive mutants, which can occur at a
frequency of ~10-7cfu, may be selected during a
course of clindamycin therapy in patients with
infections due to inducible clindamycin-resistant
strains of S. aureus
Genome and Virulence of CA-MRSA
• CA-MRSA isolate from one fatal case sent to Japan
(PFGE subtype MR 14A)
• CA-MRSA (MW2) genome sequenced
• MW2 grows faster than HA-MRSA strains
• MW2 has SCCmec type IVa (types I-III typically seen
in HA-MRSA strains)
• MW2 has unique virulence genes (including PVL)
• Lethal dose of MW2 in an animal model is five times
less than a comparison Japanese HA-MRSA strain
Baba et al. Lancet. 2002; 359:1819-27
Panton-Valentine Leukocidin (PVL)
• S. aureus cytotoxin formed from 2 synergistic
proteins
• Causes tissue necrosis (skin and mucosa) and
leukocyte destruction by forming pores in cellular
membranes
• PVL identified in 7 isolates from fatal CA-MRSA MN
patients; 6 with necrotizing pneumonia
Effects of PVL on PMNs
Without PVL
With
PVL
Exotoxin Genes and Gene Alleles
• 26 CA-MRSA and 26 HA-MRSA isolates underwent
polymerase chain reaction to detect gene sequences
• Panton-Valentine leukocidin*, staphylococcal
enterotoxins A,C, H, and K, accessory gene regulator
3 and SCCmec IV were significantly more likely to be
found among CA-MRSA isolates
• Staphylococcal enterotoxins D, G, I, J, M, N, O,
accessory gene regulator 2, and SCCmec II were
significantly more likely to be found among HA-MRSA
isolates
* Produces exotoxin causing tissue necrosis and leukocyte destruction, has
been associated with cases of necrotizing pneumonia, skin abscesses
Management of Skin and Soft
Tissue CA-MRSA Abscesses
Observational study: 69 children, TX 5/02-3/03,
ER/acute care clinic
– Incision and drainage effective management
(only 7% given initial antibiotic active against
their isolate)
– Predictor of hospitalization was initial lesion
> 5 cm (p=0.004)
Lee. Ped Infec Dis J. 2004; 23: 123-7.
Hospital Transmission of CA-MRSA
• 8 postpartum women developed skin
and soft tissue infections
– 5 re-hospitalizations, 3 required
surgical drainage
– Isolates indistinguishable by PFGE
– CA-MRSA strain (MW2)
Saiman. Clin Infect Dis. 2003; 37:1313-9.
Conclusions
• CA-MRSA strains have distinct molecular and
microbiologic features compared with HAMRSA strains
• The emergence of MRSA in the general
population has important clinical implications
because empiric therapy is generally a betalactam antimicrobial agent
• Additional evaluation needed on treatment
options for non-severe infection
• CA-MRSA susceptibility trends in other
antimicrobial classes should be monitored
Conclusions (cont.)
• More information is needed on the clinical
impact of inducible clindamycin-resistant
strains
• More information is needed on the impact of
bacterial virulence factors on severity of CAMRSA infections
• Risk factor studies are needed to identify
persons at risk and optimal methods of
prevention
• CA-MRSA strains have been detected in
hospital settings and have been associated
with nosocomial infection
Antimicrobial Resistance
“… the microbes are educated to
resist penicillin and a host of
penicillin-fast organisms is bred out
which can be passed on to other
individuals and perhaps from there
to others until they reach someone
who gets a septicemia or a pneumonia which penicillin cannot
save. In such cases the thoughtless person playing with
penicillin treatment is morally responsible for the death of the
man who finally succumbs to infection with the penicillinresistant organism. I hope this evil can be averted.”
~ Sir Alexander Fleming, New York Times, 6/26/45
Acknowledgements
Active Bacterial Core Surveillance Staff, Infection Control
Practitioners and Microbiologists in CT, GA, MD, MN;
Monica Farley, Lee Harrison
CDC:
Scott Fridkin, Jeff Hageman, Monina Klemens,
Melissa Morrison and Fred Tenover
MDH: Joanne Bartkus, John Besser, Dave Boxrud, Jessica Buck,
Elizabeth Cebelinski, Kathy Como-Sabetti, Richard Danila,
Anita Glennen, Billie Juni, Kathy LeDell, Beth Shade,
Sarah Vetter