Download BAD BUGS Healthcare Workers and Emerging Antibiotic

BAD BUGS
Healthcare Workers and Emerging
Antibiotic Resistant Organisms
JON ROSENBERG, M.D.
DIVISION OF COMMUNICABLE DISEASE CONTROL
CALIFORNIA DEPARTMENT OF PUBLIC HEALTH
(510) 622-3427 [email protected]
Bad Bugs
Staphylococcus aureus
Clostridium difficile
Streptococcus pneumoniae
Gram-negative bacilli (Pseudomonas,
Acinetobacter, E. coli, Klebsiella)
Enteric pathogens (Salmonella, Shigella,
Campylobacter)
2
Bad Bugs and Healthcare Workers
Staphylococcus aureus
Clostridium difficile
3
Staphylococcus aureus
Spherical gram-positive
bacteria
Long recognized as an
important human pathogen
and the leading cause of
suppurative (pus forming)
infections in humans
The Romans referred to
“good and laudable pus”
4
Staphylococcus aureus
Exodus 9:9 And it shall
become small dust in all
the land of Egypt, and
shall be a boil breaking
forth with blains upon man,
and upon beast, throughout
all the land of Egypt
Job 2:7 Job is smote with
boils from the sole of his
foot unto his crown
5
Staphylococcus aureus
Discovered by Sir Alexander
Ogston in 1881 and named
for staphyle (bunch of grapes)
and kokkus (grain or berry)
because it appears microscopically
in clusters resembling grapes
Isolated and grown in pure culture
by Anton Rosenbach in 1884;
who called it aureus (golden)
6
Staphylococcus aureus in culture
Staphylococcus aureus
Part of normal human flora and ecological niche is
typically the anterior nares
~ 20% of humans are persistently colonized (children
> adults), 60% are intermittently colonized and
another 20% are rarely colonized
Most often spread via contaminated hands
In 1928 Alexander Fleming first observed a mold
called “penicillium” inhibit S. aureus in a culture
plate
The first treatment of a patient with penicillin took
place in 1940
8
History of Methicillin-Resistant
Staphylococcus aureus (MRSA
S. Aureus is a borrower of genes, has few of its own
Penicillin G introduced in 1941, penicillin-resistant (beta
-lactamase producing) strains of S. aureus isolated 1942
To combat penicillin resistance, methicillin (first beta
-lactamase stable penicillin) introduced in 1960 and
methicillin-resistant strains of S. aureus first isolated in
the United Kingdom in 1961
Late 1960s MRSA identified as nosocomial pathogen and
first U.S. hospital outbreak reported in 1968
Resistance to other antimicrobials has occurred over time
9
Early Optimism about Antimicrobials
William H. Stewart, U.S. Surgeon General 1965-1969
(and Minneapolis native), is purported to have
said, “We have closed the book on infectious
disease.”
Hospital
CAMRSA 101
Community associated, not acquired
•  Absence of healthcare associations
•  Not healthcare strains invading the community
Healthcare associated (HAMRSA)
•  Presence of healthcare factors
Different strains associated with each, may be
blurred as CAMRSA strains cause HAMRSA
infections (newborns, surgical site, transmitted
in healthcare facilities)
12
CLINICAL MANIFESTATIONS
CAMRSA
Furuncle (boil),
carbuncle, abscess
Cellulitis
Pyomyositis
Necrotizing pneumonia
Toxic shock syndrome
Scalded skin syndrome
13
HAMRSA
Surgical site infection
Blood stream infection,
particularly central linse
associated
Pneumonia, particularly
ventilator associated
S. aureus Skin Infections
Furuncles (boils)
14
Cellulitis
Mild
Severe
EPIDEMIOLOGY
CAMRSA
15
Children and young
adults, increased
summertime, often no
risk factors, irregular
association with
antibiotics
Families, prisons,
IVDU, sports teams,
aboriginal
populations
HAMRSA
Hospitalized patients
(elderly), no seasonality,
risk factors (antibiotics,
medical devices,
surgery, ventilators)
Little transmission outside
healthcare facilities
VIRULENCE
CAMRSA
Rapid growth (2x in 28
minutes
Slow growth (2x in 38
minutes
Colonization:Infection ~4:1
Colonization:Infection ~10:1
10-fold increased risk of
infection vs CAMSSA
16
HAMRSA
GENOTYPE – RESISTANCE GENE
CAMRSA
SCCmec Type IV
17
HAMRSA
SCCmec Type II and III, I
Structures of SCCmec
18
Ito et al. Drug Resistance
Updates 2003
GENOTYPE – DNA TYPE
CAMRSA
19
HAMRSA
PFGE: USA 300 and
400, USA 1000,
USA 300 becoming
predominant
PFGE: USA 100, 200,
500, 600, 700, 800
MLST limited types
within continent
MLST multiple types
within continent
National Database of MRSA Pulsed-Field Types (Highlighted
PFTs: historically community-associated)
PFT
MLST
pvl
USA300
8
IV
POS
USA700
72
IV
NEG
USA100
5
II
NEG
USA800
5
IV
NEG
USA400
1
IV
POS
USA500
8
IV, I I
NEG
USA1000
59
IV
NEG/POS
USA900
15
MSSA NEG
USA600
USA200
45
36
II
II
NEG
NEG
USA1100
30
IV
POS
USA1200
McDougal et al J Clin Micro 2003;41:5113-5120
SCCmec
MSSA POS
GENOTYPE – PANTON-VALENTINE
LEUKOCIDIN (PVL) GENE
CAMRSA
Present
Highly associated with skin,
soft-tissue infections,
necrotizing pneumonia
May contribute to
pathogenesis or be marker
21
HAMRSA
Absent
Early CA-MRSA Reports
Aboriginals in the Kimberley Range,
Western Australia
Reported in indigenous people
around the world
Causal Diagram for CA-MRSA
Crowded Living Conditions/
Hygiene
Person-to-Person Transmission
Inappropriate/Increasing
Use of Antimicrobials?
Transfer of mecA gene from CNS to virulent S. aureus strains
Selection of resistant strains (e.g. use of cephalexin [Keflex®]
for SSTIs)
CA-MRSA
CA-MRSA Pyramid
Invasive
Infections
Skin Infections
Colonization
CA-MRSA Pyramid
~14,0001
Invasive
Infections / Yr
Skin Infections
Colonization
1. Klevens M et al JAMA 2007;298:1763-71
Most Invasive MRSA Infections are
Healthcare-Associated
National estimates:
94,360 infections; 18,650 deaths
31.8 cases & 6.3 deaths per 100,000 persons
28%
14%
59%
Community-Associated (CA-MRSA)
Healthcare-Associated, Community-Onset (HACO-MRSA)
Healthcare-Associated, Hospital-Onset (HAHO-MRSA)
Klevens et al JAMA 2007;298:1763-71
Severe CAMRSA Infections
Necrotizing pneumonia and empyema
•  Francis JS. CID 2005;40(1):100-7
Sepsis syndrome
•  Gonzalez BE. Pediatrics 2005;115(3):642-8
Disseminated infections with septic emboli
•  Gonzalez BE. CID 2005;41(5):583-90
Musculoskeletal infections (pyomyositis, osteomyelitis)
•  Martinez-Aguilar G. PIDJ 2004;23(8):701-6
Necrotizing fasciitis
•  Miller LG. NEJM 2005;352(14):1445-53
Purpura fulminans
•  Adem PV. NEJM 2005;353(12):1245-51
Toxic shock-like syndrome
•  Durand G. J Clin Microbiol, 2006;44(3):847-53, Chi. Clin Infect Dis
2006;42:181-5
27
CA-MRSA Pyramid
~14,0001
Invasive
Infections / Yr
11.6 million3 ambulatory
visits for skin and soft
tissue infections
~66,0002 Culture
-confirmed CA-MRSA
SSTI / Yr
80% of culture-confirmed CA-MRSA
55,0004 hospitalizations
with MRSA skin and
soft tissue infection
Colonization
1. Klevens M et al JAMA 2007;298:1763-71 2.Fridkin SK et al. N Engl J Med. 2005;352
(14):1436-44. 3.McCaig LF et al. Emerg Infect Dis. 2006;12:1715-23
4. Elixhauser A and Steiner C. HCUP Statistical Brief #35
Hospitalizations for S. aureus Skin and Soft
Tissue Infections Increasing Dramatically
Klein E et al. Emerg Infect Dis 2007:13(12);1840-46.
CA-MRSA Pyramid
~14,0001
Invasive
Infections / Yr
11.6 million4 ambulatory
visits for skin and soft
tissue infections
~66,0002 Culture
-confirmed CA-MRSA
SSTI / Yr
55,0005 hospitalizations
with MRSA skin and
soft tissue infection
Point Prevalence:
3-5 million5 persons
with MRSA nasal colonization
1. Klevens M et al JAMA 2007;298:1763-71
2.Fridkin SK et al. N Engl J Med. 2005;352(14):1436-44.
4.McCaig LF et al. Emerg Infect Dis. 2006;12:1715-23
5. Elixhauser A and Steiner C. HCUP Statistical Brief #35
3. Gorwitz RJ et al. J of Infect Dis. 2008;197
Prevalence of MRSA Nasal Colonization
has Increased but Remains Low
National Health and Nutrition
Examination Survey, 2001-04, N=18,626
USA300 / USA400: ↑d from 8% to 20% of all
MRSA-colonized (NS)
1.5%
0.8%
Gorwitz RJ et al. J of Infect
Dis. Apr 15 2008: 197
Non-Nasal MRSA Colonization?
Canada healthy newborn USA300 outbreak:
•  Sensitivity: Nares only 68%, Umbilicus only 61%, Rectum only
21%, Nares + Umbilicus 100%
Manhattan household survey
•  8/32 ♀ MRSA+ vagina or pubic (2/8 concurrent + nasal)
LA inpatients & outpatients with CA-MRSA infection:
•  40% colonized with MRSA in any of 4 sites
•  26% nares, 8% axilla, 20% inguinal, 15% rectum
Atlanta VA HIV Clinic (preliminary):
•  70 (12%) of 578 MRSA-colonized in nose or groin
–  33 (47%) both, 26 (37%) nose only, 11 (16%) groin only
MRSA in Animals
Food Animals
•  MRSA ST398 in pigs (Europe, Canada, U.S.), pig
farmers (Europe, Canada), retail pork (Europe)
•  Health risks of MRSA in food products unknown
Non-Food Animals
•  Transmission between humans and animals (both
directions) described – small % of human infections
•  Strains reflect predominant human strains
•  Pets may play role in sustained household transmission
•  Little evidence to support antimicrobial decolonization
in animals, but colonization typically short-lived
Strategies for Clinical Management of
MRSA in the Community
http:www.cdc.gov/ncidod/dhqp/ar_mrsa_ca.html
Skin Infections and MRSA Information
for California Schools
A Parent’s Guide to MRSA in California
What You Need to Know
http://www.cdph.ca.gov/HealthInfo/discond/Pages/MRSA.aspx
MRSA Among U.S. ICU Patients,
1995-2004
Source: National Nosocomial Infections Surveillance (NNIS) System
The APIC National MRSA Inpatient
Survey: MRSA prevalence rates by state
Am J Infect
Control
2007;35:6
31-7.)
Nosocomial CAMRSA
Increasing prevalence of CAMRSA strains in
healthcare-associated MRSA isolates
Increasing ICU/NICU bloodstream infections
NICU outbreaks – 9 reported to date
Healthy newborns – 5 outbreaks reported to date
Infections in postpartum women – 2 outbreaks
CAMRSA prosthetic joint infections
CAMRSA Infections in healthcare workers
38
Community-associated Methicillin
resistant Staphylococcus aureus Isolates
Causing Healthcare associated Infections
Retrospectively examined
all HA-MRSA isolates
from patients in
Harbor-UCLA Medical
Center 1999–2004
–  Emerg Infect Dis 2007;13(2)
:236-42
CAMRSA NICU
Outbreaks, Transmission
San Diego: CA-MRSA necrotizing fasciitis in a neonate
•  Dehority W et al. Pediatr Infect Dis J 2006;25(11):1080-1081
Los Angeles: Transmission of CA-MRSA from breast milk
•  Gastelum DT et al. Pediatr Infect Dis J 2005;24(12): 1122-1124
Texas: CA-MRSA necrotizing pneumonia in a neonate
•  McAdams RM et al. J Perinatol 2005;25(10)677-679
Canada: CA-MRSA outbreak
•  Rosenthal A, et al. J Clin Micro 2006;44(11):4234-4236
Switzerland: CA-MRSA outbreak from mother with mastitis and wound infection
•  Sax H et al. J Hosp Infect 2006;63(1):93-100
Israel: CA-MRSA outbreak
•  Regev-Yochay. Emerg Infect Dis 2005;11:453-455
CA-MRSA outbreak linked to HCW
•  Stein M, et al. Pediatr Infect Dis J 2006;25(6):557-559
Saudi Arabia: Father to infant transmission of CA-MRSA
•  Al-Tawfiq JA. Infect Control Hosp Epidemiol 2006;27(6):636-637
UK: Nosocomial transmission of CA-MRSA
40
•  David MD, et al. J Hosp Infect 2006;64(3):244-250
CAMRSA SSTIs Healthy Newborns
Two clusters of MRSA skin infections among newborns,
Los Angeles, 2004
–  Infect Control Hosp Epidemiol 2007;28(4):406-411
Cluster of 11 MRSA skin infections, Chicago, 2004
–  Arch Dis Child Fetal Neonatal ed 2007; Epub
Cluster cases infants and mothers, NYC, 2002
–  Emerg Infect Dis 2005;11(6):808-812
N. California hospital, April 2007
Predominant circumcised males, some colonized HCW,
uncertain mode transmission
41
CAMRSA Infections in Postpartum
Women
New York: 8 postpartum women developed
skin and soft tissue infections over 2 weeks
•  USA400, 178 HCWs negative nasal cultures
– Clin Infec Dis 2003;37:1313-9
Chicago: 16 of 17 isolates from mothers with
MRSA mastitis in 2005
– Emerg Infect Dis 2007;13(2):298-301
42
CAMRSA Infections
in Healthcare Workers
Two HCW developed MRSA skin and soft-tissue infections
•  Patient 1 cared for 15 patients with CAMRSA infections over
several months and reported I&D many abscesses
•  Patient 2 administrative position w/out patient contact
•  2 (3%)/70 HCW, 0/58 support staff colonized with MRSA
•  Seven (19%) of 36 environmental cultures grew MRSA
–  Patient examination table, computer keyboard, pulse oximeter, multiple
patient chairs; no MSSA detected
•  All strains SCCmec-IV and matched by PFGE
Infect Control Hosp Epidemiol 2006; 27:1133-1136
43
Role of Healthcare Workers in
MRSA Transmission
Carriage without colonization
•  Most common: transient carriage on hands due
to inadequate hand hygiene, improper glove
use
•  Skin and hand conditions (eczema, artificial
/diseased nails) can increase risk
Colonized HCW
44
•  Documented in presence of medical conditions
(eczema, respiratory infections)
•  Mode of transmission in absence of medical
conditions uncertain
Role of Healthcare Workers in
MRSA Transmission
In the absence of a clear role in transmission
by asymptomatic healthy HCW, the role for
screening asymptomatic healthy HCW,
either routinely or in the presence of an
outbreak is unclear
Finding a strain in HCW that matches patient’s
strains does not indicate the direction of
transmission
45
How Often Do Asymptomatic
Healthcare Workers Cause MethicillinResistant Staphylococcus aureus
Outbreaks? A Systematic Evaluation
191 outbreaks identified in 1996-2005 database
•  11 had strong epidemiological evidence for HCW
transmission
– In 3 asymptomatic carriers were the cause
The frequent practice of screening asymptomatic
HCWs should be reconsidered
Vonberg et al. Infect Control Hosp Epidemiol 2006; 27:1123-1127
Outbreaks with Evidence of HCW
Transmission
7 SSIs in a French Hospital
43 HCW screened, 1 colonized
A member of the surgical team had chronic
MRSA sinusitis. He admitted misuse of
surgical face masks and bad handwashing
procedures.
47
Outbreaks with Evidence of HCW
Transmission
5 mediastinitis infections after open heart
surgery in Taiwan hospital
33 HCW screened, 1 colonized
Only 1 HCW, an assistant surgeon who had
MRSA dermatitis of his right hand, attended
all 5 operations
48
Outbreaks with Evidence of HCW
Transmission
8 cases of postsurgical infections in U.S. hospital
64 HCW screened, 1 colonized
Cases occurred only when nasally colonized
physician had upper respiratory tract infections.
Multivariate logistic regression analysis identified
exposure to this physician as an independent
risk factor for MRSA colonization.
49
Outbreaks with Evidence of HCW
Transmission
32 cases of MRSA infection in U.S. hospital
14 HCW screened, 3 colonized
Exposure to a respiratory therapist was an
independent risk factor for infection, with an odds
ratio of 10.5 in a case-control study. This HCW had
a history of chronic sinusitis, and several
successive cultures of nasals secretions yielded
MRSA. After minor surgery to correct an anatomic
defect of the paranasal sinuses, the nasal drainage
ceased, and the therapist remained asymptomatic.
No new cases of MRSA infection were observed
50
Outbreaks with Evidence of HCW
Transmission
15 cases of obstetrical infections in British Hospital
146 HCW screened, 2 colonized
•  Healthy person with nasal carriage and student midwife with
infected eczema of hand
After mupirocin treatment was administered to both,
consecutive nasal swabs were consistently negative
for the strain
Finally, the outbreak ended after the infected midwife
was removed from duty
51
Outbreaks with Evidence of HCW
Transmission
10 patients on a burn unit in U.S. hospital positive
clinical cultures for MRSA
When cases recurred after 2 months of enhanced
infection control, all staff cultured
56 HCW screened, 3 colonized
A surgical resident, a nurse, and a nursing assistant
treated with mupirocin
During 3 years of active surveillance thereafter,
infection control personnel did not detect any
additional patients who were colonized or infected
with the epidemic MRSA strain
52
CAMRSA and Healthcare Workers
Poorly studied
Predominant strains (e.g. USA 300 precludes
molecular epidemiology)
HCW may be
•  Source or vectors of cross-infection
•  May become secondarily colonized or infected
from patients
•  Colonization may be unrelated to colonization in
patients
53
Healthcare-associated Outbreaks of
CAMRSA Colonization and Infection
Navarro et al. Current Opinion in Infectious Diseases 2008, 21:372–379
Decolonization of Healthcare
Workers
Can contribute to multifactorial approach for
termination of nosocomial MRSA if applied
early before MRSA becomes endemic in an
institution
Screening recommended for outbreaks in Europe
and other countries with low endemicity
Screening generally recommended in US only for
HCW epidemiologic implicated in outbreak
55
Resources
California Department of Public Health :
http://www.cdph.ca.gov/HealthInfo/discond/Pages/MRSA.aspx
Los Angeles County Department of Health Services:
www.lapublichealth.org/acd/MRSA.htm
Texas Department of State Health Services:
www.tdh.state.tx.us/ideas/antibiotic_resistance/mrsa/professionals/
Washington State Department of Health:
/www.doh.wa.gov/Topics/Antibiotics/providers_MRSA_guidelines.htm
Minnesota Department of Health
www.health.state.mn.us/divs/idepc/diseases/mrsa/camrsa/index.html
CDC Community-Associated MRSA:
56
www.cdc.gov/ncidod/hip/aresist/mrsa_spotlight.htm
Clostridium difficile
Spore-forming, gram-positive anaerobic bacillus
that produces two toxins: A and B
First isolated in the mid-1930s; name comes from
difficulty isolating
(and meat)
Soil, sand, hay, animal dung
15-25% of antibioticassociated
diarrhea
Increasing Prevalence and Severity of
Clostridium difficile Colitis in Hospitalized
Patients, US
Prevalence of C difficile colitis presented as
the hospital discharge rate for patients with
either a principal or a secondary diagnosis of
C difficile colitis
Case fatality for patients with either a
principal or a secondary diagnosis of
C difficile colitis
Ricciardi et al. Arch Surg. 2007;142:624-631
Yearly C difficile–related mortality rates
per million population, United States,
1999–2004
Source: multiple cause-ofdeath data from national
mortality records
Redelings et al. Emerg Infect
Dis 13:2007;1417-19
An Epidemic, Toxin Gene–Variant Strain of C
difficile
Major Genes in the Pathogenicity Locus (PaLoc) of C difficile and Relation to the
Genes for Binary Toxin
Genes tcdA and tcdB encode toxins A and B, respectively, whereas tcdD encodes a positive
regulator of the production of toxins A and B. Gene tcdE encodes a protein that may be
important for the release of toxin from the cell. Gene tcdC is a putative negative regulator of
the production of toxins A and B.
McDonald et al. N Engl J Med 2005;353:2433-41.
States with the Epidemic Strain NAP1 of C.difficile Confirmed by
CDC (N=27)
Updated 4/3/2007
DC
HI
AK
PR
Clostridium difficile Infection among Health
Care Workers Receiving Antibiotic Therapy
In two surveys 45% of health care workers had
received antibiotics within the past year
These HCW should be at increased risk of C.
difficile infection as the result of their
workplace exposure
HCW have 13-15% prevalence of C. difficile
positive stool
Few reports of infection
62
Demographic and clinical
characteristics of 4 healthcare
workers with Clostridium difficile
infection.
Arfons et al. CID 2005:40
Trends in nosocomial and community acquired
CDAD at Children’s National Medical Center
Benson et al. Infect
Control Hosp Epidemiol
2007; 28:e
Community Associated CDAD UK, 2005
Rates of
Clostridium
difficile per
100 000
Patients in
the United
Kingdom
General
Practice
Research
Database
Dial S. et al. JAMA 2005;294:2989-2995
Severe Clostridium difficile--Associated
Disease in Populations Previously at Low
Risk
Case 1. A woman aged 31 years 14 weeks pregnant with
twins went to local emergency department after 3
weeks of intermittent diarrhea, followed by 3 days of
cramping and watery, black stools 4--5 times daily
Case 2. A girl aged 10 years went to a children's hospital
ED because of intractable diarrhea, projectile vomiting,
and abdominal pain. She had not taken antimicrobials
during preceding year
MMWR. December 2, 2005/54(47);1201-1205
Is Clostridium difficile-associated Infection
a Potentially Zoonotic and Foodborne
Disease?
Clostridium difficile isolated from 12 (20%) of
60 retail ground meat samples purchased
over 10-month period in 2005 in Canada
11 isolates toxigenic
8 (67%) classified as toxinotype III (one similar to
027)
Rodriguez-Palacios. Emerg Infect Dis 13:207;485-7
There
are
also
Good
Bugs