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Nosocomial Infections
David M. Parenti, M.D.
Definitions
 sterilization:
use of physical procedures or
chemical agents to destroy all microbes,
including spores, viruses, fungi
 disinfection: use of physical procedures or
chemical agents to destroy most microbes
– high, intermediate, low level
 antisepsis:
use of chemical agents on skin or
other tissue to inhibit or kill microbes
Nosocomial Infections
 Infection
acquired in the hospital: > 48 hours
after admission
 $5 billion annually: increased hospital length
of stay, antibiotics, morbidity and mortality
 related to severity of underlying disease,
immunosuppression, invasive medical
interventions
 frequently caused by antibiotic-resistant
organisms: MRSA, VRE, resistant Gramnegative bacilli, Candida
Sites of Nosocomial Infections
Pneum
11%
SSI
20%
UTI
Other
22%
36%
BSI
11%
Klevens. Pub Health Rep 2007;122:160
Nosocomial Infection
Types of Transmission
 airborne
– tuberculosis, varicella, Aspergillus
 contact
– S. aureus, enterococci, Gram-negative
bacilli
 common vehicle
– food contamination
– Salmonella, hepatitis A
Patient 1
A 67 yo female with poorly controlled
hypertension was admitted because of a
right-sided stroke. She had confusion,
limitation of mobility of her left leg, and
urinary incontinence. A urinary (Foley)
catheter was placed and she was evaluated
for rehabilitation.
 4 days later she developed a temp to 103º F
and blood pressure of 90/60 and was
transferred to the ICU. Blood and urine
cultures grew resistant Klebsiella.

Nosocomial UTI
 Up
to 25% of hospitalized patients are
catheterized at some time during their
hospital stay.
 15% colonized (bacteruria)
– 5-10% per day of catheterization
– 50% after 14 days
 Gram-negative bacilli, VRE, Candida
– frequent antimicrobial resistance
Antibiotic-Resistant
Gram-Negative Bacilli
increasingly a problem in the ICU: UTI, pneumonia
 selective pressure from high-level antibiotic usage in
hospital and community
 E. coli, Klebsiella, Enterobacter, Pseudomonas,
Serratia, Acinetobacter
 resistance to extended spectrum penicillins,
cephalosporins, aminoglycosides, quinolones
 colonization at multiple body sites: GI, skin, pharynx

Nosocomial UTI
Pathogenesis
 external
– most common
– colonization of urethral meatus
– movement of bacteria along fluid layer
on external catheter surface
 internal
– colonization of urine in bag, ascend
through catheter lumen
Nosocomial UTI Prevention
 *avoid
catheterization
– minimize duration of catheterization
– intermittent (“in and out”) catheterization
 aseptic insertion technique
 closed system
 dependent drainage
 silver-coated catheters
Patient 2
A 45 yo male is admitted for community-acquired
pneumonia. He has a long history of iv drug use,
but has not used in several years. The intern has
difficulty starting a peripheral iv so places a
femoral venous catheter. His cough and fever
begin to improve.
 On hospital day 3 he has fever, chills and a WBC
of 18,000. Blood cultures are positive for
vancomycin-resistant Enterococcus.

Vascular Device-Associated
Bacteremia
 major
cause of morbidity and mortality in
hospitalized patients
 150 million intravascular devices are
purchased by hospitals yearly
 estimated 50,000-100,000 intravascular
device- related bacteremias in U.S./year
– non-cuffed central venous catheters
account for 90% of vascular catheterrelated bacteremias
CVC-Associated Bacteremias
GWUH 2009
Staphylococcus aureus, MRSA, S. epidermidis
 Enterococcus faecalis, VRE
 Streptococcus agalactiae (group B strep)


Acinetobacter, Klebsiella pneumoniae,
Enterobacter cloacae

Candida albicans, C. parapsilosis
Vascular Device-Associated
Bacteremia: Pathogenesis
initial step is colonization of the insertion or
access hub
 biofilm formation allows attachment of bacteria
 development of bacteremia

IV Catheter Biofilm 24 hours after
Insertion
Coagulase Negative Staphylococci
Slime-producing, Catheter Surface
Vascular Catheter Infections
Risk Factors
 type
of catheter: plastic > steel
– multiple > single lumen
 location of catheter
– central > peripheral
– internal jugular, femoral > subclavian
 duration of placement: > 72 hours
 emergent placement > elective
 skill of venipuncturist: others > i.v. team
Vascular Catheter Infections
Clinical Clues
local inflammation or phlebitis at catheter
insertion site
 bacteremia caused by associated organisms:
MRSA, CNS, VRE, Candida

above waist
38%
hand or arm
29%
inguinal area
86%
Bonten MJM . Lancet
1996; 348:1615
Vascular Catheter Infections
Diagnosis
 Maki
rollplate technique
 catheter tip or intracutaneous segment is rolled on
agar plate
 colonies are counted
 > 15 colonies correlates with colonization and
potential source of bacteremia
Maki DG. NEJM 1977;296:1305
Semipermanent Tunneled Catheters
(Groshong, Hickman, Mediport)
long term i.v. therapy
 much lower rate of infection
 dacron cuff incites inflammatory response, fibrosis
at insertion site
 prevents bacteria from migrating along external
catheter surface
 locations of infection: exit site, tunnel, tip
– tunnel infection always requires catheter removal
 septic thrombophlebitis/pulmonary emboli

Groshong
catheter
CVC-Associated Bacteremia
Prevention (Bundles)
 *minimize
duration of catheterization
 use single vs multiple lumen catheters
 site placement
 meticulous insertion technique
– drapes, gown/gloves/mask
 antibiotic impregnated catheters
 impregnated dressing (Biopatch)
 outbreak/cluster control
Chlorhexidine/Silver SulfadiazineCoated CVCs
 158
hospitalized patients with 403 triplelumen, polyurethane venous catheters
 chlorhexidine/silver sulfadiazine-coated vs
uncoated catheters-external surface
uncoated coated
p
 colonization
24.1% 13.5%
< 0.005
 bacteremia
4.7%
1%
< 0.03
Maki DG; Ann Intern Med 1997;127:257
VRE RFLP GWUH 2004
*
*
*
*
*
*
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*
Patient 3
A 52 yo male is admitted with a severe headache
and is found to have a subarachnoid hemorrhage
from a ruptured aneurysm. The neurosurgeons
evacuate the hematoma and clip his aneurysm.
Post-op he remains on a ventilator.
 On hospital day 5 he spikes a fever to 102º F and
is noted to have copious secretions from his
endotracheal tube. Increasing amounts of inspired
O2 are required. Blood and sputum cultures grow
highly resistant Enterobacter cloacae.

Nosocomial Pneumonia
 300,000
cases/year in U.S.
– 10-15% of nosocomial infections
 leading
cause of death from nosocomial
infection
– crude mortality 35-50%
 ventilator-associated
pneumonias occur 4872 h post endotracheal intubation
 organisms may originate from endogenous
flora, other patients, visitors, or
environmental sources
Ventilator Associated Pneumonia
GWUH 2009
 Staphylococcus
 Proteus
aureus, MRSA
mirabilis, Serratia marcescens,
Pseudomonas aeruginosa,
Stenotrophomonas maltophilia
Nosocomial Pneumonia
Klebsiella,
Enterobacter
S. aureus
P. aeruginosa
S. pneumoniae
E. coli
anaerobes
Episodes
30%
Mortality
40%
27%
15%
12%
10%
2%
33%
72%
43%
31%
0%
Bryan CS. Am Rev Resp Dis 1984;129:668-671
Gram-Negative Bacilli Colonization
Risk Factors
 severity
of underlying illness
 duration of hospitalization
 prior or concurrent use of antibiotics
 advanced age
 intubation
 major surgery
 achlorhydria ?
Ventilator-Associated Pneumonia
Prevention
 *limit
duration of ventilation
 handwashing/gloves
 closed ventilator circuits
 semi-recumbent positioning
– avoid large gastric volumes
 avoid
prolonged nasal intubation
– prevent sinusitis
?
maintain gastric acidity
Patient 4
A 73 yo male is admitted with chest pain and
severe coronary artery disease. He has emergent
3-vessel coronary artery bypass grafting. He
recovers fairly well from the surgery but on postop day 10 develops fever and purulent drainage
from the inferior aspect of the wound.
 He returns to the operating room for extensive
debridement of sternal osteomyelitis. Cultures
grow methicillin-resistant Staphylococcus aureus.

Patient 4
Surgical Site Infection (SSI)
usually introduction of skin organisms into the
wound
– S. aureus, Gram-negative bacilli
 risk factors
– underlying disease
– skill of the operator
– duration of operative procedure
 may not become clinically apparent until after
discharge
 risk may be decreased by appropriately timed preoperative antibiotics

MRSA
1960 methicillin-resistant S. aureus identified
 MRSA 60% of S. aureus isolates at GW are MRSA
(2007)
 Community-acquired: recent increase in incidence
 Hospital-acquired: > 48 h after admission
 Healthcare-associated community-onset:
– previous positive MRSA culture
– history of hospitalization, surgery, dialysis or
residence in long term care facility in the last year
– indwelling catheter/percutanous device

MRSA Isolates
Pulse Field Gel Electrophoresis (PFGE)
MRSA
Mechanism of Resistance
 chromosomal
mecA
gene
 *altered PBP 2´ or 2a
in cell wall
 low affinity for all ßlactam antibiotics
Hospital-acquired MRSA
 BSI
 pneumonia
 osteomyelitis
 endocarditis
 cellulitis
 skin
abscess/necrosis
 mortality
76%
13%
6%
3%
4%
1%
2.5%
www.cdc.gov/abcs
Hospital-acquired MRSA
 Risk
factors:
– prolonged hospitalization
– prolonged antimicrobial therapy
– location in an intensive care unit
– proximity to a known MRSA case
 Persistent colonization up to 4 years: nares
 Contamination of environmental surfaces
– up to 30%: bed rails, table, BP cuff
SSI Prevention
no shaving of operative site: clippers or no hair
removal
 hand hygiene; fastidious aseptic technique
 surgical site antisepsis with chlorhexidine
 prophylactic antibiotics
– single dose 30-60 minutes prior to incision
– second dose for prolonged surgeries
 laminar air flow or HEPA filtration; limit traffic
in the operating room
 pre-operative screening for S. aureus

Patient 5
A
26 yo medical student draws blood from
a patient for a classmate. He is in a hurry
and sticks his thumb while recapping (?) the
needle. The patient has been tested positive
for HIV and hepatitis C. The student has
received the hepatitis B immunization
series.
HCW Blood/Body Fluid Exposure
Risk Factors
 needlestick/sharp>>mucosal>>non-intact
 inoculum:
viral titer, volume of blood
 needle type
– hollow-bore needles > solid-bore
– large bore > small bore
 decreased
risk with glove use
skin
GWU Health Care Workers
Percutaneous Exposures: 2007-09
 Occupation
– Hospital staff
– Residents
– Students
38-49%*
39-56%*
6-11%
 Location
–
–
–
–
–
ER
ICU
OR
other floors
Pathology
7-14%
7-21%*
31-52%*
24-27%*
3-8%
Risk of Transmission following
Percutaneous Exposure
 HIV
0.3%
 Hepatitis C
1.9%
 HBeAg < 6%
 HBeAg +
30%
 estimated US transmission for yr 2000*
– 390 cases of HCV
– 40 cases of HBV
– 5 cases of HIV
Henderson DK. Clin Microbiol Rev.2003;16:546
* Prüss-Üstün A. Am J Ind Med 2005;48:482
HCW Blood/Body Fluid Exposure
Management
 baseline
serologies, including the patient if
necessary
 assessment of risk
 HIV: antiretroviral therapy
 hepatitis B: hepatitis B immune globulin
and hepatitis B vaccine if non-immune
 hepatitis C: close follow up
HCW Blood/Body Fluid Exposure
Prevention
 SLOW
DOWN
 do not recap needles
 dispose of sharps in the proper receptacle
 use needleless systems whenever possible
 heptitis B immunization
Isolation
 to
protect both patients and personnel
 Standard Precautions
– routinely consider all body fluids and moist
surfaces as potentially infectious
 airborne precautions
 droplet precautions
 contact precautions
Isolation
Airborne Precautions
 transmission
of pathogen via inhalation of
droplet nuclei
– tuberculosis, varicella, ? influenza
 private room
 negative pressure
 > 10 air exchanges per hour
 Staff: particulate respirators
Isolation
Droplet Precautions
 respiratory
secretions via close personal
contact
 group A strep, influenza
 private room
 particulate respirator
 do not need negative pressure or increased
air exchanges
Isolation
Contact Precautions
 transmitted
via hands of personnel,
inanimate surfaces
 MRSA, VRE, highly resistant GN rods
 private room
 gloves with patient contact
 handwashing
Michael Jackson Approach
Handwashing
 most
important means to prevent spread of
nosocomial pathogens
 hand cultures of medical personnel
GN bacilli
S. aureus
random sample
45%
11%
serial sample
100%
64%
persistent carrier
16%
16%
Puerpural Sepsis
Ignaz Semmelweis
 Ignaz
Semmelweis (1847) observed
differences in the incidence of puerpural
sepsis (group A strep) on 2 different wards
 one ward was staffed by obstetricians,
medical students: mortality 8%
 one ward was staffed by midwives: mortality
2%
Puerpural Sepsis
Ignaz Semmelweis
 Observation
#1: lower mortality when
students were on vacation
 Observation #2: pathologist cut during
autopsy developed similar illness
 Solution: HAND HYGIENE in the autopsy
room prevented transmission of organisms to
the delivery suite
Ignaz Semmelweis
Decreased Mortality with Improved Hand Hygiene
Chlorinated lime hand antisepsis
Ignaz Semmelweis
(1818-65)