Download outline25017 - American Academy of Optometry

I. The age of Modern Medicine
A. Alexander Fleming is considered to be the father of modern medicine
1. He discovered penicillin more than 70 years ago (1928) is considered to be
one of the most significant medical breakthroughs of the twentieth century
2. Prior to Penicillin, the # 1 war-time killer was infection
3. This marked a new era in modern medicine
4. Within 4 yrs of its release, resistance to penicillin began popping up and grew at an
alarming rate
B. By the mid-1940s and early 1950s streptomycin, chloramphenicol, and tetracycline had
been discovered and the age of antibiotic therapy was underway
1. These new antibiotics were very effective against a number of different pathogens
including Gram-(+) and gram (-) bacteria, intracellular parasites, and
tuberculosis
2. The mass production of antimicrobials provided a temporary advantage in the
struggle with microorganisms
3. Despite these rapid advances resistance quickly followed
II. How Resistance Develops
A. Bacterial become resistant when a mutation occurs in the DNA that protects the
bacteria from a chemical
B. Mutation is only significant if the bacteria colony is exposed to the drug
“Survival of the fittest” dictates survival occurs in only those capable of mutating
A. For any given bacterial population, random mutations will arise
1.
With strong external selection pressures these mutations will be favored resulting
in resistant bacteria
2.
American Academy of Microbiology: 17.8 million pounds of antibiotics are used in
animals each year, Human exposure of these antibiotics is significant
B. One significant problem is that antibiotics are used extensively topically, systemically,
Agriculturally as a growth stimulant
III. Staphylococcus Aureus
A. Common bacteria usually found on the skin or in the nose
B. Can cause a range of illnesses from minor skin infections such as pimples, impetigo,
boils, cellulitis and abscesses…To life-threatening diseases such as pneumonia,
meningitis, endocarditis, and septicemia
C. There are many different types of staphylococcus aureus
IV. Methicillin Resistant Staphylococcus Aures (MRSA)
A. MRSA is a particular strain of staphylococcus aureus that does not respond to many
antibiotics
B. Methicillin was an antibiotic used many years ago to treat patients with
Staphylococcus aureus infections
1. It is now no longer used except as a means of identifying this particular type of
antibiotic resistance
C. 1st outbreak identified in 1960 ‘s
D. Predominantly seen in hospitals, chronic care facilities and parenteral drug abusers
1.
The prevalence of MRSA isolates in hospitals in the US has risen steadily, such that
now about ¼ nosocomial isolates are methicillin resistant
E. Community-acquired MRSA is becoming a significant problem, with the prevalence of
MRSA among community isolates expected to reach as high as 25% in the next
decade
F. About 1/3 of people carry MRSA on their skin or in their nose without knowing it
1.
Most people who carry MRSA in this way don’t go on to develop an infection
G. Risk Factors for MRSA
1.
Proloned hospital stays
2.
Prior surgery
3.
Seriously ill in intensive care
4.
Immunocompromised
H. 2005: Deaths from MRSA Surpassed AIDS: In 2005, AIDS killed 17,011 Americans
CDC reports > 90,000 get the potentially deadly "superbug" infections annually
1.
Recent JAMA surveillance study, only about ¼ of MRSA infections involved
hospitalized patients, More than half were in the health care system
V. Ocular Involvement of MRSA
A. 13 Cases of MRSA Following Refractive Surgery
1. Multicenter, retrospective chart review of 13 cases of MRSA keratitis
following refractive surgery
2. 9 were either healthcare workers or exposed to a hospital surgical setting
3. 7 pts were prescribed 3rd generation FQ, 1 pt prescribed tobramycin, 1 pt was
prescribed erythromycin and 3 were prescribed a 4th generation FQ
B. Ocular MRSA Northern California: July 1, 1998 and July 31, 2006: 12.6% increase in
ocular MRSA
1. Most cases were mild and nonsight threatening
2. 78% had MRSA blepharoconjunctivitis
3. 4.6% with had keratitis, 2.4% with endophthalmitis
4. 100% of the isolates were sensitive to vancomycin
5. 93.2% sensitive to tetracycline and 63.6% were sensitive to bacitracin.
6. Ciprofloxacin and erythromycin were essentially ineffective with sensitivities of
14.8%
C. Bascom Palmer Study: Retrospective, cross-sectional study evaluating the resistance
trends for patients presenting with bacterial conjunctivitis from 1994 to 2003.
1. 1254 culture (+) pathogens were recovered from 2408 consecutive conjunctival s
sabs (52.1%)
2.
Gram (+) pathogens accounted for 52.2% of culture-positive isolates
3.
S aureus was the most frequent isolate overall (n = 471; 37.6%) in pts > 6
years
4.
Staphylococcus aureus overall: 37.6%, 47.8% in people > 8 y/o
5.
MRSA showed a significant increase in the 10-year period (4.4%-42.9%)
VI. Tracking Resistance in U.S. Today (TRUST)
A. FDA initiated program in 1996 with the introduction of levofloxacin for systemic use
Surveillance for new systemically administered antibiotics so the infectious disease
community has access to data from national surveillance programs that can put local
findings of antibiotic resistance in perspective
1.
In vitro susceptibility testing is performed by an independent central
laboratory on isolates submitted annually by 200 or more clinical laboratories
across all 50 states
2. Ocular isolates periodically have been submitted for testing in the TRUST
program, but no national surveillance program systematically has tracked in
vitro susceptibility in ocular isolates
3. Ocular Trust: Expansion of the TRUST program to include an ocular-specific
substudy that annually will monitor in vitro susceptibility of pathogens isolated
from ocular infections
4. Ocular TRUST is the only nationwide surveillance program to monitor
antimicrobial susceptibility in prospectively collected ocular isolates
VII.
The Arsenal of Antibiotic Therapy for Ophthalmic Use
A. The Fluoroquinolones
1. The first safe broad-spectrum ophthalmic agents
2. Revolutionized treatment of severe corneal infections
3. Excellent safety profile
4. 1st released for ophthalmic use in early 1990’s
5. Represented an important break-through for clinicians
6. For the 1st time strong commercially available antibiotics available to treat
bacterial conjunctivitis and ulcerative keratitis
7. The BIG problem with the fluoroquinolones has been bacterial resistance
resistance to cipro, oflox, levoflox
a. 1993 – 5.8% resistance (2 yrs after release of fluoroquinolones)
b. 1997 – 35% bacterial resistance
c. 2001 – 100% resistance to staph aureus isolates cultured in
endophthalmitis
B. 4th Generation Fluoroquinolones: developed to address the issues of resistance
and to allow for broader coverage for both gram (+) and gram (-) organisms.
They also provide much better gram (+) coverage
C. Fluoroquinolone structure
1.
Improved in vitro activity of 4th-generation fluoroquinolones against Grampositives is due to the 8-methoxy group ( not present in the
3rd-generation)
2. Mechanism of Action: Fluoroquinolones: Cause lethal breaks in the bacterial
chromosome at their target site
3. 4th-generation FQs are dual binding: DNA gyrase AND topo IV in both
Gram-positives and Gram-negatives
B. AzaSite: 1% topical azithromycin
1. Macrolide
2. Broad spectrum of action particularly against gram-positive organisms
3. It works by inhibiting protein synthesis
4. It is bacteriostatic and not bacteriacidal
5. Dosing for treating bacterial conjunctivitis: drop bid X 2 days, followed by 1
qd for 5 days
6. DuraSite®: The AzaSite™ Vehicle
a. DuraSite is an advanced synthetic polymeric mucoadhesive matrix that
stabilizes small molecules like azithromycin
b. DuraSite® allows for a stable formulation of azithromycin and increase
the bioavalability of azithromycin in tissue
7. Early studies have shown very good bacterial eradication rates of most
common pathogens
a. Haemophilus influenze: 92.7% bacterial eradication rate
b. Sterp pneumoniae: 90.2 bacterial eradication rate
c. Staph aureus: 82.5% eradication rate