CDC Threats, Flashcards

1
Q

According to the CDC, what are the 3 Urgent threats for ABX resistance?

A

■ Clostridium difficile
■ Carbapenem-resistant Enterobacteriaceae (CRE)
■ Drug-resistant Neisseria gonorrhoeae

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2
Q

According to CDC, what are serious threats for ABX Resistance?

A

■ Multidrug-resistant Acinetobacter
■ Extended spectrum β-lactamase producing Enterobacteriaceae (ESBLs)
■ Vancomycin-resistant Enterococcus ( VRE)
■ Multidrug-resistant Pseudomonas aeruginosa
■ Methicillin-resistant Staphylococcus aureus (MRSA)
■ Drug-resistant Streptococcus pneumoniae

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3
Q

According to CDC, what are Concerning threats for ABX Resistance?

A

■ Vancomycin-resistant Staphylococcus aureus (VRSA)
■ Erythromycin-resistant Group A Streptococcus
■ Clindamycin-resistant Group B Streptococcus

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4
Q

What are the 4 core actions the CDC is taking to fight the spread of ABX resistance?

A

1) preventing infections from occurring and preventing resistant bacteria from spreading,
2) tracking resistant bacteria,
3) improving the use of antibiotics
4) promoting the development of new antibiotics and new diagnostic tests for resistant bacteria

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5
Q

Each year in the United States, at least ___________ people acquire serious infections with bacteria that are resistant to one or more of the antibiotics designed to treat those infections

A

2 million

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6
Q

At least ___________ people die each year as a direct result of these antibiotic-resistant infections

A

23,000

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7
Q

What is the estimated total cost of ABX resistance to US economy?

A

$20 billion in excess direct healthcare costs, with additional costs to society for lost productivity as high as $35 billion a year

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8
Q

What % of all the antibiotics prescribed for people are not needed or are not optimally effective as prescribed?

A

Up to 50%

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9
Q

What is the estimated number of illnesses caused by antibiotic resistance?

A

2,049,442 illnesses,

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10
Q

What are the most common pathogens causing serious gram-negative healthcare-associated infections?

A
  1. Enterobacteriaceae
  2. Pseudomonas aeruginosa
  3. Acinetobacter
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11
Q

What is the large class of broad-spectrum drugs that are the main treatment for gram- negative infections?

A

B-Lactam

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12
Q

What is the most concerning Gram-negative bacteria pathway to β-lactam resistance?

A

β-lactamases, enzymes that destroy the β-lactam antibiotics

Some β-lactamases destroy narrow spectrum drugs
(e g , only active against penicillins) while newer β-lactamases (e g carbapenemases found in carbapenem- resistant Enterobacteriaceae or CRE) are active against all β-lactam antibiotics

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13
Q

What are the B-Lactam Subclasses?

A

Penicillin, aminopenicillins, and early generation cephalosporins

β-lactamase inhibitor combinations

Extended-spectrum Cephalosporins

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14
Q

A broad-spectrum β-lactam antibiotic that is considered the last resort for treatment of serious gram-negative infections

A

CARBAPENEM

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15
Q

What Gram negative bacteria is Carbapenem resistance found in?

A

Pseudomonas and Acinetobacter spp.

**Once bacteria become resistant to carbapenems, they are usually resistant to all β-lactams

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16
Q

These are broad-spectrum antibiotics that are often given orally, making them convenient to use in both inpatients and outpatients. Resistant bacteria develop quickly with increased use in a patient population Increased use is also associated with an increase in infections caused by hyper- virulent strains of Clostridium difficile

A

Fluoroquinolones

**an increase in infections caused by uoroquinolone-resistant, hyper- virulent strains of Clostridium difficile

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17
Q

These drugs are often used in combination with β-lactam drugs for the treatment of serious gram-negative infections

Despite growing resistance problems, these drugs continue to be an important therapeutic option However, clinicians rarely use these drugs alone because of concerns with resistance and side effects

A

Aminoglycosides

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18
Q

This drug is not a first-line treatment option for serious gram negative infections; however, with increasing resistance to other drug classes, they are considered
as a treatment option and are often considered for treatment of multidrug-resistant gram- negative infections

A

Tetracyclines & Glycyclines

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19
Q

This drug does not distribute evenly in the body, so it is often used in combination with other drugs depending upon the site of infection Resistance has emerged but it is still relatively uncommon

A

Tigecycline

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20
Q

These drugs are an older class that fell out of favor because of toxicity concerns Now they are often used as a “last resort” agent for treatment of multidrug- resistant gram-negative infection

A

Polymyxins

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21
Q

Because they are generic, these drugs are limited contemporary data on proper dosing In addition, resistance
is emerging, but there are limited data guiding the accurate detection of resistance in hospital labs As a result, use of these drugs present significant challenges for clinicians In the absence of a drug sponsor, FDA and NIH are funding studies to fill these critical information gaps

A

Polymyxins

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22
Q

Who are people that are especially high risk for developing an infection?

A
  1. Cancer Chemotherapy
  2. Complex Surgery
  3. RA
  4. Dialysis
  5. Organ and Bone Marrow Transplants
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23
Q

Why are people who have cancer and receiving chemo therapy at high risk for infection?

A

People receiving chemotherapy are often at risk for developing an infection when their white blood cell count is low. For these patients, any infection can quickly become serious and effective antibiotics are critical for protecting the patient from severe complications or death

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24
Q

Why are people receiving complex surgery at risk for infection?

A

Patients who receive cardiac bypass, joint replacements, and other complex surgeries are at risk of a surgical site infection (SSI). These infections can make recovery from surgery more dif cult because they can cause additional illness, stress, cost, and even death. For some, but not all surgeries, antibiotics are given before surgery to help prevent infections.

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25
Why are people with Rheumatoid Arthritis at high risk for infection?
Inflammatory arthritis affects the immune system, which controls how well the body fights off infections. People with certain types of arthritis have a higher risk of getting infections. Also, many medications given to treat inflammatory arthritis can weaken the immune system. Effective antibiotics help ensure that arthritis patients can continue to receive treatment.
26
Why are patients taking dialysis at high risk for developing an infection?
Patients who undergo dialysis treatment have an increased risk for getting a bloodstream infection. Bloodstream infections are the second leading cause of death in dialysis patients. Infections also complicate heart disease, the leading cause of death in dialysis patients. Infection risk is higher in these patients because they have weakened immune systems and often require catheters or needles to enter their bloodstream. Effective antibiotics help ensure that dialysis patients can continue to receive life-saving treatment.
27
Why are transplant patients more vulnerable to infections?
Transplant patient undergoes complex surgery and receives medicine to weaken the immune system for a year or more, the risk of infection is high. It is estimated that 1% of organs transplanted in the United States each year carry a disease that comes from the donor—either an infection or cancer.
28
ABX are responsible for 1 out of _____ ED visits for Adverse Events
1 out of 5. **Every year, there are more than 140,000 emergency department visits for reactions to antibiotics Almost four out of ve (79%) emergency department visits for antibiotic-related adverse drug events are due to an allergic reaction
29
What year was penicillin introduced?
1943
30
What year was TETRACYCLINE introduced?
1950
31
What year was ERYTHROMYCIN introduced?
1953
32
What year was METHICILLIN introduced?
1960
33
What year was GENTAMICIN introduced?
1967
34
What year was VANCOMYCIN introduced?
1972
35
What year was IMIPENEM and CEFTAZIDIME introduced?
1985
36
What year was LEVOFLOXACIN introduced?
1996
37
What year was LINEZOLID introduced?
2000
38
What year was DAPTOMYCIN introduced?
2003
39
What year was CEFTAROLINE introduced?
2010
40
What is the name of CDC's program to help improve ABX Rxing?
Get Smart- national campaign to improve ABX Rxing inpatient and outpatient settings
41
What is CDC's program to identify critical infections in the community and monitor resistance?
Active Bacterial Core surveillance (ABCs): Tracking infections caused by Neisseria meningitidis, Streptococcus pneumoniae, Groups A and B Streptococcus, and methicillin-resistant Staphylococcus aureus Healthcare-Associated Infections-Community Interface (HAIC): Tracking infections with C. difficile and with multidrug-resistant gram-negative microorganisms (Carbapenem-R Enterobacteriaceae MDR Acinetobacter)
42
This is a combination of two drugs that can be used to treat gram-positive infections (Staphylococcus Streptococcus) Because side effects are common, this drug is usually not a first choice for therapy Resistance in target pathogens has been described, but the percentage in the United States is still low
Quinupristin/ Dalfoprisitin 1999- year approved
43
This drug demonstrates broad spectrum activity, and it can be used to treat a range of infections (Enterobacteriaceae Staphylococcus Streptococcus) cross-resistance among the class, and resistance is increasing in all targeted pathogens, especially Enterobacteriaceae
Moxifloxacin 1999-year approved
44
This drug is used to treat serious gram-positive infections (Staphylococcus Enterococcus) Resistance has occurred but it is still uncommon
Linezolid 2000- year approved
45
a carbapenem that can be used to treat a wide range of infections (Enterobacteriaceae Staphylococcus Streptococcus) Dissemination of carbapenem- resistant Enterobacteriaceae (CRE) is impacting the drug’s overall effectiveness
Ertapenem 2001 - year approved
46
This drug is often used for treatment of serious gram- positive infections (Staphylococcus Streptococcus Enterococcus) Resistance is emerging in all of the targeted pathogens, but the resistance rates are currently low
Daptomycin 2003- year approved
47
This drug is often one of the only active agents for carbapenem-resistant gram-negative infections (Enterobacteriaceae Staphylococcus Streptococcus Enterococcus) and resistance is emerging **However, even in the absence of resistance, the effectiveness of this agent for treatment of the most serious infections is a concern
Tigecycline 2005- year approved
48
a carbapenem drug most commonly used to treat serious gram-negative infections (Enterobacteriaceae Pseudomonas aeruginosa Acinetobacter spp. Streptococcus spp. ) **carbapenem-resistant gram-negative pathogens like CRE is reducing the overall effectiveness of this drug
Doripenem 2007-year drug approved
49
This drug is approved for treatment of gram-positive skin and soft tissue infections (Staphylococcus Streptococcus Enterococcus) Use is limited because it is administered intravenously and is therefore difficult to use in an outpatient setting it should not be used in a woman of childbearing age without a pregnancy test
Telavacin 2008-year approved
50
A Cephalosporin drug, but unlike other cephalosporins, this one can be used to treat MRSA infections. Enterobacteriaceae Staphylococcus Streptococcus - Resistance has been identified but is rare - does not demonstrate any enhanced activity compared to other cephalosporins for Enterobacteriaceae - ESBL-producing isolates and CRE isolates are resistant to this drug
Ceftaroline 2010- year approved
51
Deaths related to C. difficile increased ___% between 2000 and 2007, in part because of a stronger bacteria strain that emerged
400%
52
In 2000, a stronger strain of c.difficile emerged. It is resistant to ________ ABX, which are commonly used to treat other infections.
Fluoroquinolones
53
Almost half of these infections occur in people younger than 65, but more than 90% of deaths occur in people 65 and older?
C.Diff
54
What testing is used for C.Diff in hospital?
nucleic acid amplification tests **Order a C. difficile test if the patient has had 3 or more unformed stools within 24 hours.
55
What % of hospital patients who get bloodstream infections from CRE bacteria die from the infection?
50%
56
According to CDC, how many healthcare-associated infections are caused by CRE each year?
9000
57
What % of U.S. short-stay hospitals had at least one patient with a serious CRE infection during the first half of 2012? .
4%
58
What % of US long-term acute care stay hospitals had one patient with a serious CRE infection during the first half of 2012?
18%
59
How many healthcare-associated Enterobacteriaceae infections occur in the United States each year?
140,000 **about 9,300 of these are caused by CRE. Up to half of all bloodstream infections caused by CRE result in death
60
What is the % of Enterobacteriacea healthcare-acquired infections are resistant to carbapenems?
Carbapenem-Resistant Klebsiella spp - 11% - 7900 infections - 520 deaths ``` Carbapenem-resistant E. coli 2% 1400 infections 90 deaths ```
61
a type of gram-negative bacteria that is a cause of pneumonia or bloodstream infections among critically ill patients. Many of these bacteria have become very resistant to antibiotics
Acinetobacter
62
What % of Acinetobacter is considered multidrug-resistant, meaning at least three different classes of antibiotics no longer cure Acinetobacter infections?
63%
63
What % of healthcare-associated infections reported to CDC’s National Healthcare Safety Network are caused by Acinetobacter, but the proportion is higher among critically ill patients on mechanical ventilators _____%?
2% 7% for critically ill pts on vents 7300 infections 500 deaths
64
An enzyme that allows bacteria to become resistant to a wide variety of penicillins and cephalosporins.
Extended-spectrum B-Lactamase Bacteria that contain this enzyme are known as ESBLs or ESBL- producing bacteria. ESBL-producing Enterobacteriaceae are resistant to strong antibiotics including extended spectrum cephalosporins.
65
Some Enterobacteriaceae are resistant to nearly all _______ & _______?
penicillins | cephalosporins
66
Nearly __________ or ______% healthcare-associated Enterobacteriaceae infections are caused by ESBL-producing Enterobacteriaceae.
26,000 or 19%
67
Patients with bloodstream infections caused by ESBL-producing Enterobacteriaceae are about ___% more likely to die than those with bloodstream infections caused by a non ESBL-producing strain.
57%
68
DC estimates that bloodstream infections caused by ESBL- containing Enterobacteriaceae result in upwards of $________ in excess hospital charges per occurrence.
$40,000 **Approximately 26,000 infections and 1,700 deaths are attributable to ESBLs
69
What is the % of Enterobacteriaceae healthcare-associated infections resistant to extended spectrum cephalosporin?
ESBL-producing Klebsiella spp. 23% 17,000 infections 1100 deaths ESBL-producing E. coli 14% 9000 infections 600 deaths
70
Enterococcus is often cause infections among very sick patients in hospitals and other healthcare-settings. Some Enterococcus strains are resistant to which drug?
vancomycin, an antibiotic of last resort, leaving few or no treatment options. ■ About 20,000 (or 30%) of Enterococcus healthcare-associated infections are vancomycin resistant.
71
a common cause of healthcare-associated infections including pneumonia, bloodstream infections, urinary tract infections, and surgical site infections.
Pseudonomas Aeruginosa
72
Some strains of Pseudomonas aeruginosa have been found to be resistant to which antibiotics ?
aminoglycosides, cephalosporins, Fluoroquinolones, and carbapenems.
73
How many healthcare-associated Pseudomonas aeruginosa infections occur in the United States each year?
51,000 More than 6,000 (or 13%) of these are multidrug-resistant, with roughly 400 deaths per year attributed to these infections.
74
What pathogen has developed resistance to drugs in the penicillin and erythromycin groups?
S Pneumoniae **Examples of these drugs include amoxicillin and azithromycin (Zithromax, Z-Pak). S. pneumoniae has also developed resistance to less commonly used drugs.
75
Name this type of bacteria? A common type of bacteria that is found on the skin. During medical procedures when patients require catheters or ventilators or undergo surgical procedures, it can enter the body and cause infections. When It becomes resistant to vancomycin, there are few treatment options available.
Staphylococcus aureus vancomycin-resistant S. aureus bacteria identified to date were also resistant to methicillin and other classes of antibiotics.
76
A total of 13 cases of vancomycin-resistant Staphylococcus aureus (VRSA) have been identified in the United States since 2002. VRSA infection continues to be a rare occurrence. What are existing factors that seem to predispose case patients to VRSA infection?
■ Prior MRSA and enterococcal infections or colonization ■ Underlying conditions (such as chronic skin ulcers and diabetes) ■ Previous treatment with vancomycin
77
A type of bacteria that can cause severe illnesses in people of all ages, ranging from bloodstream infections (sepsis) and pneumonia to meningitis and skin infections. developed resistance to clindamycin and erythromycin. Recently, the very first cases with resistance to vancomycin have been detected among adults
Group B Streptococcus (GBS)
78
Name Carbapenems currently available
DORIBAX®(doripenem) INVANZ® (ertapenem) ** also available in generic form** PRIMAXIN® (imipenem-cilastatin) MERREM® (meropenem)
79
What is the spectrum of activity of CARBAPENEMS?
- broad spectrum - ESBL and AmpC-producing G- pathogens: Enterobacteriaceae G+ Cocci Anaerobes
80
Which Carbapenem is particularly active against Pseudomonas aeruginosa?
Doripenem- DORIBAX
81
Which Carbapenem is not active against Pseudomonas?
Ertapenem - INVANZ
82
Which Carbapenem is active against Enterobacteriaceae?
Meropenem- MERREM
83
What is the dosing of DORIBAX?
500mg IV Every 8H
84
What is the dosing of INVANZ?
1g IV QD
85
What is the dosing of PRIMAXIN?
500mg IV every 8H
86
What is the dosing of MERREM?
500mg IV every 8H
87
Why do HCPs use CARBAPENEMS?
1. broad spectrum, including ESBL-producing G- pathogens 2. imipenem freq used bc it was the first drug in class 3. Ertapenem -used by surgeons for IAI bc QD dosing 4. Meropenem commonly used for Enterobacteriaceae bc of activity and less neurotoxicity that other carbapenems
88
Which carbapenem was an antipseudomonal agent that fell out of favor due to poor data in VABP trial?
Doripenem- DORIBAX
89
Neurotoxicity is associated with all agents in this class
CARBAPENEMS
90
What are the DOT for UTI when using a CARBAPENEM?
Doripenem 6.59% (297,476) Ertapenem 13.08% (589,978) Imipenem-cilastatin 5.82% (262,401) – Meropenem 11.33% (511,416)
91
What are the DOT for IAI when using a CARBAPENEM?
Doripenem 3.19% (79,133) Ertapenem 10.32% (255,892) Imipenem-cilastatin 11.14% (276,438) – Meropenem 4.41% (109,376)
92
A cephalosporin and β-lactamase inhibitor combination that is only available as a branded product. It has been approved for the treatment of cIAI in combination with metronidazole and cUTI, including pyelonephritis.
Zerbaxa
93
What class of ABX is ZERBAXA?
Combo of cephalosporin & B-Lactamase inhibitor
94
What are the approved indications for ZERBAXA?
cIAI in combo with metronidazole cUTI, including pyelonephritis
95
What is the spectrum of activity for ZERBAXA?
The spectrum of activity for ZERBAXA includes only ESBLs and other β-lactamases, like TEM (Ambler class A) and OXA (Ambler class D). It does not have activity against KPCs (Ambler class A) or metallo-β-lactamases (Ambler class B).
96
ZERBAXA has activity against these G+ & G- organisms
``` E. Coli K Pneumoniae Proteus Mirabili Pseudomonas Aeruginosa Bacteroides Fragilis Streptococcus Anginosus ```
97
ZERBAXA demonstrated in vitro activity against _________
Enterobacteriaceae in the presence of ESBLs and other B-Lactamases TEM, SHV, CTX-M, OXA P. aeruginosa in the presence of certain resistance mechanisms
98
ZERBAXA is NOT active against bacteria producing what?
KPC | Metallo-B-Lactamases
99
What is the dosage of ZERBAXA?
1.5g: 1g ceftolozane + 0.5 tazobactam IV every 8H
100
Where one place HCPs position ZERBAXA?
alternative to ZOSYN (piperacillian-tazobactam)
101
Use ZERBAXA with caution in what patient?
moderate renal impairment | (CrCl 30-50mL/min) due to demonstrated decreased clinical cure rates
102
What class of drug is COLISTIN?
polymyxin
103
What are the approved indications of COLISTIN?
acute or chronic infections due to sensitive strains of certain Gram-negative bacilli. In particular, it may be used when the infection is caused by sensitive strains of Pseudomonas aeruginosa
104
What is the spectrum of in vitro activity with COLISTIN?
Retained activity against certain multidrug-resistant strains of Gram-negative pathogens, like Pseudomonas aeruginosa and Acinetobacter baumannii.
105
What is the dosage of COLISTIN?
2.5 to 5mg/kg/day divided into 2 to 4 doses
106
Why do HCPs use COLISTIN?
they need an ABX with activity against highly resistant Gram-negative pathogens,
107
What are HCPs concerned with when using COLISTIN?
- risk for nephrotoxicity - complex dosing recommendations - dev of resistance while on therapy is often reported
108
What are COLISTIN's DOT for UTI?
0.32% (14,228)
109
What are COLISTIN's DOT for IAI?
0.20% (4917)
110
What are the two well-known infectious agents in carbapenem resistant enterobacteriaceae family ?
carbapenem resistant Klebsiella pneumonia and Escherichia coli
111
What do Carbapenamases do?
which hydrolyze not only carbapenems but also all other beta lactam antibiotics, is mostly responsible for the resistance to carbapenamases.
112
What are the 5 most common Carbapenamases?
1. imipenemase (IMP) type, veronica 2. integronmetallo beta lactamases (VIM) type, 3. Klebsiella pneumonia carbapenemase (KPC) type, 4. New Delhi metallo beta lactamases-1 (NDM-1) 5. oxacillinase 48 (OXA 48) which is the most common enzyme in Turkey [
113
Susceptibility to carbapenems is detected by performing what test which are enough for antimicrobial susceptibility categorization?
Phenotypic tests
114
What are preferable CRE treatement options?
High dose carbapenem, polymixin B, colistin, tigecycline, fosfomycin or aminoglyside can be called as preferable CRE treatment options
115
A type of carbapenemases seen in Saudi Arabia, Kuwait, Amman, United Arab Emirates and Middle East countries
NDM-1
116
often preferred for treatment of multidrug resistant Gram negative bacteria, has usage restrictions due to its nephrotoxicity
COLISTIN
117
antibiotic that is used for CRE infections because of wide tissue distribution. However, FDA defined it monotherapy as "Boxed Warning"
Tigecycline
118
The first option especially in blood, lungs and gastrointestinal tract infections and also preferred for urinary tract infections as a possible therapeutic agent
COLISTIN
119
first option in the gastrointestinal tract infections and potential therapeutic agents for the blood and lung infections.
Tigecycline
120
while a first option for urinary tract infections, is among the agents that may be preferred for other sites of infection.
Fosfomycin
121
ABX Class that has activity for G+ only
Penicillin
122
G+ & G- coverage
Cephalosporin
123
Peniciliin contains what unique structure?
b-lactam nucleus
124
4 membered cyclic amide and B represents the position of Nitrogen (N) atom relative to the carbonyl (C=0) group
B-Lactam ring
125
which aBX class is b-lactam ring fused to a five membered thiazolidine ring?
Penicillin = 6-amino-penicillanic acid nucleus along with side chain
126
Which ABX class contains a b-lactam ring and fused to a six-membered dihydrothiazine ring, making it a 7-aminocephalosporanic acid nucleus attached to side chain
cephalosporin
127
What are the largest group of beta-lactam ABX?
cephalosporins
128
What is the MOA of all Beta-Lactam ABX?
Inhibiting bacterial cell wall synthesis
129
Narrow spectrum Penems
Cloxacillin, Oxacillin, Meticillin
130
Extended Spectrum Penem
Aminopenicillin: Ampicillin, Amoxicillin Carboxypenicillin: Carbencillin, Ticarcillin Piperacillin
131
Name the B-Lactamase inhibitors
Clavulanic Acid Tazobactam Sulbactam
132
What bacterial enzymes are involved in remodeling and synthesis of cell walls?
Transglycosylase, transpeptidase, carboxypeptidase | endopeptidase
133
ceftolozane/tazobactam
ZERBAXA
134
What is dosing for Zerbaxa?
powder for reconstitution, IV 1.5g/vial (ie, 1.5g = 1g ceftolozone plus 0.5g tazobactam)
135
What are ZERBAXA indications?
Complicated Intra-abdominal Infection: Indicated for use in combination with metronidazole for complicated intra-abdominal infections cause by Enterobacter cloacae, Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa, Bacteroides fragilis, Streptococcus anginosus, Streptococcus constellatus, and Streptococcus salivarius 1.5 g IV q8hr x4-14 days Complicated Urinary Tract Infections: Indicated for complicated urinary tract infections, including pyelonephritis, caused by Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, and Pseudomonas aeruginosa 1.5 g IV q8hr x7 days
136
What are dosing adjustments for ZERBAXA?
Dosage Modifications Hepatic impairment: No dosage adjustment required Renal impairment CrCl 30-50 mL/min: 750 mg (500 mg/250 mg) IV q8hr CrCl 15-29 mL/min: 375 mg (250 mg/125 mg) IV q8hr ESRD on hemodialysis: Administer a single loading dose of 750 mg (500 mg/250 mg) followed by a 150-mg (100 mg/50 mg) maintenance dose administered q8hr for the remainder of the treatment period (on hemodialysis days, administer the dose at the earliest possible time following completion of dialysis)
137
What is MOA of ZERBAXA?
Mechanism of Action Ceftolozane: Cephalosporin that has demonstrated potent in vitro activity against Pseudomonas aeruginosa Tazobactam: Beta-lactamase inhibitor
138
What layers make up the g- cell?
``` Outer membrane Lipoproteins Peptidoglycan Periplasmic space Cytoplasmic membrane ```
139
What is the difference in the Peptidoglycan in G+ & G- bacteria?
G+ peptidoglycan layer is thicker than G-. Retaining crystal violet dye, causing G+ bacteria to remain purple
140
What color stain is G- bacteria?
Red
141
What color stain is G+ Bacteria?
Purple
142
Aerobes need _______ to survive. An example of where they are found is _____________.
Oxygen The lungs
143
Do anaerobes need oxygen to survive?
No
144
Where are anaerobes found?
Oral cavity, gi tract, female genital tract
145
In IAI physicians will add on a drug like flagil (metronitisol) to make sure they are covering for what activity?
Anaerobic
146
An example of Anaerobic bacteria would be?
Bacterodies
147
What are common gram + and gram- species associated with cUTI?
G+ Enterococcus species ``` G- E.Col Klebsiella species Proteus species Citrobacter species ```
148
What are common G+ & G- species associated with Bacteremia?
G+ MSSA,MRSA Staphylococcus epidermidis Enterococcus Species ``` G- E.Coli Klebsiella Species Proteus Species PSeudomonas Aeruginosa Acinetobacter Species ```
149
Why would a bacteriostatic ABX not be the best agent for a patient with immuno suppression, HIV, or patient with Cancer?
Static ABX in habit grow, but does not kill the bacteria and are not able to reproduce. The patient does not have the immune response to kill the bacteria.
150
What is AST?
Antimicrobial Susceptibilty Testing
151
MIC
Minimum inhibitory concentration: lowest concentration of ABX that inhibits the visual growth of an organism
152
MBC
Minimum Bacterial Concentration: lowest concentration of ABX that kills an organism in the lab
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Name the MIC Test
Broth Mircrodilution | Epsilometer (E-Test)
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Name the susceptibility only Tests
Kirby-Bauer disc measure zone diameters only. No MIC value
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Breakpoints are used to interpret what data?
MIC Testing
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Susceptibility and resistance is defined by what?
Concentration ug/mL Or inhibition zones mm
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Names that categories of breakpoints
S susceptible = MIC Breakpoint I intermediate = MIC is between S & R Breakpoint Per Drug Per Bug
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Breakpoints define susceptibility and resistance are issued by whom?
FDA CLSA EUCAST European committee
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Comparing an MIC value to the Breakpoint value reveals what?
Whether bacteria are Susceptible, Resistant, Intermediate to the ABX
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Susceptible results means what?
ABX effectively inhibited in-vitro bacterial growth at the MIC -indicating potential therapeutic success
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Four types of data necessary to establish a breakpoint are?
Clinical studies MIC Values PK/PD In-Virto Resistance Markers
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Name the Automated Susceptibility Testing Systems
Vitek 2 Micro scan BD Phoenix Sensititre ARIS 2x
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G- bacteria cell wall structure
Inner plasma membrane Thin peptidoglycan wall Outer membrane
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What is the function of outer membrane of G- cell wall?
Extra layer of protection to the organism
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What does outer membrane of G- cell wall contain?
Lipopolysaccaride -LPS - endotoxins that can enduce a strong immune response in the body: fever or shock - provides challenge when treating pts because it is another layer ABX must penetrate to reach target site
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Space between outer and inner membrane in G- bacteria is called ________
Periplasmic space: - may constitute up to 40% of cell volume of g- bacteria - this is site where g- bacteria can secrete b-lactamases into periplasmic space -
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B-Lactamases, mechanism of resistance for bacteria, can inactivate what class of ABX?
B-Lactam
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DNA of bacteria is contained in __________
Bacteria chromosome (nucleotide region)
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Plasmid
Small circular DNA molecules in G- bacteria
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Ribosomes are responsible for what?
Protein synthesis, which is needed for cell to grow and reproduce
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Aminoglycosides target what ?
Ribosomes to stop protein synthesis and shut down bacterial growth
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Which ABX are Protein Synthesis Inhibitors Acting on Ribosomes?
``` Site of Action: 5oS subunit Erythromycin Clindamycin Synercid Pleuromtilins ``` ``` Site of action: 3oS subunit Aminoglycosides Gentamycin Streptomycin Tetracyclines Glycylclines ``` Both 30S and 5oS Blocks initiation of protein synthesis Linezolid
173
Which ABX have an MOA of Folic Acid Synthesis in the Cytoplasm?
Blocks pathways and inhibits metabolism Sulfamides Trimethoprim
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Which ABX have an MOA of Cell Wall Inhibitors?
Block synthesis and repair ``` Penicillin Cephalosporins Carbapenems Vancomycin Bacitracin Fosfomycin Isoniazid ```
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Which ABX have a MOA attacking the Cell Membrane?
Cause loss of selective permeability Polymyxins Daptomycin
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Which ABX have a MOA of attacking the DNA/RNA?
Inhibit replication and transcription Inhibit garage (unwinding enzyme) Quinolones Inhibit RNA polymerase Rifampin
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What are the 5 ways ABX can attack the bacterial cell?
1. Inhibition of Cell Wall synthesis -b-lactam 2. Inhibition of cell membrane function -polymyxins 3. Inhibition of protein synthesis -quinolones 4. Inhibition of nucleic acid 5. Inhibition of bacterial enzymes or metabolic pathways
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ABX that inhibit cell wall synthesis and effect the cell wall structure act at different stages of what?
Peptidoglycan and cell wall construction
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End results of inhibiting cell wall synthesis is what?
Bacterial lysis -cell breaks open and dies