The document discusses postantibiotic effects (PAE) and sub-minimum inhibitory concentration (sub-MIC) effects of antibiotics in vitro and in vivo. It defines PAE as the suppression of bacterial growth after brief antibiotic exposure. PAE depends on antibiotic type, bacteria, concentration, and exposure duration. It is longer for Gram-positives than Gram-negatives. Sub-MICs can prolong PAE and cause sub-MIC effects, suppressing bacterial growth. Prolonged PAE and sub-MIC effects indicate antibiotics may be effective at lower doses or longer intervals than expected based solely on in vitro MICs.
Tuberculosis is a raging problem round the globe. Eradicating TB is a herculean task but is possible is efforts from all corners from the world. The diagnostics have taken a big leap and with effective medications, our dream of TB free world may come true. But unlimited efforts are need to reach our goal.
Tuberculosis is a raging problem round the globe. Eradicating TB is a herculean task but is possible is efforts from all corners from the world. The diagnostics have taken a big leap and with effective medications, our dream of TB free world may come true. But unlimited efforts are need to reach our goal.
Presented by Ms. Hindler at the 40th Annual Symposium "Diagnostic and Clinical Challenges of 20th Century Microbes", held on Nov 18, 2010 in Philadelphia.
While MIC is a good measure of antibiotic activity, it is static and reflects in vitro activity. PK and PD of the drug needs to be considered together with MIC if we wish to obtain an in vivo prediction of drug action and success.
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Al Khobar, Saudi Arabia
Quinolones are synthetic, bactericidal antibacterial agents with broad-spectrum activity. They inhibit the enzyme topoisomerase II, a DNA gyrase that is necessary for the replication of the microorganism.
Presented by Ms. Hindler at the 40th Annual Symposium "Diagnostic and Clinical Challenges of 20th Century Microbes", held on Nov 18, 2010 in Philadelphia.
While MIC is a good measure of antibiotic activity, it is static and reflects in vitro activity. PK and PD of the drug needs to be considered together with MIC if we wish to obtain an in vivo prediction of drug action and success.
Best Practice for Colistin Susceptibility Testing: Methods and Evidence (Mini...Abdullatif Al-Rashed
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Quinolones are synthetic, bactericidal antibacterial agents with broad-spectrum activity. They inhibit the enzyme topoisomerase II, a DNA gyrase that is necessary for the replication of the microorganism.
Kuliah Pakar Drs. Didiek Hasmono, MS, Apt Universitas Airlangga Surabaya Universitas Muhammadiyah Malang
Please contact me if you necessity to this presentation in gilangrizki.alfarizi@gmail.com
Therapeutic indications
Tavanic is indicated in adults for the treatment of the following infections (see sections 4.4 and 5.1):
• Acute bacterial sinusitis
• Acute exacerbations of chronic bronchitis
• Community-acquired pneumonia
• Complicated skin and soft tissue infections
For the above-mentioned infections Tavanic should be used only when it is considered inappropriate to use antibacterial agents that are commonly recommended for the initial treatment of these infections.
• Pyelonephritis and complicated urinary tract infections (see section 4.4)
• Chronic bacterial prostatitis
• Uncomplicated cystitis (see section 4.4)
• Inhalation Anthrax: post exposure prophylaxis and curative treatment (see section 4.4)
Tavanic may also be used to complete a course of therapy in patients who have shown improvement during initial treatment with intravenous levofloxacin.
Consideration should be given to official guidance on the appropriate use of antibacterial agents.
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Fluoroquinolone
Cefepime
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Carbapenem
Colistin
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Letter from the Congress of the United States regarding Anti-Semitism sent June 3rd to MIT President Sally Kornbluth, MIT Corp Chair, Mark Gorenberg
Dear Dr. Kornbluth and Mr. Gorenberg,
The US House of Representatives is deeply concerned by ongoing and pervasive acts of antisemitic
harassment and intimidation at the Massachusetts Institute of Technology (MIT). Failing to act decisively to ensure a safe learning environment for all students would be a grave dereliction of your responsibilities as President of MIT and Chair of the MIT Corporation.
This Congress will not stand idly by and allow an environment hostile to Jewish students to persist. The House believes that your institution is in violation of Title VI of the Civil Rights Act, and the inability or
unwillingness to rectify this violation through action requires accountability.
Postsecondary education is a unique opportunity for students to learn and have their ideas and beliefs challenged. However, universities receiving hundreds of millions of federal funds annually have denied
students that opportunity and have been hijacked to become venues for the promotion of terrorism, antisemitic harassment and intimidation, unlawful encampments, and in some cases, assaults and riots.
The House of Representatives will not countenance the use of federal funds to indoctrinate students into hateful, antisemitic, anti-American supporters of terrorism. Investigations into campus antisemitism by the Committee on Education and the Workforce and the Committee on Ways and Means have been expanded into a Congress-wide probe across all relevant jurisdictions to address this national crisis. The undersigned Committees will conduct oversight into the use of federal funds at MIT and its learning environment under authorities granted to each Committee.
• The Committee on Education and the Workforce has been investigating your institution since December 7, 2023. The Committee has broad jurisdiction over postsecondary education, including its compliance with Title VI of the Civil Rights Act, campus safety concerns over disruptions to the learning environment, and the awarding of federal student aid under the Higher Education Act.
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2024.06.01 Introducing a competency framework for languag learning materials ...Sandy Millin
http://sandymillin.wordpress.com/iateflwebinar2024
Published classroom materials form the basis of syllabuses, drive teacher professional development, and have a potentially huge influence on learners, teachers and education systems. All teachers also create their own materials, whether a few sentences on a blackboard, a highly-structured fully-realised online course, or anything in between. Despite this, the knowledge and skills needed to create effective language learning materials are rarely part of teacher training, and are mostly learnt by trial and error.
Knowledge and skills frameworks, generally called competency frameworks, for ELT teachers, trainers and managers have existed for a few years now. However, until I created one for my MA dissertation, there wasn’t one drawing together what we need to know and do to be able to effectively produce language learning materials.
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MASS MEDIA STUDIES-835-CLASS XI Resource Material.pdf
Post antibiotic-sub-mic-effects
1. The postantibiotic and sub-MIC
The postantibiotic and sub-MIC
effects in vitro and in vivo
effects in vitro and in vivo
Inga Odenholt, MD., Ph.D.
Department of Infectious Diseases
University hospital
Malmö
Sweden
3. Postantibiotic effect;
Postantibiotic effect;
PAE in vitro
PAE in vitro
Definition:
• Suppression of bacterial growth after short
exposure of organisms to antibiotics
PAE=T-C
T= The time required for the exposed culture to
increase one log10 above the count observed
immediately after drug removal
C= The corresponding time for the unexposed
control
5. Postantibiotic effect
Postantibiotic effect
in vitro
in vitro
The PAE is dependent on:
• Type of antibiotic
• Type of bacterial species
• Concentration of the antibiotic
• Duration of exposure
• Size of the inoculum
• Growth phase of the organism
8. PAE against P. aeruginosa
PAE against P. aeruginosa
•
•
•
•
•
Antibiotics
Penicillins
Cephalosporins
Carbapenems
Quinolones
Aminoglycosides
hours
0
0
1-2
1-2
2-3
9. The PAE at different concentrations against E. coli
8
7
6
hours
5
Rifampicin
4
Tetracykline
Cefamandole
3
2
1
0
0,5
1
2
4
xMIC
8
16
32
Craig & Gudmundsson, 1991
10. PAE at different exposure times against S. aureus
6
5
PAE (h)
4
Penicillin
Erythromycin
3
2
1
0
0
2
4
6
8
10
12hours
11. Effect on inoculum size on the PAE
120
100
Min
80
10 9 cfu/mL
10 7 cfu/mL
60
10 5 cfu/mL
10 3 cfu/mL
40
20
0
1
Ciprofloxacin
2
Tobramycin
12. PAE in vitro
PAE in vitro
Methods
Methods
1.
Viable counts
Methodological pitfalls
• may overestimate killing
• negative PAEs are common with ß-lactams
and gram-negatives due to forming of filaments
• similar inocula of the control and the preexposed culture are desirable
14. PAE in vitro
PAE in vitro
Methods
Methods
2.
Optical density
Methodological pitfalls
• killing cannot be measured due to a detection limit
of 106 cfu/ml
• control curves at different inocula and viable
counts after drug removal are necessary to be
performed to ensure that PAE culture and control
are at the same inoculum
15. PAE in vitro
PAE in vitro
Methods
Methods
3.
ATP measurement
Methodological pitfalls
• bactericidal activity is underestimated due to dead
but intact (not lysed) bacteria still containing
intracellular ATP
• PAE is overestimated due to falsely elevated ATP
content
16. PAE measured with ATP
-7
log10 M bacterial ATP
-8
-9
Control
PAE
Dilution
-10
-11
0
1
2
3
4
5
6
7
8
9
h
17. PAE in vitro
PAE in vitro
Methods
Methods
Morphology
4.
• Phase contrast microscopy
– the time it takes for the bacteria to revert to 90%
bacilli
• Ultrastructural changes
-
the changes in structure correlates well with
the PAE measured with viable counting
5. 3H-thymidine incorporation
-correlates well with the PAE measured with
viable counting
19. CERT
CERT
• Definition
CERT=T-C
T=the time required for resumption of
logarithmic growth and increase of one
log10 to occur over the preexposed inoculum
of the test tube
20. Calculation of CERT with bioluminescence
3
1.3 h
2
ATP log10 M
6h
1
PAE=4,7 h
Control
PAE
0
-1
-2
h
-2
-1
0
1
2
3
4
5
6
7
21. Calculation of CERT using viable counts
3
1.6 h
2
log10 cfu/mL
1
0
PAE=-0.3 h
Control
PAE
-1
1.3 h
-2
-3
-4
-2
-1
0
1
2
3
4
5
6
7
h
23. Postantibiotic effect in vivo
Postantibiotic effect in vivo
Definition
PAE= T-C-M
• T= the time required for the counts of cfu in thighs
of treated mice to increase one log10 above the
count closest to but not less than the time M
• C= the time required for the counts of cfu in thighs
of untreated mice to increase one log10 above the
count at time zero
• M= the time serum concentration exceeds the MIC
24. The postantibiotic effect of gentamicin against K. pneumoniae in vivo
10
9
8
log10 cfu/mL
7
6
5
4
Control
PAE
3
T>MIC
2
1
0
-2
0
2
4
6
8
10
12
Fantin et al. JAC, 1990
14
h
25. PAE in vivo
PAE in vivo
• Observed in several animal models
• In vitro data are predictive of in vivo results
except that in vivo PAE are usually longer due to
the effect of sub-MICs and/or the effect of
neutrophils
• The major unexplained discordant results are for
ß-lactams and streptococci
26. PAE in vivo
PAE in vivo
Animal models
Animal models
•Thigh infections in mice
•Pneumonia model in mice
•Infected treads in mice
•Infected tissue cages in rabbits
•Meningitis model in rabbits
•Endocarditis model in rats
27. Mechanisms of PAE
Mechanisms of PAE
• β-lactam antibiotics.
At least for S. pyogenes and penicillin
it has been shown that PAE stands for
the time it takes for the bacteria to
resynthesize new PBPs
28. Mechanisms of PAE
Mechanisms of PAE
• Erythromycin and
clarithromycin:
50S ribosomal subunits were reduced
during 90 min and protein synthesis
during 4 h (PAE) due to prolonged
binding of the antibiotics to 50S.
29. Mechanisms of PAE
Mechanisms of PAE
• Aminoglycosides:
Binding of sublethal amounts of drug enough to
disrupt DNA, RNA and protein synthesis. The
time it takes to resynthesize these proteins.
With a half-life of >2.5 h, the PAE disappears,
reflecting a sufficient time for the repair
mechanism to be restored.
31. Postantibiotic sub-MIC
Postantibiotic sub-MIC
effect; PA SME
effect; PA SME
Definition
• The effect of subinhibitory antibiotic
concentrations on bacteria previously exposed to
suprainhibitory concentrations
PA SME= TPA-C
• TPA=the time it takes for the cultures previously
exposed to antibiotics and thereafter to sub-MICs
to increase by one log10 above the counts observed
immediately after washing.
• C=corresponding time for the unexposed control
32. PA SME of telithromycin against H. influenzae
10
9
8
log10 cfu/mL
7
6
5
PAE
0.1xMIC
4
0.2xMIC
0.3xMIC
Control
3
2
1
0
3
6
9
12
15
18
21
24
h
34. PAE PASME) in vivo of amikacin against K.
PAE (( PASME) in vivo of amikacin against K.
pneumoniae in a thigh-infection model in
pneumoniae in a thigh-infection model in
mice
mice
• Normal mice (half-life 19 min)
PAE
5.5 h
• Uremic mice (half-life 98 min)
14.6 h
35. The PAE and PA SME of piperacillin against S. aureus in vivo
9,00
8,50
8,00
log10 cfu/mL
7,50
7,00
Control
PAE
PA SME
6,50
6,00
5,50
Penicillinase
5,00
4,50
T>MIC
4,00
h
-2
0
2
4
6
8
10
Oshida et al. JAC, 1990
37. Post-MIC effect; PME
Post-MIC effect; PME
Definition
• The effect of sub-MICs on bacteria previously
exposed to a constant decreasing antibiotic
concentration
PME=Tpme-C
• Tpme= The time for the counts in cfu of the
exposed culture to increase one log10 above the
count observed at the MIC level
• C= the time for an unexposed control to increase
one log10
38. The post-MIC effect of benzylpenicillin against S. pneumoniae (PcR)
10
9
8
log10 cfu/mL
7
MIC
10mg/l
100 mg/l
Control
6
5
4
PME at 10 mg/l 12.9-2.3= 10.6
3
PME at 100 mg/l 7.5-2.3= 5.2
2
1
0
2
4 MIC
6
8
10
12
14
16
18
20
22
24 h
39. Mechanism of PA SME?
Mechanism of PA SME?
• The PAE of ß-lactam antibiotics seems to
represent the time necessary to synthesize
new PBPs. When bacteria in the PA-phase
are exposed to sub-MICs, most PBPs are
still inactivated and only a small amount of
the drug is needed to prolong the inhibition
of cell multiplication until a critical number
of free PBPs are once more available
41. Postantibiotic leucocyte
Postantibiotic leucocyte
enhancement; PALE
enhancement; PALE
• Bacteria pretreated with antibiotics for a
brief period of time show increased
susceptibility to intracellular killing and
phagocytosis
• In general, antibiotics that produce the
longest PAEs exhibit maximal PALEs
43. The SME of P&G kinolon against S. pneumoniae
9
8
log10 cfu/mL
7
6
Control
0.1xMIC
0.2xMIC
0.3xMIC
5
4
3
2
h
0
3
6
9
12
15
18
21
24
44. Sub-MIC effects; SME
Sub-MIC effects; SME
Definition
• The effect of subinhibitory antibiotic
concentrations on bacteria not previously
exposed to suprainhibitory concentrations
SME= Ts-C
•Ts=the time it takes for the cultures exposed to
sub-MICs to increase by one log10 above the counts
observed immediately after washing
•C=corresponding time for the unexposed control
45. Sub-MIC effects
Sub-MIC effects
• The minimum antibiotic concentrations that
produces a structural change in bacteria seen
by light or electron microscopy
• The minimum antibiotic concentration that
produces a one log10 decrease in the bacterial
population compared to the control
• Loss or change of bacterial toxins
46. Sub-MIC effects
Sub-MIC effects
• Loss of surface antigens resulting in
decreased adhesion
• Increased rates of phagocytic ingestion
and killing
• Increased chemotaxsis and opsonization
47. Mechanism of sub-MIC
Mechanism of sub-MIC
effects
effects
• SME probably tests the distribution of
antibiotic susceptibility in the bacterial
population, in which there are
subpopulations that are inhibited by
concentrations less than the MIC. The
SME would therefore represent the time
it takes for the population with the
higher MIC to become dominant
48. Implications
Implications
• The combined effects of supra- and subinhibitory
concentrations seem to be more important for
dosing regimens then PAE itself.
• A long PA SME/PME indicate that longer dosing
intervals may be used even for antibiotics, which
are dependent on the T>MIC for efficacy