This document discusses antibiotic strategy in nosocomial pneumonia. It begins by outlining the main mechanisms of action for antimicrobial drugs, including inhibition of cell wall synthesis, protein synthesis, nucleic acid synthesis, metabolic pathways, and interference with cell membrane integrity. It then discusses the effects of drug combinations, noting that synergism can occur when two drugs together have greater effects than individually. The document also provides definitions and classifications for nosocomial pneumonias like HAP, VAP, and HCAP. It discusses diagnostic criteria and challenges, as well as risk factors for different pathogen types. Finally, it addresses considerations for empiric therapy, favoring initial monotherapy for early HAP but recommending combination therapy for late-onset and
Antibiotics in the ICU - when, what and how?scanFOAM
A presentation by Fredrik Sjövall at the 2017 meeting of the Scandinavian Society of Anaestesiology and Intensive Care Medicine.
All available content from SSAI2017: https://scanfoam.org/ssai2017/
Delivered in collaboration between scanFOAM, SSAI & SFAI.
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.
Antibiotics in the ICU - when, what and how?scanFOAM
A presentation by Fredrik Sjövall at the 2017 meeting of the Scandinavian Society of Anaestesiology and Intensive Care Medicine.
All available content from SSAI2017: https://scanfoam.org/ssai2017/
Delivered in collaboration between scanFOAM, SSAI & SFAI.
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.
Guidelines For Antibiotic Use by doctor SaleemMuhammad Saleem
Antibiotic guidelines in surgery,
especially antibiotic prophylaxis.
Prophylactic antibiotics in general surgery, cardiothoracic, vascular, orthopedic,neurosurgery,
Classification of wounds.
Guidelines of prophylactic antibiotics
By doctor Saleem
https://www.saleemplasticsurgeon.com/
Mayo Clinic Critical Care Grand Rounds (26 Feb 2015)
Pro-Con debate: The use of ultrasound assessment of the Inferior Vena Cava to guide fluid resuscitation: fact or fiction?
Anaesthesia-Critical Care.
A neglected topic for way too long, the interest in fluid therapy seems to be quickly rising as the medical community is making a shift from looking at fluids as a mere method of stabilization towards the appreciation of its relevant side effects.
Many questions remain to be answered indeed:
Is the upgrade from saline 0.9% to balanced crystalloids worth the extra cost?
Does HES still have a place in the OR?
Do we have to fill the gap left by HES on ICU with crystalloids, other colloids or even albumin?
Is it really impossible to avoid fluid overload by using only crystalloids?
Is there still a definitive place for human albumin?
How do we treat and monitor specific patient populations, like patients with trauma, liver failure, brain edema and right heart failure among others?
How do we avoid a one-size-fits-all regimen in perioperative goal-directed therapy?
What with the fluids beyond resuscitation?
And what do the authors of the big fluid trials do in real life themselves?
The 9th International Fluid Academy Day will again be a 1 day concise meeting on all aspects of fluid managament and hemodynamic monitoring in the critically ill.
Date: October 26th 2019, 8:00 - 18:00
Clinical Practice Guidelines for Traumatic Brain Injury 2556Utai Sukviwatsirikul
Clinical Practice Guidelines for Traumatic Brain Injury 2556
แนวทางเวชปฏิบัติกรณีสมองบาดเจ็บ (Clinical Practice Guidelines for Traumatic Brain Injury) พิมพ์ครั้งที่ 1 2556
http://pni.go.th/pnigoth/wp-content/uploads//2013/10/Clinical-Practice-Guidelines-for-Traumatic-Brain-Injury.pdf
Updated global adult sepsis guidelines, released in October 2021 by the Surviving Sepsis Campaign (SSC), place an increased emphasis on improving the care of sepsis patients after they are discharged from the intensive care unit (ICU) and represent greater geographic and gender diversity than previous versions.
The new guidelines specifically address the challenges of treating patients experiencing the long-term effects of sepsis. Patients often experience lengthy ICU stays and then face a long, complicated road to recovery. In addition to physical rehabilitation challenges, patients and their families are often uncertain how to coordinate care that promotes recovery and matches their goals of care.
Guidelines For Antibiotic Use by doctor SaleemMuhammad Saleem
Antibiotic guidelines in surgery,
especially antibiotic prophylaxis.
Prophylactic antibiotics in general surgery, cardiothoracic, vascular, orthopedic,neurosurgery,
Classification of wounds.
Guidelines of prophylactic antibiotics
By doctor Saleem
https://www.saleemplasticsurgeon.com/
Mayo Clinic Critical Care Grand Rounds (26 Feb 2015)
Pro-Con debate: The use of ultrasound assessment of the Inferior Vena Cava to guide fluid resuscitation: fact or fiction?
Anaesthesia-Critical Care.
A neglected topic for way too long, the interest in fluid therapy seems to be quickly rising as the medical community is making a shift from looking at fluids as a mere method of stabilization towards the appreciation of its relevant side effects.
Many questions remain to be answered indeed:
Is the upgrade from saline 0.9% to balanced crystalloids worth the extra cost?
Does HES still have a place in the OR?
Do we have to fill the gap left by HES on ICU with crystalloids, other colloids or even albumin?
Is it really impossible to avoid fluid overload by using only crystalloids?
Is there still a definitive place for human albumin?
How do we treat and monitor specific patient populations, like patients with trauma, liver failure, brain edema and right heart failure among others?
How do we avoid a one-size-fits-all regimen in perioperative goal-directed therapy?
What with the fluids beyond resuscitation?
And what do the authors of the big fluid trials do in real life themselves?
The 9th International Fluid Academy Day will again be a 1 day concise meeting on all aspects of fluid managament and hemodynamic monitoring in the critically ill.
Date: October 26th 2019, 8:00 - 18:00
Clinical Practice Guidelines for Traumatic Brain Injury 2556Utai Sukviwatsirikul
Clinical Practice Guidelines for Traumatic Brain Injury 2556
แนวทางเวชปฏิบัติกรณีสมองบาดเจ็บ (Clinical Practice Guidelines for Traumatic Brain Injury) พิมพ์ครั้งที่ 1 2556
http://pni.go.th/pnigoth/wp-content/uploads//2013/10/Clinical-Practice-Guidelines-for-Traumatic-Brain-Injury.pdf
Updated global adult sepsis guidelines, released in October 2021 by the Surviving Sepsis Campaign (SSC), place an increased emphasis on improving the care of sepsis patients after they are discharged from the intensive care unit (ICU) and represent greater geographic and gender diversity than previous versions.
The new guidelines specifically address the challenges of treating patients experiencing the long-term effects of sepsis. Patients often experience lengthy ICU stays and then face a long, complicated road to recovery. In addition to physical rehabilitation challenges, patients and their families are often uncertain how to coordinate care that promotes recovery and matches their goals of care.
GENERAL PRINCIPLES OF ANTIBIOTIC THERAPY.pptxShaanSinojia
To review about general principles of antibiotic therapy to understand more about their action and precautions while prescribing antibiotics to the patient.
1. chemotherapy principles and problems JagirPatel3
The objective of chemotherapy is to study and to apply the drugs that have highly selective toxicity to the pathogenic microorganisms in the host body and have no or less toxicity to the host, so as to prevent and cure infective diseases caused by pathogens
Oxygen Therapy is not Beneficial in COPD Patients with Moderate HypoxaemiaGamal Agmy
A Randomized Trial of Long-Term Oxygen for COPD with Moderate Desaturation
The Long-Term Oxygen Treatment Trial Research Group*
N Engl J Med. 2016 October 27; 375(17): 1617–1627
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
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Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
Pulmonary Thromboembolism - etilogy, types, medical- Surgical and nursing man...VarunMahajani
Disruption of blood supply to lung alveoli due to blockage of one or more pulmonary blood vessels is called as Pulmonary thromboembolism. In this presentation we will discuss its causes, types and its management in depth.
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
Couples presenting to the infertility clinic- Do they really have infertility...Sujoy Dasgupta
Dr Sujoy Dasgupta presented the study on "Couples presenting to the infertility clinic- Do they really have infertility? – The unexplored stories of non-consummation" in the 13th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2024) at Manila on 24 May, 2024.
The prostate is an exocrine gland of the male mammalian reproductive system
It is a walnut-sized gland that forms part of the male reproductive system and is located in front of the rectum and just below the urinary bladder
Function is to store and secrete a clear, slightly alkaline fluid that constitutes 10-30% of the volume of the seminal fluid that along with the spermatozoa, constitutes semen
A healthy human prostate measures (4cm-vertical, by 3cm-horizontal, 2cm ant-post ).
It surrounds the urethra just below the urinary bladder. It has anterior, median, posterior and two lateral lobes
It’s work is regulated by androgens which are responsible for male sex characteristics
Generalised disease of the prostate due to hormonal derangement which leads to non malignant enlargement of the gland (increase in the number of epithelial cells and stromal tissue)to cause compression of the urethra leading to symptoms (LUTS
5. MECHANISMS OF ACTION OF
ANTIBACTERIAL DRUGS
Mechanism of action
include:
Inhibition of cell wall
synthesis
Inhibition of protein
synthesis
Inhibition of nucleic acid
synthesis
Inhibition of metabolic
pathways
Interference with cell
membrane integrity
6. MECHANISMS OF ACTION OF
ANTIBACTERIAL DRUGS
Inhibition of Cell wall synthesis
Bacteria cell wall unique in
construction
Contains peptidoglycan
Antimicrobials that interfere with
the synthesis of cell wall do not
interfere with eukaryotic cell
Due to the lack of cell wall in
animal cells and differences in cell
wall in plant cells
These drugs have very high
therapeutic index
Low toxicity with high effectiveness
Antimicrobials of this class include
β lactam drugs
Vancomycin
Bacitracin
7. Inhibition of protein synthesis
Structure of prokaryotic ribosome acts as target for
many antimicrobials of this class
Differences in prokaryotic and eukaryotic ribosomes
responsible for selective toxicity
Drugs of this class include
Aminoglycosides
Tetracyclins
Macrolids
Chloramphenicol
MECHANISMS OF ACTION
OF ANTIBACTERIAL DRUGS
8. Inhibition of nucleic acid synthesis
These include
Fluoroquinolones
Rifamycins
MECHANISMS OF ACTION
OF ANTIBACTERIAL DRUGS
9. MECHANISMS OF ACTION
OF ANTIBACTERIAL DRUGS
Inhibition of metabolic
pathways
Relatively few
Most useful are folate
inhibitors
Mode of actions to
inhibit the production
of folic acid
Antimicrobials in this
class include
Sulfonamides
Trimethoprim
10. MECHANISMS OF ACTION
OF ANTIBACTERIAL DRUGS
Interference with cell
membrane integrity
Few damage cell
membrane
Polymixn B most common
Common ingredient in
first-aid skin ointments
Binds membrane of Gram
- cells
Alters permeability
Leads to leakage of cell
and cell death
Also bind eukaryotic cells
but to lesser extent
Limits use to topical
application
11. EFFECTS OF
COMBINATIONS OF DRUGS
Sometimes the chemotherapeutic effects of
two drugs given simultaneously is greater than
the effect of either given alone.
This is called synergism. For example,
penicillin and streptomycin in the treatment
of bacterial endocarditis. Damage to
bacterial cell walls by penicillin makes it
easier for streptomycin to enter.
12. EFFECTS OF
COMBINATIONS OF DRUGS
Other combinations of drugs can be
antagonistic.
For example, the simultaneous use of penicillin
and tetracycline is often less effective than
when wither drugs is used alone. By stopping
the growth of the bacteria, the
bacteriostatic drug tetracycline interferes
with the action of penicillin, which requires
bacterial growth.
13. EFFECTS OF
COMBINATIONS OF DRUGS
Combinations of antimicrobial drugs should
be used only for:
1. To prevent or minimize the emergence of
resistant strains.
2. To take advantage of the synergistic effect.
3. To lessen the toxicity of individual drugs.
18. Concepts
Pharmacokinetics
– describe how drugs behave in the human host
Pharmacodynamics
– the relationship between drug concentration
and antimicrobial effect. “Time course of
antimicrobial activity”
19. Minimum Inhibitory Concentration (MIC)
– The lowest concentration of an antibiotic that inhibits
bacterial growth after 16-20 hrs incubation.
Minimum Bacteriocidal Concentrations.
– The lowest concentration of an antibiotic required to
kill 99.9% bacterial growth after 16-20 hrs exposure.
C-p
– Peak antibiotic concentration
Area under the curve (AUC)
– Amount of antibiotic delivered over a specific time.
Concepts
20. Antimicrobial-micro-organism
interaction
Antibiotic must reach the binding site of
the microbe to interfere with the life cycle.
Antibiotic must occupy “sufficient” number
of active sites.
Antibiotic must reside on the active site for
“sufficient” time. Antibiotics are not contact
poisons.
22. Questions
Can this antibiotic inhibit/kill these bacteria?
Can this antibiotic reach the site of bacterial replication?
What concentration of this antibiotic is needed to
inhibit/kill bacteria?
Will the antibiotic kill better or faster if we increase its
concentration?
Do we need to keep the antibiotic concentration always
high throughout the day?
23. Can this antibiotic inhibit/kill these bacteria?
In vitro susceptibility testing
Mixing bacteria with antibiotic at different
concentrations and observing for bacterial
growth.
24. 32 ug/ml 16 ug/ml 8 ug/ml 4 ug/ml 2 ug/ml 1 ug/ml
Sub-culture to agar medium
MIC = 8 ug/ml
MBC = 16 ug/ml
Minimal Inhibitory Concentration (MIC)
vs.
Minimal Bactericidal Concentration (MBC)
REVIEW
25. What concentration of this antibiotic is
needed to inhibit/kill bacteria?
In vitro offers some help
– Concentrations have to be above the MIC.
How much above the MIC?
How long above the MIC?
Time
Conc
MIC
26. Patterns of Microbial Killing
Concentration dependent
– Higher concentration greater killing
Aminoglycosides, Flouroquinolones, Ketolides,
metronidazole, Ampho B.
Time-dependent killing
– Minimal concentration-dependent killing (4x
MIC)
– More exposure more killing
Beta lactams, glycopeptides, clindamycin,
macrolides, tetracyclines, bactrim
27. Persistent Effects
Persistent suppression of bacterial growth
following antimicrobial exposure.
– Moderate to prolonged against all GM
positives (In vitro)
– Moderate to prolonged against GM negatives
for protein and nucleic acid synthesis
inhibitors.
– Minimal or non against GM negatives for beta
lactams (except carabapenems against P.
aeruginosa)
28. Post-antibiotic sub-MIC effect.
– Prolonged drug level at sub-MIC augment the
post-antibiotic effect.
Post-antibiotic leukocyte killing enhancement.
– Augmentation of intracellular killing by
leukocytes.
– The longest PAE with antibiotics exhibiting this
characteristic.
Persistent Effects
29. Patterns of Antimicrobial Activity
Concentration dependent with moderate to
prolonged persistent effects
– Goal of dosing
Maximize concentrations
– PK parameter determining efficacy
Peak level and AUC
– Examples
Aminoglycosides, Flouroquinolones, Ketolides,
metronidazole, Ampho B.
30. Time-dependent killing and minimal to
moderate persistent effects
– Goal of dosing
Maximize duration of exposure
– PK parameter determining efficacy
Time above the MIC
– Examples
Beta lactam, macrolides, clindamycin, flucytosine,
linezolid.
Patterns of Antimicrobial Activity
31. Patterns of Antimicrobial Activity
Time-dependent killing and prolonged
persistent effects
– Goal of dosing
Optimize amount of drug
– PK parameter determining efficacy
AUC
– Examples
Azithromycin, vancomycin, tetracyclines,
fluconazole.
33. Antibacterial spectrum — Range of activity
of an antim icrobial against bacteria. A
broad-spectrum antibacterial drug can
inhibit a wide variety of gram -positive and
gram -negative bacteria, whereas a
narrow -spectrum drug is active only
against a lim ited variety of bacteria.
Bacteriostatic activity— -The level of
antim icro-bial activity that inhibits the
growth of an organism . This is determ ined
in vitro by testing a standardized
concentration of organism s against a
series of antim icrobial dilutions. The
lowest concentration that inhibits the
growth of the organism is referred to as
the m inim um inhibitory concentration
(M IC).
Bactericidal activity— The level of
antim icrobial activity that kills the test
organism . This is determ ined in vitro by
exposing a standardized concentration of
organism s to a series of antim icrobial
dilutions. The lowest concentration that
kills 99.9% of the population is referred to
as the m inim um bactericidal
concentration (M BC).
Antibiotic com binations— Com binations of
antibiotics that m ay be used (1) to broaden
the antibacterial spectrum for em piric
therapy or the treatm ent of polym icrobial
infections, (2) to prevent the em ergence of
resistant organism s during therapy, and (3)
to achieve a synergistic killing effect.
Antibiotic synergism — Com binations of
two antibiotics that have enhanced
bactericidal activity when tested together
com pared with the activity of each
antibiotic.
Antibiotic antagonism — Com bination of
antibiotics in which the activity of one
antibiotic interferes W ith the activity of the
other (e.g., the sum of the activity is less
than the activity of the individual drugs).
Beta-lactam ase— An enzym e that
hydrolyzes the beta-lactam ring in the
beta-lactam class of antibiotics, thus
inactivating the antibiotic. The enzym es
specific for penicillins and cephalosporins
aret he penicillinases and
cephalosporinases, respectively.
35. Resistance
Physiological Mechanisms
4. Altered target
RIF – altered RNA polymerase (mutants)
NAL – altered DNA gyrase
STR – altered ribosomal proteins
ERY – methylation of 23S rRNA
5. Synthesis of resistant pathway
TMPr plasmid has gene for DHF reductase;
insensitive to TMP
(cont’d)
REVIEW
36. Resistance to β-Lactams – Gram pos.
Mechanism of Action
CELL WALL SYNTHESIS INHIBITORS
(cont’d)
REVIEW
37. Resistance to β-Lactams – Gram neg.
Mechanism of Action
CELL WALL SYNTHESIS INHIBITORS
(cont’d)
REVIEW
38. The Ideal Drug*
1. Selective toxicity: against target pathogen but
not against host
LD50 (high) vs. MIC and/or MBC (low)
2. Bactericidal vs. bacteriostatic
3. Favorable pharmacokinetics: reach target site
in body with effective concentration
4. Spectrum of activity: broad vs. narrow
5. Lack of “side effects”
Therapeutic index: effective to toxic dose ratio
6. Little resistance development
39. 39
Pneumonias – Classification
• Community AcquiredCAP
• Health Care AssociatedHCAP
• Hospital AcquiredHAP
• ICU AcquiredICUAP
• VentilatorAcquiredVAP
Nosocomial Pneumonias
40. *HAP: diagnosis made > 48h after admission
*VAP: diagnosis made 48-72h after endotracheal
intubation
*HCAP: diagnosis made < 48h after admission
with any of the following risk factors:
(1) hospitalized in an acute care hospital for >
48h within 90d of the diagnosis;
(2) resided in a nursing home or long-term care
facility;
(3) received recent IV antibiotic therapy,
chemotherapy, or wound care within the 30d
preceding the current diagnosis; and
(4) attended a hospital or hemodialysis clinic
Definitions of NP
41. The American Thoracic Society suggests that the
diagnosis should be considered in any patient with new or
progressive radiological infiltrates and clinical features to
suggest infection:
•Fever (core temperature >38°C),
• Leukocytosis (>10000mm-3) or leukopenia (<4000mm-3),
•Purulent tracheal secretions,
•Increased oxygen requirements, reflecting new or
worsening hypoxaemia.
Diagnosis
47. Gram-negative bacilli, particularly enterobacteria, are
present in the oropharyngeal flora of patients with chronic
underlying illnesses, such as COPD, heart failure,
neoplasms, AIDS and chronic renal failure.
Infection by P. aeruginosa and other more resistant
Gram-negative bacilli such as Acinetobacter
baumannii and ESBL-producing enterobacteria should
be considered in patients discharged from ICUs,
submitted to wide-spectrum antibiotic treatment and in
those with severe underlying disease or prolonged
hospitalisation in areas with a high prevalence of these
microorganisms.
Risk Factors
48. An increased risk for Legionella spp. should be
considered in immunosuppressed patients (previous
treatment with high-dose steroids or chemotherapy.
Gingivitis or periodontal disease, depressed
consciousness, swallowing disorders and orotracheal
manipulation are usually recorded when anaerobes are
the causative agents of the pneumonia
Coma, head injury, diabetes, renal failure or recent
influenza infection are at risk from infection by S.
aureus.
Risk Factors
49. HAP due to fungi such as Aspergillusmay develop in
organ transplant, neutropenic or immunosuppressed
patients, especially those treated with corticoids.
Risk Factors
50. Risk for ventilator-associated pneumonia
due to multidrug-resistant pathogens
Hospitalisation
Especially if intubated and in the ICU for ≥5 days (late-onset
infection)
Prior antibiotic therapy
Particularly in the prior 2 weeks
Recent hospitalisation in the preceding 90 days
Other HCAP risk factors
From a nursing home
Haemodialysis
Home-infusion therapy
Poor functional status
Risk factors for specific pathogens
Pseudomonas aeruginosa
Prolonged ICU stay
Corticosteroids
Structural lung disease
Methicillin-resistant Staphylococcus aureus
Coma
Head trauma
Diabetes
Renal failure
Prolonged ICU stay
Recent antibiotic therapy
51. The optimal empiric monotherapy for nosocomial
pneumonia consists of ceftriaxone, ertapenem,
levofloxacin, or moxifloxacin. Monotherapy may be
acceptable in patients with early onset hospital-
acquired pneumonia.
Avoid monotherapy with ciprofloxacin,
ceftazidime, or imipenem, as they are likely to
induce resistance potential.
Empiric monotherapy versus
combination therapy
52. Late-onset hospital-acquired pneumonia,
ventilator-associated pneumonia, and health
care–associated pneumonia require
combination therapy using an antipseudomonal
cephalosporin, beta lactam, or carbapenem
plus an antipseudomonal fluoroquinolone or
aminoglycoside plus an agent such as linezolid
or vancomycin to cover MRSA
Empiric monotherapy versus
combination therapy
53. Optimal combination regimens for proven P
aeruginosa nosocomial pneumonia include (1)
piperacillin/tazobactam plus amikacin or (2) meropenem
plus levofloxacin, aztreonam, or amikacin.[12]
Avoid using ciprofloxacin, ceftazidime, gentamicin, or
imipenem in combination regimens, as combination
therapy does not eliminate the resistance potential of
these antibiotics.
Empiric monotherapy versus
combination therapy
54. When selecting an aminoglycoside for a combination
therapy regimen, amikacin once daily is preferred to
gentamicin or tobramycin to avoid resistance problems.
When selecting a quinolone in a combination therapy
regimen, use levofloxacin, which has very good anti– P
aeruginosa activity (equal or better than ciprofloxacin at
a dose of 750 mg).
Empiric monotherapy versus
combination therapy
55. Hospital-Acquired, Health Care-Associated, and Ventilator-
Associated Pneumonia Organism-Specific Therapy
Pseudomonas aeruginosa
*Piperacillin-tazobactam 4.5 g IV q6h plus amikacin 20 mg/kg/day
IV plus levofloxacin 750 mg IV q24h or
*Cefepime 2 g IV q8h plus amikacin 20 mg/kg/day IV plus levofloxacin
750 mg IV q24h or
*Imipenem 1 g q6-8h plus amikacin 20 mg/kg/day IV plus levofloxacin 750
mg IV q24h or
*Meropenem 2 g IV q8h plus amikacin 20 mg/kg/day IV plus levofloxacin
750 mg IV q24h or
*Aztreonam 2 g IV q8h plus amikacin 20 mg/kg/day IV plus levofloxacin
750 mg IV q24h
Duration of therapy: 10-14d
56. Hospital-Acquired, Health Care-Associated, and Ventilator-
Associated Pneumonia Organism-Specific Therapy
Klebsiella pneumoniae
Cefepime 2 g IV q8h or
Ceftazidime 2 g IV q8h or
Imipenem 500 mg IV q6h or
Meropenem 1 g IV q8h or
Piperacillin-tazobactam 4.5 g IV q6h
Extended-spectrum beta-lactamase (ESBL)strain
Imipenem 500 mg IV q6h or
Meropenem 1 g IV q8h
K pneumoniae carbapenemase (KPC) strain
Colistin 5 mg/kg/day divided q12h or
Tigecycline 100 mg IV, then 50 mg IV q12h
Duration of therapy: 8-14d
57. Hospital-Acquired, Health Care-Associated, and Ventilator-
Associated Pneumonia Organism-Specific Therapy
MRSA
Vancomycin 15 mg/kg IV q12h for 7-14 d or
Linezolid 600mg IV or PO q12h for 7-14 d
Targocid 400mg IV once daily for 7-14 d
58. Hospital-Acquired, Health Care-Associated, and Ventilator-
Associated Pneumonia Organism-Specific Therapy
MSSA
Oxacillin 1g IV q4-6h for 7-14 d or
Nafcillin 1-2 g IV q6h for 7-14 d
59. Hospital-Acquired, Health Care-Associated, and Ventilator-
Associated Pneumonia Organism-Specific Therapy
Legionella pneumophila
Levofloxacin 750 mg IV q24h, then 750 mg/day PO for 7-
14d or
Moxifloxacin 400 mg IV or PO q24h for 7-14d or
Azithromycin 500 mg IV q24h for 7-10d
60. Hospital-Acquired, Health Care-Associated, and Ventilator-
Associated Pneumonia Organism-Specific Therapy
Acinetobacter baumannii
Imipenem 1 g IV q6h or
Meropenem 1 g IV q8h or
Doripenem 500 mg IV q8h or
Ampicillin-sulbactam 3 g IV q6h or
Tigecycline 100 mg IV in a single dose, then 50 mg IV
q12h or
Colistin 5 mg/kg/day IV divided q12h
Duration of therapy: 14-21d
61. Hospital-Acquired, Health Care-Associated, and Ventilator-
Associated Pneumonia Organism-Specific Therapy
Stenotrophomonas maltophilia
Trimethoprim-sulfamethoxazole 15-20 mg/kg/day of TMP
IV or PO divided q8h or
Ticarcillin-clavulanate 3 g IV q4h or
Ciprofloxacin 750 mg PO or 400 mg IV q12h or
Moxifloxacin 400 mg PO or IV q24h
Duration of therapy: 8-14d
62. Category Circumstances Treatment
Severe HAP# Severity criteria
Cefepime 2 g every 8 h + aminoglycoside (Amikacin
20 mg·kg−1·day−1) or quinolone (Levofloxacin 750 mg i.v.
HAP with risk factors for
Gram-negative bacilli Chronic underlying disease Antipseudomonal β-lactam± aminoglycoside or quinolone
Cefepime 1–2 g every 8–12 h i.v.
Carbapenems¶: imipenem 500 mg every 6 h or 1 g every
8 h i.v.; or meropenem 1 g every 8 h i.v.; or
ertapenem+ 1 g·day−1i.v.
P. aeruginosaand multi-
resistant Gram-negative
bacilli
Wide-spectrum antibiotics, severe
underlying disease, ICU stay
Antipseudomonal β-lactam±aminoglycoside or quinolone
Cefepime 1–2 g every 8–12 h i.v.
β-lactamic/β-lactamase inhibitor: piperacillin-tazobactam
4.5 g every 6 hi.v.
Carbapenems¶: imipenem 500 mg every 6 h or 1 g every
8 h i.v.; or meropenem 1 g every 8 h i.v.
Legionella#
Hospital potable water colonisation and/or
previous nosocomial Legionellosis
Levofloxacin 500 mg every 12–24 h i.v.or 750§ mg every
24 h i.v. or azitromycin 500 mg·day−1 i.v.
Anaerobes
Gingivitis or periodontal disease,
depressed consciousness, swallowing
disorders and orotracheal manipulation
Carbapenems¶: imipenem 500 mg every 6 h or 1 g every
8 h i.v.; or meropenem 1 g every 8 h i.v.; or
ertapenem+ 1 g·day−1i.v.
β-lactam/β-lactamase inhibitor amoxicillin/clavulanate 2 g
every 8 hi.v.¶; piperacillin-tazobactam 4.5 g every 6 h i.v.
MRSA
Risk factors for MRSA or high prevalence
of MRSA
Vancomycin 15 mg·kg−1 every 12 h i.v.Linezolid 600 mg
every 12 h i.v.
Aspergillus
Corticotherapy, neutropenia or
transplantation
Amphotericyn B desoxicolate 1 mg·kg−1·day−1 i.v. or
amphotericyn liposomal 3–5 mg·kg−1·day−1 i.v.Voriconazol
6 mg·kg−1 every 12 h i.v.(day 1) and 4 mg·kg−1 every
12 h i.v.(following days)
Early-onset HAP <5 days Without risk factors and non-severe
β-lactam/β-lactamase inhibitor: amoxicillin/clavulanate 1–2 g
every 8 hi.v.
Third generation non-pseudomonal cephalosporin:
ceftriaxone 2 g·day−1i.v./i.m. or cefotaxime 2 g every 6–8 hi.v.
Fluoroquinolones: levofloxacin 500 mg every 12–24 h i.v. or
750§ mg·day−1 i.v.
Late-onset HAP ≥ 5 days Without risk factors and non-severe
Antipseudomonal cephalosporin (including pneumococcus):
cefepime 2 g every 8 h i.v.
Fluoroquinolones: levofloxacin 500 mg every 12–24 h i.v. or
750§ mg·day−1 i.v.