this presentation show how to choose abx and when and where to prescribe it in CAP , HAP AND VAP

1. Principle Of Antibiotic Use In
Pulmonary Infections from
guidelines to practice
Dr/ Sami El-Dahdouh
Associate prof. of Pulmonary and Critical care
Menoufia Faculty of Medicine

2. Appropriate Antibiotic Selection
and Adequate Dosing
• To achieve adequate therapy, it is necessary not
only to use the correct antibiotic, but also the
optimal dose and the correct route of
administration.
• Pharmaco dynamic properties of specific
antibiotics should also be considered in selecting an
adequate dosing regimen.

3. 1)Tissue versus Blood concentration
Concentration of antibiotic within lung tissues :
B-lactam antibiotics (lipid insoluble, inflammation
dependent) achieve < 50% of their serum concentration in
the lung,
Fluoroquinolones, Macrolide, clindamycn and Linezolid
(lipid soluble, not inflammation dependent) equal or
exceed their serum concentration in bronchial secretions.

4.  LOW VOLUME OF DISTRIBUTION
 INABILITY OF DIFFUSING THROUGH MEMBRANES
 INACTIVE AGAINST INTRACELLULAR PATHOGENS
 RENAL ELIMINATION AS UNCHANGED DRUG
HYDROPHILIC ANTIBIOTICS
• BETA-LACTAMS
 PENICILLINS
 CEPHALOSPORINS
 CARBAPENEMS
 MONOBACTAMS
• GLYCOPEPTIDES
• AMINOGLYCOSIDES
LIPOPHILIC ANTIBIOTICS
• MACROLIDES
• FLUOROQUINOLONES
• TETRACYCLINES
• CHLORAMPHENICOL
• RIFAMPICIN
• LINEZOLID
 HIGH VOLUME OF DISTRIBUTION
 ABILITY OF DIFFUSING THROUGH MEMBRANES
 ACTIVE AGAINST INTRACELLULAR PATHOGENS
 ELIMINATION AFTER LIVER METABOLIZATION
Pea F, Viale P, Furlanut M. Clin Pharmacokinet 2005, 44: 1009-1034

5. 2)The mechanism of action
• ABX interfere with the growth of bacteria by
Cell Wall Affection Protein Synthesis
Metabolic Pathway
• Bacteriostatic inhibit bacterial growth, don't interfere
with cell wall synthesis and rely on host defenses to
eliminate bacteria e.g. macrolides, tetracycline,
chloramphenicol, sulfa ,linezolid and clindamycin.
• Bacteriocidal kill bacteria (cell wall or metabolic
function) e.g. B lactum. Aminoglycosides, fluroquinolone,
vancomycin .
Bacteriostatic drugs not used in neutropnic patients

6. 3)Time Versus Concentration Dependent
Killing
Aminoglycosides and Quinolones are bactericidal in
a concentration-dependent fashion, killing more rapidly
at high concentrations. (Higher concentration
greater killing )
Vancomycin and the B-lactams, are bactericidal, but
in a time-dependent fashion, with the degree of killing
dependent on the time that the serum concentration is
above the organism’s minimal inhibitory concentration
(MIC). (More exposure more killing) .

7. • The B- lactams, with minimal concentration-
dependent killing and a limited post antibiotic
effect, this requires frequent dosing, or
even continuous infusion.
• On the other hand, quinolones and
aminoglycosides ,combining an entire day of
therapy into a single daily dose can take
advantage of both the concentration-dependent
killing mechanism and the post antibiotic effect.

10. Some antibiotics have a “post antibiotic effect”
(PAE), which means that these agents are able to
suppress bacterial growth even after the antibiotic
level falls below the MIC of the organism,eg.
• Aminoglycosides and Quinolones have
prolonged PAE with gram-negative bacilli,
• B-lactam antibiotics has no PAE against gram-
negative bacilli,
• Carbapenem antibiotics (Imipenem or
Meropenem), which have shown a postantibiotic
effect against gram-negative bacilli.
4)“post antibiotic effect

11. Community Associated-MRSA
Recently, an increasing incidence of pneumonia due to
CA-MRSA has been observed.
CA-MRSA appears in 2 patterns:
Typical hospital-acquired strain
Recently, strains that are epidemiologically, genotypically, and
phenotypically distinct from hospital-acquired strains.
The latter are resistant to fewer antimicrobials than are
hospital acquired MRSA strains and often contain the gene
for Panton- Valentine leukocidin, a toxin associated with
clinical features of: Necrotizing pneumonia, - Shock,
Respiratory failure, - Empyema.

12. It is a potential pathogen in patients with necrotizing post
influenza pneumonia.
This strain should also be suspected in patients who present with
cavitary infiltrates without risk factors for anaerobic aspiration
pneumonia.
The majority of CA-MRSA strains are more susceptible in vitro to:
Vancomycin (failure rates 40% with a standard dose (1 g every 12
hours).
Linezolid (Higher penetration into the epithelial lining fluid than
Vancomycin and preferred in renal insufficiency and also inhibit PVL
production).

14. Community acquired Pneumonia
• Where to treat
• What to treat with
• How long to treat
• How to follow up

15. Pneumonia Where to treat

16. Table 1. 2007 Infectious Diseases Society of
America/American Thoracic Society Criteria for
Defining Severe Community-acquired Pneumonia
Validated definition includes either one major
criterion or three or more minor criteria
Minor criteria
Respiratory rate ≥ 30 breaths/min
PaO2/FIO2 ratio ≤ 250
Multilobar infiltrates
Confusion/disorientation
Uremia (blood urea nitrogen level ≥ 20 mg/dl)
Leukopenia* (white blood cell count < 4,000
cells/μl)
Thrombocytopenia (platelet count < 100,000/μl)
Hypothermia (core temperature < 36°C)
Hypotension requiring aggressive fluid
resuscitation
Major criteria
Septic shock with need for vasopressors
Respiratory failure requiring mechanical
ventilation

17. IDSA/ATS Guidelines for CAP in Adults CID 2007:44
Outpatients
• Streptococcus
pneumoniae
• Mycoplasma
pneumoniae
• Haemophilus
influenzae
• Chlamydophila
pneumoniae
• Respiratory
viruses
Inpatient
(non-ICU)
• S. pneumoniae
• M. pneumoniae
• C. pneumoniae
• H. influenzae
• Legionella
species
• Aspiration
• Respiratory
viruses
ICU
• S.pneumoniae
• Staphylococcu
s aureus
• Legionella
species
• Gram-negative
bacilli
• H. influenzae

18. Table 3. Initial Treatment Strategies for Outpatients with Community-acquired
Pneumonia
Standard Regimen
No comorbidities or risk factors for
MRSA or Pseudomonas aeruginosa*
(prior respiratory isolation of MRSA or P.
aeruginosa or recent hospitalization AND
receipt of parenteral antibiotics (in the last 90
d).
Amoxicillin or
doxycycline or
macrolide (if local pneumococcal
resistance is <25%)†
(Amoxicillin 1 g three times daily, doxycycline 100 mg
twice daily, azithromycin 500 mg on first day then 250
mg daily, clarithromycin 500 mg twice daily, or
clarithromycin ER 1,000 mg daily).
With comorbiditieas‡
(Comorbidities include chronic heart, lung,
liver, or renal disease; diabetes mellitus;
alcoholism; malignancy; or asplenia)
Combination therapy with
amoxicillin/clavulanate or cephalosporin
AND
macrolide or doxycycline§
OR
monotherapy with respiratory
fluoroquinolone||

19. §Amoxicillin/clavulanate 500 mg/125 mg three times
daily, amoxicillin/clavulanate 875 mg/125 mg twice
daily, 2,000 mg/125 mg twice daily, cefpodoxime
200 mg twice daily, or cefuroxime 500 mg twice
daily; AND azithromycin 500 mg on first day then
250 mg daily, clarithromycin 500 mg twice daily,
clarithromycin ER 1,000 mg daily, or doxycycline
100 mg twice daily.
Levofloxacin 750 mg daily, moxifloxacin 400 mg
daily, or gemifloxacin 320 mg daily.

20. Standard Regimen
Prior Respiratory
Isolation of MRSA
Prior Respiratory
Isolation
of Pseudomonas
aeruginosa
Recent
Hospitalization and
Parenteral
Antibiotics and
Locally Validated
Risk Factors for
MRSA
Recent
Hospitalization
and Parenteral
Antibiotics and
Locally Validated
Risk Factors for P.
aeruginosa
Nonsevereinpatientpneumonia*
β-Lactam + macrolide†
or
respiratory
fluroquinolone‡
Add MRSA
coverage§ and obtain
cultures/nasal PCR to
allow de-escalation or
confirmation of need for
continued therapy
Add coverage for P.
aeruginosa|| and obtain
cultures to allow de-
escalation or
confirmation of need
for continued therapy
Obtain cultures but
withhold MRSA
coverage unless
culture results are
positive.
If rapid nasal PCR is
available, withhold
additional empiric
therapy against MRSA
if rapid testing is
negative or add
coverage if PCR is
positive and obtain
cultures
Obtain cultures but
initiate coverage
for P. aeruginosa only
if culture results are
positive
Severeinpatient
pneumonia*
β-Lactam + macrolide†
or
β-
lactam + fluroquinolone
‡
Add MRSA
coverage§ and obtain
cultures/nasal PCR to
allow de-escalation or
confirmation of need for
continued therapy
Add coverage for P.
aeruginosa|| and obtain
cultures to allow de-
escalation or
confirmation of need
for continued therapy
Add MRSA coverage§
and obtain nasal PCR
and cultures to allow
de-escalation or
confirmation of need
for continued therapy
Add coverage for P.
aeruginosa|| and
obtain cultures to
allow de-escalation or
confirmation of need
for continued therapy
Table 4. Initial Treatment Strategies for Inpatients with Community-acquired Pneumonia by Level of
Severity and Risk for Drug Resistance

21. Definition of abbreviations: ATS = American Thoracic Society; CAP = community-acquired
pneumonia; HAP = hospital-acquired pneumonia; IDSA = Infectious Diseases Society of
America; MRSA = methicillin-resistant Staphylococcus aureus; VAP = ventilator-associated
pneumonia.
*As defined by 2007 ATS/IDSA CAP severity criteria guidelines (see Table 1).
†Ampicillin + sulbactam 1.5–3 g every 6 hours, cefotaxime 1–2 g every 8 hours, ceftriaxone 1-2
g daily, or ceftaroline 600 mg every 12 hours AND azithromycin 500 mg daily or clarithromycin
500 mg twice daily.
‡Levofloxacin 750 mg daily or moxifloxacin 400 mg daily.
§Per the 2016 ATS/IDSA HAP/VAP guidelines: vancomycin (15 mg/kg every 12 h, adjust based
on levels) or linezolid (600 mg every 12 h).
||Per the 2016 ATS/IDSA HAP/VAP guidelines: piperacillin-tazobactam (4.5 g every 6 h),
cefepime (2 g every 8 h), ceftazidime (2 g every 8 h), imipenem (500 mg every 6 h),
meropenem (1 g every 8 h), or aztreonam (2 g every 8 h). Does not include coverage for
extended-spectrum β-lactamase–producing Enterobacteriaceae, which should be considered
only on the basis of patient or local microbiological data

22. Ceftaroline can be used as an alternative to these agents. It is a
fifth-generation cephalosporin that was not included in the 2007
IDSA/ATS guidelines for the management of CAP since it was not
US Food and Drug Administration (FDA) approved for CAP until
2010.
Ceftaroline has a spectrum of activity like that of ceftriaxone,
including good in vivo activity against Streptococcus pneumoniae. It
is also active against MRSA, unlike older cephalosporins. However,
it is not FDA approved for CAP involving MRSA since patients with
MRSA were excluded from the trials. Ceftaroline is more expensive
Motherapy with tigecycline may be used in patients who cannot take
either a beta-lactam or a fluoroquinolone. Tigecycline was not
included in the 2007 IDSA/ATS guidelines for the management of
CAP because it was not FDA approved for CAP until 2009. It has
been associated with increased mortality,.

23. The panel recommends using doxycycline as an
alternative to a macrolide in combination with a b-
lactam as a third option in the presence of
documented allergies or contraindications to
macrolides or fluoroquinolones or clinical failure on
one of those agents.
Of note, a newer member of the tetracycline class,
omadacycline, was recently reported to be
equivalent to moxifloxacin as monotherapy for
adults with nonsevere CAP and is effective in the
setting of tetracycline resistance

24. Table 2. Differences between the 2019 and 2007 American Thoracic Society/Infectious
Diseases Society of America Community-acquired Pneumonia Guidelines
Recommendation 2007 ATS/IDSA Guideline 2019 ATS/IDSA Guideline
Sputum culture Primarily recommended in patients with
severe disease
Now recommended in patients with severe
disease as well as in all inpatients empirically
treated for MRSA or Pseudomonas aeruginosa
Blood culture Primarily recommended in patients with
severe disease
Now recommended in patients with severe
disease as well as in all inpatients empirically
treated for MRSA or P. aeruginosa
Macrolide monotherapy Strong recommendation for outpatients Conditional recommendation for outpatients
based on resistance levels
Use of procalcitonin Not covered Not recommended to determine need for
initial antibacterial therapy
Use of corticosteroids Not covered Recommended not to use. May be considered
in patients with refractory septic shock
Use of healthcare-associated
pneumonia category
Accepted as introduced in the 2005
ATS/IDSA hospital-acquired and
ventilator-associated pneumonia guidelines
Recommend abandoning this categorization.
Emphasis on local epidemiology and validated
risk factors to determine need for MRSA or P.
aeruginosa coverage. Increased emphasis on
de-escalation of treatment if cultures are
negative
Standard empiric therapy for
severe CAP
β-Lactam/macrolide and
β-lactam/ fluoroquinolone combinations
given equal weighting
Both accepted but stronger evidence in favor
of β-lactam/macrolide combination
Routine use of follow-up chest
imaging
Not addressed Recommended not to obtain. Patients may be
eligible for lung cancer screening, which
should be performed as clinically indicated

25. Duration of therapy
Patients with CAP should be treated for a minimum
of 5 days (level I evidence), should be afebrile for
48–72 h, and should have no more than 1 CAP-
associated sign of clinical instability before
discontinuation of therapy (level II evidence)
A longer duration of therapy may be needed if
initial therapy was not active against the identified
pathogen or if it was complicated by extrapulmonary
infection, such as meningitis or endocarditis. (Weak
recommendation; level III evidence.)

26. – Outpatients
– Inpatient switch to oral therapy
• Responding to IV therapy
• Able to swallow
• Able to absorb from gastrointestinal tract
– Symptoms and Physical findings
– Chest X-ray
• Radiographic resolution will be slower than symptom
resolution
• The duration of radiographic resolution will vary but
should be near complete
• The patient should be followed until symptomatic and
radiographic resolution is complete.
Follow-up
Oral Therapy

27. A 55 year old male presents to his primary care
physician's office with cough, mild dyspnea, and fever
to 38 degrees. Symptoms have been present for the
past 3 days, and when OTC were having no effect, he
decided to seek medical attention.
On initial examination, blood pressure was 120/73,
pulse was 96 and regular, and respirations were 20.
He was febrile with a temperature of 38.5 degrees.
Lung examination revealed the presence of right lower
lung crackles with decreased breath sounds in this
area as well
Case 1 Scenario
‫ش‬

28. Laboratory studies revealed WBC of 15.6 with a left
shift, sodium of 140, potassium of 4.5, BUN of 22 and
creatinine of 1.0. Chest x-ray revealed a right lower
lobe infiltrate.
Based upon the above presentation, what is the most
appropriate course of action?
A. Admit the patient to the hospital and start
intravenous ceftriaxone and azithromycin
B. Admit the patient to the hospital and start
intravenous cefipime
C. Prescribe clarithromycin, 500 mg twice daily and
schedule a follow-up in 1 week
Slide 28

29. • A 77 year old female presents to the emergency
department with dyspnea, fever 39, hypotension and
mental status changes. Initial evaluation
demonstrates a left lower lobe infiltrate.
• Additional studies show blood pressure of 90/60,
respiratory rate of 34, and pulse of 110. Laboratory
parameters include WBC of 2.3, and BUN of 33,
with creatinine of 1.3. Pulse oximetry reveals 88%
on room air, which comes up to 99% on 4 liters.
• One month ago patient had diabtic foot receive iv
course of abx
Case 2 Scenario

30. Based upon the above presentation, which of the
following is the most appropriate course of action?
A. Discharge the patient on oral azithromycin
B. Admit the patient to the general medical ward and
begin intravenous ampicillin-sulbactam and
azithromycin
C. Admit the patient to the intensive care unit, and
begin fluid resuscitation, and intravenous 3rd
generation Cephalosporins and Levofloxacin
d. Admit to icu and prescibe levo 750,linozolid 600 and
peparacillin/tazobactam plus fluid threapy
.
Slide 30

31. Definitions of Nosocomial pneumonias
HAP: Pneumonia that occurs 48 hours or more after admission and
did not appear to be incubating at the time of admission.
Early and Late onset
VAP: A type of HAP acquired at 48-72 hours after intubation.
 Early and Late onset
HCAP(omitted 2016): Non hospital patient with healthcare contact
 IV therapy, wound care, chemotherapy within 30 days
 Nursing home or long term care facility (Nursing Home Pneumonia)
 Hospitalization >2 days or more in past 90 days
 Attendance at hospital or HD within 30 days
 Family member with a MDR pathogen
ATS/IDSA Am J Respir Crit Care Med. 2005;171: 388-416

32. TTT OF HAP

34. 1 million unit equal 80mg prodrug
equal 30 mg active drug

38. Specific Antibiotic Regimens

39. Local Instillation and Aerosolized
Antibiotics
• Local instillation or aerosolization is a way to:
– Enhance antibiotic penetration to the lower respiratory
tract.
– Treat microorganisms that are “resistant” to systemic
therapy.
• The agents most commonly administered and studied in this
fashion have been the Aminoglycosides and Polymyxin
B.
• Patients with HAP due to MDR P. aeruginosa that is
unresponsive to systemic antibiotics, but improved with the
addition of aerosolized aminoglycosides or polymyxin B.
• One side effect of aerosolized antibiotics has been
bronchospasm, which can be induced by the antibiotic or
the associated diluents present in certain preparations.

41. Combination versus Monotherapy
• Combination therapy is common practice in the
therapy of suspected and proven gram-negative
HAP.
• Combination regimens have been
recommended to:
– Prevent the emergence of resistance during
therapy, a common phenomenon when P.
aeruginosa is treated with a variety of single
agents.
– Achieve synergy in the therapy of P.
aeruginosa.
– Provide a broad-spectrum empiric regimen that
is likely to include at least one drug that is
active against the often MDR etiologic agents.

42. • In some studies, combination therapy has been
continued for less than the full course of therapy,
with discontinuation of the aminoglycoside after
5 days if the patient is improving .
• Monotherapy is also the standard when gram-
positive HAP, including MRSA, is documented.
• Agents that have been shown to be effective as
monotherapy in patients with moderate HAP not
due to MDR pathogens include:
– Ciprofloxacin, levofloxacin,
– Imipenem, Meropenem, Cefepime, and
piperacillin–tazobactam.

43. LENGTH OF THERAPY

44. Should Patients With VAP Receive 7 Days or 8–
15 Days of Antibiotic Therapy?
• 1. For patients with VAP, we recommend a 7-day
course of antimicrobial therapy rather than a longer
duration (strong recommendation, moderate-quality
evidence).
• Remarks: There exist situations in which a shorter or
longer duration of antibiotics may be indicated,
depending upon the rate of improvement of clinical,
radiologic, and laboratory parameters.

45. What Is the Optimal Duration of Antibiotic
Therapy for HAP (Non-VAP)?
• 7-day course of antimicrobial therapy (strong
recommendation, very low quality evidence).
• Remarks: There exist situations in which a shorter or
longer duration of antibiotics may be indicated,
depending upon the rate of improvement of clinical,
radiologic, and laboratory parameters.

46. Should Antibiotic Therapy Be De-escalated or
Fixed in Patients With HAP/VAP?
• Antibiotic therapy be de-escalated rather than fixed (weak
recommendation, very low-quality evidence).
• Remarks: De-escalation refers to changing an empiric broad-
spectrum antibiotic regimen to a narrower antibiotic regimen
by changing the antimicrobial agent or changing from
combination therapy to monotherapy.
• In contrast, fixed antibiotic therapy refers to maintaining a
broad-spectrum antibiotic regimen until therapy is completed.

47. Case study

48. • 76-year-old male NH resident
• History of dementia and chronic obstructive pulmonary
disease.
• Developed massive epistaxis requiring nasal packing in ED
& 2 units of packed red blood cells.
• Admitted to the ICU and required intubation for airway
protection for 3 days.
• No initial antibiotic prophylaxis on admission.
• On day 4 of hospitalization, fever developed up to 39.4°C,
hypotension and a new left-sided infiltrate was identified.
• Lab all within normal except leukocytosis 15,000 with 7%
bands.
• Had history of copd excerbation 2 month ago take oral abx

50. THANK YOU