This document discusses antibiotic strategies for community-acquired pneumonia (CAP) and exacerbations of chronic obstructive pulmonary disease (AECOPD). It outlines the mechanisms of action, testing, and spectrum of various antimicrobial drugs. It also describes methods for assessing the severity of CAP cases and determining appropriate treatment and site of care based on severity scores. Empiric antibiotic recommendations are provided for outpatient, inpatient, ICU, and specific pathogen cases of CAP.

2. Antibiotic Strategy in
CAP &AECOPD
Gamal Rabie Agmy, MD, FCCP
Professor of Chest Diseases , Assiut University

4. ANTIMICROBIAL DRUGS

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. ANTIMICROBIAL
SUSCEPTIBILITY TESTING
 Probably the most
widely used testing
method is the disk-
diffusion method, also
known as the Kirby-
Bauer test.

7. SUSCEPTIBILITY OF BACTERIAL
TO ANTIMICROBIAL DRUG
 Conventional disc diffusion
method
 Kirby-Bauer disc diffusion
routinely used to
qualitatively determine
susceptibility
 Standard concentration of
strain uniformly spread of
standard media
 Discs impregnated with
specific concentration of
antibiotic placed on plate
and incubated
 Clear zone of inhibition
around disc reflects
susceptibility
 Based on size of zone
organism can be
described as susceptible
or resistant

8. Antibacterial spectrum—Range of activity
of an antimicrobial 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 limited variety of bacteria.
Bacteriostatic activity—-The level of
antimicro-bial activity that inhibits the
growth of an organism. This is determined
in vitro by testing a standardized
concentration of organisms against a
series of antimicrobial dilutions. The
lowest concentration that inhibits the
growth of the organism is referred to as
the minimum inhibitory concentration
(MIC).
Bactericidal activity—The level of
antimicrobial activity that kills the test
organism. This is determined in vitro by
exposing a standardized concentration of
organisms to a series of antimicrobial
dilutions. The lowest concentration that
kills 99.9% of the population is referred to
as the minimum bactericidal
concentration (MBC).
Antibiotic combinations—Combinations of
antibiotics that may be used (1) to broaden
the antibacterial spectrum for empiric
therapy or the treatment of polymicrobial
infections, (2) to prevent the emergence of
resistant organisms during therapy, and (3)
to achieve a synergistic killing effect.
Antibiotic synergism—Combinations of
two antibiotics that have enhanced
bactericidal activity when tested together
compared with the activity of each
antibiotic.
Antibiotic antagonism—Combination of
antibiotics in which the activity of one
antibiotic interferes With the activity of the
other (e.g., the sum of the activity is less
than the activity of the individual drugs).
Beta-lactamase—An enzyme that
hydrolyzes the beta-lactam ring in the
beta-lactam class of antibiotics, thus
inactivating the antibiotic. The enzymes
specific for penicillins and cephalosporins
aret he penicillinases and
cephalosporinases, respectively.

9. 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

10. 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

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.

14. Resistance
Physiological Mechanisms
1. Lack of entry – tet, fosfomycin
2. Greater exit
 efflux pumps
 tet (R factors)
3. Enzymatic inactivation
 bla (penase) – hydrolysis
 CAT – chloramphenicol acetyl transferase
 Aminogylcosides & transferases
REVIEW

15. 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

17. Infection of the lung parenchyma in a
person who is not hospitalized or living in
a long-term care facility for ≥ 2 weeks.
This pneumonia develops in the outpatient
setting or within 48 hours of admission to
a hospital.
Definition of CAP

18. *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
HCAP

19. The clinical diagnosis of CAP
Symptoms:
May be preceded by URTI
• Respiratory: Cough dry or productive,
mucopurulent sputum , sometimes rusty, dyspnea,
sometimes pleuritic chest pain
• Non-respiratory: Fever, body aches, altered mental
state, vomiting or diarrhea.

20. The clinical diagnosis of CAP
Signs:
Generally: Fever, sometimes hypothermia,
tachycardia, tachypnea.
Local: signs of consolidation

21. Severity of CAP

22. 22
PORT Scoring – PSI
Clinical Parameter Scoring
Age in years Example
For Men (Age in yrs) 50
For Women (Age -10) (50-10)
NH Resident 10 points
Co-morbid Illnesses
Neoplasia 30 points
Liver Disease 20 points
CHF 10 points
CVD 10 points
Renal Disease (CKD) 10 points
Clinical Parameter Scoring
Clinical Findings
Altered Sensorium 20 points
Respiratory Rate > 30 20 points
SBP < 90 mm 20 points
Temp < 350 C or > 400 C 15 points
Pulse > 125 per min 10 points
Investigation Findings
Arterial pH < 7.35 30 points
BUN > 30 20 points
Serum Na < 130 20 points
Hematocrit < 30% 10 points
Blood Glucose > 250 10 points
Pa O2 10 points
X Ray e/o Pleural Effusion 10 points
Pneumonia Patient Outcomes
Research Team (PORT)

23. 23
Classification of Severity - PORT
Predictors
Absent
Class
I
 70
Class
II
71 – 90
Class
III
91 - 130
Class
IV
> 130
Class
V

24. 24
CAP – Management based on PSI Score
PORT Class PSI Score Mortality % Treatment Strategy
Class I No RF 0.1 – 0.4 Out patient
Class II  70 0.6 – 0.7 Out patient
Class III 71 - 90 0.9 – 2.8 Brief hospitalization
Class IV 91 - 130 8.5 – 9.3 Inpatient
Class V > 130 27 – 31.1 IP - ICU

25. 25
CURB 65 Rule – Management of CAP
CURB 65
Confusion
BUN > 30
RR > 30
BP SBP <90
DBP <60
Age > 65
CURB 0 or 1 Home Rx
CURB 2 Short Hosp
CURB 3 Medical Ward
CURB 4 or 5 ICU care

26. Indications for admitting CAP patients to ICU
Major Criteria(1/2 sufficient)
• Acute respiratory failure(mechanical ventilation)
• Severe sepsis or septic shock(need of vasopressors)
Minor Criteria (ICU admission
recommended if ≥3)
• Respiration rate ≥ 30/min • Multi lobar involvement
• PaO2:FiO2 ≤250 +/-SaO2 <90% with 6 L O2
• Confusion/ disorientation • Uremia BUN ≥20 mg/dl
• Leukopenia WBC < 4 x 109/L
• Thrombocytopenia Tc < 100.000 / mm3
• Hypothermia core temp< 36°
• Hypotension requiring aggressive fluid resuscitation

27. 27
CAP – Value of Chest Radiograph
• Usually needed to establish diagnosis
• It is a prognostic indicator
• To rule out other disorders
• May help in etiological diagnosis
J Chr Dis 1984;37:215-25

28. 28
Infiltrate Patterns and Pathogens
CXR Pattern Possible Pathogens
Lobar S.pneumo, Kleb, H. influ, Gram Neg
Patchy Atypicals, Viral, Legionella
Interstitial Viral, PCP, Legionella
Cavitatory Anerobes, Kleb, TB, S.aureus, Fungi
Large effusion Staph, Anaerobes, Klebsiella

29. 29
Normal CXR & Pneumonic Consolidation

30. 30
Lobar Pneumonia – S.pneumoniae

31. 31
CXR – PA and Lateral Views

32. 32
Lobar versus Segmental - Right Side

33. 33
Lobar Pneumonia

34. 34
Special forms of Consolidation

35. 35
Round Pneumonic Consolidation

36. 36
Special Forms of Pneumonia

37. 37
Special Forms of Pneumonia

38. 38
Complications of Pneumonia

39. 39
Empyema

40. 40
Mycoplasma Pneumonia

41. 41
Mycoplasma Pneumonia

42. 42
Chlamydia Trachomatis

43. 43
Rare Types of Pneumonia

44. Chest sonography

45. Chest sonography

46. Post-stenotic pneumonia
Posterior intercostal scan shows a
hypoechoic consolidated area that contains
anechoic, branched tubular structures in the
bronchial tree (fluid bronchogram).

47. Chest sonography

48. Chest sonography

49. 49
CAP – The Two Types of Presentations
Classical
• Sudden onset of CAP
• High fever, shaking chills
• Pleuritic chest pain, SOB
• Productive cough
• Rusty sputum, blood tinge
• Poor general condition
• High mortality up to 20% in
patients with bacteremia
• S.pneumoniae causative
• Gradual & insidious onset
• Low grade fever
• Dry cough, No blood tinge
• Good GC – Walking CAP
• Low mortality 1-2%; except
in cases of Legionellosis
• Mycoplasma, Chlamydiae,
Legionella, Ricketessiae,
Viruses are causative
Atypical

50. 50
CAP – Pathogenesis
Inhalation
Aspiration
Hematogenous

51. 51
 Age
 Obesity; Exercise is protective
 Smoking, PVD
 Asthma, COPD
 Immuno-suppression, HIV
 Institutionalization, Old age homes etc
 Dementia
CAP – Risk Factors for Pneumonia
ID Clinics 1998;12:723. Am J Med 1994;96:313

52. Diagnostic testing:
Outpatient setting: Routine diagnostic tests
to identify an etiologic diagnosis are optional
for outpatients with CAP. Microbiological tests
are not recommended.
• Inpatient setting: Routine diagnostic tests to
identify an etiologic diagnosis are required in
critically ill CAP and when specific pathogens are
suspected (e.g. TB) that would likely change
individual antibiotic management.

53. Cultures to identify the causative organism:
Sputum cultures are not recommended in
cases of CAP except in certain occasions:
• Patients admitted in hospital or ICU.
• Patients who do not respond to empirical
antibiotic therapy.
• Suspect of resistant strains of S.pneumoniae.

54. Sputum Gram stain
is a rapid and inexpensive test that can
help a lot:
• Differentiate Gm –ve from Gm +ve bacteria.
• Excess pus cells without organism suspect
atypical infection.

55. Blood Culture
:
Recommended for all patients with moderate and
high severity CAP, preferably before antibiotic
therapy is commenced.

56. Examination of sputum for Mycobacterium
Tuberculosis should be considered for patients
with a persistent productive cough, especially
if malaise, weight loss or night sweats, or risk
factors for tuberculosis (e.g., ethnic origin,
social deprivation, elderly) are present.

57. 57
Objective 2
Objective 1
Avoid emergence
of
multidrug resistant
microorganisms
Immediate Rx.
of patients with
serious sepsis
The Therapy Conundrum

58. 58
Empiric Treatment – Outpatient
Healthy and no risk factors for DR S.pneumoniae
1. Macrolide or Doxycycline
Presence of co-morbidities, use of antimicrobials
within the previous 3 months, and regions with a
high rate (>25%) of infection with Macrolide
resistant S. pneumoniae
1. Respiratory FQ – Levoflox, Gemiflox or Moxiflox
2. Beta-lactam (High dose Amoxicillin, Amoxicillin-
Clavulanate is preferred; Ceftriaxone, Cefpodoxime,
Cefuroxime) plus a Macrolide or Doxycycline

59. 59
Empiric Treatment – Inpatient – Non ICU
1. A Respiratory Fluoroquinolone (FQ) or
2. A Beta-lactam plus a Macrolide (or Doxycycline)
(Here Beta-lactam agents are 3 Generation
Cefotaxime, Ceftriaxone, Amoxiclav)
3. If Penicillin-allergic Respiratory FQ or
Ertapenem is another option

60. 60
Empiric Treatment: Inpatient in ICU
1. A Beta-lactam (Cefotaxime, Ceftriaxone,
or Ampicillin-Sulbactam) plus
either Azithromycin or Fluoroquinolone
2. For penicillin-allergic patients, a respiratory
Fluoroquinolone and Aztreonam

61. 61
Empiric Rx. – Suspected Pseudomonas
1. Piperacillin-Tazobactam, Cefepime, Carbapenums
(Imipenem, or Meropenem) plus either Cipro or Levo
2. Above Beta-lactam + Aminoglycoside + Azithromycin
3. Above Beta-lactam + Aminoglycoside + an
antipseudomonal and antipneumococcal FQ
4. If Penicillin allergic - Aztreonam for the Beta-lactam

62. 62
Empiric Rx. – CA MRSA
For Community Acquired Methicillin-Resistant
Staphylococcus aureus (CA-MRSA)
 Targocid,Vancomycin or Linezolid
 For Methicillin Sensitive S. aureus (MSSA)
B-lactam and sometimes a respiratory
Fluoroquinolone, (until susceptibility results).

63. Switching from intravenous to oral
Patients treated initially with parenteral
antibiotics should be transferred to an oral
regimen when they are hemodynamically stable
and improving clinically, are able to ingest
medications, and have a normally functioning
gastrointestinal tract.

64. Duration of the Treatment:
Patients with CAP should be treated for a
minimum of 5 days, should be afebrile for 48–72
h, and should have no more than 1 CAP-
associated sign of clinical instability before
discontinuation of therapy. Lengthening of
therapy to a minimum of 14 days is
recommended in some cases according to
severity.

65. Criteria for clinical stability
Temperature≤37.8_C
Heart rate ≤100 beats/min
Respiratory rate≤24 breaths/min
Systolic blood pressure ≥90 mm Hg
Arterial oxygen saturation ≥90% or pO2 ≥60
mm Hg on room air
Ability to maintain oral intake*
Normal mental status*

66. What to Do When a
Patient with Community
Acquired Pneumonia
Fails to improve?

67. Treatment failure is a matter of
particular concern in the management of
CAP.
Treatment failure is associated with high
morbidity and mortality rates.
Its detection and management require
careful clinical assessment.

68. Definition
Lack of response or worsening of clinical
status (i.e., hemodynamic instability,
incidence of respiratory failure, need for
mechanical ventilation, radiographic
progression , or appearance of new
metastatic infectious foci)

69. Definition
Failure to respond to antimicrobial
treatment was classified as
nonresponding or progressive
pneumonia.

70. Definition
◙Nonresponding pneumonia was defined as
persistent fever > 38°C and/or clinical symptoms
(malaise, cough, expectoration, dyspnea) after at
least 72 hours of antimicrobial treatment.
◙Progressive pneumonia was defined as clinical
deterioration in terms of the development of either
or both septic shock and acute respiratory failure
requiring ventilator support after at least 72 hours
of treatment.

71. Types
1-Early Failure: within 72 hours
2-Late failure: after 72 hours

72. Incidence
2.4 to 31% for early failure and
 from 3.9 to 11% for late failure.

73. Factors associated with
treatment failure
◙ High-risk pneumonia
◙ Liver disease ,neurological, neoplasia and
aspiration
◙ Multilobar infiltrates
◙ Legionella pneumonia
◙ Gram-negative pneumonia
◙ Pleural effusion
◙ Cavitation
◙ Leucopenia, and
◙ Discordant antimicrobial therapy.

74. Lower risk of failure
◙ Influenza vaccination
◙Initial treatment with
fluoroquinolones, and
◙ Chronic obstructive pulmonary
disease

75. Laboratory markers for
treatment failure
1-Procalcitonin
2-CRP
3- IL6, IL8
4- IL1
5-Pleural effusion
6-Multilobar affection
7-CURB 65>3
Predicting treatment failure in patients with community acquired pneumonia: a case-
control study. Loeches et al, Respiratory Research2014 ,15:75

76. Evaluating a patient who is not
responding to therapy
◙Repeating the history (including travel and pet
exposures to look for unusual pathogens), chest
radiograph, and sputum cultures, blood cultures, and
urine antigen testing for Streptococcal pneumoniae and
Legionella if not previously done .
◙If this is unrevealing, then further diagnostic
procedures,, such as chest computed tomography [CT],
bronchoscopy, and lung biopsy can be performed.

77. Chest sonography

78. Chest sonography

79. Post-stenotic pneumonia
Posterior intercostal scan shows a
hypoechoic consolidated area that contains
anechoic, branched tubular structures in the
bronchial tree (fluid bronchogram).

80. Chest sonography

81. Chest sonography

82. Chest CT
Chest CT can detect pleural effusion, lung abscess, or
central airway obstruction, all of which can cause
treatment failure.
It may also detect noninfectious causes such as
bronchiolitis obliterans organizing pneumonia .
Since empyema and parapneumonic effusion can
contribute to nonresponse, thoracentesis should be
performed in all nonresponding patients with
significant pleural fluid accumulation.

83. Chest CT

84. Bronchoscopy
Bronchoscopy can evaluate the airway for
obstruction due to a foreign body or
malignancy, which can cause a postobstructive
pneumonia.
Protected brushings and bronchoalveolar lavage
(BAL) may be obtained for microbiologic and
cytologic studies; in some cases, transbronchial
biopsy may be helpful.

85. Bronchoscopy
In addition, BAL may reveal evidence of
noninfectious disorders or, if there is a
lymphocytic rather than neutrophilic
alveolitis, viral or Chlamydia infection

86. Thoracoscopic lung biopsy
Thoracoscopic or open lung biopsy may be
performed if all of these procedures are
nondiagnostic and the patient continues to be ill.
The advent of thoracoscopic procedures has
significantly reduced the need for open lung
biopsy and its associated morbidity.

87. 87
 Age > 65
 Bacteremia (for S. pneumoniae)
 S. aureus, MRSA , Pseudomonas
 Extent of radiographic changes
 Degree of immuno-suppression
 Amount of alcohol consumption
CAP – Risk Factors for Mortality
ID Clinics 1998;12:723. Am J Med 1994;96:313

89. AECOPD
Most exacerbations of COPD are caused by
viral or bacterial infection. Approximately 50%
of exacerbations are caused by bacterial
infection. Mild to moderate exacerbations is
often caused by Haemophilus influenzae,
Streptococcus pneumoniae, Moraxella
catarrhalis,
A severe exacerbation is often caused by
Pseudomonas aeruginosa and Enterobacteriacea

90. AECOPD
Sputum cultures should not be routinely performed
expect in patients with frequent exacerbations,
worsening clinical status or inadequate response
after 72 hours on initial empiric antibiotic, and /or
exacerbation requiring mechanical ventilation

91. Uncomplicated AECOPD
H. influenzae
S. pneumoniae
M. catarrhalis
• Floroquinolones
• Advanced macrolide
(azythromycin, clarithromycin)
• Cephalosporins 2nd or 3rd
generation

92. Complicated AECOPD
As in Uncomplicated
AECOPD plus presence
of resistant organisms (s
– lactamase producing,
penicillin-resistant S.
pneumoniae), Entero-
bacteriaceae (K.
pneumoniae, E. coli,
Proteus, Enterobacter,
etc)
ß-lactam/ß-lactamase
inhibitor (Co-amoxiclav,
ampicillin/ sulbactam)
• Fluoroquinolone
(Gemifloxacin,
Levofloxacin,
Moxifloxacin)

93. Complicated AECOPD
As in complicated
AECOPD plus
P. aeruginosa
Fluoroquinolone
(Ciprofloxacin,
Levofloxacin –
high dose^)
• Piperacillin-
tazobactam

94. Risk factors for poor outcome in
patients with AECOPD
presence of comorbid diseases, severe
COPD, frequent exacerbations (>3/yr), and
antimicrobial use within last 3 months.

95. P. aeruginosa should be considered
in the presence of at least two of the
following [recent hospitalization, frequent
(>4 courses per year) or recent
administration of antibiotics (last 3 months),
severe disease (FEV1 < 30%), oral steroid
use (>10 mg of prednisolone daily in the last
2 weeks)].