This document provides guidelines for evaluating and treating patients with hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) based on the latest evidence and expert consensus. It discusses recommendations for using clinical scoring systems to decide whether to initiate antibiotics, recommendations for empiric and pathogen-directed antibiotic therapy, evaluating treatment failure, the role of inhaled antibiotics, duration of treatment, and other important management considerations. The overall aim is to guide clinicians in providing appropriate antibiotic treatment while minimizing unnecessary use of antibiotics.

2. Antibiotic Strategy in Lower
Respiratory Tract Infections
Gamal Rabie Agmy, MD,FCCP
Professor and Head of Chest Department ,
Assiut University

3. Ground glass
Ground glass (GGO) pattern is the most
common finding in COVID-19 infections.
They are usually multifocal, bilateral and
peripheral, but in the early phase of the
disease the GGO may present as a unifocal
lesion, most commonly located in the
inferior lobe of the right lung
CT Signs of COVID 19

4. CT Signs of COVID 19
CT-images of a young
male, who had fever for
ten days with
progressive coughing
and shortness of breath.
Saturation at admission
was 66%.The PCR test
was positive for COVID-
19.
There are widespread
bilateral ground-glass
opacities with a
posterior predominance.

5. Crazy paving
Sometimes there are thickened interlobular
and intralobular lines in combination with a
ground glass pattern. This is called crazy
paving.
It is believed that this pattern is seen in a
somewhat later stage.
CT Signs of COVID 19

6. CT Signs of COVID 19
Crazy-Paving

7. Vascular dilatation
A typical finding in the area of ground glass is widening of the vessels .
CT Signs of COVID 19

8. Traction Bronchiectasis
Another common finding in the areas of ground glass is traction
bronchiectasis .
CT Signs of COVID 19

9. Subpleural bands and Architectural
distortion
CT Signs of COVID 19

10. 10

14. Pneumonia
Posterior intercostal scan shows a hypoechoic
consolidated area that contains multiple
echogenic lines that represent an air
bronchogram.

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

16. Contrast-enhanced ultrasonography
of pneumonia
A: Baseline scan shows
a hypoechoic
consolidated area
B: Seven seconds after
iv bolus of contrast
agent, the lesion shows
marked and
homogeneous
enhancement
C: The lesion remains
substantially unmodified
after 90 s.

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

19. 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)

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

21. 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.

22. Definition
◙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.

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

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

25. 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.

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

27. 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

28. 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.

29. Chest sonography

30. Chest sonography

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

32. Chest sonography

33. Chest sonography

34. 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.

35. Chest CT

36. 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.

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

38. 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.

39. Algorithm for evaluation of patients suspected of having pulmonary
infection.
T. Franquet Eur Respir J 2001;18:196-208
©2001 by European Respiratory Society

41. In Patients With Suspected HAP/VAP, Should the Modified
Clinical Pulmonary Infection Score (CPIS) Plus Clinical
Criteria, or Clinical Criteria Alone, Be Used to Decide
Whether or Not to Initiate Antibiotic Therapy?
 Using clinical criteria alone, rather than using CPIS plus
clinical criteria, to decide whether or not to initiate
antibiotic therapy (weak recommendation, low-quality
evidence).

42. Clinical Pulmonary Infection Score
(CPIS)

43. CPIS

44. TREATMENT OF VENTILATOR-
ASSOCIATED
TRACHEOBRONCHITIS

45. Should Patients With Ventilator-
Associated Tracheo-bronchitis (VAT)
Receive Antibiotic Therapy?
• Not providing antibiotic therapy (weak
recommendation, low-quality evidence).

46. INITIAL TREATMENT OF VAP
AND HAP

47. Should Selection of an Empiric Antibiotic
Regimen for VAP Be Guided by Local
Antibiotic-Resistance Data?
 All hospitals regularly generate and disseminate a local antibiogram, ideally
one that is specific to their intensive care population(s) if possible
 Empiric treatment regimens be informed by the local distribution of
pathogens associated with VAP and their antimicrobial susceptibilities.
 Values and preferences: Targeting the specific pathogens and to assure
adequate treatment.
 Remarks: The frequency with which the distribution of pathogens and their
antimicrobial susceptibilities are updated should be determined by the
institution. Considerations should include their rate of change, resources,
and the amount of data available for analysis.

48. What Antibiotics Are Recommended for Empiric
Treatment of Clinically Suspected VAP?
 Coverage for S. aureus, Pseudomonas aeruginosa, and other gram-negative
bacilli in all empiric regimens (strong recommendation, low-quality evidence).
 i. We suggest including an agent active against MRSA for the empiric
treatment of suspected VAP only in patients with any of the following:
 a risk factor for antimicrobial resistance (Table 2),
 patients being treated in units where >10%–20% of S. aureus isolates are
methicillin resistant, and
 patients in units where the prevalence of MRSA is not known (weak
recommendation, very low-quality evidence).
 ii. We suggest including an agent active against methicillin sensitive S. aureus
(MSSA) (and not MRSA) for the empiric treatment of suspected VAP in patients
without risk factors for antimicrobial resistance, who are being treated in ICUs
where <10%–20% of S. aureus isolates are methicillin resistant (weak
recommendation, very low-quality evidence).

49. • 2. If empiric coverage for MRSA - vancomycin
,linezolid or Tiecoplanin (strong recommendation,
moderate-quality evidence).
• 3. Empiric coverage for MSSA (and not MRSA) -
piperacillin-tazobactam, cefepime, levofloxacin,
imipenem, or meropenem (weak recommendation,
very low-quality evidence). Oxacillin, nafcillin, or
cefazolin are preferred agents for treatment of
proven MSSA, but are not necessary for the empiric
treatment of VAP if one of the above agents is used.

51.  6. In patients with suspected VAP, we suggest avoiding
Colistin / aminoglycosides if alternative agents with
adequate gram-negative activity are available (weak
recommendation, low-quality evidence).
 Values and Preferences: These recommendations are a
compromise between the competing goals of providing
early appropriate antibiotic coverage and avoiding
superfluous treatment that may lead to adverse drug
effects, Clostridium difficile infections, antibiotic
resistance, and increased cost.

52. • If patient has structural lung disease increasing
the risk of gram-negative infection (ie,
bronchiectasis or cystic fibrosis), 2
antipseudomonal agents are recommended.

56. PHARMACOKINETIC /
PHARMACODYNAMIC
OPTIMIZATION OF ANTIBIOTIC
THERAPY

57. ROLE OF INHALED ANTIBIOTIC
THERAPY
• For patients with VAP due to gram-negative bacilli that are
susceptible to only aminoglycosides or polymyxins (Colistin
or polymyxin B), we suggest both inhaled and systemic
antibiotics, rather than systemic antibiotics alone (weak
recommendation, very low-quality evidence).
• Values and Preferences: This recommendation places a high
value on achieving clinical cure and survival; it places a lower
value on burden and cost.
• Remarks: It is reasonable to consider adjunctive inhaled
antibiotic therapy as a treatment of last resort for patients who
are not responding to intravenous antibiotics alone, whether
the infecting organism is or is not multidrug resistant (MDR).

58. PATHOGEN-SPECIFIC
THERAPY

59. What Antibiotics Should Be Used for the
Treatment for MRSA HAP/VAP?
• Treat with either vancomycin or linezolid rather than other
antibiotics or antibiotic combinations (strong recommendation,
moderate- quality evidence).
• Remarks: The choice between vancomycin and linezolid may
be guided by patient-specific factors such as blood cell counts,
concurrent prescriptions for serotonin-reuptake inhibitors,
renal function, and cost.

60. Which Antibiotic Should Be Used to Treat
Patients With HAP/VAP due to P. aeruginosa?
• The choice of an antibiotic for definitive (not empiric) therapy
be based upon the results of antimicrobial susceptibility testing
(strong recommendation, low-quality evidence).
• Recommendation is against aminoglycoside monotherapy
(strong recommendation, very low-quality evidence).
• Remarks: Routine antimicrobial susceptibility testing should
include assessment of the sensitivity of the P. aeruginosa
isolate to polymyxins (colistin or polymyxin B) in settings that
have a high prevalence of extensively resistant organisms.

61. Should Monotherapy or Combination Therapy Be
Used to Treat Patients With HAP/VAP Due to
P. aeruginosa?
• 1. Not in septic shock or at a high risk for death, and for whom the results of
antibiotic susceptibility testing are known, we recommend monotherapy using
an antibiotic to which the isolate is susceptible rather than combination
therapy (strong recommendation, low-quality evidence).
• 2. Who remain in septic shock or at a high risk for death when the results of
antibiotic susceptibility testing are known, we suggest combination therapy
using 2 antibiotics to which the isolate is susceptible rather than monotherapy
(weak recommendation, very low-quality evidence).
• 3. For patients with HAP/VAP due to P. aeruginosa, we recommend against
aminoglycoside monotherapy (strong recommendation, very low-quality
evidence).
• Remarks: High risk of death in the meta-regression analysis was defined as
mortality risk >25%; low risk of death is defined as mortality risk <15%.
• For a patient whose septic shock resolves when antimicrobial sensitivities are
known, continued combination therapy is not recommended.

62. Which Antibiotic Should Be Used to Treat Patients
With HAP/VAP Due to Extended-Spectrum β-
Lactamase (ESBL)–Producing Gram- Negative Bacilli?
 Choice of an antibiotic for definitive (not empiric)
therapy be based upon the results of antimicrobial
susceptibility testing and patient-specific factors
(strong recommendation, very low-quality evidence).
 Remarks: Patient-specific factors that should be
considered when selecting an antimicrobial agent
include allergies and comorbidities that may confer
an increased risk of side effects.

63. Which Antibiotic Should Be Used to Treat Patients
With HAP/VAP Due to Acinetobacter Species?
• 1. Treatment with either a carbapenem or ampicillin/ sulbactam if the isolate is
susceptible to these agents (weak recommendation, low-quality evidence).
• 2. Sensitive only to polymyxins, use IV polymyxin (colistin or polymyxin B)
(strong recommendation, low-quality evidence), and we suggest adjunctive
inhaled colistin (weak recommendation, low-quality evidence).
• 3. Sensitive only to colistin, we suggest not using adjunctive rifampicin
(weak recommendation, moderate-quality evidence).
• 4. Guidelines recommend against the use of tigecycline (strong
recommendation, low-quality evidence).
• Values and Preferences: Avoiding potential adverse effects due to the use of
combination therapy with Rifampicin and colistin, over achieving an
increased microbial eradication rate, as eradication rate was not associated
with improved clinical outcome.
• Remarks: Selection of an appropriate antibiotic for definitive (nonempiric)
therapy requires antimicrobial susceptibility testing.

64. Which Antibiotic Should Be Used to Treat Patients With
HAP/VAP Due to Carbapenem-Resistant Pathogens?
• Sensitive only to polymyxins, use Intravenous polymyxins (colistin or polymyxin B)
(strong recommendation, moderate-quality evidence), and we suggest adjunctive
inhaled colistin (weak recommendation, low-quality evidence).
• Values and Preferences: Higher value on Achieving clinical cure and survival; they
place a lower value on burden and cost.
• Remarks: Inhaled colistin may have potential pharmacokinetic advantages compared
to inhaled polymyxin B, and clinical evidence based on controlled studies has also
shown that inhaled colistin may be associated with improved clinical outcomes.
• The clinical evidence for inhaled Polymyxin B is mostly from anecdotal and
uncontrolled studies; we are therefore not suggesting use of inhaled Polymyxin B.
• Colistin for inhalation should be administered promptly after being mixed with
sterile water. This recommendation was made by the US Food and Drug
Administration (FDA) after a report that a cystic fibrosis patient died after being
treated with a premixed colistin formulation.

65. LENGTH OF THERAPY

66. 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.

67. 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.

68. 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.

69. Should Discontinuation of Antibiotic Therapy Be Based
Upon PCT Levels Plus Clinical Criteria or Clinical
Criteria Alone in Patients With HAP/VAP?
• Using PCT levels plus clinical criteria to guide the
discontinuation of antibiotic therapy, rather than clinical
criteria alone (weak recommendation, low-quality
evidence).
• Remarks: It is not known if the benefits of using PCT
levels to determine whether or not to discontinue
antibiotic therapy exist in settings where standard
antimicrobial therapy for VAP is already 7 days or less.

70. Should Discontinuation of Antibiotic Therapy Be
Based Upon the CPIS Plus Clinical Criteria or
Clinical Criteria Alone in Patients With
Suspected HAP/VAP?
 Not using the CPIS to guide the discontinuation of
antibiotic therapy (weak recommendation, low-
quality evidence).

72. 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

73. 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

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

75. 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)

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

77. 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.

78. 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)].

80. Lung Abscess
Standard treatment of an anaerobic lung infection is clindamycin (600 mg
IV q8h followed by 150-300 mg PO qid).
Although metronidazole is an effective drug against anaerobic bacteria,
metronidazole in treating lung abscess has been rather disappointing
because these infections are generally polymicrobial. A failure rate of 50%
has been reported.
In hospitalized patients who have aspirated and developed a lung abscess,
antibiotic therapy should include coverage against S
aureus andEnterobacter and Pseudomonas species.
Ampicillin plus sulbactam is well tolerated and as effective as clindamycin
with or without a cephalosporin in the treatment of aspiration pneumonia
and lung abscess.

94. Lung Abscess
Expert opinion suggests that antibiotic treatment should be continued until
the chest radiograph has shown either the resolution of lung abscess or the
presence of a small stable lesion.
Patients with lung abscesses usually show clinical improvement, with
improvement of fever, within 3-4 days after initiating the antibiotic therapy.
Defervescence is expected in 7-10 days. Persistent fever beyond this time
indicates therapeutic failure, and these patients should undergo further diagnostic
studies to determine the cause of failure.
Considerations in patients with poor response to antibiotic therapy include
bronchial obstruction with a foreign body or neoplasm or infection with a resistant
bacteria, mycobacteria, or fungi.
A nonbacterial cause of cavitary lung disease may be present, such as lung
infarction, cavitating neoplasm, and vasculitis. The infection of a preexisting
sequestration, cyst, or bulla may be the cause of delayed response to
antibiotics.

95. Lung Abscess
Surgery is very rarely required for patients with uncomplicated lung
abscesses. The usual indications for surgery are failure to respond to medical
management, suspected neoplasm, or congenital lung malformation. The
surgical procedure performed is either lobectomy or pneumonectomy.
When conventional therapy fails, either percutaneous catheter drainage or
surgical resection is usually considered. Endoscopic lung abscess drainage is
considered if an airway connection to the cavity can be demonstrated.
Endoscopic drainage, however, is not without significant risk to the patient

97.  Therapy has several major goals:
(1) treatment of infection, particularly during acute exacerbations (2) improved clearance of tracheobronchial secretions
(3) reduction of inflammation (4) treatment of an identifiable underlying problem
Antibiotics are the cornerstone of bronchiectasis management
 antibiotics are used only during acute episodes
 choice of an antibiotic should be guided by Gram's stain and culture of sputum
 empiric coverage (amoxicillin, co-trimoxazole,levofloxacin) is often given initially
 Infection with P. aeruginosa is of particular concern, as it appears to be associated with greater rate of deterioration of lung function and worse quality of life
 There are no firm guidelines for length of therapy, but a 10–14 day course or longer is typically administered
facilitate drainage : mechanical methods and devices & appropriate positioning
 Mucolytic agents to thin secretions and allow better clearance are controversial
 Aerosolized recombinant DNase, which decreases viscosity of sputum by breaking down DNA released from neutrophils, has been shown to improve
pulmonary function in CF but may be deleterious and should be avoided in bronchiectasis not associated with CF
 Bronchodilators to improve obstruction and aid clearance of secretions are useful in patients with airway hyperreactivity and reversible airflow obstruction
surgical therapy »»»»»»»»»»»»»»»»»»» when bronchiectasis is localized and the morbidity is substantial despite adequate medical therapy
massive hemoptysis, often originating from the hypertrophied bronchial circulation
 conservative therapy, including rest and antibiotics
 surgical resection
 bronchial arterial embolization
 Although resection may be successful if disease is localized, embolization is preferable with widespread disease