This document discusses antibiotic strategy in lower respiratory tract infections. It covers mechanisms of action of antimicrobial drugs, appropriate antibiotic selection and dosing considerations including tissue versus blood concentrations and drug mechanisms of action. It also discusses community acquired pneumonia guidelines for outpatient versus inpatient treatment including durations. Exacerbations of COPD and ventilator associated pneumonia are also summarized.

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

7. 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

8. 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.
• Pharmacodynamic properties of specific antibiotics
should also be considered in selecting an adequate
dosing regimen.

9. 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.

10.  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

11. 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

12. 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

13. • 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.

15. 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.

16. 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.

17. 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. 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

19. 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

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

22. Pneumonia Where to treat

23. 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
• Staphylococcus
aureus
• Legionella
species
• Gram-negative
bacilli
• H. influenzae

24. Outpatient treatment(oral)
1. Previously healthy and no use of antimicrobials within the previous three months:
A macrolide (azithromycin, clarithromycin, or erythromycin) (OR) Doxycyline*
2. Presence of comorbidities such as chronic heart, lung, liver, or renal disease; diabetes mellitus;
alcoholism; malignancies; asplenia; immunosuppressing conditions or use of immunosuppressing
drugs; or use of antimicrobials within the previous three months (in which case an alternative from a
different class should be selected):
 A respiratory fluoroquinolone (moxifloxacin, gemifloxacin, or levofloxacin 750 ( OR)
 oral beta-lactam (first-line agents: high-dose amoxicillin 1 gm 3 times, amoxicillin-clavulanate 2 gm
every 12hs; alternative agents: cefpodoxime, or cefuroxime) PLUS a macrolide (azithromycin,
clarithromycin, or erythromycin)*
3. In regions with a high rate (>25 percent) of infection with high-level (MIC ≥16 mcg/mL) macrolide-resistant Streptococcus pneumoniae,
consider use of alternative agents listed in (2) above.
Inpatients, non-ICU treatment (injection)
 A respiratory fluoroquinolone (moxifloxacin, gemifloxacin, or levofloxacin 750 (OR)
 An antipneumococcal beta-lactam IV (preferred agents: cefotaxime, ceftriaxone, or ampicillin-
sulbactam; or ertapenem for selected patients)
¶
PLUS a macrolide (azithromycin, clarithromycin,
or erythromycin)*
Δ
Inpatients, ICU treatment
 An antipneumococcal beta-lactam (cefotaxime, ceftriaxone, or ampicillin-
sulbactam PLUS azithromycin (OR)
 An antipneumococcal beta-lactam IV (cefotaxime, ceftriaxone, or ampicillin-
sulbactam) PLUS a respiratory fluoroquinolone (moxi, gemi or levofloxacin 750 mg) (OR)
 For penicillin-allergic patients, a respiratory fluoroquinolone (moxifloxacin, gemifloxacin, or
levofloxacin [750 mg]) PLUS aztreonam

25. 25
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

26. 26
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

27. 27
Normal CXR & Pneumonic Consolidation

28. 28
Lobar Pneumonia – S.pneumoniae

29. 29
CXR – PA and Lateral Views

30. 30
Lobar versus Segmental - Right Side

31. 31
Lobar Pneumonia

32. 32
Special forms of Consolidation

33. 33
Round Pneumonic Consolidation

34. 34
Special Forms of Pneumonia

35. 35
Special Forms of Pneumonia

36. 36
Complications of Pneumonia

37. 37
Empyema

38. 38
Mycoplasma Pneumonia

39. 39
Mycoplasma Pneumonia

40. 40
Chlamydia Trachomatis

41. 41
Rare Types of Pneumonia

42. Chest sonography

43. Chest sonography

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

45. Chest sonography

46. Chest sonography

47. 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.

48. 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.

50. 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

51. 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

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

53. 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)

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

55. 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.

56. 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)].

58. VAP
a new or progressive and persistent radiographic
abnormality developing in a patient on mechanical
ventilation (or within 48 hours of mechanical
ventilation), who must also demonstrate: one or more
systemic signs (fever, leukopenia or leukocytosis, or
altered mental status in those >70 years of age) and
selected pulmonary criteria (eg, change in respiratory
secretions, new onset of cough, dyspnea, rales,
bronchial breath sounds, or worsening oxygenation).
Additional criteria were available for reporting VAP
with laboratory evidence of infection and for VAP in
immuno-compromised patients.

59. Ventilator Associated Events
all the conditions that result in a significant and sustained
deterioration in oxygenation, defined as a greater than
20% increase in the daily minimum fraction of inspired
oxygen or an increase of at least 3 cm H2O in the daily
minimum positive end-expiratory pressure (PEEP) to
maintain oxygenation. It is imperative to understand that
both infectious conditions (such as tracheitis,
tracheobronchitis, and pneumonia) and noninfectious
conditions (such as atelectasis, pulmonary embolism,
pulmonary edema, ventilator-induced lung injury, and
others) may fulfill this VAE

60. Ventilator Associated Events
Tier 1: ventilator-associated condition (VAC) —the
patient develops hypoxemia (as defined above) for a
sustained period of more than 2 days. The etiology of the
hypoxemia is not considered.
Tier 2: infection-related ventilator-associated complication
(IVAC) —hypoxemia develops in the setting of generalized
infection or inflammation, and antibiotics are instituted for a
minimum of 4 days.

61. Ventilator Associated Events
Tier 3: probable or possible ventilator-associated
pneumonia (VAP) —additional laboratory evidence of
white blood cells on Gram stain of material from a
respiratory secretion specimen of acceptable quality, or
(=possible)/and (=probable) presence of respiratory
pathogens on quantitative cultures, in patients with IVAC.
Additional criteria are also available for use in meeting the
possible or probable VAP definitions.

62. Threshold values for cultured specimens used
in the diagnosis of pneumonia
Specimen collection/technique Values†
Lung tissue >104 CFU/g tissue
Bronchoscopically (B) obtained specimens
Bronchoalveolar lavage (B-BAL) >104 CFU/ml
Protected BAL (B-PBAL) >104 CFU/ml
Protected specimen brushing (B-PSB) >103 CFU/ml
Nonbronchoscopically (NB) obtained (blind)
specimens
Mini-BAL >104 CFU/ml
Sputum Mild,mod, Severe growth
CDC/NHSN Pneumonia (Ventilator-associated [VAP] and non-ventilator-associated Pneumonia [PNEU]) Event. January 2015, modified April 2015.

63. Clinical Pulmonary Infection Score
(CPIS)

64. CPIS

65. TREATMENT OF VENTILATOR-
ASSOCIATED
TRACHEOBRONCHITIS

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

67. INITIAL TREATMENT OF VAP
AND HAP

68. 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.

69. 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).

70. • 2. If empiric coverage for MRSA - vancomycin or
linezolid (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.

71.  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.

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

76. 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.

77. LENGTH OF THERAPY

78. 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.

79. 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.

80. 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.

81. 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.

82. 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).

84. 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.

85. 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.

86. 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

88.  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

89. Fluroflox is available in one concentration of 400mg of
moxifloxacin HCL in form of film coated tablets.
Indication
• Acute Bacterial Sinusitis.
• Acute Exacerbation of Chronic Bronchitis
• Community Acquired Pneumonia.
• Uncomplicated Skin and soft tissues Infections.
MOXIFLOXACINis fourth generation of quinolones,
Fluroflox… 400 mg Moxifloxacin

90. Fluroflox… Dual Target Action
• Topoisomerase II (i.e. gyrase) in Gram-negative bacteria
• Topoisomerase IV in Gram-positive bacteria
Relaxed DNA
Super coiled
DNA
Topoisomerase
Topoisomerase

91. The bactericidal action of moxifloxacin results from
inhibition of the topoisomerase II (DNA gyrase) and
topoisomerase IV required for bacterial(DNA)replication,
transcription, repair, and recombination
Fluroflox … Mood of Action

92. Fluroflox … Safety & Tolerability
CYP450
metaboli
sm
Dose
adjustment
for
mild/moderat
e hepatic
impairment
Dose
adjustment
for severe
renal
impairment
Fluroflox No No No
Levofloxacin2 Not stated No Yes
Amoxicillin/
clavulanate3
Not stated
Caution and
monitoring
recommended
Yes
1) AVALOX® tablets UK prescribing information, 2006
2) TAVANIC® tablets UK prescribing information, 2006
3) AUGMENTIN® tablets US prescribing information, 2006

93. Fluroflox … Dosage
1. Acute Bacterial Sinusitis. ( once daily for 10 Daye )
2. Acute Exacerbation of Chronic Bronchitis ( once daily for
5 Daye )
3. Community Acquired Pneumonia. ( once daily from 7 - 14
Daye )
4. Uncomplicated Skin and soft tissues Infections. ( once
daily from 7 - 21 Daye )