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Antibiotic Strategy in Lower Respiratory Tract Infections

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Strategy of Antibiotic Usage in Lower Respiratory Tract Infections

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Antibiotic Strategy in Lower Respiratory Tract Infections

  1. 1. Antibiotic Strategy in Lower Respiratory Tract Infections Gamal Rabie Agmy, MD, FCCP Professor and Head of Chest Department , Assiut University
  2. 2. ANTIMICROBIAL DRUGS
  3. 3. 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
  4. 4. 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.
  5. 5. 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
  6. 6. 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.
  7. 7. 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.
  8. 8.  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
  9. 9. 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
  10. 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. 11. • 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.
  12. 12. 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.
  13. 13. 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.
  14. 14. 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.
  15. 15. 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
  16. 16. 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. 17. Community acquired Pneumonia •Where to treat •What to treat with •How long to treat •How to follow up
  18. 18. Pneumonia Where to treat
  19. 19. 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
  20. 20. 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
  21. 21. 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
  22. 22. 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
  23. 23. 27 Normal CXR & Pneumonic Consolidation
  24. 24. 28 Lobar Pneumonia – S.pneumoniae
  25. 25. 29 CXR – PA and Lateral Views
  26. 26. 30 Lobar versus Segmental - Right Side
  27. 27. 31 Lobar Pneumonia
  28. 28. 32 Special forms of Consolidation
  29. 29. 33 Round Pneumonic Consolidation
  30. 30. 34 Special Forms of Pneumonia
  31. 31. 35 Special Forms of Pneumonia
  32. 32. 36 Complications of Pneumonia
  33. 33. 37 Empyema
  34. 34. 38 Mycoplasma Pneumonia
  35. 35. 39 Mycoplasma Pneumonia
  36. 36. 40 Chlamydia Trachomatis
  37. 37. 41 Rare Types of Pneumonia
  38. 38. Chest sonography
  39. 39. Chest sonography
  40. 40. Post-stenotic pneumonia Posterior intercostal scan shows a hypoechoic consolidated area that contains anechoic, branched tubular structures in the bronchial tree (fluid bronchogram).
  41. 41. Chest sonography
  42. 42. Chest sonography
  43. 43. 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.
  44. 44. 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.
  45. 45. 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
  46. 46. 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
  47. 47. Uncomplicated AECOPD H. influenzae S. pneumoniae M. catarrhalis • Floroquinolones • Advanced macrolide (azythromycin, clarithromycin) • Cephalosporins 2nd or 3rd generation
  48. 48. 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)
  49. 49. Complicated AECOPD As in complicated AECOPD plus P. aeruginosa Fluoroquinolone (Ciprofloxacin, Levofloxacin – high dose^) • Piperacillin- tazobactam
  50. 50. 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.
  51. 51. 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)].
  52. 52. 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.
  53. 53. 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
  54. 54. 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.
  55. 55. 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.
  56. 56. 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.
  57. 57. Clinical Pulmonary Infection Score (CPIS)
  58. 58. CPIS
  59. 59. TREATMENT OF VENTILATOR- ASSOCIATED TRACHEOBRONCHITIS
  60. 60. Should Patients With Ventilator- Associated Tracheo-bronchitis (VAT) Receive Antibiotic Therapy? • Not providing antibiotic therapy (weak recommendation, low-quality evidence).
  61. 61. INITIAL TREATMENT OF VAP AND HAP
  62. 62. 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.
  63. 63. 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).
  64. 64. • 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.
  65. 65.  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.
  66. 66. • If patient has structural lung disease increasing the risk of gram-negative infection (ie, bronchiectasis or cystic fibrosis), 2 antipseudomonal agents are recommended.
  67. 67. 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.
  68. 68. LENGTH OF THERAPY
  69. 69. 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.
  70. 70. 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.
  71. 71. 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.
  72. 72. 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.
  73. 73. 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).
  74. 74. 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.
  75. 75. 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.
  76. 76. 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
  77. 77.  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
  78. 78. 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
  79. 79. 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
  80. 80. 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
  81. 81. 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
  82. 82. 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 )

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