macrolides in lower respiratory tract infections
DESCRIPTION
MACROLIDES in LOWER RESPIRATORY TRACT INFECTIONS. Dr. Alpay AZAP Ankara University Medical School Infectious Diseases and Clin Micr Dept. Transparency decleration : I have no conflicts of interest. MACROLIDES. Erythromycin Roxythromycin C larithromycin Azithromycin Dyrithromycin - PowerPoint PPT PresentationTRANSCRIPT
MACROLIDES in
LOWER RESPIRATORY TRACT INFECTIONS
Dr. Alpay AZAP
Ankara University Medical School
Infectious Diseases and Clin Micr Dept
Transparency decleration:
I have no conflicts of interest
MACROLIDES
ErythromycinRoxythromycinClarithromycin AzithromycinDyrithromycinTelithromycin *
Gram pozitive bacteriaGram negative bacteriaAtypical agentsMycobacterium spp.Borrelia burgdorferiBabesia microti
Respiratory Pathogens: Streptococcus pneumoniae Haemophilus influenzae
Moraxella catarrhalis Legionella spp. Mycoplasma pneumoniae Chlamydia pneumophila
Turkish Thoracic Society:
Group IA: Amoxicillin or MACROLIDE
Group IB: “2nd/3rd gen SF or AMC” ± MACROLIDE or Doxycycline
Group II: “3rd gen SF or BLBLI + MACROLIDE” or “Fluoroquinolone alone”
Grup IIIA: “3rd gen SF or BLBLI” + “MACROLIDE or quinolone”
Grup IIIB: Anti-pseudomonal BL + ciprofloxacin/AGA + MACROLIDE
MACROLİDES: Erythromycin Azithromycin Clarithromycin Roxythromycin Dyrithromycin
J Turkish Thoracic Society 2009;10(s9):3-16
European Respiratory Society:
Clin Microbiol Infect 2011; 17 (Suppl. 6): 1–24
Outpatient: Amoxicillin or tetracycline or MACROLIDE
Inpatient: “Aminopenicillin ± MACROLIDE” or “BLI-aminopenicillin ± MACROLIDE” or“Penicillin G ± MACROLIDE” or“CTX/CRO ± MACROLIDE” or levofloxacin /moxifloxacin
ICU Patient: 3rd gen SF + MACROLIDE OR levofloxacin /moxifloxacin ± 3rd gen SF Anti-pseudomonal BL + “Ciprofloxacin or AGA + MACROLIDE”
IDSA/ATS Guideline:
Outpatient:
Healthy with no risk for PRSP : MACROLIDEσ or Doxycycline*
Underlying dis, previous ABx: Fluoroquinolone or
Beta-lactam + “MACROLIDEσ or Doxycycline”
σ : If PRSP incidence lower than %25!
Inpatient:
Fluoroquinolone or
Beta-lactam + “MACROLIDE or Doxycycline”
Clinical Infectious Diseases 2007; 44:S27–72
IDSA/ATS Guideline:
ICU Patient:
CRO/CTX/BLBLI + “Azithromycin * or Fluoroquinolone ”
ICU Patient (Pseudomonas):
Anti-pseudomonal BL + “ciprofloxacin or levofloxacin”
Anti-pseudomonal BL + AGA + Azithromycin
Anti-pseudomonal BL + AGA + respiratory quinolone
Clinical Infectious Diseases 2007; 44:S27–72
Macrolide resistance in S. pneumoniae : 4-70%
“Prospective Resistant Organism Tracking and Epidemiology for the
Ketolide Telithromycin” (PROTEKT) Study:
25 country 69 centers
3362 S. pneumoniae isolates
Macrolide resistance: France: %57.6
Italy: %42.9
Türkiye: %15.6
Sweden: %4.7
J Antimicrob Chemoth 2002; 50 (Suppl S1): 25-37.
Four provinces, 5 centers
1995-2000
283 pneumococcus isolates
Macrolide resistance: 2.3%Int J Antimicrob Ag 2002; 19: 207-11
Türkiye
1999-2005 300 S. pneumoniae isolates nvasive infections
Anti-microbial sensitivity testing by E-test
mef(A) and erm(B) genotypes were identified by PCR
Turk J Med Sci 2012; 42 (1): 137-144
erm(B) genotype: 58,8 %
mef(A) genotype: 38,2%
erm(B) + mef(A): 3 %
Mikrobiyol Bul. 2007 Jan;41(1):1-9.
2002-2003 18 center
260 respiratory isolates
Macrolide resistance: 17.3%
Tetracycline resistance: 21.5%
erm(B) genotype: 77,8%
mef(A) genotype: 17,8 %
erm(B) + mef(A): 2,2 %
e-BASKETT-II Study:
Seven centers from 5 provinces
301 isolates from community acquired infections
Child and adult patients
Journal of Antimicrobial Chemotherapy (2007) 60, 587–593
Journal of Antimicrobial Chemotherapy (2007) 60, 587–593
Seven centers from 5 provinces
380 isolates from community acquired infections
Child and adult patients
Clinical Infectious Diseases 2008; 47:S232–6
Do we need macrolides in combination?
BMJ 2005; 330: 456–60.
Beta-lactam + Macrolide combination is not synergistic
Antagonism was observed in animal studies
Selection bias:
Atypical pneumoniae has a mild course and seen in younger pts
Patients who require ICU also receive macrolides (legionella ?)
The incidence of atypical agents shows variation.
Trials comparing quinolones with macrolides don’t include severe pts
Journal of Antimicrobial Chemotherapy (2003) 52, 555–563
BL + Macrolide vs Fluoroquinolone:PSI V pts 14 day mortality; 8.2% vs 26.8% (p=0.02)
30 day mortality: 18.4% vs 36.6% (p=0.05)
Length of stay in all pts 6 days vs 5 days (p=0.01)
PSI II-IV pts 14 day, 30 day mortality and LOS were not different
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, Nov. 2007, p. 3977–3982
9 countires from Europa 27 ICUs, 218 entubated severe CAP pts
43 (19.7%) pts monotherapy 175 (80.3%) pts dual therapy
BL + Macrolide vs BL + Quinolone:
severe CAP pts: HR: 0.48 (p=0.04)
severe sepsis/septic shock: HR: 0.44 (p=0.03)
Intensive Care Med (2010) 36:612–620
Intensive Care Med (2010) 36:612–620
Intensive Care Med (2010) 36:612–620
Macrolide! Which One ?
Türk Toraks Dergisi 2009;10(s9):3-16
IDSA/ATS :
Azithromycin for ICU pts
Clinical Infectious Diseases 2007; 44:S27–72
Turkish Thoracic Society:
Macrolides: Erythromycin Roxythromycin Clarithromycin Azithromycin Dyrithromycin
to conclude…
Macrolides can be used as monotherapy agent for CAP in Türkiye
Macrolides may be superior than quinolones when used in combination with BL agents
The decision of which macrolide should be used depends on patients clincal situation.
Thank you….