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….