Betalactam Antibiotics and LRTI
Oğuz KılınçDokuz Eylul University School of Medicine
Chest [email protected]
Conflict of Interest(Last 3 years)
• Congress sponsorship– Abdi İbrahim– Actavis– Boehringer İngelheim– Chiesi– GSK– Novartis– Pfizer
• Advisory Board– Bayer– Boehringer İngelheim– Chiesi– GSK– Novartis– Pfizer
• Lecturer Fee– Astra– Bayer– Boehringer İngelheim– GSK– Novartis– Pfizer
• Clnical Research Support– Astra– Bayer– GSK– Novartis– Pfizer
• Tütün endüstrisiyle hiçbir ilişkim yoktur.
Lecture Plan
• What is LRTI?• Caracteristics of betalactam antibiotics• Betalactam antibiotics and LRTI?
What is LRTI?
• CAP• AECOPD• AE of bronchiectasis• Acute bronchitis
• M Woodhead. Clin Microbiol Infect 2011; 17(Suppl. 6): E1–E59
Betalactam antibiotics
– Penicillin– Cephalosporins– Carbapenems– Monobactams– Betalactamase inhibitors
http://yunus.hacettepe.edu.tr/~pkelicen erişim tarihi 18.03.2012
BetalactamsSubclasses Prototype Major Variants
Penicillins Limited spectrum Penicillin G Penicillin V
Betalactamase resistant
Methicillin Nafcillin, oxacillin Cloaxacillin
Wider spectrum Ampicillin, Carbenicillin Amoxacillin, ticarcillin
Cephalosporins 1. generation Sodium sefhalotin Cefazolin,Cephradin,
Cephapirin
2. generation Cefamandole Cefaclor, cephatetan, cephoxitin
3. generation Cefaperazone Cefotaxim, Ceftazidim, Ceftriaxon
Carbapenem İmipenem
Monobactam Aztreonam
Betalactamase inhibitors * Clavulanic asit Sulbactam, Tazobactam
* Negligible antimicrobial activity when given alonehttp://yunus.hacettepe.edu.tr/~pkelicen downloded 18.03.2012
Betalactams
http://yunus.hacettepe.edu.tr/~pkelicen erişim tarihi 18.03.2012
Betalactams
http://yunus.hacettepe.edu.tr/~pkelicen erişim tarihi 18.03.2012
Resistans mechanism to penicillins
• Inactivation of betalactam body because of betalactamase – Betalactamase secretion to periplasmic space
(S. aureus ve Gram (-) )– Out of membrane (Gram (+))
• Decrase of PBP affinity • Decrase of cell wall permiability
Kayaalp O. Rasyonel Tedavi Yönünden Tıbbi Farmakoloji, 10. Baskı, Hacettepe Taş, 2002.
Clinical caracteristics of cephalosporins
• A part of patients who have penicilline allergy,• Betalactamase (+) S. aureus infections • PBP
Kayaalp O. Rasyonel Tedavi Yönünden Tıbbi Farmakoloji, 10. Baskı, Hacettepe Taş, 2002.
Carbapenems
• High affinty to PBP 1 and 2• Resistant to betalaktamase• Bacterisid for betalactam resistans bacteria
Kayaalp O. Rasyonel Tedavi Yönünden Tıbbi Farmakoloji, 10. Baskı, Hacettepe Taş, 2002.
Aetiology of LRTI in the community
Aetiology of CAP(Outpatient)
Betalactamase resistans in Turkey?S. pneumoniae
• EARSS (2008)• 32 European country (Turkey data) invasiv S.
pneumonia • PNSP %34
S. pneumoniae Penicilline resistans- effect of therapy?
• PO treatment– MIC • Sensitive (≤ 0.06 mg/L), intermediate (0.12- 1 mg/L),
resistans ( ≥2 mg/L)
• Parenteral treatment– Sensitive (≤ 2 mg/L), intermediate (4 mg/L),
resistans ( ≥8 mg/L)– Good news for clinicans
Pneumococci resistans in Turkey
Gülmez D ve ark. ECCMID Congress 2010
H. influenzae betalactam resistans
• EARSS study• Main resistans mechanism beta-laktamase
production (mean %7.6)• Cephalosporin and betalactamase inhibitor +
betalactam
• PBP 3 coding gen (BLNAR)• Resistans to aminopenicilline and cephalosporine
M. catarrhalis –betalactam resistans
• No change since 1999 .• All species resistans to ampicillin,
amoxacilline, piperacilline and penicilline • BRO-1, BRO- 2 type betalaktamase resistans• betalactam betalactamase inhibitor.
M. pneumoniae- betalactam resistans
• Resistans to all betalactams
CA- MRSA
• Resistans to all betalactams
Treatment
• Penicilline G 3.2 M U x 6 IV• Ceftriaxone 1g x 2 IV/IM• Cefotaxime 2g x 4 IV
• Amoxacilline+clavulanic acid 2g/125mg x 2 PO
• Double blind, randomized controlled, monoterapy study meta-analysis
• 18 study, 6749 patients• Mild and moderate CAP
Mills GD ve ark. BMJ 2005
Mills GD ve ark.BMJ 2005
TTS CAP guideline
• Grup 1– 1A
• Amoksisilin veya Makrolid– 1B
• 2.3. kuşak oral sefalosporin veya KAM +/- Makrolid/Doksisiklin• Grup 2
• 3. kuşak antipseudomonas olmayan sefalosporin veya betalaktam+ betalaktamaz inhibitörlü aminopenisilin + Makrolid /quinolon
• Grup 3– 3A
• 3 generation non- pseudomonas cephalosporin or betalactam+ betalactamase inhibitor + Macrolid or quinolon
– 3B• Antipseudomonas betalactam+ciprofloksasin or aminoglikozid + Macrolid
Wrap up
• We have to know what we treat• Surveillance of resistans rate• Appropiate treatment
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