Betalactam Antibiotics and LRTI

Oğuz KılınçDokuz Eylul University School of Medicine

Chest Dept.oguz.kilinc@deu.edu.tr

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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