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Samenvatting antibiotica Microbiologie 1 Indicaties: enkel toepassen wanneer gebruik van een enkelvoudig antibacterieel middel ongewenst of inadequaat is. Bij infecties veroorzaakt door cotrimoxazol gevoelige luchtweginfecties: bv. acute exacerbaties van chronische bronchitis, behandeling en prevent...

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Samenvatting antibiotica Microbiologie 1

Co-trimoxazole

Indicaties: enkel toepassen wanneer gebruik van een enkelvoudig antibacterieel middel ongewenst of inadequaat is. Bij infecties veroorzaakt door cotrimoxazol gevoelige micro-organismen:   

luchtweginfecties: bv. acute exacerbaties van chronische bronchitis, behandeling en preventie van PCP (pneumocystsis jiroveci pneumonie) urineweginfecties: acute ongecompliceerde urineinfecties, recidiverende urineweginfecties maar ook: otitis media, venerische infecties (bv gonorroe), acute brucellose Spectrum: bacteriostatisch AB Het spectrum omvat de meeste gram + en - micro-organismen en ook P. jiroveci. Brucella spp. zijn intermediair gevoelig.

• Resistentie: S. pneumoniae, H. influenzae Klebsiella spp. Pseudomonas spp. • Ongevoelig:

Nocardia spp. ana0robe bacteri0n Chlamydia trachomatis Mycobacterium tuberculosis Mycoplasma Ureaplasma urealyticum Treponema pallidum sommige enterococcenstammen 2

Macroliden

Spectrum of Macrolides - Most Gram-positive bacteria (except staphylococci and enterococci) - Some Gram-negative bacteria: M.catarrhalis (100% susceptible) Haemophilus influenzae: variable activity; controversial Campylobacter / H.pylori - Mycoplasma, Chlamydophila, Legionella - Borrelia burgdorferi (Lyme) - Treponema pallidum (syphillis) - Bordetella pertussis (Pertussis) - Haemophilus ducreyi (chacroid) - Mycobacterium avium intracellulare Indications of Macrolides in Outpatients 1. Respiratory tract infections - if suspicion of atypical pneumonia (age; symptopms) - if not severe and no pneumococci (in Belgium) 2. Pharyngitis: alternative to treatment if allergy to penicillin 3. Gastroduodenaal ulcus with H.pylori 3

4. Urethritis due to Chlamydophila - one dose of azithromycin 1g: 1st choice 5. Lyme disease - if chronic erythematic stage 6. Alternative to treatment of syphillis if allergy to penicillin Indications of Macrolides in Inpatients 1. Atypical mycobacteria in AIDS patients 2. Severe interstitial pneumonia in non-HIV patients 3. IV treatment with erythromycin (Legionella, Mycoplasma, Chlamydophila)

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Clyndamycin

Spectrum of Clindamycin Gram-positive bacteria: - streptococci except enterococci - staphylococci (resistance!) - anaerobes (resistance!) Indications of Clindamycin OUTPATIENTS 1.Oropharyngeal abces (if allergy to beta-lactam antibiotics) 2. Endocarditis prophylaxis (if allergy to beta-lactam antibiotics) INPATIENTS 1. Skin and soft tissue infections 2. Osteomyelitis

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Aminoglycosides

Spectrum of aminoglycosides - Gram-negative bacilli, including P.aeruginosa - MSSA - Mycobacteri9n - Synergy with: - viridans streptococci - Enterococci (endocarditis) Indications of Aminoglycosides Only HAI: no indication in outpatients. Emperic Severe HAI Neutropenic fever Aim: - Rapid bactericidal killing - Synergy Extending spectrum, in case of small spectrum: clindamycin or imidazoles in intra-abdominal infections P. aeruginosa infections 6

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Tetracyclines

Spectrum of Tetracyclines - Comparable with macrolides - But bacteriostatic - Spectrum: - Gram-positive and and Gram-negative; - Aerobic and anaerobic bacteria - Mycoplasma – Chlamydiaphila – Legionella - Plasmodium falciparum Indications of Tetracycline 1. Respiratory tract infections - if suspicion of atypical pneumonia (age; symptopms) - if not severe and no pneumococci (in Belgium) 2. Urethritis due to Chlamydophila: second choice 8

3. Rare infections in Belgium: - Brucellosis: in association with rifampicin - Lyme disease: only if erythema migrans chronica stage - Rickettsiosis: Q fever 4. Imported infections - Vibrio cholera - Yersinia pestis 5. Malaria prophylaxis if high resistance or if treatment of Plasmodium falciparum

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Colistin

Spectrum of Colistin • Bactericidal broad-spectrum drugs • About 10 x more active against Gram- negative than Gram-positive bacteria • Inherent resistance: Burkholderia cepacia, Serratia, Proteus, Bacteroides fragilis ... and most Gram-negative cocci Indications of Colistin 1. Selective Digestive Decontamination (SDD) 2. Infections with MDR-Gram negative bacteria 10

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Glycopeptiden

Spectrum Glycopeptiden - Gram-positive bacteria including MRSA & MRSE - But not very potent drugs (large molecules) Indications of Glycopeptides 1. Documented treatment of HAI MRSA/MRSE allergy to beta-lactam antibiotics in severe streptococcal infections if endocarditis: only vancomycin ! if sepsis: only vancomycin ? 2. Empiric treatment of HAI (but try to limit!) high endemic MRSA neutropenic patients 3. Pseudomembraneus colitis only vancomycin/po preference: metronidazole (cheaper, lower risk of VRE)

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Carbapenems

Spectrum of Carbapenems - Most Gram-negative bacilli, including P. aeruginosa (20-30% are resistant!) - Very active against MSSA and streptococci - Bacteriostatic against enteroccocci - Very active against all anaerobes Indications of Carbapenems 1. HAI due to mixed aerobe and anaerobe infections: peritonitis, postop.,... 2. Infections due to MDR organisms or organisms with increased risk of developing resistance: Enterobacter, Acinetobacter 3. Treatment of neutropenic patients with fever (+/- aminoside) 4. Severe HAI in hospital wards with increased risk of resistance: e.g. Bronchopneumonia on ICU 5. Meningitis: only meropenem

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Cephalosporins

Spectrum of Cephalosporins 1 STE GENERATON most active against Gram-positive cocci (streptococci and S. aureus) limited activity against aerobic Gram-negative bacilli (only of the community) Low or no activity active against H.influenzae and anaerobes 2 DE GENERATION cefuroxime subgroup: comparative activity with 1st generation against Gram-positive cocci more active against E. coli, Klebsiella, P. mirabilis also active against H. influenzae cefamycine subgroup: less active than 1st generation against Gram-positive aerobic cocci most active against Gram-negative anaerobic bacilli 3 DE GENERATION insufficient anti-Pseudomonas activity: Excellent (streptococci) to good (staphylococci) activity 14

Most active against E. coli, Klebsiella, P. mirabillis Broadening of spectrum of second generation cephalosporins towards GNB: nosocomial Enterobactereaceae (Enterobacter, Serratia, Klebsiella,...) ! Variable resistance, but increasing Marginal activity against anaerobes increased anti-Pseudomonas activity: least activity against Gram-positive cocci Gram-negative bacilli: cfr.supra Excellent activity against P.aeruginosa 4 DE GENERATION comparable activity against aerobic Gram-positive cocci as cefotaxime/ceftriaxone most active against inducible Enterobacteriaceae comparable activity against P.aeruginosa as ceftazidime

Indications First Generation 1. PO: outpatients: - strep throat (cefadroxyl), particularly in children - infections with stahylo/strept if not severe penicillin allergy - some urinary tract infections 2. IV/IM: inpatients: - surgical prophylaxis (except colon) - some infections due to susceptible organisms (pyelonephritis...) Indications Second Generation PO: cefaclor 1. Resp tract infections

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cefuroxime-axetil 1. Resp tract infections 2. Urinary tract infections IV/IM: cefuroxime: 1. infections of in- and outpatients due to Gram-positive /Gram-negative organisms: pneumonia,... 2. prophylaxis ? (cardiac surgery,...) first generation remains first choice cefamandol: very few indications for treatment because of short t1/2 prophylaxis ? (cardiac surgery/orthopaedics) cefoxitin-cefotetan: 1. prophylaxis colonsurgery 2. Treatment of mixed infections with Gram-negative bacilli and anaerobes Indications Third Generation 1. Empercial treatment of HAI (plus aminoglycoside) 2. Empirical treatment in neutropenic patients 3. Meningitis due to GNB/ Haemophilus ± aminoside 4. Epiglotitis due to Haemophilus influenzae 5. Endocarditis due to viridans strep (ceftriaxone in outpatients) 6. Cystic fibrosis (ceftazidime) 7. Lyme disease (ceftriaxone) Indications Fourth Generation - Mixed infections Gram-positive and Gram-negative bacteria - Infection due to Gram-negative bacilli resistant against 3rd generation cephalosporines

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Penicillins

Spectrum of Small spectrum, sensitive to penicillinase (penicillin) parenteral PEN G (IV) Benzathine Pen G (Penadur®LA) (IM) oraal PEN V (Peni-oral®) Clometocillin (Rixapen®) Spectrum: Streptococci, including pneumococci Indications of Small spectrum, sensitive to penicillinase (penicillin) - PO: limited because of variation in serum levels, short t1/2 Respiratory infections (throat strep, etc) - IM retard (Benzathine): prophylaxis ARF - IV: streptococcal endocarditis (± aminoside) meningitis due to meningococci actinomycosis, Lyme disease, leptospirosis,... Spectrum of Small spectrum, resistant to staphylococcal penicillinase (oxacillin) - Streptococci - Staphylococci Indications of Small spectrum, resistant to staphylococcal penicillinase (oxacillin) 18

Staphylococcal infections outpatients: cellulitis inpatients: treatment of MSSA infecties Spectrum of Broad spectrum, not active against P. aeruginosa (amoxicillin, ampicillin) - Gram-positive: Enterococci Pneumococci Listeria - Gram-negative: H. influenzae E. coli P. mirabilis Salmonella-shigella Indications of Broad spectrum, not active against P. aeruginosa (amoxicillin, ampicillin) Pharmacology: PO: absorption ± 40% ampicillin only IV absorption > 60% amoxycillin only orally IV: ampicillin – amoxicillin: differences not clinically relevant Indications: - Outpatients: treatment of pneumococcal infections (S and I for penicillin) e - Inpatients: IV treatment of GNB susceptible to ampicillin (2 choice!); this is the only indication Spectrum and Indications of Broad spectrum, active against P.aeruginosa (Piperacillin) Spectrum: P . aeruginosa Some Gram-negative bacilli (Proteus,..) Indications: Always for inpatients P. aeruginosa infections Associated with aminoglycoside Spectrum of Broad spectrum, with beta- lactamase inhibitor (amoxicillin/clavulanic acid) 19

Activity against beta-lactamases of : S. aureus Haemophilus M. catarrhalis Several Gram-negative bacilli: Klebsiella, E.coli,... Anaerobes Indications Broad spectrum, with beta-lactamase inhibitor (amoxicillin/clavulanic acid) Outpatients: - Respiratory tract infections - Wound infections/ Bite wounds Inpatients: 1. Mixed aerobe and anaerobe infections: - intra-abdominal infections (cholecystitis, diverticulitis,...) - lungabces 2. Acute pyelonephritis (2rd choice after FQ) Spectrum of Broad spectrum, with beta- lactamase inhibitor (piperacillin/tazobactam) Activity against beta-lactamases of : Several Gram-negative bacilli: Klebsiella, E.coli,... Anaerobes Indications Broad spectrum, with beta-lactamase inhibitor (piperacillin/tazobactam) Always inpatients:

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- Brochopneumonia

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- Mixed aerobe and anaerobe infections (peritonitis)

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- Nosocomial sepsis (+aminoglycoside)

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- Risk of P. aeruginosa ! Not increased activity because of beta- lactamase inhibitor

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- Neutropenic patients

Imidazoles

Spectrum of Imidazoles    

- All anaerobes, except microaerophilic streptococci - Less active against Gram-positive anaerobic cocci - Very active against Gram-negative anaerobic bacilli (Bacteroides) - Gardnerella vaginalis, Helicobacter pylori, Trichomonas vaginalis, Giardia lamblia, Entamoeba histolytica

Indications of Imidazole       22

OUTPATIENTS - Trichomonas vaginitis (one dose) - Intestinal Giardia infection - Gastroduodenal ulcus due to H.pylori: always in combination with other antibiotic (e.g. amoxicillin) and protonpump inhibitor INPATIENTS - Anaerobic infections, below diafragma, associated with antibiotic against Gram-negative aerobic bacilli

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- C.difficile diarrhea after antibiotic treatment (to replace vancomycin) - Invasive amoebe infections (colitis, abces)

Quinolones

In Vitro Activity MIC*

50

(mg/L) of New Fluoroquinolones against Gram-

negatives

In Vitro Activity MIC

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50

(mg/L) of New Fluoroquinolones against Gram-positives

Activities of Fluoroquinolones, Macrolides and Doxycycline against Chlamydia pneumoniae, Chlamydia trachomatis, Legionella pneumophila and Mycoplasma pneumoniae

In Vitro Activity MIC

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50

(mg/L) of New Fluoroquinolones against Anaerobes

Indications for Fluoroquinolones All fluoroquinolones • Infection with Gram-negatives: - cystitis, pyelonefritis - osteomyelitis - nosocomial infections New fluoroquinolones • Respiratory tract infections? - Sinusitis: NO INDICATION ! - acute exacerbations of chronic bronchitis - community acquired pneumonia: selected patients

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