Antibiotic therapy(presentation provided by

doc. MUDr. J. Beneš, CSc.)

History of antibiotics19101910 salvarsansalvarsan P.Ehrlich, S.HataP.Ehrlich, S.Hata19321932 prontosilprontosil E.DomagkE.Domagk1928/411928/41 penicillinpenicillin

A.Fleming,A.Fleming,H.Florey,E.ChainH.Florey,E.Chain

19441944 streptomycin.streptomycin. S.A.WaksmanS.A.Waksman19451945 cefalosporin Ccefalosporin C G.BrotzuG.Brotzu19471947 chloramchloramphphenieniccolol.. I.EhrlichI.Ehrlich19481948 chlortetracychlortetracycclinlin.. B.M.BuggarB.M.Buggar19521952 erythromycinerythromycin.. J.M.J.M.Mc.GuireMc.Guire19541954 spiramycin.spiramycin. S. Pinnert-SyndicoS. Pinnert-Syndico19551955 vancomycinvancomycin.. M.H.CormickM.H.Cormick19571957 kanamycinkanamycin.. H.UmezawaH.Umezawa19591959 rifamrifampipicincin.. P.SensiP.Sensi

--. = drugs produced by Streptomycetes

History of antibiotics II19601960 ampicillinampicillin19601960 methicillinmethicillin19621962 cefalotincefalotin19661966 doxycyclindoxycyclin19681968 co-trimoxazolco-trimoxazol19811981 amoxicillin/clavulanic acidamoxicillin/clavulanic acid19821982 ciprofloxacinciprofloxacin19901990 azithromycinazithromycin19911991 clarithromycinclarithromycin20002000 linezolidlinezolid

many drugs are semi-synthetic

Groups of antibiotics

A) ATB inhibiting bacterial cell wall synthesis A) ATB inhibiting bacterial cell wall synthesis (peptidoglycan synthesis)(peptidoglycan synthesis)

B) ATB inhibiting bacterial DNA metabolismsB) ATB inhibiting bacterial DNA metabolisms

C) ATB inhibiting bacterial proteosynthesisC) ATB inhibiting bacterial proteosynthesis

D) ATB inhibiting bacterial metabolic D) ATB inhibiting bacterial metabolic pathwayspathways

E) ATB damaging bacterial cell membranesE) ATB damaging bacterial cell membranes

Groups of antibioticsA) A) ATB inhibitingATB inhibiting bacterial cell wall synthesisbacterial cell wall synthesis

(peptidoglycan synthesis)(peptidoglycan synthesis)beta-lactamsbeta-lactams

penicillinspenicillinscefalosporinscefalosporinsmonobactamsmonobactamscarbapenemscarbapenems

glycopeptidesglycopeptidesB) ATB inhibiting bacterial DNA metabolismsB) ATB inhibiting bacterial DNA metabolismsC) ATB inhibiting bacterial proteosynthesisC) ATB inhibiting bacterial proteosynthesisD) ATB inhibiting bacterial metabolic pathwaysD) ATB inhibiting bacterial metabolic pathwaysE) ATB damaging bacterial cell membranesE) ATB damaging bacterial cell membranes

Beta-lactams

carbapenems: imipenem

monobactams: aztreonam

penicillins cefalosporins

Penicillin

dosage: therapy of tonsillitis 1,5 mil.U./day erysipelas 6-12 mil.U. endocarditis 12-30 mil.U.

G+ cocci: streptococci, pneumococci, enterococciG+ rods: B. anthracis, C. diphtheriae, L.

monocytogenesG- cocci: Neisseria spp.others: anaerobes, spirochetes

strong effect no interactions no toxicity

Penicillins

Penicillin Gstrong and nontoxic - but ..- narrow spectrum- half time 30 min- acid labile (not orally)

longer effect:- procain PNC (24 h)- benzathin PNC (3 weeks)

oral forms:- penicillin V- penamecillin

anti-staphylococcal penicillins methicilin, nafcilin, oxacillin

broader spectrum penicillins(E. coli, H. influenzae, ..., enterococci)ampicillin, amoxicillin

anti-Pseudomonas penicillinsCARB, TIC, AZL, MEZpiperacillin

Mechanisms of resistance

inactivation of antibiotic (exoenzymes)inactivation of antibiotic (exoenzymes) cleavage of the moleculecleavage of the molecule adding a side chainadding a side chain

inhibition of ATB entry in the G- bacteria inhibition of ATB entry in the G- bacteria cellcell

changes in the target structurechanges in the target structure alternative metabolic pathwayalternative metabolic pathway effluxefflux combination of several mechanisms combination of several mechanisms

Inhibitors of beta-lactamases

clavulanic acidclavulanic acid + amoxicillin + amoxicillin = Augmentin, = Augmentin, Amoksiklav, ....Amoksiklav, ....

sulbactamsulbactam + ampicillin = Unasyn (only i.v.)+ ampicillin = Unasyn (only i.v.) + cefoperazon = Sulperazon (only i.v.)+ cefoperazon = Sulperazon (only i.v.)

tazobactamtazobactam + piperacilin = Tazocin (only i.v.)+ piperacilin = Tazocin (only i.v.)

sulbactam

clavulanic acid

Cefalosporins

I. genI. gen II. genII. gen III. genIII. gen IV. genIV. gen

streptococcistreptococci ++++++ ++++++ ++++ ++++++

staphylococcistaphylococci ++++++ ++++ ++ ++++++

G- rods (G- rods (E. coliE. coli)) ++ ++++ ++++++ ++++++

PseudomonasPseudomonas -- -- some some (ceftazidim)(ceftazidim)

++++

anaerobsanaerobs ++ ++ ++ ++

Generations vary in anti-bacterial spectrum, resistance against β-lactamases, and pharmacokinetics (penetration in tissues, half-time)

Penicillins and cefalosporins

PENs more effective against G+, CEFs against G-PENs more effective against G+, CEFs against G-

CEFs I. gen CEFs I. gen ≈ PEN + OXA≈ PEN + OXAwound infections, profylaxis in surgery (i.v., wound infections, profylaxis in surgery (i.v.,

orally)orally)

CEFs II. gen ≈ aminoPEN + CEFs II. gen ≈ aminoPEN + ββ-lactamase inhibitor-lactamase inhibitorUTI, abdUTI, abdoominal a respiratory infections (i.v., minal a respiratory infections (i.v.,

orally)orally)

CEFs III. gen ≈ anti-CEFs III. gen ≈ anti-PseudomonasPseudomonas PENs PENsG- sepsis, meningitis (ICU needed, i.v.)G- sepsis, meningitis (ICU needed, i.v.)

CEFs IV. genCEFs IV. gennozocomial infections/sepsis (ICU, i.v.)nozocomial infections/sepsis (ICU, i.v.)

Conclusions: beta-lactamsBacterial killing:

rapid, strong, no post-ATB effect

Pharmacokinetics:short half time (t1/2 0,5-2 hod)good levels in plasma and ECF, not in cells

Toxicity, side effects: nontoxic ATB, good for children, pregnant

womenallergy (PENs > CEFs)dysmicrobia (candidoses, post-ATB colitis)

Indications:Acute infections >> chronic infectionsSevere infections, sepsis >> mild infections

Glycopeptidesvancomycinteicoplanin, daptomycin

large molecule not permitting transport through an outer wall of Gram-negative bacteria

bactericidal against most Gram-positive bacterianot absorbed from GIT, active only in blood and

extracellular fluid (no transport into cells), elimination in urine

nephrotoxicity, blood levels should measured !

Conclusion: - reserve ATBs against (multi)resistant Gram-positive

bacteria- good for treatment sepsis and severe acute infections

Groups of antibioticsA) ATB inhibiting bacterial cell wall synthesis A) ATB inhibiting bacterial cell wall synthesis

(peptidoglycan synthesis)(peptidoglycan synthesis)

beta-lactamsbeta-lactams

glycopeptidesglycopeptides

B) ATB inhibiting bacterial DNA metabolismB) ATB inhibiting bacterial DNA metabolism

(fluoro)chinolons(fluoro)chinolons

rifampicinrifampicin

C) ATB inhibiting bacterial proteosynthesisC) ATB inhibiting bacterial proteosynthesis

D) ATB inhibiting bacterial metabolic pathwaysD) ATB inhibiting bacterial metabolic pathways

E) ATB damaging bacterial cell membranesE) ATB damaging bacterial cell membranes

FluoroquinolonsI. gen.:I. gen.: weak effect; limited spectrum (Gram-neg. only); weak effect; limited spectrum (Gram-neg. only);

limited absorbtion; effective only in UTIlimited absorbtion; effective only in UTI

NAL, OXO, PIP;;NAL, OXO, PIP;; norfloxacinnorfloxacin

II. gen.:II. gen.: fluoroquinolons, systemic distribution; fluoroquinolons, systemic distribution; broader spectrum (+ staphylococci, chlamydiae, broader spectrum (+ staphylococci, chlamydiae, MycoplasmaMycoplasma spp., spp., MycobacteriumMycobacterium spp.) spp.)

ciprofloxacin, ofloxacinciprofloxacin, ofloxacin,, PEF, LEVOPEF, LEVO

III. gen.:III. gen.: excellent absorbtion, half-time 6-20 hrs; excellent absorbtion, half-time 6-20 hrs; high concentrations in lungs;high concentrations in lungs; broader spectrum (pneumococci); higher costbroader spectrum (pneumococci); higher cost

moxifloxacin, ...moxifloxacin, ...

Characteristics of fluoroquinolonesbroad spectrum (Gram-negative bacteria, staphylococci, broad spectrum (Gram-negative bacteria, staphylococci,

intracellular bacteria)intracellular bacteria)bactericidalbactericidalgood pharmacokinetics: good pharmacokinetics: good absorbtion from GITgood absorbtion from GIT

good penetration in tissues and cellsgood penetration in tissues and cellselimination in various routeselimination in various routes

low costlow cost

adverse events:adverse events:GIT complaints: nauzea, anorexiaGIT complaints: nauzea, anorexiaallergy, fotosensibilizationallergy, fotosensibilizationCNS: dizziness, agitation, insomnia, seizuresCNS: dizziness, agitation, insomnia, seizuresconnective tissues: tendinitis, tendon rupturesconnective tissues: tendinitis, tendon rupturesarrythmia, torsade de pointesarrythmia, torsade de pointes

not allowednot allowed for children and pregnant women for children and pregnant womeninteraction with other drugs (Pinteraction with other drugs (P450450, CYPIA2), CYPIA2)

theophyllin, warfarin, Htheophyllin, warfarin, H2 2 blockers, ...blockers, ...

resistance can develop very easilyresistance can develop very easily

Torsade de pointes

ATB rezistance (%) in invasive isolates E. coli in the Czech Republic in 2000-2006

0

5

10

15

20

25

2001

(n=1189)

2002

(n=1598)

2003

(n=1777)

2004

(n=1982)

2005

(n=2257)

2006

(n=1045)

red line – fluoroquinolones, black line – aminoglycosides, blue line – 3rd gen. cefalosporins

Appropriate usage of FQ (with respect to ATB policy)

enteric fever, extra-intestinal salmonellosisenteric fever, extra-intestinal salmonellosis zoonoses (tularemia, brucellosis etc.)zoonoses (tularemia, brucellosis etc.) prostatitisprostatitis acute exacerbation of chronic bronchitisacute exacerbation of chronic bronchitis lower respiratory tract infections in cystic fibrosislower respiratory tract infections in cystic fibrosis

common UTIcommon UTI gastroenteritis, enterocolitisgastroenteritis, enterocolitis biliary infections (+ prophylaxis)biliary infections (+ prophylaxis) uretritis (STD)uretritis (STD) nosocomial infections, sepsisnosocomial infections, sepsis

RifampicinBroad spectrum: Gram-positive and -negative bacteria, Broad spectrum: Gram-positive and -negative bacteria,

including intracellular pathogens – but it is registered for including intracellular pathogens – but it is registered for therapy of mycobacterial infection therapy of mycobacterial infection

Resistance can develop very easily, it should not be used in Resistance can develop very easily, it should not be used in monotherapy !monotherapy !

Good absorbtion from GIT if taken without food. Good Good absorbtion from GIT if taken without food. Good distribution into tissues and cells. The drug is metabolized distribution into tissues and cells. The drug is metabolized in liver (cytochromes P450). Elimination in urine.in liver (cytochromes P450). Elimination in urine.

Adverse events: hepatotoxicity, drug interactionsAdverse events: hepatotoxicity, drug interactions

Groups of antibioticsA) ATB inhibiting bacterial cell wall synthesis A) ATB inhibiting bacterial cell wall synthesis

(peptidoglycan synthesis)(peptidoglycan synthesis)B) ATB inhibiting bacterial DNA metabolismB) ATB inhibiting bacterial DNA metabolismC) ATB inhibiting bacterial proteosynthesisC) ATB inhibiting bacterial proteosynthesis

macrolides macrolides (+ azalides + ketolides)(+ azalides + ketolides)lincosamidslincosamidstetracyclinestetracyclineschloramphenikolchloramphenikoloxazolidinonsoxazolidinons

+ aminoglycosides+ aminoglycosidesD) ATB inhibiting bacterial metabolic pathwaysD) ATB inhibiting bacterial metabolic pathwaysE) ATB damaging bacterial cell membranesE) ATB damaging bacterial cell membranes

Macrolides12-chain: veterinary drugs 14-chain: erythromycin, clarithromycin, roxithromycin16-chain: spiramycin – less interaction potential than

above

azalides (15-chain): azithromycinketolides: telithromycin

• streptococci, pneumococci, Branhamella catarrhalis, Bordetella pertussis, Legionella spp.

• oral anaerobic flora, actinomycetes• mycoplasmata, chlamydiae• Borrelia burgdorferi and other spirochetes• Campylobacter spp., Helicobacter spp. (clarithromycin)

(+ mycobacteria)

Macrolides

Disadvantages • static effect on bacteria• weak effect • drug interactions (P450)• ERY: nauzea, vomiting• resistance develops easily

Advantages• excellent penetration in

many tissues and cells• high concentration in

leucocytes• leucocytes transport the

antibiotic into the site

of infection• absence of toxicity• comfort dosage

erythromycin molecule

MacrolidesUsage:- mild infections, mucosal infections - infections in young persons

with good immunity- infections with intracellular pathogens

(respiratory infections, urogenital infections)

Not recomendable:- usage in severe infections (sepsis)- usage in persons with decreased immunity- frequent usage (→ resistance)

Lincosamides lincomycin clindamycin

Partial absorbtion from GIT, good penetration into tisues and cells, metabolization in liver, elimination in bile in urine

Spectrum: • only Gram-positive microbes (streptococci and staphylococci)• anaerobes• protozoa (Toxoplasma, Plasmodium, Entamoeba)

No toxicity, can be used in children or pregnant women – but there is a risk of post-antibiotic colitis (Clostr. difficile)

Lincosamides lincomycin clindamycin

Usage: infections due to streptococci, staphylococci, anaerobesmild to moderate infections – not sepsissubacute or recurrent infections

• infections in mouth cavity• wound infections, skin and soft tissue infections • infections of bones and joints• pneumonia after aspiration

+ malaria, toxoplasmosis, amebosis

Tetracyclins1. generation: tetracyclin, oxytetracyclin2. generation: doxycyclin, minocyclin3. generation: tigecyclin

Good absorbtion from GIT, good penetration into tissues and cells, metabolization in liver, elimination into bile and urine. Long half-time.

Spectrum: • very broad originally (various Gram-positive and –negative pathogens, anaerobes, chlamydiae, mycoplasmata)• but many resistant strains nowadays• never effective against Pseudomonas spp., enterococci, Bacteroides fragilis

Tetracyclins1. gen. tetracyclin, oxytetracyclin2. gen. doxycyclin, minocyclin3. gen. tigecyclin

Indications:• infections caused by mykoplasmata, chlamydiae, rickettsiae

- especially „atypical pneumonia“- STD like uretritis, prostatitis

• zoonoses (lyme borreliosis, tularemia, brucellosis, ...)Adverse events: nausea, vomitinghepatotoxicitystorage in bones and teeth (= not allowed

for pregnant women and children up to 8

years)Candida superinfections

Aminoglycosidesstreptomycinneomycingentamicin, tobramycin, ..amikacin, isepamicin, ..

Mode of action:• inhibition of proteosynthesis• damage of cell wall in Gram-positive and –negative bacteria

→ synergy with beta-lactams and glycopeptidsSpectrum: • Gram-negative rods (E. coli, Pseudomonas spp, ...) and staphylococci → direct bactericidal effect• Streptococci and enterococci: only synergic with other ATBAminoglycosides do not affect anaerobes, intracellular pathogens, and encapsulated bacteria!

Aminoglycosidesstreptomycin for tuberculosis treatmentneomycin for external usage onlygentamicin, tobramycin, .. sepsis (community-acquired)amikacin, isepamicin, .. sepsis (nosocomial)

Adverse events:• nephrotoxicity (cumulative)• ototoxicity (especially high doses)• neurotoxicity (when combined with myorelaxant drugs)

Usage: narrow therapeutic window, serum levels should be monitoredonce daily dosing in most situations

Groups of antibioticsA) ATB inhibiting bacterial cell wall synthesis A) ATB inhibiting bacterial cell wall synthesis

(peptidoglycan synthesis)(peptidoglycan synthesis)B) ATB inhibiting bacterial DNA metabolismB) ATB inhibiting bacterial DNA metabolismC) ATB inhibiting bacterial proteosynthesisC) ATB inhibiting bacterial proteosynthesisD) ATB inhibiting bacterial metabolic pathwaysD) ATB inhibiting bacterial metabolic pathways

- inhibition of folic acid synthesis- inhibition of folic acid synthesis- sulphonamides- sulphonamides- trimethoprim- trimethoprim

- unspecific inhibitors of bacterial metabolism- unspecific inhibitors of bacterial metabolism- nitroimidazols (metronidazol)- nitroimidazols (metronidazol)- nitrofurantoin- nitrofurantoin

E) ATB damaging bacterial cell membranesE) ATB damaging bacterial cell membranes

Sulphonamides and trimethoprimInhibition of folic acid synthesis Inhibition of folic acid synthesis ((→ lack of thymin)→ lack of thymin)

Gram-positive bacteria: pneumococi, staphylococciGram-positive bacteria: pneumococi, staphylococciGram-negative bacteria: Gram-negative bacteria: E. coliE. coli and other enterobacteria and other enterobacteriaplus: plus: Pneumocystis jiroveciPneumocystis jirovecisulphonamides also active against sulphonamides also active against Toxoplasma gondii Toxoplasma gondii and and

PlasmodiumPlasmodium spp. spp. enterococci are always resistant enterococci are always resistant in vivoin vivo, independently on , independently on

results of results of in vitroin vitro tests tests

sulphamethoxasol + trimethoprim = co-trimoxazol (5 : 1)sulphamethoxasol + trimethoprim = co-trimoxazol (5 : 1)

Good absorbtion from GIT, good penetration into tissues;Good absorbtion from GIT, good penetration into tissues;metabolization in liver metabolization in liver →→ various drug interactions; various drug interactions;elimination via urine above all elimination via urine above all

Co-trimoxazol urinary tract infectionsurinary tract infections diarrhea due to enteric bacteriadiarrhea due to enteric bacteria enteric feverenteric fever mild to moderate infections caused by pneumococci and mild to moderate infections caused by pneumococci and

staphylococci staphylococci pneumonia due to pneumonia due to Pneumocystis jiroveciPneumocystis jiroveci

(including HIV/AIDS prophylaxis)(including HIV/AIDS prophylaxis)

Adverse events: Adverse events: mainly sulphonamidesmainly sulphonamides allergy, incl. Stevens-Johnson syndromeallergy, incl. Stevens-Johnson syndrome drug feverdrug fever myelotoxicitymyelotoxicityDrug interactions: warfarin, hydantoin, salicylates, indomethacin ..Drug interactions: warfarin, hydantoin, salicylates, indomethacin ..

Nitroimidazolesmetronidazole,metronidazole, ornidazole, tinidazoleornidazole, tinidazole

anaerobic bacteria incl. anaerobic bacteria incl. Bacteroides fragilisBacteroides fragilis protozoa: protozoa: Trichomonas, Entamoeba, GiardiaTrichomonas, Entamoeba, Giardia

Excellent absorbtion and tissue penetration. Metabolization in liver.Excellent absorbtion and tissue penetration. Metabolization in liver.

infections due to anaerobic bacteria, especially in infections due to anaerobic bacteria, especially in abdominal cavityabdominal cavity

postantibiotic colitis (postantibiotic colitis (Clostridium difficileClostridium difficile)) protozoal infections (see above)protozoal infections (see above)

Adverse events: GIT intolerance, disulphiram effect, encephalopathyAdverse events: GIT intolerance, disulphiram effect, encephalopathyAcquired rezistance is rare.Acquired rezistance is rare.

Nitrofurantoin„„urinary antiseptic agent“urinary antiseptic agent“therapeutical concentrations only in urinetherapeutical concentrations only in urineshort half-time, metabolization in various tissuesshort half-time, metabolization in various tissues

Spectrum:Spectrum: E. coli E. coli and other enterobacteria, + enterococci and other enterobacteria, + enterococci

urinary tract infections - therapyurinary tract infections - therapy urinary tract infections – long term prophylaxisurinary tract infections – long term prophylaxis external usage: vaginal globules, pastae in dermatologyexternal usage: vaginal globules, pastae in dermatology

Adverse events: GIT intolerability, allergy Adverse events: GIT intolerability, allergy Acquired rezistance is very rare!Acquired rezistance is very rare!

Groups of antibioticsA) ATB inhibiting bacterial cell wall synthesis A) ATB inhibiting bacterial cell wall synthesis

(peptidoglycan synthesis)(peptidoglycan synthesis)

B) ATB inhibiting bacterial DNA metabolismB) ATB inhibiting bacterial DNA metabolism

C) ATB inhibiting bacterial proteosynthesisC) ATB inhibiting bacterial proteosynthesis

D) ATB inhibiting bacterial metabolic pathwaysD) ATB inhibiting bacterial metabolic pathways- inhibition of folic acid synthesis- inhibition of folic acid synthesis- unspecific inhibitors of bacterial metabolism- unspecific inhibitors of bacterial metabolism

E) ATB damaging bacterial cell membranesE) ATB damaging bacterial cell membranes- colistin- colistin

Colistin

bactericidal against various Gram-negative bacteria, bactericidal against various Gram-negative bacteria, including including PseudomonasPseudomonas spp. spp.

ultimum refugiumultimum refugium in therapy of multiresistant infections in therapy of multiresistant infections

a) parenteral application: a) parenteral application:

nephrotoxicity, neurotoxicitynephrotoxicity, neurotoxicity

b) external application: b) external application:

used in dermatologyused in dermatology

MUDr. P. Potměšil, PhD.

Selected topics about antibiotics/antivirals

Some important interactions or adverse effects of selected antibiotics

Ciprofloxacin cannot be used with agomelatine (newer antidepressant)

Clarithromycin (e.g. for respiratory infections) should not be used with buspirone (anxiolytic) or dosage of buspirone should be reduced

Tetracyclines (e.g. Doxycyklin for borreliosis) make complexes with Ca, Al, Fe and Mg cations (take doxycyclin 2-3h before or 4-5h after use of food supplements, milk products, antacides etc.)

Macrolides can cause damage of vestibulocochlear nerve or hepatic impairment in high and longterm dosage

Antibiotics used in eradication of Helicobacter pylori infection Amoxycillin Clarithromycin – contraindicated with statins

that lower cholesterol (simvastatin etc.) or with antineoplastic agents lapatinib, dasatinib

(azitromycin) Metronidazol Antibiotics have to be used together with

proton pump inhibitor = PPI (omeprazol, pantoprazol etc.)

1/ Amoxycylin + metronidazol + PPI 2/ Claritromycin + PPI

Antibiotics used for therapy of acne I. Topical use 1/ Erytromycin, or erytromycin in combination with zinc (Zineryt lot.) 2/ Clindamycin, or clindamycin in combination with benzoylperoxide (Duac gel) 3/ Metronidazol - acne rosacea 4/ Chloramphenicol 5/ Acidum fusidicum – (Fucidin cream) II. Peroral therapy A/ Tetracyclines 1/ Doxycyclin (some forms of acne)2/ Tetracyclin

B/ Macrolides 1/ Erytromycin2/ Azitromycin – less effective than tetracyclines but can be better tolerated, pulse therapy recommendedC/ Clindamycin

Antibiotics for therapy of borreliosis (caused by borrelia burgdorferi)

Doxycycline (tetracycline) Cefuroxim-axetil (cephalosporin II. gen.) Azitromycin (macrolide)

Pharmacotherapy of HIV infectiondrugs are applied in combinations – combined antiretroviral therapy (cART)

A) Inhibition of HIV entry

1/ maraviroc

- peroral antagonist of CCR5 receptor (chemokine co-receptor for HIV entry)

- patients have to be scrreened for CCR5 genotype before prescription

2/ enfuvirtide

- inhibiton of HIV fusion with cell

- only s.c.

B) Inhibition of HIV replication

1/ reverse transcriptase inhibitors zidovudine

tenofovir,stavudine,zalcitabine, didanosine, nevirapine, efavirenz

2/ inhibitors of HIV integrase. Raltegravir

3/ HIV protease inhibitors ritonavir, nelfinavir, fosamprenavir,

saquinavir, indinavir

Acyclic nucleoside phosphonates (ANP) N-(2-fosfonometoxyalkyl) purines. Antivirals effective against DNA viruses and

retroviruses. Approved are:

tenofovir (HIV),

adefovir (HBV) and cidofovir (CMV). Tenofovir increases production of cytokine

IL-10 and chemokines RANTES,MIP-1α that can block HIV entry/replication thus tenofovir has low risk of resistance.

Therapy of chronic viral hepatitis B/C

Hepatitis B

1/ tenofovir or entekavir first line choice for longterm use today because of very good efficacy and low resistance

2/ other drugs: adefovir, lamivudine, telbivudine or pegylated interferon alfa

Hepatitis C

1/ standard therapy is

combination of

peg. interferon-alfa + ribavirin

2/ New drugs

Boceprevir, telaprevir

Possible ATB for selected nosocomial infections Resistent Staph. Resistent Staph.

Aureus:Aureus: 1/ Vancomycin + 1/ Vancomycin +

rifampicin or rifampicin or gentamicingentamicin

2/ Teicoplanin2/ Teicoplanin

(for Vanc. resistent (for Vanc. resistent

Staph. A.)Staph. A.)

Pseudomonas aerug.:Pseudomonas aerug.: 1/ ticarcillin 1/ ticarcillin

(co-ticarcillin not actually (co-ticarcillin not actually registered in Czech Rep.)registered in Czech Rep.)

2/ ceftazidim + 2/ ceftazidim + aminoglycosidesaminoglycosides

3/ imipenem, 3/ imipenem, meropenemmeropenem

4/ fluoroquinolones4/ fluoroquinolones