1. BRONCHOPNEUMONIA

2. Bronchopneumonia
= acute inflammatory process in the area of respiratory bronchioli, alveolar structures and/or lung interstitium
caused by espec. infectious agent
complications: pleuritis, parapneumonic empyema, lung abscess, lung gangrene and sepsis
risk factors: age, CV and respiratory comorbidities, smoking, immunodeficiency
= mortality over 70 yr. to 25%!
Division according to agent:
viral
bacterial
mycotic
parasitic
Division of clinical terms:
CAP – community
HAP – hospital
acquired pneumonia

3. Clinical signs of disease
= may start suddenly with chills and fever, especially when bacterial etiologic agent
in viral diseases - development is slower, it may follow inflammation of the upper respiratory tract
temperature in children usually relatively high, in elderly subfebrile to afebrile
cough - first dry, irritable, and later with various expectoration. At the inflammatory response on the pleura, is manifested chest pain linked to cough and breathing
tachypnoea and dyspnoea, in children alar breathing and cyanosis

5. Therapy of Bronchopneumonia
+ bronchodilators mucolytics expectorances antitussics + rest in bed fluid intake calories intake vitamin intake
immediately begin initial empirical anti-infective therapy, with the spectrum of effect covering the most prevailing pathogens, also taking into account individual risk factors
knowledge of the epidemiological situation + resistance of respiratory pathogens to antibiotics in the region
antimicrobial therapy should be directed = necessity to determine etiology and sensitivity of microorganisms to antibiotics /after identification of the pathogen, initial therapy adequately adjusted /

6. Etiologic Agents according to Frequency of Occurance
LUNGS
respiratory viruses
Str. pneumoniae
H. influenzae
S. aureus
Klebsiella speciei
M. pneumoniae
Str. pyogenes
Chl. psittaci
BRONCHI
respiratory viruses
Str. pneumoniae
H. influenzae
Str. pyogenes
S. aureus
Escherichia coli

7. Antimicrobial Drugs
with targeted mechanism affect the structure or function of microorganism cells, and thus they either kill - bactericidal effect, or inhibit their growth and multiplication - bacteriostatic effect/immunodeficiency and cachect. patients! /
selective action on the cells of microorganisms: effect on the synthesis of cell wall - bactericid effect on protein and NA synthesis + inhibition of metabolic procedures – bacteriostatic

8. Division of Antimicrob. Substances
chemical – according to similar structure, substance with the same mechanism of action have usually the same AE
baktericid: ß-laktamic ATB, aminoglycosides, bacitracin, isoniazid, metronidazole, quinolones, vancomycin, teicoplanin, rifampin
bacteriostatic: macrolides, tetracyclines, chloramphenicol, sulfonamides, trimetoprim, linkomycin, klindamycin, ethambutol, nitrofurantoin

9. Division of Antibiotics According to Mechanism of Action
Drugs affecting cell wall: Beta-lactam antibacterials: PNC, Cephalosporins, Monobactams, Carbapenems Glycopeptides: teicoplanim, vancomycin Lipopeptides: daptomycin Polymyxins: colistimethate sodium Drugs affecting bacterial DNA: Quinolones, Fluoroquinolones: ciprofloxacin, moxifloxacin, norfloxacin Metronidazole, Tinidazole Nitrofurantoin

10. Division of Antibiotics According to Mechanism of Action
Drugs affecting bacterial protein synthesis:
Macrolides: azithromycin, clarithromycin, erythromycin, telithromycin
Aminoglycosides: gentamycin, netilmycin, streptomycin, tobramycin
Tetracyclines: doxycycline, minocycline
Chloramphenicol
Lincosamides: clindamycin
Fusidic acid
Oxazolidinones: linezolid
Drugs affecting bacterial metabolism:
Sulphonamides: sulfadiazine, sulphametoxazole
Trimethoprim

11. Ideal Antibiotic Wide spectrum Rapid action Bactericid
High selectivity, without AE, not causing allergy
Not to occur resistance
High biologiavailability, good penetration to tissues, long biolog. half-life
Low price

12. Choice of Antimicrobial Substance
Ideal antibiotic drug
absorption
distribution
elimination
ADR
price
Which available ATB is close to ideal?
ß-lactams
Macrolides
Quinolones
Tetracyclines
Cotrimoxazol

13. Principles of Antimicrob. Therapy for Respiratory Diseases
racional indication
take into account the nature and severity of infection
take into consideration the clinical condition of the patient
Individual choice of drug
prevent the increase in resistance due to :
incorrect prescription
incorrect dosage
not keeping the optimal length of therapy

14. Choice of the Right Antibiotic
Targeted administration on the basis of identification of causative agent of infection
Consider pharmacokinetic properties
Choosing the most appropriate route of administration and site of administration. At severe infections we begin with parenteral therapy. At limited function of elimination organs we reduce the dose or prolong dosing interval
Reducing the risk of administration by revealing of predisposing factors such as drug allergy
Determination of the risk groups of patients

15. Problematic of ATB Resistance
= the ability of the bacterial population to survive inhibitory concentration of the given antimicrobial drug, becomes a significant problem nowadays
1. Primary resistance = natural resistance of microbial species, which are outside the range of ATB action /missing are „mechanisms“ (receptors) for the effect of antimicrobial drugs/ absolut resistance + relevant resistance /mikroorganism not sensitive to antibiotic concentrations reachable in human organism, but sensitive to high concentration of antibiotic reached in vitro
2. Secondary resistance occurs during antibiotic therapy, when initially sensitive bacterial population during antibiotic treatment become resistant to them.

16. Resistance to ATB mechanism of resistance:
productions of enzymes, which change structure of antimicrob. substance the way that it looses antimicrobial effect (betalactamases – inactivating some PNC, acetylating enzymes inactivating aminoglycosides)
modification of bacterium so that penetration of the drug is reduced (absence of D2 porin in resistant Pseudomonas aeruginosa – resistance to imipenem)
acquisition of efflux pumps that remove the antibiotic from the cell faster than it can enter (quinolone efflux pumps in Staphylococcus aureus)
structural change in the target molecule for antibiotic (mutated penicillin-binding proteins in enterococci, mutated dihydrofolate reductase not inhibited by trimetoprim)
The major mechanisms by which bacteria acquire resistance to antibiotics are:
spontaneous mutation, conjugation, transduction and transformation.

17. Possibilities of Slowing Down Resistance Appearance
the right choice of antimicrobial drug
optimal and enough long administration
right dose
in special cases stable combinations /treatment of TBC/

18. Development of Actual Resistance
Penicillin resistant pneumococs (PRP)
Meticillin resistant staphylococs (MRSA)
CA-MRSA (Community-Associated Methicillin-Resistant Staphylococcus Aureus)
Streptococcus pyogenes/macrolides
Quinolone resistant E. coli

19. Agents Causing Pneumonia of Adults
lobal: S. pneumoniae, H. influenzae, K pneumoniae
bronchopneumonia: S. pneumoniae, S. aureus, L. pneumophilla
atypical: influensa virus, RSV, adenoviruses, HZV, Mycoplasma pneumoniae, Chlamydia pneumoniae

20. Pharmacotherapy of Bronchopneumonia Caused by Streptococcus pneumoniae
Aminopenicillins at high doses
Aminopenicillins protected with inhibitors of betalactamases /ampicillin-sulbactam, amoxicillin-clavulanic acid/
Cephalosporins III. generation
Fluoroquinolones /levofloxacin, moxifloxacin/ = advantage is higher concentration in the site of action /alveol. fluid, macrophages/ than in plasma!

21. Betalactamic Antibiotics
- in structure betalactamic circle
bactericid
inhibit synthesis of cell wall of mikroorganisms in the last phase of its consolidation with peptidoglycan
hydrophil
low direct toxicity
low occurance of AE
spectrum of effect depends on substance
here belong PNC
cephalosporins
monobactams
carbapenems

22. Penicillins
absorption of peroral PNC after p.o. administration better from empty stomach
G-penicillin, meticillin, carboxypenicillin, ureidopenicillin – unstable in acid environment of stomach - administration parenteral
don´t cross intracelullarly, metabolised a little, excreted through kidneys through glom. filtr. and also tubul. secretion, high concentrations reached in urine
minimal AE, also in high doses not toxic, allergy 5-8%

23. PNC with Narrow Spectrum
Benzylpenicillin (Penicillin G) – natural PNC, acidolabile, only parenteral administration (i.m., i.v.)
mainly aerobic Gram-positive bacteria (streptococci, pneumococci), limited to Gram-negative bacteria (gonococci and meningococci), anaerobic bacteria
only effective to microorganisms that don´t produce betalactamases
medium serious inf. caused mailnly by betahaemol. streptococci
serious infections – high plasmat. concentrations of Na or K salts
of crystalic PNC i.v. /renal diseases!/
depot preparations – i.m.- Procain PNC – 2 times per day 1g
Phenoxymethylpenicillin (Penicillin V) – biosynthet., acidostable (p.o.), similar spectrum of activity as PNC G but generally less effective
Penamecillin – prolonged effect, á 8h.
Oxacillin, cloxacillin, dicloxacillin, meticillin
antistaphylococcal, resistant against betalactamases produced
by staphylococci, very narrow spectrum, peroral also perenteral
administration, á 4 till 6 h.

24. PNC with Broader Spectrum
- also G- microorg./E. coli, salmonellas, shigellas, H. influensae/
Aminopenicillins - ampicillin, amoxicillin /=better penetration,
higher plasm. conc./ acidostable, aren´t resistant against betalactam.
uncomplic. infections of urinary, airway and gallbladder pathways mainly in
combination with inhibitors of betalactamases (amoxicillin + clavulanic acid, ampicillin + sulbactam) , peror. also parent. admin.
Carboxypenicillins /carbenicillin, tikarcillin/
semisynthet. PNC, also Pseudomonas aeruginosa, Proteus - at syst.
infections alone or in combination with aminoglykosides
acidolabile – parenter. adm., tikarcillin in comb. with inh. of betalactamases
Ureidopenicillins /azlocillin, mezlocillin,
piperacillin/
acidolabile, good penetration to tissues, more intensive on Proteus,
Pseudomonas aeruginosa, piperacillin also to some anaerobes,
the highest effectivity, reserved to serious infections

25. Cephalosporines similar mechanism of action as PNC
have beta-lactam ring like PNC
wide use, in pediatria and geriatria
good efficacy and low toxicity
good penetration to tissues
excretion through kidneys by glom. filtr., tub. secretion
according to pharmacodynamic – spectrum of efficacy, ability to penetrate to cells, stability against betalactamases - 4th generation
successive generations tend to have increased activity against G-bacterias at the expense of decreased activity against G+bacterias
and increased activity to cross blood-brain barrier
succesive generations are more resistant to betalactamases
several drugs are acidolabile and have to be administered by parenteral route
cefuroxime has been formulated as a prodrug for oral use (cefuroxime axetil)

26. Cephalosporins of 1st and 2nd Generation
1st generation
cefalotin, cefazolin, cephalexin,cefradil
narrow spectrum, against G+/also staphylococci/,
G-sticks, airway, urinary and skin infections
2nd generation
cefoxitin, cefaclor, cefamandol, cefuroxime
expanded spectrum to G-bact., resistant against
betalactamases, act against H. influenzae +
some anaerobes, less against staphylococci

27. Cephalosporins of 3rd and 4th Generation
3rd generation
cefotaxime, ceftazidime, ceftriaxon,
empir. treatment of severe life threatening infections
targeted treatment of microorg. resist. to PNC and
ceph. of lower gen. - parent. adm. - oft aplication
infections of airways – p.o. – 1 times per day
4th generation
cefepime, cefpirom
intensified effect against staphyloc.,
streptococci and pseudomonads
severe nosocomial infections

28. Rezistance of Pneumococci to Antibiotics
increase of rezistance to pneumococci to natural penicillins, also to cephalosporins, macrolides, doxycycline = drug-resistant Streptococcus pneumoniae
risk factors of occurance:
age over 65 years
ATB therapy in last 3 months immunodeficiency
comorbidities

29. Fluoroquinolones chemotherapeutic with high ATB activity
baktericid effect – select. inh. of bacterial gyrase activity and so inhibiton of the replication of bacterial DNA
resistance – mutation of DNA gyrase
broad spectrum antibiotics
fluor – increased efficacy, better kinetic properties – use at systemic infections, also serious, serious nosocomial pneumonias, uroinfections, gynecol. infections, GIT infections, infections of airways
good absorption after peror. administration, some also parenter. administration /ciprofloxacin/, possible parenteral. starting therapy, than peroral administration
good penetration to soft tissues, bones and lungs

30. Levofloxacin (quinolone)
high bioavailability
good penetration to bronchial mucosa and lung parenchyma
at middle serious and serious inf. of airways, complic. uroinfections, inf. of skin and soft tissues
interactions at absorption are occuring at simultaneous administration of iron salts, or antacides containing magnesium and alluminium
„respiratory quinolone“ – effect on G+ causative agents of respiratory infections
AE: nausea, diarrhoea, increases hepatic enzymes

31. Moxifloxacin (quinolone)
fast perfect absorption after peroral administration, quickly distributed to extravasc. space
at metabolism doesn´t undergo oxidation, that´s why not showing signs of interaction with other substances, which are metab. through cytochrome P-450
excretion by faeces, less by urine
„respiratory quinolone“ – effect on G+ causative agents of respiratory infections

32. Bronchopneumonia Caused by Pseudomonas aeruginosa
risk factors of occurance:
structural changes of airways and lungs, systemic therapy with glucocorticoids, wide-spectrum ATB therapy in the last month, malnutrition
antipseudomonad betalactamic ATB:
cefepime, piperacillin-tazobactam / both also effective on pneumococci/, at allergy to betalactams monobactam aztreonam
always combined therapy with aminoglykosides /gentamicin/ and antipseudomonad fluoroquinolone /ciprofloxacin/

33. Atypical Bronchopneumonia
disease development and a mild physical symptoms does not correspond to significant signs on X-ray of lungs, but some of them have severe acute development with the possible occurance of serious complications / ARDS /
30 – 40% of bronchopneumonias
causative agents = intracelular parasits /Mycoplasma pneumonie, Chlamydia pneumoniae, Legionella pneumophila, Coxiella burnetii/ + respiratory viruses
occurance mainly in societies of young people
ATB therapy which penetrates intracelullarly and interferes with proteosynthesis of atypical microorganisms

34. Occurance of Bronchopneumonias Caused by Mycoplasmas according to Age

35. Pharmacotherapy of Atypical Pneumonias
Macrolides
/erythromycin, klarithromycin, azithromycin/
Tetracyclines
/doxycycline/
Fluoroquinolones
/antipneumococcal/

36. Macrolides
bakteriostatic effect – inhibit proteosynthesis of microorganisms by binding to 50S subunit of bacterias
broad-spectrum atb with similar spectrum as broad-spectrum PNC (often used to treat patients allergic to PNC)
spectrum mainly G+ bacterias, anaerobic bacterias
also penetration to cells and influence on intracel. pathogens /mycoplasma, chlamydia, legionella, bordetella pertussis/
good penetration to tissues
metabolis. in liver by cytochr. P-450 interactions: increases plasmat. conc. of theophylline, digoxin, anticoagulants. Interaction with antihistaminics causings severe ventricular arrhytmia

37. Macrolides slower and lower development of resistance
stability in acidic surrounding
longer biologic half-life
high concentration in tissues and serum
2nd generation /erythromycin+spiramicin/ roxithromycin, azithromycin, clarithromycin = better pharmacokinetics and tollerability/
little toxic, good tolleration
AE: GIT + liver functions

38. Clarithromycin (macrolide)
semisyntetic
verry good tollerance
biotransformation to antimicrobically more effective 14-OH-clarithromycin
typical, atypical, intracelular and ß-laktamase producing pathogens
8 times more effective as erythromycin to Chl. pneumoniae and M. pneumoniae
very good at infections caused by Legionella pneumophilla and Moraxella catarrhalis

39. Tetracyclines
bakteriostatic, inhibit bacterial protein synthesis by binding reversively to 30S subunit of ribosome
broad-spectrum atb active against many G+ and G- bacterias, infections caused by mykoplasmas, chlamydias, rickettsias
resorption at fasting good, not with milk, antacids, Fe 3+, which prevent their resorption
good penetration to tissues except to CNS
at renal diseases needed dose reduction
2nd generation: tetracyclin
doxycyclin – better pharmacokin. properties /higher bioavailability, longer half-life = administratio 1-2 times per day/
AE: oft but not severe, GIT, disorders of bones and teeth by calcium chelation = contraindic. at children

40. Aminoglycosides
bakteriostatic, inhibit bacterial protein synthesis by binding irrreversively to 30S subunit of ribosome
active against many G- bacterias (including Pseudomonas) and some G+ bacterias
inactive against anaerobes
useful in serious G-negative infections, when they have synergistic action with drugs that disrupt cell wall synthesis (PNC)
poorly absorbed from gut and given parenterally
ototoxic, nephrotoxic
gentamycin, netilmicin, streptomycin, tobramycin

41. Super-Resistant Bacterias
superbugs or extensively drug-resistant microorganisms
gramnegative bacterias (Pseudomonas aeruginosa, Klebsiella, Enterobacter a Enterobacteriaceae)
carry genes producing metallo-beta-lactamases
/broad-spectrum beta-lactamases containing Zn, which break down also ATB, which were so far to gramnegative bacterias the most effective – carbapenems/
are resistant to all cephalosporis and penicillins, quinolones, aminoglycosides - are resistant also to so called reserve ATB

42. Tigecycline (glycylcycline antibiotic)
Broad spectrum antibiotic from new group of glycylcyclines, derived from TTC,
since the year 2005
Mechanism of action: inhibition of proteosynthesis in bacterias
spectrum:
G+ and G- including multiresistant
methicillin/oxacillin-resistant strains of Staph.aureus
penicillin-resistant streptococci
vancomycin-resistant enterococci
bacterias producing broad spectrum betalactamases
anaerobes (group Bacteroides)
mycoplasmas, chlamydia
rapidly growing mycobacteria

43. Tigecycline (glycylcycline antibiotic)
treatment of complicated skin and intra-abdominal infections, which are often caused simultaneously by more bacteria (not rarely by multiresistant strains)
it can be used in the treatment of documented infections, as well as initial empiric therapy, before definitive identification of the pathogen
i.v. application

44. Linezolid (oxazolidinone)
yet the only representative of new group of
oxazolidinones
broad spectrum of effectiveness including
community-acquired
and nosocomial G+ pathogens
oxacillin-resistant staphylococci
(S. aureus, S. epidermidis)
vankomycin-resistant enterococci
(E. faecalis, E. faecium)
penicillin and erythromycin-resistant pneumococci
interaction potential of linezolid is low, enzyme complex cytochrome P-450 is not participating in metabolism of linezolid

45. Linezolid (oxazolidinone)
oral form achieves the same pharmacologic parameters as parenteral
(serum and tissue concentrations)
reaches high concentrations in bones, cerebrospinal liquor and mainly in lung parenchyma
therapy of nosocomial pneumonias
and severe infections of skin and soft tissues
bioavailability is very good, what allows administration also initially in p.o. form or as follow-on treatment - p.o. after initial i.v. therapy

46. Daptomycin (lipopeptide ATB)
representative of lipopeptide antibiotics
effective only against G+ microorganisms except enterococci
treatment of skin and soft tissue infections
potentially also for treatment of catether infections

47. ANTITUSSIVES
cough = reflex. protective mechanism, with witch airways are getting rid of any foreign materiala, and also secretory products
complete cough supression is unwanted and unreal
but long-lasting cough cand weaken patient and strained breathing muscles are painful, that´s when are indicated antitussives
antitussives we use only when we know ethiology of cough and when we treat causally given disease!
Division:
antitussives with central effect and with the
structure of opioids
2. antitussives with central effect and peripheral effect with different structure

48. CODEINE = decreases sensitivity of center for cough
properties similar to morphine, less effective
p.o. administered good absorption from GIT, metabolis.
in liver to morphine and norcodeine, excreted by kidneys unchanged or as glucuronide, transfer to breast milk = supress of child´s breathing
interactions: + IMAO, thymoleptics, physostigmine, neostigmine
- naloxone, nalorphine, pentazocine
= increases analgetic effect of analgetics-antipyretics
= potentiation of suppressive effect of other CNS drugs
= with opioid analgetics – deepening depression of CNS and breathing center

49. CODEINE
indication: symptomat. supressing of irritating non-productive cough of known etiology in combination with causal therapy of given disease
contraindications: difficult expectoration, mainly at advanced stage of bronchopulmonal disease, hypersensitivity to drug, prohibition of alcohol /strongly increases depressive effect on CNS/!
dose: 15 – 30 mg 3 times per day

50. FOLCODINE
= derivate of codeine with bigger efficacy, doesn´t decrease bronchial secretion, isn´t usually cause of dependence, supresses cough reflex inhib. by inhibition of centrum for cough in medulla
therapy of dry irritating cough
increases depressive effect of substances supressing CNS and also alcohol
dosage: 10 – 20mg 3 times per day

51. ANTITUSSIVES OF CODEINE TYPE
Etylmorphine = derivate of morphine similar to codeine, stronger analgetic and antitussic effect
at dry irritating cough at acute inflammation of airway system, TBC, spontaneous pneumothorax and before diagnostic procedure
long-lasting aplication in pregnancy = abstinent signs at newborn, passes to milk!
Dextromethorphan = antitussive drug without analgetic. effect, doesn´t supress breathing center, minimal risk of dependence, minimal AE
not at patients with bronchial asthma!

52. ANTITUSSIVES OF NONCOD. TYPE
central effect: pentoxyverine /one-third effect of codeine, lower effects, at antitus. doses proven no depressive influence on breathing center/, butamirate /effective antitussic used in pediatria, minimum AE/, clobutinol /contraindicated in pregnancy and at breast feeding/
peripheral effect: benzonatate, dropropizine /strong antitussive with properties similar to butamirate, mild antihistaminic effect, minimal effect on on breathing center /

53. EXPECTORANTS = getting rid of viscous mucus from airways
Mucolytics and secretolytics – lower viscosity of mucus, resp. increase production of mucus
CAREFUL AT SIMULTANEOUS ADMINISTRATION OF ANTITUSSÍVE AGENTS!
BROMHEXINE – increasing proportion of liquid bronchial mucus and reduces its viscosity by reduction of transversal bonds of acid mucopolysaccharides, promotes secretion of mucus, improves cilliar function, pharmaco-therapeutically active is metabolite ambroxol
AMBROXOL – mukolytic and secretolytic effects, activation of cilliar epithelium
N-ACETYLCYSTEINE - cleaves disulfidic bridges connecting mucopolysacharid fibers in sputum, at difficult expectoration, at chronic bronchitis and mucoviscidosis, also prophylactically
2. Secretomotorics – are increasing activity of cilliar epithelium /β-sympathomimetics, eteric oils/