BRONCHOPNEUMONIA

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BRONCHOPNEUMONIA
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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
• parasite
• Division of clinical terms
• CAP community
• HAP hospital
• acquired pneumonia

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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 subfebrileto 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 alarm
  breathing and cyanosis

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Therapy of Bronchopneumonia

• bronchodilators
• mucolytics
• expectorances
• antitussics
• rest in bedfluid intakecalories 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 /

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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

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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
  microorganismseffect on the synthesis of cell
  wall - bactericideffect on protein and NA
  synthesis inhibition of metabolic procedures
  bacteriostatic

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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

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Ideal Antibiotic

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

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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

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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

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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

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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.

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Resistance to ATB

• mechanism of resistance
• - productions of enzymes, which change structure
  of
• antimicrob. substance the way that it looses
• antimicrobial effect
• - mutation changes on the level of intracelular
  recep.
• /betalact. ATB structure change of binding
  place for
• PNC/
• - preventing penetration of ATB through cell wall
  
• /making impossible binding of ATB to the site of
  action
• on intracel.rec./
• - change of metabolic pathway

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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/

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Development of Actual Resistance

• Penicillin resistant pneumococs (PRP)
• Meticillin resistant staphylococs (MRSA)
• CA-MRSA (Community-Associated Methicillin-Resistan
  t Staphylococcus Aureus)
• Streptococcus pyogenes/macrolides
• Quinolone resistant E. coli

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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

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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!

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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

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Penicillins

• absorption of peroral PNC after p.o.
  administration better from empty stomach
• G-penicillin, meticillin, karboxypenicillin,
  ureidopenicillin unstable in acid environment
  of stomach - administration parenteral
• dont 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
• resistance enzyme type betalactamases
• mutations not letting to recognise of
  recept. site

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PNC with Narrow Spectrum

• Benzylpenicillin natural PNC, acidolabile, only
  parent.
• mainly g, streptococci, pneumococci,
  meningococci
• 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
• Penicillin V biosynthet., acidostable, g
  microorg., identical
• effect spectrum, lower plasm. concentration
  mild streptoc.
• infections and their healing 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.

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PNC with Broader Spectrum

• - also G- microorg./E. coli, salmonellas,
  shigellas, H. influensae/
• Aminopenicillins - ampicillin, amoxicillin
  /better penetration,
• higher plasm. conc./ acidostable, arent
  resistant againstnie betalactam.
• uncomplic. infections of urinary,airway and
  gallbladder pathways mainly in
• combination with inhibitors of betalactamases,
  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

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Cephalosporines

• similar mechanism of action as 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

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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
• expanded spectrum to G-bact., resistant against
• betalactamases, act against H. influenzae
• some anaerobes, less against staphylococci

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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

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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

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Fluoroquinolones

• chemotherapeutic with high ATB activity
• baktericid effect select. inh. of bacterial
  gyrase activity , which catalyses creating of
  loops and by twisting allows the sdepositing of
  DNA in the cell nucleus
• rezistance mutation of DNA gyrase
• 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
  

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Levofloxacin

• 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

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Moxifloxacin

• fast perfect absorption after peroral
  administration, quickly distributed to extravasc.
  space
• at metabolism doesnt undergo oxidation, thats
  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

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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/

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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

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Occurance of Bronchopneumonias Caused by
Mycoplasmas according to Age
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Pharmacotherapy of Atypical Pneumonias

• Macrolides
• /erythromycin, klarithromycin, azithromycin/
• Tetracyclines
• /doxycycline/
• Fluoroquinolones
• /antipneumococcal/

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Macrolides

• bakteriostatic effect inhibit proteosynthesis
  of microorganisms
• spectrum mainly G bacterias, H. influenzae, some
  anaerobic bacterias
• penetration to cells and influence on intracel.
  pathogens /M. pneumoniae, chlamydias/
• 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

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Macrolides

• slower and lower development of resistance
• stability in acidic surrounding
• longer biologic half-life
• high concentration in tissues and serum
• 2nd generation /erythromycinspiramicin/
  roxithromycin, azithromycin, clarithromycin
  better pharmacokinetics and tollerability/
• little toxic, good tolleration
• AE GIT liver functions

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Clarithromycin

• 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

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Tetracyclines

• bakteriostatic, strong occurance of resistance
• 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

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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, thats
  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

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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 childs 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

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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

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FOLCODINE

• derivate of codeine with bigger efficacy,
  doesnt decrease bronchial secretion, isnt
  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

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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, doesnt supress breathing
  center, minimal risk of dependence, minimal AE
• not at patients with bronchial asthma!

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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 /

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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-therapeuticall
  y 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 /ß-sympathomimetics,
  eteric oils/