Download bronchopneumonia

BRONCHOPNEUMONIA
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
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
Therapy of Bronchopneumonia
• 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 /
+ bronchodilators
mucolytics
expectorances
antitussics
+ rest in bed
fluid intake
calories intake
vitamin intake
Etiologic Agents according to
Frequency of Occurance
• LUNGS
respiratory viruses
• Str. pneumoniae
• H. influenzae
• S. aureus
• Klebsiella speciei
• M. pneumoniae
• Str. pyogenes
• Chl. psittaci
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BRONCHI
respiratory viruses
Str. pneumoniae
H. influenzae
Str. pyogenes
S. aureus
Escherichia coli
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
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
Ideal Antibiotic
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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
Choice of Antimicrobial
Substance
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Ideal antibiotic drug
absorption
distribution
elimination
ADR
price
• Which available ATB
is close to ideal?
• ß-lactams
• Macrolides
• Quinolones
• Tetracyclines
• Cotrimoxazol
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
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
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.
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
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/
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
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
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!
Betalactamic Antibiotics
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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
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%
• resistance: enzyme type – betalactamases +
mutations – not letting to recognise of recept.
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
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 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
Cephalosporines
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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
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
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
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
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
• 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
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
Moxifloxacin
• 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
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/
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
Occurance of Bronchopneumonias Caused
by Mycoplasmas according to Age
Pharmacotherapy of Atypical
Pneumonias
• Macrolides
/erythromycin, klarithromycin, azithromycin/
• Tetracyclines
/doxycycline/
• Fluoroquinolones
/antipneumococcal/
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
Macrolides
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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
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
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
Tigecycline
• Broad spectrum antibiotic from new group
of glycylcyclines, derived from TTC,
since the year 2005
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
Tigecycline
• treatment of complicated skin and intraabdominal 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
Linezolid
• 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
Linezolid
• 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
Daptomycin
• 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
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
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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, that´s when are
indicated antitussives
antitussives we use only when we know ethiology of
cough and when we treat causally given disease!
Division:
1. antitussives with central effect and with the
structure of opioids
2. antitussives with central effect and peripheral effect
with different structure
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
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
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
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!
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 /
EXPECTORANTS
= getting rid of viscous mucus from airways
1. 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/