MANAGEMENT OF LOWER RTI IN BULGARIA THE PROBEMS
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MANAGEMENT OF LOWER RTI IN BULGARIATHE PROBEMS
Kosta Kostov
Clinic of pulmonary diseasesMilitary Medical Academy, Sofia, [email protected]
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Europe
& the
Balkan
countries RO
MC
BG
HRSL
BA
AL
SB&MN
TR
RU
UA
GR
BY
Antalya, 2007Antalya, 2007
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ARTI: The KILLER
World Health Organization, 1999.
0
0.5
1
1.5
2
2.5
3
3.5
ARTI Malaria AIDS Diarrhoea TB Measles
> 5 y.
< 5 y.
Mill
ion
dea
ths
Antalya, 2007Antalya, 2007
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THE PROBLEMS• Poverty of the bigger part of the population esp. elderly• The diagnosis of pneumonia is often incorrect (false
positive)• Some of the GP’s are not familiar with the most probable
causative agents (etiology data of RTI) and with the principals of empirical treatment
• Frequent and unneeded use of antibiotics (esp. betalactams) and the Stoichkov syndrome.
• Bacterial resistance• Many GP’s are not familiar with the risk groups of patients
who need more precise treatment options• Low reimbursement of antibiotics
Antalya, 2007Antalya, 2007
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Demografic / health indicators
• Total population: 7.866.000
• GDP per capita ($): 5.021
• Total health expenditure per capita ($): 198
• Total health expenditure as % of GDP: 4.4
Antalya, 2007Antalya, 2007
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BULGARIAN CAP GUIDELINES2007
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Definition of CAP
Acute infection of lung parenchyma, running with:• (а) minimum 2 of following symptoms: fever, shiver,
acute cough with or without sputum (not obligatory symptom) or chronic cough with changed sputum colour, pleural pain, dyspnea;
• (б) auscultatory signs of pneumonia (crepitations or cracles, bronchial breath);
• (в) new infiltrates on chest XR, without any explanation (pulmonary oedema or embolia).
Guidelines of CAP, 2007
Antalya, 2007Antalya, 2007
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When CAP is sure?
According the definition CAP is sure only when the clinical suspicion of CAP is radiologicaly confirmed!
Woodhead M. et al. Guidelines for the management of adult lower respiratory tract infections. Eur Respir J, 2005; 26: 1138-1180
Antalya, 2007Antalya, 2007
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Pneumococcal pneumoniaPneumococcal pneumonia
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CAP AGENTS(1998-2001)
Str. Pneumoniae - 26,5% Haemophhilus influenzae - 3,5% Moraxella catarrhalis - 1,2%
Klebsiella pneumoniae - 6,1% Staphylococcus aureus - 9,5% Escherichia coli - 7,5%
Chlamidia pneumoniae and Mycoplasma pneumoniae are not involved
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H.influenzae12.2%
M.catarrhalis12.0%
K.pneumoniae8.3%
S.pyogenes2.9%
ДРУГИ8.5%
S.pneumoniae43.3%
S.aureus 12.9%
Етиологична структура на изолатите от Храчки - Амбулаторни пациенти (БулСТАР - 2005)
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P.aeruginosa 10.7%
K.pneumoniae9.8%
H.influenzae8.0%
M.catarrhalis7.8%
Candida spp.4.4%
ДРУГИ7.5%
A.baumannii3.2%
E.coli 3.5%
S.pneumoniae33.5%
S.aureus 11.6%
Етиологична структура на изолатите от Храчки - Болнични пациенти (БулСТАР - 2005)
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EMPIRICAL APPROACH
Too many prescriptions of:
BETALACTAM’S and CIPROFLOXACIN
Antalya, 2007Antalya, 2007
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Таbl 5. Guidelines for initial empirical CAP treatment - 2007.
Място Тежест/подгрупаЛечение
Препоръчително Алтернативно
Амбулаторно Всички -лактам и/или макролид* levofloxacin, moxifloxacin**
Болница Лека/средно тежка
penicillin ± макролид -лактам ± макролид co-amoxiclav ± макролидцефалоспорин II-III ± макролид
levofloxacin, moxifloxacin**
Болница Тежка цефалоспорин ± макролидIII генерация цефалоспорин ± levofloxacin, moxifloxacin**
БолницаТежка и риск за P. aeruginosa
антипсевдомонасен цефалоспорин + ciprofloxacin***
Ацилуреидопеницилин с -лактамазен инхибитор + ciprofloxacin или карбапенем + ciprofloxacin
•Макролид – clarithromycin, azithromycin или roxithromycin; ** с най-висока активност спрямо S. pneumoniae от флуорохинолоните; •*** монотерапията често води до развитие на резистентност и затова се предпочита комбинация на -лактам с флуорохинолон. •Аминогликозидите са свързани с по-висока токсичност. Орални цефалоспорини не са за препоръчване поради не особено добра фармакокинетика.
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STOICHKOV SYNDROME
Everybody knows
how
to treat
himself
(great self-confidence) !
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Resistance of S. pneumoniae/ penicillin use
0
10
20
30
40
50
0 5 10 15 20 25 30
% of penicillin
resistance
Ton’s of penicilins pro year
Baquero, et al. JAC. 1991.
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Penicillin-nonsusceptible S. pneumoniae (2000–2001)
Pen
icil
lin
-no
n-s
usc
epti
ble
iso
late
s
23
52 50
36
4954
15
46
69
44
0
10
20
30
40
50
60
(%)
Penicillin MICs 0.12 mg/L.Bozdogan et al. Clin Microbiol Infect 2003;9:653–661.
Bulgar
ia
Czech
Rep
.
Latvi
a
Polan
dOve
rall
Croat
ia
Roman
iaSlo
vak
Rep.
Lithuan
ia
Hungary
Slove
nia
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PENICILLIN RESISTANCE
NCIPD, 2001
S. pneumoniae
22%
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RESISTANCE
European antibiotic resistance surveillance study project (EARSS, 1999):
Erythromycin resistance of S. pneumoniae in BG is:
• 16% (interview) and • 8 % (through EARSS project);
Emma Keuleyan et al. Antimicrobial agents, 2004; 24: 199-204
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RESISTANCE
NCIPD, 2001
Macrolide resistance of S. pneumoniae - 15% !
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Visible increase of penicillin - 1-4 and macrolide - resistant S. pneumoniae3-6
1. Spika JS, et al. J Infect Dis. 1991;163:1273-1278; 2. Jorgensen JH, et al. Antimicrob Agents Chemother. 1990;34:2075-2080; 3. Doern GV, et al. Antimicrob Agents Chemother. 2001;45:1721-1729; 4. Doern GV, Brown SD. J Infect. 2004;48:56-65; 5. Doern GV, et al. Antimicrob Agents Chemother. 1996;40:1208-1213; 6. Doern GV, et al. Emerg Infect Dis. 1999;5:757-765.
Penicillin-resistant
Macrolide-resistant
(MIC ≥ 2 mg/L)
1979-87 1988-89 1990-91 1994-95 1997-98 1999- 2000- 2002- 2000 2001 2003
0
10
15
5
25
30
35
20
%
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R на болнични S.pneumoniae, S.aureus към АБ (BulSTAR 2005)
28.6
23.4
13.6
0.6
17.5
5.0
0.7
8.0
14.5
18.4
10.4
17.8
8.9 7.8
OXA AMC CRO CEF IV ERY CIP LVX
S.pneumoniae (n=4945) S.aureus (n=1710)
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R на болнични гр(-) изолати (BulSTAR 2005)
84.4
20.3
11.3 10.76.9
0.0
12.9
1.4
25.9
5.5 3.0 3.1 3.2 0.0 1.7 0.0
48.5
2.9 4.3 5.9 4.20.0 0.0 0.0
AMP AMC CAZ CRO CIP IMP CEF IV LVX
K.pneumoniae (n=1441) H.influenzae (n=1186) M.catarrhalis (н=1147)
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Methicillin-resistant S.aureus 2002 - 2005
6.3%
8.6%
13.9%
10.5%
0
2
4
6
8
10
12
14
16
2002 (n=10 347) 2003 (n=11 682) 2004 (n=18 664) 2005 (n=19 742)
Screen agar (n = All isolates)
% R (of all isolates)
2595
1003
625
2073
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RESISTANCE2001
Haemophilus influenzae (pen)
33%
Gram stained sputum (AECB) Haemophilus influenzae
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P.aeruginosa 2002 - 2004
39.7 38.7
32.930.7
34.5
9.2 8.6
18.7
45.0
05
101520253035404550
2002 (n=5643) 2003 (n=6853) 2004 (n=8200)
Gentamicin Ciprofloxacin Imipenem (n=Total)
%R of Tested
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ONE OF THE MOST FREQUENT PROBLEMS IS:
COMORBIDITY, which needs more precise treatment options and it isn’t taken in consideration!
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RISK PATIENTS GROUPS FOR BACTERIAL RESISTANCE
frequent suffering
> 65 y. old.
antibiotic therapy during last 3 months
immunosuppressed
comorbidity
nursing homes residents
Wise R. A review of the mechanisms of action and resistance of antimicrobial agents. Can Respir J 1999; 6(SupplA):A20-2.
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The influence of good clinical evaluation on the treatment success of CAP?
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How often АB is inappropriate?
Kollef M. et al. Chest 1999;115:462–474
Inappropriate (%)
0
30
50
10
CAP
20
40
HAP HAP following CAP therapy
17
34
45
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Effect of inappropriate AB therapy in ICU
0
10
20
30
40
50
60
Inappropriateempirical therapy
appropriateempirical therapy
52
12
Deaths (%)
Kollef M. et al. Chest 1999;115:462–474
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QUORUM SENSING
What about the whisper among bacterias?
Maybe, that they where before and will be after us and we are only a surmountable obstacle on their way!
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after years...
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THE BETTER ALTERNATIVE