MANAGEMENT OF LOWER RTI IN BULGARIATHE PROBEMS

Kosta Kostov

Clinic of pulmonary diseasesMilitary Medical Academy, Sofia, BGkoro_55@mail.bg

Europe

& the

Balkan

countries RO

MC

BG

HRSL

BA

AL

SB&MN

TR

RU

UA

GR

BY

Antalya, 2007Antalya, 2007

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

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

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

BULGARIAN CAP GUIDELINES2007

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

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

Pneumococcal pneumoniaPneumococcal pneumonia

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

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)

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)

EMPIRICAL APPROACH

Too many prescriptions of:

BETALACTAM’S and CIPROFLOXACIN

Antalya, 2007Antalya, 2007

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.

STOICHKOV SYNDROME

Everybody knows

how

to treat

himself

(great self-confidence) !

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.

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

PENICILLIN RESISTANCE

NCIPD, 2001

S. pneumoniae

22%

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

RESISTANCE

NCIPD, 2001

Macrolide resistance of S. pneumoniae - 15% !

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

%

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)

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)

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

RESISTANCE2001

Haemophilus influenzae (pen)

33%

Gram stained sputum (AECB) Haemophilus influenzae

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

ONE OF THE MOST FREQUENT PROBLEMS IS:

COMORBIDITY, which needs more precise treatment options and it isn’t taken in consideration!

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.

The influence of good clinical evaluation on the treatment success of CAP?

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

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

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!

after years...

THE BETTER ALTERNATIVE

Thank you for theattention!

koro_55@mail.bgMobile: 0888231921