INTERNATIONAL EPIDEMIOLOGICAL STUDY ON MICROBIOLOGY OF UNCOMPLICATED UTIs. PROSPECTIVE MULTICENTER,...
-
Upload
primo-arellanes -
Category
Documents
-
view
239 -
download
0
Transcript of INTERNATIONAL EPIDEMIOLOGICAL STUDY ON MICROBIOLOGY OF UNCOMPLICATED UTIs. PROSPECTIVE MULTICENTER,...
INTERNATIONAL EPIDEMIOLOGICAL STUDY ON
MICROBIOLOGY OF UNCOMPLICATED UTIs.
PROSPECTIVE MULTICENTER,
OBSERVATIONAL EPIDEMIOLOGICAL SURVEY
SURVEILLANCE STUDIESON THE
EPIDEMIOLOGY OF RESISTANCEBECOME INSTRUMENTAL
IN GUIDINGEMPIRIC THERAPY
OFUNCOMPLICATED UTIs
ARESC STUDY
September 2003 June 2006
ARESC STUDY END-POINTS
PRIMARY:
Prevalence and susceptibility of pathogens in uncomplicated lower, community acquired UTIs
SECONDARY:
Prevalence and susceptibility of pathogens in patients with recurrent UTIs and during pregnancy
Female patients aged between 18 and 65 years Pregnant women included
Symptoms of uncomplicated UTI
Positive culture defined as a sample with 104 cfu/ml in midstream urine
Recurrent uncomplicated UTI (defined as 3 episodes of UTI in the last year ) included
Informed consent
INCLUSION CRITERIA
ARESC STUDY
4264 patients enrolled
3018bacterial pathogens analyzed
AUSTRIA: 3
BRASIL: 6
FRANCE:10
GERMANY: 8
HUNGARY: 5
ITALY: 6
NETHERLANDS: 2
POLAND: 6
RUSSIA: 10
SPAIN: 9
SITES DISTRIBUTION
RUSSIA
BRASIL
SPAIN
GERMANY
ITALY
AUSTRIA
HUNGARY
FRANCE
THE NETHERLANDS
POLAND
10 COUNTRIES
65 CENTERS
Patient characteristics
50,80%
52,17%
33%
30,06%
16,20%
17,77%
0%
10%
20%
30%
40%
50%
60%
18-35y 36-55y 56-65y
Mean: 38.2 years Mean: 38,0 years
SPAIN
GLOBAL
Patient characteristics
94,80% 96,30%
5,20% 3,70%
0%
20%
40%
60%
80%
100%
Pregnant Not-pregnant
Mean: 38.2 years Mean: 38,0 years
SPAIN
GLOBAL
2,90% 4,20%
22,30% 24,00% 24,80% 25,70%
55,10%
50,10%
56,70%57,40%
77,10%75,00%
0%
10%
20%
30%
40%
50%
60%
70%
80%
Diabetes Constipation Menopause Contraceptivemethod
Children Sexualintercourse
Patient Characteristics
SPAINGLOBAL
Patient Symptoms
67,25%
75,35%
91,53% 92,72%90,24%
88,63%
94,53%91,83%
16,52%
28,76%
15,20% 17,88%
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
0-3 d onset Dysuria Urgency Frequency Hematuria Fever
SPAINGLOBAL
TYPES OF INFECTION
90%
10%
Recurrent UTI Non-recurrent UTI
86%
14%
SPAIN
GLOBAL
TYPES OF INFECTION
4%
96%
Single pathogen Mixed infections
1%
99%
SPAIN
GLOBAL
URINEANALYSIS
89%
11%
CFU = 10E4 CFU >10E4
99%
1%
SPAIN
GLOBAL
URINEANALYSIS
6%
94%
Midstream urine S. Cateter urine
0%
100%
SPAIN
GLOBAL
PATHOGENS TESTED
Country Strain N°
Spain 650
Brasil 506
France 488
Russia 416
Italy 329
Germany 317
Poland 119
Austria 91
Hungary 66
The Netherlands 36
Total 3018
AETIOLOGYof uncomplicated UTIs
E.coli 76.7%
3018 uropathogens
Other ENT: Klebsiella spp., Enterobacter spp., Citrobacter spp., H.alvei, M.morganii, Pantoea spp., Serratia spp., Salmonella spp.Other not-ENT: P.aeruginosa, B.cepacia
Other G+: Enterococcus spp., S.aureus, Staphylococcus coagulase -, Streptococcus spp.
E.coli 515 (79.23)%)K.pneumoniae 15 (2.31%)S.saprophyticus 29 (4.46%)P. mirabilis 28 (4.31%)Other ENT 12 (1.85%)Others 4 (0.62)Other G+ 47 (7.23%)
AETIOLOGYof uncomplicated UTIs
(Spain
E.coli 79.2%
650 uropathogens
Other ENT: Klebsiella spp., Enterobacter spp., Citrobacter spp., H.alvei, M.morganii, Pantoea spp., Serratia spp., Salmonella spp.Other not-ENT: P.aeruginosa, B.cepacia
Other G+: Enterococcus spp., S.aureus, Staphylococcus coagulase -, Streptococcus spp.
0
10
20
30
40
50
60
70
80
%
18-35 y (2158) 36-55 y (1402) 56-65 y (685)
E.coli S.saprophyticus P.mirabilis K.pneumoniae Other ENT * Others °
AETIOLOGYage groups
*Enterobacter spp., Citrobacter spp., Klebsiella spp., H.alvei, M.morganii, Pantoea spp., Serratia spp., Salmonella spp.°P.aeruginosa, B.cepacia, Enterococcus spp., S.aureus, Staphylococcus coagulase -, Streptococcus spp.
•
Country % N°
France 83.8 409
The Netherlands 80.6 29
Spain 79.2 515
Hungary 78.8 52
Germany 76.7 243
Poland 75.6 90
Brasil 73.9 374
Italy 72.6 239
Russia 72.6 302
Austria 68.1 62
Total 76.7 2315
E.coli INCIDENCE
0
10
20
30
40
50
60
70
80
90
RecurrentITU
Diabetes Pregnancy BactCharge >
10E4
Nitrites Hematuria
% incidence
NO
YES
Influence of patient’ characteristics on E. Coli incidence
On the other parameters as: Menopause, Sexual intercouse, Constipation, Kind of sample or Fever: No significant differences were observed
Mean76,7
Antibiotic
%
S I + R
Fosfomycin 98.2 1.8
Mecillinam 95.9 4.1
Nitrofurantoin 95.2 4.8
Ciprofloxacin 91.3 8.7
Amoxi/clav. 81.9 18.2
Nalidixic acid 81.4 18.6
Cefuroxime axetil 81.0 19.0
Co-trimoxazole 70.6 29.4
Ampicillin 45.1 54.9
2315 E.coli GLOBAL SUSCEPTIBILITY PATTERNS
AntibioticMIC (mg/L) %
Range MIC50 MIC90 S I R
Fosfomycin <1-512 2 8 97.3 1.5 1.2
Mecillinam <0.12->128 0.5 4 94.2 1.7 4.1
Nitrofurantoin <0.5-256 16 32 94.2 3.7 2.1
Amoxi/clav. 0.25/0.12- 128/64 8/4 16/8 77.7 18.6 3.7
Cefuroxime axetil 0.25->128 4 8 75.3 22.9 1.8
Ciprofloxacin <=0.015->16 <0.015 8 88.1 0.2 11.7
Nalidixic acid <0.12->128 4 >128 73.6 / 26.4
Co-trimoxazole <0.015/0.30->16/304 0.5/9.5 >16/304 66.2 / 33.8
Ampicillin 1->128 >128 >128 35.3 4.7 60.0
E.coli SUSCEPTIBILITY PATTERNS
(650) Spain(650) Spain
Antibiotic%
S I + R
Ciprofloxacin 94.4 5.6
Amoxi/clav. 90.7 9.3
Fosfomycin* 87.9 12.1
Nalidixic acid 82.2 17.7
Cefuroxime axetil 78.5 21.5
Co-trimoxazole 76.6 23.4
Nitrofurantoin 17.8 82.2
Ampicillin 0 100
107 K.pneumoniaeGLOBAL SUSCEPTIBILITY PATTERNS
* : presumptive breakpoint (S< 64 mg/L)
Antibiotic%
S I + R
Amoxi/clav. 94.2 5.8
Cefuroxime axetil 93.3 6.7
Ciprofloxacin 90.4 9.6
Fosfomycin * 86.4 13.6
Nalidixic acid 78.8 21.2
Ampicillin 67.3 32.7
Co-trimoxazole 62.5 37.5
Nitrofurantoin 0 100
104 P.mirabilisGLOBAL SUSCEPTIBILITY PATTERNS
* : presumptive breakpoint (S< 64 mg/L)
ARESC STUDY: CONCLUSIONS
• E.coli has been confirmed to represent the most common agent of uncomplicated UTIs
• AMPICILLIN and SXT most affected by resistance
• Agents used specifically in UTIs- FOSFOMYCIN- MECILLINAM- NITROFURANTOINexhibited low levels of R in all participating countries both in recurrent and not recurrent UTIs
• For FQ and other β-lactams local epidemiological data are mandatory for a correct empiric therapy (R rates >10-20%)
First line therapy of uncomplicated UTI with fosfomycin: CM advantages
• Appropriate spectrum
• Minimal resistance in the primary pathogen
• Resistant clones crippled
• Overcomes resistance to unrelated drugs
INITIAL EMPIRIC THERAPY:
FOSFOMYCIN TROMETAMOL: 1dNITROFURANTOIN: 5-7d
PIVMECILLINAM: 7d
Only after consideration of LOCAL Resistance rates:
Co-trimoxazole (3 d)Trimethoprim (5-7 d)
Fluoroquinolones (3 d)Naber et al., 2006
EUROPEAN ASSOCIATION OF UROLOGY2006 GUIDELINES
FOR TREATMENT OF UNCOMPLICATED UTIs
Objetivos de la guía
Pacientes diana: criterios de inclusión
• El paciente diana es toda mujer afecta de cistitis no complicada, definida como
aquella infección urinaria que ocurre en personas que tienen un tracto urinario
normal, sin alteraciones funcionales o anatómicas, sin historia reciente de
instrumentación (sondaje, uretrocistoscopia) y cuyos síntomas se presentan
confinados en la vejiga.
• Las pacientes diana presentan una edad comprendida entre los 16 años y sin
límite de edad máxima. Esta decisión está basada en la edad de inicio de las
relaciones sexuales entre los jóvenes españoles[i]. No obstante, también se
incluirán las pacientes de 14 y 15 años que sean sexualmente activas.
[i] Informe juventud en España 2004, capítulo 6, página 120.
• Escherichia coli sigue siendo el principal uropatógeno (70-80%) y pone de manifiesto un aumento paulatino y sostenido de su resistencia a algunos de los antibióticos de mayor uso terapéutico en la comunidad.
• Entre los criterios de elección de un determinado antibiótico para el tratamiento empírico de la infección urinaria no complicada es importante considerar dos aspectos:
– Que presente una baja prevalencia de resistencias bacterianas (< 20%)
– Que sea de fácil cumplimiento (pauta corta que asegure el mantenimiento de los niveles de asntibiótico durante 3 días)
• Estas recomendaciones se han priorizado en función de los siguientes criterios:
– Sensibilidades de los gérmenes más frecuentemente implicados
– Eficacia
– Coste y duración del tratamiento
RECOMENDACIONES FINALES
RECOMENDACIONES FINALES
Tratamiento de 1ª elección:
Fosfomicina trometamol en una única monodosis de 3 g
Tratamiento de 2ª elección:
Sulfametoxazol-Trimetoprim, 800/160 mg/12 horas durante 3 días (en aquellas áreas con resistencias a E. Coli inferior al 20%)
Norfloxacino, 400 mg/12 horas durante 3 días
Ciprofloxacino, 250 mg/12 horas durante 3 días
Amoxicilina-ácido clavulánico, 500/125 mg/8 horas durante 5 días
Cefixima, 400 mg/24 horas durante 3 días