INTERNATIONAL EPIDEMIOLOGICAL STUDY ON MICROBIOLOGY OF UNCOMPLICATED UTIs. PROSPECTIVE MULTICENTER, OBSERVATIONAL EPIDEMIOLOGICAL SURVEY

SURVEILLANCE STUDIES ON THE EPIDEMIOLOGY OF RESISTANCE BECOME INSTRUMENTAL IN GUIDING EMPIRIC THERAPY OF UNCOMPLICATED 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  10 4 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 3018 bacterial 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 Mean: 38.2 years Mean: 38,0 years SPAIN GLOBAL

Patient characteristics Mean: 38.2 years Mean: 38,0 years SPAIN GLOBAL

Patient Characteristics SPAIN GLOBAL

Patient Symptoms SPAIN GLOBAL

TYPES OF INFECTION SPAIN GLOBAL

TYPES OF INFECTION SPAIN GLOBAL

URINEANALYSIS SPAIN GLOBAL

URINEANALYSIS SPAIN GLOBAL

PATHOGENS TESTED CountryStrain N° Spain650 Brasil506 France488 Russia416 Italy329 Germany317 Poland119 Austria91 Hungary66 The Netherlands36 Total3018

AETIOLOGY of 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.

AETIOLOGY of 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.

AETIOLOGY age 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 The Netherlands Spain Hungary Germany Poland Brasil Italy Russia Austria Total E.coli INCIDENCE

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 Mean 76,7

Antibiotic % SI + R Fosfomycin Mecillinam Nitrofurantoin Ciprofloxacin Amoxi/clav Nalidixic acid Cefuroxime axetil Co-trimoxazole Ampicillin E.coli GLOBAL SUSCEPTIBILITY PATTERNS

Antibiotic MIC (mg/L)% RangeMIC 50 MIC 90 SIR Fosfomycin< Mecillinam Nitrofurantoin< Amoxi/clav.0.25/ /648/416/ Cefuroxime axetil0.25-> Ciprofloxacin 16< Nalidixic acid 1284> /26.4 Co-trimoxazole 16/3040.5/9.5>16/ /33.8 Ampicillin1->128> E.coli SUSCEPTIBILITY PATTERNS (650) Spain

Antibiotic % SI + R Ciprofloxacin Amoxi/clav Fosfomycin* Nalidixic acid Cefuroxime axetil Co-trimoxazole Nitrofurantoin Ampicillin K.pneumoniae GLOBAL SUSCEPTIBILITY PATTERNS * : presumptive breakpoint (S< 64 mg/L)

Antibiotic % SI + R Amoxi/clav Cefuroxime axetil Ciprofloxacin Fosfomycin * Nalidixic acid Ampicillin Co-trimoxazole Nitrofurantoin P.mirabilis GLOBAL SUSCEPTIBILITY PATTERNS * : presumptive breakpoint (S< 64 mg/L)

Antibiotic % SI + R Amoxi/clav.1000 Ciprofloxacin Nitrofurantoin Cefuroxime axetil Co-trimoxazole Ampicillin Fosfomycin * S.saprophyticus GLOBAL 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 - NITROFURANTOIN exhibited 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: 1d NITROFURANTOIN: 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 UROLOGY 2006 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] [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

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