[Diagnosis, treatment and follow-up of community-acquired bacterial infections of the urinary system of men and women (acute cystitis and acute pyelonephritis) and of the genital system of men (acute prostatitis): general remarks]. / Généralités.

Urinary tract infections are frequent. The aim of these guidelines is to improve the management of urionary tract infections. Increasing antibiotic prescriptions may increase bacterial drug resistance. Asymptomatic bacteriuria, bacterial count, pyuria are defined and the clinical value of the bacterial culture and urinary dipstick test are discussed. The good antibiotic use depends on bacteriological, pharmaceutical, patient characteristics and economic findings which are precised in these guidelines.

[Acute cystitis]. / Cystites aiguës.

The management of uncomplicated lower urinary tract infections (UTI) implicate to look for risk factors and complications. Bacterial or radiological exams are not recommanded and short course of antibiotic is effective for treating uncomplicated UTI. Complicated UTI needs clinical, bacteriological and radiological exams, longer treatments are recommanded. Recurrent UTI definition is precised in these guidelines.

Long-term efficacy of mupirocin in the prevention of infections with meticillin-resistant Staphylococcus aureus in a gastroenterology unit.

The long-term efficacy (55 months) of eradication of nasal carriage of meticillin-resistant Staphylococcus aureus (MRSA) by mupirocin was assessed for MRSA infections in a gastroenterology unit receiving patients for long hospital stays. In total, 2242 patients were included in the study; 92% had been hospitalized in another hospital before admission to the study department, 64% had chronic liver diseases (LD), 25% had miscellaneous medical conditions and 11% were admitted following gastroenterological surgery. Three consecutive periods were considered in the analysis. Nasal carriage at admission was similar in all three periods (10.9 vs 7.5 vs 8.6% in Periods 1, 2 and 3, respectively), while acquired nasal carriage decreased in the whole population (14.3 vs 16.2 vs 10.2% in Periods 1, 2 and 3, respectively, P=0.006) and in LD patients (15.8 vs 18.7 vs 11.9% in Periods 1, 2 and 3, respectively, P=0.018). The incidence of MRSA infections (N per total number of hospitalization-days) was 1.41 per 1000 in the year before initiation of eradication, 1.40 in Period 1, 0.74 in Period 2 and 0.59 in Period 3 (P=0.022). The incidence of MRSA infections among patients was 7.0% in Period 1, 3.7% in Period 2 and 3.1% in Period 3 in LD patients (P=0.0062). The corresponding figures were 5.5, 3.0 and 2.4% for the whole population (P=0.0024). The mortality caused by MRSA was 0.31, 0.19 and 0.13% (P=0.035) in Periods 1, 2 and 3, respectively. The numbers of resistant strains among those acquired during hospitalization were 12 in Period 1, four in Period 2 and six in Period 3. Long-term intranasal mupirocin treatment in MRSA carrier patients with long hospital stay is associated with a decrease in acquired carriage and MRSA infections, while resistance of the strains to mupirocin does not increase provided that colonized patients are only treated once.

Clarithromycin resistance of Helicobacter pylori has a major impact on the efficacy of the omeprazole-amoxicillin-clarithromycin therapy.

Clarithromycin resistance of Helicobacter pylori is relatively frequent in France and is assumed to be the main cause of failure of the proton pump inhibitor-amoxicillin-clarithromycin (PPI-AC) therapy, which is the first-line regimen in our country. We determined the respective effects of clarithromycin primary and secondary resistances on efficacy of the PPI-AC regimen and examined whether failures were associated with persistence of the same strain or with emergence of a new one. Hundred and twenty three H. pylori-infected patients were treated for seven days with omeprazole 20 mg b.d., amoxicillin 1 g b.d., and clarithromycin 500 mg b.d. Eradication was assessed by breath test in 102 patients. MICs of clarithromycin were determined by E-test. Strain genotyping was performed by random amplified polymorphic DNA. The pre-treatment and post-treatment prevalences of clarithromycin resistance were 18.7% (23/123) and 69.2% (9/13), respectively. The rates of eradication were 67.6% (69/102), 78.8% (67/85), and 11.8% (2/17) for all, susceptible and resistant strains, respectively. The post-treatment isolate was available for six patients with a susceptible pre-treatment isolate and a persistent infection; resistance emerged in two patients and was associated with persistence of the pre-treatment strain in one and with selection of a new strain in the other. In conclusion, in our hospital, failures of the PPI-AC therapy are related to both clarithromycin primary and secondary resistances but emergence of secondary resistance does not explain all failures in the initial clarithromycin-susceptible group. In that group a new strain can emerge after failure.

Co-detection of Helicobacter pylori and of its resistance to clarithromycin by PCR.

Our aim was to develop a rapid molecular test based on polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and making it possible to detect Helicobacter pylori directly from gastric biopsy samples, and to test its susceptibility to clarithromycin. A 629-bp fragment of the 23S rRNA gene of H. pylori was amplified by PCR and the mutations responsible for clarithromycin resistance were detected with Bsa1 and Bbs1 restriction endonucleases. Thirty-five gastric samples were tested in parallel by standard microbiologic methods (culture and clarithromycin susceptibility testing with E-test strips) and by PCR-RFLP. The 10 culture-negative samples were also PCR-negative. Sixteen out of the 25 culture-positive samples (64%) were PCR-positive. RFLP analysis could be done in 12 cases and the results were in agreement with those of the E-test: susceptibility in five cases, resistance in seven (six A2144G mutations and one A2143G mutation).

Genetic complexity of the hypervariable region 1 (HVR1) of hepatitis C virus (HCV): influence on the characteristics of the infection and responses to interferon alfa therapy in patients with chronic hepatitis C.

HCV exists within its host as pools of related genetic variants referred to as quasispecies. The hypervariable region 1 (HVR1) of the E2 envelope gene is subjected to strong selective pressure from neutralizing antibodies. The genetic complexity of this region is defined as the total number of genetic variants within the quasispecies population. The genetic complexity of the HVR1 region was examined in patients with chronic hepatitis C and its relationship with the epidemiology of HCV infection, and its influence on liver disease and the response to interferon treatment were determined in 114 patients with chronic hepatitis C. The genetic complexity of the HVR1 major variants was measured before treatment by using a polymerase chain reaction (PCR)-single-strand conformation polymorphism (SSCP) technique, and was compared with epidemiological, clinical, virological and histological features. The patients were treated with 3 megaunits of interferon (IFN) alfa for 3 to 6 months and the response to treatment was assessed at 3, 6 and 12 months. The HVR1 could be studied in 101 of the 114 patients (89%). Genetic complexity was significantly higher in patients infected through blood transfusion than intravenous drug use (mean complexity index: 5.7 +/- 2.3 vs. 4.7 +/- 1.5, respectively; P = 0.04). This relationship was independent of age and the estimated time since infection. No significant relationship was found with other parameters of infection or liver disease. In univariate analysis, the genetic complexity of HVR1 major variants did not affect the rates of ALT normalization at months 3 and 6 of IFN treatment. HVR1 genetic complexity was lower in patients with a sustained virological response than in non-responders (4.0 +/- 1.7 vs. 5.4 +/- 2.0, respectively; P = 0.07). In multivariate analysis of pretreatment parameters associated with a sustained virological response to treatment, three parameters appeared to be independent predictors of such a response: a low viral load (P < 0.04), a low anti-HCV core IgM titer (P = 0.03) and a low genetic complexity of HVR1 major variants (P < 0.04). In conclusion, the HVR1 of HCV has a quasispecies distribution in infected individuals. Its genetic complexity is significantly higher in transfusion recipients than in intravenous drug users, suggesting that the size of the initial inoculum affects the later emergence and development of viral quasispecies. The genetic complexity of HVR1, together with viral load and the anti-HCV IgM titer, are independent predictors of a sustained virological response to IFN alfa in patients with chronic hepatitis.

GB virus C (GBV-C) infection in patients with chronic hepatitis C. Influence on liver disease and on hepatitis virus behaviour: effect of interferon alfa therapy.

The aim of this study was to evaluate, in patients with chronic hepatitis C, 1) the prevalence and the epidemiological characteristics of GB virus C (GBV-C) infection, 2) the influence of GBV-C on hepatitis C virus (HCV) infection, 3) the pathogenicity of GBV-C in the absence of treatment and under interferon therapy, and 4) the effect of interferon alfa on GBV-C and HCV replications. One hundred fifteen patients with chronic hepatitis C were studied. Before treatment, they were tested for GBV-C RNA by PCR and GBV-C genotype was determined for positive samples. Pretreatment information was collected, including age, gender, source of HCV, estimated duration of HCV infection, alanine aminotransferase and gamma-glutamyl transpeptidase activities, cirrhosis and Knodell's score on liver biopsy, HCV genotype, HCV viral burden and anti-HCV core IgM antibodies. The genetic complexity of the hypervariable region 1 (HVR1) of HCV was studied by PCR-Single Strand Conformation Polymorphism. All patients were treated with 3 to 9 mega units of interferon alfa-2a three times per week for 3 to 6 months. The influence of GBV-C on the evolution of ALT and HCV replication during and after treatment was studied, and GBV-C and HCV RNA were monitored monthly by PCR during this period. Eighteen patients (16%) were GBV-C RNA-positive. Among 11 samples studied, GBV-C genotype 2a was present in 9 cases, 2b in one case and type 3 in one case. GBV-C RNA-positive patients were significantly younger than GBV-C RNA-negative ones (38.4 +/- 11.5 vs. 47.4 +/- 14.0, P = 0.012), a result independent of the route of transmission and the disease duration. No difference between GBV-C RNA-positive and -negative patients was found for other epidemiological parameters (e.g. gender, risk factor for parenteral viral infections, disease duration and HCV genotypes), or for the characteristics of HCV infection and related liver disease (e.g. HCV RNA level, genetic complexity of the HVR1, anti-HCV core IgM, alanine aminotransferase and gamma-glutamyl transpeptidase activities, cirrhosis and Knodell's score). GBV-C did not influence the rates of ALT normalization at months 3, 6 and 12 and of sustained hepatitis C virological response at month 12 of treatment follow-up. During treatment, GBV-C viremia became undetectable in 12 patients (67%) but relapse occurred after treatment withdrawal in all the nine patients with sufficient follow-up. In the remaining six patients (33%), GBV-C resisted interferon. Whatever the effect of interferon on GBV-C replication, the ALT levels correlated with the presence of HCV RNA. In conclusion, GBV-C infection is frequent in patients with chronic hepatitis C, who are mainly, but not exclusively, infected by GBV-C genotype 2a. GBV-C positive patients are significantly younger than GBV-C negative ones. GBV-C does not seem to affect HCV replication, liver disease and responses of HCV infection and liver disease to interferon therapy. GBV-C is sensitive to 3 mega units of interferon alfa administered three times per week in two-thirds of the patients, but relapse is constant with this dosage after treatment withdrawal.

What technique should be used for routine detection and quantification of HBV DNA in clinical samples?

Detection of hepatitis B virus (HBV) DNA in serum allows monitoring of HBV replication and assessing responses to antiviral treatment. HBV DNA quantification measures virus replication and can be used as a prognosis indicator of liver disease and an index of response to antiviral drugs. The aim of this study was to compare the performances of three HBV DNA detection and/or quantification techniques for assessing HBV replication. Three hundred unselected sera with a request for HBV DNA detection and quantification were tested with a molecular hybridisation technique without amplification (Digene Hybrid-Capture, Murex Diagnostics Ltd), a signal amplification assay based on branched DNA technology (Quantiplex HBV DNA, Chiron diagnostics), and an 'in-house' qualitative, non quantitative target amplification assay based on the polymerase chain reaction (PCR) with primers located in the S gene of the HBV genome. Hybrid-capture and branched DNA gave concordant results in 278 cases (93%). In the 128 samples positive by both assays, DNA titres in pg/ml were related significantly (r = 0.70, P < 0.0001). but branched DNA titres increased more rapidly than hybrid-capture titres when the amount of HBV DNA in the sample increased. Twenty-two sera (7%) were negative by hybrid-capture, but positive in branched DNA (detection rate gain: 15%). In these 22 patients, DNA titres were low, HBsAg was present in all instances and alanine aminotransferase activity was elevated in 18 patients (82%); HBeAg was present in seven patients (32%) and anti-HBe antibodies in 18 patients (82%); liver biopsy, undertaken in 18 patients, revealed chronic active hepatitis in all instances, associated with cirrhosis in eight cases. Qualitative, non-quantitative HBV DNA PCR was positive in 75 (50%) of the 150 hybrid-capture-negative, branched DNA-negative samples, including a significant proportion of patients without evidence of ongoing HBV-related liver disease. The results show that in general, the branched DNA assay detects HBV DNA in more patients than hybrid-capture and that this improved detection rate is relevant clinically and genome equivalents/ml are preferred to pg/ml to quantify HBV DNA in clinical specimens and finally qualitative, non-quantitative polymerase chain reaction can detect HBV DNA in patients without evidence of active HBV-related liver disease. This study emphasizes the need for more sensitive, university standardised quantitative HBV DNA assays and for the definition of clinically relevant cutoffs with these assays.

Acute gastroduodenal lesions related to severe sepsis.

To determine the incidence of acute gastroduodenal lesions during severe sepsis, prospective endoscopies were performed in two groups of critically ill patients. The criteria of selection ruled out the incidence of other factors, such as shock, acute renal or respiratory failure. Evaluation of sepsis by clinical and bacteriologic criteria and endoscopic examination were performed in a double blind study. In the group of 14 patients with sepsis, 19 fibroscopies showed abnormalities of mucosa in all of them. In the group of 16 patients with sepsis, 23 fibroscopies showed either superficial lesions or normal mucosa. The difference between the incidence and the severity of acute lesions in the two groups studied was highly significative, p less than 0.001. Besides, gastroduodenal lesions became worse when sepsis prolonged, while they improved dramatically when focal infection and septicemia were eradicated. These data strongly suggest that severe sepsis per se can provoke acute digestive damage.