[Recurrent epididymitis, associated with Behçet disease, in an indigenous patient in France].
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Biomedical subjects
Publications and source records attributed to J Guibert.
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OBJECTIVES: A multicentric double-blind double-placebo randomized trial was conducted to compare the effectiveness and safety of ciprofloxacin versus pefloxacin given in a single oral dose in female out-patients with acute cystitis. METHODS: A series of 561 female patients (age range 18-65 years) with signs of uncomplicated community acquired acute cystitis were randomly assigned to parallel groups given a single oral dose of ciprofloxacin (500 mg + placebo) or pefloxacin (800 mg + placebo). Clinical and bacteriological effectiveness was evaluated 12 +/- 2 days after the treatment day. RESULTS: The clinical outcome was equivalent for the two groups (92 vs 88.9% clinical cure for ciprofloxacin and pefloxacin respectively). Mean time to clinical resolution was about 40 hours in both groups. Urine sterilization was comparable in the two groups (80.8 and 81.1% respectively). Undesirable side effects (mostly digestive tract disorders and neurosensorial complaints) were reported in 16.1% of the patients taking ciprofloxacin and 18.1% of those taking pefloxacin (NS). Single-dose treatment was well accepted by 82.3 and 84.8% of the women respectively. CONCLUSION: These findings demonstrate that ciprofloxacin and pefloxacin are equally effective and equally well tolerated as single-dose oral curative therapy for acute cystitis in women.
OBJECTIVES: The aim of this randomized double-blind trial was to compare two 400 mg pefloxacin regimens either once-a-week or once-a-month applied for 48 weeks for the prophylaxis of recurrent urinary tract infection in women. METHODS: The main outcome measures were symptomatic and bacteriological reinfections during the period of prophylaxis and rates of reinfections during the three months of surveillance following the end of prophylaxis. 361 women of 18 to 51 years of age suffering from recurrent lower urinary tract infection were randomly allocated to receive pefloxacin 400 mg once-a-week (group A: n = 185) or 400 mg once-a-month (groupe B: n = 176) for 48 weeks. RESULTS: Seventeen of the 185 patients in group A (9.1%) and 52/176 patients in group B (29.5%) experienced at least one reinfection during the period of prophylaxis (p < 0.0001). The rates of reinfection during the three months of surveillance following the end of the treatment were not significantly different between the two groups with 14/101 (13.8%) patients with at least a reinfection in group A and 8/75 patients (10.6%) in group B (p = 0.51). In group A, 49/174 (28.1%) patients reported at least an adverse event compared with 33/169 (19.5%) patients in group B (p = 0.06). CONCLUSIONS: Once-a-week treatment with 400 mg of pefloxacin can be considered as a new effective and well tolerated approach for the prophylaxis of recurrent urinary tract infection in women and does not entail excessive emergence of pefloxacin resistant bacteria, even after 48 weeks of treatment.
Antibacterial activity of ciprofloxacin was studied in the urine after a single 500 mg and 750 mg oral dose in ten healthy female volunteers. Urine was collected, after each single oral dose, during seven time periods: 0-3 h, 3-6 h, 6-12 h, 12-24 h, 24-48 h, 48-72 h, 72-96 h. Ciprofloxacin concentrations were assayed by microbiological method. Urine antibacterial activity was determined for five bacterial strains isolated in urine: 2 E. coli strains, one sensitive and the other resistant to nalidixic acid (Nal-A), 1 Klebsiella pneumoniae resistant to nalidixic acid (Nal-B), 1 Staphylococcus saprophyticus and 1 Enterococcus faecalis. MICs of ciprofloxacin against these strains were respectively 0.003, 0.06, 0.25, 0.06 and 0.5 micrograms/ml. Ciprofloxacin mean concentrations in the seven urine samples were 292.5 +/- 55.8, 81.1 +/- 16.9, 43.7 +/- 11.6, 11.5 +/- 1.9, 1.3 +/- 0.2, 0.3 +/- 0.05 et 0.1 +/- 0.05 micrograms/ml after a single 500 mg oral dose and 215.1 +/- 68.1, 56.1 +/- 17.8, 43 +/- 8.8, 14.4 +/- 5.5, 1.4 +/- 0.2, 0.4 +/- 0.1 and 0.2 +/- 0.05 micrograms/ml after a single 750 mg oral dose. Urine bacteriostatic activity was not very different after a 500 mg dose and a 750 mg dose. Against enterobacteriacae, after a 500 mg dose it was > or = 16 the first day; it was > or = 512 for the Nal-S E. coli. It was > or = 64 the first day, and remained between 2 and 32 the second day for the Nal-R strains (E. coli and Klebsiella).(ABSTRACT TRUNCATED AT 250 WORDS)
Cytobacteriological examination of urine is indispensable in patients with acute or chronic pyelonephritis. Direct examination through the microscope is fundamental in acute pyelonephritis where immediate antibiotic therapy is mandatory. A significant bacteriuria points to an obstacle to urine flow. Escherichia coli is the most common pathogen in acute and chronic pyelonephritis. Isolating a Proteux strain suggests that lithiasis is present. Pseudomonas aeruginosa always has a nosocomial origin and is often responsible for chronic asymptomatic pyelonephritis. Staphylococci and enterococci may produce pyelonephritis, notably when it is associated with urinary stones. Since hospital- or community-acquired strains of E. Coli are strongly resistant to aminopenicillins and cotrimoxazole, these antibacterials must not be used as first-line treatment of pyelonephritis.
This multicentre, open, randomized trial, involving 482 patients and conducted by private practitioners, compared the effectiveness and safety of a single 800 mg dose of pefloxacin and of a 10 days' course of norfloxacin 400 mg bid. in the treatment of uncomplicated acute cystitis in women aged over 50 years. Clinical effectiveness was evaluated on days 17-19 and 28-32 respectively, and bacteriological effectiveness on days 15-17 and 26-28 respectively. The median time taken for the symptoms to disappear was 2 days with pefloxacin and 3 days with norfloxacin (P < 0.001). Irrespective of the nature of cystitis and the patients' age, no significant difference could be found in eradication of the pathogens. Undesirable side-effects were recorded in 7.8 percent of patients under pefloxacin and in 8.8 percent of those under norfloxacin (P = 0.68); gastrointestinal disorders were predominant. The acceptability of treatment, as judged by the patients themselves, was regarded as excellent by 55 percent of women treated with single dose pefloxacin and by 37.6 percent of those treated with norfloxacin (P = 0.001).
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Data were collected from 14 French centres which participated in a randomized study to compare the safety and efficacy of 400 mg lomefloxacin taken orally once daily by 62 patients with 160/800 mg trimethoprim/sulphamethoxazole (TMP/SMX) taken orally twice daily by 64 patients with uncomplicated urinary tract infections. Most patients were infected with Escherichia coli at baseline (72.4% in the lomefloxacin group and 69.0% in the TMP/SMX group) and all patients were treated for 5 days. At 5-9 days post-treatment, lomefloxacin had eradicated the causative organism of infection in 100% of evaluable patients treated with lomefloxacin compared with 86.7% of those treated with TMP/SMX. At 4-6 weeks post-treatment, there were no marked differences in eradication rates between the two treatment groups: 83.3% and 80.0% for the lomefloxacin and TMP/SMX groups, respectively. Clinical cure rates showed no marked differences between treatment groups at 5-9 days or at 4-6 weeks post-treatment. At 5-9 days post-treatment, lomefloxacin achieved a clinical cure rate of 78.6% compared with 86.7% for TMP/SMX evaluable patients. At 4-6 weeks post-treatment, the clinical cure rates were 66.7% and 86.7% for the evaluable lomefloxacin- and TMP/SMX-treated patients, respectively. Both treatment regimens were well tolerated with a low incidence of adverse events. In conclusion, once-daily oral dosing with lomefloxacin is a safe and efficacious alternative to twice-daily dosing with TMP/SMX in the treatment of uncomplicated urinary tract infections.
The term pyelonephritis, which denotes infection of the renal pelvis and of the renal tissue, covers a spectrum of entities, the gravity and hence treatment of which depend upon the organism, its sensitivity to antibiotics, the presence or absence of urinary tract obstruction, and the host's background. The common form affects young females, is due to uropathogenic but multisensitive strains of Escherichia coli, and is easily treated by a 10- to 20-day course of antibiotic(s). In males, children and immunocompromised patients, renal and urinary tract imaging is necessary to determine the cause of the infection, the severity of the lesions and thus to guide the duration of treatment, which comprises antibiotic combinations for several weeks. Pyelonephritis during pregnancy may be serious, and treatment is restricted to certain antibiotics. Aminoglycosides, amino- or carboxypenicillins (alone or associated with clavulanic acid), ureidopenicillins (e.g. mezlocillin, piperacillin), fluoroquinolones (e.g. ciprofloxacin, ofloxacin, pefloxacin), cephalosporins, monobactams (e.g. aztreonam), carbapenems (e.g. imipenem) and the combination of trimethoprim plus a sulphonamide [e.g. cotrimoxazole (trimethoprim/sulfamethoxazole)] offer a wide choice of bactericidal agents which may be used for the treatment of pyelonephritis. However, the selection among them also depends on availability, antimicrobial spectrum, tolerance and cost.
Two associated resistance mechanisms were found in a nalidixic acid-susceptible (4 micrograms/ml) but fluoroquinolone-resistant (8 to 16 micrograms/ml) strain of Escherichia coli Q2 selected under norfloxacin therapy. As compared with the susceptible E. coli Q1 isolated before treatment, changes in outer membrane proteins and lipopolysaccharides in Q2 were associated with a 1.5- to 3-fold decrease in the uptake of fluoroquinolones but not nalidixic acid. A 50% inhibition of DNA synthesis in toluene-permeabilized cells of the resistant strain E. coli Q2 required up to 500-fold increased quantities of fluoroquinolones, whereas such inhibition was obtained in both E. coli Q1 and Q2 with similar amounts of nalidixic acid. Selection from E. coli Q1 on norfloxacin of one-step resistant mutants resembling E. coli Q2 was unsuccessful. From these results we infer that a decrease in outer membrane permeability, associated with a peculiar alteration of the DNA gyrase, was responsible for the unusual quinolone resistance phenotype of E. coli Q2.
Bacteriological examination of urine is sufficient to assert the presence of a urinary tract infection (UTI). Specimens must be collected under strictly aseptic conditions. The midstream jet method is the best, but when it is not feasible bladder puncture, sterile pouches or catheterization may be used. The urine obtained must be correctly preserved and transported. In the practitioner's office, UTI can be detected by reagent strips or agar-coated plates. In the laboratory, direct examination is used to count leucocytes and characterize Gram-positive and Gram-negative bacteria. Bacteriuria at 10(5)/ml is significant of infection. The micro-organisms most frequently responsible for UTI are Enterobacteriaceae (mostly E. coli), Proteus mirabilis, Klebsiella spp. and staphylococci (Staph. aureus, Staph. saprophyticus, Staph. epidermidis). In most cases disc sensitivity tests are indispensable, but bacteriological examination of urine is not always needed in women with uncomplicated lower urinary tract infection.
The pharmacokinetics of sodium fusidate were studied in eight healthy volunteers (five males and three females) aged 21 to 33 years (29.1 +/- 1.5), weight 46 to 79 kg (61.6 +/- 4.0 kg). First, the subjects were given 500 mg of sodium fusidate by infusion over two hours; secondly, one month later, the volunteers were given 500 mg of fusidate by infusion every eight hours for three days; thirdly, two 250 mg tablets of a new film coated formulation were administered as a single dose. Plasma concentrations of fusidate were measured by HPLC. Peak plasma concentrations reached at the end of the first and the last infusions were 52 +/- 5 mg/l and 123 +/- 12 mg/l respectively. The following mean pharmacokinetic parameters were obtained after single intravenous administration: elimination half-life 10 +/- 1 h, total clearance 22 +/- 2 ml/min and volume of distribution 0.30 +/- 0.04 l/kg. After repeated administration the half-life and the volume of distribution remained unchanged whereas total clearance was halved (11 +/- 1 ml/min). This leads to an experimental accumulation ratio (3.6 +/- 0.2) higher than the theoretical one (1.8 +/- 0.1; P less than 0.01). Consequently, mean trough and peak steady state plasma concentrations (81 +/- 9 and 123 +/- 12 mg/l respectively) are higher than those expected from the single dose kinetics (33 +/- 4 and 76 +/- 7 mg/l respectively). This dose regimen leads to concentrations well above the MIC for most sensitive strains.(ABSTRACT TRUNCATED AT 250 WORDS)
Thirty-one patients with initial, recurrent or chronic prostatitis mainly caused by Enterobacteriaceae were treated with pefloxacin 400 mg bd for three to 105 days (median, 28 days). The clinical and bacteriological results four weeks after the end of the treatment, were: 23 patients (74%) cured, 21 without reinfection and two with reinfection, failure in two and relapse in six patients. Side-effects, which were definitely related to pefloxacin, occurred in seven patients (22.5%) and were of a photosensitization-, muscular- and neuropsychic-type. A high eosinophil count was observed in another patient. In one patient, treatment was withdrawn because of side-effects.
Urinary tract infection is the most common of nosocomial infections, as demonstrated by numerous prospective surveys, especially the American NNIS. 2.5 p. 100 of hospitalized patients are likely to acquire a nosocomial urinary tract infection, usually directly due to indwelling urinary catheters. The prognosis is very good in most cases, but relapsing of persistent infections are extremely frequent and may raise very difficult therapeutic problems, as with chronic prostatitis. Such infections can be prevented, at least in 30 to 40 p. 100 of the cases, by applying simple and well-defined guidelines. However, infection remains difficult to control in hospitals since a precise management of its incidence and a sustained teaching programme are mandatory.
Antibacterial activity of pefloxacin was studied in the urine after a single 800 mg oral dose in ten healthy female volunteers. Urine was collected in 9 periods: 0-6 h, 6-12 h, 12-24 h, 24-28 h, 48-72 h, 72-96 h, 96-120 h, 120-144 h, 144-168 h. Pefloxacin concentrations were assayed in all samples by a microbiological method and by HPLC. Urine antibacterial activity was determined towards five bacterial strains isolated in urine: 2 E. Coli strains, one sensitive and the other resistant to nalidixic acid (Nal-A), 1 Klebsiella pneumoniae resistant to nalidixic acid (Nal-B), 1 Staphylococcus saprophyticus and 1 Streptococcus faecalis; MIC's of pefloxacin against these strains were respectively 0.015, 0.25, 1, 0.50 and 2 micrograms/ml. Pefloxacin mean concentrations as determined by the microbiological method were 91.8 +/- 11.9, 71.7 +/- 7, 44.5 +/- 4.3, 24.4 +/- 4 and 5.4 +/- 0.8 micrograms/ml in the five first urine samples; low levels were present in the urine until the 7th day in 8 volunteers. HPLC results completed the already known data concerning pefloxacin elimination and metabolism; unchanged pefloxacin was excreted at the highest concentration during the 6 first hours; then demethylpefloxacin was eliminated at higher levels than pefloxacin with a ratio of 2/1 after the 24th hour. These two compounds were detectable in the urine during 5 to 7 days; oxodemethylpefloxacin and N-oxyde-pefloxacin were present in lower amounts and during a shorter period.(ABSTRACT TRUNCATED AT 250 WORDS)
Antibacterial activity of lomefloxacin was studied in the urine after single dose of 400 mg in ten healthy female volunteers. Urine was collected in 7 periods: 0-3 h, 3-6 h, 6-12 h, 12-24 h, 24-48 h, 48-72 h, 72-96 h. Lomefloxacin concentration were assayed in all samples by microbiological method. Urine antibacterial activity was determined towards five strains isolated in urine: 2 E. Coli strains one sensitive and the other resistant to nalidixic acid (Nal-A), 1 Klebsiella pneumoniae resistant to nalidixic acid (Nal-B), 1 Staphylococcus saprophyticus and 1 Streptococcus faecalis. MIC's of lomefloxacin against these strains were respectively 0.06, 0.50, 0.50, 0.25 and 4 micrograms/ml. Lomefloxacin mean concentrations were 208.5 +/- 44.2, 104.3 +/- 15.2, 100.5 +/- 17.9, 36.8 +/- 8.2, 9.6 +/- 2.2 micrograms/ml in the five first urine samples. Low levels were present in urine the 4th day. Mean urine elimination percentage was 62.2 +/- 4.2% for the four days, with extreme values from 91.2 to 41.8%. Urine bacteriostatic activity against enterobacteriacae was greater than or equal to 32 the first day reaching 8,192 for the Nal-S E. Coli, it was greater than or equal to 4 the second day. Against staphylococcus it was greater than or equal to 64 the first day, greater than or equal to 16 the second day. Against enterococcus it was greater than or equal to 4 the first day. Against the strains implicated in UTI a bacteriostatic activity was present during 2 days in all subjects.
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New quinolones are very potent compounds against Gram-negative bacteria, including Pseudomonas, and staphylococci. They are particularly interesting because of their oral availability and their pharmacokinetic properties. When combined with other common antibiotics they appear to have mostly indifferent effects in vitro. Clinical results have shown their efficacy when used alone for the treatment of osteomyelitis, complicated urinary tract infections and prostatitis. Nevertheless, in 6% of cases resistant strains were selected (Klebsiella, Enterobacter, Serratia, P. aeruginosa and staphylococci). The use of combinations of quinolones with other antibiotics was successful in the treatment of osteomyelitis and severe nosocomial infections including bacteraemia, and seems to prevent emergence of resistant strains.