[Lower urinary tract infections. Epidemiology, etiology, physiopathology, diagnosis, development, treatment].
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Biomedical subjects
Publications and source records attributed to J Guibert.
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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.
Co-trimazine (sulphadiazine, 410 mg + trimethoprim, 90 mg) is a new drug combination developed especially for use in the treatment of urinary tract infections. In cross-over experiments in volunteers receiving daily doses of co-trimazine (2 X 500 mg and 1 X 1000 mg), co-trimoxazole (2X960 mg), or nitrofurantoin (3X50 mg), the degree of antibacterial activity of co-trimazine in the urine was at least as high as that of co-trimoxazole and much higher and more consistent than that of nitrofurantoin. In further cross-over experiments in volunteers receiving co-trimazine 2X1000 mg or co-trimoxazole 2X960 mg for four days no or only slight activity was found in the urine against a sulphonamide-resistant Group D streptococcus, but distinct synergistic activity between the components was found against four Escherichia coli strains sensitive to trimethoprim and sensitive or resistant to sulphonamides. Against three of the latter strains the degree of activity in the urine was higher after co-trimazine than after cotrimoxazole. The synergistic action of trimethoprim and sulphonamide in the urine appeared greater with the former than with the latter combination.
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The presence of antibody coated bacteria in the urinary sediment was correlated with the infection site in 151 patients. 86 patients were followed regularly and support sequential data. A positive test is noted in most of the chronic pyelonephritis cases in all the prostatitis cases and in some of the chronic infection on bladder disease. In recurrent cystitis the test is generally negative as in acute pyelonephritis seen within 24 hours.
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