Leiomyosarcoma of spermatic cord.

A case of leiomyosarcoma of the spermatic cord is presented, bringing the total number of reported cases to 39. A review of diagnostic and therapeutic approaches along with our experiences stress the need for a uniform treatment schedule.

New 4-quinolones in the treatment of urinary tract infections.

The new fluorinated quinolones norfloxacin, ciprofloxacin and pefloxacin were evaluated in urinary infections. Bacteriological cure rates in both uncomplicated and complicated urinary tract infections ranged from 85% to 99%. Clinical cure rates were often lower due to the underlying conditions in the urinary tract. Patients with neurological bladder disease were cured in a relatively high percentage of their Pseudomonas infection after three months treatment with norfloxacin. Pharmacokinetics of ciprofloxacin in prostatic tissue and fluid will probably offer an advance in the treatment of chronic urinary infections due to an infectious prostatic focus. Definitely drug related side effects (of gastro-intestinal, neurological or allergic nature) were mild in most cases. The new 4-quinolones should be followed with interest concerning their activity in urological infections in general as well as specifically. The minor influence on the natural human flora and the possibility to decrease plasmid-mediated resistance are of major importance.

Fosfomycin trometamol in a single dose versus norfloxacin for seven days in the treatment of uncomplicated urinary infections in general practice.

The efficacy and tolerability of fosfomycin trometamol in a single dose of 3 g was compared with norfloxacin 400 mg b.i.d. for seven days in the treatment of adult female patients with uncomplicated urinary infections. 158 female patients with a mean age of 30 years who presented symptoms of dysuria and frequency with documented pyuria and bacteriuria on urinalysis (greater than or equal to 10(5) cfu/ml of urine) were initially included in the study. The total number of clinically and bacteriologically evaluable patients was 111, of which 61 received fosfomycin trometamol and 50 norfloxacin. One to two days after the double blind medication schedule for seven days, 55 of 60 patients (92%) in the fosfomycin trometamol group and 48 of 50 patients (96%) in the norfloxacin group were clinically cured. 37 patients without significant bacteriuria showed a clinical cure rate of over 90% in both therapy groups. Two to three days after the single dose treatment with fosfomycin trometamol the initial infecting pathogen was eradicated in 60 of the 61 patients (98%). One to two days after a seven day treatment with norfloxacin 48 of 50 patients (96%) showed an eradication of the initial infecting pathogen. Six weeks after the start of therapy 39/60 patients (65%) and 32/49 (65%) in the fosfomycin trometamol and norfloxacin groups respectively, remained free from urinary infection. The reinfection rate in both treatment groups was approximately 25%. The relapse rate in the post treatment evaluation period of four weeks was relatively low in both therapy groups, 5/49 patients (10%) in the norfloxacin group and 3/55 patients (6%) in the fosfomycin trometamol group, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Norfloxacin treatment in complicated urinary tract infection.

Twenty-four patients with complicated urinary tract infections were treated with norfloxacin for three months. Group I (n = 12), received 400 mg b.i.d. during three months and Group II (n = 12) received 400 mg b.i.d. during one month, followed by 400 mg as a single dose for two months. Most of the infections (67%), were due to Pseudomonas spp. A bacteriological cure rate of 75% (9/12) and 92% (11/12) in groups I and II, respectively, was achieved after three months therapy. One month after cessation of therapy patients were free of their initial infection in 75% (9/12) and 83% (10/12), respectively. Clinical cure was achieved in 75% of the patients in both groups. This remained the case in group I after cessation of treatment. In group II, 50% remained free of symptoms one month post-therapy. Both clinical and laboratory adverse reactions were minor and none of the patients discontinued treatment due to side effects. Norfloxacin therapy was effective in the long term treatment of chronic recurrent infections in patients with severe urological conditions. Prevention of relapse or reinfection from the primary endogenous faecal reservoirs (Enterobacteriaceae), was probably due to the high effect of norfloxacin against these organisms. The relatively good effect on pseudomonas infection in this group of patients, was probably due to a high concentration of norfloxacin in the urine.

Comparative human bioavailability study of macrocrystalline nitrofurantoin and two prolonged-action hydroxymethylnitrofurantoin preparations.

This single-blind crossover study compared the human bioavailability of macrocrystalline nitrofurantoin (Furadantine MC) and two prolonged-action hydroxymethylnitrofurantoin formulations (Urfadyn PL, bid, and Uridurine, tid), based on plasma nitrofurantoin concentrations and urinary nitrofurantoin excretion. The drugs were administered to 16 healthy females for a single day according to the recommended daily dosages. For comparison, Furadantine MC was administered both at the qid dosage recommended by the manufacturer and at tid dosage. Pharmacokinetic parameters determined were maximum plasma concentration after first dose, minimum plasma concentration after first dose, area under the plasma concentration-time curve (AUC), cumulative renal excretion over 30 hours (ARE), overall renal clearance, total body clearance, and bioavailability relative to Furadantine MC qid, based on plasma AUC (F) and ARE (Fren). F for Furadantine MC 100 mg tid was 108 +/- 25 percent (mean +/- SD); for Uridurine 100 mg tid and Urfadyn PL 100 mg bid, F equalled 86 +/- 33 percent and 53 +/- 20 percent (p less than 0.05), respectively. A similar relationship was observed between Fren for Furadantine MC 100 mg qid and the respective Fren of Furadantine MC 100 mg tid, Uridurine 100 mg tid, and Urfadyn PL 100 mg bid. No significant difference was found between the respective F and Fren of each of the drugs studied. Although bioavailability was comparable for Furadantine MC tid and qid, the single-day design of these studies precludes inferring that these dosage schedules are therapeutically equivalent. However, the significantly lower relative bioavailabilities for the prolonged-action hydroxymethylnitrofurantoin formulations suggest that Urfadyn PL 100 mg bid and Uridurine 100 mg tid are not pharmacokinetically equivalent to Furadantine MC.

Efficacy and safety of pefloxacin in the treatment of patients with complicated urinary tract infections.

One hundred and four patients with complicated urinary tract infections (prolonged severe chronic infections or with complicated postoperative conditions) were treated for ten days with pefloxacin 400 mg bid. Bacteriological eradication of the initial pathogen was achieved in 98% of the patients. After six weeks 93% of the patients were still free of the initial infecting microorganism. Clinical improvement was achieved in 77% of the patients five to seven days after cessation of treatment. The side-effects which were definitely related to pefloxacin occurred in 9% of patients and were mostly of a gastro-intestinal, a neurological, or an allergic nature. No significant biochemical or haematological adverse reactions occurred.

Record-linked audit of drug utilization data in a hospital: antimicrobial use on a urology ward.

Antimicrobial drug utilization patterns were studied on a urology ward with a view to establishing base-line data and subsequently determining drug usage data during the implementation of antimicrobial prescribing guidelines. Methods of data collection, storage and interpretation are described. The results of therapeutic audit of the use of antimicrobial agents over a period of time during which discussion, constitution and acceptance of guidelines took place, are described. The effectiveness of a multidisciplinary approach in rationalizing drug prescribing and the effects of intensive monitoring on prescribing patterns are illustrated.

Penetration of rufloxacin into human prostatic tissue and fluid.

The penetration of rufloxacin into prostatic tissue and prostatic fluid was investigated in 16 patients undergoing elective transurethral prostate resection. Rufloxacin 400 mg was given orally approximately 16 h before surgery with a further dose of 200 mg approximately 5 h before surgery. Sampling was inadequate in three patients. One patient reported transient flushing and headache after the first dose of rufloxacin and was hence withdrawn from the study. In the remaining 12 evaluable patients, the mean ratios of rufloxacin concentrations (determined by HPLC) in prostatic tissue and fluid to the plasma concentration were 1.9 and 1.5, respectively. There were no significant differences between the tissue penetration ratios in different parts of the prostate. The levels of rufloxacin found in prostate tissue and fluid, in this study, exceeded the MICs for most micro-organisms causing chronic bacterial prostatitis.

Ciprofloxacin distribution in prostatic tissue and fluid following oral administration.

The penetration of ciprofloxacin into prostatic tissue was studied following oral administration of 500 mg either once or repeatedly in 12-hourly intervals. Following single administration ciprofloxacin was rapidly absorbed from the gastrointestinal tract peaking 1-2 h after administration. Elimination from serum was slow, the half life being 4.3 h. No significant rise in serum concentrations was noticed following repeated administration. Ciprofloxacin was concentrated in the prostatic tissue, levels being on average twice as high as the corresponding serum concentrations. The ratios between prostate and serum levels following single and repeated administration were 227 and 214%, respectively. Intraindividual analysis of prostate concentrations in different areas of the prostatic gland revealed a homogeneous distribution within the prostate. Penetration of ciprofloxacin into prostatic fluid was studied in 11 patients 2-4.5 h after administration. At these points ratios between prostatic fluid and serum ranged between 1.5 and 450%.

Imipenem as monotherapy in the treatment of intensive care patients with severe infections.

In an open study, 24 intensive care patients were treated with imipenem/cilastatin as monotherapy for serious bacterial infections. Twenty-one patients were treated for bronchopulmonary infection, two patients for septicaemia, and one patient for an empyema. Initially all strains were susceptible to imipenem. Gram-negative bacilli accounted for 80% of these isolates. The most frequently isolated species were Proteus mirabilis, Escherichia coli and Pseudomonas aeruginosa. All 24 patients were considered clinically cured. Sixteen of these patients (67%) were both clinically and microbiologically cured. In eight of the 24 patients (33%), the strains isolated initially persisted. In eight of the 24 patients (33%), colonization of the respiratory tract developed. Two of the five Ps. aeruginosa isolates developed resistance during therapy but in none of these patients was therapy considered to have failed. In 12 patients (50%), transient elevations in hepatic function tests were observed and these were probably drug-related. The present study supports the view that imipenem/cilastatin may be useful as monotherapy in the treatment of severe infections in intensive care patients.

Effects of norfloxacin on the faecal flora in patients with complicated urinary tract infections.

The effects on the long-term use of norfloxacin, a fluorinated 4-quinolone, on the intestinal flora (both aerobic and anaerobic), were evaluated in patients suffering from recurrent complicated urinary tract infections. Eight patients received norfloxacin 400 mg b.i.d. for three months, and 11 patients received 400 mg b.i.d. for one month, and then 400 mg as an evening dose for two months. The concentration of Enterobacteriaceae, staphylococci, Streptococcus faecalis, and yeasts in stool specimens, together with the norfloxacin concentration were measured every month. The beta-aspartyl-glycine test was carried out at the same time. No urinary tract infections, either of exogenous (Pseudomonas spp.) or endogenous origin could be diagnosed during norfloxacin therapy. At both dosages of norfloxacin the faecal samples were free of Enterobacteriaceae due to low minimal bactericidal concentrations and high faecal drug concentrations. The suppressive effect was selective in that the anaerobic flora was left intact. A suppression of the aerobic intestinal flora could lead to an important reduction of recurrent infections of the urinary tract in these patients.

The defined daily dose per 100 bed-days as a unit of comparison and a parameter for studying antimicrobial drug use in a university hospital. A retrospective study of the effects of guidelines and audit on antimicrobial drug use.

Growing awareness of problems arising from over-use of antimicrobial agents has led to attempts to develop policies or guidelines for rational treatment. To follow the effects of guidelines, the percentage of patients receiving anti-microbial drug therapy, acquired from patient records, has been a frequently used parameter. In this paper the Defined Daily Dose (DDD) per 100 bed-days has been used instead. This parameter can be calculated by converting the number of units of antimicrobials, delivered to individual wards, to defined daily doses per bed-day. This parameter determines the probability of treating a patient with a particular drug, based on pooled data. The DDD per 100 bed-days has been used to follow changes in prescribing habits arising from the acceptance of and adherence to guidelines over a period of 5 years in a University Hospital.

An open multicentre study on the efficacy and safety of rufloxacin in patients with chronic bacterial prostatitis.

In an open study, 27 patients with chronic bacterial prostatitis were treated for four weeks with rufloxacin. They received 400 mg on the first day, and then 200 mg once daily. The patients were studied for up to one month after completion of therapy. One patient was lost to follow-up, but was included in the safety analysis. One patient did not meet all the inclusion criteria (WBC less than 10/HPF in the prostatic fluid sample) and was evaluated separately (cure). One month after treatment, clinical success (cure and improvement) was obtained in 23 of 25 patients (92%) and bacteriological eradication was achieved in 19 of 24 patients (79%). The only adverse event possibly related to the study drug was a case of transient mild tiredness and nervousness. Rufloxacin did not accumulate in plasma during therapy. Hence, a single daily dose of rufloxacin 200 mg appears to be a safe treatment for chronic bacterial prostatitis.

The in-vitro comparative activity of quinolones against bacteria from urinary tract infections in general practice.

In a study of lower urinary tract infection in general practice over twelve hundred strains have been isolated. Eight hundred and sixty-six consecutive strains were tested against four quinolone compounds. Sixty-nine per cent of the isolates were Escherichia coli and 15% coagulase-negative staphylococci (mostly Staphylococcus saprophyticus). The diffusion method, according to I.C.S. recommendation, was used and standardized for extrapolation of MIC results. Ciprofloxacin followed by norfloxacin and pefloxacin, was the most active quinolone compound (MIC 0 X 015-2 mg/l) against all strains, including multiresistant ones.

An assessment of temafloxacin in the treatment of chronic bacterial prostatitis.

Based on its in-vitro activity against the majority of organisms associated with bacterial prostatitis and its excellent penetration into prostatic tissue, prostatic secretions and seminal fluid, temafloxacin appears to be a suitable agent for the treatment of prostatic infections. The efficacy and safety of temafloxacin 400 mg bd for 28 days were assessed in 61 patients from ten centres in Germany with symptomatic bacterial prostatitis diagnosed by segmented localizing cultures. Urine and prostatic secretions were obtained for culture. Clinical signs and symptoms were evaluated at two weeks during treatment, and at 5 to 9 days and 26 to 30 days after treatment. Safety was monitored during and at the end of treatment. Escherichia coli and Enterococcus spp. were the most frequent pathogens. In 41 clinically and bacteriologically evaluable patients, 37 (90%) were successfully treated at 5 to 9 days; four of these patients did not return for follow-up at the final visit and the remaining patients (33) continued to be clinically cured or improved. Thirty-seven patients (90.2%) had eradication of pre-treatment pathogens at 5 to 9 days after treatment; three of these patients did not return for this final follow-up visit. There were six patients with persistent or recurrent pathogens isolated and six patients with reinfecting pathogens. Thus, 26 of 38 (68%) evaluable patients at visit 5 were free from infection (from either a pre-treatment pathogen or any subsequent new infecting pathogen) up to 26 to 30 days after treatment. One clinically evaluable but bacteriologically non-evaluable patient was classified as a therapeutic failure after nine days of treatment and was not included in the final assessment. Improvement in the severity of specific signs and symptoms was observed in greater than 90% of cases. Mild to moderate adverse events, mostly occurring during the first or second weeks of long-term therapy, were reported in 11.5% of patients. Temafloxacin 400 mg bd, for four weeks was very effective and well tolerated by the majority of patients with documented bacterial prostatitis.

Recent developments in the treatment of acute urinary tract infections.

A review of the recent literature on acute urinary tract infections reveals some unresolved problems and considerable discussion and reappraisal of the current diagnostic and therapeutic methods. In this review, the rationale for the diagnostic confirmation of the presence, extent and site of infection is presented. Recent developments in the treatment of acute urinary tract infections are discussed. Factors affecting the choice of drug and recent studies concerning the duration of therapy are detained. Studies concerning the treatment of urinary tract infections with trimethoprim alone are reviewed and results of the treatment of acute urinary tract infection with a single dose of trimethoprim at St Radboud Hospital are presented.