Kelfiprim,a new sulpha-trimethoprim combination,versus cotrimoxazole,in the treatment of urinary tract infections: A multicentre,double-blind trial

Summary A new combination of trimethoprim with a sulphonamide, named Kelfiprim, differs from cotrimoxazole in that: a) the sulpha drug is sulphamethopyrazine instead of sulphamethoxazole; b) the trimethoprim to sulpha ratio is 5:4 instead of 1:5;c) the presence of a long-acting sulphonamide allows the administration of a daily dose of one capsule, following an initial loading dose of two capsules; d) a reduced amount of trimethoprim is given, as compared to cotrimoxazole, without any decrease of efficacy. Kelfiprim [KP] was compared to contrimoxazole [Co] in a multicentre double blind trial. Sixty four patients suffering from acute and chronic infections of the upper and lower urinary tract entered the study. Urine sterilisation and clinical improvement without relapses showed no differences from the two treatment groups. Tolerance was excellent except in two patients, one treated with KP and the other treated with Co, who showed a transient exanthema.     

Long-term oral treatment of urinary tract infections with single daily doses of a new antibacterial drug combination (Kelfiprim)

Of 30 patients with severe, complicated U.T.I. 27 have been given single daily doses of Kelfiprim (KP), a new sulfatrimethoprim combination, for 8 weeks. In 24 bacteriuria was lastingly controlled, one had a relapse, one had a reinfection, and in one, with bladder carcinoma, bacteriuria persisted. Three other patients received KP for shorter periods, as they presented gastric intolerance or skin hypersensitivity, but in two of them a lasting sterilization of the urine has been obtained. The usefulness of a single daily dose schedule is stressed.     

Selective intestinal decontamination for prevention of wound colonization in severely burned patients: a retrospective analysis.

In this study the effect of selective intestinal decontamination of the digestive tract (SDD) on wound colonization was investigated. Ninety-one patients with at least 25 per cent total burned surface area (TBSA) were included in this study. All patients received oral polymyxin. In 63 patients oral co-trimoxazole and amphotericin B were added to the regimen. The addition of co-trimoxazole decreased the incidence of Enterobacteriaceae wound colonization from 71 per cent to 11 per cent (P less than 0.005). Colonization with Proteus was eliminated in patients treated with co-trimoxazole, compared with an incidence of 36 per cent in the group treated with polymyxin alone (P less than 0.001). The addition of amphotericin B decreased yeast colonization of the burn wound from 39 per cent to 10 per cent (P less than 0.005). A close relation was observed between burn wound colonization and colonization of the gastrointestinal tract. No resistant bacterial strains emerged during the period of study. These results suggest that SDD is an effective method for prevention of wound colonization. Further controlled studies are needed to establish the role of SDD in preventing burn wound colonization and wound sepsis.     

Comparison of cefixime and co-trimoxazole in acute uncomplicated urinary tract infection. A double-blind general practice study

Five hundred and twenty-eight patients with presumptive acute uncomplicated urinary tract infection (UTI) were randomly assigned to receive cefixime 400 mg once daily, cefixime 200 mg twice daily or co-trimoxazole 2 tablets twice a day for 10 days; 477 completed at least 5 days of therapy. Of the patients 342 (65%) had positive baseline urine cultures, yielding 353 pathogens. A microbiological response was determined for 280 pathogens (79%), eradication being observed in over 94% of isolates; 153 pathogens (43%) were sensitive to both cefixime and co-trimoxazole and eradication was observed in over 96% of cases. Clinical response correlated well with microbiological response. The incidence of diarrhoea and stool changes was higher (P less than 0.005) in the patients who received cefixime once daily than in the other groups. There was a significantly higher incidence of stool changes with cefixime twice daily than with co-trimoxazole (P less than 0.05), but these did not necessitate discontinuation of therapy. Nausea was commoner with co-trimoxazole (P less than 0.05). The majority of pathogens isolated were Escherichia coli, Proteus mirabilis and staphylococci. Approximately 24% of E. coli were resistant in vitro to co-trimoxazole (P less than 0.005). Cefixime 200 mg twice daily is an effective and safe alternative to co-trimoxazole in the management of acute uncomplicated UTI.     

Bacillus Calmette-Guerin for treatment of superficial transitional cell carcinoma of the bladder in patients who have failed thiotepa and/or mitomycin C

Thirty patients with stage Ta carcinoma in situ or T1 superficial bladder cancer received 6 weeks of intravesical bacillus Calmette-Guerin. All patients had persistent or recurrent tumor despite thiotepa and/or mitomycin C. Response was determined by the results of endoscopy, bladder wash cytology and biopsy performed 4 weeks after the last dose of bacillus Calmette-Guerin. Of the 30 patients 15 (50 per cent) had a complete response. The likelihood of a complete response was better for those with initial Ta lesions (62 per cent) and carcinoma in situ (56 per cent) than for patients with an initial T1 lesion (25 per cent). Although the longest followup is only 36 months (mean 16 months) patients with a complete response have a much better prognosis in terms of subsequent tumor, need for cystectomy and death of bladder cancer.     

Prophylactic co-trimoxazole and trimethoprim in the management of urinary tract infection in children

In a prospective study of low-dose antibacterial prophylaxis of childhood urinary tract infection (UTI), co-trimoxazole and trimethoprim (TMP) have been compared for efficacy in preventing UTI, for their effect on the rectal flora and for secular selection of TMP-resistant organisms.Between 1979 and 1986, 334 children who had proven infection of an unobstructed urinary tract complied in a regimen of low-dose prophylaxis together with measures to eliminate residual urine for at least 6 months. Of these children, 167 had vesico-ureteric reflux and 27 had renal scarring. There was no difference between the two drugs in compliance, which was very good, or in the occurrence of side-effects, which were minimal. Recurrence rates of further infection were 1 per 22 child years for the 226 children receiving cotrimoxazole and 1 per 18 child years for the 108 receiving TMP. All but one of these urinary pathogens were resistant to TMP and reinfection of the urinary tract generally occurred following lapses in attention to complete bladder emptying. Neither a secular increase in recurrent infections during this period, nor a significant change in the proportions of TMP-resistant faecal coliform organisms, was observed. TMP and co-trimoxazole appeared to be equally effective prophylactic agents.     

Intravesical mitomycin C instillation as a prophylactic treatment of superficial bladder tumor

A study was performed to determine the prophylactic efficacy of intravesical mitomycin C instillation in 43 patients with recurrent (more than 3), multiple (more than 3) or large (more than 3 cm.) superficial bladder tumors (stage Ta or T1). Of the patients 21 were treated with 8 weekly intravesical instillations of 40 mg. mitomycin C after transurethral resection and 22 were followed conventionally. The recurrence rate was 42.9 per cent in the mitomycin C group and 40.9 per cent in the controls during the first 3 months, and it was 81.0 and 77.3 per cent, respectively during 24 months. Recurrences per 100 patient-months were 8.7 and 8.9, respectively. Two patients in the mitomycin C group and 4 controls had recurrent tumors with progression in stage. We conclude tentatively from these observations that intravesical mitomycin C instillation is not effective in the prophylaxis of tumor recurrence in patients at high risk. This finding is contrary to other reports indicating a marked decrease in recurrence with mitomycin C.     

Does low urinary sIgA predispose to urinary tract infection?

Median urinary secretory IgA (sIgA) (ELISA technique in unprocessed urine) was 1.36 mg/liter (range, 0.29 to 2.31) in healthy female controls at various times of the menstrual cycle. It was significantly lower in women with urinary tract infection (UTI) without antibody-coated bacteria. Such decrease was found both in women with acute UTI episodes (median, 0.16; range, 0.06 to 1.71) and in asymptomatic nonbacteriuric women with a history of UTI (median, 0.52; range, 0.05 to 2.13). In the latter women, sIgA in nasal secretions tended to be low, but salivary sIgA was unchanged. Urinary sIgA was elevated significantly in individuals with nephrostomy and antibody-coated bacteria (14.4 mg/liter, range, 3.6 to 20). The study showed that locally synthesized sIgA immunoglobulins were low in the urine of individuals with recurrent UTI independent of the presence or absence of bacteriuria at the time of the study. UTI per se did not interfere with sIgA secretion as shown by high sIgA in patients with upper UTI. Low urinary sIgA may represent one factor predisposing to recurrent UTI.     

Effective postcoital prophylaxis of recurrent urinary tract infections in premenopausal women: A review

A total of 77 sexually active premenopausal women, susceptible to recurrent urinary tract infections (UTI) but otherwise healthy, were subjected to postcoital prophylaxis consisting of a single oral dose of either cotrimoxazole (80 mg trimethoprim+400 mg sulfamethoxazole), 50 mg nitrofurantoin macrocrystals, 500 mg nalidixic acid, 250 mg cinoxacin or 250 mg cephalexin. Postcoital prophylaxis reduced the incidence of recurrent UTI from 5-8 UTI per patient/year prior to prophylaxis, to a mere 0.03 UTI per patient/ year following prophylaxis. The differences in the incidence of UTI prior to and following institution of postcoital prophylaxis were statistically highly significant. A mean of 106–120 antibacterial tablets per patient were administered per year.Postcoital prophylaxis of recurrent UTI in premenopausal women is highly effective because of easy compliance, the high urinary concentration achieved and the minimal induction of resistance in the introital Gram-negative bacterial flora, irrespective of the length of time this prophylaxis is used. Furthermore, postcoital prophylaxis is significantly more effective than daily, as it achieves the same effect but requires only one third or fewer of the antibacterial tablets used in daily prophylaxis. At present, postcoital prophylaxis with cotrimoxazole, nitrofurantoin macrocrystals or cephalexin is recommended.     

5-year experience with intravesical therapy of carcinoma in situ: an inquiry into the risks of "conservative" management

Recent reports of disease progression in patients being treated with intravesical agents for carcinoma in situ of the bladder led us to examine our 5-year experience with 26 consecutive patients with carcinoma in situ treated with intravesical therapy for this lesion. Nine patients with isolated carcinoma in situ and 17 with carcinoma in situ associated with papillary lesions were treated intravesically with a variety of agents in a closely monitored program for a mean of 22 months. All patients wished to exhaust conservative options before accepting cystectomy. Of 26 patients treated 9 (35 per cent) have no evidence of disease with a functional bladder after 27 months, 13 (50 per cent) are treatment failures and 4 (15 per cent) maintain an equivocal status to date. Successful treatment results with each drug were 6 of 24 thiotepa, 0 of 7 mitomycin, 0 of 6 doxorubicin and 3 of 8 bacillus Calmette-Guerin. Treatment failure was associated with disease progression to muscle invasion, adjacent organ invasion or metastases in 7 patients (27 per cent). Significant reduction in bladder capacity after prolonged therapy occurred in 3 patients. Our results suggest that persistent, intensive, "conservative" intravesical therapy in the face of recurrent or persistent disease is associated with substantial patient risk.     

Bladder cancer in men and women treated by radiation therapy and/or radical cystectomy

Four-hundred fifty-one patients with bladder cancer, 348 men and 103 women, were treated by radiation therapy and/or radical cystectomy during the last two decades at Memorial Sloan-Kettering Cancer Center. Radical cystectomy alone was the treatment in 98 men and 39 women. Radical radiation therapy to an average tumor dose of 6,000 rad in six weeks was given to 79 men and 30 women ± one year before salvage cystectomy was done for recurrent or persistent tumors. Planned preoperative irradiation was delivered to the true pelvis either 4,000 rad in four weeks in 95 men and 24 women or 2,000 rad in one week in 76 men and 10 women ± six weeks and two days, respectively, before radical cystectomy. Over-all survival and recurrence results in both sexes were similar; 40 per cent of men and 36 per cent of women were alive at five years without recurrence, 45 per cent of men and 48 per cent of women died in five or more years with local and/or distant recurrences, and 21 per cent of men and 15 per cent of women died before five years from causes other than cancer recurrence. Higher five-year survival for high clinical stage B₂ to D₁ tumors was noted similarly in the irradiated men (30 per cent) and women (37 per cent) than in the cystectomy alone patients (19 per cent in men and 4 per cent in women). Similar survival rates (52 to 57 per cent) were observed in men and women with low clinical stage O to B1 tumors treated with or without irradiation.     

Clinical studies of antimicrobial prophylaxis of recurrent urinary infection in women. Long-term, low-dose pipemidic acid for prophylaxis

The prophylactic efficacy of long-term, low-dose antimicrobial treatment in urinary tract infection (UTI) was studied. Fifty-eight female adult patients with a history of at least two recurrent episodes of UTI in the past year were entered into this study, and the prophylactic regimen was not started until the existing UTI had been eradicated. Patients took 250 mg of pipemidic acid (PPA) daily at bedtime after voiding for 6 consecutive months. Incidence of recurrence of UTI in 48 patients with uncomplicated UTI and 10 patients with complicated UTI decreased to 0.15 and 0.29 per year, respectively, during the treatment compared with 3.5 per year before the treatment. At the end of the 6 months of prophylactic treatment, the patients were divided into two groups by the envelope method. Seventeen patients were treated for a further 6 months and 11 patients were followed up without further medication. Prophylactic efficacy of UTI was obtained in both groups, and there was no significant difference in the incidence of recurrence between the two groups. These findings suggest that the 6-month period of prophylaxis might be sufficient. Examination of the periurethral swab showed that E. coli and Klebsiella sp. were decreased during the treatment. This prophylactic treatment produced no resistant strains. Urinary levels of PPA in the morning urine of patients administered 250 mg of PPA at bedtime averaged 513 micrograms/ml. These values were about 2 times higher than those found in the evening urine after administration of the same dose in the morning.     

Symptomatic and functional outcome after laparoscopic reoperation for failed antireflux surgery

BACKGROUND: The aim was to determine symptomatic and functional outcome after reoperative antireflux surgery for recurrent reflux, persistent dysphagia and severe gas bloat, using a primarily laparoscopic surgical approach. METHODS: This was a retrospective analysis of prospectively collected data from 118 patients, of whom 70 had reoperative surgery for recurrent reflux, 35 for dysphagia and 13 for gas bloat. DeMeester scores before and 1 year after surgery, functional symptoms after surgery and overall patient satisfaction were analysed. RESULTS: Reoperation was completed laparoscopically in 101 patients (85.6 per cent), in 28 after previous open hiatal surgery. The operation was converted from an initial laparoscopic approach to open surgery in 17 patients. One-year follow-up data were available for 104 patients (88.1 per cent). After reoperation for recurrent reflux, 84 per cent had a DeMeester heartburn score of zero or one, and 87 per cent had a regurgitation score of zero or one. After reoperation for dysphagia, 21 of 32 patients had a dysphagia score of zero or one, with improvement observed in 25. All patients undergoing reoperation for severe gas bloat were satisfied with the outcome 1 year after operation. CONCLUSION: Revisional surgery for recurrent reflux using a laparoscopic approach offered high rates of success and patient satisfaction. Swallowing returned to normal in two-thirds of patients after reoperation.     

Limits and drawbacks of video-assisted parathyroidectomy

BACKGROUND: Minimally invasive video-assisted parathyroidectomy (MIVAP) is a novel minimally invasive approach to primary hyperparathyroidism (PHPT). It is a gasless operation characterized by a single central incision and external retraction. This paper describes the drawbacks and limitations of this procedure based on a 5-year experience and 260 operations. METHODS: Of 364 patients with PHTP, 260 were selected for MIVAP. In most patients a unilateral minimally invasive exploration was performed. RESULTS: MIVAP was carried out successfully in 239 patients with a mean operating time of 40 (range 20-180) min. Conversion to cervicotomy was required in 21 patients (8.1 per cent). Complications included recurrent nerve palsy in two patients (0.8 per cent), haemorrhage that required reoperation 6 h after parathyroidectomy in one patient (0.4 per cent) and transient hypoparathyroidism in six patients (2.5 per cent). In five patients (2.1 per cent) persistent PHPT developed shortly after surgery. CONCLUSION: After 5 years of experience, MIVAP appears to be feasible, safe and applicable to the majority of patients with PHPT.     

Neostigmine,pyridostigmine and edrophonium as antagonists of deep pancuronium blockade

To compare the ability of equipotent doses of neostigmine, pyridostigmine and edrophonium to antagonize intense pancuronium neuromuscular blockade, one hundred and twenty ASA physical status I or II patients scheduled for elective surgery received 0.06 mg.kg-1 pancuronium during a thiopentone nitrous oxide-enflurane anaesthetic. Train-of-four stimulation was applied every 12 s and the force of contraction of the adductor pollicis muscle was recorded. In the first 60 patients, spontaneous recovery was allowed until ten per cent of initial first twitch height. Then neostigmine (0.005, 0.01, 0.02 or 0.05 mg.kg-1), pyridostigmine (0.02, 0.04, 0.1 or 0.2 mg.kg-1), or edrophonium (0.1, 0.2, 0.4 or 1 mg.kg-1) was injected by random allocation. Dose-response relationships were established from the measurement of first twitch height (T1) ten minutes later. From these, neostigmine, 0.04 and 0.08 mg.kg-1 was found to be equipotent to pyridostigmine, 0.2 and 0.38 mg.kg-1, and edrophonium, 0.54 and 1.15 mg.kg-1, respectively. These doses were given by random allocation to the next 60 patients, but at one per cent spontaneous recovery. Neostigmine, 0.04 mg.kg-1, produced a T1 of 73 +/- 4 per cent (mean +/- SEM), and a train-of-four ratio (TOF) of 39 +/- 3 per cent. This was significantly greater than with pyridostigmine, 0.2 mg.kg-1 (T1 = 50 +/- 6 per cent; TOF = 25 +/- 3 per cent), and edrophonium, 0.54 mg.kg-1 (T1 = 54 +/- 3 per cent; TOF = 17 +/- 2 per cent).(ABSTRACT TRUNCATED AT 250 WORDS)     

Understaging and undergrading of prostate cancer. Argument for postoperative radiation as adjuvant therapy

This report reviews the staging and grading errors that occurred in a consecutive series of 14 patients treated for prostate cancer by radical prostatectomy and of 58 patients treated by both radical prostatectomy and pelvic lymphadenectomy. Almost half of the patients who were in Stages A2, B1, or B2 by clinical criteria were in pathologic Stage C when both capsular perforation and seminal vesicle invasion were used as the criteria for Stage C disease. Seminal vesicle invasion was the more important prognostic factor. Moreover, the pathologic grade of cancer, as determined by needle or transurethral biopsy, was underestimated in 39 per cent of the cases; when the grade was corrected, the patient often was in a worse prognostic group than the one originally assigned. Thus, in this series, more than 40 per cent of the patients were at high risk of persistent or recurrent disease after radical prostatectomy. Radiation was given after operation to 22 such high-risk patients and was well tolerated.     

Two-stage reconstruction of a total hip arthroplasty because of infection

From 1969 to 1985, eighty-one patients (eighty-two hips) who had an infection after a previous total hip arthroplasty were treated with a resection arthroplasty, followed by delayed reconstruction in the form of a repeat total hip arthroplasty. For all of the reconstructions, the femoral and acetabular components were fixed to bone with cement that did not contain antibiotics. An average of 5.5 years (range, 2.0 to 13.6 years) after reimplantation, infection had recurred in eleven hips (13 per cent). The presence of retained cement at the time of the resection arthroplasty appeared to be associated with recurrent sepsis, as three of seven patients who had retained cement had a recurrent infection, compared with only eight (11 per cent) of seventy-five patients from whom the cement had been completely removed (p less than 0.01). The twenty-six patients (twenty-six hips) who had the reimplantation less than one year after the resection arthroplasty had seven recurrent infections (27 per cent), while the fifty-six patients who had reimplantation more than one year after the resection arthroplasty had only four recurrences (7 per cent) (p less than 0.001). Three of the seven patients in whom the infection was caused by gram-negative bacilli and group-D streptococcal organisms (which are considered highly virulent) and who received systemic antimicrobial therapy for less than twenty-eight days had a recurrence. In contrast, only one of the thirteen patients in whom the infection was caused by a virulent organism and who were treated for longer than twenty-eight days had a recurrence (p = 0.055). The two-stage reconstruction is an effective, safe technique even when the infection is caused by a virulent organism.     

Prevention of recurrent bacterial cystitis by intravesical administration of hyaluronic acid: a pilot study

OBJECTIVES: To assess the effect of bladder instillations of hyaluronic acid (HA) on the rate of recurrence of urinary tract infection (UTI). PATIENTS AND METHODS: Forty women (mean age 35 years) with a history of recurrent UTI received intravesical instillations of HA (40 mg in 50 mL phosphate-buffered saline) once weekly for 4 weeks then once monthly for 4 months. The UTI status was assessed over a prospective follow-up of 12.4 months and compared with the rates of UTI before instillation, determined by a retrospective review of patient charts covering 15.8 months. RESULTS: After HA treatment no patients had a UTI during the 5-month treatment phase and 28 (70%) were recurrence-free at the end of the follow-up. The mean (sd) rate of UTI per patient-year was 4.3 (1.55) before treatment and 0.3 (0.55) afterward (P < 0.001). The median time to recurrence after HA treatment was 498 days, compared with 96 days beforehand (P < 0.001). The tolerability was excellent, as side-effects were limited to nine patients who reported mild bladder irritation; no patient interrupted the treatment. CONCLUSIONS: In this preliminary study, bladder instillations of HA had a significant effect on the rate of UTI in women with a history of recurrent UTIs. The bladder instillation of HA is an acceptable and promising therapeutic alternative in patients with recurrent UTI. Expanded placebo controlled clinical trials examining this application of HA are currently underway.     

Treatment of mesenteric infarction

Eighty-one cases of mesenteric infarction documented by angiography, laparotomy or autopsy were reviewed to assess the cause of the persistently high mortality. Thirty-seven patients (46 per cent) were felt to have inoperable lesions and were treated by supportive care only, while forty-four (54 per cent) underwent bowel resection and/or revascularization. Of these 44 patients 20 (45 per cent) survived, 14 (32 per cent) died of an early recurrence of infarction and 10 (23 per cent) died of an unrelated cause. In view of the high recurrence rate in the early postoperative period, treatment must prevent the causes of persistent or recurrent ischaemia such as vasoconstriction and reperfusion tissue damage. On the basis of recent clinical and experimental research we suggest that treatment should include routine angiography with selective perfusion of vasodilators through the superior mesenteric artery, pharmacological prevention of ischaemic and reperfusion tissue damage before surgery, and postoperative anticoagulation.     

Secondary hyperparathyroidism. The role of surgery

A retrospective analysis was undertaken to better define the clinical presentation and therapy of patients with secondary hyperparathyroidism and the timing of surgical removal of the parathyroid glands in secondary hyperparathyroidism. Sixty-eight patients with end-stage renal disease (ESRD) underwent 74 parathyroid procedures over a 10-year period. There were 38 per cent women and 62 per cent men in this population--the same proportion of men and women with ESRD. These proportions are reversed when compared with patients with primary hyperparathyroidism. The mean time between initiation of dialytic therapy and parathyroidectomy was 5.4 years. Preoperative mean serum calcium and phosphorus levels were 10.1 +/- 0.2 and 6.1 +/- 0.2 mg/dl, respectively. All patients were symptomatic and 60 per cent of the patients had at least two symptoms before surgery. Renal osteodystrophy was the most common symptom (74%), whereas pruritus was noted in 65 per cent of this population. Patients underwent either subtotal (88%) or total (12%) parathyroidectomy with autotransplantation. Six patients required reoperation: five for recurrent disease (2 to 5 years after the initial surgery) and one for persistent disease. All patients were symptomatically improved after the surgery. Complications included the following: transient hoarseness (7%), hypocalcemia requiring calcium, and/or vitamin D therapy (32%) for 6 months after surgery. This analysis demonstrates that although the initial therapy of secondary hyperparathyroidism is medical, surgical therapy should be instituted before multiple symptoms develop in the ESRD population.