Bioactivity of Isostructural Hydrogen Bonding Frameworks Built from Pipemidic Acid Metal Complexes.

We report herein three novel complexes whose design was based on the approach that consists of combining commercially available antibiotics with metals to attain different physicochemical properties and promote antimicrobial activity. Thus, new isostructural three-dimensional (3D) hydrogen bonding frameworks of pipemidic acid with manganese (II), zinc (II) and calcium (II) have been synthesised by mechanochemistry and are stable under shelf conditions. Notably, the antimicrobial activity of the compounds is maintained or even increased; in particular, the activity of the complexes is augmented against Escherichia coli, a representative of Gram-negative bacteria that have emerged as a major concern in drug resistance. Moreover, the synthesised compounds display similar general toxicity (Artemia salina model) levels to the original antibiotic, pipemidic acid. The increased antibacterial activity of the synthesised compounds, together with their appropriate toxicity levels, are promising outcomes.

Cross-reactivity between quinolones. Report of three cases.

Cross-reactivity between quinolones is uncertain. Recently, we studied three patients who had developed suspected allergic reactions to a quinolone. For all of them we performed skin test, histamine release test, RAST, and oral provocation with the suspected quinolone and also with another quinolone of the opposite generation. Five atopic and five nonatopic subjects were used as controls. Neither skin test, histamine release test, nor RAST was useful in the diagnosis. By means of oral controlled provocation, the reactions were reproduced, and all the patients also reacted to another quinolone. We concluded that cross-reactivity between quinolones seems to be very important, and avoidance of any quinolone should be recommended to any patient who has suffered an allergic reaction to one of these drugs.

The transmandibular implant: a 13-year survey of its use.

During the period from August 1976 until July 1989 the transmandibular implant was introduced in a total of 31 oral and maxillofacial surgery departments in the Netherlands and 1,466 patients were treated. This study includes 1,356 treated patients from 28 departments. The treatment course of 1,201 patients (89.6%) was uneventful. Of the 157 complications, 58 related to the anatomic contour of the mandible, 49 to the surgery, 25 to the prosthetic reconstruction, 8 to the psychosocial attitude of the patient, 8 to the use of medication, 5 to trauma, and 4 to the presence of a skin graft. Treatment of the complications included removal of the implant in 44 patients; in 106 patients the complication was treated satisfactorily. In the remaining 7 patients, hypesthesia was present. The reasons for the removal of the 44 implants were infection (11), operative error (5), premature loading of the implant (3), insufficient width of the mandible after a visor osteotomy (1), loss of osseointegration caused by the prosthesis (14), psychological problems (4), trauma (3), drug-related gingival hyperplasia (2), and inexplicable pain (1). The present survey shows a consistent success rate of 96.8%.

Fixed drug eruption due to pipemidic acid.

A 71-year-old woman with fixed drug eruption caused by pipemidic acid is reported. The patient developed typical lesions on rechallenge with pipemidic acid, but not with nalidixic acid, an analogue of pipemidic acid.

A general practitioner multicenter study: fosfomycin trometamol single dose versus pipemidic acid multiple dose.

In order to evaluate the efficacy and safety of fosfomycin trometamol as single dose oral treatment for acute cystitis in women, an open, multicenter comparative study was carried out in general practices in France, 386 women, aged 16 to 75 years, with clinical symptoms of acute cystitis were enrolled in the study to receive either a single 3 g oral dose of fosfomycin trometamol or a five-day course of 400 mg pipemidic acid twice daily. The diagnosis of cystitis was based on clinical symptoms and significant bacteriuria (greater than or equal to 10(5) cfu/ml midstream urine). Follow-up examinations were carried out five to ten and 28 days after the end of treatment, 289 and 244 patients, respectively, were available for clinical and bacteriological evaluation at short-term (five to ten days) and medium-term (28 days) post-treatment follow-up. Both regimens were comparable for clinical and bacteriological efficacy with short-term eradication rates of 122/146 in the fosfomycin trometamol group and 130/143 in the pipemidic acid group. The results of medium-term follow-up were 113/122 and 114/122 for the eradication rates of the respective groups. Both drugs were well tolerated. Side effects were mild and of significantly shorter duration in the fosfomycin trometamol group.

Combination of pipemidic acid, colistin sodium methanesulfonate and nystatin may be less effective than nystatin alone for prevention of infection during chemotherapy-induced granulocytopenia in acute leukemia.

Pipemidic acid (PPA) and colistin sodium methanesulfonate (CLM) may selectively suppress aerobic gram-negative bacilli. Twenty-nine patients with acute leukemia were randomized after each course of consolidation chemotherapy to receive a single agent of nystatin (NYS) (34 courses) versus a combination of NYS, PPA and CLM (36 courses). The duration of fever over 39 degrees C was longer with the three drug combination (4.6 +/- 5.1 days) than with NYS alone (1.8 +/- 1.8 days) (P less than 0.01). Four cases of pneumonia occurred and four patients including one having pneumonia died of infection with the three drug combination, while no pneumonia or death occurred with NYS alone (P = 0.06 and P = 0.06, respectively). The combination of NYS, PPA and CLM may be less effective than NYS alone for the prevention of infection in acute leukemia patients with chemotherapy-associated granulocytopenia.

[Pipemidic acid in the prevention of recurring cystitis in women]. / L'acide pipémidique dans la prophylaxie des cystites récidivantes chez la femme.

The efficacy, safety and acceptability of pipemidic acid in the treatment and the prophylaxis of cystitis in women have been evaluated. After curative treatment, patients received prophylaxis using the compound for a duration of 6 months, and were followed up a further 4 month-period without specific therapy. During the prophylaxis period, no relapse was observed in over 85% of the treated patients. In 15% of cases, a pathogen reappeared along with recurrence of the preexisting symptoms. An increase to 29% of the cases was noted after the withdrawal of the treatment over a month study period. The pathogens involved in the cases of relapse during the prophylaxis period were sensitive to pipemidic acid in 1/3 of cases (6/18 cases), and resistant in 2/3 (12/18 cases) of cases. Those involved in relapses during the observation period were sensitive in 1/2 of the cases (8/16 cases), resistant or intermediate in 1/2 of the cases (8/16 cases). Thus, prophylactic treatment with pipemidic acid has a favorable influence on the number of relapses in patients with recurrent cystitis.

[Clinical trial of drugs for treating urological infections--pipemidic acid]. / Klinichno izpitvane na lekarstveni sredstva za lechenie na uroinfektsii--pipemidinova kiselina.

A method was elaborated for clinical trial of pharmaceuticals for the treatment of infections of kidneys and urinary ducts. The main requirements are as follows: definitive diagnostic criteria for urological infection, monotherapy, systematic control for the drug intake, precisely formulated indices for assessment of the effect, strict follow-up of adverse and toxic effects. The effect was assessed according to a three-stage scale: very good, good and poor, consideration given not only to the clinical and laboratory indices but to adverse effects as well. Pipemidic acid was studied according to that model--the acid being a new chemotherapeutic, similar to nalidixic acid according to chemical composition and action. Out of all 29 patients treated, 19 were with very good effect, with good--6, and with poor--4. The adverse effects were negligible--one patient had light urticarial rash and pruritus.

[Utilisation of pipemidic acid as antibiotic in patients with renal failure insufficiency. Kinetics of serum and urinary concentrations (author's transl)]. / Utilisation de l'acide pipémidique comme antibiotique chez l'insuffisant rénal. Cinétique des concentrations sériques et urinaires.

In 23 chronic renal patients serum and urinary concentrations of pipemidic acid were studied, the drug being given orally for 3 to 105 days. In 13 non-dialyzed patients, whose GFR varied from 4.5 to 36 ml/mn the dosage was 11.2 to 30 mg/kg/day. Maximum serum concentrations were comprised between 6 and 29 micrograms/ml. In 2 patients minor clinical side-effects indicated a maximum tolerance level of 25 micrograms/ml. Urinary concentrations remained elevated in spite of severe renal failure. In 10 hemodialyzed patients maximum predialysis levels varied from 5.6 to 28 micrograms/ml. No side-effects were noticed. The dialysance of pipemidic acid was high, due to a low molecular weight and to a binding to proteins which seems to be lower in uremics than in normal subjects. We conclude that pipemidic acid can be utilized in chronic renal patients, in taking advantage of low GFR's for obtaining serum bactericidal concentrations on susceptible organisms.