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Biomedical subjects

P Periti

Publications and source records attributed to P Periti.

At least 55 records · Page 3Linked to original sources
PubMed1994

Antibiotic treatment of burned patients: an Italian multicentre study.

Antibiotic therapy in burn centres with highly specialized ICUs has reduced the mortality and morbidity in burn and trauma but, in spite of constantly improving supportive surgical and resuscitation methods, infection remains a major problem. Indeed, the clinical experience, as recorded in Europe and the USA, using different antimicrobial drugs and regimens, emphasizes a constantly evolving pattern of pathogenic microorganisms in the wound and in the rest of the patient's body, and their increasing chemoresistance. We report the preliminary results of 559 patients in a large controlled multicentre clinical study (mean age 41.4 +/- 17.8 years and burns covering a mean body surface area of 35.7%), with the collaboration of 13 of the 15 major Italian burn centres. The antibiotic treatment consisted of prophylactic administration of pefloxacin (800 mg i.v. OD for 4 days) for all patients as a first treatment while waiting for an antibiogram, and chemotherapy with teicoplanin (800 mg i.v. OD) together with netilmicin (300 mg i.m. OD) in one or more cycles. At random, half of the patients received thymostimulin (70 mg i.m. OD pro die for the first month and every other day thereafter until discharge from hospital). Of the bacterial pathogens involved in septic complications, 63.3% were Gram-positive (Staphylococcus spp. and Streptococcus spp.). The mortality rate was 15.5%. Pefloxacin chemoprophylaxis was successful in 19.4% of patients and cure or improvement was seen with combination chemotherapy in 66.7% of patients, mainly with only one treatment cycle. The incidence of mortality and sepsis was not significantly influenced by treatment with thymostimulin.

Adolescent↗
PubMed1994

Penetration of cefotetan into suction skin blister fluid and tissue homogenates in patients undergoing abdominal surgery.

The penetration of cefotetan (2-g intravenous bolus) into the suction blister fluid and tissue homogenates of 11 patients was investigated. Mean concentrations in tissue were significantly lower than contemporary suction blister fluid levels. These data show that the determination of beta-lactam concentrations by the tissue homogenate method may seriously underestimate the actual antibiotic levels in extracellular fluid.

Abdomen↗
PubMed1993

Treatment of FIGO (1971) stage I endometrial carcinoma with intensive surgery, radiotherapy and hormonotherapy according to pathological prognostic groups. Long-term results of a randomised multicentre study.

A multicentre trial on patients with apparent stage I endometrial carcinoma was conducted with the aims of defining a treatment plan on the basis of the pathological disease extension and of evaluating the effectiveness of adjuvant medroxyprogesterone acetate (MPA). After surgery, patients with disease limited to the endometrium did not receive any further treatment. Patients with inner myometrial invasion and well or moderate differentiation were randomised to no further treatment vs. MPA 100 mg orally twice a day for 12 months; patients with moderate or deep myometrial invasion or undifferentiated grade were randomised to radiotherapy on pelvis vs. radiotherapy plus MPA, and patients with node-positive disease (N+) were submitted to radiotherapy on pelvis and para-aortic nodes vs. radiotherapy plus MPA. At 84 months, analysis as intention to treat on 856 patients shows a high relapse-free survival, whereas it did not show any significant difference between the MPA-treated and untreated groups. The study indicates that relapse-free survival is influenced by a treatment based on the pathological extension of the disease and that adjuvant hormonotherapy does not improve the cure rate.

Adult↗
PubMed1993

Antimicrobial chemoimmunoprophylaxis in colorectal surgery with cefotetan and thymostimulin: prospective, controlled multicenter study. Italian Study Group on Antimicrobial Prophylaxis in Abdominal Surgery.

Surgical antimicrobial prophylaxis was performed with a controlled study on 859 evaluable patients randomized into two groups treated with chemoprophylaxis only or chemo- and immunoprophylaxis in colorectal surgery. Immuno and chemoprophylactic treatment (425 patients) consisted of 70 mg i.m. thymostimulin per day for 7 days beginning 48 h before surgery plus 2 g cefotetan at the moment of induction of anesthesia; the other group (434 patients) received only the single dose of antibiotic. Results in the two different groups were significantly different regarding abdominal abscess and the total infectious episodes in the surgical site with lower frequency in patients receiving both thymostimulin and the antibiotic (cefotetan). Moreover the respiratory tract infections were more than double in those patients not treated with perioperative immunotherapy. Stratifying patients on the basis of grade of skin test reaction, we observed a significantly lower percentage of surgical site infection in hypoergic patients receiving chemo- and immunoprophylaxis.

Adjuvants, Immunologic↗
PubMed1993

Chemistry and mode of action of macrolides.

After the discovery of erythromycin and other natural compounds, including oleandomycin, spiramycin, josamycin and midecamycin, much research has been devoted to synthesizing derivatives or analogues with improved chemical, biological and pharmacokinetic properties. These new macrolides are semisynthetic molecules that differ from the original compounds in their substitution pattern of the lactone ring system. The chemical structure of macrolides is characterized by a large lactone ring containing from 12 to 16 atoms to which are attached, via glycosidic bonds, one or more sugars. The lactone ring is substituted by hydroxyl or alkyl groups, one ketone at C7 in 12-membered macrolides and at C9 in 14-membered macrolides, and one aldehyde group in 16-membered macrolides. The only compound with a 15-membered ring contains a tertiary amino group. Although the 12-membered macrolides have never become important in clinical practice, in recent years numerous new 14-membered macrolide derivatives of erythromycin A have shown improved pharmacokinetics due to chemical modifications of a hydroxyl group at C6, a proton at C8, or a ketone at C9. Derivatives, such as dirithromycin, roxithromycin, clarithromycin and flurithromycin, have all been synthesized with the aim of inhibiting their decomposition under acidic conditions to inactive anhydrohemiketal derivatives. A new 15-membered macrolide, azithromycin, with a methylated nitrogen inserted into the lactone ring shows good activity against Gram-negative bacteria. The efforts expended in chemical and biochemical modifications of 16-membered macrolides have been less successful, with only a few new molecules, such as rokitamycin and miocamycin, showing improved bioavailability and activity against some resistant micro-organisms.(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-Bacterial Agents↗
PubMed1993

Pharmacokinetics of azithromycin in patients with impaired hepatic function.

The pharmacokinetics of azithromycin were determined over a 192-h period following oral administration of a single 500-mg dose to six healthy volunteers and to 16 cirrhotic patients (ten class A and six class B; Pugh's classification). Plasma and urinary levels were determined by microbiological assay. The mean Cmax, obtained 2-3 h after administration, was 0.29 mg/L in volunteers, and 0.39 and 0.51 mg/L in class A and class B cirrhosis, respectively. The elimination half-life was 53.5 h in control subjects, and 60.6 and 68.1 h in class A and class B cirrhotic patients, respectively. The mean residence time was significantly higher in class B patients, but AUC, Vd, Cltot and Clr values appeared to be similar in all groups. The mean urinary recovery of azithromycin at 192 h varied from 11-15.7%, and did not differ significantly among groups. These results demonstrate that azithromycin pharmacokinetics do not differ consistently in patients with mild or moderate hepatic impairment in comparison with healthy volunteers. Therefore, no dosage modifications of azithromycin seem to be required for patients with class A or B liver cirrhosis.

Adult↗
PubMed1993

Regional and systemic prophylaxis with teicoplanin in monolateral and bilateral total knee replacement procedures: study of pharmacokinetics and tissue penetration.

Twenty-four patients undergoing monolateral or bilateral total knee replacement (TKR) procedures were randomized to receive teicoplanin (T) either systemically or regionally. Subjects scheduled for systemic prophylaxis and undergoing monolateral (six patients) or bilateral (five patients) TKR received a single 800-mg dose of T in 100 ml of saline as a 5-min infusion into a forearm vein 2.5 h before surgery. For regional prophylaxis, patients undergoing monolateral surgery (eight subjects) received 400 mg of T in 100 ml of saline as a 5-min infusion into a foot vein of the leg to be operated on immediately after the tourniquet was inflated. For the five patients scheduled for bilateral operation and regional prophylaxis, the administration of T was also repeated for the second knee operation. The tourniquet, as the standard TKR surgical technique, was inflated to 400 mm Hg (c. 50 kPa) in all 24 patients immediately before the beginning of surgery and kept in place for the duration of the operation. Samples of serum, bone, skin, synovia, and subcutaneous tissue were collected at timed intervals during surgery. They were microbiologically assayed for T by using Bacillus subtilis as the test organism. Overall, the mean T concentrations obtained with regional route prophylaxis were found to be 2 to 10 times higher than those achieved following systemic prophylaxis. Moreover, peak levels in different tissues after regional prophylaxis were significantly higher (P < 0.05). None of the patients experienced adverse effects due to regional or systemic T administration; no prosthetic or wound infections were observed in the follow-up period (from 12 to 26 months).

Aged↗
PubMed1993

Adverse effects of macrolide antibacterials.

The renewed interest in macrolide antibacterials with expanded indications for clinical use, as well as their markedly increased usage, justifies the continuous search for new compounds designed to offer the patient not only enhanced bioavailability but also a reduced incidence of adverse effects. Macrolides are an old and well established class of antimicrobial agents that account for 10 to 15% of the worldwide oral antibiotic market. Macrolides are considered to be one of the safest anti-infective groups in clinical use, with severe adverse reactions being rare. Newer products with improved features have recently been discovered and developed, maintaining or significantly expanding the role of macrolides in the management of infection. This review deals with the tolerability of the clinically available macrolide antibacterials. With the exception of drug interactions, adverse effects have been analysed during the last 40 years in many thousands of adult and paediatric patients. Recently developed derivatives have been compared with the older compounds, and the expected and well assessed adverse effects have been set apart from those which are unusual, very rare or questionable. Gastrointestinal reactions represent the most frequent disturbance, occurring in 15 to 20% of patients on erythromycins and in 5% or fewer patients treated with some recently developed macrolide derivatives that seldom or never induce endogenous release of motilin, such as roxithromycin, clarithromycin, dirithromycin, azithromycin and rikamycin (rokitamycin). Except for troleandomycin and some erythromycins administered at high dose and for long periods of time, the hepatotoxic potential of macrolides, which rarely or never form nitrosoalkanes, is low for josamycin, midecamycin, miocamycin, flurithromycin, clarithromycin and roxithromycin; it is negligible or absent for spiramycin, rikamycin, dirithromycin and azithromycin. Transient deafness and allergic reactions to macrolide antibacterials are highly unusual and have definitely been shown to be more common following treatment with the erythromycins than with the recently developed 14-, 15- and 16-membered macrolides. There have been case reports in the literature of 51 patients during the last 30 years who experienced uncommon or dubious adverse effects after treatment with older compounds and in which there appears to be strong evidence of a causal relationship with the drug. Only 3 cases had an unfavourable outcome, and these were patients administered erythromycin lactobionate intravenously too rapidly or at high dose. Targets of these occasional reactions are generally the heart, liver and central nervous system. Other unusual organ pathologies are related to immunomediated disorders more than to primary parenchymal toxicity, or to the rarely serious consequences of macrolide-induced alterations in intestinal microflora.(ABSTRACT TRUNCATED AT 400 WORDS)

Anti-Bacterial Agents↗
PubMed1993

In vitro brodimoprim activity on nosocomial bacterial strains.

The activity of brodimoprim, a new diaminopyrimidine, against 385 recent clinical isolates of Gram-positive cocci and Gram-negative bacilli was in vitro tested by the disk sensitivity test (DST) of Bauer et al. with disk concentration of 2.5 micrograms and by the agar dilution method. The postantibiotic effect (PAE) and the postantibiotic leukocyte killing enhancement (PALE) were determined on selected pathogens. The MICs were determined with Müller Hinton II agar (BD) and a multipoint inoculator (Denley A 400); thymidine phosphorylase (0.08 U/ml) was added to the test agar. Brodimoprim was very active against S. pyogenes (27), Salmonella sp. (30), methicillin susceptible S. aureus (36) and E. faecalis (34). The geometric means (GM) of MICs ranged from 0.08 to 0.63 and % of resistance from 0.0 to 14.7. Higher MICs (GM from 1.02 to 2.67) were shown against Citrobacter sp. (32), Klebsiella sp. (27), E. coli (36), methicillin-resistant S. aureus (33), Enterobacter sp. (32), Proteus sp. (31) and methicillin-susceptible coagulase negative staphylococci (34); resistant strains ranged from 18.7 to 41.2%. The in vitro activity against methicillin-resistant coagulase-negative staphylococci (33) (72.7% of resistance to brodimoprim) was very low. Regression analysis, obtained correlating the results of MICs with those of agar diffusion, shows that the resistant strains have a diameter less than 11 mm, the intermediate ones a diameter of 11-13 mm and susceptible strains a diameter greater than 13 mm. The PAE was determined using the Abbott AVANTAGE system. Strains were exposed to brodimoprim (1/4 x MIC - 4 x MIC range) for 2 or 6 h.(ABSTRACT TRUNCATED AT 250 WORDS)

Cross Infection↗
PubMed1993

Pharmacokinetics and blister fluid penetration of brodimoprim in adults.

We investigated the pharmacokinetic properties of brodimoprim (B), a new diaminopyrimidine, including its penetration into suction blister fluid (SBF) after a single or multiple oral dose in 15 patients with a mean age of 61.5 +/- 9.3 yrs, suffering from respiratory tract infections with normal renal and hepatic function. Patients were divided into 3 groups of 5 cases each, according to treatment plan: Group I = B 400 mg single dose day 1; Group II = B 400 mg qD day 1 and 200 mg qD days 2 to 4; Group III = B 200 mg BID day 1 and 200 mg qD days 2 to 4. Concentrations were determined microbiologically using B. subtilis ATCC 6633 as the test organism with a lower limit of sensitivity of 0.37 mg/l. With a single oral dose of 400 mg (Group I) a computed serum Cmax of 2.9 +/- 0.6 mg/l was observed 5.6h after administration, with a elimination half-life (t1/2 beta) of 32.3 +/- 4.1 h. In SBF a mean peak of 1.9 +/- 0.6 mg/l was reached after 6h with a t1/2 beta of 34.7 +/- 5.4 h and a penetration index (Pl), obtained by the AUCSBF/AUCs percent ratio of 61%. With multiple doses serum peak concentrations increased significantly, while the time to reach the peak (Tmax) was shorter (3.7-4.2 h) than after a single dose. Main kinetic parameters, such as t1/2 beta, mean residence time (MRT), elimination rate constant (Kel) and AUC, were significantly higher in Group II and III patients than in Group I cases. Similar differences were observed among the main SBF kinetic parameters.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

In vitro effects of brodimoprim on human polymorphonuclear leukocyte functions. Preliminary results.

The in vitro effects of brodimoprim and trimethoprim on the functions of human polymorphonuclear (PMN) leukocytes have been studied comparatively evaluating chemotaxis, phagocytosis and production of superoxide anion. No significant effects of both diaminopyrimidines on chemotaxis and phagocytic activity of PMNs have been observed while both brodimoprim and trimethoprim enhanced the oxidative burst. A synergistic activity between the host immune system and the direct antimicrobial action of brodimoprim may occur while using this diaminopyrimidine in vivo.

Cells, Cultured↗
PubMed1992

Pharmacokinetic drug interactions of macrolides.

The macrolide antibiotics include natural members, prodrugs and semisynthetic derivatives. These drugs are indicated in a variety of infections and are often combined with other drug therapies, thus creating the potential for pharmacokinetic interactions. Macrolides can both inhibit drug metabolism in the liver by complex formation and inactivation of microsomal drug oxidising enzymes and also interfere with microorganisms of the enteric flora through their antibiotic effects. Over the past 20 years, a number of reports have incriminated macrolides as a potential source of clinically severe drug interactions. However, differences have been found between the various macrolides in this regard and not all macrolides are responsible for drug interactions. With the recent advent of many semisynthetic macrolide antibiotics it is now evident that they may be classified into 3 different groups in causing drug interactions. The first group (e.g. troleandomycin, erythromycins) are those prone to forming nitrosoalkanes and the consequent formation of inactive cytochrome P450-metabolite complexes. The second group (e.g. josamycin, flurithromycin, roxithromycin, clarithromycin, miocamycin and midecamycin) form complexes to a lesser extent and rarely produce drug interactions. The last group (e.g. spiramycin, rokitamycin, dirithromycin and azithromycin) do not inactivate cytochrome P450 and are unable to modify the pharmacokinetics of other compounds. It appears that 2 structural factors are important for a macrolide antibiotic to lead to the induction of cytochrome P450 and the formation in vivo or in vitro of an inhibitory cytochrome P450-iron-nitrosoalkane metabolite complex: the presence in the macrolide molecules of a non-hindered readily accessible N-dimethylamino group and the hydrophobic character of the drug. Troleandomycin ranks first as a potent inhibitor of microsomal liver enzymes, causing a significant decrease of the metabolism of methylprednisolone, theophylline, carbamazepine, phenazone (antipyrine) and triazolam. Troleandomycin can cause ergotism in patients receiving ergot alkaloids and cholestatic jaundice in those taking oral contraceptives. Erythromycin and its different prodrugs appear to be less potent inhibitors of drug metabolism. Case reports and controlled studies have, however, shown that erythromycins may interact with theophylline, carbamazepine, methylprednisolone, warfarin, cyclosporin, triazolam, midazolam, alfentanil, disopyramide and bromocriptine, decreasing drug clearance. The bioavailability of digoxin appears also to be increased by erythromycin in patients excreting high amounts of reduced digoxin metabolites, probably due to destruction of enteric flora responsible for the formation of these compounds. These incriminated macrolide antibiotics should not be administered concomitantly with other drugs known to be affected metabolically by them, or at the very least, combined administration should be carried out only with careful patient monitoring.(ABSTRACT TRUNCATED AT 400 WORDS)

Anti-Bacterial Agents↗
PubMed1992

Teicoplanin--its role as systemic therapy of burn infections and as prophylaxis for orthopaedic surgery. Italian Study Groups for Antimicrobial Prophylaxis in Orthopaedic Surgery and Burns.

Two randomized studies have been initiated to establish the role of teicoplanin as systemic therapy for infections in burns patients and as short-term prophylaxis for orthopaedic implant surgery. Opportunistic micro-organisms causing infections in burn patients are often acquired in hospital. These infections commonly involve Gram-positive organisms which may be resistant to several antibiotics. Teicoplanin, alone and in combination with additional antibacterial drugs, is effective in the treatment of Gram-positive infections of various types. In addition, teicoplanin has proved useful as prophylaxis against infection in orthopaedic surgery. Deep prosthetic infections are very difficult to cure without removing the infected device; the outcome can be devastating, such as total loss of joint function, amputation, and, occasionally, death. Preliminary results from the two studies are encouraging and show that teicoplanin has a role to play both in treatment of infection and as prophylaxis against hospital-acquired infection.

Adult↗
PubMed1991

Chromosomal characterization of methotrexate-resistant human T-lymphoblast leukemia cells (CCRF-CEM) with impaired polyglutamylation.

Two sublines of the human T-lymphoblast leukemia cell line CCRF-CEM, which were resistant to methotrexate (MTX) due to defective MTX polyglutamate synthesis, were karyologically characterized. No statistically significant differences in the modal number of chromosomes were noted in resistant cells (CCRF-CEM/P) as compared to parent cells (91, range, 86-123; and 93, range; 78-103, respectively). Fifteen marker chromosomes were identified and their origins at least partially established. An isochromosome 7q, (marker 13) was present in all MTX-resistant cells but was not found in any sensitive cell karyotype. This marker chromosome may be involved in the emergence of drug-resistant cells from the parental population of CCRF-CEM cells. In all cell lines, chromosomes 8, 9 and 14 appear to be highly unstable and are involved in the genesis of many marker chromosomes. These chromosomes are also implicated in the in vivo genesis of various leukemias and lymphomas, which suggests that both in vivo tumor progression and in vitro cellular adaptation are marked by chromosome mutations that may activate multiple oncogenes.

Cell Line↗
PubMed1991

Systemic absorption of 3H-fenticonazole after vaginal administration of 1 gram in patients.

Fourteen women, five with normal cervicovaginal mucosa (Group 1), five with cervical carcinoma (Group 2) and four with relapsing vulvovaginal candidiasis (Group 3) were enrolled and completed this open clinical trial. Each subject received a single dose of 1.82 +/- 0.3 g on average of vaginal paste (for ovules) containing about 1000 mg of 3H-fenticonazole nitrate (266 microCi). Twelve hours after vaginal administration, the paste was removed by vaginal washing. Blood, urine and stool samples were collected at specified time intervals for five days. Plasma, urine, stools and all used material in contact with the paste were assayed for radioactivity. No measurable levels of radioactivity were detected in plasma of subjects of Groups 1 and 3 while in 4 of the 5 subjects with cervical carcinoma (Group 2) fenticonazole was detected during the 24 h after administration with a peak level at about 8 hours. For a period of 5 days, 0.4-1.5% of the dose on average was recovered from urine, and 0.18-0.32% from feces. Based on the excretion data, the extent of vaginal absorption of fenticonazole nitrate in women with vulvovaginal candidiasis was 1.81 +/- 0.57% of the dose, while in women with normal cervicovaginal mucosa it accounted for 0.58 +/- 0.28% of the administered dose. In patients with cervical carcinoma, absorption was 1.12 +/- 0.53%. The maximum amount absorbed corresponds to an exposure of about 0.4 mg/kg of fenticonazole nitrate (for a subject weighing 50 kg). Consequently, the vaginal administration of one ovule containing 1000 mg of fenticonazole nitrate seems to be devoid of risk for patients.

Absorption↗
PubMed1991

Tissue distribution of cefotetan in patients with Crohn's disease.

Concentrations of cefotetan in the intestinal wall of patients with Crohn's disease were investigated with the method of tissue homogenates with the aim to evaluate the effects of inflammation on tissue distribution. Twenty-four patients who underwent surgery were treated with a 2-gram single dose of cefotetan intravenously before the operation. The mean tissue levels in inflamed intestinal wall were constantly higher than in normal wall, but the difference was statistically significant only in samples taken more than 2 h after cefotetan administration (31.0 +/- 17.8 vs 14.7 +/- 11.4 mg/kg; p less than 0.05). The mean residence time was 284.3 min for inflamed tissue and 123.9 min for normal. The areas under the curve were significantly higher in inflamed wall than in normal, with mean values of 4,789 and 3,020.2 mg/l.h, respectively (p less than 0.05). Inflammation seems to facilitate the penetration of cefotetan into the intestinal wall of patients with Crohn's disease but above all, it increases the mean residence time in inflamed tissue.

Adult↗