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Biomedical subjects

P Periti

Publications and source records attributed to P Periti.

At least 37 records · Page 2Linked to original sources
PubMed1998

Increased burn patient survival with once-a-day high dose teicoplanin and netilmicin. An Italian multicenter study.

This is the final report of a large, controlled, multicenter Italian study on immuno- and chemotherapy in adult patients with burns affecting 20 to 95% of total body surface area (mean 35%). The antibiotic treatment of burn patients consisted of topical silver sulfadiazine, short-term antimicrobial chemoprophylaxis with pefloxacin (800 mg i.v. qd) for the first 4 days and polychemotherapy with teicoplanin (800 mg i.v. qd) together with netilmicin (300 mg i.m. qd) in one or more cycles of 5-12 days. At random, half of the patients received thymostimulin, 70 mg i.m. qd for the first month and every other day thereafter. The analysis at completion of 634 valid cases showed that when the results are stratified by means of the Roi risk index, 396 of the 530 patients who contracted wound infection (84%) after chemoprophylaxis were in the first three categories and a mean of 95% survived. Of the remaining 134 patients (Roi index 4-5) only 50% survived. There was no difference in survival of the immunotherapy group in comparison with the parallel group without thymostimulin. The short-term antimicrobial prophylaxis prevented wound infection in only 104 of 634 patients (16%) and they were at low risk (84% Roi index 1). Of the bacterial pathogens involved in septic complications Staphylococcus aureus and Pseudomonas aeruginosa were prevalent (86%): eradication was achieved in 43% of patients and clinical cure or improvement were seen with combination chemotherapy in 64% of all patients, mainly with only one treatment cycle. This value increased to 79% for the 395 protocol-complying patients and went down to 20% in the 135 non-compliers. The total survival of complier and non-complier patients was 447 of the 530 valid patients (84%). The overall mortality of the 634 evaluable patients was 13.1%, ranging from less than 2% to 68%. Burn mortality was directly proportional to the percentage of burned body surface area, to increasing age and other variables of the Roi index, a 50% mortality being associated with a 72.5% total body surface area burned. Normoergic burn patients had a mortality rate of 9.1% versus 35.7% in anergic patients.

Adolescent↗
PubMed1998

Selecting antibacterial agents for the control of surgical infection: mini-review.

An analysis of the recent literature on the control of surgical infections confirms the role of antimicrobial agents which guarantee valid perioperative antisepsis in both clean and clean-contaminated surgery. Current chemotherapy is able to check serious postoperative infectious complications by reducing the risk of septic shock with use of a glycopeptide-aminoglycoside-betalactam combination together with anti-inflammatory drugs.

Aminoglycosides↗
PubMed1998

Immunopharmacology of oral betalactams.

Among the oral beta-lactam antibiotics only cefaclor has demonstrated a consistent in vitro and in vivo immunopharmacological effect which favors phagocytic chemotaxis and antimicrobial potential by inducing a T-helper 1 or pro-inflammatory response. Together with cefpimizole, cefaclor significantly reduces the minimum bactericidal concentration (MBC) against some bacterial species when cultured together with a suspension of polymorphonuclear leukocytes, as opposed to some other oral beta-lactams, co-amoxiclav and cefixime, which do not show this effect. The pro-inflammatory component of cefaclor's activity explains the clinical success of this antibiotic in a high percentage of cases, even when laboratory tests indicate in vitro resistance by the pathogen.

Adjuvants, Immunologic↗
PubMed1998

Antibiotic-induced release of bacterial cell wall components in the pathogenesis of sepsis and septic shock: a review.

This article reviews the new criteria for selecting the proper antimicrobial agent and dosage regimen for standard treatment of severe sepsis, with the intention of preventing septic shock. After introducing new concepts on the pathogenesis of sepsis and septic shock, the authors analyze the parameters of betalactam antibacterial activity, the antibiotic-induced release of bacterial endotoxin and the interrelationships between pharmacokinetics and pharmacodynamics of antibiotics in the search for an optimum dosage regimen of antimicrobial mono- or polytherapy for severely ill septic patients admitted to the intensive care unit.

Anti-Bacterial Agents↗
PubMed1997

Methicillin-resistant staphylococci in clean surgery. Is there a role for prophylaxis?

The incidence of infection in clean surgery (i.e. surgery with no major contamination of the operative site) should be less than 2%, although the incidence of postoperative infections can be higher in patients with various risk factors (namely insertion of foreign bodies, a compromised immune status or prolonged duration of surgery). Although antibiotic prophylaxis has been shown to reduce the incidence of postoperative infections in clean surgery, there is still no consensus regarding its use in this area. However, for clean surgical procedures that involve implantation of foreign material, grafts or prosthetic devices, prophylaxis is well accepted and justifiable, since this practice is indicated when the benefits exceed the expected risks. Staphylococcus aureus and coagulase-negative staphylococci are responsible for 70 to 90% of wound infections in this type of surgery. First and second generation cephalosporins are considered the drugs of choice for surgical prophylaxis. Cefazolin and other cephalosporins have good tissue penetration but poor coverage against methicillin-resistant staphylococci. The frequency with which methicillin-resistant staphylococci have been recovered in nosocomial infections has increased steadily during recent years. This provides a rationale for the use of alternative antibiotics, such as the glycopeptides (vancomycin and teicoplanin), for prophylaxis in clean surgery in hospitals where the prevalence of methicillin-resistant staphylococci is high. The effectiveness and tolerability of teicoplanin as prophylaxis for orthopaedic surgery involving joint replacement were analysed in 4 randomised controlled trials. Two compared teicoplanin with cefamandole, while the others compared teicoplanin with either cefuroxime or cefazolin. The overall early wound infection rates (within 3 months) in these studies were 1.1% for teicoplanin and 1.7% for the comparator cephalosporin. The overall late infection rate was 0.2% for both treatment groups. Adverse events were attributed to the drug in 1% of patients in both treatment groups. Therefore, on the basis of these trials, single dose teicoplanin is as efficacious and as well tolerated as multiple dose cephalosporin regimens for prophylaxis in prosthetic joint surgery.

Anti-Bacterial Agents↗
PubMed1996

Clinical pharmacokinetics of meropenem after the first and tenth intramuscular administration.

We investigated the pharmacokinetics of meropenem after the first and tenth i.m. administration in patients with respiratory tract infections. Ten patients (mean age 63.8 +/- 5.2 years) received meropenem 500 mg tds for at least ten doses, and plasma and urine antibiotic concentrations were determined by microbiological assay. After the first injection a mean peak plasma concentration of 7.93 +/- 1.29 mg/L was observed at 1 h. Trough levels at 8 h (0.29 +/- 0.16 mg/L) were detectable in five of ten treated patients. The mean terminal half-life was 1.08 +/- 0.2 h with an area under the curve (AUC) value of 23.8 +/- 4.59 mg/L.h, and a cumulative urinary recovery at 8 h of 48.43 +/- 3.12%. There was no evidence of change in the pharmacokinetics of meropenem after repeated i.m. administration, though the mean peak plasma concentration and AUC value were slightly increased. The accumulation ratio (assessed using AUC values) was 1.18 +/- 0.19 after multiple doses and was considered to be of little kinetic and clinical importance. Moreover, many of the trough concentrations of meropenem were below the limit of detection of the assay. After i.m. administration meropenem concentrations exceeded 0.5 mg/L for longer than previously described following i.v. infusion. No adverse events were reported.

Aged↗
PubMed1996

[Tobramycin--clinical pharmacology and chemotherapy].

Aminoglycosides are potent water-soluble antibiotics, with peak concentration-dependent bactericidal activity against many pathogenic aerobic Gram-negative bacilli and Staphylococcus aureus: they exhibit enduring antibacterial activity many hours after tissue concentrations become negligible and appreciation of this postantibiotic effect is leading to replacement of conventional multiple daily doses by large once-daily doses. Cotreatment with betalactams is commonly employed in order to exploit a synergism between these antimicrobial agents, particularly in severe Gram-negative sepsis. Resistance to aminoglycosides may be observed at several levels and is generally high when due to the acquisition of aminoglycoside modifying enzymes which may be plasmid-borne or transferred by transposable elements. Tobramycin is more effective than gentamicin and the other aminoglycosides against Pseudomonas aeruginosa and is less nephrotoxic than gentamicin. Higher serum tobramycin concentrations at the peak are associated with a longer postantibiotic effect and increased bactericidal activity. A longer dosage interval may decrease the risk of nephrotoxicity because higher transient serum aminoglycoside levels appear to be less nephrotoxic than lower but more persistent serum concentrations. Once-daily administration may also reduce the risk of ototoxicity through a similar mechanism. In a multicenter Italian study of 104 adult patients with severe bacterial lower respiratory tract infections, the safety and efficacy of a regimen of high dose, once-daily tobramycin alone or in combination with antipseudomonas betalactams was assessed. The overall bacteriological response was an elimination of the original pathogen in 70% of the patients while the clinical response mirrored the bacteriological results with a successful clinical outcome in 78% of patients. Adverse experiences were, in general, few and mild without oto- or nephrotoxicity. The once-daily, high dose regimen of tobramycin proved to be a safe and efficacious therapy for severe lower respiratory tract infections in adult patients.

Anti-Bacterial Agents↗
PubMed1995

Brodimoprim, a new bacterial dihydrofolate reductase inhibitor: a minireview.

This brief review article synthesizes the principal literature regarding the clinical status of co-trimoxazole compared to monotherapy with one of the two diaminopyrimidines available commercially: trimethoprim or brodimoprim. Both these inhibitors of bacterial dihydrofolate reductase compare favorably to co-trimoxazole as antimicrobial chemotherapy. Brodimoprim is characterized by its advantageous pharmacokinetics in comparison to both co-trimoxazole and trimethoprim.

Anti-Bacterial Agents↗
PubMed1995

Preclinical and clinical evaluation of once-daily aminoglycoside chemotherapy.

The rationale for and effectiveness of extended dosage intervals for aminoglycosides are reviewed. Aminoglycoside antibiotics have a prolonged postantibiotic effect against a variety of common Gram-negative and Gram-positive organisms: higher serum aminoglycoside levels are associated with a longer postantibiotic effect and increased bactericidal activity. Moreover once daily aminoglycoside administration may reduce the potential for adaptive postexposure resistance by allowing less contact time between bacteria and antibiotic. A longer dosage interval may decrease the risk of nephro- and ototoxicity. At least 33 published clinical trials suggest that once-daily administration of aminoglycosides and conventional regimens involving shorter dosage intervals are equally effective in patients with normal renal function and Gram-negative infections: besides, once-daily administration may reduce the frequency of aminoglycoside toxicity or delay it.

Aminoglycosides↗
PubMed1995

Tissue penetration and pulmonary disposition of tobramycin.

The pharmacokinetics of tobramycin, including the penetration into suction blister fluid (SBF), has been investigated in 12 patients with a mean age of 69.8 +/- 4.6 yrs, after a single i.m. administration of either 150 or 300 mg. Tobramycin demonstrated a concentration-independent pharmacokinetics and a high diffusion into the extravascular compartment with a penetration index (obtained by the SBF and serum AUC ratio) of 135% with no significant differences between the two groups of patients. Tobramycin was also administered as a single or multiple i.m. dose of 300 mg in 10 intensive care patients undergoing fiberoptic bronchoscopy for diagnostic purposes. The aminoglycoside mean concentration 6h after the single or last administration ranged from 5.3 to 5.5 mg/l and from 3.0 to 3.3 mg/l in alveolar lining fluid (ALF) and macrophages (AM), respectively, thus demonstrating that the once-daily dosage schedule leads to high and persistent levels in the bronchial alveolar tree, exceeding the minimum inhibitory concentrations in vitro for susceptible respiratory pathogens.

Adolescent↗
PubMed1995

Once-daily tobramycin therapy in lower respiratory tract infections.

In a multicenter Italian study of 104 adult patients with severe bacterial lower respiratory tract infections, the safety and efficacy of a regimen of high dose, once-daily tobramycin alone or in combination with antipseudomonas betalactams was assessed. The overall bacteriological response was an elimination of the original pathogen in 70% of the patients while the overall clinical response mirrored the bacteriological results with a successful clinical outcome in 78% of patients. Adverse experiences were, in general, few and mild without oto- or nephrotoxicity. The once-daily, high dose regimen of tobramycin proved to be a safe and efficacious therapy for severe lower respiratory tract infections in adult patients.

Adult↗
PubMed1995

Pharmacoeconomic evaluation of once-daily aminoglycoside treatment.

A special topic in pharmacoeconomics concerns antimicrobial therapy. The cost of antimicrobial therapy and an economic evaluation of aminoglycoside antibiotics in the last 30 years are reviewed. Some innovative approaches have been found to be effective in the control of the use of aminoglycosides and those are: 1) selecting the appropriate aminoglycoside, 2) therapeutic drug monitoring and, 3) once-daily administration. The practical advantages of once-daily aminoglycoside dosing are discussed and the conclusion is that combination therapy continues to be a mainstay in several serious Gram-negative infections. Concerns about breakthrough infection with extended aminoglycoside dosing intervals can be resolved by combination with a betalactam antibiotic. The lower costs associated with once-daily aminoglycoside dosing are the consequence of a straightforward dosage calculation, a guaranteed peak serum concentration in the therapeutic range, potential reduction in treatment period, easier quality control of preparation and administration, decreased personnel time, and fewer assays. However, some practical considerations remain unanswered.

Aminoglycosides↗
PubMed1995

Survival and therapy of burn patients at the threshold of the twenty-first century: a review.

This review summarizes the progress achieved in care of burned patients over the last half century by analyzing the most significant results published between 1949 and 1995. Improved survival has paralleled the development of new antibiotics as well as major advances in resuscitation, nutritional support, immunomodulating agents, surgical techniques and wound care. Today the average burn size associated with a 50% mortality breakpoint is about 70% of the total body surface area--a notable increase over figures from the past.

Adult↗