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Biomedical subjects

H Giamarellou

Publications and source records attributed to H Giamarellou.

At least 37 records · Page 2Linked to original sources
PubMed2003

Pancreatic concentrations of cefepime in experimental necrotizing pancreatitis.

To evaluate the penetration of cefepime in the inflamed pancreas, three doses of 50 mg/kg were administered intramuscularly at 8-h intervals after induction of acute necrotizing pancreatitis using intraperitoneal injection of DL-ethionine in 35 rabbits and in 33 controls. Animals were sacrificed and concentrations of cefepime were determined by a microbiological assay. Cefepime reached its peak concentrations 60 min after the last drug dose when mean values of 46.05 microg/ml, 22.34 microg/g and 34.74 microg/ml were found in serum, pancreas and bile, respectively, in rabbits with acute necrotizing pancreatitis and 45.19 microg/ml, 12.68 microg/g and 20.77 microg/ml respectively in controls. Tissue/serum ratios of cefepime were 0.48, 0.23, 0.15 and 0.09 at 60, 90, 120 and 180 min, respectively, after the last dose of cefepime in rabbits with acute necrotizing pancreatitis and 0.28, 0.18, 0.16 and 0.16, respectively at 60, 90, 120 and 180 min in controls. It is concluded that the administration of cefepime in rabbits with acute necrotizing pancreatitis resulted in pancreatic tissue levels well above the MIC90s of the common pathogens involved in pancreatic superinfection, so that its administration might be proposed for the therapy of superinfection following acute necrotizing pancreatitis in humans.

Animals↗
PubMed2003

In vitro interaction of colistin and rifampin on multidrug-resistant Pseudomonas aeruginosa.

The administration of colistin is considered as the last alternative for infections by multidrug-resistant isolates of Pseudomonas aeruginosa; however its use is limited due to its considerable toxicity and poor pharmacokinetics. In order to define the in vitro activity of colistin combined with rifampin, 28 isolates resistant to piperacillin, ceftazidime, imipenem, meropenem, ciprofloxacin, amikacin, rifampin and colistin were tested. Seventeen of them that were found by PFGE to be genetically distinct were over time exposed to 2 microg/ml of colistin, to 2 microg/ml of rifampin and to their combination. Applied concentrations were selected to correspond to the mean serum level of the tested antimicrobials. Synergy between colistin and rifampin was found in four (23.5%), six (35.3%), seven (41.7%) and two (11.8%) isolates after 2, 4, 6 and 24 hours of growth, respectively. Bacterial re-growth was detected after 24 hours of exposure to the tested interaction. It is concluded that colistin and rifampin express a considerable in vitro synergistic effect on multidrug-resistant P. aeruginosa. The reported interaction should be tested in animal studies before introduction in clinical practice.

Colistin↗
PubMed2002

Transferable plasmid mediating resistance to multiple antimicrobial agents in Klebsiella pneumoniae isolates in Greece.

OBJECTIVE: To investigate the underlying resistance mechanisms in 10 Klebsiella pneumoniae isolates. METHODS: Ten K. pneumoniae strains according to distinct bacteriocin typing and REP-PCR, were examined for their plasmid content, their ability to transfer their resistance to aminoglycosides and third-generation cephalosporins, and their production of aminoglycoside-modifying enzymes and beta-lactamases. RESULTS: Transfer of resistance to the above-mentioned antibiotics as well as to co-trimoxazole and tetracycline in Escherichia coli strain RC 85 at a frequency of 5-106 was achieved for all strains by conjugation. Similar strains harbor a self-transferable multiresistant plasmid (80 kb) with similar EcoRI and HindIII restriction patterns. This plasmid encodes an extended-spectrum beta-lactamase which confers high-level resistance to third-generation cephalosporins and aztreonam. It produces SHV-5 beta-lactamase, as demonstrated by isoelectric focusing and DNA sequencing. Aminoglycoside resistance was co-transferred, and AAC(6')-I, mediating resistance to gentamicin, tobramycin, netilmicin and amikacin, and AAC(3)-I, mediating resistance to gentamicin and sisomycin, were encoded in all isolates and their transconjugants, while APH(3')-I, mediating resistance to kanamycin and neomycin, was encoded in seven strains. CONCLUSIONS: It appears that a multiresistant transferable plasmid encoding the SHV-5 beta-lactamase, causing unusually high resistance to ceftazidime and aztreonam, and the combination AAC(6')-I + AAC(3)-I of acetylating enzymes causing, also resistance to all clinically available aminoglycosides, is established in K. pneumoniae in Greece.

Anti-Bacterial Agents↗
PubMed2002

Nosocomial cardiac infections.

The most important nosocomial cardiac infections include nosocomial infective endocarditis on native and prosthetic valves, and nosocomial infections related to transvenous permanent pacemakers, implantable cardioverter-defibrillators and left ventricular assist devices. Although representing rare complications, they are of great importance because they are associated with high morbidity and mortality. Most of them are encountered in older-age groups, related to nosocomial invasive procedures performed within the preceding four to eight weeks of hospital admission. Nosocomial bacteraemia associated with infected central intravascular devices, genitourinary or gastrointestinal tract surgery and instrumentation, breaks in sterile surgical techniques at the implantation of prosthetic valves and cardiac devices as well as wound and skin infections, represent the most important risk factors. Staphylococcus aureus in native valve endocarditis and S. epidermidis in the presence of foreign bodies are the main implicated pathogens. However, because of the steeply increasing incidence of candidaemia in tertiary hospitals, nosocomial cardiac infections caused by Candida spp. have also been steadily increasing over the last decades. Diagnosis of nosocomial cardiac infections, particularly in the presence of foreign bodies, is often difficult because of the severity of patients' co-morbid illnesses and the co-existence of several risk factors. Diagnosis should be based on positive blood cultures and transoesophageal echocardiographic findings in febrile high-risk patients. Therapy necessitates a combination of antibiotics and surgical removal of foreign bodies. Prophylaxis should mainly target the prevention and/or appropriate treatment of bacteraemias secondary to infected intravascular devices, as well as application of prophylaxis guidelines whenever invasive hospital-based procedures are performed in high-risk individuals.

Candidiasis↗
PubMed2002

Rapid alterations of serum oxidant and antioxidant status with the intravenous administration of n-6 polyunsaturated fatty acids.

In an attempt to achieve the safe intravenous administration of two n-6 polyunsaturated fatty acids (PUFAs), gamma-linolenic acid (GLA) and arachidonic acid (AA), and to study the subsequent changes on the total oxidant and antioxidant status, various steadily increasing doses of each acid were injected intravenously at different infusion times in 28 male rabbits. Blood samples were collected at 15-min time intervals by the hepatic veins and from the carotid artery; oxidant status was determined by the thiobarbiturate assay and total antioxidant status (TAS) was assessed by a colorimetric assay. Both n-6 PUFAs were administered with safety at a dose of 25 mg/kg within 10 min accompanied by an increase of malonodialdehyde concentrations in the hepatic veins and in the carotid artery 30-45 min, respectively, after the end of the infusion of GLA and/or AA. Similar changes did not occur in red cell membranes after the infusion of AA. TAS presented reciprocal changes to malonodialdehyde production; the main consumption of TAS was observed in all samples 30-60 min after the end of the infusion of n-6 PUFAs. The above-mentioned rapid alterations occurring in both serum oxidant and antioxidant status after GLA might have a future clinical therapeutic significance in conditions like cancer and disseminated infectious diseases.

Animals↗
PubMed2001

Assessment of procalcitonin as a diagnostic marker of underlying infection in patients with febrile neutropenia.

The novel inflammatory marker procalcitonin (PCT) was assessed as an index of infection in patients with febrile neutropenia. Blood samples were obtained from 115 patients with febrile neutropenia for determination of PCT levels before onset of fever and daily until the resolution of fever. The median PCT level on the first day of fever was 8.23 ng/mL in patients with bacteremia, compared with 0.86 ng/mL in patients with localized bacterial infections (P=.017). The median PCT level on the first day of fever was 2.62 ng/mL in patients with severe sepsis, compared with 0.57 ng/mL in patients with clinically localized infections (P<.001). A dramatic decrease in PCT levels was documented after resolution of the infection; PCT levels were elevated when the infection worsened. Pronounced PCT levels were also found in patients with fever of unknown origin who were responding to antimicrobial chemotherapy, compared with those not responding to treatment with antibiotics. PCT levels were particularly elevated in patients with bacteremia and severe sepsis. These findings provide new insight into the application of PCT in clinical trials as a diagnostic tool of the severity of an infection in patients with febrile neutropenia and of the need to change antimicrobial regimen.

Bacteremia↗
PubMed2001

Antipseudomonal antibiotics.

Pseudomonas aeruginosa is responsible for a variety of nosocomial infections associated with high morbidity and mortality, involving the immunocompromised and immunocompetent host. There are several groups of antipseudomonal antibiotics available today: antipseudomonal penicillins (carboxy and ureido penicillins), antipseudomonal cephalosporins, monobactams, quinolones, aminoglycosides, and carbapenems. This article reviews the newer antipseudomonal compounds and focuses on recent and important pieces of information for older compounds. Antibacterial spectrum, with particular emphasis on contemporary resistance mechanisms, and recent global resistance surveillance reports, pharmacokinetics, in vitro combination studies and in vivo interactions, and adverse effects and dosage schedules are described in an effort to approach the clinicians' needs.

Anti-Bacterial Agents↗
PubMed2001

Interactions of colistin and rifampin on multidrug-resistant Acinetobacter baumannii.

The increased incidence of nosocomial infections by multidrug-resistant Acinetobacter spp creates demand on the application of some combinations of older antimicrobials on that species. The in vitro activities of colistin and of rifampin and of their interaction were tested on 39 nosocomial isolates of Acinetobacter baumannii. All isolates were resistant to ampicillin/sulbactam, to 3(rd) and 4(th) generation cephalosporins, to amikacin and to ciprofloxacin. MICs were determined by a microdilution technique and interactive studies between 1x or 4x MIC of colistin and rifampin were performed by the time-kill assay. Rifampin was applied at a concentration of 2 microg/mL which is equal to its mean serum level. All isolates were inhibited by colistin and only 15.2% by rifampin. Synergy between 1x MIC of colistin and rifampin was detected in 15.4% of isolates at 6 h of growth and in 51.3% of isolates at 24 h of growth. Synergy between 4x MIC of colistin and rifampin was detected in 15.4% of isolates at 6 h of growth and in 66.7% of isolates at 24 h of growth. It is concluded that colistin is highly active on multidrug-resistant Acinetobacter spp and its activity on A.baumannii is increased in the presence of rifampin, so that their administration might be proposed for nosocomial infections by these isolates.

Acinetobacter↗
PubMed2001

Infectious complications of febrile leukopenia.

It can be foreseen that in the years to come major improvements in neutropenic host infections will be achieved regarding the exact identification of risk factors, allowing better patient stratification; the application of molecular techniques to recognize pathogens; the development of effective new oral antimicrobials allowing home therapy or abbreviated hospitalization; the development of new antifungals; and the development of new effective immunomodulators and cytokines to ameliorate chemotherapy-induced neutropenia. In the years to come the threat of nosocomial infections unfortunately will not be eliminated, while the development of major new parenteral antibiotics cannot be foreseen. It is therefore the caregiver/physician himself who, by applying rational antibiotic policies and strict handwashing rules, will probably escape, for his neutropenic patient's sake, the imminent threat of multiresistant pathogens.

Anti-Infective Agents↗
PubMed2001

Pharmacokinetics of intravenously administered pefloxacin in the prostate; perspectives for its application in surgical prophylaxis.

In an attempt to define whether intravenously administered pefloxacin might be appropriate for surgical prophylaxis in prostatectomy, 50 patients undergoing transvesical prostatectomy for benign prostate hyperplasia were given a single intravenous dose of 800 mg; surgery was then performed after 2, 4, 6, 8 or 10 h. Concentrations of pefloxacin were determined in serum and in both the centre and periphery of the prostate adenoma using a microbiological plate assay. Elevated concentrations of pefloxacin were found in the adenoma from 2 h onwards. The central and peripheral concentrations were similar and had a mean value of 4.39 microg/g of tissue. These concentrations were similar to those achieved in serum. Although concentrations of pefloxacin were not determined separately in the intercellular, interstitial or excreted fluid, the tissue levels found were well above the MICs of pefloxacin for the bacteria commonly causing acute and chronic prostatitis. These data suggest the intravenous administration of pefloxacin to be a satisfactory alternative for the surgical prophylaxis before prostatectomy as well as in the therapy of acute prostatitis.

Aged↗
PubMed2001

Classification of oral cephalosporins. A matter for debate.

There are many cephalosporins available and various ways of classifying them for clinical use. Oral cephalosporins probably need a classification of their own. This informal discussion was prompted by the appearance of the recommendations of an expert committee of the Paul Ehrlich Gesellschaft. The views of several other commentators are included. There is considerable individual variation in preference for different styles of classification depending on what the classification is for.

Administration, Oral↗
PubMed2001

Vancomycin levels in human aqueous humour after intravenous and subconjunctival administration.

The purpose of the present study was to evaluate the level of vancomycin in human aqueous humour after intravenous (i.v.) and subconjunctival administration. One hundred patients scheduled to undergo cataract extraction participated in the study. Fifty-three of them received 20 mg vancomycin subconjunctivally and 47 received two doses of vancomycin i.v. (1 g b.i.d.). Specimens of aqueous humour from the first group were collected 1, 2, 2.5, 3, 3.5, 5, 6, 7, and 8 h after the subconjunctival injection. In the second group, specimens of blood and aqueous humour were collected 1, 2, 4, 6, 8, 10, and 12 h after the end of infusion of the second dose of the antibiotic. The levels of vancomycin were determined by fluorescent polarization immunoassay. In the first group peak levels of 24.82+/-3.55 microg/ml were achieved in aqueous humour at 5 h, whereas in the second group peak levels of 1.42+/-0.47 microg/ml were detected at 6 h. The latter levels, although higher than the MICs of most of the Gram-positive pathogens causing eye infections, are inadequate for the treatment of infections in vivo. These results support the need for subconjunctival instead of i.v. administration of vancomycin in order to achieve therapeutic levels of the drug in human aqueous humour or for prophylactic use whenever indicated.

Administration, Topical↗
PubMed2001

Pharmacokinetics of fluoroquinolones in uncompensated cirrhosis: the significance of penetration in the ascitic fluid.

In order to study the penetration of routinely used fluoroquinolones in the ascitic fluid of patients with uncompensated cirrhosis the following doses were given. Three patients received three consecutive iv doses of 200 mg of ciprofloxacin, six patients, three consecutive iv doses of 300 mg of ciprofloxacin, seven others, three consecutive iv doses of 400 mg of pefloxacin and six, three consecutive iv doses of 400 mg of ofloxacin. Drug levels in serum and the ascitic fluid were monitored at regular time intervals. Peak levels of the 200 mg dose of ciprofloxacin, of the 300 mg dose of ciprofloxacin, of pefloxacin and of ofloxacin in serum were 2.11,2.45,9.21 and 8.86 microg/ml, respectively and in the ascitic fluid 0.67, 0.45, 6.09 and 5.83 microg/ml, respectively T(1/2) was 3.19+/-0.73, 3.55+/-1.68, 15.60+/-12.40 and 9.45+/-3.14 h, respectively with AUC of 3.62+/-4.02, 7.39+/-4.70, 137.85+/-63.96 and 119.8+/-16.83 mg/l h. Urinary excretion of ciprofloxacin and of ofloxacin was similar to healthy individuals but pefloxacin showed a mean urinary excretion of 30.11%. It is concluded that pefloxacin and ofloxacin at the administered iv doses result in serum and ascitic fluid levels above the MICs of the common pathogens causing spontaneous bacterial peritonitis and that they should be administered to cirrhotic patients in dosing regimens similar to those in patients with normal hepatic function. The use of ciprofloxacin requires further studies to define the appropriate dose.

Aged↗
PubMed2001

Case report. Successful treatment of two cases of post-surgical sternal osteomyelitis, due to Candida krusei and Candida albicans, respectively, with high doses of triazoles (fluconazole, itraconazole).

Two female patients, aged 75 and 59 years, respectively, with candidal sternal osteomyelitis were successfully treated by the administration of triazoles. Both had developed post-operative wound infection after sternotomy for coronary artery by-pass grafting. Sternal osteomyelitis was confirmed by bone scans with technetium 99Tc and gallium 67Ga. The cultures, from the pus draining at the site of the sternotomy scar, grew Candida krusei in the first case. The fistula closed after a 9-week course of itraconazole therapy (800 mg daily, followed by 600 mg daily) and the patient completed a 6-month period of therapy. The second patient had underlying diabetes mellitus. Post-operatively she developed two fistulae draining pus on the sternum. The pus cultures grew C. albicans. Initial treatment with oral fluconazole (400 mg daily) failed. Subsequent treatment with liposomal amphotericin B also failed. A dramatic improvement was noted when the patient received high doses of fluconazole (800 mg daily). The fistulae gradually closed after 1 month. Oral fluconazole was continued for 6 months. The cure was confirmed by bone scans. Three years later, both patients remained well.

Aged↗
PubMed2001

The effect of acetazolamide on the kinetics of four newer beta-lactams in the aqueous humor.

OBJECTIVE: To evaluate whether the effect of acetazolamide on piperacillin's aqueous humor concentrations observed in animals exists also in humans for ceftazidime, cefotaxime, ceftriaxone and aztreonam. METHODS: One hundred and eighty-eight patients undergoing eye cataract surgery were randomly allocated to receive intravenous ceftazidime, cefotaxime, aztreonam or ceftriaxone with (subgroup A) or without (subgroup B) concomitant oral administration of acetazolamide. Antibiotic concentrations in serum and the aqueous humor, simultaneously sampled during the operation, were measured using an agar well diffusion technique, and the ratios of the concentrations of aqueous humor to serum were calculated and compared. Statistical analysis was performed by using the paired t-test. RESULTS: Mean aqueous humor ceftazidime concentrations at 2, 4 and 6 h were 24.65, 16.4 and 8.6 mg/L (subgroup A), and 4.26, 8.66 and 5.61 mg/L (subgroup B). Corresponding concentrations of cefotaxime were 1.75, 1.0 and 0.77 mg/L (subgroup A), and 1.11, 0.81 and 0.58 mg/L (subgroup B), and of aztreonam 6.9, 5.84 and 3.61 mg/L (subgroup A), and 3.38, 2.57 and 1.48 mg/L (subgroup B). Ceftriaxone concentrations at 2, 4, 6 and 12 h were 1.78, 1.49, 1.57 and 1.41 mg/L (subgroup A), and 1.35, 0.95, 1.08 and 0.85 mg/L (subgroup B). The differences in aqueous humor concentrations when acetazolamide was administered were statistically significant (P < 0.05), with the exception of ceftazidime 6 h, cefotaxime 6 h and ceftriaxone 2 h. CONCLUSIONS: Although acetazolamide resulted in statistically significant increases in the aqueous humor concentrations of all the antibiotics tested, this effect was most marked for ceftazidime.

Acetazolamide↗
PubMed2001

Pharmacokinetics of clarithromycin in the prostate: implications for the treatment of chronic abacterial prostatitis.

PURPOSE: We studied the pharmacokinetics of orally administered clarithromycin in prostatic tissue to define its role in the treatment of chronic abacterial prostatitis caused by intracellular pathogens. MATERIALS AND METHODS: A total of 45 men receiving 3 oral doses of 750 mg. clarithromycin at 12-hour intervals underwent suprapubic prostatectomy for benign prostate hyperplasia 4, 5, 6 and 7 hours after the last drug dose in 13, 12, 10 and 10 patients, respectively. Concentrations were determined in the prostate tissue and in plasma by an agar diffusion assay. RESULTS: A mean peak level of clarithromycin of 3.22 and 3.08 microg./gm. of tissue was achieved 4 hours after the third drug dose at the center and periphery of the adenoma, respectively. Tissue levels remained statistically superior to plasma levels at all intervals. CONCLUSIONS: The oral administration of clarithromycin achieved a prostate level much higher than the minimal inhibitory concentration of clarithromycin for the intracellular pathogens of chronic prostatitis. Thus, clarithromycin may be considered for treating chronic abacterial prostatitis.

Administration, Oral↗
PubMed2001

Evidence of less severe aortic valve destruction after treatment of experimental staphylococcal endocarditis with vancomycin and dexamethasone.

The beneficial effects of therapy combining an antibiotic and dexamethasone have been reported in human studies on meningitis and in experimental studies on septic arthritis, nephritis, and endophthalmitis. Since most patients with staphylococcal endocarditis need a combination of medical and surgical treatment, the purpose of this study was to determine whether the addition of dexamethasone to vancomycin has any beneficial effect regarding the degree of valve tissue damage or the course of experimental aortic valve endocarditis caused by a methicillin-resistant strain of Staphylococcus aureus. Rabbits with catheter-induced aortic valve vegetations were randomly assigned to a control group and to groups receiving dexamethasone (0.5 mg/kg of body weight, intravenously [i.v.], twice a day [b.i.d]), vancomycin (30 mg/kg, i.v., b.i.d), or dexamethasone plus vancomycin, for a total of 10 doses (two doses per day for 5 days). The severity of valve tissue damage was significantly less in groups receiving vancomycin plus dexamethasone compared with that of the group receiving vancomycin alone (P < 0.001). The severity of tissue damage was inversely correlated with the mean polymorphonuclear leukocyte number in valve tissue. No statistically significant differences were observed between the vancomycin-treated group and the vancomycin-plus-dexamethasone-treated group in survival, blood culture sterilization rate, or reduction of the microbial burden (in CFU per gram) in valvular tissue. In conclusion, treatment with a combination of vancomycin and dexamethasone for 5 days reduces the severity of valve tissue damage in experimental staphylococcal aortic valve endocarditis. These findings could have significant implications in the treatment of staphylococcal endocarditis and deserve further confirmation in clinical trials.

Animals↗