Search PubMed⌕ Search

Biomedical subjects

H Giamarellou

Publications and source records attributed to H Giamarellou.

At least 55 records · Page 3Linked to original sources
PubMed2001

In vitro activities of ertapenem (MK-0826) against recent clinical bacteria collected in Europe and Australia.

Ertapenem (MK-0826, L-749,345) is a 1-beta-methyl carbapenem with a long serum half-life. Its in vitro activity was determined by broth microdilution against 3,478 bacteria from 12 centers in Europe and Australia, with imipenem, cefepime, ceftriaxone, and piperacillin-tazobactam used as comparators. Ertapenem was the most active agent tested against members of the family Enterobacteriaceae, with MICs at which 90% of isolates are inhibited (MIC(90)s) of < or =1 microg/ml for all species. Ertapenem also was more active than imipenem against fastidious gram-negative bacteria and Moraxella spp.; on the other hand, ertapenem was slightly less active than imipenem against streptococci, methicillin-susceptible staphylococci, and anaerobes, but its MIC(90)s for these groups remained < or =0.5 microg/ml. Acinetobacter spp. and Pseudomonas aeruginosa were also much less susceptible to ertapenem than imipenem, and most Enterococcus faecalis strains were resistant. Ertapenem resistance, based on a provisional NCCLS MIC breakpoint of > or =16 microg/ml, was seen in only 3 of 1,611 strains of the family Enterobacteriaceae tested, all of them Enterobacter aerogenes. Resistance was also seen in 2 of 135 anaerobes, comprising 1 Bacteroides fragilis strain and 1 Clostridium difficile strain. Ertapenem breakpoints for streptococci have not been established, but an unofficial susceptibility breakpoint of < or =2 microg/ml was adopted for clinical trials to generate corresponding clinical response data for isolates for which MICs were as high as 2 microg/ml. Of 234 Streptococcus pneumoniae strains tested, 2 required ertapenem MICs of 2 microg/ml and one required an MIC of 4 microg/ml, among 67 non-Streptococcus pyogenes, non-Streptococcus pneumoniae streptococci, single isolates required ertapenem MICs of 2 and 16 microg/ml. These streptococci also had diminished susceptibilities to other beta-lactams, including imipenem as well as ertapenem. The Etest and disk diffusion gave susceptibility test results in good agreement with those of the broth microdilution method for ertapenem.

Anti-Bacterial Agents↗
PubMed2000

In-vitro activity of FK 037 (Cefoselis), a novel 4(th) generation cephalosporin, compared to cefepime and cefpirome on nosocomial staphylococci and gram-negative isolates.

The novel 4(th) generation cephalosporin FK037 was in vitro compared to cefepime and cefpirome on 563 multiresistant nosocomial isolates including methicillin-susceptible (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA). Their time-kill effect was studied on MSSA, Escherichia coli, Klebsiella pneumoniae, and isolates of Enterobacter cross-resistant to cefotaxime, ceftriaxone, and to ceftazidime, their interaction with amikacin being also evaluated on the latter isolates. Results revealed that FK037 possessed a superior antistaphylococcal activity on MSSA isolates to both other compounds being however equal active to cefepime and cefpirome on multiresistant enterobacteriaceae. Synergy was documented between 4(th) generation cephalosporins and amikacin on K. pneumoniae and on Enterobacter spp. cross-resistant to 3(rd) generation cephalosporins. In the latter species 4(th) generation cephalosporins remained inactive. The presented results support the need of clinical studies with FK037 as monotherapy for nosocomial infections based on the local surveillance data of the level of antimicrobial resistance of each hospital.

Acinetobacter↗
PubMed2000

Therapeutic guidelines for Pseudomonas aeruginosa infections.

Pseudomonas aeruginosa nowadays is encountered among the leading pathogen in (i) ICU pneumonia; (ii) nosocomial bacteremia and AIDS primary bacteremia; (iii) iv drug users endocarditis; (iv) exacerbations of cystis fibrosis; (v) malignant external otitis and 'swimmers's ear', and (vi) contact lenses keratitis and traumatic endophthalmitis. The most vulnerable nosocomial hosts are the neutropenics and the mechanically ventilated patients in whom mortality rate exceeds 30%. Virulence of P. aeruginosa is attributed to the elaboration of various enzymes and toxins. There is also worldwide emergence of multiresistant phenotypes to antipseudomonal antibiotics. Therapeutic guidelines should therefore be based on (i) continuous resistance surveillance; (ii) in vitro synergistic interactions of antibacterial agents; (iii) pharmacodynamic properties of antibiotics interpreted by optimal dosing and appropriate frequency of administration; and (iv) current information on the necessity for combination therapy using an aminoglycoside.

Anti-Bacterial Agents↗
PubMed2000

Anaerobic infection therapy.

Anaerobes are involved mainly in abdominal surgical infections and the Bacteroides fragilis group is still predominant in such infections. By definition surgery itself plays the major role in therapy while antibiotics have an adjunctive role. Depending on the source of the infection, several combinations of either an older cephalosporin for community acquired infections or a more advanced cephalosporin, an aminoglycoside, aztreonam or a quinolone with metronidazole or clindamycin for nosocomial infections, are acceptable therapeutic regimens. Cefoxitin, cefotetan, carbapenems and the inhibitors may also be used as monotherapy. However whenever selecting an antibiotic to combat anaerobes the following points should be seriously considered. The value of anaerobic cultures which should always be obtained in order to be used for local resistance surveillance. There is a lack of important newer antimicrobials active against anaerobes. Studies of newer antibiotics generally exclude critically ill patients and are chiefly made up of appendicitis cases which by definition end up with >90% cure rate. The importance of hyperbaric oxygen in selected cases should be considered.

Bacteria, Anaerobic↗
PubMed2000

Treatment of experimental osteomyelitis caused by methicillin-resistant Staphylococcus aureus with a biodegradable system of lactic acid polymer releasing pefloxacin.

A novel biodegradable system of D-,L-dilactide delivering pefloxacin was implanted in 104 rabbits with experimental osteomyelitis caused by methicillin-resistant Staphylococcus aureus (MRSA), 26 serving as controls. Animals were killed on each third day and viable bacterial counts and levels of pefloxacin in bone tissue were determined. A 99. 9% decrease in viable count of bacteria was achieved by day 12 and complete bacterial eradication on day 33. Pefloxacin was released gradually, reaching its peak on day 15 at levels 100 times the MIC of pefloxacin for MRSA. The biodegradable system described may have a future role in the therapeutic approach to osteomyelitis.

Animals↗
PubMed2000

Monotherapy with intravenous followed by oral high-dose ciprofloxacin versus combination therapy with ceftazidime plus amikacin as initial empiric therapy for granulocytopenic patients with fever.

The aim of the present study was to obtain clinical experience with the use of high-dose ciprofloxacin as monotherapy for the treatment of febrile neutropenia episodes (granulocyte count, <500/mm(3)) compared to a standard regimen and to clarify whether ciprofloxacin administration may be switched to the oral route. In a prospective randomized study ciprofloxacin was given at 400 mg three times a day (t.i.d.) for at least 72 h followed by oral administration at 750 mg twice a day (b.i.d). That regimen was compared with ceftazidime given intravenously at 2 g t.i.d. plus amikacin given intravenously at 500 mg b.i.d. The frequency of successful clinical response without modification at the end of therapy was almost identical for ciprofloxacin (50% [62 of 124 patients]) compared with that for ceftazidime plus amikacin (50.8% [62 of 122 patients]) in an intent-to-treat analysis; the frequencies were 48.3% (57 of 118 patients) versus 49.6% (56 of 113 patients), respectively, in a per-protocol analysis (P values for one-sided equivalence, 0.0485 and 0.0516, respectively; delta = 10%), with no significant differences among patients with bacteremia and other microbiologically or clinically documented infections and fever of unknown origin. For 82 (66.1%) patients, it was possible to switch from parenteral ciprofloxacin to the oral ciprofloxacin, and the response was successful for 61 (74.4%) patients. The efficacies of the regimens against streptococcal bacteremias were 16.6% (one of six patients) for the ciprofloxacin group and 33.3% (one of three patients) for the combination group (it was not statistically significant), with one breakthrough streptococcal bacteremia observed among the ciprofloxacin-treated patients. Adverse events were mostly self-limited and were observed in 27 (20.6%) ciprofloxacin-treated patients and 26 (19.7%) patients who were receiving the combination. This study demonstrates that high-dose ciprofloxacin given intravenously for at least 3 days and then by the oral route is therapeutically equivalent to the routine regimen of intraveneous ceftazidime plus amikacin even in febrile patients with severe neutropenia (polymorphonuclear leukocyte count, <100 mm(3)). However, it is very important that before an empirical therapy is chosen each hospital determine bacteriologic predominance and perform resistance surveillance.

Administration, Oral↗
PubMed2000

Single-oral-dose azithromycin prophylaxis against experimental streptococcal or staphylococcal aortic valve endocarditis.

Azithromycin and ampicillin protected 94 and 72% of animals challenged with Streptococcus oralis, respectively (P = 0.177), while azithromycin and vancomycin protected 59 and 94% of the methicillin-resistant Staphylococcus aureus (MRSA)-challenged animals, respectively (P = 0.018). Azithromycin is effective in preventing experimental streptococcal endocarditis, but against MRSA it is less effective than vancomycin.

Administration, Oral↗
PubMed2000

Impact of n-6 polyunsaturated fatty acids on growth of multidrug-resistant Pseudomonas aeruginosa: interactions with amikacin and ceftazidime.

Twenty-six multidrug-resistant Pseudomonas aeruginosa isolates were exposed over time to 300 microg of gamma-linolenic acid or arachidonic acid per ml or to the combination of both acids at 150 microg/ml each with ceftazidime and amikacin with or without albumin to observe the in vitro interactions of the antibiotics. Antibiotics and albumin were applied at their levels found in serum. Synergy between acids and antibiotics was found against 13 isolates, and it was expressed after 5 h of growth in the presence of albumin. The results indicate that further application in experimental infection models is merited.

Amikacin↗
PubMed2000

Successful trovafloxacin prophylaxis against experimental streptococcal aortic valve endocarditis.

Single-dose trovafloxacin (15 mg/kg given intravenously [i.v.]) and ampicillin (40 mg/kg given i.v.) protected 38 and 33% of animals challenged with an ampicillin-tolerant strain of Streptococcus oralis, respectively. As a double-dose regimen, trovafloxacin afforded total protection (100%; P < 0.001 versus controls). Trovafloxacin is the first fluoroquinolone effective in preventing experimental streptococcal endocarditis.

Ampicillin↗
PubMed1999

Sitafloxacin (DU-6859a) and trovafloxacin: postantibiotic effect and in vitro interactions with rifampin on methicillin-resistant Staphylococcus aureus.

Sitafloxacin (DU-6859a) and trovafloxacin are novel quinolones potent on methicillin-resistant Staphylococcus aureus (MRSA) that are designed for once daily administration. In order to define the adequacy of the above regimen for the therapy of infections by multiple drug-resistant MRSA, their postantibiotic effect (PAE), their bactericidal activity, and their interactions with rifampin were determined on 14 MRSA isolates resistant to both ciprofloxacin and rifampin. PAE was defined after 1-h exposure to 1x, 4x, and 10x MIC and the killing effect after exposure to 1x and 4x MIC. Rifampin was applied for interactive studies at a concentration of 2 micrograms/mL, which is equal to its mean serum level. Median PAEs produced by 1x, 4x, and 10x MIC of sitafloxacin were 1.39, 3.75, and 6.61 h respectively, and by 1x, 4x, and 10x MIC of trovafloxacin 0.87, 2.07, and 2.23 h respectively. PAEs achieved by sitafloxacin were statistically shown to be longer than those achieved by trovafloxacin; PAEs achieved by a concentration of 10x MIC of each quinolone did not differ significantly from those achieved by a concentration of 4x MIC. Both the 4x and 10x MIC concentrations produced a more prolonged PAE than the 1x MIC concentration. A rapid bactericidal activity was expressed over the first 6 h of growth by each quinolone involving 80% of isolates enhanced in some isolates by their interaction with rifampin. The above findings revealed an extended PAE and a rapid killing effect of both sitafloxacin and trovafloxacin on MRSA resistant to ciprofloxacin and to rifampin, thus supporting their once daily administration in the therapy of infections by multiple drug-resistant MRSA. However little in vitro benefit is derived by their interaction with rifampin.

Anti-Infective Agents↗
PubMed1999

Impact of cefuroxime administration on endotoxin (LPS) and tumour necrosis factor-alpha (TNFalpha) blood levels in patients suffering from acute pyelonephritis: a preliminary report.

It has been suggested that treatment of systemic infections caused by Gram-negative bacteria with beta-lactam agents might add to the inflammatory process by resulting in the release of endotoxins (LPS) upon death of the Gram-negative bacteria. To evaluate that hypothesis, 25 patients with acute pyelonephritis of Gram-negative aetiology were given intravenous cefuroxime 1.5 g tid. Blood samples were collected at various time intervals for blood culture and for the determination of LPS, tumour necrosis factor-alpha (TNFalpha) and cefuroxime levels. LPS remained elevated at levels equal to those before the administration of cefuroxime over the first 24 h of therapy. A positive correlation was detected between LPS and drug levels 6 h after the initiation of therapy. Fever persisted in 50, 37.5 and 16.7% of patients 48, 72 and 96 h after the start of treatment, respectively, followed by a rise of LPS at levels above the baseline. Blood cultures taken at the same time were sterile. A wide range of TNFalpha levels were found at similar times of sampling, indicating that LPS triggers considerable TNFalpha production in the serum of some patients but not in others. It is concluded that antibiotic-induced endotoxaemia is a phenomenon that might be observed in patients receiving cefuroxime and that might be responsible for the persistence of fever despite negative blood cultures.

Acute Disease↗
PubMed1999

Visceral leishmaniasis in renal transplant recipients: successful treatment with liposomal amphotericin B (AmBisome).

Visceral leishmaniasis (VL) is a rare disease in renal transplant recipients. Liposomal amphotericin B (AmBisome) is known to be effective against VL. However, previously there has been no experience with administration of such treatment to renal transplant recipients. We report herein four patients with VL complicating renal transplantation who were treated successfully with liposomal amphotericin B (total dose, 23-40 mg/kg). Neither adverse reactions nor clinical relapses of VL were observed.

Adult↗
PubMed1999

Lactic acid polymers as biodegradable carriers of fluoroquinolones: an in vitro study.

A biodegradable polymer of DL-dilactide that facilitates release of ciprofloxacin or pefloxacin at levels exceeding MICs for the causative microorganisms of chronic osteomyelitis is described. Duration and peak of release were found to depend on the molecular weight of the polymer. Its characteristics make it promising for treating chronic bone infections.

Anti-Infective Agents↗
PubMed1999

Fourth generation cephalosporins in the antimicrobial chemotherapy of surgical infections.

Surgical infections include a variety of entities such as secondary peritonitis, intra-abdominal abscesses, obstetric and gynecological infections as well as bone-joint and soft-tissue infections. By definition the term "surgical infection" implies that surgery itself plays the major role in therapy, while antimicrobial chemotherapy is only supplementary. Broad-spectrum empirical regimens employed include the combination of a 1st or 2nd generation cephalosporin plus clindamycin or metronidazole +/- aminoglycoside (depending on the severity of the condition). Cefepime and cefpirome are new 4th generation parenteral cephalosporins with a spectrum of activity which makes them suitable for the treatment of infections caused by a wide variety of bacteria. They are active against both gram-positive and gram-negative organisms, including Staphylococcus aureus and Pseudomonas aeruginosa with activity comparable to or greater than that of cefotaxime or ceftazidime respectively. Cefepime in particular is also very active against strains of Enterobacter and Pseudomonas spp resistant to these two agents. In comparison with 3rd generation cephalosporins, cefepime appears to be less likely to induce resistance, due to a lower rate of hydrolysis by beta-lactamases, a low affinity for these enzymes and more rapid permeation into the cell. Despite the fact that a 4th generation cephalosporin is well-suited for the treatment of polymicrobial infections, the following should be kept in mind: (I) MRSA strains and Bacteroides fragilis group are not included in their spectrum of activity. (II) Cefpirome is the only cephalosporin with in vitro activity against Enterococci. (III) Severe surgical infections of nosocomial origin, and particularly in settings where Enterobacter spp predominate, represent the major indication for empirical use of a 4th generation cephalosporin in combination with a nitroimidazole.

Abdomen↗
PubMed1998

In vitro activity of quinupristin/dalfopristin and newer quinolones combined with gentamicin against resistant isolates of Enterococcus faecalis and Enterococcus faecium.

In a study designed to obtain data on compounds active against enterococci, the minimum inhibitory concentrations (MICs) of quinupristin/dalfopristin (RP 59500) and the novel quinolones DU-6859a, trovafloxacin, levofloxacin, and sparfloxacin were determined for 122 Enterococcus faecalis and seven Enterococcus faecium isolates. In addition, 15 Enterococcus faecalis isolates resistant to gentamicin, DU-6859a, and trovafloxacin were exposed over time to combinations of DU-6859a plus gentamicin and trovafloxacin plus gentamicin. DU-6859a and trovafloxacin were found to be the most active compounds against Enterococcus faecalis and DU-6859a and RP 59500 against Enterococcus faecium. Synergy between either DU-6859a or trovafloxacin and gentamicin was observed with 27 to 35% of the isolates. It is concluded that DU-6859a and trovafloxacin are very potent against enterococci, especially when combined with gentamicin.

Anti-Bacterial Agents↗
PubMed1998

In vitro activity of polyunsaturated fatty acids on Pseudomonas aeruginosa: relationship to lipid peroxidation.

Based on previous findings that gamma-linolenic acid (GLA) inhibits Escherichia coli growth and provokes the induction of strains resistant to aminoglycosides, 19 Pseudomonas aeruginosa strains were exposed in vitro over time to GLA, to arachidonic acid (AA) and to their combination in the presence or absence of vitamin E. All acids were used at a 300 microg/ml concentration, whereas vitamin E was added as an antioxidant. Lipid peroxidation was evaluated by the thiobarbiturate assay measuring malonodialdehyde (MDA) production. It was found that GLA or AA killed 5-10% of strains at 24 h of growth, whereas when applied in combination their effect involved 100% of strains at 24 h and was limited to 68% of strains in the presence of vitamin E (P< 0.01). MDA production was time-dependent and it was restrained by vitamin E (P < 0.01). Post acid exposure, 27% to 37% of the survived strains became resistant to diverse antimicrobial agents and mainly to ticarcillin, to ceftazidime and to amikacin; no strain developed resistance in the presence of vitamin E. It is concluded that GLA and AA interact bactericidally on P. aeruginosa isolates, inducing the development of strains resistant to beta-lactams and to aminoglycosides; their action might be mediated through their peroxides. Further research is necessary to establish the clinical application of these in vitro findings.

Amikacin↗
PubMed1998

In-vitro activity and killing effect of quinupristin/dalfopristin (RP59500) on nosocomial Staphylococcus aureus and interactions with rifampicin and ciprofloxacin against methicillin-resistant isolates.

Quinupristin/dalfopristin (RP59500) is a novel streptogramin and a semisynthetic derivative of pristinamycins IA and IIB. The following properties of RP59500 were investigated: (i) its in-vitro activity against 164 hospital isolates of Staphylococcus aureus, 101 of which were methicillin-resistant (MRSA); (ii) its killing effect against 24 MRSA and seven methicillin-susceptible (MSSA) isolates; (iii) its interactions with rifampicin and ciprofloxacin against 18 MRSA isolates, six susceptible to both rifampicin and ciprofloxacin and 12 resistant to both, at 1 x MIC, 2 x MIC and 4 x MIC. Rifampicin and ciprofloxacin were applied at a concentration equal to their mean serum levels in order to establish the clinical relevance of the results. The MIC50, MIC90, MBC50 and MBC90 of quinupristin/dalfopristin were, respectively, < or = 0.015, 2, 0.12 and 2 mg/L for MRSA isolates and < or = 0.015, 0.06, < or = 0.015 and 0.25 mg/L for MSSA isolates. All isolates were inhibited by quinupristin/dalfopristin. Its killing effect varied with concentration and time, being optimal at 4 x MIC and after 24 h growth. Strains surviving 24 h exposure to this agent had much higher MICs than the parent strain, but only a limited number of them became resistant. Quinupristin/dalfopristin at 2 x MIC and 4 x MIC showed in-vitro synergy with rifampicin against highly resistant isolates mainly at 6 h and 24 h of growth involving 50-83% of MRSA isolates, and showed synergy with ciprofloxacin at 24 h involving 42-75% of isolates. The MIC increase in colonies surviving at 24 h was restricted by the presence of rifampicin or ciprofloxacin. In contrast, the above combinations acted synergically over the total number of MRSA strains susceptible to both rifampicin and ciprofloxacin. The above findings show that quinupristin/dalfopristin is a very potent antistaphylococcal agent, and that its activity against MRSA isolates is enhanced when it is combined with rifampicin or ciprofloxacin.

Anti-Bacterial Agents↗