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Biomedical subjects

H Giamarellou

Publications and source records attributed to H Giamarellou.

At least 19 recordsLinked to original sources
PubMed1997

The effect of monitoring of antibiotic use on decreasing antibiotic resistance in the hospital.

In Greece, antibiotic over-consumption and high resistance rates run in parallel. In the spring of 1989 surveillance of 12500 Gram-negative strains, derived from 55 hospitals from all over Greece, revealed that resistance rates of Pseudomonas aeruginosa, Enterobacter spp., Klebsiella spp. and Acinetobacter spp. to antimicrobial agents introduced after 1985 exceeded 50%. As a consequence, the application of (1) rules of hospital hygiene, (2) educational small group programs, and (3) an antibiotic policy aiming to restrict antibiotic use, was decided in Laiko General Hospital. Since 1989, imipenem, the newer quinolones, vancomycin, aztreonam and third-generation cephalosporins were only ordered to the hospital pharmacy after completion of a specific request form, which since 1991 has been more detailed and which can be signed only by physicians with interest in infectious diseases. In 1991, in cooperation with the pharmacy, an audit program was added requiring a final inspection of the already approved request forms by an infectious diseases specialist. Any disagreement was discussed with the physicians in charge. Consumption data were analysed monthly and discussed with each department. Newer antibiotic consumption in a selected month (November) of three consecutive years, before (1991) and after the application of the audit program (1992-1995) has been analysed. Results reveal a decrease in consumption of restricted antibiotics, especially in surgical departments and in kidney transplantation units, without simultaneous increase in consumption of the non-restricted compounds. Since 1994, resistance has decreased remarkably. However, the resistance of quinolones is increasing steeply. Consequently, for the last 12 months quinolones have been removed from the hospital formulary. An audit program requires close co-operation of physicians, pharmacists and, particularly, of surgeons, in the application of a correct prophylaxis regimen. It seems to be efficacious in reducing both resistance rates and total antibiotic consumption.

Anti-Bacterial Agents↗
PubMed1997

Comparative in vitro interactions of ceftazidime, meropenem, and imipenem with amikacin on multiresistant Pseudomonas aeruginosa.

To evaluate the possibility of an enhanced killing effect by ceftazidime, meropenem, or imipenem with amikacin 26 multiresistant Pseudomonas aeruginosa isolates, to nine anti-pseudomonal antimicrobials of diverse chemical classes were studied. A modified time-kill curve procedure was used with a 16 micrograms/ml concentration of each antimicrobial, i.e. within the range of their serum level; a total of 248 killing-curves were performed. Any > or = 2 log10 decrease of viable cell counts by a combination compared to the most active single agent was considered an adequate enhanced killing effect. The latter was found to be mainly expressed at 24 h of growth and involved 30-50% of the tested isolates. The above findings were independent of the MIC level to any individual beta-lactam or to amikacin. It is concluded that there is no difference between the activity of the ceftazidime and amikacin combination and those of meropenem or imipenem with amikacin on multiresistant P. aeruginosa.

Amikacin↗
PubMed1997

Chronic osteomyelitis caused by multi-resistant Gram-negative bacteria: evaluation of treatment with newer quinolones after prolonged follow-up.

We evaluated ciprofloxacin, ofloxacin and pefloxacin regimens for the treatment of chronic osteomyelitis due to Gram-negative multiresistant organisms. The study was open, nonrandomized and included 28, 21 and 16 patients, respectively. The 4-fluoroquinolone regimens were 1000 mg, 400 mg and 400-800 mg bd, for a mean duration of 137, 163 and 134 days, respectively. Pseudomonas aeruginosa was the most common pathogen, isolated in 33 individuals. Patients were followed clinically, bacteriologically and radiologically during treatment and for 2-5 years after discontinuation of therapy. Clinical outcome at the end of therapy was successful in 79%, 81% and 75%, improvement occurred in 11%, 10% and 19%, and the failure rate was 11%, 10% and 6%, while 11%, 5% and 6% relapsed, respectively. At the end of follow-up the bacterial eradication rate was 68%, 76% and 69%, respectively. Fluoroquinolone resistance emerged in 18%, 19% and 13% of ciprofloxacin, ofloxacin and pefloxacin recipients, respectively. The newer quinolones were safe and well tolerated and should be considered as the contemporary treatment of choice for chronic Gram-negative osteomyelitis, particularly whenever P. aeruginosa is implicated.

Adolescent↗
PubMed1997

Successful single-dose teicoplanin prophylaxis against experimental streptococcal, enterococcal, and staphylococcal aortic valve endocarditis.

Teicoplanin is a glycopeptide antibiotic that is administered both intramuscularly and intravenously. It has a prolonged half-life and a less toxic profile in comparison to those of vancomycin. The efficacy of a single dose of teicoplanin (18 mg/kg of body weight given intramuscularly) for the prevention of endocarditis due to Streptococcus oralis, Enterococcus faecium, and methicillin-resistant Staphylococcus aureus (MRSA) was evaluated after applying the rabbit model. Vancomycin at a single dose of 30 mg/kg given intravenously was used as the comparative agent for the prevention of endocarditis due to MRSA and E. faecium, while ampicillin at a single dose of 40 mg/kg given intravenously was used as the comparative agent for the prevention of endocarditis due to S. oralis. Rabbits in the teicoplanin group were infected at 1 h postdosing with approximately 10(7) CFU of each strain. Rabbits in the other groups were infected at 0.5 h postdosing with approximately 10(7) CFU of S. oralis (ampicillin group) or E. faecium and MRSA (vancomycin group). All rabbits were sacrificed 5 days later. Teicoplanin and vancomycin protected the animals challenged with E. faecium by 87.5 and 50%, respectively, and protected the animals challenged with MRSA by 100 and 92%, respectively. Teicoplanin and ampicillin protected the animals challenged with S. oralis by 100 and 77%, respectively. Prevention of endocarditis by teicoplanin was likely to be due to a prolonged inhibition of bacterial growth by the sustained supra-MICs. It is concluded that teicoplanin is very effective in preventing experimental streptococcal, enterococcal, and staphylococcal endocarditis and may be an attractive alternative antibiotic in patients allergic to beta-lactams, especially in the outpatient setting.

Animals↗
PubMed1996

Epidemiology, diagnosis, and therapy of fungal infections in surgery.

Over the past decade, the incidence of hospital-acquired bloodstream infections caused by Candida strains has risen, while the implicated species have changed. Candida tropicalis, Candida parapsilosis, and Candida glabrata all have increased in incidence. Data from the Centers for Disease Control and Prevention reveal that, between 1980 and 1990, Candida emerged as the sixth most common nosocomial pathogen (7.2%) and was the fourth most common pathogen in nosocomial bloodstream infections, surpassed only by coagulase-negative staphylococci, Staphylococcus aureus, and enterococci. The incidence of candidemia is dramatically higher in high-risk critical-care units: 25% of cases occur in surgical intensive-care units (ICUs) versus 25% in bone marrow transplantation units, 20% in medical ICUs, 20% in general medical wards, and 10% in oncology-hematology units. Burns and gastrointestinal surgery predispose to nosocomial candidemia. Independent risk factors include prior therapy with multiple antibiotics, isolation of Candida from sites other than blood, and prior hemodialysis. Crude mortality exceeds 55% and is associated with older age and concomitant renal failure, hepatic failure, acute respiratory diseases, or postoperative shock. In addition to extreme vigilance for early recognition of Candida sepsis in critically ill surgical patients, the high risk for candidemia probably necessitates fungal surveillance cultures and initiation of preemptive antifungal therapy in high-risk surgical patients.

Antifungal Agents↗
PubMed1996

In-vitro interactions of DX-8739, a new carbapenem, meropenem and imipenem with amikacin against multiresistant Pseudomonas aeruginosa.

In order to investigate the antimicrobial interactions against multiresistant Pseudomonas aeruginosa, thirty-seven strains resistant to antimicrobial agents of five different chemical classes were exposed in vitro to the combination of three carbapenems. DX-8739, a novel DHP-I stable analogue, meropenem and imipenem with amikacin. The tested combinations expressed an enhanced killing activity against 38-46% of strains and an additive effect against 5-13%. These effects were the same whether the applied carbapenem was DX-8739, meropenem or imipenem; they were also independent of the MIC of any antimicrobial.

Amikacin↗
PubMed1996

Characterization of the plasmidic beta-lactamase CMY-2, which is responsible for cephamycin resistance.

The phenotype of Klebsiella pneumoniae HEL-1 indicates a plasmidic cephamycinase gene (blaCMY-2). Its sequence shows one open reading frame coding for a protein of 381 amino acids. CMY-2 is classified as class C beta-lactamase that is closely related to the plasmidic enzymes BIL-1 and LAT-1 and the chromosomal AmpC of Citrobacter freundii. The blaCMY-2 gene possibly was translocated onto a plasmid of C. freundii which spread to K. pneumoniae.

Amino Acid Sequence↗
PubMed1996

Fleroxacin in complicated urinary tract infections.

The clinical evaluation of antimicrobial agents for the treatment of urinary tract infections (UTIs) requires clinically useful categorization of patients plus concurrent laboratory diagnosis. Appropriate diagnostics include (1) proper collection techniques, (2) quantitative urine culture, (3) urinalysis to determine pyuria, and (4) radiological, urological and gynecological evaluation. Categorization of patients suffering from UTIs should take into consideration (1) the site of infection, (2) the clinical presentation, (3) the frequency of infections, and (4) the coexistence of complicating factors. UTIs in men and older women are mostly complicated. The characterization of a UTI as complicated or uncomplicated is important since in the former condition, multiresistant nosocomial microorganisms are frequently encountered. Experience with fleroxacin 200 or 400 mg once daily (o.d.) in > 1,000 patients with complicated UTIs in noncomparative and comparative trials with other quinolones and cephalosporins has been very promising, with overall clinical and bacteriological cure rates of 86-95 and 89-95%, respectively. As with other quinolones, relapses and superinfections were mostly attributed to Enterococcus, Staphylococcus and Pseudomonas spp. The reported results make oral o.d. fleroxacin appropriate as an alternative to parenteral antimicrobials or for intravenous-to-oral switch therapy in complicated UTIs.

Anti-Bacterial Agents↗
PubMed1996

Greek physicians' and dentists' compliance with the British society for antimicrobial chemotherapy (BSAC) guidelines for preventing bacterial endocarditis.

Two thousand questionnaires inquiring about applied prophylaxis for bacterial endocarditis were sent to practicing doctors in Greece. Two hundred and ninety-nine questionnaires were completed and returned (15% response rate) and were subsequently divided into two groups: Group A (163) consisting of responses from dentists, chest physicians and ear, nose and throat (ENT) specialists and group B (136) including responses from gastroenterologists, gynecologists, urologists and radiologists. The percentage of correct answers given in response by clinicians in Groups A and B to the main questions and in accordance with the 1992 guidelines of the British Society for Antimicrobial Chemotherapy (BSAC) were respectively: (a) 53% vs 35% asked patients their previous history pertaining to valve disease, rheumatic fever or prosthetic valve surgery; (b) 55% vs 33% administered prophylaxis to patients with relevant history prior to medical procedures; (c) 67% vs 0% of prescribing doctors administered the appropriate antibacterials; (d) 33% vs 31% initiated prophylaxis in proper timing prior to medical procedure; (e) 14% vs 13% administered antibiotics in correct time/route/duration of infusion where applicable, prior to medical procedure; (f) 7% of group A doctors administering recommended antibiotics, implemented prophylaxis with correct time/route/dosage while, although none of group B doctors administered recommended antibiotics, 7% implemented prophylaxis with correct time/route recommendations; (g) an overall 2% of doctors from both groups met the BSAC recommendations. In conclusion, it is imperative that the appropriate training of doctors in all subspecialties regarding prophylaxis of bacterial endocarditis and according to current recommendations be carried out.

Anti-Bacterial Agents↗
PubMed1996

Clinical experience with the fourth generation cephalosporins.

The author reviews the comparative and non-comparative studies of cefepime and cefpirome, from which it is evident that both cephalosporins are extremely effective both clinically and bacteriologically. Success rates of about 90% have been reported for both drugs as therapy for complicated urinary tract infections, lower respiratory tract infections of the community as well as of nosocomial origin, including a large number of penicillin-resistant Streptococcus pneumoniae infections, skin and soft-tissue infections, surgical infections, as well as therapy for infections in neutropenic hosts. Cure rates are similar to or better than those obtained with ceftazidime, cefotaxime and ceftriaxone. The author also points out the various precautions necessary in utilizing these two antimicrobial agents.

Bacterial Infections↗
PubMed1996

Sustained release of fleroxacin in vitro from lactic acid polymer.

The time-delayed release of fleroxacin, a newer fluoroquinolone, from a mixture of racemic D-L-Lactic acid is reviewed. Ten in vitro experiments for each fleroxacin concentration of 1% and 10%, were performed. Pre-formed D-L-Lactic acid, plus fleroxacin clots were preserved in sterile 1 cm diameter tubes with one ml of nutrient broth at 37 degrees C until they were fully disintegrated. Every 24 hours the tubes were sampled and replaced by standard broth volumes. Fleroxacin levels were measured by a microbiological method. The release of fleroxacin impregnated in D-L-Lactic acid clots in these two concentrations (1% and 10%) is very promising; the levels obtained over a two month period were much higher than the minimum bacterial concentration of the expected pathogens implicated in bone infections.

Delayed-Action Preparations↗
PubMed1995

Pharmacokinetic study of fibrin clot-ciprofloxacin complex: an in vitro and in vivo experimental investigation.

We prepared a composite of fibrin clot and ciprofloxacin for use as a biodegradable antibiotic delivery system with sustained effect for the treatment of chronic osteomyelitis. In vitro, ten experiments were performed in which 10 mg of ciprofloxacin were incorporated into 4 ml of fibrin clot. The clots were preserved in nutrient broth and incubated at 37 degrees C for a total of 60 days. Every 24 h a broth specimen was obtained, and the ciprofloxacin concentration was determined by microbiological assay. The maximum level of antibiotic was noted on the first day (49.9 +/- 5.1 mg/l). The ciprofloxacin-fibrin clot complexes usually disintegrated after 60 days. In vivo, the fibrin-ciprofloxacin clots were made as previously described. The composite was implanted in the medullary canal of rabbit tibiae, and the antibiotic concentration was measured in bone, muscle, skin and serum. In all tissues around the implant, the concentration of antibiotic exceeded the minimum inhibitory concentration against the common causative organisms of osteomyelitis for 10 days. The implant caused no systemic side-effects, and it is likely to prove clinically useful as a drug delivery system for treating chronic osteomyelitis.

Animals↗
PubMed1995

Yersinia enterocolitica endocarditis: case report and literature review.

Endocarditis is a rare manifestation of Yersinia enterocolitica infection. The case of a 45-year-old man who presented with high fever and in whom prosthetic valve Yersinia enterocolitica endocarditis was diagnosed is described. The patient was successfully treated with ceftriaxone plus tobramycin, as proved by negative cultures of the prosthesis removed at the end of therapy. Including the patient reported, only 12 cases of Yersinia enterocolitica endocarditis have been published to date, two of which describe prosthetic cardiac valve endocarditis. The clinical characteristics do not distinguish septicemia from involvement limited to the cardiac valves. Diagnosis, however, has been improved by progress in echocardiography. Prognosis is grave but can be ameliorated if appropriate antimicrobial agents are administered, i.e. the combination of a third-generation cephalosporin plus an aminoglycoside. Fluroquinolones may also constitute an attractive therapeutic alternative.

Ceftriaxone↗
PubMed1995

Empiric therapy for infections in the febrile, neutropenic, compromised host.

In the years to come, it is likely that with the advent of cytokines and even more with possibility to insert drug-resistant genes into hematopoietic stem cells, the risk of infection will be decreased because the severity and duration of neutropenia will be minimized. It is true that the ideal empiric antimicrobial regimen--a single antibiotic with a low incidence of superinfection and a low toxicity, without need for subsequent additions and readjustments--is still a wish. In the meantime and while living in the neutropenic area, physicians, for the benefit of patients, have to follow guidelines and create algorithms (see Fig. 1). Recommendations, however, should be always adjustable to the individual characteristics of the patient and the institution and to progress in antimicrobial chemotherapy. It is inevitable that research and clinical practice should go "hand in hand" in these "difficult-to-manage" and "difficult-to-treat" patients. After all, it should never be forgotten that the ultimate goal of empiric antimicrobial regimens in febrile neutropenia is to ensure patients' survival.

Algorithms↗
PubMed1995

In-vitro inhibitory activity of gamma-linolenic acid on Escherichia coli strains and its influence on their susceptibilities to various antimicrobial agents.

Recent experimental evidence implies that polyunsaturated fatty acids (PUFAs) possess anti-infective activity which is unrelated to any alteration of eicosanoid biosynthesis or cytokine production provoked by PUFAs and it seems necessary to establish their possible influence on Gram-negative bacteria. Forty-two Escherichia coli strains were cultured in vitro in the presence of gamma-linolenic acid (GLA) at concentrations of 50 mg/L and 300 mg/L and a total of 77 killing curves were performed with GLA concentrations of 100, 200 and 300 mg/L GLA. At 50 and 300 mg/L, GLA inhibited 9.5% and 33.3% of strains respectively; GLA killing curves demonstrated a > or = 1 log GLA inhibitory effect in 0%, 18.2% and 72.7% of strains after the 5 h sequential exposures at 100, 200 and 300 mg/L GLA but this was not observed after the 24 h GLA exposure. Following removal of the E. coli strains from the culture medium with GLA, > or = four-fold increases in MICs and/or MBCs of various antimicrobials, were observed in 42.9% and 60% of strains after exposure to 50 and 300 mg/L GLA respectively; most of these increases involved aminoglycosides. The reproducibility of GLA inhibitory effects and increase in MICs and/or MBCs for E. coli in the two different experimental procedures used, was 82% and 73% respectively. Further studies are necessary to clarify the mechanism of GLA action on E. coli and assess the clinical relevance of these findings.

Anti-Bacterial Agents↗
PubMed1995

Vancomycin or vancomycin plus netilmicin for methicillin- and gentamicin-resistant Staphylococcus aureus aortic valve experimental endocarditis.

Using a rabbit model of aortic valve endocarditis, we studied the efficacy of vancomycin alone or in combination with netilmicin and/or rifampin against a methicillin- and gentamicin-resistant strain of Staphylococcus aureus (MGRSA). Antibiotics were given for 6 to 12 days, as follows: vancomycin (15 mg/kg of body weight every 12 h [BID] intravenously), vancomycin plus netilmicin (2.5 mg/kg BID intramuscularly), vancomycin plus rifampin (10 mg/kg BID intramuscularly), and vancomycin plus netilmicin plus rifampin at the same routes, dosages, and schedules mentioned above. Netilmicin was given to two additional groups at a higher dosage (6 mg/kg every 24 h intramuscularly) alone or in combination with vancomycin (15 mg/kg BID intravenously) for 12 days. All regimens resulted in undetectable bacterial counts in a significant proportion of vegetations (except netilmicin alone) or reduced the bacterial counts in the vegetations compared with the counts in the untreated controls (P<0.01 to P<0.001). No resistance to rifampin or netilmicin developed during therapy. It is concluded that in the treatment of experimental aortic valve endocarditis caused by MGRSA (i) vancomycin as monotherapy is as efficacious as the triple combination, (ii) the addition of netilmicin (once daily or BID) to vancomycin does not improve the efficacy of the latter antibiotic, even in the presence of rifampin, and (iii) a 12-day course in more effective than a 6-day one, but not at a statistically significant level.

Animals↗
PubMed1995

In vitro activity and killing effect of DX-8739, a new carbapenem, compared with those of meropenem and imipenem against multiresistant Pseudomonas aeruginosa.

DX-8739 is a new dehydropeptidase I-stable carbapenem. In order to evaluate its activity in comparison with those of meropenem and imipenem, 147 multiresistant Pseudomonas aeruginosa isolates acquired nosocomially were simultaneously exposed to the actions of the three carbapenems in vitro, whereas to compare their killing effects on 14 strains, 56 killing curve studies were performed. Overall DX-8739 was found to possess inhibitory activity as well as bactericidal activity statistically superior to those of meropenem and imipenem. At a concentration of 4 micrograms/ml, 106 strains (72.1%) were found to be imipenem resistant; 33 and 27.4% of these strains were inhibited by DX-8739 and meropenem, respectively, a statistically significant difference (P < 0.05). DX-8739 was also shown to possess intrinsic activity in vitro superior to those of meropenem and imipenem against the imipenem-susceptible population of strains. However, no statistically significant difference regarding the comparative killing activities of the three studied carbapenems was observed. Following exposure to carbapenem for 24 h, 33.3, 44.4, and 70% of the strains which survived became resistant to DX-8739, meropenem, and imipenem, respectively. The reported results demonstrate the significant activity of DX-8739 against multiresistant P. aeruginosa strains acquired nosocomially. The mechanism of action of DX-8739 on P. aeruginosa is unknown, and various hypotheses that might explain its in vitro superiority over meropenem and imipenem are proposed.

Anti-Bacterial Agents↗