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Biomedical subjects

J F Acar

Publications and source records attributed to J F Acar.

At least 19 recordsLinked to original sources
PubMed2006

Antimicrobial resistance at farm level.

Bacteria that are resistant to antimicrobials are widespread. This article reviews the distribution of resistant bacteria in farm environments. Humans, animals, and environmental sites are all reservoirs of bacterial communities that contain some bacteria that are susceptible to antimicrobials and others that are resistant. Farm ecosystems provide an environment in which resistant bacteria and genes can emerge, amplify and spread. Dissemination occurs via the food chain and via several other pathways. Ecological, epidemiological, molecular and mathematical approaches are being used to study the origin and expansion of the resistance problem and its relationship to antibiotic usage. The prudent and responsible use of antibiotics is an essential part of an ethical approach to improving animal health and food safety. The responsible use of antibiotics during research is vital, but to fully contribute to the containment of antimicrobial resistance 'prudent use' must also be part of good management practices at all levels of farm life.

Animal Husbandry↗
PubMed2001

A comparison of side effects of levofloxacin to other agents concerning the ecological and microbiological effects on normal human flora.

The safety of levofloxacin was compared to that of non-fluoroquinolone alternatives used for respiratory tract infections. Results from five randomised controlled trials revealed that the incidence of any adverse events possibly associated with levofloxacin ranged from 5.8% to 22.7%, whereas that of comparators (ceftriaxone, cefuroxime axetil, clarithromycin and amoxicillin-clavulanic acid) ranged from 8.5% to 39.3%. The rate of adverse drug reactions (ADRs) was lower for levofloxacin in all trials. The most common adverse events for all agents tended to be gastrointestinal in nature. Levofloxacin was associated with a mild effect on the normal microflora, reaching a maximum at four days of therapy, with complete recovery being achieved by seven days post-therapy. No colonisation with resistant strains was observed during the period of levofloxacin therapy. Amoxicillin-clavulanic acid administration selected for resistant strains of Enterobacteriaceae, and ampicillin administration was associated with both resistant strains of Enterobacteriacae as well as Candida spp. Ceftriaxone selected resistant strains of Clostridium difficile and Candida spp. Thus, microflora effects favoured levofloxacin over all of the agents tested, including macrolides and tetracyclines. These results confirm that the ecological impact of levofloxacin is markedly less than that associated with non-fluoroquinolone comparators.

Anti-Infective Agents↗
PubMed2000

Antibiotic synergy and antagonism.

The field of synergistic combinations of antibiotics is extremely broad and mostly has been explored in vitro. Some fixed combinations were successfully developed commercially. A few combinations were tested in animal models, and a smaller number was studied in human patients. Any practitioner in infectious diseases has some individual cases, published or unpublished, which add some evidence to the role of synergistic combinations in difficult therapy problems--either on the side of the patient when immunosuppressed or on the side of the bacterial strain, when multiply resistant. MRSA, VISA, E. faecium resistant to penicillin G and highly resistant to aminoglysocides and to vancomycin, P. aeruginosa resistant to ceftazidime and imipenem, and Acinetobacter baumani resistant to imipenem are some of the bacterial strains dangerous for the patient and the hospital, which trigger the imagination of the microbiologist and physician to find a satisfactory treatment. On the side of the drug industry, the increasing knowledge of resistance mechanisms and of synergistic mechanisms may open some new approach, such as efflux inhibitors, a membrane-active compound that can be combined with a partner antibiotic. Antagonism between antibiotics would be worthwhile to study because it likely contributes to the disadvantages of the inappropriate use of antimicrobial combinations.

Animals↗
PubMed1999

In-vitro activity of levofloxacin, a new fluoroquinolone: evaluation against Haemophilus influenzae and Moraxella catarrhalis.

The in-vitro activity of levofloxacin was studied against 10 beta-lactamase-negative and 93 beta-lactamase-positive Moraxella catarrhalis isolates, and 65 beta-lactamase-negative and 35 beta-lactamase-positive Haemophilus influenzae isolates. The MICs of levofloxacin were determined by agar dilution on Mueller-Hinton agar (with the addition of 5% horse blood for M. catarrhalis) or on Haemophilus Test Medium for H. influenzae, and were compared with those of ofloxacin, ciprofloxacin and sparfloxacin, as well as pefloxacin and D-ofloxacin for M. catarrhalis. The fluoroquinolones showed similar activity against isolates of H. influenzae and M. catarrhalis, irrespective of beta-lactamase production. Levofloxacin (MIC50/90 0.06 mg/L) was 64 times more active against M. catarrhalis than D-ofloxacin (MIC50/90 4/8 mg/L) and twice as active as ofloxacin (MIC50/90 0.125 mg/L). Ciprofloxacin had an MIC50/90 of 0.03/0.06 mg/L and sparfloxacin showed an MIC50/90 of 0.015 mg/L against M. catarrhalis irrespective of the resistance phenotype of the isolates. Against H. influenzae, levofloxacin was twice as active as ofloxacin (MIC90 values 0.03 mg/L versus 0.06 mg/L), while the MIC90s of ciprofloxacin and sparfloxacin were both 0.015 mg/L. Our results therefore suggest that levofloxacin has potential for treating respiratory tract infections caused by H. influenzae and M. catarrhalis.

Anti-Infective Agents↗
PubMed1999

Resistance patterns of Haemophilus influenzae.

Haemophilus influenzae is an important respiratory tract pathogen, and the prevalence of strains resistant to the antibiotics used to treat it has increased since the 1970s. Data on H. influenzae have been gathered in the Alexander Project, an ongoing, international surveillance study. They reveal that beta-lactamase production is the primary mechanism for H. influenzae resistance and that the resistance has a wide geographical variation, reaching critical levels in some countries. Unlike many techniques used in the past, Alexander Project methods provide accurate, reproducible susceptibility data, allowing the comparison of resistance prevalence over time and between areas. Traditional antimicrobial breakpoints are being superseded by more accurate and clinically relevant methods of predicting drug efficacy, such as time above the MIC, AUC:MIC ratios and pharmacodynamic breakpoints. Continued surveillance for resistance and susceptibility testing of H. influenzae is vital to maximize the benefits of antimicrobial therapy and to contain the spread of infection.

Adolescent↗
PubMed1998

Low rate of Clostridium difficile colonization in ambulatory and hospitalized HIV-infected patients in a hospital unit: a prospective survey.

OBJECTIVE: To determine the frequency of Clostridium difficile carriage in HIV-infected in- and out-patients, and to assess the role of this carriage in nosocomial transmission of C. difficile. PATIENTS AND METHODS: Prospective study in a university hospital. Forty-five consecutive HIV-infected out-patients and 120 hospitalized patients (52 HIV and 68 non HIV-infected-patients) were studied. During the period of hospitalization, 44 patients (24 HIV and 20 non-HIV-infected patients) with a negative culture within 48 h of admission were followed weekly for fecal carriage. Clostridium difficile culture and latex agglutination were performed on the fecal samples of each patient. In the case of positive culture and/or latex agglutination, C. difficile toxin assays were performed by microtitre cytotoxicity method. RESULTS: Out-patients: one patient was a carrier and one patient with diarrhoea was infected with a toxigenic strain (2/45, 4.5%, 95% CI = 1-17). Eighty percent of the HIV-infected out-patients had received antimicrobial agents previously. In-patients: in the first 48 h, five asymptomatic patients were carriers (three non-HIV and two HIV-infected patients). Among 20 patients who complained of diarrhoea, one HIV-infected patient had only a positive latex agglutination and one HIV-infected patient was infected with a toxigenic strain. Overall, 7/120 (5.8%, 95% CI = 2-10) patients were infected or colonized with C. difficile. During the hospitalization (743 patient-days), none of the 44 patients acquired C. difficile. CONCLUSION: This study suggests that in this given unit, C. difficile carriage is low, at least with single room accommodation, and in the absence of clusters of cases. This carriage is not different in HIV and non-HIV infected patients despite treatment with multiple antibiotics, and is not different in patients managed in different care environments. The systematic identification of C. difficile carriers for isolation and prophylactic treatment is not useful under these circumstances.

Ambulatory Care↗
PubMed1998

Consequences of increasing resistance to antimicrobial agents.

The correlation between in vitro bacterial susceptibility results and clinical outcome has been debated for many years. Bacterial resistance traits are more significantly correlated with failure of therapy than is an organism's susceptibility to an antimicrobial agent. We review the situations that have supported the clinical relevance of in vitro bacterial resistance. Those situations include: emergence, during therapy, of a new resistance marker not known before; selection of a resistant mutant or acquisition of a resistance gene during therapy; failure to recognize or take into account a new resistance mechanism; and superinfection with resistant bacteria. More information should be obtained in the future by performing studies oriented toward bacteriologically documented clinical failures and by better communication between microbiologists and physicians to correlate the in vitro data with host status, the pharmacokinetics of the antimicrobial agent, and the bacteriologic and clinical outcome.

Bacterial Infections↗
PubMed1998

[Antibacterial activity of ofloxacin in urine for 4 days after a single oral dose of 400 mg].

Antibacterial activity of ofloxacin in urine after a single oral dose of 400 mg was evaluated in ten healthy female volunteers. Urine was collected over six periods, i.e., 0-6 h, 6-12 h, 12-24 h, 24-48 h, 48-72 h, and 72-96 h postdose. Ofloxacin levels were assayed in all samples using a microbiological method and HPLC. Urinary ofloxacin MICs were determined for five bacterial strains recovered from urine, two E. coli strains of which one was susceptible and the other resistant to nalidixic acid (Nal-A), one Klebsiella pneumoniae resistant to nalidixic acid (Nal-B), one Staphylococcus saprophyticus strain, and one Enterococcus faecalis strain; MICs were 0.06, 0.25, 1, 0.25, and 2 mg/L, respectively. Mean urinary ofloxacin levels by the microbiological method during the six collection periods were 193.3 +/- 30.3, 138.1 +/- 31, 53.2 +/- 7.3, 8.3 +/- 0.8, 1.4 +/- 0.2, and 0.6 +/- 0.1 mg/L, respectively. HPLC provided similar results: 216.7 +/- 31.6, 130.7 +/- 20.5, 56.5 +/- 7.1, 8.3 +/- 0.9, 1.5 +/- 0.3, and 0.5 +/- 0.05 mg/L, respectively. Mean urinary ofloxacin excretion over 96 h was 67.4 +/- 3.6% of the dose by the microbiological method was 72.5 +/- 2.5% of the dose by HPLC. On the first day, bacteriostatic activity of urine against enterobacteria exceeded 32 and was greater than 8192 for the nalidixic acid-susceptible E. coli strain; on the next day, overall values were equal or greater than 8 for the nalidixic acid-resistant E. coli and K. pneumoniae strains. Bacteriostatic activity was equal to or greater than 32 for the S. saprophyticus strain during the first two days and equal to 8 on the first day and 4 on the second day for the E. faecalis strain.

Administration, Oral↗
PubMed1997

Trends in bacterial resistance to fluoroquinolones.

The emergence of resistance to fluoroquinolones in virtually all species of bacteria was recognized soon after the introduction of these compounds for clinical use more than 10 years ago. Various resistance mechanisms, often interdependent, may explain different levels of resistance. Epidemiological factors, local antibiotic policies, patients' characteristics, origin of the strains, and geographic location are among the factors contributing to highly variable resistance rates. During the last several years, resistance to fluoroquinolones has remained very high among methicillin-resistant Staphylococcus aureus strains and in intensive care unit patients, and it has increased among nosocomial isolates of Klebsiella pneumoniae, Serratia marcescens, and Pseudomonas aeruginosa. More worrisome are recent reports of an overall increase in resistance to fluoroquinolones among bacteria responsible for community-acquired infections, such as Escherichia coli, Salmonella species, Campylobacter species and Neisseria gonorrhoeae.

Anti-Infective Agents↗
PubMed1996

A multinational European survey on the in-vitro activity of rufloxacin and other comparative antibiotics on respiratory and urinary bacterial pathogens.

The antibacterial activity of rufloxacin was confirmed against a large number of respiratory and urinary tract pathogens collected in five European countries. In terms of both MIC90 values and percentages of susceptible isolates found, this new quinolone showed useful in-vitro activity against Mycoplasma catarrhalis, Haemophilus influenzae and Klebsiella pneumoniae, with a large proportion of Staphylococcus aureus also covered, while, as expected Streptococcus pneumoniae and Streptococcus pyogenes were not included in its antibacterial spectrum. Rufloxacin was comparable with the other antibiotics against these pathogens with the exception of streptococci. Against these microorganisms, beta-lactams were the most active agents. Against the urinary pathogens the in-vitro activity of rufloxacin is similar to that of norfloxacin although this latter drug is more active in terms of MIC90 values and in percentages of strains inhibited. In many cases more isolates were susceptible to the remaining comparator agents than to rufloxacin. However, there were no significant differences between the numbers of microorganisms inhibited by the various drugs and rufloxacin. The findings of this survey do not seem to modify the general picture which emerged in previous studies and further confirms its useful spectrum in different geographic settings.

Anti-Bacterial Agents↗
PubMed1996

Antimicrobial resistance among lower respiratory tract isolates of Streptococcus pneumoniae: results of a 1992-93 western Europe and USA collaborative surveillance study. The Alexander Project Collaborative Group.

One thousand, eight hundred and fifty-six Streptococcus pneumoniae strains, collected in 1992 and 1993 from 15 centres in Western Europe and USA were tested for susceptibility to 16 antibiotics. The overall resistance to penicillin was 23% (range 6-54%), with the highest prevalences in Madrid, Barcelona, Toulouse and Cleveland. Seven centres reported low-level penicillin resistance only. Amoxycillin was more active than ceftriaxone against strains with intermediate resistance to penicillin, and at least four-fold more active than cefuroxime; cefaclor and cefixime had poor activity. Against penicillin-resistant strains, ceftriaxone was slightly more active than amoxycillin, cefuroxime exhibited borderline activity and cefixime and cefaclor were inactive. Ten strains fully susceptible to penicillin had MICs of ceftriaxone > or = 0.1 mg/L; this may represent a first step towards the development of cephalosporin resistance. With the exception of fluoroquinolones, resistance to non-beta-lactam antibiotics (chloramphenicol, doxycycline, co-trimoxazole, erythromycin, clarithromycin and azithromycin) was considerably higher in penicillin-resistant strains compared with penicillin-susceptible isolates. Erythromycin-resistant isolates were also resistant to the other macrolides tested.

Anti-Bacterial Agents↗
PubMed1995

Epidemiology of antibiotic resistance in Haemophilus influenzae.

During the last 10 years, a continuous increase in the incidence of beta-lactamase-producing Haemophilus influenzae has been observed; in addition, beta-lactamase-negative ampicillin-resistant strains are better identified and more frequently isolated. During the same period, resistance to tetracyclines and chloramphenicol decreased to a very low level. The incidence of resistant bacteria is highly variable according to the site of infection, patient's age, type of Haemophilus, and country or region, according to local epidemiological factors. Follow-up multicenter studies are needed to monitor the evolution of resistance to these antibiotics and also emergence and spread of resistance to other antibiotics, such as new fluoroquinolones, new beta-lactams, and new macrolides.

Anti-Bacterial Agents↗
PubMed1995

Decreased teicoplanin susceptibility of methicillin-resistant strains of Staphylococcus aureus.

Between February 1992 and February 1993, 12 patients were seen who were infected or colonized with methicillin-resistant strains of Staphylococcus aureus. The strains had decreased susceptibility to teicoplanin (MICs, 8-16 micrograms/mL). Field inversion gel electrophoresis showed the strains belonged to three related clones (A1, A2, and A3). The patients were though to have acquired the strains nosocomially. Consistent with results of laboratory studies of teicoplanin-resistant S. aureus, all but 1 strain expressed a 35-kDa membrane protein, and 9 strains expressed increased levels of penicillin-binding protein 2 complex. Six strains were isolated from patients treated with glycopeptides. These data suggest that nosocomial transmission of S. aureus with decreased teicoplanin susceptibility may occur during glycopeptide use and that such strains develop resistance by a mechanism associated with the appearance of a 35-kDa membrane protein. Surveillance is necessary to monitor for the potential selection of resistant clones that may be capable of dissemination.

Adult↗