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Biomedical subjects

D Raoult

Publications and source records attributed to D Raoult.

At least 469 records · Page 26Linked to original sources

Antibiotic treatment of rickettsiosis, recent advances and current concepts.

The author reviews the recent advances in the treatment of Mediterranean Spotted Fever and Q fever. In mediterranean spotted fever (M.S.F.), in vitro and preliminary in vivo data support the place of quinolones and josamycin in the treatment of M.S.F. In children josamycin could become the first choice drug as well as in pregnant woman. In Q fever chronic disease should be treated using a combination of antibiotic (doxycycline + quinolones) for a minimum of 3 years.

4-Quinolones↗

Studies of a "new" rickettsiosis "Astrakhan" spotted fever.

The acute febrile disease with characteristic rash seen in Astrakhan region and named as "viral exanthema of unknown etiology" was proved to be a spotted fever group rickettsiosis. Serological examination of humans from endemic areas by complement fixation test revealed antibodies to R. conorii, R. akari and strains Netsvetaev and AR-74 of R. sibirica in titres from 20 to 640 in sera from ill persons. Of 429 sera from healthy persons, 5.1% were serologically positive in a titre of 20-40. The presence of spotted fever group rickettsiae was detected in 8 of 104 Rhipicephalus sanguineus ticks removed from dogs and tested by haemocyte test with Gimenez staining and indirect immunofluorescence technique. Attempts at isolation of rickettsiae in guinea pigs and cell cultures resulted in appearance of specific spotted fever group rickettsiae antibodies in guinea pigs (4 of 8 samples examined were positive) and detection of rickettsiae by immunofluorescence technique in cell cultures (in 2 of 12 samples tested).

Animals↗

Q fever meningoencephalitis in five patients.

Within the last four years, we have observed five patients with epidemiological, clinical, and serological features that were consistent with Q fever meningoencephalitis. Attempts to isolate Coxiella burnetii from the cerebrospinal fluid of two patients were unsuccessful. Neurological features ranged from coma, general seizures, confusion, to palsy and meningitis. All patients were febrile. These patients were neuroradiologicaly investigated. Since 1984, four other cases have been reported in the literature. Antibiotics with good penetration into the cerebrospinal fluid, such as new quinolones, may be useful for treatment of confirmed cases. Q fever should be considered as a possible etiology of meningitis in endemic areas, and diagnosis should be confirmed by serology.

Adolescent↗

Serological evaluation of Ehrlichia canis infections in military dogs in Africa and Reunion Island.

Sixty-eight dogs from four African countries and Reunion Island were tested for antibodies against Ehrlichia canis. Twenty-six dogs (50%) in Tunisia, Senegal and Chad were found positive using the indirect fluorescence antibody test. Dogs from both the Central African Republic and Reunion Island were all negative. Thus, this preliminary report confirms the presence of E. canis in Africa. Larger studies will be necessary to evaluate the current epidemiologic situation of canine ehrlichiosis in these countries.

Animals↗

In vitro susceptibilities of Coxiella burnetii, Rickettsia rickettsii, and Rickettsia conorii to the fluoroquinolone sparfloxacin.

In vitro susceptibilities of Rickettsia rickettsii, Rickettsia conorii, and Coxiella burnetii to the new fluoroquinolone sparfloxacin (AT-4140; RP 64206) were determined. Plaque and dye uptake assays were used to measure the MICs against R. rickettsii and R. conorii. The susceptibilities of C. burnetii Nine Mile and Q 212 were determined in two acute-infection models and in two chronic-infection models. The MICs were 0.125 to 0.25 microgram/ml for R. rickettsii and 0.25 to 0.5 microgram/ml for R. conorii. Sparfloxacin (1 microgram/ml) cured cells recently infected with C. burnetii Nine Mile and Q 212 within 4 to 9 days and cured multiplying, persistently infected cells within 10 days. As previously described with other fluoroquinolones (D. Raoult, M. Drancourt, and G. Vestris, Antimicrob. Agents Chemother. 34:1512-1514, 1990), sparfloxacin failed to cure cells persistently infected with C. burnetii and blocked from dividing with cycloheximide. As determined by the dye uptake assay, no cellular toxicity was noted with sparfloxacin at up to 128 micrograms/ml. These results are consistent with those previously obtained with fluoroquinolones (D. Raoult, M. Yeaman, and O. Baca, Rev. Infect. Dis. 11[Suppl. 5]:S986, 1989), although sparfloxacin may be slightly more active.

4-Quinolones↗

Shell-vial assay: evaluation of a new technique for determining antibiotic susceptibility, tested in 13 isolates of Coxiella burnetii.

Coxiella burnetii is a strictly intracellular bacterium. Bacteriostatic effects have been described previously on a few isolates in embryonated eggs (A. J. Spicer, M. G. Peacock, and J. C. Williams, p. 375-383, in W. Burgdorfer and R. L. Anacker, ed., Rickettsiae and rickettsial diseases, 1981). We used the shell-vial technique (D. Raoult, G. Vestris, and M. Enea, J. Clin. Microbiol. 28:2482-2484, 1990) to determine the susceptibility of C. burnetii to amoxicillin, amikacin, erythromycin, co-trimoxazole, pefloxacin, ofloxacin, ciprofloxacin, chloramphenicol, tetracycline, doxycycline, minocycline, and rifampin antibiotics at a single dilution. Human embryonic lung fibroblast monolayers in shell vials were seeded with 13 different C. burnetii isolates, including 3 reference strains (Nine Mile, Q212, and Priscilla) and 10 new isolates, in order to obtain 30% infected cells 6 days later. After inoculation, antibiotics were added, shell vials were incubated for 7 days, and immunofluorescence was revealed and compared with that of the positive controls. Strain Nine Mile was more susceptible than strains Q212 and Priscilla were. The heterogeneity of susceptibility to fluoroquinolones, chloramphenicol, and erythromycin was noted among the strains; all were resistant to amoxicillin and amikacin, and all were susceptible to rifampin, co-trimoxazole, tetracycline, and tetracycline analogs.

Anti-Bacterial Agents↗

Comparison of different antibiotic regimens for therapy of 32 cases of Q fever endocarditis.

We studied 32 cases of Q fever endocarditis diagnosed in France between January 1985 and December 1989 to evaluate the efficacies of the different regimens of antibiotics used for treatment. Each patient was monitored during the treatment (range, 12 to 60 months), and clinical and biological information was computerized. Various treatments were prescribed, including doxycycline alone (9 cases) or in association with rifampin (4 cases), quinolones (16 cases), or sulfamethoxazole-trimethoprim (1 case). Two patients died before the beginning of the treatment. Nineteen patients had hemodynamic failure and subsequently underwent valve replacement. Nine valve tissue cultures were positive despite previous antibiotic treatment. In terms of their effects on mortality, the difference between doxycycline alone and doxycycline plus quinolones is statistically significant. We conclude that the addition of quinolones to doxycycline is beneficial. On the basis of clinical, serological, and valve tissue culture results, no treatment was able to cure Q fever endocarditis within 2 years, even with a combination of antibiotics. We advise a minimum duration of treatment of 3 years with therapy combining quinolones and doxycycline.

4-Quinolones↗

[Value of the technique of cellular lysis by thermic shock in the isolation of bacteria causing osteoarticular infections].

The purpose of this work is to compare, a conventional technique, for bacterial isolation, with a lysis-centrifugation method using a rapid freezing in liquid nitrogen, followed by decongelation at 37 degrees C for bone and joint samples. The bone and joint specimens were biopsies and punctions (35 cases) or fistula (10 cases). The residual antibiotic activity of the sample was determined using a susceptible strain of Micrococcus luteus and of Staphylococcus epidermidis. Among the 45 samples, 20 were sterile with both methods among which 8 exhibited a residual antibiotic activity which may have contributed to isolation failure. In 12 cases, bacterial isolates were obtained with both methods. Cultures were obtained from 13 samples with the lysis centrifugation method alone. The isolates were 4 Staphylococcus aureus, 8 coagulase-negative Staphylococcus and 1 Acinetobacter sp. These results suggest that the intracellular location of bacteria may be responsible for the negative cultures from bone or joint specimens.

Aged↗

Seroepidemiology of spotted fever group rickettsial infections in humans in Zimbabwe.

In sera collected throughout Zimbabwe the prevalence of antibodies reactive with Rickettsia conorii (Kenya) and a Zimbabwean spotted fever group rickettsia (ZSFR) was investigated using an indirect immunofluorescence assay (IFA). A random sample of these sera was also tested using a commercial IFA test. There was close agreement between IFA titres using the African rickettsial antigens and the commercial antigen slides. When differences in titre were detected, these were rarely greater than a twofold serum dilution. In Western blot immunoassays, IFA positive human sera detected immunogens of ZSFR and R. conorii (Kenya) that could also be demonstrated with homologous mouse antisera. The overall seroprevalence was 52% to R. conorii (Kenya) and 55% to ZSFR. For both antigens the highest seroprevalence was recorded from the south of the country, where the highest incidence of clinical tick-bite fever was reported in a questionnaire survey to medical practitioners. No difference was found between the seroprevalence in males and females, but high titres of antibody were common in samples from young people.

Adolescent↗

Relationships between the Rhipicephalus sanguineus complex ecology and Mediterranean spotted fever epidemiology in France.

The authors examine the epidemiologic features of Mediterranean spotted fever in France in light of the bioecological peculiarities of each of the three known member of the Rhipicephalus sanguineus tick group (R. sanguineus, R. turanicus, R. pusillus). The results show that R. sanguineus is the main vector. Certain aspects of this tick species are of interest: affinity for man, close contact with humans for a long periods, peak of tick population (preimaginal stages) at the same time as the peak of the disease. The largest populations of R. sanguineus are noted in the endemic zone of human rickettsiosis. The fact that immature stages are more prevalent during the hot season and these forms' ability to bite humans is important and may suggest a role for them in the epidemiology of the disease. The sporadic isolation of this species outside the endemic zone may explain the occurrence of isolated cases of the disease in these areas. We cannot currently exclude vector roles for the two other species, which can parasitize humans, though none of our data supports this hypothesis.

Animals↗

Host factors in the severity of Q fever.

The author has reviewed different aspects of the role of immunocompetence in the development of Q fever. Coxiella burnetii lives within the phagolysosomes of infected cells. In animals, the immunosuppression caused by either cortisone or X-irradiation reactivates Q fever. In humans, cases of Q fever are reported in immunocompromised hosts suffering from leukemia, cancer, and human immunodeficiency virus infection (AIDS). Similar data are reported with strict or facultative intracellular parasites living within the phagolysosome. Sporadic publications reported the appearance of auto-antibodies during Q fever which may change the clinical picture of the disease. The pathological findings of hepatitis diagnosed during acute Q fever and those with C. burnetii chronic endocarditis are quite different and may reflect a different immunological response to C. burnetii. These facts emphasize the importance of host factors in the clinical expression and outcome of Q fever.

Humans↗

Chronic Q fever: diagnosis and follow-up.

Sera from 40 patients (25 men, and 15 women) with clinical features compatible with the diagnosis of chronic Q fever were received. Total or partial clinical data were available. All of them had serological evidence of chronic Q fever (IgG class anti-phase I titer greater than 800). The final diagnosis was vascular infection in four cases (with two positive cultures for Coxiella burnetii), bone infection in two patients (one positive culture), chronic hepatitis in one patient, and endocarditis in 32. The last patient had an isolated fever with a chronic Q fever serologic profile. Among the 32 with endocarditis, valve replacement was performed in 59%, and valve cultures were positive in 14/18 patients. Twenty-nine of these patients had previously known valvulopathy; 23 were exposed to cattle, sheep or goats; and four had an immunocompromised situation. Ten patients died; two before any treatment, five of cardiac failure during or a few weeks after surgery, and three during the medical treatment. For antibiotic treatment, tetracycline alone was employed in seven cases. For the other patients, combined therapy including tetracycline and another drug (rifampin, fluoroquinolones, cotrimoxazole, or erythromycin) was initiated. Three patients were considered to be completely cured.

Adolescent↗

Bactericidal effect of doxycycline associated with lysosomotropic agents on Coxiella burnetii in P388D1 cells.

There is no consistently reliable treatment for endocarditis resulting from chronic Coxiella burnetii infection, the causative agent of Q fever. Although certain antibiotics are recommended on the basis of their in vitro bactericidal activities, results of therapy with these antibiotics are often disappointing. To evaluate whether the currently recommended antibiotic susceptibility tests for C. burnetii give misleading results because of continued division of uninfected cells, thereby resulting in the dilution of infected cells and, hence, a false picture of antibiotic efficacy, we blocked cell division during antibiotic susceptibility testing with cycloheximide. Using this new method, we found that the currently recommended antibiotics for the treatment of Q fever, doxycycline, pefloxacin, and rifampin, did not reduce the ratio of infected to noninfected cells (either L929 or P388D1) by 9 days postinfection. To test the hypothesis that this lack of antibacterial activity is due to antibiotic inactivation by the low pH of the phagolysosomes in which C. burnetii is found, we used alkalinizing lysosomotropic agents (chloroquine or amantadine) concurrently with doxycycline. This resulted in the sterilization of C. burnetii infection in P388D1 cells. This finding seems to confirm our suspicion that the acidic conditions of the phagolysosomes in which C. burnetii is located inhibit antibiotic activity. This inhibition can be reversed in vitro when lysosomotropic alkalinizing agents are used.

Amantadine↗