[Absence of regular medical follow-up: main cause of pneumocystosis diagnosed in patients with HIV infection in France in 1992].
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Biomedical subjects
Publications and source records attributed to C Pradier.
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OBJECTIVES: To determine the epidemiologic, clinical and aetiologic features of chronic diarrhoea in patients with human immunodeficiency virus (HIV) infection. METHODS: Between January 1992 and April 1993, all HIV positive patients with chronic diarrhoea were enrolled in a prospective study. There were 46 patients in the study group including 33 (22 homosexuals) in stage C according to the 1993 Centers for Disease Control classification. RESULTS: Thirty-four pathogenic agents were isolated in 26 of the patients (57%). Enterocytozoon bieneusi was the most frequently found pathogen (11 patients, 24%) followed by Cryptosporidium sp (8 patients). Enterocytozoon bieneusi was found in association with other pathogens in 7 patients. All patients with microsporidiosis were in stage C (p = 0.04) and had a longer duration of diarrhoea (19.6 vs 9.8 weeks, p = 0.03), greater weight loss (9.6 vs 2.1 kg, p = 0.0003) and a lower Karnofsky index (48% vs 67%, p = 0.01). Prophylaxy with dapsone or pyrimethamine during the 3 months prior to inclusion had been more frequent (p = 0.04 and p = 0.05 respectively) in patients without microsporidiosis. CONCLUSION: Microsporidiosis should be suspected as a probable cause of chronic diarrhoea in HIV positive patients with a CD4 count < 100/mm3. Multiple infections may be a factor leading to treatment failure. Microsporidiosis seems to be linked to homosexual intercourse.
In recent years, increasing numbers of Streptococcus pneumoniae strains displaying relative resistance to penicillin have been reported. Epidemiological studies have shown a correlation between aminopenicillin administration and resistance. We investigated the development of resistance in six strains (four sensitive and two intermediate-resistant to penicillin) by serial daily passages in subinhibitory concentrations of amoxicillin (AMX), amoxicillin + clavulanic acid (AMC), imipenem (IMP), cefixime (CFM), cefatrizine (CTZ), cefadroxil (CDX), and cefuroxime (CXM). MICs were determined by the macrodilution method in brain-heart broth for each daily passage. The number of daily passages needed to increase the MIC by a factor of 8 was achieved with AMX, AMC, and CFM for most of the strains after a mean of 24, 20, and 11 passages, respectively, and for one-third of the strains, with CDX, IMP, and CTZ after 11, 11, and 21 passages, respectively. Decreased susceptibility to breakpoints for intermediate-resistant S. pneumoniae populations was noted for all strains with CFM, AMX, and AMC after a mean of 10, 18, and 21 serial passages, respectively, and for four of five strains with IMP and CTZ after 12 and 13 passages. CTZ-, CDX-, and CXM-passaged variants had increased MIC values only for cephalosporins, while AMX-, AMC-, IMP-, and CFM-passaged variants exhibited increased MICs to all antibiotics tested. These in vitro data appear to be in agreement with epidemiological studies and warrant further exploration with respect to possible clinical implications.
Selection of resistant mutants was induced in broth by exposing pneumococci to serial sub-inhibitory concentrations of various beta-lactam antibiotics. Aminopenicillins selected for resistance to themselves and to cephalosporins although cephalosporins tended to select for resistance to their own class, with the exception of cefixime which seems to select cross-resistant organisms.
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Blood counts of CD4 cells remain the best prognostic factor in patients infected with human immunodeficiency virus (HIV). However, the small number of infected cells contrasts with the importance of lymphocyte depletion. Several mechanisms might explain this depletion including: antibody-dependent cytotoxicity. Twenty to 50% of the antibodies produced in vitro by B lymphocytes are directed against HIV antigens, especially the gp120 and gp41 viral envelope antigen. If this cytotoxicity effect occurs in vivo, it could reduce of lymphocytes carrying the viral genome and partially explain the major lymphopenia in HIV-infected patients. It is not yet known whether the long-term effect of these antibodies is immunoprotective or deleterious, but they may play a protective role at least in the initial stages of the disease. autoimmunity. Sequence homology between the HLA II molecules and the glycoproteins of the viral envelope has been clinically and biologically documented in many manifestations of HIV infection. It has been suggested that alloreactivity, similar to the graft-versus-host reaction could be involved. In addition, programmed cell-death of the CD4 lymphocytes appears to be overactivated in HIV-positive subjects, possibly because the gp120 viral antigen perturbs the CD4-dependent signal for cell death. deleterious effects of cytokines. Tumour necrosis factor, for example, is known to play a role in the regulation of viral replication; it may favour the destruction of contaminated cells but also the initiation of provirus replication and integration into the cell genome. supra-antigens and/or infectious factors. Supra-antigenes, which can link with HLA molecules, are capable of oligoclonal activation without being "processed" in the cell presenting the antigen. This activation might affect cell death. Certain germ toxins could also play a role as cofactors. Cohort studies of asymptomatic HIV patients are needed to improve our understanding of these mechanisms. A therapeutic approach tailored to the stage reached by HIV-infected subjects will then be possible.
The development of resistance in vitro in five strains of Streptococcus pneumoniae (3 with full susceptibility and 2 with intermediate susceptibility to penicillin) was investigated by serial passages in the presence of subinhibitory concentrations of amoxicillin and ampicillin. At the end of passaging, MICs of antibiotics for all the strains increased by a factor of four or more, reaching at least intermediate levels. MICs of cephalosporins, ampicillin and amoxicillin increased for almost all variants obtained. Similar results were obtained with amoxicillin plus clavulanic acid at a ratio of 2:1 and at a constant concentration of 2 micrograms/ml, and with ampicillin plus sulbactam at a ratio 2:1. In contrast, no significant modification of MIC was seen with ampicillin plus sulbactam at a constant concentration of 4 micrograms/ml sulbactam. These results suggest interaction of sulbactam with penicillin binding proteins as described previously for other bacterial species, and merit further investigation.
Two complementary surveys were carried out in the 89 hospital units of South-Eastern France which deal with pregnant women. Firstly, in November 1991, medical chiefs of these units were interviewed face-to-face about their current HIV screening policy. Secondly, between Jan 27 and March 22, 1992, all women at the end of their pregnancy attending these units were included in an anonymous unlinked seroprevalence survey, irrespective of pregnancy outcome (n = 11,056). The goal of the research was to compare HIV prenatal screening policies and seroprevalences by pregnancy outcomes in order to contribute to the public debate initiated on that issue by the French health authorities. The seroprevalence survey showed a global prevalence rate of 0.43% (CI 95% = 0.32-0.54) with the prevalence among women who had an elective abortion (0.56%) being more than twice that among women who delivered (0.22%). However, routine HIV screening was more frequent toward women coming for regular prenatal care than for women seeking abortion. A systematic procedure for obtaining women's consent for HIV testing only existed in a minority of units. Only 23 out of the 62 units offering both antenatal and termination services to women had the same screening policy for women attending the different services. The research confirmed that a mandatory requirement would not improve HIV screening policy during prenatal care. However, less emphasis on women who have opted for termination of pregnancy, an absence of appropriate counselling and information procedures, and pressures on HIV-infected women to terminate current pregnancies and discourage future ones strongly suggest that HIV prenatal screening in French hospitals remains mainly focussed on fetal concerns, without sufficient attention towards the needs of women at risk of HIV infection.
HIV risk behaviours among intravenous drug users (IVDUs) were studied in southeast France, where the prevalence of HIV infection is high. Data were collected from a self-reported questionnaire distributed to drug addicts admitted in the health care or social institutions of the Alpes Maritimes department during November 1991. Among the 195 IVDUs who answered the questionnaire, 142 (73 percent) were male and 53 (27 percent) were female. One hundred and seventeen (62 percent) were HIV positive, 21 (11 percent) had an unknown HIV status, and 51 (27 percent) where HIV negative. Significant differences in HIV risk behaviours were found between HIV negative, unknown HIV status and HIV positive IDVUs: 37 percent of unknown status and 47 percent of HIV negative IVDUs continued to lend their syringe, compared with less than 20 percent HIV positive IVDUs (P < 0.001). Conversely, 57 percent of unknown HIV status and 39 percent of HIV negative IVDUs borrowed used syringes in the previous 6 months, compared with 73 percent of HIV positive IVDUs (p < 0.001). Regarding sexual prevention behaviours of patients who had had sexual intercourse during the previous 6 months: less than 20 percent of HIV negative IVDUs used condoms regularly, as against 47 percent of HIV positive IVDUs (P < 0.001). More than 70 percent of HIV negative versus 46 percent of HIV positive reported sexual intercourse without condom (p < 0.001). Logistic regression showed that the systematic use of condom was associated with a reduction of needle sharing, which suggests that IVDUs who use condoms have the best perception of risk. But the only factor associated with an increase in condom use is a HIV positive serology. These results indicate that in southeast France more efforts should be devoted to specific programmes aimed at increasing the use of condoms in the IVDU population.
Bacterial adhesion is the first step in infection of medical devices. Staphylococcus aureus and Staphylococcus epidermidis are the pathogens recovered most often. The effects of subinhibitory concentrations of vancomycin and teicoplanin on the adherence of eight clinical strains of S. aureus and eight strains of S. epidermidis to tissue culture plates in vitro were tested. The mean relative inhibitions of adherence at one-fourth and one-eighth the MIC were statistically different for teicoplanin and vancomycin. Slime production seemed not to be involved in adherence.
After describing two cases of Hashimoto's thyroiditis associated with chronic hepatitis C, we set up a prospective study to assess the prevalence of thyroid autoantibodies (thyroglobulin and thyroid microsomal autoantibodies) in 72 chronic hepatitis C patients (43 men and 29 women; mean age = 51 +/- 2.1 yr) before interferon therapy admitted between January and December 1991 to our liver unit. Thyroid autoantibodies were systematically assayed in 60 chronic HBsAg-positive patients (34 men and 26 women; mean age = 50 +/- 2.2 yr), who served as controls. Antibody to hepatitis C virus was detected with a second-generation enzyme immunoassay and then confirmed with a recombinant immunoblot assay and a supplemental enzyme immunoassay using two beads. In chronic hepatitis C patients, no men had thyroid autoantibodies. Nine of 29 women (31%) had thyroid autoantibodies. Among them, six (20.7%) had high titers of thyroid autoantibodies, and two had hypothyroidism. In all nine of these women, hepatitis C virus viremia was detected on nested polymerase chain reaction (with primers located in the 5' untranslated region). One year later, titers of thyroid autoantibodies had increased in one patient. Three other patients progressed to hypothyroidism. We judged four of 29 patients (13.8%) to have Hashimoto's thyroiditis on the basis of their high titers of thyroid autoantibodies and biological features of hypothyroidism. In the control group, only one man had thyroid microsome autoantibodies, at a very low titer (1:100). The association between chronic hepatitis C and presence of thyroid autoantibodies is clearly confirmed (p = 0.021) by this study.
Non-typhoid Salmonella infections associated with HIV infection are 20 times more frequent than those observed in the general population. Drug addicts and homosexuals are equally infected. Concerning physiopathology, a deficit in gastric acid secretion has been blamed as an etiological factor, together with T-cell deficit, except for reduction in the number of CD4 cells. This type of infection usually presents as fever; diarrhea is noted in only 20% of the cases. Several viscera can be involved. The best treatment seems to be fluoroquinones administered during 3 weeks, and several months in case of relapse. Patients under AZT therapy are less often affected with salmonellosis due to the antibiotic activity of this anti-retrovirus agent.
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Adhesion is the first step leading to colonization and infection of a foreign body (FBI). To assess the ability of a subinhibitory concentration (subMIC) of pefloxacin (P) to prevent such infection, an experimental model was developed in Swiss albino mice. Subcuts of polyurethane catheters (Vygon) were placed in the peritoneal cavity of animals and 24 hours later, different inocula of an adherent strain of Staphylococcus aureus (SA) (MIC of P:0.8 mg/l) were injected i.p. Unexposed SA served as controls. Two days later the removed catheters, blood and spleen specimens were quantitatively cultured for bacterial content and identity. Infection was defined as more than 10 CFU/ml of SA recovered. Significant protection of mice, with lower dissemination, was found with inoculum sizes of 10(5) and 10(6). These results suggest that subMICs of P may confer protection against foreign body infection.
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Determination of minimal inhibitory concentrations (MICs) provides data on the susceptibility or resistance of a bacteria; however, in susceptible bacteria this parameter is not predictive of effectiveness of the antimicrobial agent. Bactericidal activities of cefadroxil, of amoxicillin, and of the amoxicillin-clavulanic acid combination on bacteria commonly found in ENT and lower respiratory tract disease were studied comparatively. The antibiotics were given by the oral route to six healthy volunteers. With beta-lactamase-producing and non-beta-lactamase-producing strains of Escherichia coli, amoxicillin produced MICs consistent with susceptibility but failed to exhibit a bactericidal effect, whereas cefadroxil was bactericidal. Combination of amoxicillin with an inhibitor did not modify this activity on E. coli and failed to produce a bactericidal effect on Klebsiella pneumoniae similar to that seen with cefadroxil. Amoxicillin with and without clavulanic acid exhibited comparable effectiveness on Streptococcus pyogenes and S. Pneumoniae. The bactericidal effect of cefadroxil on S. pneumoniae was of similar magnitude but shorter duration than that of amoxicillin. Cefadroxil and the amoxicillin-clavulanic acid combination had similar bactericidal effects against Staphylococcus aureus. These antibiotics exhibited a time-dependent effect on Gram positive microorganisms. These pharmacodynamic data, together with measures of bactericidal activity, may be very helpful for selecting the appropriate antibiotic and dosage.