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Biomedical subjects

J C Petit

Publications and source records attributed to J C Petit.

At least 19 recordsLinked to original sources

Clostridium difficile-associated diarrhea in HIV-infected patients: epidemiology and risk factors.

A retrospective analysis of all the cases of Clostridium difficile-associated diarrhea (CDAD) in hospitalized patients infected with HIV was performed over a 52-month period to assess the incidence, epidemiology, and risk factors of CDAD. A case of CDAD was defined as a patient with diarrhea and a positive stool cytotoxin B assay. Sixty-seven cases of CDAD were recorded in HIV-infected patients between January 1991 and April 1995. The annual incidence of CDAD ranged from 1.7 to 6.4 per 100 HIV-infected patients discharged from hospital. The 67 CDAD cases included 48 (72%) first episodes and 19 (28%) relapses. Serogroup C accounted for 69% of strains from initial episodes of CDAD. To identify risk factors for CDAD, 34 HIV-infected patients with a first episode were compared with 66 HIV-infected controls matched for the length of hospital stay. Three independent factors remained significantly associated with CDAD among HIV-infected patients: CD4+ cell counts <50/mm3 (OR = 5.2; 95% CI = 1.4-19.3; p = 0.01), clindamycin use (OR = 5.0; 95% CI = 1.3-18.3; p = 0.02) and penicillin use (OR = 4.6; 95% CI = 1.1-18.8; p = 0.03). C. difficile is a common enteric pathogen responsible for nosocomial diarrhea in HIV-infected patients. Clinicians should keep this pathogen in mind when searching for the cause of diarrhea in these patients, especially those who are severely immunocompromised or have received clindamycin or penicillin.

Adult

Even individuals considered as long-term nonprogressors show biological signs of progression after 10 years of human immunodeficiency virus infection.

Despite a decade of human immunodeficiency virus (HIV) seropositivity, a few individuals termed as long-term nonprogressors (LTNPs) maintain a stable CD4+ T-cell count for a period of time. The aim of this study was to establish, through the sequential determination of all known predictors of HIV disease, the proportion of such patients having stringent criteria of true long-term nonprogression. Among 249 individuals who were HIV-infected and prospectively followed up over a 10-year period (1985 to 1995), 12 having a CD4+ T-cell count greater than 500/microL (LTNP I group) and 9 having a CD4+ T-cell count less than 500 but stable over time (LTNP II group) after at least 10 years of infection without intervention of antiviral therapy, were studied over the entire follow-up period. The plasma HIV RNA copy number and the serum concentrations of p24 antigen, each anti-HIV antibody, neopterin, beta-2-microglobulin, Immunoglobulin (Ig) G and IgA were determined every 18 months over the study period. Cellular and plasma viremias were cross-sectionaly assayed in all 21 patients. Only two patients had strictly no marker of progression over the follow-up period. They were the only ones who had, over the 10-year period, a viral copy number too low to be detected. The other patients had a viral copy number higher than 400/mL at at least one visit and increasing over the follow-up period, and they evidenced one or more markers of virological or immunological deterioration. Cellular viremia was positive in all patients but two, while plasma viremia was negative in all but one. The population of individuals termed as LTNPs is not virologically and immunologically homogeneous. The majority present biological signs of HIV disease progression. A new pattern of true LTNP can be drawn through stringent criteria based on the whole known predictors. This pattern appears to be rare in HIV-positive population.

Adult

[Prospective study of pathogenic agents isolated from feces of patients with HIV infections].

OBJECTIVE: Determine the frequency of enteropathogenic agents isolated in diarrheic feces of patients with HIV infection and to compare findings with a control group (HIV + without diarrhea) in order to identify risk factors. PATIENTS AND METHODS: All HIV seropositive inpatients and outpatients seropositive for HIV, with or without diarrhea, seen between 1 November 1994 and 30 April 1995 were included. Samples of feces were obtained for culture, virology examination, parasite examination and search for Clostridium difficile. The same samples were obtained in case of diarrhea during the course of hospitalization. RESULTS: There were 113 samples. Analyses demonstrated a pathogenic agent in 73.6% of the samples in patients with diarrhea and in 31.6% of those without diarrhea. Clostridium difficile and parasites were the most frequently identified agents. An infectious agent was identified in one-fourth of the patients without clinical signs of diarrhea, and in one-fourth of those with diarrhea no pathogen could be demonstrated. No factor of risk for finding a particular microorganism in feces of patients with diarrhea could be identified. DISCUSSION: The exact pathogenic roles of Pseudomonas aeuriginosa, yeast, and adenovirus remain to be determined. It is hypothesized that the HIV has a direct effect on the host digestive tract.

AIDS-Related Opportunistic Infections

Risk factors for cirrhosis in patients with chronic hepatitis C virus infection: results of a case-control study.

The role of the viral genotype, especially genotype 1b, in the severity of liver injury induced by chronic hepatitis C virus (HCV) infection is unclear, probably because of confounding factors such as the date and mode of contamination. Host genetic or environmental factors such as heterozygous MZ alpha1-antitrypsin deficiency or alcoholism, could also be potential risk factors for the development of cirrhosis. The aim of this study was to compare the prevalence of genotypes, alpha1-antitrypsin phenotype, past hepatitis B virus infection, and alcohol consumption in cirrhotic and noncirrhotic patients with chronic hepatitis C. We conducted a case-control study comparing 84 consecutive cirrhotic patients with chronic hepatitis C (cases) with 84 noncirrhotic patients with chronic hepatitis C (controls) selected from a cohort of 464 patients hospitalized during the same period. Controls were paired with cases according to age, sex, risk factors, and date of infection. HCV genotypes were determined using the InnoLiPA technique (Innogenetics, Zwijnaarde, Belgium) and classified according to the method of Simmonds. Patients were divided in three groups according to alcohol consumption: <30 g/d (light), 30 to 80 g/d (moderate), and >80 g/d (heavy). Cirrhotic and noncirrhotic patients were not significantly different in terms of genotype distribution (1a/1b/2a/3a/others/undetermined: 10/48/7/17/0/2 versus 11/43/10/10/5/5), alpha1-antitrypsin phenotype distribution (MM/MS/MZ: 84%/14%/2% vs. 87%/11%/2%, respectively), and prevalence of antibody to hepatitis B core antigen positivity (29% vs. 23%). Alcohol consumption was significantly different between cases and controls (L/M/H: 58%/27%/16% vs. 76%/15%/9%, respectively; P < .05). Two conclusions regarding patients with chronic hepatitis C virus infection can be drawn from this study: 1) viral genotype, especially 1b, past hepatitis B virus infection, and heterozygous MZ alpha1-antitrypsin deficiency are not risk factors for cirrhosis; and 2) alcohol consumption, even moderate, is a risk factor for cirrhosis.

Adult

Full or partial seroreversion in patients infected by hepatitis C virus.

Cases of partial seroreversion have been reported in hemodialyzed or immunodepressed patients, but spontaneous clearance of viremia associated with a disappearance of specific antibodies or clearance while receiving therapy has not been precisely documented in immunocompetent hepatitis C virus (HCV)-infected persons. A longitudinal study of markers of HCV infection in a cohort of 178 multitransfused patients followed over an 8-year period was done to establish well-documented cases of partial or full seroreversion. Thirty (16.8%) of 178 patients were HCV-infected; among them, 5 had partial or full seroreversion. Seroreversion to an anti-HCV-negative state is characterized by a quantitative decrease in antibody. A seroreversion may be observed in three circumstances: spontaneously, induced by therapy, and in conjunction with human immunodeficiency virus infection. Long-term follow-up of seroreverters will establish whether they have definitively eradicated HCV from their systems.

Alanine Transaminase

Killing kinetics of RP 59500 and pristinamycin against penicillin-resistant pneumococci.

The killing kinetics of two streptogramins, RP 59500 and pristinamycin against seventeen isolates of penicillin-susceptible and resistant pneumococci were studied. The antibiotics were tested at 1x, 2x and 4x the MIC for each individual isolate. The results showed a very good and rapid bactericidal activity within 1 hour for concentrations equal or greater to the MIC. These antibiotics are very promising agents for the treatment of infections due to multiresistant pneumococci.

Anti-Bacterial Agents

Direct infection of CD34+ progenitor cells by human cytomegalovirus: evidence for inhibition of hematopoiesis and viral replication.

We successfully infected fluorescence-activated cell-sorted CD34+ cells from normal cord blood by the human cytomegalovirus (HCMV) laboratory strain Towne. An inhibitory effect of HCMV on clonogenic myeloid progenitors was observed in primary methylcellulose cultures. After an initial 7-day liquid culture of CD34(+)-infected cells, this inhibition was further amplified in secondary methylcellulose cultures, then involving both the myeloid and erythroid lineages. Under these conditions, viral DNA was detected both in erythroid and myeloid colonies using the polymerase chain reaction (PCR), but reverse transcription PCR (RT-PCR) failed to detect viral RNA. In contrast, when CD34(+)-infected cells were maintained in liquid suspension, both immediate, early, and late transcripts were detected as soon as day 3. In addition, viral production was demonstrated in the culture supernatants, thus confirming that a complete viral cycle occurred under liquid conditions. Furthermore, by resorting cells into CD34+ and CD34- fractions, we showed by RT-PCR that viral replication took place in cells still expressing CD34 antigen, whereas no RNA was found in more differentiated cells that had subsequently lost their CD34 antigen. These findings suggest that HCMV replication can occur at the early steps of progenitor differentiation and may be involved in the viral-induced myelosuppression.

Antigens, CD34

Prevalence and pathogenicity of Clostridium difficile in hospitalized patients. A French multicenter study.

BACKGROUND: Although Clostridium difficile is the main agent responsible for nosocomial diarrhea in adults, its prevalence in stool cultures sent to hospital microbiology laboratories is not clearly established. OBJECTIVES: To determine the prevalence of C difficile in inpatient stools sent to hospital microbiology laboratories and to assess the relationship between serotypes and toxigenicity of the strains isolated and the clinical data. METHODS: From January 18, 1993, to July 31, 1993, the presence of C difficile was systematically investigated in a case-control study on 3921 stool samples sent for stool culture to 11 French hospital microbiology laboratories. The prevalence of C difficile in this population (cases) was compared with that of a group of 229 random hospital controls matched for age, department, and length of stay (controls). Stool culture from controls was requested by the laboratory although not prescribed by the clinical staff. Serotype and toxigenesis of the strains isolated were compared. RESULTS: The overall prevalence of C difficile in the cases was twice the prevalence in the controls (9.7% vs 4.8%; P < .001) and was approximately 4 times as high in diarrheal stools (ie, soft or liquid) as in normally formed stools from controls (11.5% vs 3.3%; P < .001). The strains isolated from diarrheal stools were more frequently toxigenic than those isolated from normally formed stools. Serogroup D was never toxigenic, and its proportion was statistically greater in the controls than in the cases (45% vs 18%; chi 2 = 5.2; P < .05). Conversely, serogroup C was isolated only from the cases. Clostridium difficile was mainly found in older patients ( > 65 years), suffering from a severe disabling disease, who had been treated with antibiotics and hospitalized for more than 1 week in long-stay wards or in intensive care. CONCLUSIONS: This multicenter period prevalence study clearly supports the hypothesis of a common role of C difficile in infectious diarrhea in hospitalized patients. Disease associated with C difficile should therefore be systematically evaluated in diarrheal stools from inpatients.

Anti-Bacterial Agents

[Acid-alcohol-resistant bacilli detected by microscopic analysis of exhaled air from HIV-infected patients: tuberculosis or mycobacteriosis?].

OBJECTIVES: The incidence of atypical mycobacterial infections has increased with the AIDS epidemic. To present, microscopic examinations of airway specimens positive for acid-fast bacteria were highly suggestive of tuberculosis. However, since the AIDS epidemic, certain authors have reported an increase in Mycobacterium avium intracellulare found in respiratory specimens. The aim of this work was to determine what factors might distinguish between these two infections revealed discovery of an acid-fact bacilli. METHODS: Hospital files of all HIV seropositive patients seen between November 1992 and March 1995 and with at least one airway specimen positive for acid-fast bacilli were studied retrospectively. RESULTS: Mycobacterium tuberculosis was isolated in 19 patients, Mycobacterium avium intracellulare in 8 and culosis and M. avium intracellulare. There was no difference for age, sex, geographical origin, transmission mode, antigen positivity, radiologic findings or clinical signs between patients with the different types of mycobacterium. The CD4 count was however significantly lower in patients with an atypical mycobacteriosis (14.5/mm3) than in patients with tuberculosis (91.7 +/- 83.7) (p = 0.004). CONCLUSION: These findings show that in HIV-infected patients with a CD4 count under 100/mm3, the presence of acid-fact bacilli can indicate either M. tuberculosis or M. avium intracellulare. Combined anti-tuberculosis and antimycobacteriosis therapy thus would appear to be justified until the germ can be identified.

AIDS-Related Opportunistic Infections

Quantitation of passively acquired human immunodeficiency virus (HIV) antibodies in AIDS patients transfused with a plasma that is rich in HIV antibodies.

BACKGROUND: Passive immunotherapy in human immunodeficiency virus (HIV) infection is based on transfusions of plasma that is rich in HIV antibodies. STUDY DESIGN AND METHODS: To verify whether the clearance of transfused antibodies will maintain an elevated titer of specific antibodies between biweekly transfusions of plasma, the titers of anti-HIV-1 in plasma and in transfusion recipients were measured. Samples from 12 recipients were analyzed by automated scanning of Western blot, before transfusion and at Days 2, 7, and 14 after transfusion. RESULTS: The p24 antibody became detectable or higher than the baseline after transfusion and remained detectable until the second transfusion. Anti-p24 titers were variable and dependent on the antibody titer of the transfused plasma and the baseline p24 antigen titer. CONCLUSION: Biweekly transfusion of plasma with a high anti-HIV titer maintains a high anti-p24 titer between transfusions in AIDS patients treated with passive immunotherapy.

Acquired Immunodeficiency Syndrome

Risk factors for isolation of Streptococcus pneumoniae with decreased susceptibility to penicillin G from patients infected with human immunodeficiency virus.

We conducted a retrospective study of all hospitalized human immunodeficiency virus (HIV)-infected patients from whom a strain of Streptococcus pneumoniae was isolated (n = 45) between January 1992 and September 1994, in order to determine the clinical manifestations and outcome of and risk factors for infection by S. pneumoniae with decreased susceptibility to penicillin G. Such strains were isolated from 14 patients (31%), of whom 8 had pneumonia, 2 had bronchial superinfection, 2 had sinusitis, and 2 were colonized. All infected patients made a clinical recovery regardless of the MIC of the isolate. Indexes of HIV disease stage (CD4+ cell count and p24 antigenemia), antiretroviral treatment, and hospital admission in the previous 3 months did not influence the susceptibility of the isolates. For HIV-infected patients, treatment with antibacterial agents--particularly trimethoprim-sulfamethoxazole--in the previous 3 months is associated with an increased risk for isolation of S. pneumoniae with decreased susceptibility to penicillin G (relative risk, 5.0; 95% confidence interval, 1.9-13.3).

AIDS-Related Opportunistic Infections

Killing kinetics of meropenem against penicillin-resistant pneumococci.

The killing kinetics of meropenem against sixteen clinical isolates of pneumococci (12 penicillin-resistant, three penicillin-intermediate and one penicillin-sensitive) were studied. Meropenem was tested at 1x, 2x and 4x the MIC for each individual isolate. The results showed a good bactericidal activity with rapid killing of pneumococci (killing > 3 log10 cfu/mL was obtained for nine strains). This strategy needs clinical assessment and might prove to be a suitable alternative to penicillin and cephalosporins for the treatment of mixed infections involving multiresistant pneumococci.

Meropenem

Monitoring of cytomegalovirus infection and disease in bone marrow recipients by reverse transcription-PCR and comparison with PCR and blood and urine cultures.

Preemptive therapy is a promising strategy for the prevention of serious cytomegalovirus (CMV) disease after bone marrow (BM) transplantation but requires relevant diagnostic tests. We compared the clinical value of a reverse transcription (RT)-PCR method, which detected a late viral mRNA in peripheral blood leukocytes (PBL), with a PCR method that detected the viral DNA in PBL and with viral culture from leukocytes and urine for the diagnosis of symptomatic CMV infection after BM transplantation. Forty-five consecutive BM recipients were prospectively tested at weekly intervals by the four methods. CMV infection, demonstrated either by the culture of CMV or by repeated detection of viral DNA, was observed in 28 patients, but only 14 developed CMV-related clinical symptoms. The clinical sensitivity and specificity of each technique for detection of symptomatic infection were, respectively, 36 and 74% for urine culture, 43 and 84% for leukocyte culture, 100 and 65% for PCR, and 71 and 94% for RT-PCR. Although PCR detection of DNA in PBL was the earliest and most sensitive technique for the diagnosis of CMV infection, RT-PCR was more predictive of the onset of CMV-related clinical symptoms. These data suggest that both molecular methods should be used for identifying BM recipients at highest risk of CMV disease.

Adolescent

[In vitro study of the bacteriostatic and bactericidal activity of meropenem against strains of Pseudomonas aeruginosa multiresistant to antibiotics].

Meropenem is a new dehydropeptidase stable carbapenem which has an in vitro bacteriostatic activity superior to imipenem against Pseudomonas aeruginosa. Minimal inhibitory concentrations of meropenem (MEM) and imipenem (IPM) were determined on twelve strains: two were genetically characterized reference strains and ten isolated from patients. Killing curves were performed for MEM used at 1,2 and 4 fold the MIC and 32 mg/l; survivors were counted at baseline and after 5 and 24 hours of incubation by spiral plating. Five strains were susceptible to MEM and IPM; five were intermediate and two resistant to MEM; these seven strains were resistant to IPM. A weak bactericidal effect was obtained after 5 h at each concentration. Only one strain achieved a 3 log 10 reduction after 5 h at 2 x MIC. A regrowth of all the strains tested was observed after 24 h.

Dose-Response Relationship, Drug

Correlation between viral DNA load and serum anti p19 antibody concentration in symptomless human T-lymphotropic virus type-I (HTLV-I)-infected individuals.

In order to determine whether serum anti-human T-cell lymphotropic virus type I (HTLV-I) antibody concentration is correlated with cellular viral DNA load, these 2 biological parameters were established in 22 symptomless HTLV-I carriers. The proviral copy (PVC) number was determined through quantificative polymerase chain reaction. Specific antibody titers were determined by Western blot with the end-point dilution method; the quantification of each antibody was performed through ScanBlot by determination of the peak height of each Western-blot band. A positive correlation was observed between the PVC number and the titer of total antibodies. When the association between the peak height of each antibody and the PVC number was studied, a significant positive correlation was observed only with anti-p 19. Further evaluation through follow-up studies of symptomless HTLV-I individuals is needed to clarify the value of anti-HTLV-I antibody titer as a predictor of disease progression.

Adult

Serum anti-p24 antibody concentration has a predictive value on the decrease of CD4 lymphocyte count higher than acid-dissociated p24 antigen.

We studied the prognostic value on the decrease of CD4 lymphocyte count of anti-p24 antibody (ab) titer and compared this value with that of polyclonal and monoclonal p24 (ag) titer before and after immune complex dissociation (ICD); 53 human immunodeficiency virus (HIV)-infected patients having CD4+ counts above 400/mm3 when first examined were followed up over a 3-year period including at least four visits; HIV disease progressors (n = 18) were defined as having CD4+ counts below 200/mm3 and non-progressors (n = 35) as having CD4+ counts still above 400/mm3 at the end of follow-up. Sera were collected at each visit and assayed for p24 ag with and without ICD and for anti-p24 ab titer. The mean anti-p24 ab titer of progressors and of non-progressors at entry was significantly different. A threshold of anti-p24 ab titer indicating a HIV progression was determined at 1/300. The proportion of individuals with an anti-p24 ab titer lower than 1/300 at least once during the study period was 34% in non-progressors and 94% in progressors. The difference between progressors and non-progressors at entry was significant with monoclonal p24 ag without ICD and more significant with monoclonal p24 ag after ICD. The marker having the highest predictive value was the anti-p24 ab titer, then monoclonal p24 ag with ICD, then polyclonal p24 ag with ICD. Anti-p24 ab is an earlier and stronger marker of the decrease of CD4 lymphocyte count than p24 ag even after ICD.

Acids