[Cytomegalovirus enteritis in AIDS. 2 cases]. / Entérite à cytomégalovirus au cours du SIDA. 2 observations.

BACKGROUND: It is uncommon for manifestations of cytomegalovirus infection to be limited to the small bowel in AIDS patients. CASE REPORTS: Two HIV-positive patients developed cytomegalovirus infection involving the small bowel with no other visceral localization. Recurrences were frequent despite medical therapy. DISCUSSION: The clinical manifestations, diarrhea, fever, vomiting and abdominal pain, suggest the diagnosis of cytomegalovirus enteritis in AIDS patients. Confirmation is obtained from the small bowel study and pathology examination of biopsy specimens. Treatment is generally based on medical and surgical management using intravenous anti-cytomegalovirus drugs and partial resection. Prognosis often remains less than satisfactory in this condition which is often diagnosed late.

Usefulness of the cytomegalovirus (CMV) antigenemia assay for predicting the occurrence of CMV disease and death in patients with AIDS.

A cohort study of 214 human immunodeficiency virus (HIV)-infected patients was performed to assess the usefulness of the cytomegalovirus (CMV) antigenemia assay for predicting the occurrence of CMV disease and death. Multivariate analysis revealed that only positive baseline CMV antigenemia assays (relative risk [RR], 7.2; 95% confidence interval [CI], 3.7-14.2; P = .0001) and CD4 cell counts (RR, 0.98; 95% CI, 0.97-0.99; P = .009) were associated with CMV disease. A positive baseline CMV antigenemia assay was also associated with death by multivariate analysis (RR, 2.2; 95% CI, 1.5-3.4; P = .0003). Increasing levels of CMV antigenemia during follow-up were associated with increased risks of CMV disease and death. A positive CMV antigenemia assay that showed > 10 cells per 2 x 10(5) polymorphonuclear leukocytes during follow-up was 91% sensitive and 84% specific for predicting a diagnosis of CMV disease; the negative predictive value for this positive test was high (97%). Therefore, the CMV antigenemia assay appears to be a simple, rapid, and inexpensive test for predicting the occurrence of CMV disease and death in patients with advanced HIV infection.

High-dose intravenous fluoroquinolones in the treatment of severe infections.

A bacterial infection should be considered "serious" in case of underlying disease, nosocomial origin, antibiotic resistant pathogen, and/or poor delivery of antibiotics at the site of infection. Treatment of most serious infections requires parenteral administration of antimicrobial agents. Intravenous fluoroquinolones are a class of antimicrobial agents from which physicians must choose when treating nosocomial infections. Fluoroquinolones are bactericidal antimicrobial agents that act by inhibiting DNA gyrase. They are active in vitro against most gram-negative bacteria and methicillin-susceptible staphylococci. Activity against anaerobic bacteria and streptococci is poor. The rapid development of bacterial resistance in centers with high quinolone usage is of great concern. Resistance develops most commonly in Pseudomonas aeruginosa and staphylococci. Most clinical trials with ciprofloxacin, ofloxacin, pefloxacin, the fluroquinolones currently available in France for parenteral use, are almost 10 years old. There are few studies with higher dosage and most of them have been carried out with ciprofloxacin. The findings of these studies indicate that higher dosage regimens of i.v. ciprofloxacin are much more effective against severe nososcomial infections than is the dosage of 200 mg twice daily. The higher dosage regimens resulted in greater rates of clinical cure and improvement in both monomicrobial and polymicrobial infections. Although the overall frequency of side effects to fluoroquinolones is low, seizures and allergic reactions have been attributed to their use.

[Anterior uveitis in HIV-infected patients. 3 cases in patients treated with an antiprotease]. / Uvéite antérieure chez des patients infectés par le VIH. 3 cas chez des patients traités par une antiprotéase.

OBJECTIVES: Uveitis is an ocular manifestation rarely observed in HIV-infected patients. We observed three cases of anterior uveitis without progressive retinitis in HIV patients receiving antiprotease treatment. CASE REPORT: The first patient developed a first episode of uveitis during ritonavir therapy. Two other episodes occurred with indinavir. The second patient developed uveitis when treated with indinavir. In the third patient, the first episode developed with indinavir and a second with a ritonavir-saquinavir combination. Uveitis was unilateral in 4 episodes. Clinical manifestations were red irritable eyes and, in 2 episodes, reduced visual acuity. The antiprotease was interrupted in 4 of the 6 episodes and clinical course was rapidly favorable. DISCUSSION: Pure anterior uveitis should suggest drug induction in HIV infected patients; rifabutin is often the cause. Infectious causes predominate in case of total uveitis associating choroid and retinal involvement. Cytomegalovirus, herpes zoster, syphilis, and toxoplasmosis have been incriminated. Antiproteases would appear to be a new cause of anterior uveitis in HIV-infected patients.

Risk factors for intestinal microsporidiosis in patients with human immunodeficiency virus infection: a case-control study.

A prospective unmatched case-control study was conducted to determine risk factors for intestinal microsporidiosis in persons infected with human immunodeficiency virus (HIV) who had < or = 200 CD4 cells/mm3. In multivariate analysis, case-patients (n = 30) were more likely than were control-subjects (n = 56) to have < or = 100 CD4 cells/mm3 (odds ratio [OR], 6.5; 95% confidence interval [CI], 1-42), to report male homosexual preference (OR, 7.6; 95% CI, 1-59.5), and to report swimming in a pool in the previous 12 months (OR, 9.2; 95% CI, 2.1-38.9). In summary, intestinal microsporidiosis in persons with HIV infection and < or = 200/mm3 CD4 cells is associated with male homosexuality and swimming in pools, suggesting fecal-oral transmission, including sexual and waterborne routes.

Albendazole for treatment and prophylaxis of microsporidiosis due to Encephalitozoon intestinalis in patients with AIDS: a randomized double-blind controlled trial.

A double-blind placebo-controlled trial was conducted to assess the efficacy and safety of albendazole (400 mg twice daily for 3 weeks) for the treatment of Encephalitozoon intestinalis infection in patients with AIDS. Clearance of microsporidia from the intestinal tract was obtained in 4 of 4 patients in the albendazole group versus 0 of 4 in the control group (P = .01, one-sided Fisher's exact test) and was associated with significant clinical benefit. All 4 controls subsequently cleared microsporidia following open-labeled albendazole treatment. To investigate the effect of albendazole in preventing relapse, these 8 patients were then randomly assigned to receive either albendazole (400 mg twice daily) or no treatment for the next 12 months. Albendazole significantly delayed the occurrence of relapse (P = .04, one-sided log-rank test). In human immunodeficiency virus-infected patients with E. intestinalis infection, albendazole has parasitologic and clinical efficacy and reduces the risk of relapse.

Use of the cytomegalovirus (CMV) antigenemia assay for the rapid diagnosis of primary CMV infection in hospitalized adults.

We assessed the value of the cytomegalovirus (CMV) antigenemia assay for diagnosing primary CMV infection in adults. The CMV antigenemia assay was performed for 40 patients admitted to our unit over a 2-year period with unexplained fever and suspected primary CMV infection. Nine of the 10 patients with primary CMV infection had positive CMV antigenemia assays, and the results were available within 5 hours. All 10 patients had a mononucleosis-like syndrome. All but one of the 30 other patients had negative CMV antigenemia assays. A false-positive result was obtained for a patient with systemic lupus erythematosus. Overall, the CMV antigenemia assay was 90% sensitive and 96% specific for the diagnosis of primary CMV infection. Therefore, the CMV antigenemia assay appears to be a simple, rapid, inexpensive test for the diagnosis of primary CMV infection in hospitalized adults.

Pulmonary Mycobacterium avium complex disease without dissemination in HIV-infected patients.

Pulmonary disease due to Mycobacterium avium complex (MAC) without evidence of dissemination is uncommon in HIV-infected patients. Five cases were observed over a 2-year period. All patients had AIDS and the median CD4 cell count at the time of presentation was 90 x 10(6)/L. Radiographic patterns included unilobar alveolar infiltrates or diffuse alveolar densities. All patients had a favorable clinical response to antimycobacterial chemotherapy with a median follow-up period of 10 months. MAC should be considered in HIV-infected patients with positive respiratory samples for acid-fast bacilli and pulmonary infiltrates. Patients with such findings in whom presumptive therapy for tuberculosis has failed should receive broad-spectrum antimycobacterial chemotherapy until final identification is available.

Cerebral tuberculosis in patients with the acquired immunodeficiency syndrome (AIDS). Report of 6 cases and review.

Cerebral tuberculosis (TB) was diagnosed in 6 (4%) of 156 HIV-infected patients with TB seen at our institution over 6 years. We describe here the clinical and radiologic features of these cases and of 15 others reported in the literature. Of the 21 patients, 59% were intravenous drug users. Presenting symptoms were fever (76%), confusion (52%), seizures (38%), and headache (38%). Fourteen patients (66%) had previous or active extracerebral TB at presentation. Cranial CT scan showed ring-(62%) or nodular-(24%) enhancing lesions or mixed forms (14%). Among the 12 patients who underwent a brain biopsy, bacteriologic evidence of TB was found in 9. Four patients (19%) died during hospitalization. Among the 17 others who received antituberculous therapy, only 1 developed neurologic sequelae. Five patients also received steroid therapy to control cerebral edema or paradoxical growth of the cerebral mass lesions. TB should be considered as a cause of cerebral mass lesions in HIV-infected patients, especially if tuberculous infection is suspected at other sites.

Potential efficacy of fumagillin in intestinal microsporidiosis due to Enterocytozoon bieneusi in patients with HIV infection: results of a drug screening study. The French Microsporidiosis Study Group.

OBJECTIVE: Intestinal microsporidiosis due to Enterocytozoon bieneusi is a frequent cause of chronic diarrhoea in patients with HIV infection for which there is no available therapy. This study was designed to search for a drug with activity against this organism. DESIGN: Prospective open-labelled Phase II multicentre study. SETTING: University hospitals. PATIENTS: Sixty HIV-infected men with intestinal E. bieneusi infection. INTERVENTIONS: Ten drug regimens were consecutively tested orally for 3 weeks: albendazole plus metronidazole, sulphadiazine plus pyrimethamine, atovaquone, doxycycline plus nifuroxazide, itraconazole, flubendazole, chloroquine, paromomycin, sparfloxacin and fumagillin. Nine evaluable patients per regimen were required, but each patient could be enrolled up to three times in the study. OUTCOME MEASURE: Efficacy was assessed primarily by the clearance of E. bieneusi from stools and intestinal biopsies. The safety of each regimen was also assessed. RESULTS: Only purified fumagillin was able to clear E. bieneusi from stools as well as intestinal biopsies, whereas all other regimens failed to show antiparasitic efficacy. However, only four patients received fumagillin because of drug-induced thrombocytopenia. The four patients who received fumagillin remained free of E. bieneusi infection after a mean follow-up of 10 months. CONCLUSION: Eradication of E. bieneusi from the intestinal tract of patients with HIV infection and persistent immunosuppression is an achievable goal. Our study allowed the identification of oral fumagillin as a potential treatment for intestinal microsporidiosis due to E. bieneusi.

Impact of protease inhibitors on AIDS-defining events and hospitalizations in 10 French AIDS reference centres. Fédération National des Centres de Lutte contre le SIDA.

OBJECTIVE: To assess the clinical and economic consequences of the use of protease inhibitors in the treatment of HIV infection. DESIGN: Multicentric, observational, retrospective cohort study. SETTING: Ten AIDS reference centres in France. PATIENTS: All patients followed in each centre from September 1995 through October 1996. MAIN OUTCOME MEASURES: AIDS-defining events, death, health-care resources use, administration of antiretroviral therapy. RESULTS: Data from 7749 patients in 10 centres showed a drop in hospitalization days by 35%, new AIDS cases by 35%, and deaths by 46%. In the same period, the proportion of patients receiving antiretrovirals rose from 36 to 53% including highly active antiretroviral therapy (HAART), which rose from 0.3 to 18%. Overall cost evaluation showed a slight increase of monthly treatment cost of US$ 12 per patient. Comparison of the three centres that used HAART earliest to the three centres that used it latest showed a clear benefit to early HAART with a drop in hospitalization days by 41%, new AIDS cases by 41% and deaths by 69%. The proportion of patients with HAART rose to 27% and monthly health-care cost decreased by US$ 248852 (i.e., by US$ 101 per patient per month). Late prescribing centres experienced a less marked effect with a drop in hospitalization days by 22%, new AIDS cases by 31%, and deaths by 32.5%. Proportion of patients with HAART rose to 12% and monthly health-care costs increased by US$ 113578 (i.e., by US$ 38 per patient per month). CONCLUSIONS: This study supports the extensive use of HAART in HIV-infected patients.

Evaluation of sorivudine (BV-araU) versus acyclovir in the treatment of acute localized herpes zoster in human immunodeficiency virus-infected adults. The Multinational Sorivudine Study Group.

The clinical efficacy and safety of sorivudine as treatment for acute cutaneous zoster in human immunodeficiency virus-infected adults was compared with that of acyclovir in a double-blinded randomized study. A total of 125 patients with laboratory-confirmed zoster rash present for < or =72 h were assigned treatment with either 40 mg of sorivudine once daily or 800 mg of acyclovir five times daily, both taken orally for 7 days. Patients were assessed daily until all lesions crusted and then monthly for 6 months for postherpetic neuralgia (PHN) and for 12 months for recurrent or new episodes of zoster. Sorivudine significantly shortened the median period of new vesicle formation from 3.0 to 4.0 days (log rank P = .0001). Sorivudine was effective regardless of duration of rash before treatment. Zoster recurrences and new episodes were experienced by fewer patients assigned sorivudine (11%) than acyclovir (26%, P = .037). No differences were seen in incidence, severity, or duration of either acute neuritis or PHN. Both treatments were well tolerated.

[Primary cerebral lymphoma in AIDS. Retrospective study of 20 patients]. / Lymphome cérébral primitif au cours du SIDA. Etude rétrospective de 20 patients.

OBJECTIVES: Analyze the epidemiological pattern of primary central nervous system lymphoma in AIDS patients together with the clinical expression and course under treatment. METHODS: We retrospectively reviewed 20 patients with AIDS-associated primary central nervous system lymphoma hospitalized in our unit between April 1992 and July 1996. Diagnosis was considered probable when an expansive intracranial process was associated with CT-scan enhancement and antitoxoplasma therapy failure in patients with extraneurological localization. Diagnosis was considered to be certain after histological confirmation. RESULTS: Most-patients were male (19/20), with a median CD4 cell count of 9/mm3 (range 0-138). Ninety percent had AIDS before diagnosis. The presenting symptoms were mental status changes (70%), neurologic deficits (55%), fever without another cause (30%), increased intracranial pressure (25%) or seizures (25%). Opportunistic diseases were usually associated (60%). CT-scan (18/20) showed spontaneous iso or hyperdense lesions, most often solitary (67%), with nodular contrast enhancement (72%). When performed (7/20), magnetic resonance imaging showed hypointense lesions on T1-weighted images with marked contrast enhancement. Diagnosis of primary central nervous system lymphoma was suspected in 19 patients because of the failure of antitoxoplasma treatment; 4 patients had stereotactic biopsy which confirmed the diagnosis. Patients were treated with either total brain radiation therapy (10%), corticosteroids (30%), or both (60%). The median survival time after onset of symptoms was better with combined therapy or radiation therapy alone than with steroids alone (6 vs. 2 months). Interestingly, most of the patients died from neurological complications of lymphoma (85%). DISCUSSION: The frequency of lymphoma-related death is probably due to better management of opportunistic infections and the effect of antiretroviral therapy. Further studies combining antiretroviral therapy, radiation and chemotherapy in patients with good performance status should be considered to improve the poor prognosis of AIDS-associated primary central nervous system lymphoma.

Diagnosis of infections caused by Enterocytozoon bieneusi and Encephalitozoon intestinalis using polymerase chain reaction in stool specimens.

OBJECTIVE: To study the usefulness of polymerase chain reaction (PCR) for the species identification of microsporidia in stool specimens obtained from HIV-infected patients with Enterocytozoon bieneusi or Encephalitozoon intestinalis infections. SETTING: Infectious disease clinic in a university hospital. PATIENTS: Thirty-seven stool specimens from 29 HIV-infected patients with microsporidiosis were tested. The diagnosis of microsporidian infection was made by light microscopy of stool specimens and species identification was made by transmission electron microscopy of duodenal biopsies. Sixty-one stool specimens from 45 HIV-infected patients without microsporidiosis served as controls. METHODS: PCR was performed using DNA extracted from stools with two primers sets, one specific for E. bieneusi and one specific for E. intestinalis. RESULTS: A 1265 base-pair fragment of the small subunit ribosomal RNA (rrs) gene could be amplified from all 31 stool specimens infected with E. bieneusi. In addition, a 930 base-pair fragment of the rrs gene could be amplified from all six stool specimens infected with E. intestinalis. The 61 control stools were negative with both primers. CONCLUSIONS: These results suggest that a PCR based assay using species-specific primers sets can be used successfully for microsporidian species differentiation from stool specimens, thus obviating the need for invasive biopsy procedures.

Prevalence of and risk factors for Clostridium difficile colonization at admission to an infectious diseases ward.

A study of 240 consecutive admissions to a single hospital ward over a 6-month period was conducted to determine the prevalence of and risk factors for Clostridium difficile colonization at admission. The prevalence rate of C. difficile colonization at admission was 13.3%. Seventy-four percent of the patients admitted to the ward were infected with human immunodeficiency virus (HIV). Multivariate analysis identified three risk factors for C. difficile colonization: clindamycin use (adjusted odds ratio [OR], 9.4; P < .001), penicillin use (adjusted OR, 3.9; P = .018), and a history of cytomegalovirus infection (adjusted OR, 4.2; P = .02). C. difficile colonization at admission to our infectious diseases ward was common. Antibiotic treatments received before admission were the main risk factors for C. difficile colonization. HIV infection per se was not associated with C. difficile colonization. It is interesting that there was an association between C. difficile colonization and a history of cytomegalovirus infection.

[Spinal tuberculous arachnoiditis]. / Arachnoïdites tuberculeuses spinales.

Tuberculous arachnoiditis of the spine is a rare complication of tuberculous meningitis and can occur despite correct treatment. We report two cases of arachnoiditis in patients with tuberculous meningitis. In both cases, clinical signs included flaccid paraparesia and sphincter dystonia. Evidence for diagnosis was obtained with magnetic resonance imaging of the lombosacral spine after a 3 or 11 week course. Adding corticosteroids to the anti-tuberculosis therapy provided spectacular clinical improvement within 8 days in both cases. The diagnosis of tuberculous arachnoiditis of the spine is often made late but can be confirmed easily with magnetic resonance imaging. Our cases emphasize the importance of oral corticosteroid therapy to avoid severe sequellae.

[Treatment of bacterial pneumonias with cefuroxime-axetil. Predictive value of measurement of the in vitro susceptibility]. / Traitement des pneumonies bactériennes par le céfuroxime-axetil. Valeur prédictive de la mesure de la sensibilité in vitro.

Cefuroxime axetil is an oral cephalosporin with proven efficacy in adult lower respiratory tract infections. Indeed, it has a broad spectrum of activity in vitro, covering most pathogens isolated in this setting and showing good stability in the presence of betalactamases. In vitro susceptibility data are a major element in the choice of antimicrobial agent. The aim of this study was to determine the predictive value of the cefuroxime minimal inhibitory concentration (MIC) on the clinical outcome of infections treated with cefuroxime axetil. One hundred-and-seventeen (117) patients with radiologically confirmed community-acquired pneumonia of presumed bacterial origin were enrolled in a prospective multicenter trial of cefuroxime axetil therapy (500 mg twice daily). The pathogen was identified in 44 patients who were treated for a mean of 8.8 days. Most isolates were S. pneumoniae (65.9%) and H. influenzae (15.9%). The MIC was known for 35 isolates and was < or = 4 micrograms/ml in 30 cases (85.7%). The MIC value was a good predictor of clinical efficacy with a sensitivity of 100%, a specificity of 83% and a positive predictive value of 97%; the latter value indicates that therapeutic success is virtually certain when the bacterium causing pneumonia is susceptible to cefuroxime.