[Degree of emergency for antibiotherapy in patients with presumed bacterial meningitis: experimental and clinical data]. / Degré d'urgence de l'antibiothérapie d'un patient présentant une méningite présumée bactérienne : modèles expérimentaux et données cliniques.

No prospective randomized clinical studies are available to determine exactly how much time should be spent on investigation before initiating antibiotherapy in a patient with presumed bacterial meningitis. Experimental models show that antibiotics should be administered before the inflammatory response, but at this time the patient's symptoms are often unspecific. Models also demonstrate that a gain of time is beneficial at any time, in terms of inflammation, magnitude of bacteremia, or loss of hearing. Very few clinical studies address the acceptable delay between admission and administration of antibiotics and two of these show a correlation with outcome in adult meningitis. The available data supports the recommendation that hospital investigation of a patient with presumed bacterial meningitis should be conducted in such a way that efficient antimicrobial chemotherapy will be initiated within one hour after arrival.

Evaluation of current practices in surgical antimicrobial prophylaxis before and after implementation of local guidelines.

The aim of antibiotic prophylaxis (ABP) is to prevent or at least decrease the incidence of postoperative surgical wound infections. In 1992 and 1995, ABP was the subject of two French consensus conferences. Following these conferences, the local Antibiotics Committee of Hopital Saint-Louis has undertaken a study to evaluate and eventually improve the current practices of ABP. This study was carried out in three steps: a first survey of ABP, the writing of local ABP guidelines and a second survey of ABP after the implementation of these recommendations. Concerning all surgical wards, the first survey found 69% (N = 100/145) of ABP practice is to be inappropriate vs. 18% (N = 25/139) in the second survey. Indications, choice of drugs, selection of dosage, administration timing and treatment duration were significantly improved in the second survey. Writing and implementing local recommendations promoted a more rational use of ABP. In addition, this study allowed Saint-Louis Hospital to set up recommendations for plastic surgery; such recommendations are poorly described in the literature.

Famciclovir vs. aciclovir in immunocompetent patients with recurrent genital herpes infections: a parallel-groups, randomized, double-blind clinical trial.

BACKGROUND: Twice-daily therapy with famciclovir (FCV) was shown to be effective for episodic therapy for recurrent genital herpes in a large placebo-controlled trial. However, no study has been published to date comparing FCV and aciclovir (ACV). OBJECTIVES: We have evaluated the effectiveness of FCV vs. ACV in the treatment of recurrent genital herpes infection. METHODS: A multicentre, double-blind, double-placebo, randomized, parallel-design study, assessed for equivalence, was conducted. As the analysis was based on confidence intervals, a difference of lesion healing time between ACV and FCV (Delta) of 1.05 days with a standard deviation of 2.30 days was chosen. Two hundred and four outpatients were included. Patients self-initiated oral therapy with 125 mg of FCV twice daily or ACV 200 mg five times daily for 5 days. The principal end-point of the study was the complete healing of lesions. Duration of the complete resolution of all symptoms, and safety were also considered. RESULTS: The mean healing time was 5.1 days and 5.4 days for FCV and ACV, respectively, with a crude value of Delta = 0.25 days (CI 95%: -0.32; 0.82) in the intent-to-treat population. Therefore, the confidence interval for the difference between the two treatments lies entirely within the equivalence range (-1.05-1.05). The value of Delta in the per-protocol population [0.35 day (CI 95%: -0.24; 0.93)] was comparable between the two groups. No differences were detected in the proportion of patients having complete healing at the different days of evaluation as well as in the duration until the complete resolution of all the symptoms. The frequency, nature and severity of adverse events did not differ among the two treatment groups. CONCLUSIONS: Twice-daily FCV was as effective and safe in the treatment of recurrent genital herpes simplex virus infection as five times daily ACV.

Trial of oral fumagillin for the treatment of intestinal microsporidiosis in patients with HIV infection. ANRS 054 Study Group. Agence Nationale de Recherche sur le SIDA.

OBJECTIVE: Intestinal microsporidiosis caused by Enterocytozoon bieneusi is a cause of chronic diarrhoea in patients with HIV infection for which there is no current therapy. This study was designed to assess the safety and efficacy of oral fumagillin in this infection. DESIGN: A dose-escalation trial. METHODS: Twenty-nine HIV-infected patients with E. bieneusi infection were consecutively enrolled in the trial. Oral doses of fumagillin were given to four groups of patients for 14 days: 10 mg/day (group 1), 20 mg/day (group 2), 40 mg/day (group 3), and 60 mg/day (group 4). Patients were seen at weeks 1, 2, 4 and 6 to assess safety and efficacy. Efficacy was assessed primarily by the clearance of microsporidia from stools and follow-up duodenal biopsies. RESULTS: Thirteen patients complained of abdominal cramps, vomiting or diarrhoea during the study, and three patients had fumagillin withdrawn because of adverse events. Thrombocytopenia, neutropenia and hyperlipasaemia were the most frequent biological adverse events. Twenty-one out of 29 patients transiently cleared microsporidia from their stools during the study. By week 6, however, all patients in groups 1, 2 and 3 had parasitic relapse. Interestingly, eight out of 11 (72%) patients treated with 60 mg/day (group 4) apparently cleared microsporidia from their gastrointestinal tract and gained weight. No parasitic relapse was documented in these eight patients during a mean follow-up of 11.5 months. CONCLUSION: Treatment with fumagillin at 60 mg/day for 14 days has promise as an effective oral treatment for E. bieneusi infections.

Once-daily combination therapy with emtricitabine, didanosine, and efavirenz in human immunodeficiency virus-infected patients.

The safety and efficacy of a once-daily regimen that combines emtricitabine, didanosine, and efavirenz was studied among 40 previously untreated human immunodeficiency virus (HIV)-infected patients. The median plasma HIV RNA level was 4.77 log(10) copies/mL at baseline and decreased by a median of 3.5 log(10) copies/mL at 24 weeks, with 98% and 93% of patients achieving plasma HIV RNA levels <400 and <50 copies/mL, respectively. The median CD4 cell count was 373 cells/microL at baseline and increased by a median of 159 cells/microL at week 24. The most common treatment-related adverse events were mild to moderate central nervous system symptoms (73% of patients), diarrhea (33%), rashes (10%), and biochemical abnormalities. Adverse reactions led to permanent drug discontinuation in only 1 patient. The once-daily combination therapy of emtricitabine, didanosine, and efavirenz was safe and demonstrated strong antiviral and immunologic effects that lasted for the 24-week period of the study.

Disseminated infection due to Encephalitozoon cuniculi in a patient with AIDS: case report and review.

OBJECTIVE AND METHODS: Infections due to microsporidia are increasingly recognized as opportunistic infections in patients with AIDS. We describe here a case of disseminated infection due to Encephalitozoon cuniculi and review the literature on this microsporidial infection. RESULTS: All 12 patients reported in the literature had AIDS and nine presented with disseminated infection involving the kidneys, sinuses, lungs, brain and conjunctiva. Asymptomatic infection was seen in three patients. Microsporidia were detected by light microscopy examination of urine samples in all the cases. Species identification was performed by various genotypic methods or transmission electron microscopy. Eight of 12 patients who received albendazole therapy experienced clinical improvement with documented clearance of spores in five of these eight patients. Two patients relapsed. CONCLUSIONS: E. cuniculi infection should be considered in severely immunocompromised HIV-infected patients with multi-organ involvement and fever, especially when renal failure is present. Microsporidial spores are usually seen in urine samples and in the involved organ. Albendazole therapy seems to be effective.

The ALBI trial: a randomized controlled trial comparing stavudine plus didanosine with zidovudine plus lamivudine and a regimen alternating both combinations in previously untreated patients infected with human immunodeficiency virus.

A total of 151 previously untreated patients infected with human immunodeficiency virus type 1 (HIV-1) with CD4 cell counts >/=200/microL and plasma HIV-1 RNA levels of 10,000-100,000 copies/mL were randomly assigned to 24 weeks of open-labeled stavudine plus didanosine (group 1), zidovudine plus lamivudine (group 2), or stavudine plus didanosine followed by zidovudine plus lamivudine (group 3). The mean decrease in HIV-1 RNA level was greater in group 1 (2.26 log10 copies/mL) than in groups 2 (1.26 log10 copies/mL) or 3 (1.58 log10 copies/mL; P<.0001). The mean increase in CD4 cell counts was greater in groups 1 (124 cells/microL) and 3 (118 cells/microL) than in group 2 (62 cells/microL; P=.02). All regimens were generally well tolerated. The combination of stavudine plus didanosine reduced plasma HIV-1 RNA concentrations and increased CD4 cell counts more effectively than did the combination of zidovudine plus lamivudine or the regimen alternating both combinations.

[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.

Results of the ALBI trial: a randomized comparison of stavudine/didanosine, zidovudine/lamivudine and alternating treatment in antiretroviral-naive patients.

In the ALBI trial, 151 antiretroviral-naive patients with plasma human immunodeficiency virus type 1 (HIV-1) RNA levels of 10,000 to 100,000 copies/ml and CD4 cell counts > or = 200 cells/mm3 received 24 weeks of treatment with stavudine/didanosine (n=51), zidovudine/lamivudine (n=51) or stavudine/didanosine for 12 weeks followed by zidovudine/lamivudine (n=49). Baseline plasma HIV-1 RNA and CD4 cell counts were comparable in the treatment groups. The mean decrease in plasma HIV-1 RNA at 24 weeks in the stavudine/didanosine group (2.26 log10) was significantly greater than that in either the zidovudine/lamivudine group (1.26 log10) or the alternating treatment group (1.58 log10) (P<0.0001 for both). Proportions of patients with plasma HIV-1 RNA level <500 copies/ml (91% vs 42% and 60%) and <50 copies/ml (47% versus 4% and 9%) were significantly greater in the stavudine/didanosine group (P<0.001 for pairwise comparisons). Stavudine/didanosine was associated with a mean increase in CD4 cell count (124 cells/mm3) significantly greater than that in the zidovudine/lamivudine group (62 cells/mm3, P<0.01) and comparable to that in the alternating group (118 cells/mm3). All study regimens were well tolerated. These findings, indicating superiority of stavudine/didanosine over zidovudine/lamivudine in virological and immunological response over 24 weeks, suggest that the combination should be considered as a basis for highly active antiretroviral therapy.

[Peripheral adrenal insufficiency in AIDS]. / Insuffisance surrénale périphérique au cours du SIDA.

BACKGROUND: Lesions of adrenal glands are common findings at autopsy of patients with acquired immunodeficiency syndrome (AIDS). In contrast the diagnosis of symptomatic adrenal insufficiency is rarely established during the lifetime of these patients. PATIENTS: We report four new cases and review the literature. All four patients had full blown AIDS with a mean CD4 cell count of 19 mu/L. One or more opportunistic disease was present at the time of diagnostic: cytomegalovirus retinitis in two cases, disseminated Mycobacterium avium infection in two, Kaposi's sarcoma in two and Candida esophagitis in one. RESULTS: The clinical presentation constantly included fatigue, weight loss, severe orthostatic hypotension and gastrointestinal disturbances. Cutaneous hyperpigmentation was present in three cases. In most cases biological abnormalities were typical, such as hyponatremia, urinary Na/K ratio > or = 1, and hyperkalemia. Serum cortisol levels were within the range of normal in three cases but response to the cosyntropin challenge was typically impaired in all cases. Clinical and biological manifestations returned to normal in 1 to 3 weeks after initiation of therapy with cortisol, associated to fludrocortisone in three cases. However, 13 months after diagnosis, three patients were dead. CONCLUSION: Usually asymptomatic, diagnostic of symptomatic adrenal insufficiency must be suspected even when clinical presentation is atypical because rapid efficiency of hormonal treatment.

[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.

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.

[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.

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.

[Pneumococcal infections in patients with HIV infections]. / Infections à pneumocoque chez le patient infecté par le VIH.

UNLABELLED: VERY HIGH INCIDENCE: Streptococcus pneumoniae is the most frequent causal agent of bacterial pneumonia in HIV-positive patients. SPECIFIC COURSE: Clinical manifestations are similar to those in normal hosts except for increased rates of bacteremia and recurrent disease, but mortality from pneumococcal disease is substantial in patients with AIDS. THERAPEUTIC MANAGEMENT: Although the independent influence of HIV infection has not been well assessed, antibiotics effective against penicillin-resistant strains such as the amoxicillin-clavulanic acid combination or cephalosporines (cefatoxime, ceftriaxone) must be considered in the empirical treatment of HIV-infected patients with pneumococcal disease. PROPHYLAXIS: Since the effectiveness of pneumococcal vaccine has not been demonstrated, clinical trials of vaccination performed early in the course of HIV infection are warranted.