[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.

Risk factors for Clostridium difficile-associated diarrhoea in HIV-infected patients.

OBJECTIVE: To identify risk factors associated with a first episode of Clostridium difficile-associated diarrhoea (CDAD) in patients with HIV infection. DESIGN: A case-control study. SETTING: University teaching hospital HIV inpatient unit. PATIENTS AND METHODS: Nineteen HIV-infected patients with CDAD, defined as diarrhoea with positive stool culture for Clostridium difficile (CD) and positive stool cytotoxin B assay, were compared with 38 randomly selected controls (HIV-infected patients hospitalized on the ward on the day the matched case was diagnosed). CD isolates were phenotyped by electrophoretic protein patterns. RESULTS: The incidence of CDAD among HIV-infected patients was 4.1/100 of patient-admissions. On univariate analysis, cases were more likely to have used clindamycin [11 out of 19 compared with four out of 38; odds ratio (OR) 19; 95% confidence interval (CI), 2-160; P = 0.0007], and pyrimethamine (14 out of 19 compared with 13 out of 38; OR, 4.8; 95% CI, 1.4-16, P = 0.02) in the month before diagnosis, and to have had cerebral toxoplasmosis (12 out of 19 compared with 13 out of 38; OR, 2.8; 95% CI, 0.9-8.6; P = 0.09). There was also a significant increase of the risk of CDAD as duration of hospitalization in the ward increased (chi 2 for trend, P = 0.007). Multivariate models associated two risk factors with CDAD: clindamycin use (OR, 42; 95% CI, 2-813; P = 0.01), and prolonged hospitalization in the ward (OR, 3.6 per week in the ward; 95% CI, 1-13, P = 0.048). Of 18 available CD isolates, 15 (83%) had identical electrophoretic protein pattern. CONCLUSIONS: Clindamycin use and prolonged hospitalization in the ward were the main risk factors associated with CDAD in this study. These observations, together with the occurrence of one major phenotype of CD, suggest nosocomial transmission of CD in the ward.

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.

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.

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.

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.

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.

[Role of invasive candidiasis in hospital pathology]. / Place des candidoses invasives en pathologie hospitalière.

The frequency, mode of occurrence, diagnostic criteria and main features of systemic and visceral candidiasis have been evaluated in a retrospective study of all cases managed in St Louis Hospital, Paris, during the [June 1, 1985-May 31, 1986] period. During this one year period 23 patients suffered from systemic or visceral candidiasis and Candida spp. accounted for 9.6% of all positive blood cultures, fourth in number after Enterobacteriaceae, Staphylococcus and Pseudomonas. Abnormal underlying condition was present in all patients, mainly haematologic malignancies, serious abdominal surgery and AIDS. In patients with haematologic malignancies C. tropicalis was the main species involved in contrast with surgical patients in whom the dominant responsible species was C. albicans. No Candida oesophagus was common. Therapeutic regimens included amphotericin B in all patients with systemic disease. We conclude that in an institution mainly oriented toward management of cancer and surgical patients, systemic and visceral candidiasis are common and represent a serious problem.

[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.

[Radiologic aspects of noncalculous inflammation of the biliary tract in AIDS]. / Aspects radiologiques des inflammations non calculeuses des voies biliaires au cours du SIDA.

Six cases of non-lithiasic cholecystitis and 7 cases of inflammatory cholangitis caused by cryptosporidium and/or cytomegalovirus infections have been studied in HIV-1 + patients. All patients were examined with ultrasound and 5 with computed tomography (CT). The appearance is the same as that described for non-lithiasic cholecystitis (pain when the ultrasound probe is applied, thickened gallbladder wall) and sclerosing cholangitis (dilatation and/or stenosis of the bile duct, thickened gallbladder wall). The ultrasound or CT examination of HIV + patients with gallbladder involvement is sufficient to guide treatment when a thickened gallbladder wall is demonstrated. On the other hand, bile duct opacification is the only method allowing the accurate assessment of the extent of lesions in cholangitis, on which the indication for eventual sphincterotomy is based.

[Pharmacokinetics of ceftazidime in the cerebrospinal fluid]. / Pharmacocinétique de la ceftazidime dans le liquide céphalorachidien.

A compound potentially effective in the treatment of meningitis should reach high concentrations in CSF. In animal experimental models, ceftazidime levels of 5-25 micrograms/ml were demonstrated during administration of doses generating serum levels similar to those achieved in humans. Human studies later confirmed CSF levels of 5-10 micrograms/ml in patients with meningitis. Ceftazidime CSF kinetic properties are adequate for use of this compound in patients with meningitis due to susceptible organisms.

[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.

[Treatment of 18 cases of purulent meningitis with moxalactam. Pharmacokinetic data]. / Traitement de 18 méningites purulentes par le moxalactam. Données pharmacocinétiques.

The diffusion of moxalactam into cerebrospinal fluid was studied in 18 hospital patients with purulent meningitis treated with this antibiotic. Moxalactam was administered by intravenous infusion in doses of 2 g 8-hourly (6 g/24 h). Treatment lasted from 10 to 30 days depending on the pathogen involved. The antibiotic was assayed by high performance liquid chromatography simultaneously in serum and CSF at the time of lumbar puncture. Depending on the time elapsed since the end of the infusion, the mean CSF concentrations ranged from 32.8 to 9.37 micrograms/ml at the beginning of the disease and from 23.75 to 3.78 micrograms/ml toward the end of treatment. These values were notably higher than the MIC for most of the micro-organisms encountered. All patients were cured.

[Penetration of piperacillin into the cerebrospinal fluid of patients with purulent meningitis]. / Pénétration de la pipéracilline dans le liquide céphalo-rachidien des malades atteints de méningite purulente.

Ten patients with purulent meningitis received 3 intravenous injections of 4 g piperacillin at intervals of 8 hours, in addition to the usual antimicrobial treatment. Piperacillin was assayed in serum and CSF by high performance liquid chromatography. The mean CSF concentration of the drug was 9.2 micrograms/ml and its mean percentage of penetration was 22,7%. There were no significant differences in CSF concentrations between days 2 to 4 (inflamed meninges) and days 10 to 20 (patient cured). It is concluded that piperacillin shows good CSF penetration and could be useful to treat selected cases of meningitis due to Gram-negative bacilli.

[Treatment of enterobacterial meningitis in adults with intravenous lamoxactam]. / Traitement des méningites à entérobactéries de l'adulte par le lamoxactam intraveineux.

Meningitis caused by Gram-negative bacilli creates difficult problems since most strains are multiresistant. The purpose of this study was to evaluate the effectiveness of lamoxactam administered intravenously. Eleven patients admitted to an intensive care unit with meningitis due to Gram-negative bacilli were treated with this antibiotic, administered alone in 9 cases. Three patients had ventriculitis. Eight survived. The MICs ranged from 0.06 to 0.5 microgram/ml in 10 cases. The CSF was sterilized and rapidly became normal. Meningeal concentrations varied from 1-5 to 62 micrograms/ml and the CSF was bactericidal. In one female patient the CSF was sterile on the 5th day of treatment but remained abnormal; the meningeal concentration of lamoxactam (35 micrograms/ml) was much higher than the MIC (2 micrograms/ml) but below the MBC (128 micrograms/ml), which was consistent with the absence of bactericidal effect of the CSF. Owing to its very low CMIs and satisfactory passage through the blood-brain barrier, lamoxactam administered alone can be successful in the treatment of Gram-negative meningitis and ventriculitis. However, the bactericidal effect of the CSF should be rapidly assessed.

[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.

[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.

[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.

[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.

[Contributions of experimental models to the physiopathology and treatment of bacterial meningitis]. / Apports des modèles expérimentaux à la physiopathologie et à la thérapeutique des méningites bactériennes.

Access to the cerebrospinal fluid, which is the only objective reflection of the essential parametres, is very limited. Investigators have long tried to design an animal model. Presently, the experimental model of the newborn rat is most often used for studying pathogenic factors in haematogenous meningitis. In contrast, the rabbit model is more adapted to therapeutic investigation The main advances have been therapeutic and pathophysiologic. Good examples are the identification of optimum antibiotic levels in the cerebrospinal fluid, and the demonstration of the responsibility of mediators produced by the host in triggering the inflammation. The principle of corticosteroid treatment before induction of bacterial lysis by antibiotics in Haemophilus meningitis is a result of such work.