Frequency and risk factors of infectious complications in neutropenic patients infected with HIV.

OBJECTIVE: To determine causes, incidence and factors associated with infections in neutropenic [polymorphonuclear neutrophil (PMN), 1000 x 10(6)/l] HIV-infected patients. DESIGN: Prospective study. SETTING: Infectious disease service of a 1000-bed university teaching hospital in Paris, France. PATIENTS: HIV-infected patients with a PMN count of < 1000 x 10(6)/l confirmed on two occasions were included in the study. Baseline characteristics, cause of neutropenia and occurrence of infectious episodes were analysed. RESULTS: The cause of neutropenia was lymphoma in four cases (6.5%), antineoplastic chemotherapy in seven (11.3%), zidovudine in 32 (51%), trimethoprim-sulphamethoxazole (TMP-SMX) in 28 (45%) and ganciclovir in 11 (18%). Fifteen patients (24%) developed infectious complications. Neutropenia induced by chemotherapy or lymphoma was more frequently complicate by infectious episodes (P = 0.02). Neutropenia in the previous 3 months (P = 0.05), presence of a central venous catheter (P = 0.05) and a trough PMN count (P = 0.02) were the three risk factors of infection retained in a logistic model. CONCLUSION: Neutropenia induced by zidovudine, gangiclovir or TMP-SMX, are less complicated by infectious episodes than neutropenia induced by antineoplastic chemotherapy. Overall, infectious episodes in neutropenic HIV-infected patients appear lower than in patients with haemobiologic malignancies.

Clinical and echocardiographic observations in pulmonary valve endocarditis.

Clinical and echocardiographic data from 12 patients with pulmonary valve endocarditis are described. Seven patients had isolated pulmonary endocarditis and in 5 patients other valves were infected (aortic, tricuspid, mitral or all 3). Two patients were heroin addicts and 4 had underlying heart disease (congenital heart disease in 3 and aortic regurgitation in 1 patient). The organisms involved were alpha streptococci in 3 patients (all with underlying heart disease), Staphylococcus aureus in 4, Streptococcus D bovis in 1 patient and Candida guillermondii in 1. M-mode and 2-dimensional echocardiography was performed in 10 patients and revealed vegetations in 8. Pulsed Doppler echocardiography was performed in 6 patients and revealed pulmonary regurgitation in all 6. Seven patients had pulmonary emboli. Four patients underwent surgery. Four patients died, including 1 after cardiac surgery. Five patients, including the patient infected with Candida guillermondii, recovered with antibiotic treatment.

Cutaneous sparganosis in France: the second case described from Europe. Case report.

The first case of sparganosis is reported from France. The patient, a 21-year-old man, presented with a subcutaneous lump on the chest, and the diagnosis was made on histological examination after needle biopsy. He achieved a complete recovery.

Investigation of a nosocomial outbreak of Clostridium difficile-associated diarrhoea among AIDS patients by random amplified polymorphic DNA (RAPD) assay.

Clostridium difficile is now well-established as the main cause of antibiotic-associated diarrhoea or colitis. Nosocomial acquisition of C. difficile has been described among various immunocompromised patient populations. From January to December 1992, 19 cases of antibiotic-associated diarrhoea occurred among AIDS patients in the same ward of a hospital. They all harboured C. difficile in their stools. All the strains were retrospectively typed by the random amplified polymorphic DNA (RAPD) method using two different 10-mer oligonucleotides. Twenty-five C. difficile strains (isolated from 15 patients) yielded the same RAPD pattern, suggesting they were identical. The timing and location of infections indicated that transmission of this highly resistant spore-forming bacterium can occur not only by direct patient-patient contact but also at a distance in time and space. This is the first report of an outbreak of C. difficile-associated diarrhoea in AIDS patients. Epidemiological markers are needed to recognize and control common-source outbreaks; RAPD assay is a simple, rapid and effective way of distinguishing isolates of C. difficile.

Two cases of cytomegalovirus infection revealed by hearing loss in HIV-infected patients.

Neurological complications are particularly common during HIV infection. Among various opportunistic diseases, cytomegalovirus (CMV) is one of the most frequent causes of central and peripheral neurological manifestations. Previously, there have been several reports of cranial nerve infection by CMV, but to our knowledge, no cases of auditory nerve involvement have been described. We report two cases in which CMV infection was revealed by involvement of the VIIIth cranial nerves. Cytomegalovirus (CMV) infection is frequent in severely immunodeficient patients infected by human immunodeficiency virus (HIV). The main targets of CMV are the retina, gastrointestinal tract and central nervous system. We describe two cases in which neurologic CMV infection was revealed by hearing loss.

Pseudomonas aeruginosa infection in human immunodeficiency virus infected patients.

OBJECTIVES: (1) To determine the incidence and outcome of Pseudomonas aeruginosa infection in HIV-infected patients. (2) To study the antimicrobial susceptibility of P. aeruginosa isolates in this particular population. (3) To identify risk factors for these infections. PATIENTS AND METHODS: A retrospective case-control study performed in a 28-bed infectious-diseases unit in a 940-bed university hospital. All cases were defined as HIV-infected patients with severe infections due to P. aeruginosa, including bacteremia, lower or upper respiratory tract infections, infections related to a central venous catheter, and cutaneous/muscular infection. Each case was matched with an HIV-seropositive control not infected by P. aeruginosa and hospitalized on the same dates as the cases. RESULTS: One thousand and thirty-five HIV-infected patients were hospitalized during the study period. A first severe P. aeruginosa infection was documented in 41 patients, giving an overall annual incidence note of 2.51 episodes per 100 admissions. Forty of the 41 case notes were available for analysis. They consisted of 17 cases of bacteraemia, four upper respiratory tract infections, 10 lower respiratory tract infections, three catheter-related infections, and six cutaneous/muscular infections. Of these 40 cases, 60% were nosocomial and the remainder were community-acquired. The overall mortality rate was 22% (47% in bacteraemic forms). Twenty five percent of patients relapsed after an average of 37 days. The case-control comparison showed that AIDS was more frequent among the cases (92% vs. 74%, P = 0.04), who also had a lower PN count (P = 0.005), and a lower CD4 cell count (15.7 +/- 18.8/mm3 vs. 118 +/- 211/mm3; P = 0.0007). The number of days spent in hospital in the previous 3 months (29.3 +/- 20.7 vs. 19.7 +/- 14, P = 0.04) was significantly higher among the cases. In a multivariate analysis, examining treatments received in the previous month, only co-trimoxazole [OR = 5.5 (1.1-26.9)], penicillins [OR = 5.2 (1.1-25.3)], steroids [OR = 5.5, (1.2-25.5)] and a CD4 cell count below 50/mm3 [OR = 13.2 (1.4-129.4)] were identified as risk factors. CONCLUSION: P. aeruginosa infection is a not frequent bacterial disease in highly immunodeficient HIV-infected patients. It is frequently fatal and must be borne in mind in the advanced stages of HIV disease, especially when patients have received co-trimoxazole (trianthoprim-sulphamethoxazole), penicillins or steroids.

Treatment of non-meningeal cryptococcosis in patients with AIDS. Centre d'Informations et de Soins de l'Immunodéficience Humaine de l'Est Parisien.

Amphotericin B, alone or combined with flucytosine, is the reference curative treatment for neuromeningeal cryptococcosis associated with the acquired immune deficiency syndrome (AIDS). Treatment of non-meningeal forms is less well standardized. Out of 75 human immunodeficiency virus (HIV)-infected patients with cryptococcosis, 16 had no meningeal involvement. One died before receiving any treatment, another received amphotericine B and recovered, and the remaining 14 received curative therapy with fluconazole (200-400 mg/day); 11 of the latter entered complete remission, while three deteriorated during the first week of treatment but recovered on amphotericin B combined, in two cases, with fluconazole. Only one relapse occurred during maintenance treatment with low-dose fluconazole (100 mg/day). No adverse effects of fluconazole treatment were observed. One of the patients on amphotericin B developed acute renal impairment requiring drug withdrawal. These results suggest that first-line fluconazole therapy is effective and well tolerated in patients with AIDS-associated non meningeal cryptococcosis.

Exploration of the cellular mediated immunity by the blastogenesis test during chronic brucellosis in human.

The diagnosis of the chronic, human brucellosis is frequently difficult and usually needs experimental methods. This paper describes a lymphocyte stimulation test with a Brucella antigen and the results of this test concerning 45 brucellic or not brucellic patients. It is concluded that this test is interesting, especially for the chronic and sero-negative Brucellosis diagnosis.

[Aortic and mitral endocarditis caused by Haemophilus paraphrophilus with abscess of the aortic ring and cerebral embolism]. / Endocardite aortique et mitrale à Haemophilus paraphrophilus avec abcès de l'anneau aortique et embolies cérébrales.

We report the first case of aortic and mitral Haemophilus paraphrophilus endocarditis complicated by abscess of the aortic annulus in a 30-year old man with post-rheumatic mitral regurgitation. We recall the peculiar clinical features and course of this bacterial endocarditis of uncommon origin. We insist, in particular, on the occurrence of cerebral embolism and on the two-dimensional echocardiographic diagnosis of an aortic annulus abscess confirmed at surgery. Cure was obtained by aortic and mitral valve replacement and by the prolonged antibiotic therapy made necessary by the presence of cerebral lesions. After 3 months, there were no neurological sequelae, but doppler-echocardiography showed a persistent washed out pouch the reports of which with the surrounding structures were determined by transoesophageal echocardiography: moderate aortic regurgitation was detected at that level.

[Problems posed by therapeutic combinations of zidovudine during the treatment of opportunistic infections in AIDS]. / Problèmes posés par les associations thérapeutiques de la zidovudine lors du traitement des infections opportunistes au cours du SIDA.

Opportunistic infections in patients with acquired immunodeficiency syndrome (AIDS) require hematotoxic drugs. Neutropenia and anemia are the major hematologic abnormalities attributed to zidovudine (AZT). Concomitant medications associated with an increased frequency of toxicity are trimethoprim-sulfamethoxazole (cotrimoxazole), sulfadiazine, pyrimethamine, ganciclovir. AZT is stopped during initial treatment then reintroduced at full dosage with cotrimoxazole, at reduced dosage with sulfadiazine + pyrimethamine or ganciclovir.

[Cerebral glioblastoma: a new complication of HIV-1 infection]. / Glioblastome cérébral: nouvelle complication de l'infection par le VIH 1.

A new case of supratentorial malignant glioma is reported in an HIV-1 infected male homosexual. Tumours of the nervous system account for only 5 to 10 percent of neurological complications of AIDS, and most of them are lymphomas or metastases from Kaposi's sarcomas. In fact, HIV-1 is a neurotropic lentivirus, not transforming by definition. Our patient had a frontal tumoral syndrome resistant to the conventional anti-toxoplasmic treatment. Pathological examination of a tumoral fragment obtained by stereotactic biopsy showed that according to the WHO criteria the tumour was a glioblastoma. The mechanism through which HIV infection results in malignant transformation of astrocytes is conjectural. There is no consensus on whether the virus is located in glial cells, but the transgenic animal technique suggests that the tat gene might play a certain role. Other hypotheses concerning the indirect neurotoxicity of HIV have been put forward, notably that of viral coinfection with viruses of the papova group.

[Failure of new beta-lactam antibiotics in the treatment of severe Enterobacter cloacae infections]. / Echecs des nouvelles bêta-lactamines dans le traitement d'infections sévères à Enterobacter cloacae.

In 12 patients infected with an Enterobacter cloacae (E. cl.) initially susceptible to the 3rd generation cephalosporins, we observed the emergence in vivo of variants resistant to most of the new beta-lactam antibiotics (carboxy-penicillins, ureido-penicillins, 3rd generation cephalosporins and aztreonam). These variants remained susceptible to mecillinam and imipenem. The variant emerged under treatment with cefotaxime in 3 cases, with moxalactam in 3 cases, with aztreonam, carbenicillin, and ticarcillin in 1 case each and without treatment in 1 case. An aminoglycoside was combined with the beta-lactam antibiotic in 6 cases. Therapeutic failure was attributed to emergence of the resistant variant in 6 out of 12 cases (with an aminoglycoside in 3 cases, with the beta-lactam antibiotic alone in 3 cases). These case reports underline the importance of bacteriological monitoring of patients infected with E. cl. treated with a beta-lactam antibiotic. The susceptibility to beta-lactam antibiotics of the E. cl. strains isolated during treatment should be systematically retested.

[Severe immunoallergic reaction in a patient treated for two months continuously with rifampicin]. / Accident immunoallergique grave chez un patient traité quotidiennement depuis deux mois par rifampicine.

BACKGROUND: Rifampicin is a major drug used for the treatment of mycobacterial infections. It is usually well tolerated although cases of immunoallergic events have been reported in discontinuous regimens. CASE REPORT: We report the case of a 55-year-old man who developed a severe drug reaction after taking rifampicin daily for two months with no interruption. The clinical course was favorable after drug withdrawal. Challenge with other antituberculous drugs did not induce any adverse reaction. CONCLUSION: Despite the few cases reported, antituberculous regimens containing rifampicin can cause severe adverse reactions which subside progressively after drug withdrawal.

[Early anomalies of CD4 and CD20 lymphocyte cycles in human immunodeficiency virus]. / Anomalies précoces des cycles lymphocytaires CD4 et CD20 au cours de l'infection par le virus de l'immunodéficience humaine.

Circadian variations in the number of circulating lymphocytes and their subpopulations have been observed in healthy subjects. These cyclic changes are characterized by a trough at 8:00 a.m. and a peak at midnight. Using multiple peripheral blood samplings, we were able to confirm that this cycle applied to CD4 T-cells (helpers) and to B-cells (CD20). No cycle of CD8 lymphocytes was observed. In a second stage, for greater comfort of the patient the number of samplings was reduced to two: one at 8:00 a.m. (trough) and one at midnight (peak). This method enabled us to calculate the amplitude of lymphocytes cycles in 18 controls and 74 human immunodeficiency virus (HIV) seropositive patients. In asymptomatic HIV carriers the amplitude of CD4 cycles was normal in 6/26 cases and that of B-cell cycles in 2/17 cases. In the group of asymptomatic HIV carriers the mean amplitude of the cycles was much less reduced than in the other two groups. These results incite us to believe that the loss of the CD4 T-cell cycles is an early sign of HIV infection antedating the decrease observed in the number of these cells.

[Blood histamine levels in patients infected with the human immunodeficiency virus]. / Histaminémie des malades infectés par le virus de l'immunodéficience humaine.

Serum histamine levels are significantly lowered in patients with human immunodeficiency virus (HIV) infection. Treatment with zidovudine has no effect on histaminaemia, but HIV-positive patients with thrombocytopenic purpura who underwent splenectomy are known to have had a rise in serum histamine levels after the operation. This parameter might be used as prognostic factor in the evaluation of patients with HIV infection.

[Tuberculous meningitis: clinical, biological and x-ray computed tomographic comparison between patients with or without HIV infection]. / Méningites tuberculeuses: comparaison clinique, biologique et scanographique entre des patients infectés ou non par le VIH.

OBJECTIVES: Determine possible differences in clinical manifestations, laboratory findings and neuroimaging results in tuberculous meningitis patients with and without HIV infection. PATIENTS AND METHODS: We retrospectively reviewed data of 38 patients with positive cerebrospinal fluid cultures for Mycobacterium tuberculosis who were hospitalized in 3 university hospitals in Paris over the last 11 years. RESULTS: There were 24 HIV-infected patients and 14 without HIV infection. Mean CD4 lymphocyte count was 103 +/- 180/mm3 in the HIV group. Age (median age = 33 years for the HIV group vs. 53 for the non-HIV group), sex ratio (3 vs. 0.75), and prior history of tuberculosis (46% vs. 43%) were similar in both groups. Clinical presentation was similar for headache (83% in HIV group vs. 50% in non-HIV group; p = 0.02) and confusion (54% vs. 93% in non-HIV group p = 0.05). Serum natremia (mmol/l) (131 +/- 5 vs. 125 +/- 8; p = 0.024), white blood cell count (x 10(9)/l) (5.8 +/- 4.7 vs. 10.7 +/- 1.7; p = 0.37) and erythrocyte sedementation rate (mm/h) (68 +/- 34 vs. 31 +/- 35; p = 0.003) were significantly different in the 2 groups. Median cerebrospinal fluid findings were similar in the 2 groups: leukocytes (x 10(6)/l) (375 +/- 860 vs 218 +/- 250), glucose (mmol/l) (2.3 +/- 0.9 vs 2.7 +/- 1.9) and protein (g/l) (3.8 +/- 7.1 vs. 2.6 +/- 1.6). CT-scans of the brain were similar in the 2 groups. Mortality during hospitalization was similar (42% vs 36%; NS). CONCLUSION: HIV infection appears to have little impact on the presentation of tuberculous meningitis.

[Prospective study of pathogenic agents isolated from feces of patients with HIV infections]. / Etude prospective des agents pathogènes isolés dans les selles de patients infectés par le VIH.

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.

[Paragonimiasis: a rare little known disease]. / La paragonimose: une affection rare à ne pas méconnaître.

BACKGROUND: Paragonimiasis, caused by a lung fluke, is an parasitic disease rarely encountered in France. CASE REPORT: A 52-year-old man developed dyspnea, cough, mild fever and chest pain. Pleural effusion suggested possible pulmonary embolism or tuberculosis. Cell counts in blood and pleural effusion fluid revealed major eosinophila in this patient who had recently returned from a trip to Japan. Paragonimiasis was confirmed by ELISA. Treatment with praziquantel led to complete clinical and radiographic recovery. DISCUSSION: The clinical and radiographic features of paragonimiasis are often similar to tuberculosis with pleuropneumopathy, mild fever and dyspnea. ELISA has now replaced parasitologic diagnosis. Cure is achieved with praziquantel.

[Acid-alcohol-resistant bacilli detected by microscopic analysis of exhaled air from HIV-infected patients: tuberculosis or mycobacteriosis?]. / Bacilles acido-alcoolo-résistants à l'examen microscopique de prélèvements respiratoires chez les patients infectés par le VIH: tuberculose ou mycobactériose?

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.

[Predictive factors of virologic response to antiretroviral treatment with a protease inhibitor in HIV infection]. / Facteurs prédictifs de réponse virologique à un traitement antirétroviral avec inhibiteur de protéase au cours de l'infection à VIH.

OBJECTIVE: To investigate factors related to early virological response among a cohort of 224 patients who started a protease inhibitor (PI) for the first time. To determine which factors are associated with persistent response among patients with early response. PATIENTS AND METHODS: Early complete response was defined as an undetectable plasma viral load 2 to 3 months after treatment onset (< 400 copies/ml, Quantiplex HIV 2.0 Chiron diagnostics), incomplete response as at least 1 log reduction of viral load. In patients with an undetectable plasma viral load at 2 or 3 months, we also assessed the persistence of the response on the same regimen. Virology failure was defined by two consecutive viral load levels above the detection limit. RESULTS: In the total cohort, 66% of the patients had an early complete response, 11% a partial response and 23% no response. Complete virological response was significantly more frequent in naive (89%) than in pretreated (59%) patients (p < 0.001). Multivariate analysis of factors predictive of early response in pretreated patients (n = 169) showed that viral load (p = 0.001), the number of nucleoside analogs previously received (p = 0.06) and a full or partial treatment switch (p = 0.10) were associated with complete response. Analysis of later response in the 45 naive patients with prolonged follow-up showed that 22% had treatment failure after 3 to 16 months. None of the baseline variables (viral load, CD4+ cell count or nature of the PI) were associated with duration of response. The only factor associated with persistent response in pretreated patients was a low number of antiretroviral drugs previously received (log-rank test, p = 0.04). CONCLUSIONS: The absence of previous antiretroviral treatment as the main factor associated with an early complete virological response. In patients pretreated with nucleoside analogs who presented early virological success, the number of drugs previously received, often associated with full or partial switch of nucleoside analog, significantly influence the persistence of response to a given triple-drug regimen.