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Biomedical subjects

B Gachot

Publications and source records attributed to B Gachot.

At least 19 recordsLinked to original sources

Resurgence of blackwater fever in long-term European expatriates in Africa: report of 21 cases and review.

Blackwater fever (BWF) is a severe clinical syndrome, characterized by intravascular hemolysis, hemoglobinuria, and acute renal failure that is classically seen in European expatriates chronically exposed to Plasmodium falciparum and irregularly taking quinine. BWF virtually disappeared after 1950, when chloroquine superseded quinine. We report 21 cases of BWF seen in France from 1990 through 1999 in European expatriates who lived in sub-Saharan Africa. All patients had macroscopic hemoglobinuria, jaundice, and anemia. Acute renal failure occurred in 15 patients (71%), 7 of whom required dialysis. The presumed triggers of BWF were halofantrine (38%), quinine (24%), mefloquine (24%), and halofantrine or quinine (14%). Glucose-6-phosphate dehydrogenase (G6PD) activity was normal in the 14 patients who underwent this test. Low-level P. falciparum parasitemia was found in 8 patients. All 21 patients survived. Our data and 13 cases reported in the literature suggest a resurgence of classic BWF among Europeans living in Africa and a need to discuss attendant therapeutic implications.

Adolescent↗

[Severe malaria].

Falciparum malaria remains a major killer in developing countries, particularly for African children. Moreover, France is the leading European country in term of incidence of imported malaria. Parasitized erythrocytes, which can form rosettes or auto-agglutinate, are sequestrated in the deep microvasculature and stick to activated endothelium by the mean of various receptors. Activation of T lymphocytes and macrophages induces secretion of proinflammatory cytokines, including tumour necrosis factor, which contributes to severe disease. However, the pathophysiology of coma remains poorly understood. In nonimmune adults, besides cerebral malaria, pictures of severe sepsis with shock, acute renal failure and respiratory distress syndrome are common. Although chemotherapy of malaria is challenged by the continuing evolution of antimalarial resistance, quinine remains the first-line drug for severe imported disease. In addition, early symptomatic management in the intensive care unit setting is of paramount importance. Prevention of severe imported malaria lays on prophylactic measures during travel, as well as adequate management of uncomplicated disease after return. In developing countries, early and adequate treatment of uncomplicated disease using cheap alternatives to classical compounds should contribute to "roll back" malaria, particularly in sub-Saharan Africa.

Africa↗

Rapid effect of interleukin-2 therapy in human immunodeficiency virus-infected patients whose CD4 cell counts increase only slightly in response to combined antiretroviral treatment.

Combined antiretroviral treatment in some human immunodeficiency virus-infected persons does not lead to a rapid increase in CD4 cell counts, and these patients may remain susceptible to opportunistic infections. A group of 13 patients with CD4 cell counts <200 cells/mm3 after > or =9 months of combined antiretroviral treatment received interleukin (IL)-2 immunotherapy (4.5x106 IU twice daily for 5 days every 6 weeks). After only 3 cycles, their CD4 cell counts increased from 123 cells/mm3 (range, 104-134 cells/mm3) to 229 cells/mm3 (range, 176-244 cells/mm3). A marked increase was noted in the naive CD45RA subpopulation of CD4 T lymphocytes. Furthermore, the magnitude of the CD4 cell count response correlated with the baseline expression levels of the antiapoptotic molecule Bcl-2. This study demonstrates that IL-2 immunotherapy can accelerate the recovery of CD4 lymphocytes in persons whose CD4 cell counts fail to increase rapidly in response to combined antiretroviral treatment.

AIDS-Related Opportunistic Infections↗

Usefulness of a strategy based on bronchoscopy with direct examination of bronchoalveolar lavage fluid in the initial antibiotic therapy of suspected ventilator-associated pneumonia.

OBJECTIVES: To evaluate (a) the routine accuracy of bronchoalveolar lavage by direct examination (BAL-D) in diagnosing ventilator-associated pneumonia (VAP), and (b) the impact of a diagnostic strategy including clinical judgment, bronchoscopy, and BAL-D on the initial diagnosis and appropriateness of treatment when VAP is suspected. DESIGN AND SETTING: Prospective cohort study in two academic ICUs in Paris, France. PATIENTS AND PARTICIPANTS: Mechanically ventilated patients with suspected VAP underwent bronchoscopy with BAL and protected specimen brush (PSB). BAL-D results were available within 2 h, BAL on culture and PSB results after 24 h, and antibiotic susceptibility after 48 h. At each step in the strategy the senior and the resident in charge of the patient were asked their diagnosis and their therapeutic plan on the basis of presently available data. Definite diagnosis of suspected VAP was based on histology, appearance of cavitation, positive pleural fluid culture, results of PSB and BAL culture, and follow-up. MEASUREMENT AND RESULTS: A total of 110 episodes of suspected VAP were studied; 94 definite diagnoses were made (47 VAP, 47 no VAP). Using a threshold 1% of infected cells, BAL-D discriminated well between patients with and those without VAP (sensitivity 93.6%, specificity 91.5%, area under the receiver-operating characteristic curve 0.953). The senior clinical judgment was correct in 71% cases. It was correct in 78% and 94% of cases after airway visualization and BAL-D findings, respectively. After BAL-D the positive and negative predictive values in diagnosing VAP were 90% and 98%, respectively. However, the therapeutic plan was correct in only 65% using clinical judgment (15 untreated patients, 3 ineffective treatment, 15 useless treatment), 66% using airway visualization (14 untreated VAP, 4 ineffective treatment, 14 useless treatment), and 88% using BAL-D results (1 untreated patients, 6 ineffective, 4 useless), according to definite diagnosis and final antibiotic susceptibility testings. CONCLUSIONS: A strategy based on bronchoscopy and BAL-D generally leads to a rapid and appropriate treatment of nosocomial pneumonia in ventilated patients.

Anti-Bacterial Agents↗

Comparison of direct examination of three types of bronchoscopy specimens used to diagnose nosocomial pneumonia.

OBJECTIVE: To compare direct examination of bronchial aspirate and plugged telescopic catheter specimens (PTC) with infected cell counts in bronchoalveolar lavage (BAL) specimens for the diagnosis of nosocomial pneumonia. DESIGN: Prospective study of critically ill patients. SETTING: Intensive care unit in a university hospital. PATIENTS: A total of 64 patients hospitalized for >48 hrs with suspected nosocomial pneumonia. INTERVENTIONS: Fiberoptic bronchoscopy with bronchial aspirate and quantitative protected specimen brush, PTC, and BAL cultures. PTC and bronchial aspirate specimens were Gram-stained. BAL specimens for infected cell counts were examined as described previously in the literature. MEASUREMENTS AND MAIN RESULTS: Nosocomial pneumonia was diagnosed by the medical staff based on all available clinical, radiologic, laboratory test, and microbiological data and on the course before and after appropriate therapy. A total of 71% of patients were ventilated, and 70.1% were receiving antibiotics. Nosocomial pneumonia was diagnosed in 54% of the cases. On direct examination, sensitivity (Se) and specificity (Sp) of bronchial aspirate specimens were Se, 82% and Sp, 60%; of BAL with 5% infected cells, Se, 56% and Sp, 100%; of BAL with 3% infected cells, Se, 74% and Sp, 96%; of PTC specimens, Se, 65% and Sp, 76%; and of PTC specimens plus BAL with 3% infected cells, Se, 83% and Sp, 78%. BAL with 3% infected cells was significantly better for predicting nosocomial pneumonia than direct examination of bronchial aspirate or PTC specimens (p = .0012). When the BAL showed 3% infected cells, neither direct examination of bronchial aspirate nor direct examination of PTC specimens was useful (p = .24 and p = .38, respectively). Combined use of direct examination of PTC specimens plus BAL with 3% infected cells markedly improved sensitivity. The total cost of each procedure was taken into account for the final evaluation. CONCLUSIONS: Our data suggest that BAL with 3% infected cells is currently the only test whose predictive value for nosocomial pneumonia is sufficiently high to be of use for guiding the initial choice of antimicrobial class while waiting for quantitative culture results.

Adult↗

Pneumocystis carinii pneumonia requiring intensive care management: survival and prognostic study in 110 patients with human immunodeficiency virus.

OBJECTIVE: To perform a descriptive study of patients with acute respiratory failure secondary to acquired immunodeficiency syndrome-related Pneumocystis carinii pneumonia and to identify variables that are predictive of death within 3 months. DESIGN: Case series study. SETTING: Infectious disease intensive care unit (ICU) in a university hospital. PATIENTS: Detailed clinical, laboratory, and ventilatory data were collected prospectively within 48 hrs of admission and during the ICU stay in 110 consecutive human immunodeficiency virus-infected patients requiring ICU management with or without mechanical ventilation for P. carinii pneumonia-related acute respiratory failure. MEASUREMENTS AND MAIN RESULTS: Continuous positive airway pressure was used initially in 66 (60%) patients. Among the 34 patients (31%) who required mechanical ventilation, including 12 at admission and 22 after failure of continuous positive airway pressure, 76% died. The 3-month mortality rate after ICU admission was estimated at 34.6% (95% confidence interval [CI], 25%-44%). The 1-yr survival rate was estimated at 47% (95% CI, 36%-58%). With successive multiple logistic regression models analyzing the relative prognostic importance of baseline clinical and laboratory tests variables, ventilation variables, and events in the ICU, only delayed mechanical ventilation after 3 days (odd ratio [OR], 6.7; 95% CI, 1.9-23.9), duration of mechanical ventilation of > or = 5 days (OR, 2.8; 95% CI, 1.1-6.9), nosocomial infection (OR, 5.2; 95% CI, 2.1-12.9), and pneumothorax (OR, 5; 95% CI, 1.7-14.7) were predictive of death within 3 months of ICU admission. Among patients with delayed mechanical ventilation on day 3 or later and with a pneumothorax associated or not associated with a nosocomial infection, the predicted probability of 3-month death was close to 100%. CONCLUSIONS: Our data suggest that the most significant predictive factors of death were identifiable during the course of P. carinii pneumonia-related acute respiratory failure rather than at admission and can help in bedside decisions to withdraw intensive care support in such patients.

AIDS-Related Opportunistic Infections↗

[Severe malaria].

Falciparum malaria remains a major killer in developing countries, particularly for African children. The sequestration of parasitized erythrocytes in the deep microvasculature is mostly mediated by their cytoadherence to activated endothelium. Proinflammatory cytokines and particularly tumor necrosis factor contribute to severe disease but the pathophysiology of coma remains poorly understood. In young children, features of severe malaria include severe anemia, hypoglycemia and cerebral malaria. Half of the children with neurological impairment actually have raised intracranial pressure, and seizures are extremely common. Clinical respiratory distress usually reflects severe lactic acidosis. In non immune adults, pictures of severe sepsis with shock, acute renal failure and respiratory distress syndrome are common and often associated with bacterial coinfection. Although chemotherapy of malaria is challenged by the continuing evolution of antimalarial resistance, quinine remains the first-line drug for severe disease. The optimization of symptomatic management of severe malaria remains a major concern in developing countries.

Adult↗

Clinical and bacteriologic epidemiology of extended-spectrum beta-lactamase-producing strains of Klebsiella pneumoniae in a medical intensive care unit.

The epidemiology of extended-spectrum beta-lactamase (ESBL)-producing strains of Klebsiella pneumoniae was studied over a 16-month period in a medical intensive care unit (ICU). A control program involving enhanced isolation procedures, surveillance cultures at admission and then at 1-week intervals, and selective digestive decontamination (SDD) was instituted. Phenotypic and genotypic markers (plasmid content and DNA macrorestriction polymorphism determined by pulsed-field gel electrophoresis) were used to compare 138 strains of ESBL-producing K. pneumoniae. The incidence of colonization and/or infection with ESBL producers was 11.9%. ESBL-producing K. pneumoniae strains were isolated from 64 of 65 patients. Fifty-five cases were considered acquired in the ICU, while nine cases were imported. Forty-five infections occurred in 32 patients; 20 infections involved the urinary tract. SDD failed to reduce the incidence of acquisition of ESBL-producing K. pneumoniae. Combined use of markers was necessary to achieve accurate differentiation of strains. A single epidemic clone (SHV-4 beta-lactamase-producing K. pneumoniae) was the cause of 85% of the ICU-acquired cases. Sporadic occurrence of SHV-5, TEM-3, SHV-2, and SHV-3 producers accounted only for a few cases.

Cross Infection↗

Diagnostic accuracy of protected specimen brush and bronchoalveolar lavage in nosocomial pneumonia: impact of previous antimicrobial treatments.

OBJECTIVE: To determine whether the diagnostic accuracy of bronchoscopy samples in patients with suspected ventilator-associated pneumonia is affected by prior antibiotic treatment given for a previous infection, and/or by antibiotic treatment recently started to treat suspected ventilator-associated pneumonia. DESIGN: Study of critically ill patients. SETTING: Intensive care unit in a university hospital. PATIENTS: Sixty-three episodes of suspected ventilator-associated pneumonia were prospectively evaluated. Based on prior antibiotic treatment, three groups were defined: no antibiotic group (no previous antibiotic treatments), n = 12; current antibiotic group (antibiotic treatment initiated >72 hrs earlier), n = 31; and recent antibiotic group (new antibiotic treatment class started within the last 24 hrs), n = 20. INTERVENTIONS: Fiberoptic bronchoscopy with quantitative protected specimen brush cultures, bronchoalveolar lavage cultures, and intracellular organism counts of bronchoalveolar lavage cells. MEASUREMENTS AND MAIN RESULTS: The diagnosis of ventilator-associated pneumonia was made in 35 cases, based on histology (n = 2), cavitation (n = 2), blood cultures (n = 4), or outcome under appropriate antibiotic treatment (n = 27). The discriminative value of the tests, based on the area under the receiver operating characteristic curve, was high (> or =0.85) in both current antibiotic treatment and recent antibiotic treatment patients. Sensitivities for a 5% intracellular organism count of bronchoalveolar lavage cells, a protected specimen brush culture threshold of 10(3) colony-forming units (cfu)/mL, and a bronchoalveolar lavage culture threshold of 10(5) cfu/mL were as follows, respectively, in the three groups: 0.71, 0.88, and 0.71 (no antibiotic treatment group); 0.5, 0.77, and 0.83 (current antibiotic group); and 0.67, 0.40, and 0.38 (recent antibiotic group). Specificity was consistently > or =0.9. In the recent antibiotic group, protected specimen brush and bronchoalveolar lavage cultures had lower sensitivities (p < .05), and the best threshold values for these two tests were 10(2) cfu/mL and 10(3) cfu/mL, respectively. CONCLUSIONS: After recent introduction of an antibiotic treatment for suspected ventilator-associated pneumonia, protected specimen brush and bronchoalveolar lavage culture thresholds must be decreased to maintain good accuracy. In contrast, current antibiotic treatment prescribed for a prior infectious disease does not modify the diagnostic accuracy of protected specimen brush or bronchoalveolar lavage.

Adult↗

Successful rescue in a patient with high dose methotrexate-induced nephrotoxicity and acute renal failure.

We describe the case of a 35-year old male who developed acute renal failure following high dose methotrexate therapy for Burkitt's non Hodgkin lymphoma. Serum methotrexate levels reached 37 micromol/l, and remained higher than 1 micromol/l for more than a week. Folinic acid rescue was intensified to 200-400 mg intravenously every 4 hours. As methotrexate binds markedly to proteins, plasma exchange was initially chosen, 4 sessions being performed from day 2 to day 4. The methotrexate pharmacokinetic profile was not significantly modified during plasma exchange, and serum drug level was 3 micromol/l. Continuous veno-venous hemodiafiltration was therefore performed from day 5 to day 10. This procedure also seemed ineffective, with evidence of low ultrafiltrate clearance. No extrarenal toxicity was observed in our patient. Thus, conventional extrarenal procedures appear to have a limited role in the setting of overexposure to methotrexate. The use of very high doses of folinic acid in our case probably played a major role in the eventual favorable outcome.

Acute Kidney Injury↗

Shock complicating severe falciparum malaria in European adults.

OBJECTIVE: To study adult patients with severe falciparum malaria who developed shock. DESIGN: Retrospective study from 1987 to 1993. SETTING: Medical intensive care unit in a university hospital. PATIENTS: 14 patients admitted with severe falciparum malaria who developed shock. All received intravenous quinine. MEASUREMENTS AND RESULTS: The mean Simplified Acute Physiology Score II was 59.5 +/- 7.1; 2.6 +/- 0.4 criteria defining severe disease were present on admission in 12 patients; and initial parasitemia was 21 +/- 6%. Twelve patients received inotropic drugs. Pulmonary artery catheterization showed the following results in 7 patients: mean arterial pressure 57 +/- 4 mmHg; pulmonary artery occlusion pressure 11 +/- 1 mmHg; cardiac index 5.5 +/- 0.91.min-1.m-2, and systemic vascular resistance index 783 +/- 122 dyne.s.cm-5.m-2. Seven patients had evidence of bacterial infection at the time of shock. Of the 7 deaths (50%), 5 were due to shock, with documented bacterial infection in all patients and persistent parasitemia in 4. CONCLUSIONS: Shock complicating severe falciparum malaria in adults is associated with peripheral vasodilation and carries a poor prognosis. In falciparum malaria with shock, bacterial coinfection should be suspected immediately and treated empirically with broad-spectrum antibiotics. Nevertheless, Plasmodium falciparum may contribute directly or indirectly to the onset of shock.

Adult↗

Septic shock in patients with the acquired immunodeficiency syndrome.

OBJECTIVE: To evaluate the prognosis of patients with septic shock admitted to an intensive care unit (ICU), according to their HIV serostatus. DESIGN: Retrospective study. SETTING: Medical ICU of a university hospital. PATIENTS: 76 patients with septic shock admitted to the same ICU, of whom 28 were HIV positive and 48 were HIV negative. MEASUREMENTS AND RESULTS: Severity scores, number and type of organ failures, and survival rates were assessed in the two groups of patients. Glasgow Coma Scale and general severity scores [Acute Physiology and Chronic Health Evaluation II and Simplified Acute Physiology Score (SAPS)] were significantly worse in HIV-infected patients. The total number of organ failures was also higher in the HIV-positive group: 3.7 +/- 0.2 vs 3.1 +/- 0.2 in the HIV-negative group (p < 0.001). On day 28, 21 (46%) HIV-negative patients were dead compared to 26 (93%) patients in the HIV-positive group (p < 0.001). In the multivariate analysis, HIV infection was an independent risk factor for mortality, as were the SAPS score, use of mechanical ventilation, and the McCabe score. CONCLUSIONS: This study reports a considerable excess mortality in HIV-infected patients with septic shock. Although severity of illness was clearly much more pronounced in HIV-positive patients, retroviral infection was independently associated with death. Improving survival in HIV-positive patients with septic shock may require earlier diagnosis and treatment of the causative infection.

AIDS-Related Opportunistic Infections↗