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.

[Septic shock with liver abscess in an immunocompetence patient. Presentation of an unusual Fusobacterium nucleatum infection]. / Choc septique avec abcès hépatiques chez une patiente immunocompétente. Présentation inhabituelle d'infection à Fusobacterium nucleatum.

BACKGROUND: Fusobacterium septicemia with septic metastasis is a very rare and potentially serous condition when complicated by septic shock. Most cases have been described in patients with humoral immunity disorders and/or severe underlying chronic disease. CASE REPORT: A 24-year-old immunocompetent woman with a tonsil infection developed F. nucleatum septic shock with liver abscess formation. Outcome was rapidly favorable with antibiotic treatment and adapted intensive care, probably favored by the absence of an associated immune deficit. DISCUSSION: Despite its low incidence, F. nucleatum should be entertained as a possible cause of septicemia originating from a pelviperitoneal, pulmonary with abscess formation, or upper airway infection. Proper diagnosis is essential due to the risk of poor prognosis. Fusobacterium nucleatum is a commensal strictly anaerobic bacteria of the buccal cavity. It can cause dental and upper airway infections. Septicemia with secondary localization of F. nucleatum is very rare and the severity depends on the presence of associate septic shock. The immunopathological implications of these infections remain to be elucidated.

Isolated right-sided Bartonella quintana endocarditis in an immunocompetent adult.

Bartonella quintana is a recently recognized cause of culture-negative left-sided endocarditis. We report a case of isolated tricuspid endocarditis caused by B. quintana in a 65-year-old alcoholic man, who also had immune-complex glomerulonephritis. B. quintana was established as the cause of the endocarditis based on serological tests and on failure of extensive efforts to isolate an alternative organism. The patient improved gradually on antibiotic therapy and did not require surgery. To our knowledge, this is the first report of isolated right-sided endocarditis caused by B. quintana. Although uncommon, Bartonella should be considered in patients with isolated right-sided culture-negative endocarditis.

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.

[Prognostic factors of prosthetic valve endocarditis. Apropos of 122 cases]. / Facteurs pronostiques des endocardites sur prothèse valvulaire. A propos de 122 observations.

The prognostic factors of 122 patients suffering from prosthetic valve endocarditis between 1978 and 1992 were studied by univariate and multivariate analysis. The principal causative organisms were Staphylococcus aureus (33%), streptococci (20%), coagular-negative staphylococci (12%), enterococci (10%) and gram-negative bacilli (9%). The 4 month survival rate was 66% (42 deaths). The main predictive factor for death was infection with S. aureus (75% vs 15% with other organisms). In S. aureus infection, multivariate analysis identified the following predictive factors for death: a prothrombin ratio less than 30% (RR = 8.3), mediastinitis (RR = 4.9), cardiac failure (RR = 4.4) and septic shock (RR = 2.6). In cases of infection with other organisms, the following factors were predictive of death: a prothrombin ratio of less than 30% (RR = 32.26), renal failure (RR = 7.31) and cardiac failure (RR = 6.07). In patients with S. aureus infection, survival was better after than without surgery: 9/20 (45%) versus 0/20 (p < 0.001). In infection with other organisms, there was no difference in a survival after surgical (89%) or medical therapy (81%). Chronic endocarditis relapses over 1 to 5 years was observed in 9 cases. All patients were reoperated a total number of 18 times with 5 deaths. Very prolonged antibiotic therapy is recommended in these patients. The authors conclude that endocarditis not due to S. aureus and without complications may be treated medically. Rapid reoperation is necessary in all other cases.

Short-term effects of methylene blue on hemodynamics and gas exchange in humans with septic shock.

OBJECTIVE: The aim of this study was to investigate the acute effects of methylene blue (MB), an inhibitor of the L-arginine nitric oxide pathway, in patients with septic shock. DESIGN: A prospective, open, single-dose study. SETTING: The medical ICU of a university hospital. PATIENTS: Six patients with severe septic shock. INTERVENTIONS: Complete hemodynamic values were recorded before and 20 min after the infusion of intravenous MB (3 mg kg(-1)). Arterial pressure was then monitored during the next 24 h or until death. MEASUREMENTS AND RESULTS: Methylene blue increased the mean arterial pressure from 69.7 +/- 4.5 to 83.7 +/- 5.1 mmHg (p = 0.028) and the mean pulmonary artery pressure, from 34.3 +/- 7.2 to 38.7 +/- 8.0 mmHg (p = 0.023). Systemic vascular resistance index was increased from 703.1 +/- 120.6 to 903.7 +/- 152.2 dyne.s.cm(-5).m(-2) (p = 0.028) and pulmonary vascular resistance index, from 254.6 +/- 96.9 to 342.2 +/- 118.9 dyne.s.cm(-5) .m(-2) (p = 0.027). The PaO2/FIO2 decreased from 229.2 +/- 54.4 to 162.2 +/- 44.1 mmHg (p = 0.028), without significant modification of intrapulmonary shunting. Heart rate, cardiac index, right atrial pressure, DO2, VO2, oxygen extraction and arterial lactate were essentially unchanged. Sequential measurements of arterial pressure demonstrated a return to baseline level in 2-3 h. All but one patients died, three in shock and two in multiple organ failure. CONCLUSIONS: MB induces systemic and pulmonary vasoconstriction in patients with septic shock, without significant decrease in cardiac index. The worsening of arterial oxygenation following MB injection may limit its use in patients with the adult respiratory distress syndrome. Larger studies are required to determine whether MB improves the outcome of patients with septic shock.

Prosthetic valve endocarditis in the ICU. Prognostic factors of overall survival in a series of 122 cases and consequences for treatment decision.

We carried out univariate and multivariate analysis of outcome among 122 patients with prosthetic valve endocarditis (PVE) admitted to our ICU between 1978 and 1992. The predominant pathogens were Staphylococcus aureus (33%), streptococci (20%), coagulase-negative staphylococci (12%), enterococci (10%), and Gram-negative bacilli (9%). At 4 months, overall survival was 66% (42 deaths). Staphylococcus aureus was the main predictor of death (75% vs 15% with other pathogens). In S aureus PVE, multivariate analysis identified the following predictors of death: prothrombin time < 30% (relative risk [RR]: 8.3), concomitant mediastinitis (RR: 4.9), heart failure (RR: 4.4), and septic shock (RR: 2.6). In PVE due to other pathogens, prothrombin time < 30% (RR: 32.26), renal failure (RR: 7.31), and heart failure (RR: 6.07) were associated with death. In S aureus PVE, survival was higher in patients who received medical-surgical therapy than in those who received medical therapy alone (9/20 [45%] vs 0/20) (p < 0.01). In PVE due to other pathogens, there was no difference in survival between patients who underwent prosthesis replacement (89%) and those who received only medical treatment (81%). Among the 65 patients who underwent heart surgery, the mortality rate and incidence of postoperative paravalvular leakage did not correlate with positive prosthesis cultures. We conclude that non-S aureus and uncomplicated PVE may be managed without valve replacement but that prompt surgical intervention should be required in all other situations.

[Antiretroviral treatments and their therapeutical trials]. / Les traitements antirétroviraux et leurs essais thérapeutiques.

Efficacity of antiretroviral treatments is limited by the fact that available drugs are only virostatic and by the progressive impairment of the immune system during HIV infection. Antiviral compounds active on the various steps of viral invasion and replication are described. Further progress in the association of several drugs may improve efficiency and reduce the emergence of resistant strains, which would allow treatment at an earlier stage of the disease. In the absence of relevant animal models, additional clinical trials are mandatory. Their methodological quality must not be influenced by the extreme sensitivity of public opinion to AIDS.

[Infectious pneumopathies in immunosuppressed patients]. / Pneumopathies infectieuses de l'immunodéprimé.

Infective pneumonia occurring in immunocompromised patients is characterized by its multiple causes which create diagnostic problems and by the need for a prompt treatment. The principal criteria pointing to a specific organism are the causes of immunodeficiency (now usually due to treatment of blood diseases or cancers, organ transplantation and AIDS) and the radiological features of the pneumonia. Confirming the diagnosis frequently requires features of the pneumonia. Confirming the diagnosis frequently requires invasive explorations which in any case are limited by the patient's fragility. Consequently, empirical therapeutic measures are initiated, at least initially, taking into account all likely assumptions. The severity and frequency of these lung infections make it desirable to develop preventive measures applying to the patient himself (antibiotic prophylaxis) or to his environment.

Intestinal infections in patients with acquired immunodeficiency syndrome. A prospective study in 132 patients.

We studied prospectively 132 patients with acquired immunodeficiency syndrome to define the spectrum of enteric pathogens during this disease, with special reference to the correlation between the lesions, the infections, and the symptoms. Forty-four percent of the patients harbored at least one enteric pathogen: the most frequently recovered were Cryptosporidium (28), cytomegalovirus (16), Entamoeba histolytica (13), Giardia lamblia (9), and Mycobacterium avium intracellulare (7). Patients harboring pathogens were more likely to be diarrheics (69%) than patients without a pathogen (38%; P = 0.01) and more likely to have endoscopic lesions (29%) than patients without a pathogen (4%; P less than 0.001). The most common pathogen associated with diarrhea was Cryptosporidium. Cytomegalovirus, Entamoeba histolytica, and Salmonella typhimurium were each significantly associated with endoscopic lesions. Patients with cytomegalovirus infection tended to have a greater incidence of ulcer than patients without cytomegalovirus infection. Stool analysis diagnosed 61% of the infections, while endoscopy diagnosed 44%. Seven percent were recognized by stool analysis and endoscopy. When considering the 24 patients in whom accurate diagnosis warranted endoscopic biopsies, stool examination alone would have given an incomplete diagnosis in 14 patients (due to the presence of polyinfection). The frequency of inaccurate diagnosis of infection by stool determination alone, plus the development of new antiviral agents that suppress cytomegalovirus, may favor the earlier application of endoscopic evaluation in these patients.

Cytomegalovirus colitis in patients with acquired immunodeficiency syndrome.

Twenty-four AIDS patients, who underwent gastrointestinal evaluation, died from their disease and were autopsied. Seven had Cytomegalovirus colitis (group I) and 17 did not (group II). Clinical manifestations, digestive lesions, and infections were compared in the two groups. Chronic watery diarrhea was present in all the patients with colitis but was also present in 65% of the patients without colitis. Hematochezia was present only in the group with colitis (one of seven patients) but appeared late in the diarrheal course, due to necrotizing colitis. No other difference were noted between the two groups (mean duration of diarrhea, frequency and nature of the other infections). As for group I specifically, colonic ulcerations due to Cytomegalovirus were present in all the patients, varying from punctate and superficial erosions to deep ulcerations, with granular and friable intervening mucosa. Severe colonic lesions appeared during the course of Cytomegalovirus colitis in two patients who developed lethal necrotizing colitis. Finally, the clinical and pathologic features of these seven cases were compared to other reports of Cytomegalovirus infection of the colon.

Pseudomonas aeruginosa sepsis presenting as peripheral subcutaneous nodules. Report of 2 cases.

Two patients developed disseminated subcutaneous nodules with febrile illness. In both cases, Pseudomonas aeruginosa was isolated from the lesions; blood cultures yielded the same organism in one case, and were negative in the other. The portal of entry was thought to be a jugular hemodalysis catheter in the first case and a necrotic zoster complicating lymphoma in the second case. Both patients' condition improved with antibiotic therapy and the Pseudomonas nodules resolved without surgical drainage.

[Cerebral toxoplasmosis in immunosuppressed patients: diagnosis and treatment]. / Toxoplasmose cérébrale de l'immunodéprimé: diagnostic et traitement.

Central nervous system toxoplasmosis was diagnosed in 12 immunosuppressed patients, eleven of whom had AIDS. Fever (9/12), confusion (7/12) and focal neurological manifestations (6/12) were the main clinical signs. Lumbar puncture yielded abnormal cerebrospinal fluid in 6/6 cases. Cerebral computed tomographic scan abnormalities, homogenous (2/12) or ring-like (9/12) contrast-enhancing mass lesions and/or low density lesions (6/12), were present in all patients. Brain biopsy confirmed T. gondii infection in 7/8 cases. The combination pyrimethamine-sulfadiazine accounted for complete resolution (4/8) or partial improvement (4/8) in eight out of 12 patients. Mean duration of therapy was 6.5 months (1-21.5 months) in 11 patients. No relapse was observed. In three cases spiramycin was ineffective in the prevention of neurotoxoplasmosis.

Two-year evaluation of misoprostol for carcinogenicity in CD Sprague-Dawley rats.

The carcinogenic potential of misoprostol, a synthetic prostaglandin E1 analogue with anti-ulcer potential, was evaluated in CD Sprague-Dawley rats. The compound was given daily by gavage at 24, 240, and 2,400 micrograms/kg, up to 150 times the daily human dose for 2 years. Necropsies were done on all animals and the incidences of non-neoplastic and neoplastic changes analyzed for significance by life table methods. The only statistically significant non-neoplastic finding was epithelial hyperplasia and hyperkeratosis of the gastric mucosa. These changes, which are characteristic of some prostaglandins, were expected. Other non-neoplastic findings were typical of known spontaneous conditions in this strain of rats. The most frequent neoplasm was the pituitary adenoma, followed by the mammary fibroadenoma, mammary adenoma, mammary adenocarcinoma, and thyroid C-cell adenoma. A rare neoplasm, squamous cell carcinoma of the ovary was found in two rats. There was no evidence that misoprostol is carcinogenic for CD Sprague-Dawley rats.

Twenty-one-month evaluation of misoprostol for carcinogenicity in CD-1 mice.

Misoprostol, a synthetic prostaglandin E1 methyl ester analogue with anti-ulcer potential, was evaluated for its carcinogenic potential in CD-1 strain mice. The compound was given daily by gavage at 160, 1,600, and 16,000 micrograms/kg for 21 months. Necropsies were done on all animals and the incidences of non-neoplastic and neoplastic changes analyzed for significance by life table methods. The only statistically significant non-neoplastic compound-related findings were epithelial hyperplasia and hyperkeratosis of the gastric mucosa and hyperostosis of bone in the marrow cavity of sternebrae and femurs. The changes in the gastric epithelium are characteristic of some prostaglandins and were expected. The bone hyperostosis was associated with misoprostol in high dosages, and was considered unique to the mouse. Other non-neoplastic findings were typical of known spontaneous conditions in mice. The most frequent neoplasm was the hepatocellular adenoma followed by lymphosarcoma, lung alveolar carcinoma, and Harderian gland adenoma. Several proliferative lesions of the duodenum were considered to be spontaneous. These were focal avillous hyperplasia, focal atypical hyperplasia, and junctional polyp. There was no evidence that misoprostol is carcinogenic for CD-1 mice.

Preclinical toxicology profile of misoprostol.

The toxicity of misoprostol has been extensively examined in a variety of in vitro and in vivo studies. Preclinical studies evaluated acute and chronic toxicity, mutagenicity and carcinogenicity, and reproductive toxicity. Single oral dose studies in rodents and non-rodents indicate a safety margin of at least 500 to 1000 fold between lethal doses in animals and therapeutic doses in humans. Chronic toxicity studies (52 weeks) have been performed at daily oral doses of up to 300 and 9000 micrograms/kg body weight in dogs and rats, respectively. Rectal temperatures were increased at 100 and 300 micrograms/kg in dogs and serum iron was increased at 9000 micrograms/kg in rats. Stomach weights were increased in dogs and rats in a dose-correlated manner related, at least in part, to an increase in the number of normal epithelial cells (gastric hyperplasia). When drug treatment was stopped rectal temperatures, serum iron and stomach weights reverted to normal. Electron microscope studies on hyperplastic tissue showed that the ultrastructure was not affected. Hyperostosis has been observed, mainly in female mice, following prolonged drug treatment at high doses. Histological studies of bone tissues of rats and dogs and radiological studies of long bones of dogs following chronic administration of misoprostol showed that bone development was normal in all respects. Mutagenicity studies were negative and misoprostol was not fetotoxic or teratogenic in rats at oral doses up to 10000 micrograms/kg body weight, or in rabbits at doses up to 1000 micrograms/kg body weight.(ABSTRACT TRUNCATED AT 250 WORDS)

[Digestive manifestations of the acquired immunodeficiency syndrome (AIDS): study in 26 patients]. / Manifestations digestives du syndrome d'immunodéficience acquise (SIDA): étude chez 26 patients.

We studied the gastrointestinal manifestations in 26 cases of AIDS. The patients belonged to two different epidemiological groups: the first group included thirteen french homosexual men, the second group included 6 Haitians, 6 Africans and a Pakistanian, none of them admit homosexual activity. The clinical manifestations were: chronic watery diarrhea in 17 cases, bloody diarrhea in 2 cases; loss of weight in the 26 cases; dysphagia in five cases; jaundice in one patient (due to Kaposi sarcoma of the ampulla of Vater). The digestive lesions found, alone or associated, were necrotizing enteritis (2), ulcerative colitis (1), pseudomembranous colitis (1), Candida esophagitis (10), erythematous duodenitis (6), proctitis (4), Kaposi sarcoma (3), diffuse (2) or localized (1). Thirteen patients out of the 26 presented opportunistic digestive infections due to one or several germs. These were 10 cases of esophageal infection (due to Candida albicans) and 8 cases of enterocolonic infection due to Cytomegalovirus (3 cases), Cryptosporidium (3 cases), Mycobacterium avium intracellulare (1 case), Cryptococcus neoformans (1 case). The other digestive infections cases were due to non-opportunistic pathogens: Entamoeba histolytica (3 cases); Giardia lamblia (3 cases); Strongyloides stercoralis (2 cases); Salmonella typhi (2 cases); Shigella (1 case); Herpes simplex virus (1 case). No difference was noticed between the homosexual and the heterosexual groups with respect to the nature and the frequency of the digestive infections.