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Les staphylocoques ont développé depuis longtemps une résistance à la méticilline et plus de 30 % des souches de staphylocoque doré sont maintenant résistantes à la méticilline. Plusieurs cas d’échec d’un traitement par la vancomycine ont été récemment rapportés, correspondant à des souches de sensibilité diminuée à la vancomycine. Il convient donc pour traiter les infections sévères de s’assurer d’une concentration de vancomycine à la vallée entre 15 et 20 mg/L, de telle sorte que les concentrations sériques excèdent largement la CMI. L’utilisation d’autres antibiotiques actifs contre les staphylocoques est passée en revue et les avantages potentiels des nouveaux antistapylococciques sont discutés.

An unusual Helicobacter sp. was isolated from the blood of a human immunodeficiency virus (HIV)-infected patient. This organism had spiral morphology, with single amphitrichous flagella, and was negative for hippurate hydrolysis, production of urease, and reduction of nitrate. 16S rRNA gene sequence analysis verified that the isolate was a species of Helicobacter, most closely related to an undescribed Helicobacter-like isolate from Vancouver, British Columbia, Canada, and to Helicobacter westmeadii, a recently described species from Australia. Both organisms had also been isolated from the blood of HIV-infected patients. These blood isolates, along with Helicobacter cinaedi, form a cluster of closely related Helicobacter spp. that may represent an emerging group of pathogens in immunocompromised patients.

Overdosage of muscle relaxant has been given as a possible explanation for the hypotensive episodes occurring during the management of tetanus. The aim of the present work was to study the pharmacokinetics of pancuronium during long term infusion. Pancuronium was administered to eight patients with severe tetanus for a period varying from 8 to 24 days. The concentration of pancuronium was measured daily in plasma and urine using a fluorimetric method. The plasma concentration varied from 0.27 to 0.48 µg/ml. No tendency to accumulation was observed. The plasma concentration fell rapidly below the level associated with muscle relaxation when pancuronium was discontinued. This absence of accumulation can be explained by a rapid elimination of pancuronium through the kidney according to a process of ultrafiltration.

The pharmacokinetics of teicoplanin were studied in 15 adult patients in the acute phase of severe infections caused by gram-positive cocci. All the subjects were given a daily intravenous bolus dose of 6 mg of teicoplanin kg-1 (body weight). The pharmacokinetic study was performed over a 48-h period after injection 4. The subjects were categorized according to their mean creatinine clearances (ml.min-1.kg-1) during the study period: group 1 (n = 3), greater than 1.6; group 2 (n = 6), 0.8 to 1.6; and group 3 (n = 6), 0.15 to 0.8. Mean concentrations of teicoplanin in serum at 1, 24, and 48 h were 33 +/- 8, 9 +/- 3, and 6 +/- 2.5 micrograms.ml-1, respectively. The mean half-lives of the concentration-time curve from 12 to 48 h were 28 +/- 4, 44 +/- 24, and 48 +/- 14 h in groups 1, 2, and 3, respectively (group 3 versus group 1: P less than 0.05). The mean area under the serum concentration-time curve from time zero to 24 h was 344 +/- 92 mg.h.liter-1, and the mean hybrid volume of distribution was 1.09 +/- 0.46 liter.kg-1. These values were similar for the three groups, with a trend for larger areas under the curve in group 3. Creatinine clearance correlated directly with the total body clearance of teicoplanin (r = 0.70) and with the renal clearance of teicoplanin (r = 0.82). However, in critically ill patients, the wide interindividual variations in pharmacokinetic parameters are more relevant than those related to the variations in renal function when creatinine clearance is above 0.30 ml.min-1.kg-1. We concluded that, in such conditions, monitoring of concentrations of teicoplanin in serum is mandatory.

The penetration of roxithromycin (RU 28965), an ether oxime derivative of erythromycin, into the cells and fluid lining the epithelial surface of the lower respiratory tract was studied by performing fiber-optic bronchoscopy with bronchoalveolar lavage on eight patients who had received roxithromycin at 300 mg perorally every 12 h for 5 days. The apparent volume of epithelial lining fluid recovered by bronchoalveolar lavage was determined by using urea as an endogenous marker. There was a significant relationship (r = 0.75; P less than 0.02) between roxithromycin levels in plasma and epithelial lining fluid, with a correlation whose slope suggested that the level of drug penetration into the lining fluid was 0.2. Concentrations of the antibiotic in cells recovered by bronchoalveolar lavage (21 +/- 10 micrograms/ml) were 2 and 10 times higher than in plasma (11.4 +/- 5.7 micrograms/ml) and epithelial lining fluid (2.0 +/- 1.7 micrograms/ml), respectively. Thus, when administered perorally in humans, roxithromycin is markedly accumulated by resident alveolar macrophages in concentrations largely exceeding the MBCs of the drug for most facultative intracellular pathogens including Legionella pneumophila, despite low concentrations in the epithelial lining fluid.

The effect of short-term antibiotic prophylaxis on postoperative infection with 2 injections of cefotaxime begun preoperatively was evaluated in a double-blind, randomized, placebo-controlled trial at 1 center on 181 patients with preoperative sterile urine undergoing transurethral resection (90) or open prostatectomy (91). Antibiotic prophylaxis reduced the number of urinary infections significantly in both groups without altering the level of resistant pathogens. Cefotaxime lowered the incidence of postoperative infection in the early postoperative period from 30 to 4 per cent in the transurethral resection group and from 46 to 4.5 per cent in the open prostatectomy group. A significant difference was found between the 2 treatment groups in the incidence of perioperative bacteremia and postoperative fever. Among the patients undergoing an open prostatectomy a reduced rate of wound infection and a shorter duration of hospital stay were witnessed in the treated group. Thus, short-term chemoprophylaxis by cefotaxime is of benefit in reducing morbidity and hospital cost for prostatectomy by either procedure.

Patients with organ failure or severe infection after cardiac operations may require prolonged stays in the intensive care unit. This study examined long-term mortality and determined quality of life for surviving patients in this group. This observational cohort study was conducted at Bichat Hospital, Paris, an academic tertiary care center. The study group consisted of 116 consecutive patients who underwent cardiac operations and were transferred to the multidisciplinary intensive care unit between January 1986 and December 1987. Patients referred for mediastinitis were automatically excluded. Respiratory failure (88.8%) and hemodynamic instability (81.9%) were the main causes of transfer; an infection was present in 23.3% of patients at entry into the intensive care unit. Twenty-seven patients (23.3%) died in the intensive care unit. Presurgical New York Heart Association functional class, postoperative bacteremia before admission to the intensive care unit, and severity of illness on admission to the intensive care unit were independent predictors of death in the intensive care unit. After an average follow-up of 81 months (range 70 to 93 months), 69% of the patients alive at transfer from the intensive care unit were still alive. Preoperative New York Heart Association functional class was the only long-term independent prognostic factor. Quality of life, as evaluated by the Nottingham Health Profile, was good for more than 70% of the survivors and was not influenced by any recorded variables, with the exception of age. (J THORAC CARDIOVASC SURG 1996;112:926-34)

The optimal technique for diagnosing nosocomial bacterial pneumonia in critically ill patients cared for in the intensive care unit remains unclear, especially in the subgroup of patients requiring mechanical ventilation. An important advance has been the development of the protected specimen brush technique. We and others have demonstrated that secretions obtained using this technique and evaluated by quantitative cultures are useful in distinguishing patients with and without pneumonia. However, this procedure has important limitations in that results are not available immediately and in that a few false negative or false positive results may be observed. Recently, the use of bronchoalveolar lavage has been suggested to be of value in establishing the diagnosis of pneumonia, since the cells and liquid recovered can be examined microscopically immediately after the procedure and are also suitable for quantitative culture. We believe that microscopic identification of bacteria within cells recovered by lavage may provide a sensitive and specific means for early and rapid diagnosis of pneumonia in this setting and that the lavage technique can be conveniently incorporated into a protocol along with the quantitative culture of samples obtained using the protected specimen brush. This combination will probably improve the overall accuracy of diagnosis while allowing the administration of prompt empiric antimicrobial therapy in the majority of patients with pneumonia.

Techniques usually employed for the detection of rabies' antibodies are costly, time consuming, and sometimes fail to detect early antibodies. The introduction of immunoenzymatic techniques in the serology of viral disease represents a new and important advance. We therefore adapted this technique to the detection of rabies antibodies.

A total of 32 patients with Plasmodium falciparum malaria were studied. Of these, 23 had benign infections, and 9 had typical cerebral malaria. Cryoglobulins, circulating immune complexes detected by a C1q-binding assay, and hypocomplementemia were found in eight of nine patients with cerebral malaria. Raised levels of complement component 3 breakdown products (C3d) were found in the seven patients tested. Peak levels of circulating immune complexes and C3d were associated with thrombocytopenia. In contrast, in patients with benign Plasmodium falciparum malaria, cryoglobulins and circulating immune complexes were found only in 3 of 23 patients. Similarly, hypocomplementemia was detected only in 5 of 23 patients. These observations suggest that the intensity of the immune response and of the associated complement activation may be important factors in the pathogenesis of cerebral malaria.

From January 1978 to December 1988, 71 patients underwent surgical intervention at our institution for prosthetic valve endocarditis with ring abscesses. These procedures involved 59 aortic prostheses and 12 mitral prostheses. No causative agent could be identified in 19 patients (26.7 %). The operation was performed during antibiotic therapy in 63 patients and after a planned course of antibiotic therapy in 8 patients. At the aortic level, abscesses were remedied by suturing in 3 cases, by pericardial patches in 34 cases, and by complex procedures in 22 cases (subcoronary valved conduit in 11 cases, supracoronary valved conduit with coronary bypass grafts in 10 cases, apicoaortic valved conduit in 1 case). At the mitral level, ring abscesses were cured in 10 cases by intraatrial implantation of the prosthesis. In one case, the prosthesis was anchored inside the left ventricle; and in one case the valve could be seated on the anulus. The overall operative mortality rate was 17%. Long-term survival was 54% ±8% at 6 years. Fifteen (26%) of the survivors needed a third valve replacement (four operative deaths); a complex reconstruction was performed in seven patients. Better detection of ring abscesses and earlier surgical intervention before annular destruction and hemodynamic failure can improve the operative mortality rate for prosthetic valve endocarditis. When it is necessary, complex reconstruction, in spite of a high mortality rate, seems to eradicate the infectious seat, and the outlook for the patient's condition appears good. (J ThoracCardiovascSurg1993;105:1106-13)

There is ample experimental evidence that polymorphonuclear neutrophils (PMN) play a critical role in the pathogenesis of the adult respiratory distress syndrome (ARDS). Since interleukin-8 (IL-8) is a strong chemotactic factor for PMN, we measured IL-8 levels in plasma and bronchoalveolar lavage (BAL) fluid of 18 patients, 12 with ARDS and 6 with severe pneumonia uncomplicated by ARDS, all of whom had an increased number of PMN in BAL fluid. Seven healthy subjects served as controls. We found elevated levels of IL-8 in the alveolar spaces of all patients tested. Elevated BAL IL-8 levels were related to a fatal outcome and the presence of shock and correlated with a general clinical severity index (simplified acute physiological score). BAL fluid levels of IL-8 were significantly higher in patients with ARDS than in patients with pneumonia. In plasma, IL-8 levels were increased similarly in all patients and did not correlate with survival or the presence of shock. The BAL fluid-to-plasma ratio of IL-8 was significantly greater than that of tumor necrosis factor alpha, indicating higher local production of IL-8. Moreover, the presence of a primed subpopulation of blood PMN with respect to H2O2 production indicates that IL-8 may contribute to the neutrophil-mediated process in the pathogenesis of ARDS and pneumonia.

Abstract

Vancomycin penetration into the fluid lining the epithelial surface of the lower respiratory tract was studied by performing fiberoptic bronchoscopy with bronchoalveolar lavage on 14 critically ill, ventilated patients who had received the drug for at least 5 days. The apparent volume of epithelial lining fluid (ELF) recovered by bronchoalveolar lavage was determined by using urea as an endogenous marker. Vancomycin levels in ELF ranged from 0.4 to 8.1 micrograms/ml (mean, 4.5 micrograms/ml), while the mean simultaneous level of the drug in plasma was 24 micrograms/ml (range, 9 to 37.4 micrograms/ml). There was a significant relationship (r = 0.64, P < 0.02) between vancomycin levels in plasma and those in ELF, with a correlation whose slope (0.15) indicated that the blood-to-ELF ratio of drug penetration was 6:1. Using the albumin concentration in ELF as a marker of lung inflammation, we found that vancomycin penetration was higher in patients with ELF albumin values of > or = 3.4 mg/ml than in patients with normal values (< 3.4 mg/ml) (P < 0.02). These results suggest that the vancomycin distribution includes the ELF of the lower respiratory tract at a concentration that is dependent upon the levels in blood and the alveolar capillary membrane protein permeability. These concentrations were well above the MICs for most staphylococci and enterococci.

Forty-seven nosocomial cases of legionellosis due to Legionella pneumophila serogroup 1 were diagnosed in one major outbreak from November 1982 to March 1983 in a 960-bed teaching hospital. Contaminated water was considered to be a possible source of infection because, during that period, monthly samples were found to be positive with averages of 104 CFU/1. After chlorination of hot water associated with flushing of outlets, nearly all samples taken in the next two years were found to be negative. A case-control study was performed to examine potential risk factors. Three groups of controls were randomly selected among eligible patients: In a multivariate analysis, only three clinical factors were found to be associated with legionellosis patients: malignant illness (relative risk, RR = 3.5), presence of an ultimately fatal disease (RR = 2.6), and exposure to corticosteroids prior to admission (RR = 7.9). Investigations of in-hospital exposures suggest that during this nosocomial outbreak diagnostic or therapeutic respiratory procedures had not increased the risk of illness. Although the epidemiological association between water contamination and disease remains unclear, the eradication of L. pneumophila from the identified supply seems to have been effective in preventing disease in this hospital.