- Email: [email protected]
102. Dexamethasone, but not chlorpromazine, decreases ex-vivo tumor necrosis factor-α and interleukin-1β production in human volunteers
A38
Abstracts/Netherlands
Journal
in 50% and 40% of the patients after 4-8 weeks and 5-6 months respectively The mean VL at the start of therapy in ATNN patients was 87008 c/ml, after 4-8 weeks: 15.342 and after 5-6 months in 14 patients: 12 137 c/ml. The decrease in VL was statistically significant from start to 4-8 weeks and from start to 5-6 months, there was no significant difference between 4-8 weeks and 5-6 months. The VL was undetectable in 38% and 32% after 4-8 weeks and 5-6 months. Conclusion: Although we only have relatively short-term follow-up data it seems that in ATN HIV+ patients initiation of triple therapy induces a stronger reduction in VL and a more pronounced increase in CD4+ cells, compared to ATNN HIV+ patients. But in both groups it seems that the reduction in viral load is a longstanding effect. More data are needed, both in numbers and in time, in order to be able to appreciate fully the effect of triple therapy.
102. Dexamethasone, but not chlorpromazine, decreases exvivo tumor necrosis factor-a and interleukin-lp production in human volunteers. M.W.P. Bleeker, M.G. Netea, B.J. Kullberg, J.W.M. van der Meer. Department of Medicine, University Hospital, Nijmegen, Netherlands. Tumor necrosis factor-a (TNF) and interleukin-1B (IL-l) play an important role in severe infections. Dexamethasone (DEX) and chlorpromazine (CPZ) protect mice against lethal endotoxemia by decreasing serum levels of TNF and IL-1 (Netea et al., J Infect Dis 1995; 171:393). We investigated whether CPZ or DEX administered to human volunteers are able to inhibit IL-l and TNF production. Eighteen healthy volunteers randomly received CPZ (3 X 25 mg), DEX (3 X 1.5 mg) or placebo at 8 h intervals. Blood samples were taken before and after medication. Circulating TNF and IL-l concentrations were measured, and the LPS-induced production of these cytokines by whole blood and isolated peripheral mononuclear cells (PMNC) was assessed by radioimmunoassay. Circulating cytokines remained low in all groups. Production capacity of both TNF (from 5.5 k 0.9 rig/ml to 1.8 * 0.4 rig/ml, P < 0.05) and IL-l (7.4 f 1.8 rig/ml to 2.2 + 0.5 “g/ml, P < 0.05) decreased after DEX treatment, whereas no effect was observed after CPZ. Moreover, there was no influence of CPZ on cytokine production by PMNC. Serum concentrations of CPZ in human volunteers were much lower than the protective concentrations in mice (2.5 + 0.3 rig/ml versus 41.0& 3.0 rig/ml). Conclusion: CPZ inhibits TNF and IL-l production at serum concentrations that can hardly be reached in humans, thus precluding its usage in clinical anti-cytokine strategies.
103. The effect of infection control compliance, prevalence of colonization, and other risk factors on spread of vancomycinresistant enterococci (VRE). M. Bonten, S. Slauhter, M. Hayden, C. Nathan, R.A. Weinstein. University Hospital, Maastricht, Netherlands; Cook County Hospital and Rush Medical School, Chicago, IL, USA. Spread of multiresistant nosocomial pathogens is influenced by variables such as compliance with infection control measures and antibiotic use. We hypothesized that colonization pressure (i.e. the proportion of other patients already colonized) also is an
of Medicine
50 (1997)
Al-A44
important variable. Using VRE as a marker organism we studied the effect of compliance with handwashing, donning and removing of gloves, of antibiotic use, of colonization pressure, and of other risk factors on VRE-acquisition in a medical ICU (MICU) where colonization with VRE is endemic. During 19 weeks rectal swabs were obtained from patients daily and compliance was monitored by unobtrusive observers. A statistical model was created using Cox regression, including length of stay in MICU until acquisition of VRE, personnel compliance with infection control measures, colonization pressure, APACHE II scores, and the proportion of days that a patient received vancomycin and/or third generation cephalosporins, sucralfate and enteral feeding. In all 190 pts were analyzed, and 153 were not colonized with VRE on admission. In Cox regression, colonization pressure was the most important variable influencing acquisition of VRE (Hazard ratio = 1.032, 95% CI 1.012-1.052, P = 0.002) in combination with either use of enteral feeding (HR = 1.009, 95% Cl l.OOO1.017, P = 0.048) and third-generation cephalosporins (HR = 1.007, 95% CI 0.999-1.015, I’ = 0.106). Conclusion: Acquisition of VRE is influenced by colonization pressure, and the use of antibiotics and enteral feeding. However, once colonization pressure is high. it became the major variable affecting acquisition of VRE, which may explain the difficulty that hospitals have encountered in controlling spread of VRE.
104. Defective bactericidal capacity of monocytes from a patient with malakoplakia. R. van Crevel, J. Curfs * , A.J.A.M. van der Ven, J.W.M. van der Meer. Department of General Internal Medicine and * Department of Microbiology, University Hospital, Nijmegen, Netherlands. Background: Malakoplakia is a rare and enigmatic chronic inflammatory disorder which may affect any organ system. Its etiology is unknown but an infectious cause, possibly in the context of a host defense defect, has been suspected, and patients have been successfully treated with antibiotics only. Patient: We report a 63-year-old woman with a large intra-abdominal process involving bladder, uterus, small and large bowel with intestinal-vesical fistula. Histopathology showed numerous large histiocytes with peculiar inclusions, which is specific for malakoplakia. Methods: Purified and fixed blood monocytes revealed electron-dense inclusions and spicular calcium deposits on electron microscopy. Bactericidal assays with patient monocytes were performed. Survival of S. typhimurium and P. mirubilis inside patient monocytes was much higher than in control monocytes (122.6% vs 19.1%, respectively 71.3% vs 4.6%). Killing of S. aureus, E. coli and Y. enterocolitica, opsonization, phagocytosis and respiratory burst were normal. The mass lesion became smaller after treatment with ciprofloxacin, initially combined with metronidazole. Conclusion: The antibiotic response in this patient favor a bacterial factor in the etiology of malakoplakia. In addition, the morphological and functional abnormalities of peripheral blood monocytes strongly support the presence of a host factor. This is the first report of defective in vitro killing of Salmonella and Proteus in a patient with malakoplakia.
Abstracts/Netherlands
Journal
in 50% and 40% of the patients after 4-8 weeks and 5-6 months respectively The mean VL at the start of therapy in ATNN patients was 87008 c/ml, after 4-8 weeks: 15.342 and after 5-6 months in 14 patients: 12 137 c/ml. The decrease in VL was statistically significant from start to 4-8 weeks and from start to 5-6 months, there was no significant difference between 4-8 weeks and 5-6 months. The VL was undetectable in 38% and 32% after 4-8 weeks and 5-6 months. Conclusion: Although we only have relatively short-term follow-up data it seems that in ATN HIV+ patients initiation of triple therapy induces a stronger reduction in VL and a more pronounced increase in CD4+ cells, compared to ATNN HIV+ patients. But in both groups it seems that the reduction in viral load is a longstanding effect. More data are needed, both in numbers and in time, in order to be able to appreciate fully the effect of triple therapy.
102. Dexamethasone, but not chlorpromazine, decreases exvivo tumor necrosis factor-a and interleukin-lp production in human volunteers. M.W.P. Bleeker, M.G. Netea, B.J. Kullberg, J.W.M. van der Meer. Department of Medicine, University Hospital, Nijmegen, Netherlands. Tumor necrosis factor-a (TNF) and interleukin-1B (IL-l) play an important role in severe infections. Dexamethasone (DEX) and chlorpromazine (CPZ) protect mice against lethal endotoxemia by decreasing serum levels of TNF and IL-1 (Netea et al., J Infect Dis 1995; 171:393). We investigated whether CPZ or DEX administered to human volunteers are able to inhibit IL-l and TNF production. Eighteen healthy volunteers randomly received CPZ (3 X 25 mg), DEX (3 X 1.5 mg) or placebo at 8 h intervals. Blood samples were taken before and after medication. Circulating TNF and IL-l concentrations were measured, and the LPS-induced production of these cytokines by whole blood and isolated peripheral mononuclear cells (PMNC) was assessed by radioimmunoassay. Circulating cytokines remained low in all groups. Production capacity of both TNF (from 5.5 k 0.9 rig/ml to 1.8 * 0.4 rig/ml, P < 0.05) and IL-l (7.4 f 1.8 rig/ml to 2.2 + 0.5 “g/ml, P < 0.05) decreased after DEX treatment, whereas no effect was observed after CPZ. Moreover, there was no influence of CPZ on cytokine production by PMNC. Serum concentrations of CPZ in human volunteers were much lower than the protective concentrations in mice (2.5 + 0.3 rig/ml versus 41.0& 3.0 rig/ml). Conclusion: CPZ inhibits TNF and IL-l production at serum concentrations that can hardly be reached in humans, thus precluding its usage in clinical anti-cytokine strategies.
103. The effect of infection control compliance, prevalence of colonization, and other risk factors on spread of vancomycinresistant enterococci (VRE). M. Bonten, S. Slauhter, M. Hayden, C. Nathan, R.A. Weinstein. University Hospital, Maastricht, Netherlands; Cook County Hospital and Rush Medical School, Chicago, IL, USA. Spread of multiresistant nosocomial pathogens is influenced by variables such as compliance with infection control measures and antibiotic use. We hypothesized that colonization pressure (i.e. the proportion of other patients already colonized) also is an
of Medicine
50 (1997)
Al-A44
important variable. Using VRE as a marker organism we studied the effect of compliance with handwashing, donning and removing of gloves, of antibiotic use, of colonization pressure, and of other risk factors on VRE-acquisition in a medical ICU (MICU) where colonization with VRE is endemic. During 19 weeks rectal swabs were obtained from patients daily and compliance was monitored by unobtrusive observers. A statistical model was created using Cox regression, including length of stay in MICU until acquisition of VRE, personnel compliance with infection control measures, colonization pressure, APACHE II scores, and the proportion of days that a patient received vancomycin and/or third generation cephalosporins, sucralfate and enteral feeding. In all 190 pts were analyzed, and 153 were not colonized with VRE on admission. In Cox regression, colonization pressure was the most important variable influencing acquisition of VRE (Hazard ratio = 1.032, 95% CI 1.012-1.052, P = 0.002) in combination with either use of enteral feeding (HR = 1.009, 95% Cl l.OOO1.017, P = 0.048) and third-generation cephalosporins (HR = 1.007, 95% CI 0.999-1.015, I’ = 0.106). Conclusion: Acquisition of VRE is influenced by colonization pressure, and the use of antibiotics and enteral feeding. However, once colonization pressure is high. it became the major variable affecting acquisition of VRE, which may explain the difficulty that hospitals have encountered in controlling spread of VRE.
104. Defective bactericidal capacity of monocytes from a patient with malakoplakia. R. van Crevel, J. Curfs * , A.J.A.M. van der Ven, J.W.M. van der Meer. Department of General Internal Medicine and * Department of Microbiology, University Hospital, Nijmegen, Netherlands. Background: Malakoplakia is a rare and enigmatic chronic inflammatory disorder which may affect any organ system. Its etiology is unknown but an infectious cause, possibly in the context of a host defense defect, has been suspected, and patients have been successfully treated with antibiotics only. Patient: We report a 63-year-old woman with a large intra-abdominal process involving bladder, uterus, small and large bowel with intestinal-vesical fistula. Histopathology showed numerous large histiocytes with peculiar inclusions, which is specific for malakoplakia. Methods: Purified and fixed blood monocytes revealed electron-dense inclusions and spicular calcium deposits on electron microscopy. Bactericidal assays with patient monocytes were performed. Survival of S. typhimurium and P. mirubilis inside patient monocytes was much higher than in control monocytes (122.6% vs 19.1%, respectively 71.3% vs 4.6%). Killing of S. aureus, E. coli and Y. enterocolitica, opsonization, phagocytosis and respiratory burst were normal. The mass lesion became smaller after treatment with ciprofloxacin, initially combined with metronidazole. Conclusion: The antibiotic response in this patient favor a bacterial factor in the etiology of malakoplakia. In addition, the morphological and functional abnormalities of peripheral blood monocytes strongly support the presence of a host factor. This is the first report of defective in vitro killing of Salmonella and Proteus in a patient with malakoplakia.