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Biomedical subjects

R O Darouiche

Publications and source records attributed to R O Darouiche.

At least 19 recordsLinked to original sources

Proteus bacteriuria is associated with significant morbidity in spinal cord injury.

STUDY DESIGN: Retrospective chart review. OBJECTIVES: We investigated the morbidity associated with Proteus bacteriuria in a spinal cord injured (SCI) population. SETTING: Michael E DeBakey Veterans Affairs Medical Center in Houston, Texas, USA. METHODS: We reviewed the medical records of all veterans with SCI who received care in our medical center during the past 3 years. Proteus bacteriuria was defined as the growth of Proteus species in any urine culture during the study period. Urinary stones were defined as either renal or bladder calculi. RESULTS: During the study period, 71 of the 501 subjects (14%) had Proteus and 90 (18%) had urinary stones. Twenty-seven percent of the subjects with Proteus had stones, and the association of Proteus with stones was significant (P<0.05). Proteus bacteriuria was likewise associated with complete injury, hospitalization, decubitus ulcers, and history of stones (P<0.001). Subjects using indwelling catheters, either transurethral or suprapubic, were significantly more likely to have Proteus, whereas subjects practising spontaneous voiding and clean intermittent catheterization were significantly less likely to have Proteus. In the 90 patients with stones, Proteus was associated with requiring treatment for stones and having multiple stones (P<0.01). Twenty-five of the 90 patients with stones (28%) required treatment, most often with lithotripsy, and 6 (7%) developed urosepsis. CONCLUSIONS: In persons with SCI, Proteus was found in subjects with a greater degree of impairment who were more likely to be hospitalized, to have decubiti, and to use indwelling catheters. Bacteriuria with Proteus predicted urologic complications in persons with SCI. STATEMENT OF ETHICS: All applicable institutional and governmental regulations concerning the ethical use of human volunteers were followed during the course of this research.

Bacteriuria↗

Antifungal activity of antimicrobial-impregnated devices.

The in-vitro and in-vivo efficacy against Candida albicans and Candida krusei of devices impregnated with chlorhexidine and chloroxylenol was examined. The impregnated devices produced large zones of inhibition against both organisms (mean size, 39 mm and 38 mm, respectively). In a rabbit model in which segments of silicone catheters were placed percutaneously, non-impregnated devices were twice as likely as impregnated devices to become colonised with either C. albicans or C. krusei. Impregnated devices also had significantly lower colony counts of C. albicans (58 vs. 1361 CFU; p 0.008) and C. krusei (19 vs. 764 CFU; p 0.008).

Animals↗

Dalbavancin compared with vancomycin for prevention of Staphylococcus aureus colonization of devices in vivo.

OBJECTIVES: Although active against free-floating bacteria, vancomycin displays a poor activity against organisms embedded within the biofilm surrounding implanted devices. Dalbavancin is a novel glycopeptide antibiotic with strong activity against staphylococci and a long half-life that allows for once-a-week dosing. The objective of this animal study was to examine the ability of dalbavancin and vancomycin to prevent Staphylococcus aureus colonization of devices. METHODS: Twelve rabbits were randomized, in three groups of four each, to receive intravenous injections of dalbavancin, vancomycin or normal saline (control). Eight polyurethane catheter segments were subcutaneously implanted in the back of each rabbit, then inoculated with S. aureus. Rabbits were sacrificed a week later and explanted devices were cultured. RESULTS: The rates of device colonization were comparable in the vancomycin (53%) and control (47%) groups, whereas only 28% of devices in the dalbavancin group became colonized. There was a trend (although not statistically significant) toward a lower rate of device colonization following receipt of dalbavancin vs. vancomycin (P = 0.07) or saline (P = 0.02). CONCLUSIONS: The demonstrated efficacy of dalbavancin in this animal study suggest that this novel antibiotic may have an important role in the prevention and treatment of device-related infection.

Animals↗

Comparison of adherence of Candida albicans and Candida parapsilosis to silicone catheters in vitro and in vivo.

OBJECTIVE: Although Candida parapsilosis has been associated with device-related infections in the clinical settings, factors that contribute to this association have not been previously examined. The objectives of this study were to compare in vitro and in vivo the adherence to silicone catheters of: (1) Candida albicans vs. C. parapsilosis, and (2) invasive vs. colonizing isolates of C. albicans and C. parapsilosis. METHODS: The records of 840 patients who had had Candida species isolated at three teaching hospitals during a three-month period were reviewed. A total of 20 clinical isolates of each of C. parapsilosis and C. albicans were examined for their adherence to silicone catheters in vitro and in a rabbit model of percutaneously placed catheters. For each Candida species, ten invasive isolates that had caused clinical device-related infection and 10 colonizing isolates that had caused only device colonization were studied. RESULTS: Candida parapsilosis accounted for <5% of yeast isolates from all sites, while three-quarters were C. albicans. Candida parapsilosis was isolated proportionately more often from blood and/or devices than C. albicans (34.3% vs. 8.5%, respectively, P < 0.0001). There were no significant differences in the degrees of adherence in vitro and in vivo between C. albicans and C. parapsilosis or between invasive and colonizing Candida. CONCLUSION: Although C. parapsilosis was isolated proportionately more often from blood and/or devices than C. albicans in our studied population, there was no significant difference in the adherence of the two Candida species to silicone, nor between invasive and colonizing Candida in our in vitro and in vivo models. Factors other than microbial adherence may help explain the observed association of C. parapsilosis with device-related infections.

Animals↗

Device-associated infections: a macroproblem that starts with microadherence.

Medical devices are responsible for a large portion of nosocomial infections, particularly in critically ill patients. Device-associated infections can cause major medical and economic sequelae. Bacterial colonization of the indwelling device can be a prelude to both infection and malfunction of the device. The pathogenesis of device-associated infection centers around the multifaceted interaction among the bacteria, the device, and the host. Bacterial factors are probably the most important in pathogenesis of infection, whereas device factors are the most amenable to modification with the objective of preventing infection. Some, but not all, of the studied bacterial receptors satisfy the proposed "adherence/infection" version of Koch's postulates. Traditional surface-modifying preventive approaches have largely focused on antimicrobial coating of devices and resulted in variable clinical success in preventing device-associated infections. The potential protective role of newer innovative approaches, such as biofilm modification and bacterial interference, ought to be further investigated.

Bacterial Adhesion↗

Tuberculous pericarditis: optimal diagnosis and management.

Pericarditis is a rare manifestation of tuberculous disease. The appropriate diagnostic workup and optimal therapeutic management are not well defined. We present 10 new cases of tuberculous pericarditis and review the relevant literature. The specific topics addressed are (1) the importance of tissue for diagnosis, (2) the optimal surgical management, (3) the role of corticosteroids, and (4) the impact of human immunodeficiency virus (HIV) on the management of this disease. The cases and the literature suggest that the optimal management includes an open pericardial window with biopsy, both for diagnosis and to prevent reaccumulation of fluid. Corticosteroids probably offer some benefit in preventing fluid reaccumulation as well. The data are inconclusive regarding whether open drainage or corticosteroid use prevents progression to constrictive pericarditis. No studies have addressed these issues specifically in HIV-positive patients, but the 3 HIV-positive patients in our series had an excellent response to drainage and antituberculous therapy.

AIDS-Related Opportunistic Infections↗

Diagnosis of catheter-related bloodstream infections: is it necessary to culture the subcutaneous catheter segment?

In order to determine the diagnostic usefulness of culturing the subcutaneous catheter segment, an analysis was performed using data derived from two prospective, randomized studies that included 479 patients with central venous catheters and 13 episodes of catheter-related bacteremia. The results indicate that quantitative culture, using the roll-plate and sonication methods, of the subcutaneous catheter segment did not add to the diagnostic yield (sensitivity, 83-100%; specificity, 82-97%; negative predictive value, 100%) of semiquantitative and quantitative catheter-tip cultures or aid in identifying catheter-related bloodstream infections.

Bacteremia↗

Pilot trial of bacterial interference for preventing urinary tract infection.

OBJECTIVES: To examine the safety and efficacy of bacterial interference in preventing symptomatic urinary tract infection (UTI). METHODS: A prospective, nonrandomized, pilot clinical trial was conducted in patients with spinal cord injury who had neurogenic bladder and had frequent episodes of symptomatic UTI. The bladder of patients was inoculated with a nonpathogenic prototype of Escherichia coli 83972. The rate of symptomatic UTI in successfully colonized patients while colonized with E. coli 83972 was compared with (a) their own baseline prestudy rate and (b) the rate of symptomatic UTI in patients who were not successfully colonized. RESULTS: Of 44 inoculated patients, 30 (68%) became colonized with E. coli 83972 for 1 month or longer. Only two episodes of symptomatic UTI occurred in the group of 30 patients while colonized with E. coli 83972 (a total of 34 patient-years), and none was attributed to E. coli 83972. The group of 30 patients experienced a 63-fold reduction in the rate of symptomatic UTI while colonized with E. coli 83972 versus their baseline prestudy period (mean 0.06 versus 3.77 episodes of symptomatic UTI/patient-year, P <0.001). The rate of symptomatic UTI was also 33-fold lower in this group of 30 patients while colonized with E. coli 83972 than in the well-matched group of 14 patients who were not successfully colonized (mean 0.06 versus 1.80 episodes of symptomatic UTI/patient-year, P <0.001). CONCLUSIONS: The results of this pilot study indicate that bacterial interference using E. coli 83972 may be safe and effective in preventing UTI.

Adult↗

Direct confocal microscopy studies of the bacterial colonization in vitro of a silver-coated heart valve sewing cuff.

The antimicrobial coating of prosthetic heart valve sewing cuffs has been considered a potentially effective method for preventing prosthetic valve endocarditis. Although traditional in vitro bacterial adherence studies are often useful as screening tools, they can be inadequate in examining the antiinfective efficacy of antimicrobial-coated devices. We conducted a pilot in vitro study to directly assess the antimicrobial activity of a silver-coated sewing cuff versus uncoated cuff using confocal scanning laser microscopy. Staphylococcus epidermidis adhered more to the surfaces of the silver-coated sewing cuff compared with the uncoated cuff. These pilot in vitro results cast a doubt on the antiinfective efficacy of silver-coated prosthetic heart valve sewing cuffs and suggest further assessment should be carried out using animal studies.

Anti-Bacterial Agents↗

Bacterial interference for prevention of urinary tract infection: an overview.

Urinary tract infection (UTI) is the most common infection in patients with spinal cord injury (SCI) and is a major cause of morbidity and mortality in this population. The bladders of patients with SCI, particularly those with indwelling bladder catheters, can become colonized by a variety of organisms, including those that may, and others that may not, cause symptoms of infection. The latter group of bacteria, so-called benign colonizers, are often left untreated because they may provide some protection against symptomatic infection with more pathogenic bacteria. In recent years, deliberate urogenital tract colonization with benign bacterial strains was studied with the objective of offering some protection against invasion by uropathogenic strains. When well-characterized strains of Lactobacillus sp. were used to colonize the vagina of women prone to frequent UTI, a moderate reduction in the rate of recurrent UTI was observed. In other studies, a non-pathogenic prototype of Escherichia coli (strain 83,972) causing asymptomatic bacteriuria was used for deliberate bladder colonization. These preliminary observations encourage the examination of the safety and preventive efficacy of this approach in human subjects.

Antibiosis↗

Infection-resistant alloplasts.

Prosthesis-related infection accounts for nearly half of nosocomial infections, resulting in significant morbidity, mortality, prolonged hospitalization, and higher healthcare costs. Although numerous antimicrobial-coated surfaces have been suggested to guard against prosthesis-related infection, only a few, such as minocylcine plus rifampin, are clinically protective. The differences in clinical efficacy can be attributed at least in part to differences in the magnitude of leaching of the antimicrobial agent off the surface. There is a pressing need to explore the clinical efficacy of antimicrobial surfaces suitable for use in devices intended for long-term use.

Animals↗

Characterization of a fish antimicrobial peptide: gene expression, subcellular localization, and spectrum of activity.

Antimicrobial peptides are proposed to act as the first line of mucosal host defense by exerting broad-spectrum microbicidal activity against pathogenic microbes. Pleurocidin, a new 25-residue linear antimicrobial peptide, was recently isolated from the skin secretions of winter flounder (Pleuronectes americanus). The present study identifies the cDNA and gene encoding pleurocidin. The pleurocidin gene comprises four exons. Its upstream region demonstrates consensus binding sequences for transcription factors found in host defense genes in mammals, including sequences identical to the NF-IL6 and alpha and gamma interferon response elements. Pleurocidin is predicted to exist as a 68-residue prepropeptide that undergoes proteolytic cleavage of its amino-terminal signal and carboxy-terminal anionic propiece to form the active, mature peptide. Transmission electron microscopy localized pleurocidin to the mucin granules of skin and intestinal goblet cells. Significant synergy was shown to occur between pleurocidin and D-cycloserine targeting Mycobacterium smegmatis. Pleurocidin was functionally active at physiologic concentrations of magnesium and calcium; however, high concentrations of these divalent cations ablated pleurocidin's activity against a standard test strain, Escherichia coli D31. Pleurocidin was tested against bacterial and fungal clinical isolates and showed broad-spectrum antimicrobial activity. Together, these data support the hypothesis that pleurocidin participates in innate mucosal immunity, and it may prove to be a beneficial therapeutic agent.

Amino Acid Sequence↗

A comparison of two antimicrobial-impregnated central venous catheters. Catheter Study Group.

BACKGROUND: The use of central venous catheters impregnated with either minocycline and rifampin or chlorhexidine and silver sulfadiazine reduces the rates of catheter colonization and catheter-related bloodstream infection as compared with the use of unimpregnated catheters. We compared the rates of catheter colonization and catheter-related bloodstream infection associated with these two kinds of antiinfective catheters. METHODS: We conducted a prospective, randomized clinical trial in 12 university-affiliated hospitals. High-risk adult patients in whom central venous catheters were expected to remain in place for three or more days were randomly assigned to undergo insertion of polyurethane, triple-lumen catheters impregnated with either minocycline and rifampin (on both the luminal and external surfaces) or chlorhexidine and silver sulfadiazine (on only the external surface). After their removal, the tips and subcutaneous segments of the catheters were cultured by both the roll-plate and the sonication methods. Peripheral-blood cultures were obtained if clinically indicated. RESULTS: Of 865 catheters inserted, 738 (85 percent) produced culture results that could be evaluated. The clinical characteristics of the patients and the risk factors for infection were similar in the two groups. Catheters impregnated with minocycline and rifampin were 1/3 as likely to be colonized as catheters impregnated with chlorhexidine and silver sulfadiazine (28 of 356 catheters [7.9 percent] vs. 87 of 382 [22.8 percent], P<0.001), and catheter-related bloodstream infection was 1/12 as likely in catheters impregnated with minocycline and rifampin (1 of 356 [0.3 percent], vs. 13 of 382 [3.4 percent] for those impregnated with chlorhexidine and silver sulfadiazine; P<0.002). CONCLUSIONS: The use of central venous catheters impregnated with minocycline and rifampin is associated with a lower rate of infection than the use of catheters impregnated with chlorhexidine and silver sulfadiazine.

Analysis of Variance↗

Efficacy of antimicrobial-impregnated bladder catheters in reducing catheter-associated bacteriuria: a prospective, randomized, multicenter clinical trial.

OBJECTIVES: To examine the efficacy of bladder catheters impregnated with minocycline and rifampin in reducing catheter-associated bacteriuria. METHODS: A prospective, randomized clinical trial was conducted at five academic medical centers. Patients undergoing radical prostatectomy were randomized to receive intraoperatively either regular silicone bladder catheters (control catheters) or silicone bladder catheters impregnated with minocycline and rifampin (antimicrobial-impregnated catheters). Catheters remained in place for a mean of 2 weeks. Urine cultures were obtained at about 3, 7, and 14 days after catheter insertion. Bacteriuria was defined as the growth of organism(s) in urine at a concentration of 10(4) colony-forming units per milliliter or greater. RESULTS: Kaplan-Meier analysis demonstrated that it took significantly longer for patients (n = 56) who received the antimicrobial-impregnated catheters to develop bacteriuria than those (n = 68) who received the control catheters (P = 0.006 by the log-rank test). Patients who received the antimicrobial-impregnated catheters had significantly lower rates of bacteriuria than those in the control group both at day 7 (15.2% versus 39.7%) and at day 14 (58.5% versus 83.5%) after catheter insertion. Patients who received the antimicrobial-impregnated catheters had significantly lower rates of gram-positive bacteriuria than the control group (7.1% versus 38.2%; P <0.001) but similar rates of gram-negative bacteriuria (46.4% versus 47.1%) and candiduria (3.6% versus 2.9%). The antimicrobial-impregnated catheters provided zones of inhibition against Enterococcus faecalis and Escherichia coli, both at baseline and on removal. CONCLUSIONS: Bladder catheters impregnated with minocycline and rifampin significantly reduced the rate of gram-positive catheter-associated bacteriuria up to 2 weeks after catheter insertion.

Anti-Bacterial Agents↗

Prevention of vascular catheter-related infections.

Infection is the most common serious complication of intravascular catheters. Most cases of catheter-related infection are caused by staphylococci that originate either from the skin of the patient and migrate along the external surface of the catheter or from a contaminated catheter hub and migrate along the internal surface of the catheter. Major risk factors predisposing to catheter-related infection include prolonged duration of catheter placement, frequent manipulation of the catheter, use of thrombogenic catheter material, location of the catheter, and use of occlusive transparent plastic dressings. A number of measures have been reported in prospective, randomized clinical trials to protect against vascular catheter-related infection. This paper summarizes the clinical efficacy of various preventive measures, such as placement and maintenance of vascular catheters by a skilled infusion therapy team, institution of maximal sterile barriers, use of silver-impregnated subcutaneous cuff, antimicrobial coating of catheters with either antibiotics or antiseptics, use of an antiseptic catheter hub, application of topical disinfectants, and flushing catheters with the combination of antimicrobial and antithrombotic agents.

Bacterial Infections↗

Virulence properties of Escherichia coli 83972, a prototype strain associated with asymptomatic bacteriuria.

Little is known about bacteria associated with asymptomatic bacteriuria (ABU) with regard to urinary tract colonization mechanisms. In this study, virulence properties of Escherichia coli 83972, a strain that was isolated from a clinical ABU episode, were examined. The genetic potential for expression of P and type 1 pili was demonstrated, and DNA sequences related to type 1C and G (UCA) pilus genes were also detected. However, E. coli 83972 did not express D-mannose-resistant or D-mannose-sensitive hemagglutination after growth under standard conditions in vitro or upon isolation from the urine of colonized test subjects. Limited uroepithelial cell adherence was observed in vivo, and weak D-mannose-sensitive hemagglutination was detected after extended growth in urine in vitro.

Adhesins, Escherichia coli↗

Randomized trial of itraconazole oral solution for oropharyngeal candidiasis in HIV/AIDS patients.

PURPOSE: Oropharyngeal candidasis (thrush) is the most common opportunistic infection in individuals who are positive for the human immunodeficiency virus (HIV) and those who have progressed to AIDS. Itraconazole has a broad in vitro spectrum of activity, including a wide variety of Candida species. Our study determined the relative efficacy of a new oral solution formulation of itraconazole and fluconazole tablets in the treatment of oropharyngeal candidiasis. PATIENTS AND METHODS: This was a prospective randomized, third-party-blind, multicenter trial conducted at 12 centers in the United States. One hundred seventy-nine HIV-positive patients with mycologically documented oropharyngeal candidiasis were treated with itraconazole oral solution 200 mg/ day for 7 or 14 days, or fluconazole tablets 100 mg/day for 14 days. Severity of disease was scored clinically before treatment and at clinical evaluations on days 3, 7, 14, 21, 35, and 42. Semi-quantitative cultures of mouth washings were also obtained on these days. RESULTS: Both 14-day and 7-day regimens of itraconazole oral solution were equivalent to fluconazole for most efficacy parameters. The clinical response rate was 97% after 14 days of itraconazole and 87% after 14 days of fluconazole. Itraconazole oral solution given for 7 days was also equivalent to fluconazole treatment for 14 days. Approximately one half of patients in all three groups relapsed by 1 month after completion of treatment. There were few adverse reactions to either drug. CONCLUSION: Itraconazole oral solution is well tolerated and offers an alternative at least as effective as fluconazole in the treatment of oropharyngeal candidiasis.

AIDS-Related Opportunistic Infections↗