A painless, enlarging skin ulcer in a young immigrant.
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Biomedical subjects
Publications and source records attributed to R A Larsen.
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BACKGROUND: Preconnected catheter systems with sealed junctions have been associated with reduced rates of bacteriuria and mortality. A clinical trial was undertaken to evaluate the effectiveness of a junction seal applied after catheter insertion for preventing bacteriuria and reducing mortality. METHODS: Patients undergoing transurethral catheterization at a community hospital were randomized within 24 hours of catheter insertion to receive either a tape seal applied to the catheter-drainage tubing junction or no tape seal. Catheter urine cultures and catheter care violations were monitored daily until catheter removal or patient discharge. RESULTS: Overall, 124 (13.7%) of 903 patients in the group receiving a junction seal acquired bacteriuria, compared with 125 (14.9%) of 837 patients in the control group (P = .52, odds ratio = 0.91, 95% confidence interval, 0.69 to 1.20). Multivariate analysis revealed that only female gender and lack of systemic antibiotic use independently correlated with the development of bacteriuria; neither junction treatment randomization nor disconnection of the junction was associated with bacteriuria. Survival curve analysis of patients stratified by gender and antibiotic use revealed no significant differences in the rate of bacteriuria between treatment groups. The overall mortality in the tape seal group was less than that in the control group (6.6% vs. 8.0%, respectively), but not to a statistically significant extent despite stratification by antibiotic use. CONCLUSIONS: The use of a tape seal applied to the catheter-drainage tubing junction within 24 hours of catheter insertion was not associated with significantly lower rates of bacteriuria and mortality in patients undergoing short-term catheterization.
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BACKGROUND AND METHODS: In patients with the acquired immunodeficiency syndrome (AIDS), the rate of relapse after primary treatment for cryptococcal meningitis remains high. We conducted a controlled, double-blind trial to evaluate the efficacy of maintenance therapy with fluconazole. At entry into the study, all participants had sterile cultures of cerebrospinal fluid, blood, and urine after following a standardized course of therapy for culture-proved cryptococcal meningitis. The patients were randomly assigned to take either fluconazole or placebo as maintenance therapy. The dose of fluconazole was 100 mg daily in the first phase of study and 200 mg daily in the second phase. RESULTS: Of 84 patients initially enrolled, 16 (19 percent) were found to have silent, persistent infection on the basis of cultures that became positive after entry into the study; 7 other patients were lost to follow-up shortly after entry. Of the remaining 61 patients, 10 of 27 assigned to placebo (37 percent) and 1 of 34 assigned to fluconazole (3 percent) had a recurrence of cryptococcal infection at any site (difference in risk, 34 percent; 95 percent confidence interval, 15 to 53). Of the 11 recurrent infections, 7 were detected in urine obtained after prostatic massage. There were four recurrent meningeal infections in the patients taking placebo, but none in those taking fluconazole (mean duration of follow-up, 164 days) (P = 0.03). In multivariate analyses, the best predictors of recurrence-free survival were fluconazole treatment (P = 0.02; relative hazard, 13.2), a lower serum cryptococcal-antigen titer (P = 0.05; relative hazard, 1.2), and more prolonged primary therapy with flucytosine (P = 0.09; relative hazard, 1.1). Survival and toxicity were similar in the two maintenance-treatment groups. CONCLUSIONS: In patients with AIDS, silent persistent infection is common after clinically successful treatment for cryptococcal meningitis. Maintenance therapy with fluconazole is highly effective in preventing recurrent cryptococcal infection.
The simultaneous use of methods to block all three known pathways of bacterial entry into the bladders of catheterized patients has been suggested because of the limited effectiveness of individual methods that block single pathways. We conducted a randomized controlled trial to assess the prevention of bacteriuria in patients, using a three-way system that included a hydrophilic polymer-coated and preconnected sealed catheter system, daily catheter care, and disinfection of the outflow tube of the drainage bag with povidone-iodine (i.e., methods to block bacterial entry at the urethral insertion site, at the catheter drainage tube junction, and at the outflow tube). Among treated patients, 14 (4.7%) of 300 acquired bacteriuria as compared with 15 (4.9%) of 306 who did not receive the protocol treatments. Only 3 of 29 episodes of bacteriuria occurred in patients whose meatal cultures did not contain gram-negative bacilli or enterococci; thus migration of bacteria in the periurethral mucous sheath appeared to be the most common pathway by which bacteria gained entry into the bladder in this study. Catheter care and disinfection of the drainage bag outflow tube as used in this study remain unproven methods of preventing catheter-associated bacteriuria. Preconnected catheters with junction seals were used in both treated and untreated patients and, on the basis of previous studies, appear to be effective in reducing junction disconnections and bacteriuria. Therefore we conclude that the use of several simultaneous measures to prevent catheter-associated urinary infections is no more effective than the use of preconnected catheters with junction seals alone and is clearly more expensive.
OBJECTIVE: To determine the efficacy of meatal treatment with a polyantibiotic cream in the prevention of bacteriuria during transurethral bladder catheterization. DESIGN: Randomized controlled trial. SETTING: Community teaching hospital. PATIENTS: Adult patients who underwent closed urinary catheter drainage for short and intermediate durations (two to 30 days). INTERVENTION: Polyantibiotic cream containing polymyxin B sulfate, neomycin sulfate, and gramicidin was applied to the urethral meatus-catheter interface three times daily from the first day of catheterization until bacteriuria was found. The onset of bacteriuria was defined as the day the colonizing species first achieved a colony count of greater than or equal to 1000 colonies/ml. Patients randomized to the control group received routine meatal care with cleansing of the meatal surface during daily bathing. RESULTS: Among 2,923 patients who were randomly allocated to receive either the protocol meatal care or routine care, the evaluable study population consisted of 747 patients who were nonbacteriuric and who remained catheterized for more than two days. Overall, 26 (6.8%) of 383 patients given the polyantibiotic treatment acquired bacteriuria, as compared to 37 (10.1%) of 364 patients not given this treatment (p = .167). A Cox proportional hazards regression analysis showed that, among putative risk factors including lack of meatal care, only female gender, a meatal swab culture yielding gram-negative rods or enterococci, and lack of antibiotic use during catheterization were independently associated with the development of bacteriuria. CONCLUSIONS: The adverse effect of meatal care noted in earlier studies of a disinfectant ointment applied twice daily was not found in this study of an antimicrobial preparation in a cream vehicle applied three times daily. However, the results do not support meatal care as an efficacious method to prevent catheter-associated bacteriuria in all patients.
OBJECTIVE: To compare the efficacy of fluconazole with amphotericin B plus flucytosine in the treatment of cryptococcal meningitis. DESIGN: Patients were randomly assigned to oral fluconazole, 400 mg/d, for 10 weeks or to amphotericin B, 0.7 mg/kg body weight daily for 1 week, then three times weekly for 9 weeks combined with flucytosine, 150 mg/kg d, in four divided doses. SETTING: Los Angeles County-University of Southern California Medical Center. PATIENTS: Between 15 February and 7 December 1988, 42 patients had evidence of their first episode of cryptococcal meningitis, of whom 21 participated in the trial. All patients enrolled were men with the acquired immunodeficiency syndrome (AIDS) except one woman who was receiving prednisone therapy and was excluded from the final analysis. RESULTS: Of 14 patients with AIDS assigned to fluconazole, 8 (57%; 95% CI, 29% to 82%) failed; none of the 6 patients with AIDS failed who were assigned to amphotericin B plus flucytosine therapy (0%; CI, 0% to 46%) (Fisher exact test, P = 0.04). The mean duration of positive cerebrospinal fluid cultures was 40.6 +/- 5.4 days in patients receiving fluconazole and 15.6 +/- 6.6 days in patients receiving amphotericin B plus flucytosine (Mann-Whitney test, P = 0.02). Overall, 4 patients assigned to fluconazole therapy died whereas no patient assigned to amphotericin B plus flucytosine therapy died (Fisher exact test, P = 0.27). CONCLUSION: Amphotericin B used in combination with flucytosine has superior mycologic and clinical efficacy compared with fluconazole for the treatment of cryptococcal meningitis in patients with AIDS.
Comparative flow microfluorimetric (FMF) analysis was used to identify and characterize 27 monoclonal antibodies (MoAbs) reactive with bovine T-lymphocytes. Determinants present on all circulating T-lymphocytes were recognized by 11 MoAbs, 8 of which blocked E rosette formation. Determinants present on only the BoCD4+ T-lymphocyte subset were detected by 9 MoAbs, while determinants restricted to the BoCD8+ T-lymphocyte subset were recognized by 7 MoAbs. Competitive labeling experiments demonstrated that determinants recognized by subset-specific MoAbs were present on BoCD4 or BoCD8 molecules. Comparative studies revealed that some determinants, both pan-T specific and subset-specific, were conserved on homologous (orthologous) molecules expressed on leukocytes from other species of ruminants. Polymorphism was evident with several determinants.
A 36-year-old Hispanic man came into the emergency department with nonspecific symptoms (headache, myalgias, low-grade temperature, and low white blood cell count) and was diagnosed with brucella meningitis. The patient said he had consumed unpasteurized goat's milk and cheese in Mexico, and had been treated 3 months previously for a febrile illness diagnosed as Malta fever (brucellosis). Cultures of both the blood and cerebrospinal fluid yielded Brucella melitensis. Blood agglutinin results for B abortus were positive at greater than 1:160. Unpasteurized milk and cheese are consumed in many countries where brucellosis is endemic. Emergency physicians are occasionally confronted with patients from developing countries with diseases that require rapid and specific diagnosis for optimal treatment.
The treatment of opportunistic infections in AIDS patients is changing rapidly as new drugs become available and new studies of old drugs are completed. I have tried to use the AIDS commentaries to keep up with these advances. Since fluconazole has just recently been approved by the US Food and Drug Administration, I asked Dr. Robert A. Larsen, an active clinical investigator at the University of Southern California School of Medicine, to review his current recommendations for the use of the azoles in AIDS patients. The response to therapy of the various mycoses in patients with advanced human immunodeficiency virus (HIV) infection is dramatically different from that in other patient populations and has different end points in each group. Cure is uncommon in HIV-infected patients, and relapsing infection when antifungal therapy is stopped is the rule. Control of infection with relief of symptoms and return to productive, high-quality life is therefore a commendable goal and a reasonable end point. Thus, the azoles, especially fluconazole, are important additions. From the data presented here it appears that amphotericin may still have an edge over fluconazole for acute therapy of cryptococcal meningitis in sicker patients, at least for the first several weeks (although fluconazole may be as good and is certainly less toxic and easier to administer for patients who can take oral medications). Whether 5FC should be added when amphotericin is used for acute therapy is still controversial. Dr. Larsen appears to favor it while my group feels that the potentiation of bone marrow toxicity without any clear evidence of enhanced efficacy in AIDS patients argues against its use.(ABSTRACT TRUNCATED AT 250 WORDS)
Serologic testing for complement-fixing antibodies to Coccidioides immitis is commonly employed to assist in the diagnosis and management of this infection, but its usefulness in an HIV-coinfected population is unknown. In this study we reviewed all the mycologically or histologically proven cases of disseminated C. immitis infection after 1982. Disseminated C. immitis and proven HIV infection were present in eight patients. We performed serum complement-fixing antibody titers on all eight patients, six of whom gave positive tests, while two patients (25%) gave repeatedly negative results despite widely disseminated disease. We conclude that histopathology and culture remain the most reliable methods for the diagnosis of disseminated coccidioidomycosis in the HIV-infected host.
We report four cases of acute reversible renal failure in patients with acquired immune deficiency syndrome who received both amphotericin B (for systemic mycoses) and pentamidine isethionate (for Pneumocystis carinii pneumonia). The concurrent use of amphotericin B with either inhaled pentamidine or trimethoprim-sulfamethoxazole did not cause significant renal impairment.
The use of antibiotic prophylaxis for unnecessarily prolonged periods after surgical procedures can contribute to increased health care costs and adverse drug reactions as well as the development of antibiotic-resistant infections. Hospitals are under economic pressures to develop methods to control the excessive use of these drugs. We expanded the capabilities of our hospital information system to monitor the duration of surgical antibiotic prophylaxis. For six months during one year we used the computer system to monitor antibiotics received by every surgical patient and to identify patients receiving antibiotic prophylaxis longer than was deemed necessary according to generally accepted guidelines. For six months in the following year we used the system to monitor and identify the same types of patients and clinical pharmacists placed antibiotic "stop orders" in the charts of the patients identified by the computer. Surgical patients received an average of 19 doses of antibiotics in the first year compared with 13 doses in the second year (p less than 0.001). The average cost of antibiotics received more than 48 hours after the operation was $42 less per patient in year 2 than in year 1, resulting in a potential cost savings of $44,562 in six months. The computer system was found to be an efficient tool for monitoring all antibiotics given to surgical patients and identifying patients receiving antibiotic prophylaxis longer than necessary. Clinical use of this system appears to have resulted in improved usage of antibiotic prophylaxis.
STUDY OBJECTIVE: To assess the frequency of persistent Cryptococcus neoformans infection in patients with the acquired immunodeficiency syndrome (AIDS) after receiving apparently adequate treatment for meningitis. DESIGN: Blood, urine, and cerebrospinal fluid were cultured at the conclusion of primary therapy to assess the adequacy of treatment. SETTING: Outpatient clinics at three medical centers. PATIENTS: Patients had C. neoformans grown in culture from cerebrospinal fluid. Primary therapy consisted of either 2.0 g of amphotericin B alone; 6 weeks of combination therapy with flucytosine; or, if flucytosine was poorly tolerated, an adjusted minimum total amphotericin B dose. To meet criteria for adequate treatment of meningitis all patients had two sequential cerebrospinal fluid samples which were culture negative. MEASUREMENTS AND MAIN RESULTS: Nine of forty-one patients grew C. neoformans from urine after completion of primary treatment, but none had urinary symptoms. Fungi were visualized in expressed prostatic secretions in 4 of these patients. One patient refused further treatment and developed cryptococcemia within 5 weeks. Three patients received additional amphotericin B; all had persistent funguria without systemic relapse. Six patients received fluconazole; 4 became urine culture negative, and 2 had systemic relapse. CONCLUSION: The persistence of urinary C. neoformans after adequate therapy for meningitis suggests that the urinary tract (probably the prostate) is a sequestered reservoir of infection from which systemic relapse may occur.
A prospective study was performed over a two-year period to determine whether computer-generated reminders of perioperative antibiotic use could improve prescribing habits and reduce postoperative wound infections. During the first year, baseline patterns of antibiotic use and postoperative infection rates were established. During the second year, computer-generated reminders regarding perioperative antibiotic use were placed in the patient's medical record prior to surgery and patterns of antibiotic use and postoperative wound infections monitored. Hospitalized patients undergoing non-emergency surgery from June to November 1985 (3,263 patients), and from June to November 1986 (3,568) were monitored with respect to indications for perioperative antibiotic use, timing of antibiotic use and postoperative infectious complications. Perioperative antibiotic use was considered advisable for 1,621 (50%) patients in the 1985 sample and for 1,830 (51%) patients in the 1986 sample. Among these patients, antibiotics were given within two hours before the surgical incision in 638 (40%) of the 1985 sample and 1,070 (58%) of the 1986 sample (p less than 0.001). Overall, postoperative wound infections were detected in 28 (1.8%) of 1,621 patients in 1985 compared with 16 (0.9%) of 1,830 such patients in 1986 (p less than 0.03). We conclude that computer-generated reminders of perioperative antibiotic use improved prescribing habits with a concurrent decline in postoperative wound infections.
The results of a physician-performed prevalence survey of infections and antibiotic use at the Salt Lake City LDS Hospital in 1984 were compared with results of surveys done in 1971 and 1979. The hospital census and length of stay declined in successive surveys, contributing to the changes observed. Community-acquired infections were more prevalent in 1984 than in the previous surveys, whereas hospital-acquired infections were seen with similar frequencies. Among hospital-acquired infections, lower respiratory tract and soft-tissue infections were more prevalent in 1984. Gram-negative bacilli accounted for 34% of hospital-acquired infections in 1984 versus rates of 60% or more found in the 1970s. Although the overall prevalences of antibiotic use were similar in the three surveys, the proportion attributed to cephalosporins increased from 17.5% (1971) to 49.2% (1979) and 59.1% (1984). Antibiotic prophylaxis was less frequent in 1984 (14.4%) than in 1979 (24.1%) and reversed the trend found after 1971 (11.0%). Despite extensive educational efforts since the prevalence survey of 1979, perioperative antibiotics were used for durations longer than 48 hours after surgery in 43% of the patients receiving such prophylaxis in 1984. The LDS Hospital has adopted a restrictive antibiotic formulary in part as a result of the present survey.