Dima Abi-Said

The Epidemiology of Hematogenous Candidiasis Caused by Different Candida Species

The medical records of patients with hematogenous candidiasis at M. D. Anderson Cancer Center (Houston) between 1988 and 1992 were retrospectively reviewed. There were 491 episodes of infection (6 per 1,000 admissions), 79% of which occurred outside the intensive care unit setting. A significant decrease in incidence was observed among patients with leukemia over the study period, together with a relative decrease in Candida albicans and Candida tropicalis infections and an increase in Candida krusei and possibly Candida glabrata infections. In the multivariate analysis, fluconazole prophylaxis provided strong protection against the development of C. tropicalis infection (odds ratio [OR] = 0.08) and C. albicans infection (OR = 0.15), in comparison with protection against infections due to other species, but it was the single most important determinant for the relative increase in C. krusei (OR = 27.07) and C. glabrata (OR = 5.08) infections. In conclusion, there has been a substantial shift in the epidemiology of hematogenous candidiasis caused by different Candida species in recent years. Fluconazole appears to be playing a major role in this observed shift.

Central Venous Catheters Coated with Minocycline and Rifampin for the Prevention of Catheter-Related Colonization and Bloodstream Infections: A Randomized, Double-Blind Trial

See related articles on pp 257-266 and 275-280 and editorial comment on pp 304-306. Central venous catheters are indispensable in the treatment of critically and chronically ill patients, but they are the leading cause of primary nosocomial bloodstream infection [1, 2]. A study of hospitals in the National Nosocomial Infection Surveillance System, conducted between 1986 and 1990, showed that rates of bloodstream infection were substantially higher in patients who were in intensive care units and had intravascular devices than in those who did not have such devices [3]. To decrease the risk for catheter colonization and infection, antiseptic and antibiotic agents have been applied topically at the insertion site [4-6]. More recently, the use of antimicrobial flush solutions has been proposed [7]. However, coating venous catheters with antiseptic or antimicrobial agents may have an even more pronounced protective effect against colonization and infection, particularly if both the external and internal surfaces of the device are coated. Since 1990, several types of antiseptic or antimicrobial vascular catheter coatings have been developed and studied [8, 9]. Maki and colleagues [9] investigated central venous catheters coated with chlorhexidine-silver sulfadiazine; the coated catheters seemed less likely than the uncoated catheters to be associated with bloodstream infections. We recently coated vascular catheters with a combination of minocycline and rifampin after treatment with the tridodecylmethyl-ammonium chloride surfactant. In vitro, these catheters were shown to have broad-spectrum antimicrobial inhibitory activity that was significantly superior to the activity of catheters coated with chlorhexidine-silver sulfadiazine [10, 11]. The catheters coated with minocycline and rifampin were also found to be highly efficacious in preventing catheter colonization and subcutaneous infection in a rabbit model [11]. In a double-blind, randomized clinical trial, we studied the efficacy of catheters that were treated with tridodecylmethyl-ammonium chloride and coated with minocycline and rifampin in preventing catheter colonization and bloodstream infection in hospitalized patients. Methods Study Sample Our study was conducted simultaneously at five university-based hospitals in the Texas Medical Center in Houston: The University of Texas M.D. Anderson Cancer Center (518 beds), Veterans Administration Medical Center (1050 beds), Hermann Hospital (600 beds), Ben Taub General Hospital (580 beds), and The Methodist Hospital (904 beds). The study began on 1 September 1994 and ended on 27 March 1995. Hospitalized patients 18 years of age or older who required a triple-lumen polyurethane central venous catheter at a new insertion site were asked to participate. We excluded pregnant women, patients who were allergic to rifampin or tetracycline, patients with dermatitis or a burn over the insertion site, and patients for whom the anticipated duration of catheterization was less than 3 days. All patients gave informed consent. Randomization All catheters were triple-lumen, polyurethane, 7 French, and 20 cm long (Cook Critical Care, Bloomington, Indiana). The coated catheters were pretreated with tridodecylmethyl-ammonium chloride and then coated, 18 hours later, with minocycline and rifampin. The levels of minocycline and rifampin on the external and internal surfaces of coated catheters before insertion, as determined by high-performance liquid chromatography, were 139.3 g/cm and 13.9 g/cm, respectively. Control catheters were untreated and uncoated. All catheters were gas sterilized and placed in identical trays, and each tray was assigned an identification number. The trays were then randomly assigned into blocks of six: three with coated catheters and three with control catheters. Each block of trays was placed in boxes by Cook Critical Care, and the boxes were shipped to the five hospitals. When a patient was determined to be eligible, a tray was removed from the box (trays were removed one at a time, in sequential order from top to bottom), and that catheter was used for the patient. The catheter identification number was recorded on a data entry form and on the patients medical chart; neither the patient nor the clinician who inserted the device knew which catheter (coated or uncoated) had been used. Catheter Insertion and Care Study catheters were inserted into the subclavian vein, internal jugular vein, or femoral vein of patients who had no other indwelling catheter. Study catheters were not exchanged over guidewires. Maximal sterile barrier precautions were taken, including use of a sterile gown, sterile gloves, full sterile drapes, a mask, and a cap. At the time of catheter insertion and at each dressing change, the insertion site was cleaned with chlorhexidine gluconate (at The Methodist Hospital) or 10% povidone-iodine scrub (at all other hospitals). In each case, the preparation was applied to the skin for 2 minutes before catheter insertion. The insertion site was then covered with sterile gauze and taped securely. The insertion site was inspected every 72 hours (during a dressing change) for evidence of infection, such as erythema, purulence, swelling, or tenderness over the catheter. During follow-up, the following information was obtained for all patients: site of catheter insertion; dates of catheter placement and removal; occurrence of difficulties and violations of aseptic technique during insertion or removal, if any; reason for using the catheter (chemotherapy, total parenteral nutrition, administration of blood products, or a combination of these reasons); type of dressing; and reason for catheter removal. In addition, clinical data were obtained on underlying disease, neutrophil and platelet counts, antibiotic therapy administration, other therapeutic interventions administered during the period of catheterization, and the presence or absence of fever and infection during catheterization. The catheter remained in place until it was no longer needed; until a specific event, such as catheter-related infection, necessitated its removal; or for 28 days, whichever occurred first. Microbiological Methods Quantitative Cultures of Central Venous Catheters The entire catheter was removed aseptically, and 4-cm segments were cut from the catheter tip and the subcutaneous section. These segments were semiquantitatively cultured by using the roll-plate method; the same segment was then quantitatively cultured by using the sonication method [12-14]. Organisms recovered by either method were fully identified according to standard microbiological methods. Coagulase-negative staphylococci were classified as gram-positive cocci in clusters that produced catalase but not coagulase and were categorized according to species by using the Staph-Ident System (Analytab Products, Plainview, New Jersey). All hospitals used the same methods for culture. Skin Cultures To determine whether bacteria became resistant to the antibiotics that coated the study catheters, skin samples obtained from the insertion site were cultured at the time of insertion and within 24 hours after catheter removal, as described elsewhere [15]. Organisms recovered from the insertion site were fully identified by using standard microbiological methods. Antimicrobial Resistance We used the modified Kirby-Bauer technique to test the antimicrobial activity of the catheters coated with minocycline and rifampin against all organisms isolated from indwelling coated catheters at the time of catheter removal [16]. The zones of inhibition against staphylococci cultured from coated catheters were compared with those of uncoated catheters. The minimal inhibitory concentration (MIC) of minocycline hydrochloride (Lederle Laboratories, Pearl River, New York) and rifampin (Ciba-Geigy Corp., Summit, New Jersey) against staphylococcal organisms that colonized the catheter tip, subcutaneous segments, and adjacent skin insertion sites of the coated catheters was determined. A microbroth dilution method was used to determine the MIC in accordance with guidelines established by the National Committee for Clinical Laboratory Standards [17]. Definitions The definitions adopted for our study were proposed by the Centers for Disease Control and Prevention [18]. Colonization of a central venous catheter was defined as 1) the isolation from either the tip or the subcutaneous segment of 15 or more colony-forming units of any organism by the rollplate technique or 2) isolation of more than 1000 colony-forming units of any organism by the sonication technique. Catheter-related bloodstream infection was defined as the isolation of microorganisms from the bloodstream (blood was obtained through venipuncture, not through the catheter) of a patient who had concurrent clinical manifestations of sepsis and no source for the bloodstream infection other than the vascular catheter. In addition, the catheter had to be colonized with the same organism (same species and same antibiogram). To confirm the diagnosis of catheter-related bloodstream infection, DNA molecular typing done using pulse-field gel electrophoresis was performed on organisms that were of the same species, had the same antibiogram, and were isolated from the catheter and blood during the period of catheterization. Patients were considered to have fever if the oral body temperature was greater than 38 C. Neutropenia was defined as a polymorphonuclear count of fewer than 1000 cells/mm3. Thrombocytopenia was defined as a platelet count of fewer than 100 000 cells/mm3. Molecular Typing Molecular typing was performed by using pulse-field gel electrophoresis. Identical organisms with similar DNA profiles that were isolated from a segment of the colonized catheter and from the bloodstream confirmed the diagnosis of catheter-related bloodstream infection. However, a mismatch did not rule out such a diagnosis because catheter coloniza

Sacral chordoma: 40-Year experience at a major cancer center

OBJECTIVE Sacral chordomas are relatively rare, locally invasive, malignant neoplasms. Despite surgical resection, adjuvant radiation therapy, and chemotherapy, recurrence is common. This study reviews our experience during the last 40 years at The University of Texas M.D. Anderson Cancer Center, to determine the effects of various treatment methods on the overall course of this disease process. METHODS A retrospective study was performed. From 1954 to 1994, 27 patients with sacral chordomas were evaluated at our institution. RESULTS There were 19 male and 8 female patients, with a mean age of 56 years (range, 27-80 yr). All except one of the patients presented with pain, and 17 of 27 showed evidence of autonomic dysfunction at initial presentation. Based on microscopic examination of surgical specimen margins, surgical procedures were categorized as either radical resection or subtotal excision. All patients underwent at least one surgical procedure, for a total of 67 procedures (28 radical resections and 39 subtotal excisions). Twelve patients underwent one operation, whereas nine underwent two procedures and six underwent more than two operations (range, 3-16 operations). Radiation therapy was used in conjunction with 13 of the 67 surgical procedures. The median Kaplan-Meier estimate of the overall survival time for the entire group was 7.38 years (range, 4 mo to 34 yr). Tumors recurred after 47 of the 67 procedures. The overall disease-free interval for patients undergoing radical resection was 2.27 years for each procedure, compared with 8 months for each procedure for patients treated with subtotal excision (log-rank test for the inequality between the two curves, 19.58; P<0.0001). The addition of radiation therapy prolonged the disease-free interval for patients undergoing subtotal resection (2.12 yr versus 8 mo; log-rank test for the inequality between the two curves, 5.82; P<0.02). CONCLUSION Our results suggest frequent recurrences in the majority of patients with chordomas. Radical resection is associated with a significantly longer disease-free interval, compared with subtotal removal of the tumor. Addition of radiation after subtotal resection improves the disease-free interval, although radiation therapy can generally be used only once. Based on these findings, we think that, whenever possible, radical resection should be the treatment of choice for sacral chordomas.

Fluconazole versus Amphotericin B in the treatment of Hematogenous Candidiasis: A matched cohort study

PURPOSE To compare the efficacy and toxicity of fluconazole and amphotericin B in the treatment of hematogenous candidiasis in cancer patients. PATIENTS AND METHODS A matched cohort study of cancer patients with hematogenous candidiasis was conducted. Forty-five patients with hematogenous candidiasis who received fluconazole (200 to 600 mg/day) in an open-label trial at the University of Texas M. D. Anderson Cancer Center, Houston, Texas, between February 1990 and June 1992 were matched to 45 patients treated with amphotericin B (0.3 to 1.2 mg/kg/day) for the same diagnosis. Criteria for matching included the following prognostic variables at the initiation of therapy: pneumonia, neutropenia (< 1,000 cells/mm3), number of positive blood cultures before therapy, infecting Candida species, underlying disease, and the simplified acute physiology score. Response and survival at 48 hours, after 5 days of therapy, and at the end of therapy, as well as toxicity rates were obtained. Other post hoc analyses were performed. Differences in outcomes were assessed by the McNemar, the sign, and the log rank tests. RESULTS Patients were similar with respect to the matching criteria, age, sex, status of underlying disease, use of antibiotics and growth factors, duration of treatment, presence and removal of central venous catheters, disseminated disease, and concomitant infections. Response rates at 48 hours and 5 days were similar between the two study groups. Overall response rates at the end of therapy were 73% for patients treated with fluconazole and 71% for patients treated with amphotericin B (P = 0.78). There were no differences in survival rates or causes of death. Toxicity was observed in 9% of patients treated with fluconazole and in 67% of patients treated with amphotericin B (P < 0.0001). Toxic effects of amphotericin B included nephrotoxicity, hypokaliemia, and fever and chills. CONCLUSION Fluconazole is effective and better tolerated than amphotericin B for the treatment of hematogenous candidiasis in cancer patients.

Randomized comparison between antibiotics alone and antibiotics plus granulocyte-macrophage colony-stimulating factor (Escherichia coli-derived) in cancer patients with fever and neutropenia

PURPOSE A prospective, randomized study was conducted to determine if recombinant human granulocyte-macrophage colony-stimulating factor (rh-GMCSF) (Escherichia coli-derived) could improve response rates to antibiotic therapy and shorten the duration of neutropenia in cancer patients. PATIENTS AND METHODS A total of 107 febrile neutropenic cancer patients were randomly assigned to empiric therapy with ticarcillin-clavulanate (4 g ticarcillin + 0.1 g clavulanate i.v. every 4 hours) plus netilmicin (2 mg/kg i.v. every 8 hours) with or without rh-GMCSF (3 micrograms/kg per day i.v.). Clinical improvement, duration of neutropenia, and toxicity were monitored. RESULTS Addition of rh-GMCSF to the antibiotics significantly improved the response rate (96% versus 82%, P = 0.03), but not the survival rate (93% versus 93%), in the evaluable patients. This difference in response rate was not significant when considering all patients in an intent-to-treat analysis. The number of patients who recovered from severe neutropenia ( < 100 cells/microliter) during the period of observation in the study was significantly greater among patients receiving the colony-stimulating factor, although the median duration of neutropenia was not affected. Superinfections and subsequent infections were not significantly different among the two treatment regimens. Side effects were more common among patients treated with the colony-stimulating factor. CONCLUSIONS Our data do not support the routine administration of rh-GMCSF with antibiotics for patients with fever and neutropenia. Further studies should be conducted to identify those patients most likely to benefit from rh-GMCSF therapy, such as patients with persistent profound neutropenia and refractory infections.

Antimicrobial durability and rare ultrastructural colonization of indwelling central catheters coated with minocycline and rifampin.

OBJECTIVE To determine the duration of antimicrobial activity and the efficacy of indwelling catheters coated with minocycline and rifampin in preventing ultrastructural colonization. DESIGN Multicenter, prospective, randomized, clinical trial. SETTING Five university-based medical centers. PATIENTS Cohort 1 consisted of 40 randomized patients in whom an equal number of minocycline- and rifampin-coated and uncoated catheters were inserted and studied using scanning electron microscopy. Cohort 2 consisted of 118 patients who received coated catheters that were tested for the antimicrobial activity and levels of the antibiotics at the time of removal. INTERVENTIONS Catheters pretreated with tridodecylmethylammonium chloride and subsequently coated with minocycline and rifampin; uncoated catheters (control). MEASUREMENTS AND MAIN RESULTS Quantitative scanning electron microscopy was utilized to determine both the ultrastructural colonization in biofilm on coated and uncoated catheters. The zones of inhibition of coated catheters from studied patients against Staphylococcus epidermidis was used to determine the antimicrobial durability. High-performance liquid chromatography was used to determine antibiotic levels on indwelling coated catheters and in serum. Mild-to-heavy ultrastructural colonization was detected in 7 (35%) of 20 coated catheters and in 16 (80%) of 20 uncoated catheters (p = .004). Significant antimicrobial inhibitory activity against S. epidermidis was maintained for 16 days. Rifampin and minocycline continued to be detected on the surfaces of coated catheters for at least 2 wks after placement. Neither antibiotic was detected in the 60 serum samples obtained from 15 patients during catheterization. CONCLUSION Coating catheters with minocycline and rifampin inhibits ultrastructural colonization of indwelling catheters and maintains effective antimicrobial activity for at least 2 wks.

Nosocomial respiratory syncytial virus infections: Prevention and control in bone marrow transplant patients

OBJECTIVE To assess the effectiveness of a multifaceted infection control strategy in limiting the nosocomial transmission of respiratory syncytial virus (RSV) infection to patients in a bone marrow transplant (BMT) unit. DESIGN Before/after trial. SETTING University-affiliated tertiary cancer center. PATIENTS Adult BMT recipients hospitalized during two consecutive wintertime community outbreaks of RSV infection. INTERVENTIONS An infection control strategy against nosocomial RSV infection was implemented in the BMT unit in February 1993. The strategy involved prompt identification, isolation, and cohorting of RSV-infected patients; prompt therapy with aerosolized ribavirin; use of masks and gloves by anyone entering an infected BMT patients room; screening visitors for respiratory symptoms; restricting visitation by all children under 12 years of age and all family members and other visitors with RSV symptoms; and restricting symptomatic hospital staff from working in the BMT unit. RESULTS After implementation of the multifaceted infection-control strategy, there were four cases of nosocomial RSV infection in 3,870 patient days (incidence density, 1.0 case/1,000 patient days) compared with 14 cases of nosocomial RSV infection in 3,152 patient days (incidence density, 4.4 cases/1,000 patient days) during the 1992-1993 RSV season (rate ratio, 4.4; 95% confidence interval [CI95]. 1.4-17.9: P < .01). This decrease in incidence occurred despite a comparable prevalence of community-acquired RSV cases between the two seasons (2.2% vs 3.2% in 1992-1993 and 1993-1994, respectively; prevalence ratio, 0.7; CI95, 0.2-2.1; P = 0.5). CONCLUSION Institution of a multifaceted infection control strategy significantly reduced the frequency of nosocomial RSV infection in a high-risk group of adult BMT recipients.

A prospective crossover randomized trial of novobiocin and rifampin prophylaxis for the prevention of intravascular catheter infections in cancer patients treated with interleukin-2.

The aim of this study was to determine the efficacy of novobiocin and rifampin as oral antibiotic prophylaxis for the prevention of catheter‐related infection in melanoma patients treated with interleukin‐2 (IL‐2) plus interferon‐α and chemotherapy (biochemotherapy).

Infusion therapy team and dressing changes of central venous catheters.

OBJECTIVE To determine whether central venous catheter (CVC) dressing changes could be performed by ward nurses rather than by the infusion therapy team (ITT) nurses without increasing the risk of catheter-related infection. DESIGN Retrospective cohort study using prospectively collected data. The study extended from January 1995 to June 1996. SETTING The University of Texas M.D. Anderson Cancer Center, a referral cancer center. PATIENTS The study group was a random sample of 483 patients who received CVC dressing changes by ward nurses during the study period. A random sample of 483 patients who received CVC dressing changes by the ITT constituted the control group. RESULTS The risks of catheter-related septicemia were 1.7% among cases and 1.4% among controls (risk ratio, 1.14; 95% confidence interval [CI95], 0.26-6.42; P=.70). There also were no significant differences between the two groups in the risks of catheter-related site infection (risk ratio, 0.50; CI95, 0.02-4.12; P=.25) or any catheter-related infection (risk ratio=1.00; CI95, 0.27-3.64; P=.59). CONCLUSIONS Provided that aseptic techniques (including maximal barrier precautions during insertion) are maintained, the responsibility of CVC dressing changes could be delegated to the ward nurses without increasing the low risk of CVC-related infection, resulting in an estimated cost saving in excess of

A comparison of aztreonam plus vancomycin and imipenem plus vancomycin as initial therapy for febrile neutropenic cancer patients

90,000 per year.