Biomedical subjects
Publications and source records attributed to I I Raad.
The significance of blood cultures positive for Aspergillus species for patients with cancer remains unclear. The significance of aspergillemia in 36 cancer patients over a 10-year period was evaluated. True aspergillemia was rare, occurred late in the course of aspergillosis, and was seen exclusively in patients with hematologic malignancies.
Nocardia bacteremia is very rare. We report 2 cases of central venous catheter-associated Nocardia bacteremia and review the literature. The limited clinical experience suggests that discontinuing the catheter and embarking on a relatively short course of appropriate antibiotics results in a good outcome.
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.
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.
The occurrence of surgical wound infections and/or bacteremia associated with central venous catheter use are of growing concern to all physicians who treat critically ill patients. The physician must be aware that some patients have an even greater risk for infection, such as those with multiple risk factors, those who are on central lines, or those patients who undergo multiple invasive diagnostic or therapeutic procedures. The emergence of resistant pathogens, particularly Gram-positive pathogens, is an important factor in the morbidity and mortality of hospitalized patients. In the face of this growing resistance among target organisms, the selection of the correct antimicrobial and nonpharmacologic interventions, based on correct identification and susceptibility test data, has become increasingly challenging. Methicillin-resistant Staphylococcus aureus and, more recently, glycopeptide-resistant enterococci and staphylococci represent a significant danger to the patient. As a consequence, earlier and more precise identification of the pathogens most frequently associated with infection is essential. The role of exacting surgical technique, infection control measures, and the appropriate use of prophylactic and therapeutic antibiotics cannot be overestimated in helping to reduce potential morbidity and mortality associated with severe surgical infection. The development of new antibiotics may help treat the difficult cases attributable to resistant Gram-positive bacteria.
BACKGROUND: Discrepancies between the severity of toxicities reported in early clinical trials and recent clinical experience with vancomycin have led to confusion regarding the need for routine serum vancomycin level monitoring and discontinuation of vancomycin when toxicities occur. Therefore, the authors examined the incidence, outcomes, and predictive factors of vancomycin-associated toxicities in general oncology practice with the goal of developing clinically relevant prediction rules and guidelines. METHODS: All 742 consecutive cancer patients who received vancomycin at a comprehensive cancer center during a 3-month period were followed prospectively for the development and outcome of phlebitis, rash, ototoxicity, and nephrotoxicity. Logistic regression was used to derive a multiple variable model of the risk of nephrotoxicity. A clinical prediction rule, the Nephrotoxicity Risk Score, was developed from the risk model and validated prospectively. RESULTS: Phlebitis occurred in 3% of patients (95% confidence interval [95% CI], 2-4%), predominantly those with recently inserted central venous catheters. Rashes occurred in 11% of patients (95% CI, 9-13%); however, all but 4 patients also were receiving beta-lactam antibiotics. Clinical evidence of ototoxicity developed in 6% of patients (95% CI, 4-9%) who were receiving vancomycin plus other ototoxic agents and only 3% of patients (95% CI, 2-5%) not receiving other ototoxic agents (P = 0.08). Nephrotoxicity occurred in 17% of patients (95% CI, 15-20%). Logistic regression revealed that factors associated with an increased risk of nephrotoxicity included administration of other mild to moderate (P = 0.01) or severely nephrotoxic agents (P < 0.001) or an acute physiology and chronic health evaluation (APACHE) score > 40 (P = 0.002). Elevated serum vancomycin peak levels did not reliably predict subsequent nephrotoxicity. CONCLUSIONS: Vancomycin-associated toxicities usually are mild and self-limiting. Some patients are at a significantly higher risk of nephrotoxicity but the authors believe these individuals can be identified reliably with the Nephrotoxicity Risk Index using information available at vancomycin initiation. Further testing of the Nephrotoxicity Risk Index is ongoing.
BACKGROUND: Imipenem-cilastatin (referred to hereafter as imipenem) is administered at different doses as monotherapy or with other agents. Limited comparisons of the alternatives exist. The authors compared the efficacy and safety of several imipenem-containing regimens (ICRs) to determine the appropriate dose and the need for combination therapy. METHODS: Between 1985 and 1994, febrile neutropenic patients were given ICRs according to the same methodology on prospective trials at a referral cancer center. The ICRs were high dose imipenem (HIP), high dose imipenem and amikacin (HIPA), high dose imipenem and vancomycin (HIPV), and low dose imipenem and vancomycin (LIPV). RESULTS: The overall response rates were comparable (70-77%). There was a univariate trend toward better response among patients with pneumonia and documented infections with unidentified organisms who received HIPV versus LIPV (P=0.06), as well as a significantly better response among patients with gram positive infections who received HIPV versus HIP (P=0.02) and HIPA (P=0.002). HIPV was a more effective treatment for documented infections with identified organisms (P=0.05) and bloodstream infections (P=0.04) than HIP; there was a univariate trend toward better response among patients infected with gram negative organisms who received HIPA versus HIP (P=0.12). Multivariate adjustment for baseline and prognostic factors did not reveal a relative advantage for any regimen. No differences in overall toxicities were observed between HIPV and LIPV. CONCLUSIONS: Imipenem monotherapy is adequate treatment for most febrile neutropenic cancer patients. Low dose imipenem could be effective and safe in uncomplicated cases without pneumonia. Further studies are needed to establish the usefulness of low dose imipenem in this context.
BACKGROUND: 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-alpha and chemotherapy (biochemotherapy). METHODS: Patients with advanced melanoma who were treated with biochemotherapy at the University of Texas M. D. Anderson Cancer Center were randomized in a crossover study to receive either oral antibiotic prophylaxis consisting of novobiocin and rifampin or observation alone over a 35-day course period. Patients were subsequently "crossed over" to the opposite arm of the study for an additional 35-day period, with each serving as his or her own control. RESULTS: Twenty-six patients were enrolled. Nine patients (35%) failed to tolerate oral antibiotics because of severe nausea and vomiting; 17 patients (65%) were crossed over and considered evaluable. During the control patient courses, 71% of evaluable patients had infectious complications, 41% had a catheter-associated bacteremia, and 53% had a local catheter infection. In contrast, of the patients treated with antibiotic prophylaxis, only 12% had an infectious complication (P = 0.001), 12% had a local catheter infection (P = 0.008), and 6% had catheter-associated bacteremias (P = 0.04). Thirty-six episodes of catheter infections occurred during the 17 control courses, whereas only 3 episodes occurred during antibiotic prophylaxis (P < 0.001). CONCLUSIONS: Although more than one-third of patients receiving IL-2 treatment with biochemotherapy failed to tolerate novobiocin and rifampin, this oral antibiotic regimen was efficacious in preventing the infectious complications, especially those associated with vascular catheters, in this high risk patient population.
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.
BACKGROUND AND AIMS OF THE STUDY: Antimicrobial coating of medical devices has recently emerged as a potentially effective method for preventing device-related infections. The objective of this animal study was to examine in vivo the antimicrobial efficacy of prosthetic heart valve sewing ring fabric coated with: (i) silver; (ii) combined minocycline and rifampin (M/R); or (iii) combined chlorhexidine and chloroxylenol (CH/CX). METHODS: A rabbit model of Staphylococcus aureus colonization and infection of subcutaneously implanted fabric of prosthetic heart valve sewing rings was used. Following administration of anesthesia and preoperative antibiotic prophylaxis, 0.5 x 0.5 cm samples of fabric were placed subcutaneously into the back of rabbits. Each rabbit received a total of eight samples: (i) two uncoated; (ii) two silver-coated; (iii) two M/R-coated; and (iv) two CH/CX-coated. After injecting a bacterial inoculum of 2 x 10(5) c.f.u. of S. aureus onto each implanted sample, the wounds were sutured. Rabbits were monitored daily for one week, killed and the test fabrics removed and cultured. RESULTS: Rates of device colonization, device-related infection and device-related abscess were similar between the uncoated and silver-coated devices. Devices coated with M/R were less likely to be colonized or cause device-related infection when compared with uncoated devices, and less likely to be associated with abscess formation than silver-coated devices. There was a tendency for CH/CX-coated devices to be less colonized than uncoated devices. Only M/R-coated and CH/CX-coated devices produced zones of inhibition in vitro. Implantation of M/R-coated and CH/CX-coated devices in rabbits did not result in detectable systemic concentrations of the antimicrobial coating agents. Colonization of antimicrobial-coated devices was not associated with resistant S. aureus isolates. CONCLUSIONS: These results suggest that silver-coated sewing rings may not prove to be clinically anti-infective. In contrast, antimicrobial-coated sewing rings that produce effective zones of inhibition, particularly those coated with M/R, are likely to be clinically protective.
Although intravascular devices have become indispensable tools in the care of seriously ill patients, the morbidity and mortality resulting from catheter-related infections and the high cost of managing such complications may offset the benefits derived from these devices. A scientific understanding of the pathogenesis, microbiology, and risk factors involved in catheter-related infection is the cornerstone of any effective preventive approach. Prevention of vascular catheter-related infection mostly centers around inhibiting the adherence to the catheter of microorganisms originating from either the skin or the catheter hub. Two general approaches can be used nonexclusively for successful prevention of vascular catheter-related infection. The first approach does not use antimicrobial agents and includes measures such as placement and maintenance of vascular catheters by a skilled infusion therapy team and use of maximal sterile barriers. The second approach uses antimicrobial agents and involves the application of topical disinfectants such as chlorhexidine, use of silver-impregnated subcutaneous cuffs (for short-term central venous catheters), flushing catheters with a combination of antimicrobial and antithrombotic agents, and coating of catheters with either antiseptic (chlorhexidine and silver sulfadiazine) or antimicrobial agents (minocycline and rifampin).
Most cases of catheter-related urinary tract infection are probably caused by organisms that migrate from the urethral meatus-catheter interface along the external surface of the catheter into the bladder. To examine the ability of bladder catheters coated with minocycline and rifampin to inhibit bacterial migration along the external surface of the catheter, a novel in vitro bladder model was used. Compared with uncoated catheters, antimicrobial-coated bladder catheters significantly impeded the migration of Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Enterococcus faecalis, and Candida albicans (bacteriuria developed at a mean of 2-5 days vs. 9-34 days, respectively, after bacterial contamination of the catheter). Although production of zones of inhibition by coated catheters may provide some protection against infection, there was no correlation between the size of zones of inhibition and level of efficacy in inhibiting bacterial migration in vitro. Examination of the clinical efficacy of these antimicrobial-coated bladder catheters is prudent.
In a recent clinical trial, 248 triple-lumen catheters were removed from patients in an intensive care unit, and their tip and subcutaneous segments were cultured by both the sonication and roll plate methods; for 191 of these catheters, flush cultures of all three catheter lumens were also performed. Previously published quantitative endpoints were used to define significant catheter colonization. By using a composite index as a definition of colonization (any of the seven types of cultures meeting quantitative criteria), sonication of the subcutaneous segment was the most sensitive at detecting colonization (58%), followed by sonication of the catheter tip (53%). Sonication of both the subcutaneous and tip segments was 20% more sensitive than sonication of an adjacent catheter segment by the roll plate method (P < 0.05). The greater sensitivity of the sonication method could be attributed to its greater ability than the roll plate method to detect catheter lumen colonization (82 versus 57%, respectively; P = 0.01). A greater number of positive catheter segment cultures were found for colonized catheters from patients with associated bacteremia than for colonized catheters from patients without bacteremia (57 versus 37%; P = 0.004), making any culture method more likely to identify them. For catheters with significant colonization of only one site, the localization was as follows: 36.7% subcutaneous segment, 36.7% catheter lumen, and 26.6% tip segment. These findings suggest that the current practice of culturing a single segment of a central vascular catheter is inadequate and needs to be reexamined. They further suggest that initial colonization of the catheter lumen and tip segments may be more important than previously thought and may require a change in thinking of strategies designed to prevent catheter infection.
BACKGROUND: The improved efficacy of imipenem over other beta-lactam antibiotics in the treatment of febrile neutropenic patients has been attributed to its broad spectrum of activity. METHODS: A prospective, randomized, clinical trial was performed comparing vancomycin 1 g every 12 hours plus imipenem/cilassatin 500 mg every 6 hours and the same dose of vancomycin plus aztreonam 2 g every 6 hours for empiric treatment of febrile episodes in neutropenic patients with cancer. RESULTS: The imipenem regimen cured 76% of the 148 evaluable episodes compared with a 67% cure rate for the 152 episodes treated with the aztreonam regimen (p = 0.1). Most of the polymicrobial infections (77% or 10/13) treated with the imipenem responded, whereas only 38% (5/13) of these infections responded to the aztreonam regimen. Although the cost of the imipenem regimen was less than the cost of the aztreonam regimen, it was associated significantly more with skin rashes (12/194 vs 3/189, p = 0.02). In a multivariate analysis, a poor outcome was independently associated in both instances with the persistence of neutropenia and the presence of pneumonia (p < 0.001). CONCLUSIONS: Overall, in a multifactorial analysis that included efficacy, toxicity, and cost, the imipenem and aztreonam regimens were comparable.
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.
In a randomized, double-blind trial, gamma radiation-sterilized, chlorhexidine-coated triple-lumen catheters were compared with uncoated control catheters for their ability to prevent catheter infection in 254 intensive care unit patients. The chlorhexidine coating was not efficacious, and a rabbit model demonstrated that reduction of chlorhexidine activity by gamma radiation sterilization was the likely explanation for the failure.
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The results of quantitative skin cultures have been proposed as predictors of central venous catheter infection. We prospectively observed 132 patients for 3 months after catheter insertion. Specimens were obtained from all patients for routine surveillance quantitative skin cultures. Targeted quantitative skin cultures and quantitative catheter cultures were done at the time of removal of the central venous catheter. At a positivity level of > or = 10(3) colony-forming units per 24-cm2 area of skin around the insertion site, the surveillance and targeted quantitative skin cultures had specificities and negative predictive values that exceeded 90%. However, they had sensitivities of 18% and 75%, respectively, and they had positive predictive values of 25% and 100%, respectively. Unlike surveillance quantitative skin cultures, targeted quantitative skin cultures that are done when catheter infection is suspected are highly sensitive, specific, and predictive.