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Biomedical subjects

Issam Raad

Publications and source records attributed to Issam Raad.

At least 37 records · Page 2Linked to original sources

Intravenous itraconazole for prophylaxis of systemic fungal infections in patients with acute myelogenous leukemia and high-risk myelodysplastic syndrome undergoing induction chemotherapy.

BACKGROUND: Systemic fungal infections remain the leading cause of mortality in patients with newly diagnosed acute myelogenous leukemia (AML) and high-risk myelodysplastic syndrome (MDS). The objective of the current study was to determine whether intravenous itraconazole (i.v. ITRA) reduced the incidence of probable/proven fungal infections in this group of patients, and compare the results with those of a historic control group treated with fluconazole plus itraconazole capsules (F+I). METHODS: Patients with AML and high-risk MDS who underwent induction chemotherapy received 200 mg of i.v. itraconazole over 60 minutes every 12 hours during the first 2 days followed by 200 mg given i.v. once daily. RESULTS: One hundred patients were enrolled, 96 of whom were evaluable. Approximately 48% of the patients in the group of patients treated with i.v. ITRA as well as in the F+I group completed prophylaxis. Nine patients (9%) in the study group developed either proven/probable fungal infections (Candida glabrata in 5 patients, C. tropicalis in 1 patient, C krusei in 1 patient, and Fusarium in 2 patients) compared with 3 patients (4%) with proven fungal infection in the historic control group (C. tropicalis in 1 patient and Aspergillus in 2 patients). There were no significant differences noted between the two groups with regard to the percentage of patients who developed proven/probable or possible fungal infection as well as with regard to survival. These results also were obtained after adjusting for relevant prognostic factors (creatinine and bilirubin). The most common toxicity encountered with the use of i.v. ITRA was NCI Grade 3-4 hyperbilirubinemia (6%). CONCLUSIONS: Despite its theoretic advantages, the authors found no evidence that i.v. ITRA is superior to itraconazole capsules, at least when the latter is combined with fluconazole.

Adult↗

Differential time to positivity: a useful method for diagnosing catheter-related bloodstream infections.

BACKGROUND: Catheter-related bloodstream infections are associated with recognized morbidity and mortality, especially in critically ill patients. Accurate diagnosis of such infections results in proper management of patients and in reducing unnecessary removal of catheters. OBJECTIVE: To evaluate differential time to positivity as a method for diagnosing catheter-related bacteremias caused by both short-term and long-term use of central venous catheters. DESIGN: Prospective study design. SETTING: M.D. Anderson Cancer Center, Houston, Texas, a tertiary care cancer center. PATIENTS: All patients, between September 1999 and November 2000, who had the same organism isolated from blood cultures drawn simultaneously through the central venous catheter and the peripheral vein. MEASUREMENTS: Time necessary for the blood cultures from the central venous catheter and the peripheral vein to become positive, as well as other relevant patient information. RESULTS: 191 bloodstream infections with positive simultaneous central venous catheter and peripheral vein blood cultures were included. One hundred eight patients had catheter-related bacteremias, and 83 had non-catheter-related bacteremias. Catheter-related bacteremias were more frequently caused by staphylococci and less likely to be associated with underlying hematologic malignant conditions, neutropenia, and longer duration of hospitalization. As a diagnostic tool for catheter-related bacteremia (using a composite definition reference standard according to the Infectious Diseases Society of America guidelines), differential time to positivity of 120 minutes or more was associated with 81% sensitivity and 92% specificity for short-term catheters and 93% sensitivity and 75% specificity for long-term catheters. CONCLUSION: Differential time to positivity of 120 minutes or more is highly sensitive and specific for catheter-related bacteremia in patients who have short- and long-term catheters.

Bacteremia↗

Differential quantitative blood cultures for the diagnosis of catheter-related bloodstream infections associated with short- and long-term catheters: a prospective study.

We prospectively evaluated the value of two levels of differential quantitative blood culture (DQBC) ratio (> or =2:1 or > or =5:1) in diagnosing catheter-related bloodstream infections (CRBSIs) in patients with malignancy that have short-term and long-term central venous catheters (CVCs) (<30 and > or =30 days of placement). Diagnosis of CRBSIs was based on results of semiquantitative cultures of removed catheters. For short-term CVCs a 5:1 or greater DQBC ratio had an 18% sensitivity, 67% specificity, 18% positive predictive value (PPV) and 67% negative predictive value (NPV), whereas a 2:1 or greater cut-off point for the DQBC was associated with a 45% sensitivity, 48% specificity, 26% PPV, and 68% NPV for the diagnosis of CRBSIs. For long-term CVCs, a cut-off point of 5:1 or greater of the DQBC had an 81% sensitivity, 40% specificity, 36% PPV, and 83% NPV for the diagnosis of CRBSIa, whereas a 2:1 or greater cut-off point had a 90% sensitivity, 30% specificity, 35% PPV, and 88% NPV for the diagnosis of CRBSIs. In conclusion, DQBCs are not diagnostic of CRBSIs for short-term CVCs. In long-term CVCs, DQBCs at 2:1 or greater or 5:1 or greater are sensitive but associated with low specificity and positive predictive value.

Adult↗

Impact of surveillance for vancomycin-resistant enterococci on controlling a bloodstream outbreak among patients with hematologic malignancy.

OBJECTIVE: To determine the impact of stool surveillance cultures of critically ill patients on controlling vancomycin-resistant enterococci (VRE) outbreak bacteremia. DESIGN: Stool surveillance cultures were performed on patients who had hematologic malignancy or were critically ill at the time of hospital admission to identify those colonized with VRE. Hence, contact isolation was initiated. SETTING: A tertiary-care cancer center with a high prevalence of VRE. PARTICIPANTS: All patients with hematologic malignancy who were admitted to the hospital as well as all of those admitted to the intensive care unit were eligible. RESULTS: Active stool surveillance cultures performed between 1997 and 2001 decreased the incidence density of VRE bacteremias eightfold while vancomycin use remained constant. In fiscal year (FY) 1997 and FY 1998, there were five and three VRE outbreak bacteremias, respectively. The outbreak clones were responsible for infection in 69% of those patients with VRE bacteremia. However, the stool surveillance program resulted in the complete control of VRE bacteremia by FY 1999 until the end of the study. CONCLUSION: Despite the steady use of vancomycin, the active surveillance program among high-risk patients with hematologic malignancy and those who were critically ill resulted in the complete control of VRE outbreak bacteremia at our institution.

Bacteremia↗

Central venous catheter-related bacteremia due to gram-negative bacilli: significance of catheter removal in preventing relapse.

OBJECTIVE: To study the characteristics of catheter-related, gram-negative bacteremia (GNB) and the role of central venous catheter (CVC) removal. DESIGN: This retrospective study involved a search of the microbiological department records of CVC and blood cultures and patients' medical records. SETTING: University of Texas M. D. Anderson Cancer Center, a tertiary-care hospital in Houston, Texas. PATIENTS: Patients with cancer who had catheter-related GNB, defined as (1) a positive catheter tip culture with at least 15 colony-forming units semiquantitatively, (2) isolation of the same organism from the tip and peripheral blood cultures, (3) no other source for bacteremia except the CVC, and (4) clinical manifestations of infection (fever or chills). RESULTS: Between January 1990 and December 1996, 72 cases of catheter-related GNB were available for review. Most of the patients (67; 93%) had their CVCs removed in response to the bacteremia. Few patients (5; 7%) retained their CVCs and were treated with appropriate antibiotics. When CVCs were removed, only 1 patient (1%) relapsed with the same organism, whereas all 5 patients with retained CVCs relapsed after having responded (P < .001). The most commonly isolated organisms were Enterobacter, Klebsiella, Stenotrophomonas, Pseudomonas, and Acinetobacter species. Catheter removal within 72 hours of the onset of the catheter-related GNB was the only independent protective factor against relapse of the infection (odds ratio, 0.13; 95% confidence interval, 0.02-0.75; P = .02). CONCLUSION: In patients with documented catheter-related GNB, CVCs should be removed within 48 to 72 hours to prevent relapse.

Anti-Bacterial Agents↗

Antibiotic-coated hemodialysis catheters for the prevention of vascular catheter-related infections: a prospective, randomized study.

PURPOSE: To determine the efficacy of minocycline-rifampin-coated hemodialysis catheters in reducing catheter-related infections in patients requiring hemodialysis for acute renal failure. METHODS: Between May 2000 and March 2002, 66 patients were randomly assigned to receive a minocycline-rifampin-impregnated central venous catheter and 64 were randomly assigned to receive an unimpregnated catheter. Patients were followed prospectively until the catheter was removed. Catheter-related infection was determined through quantitative catheter cultures, quantitative blood cultures, or both. RESULTS: Both groups of patients were similar in age, sex, underlying disease, type of dialysis (continuous vs. intermittent), neutropenia during catheterization and its duration, catheter insertion difficulties, and administration of blood products or medication. The mean (+/- SD) catheter dwell time was the same in both groups (8 +/- 6 days, P = 0.7). There were seven catheter-related infections (11%), all associated with the use of unimpregnated catheters. Kaplan-Meier estimates for the risk of catheter-related infection showed that coated catheters were less likely to be associated with infection (P = 0.006). CONCLUSION: The use of polyurethane hemodialysis catheters impregnated with minocycline and rifampin decreases the risk of catheter-related infection in patients with acute renal failure.

Acute Kidney Injury↗

Myelosuppression and serotonin syndrome associated with concurrent use of linezolid and selective serotonin reuptake inhibitors in bone marrow transplant recipients.

We report 2 cases of serotonin syndrome and myelosuppression in bone marrow transplant recipients who received linezolid in combination with a selective serotonin reuptake inhibitor (SSRI). Given the risks to patients in this high-risk group, we recommend that this combination of medications be avoided if alternative antibiotic therapy is possible. If no alternative therapy is possible, prescribers should discontinue SSRI therapy and monitor these patients closely for evidence of serotonin syndrome or the development of hematological toxicity.

Acetamides↗

Liposomal amphotericin B versus the combination of fluconazole and itraconazole as prophylaxis for invasive fungal infections during induction chemotherapy for patients with acute myelogenous leukemia and myelodysplastic syndrome.

BACKGROUND: Fungal infections are a major cause of morbidity and mortality in patients undergoing induction chemotherapy for acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS). The authors evaluated the efficacy and toxicity of liposomal amphotericin B (L-AmB) compared with a combination of fluconazole plus itraconazole (F+I) as prophylaxis in this setting. METHODS: Patients with newly diagnosed AML or high-risk MDS who were undergoing initial induction chemotherapy were randomized to receive either F+I (fluconazole 200 mg orally every 12 hours plus itraconazole tablets 200 mg orally every 12 hours) or L-AmB (3 mg/kg intravenously 3 times per week) in this prospective, open-label study. RESULTS: Seventy-two L-AmB-treated patients and 67 F+I-treated patients were enrolled in the study. Of these, 47% of patients completed antifungal prophylaxis without a change in therapy for proven or suspected fungal infection. Three patients in each arm developed a proven fungal infection. Twenty-three percent of the L-AmB-treated patients and 24% of the F+I-treated patients were changed to alternative antifungal therapy because of persistent fever (P value not significant). Nine percent of the L-AmB-treated patients developed pneumonia of unknown etiology compared with 16% of the F+I-treated patients (P value not significant). Increases in serum creatinine levels to > 2 mg/dL (20% for the L-AmB arm vs. 6% for the F+I arm; P = 0.012) and increases in serum bilirubin levels to > 2 mg/dL (43% vs. 22%, respectively; P = 0.021) were more common with L-AmB. Infusion-related reactions were noted in five L-AmB-treated patients. Responses to chemotherapy and induction mortality rates were similar for the two arms. CONCLUSIONS: L-AmB and F+I appear similar in their efficacy as antifungal prophylaxis during induction chemotherapy for patients with AML and MDS. L-AmB was associated with higher rates of increased serum bilirubin and creatinine levels.

Adult↗

Clinical experience with minocycline and rifampin-impregnated central venous catheters in bone marrow transplantation recipients: efficacy and low risk of developing staphylococcal resistance.

In this retrospective evaluation of the 4-year clinical use of minocycline and rifampin-impregnated catheters in bone marrow transplantation (BMT) patients, we report low risk of development of staphylococcal resistance to the antibiotics coating the catheters and efficacy in preventing primary staphylococcal bloodstream infections.

Adult↗

Fungal sinusitis in the immunocompetent patient: risk factors and surgical management.

BACKGROUND: Fungal sinusitis has been reported increasingly in immunocompetent patients. However, the most effective, appropriate mode of therapy has not been determined. MATERIALS AND METHODS: In this retrospective study, we examined the records of 110 immunocompetent patients with chronic sinusitis who had undergone sinus surgery at our institution between 1983 and 1994. Five patients (4.5%) with fungal sinusitis were identified. Information on those patients was compared with that of the 105 patients with nonfungal sinusitis. RESULTS: Prolonged use of topical steroids was no more common in patients with fungal sinusitis (20%) than it was in patients with nonfungal sinusitis (4.8%) (p = 0.25). Differentiating features of fungal sinusitis were the presence of a metallic density and areas of high- and low-density on radiologic examination (p < 0.01). All five of the patients with fungal sinusitis were cured by surgical intervention, primarily endoscopic sinus surgery, without undergoing anti-mycotic therapy. Four of the five patients were followed up for at least 3 years without any recurrence. CONCLUSION: Endoscopic sinus surgery is and should remain the mainstay of treatment for fungal sinusitis in immunocompetent patients. Adjunctive anti-mycotic therapy may not be necessary.

Adult↗

In vitro and ex vivo activities of minocycline and EDTA against microorganisms embedded in biofilm on catheter surfaces.

Minocycline-EDTA (M-EDTA) flush solution has been shown to prevent catheter-related infection and colonization in a rabbit model and in hemodialysis patients. We undertook this study in order to determine the activities of M-EDTA against organisms embedded in fresh biofilm (in vitro) and mature biofilm (ex vivo). For the experiment with the in vitro model, a modified Robbin's device (MRD) was used whereby 25 catheter segments were flushed for 18 h with 10(6) CFU of biofilm-producing Staphylococcus epidermidis, Staphylococcus aureus, and Candida albicans per ml. Subsequently, each of the catheter segments was incubated in one of the following solutions: (i) streptokinase, (ii) heparin, (iii) broth alone, (iv) vancomycin, (v) vancomycin-heparin, (vi) EDTA, (vii) minocycline (high-dose alternating with low-dose), or (viii) M-EDTA (low-dose minocycline alternating with high-dose minocycline were used to study the additive and synergistic activities of M-EDTA). All segments were cultured quantitatively by scrape sonication. For the experiment with the ex vivo model, 54 catheter tip segments removed from patients and colonized with bacterial organisms by roll plate were longitudinally cut into two equal segments and exposed to either saline, heparin, EDTA, or M-EDTA (with high-dose minocycline). Subsequently, all segments were examined by confocal laser electron microscopy. In the in vitro MRD model, M-EDTA (with a low concentration of minocycline) was significantly more effective than any other agent in reducing colonization of S. epidermidis, S. aureus, and C. albicans (P < 0.01). M-EDTA (with a high concentration of minocycline) eradicated all staphylococcal and C. albicans organisms embedded in the biofilm. In the ex vivo model, M-EDTA (with a high concentration of minocycline) reduced bacterial colonization more frequently than EDTA or heparin (P < 0.01). We concluded that M-EDTA is highly active in eradicating microorganisms embedded in fresh and mature biofilm adhering to catheter surfaces.

Anti-Bacterial Agents↗

Development of Varicella-Zoster virus infection in patients with chronic myelogenous leukemia treated with imatinib mesylate.

PURPOSE: Infection with Varicella-Zoster virus (VZV) is an exceptionally rare complication of chronic myelogenous leukemia (CML) without stem cell transplantation. We report 16 patients with CML who developed VZV infection during imatinib mesylate therapy. PATIENTS AND METHODS: From July 1998 until February 2002, 771 patients were included in 11 imatinib mesylate studies for all CML phases in the Departments of Leukemia and Bioimmunotherapy at The University of Texas M. D. Anderson Cancer Center. Sixteen patients developed VZV infection. Charts and follow-up information of were reviewed and analyzed. RESULTS: Sixteen patients (2%) developed a VZV infection [15 episodes of herpes zoster (HZ), 1 varicella]. The baseline characteristics of the 16 patients with infection do not differ significantly from those who did not develop VZV infection, except for time from diagnosis of CML to imatinib (median: 55 versus 25 months, P = 0.0056) and the number of prior therapies (3 versus 1, P < 0.001). All patients received therapy with antiviral agents with good response. Six patients developed postherpetic neuralgia. CONCLUSIONS: Our results suggest that imatinib therapy in CML is associated with low incidence of HZ infection. VZV infection is more frequent with longer duration of CML disease and with prior therapy, does not disseminate, responds well to therapy, and does not mandate a recommendation for HZ prophylaxis in such patients.

Adolescent↗

Minocycline-ethylenediaminetetraacetate lock solution for the prevention of implantable port infections in children with cancer.

In this prospective cohort study, minocycline-ethylenediaminetetraacetate (M-EDTA) was used as a lock solution in indwelling ports inserted in 14 children with cancer. No port infections, thrombotic events, or other adverse events were observed, compared with 10 port infections that occurred in 48 control patients whose ports were flushed with heparin. M-EDTA is a promising lock solution in long-term catheters.

Anti-Bacterial Agents↗

Polymerase chain reaction on blood for the diagnosis of invasive pulmonary aspergillosis in cancer patients.

BACKGROUND: The premortem diagnosis of invasive pulmonary aspergillosis (IPA) is difficult to make and often missed. Several retrospective studies have suggested that Aspergillus polymerase chain reaction (PCR) performed on serum or whole blood is useful in diagnosing IPA. Two prospective studies confirmed this finding but included a small number of IPA cases. METHODS: The current study was performed to determine the diagnostic role of Aspergillus PCR performed on whole blood specimens from 54 patients with cancer and pulmonary infiltrates for which bronchoscopy with fungal stains and cultures were performed. PCR through amplified Aspergillus mitochondrial DNA and alkaline protease genes was performed on whole blood samples. RESULTS: The cohort in the current study was comprised of 4 patients with definite IPA, 7 patients with probable IPA, 7 patients with possible IPA, and 36 control patients with no evidence of IPA. The sensitivity, specificity, and positive and negative predictive values all were 100% for definite IPA cases and 57%, 100%, 100%, and 92%, respectively, for each of the probable and possible IPA cases. CONCLUSIONS: Aspergillus PCR on whole blood samples is highly sensitive for the detection of IPA and is predictive for IPA. The sensitivity appears to be correlated with the certainty of diagnosis as proven by tissue invasion.

Adolescent↗

Skin lesions associated with Fusarium infection.

Infections caused by Fusarium species are increasing in frequency among immunocompromised hosts. We identified 35 patients with cancer who had Fusarium skin lesions. Twenty patients had disseminated infection, 6 had primary localized skin infections, 4 had skin lesions associated with sinus infections, and 5 had onychomycosis. All patients (except 3 with onychomycosis) had hematologic malignancies and neutropenia. Skin lesions associated with disseminated infection included red or gray macules, papules (some with central necrosis or eschar), pustules, and subcutaneous nodules. Most patients had a variety of lesions simultaneously. Multiple red or gray macules with central ulceration or black eschar are characteristic of Fusarium infection. Disseminated infection may originate from skin lesions or onychomycosis. Most infections fail to respond to antifungal therapy unless there is resolution of the patient's neutropenia.

Adult↗

Prevention and management of long-term catheter related infections in cancer patients.

Long-term central venous catheters (CVC) are necessary in the care of cancer patients. However, catheter-related bloodstream infection (CRBSI) is commonly associated with serious complications resulting in considerable morbidity and mortality. The diagnosis of CRBSI frequently requires catheter removal to confirm the diagnosis by either quantitative or semiquantitative catheter culture method. Differential time to positivity, whereby a nonquantitative blood culture drawn from the CVC that becomes positive at least 2 hr earlier than the peripheral blood culture, is a new method for the diagnosis of CRBSI without removing the catheter. Prevention of CRBSI may be accomplished with the use of strict infection control measures, antimicrobial-impregnated catheters; and antibiotic-lock technique, as well as other methods. Once infection develops, management of long-term CRBSI is dictated by the type of organism, the severity of the infection, and availability of other venous access sites. If the infection is caused by Staphylococcus aureus, gram-negative bacilli, or Candida, the catheter should be removed and systemic antimicrobial therapy given for 10-14 days or longer in cases of complicated or deep-seated infection. In some cases, where there is no other venous access site, the catheter can remain in place, but a combination of systemic antimicrobials and antibiotic-lock therapy should be used.

Antibiotic Prophylaxis↗

Masking of neutropenic patients on transport from hospital rooms is associated with a decrease in nosocomial aspergillosis during construction.

To prevent nosocomial pulmonary aspergillosis during hospital construction, neutropenic patients with hematologic malignancy were required to wear high-efficiency masks when leaving their rooms. The rate of nosocomial aspergillosis decreased from 0.73 per 1,000 hospital patient-days during fiscal years 1993 to 1996 to 0.24 per 1,000 hospital patient-days during fiscal years 1996 to 1999 (P < .001). High-efficiency masks reduced nosocomial aspergillosis during hospital construction.

Air Pollutants↗