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I Raad

Publications and source records attributed to I Raad.

At least 19 recordsLinked to original sources

blaVIM-2 and blaVIM-7 carbapenemase-producing Pseudomonas aeruginosa isolates detected in a tertiary care medical center in the United States: report from the MYSTIC program.

Two Pseudomonas aeruginosa strains resistant to beta-lactams, fluoroquinolones, aminoglycosides, tetracyclines, and carbapenems and susceptible only to polymyxin B (MIC <or= 2 microg/ml) were identified as part of the Meropenem Yearly Susceptibility Test Information Collection program. Metallo-beta-lactamase screening tests were positive, PCR yielded products with blaVIM primers, and sequence analysis revealed blaVIM-7 and blaVIM-2. The isolates had distinct ribotype and pulsed-field gel electorphoresis patterns and appeared independently, remote in time and location, at the same cancer center.

Academic Medical Centers↗

Posaconazole as salvage therapy for zygomycosis.

Zygomycosis, an infection that is associated with significant morbidity and mortality, is becoming common in immunocompromised patients. Posaconazole is a new extended-spectrum azole antifungal that has demonstrated in vitro and in vivo activity against zygomycetes. This report provides the results from the first 24 patients with active zygomycosis who were enrolled in two open-label, nonrandomized, multicentered compassionate trials that evaluated oral posaconazole as salvage therapy for invasive fungal infections. Posaconazole was usually given as an oral suspension of 200 mg four times a day or 400 mg twice a day. Eleven (46%) of the infections were rhinocerebral. Duration of posaconazole therapy ranged from 8 to 1,004 days (mean, 292 days; median, 182 days). Rates of successful treatment (complete cure and partial response) were 79% in 19 subjects with zygomycosis refractory to standard therapy and 80% in 5 subjects with intolerance to standard therapy. Overall, 19 of 24 subjects (79%) survived infection. Survival was also associated with surgical resection of affected tissue and stabilization or improvement of the subjects' underlying illnesses. Failures either had worsening of underlying illnesses or requested all therapy withdrawn; none of the failures received more than 31 days of posaconazole. Posaconazole oral solution was well tolerated and was discontinued in only one subject due to a drug rash. Posaconazole appears promising as an oral therapy for zygomycosis in patients who receive required surgery and control their underlying illness.

Administration, Oral↗

Pharmacokinetics, safety, and efficacy of posaconazole in patients with persistent febrile neutropenia or refractory invasive fungal infection.

The pharmacokinetic profiles, safety, and efficacies of different dosing schedules of posaconazole oral suspension in patients with possible, probable, and proven refractory invasive fungal infection (rIFI) or febrile neutropenia (FN) were evaluated in a multicenter, open-label, parallel-group study. Sixty-six patients with FN and 32 patients with rIFI were randomly assigned to one of three posaconazole regimens: 200 mg four times a day (q.i.d.) for nine doses, followed by 400 mg twice a day (b.i.d.); 400 mg q.i.d. for nine doses, followed by 600 mg b.i.d.; or 800 mg b.i.d. for five doses, followed by 800 mg once a day (q.d.). Therapy was continued for up to 6 months in patients with rIFI or until neutrophil recovery occurred in patients with FN. The 400-mg-b.i.d. dose provided the highest overall mean exposure, with 135% (P = 0.0004) and 182% (P < 0.0001) greater exposure than the 600-mg-b.i.d. and 800-mg-q.d. doses, respectively. However, exposure in allogeneic bone marrow transplant (BMT) recipients (n = 12) was 52% lower than in non-BMT patients. Treatment-related adverse events (occurring in 24% of patients) were mostly gastrointestinal in nature. Twenty-four percent of patients had adverse events leading to premature discontinuation (none were treatment related). In efficacy-evaluable patients, successful clinical response was observed in 43% with rIFI (56% of patients receiving 400 mg b.i.d., 17% receiving 600 mg b.i.d., and 50% receiving 800 mg q.d.) and 77% with FN (74% receiving 400 mg b.i.d., 78% receiving 600 mg b.i.d., and 81% receiving 800 mg q.d.). Posaconazole is well tolerated and absorbed. Divided doses of 800 mg (400 mg b.i.d.) provide the greatest posaconazole exposure.

Adult↗

Adenovirus infections in adult recipients of blood and marrow transplants.

Adenoviruses are increasingly recognized pathogens that affect blood and marrow transplant (BMT) recipients. Experiences with 2889 adult BMT recipients were reviewed to study the incidence, clinical spectrum, risk factors for dissemination, response to therapy, and outcome of adenovirus infections. Eight-five patients (3%) were diagnosed by means of culture (n=85) or culture and histopathological examination (n=6). Nine patients had asymptomatic viruria, and 76 had symptomatic infections, which included upper respiratory tract infection (n=20), enteritis (n=18), hemorrhagic cystitis (n=10), pneumonia (n=15), and disseminated disease (n=13). The overall mortality rate was 26%. A higher mortality rate was observed among patients with pneumonia (73%) and disseminated disease (61%). Risk factors for dissemination included receipt of an allogeneic transplant, presence of graft-versus-host disease (GVHD), and receipt of concurrent immunosuppressive therapy. Intravenous ribavirin was not associated with an appreciable benefit among 12 patients who received this treatment. In conclusion, adenovirus infections are an important cause of morbidity and mortality in adult BMT recipients, particularly allogeneic transplant recipients with GVHD who are receiving immunosuppressive therapy. The need for an effective, nontoxic antiviral therapy is apparent.

Adenoviridae Infections↗

Cytomegalovirus pneumonia in adults with leukemia: an emerging problem.

Cytomegalovirus (CMV) pneumonia is reportedly unusual among adults with leukemia who have not undergone transplantation. To assess the frequency of CMV pneumonia and its outcome during the present time, we reviewed the experience of 2136 hospitalized adults with leukemia. Sixty-one patients (2.9%) had CMV pneumonia diagnosed. The frequency doubled from 1.4% in 1992--1994 to 2.8% in 1995--1997 (P<.05). Fifty-four patients (89%) had received treatment with an immunosuppressive chemotherapeutic regimen that contained fludarabine (n=37), high-dose cytoxan (n=17), or both (n=10), and 15 patients (25%) had received granulocyte transfusions that were stimulated with hematopoietic growth factors from unscreened donors. The overall CMV pneumonia--associated mortality rate was 57%. Among autopsied patients who had leukemia, the frequency of CMV pneumonia increased from 0%, 2.3%, and 0% in 1992, 1993, and 1994, respectively, to 4.6%, 6.5%, and 16% in 1995, 1996, and 1997, respectively (P<.05). CMV has emerged as an important cause of life-threatening pneumonia in adults with leukemia who have received potent immunosuppressive therapies and stimulated granulocyte transfusions from unscreened donors.

Adult↗

Treatment of nosocomial postoperative pneumonia in cancer patients: a prospective randomized study.

BACKGROUND: Nosocomial pneumonia continues to be associated with high morbidity and mortality in cancer patients. METHODS: In an attempt to find an optimal treatment for this infection, nonneutropenic cancer patients with postoperative nosocomial pneumonia were randomized to receive either piperacillin/tazobactam (P/T) 4.5 g i.v. every 6 hours (30 patients) or clindamycin (Cl) 900 mg plus aztreonam (Az) 2 g i.v. every 8 hours (22 patients). Amikacin 500 mg i.v. every 12 hours was given to all patients for the first 48 hours. RESULTS: The two groups were comparable for the characteristics of pneumonia that included gram-negative etiology and duration of intubation. Response rates were 83% for patients who received P/T and 86% for those who received Cl/Az (P > .99). There were no serious adverse events; however, at our center the cost of the P/T regimen was $73.86 compared with $99.15 for the Cl/Az regimen. CONCLUSIONS: The two regimens had comparable high efficacy, and P/T had a slight cost advantage. Either of these antibiotic regimens combined with an aminoglycoside could lead to favorable outcome in cancer patients at high risk for nosocomial pneumonia.

Aged↗

Cytomegalovirus pneumonia in adult autologous blood and marrow transplant recipients.

CMV pneumonia is a major cause of morbidity and mortality among allogeneic BMT recipients. To assess the frequency, timing, risk factors and response to therapy of CMV pneumonia among autologous BMT recipients, we reviewed our experience with 795 patients. Sixteen (2%) patients were diagnosed with CMV pneumonia. The frequency was higher among patients who were seropositive than those who were seronegative (3.3% vs 0%, P = 0.008). Among seropositive patients, the frequency was higher among patients with hematological malignancies than patients with solid tumors (5.0 % vs 1.0%, P = 0.019). Eleven cases occurred <30 days, and five cases occurred >100 days post transplant. The overall CMV pneumonia-related mortality rate was 31%. Seven (78%) of nine patients treated with ganciclovir and IVIG prior to respiratory failure survived; neither of two patients treated after respiratory failure survived. Four of five (80%) untreated patients survived. In conclusion, CMV is a not infrequent cause of pneumonia among autologous BMT recipients. Risk factors include CMV seropositivity and an underlying hematological malignancy. A favorable response hinges on the prompt initiation of therapy. The survival of 25% of the patients without antiviral therapy suggests that the isolation of CMV from a BAL specimen occasionally reflects oropharyngeal contamination or that CMV pneumonia may sometimes be self-limited in more immunocompetent autologous BMT recipients.

Adult↗

Respiratory syncytial virus infections in autologous blood and marrow transplant recipients with breast cancer: combination therapy with aerosolized ribavirin and parenteral immunoglobulins.

Scant data are available concerning the impact and response to therapy of respiratory syncytial virus (RSV) infections in patients undergoing autologous blood and marrow transplantation (BMT) for breast cancer. During eight winter seasons from 1992-1993 to 1999-2000, nine (4%) of 249 such patients were hospitalized with RSV infections. Six patients, including all five patients who were early post transplant in the pre-engraftment period, developed pneumonia and were treated with a combination of aerosolized ribavirin and IVIG. Among five patients with pneumonia in whom therapy was initiated prior to respiratory failure, one (20%) died. The sixth patient, in whom therapy was initiated after respiratory failure developed, also died. In total, two (1%) patients, both of whom were in the pre-engraftment period, died of progressive pneumonia. In conclusion, RSV is a significant cause of life-threatening pneumonia in autologous BMT recipients with breast cancer during the early post-transplant period, and accounted for a substantial portion of the overall transplant-related mortality, which in recent years has been minimal.

Aerosols↗

Optimal frequency of changing intravenous administration sets: is it safe to prolong use beyond 72 hours?

OBJECTIVE: To determine the safety and cost-effectiveness of replacing the intravenous (IV) tubing sets in hospitalized patients at 4- to 7-day intervals instead of every 72 hours. DESIGN: Prospective, randomized study of infusion-related contamination associated with changing IV tubing sets within 3 days versus within 4 to 7 days of placement. SETTING: A tertiary university cancer center. PATIENTS AND METHODS: Cancer patients requiring IV infusion therapy were randomized to have the IV tubing sets replaced within 3 days (280 patients) or within 4 to 7 days of placement (232 patients). Demographic, microbiological, and infusion-related data were collected for all participants. The main outcome measures were infusion- or catheter-related contamination or colonization of IV tubing, determined by quantitative cultures of the infusate, and infusion- or catheter-related bloodstream infection (BSI), determined by quantitative culture of the infusate in association with blood cultures in febrile patients. RESULTS: The two groups were comparable in terms of patient and catheter characteristics and the agents given through the IV tubing. Intent-to-treat analysis demonstrated a higher level of tubing colonization in the 4- to 7-day group versus the 3-day group (median, 145 vs 50 colony-forming units; P=.02). In addition, there were three episodes of possible infusion-related BSIs, all of which occurred in the 4- to 7-day group (P=.09). However, when the 84 patients who received total parenteral nutrition, blood transfusions, or interleukin-2 through the IV tubing were excluded, the two groups had a comparable rate of colonization (0.4% vs 0.5%), with no catheter- or infusion-related BSIs in either group. CONCLUSION: In patients at low risk for infection from infusion- or catheter-related infection who are not receiving total parenteral nutrition, blood transfusions, or interleukin-2, delaying the replacement of IV tubing up to 7 days may be safe, as well as cost-effective

Adolescent↗

Blood products: a significant risk factor for long-term catheter-related bloodstream infections in cancer patients.

Data obtained from a previous prospective randomized study in cancer patients conducted at our institution were analyzed to investigate risk factors for catheter-related (CR) bloodstream infections (BSIs). Our recent analysis showed that the administration of blood products through central venous catheters was a risk factor for CR BSI, whereas thrombocytopenia during catheterization may have provided protection against CR BSI, as did central venous catheter insertion under maximal sterile barrier precautions

Adolescent↗

Management of an outbreak of vancomycin-resistant enterococci in the medical intensive care unit of a cancer center.

Between November 1996 and February 1997, 17 episodes of vancomycin-resistant enterococci (VRE) infection or colonization (9 infections, 8 colonizations), all with the same or a similar genomic DNA pattern, were identified in the medical intensive care unit (MICU) of a tertiary-care cancer hospital. The cases were genotypically traced to a patient who was admitted to the hospital in September 1996 and who, by December 1996, had four different admissions to the MICU. Multifaceted infection control measures, including decontamination of the environment and of nondisposable equipment, halted the nosocomial transmission of VRE in the MICU.

Cancer Care Facilities↗

Treatment of vancomycin-resistant enterococcal infections in the immunocompromised host: quinupristin-dalfopristin in combination with minocycline.

Between February 1994 and November 1998, 56 oncology patients infected with vancomycin-resistant enterococci (VRE) were treated with quinopristin-dalfopristin (Q-D) plus minocycline (MIN). Infections included bacteremia, urinary tract infection, pneumonia, and wound infection. The response rate was 68%, and the most frequent adverse event was arthralgia or myalgia (36%). Q-D-MIN is effective for VRE infection in cancer patients but is associated with a substantial frequency of arthralgia or myalgia.

Adolescent↗

Comparison of amphotericin B lipid complex (ABLC) vs. ambisome in the treatment of suspected or documented fungal infections in patients with leukemia.

Fungal infections remain a major cause of treatment failure and death in acute leukemia. New liposomal preparations of amphotericin B are now available. While less toxic, their comparative efficacy and toxicity profiles are unknown. In this study the comparative efficacy and safety of ABLC vs. AmBisome was evaluated in seventy-five patients with leukemia who developed 82 episodes of suspected or documented mycosis, and were treated (1:1) with either ABLC (n=43) or AmBisome (n=39). Both drugs were dosed accordingly from 3 to 5 mg/kg/day. Using an intent-to-treat analysis, the overall response to therapy was 27/43 (63%) for ABLC and 15/39 (39%) for AmBisome (p=0.03). Median dose and duration of treatment was 10 days at 3 mg/kg for ABLC and 15 days at 4 mg/kg for AmBisome. Acute, not dose-limiting infusion side effects were seen in 70% vs. 36% (p=0.002), ABLC vs. AmBisome. Increase of bilirubin > 1.5 times from baseline was 38% vs. 59%, ABLC vs. AmBisome (p=0.05). ABLC and AmBisome were equally effective for the treatment of suspected or documented fungal infections. While, acute infusion-toxicity was greater with ABLC, infusion toxicity requiring discontinuation was similar for both drugs. AmBisome was better tolerated than ABLC but was associated with mild abnormalities in liver function tests at the end of therapy.

Acute Disease↗

Candida lusitaniae: a cause of breakthrough fungemia in cancer patients.

Candida lusitaniae is an infrequent cause of fungemia. We identified 12 cases of C. lusitaniae fungemia that occurred at the University of Texas M. D. Anderson Cancer Center from 1988 to 1999. The mean age of patients was 48 years (range 20--70 years). Eight patients had hematologic malignancy or had received a bone marrow transplant, and 4 had a solid tumor. Most patients (75%) were neutropenic (<10(3)/mm(3)). Treatment with amphotericin B alone failed for 3 of 6 patients, irrespective of neutropenic status. Fluconazole was effective as a single agent in 3 patients with solid tumors. The combination of amphotericin B plus fluconazole was effective treatment for two-thirds of patients with hematologic malignancy, despite persistence of neutropenia. The mortality rate associated with C. lusitaniae infection was 25%. C. lusitaniae presents as breakthrough fungemia in immunocompromised patients and is associated with failure of amphotericin B therapy. Fluconazole may be a useful agent in the treatment of this infection.

Adult↗

Candida krusei fungemia. An escalating serious infection in immunocompromised patients.

BACKGROUND: Candida krusei is inherently resistant to fluconazole and is emerging as a frequent cause of fungemia in patients with hematologic malignant neoplasms. OBJECTIVE: To determine the risk and prognostic factors associated with C krusei fungemia in comparison with Candida albicans fungemia in patients with cancer. METHODS: Retrospective study of 57 cases of C krusei fungemia occurring at the M. D. Anderson Cancer Center, Houston, Tex, from 1989 to 1996. The C krusei cases were compared with 57 cases of C albicans fungemia with respect to demographics, underlying cancer, Acute Physiology and Chronic Health Evaluation II score, immunosuppression status, chemotherapy, and the use of central venous catheters, as well as fluconazole prophylaxis. RESULTS: At our institution, C krusei accounted for 5% of fungemias during 1989 through 1992 and for 10% during 1993 through 1996. Patients with C krusei fungemia more often had leukemia than patients with C albicans (77% vs 11%; P =.02), whereas catheter-related infections were more common among patients with C albicans fungemia (42% vs 0%; P<.001). Patients with C krusei fungemia had a lower response rate (51% vs 69%; P =.05), largely because they more frequently were neutropenic and had disseminated infection. Mortality related to fungemia was 49% in the cases with C krusei vs 28% in C albicans. Multiple logistic regression analysis showed that persistent neutropenia (P =.02) and septic shock (P =.002) were predictors of poor prognosis. CONCLUSION: In neutropenic patients, C krusei fungemia is associated with high mortality. It should be suspected in patients with leukemia who are receiving fluconazole prophylaxis and should be treated aggressively with an amphotericin B regimen.

Adolescent↗

Respiratory syncytial virus upper respiratory tract illnesses in adult blood and marrow transplant recipients: combination therapy with aerosolized ribavirin and intravenous immunoglobulin.

Respiratory syncytial virus (RSV) is an important cause of serious respiratory illness in blood and marrow transplant (BMT) recipients. In some subsets of these immunocompromised patients, RSV upper respiratory illnesses frequently progress to fatal viral pneumonia. The frequency of progression to pneumonia is higher during the pre-engraftment than during the post-engraftment period. Once pneumonia develops, the overall mortality is 60-80%, regardless of the treatment strategy. We performed a pilot trial of therapy of RSV upper respiratory illnesses using aerosolized ribavirin and IVIG (500 mg/kg every other day), with the goal of preventing progression to pneumonia and death. Two dosages of ribavirin were used: a conventional regimen (6 g/day at 20 mg/ml for 18 h/day) and a high-dose short-duration regimen (6 g/day at 60 mg/ml for 2 h every 8 h). Fourteen patients were treated for a mean of 13 days (range: 7-23 days). In 10 (71%) patients, the upper respiratory illness resolved. The other four (29%) patients, three of whom were in the pre-engraftment period, developed pneumonia, which was fatal in two. The most common adverse effect was psychological distress at being isolated within a scavenging tent. In conclusion, prompt therapy of RSV upper respiratory illnesses in BMT recipients with a combination of aerosolized ribavirin and IVIG was a safe and promising approach to prevent progression to pneumonia and death.

Adult↗