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Biomedical subjects

M Laverdiere

Publications and source records attributed to M Laverdiere.

At least 19 recordsLinked to original sources

A randomized, open-label, multicenter comparative study of the efficacy and safety of piperacillin-tazobactam and cefepime for the empirical treatment of febrile neutropenic episodes in patients with hematologic malignancies.

BACKGROUND: The empirical treatment of febrile, neutropenic patients with cancer requires antibacterial regimens active against both gram-positive and gram-negative pathogens. This study was performed to demonstrate the noninferiority of monotherapy with piperacillin-tazobactam, compared with cefepime. METHODS: We conducted a randomized-controlled, open-label, multicenter clinical trial among high-risk patients from 34 university-affiliated tertiary care medical centers in the United States, Canada, and Australia who were undergoing treatment for leukemia or hematopoietic stem cell transplantation and were hospitalized for empirical treatment of febrile neutropenic episodes. Patients received piperacillin-tazobactam (4.5 g every 6 h) or cefepime (2 g every 8 h) intravenously. The primary outcome was success (defined by defervescence without treatment modification) at 72 h of treatment, end of treatment, and test of cure in the modified intent-to-treat analysis. Secondary outcomes included time to defervescence, microbiological efficacy, the additional use of glycopeptide antibiotics, emergence of resistant bacteria, and safety. RESULTS: For 528 subjects (265 received piperacillin-tazobactam and 263 received cefepime), success rates were 57.7% and 48.3%, respectively (P = .04) at the 72-h time point, 39.6% and 31.6% (P = .06) at end of treatment, and 26.8% and 20.5% (P = .11) at the test-of-cure visit. The analyses demonstrated noninferiority for piperacillin-tazobactam at all time points (P< or = .0001). Treatment with piperacillin-tazobactam was independently associated with treatment success in multivariate analysis (odds ratio, 1.65; 95% confidence interval, 1.04-2.64; P = .035). Both regimens were well tolerated. CONCLUSIONS: This study demonstrates the noninferiority and safety of piperacillin-tazobactam monotherapy, compared with cefepime, for the empirical treatment of high-risk febrile neutropenic patients with cancer.

Adolescent↗

What is the clinical significance of infusing hematopoietic cell grafts contaminated with bacteria?

Although hematopoietic stem cell (HSC) products are routinely cultured for sterility, bacterial contamination of these products is rarely observed and little is known about the clinical consequences of infusing contaminated grafts. We retrieved the sterility cultures of bone marrow and peripheral HSC grafts from 938 patients transplanted at our center from January 1990 to July 2005. Fever, septicemia and other adverse events were assessed for up to 14 days following infusion of the graft. Out of the 1502 grafts collected during this 15-year period, 15 (1.0%) had a positive sterility culture (11 Gram-positive cocci, 2 Gram-positive bacilli and 2 Gram-negative bacilli). No correlation was observed between the graft contamination rate and the extent of graft manipulation or the patient's underlying condition. Thirteen recipients were transplanted with contaminated grafts. Five patients were treated with specific pre-emptive antibiotics. Only one episode of Staphylococcus epidermidis bacteremia possibly related to a contaminated graft was observed on day +5. As the infusion of contaminated grafts with Gram-positive skin contaminants rarely results in unfavorable clinical outcomes, close patient monitoring without the use of specific pre-emptive antibiotics could be appropriate and could avoid antibiotic-associated adverse events.

Adult↗

Evaluation of the in vitro activity of caspofungin against bloodstream isolates of Candida species from cancer patients: comparison of Etest and NCCLS reference methods.

The in vitro activity of caspofungin (CAS) was compared with the activity of fluconazole, itraconazole and amphotericin B against 178 bloodstream Candida spp. from cancer patients. The activities were assessed using the reference NCCLS M-27A microdilution method and the Etest method. With both the NCCLS microdilution reference method and the Etest method, CAS was the most active agent (MIC90s 0.19-0.5 mg/l) against Candida albicans, C. glabrata and C. tropicalis. CAS showed substantial activity against azole-resistant Candida. The percentages of agreement within +/-2 dilutions between the NCCLS reference microdilution method and Etest MICs ranged from 81 to 97%. CAS showed good in vitro activity against invasive azole-susceptible and azole-resistant Candida isolates. The CAS Etest MICs correlated well with the NCCLS reference MICs and may provide more choice for laboratories in assessing the activity of antifungal agents. The clinical correlation of these in vitro observations needs to be established.

Antifungal Agents↗

In vitro activity of three new triazoles and one echinocandin against Candida bloodstream isolates from cancer patients.

The in vitro activities of voriconazole, posaconazole, ravuconazole and micafungin were compared with those of fluconazole, itraconazole, ketoconazole, flucytosine and amphotericin B against 164 candidaemia isolates recovered from cancer patients in two Canadian centres. The MIC(50) results for ravuconazole, voriconazole, posaconazole and micafungin were 0.01, 0.03, 0.12 and 0.25 mg/L, respectively. The new antifungal agents showed substantial activity against isolates demonstrating in vitro resistance to fluconazole and itraconazole. These results suggest that the newer antifungal agents possess promising activity against invasive Candida isolates, particularly against those with reduced susceptibility to fluconazole and itraconazole.

Antifungal Agents↗

In vitro activity of a novel ketolide ABT-773 against invasive strains of Streptococcus pneumoniae.

New ketolides such as ABT-773 are a promising group of antibiotics in an era of increasing antibiotic resistance. We tested 704 invasive strains of Streptococcus pneumoniae collected from 1990 to 1998. Overall resistance was 8.3, 4.6, 4.5 and 3.6% for penicillin, cefuroxime, erythromycin and clarithromycin, respectively. By using a recommended breakpoint for susceptibility of <0.5 mg/L, no strains showed reduced susceptibility to ABT-773. ABT-773 was very active against all penicillin-resistant strains (MIC > 2 mg/L, with a mean geometric mean <0.06 mg/L), and against all 33 erythromycin-resistant strains, irrespective of the mode of resistance [mef- or erm(B)-mediated]. ABT-773 is a very active and promising agent against invasive strains of S. pneumoniae, including multiresistant strains.

Anti-Bacterial Agents↗

Comparative evaluation of the MB/BacT and BACTEC 460 TB systems for the detection of mycobacteria from clinical specimens: clinical relevance of higher recovery rates from broth-based detection systems.

New broth-based detection systems have higher recovery rates of mycobacteria from clinical specimens than traditional cultures on solid media. The clinical significance of this higher sensitivity rate is largely unknown. We prospectively evaluated the performances of two liquid media detection systems (the MB/BacT system and the BACTEC 460 TB system) and an egg-based Lowenstein-Gruft solid medium (LG) on the recovery rates of mycobacteria from 849 clinical specimens. Mycobacteria (other then M. gordonae) were detected in 51 (6.0%) specimens. In 12/51 (23%) specimens, mycobacteria (five mycobacterium tuberculosis (MtB) and seven non-M tuberculosis complex (MOTT) were recovered only from the broth-based systems. Review of the patients' clinical charts revealed that failure of LG to recover Mtb were due to nonmycobacterial overgrowth and antibiotic treatment. The recovered MOTT were all clinically nonsignificant. Higher sensitivity of broth-based mycobacteria detection systems is largely due to their capability to recover mycobacteria from treated tuberculous patients or from partially decontaminated specimens. The high recovery rates of nonclinically significant MOTT could potentially increase inappropriate use of antibiotics.

Bacterial Typing Techniques↗

Randomized placebo-controlled trial of fluconazole prophylaxis for neutropenic cancer patients: benefit based on purpose and intensity of cytotoxic therapy. The Canadian Fluconazole Prophylaxis Study Group.

A randomized, double-blind trial comparing oral fluconazole (400 mg daily) with placebo as prophylaxis for adult patients receiving intensive cytotoxic therapy for acute leukemia or autologous bone marrow transplantation was conducted in 14 Canadian university-affiliated hospitals. Although fluconazole prophylaxis did not obviate the need for parenteral antifungal therapy compared with placebo (81 [57%] of 141 vs. 67 [50%] of 133, respectively), its use resulted in fewer superficial fungal infections (10 [7%] of 141 vs. 23 [18%] of 131, respectively; P = .02) and fewer definite and probable invasive fungal infections (9 vs. 32, respectively; P = .0001). Fluconazole recipients had fewer deaths attributable to definite invasive fungal infection (1 of 15 vs. 6 of 15, respectively; P = .04) and achieved more frequent success without fungal colonization (52 [37%] of 141 vs. 27 [20%] of 133, respectively; P = .004; relative risk reduction, 85%) than did placebo recipients. Patients benefiting the most from fluconazole prophylaxis included those with acute myeloid leukemia who were undergoing induction therapy with cytarabine plus anthracycline-based regimens and those receiving marrow autografts not supported with hematopoietic growth factors. Fluconazole prophylaxis reduces the incidence of superficial fungal infection and invasive fungal infection and fungal infection-related mortality among patients who are receiving intensive cytotoxic chemotherapy for remission induction.

Adolescent↗

Comparative activity of trovafloxacin and Bay 12-8039 against 452 clinical isolates of Streptococcus pneumoniae.

The principal aim of this study was to evaluate the in-vitro activity of new quinolones against clinical strains of Streptococcus pneumoniae. Four hundred and fifty-two single clinical isolates (of which 362 were susceptible to penicillin, 54 intermediate and 36 highly resistant) were tested against penicillin, cefuroxime, ciprofloxacin, levofloxacin, trovafloxacin and Bay 12-8039. Of the tested S. pneumoniae strains, 97.1 % had MICs of trovafloxacin of < or = 0.25 mg/L, and 96.7% had MICs of Bay 12-8039 of < or = 0.25 mg/L (difference not statistically significant); 81.9% of strains had MICs of cefuroxime of < or = 0.25 mg/L (P < or = 0.001 against both quinolones). Only 4% and 0.7% of the strains had MICs of levofloxacin and ciprofloxacin respectively of < or = 0.25 mg/L. Compared with older quinolones, trovafloxacin and Bay 12-8039 have good in-vitro activity against S. pneumoniae.

Anti-Infective Agents↗

A new urea broth-based test to detect Helicobacter pylori presence in upper gastrointestinal biopsies.

The aim of this study was to evaluate the performance of a simple and inexpensive homemade urea test (U-test) to detect Helicobacter pylori in upper digestive tract biopsies. We tested and compared the U-test with three other diagnostic methods: the Clo-test, and culture and pathology in 110 patients randomly chosen at the endoscopy clinic. When using culture and/or pathology as the "gold standard," H. pylori was found to exist in 54 patients. Pathology was positive in 50 cases (92.5%), culture in 49 (90.7%), the U-test in 45 (83.3%), and the Clo-test in 43 (79.6%). With regard to culture pathology, the sensitivities of the U-test and the Clo-test were 83.3% and 79.5%, respectively. Specificity was 100% for both methods. The kappa coefficient calculation between the U-test and the Clo-test was 0.98. The results show that the U-test is a reliable, fast, and inexpensive method for detecting H. pylori in upper gastrointestinal biopsies.

Adult↗

Prospective randomized study of piperacillin/tazobactam therapy of surgically treated intra-abdominal infection. The Piperacillin/Tazobactam Intra-Abdominal Infection Study Group.

A randomized prospective trial was undertaken in adult patients with serious intra-abdominal infections to determine whether a new combination of antibiotic therapy could prove as efficacious as the combination that has been widely used in practice in the recent decade (clindamycin and gentamicin). Three hundred thirty-one patients were randomized in a 2:1 ratio, with the larger number of patients being treated parenterally with piperacillin and tazobactam. The results showed that both the clinical and microbiologic performance of the piperacillin/tazobactam combination was better than that of clindamycin and gentamicin. This clinical equivalence permits overall cost savings without compromising the existing quality of antimicrobial therapy for intra-abdominal infection.

Abdomen↗

Severe bronchospasm followed by respiratory arrest during thallium-dipyridamole imaging.

We describe the occurrence of sudden severe bronchospasm and respiratory arrest following dipyridamole infusion in a patient with chronic obstructive pulmonary disease predominantly of the emphysematous type. The severe reaction was unexpected because the patient had tolerated well withdrawal of aminophylline derivatives for 48 hours and was receiving chronic prednisone 20 mg qd. Although the diagnostic and prognostic gains from dipyridamole imaging far outweigh the small risk associated with the test, patients with chronic pulmonary obstructive disease must be closely monitored during thallium-dipyridamole imaging.

Aged↗

14q+ abnormality with probable t(8;14)(q24;q32) in a young Haitian immigrant with acquired immunodeficiency syndrome and concomitant Burkitt's-like lymphoma.

Cytogenetic analyses were carried out in a young Haitian immigrant with acquired immunodeficiency syndrome and concomitant Burkitt's-like lymphoma associated with massive bone marrow infiltration. A characteristic 14q+ abnormality was found in all bone marrow cells examined. Although chromosome abnormality involving band 8q24 was not evident in all the cells examined, some karyotypes show that the typical t(8;14)(q24;q32) is most probably present. No other complex rearrangements could be identified. This is the first report of concomitant acquired immunodeficiency syndrome and Burkitt's-like lymphoma in the Haitian community. Our cytogenetic findings provide further evidence for the role of specific chromosomal rearrangements in Burkitt's-like lymphoma oncogenesis in the setting of acquired immunodeficiency syndrome.

Acquired Immunodeficiency Syndrome↗

Brain abscess due to Petriellidium boydii.

A 22 year-old man died from multiple cerebral abscesses due to Petriellidium boydii 4 1/2 months after an episode of near drowning. The autopsy showed dissemination to heart and kidney. This patient had no immunocompromising disease but was treated with corticosteroids. The treatment of this condition with ventricular shunting and amphotericin B is discussed and compared with the experience of ten other cases reported in the literature.

Adult↗

Outbreak of central-nervous-system toxoplasmosis in western Europe and North America.

Acute encephalitis caused by Toxoplasma gondii was diagnosed in ten patients in Belgium, the U.S.A., and Canada. None had underlying conditions usually associated with toxoplasmosis. Three had evidence of extraneural infection at necropsy. Nine patients died. Only two of the patients had a history of homosexuality, and one was a heroin addict. Five were Haitian, and four of them had lived in North America for 2-5 years. Eight of the patients had pronounced lymphopenia. Diagnosis of toxoplasmosis was hampered by a lack of suspicion that Toxoplasma could be the agent causing necrotising encephalitis in the non-immunocompromised host, the protean manifestations of the encephalitis, and a lack of a specific antibody response. The large number of cases appearing in western Europe and North America emphasise the necessity of including toxoplasmosis in the differential diagnosis of encephalitis of unknown aetiology.

Acute Disease↗

Nephrogenic adenoma of the bladder after kidney transplantation: spontaneous improvement with azathioprine removal; surgical trauma and cytomegalovirus infection as possible etiologic factors.

We report 2 cases of nephrogenic adenoma several years after successful cadaver kidney transplantation. In 1 case the lesion had cytomegalovirus inclusions, and we observed a marked and sustained reduction in the extension of the lesion with cessation of azathioprine. Surgical trauma and cytomegalovirus infections are discussed as etiologic factors. Conservative treatment seemed appropriate.

Adenoma↗