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Biomedical subjects

J M Conly

Publications and source records attributed to J M Conly.

At least 19 recordsLinked to original sources
PubMed2001

A comparison of multifaceted versus Clostridium difficile-focused VRE surveillance strategies in a low-prevalence setting.

We compared our current screening strategy for vancomycin-resistant Enterococcus (VRE) with a focused strategy that screens all stool samples sent for Clostridium difficile toxin assay but limits rectal swab screening to wards with new VRE cases detected via C. difficile samples. The proposed strategy detects 72.7% of new VRE cases, with substantial cost savings.

Clostridioides difficile↗
PubMed2000

Prospective randomized trial of 10% povidone-iodine versus 0.5% tincture of chlorhexidine as cutaneous antisepsis for prevention of central venous catheter infection.

A multicenter prospective, randomized, controlled trial, with 0.5% tincture of chlorhexidene versus 10% povidone-iodine as cutaneous antisepsis for central venous catheter (CVC) insertion, was conducted for patients in intensive care units. Of 374 patients, 242 had a CVC inserted for >3 days and were used for the primary analysis. Outcomes included catheter-related bacteremia, significant catheter colonization (> or = 15 colony-forming units [cfu]), exit-site infection, serial quantitative exit-site culture (every 72 h), and molecular subtyping of all isolates. Patients in both study groups were comparable with respect to age, sex, underlying disease, length of hospitalization, reason for line insertion, and baseline APACHE II score. Documented catheter-related bacteremia rates were 4.6 cases per 1000 catheter-days in the chlorhexidine group (n=125) and 4.1 cases per 1000 catheter-days in the povidone-iodine group (n=117; not significant [NS]). Significant catheter-tip colonization occurred in 24 (27%) of 88 patients in the povidone-iodine group and in 31 (34%) of 92 patients in the chlorhexidine group (NS). A mean exit-site colony count of 5.9 x 10(5) cfu/mL per 25 cm(2) of the surface area of skin in the povidone-iodine group versus 3.1 x 10(5) cfu/mL per 25 cm(2) in the chlorhexidine group (NS) was found. There was a trend toward fewer exit-site infections in the chlorhexidine group (0 of 125 patients) versus those in the povidone-iodine group (4 of 117 patients; P=.053). Results of an intention-to-treat analysis were unchanged from the primary analysis. No difference was demonstrable between 0.5% tincture of chlorhexidine and 10% povidone-iodine when used for cutaneous antisepsis for CVC insertion in patients in the intensive care unit.

Adult↗
PubMed1999

Orally administered dextran sulfate is absorbed in HIV-positive individuals.

Preliminary in vivo studies suggested that oral dextran sulfate was poorly absorbed, but investigations were limited by inadequate methods for measuring the drug in the body. To determine absorption in HIV-positive subjects, hydrogenated dextran sulfate, average molecular weight 8000 (Usherdex 8), was orally administered in a short-term (single dose, 4 g/day for 5 days, 7 subjects) and in a long-term study (1 g, 4 times per day for 29 to 335 days, 8 subjects), which was a continuation of the short-term study with the inclusion of an additional subject. When an agarose gel electrophoresis technique with toluidine blue staining was used, the drug was recovered from plasma (67%, peak 2.2 microg/mL) and circulating peripheral blood lymphocyte (PBL) samples (50%, peak 333 microg/L blood) obtained at 5 and 15 minutes and 1, 3, 6, and 24 hours after the first day's dose and from plasma (56%) and PBL samples (38%) obtained 5 minutes after administration on 4 subsequent days in the short-term study. In the long-term study, the drug was found in plasma (67%, peak 2.4 microg/mL) and PBL samples (25%, peak 126 microg/L blood) obtained at monthly visits within 4 hours of the last dose. The drug was found in all urine samples from all subjects in both studies (short-term study, 24-hour samples up to 4 days after the final dose; long-term study, monthly samples within 4 hours of the last dose). In the long-term study, bone marrow preparations from 3 subjects showed metachromatic inclusions present in reticular cells when the cells were stained with toluidine blue, indicating the presence of sulfated polyanions. A significant rise in activated partial thromboplastin time and a drop in platelet count (P < .025) were demonstrated, with thrombocytopenia developing in 3 patients. Mild-to-moderate gastrointestinal disturbances were experienced by 6 subjects in the short-term study and by all subjects in the long-term study. One subject experienced mild central nervous system symptoms in the short-term study. These results indicate that dextran sulfate is absorbed after oral administration; therefore, further studies on its efficacy, particularly in the early stages of the disease, along with additional observations on its toxicity, are warranted.

Absorption↗
PubMed1999

Antibiotic prescribing for Canadian preschool children: evidence of overprescribing for viral respiratory infections.

Antibiotic resistance is associated with prior receipt of antibiotics. An analysis of linked computerized databases for physician visits and antibiotic prescriptions was used to examine antibiotic prescribing for different respiratory infections in preschool children in Canada. In 1995, 64% of 61,165 children aged <5 years made 140,892 visits (mean, 3.6 visits per child) for respiratory infections; 74% of children who made visits received antibiotic prescriptions. Antibiotics were prescribed to 49% of children with upper respiratory tract infection, 18% with nasopharyngitis, 78% with pharyngitis or tonsillitis, 32% with serous otitis media, 80% with acute otitis media, 61% with sinusitis, 44% with acute laryngitis or tracheitis, and 24% with influenza. Acute otitis media accounted for 33% of all visits and 39% of all antibiotic prescriptions. The estimated Canadian-dollar cost of overprescribing was $423,693, or 49% of the total cost of antibiotics ($859,893) used in this group. This population-based study confirms antibiotic overprescribing in Canada.

Anti-Bacterial Agents↗
PubMed1999

Lack of efficacy of oral bacitracin plus doxycycline for the eradication of stool colonization with vancomycin-resistant Enterococcus faecium.

In a prospective observational cohort study designed to assess the role of oral bacitracin solution plus doxycycline in the eradication of intestinal carriage of vancomycin-resistant Enterococcus faecium (VREF) in patients on a renal ward, rectal swab specimens were obtained from 15 treated and 24 control patients. Cultures of the rectal swabs were negative for 15 (100%) of the antibiotic-treated vs. eight (33.3%) of the untreated patients (P < .001) on day 14. However, follow-up for a mean of 127 and 130 days revealed 9 of 15 (60%) and 15 of 24 (62.5%) in the treated and untreated cohorts (P = .86), respectively, carried VREF intermittently or persistently. Quantitative VREF stool cultures in the treated cohort revealed an initial 3.1-log10/g decrease, but there was an increase to pretreatment levels at 2-4 and 5-7 weeks post-treatment (7.8 and 7.4 log10/g). Oral bacitracin and doxycycline were not efficacious in reducing the carriage of VREF beyond the 2-week interval during which they were given.

Administration, Oral↗
PubMed1997

Multicenter randomized trial of fluconazole versus amphotericin B for treatment of candidemia in non-neutropenic patients. Canadian Candidemia Study Group.

A randomized trial was conducted to compare the efficacy and safety of fluconazole versus that of amphotericin B in the treatment of candidemia in non-neutropenic adults. Enrollment was stratified by disease severity (APACHE II score). Patients were randomized (1:1) to receive amphotericin B 0.6 mg/kg/day (cumulative dose 8 mg/kg) or fluconazole 800 mg intravenous loading dose, then 400 mg daily for four weeks (intravenous for at least 10 days). Patients were monitored for six months. A total of 106 patients were enrolled. A protocol amendment implemented midway through the trial required patients to be removed from the study and treated with amphotericin B if species identification indicated candidemia due to Candida glabrata or Candida krusei. Baseline characteristics were similar for the two groups; 103 patients (fluconazole, 50; amphotericin B, 53) met the major enrollment criteria. The intention-to-treat analysis indicated successful therapy in 50% of fluconazole recipients compared to 58% of the amphotericin B group (p = 0.39; one-sided 95% CI, -8 to 24%). The efficacy analysis included 84 patients (fluconazole, 42; amphotericin B, 42); successful outcomes were observed in 57% and 62% of cases in the fluconazole and amphotericin B groups, respectively (p = 0.66: one-sided 95% CI, -12 to 22%). The mortality at day 14 for the fluconazole group was 26% and for the amphotericin B group 21% (p = 0.52; chi-square test) and remained similar throughout the course of follow-up, Drug-related adverse events were more frequent with amphotericin B than with fluconazole and prompted switching of therapy for two (4%) and zero cases, respectively. Fluconazole and amphotericin B were associated with similar clinical response rates and survival in the treatment of candidemia among non-neutropenic patients; however, drug-related adverse events were more frequent with amphotericin B.

Adult↗
PubMed1997

Development of an intravenous-to-oral route conversion program for antimicrobial therapy at a Canadian tertiary care health facility.

OBJECTIVE: To describe the effect of introducing a route conversion program on the prescribing of antimicrobials for the treatment of respiratory tract infections and skin/soft tissue infections in a sample population. DESIGN: Concurrent, pre- and postintervention study. SETTING: Four general internal medicine wards at The Toronto Hospital, a 1170-bed, tertiary care health center in Toronto, Ontario, Canada. PARTICIPANTS: Patients receiving antimicrobial therapy for respiratory tract infections and skin/soft tissue infections. INTERVENTION: Written guidelines and education sessions were presented to residents, interns, medical students, and pharmacists responsible for the care of patients admitted to four general internal medicine wards. MAIN OUTCOME MEASURES: Clinical and laboratory parameters related to the status of the infection were monitored prospectively and compared with the course of drug therapy, with consideration of the patient's ability to meet the criteria established in the guidelines. The number of days of intravenous therapy prescribed despite appropriateness of oral therapy was tallied. RESULTS: Twenty-seven patients (28 infections) were identified for inclusion in the 7-week preliminary audit, and 30 patients (32 infections) were included in the audit after the program, which continued for 5 weeks. Following implementation of the program, the number of days that intravenous therapy was continued despite the appropriateness of oral therapy was reduced from 41% to 26% of the total days of intravenous therapy prescribed. CONCLUSIONS: The program had a positive influence on antimicrobial prescribing behavior in the population studied. Strategies to ensure continued benefit from the program have been developed.

Administration, Oral↗
PubMed1995

Molecular typing of Stenotrophomonas (Xanthomonas) maltophilia by DNA macrorestriction analysis and random amplified polymorphic DNA analysis.

Stenotrophomonas (Xanthomonas) maltophilia is a multidrug-resistant, nosocomial pathogen for which optimal typing methods in epidemiologic investigations of nosocomial outbreaks have not been defined. We compared DNA macrorestriction analysis by pulsed-field gel electrophoresis (PFGE) with random amplified polymorphic DNA (RAPD) analysis by arbitrarily primed PCR for molecular typing of 109 multidrug-resistant strains of S. maltophilia from multiple outbreaks at our institution over a 10-month period in 1993. PFGE after digestion with restriction endonuclease DraI revealed 62 unique DNA restriction profiles among the 109 strains, with 23, 11, 6, 6, and 3 strains having concordant profiles in each of five types. There were four concordant profiles among 8 strains (2 strains with each profile), while unique profiles were present in each of the remaining 52 strains. Further RAPD analysis with a decanucleotide primer showed the same number of distinct strain types as PFGE but more subtype diversity within each clonal type. We concluded that DNA macrorestriction analysis and RAPD analysis are sufficiently discriminatory and useful for differentiation of S. maltophilia strains in epidemiologic investigations of nosocomial outbreaks. However, RAPD analysis by arbitrarily primed PCR is faster and less laborious method of molecular typing.

Bacterial Typing Techniques↗
PubMed1994

Comparison of single-dose cefotetan and multidose cefoxitin as intravenous prophylaxis in elective, open biliary tract surgery: a multicentre, double-blind, randomized study.

OBJECTIVE: To compare the safety, tolerance and prophylactic effectiveness of a single 2-g dose of cefotetan with a standard prophylactic regimen of cefoxitin in reducing the incidence of postoperative infections after elective, open biliary tract surgery. DESIGN: Multicentre, double-blind, randomized comparative study with a 4-week follow-up. SETTING: Five Canadian university centres. PARTICIPANTS: One hundred and eleven patients scheduled to undergo elective, open biliary tract surgery. INTERVENTIONS: The patients were randomly assigned to receive either cefotetan or cefoxitin in a ratio of 2:1; 76 patients received cefotetan and 35 received cefoxitin. MAIN OUTCOME MEASURES: Wound infection as defined by the Centers for Disease Control and Prevention and by clinical evaluation, adverse events and laboratory parameters. RESULTS: Two incisional wound infections were reported by patients in the cefotetan group, for an overall infection rate of 1.8% (2 of 111). No significant differences were found in the failure rate or in any other indicator of efficacy. The incidence of adverse events for cefotetan (12.6%) was not statistically different from that for cefoxitin (10.4%), and none of the 16 adverse events in the cefotetan group and 5 in the cefoxitin group was serious or severe. Only one event (rash) was possibly related to the study drugs. Several hematologic and biochemical parameters were found to be normal preoperatively and abnormal postoperatively, but no relation was found between these variations and the study drugs. These changes were mainly attributable to the operation. CONCLUSION: Cefotetan was found to be effective and comparable to cefoxitin, both in safety and in reducing the incidence of infection after elective, open biliary tract surgery.

Adolescent↗
PubMed1994

The contribution of vitamin K2 (menaquinones) produced by the intestinal microflora to human nutritional requirements for vitamin K.

BACKGROUND: Coagulopathy manifest by elevation of the prothrombin time (PT) in patients receiving broad spectrum antimicrobials indirectly suggests a role for intestinal microflora synthesized menaquinone (MK) in the maintenance of normal coagulation. Nonetheless, no direct evidence is available to support this contention. OBJECTIVE: Our objective was therefore to provide evidence that bacterially produced MK may be absorbed by the distal small bowel of humans. METHODS: Using a cell harvester, Staphylococcus aureus (ATCC 29213) was grown in 12-L batches, harvested, and extracted by high performance liquid chromatography (HPLC) to obtain 8 mg of pure MK. Four normal volunteers were placed on a diet severely restricted in vitamin K1 (median 32-40 U/day), and were given warfarin to maintain an International Normalized Ratio of approximately 2.0. On the 10th day of warfarin administration, naso-ileal intubation was performed and 1.5 mg of MK was delivered into the ileum. PT, factor VII, II and serum vitamin K1 levels were monitored throughout the study. RESULTS: Mean serum vitamin K1 levels were reduced to 30% of the pre-diet value at the time of MK administration. Within 24 h of ileal MK administration, there was a significant (p < 0.05) increase in the factor VII level of 0.28 +/- 0.10 U/ml (mean +/- SEM) and a significant decrease of 2.5 (+/- 0.1) s in the PT, whereas in the control phase (during which no MK was administered), there were no significant changes in the PT or factor VII at corresponding time intervals. CONCLUSION: These data provide direct evidence for the absorption of vitamin K2 from the distal small bowel, supporting a definite role for bacterially synthesized vitamin K2 in contributing to the human nutritional requirements of this vitamin.

Adult↗
PubMed1993

Treatment of acute uncomplicated urinary tract infections with 3 days of lomefloxacin compared with treatment with 3 days of norfloxacin.

The bacteriologic and clinical efficacies of 3 days of lomefloxacin therapy were compared with those of 3 days of norfloxacin therapy for the treatment of acute uncomplicated urinary tract infections in a prospective, randomized, double-blind study. One hundred sixty-four subjects were enrolled at five Canadian centers; 84 received lomefloxacin, and 80 received norfloxacin. Escherichia coli (84%) and Staphylococcus saprophyticus (11%) were the most common organisms isolated. Forty subjects (24%) had low quantitative counts in their pretherapy urine specimens. In the intent-to-treat analysis, 76 lomefloxacin subjects (91%) and 76 norfloxacin subjects (95%) were cured or improved at follow-up 5 to 9 days posttreatment and 73 (87%) and 71 (89%) subjects from the lomefloxacin and norfloxacin groups, respectively, were cured or improved at 4 to 6 weeks posttreatment. Bacteriologic eradication occurred in 61 of 63 lomefloxacin subjects (97%) with > or = 10(8) CFU/liter in their pretherapy specimens and 56 of 59 norfloxacin subjects (95%) at 5 to 9 days and 55 (87%) and 53 (90%) subjects from the lomefloxacin and norfloxacin groups, respectively, at 4 to 6 weeks. There were no statistically significant differences in outcome. Adverse effects which were potentially related to the study medications were reported by 26% of the subjects who received lomefloxacin and 25% of the subjects who received norfloxacin. There were no severe adverse events, and only one subject discontinued therapy. These data suggest that 3 days of therapy with either lomefloxacin or norfloxacin is effective in the treatment of acute uncomplicated urinary tract infections.

Acute Disease↗
PubMed1993

Contamination study of multiple-dose vials.

OBJECTIVE: To document the number of opened, dated, and expired multiple-dose vials (MDVs) in patient-care areas and to determine what proportion of MDVs were contaminated with bacteria or cellular debris. DESIGN: Every tenth opened MDV (69/656) identified on the wards was collected, ensuring representation from each nursing unit. Contents were examined for contamination. SETTING: Medical-school-affiliated, tertiary care center. MAIN OUTCOME MEASURES: (1) Visual inspection for debris, medication type, location, lot number, manufacturer's expiration date, and date of opening; (2) culture in solid and broth media for bacterial growth; and (3) staining and microscopic examination for cellular constituents. RESULTS: No vials had been dated after opening and 4.6 percent were expired according to the manufacturer's expiration date. No bacterial contamination was evident; however, one vial was contaminated with red blood cells. CONCLUSIONS: Transmission of infection via contaminated MDVs has been well documented and contamination with red blood cells raises concerns about potential for transmission of bloodborne pathogens. Recommendations include dating MDVs after opening, emphasizing the need for proper aseptic technique, and discarding MDVs on the manufacture's date of expiration.

Drug Contamination↗
PubMed1993

The absorption and bioactivity of bacterially synthesized menaquinones.

After optimizing conditions for maximal production of menaquinones (MK), S. aureus and B. vulgatus were grown in batches, harvested and extracted for qualitative and quantitative MK content utilizing HPLC (high performance liquid chromatography) until a total of 6 mg was available. Five normal healthy male volunteers were placed on a vitamin K1 deficient diet (< or = 25 micrograms/day) and were subsequently warfarinized to maintain a prothrombin time (PT) 1.5-2 times control. Following stabilization of daily warfarin dosage 1 mg doses of the extracted MK were orally administered. As a control, the same volunteers were later warfarinized but no MK was given. Within 24 h of MK administration the prothrombin time (PT) decreased (mean +/- SEM) 3.6 +/- 1.0 s (p < 0.005) and the Factor VII level increased 0.36 +/- 0.3 u/ml (p < 0.005) vs a PT increase of 1.0 +/- 1.0 s (p > 0.1) and a Factor VII level increase of 0.03 +/- 0.1 u/ml (p > 0.1) in the control phase. Within 48 h of MK administration the PT was normal in all subjects but remained > or = 1.5 times control in the control phase. These data demonstrate for the first time the absorption and bioactivity of bacterially synthesized vitamin K in humans.

Administration, Oral↗
PubMed1992

A multicenter, open comparative study of parenteral cefotaxime and ceftriaxone in the treatment of nosocomial lower respiratory tract infections.

A multicenter Canadian study enrolled 74 persons to compare low-dose cefotaxime at 1 g every 8 hr to ceftriaxone 1 g every 12 hr in patients with nosocomial pneumonia. Of 57 evaluable patients (30 cefotaxime and 27 ceftriaxone) in this preliminary report, 93% responded to therapy in both groups. Ceftriaxone patients tended to have more side effects (14.2%). This study is continuing to accrue patients to achieve 100 evaluable patients. Interim data, however, support the continued use of low-dose cefotaxime as an appropriate alternative for clinically effective and cost-effective management of nosocomially acquired pneumonia.

Adult↗
PubMed1992

Quantitative and qualitative measurements of K vitamins in human intestinal contents.

Little data are available with regard to the amount and types of bacterially synthesized menaquinones within the human intestinal tract. Quantitative reverse phase high performance liquid chromatographic (HPLC) analysis of the distal colonic contents of 10 male volunteers revealed the following: (mean +/- SEM) micrograms/g dry weight: MK-4 to MK-7 5.55 (+/- 0.27); MK-9,10 14.54 +/- 0.29; K1 1.31 (+/- 0.14). Similar analyses of the colostomy contents of subjects revealed a total menaquinone content of 8.85 micrograms/g dry weight. The total intestinal contents obtained from five subjects after isotonic saline purgation qualitatively revealed MK-4 to MK-11 with a mean (+/- SEM) content of MK-4 to MK-10 of 5.4 +/- 2.1 micrograms/g dry weight or a mean (+/- SEM) of 1.6 +/- 0.7 mg dry weight of the total contents (243 g). The quantitative mean growth for the major menaquinone producers Escherichia coli and Bacteroides species was 5.2 +/- 3.2 and 9.2 +/- 1.8 log10 CFU/g dry weight, respectively. These results indicate that menaquinones are present in significant concentration in the human intestinal tract, and a potentially large reservoir of vitamin K may be available to the host.

Adult↗