Biomedical subjects

A Fraser

Publications and source records attributed to A Fraser.

At least 19 recordsLinked to original sources

PubMed2006

Antibiotics for preventing meningococcal infections.

BACKGROUND: Meningococcal disease is a contagious bacterial disease caused by Neisseria meningitidis (N. meningitidis). Household contacts have the highest documented risk of the disease during the first seven days of a case being detected. Prophylaxis is, therefore, considered for those in close contact with people with a meningococcal infection and in populations with known high carriage rates as carriers are at increased risk of disease and may pose a risk of infection to others. OBJECTIVES: To study the effectiveness of different prophylactic treatment regimens in: (1) preventing secondary cases of meningococcal disease after contact with someone with the disease; (2) preventing cases of meningococcal disease in populations with a high rate of N. meningitidis carriers; (3) eradicating N. meningitidis from the pharynx in healthy carriers of N. meningitidis. This review also addresses the issues of adverse effects of prophylaxis and development of drug resistance. SEARCH STRATEGY: Electronic searches on the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 3, 2006), MEDLINE (January 1966 to June 2006), EMBASE (1980 to June 2006), LILACS (1982 to June 2006); and searching of references of all identified studies were performed. SELECTION CRITERIA: Randomised or quasi-randomised clinical trials addressing the effectiveness of different antibiotic treatments for: (a) prophylaxis against meningococcal disease; (b) eradication of N. meningitidis. DATA COLLECTION AND ANALYSIS: Two reviewers independently appraised the quality of each trial and extracted data from the included trials. Dichotomous data were analysed by calculating the relative risk (RR) and 95% confidence interval for each trial. MAIN RESULTS: There were no cases of meningococcal disease during follow up in any of the trials, thus effectiveness regarding prevention of future disease cannot be directly assessed. Ciprofloxacin (RR 0.04; 95% CI 0.01 to 0.12), rifampin (rifampicin) (RR 0.17; 95% CI 0.12 to 0.24), minocycline (RR 0.30; 95% CI 0.19 to 0.45) and ampicillin (RR 0.41; 95% CI 0.25 to 0.66) proved effective at eradicating N. meningitidis one week after treatment when compared with placebo. However, only rifampin (RR 0.20; 95% CI 0.14 to 0.29) and ciprofloxacin (RR 0.03; 95% CI 0.00 to 0.42) still proved effective at one to two weeks. Rifampin continued to be effective compared to placebo for up to four weeks after treatment but resistant isolates were seen following prophylactic treatment. No trials evaluated ceftriaxone against placebo but ceftriaxone was more effective than rifampin after one to two weeks of follow up (RR 5.93; 95% CI 1.22 to 28.68). AUTHORS' CONCLUSIONS: Given the fact that the use of rifampin in an outbreak setting might lead to the circulation of isolates resistant to rifampin, use of ciprofloxacin or ceftriaxone should be considered. Evidence suggests that all three agents are effective with up to two weeks follow up. Placebo-controlled trials do not seem ethical as prophylactic treatment has been proven to reduce the risk of disease among household contacts. More trials comparing the effectiveness of ceftriaxone, ciprofloxacin and rifampin for eradicating N. meningitidis would provide important insights.

Ampicillin↗

PubMed2006

The significance of Acinetobacter baumannii bacteraemia compared with Klebsiella pneumoniae bacteraemia: risk factors and outcomes.

Risk factors and outcomes for patients with nosocomial Acinetobacter baumannii bacteraemia were compared with those for patients with nosocomial Klebsiella pneumoniae bacteraemia in a single centre in Israel between 2000 and 2003. Data were collected retrospectively through patient chart review. In total, 112 patients with A. baumannii bacteraemia and 90 patients with K. pneumoniae bacteraemia were identified. A. baumannii was significantly associated with poorer performance status, mechanical ventilation, presence of devices, prior treatment with carbapenems, pneumonia as the source of infection and inappropriate empirical antibiotic treatment. All-cause 30-day mortality was higher for A. baumannii bacteraemia compared with K. pneumoniae bacteraemia (61.6% vs 38.9%, P=0.001). Variables significantly associated with mortality at the univariate level (P<0.1) were entered into a multi-variable logistic regression model for mortality. A. baumannii remained significantly associated with mortality when adjusted for all other risk factors (odds ratio 3.61, 95% confidence interval 1.55-8.39). This result did not change when the analysis was repeated for subgroups of less severely ill patients, i.e. those who were not ventilated and those who did not present with septic shock. These results support the view that nosocomial bacteraemia due to A. baumannii is associated with increased mortality.

Acinetobacter Infections↗

PubMed2006

Drugs for preventing tuberculosis in people at risk of multiple-drug-resistant pulmonary tuberculosis.

BACKGROUND: The emergence and spread of multiple-drug-resistant tuberculosis (MDR-TB), caused by strains of Mycobacterium tuberculosis resistant to at least isoniazid and rifampicin, is a potential threat to global tuberculosis control. Treatment is prolonged, expensive, more toxic than treatment of susceptible tuberculosis, and often unsuccessful. Experts are still undecided on the management of people exposed to MDR-TB. OBJECTIVES: To evaluate antituberculous drugs given to people exposed to MDR-TB in preventing active tuberculosis. SEARCH STRATEGY: We searched the Cochrane Infectious Diseases Group Specialized Register (January 2006), CENTRAL (The Cochrane Library 2006, Issue 1), MEDLINE (1966 to January 2006); EMBASE (1974 to January 2006), LILACS (1982 to January 2006), conference proceedings, and reference lists. We also contacted researchers and organizations. SELECTION CRITERIA: Randomized controlled trials comparing antituberculous drug regimens with an alternative antituberculous drug regimen, placebo, or no intervention given to people exposed to MDR-TB for preventing active tuberculosis. DATA COLLECTION AND ANALYSIS: Two authors independently inspected titles and abstracts identified by the search in order to identify potentially relevant publications for inclusion and analysis. MAIN RESULTS: No randomized controlled trials met the inclusion criteria. AUTHORS' CONCLUSIONS: The balance of benefits and harms associated with treatment for latent tuberculosis infection in people exposed to MDR-TB is far from clear. Antituberculous drugs should only be offered within the context of a well-designed randomized controlled trial, or when people are given the details of the current evidence on benefits and harms, along with the uncertainties.

Antitubercular Agents↗

PubMed2006

MDR1 C3435T polymorphisms correlate with cyclosporine levels in de novo renal recipients.

BACKGROUND: Single nucleotide polymorphisms (SNPs) in the multidrug resistance (MDR1) gene correlate with the intestinal function of P-glycoprotein (PGP). PGP serves as a hydrophobic export pump that extrudes cyclosporine (CsA) across the luminal membrane thus preventing CsA absorption. These genetic variants may predict CsA exposure levels in the early posttransplantation period. METHODS: CsA absorption profiles were established in 75 renal transplant patients using total daily dose and body weight adjusted 4-hour area under the time-concentration curve, AUC(0-4)/mg dose/kg body weight, on posttransplant day 3. These patients were subsequently genotyped for C3435T and G2677T polymorphisms using real-time polymerase chain reaction. An analysis was conducted to assess the independent impact of C3435T and G2677T SNPs on CsA bioavailability. RESULTS: C3435T polymorphisms were found to be an independent predictor of CsA AUC(0-4)/mg dose/kg levels on postoperative day 3. An inverse correlation was found between the number of T alleles and AUC values such that every T allele was associated with an approximate 15% decrement in AUC(0-4)/mg dose/kg (P = .034). A similar nonsignificant trend was observed for G2677T polymorphisms. CONCLUSIONS: MDR1 SNPs are correlated with CsA exposure in the early post-transplant period. Polymorphisms, in conjunction with other criteria, may become a useful tool to optimize initial drug dosing in renal transplantation.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2006

Salmonella enterica serotype Virchow: epidemiology, resistance patterns and molecular characterisation of an invasive Salmonella serotype in Israel.

This study outlines the unique epidemiology of Salmonella enterica serotype Virchow in Israel. Between 1997 and 2002, the overall incidence of non-typhoid Salmonella enterica (NTS) decreased from 69.3 to 53.3 infections/100,000 population, but the incidence of S. Virchow increased (from 7.2 to 9.1 infections/100,000). Since 2000, S. Virchow has become the second-ranking NTS isolate, accounting for 17% and 27% of all stool and blood NTS isolates, respectively. Infants aged < 1 year had the highest incidence of isolation from stools (92.8/100,000). The incidence of isolation from blood was highest for infants aged <1 year (4.4/100,000). Only 6% of isolates were susceptible to all ten antibiotic agents tested; 34% were resistant to one agent, 54% to one to three agents, and 40% to four to six agents. A high proportion of the tested isolates were resistant to nalidixic acid (89%), streptomycin (56%), tetracycline (43%), trimethoprim-sulphamethoxazole (38%) and chloramphenicol (28%), but none to ciprofloxacin or ceftriaxone. Pulsed-field gel electrophoresis revealed two closely related clusters, each containing a predominant pulsotype. Coupled with its invasive propensity, the increasing incidence of highly resistant S. Virchow in Israel is of real concern. Future research should focus on the sources of S. Virchow in the food chain in order to institute effective control measures.

Adolescent↗

PubMed2006

Autoimmune hemolytic anaemia in the antiphospholipid syndrome.

Antiphospholipid syndrome (APS) is a multisystem disease with recurrent thrombosis in the presence of antiphosphlipid antibodies, which may include cardiac, neurological, gastrointestinal, hematologic or cutaneous manifestations. The occurrence of autoimmune hemolytic anaemia (AIHA) in APS has not been well established. The purpose of this study was to review the occurrence of AIHA in patients with APS and its relation to other disease manifestations. Three-hundred and eight patients with APS from seven medical centers in Israel, Serbia and the Slovac Republic were included and evaluated for associations between AIHA and various manifestations of APS. AIHA was documented in 32 patients (10.4%). The odds ration for AIHA was increased in the presence of anticardiolipin antibodies and livedo reticularis (5.4 and 7.8, respectively). There was a highly significant association between AIHA and cardiac valvular vegetations and thickening (P < 0.0001), arterial thrombosis (P < 0.02), livedo reticularis (P < 0.0001) and CNS signs of epilepsy or chorea (P < 0.02 and P < 0.03, respectively). Thus, APS patients with AIHA are at risk of developing these manifestations, and should therefore be investigated for them. In addition, the occurrence of AIHA may define a subgroup of patients with a significant risk for subsequent development of SLE.

Adult↗

PubMed2006

Treatment of latent tuberculosis in persons at risk for multidrug-resistant tuberculosis: systematic review.

SETTING: The emergence and spread of multidrug-resistant tuberculosis (MDR-TB), caused by Mycobacterium tuberculosis resistant to at least isoniazid (INH) and rifampicin, is a threat to global TB control. OBJECTIVE: To appraise evidence of the effectiveness of treatment of latent TB infection (LTBI) in people at risk for developing active MDR-TB. DESIGN: Systematic review of comparative studies of people treated and not treated for LTBI following exposure to MDR-TB. DATA SOURCES: PubMed, EMBASE, LILACS and the Cochrane Library (December 2004). RESULTS: Two observational studies met inclusion criteria. A prospective cohort study found individualised tailored treatment to be effective for preventing active TB in children (OR = 0.20, 95%CI 0.04-0.94), while a retrospective cohort study found INH not to be effective (OR = 0.46, 95%CI 0.07-2.32). CONCLUSION: Evidence of the effects of treatment of LTBI in people exposed to MDR-TB is extremely limited in both quantity and quality. The increasing global spread of MDR-TB and the difficulties in treating it emphasise the need for effective preventive measures. Ideally, this issue should be addressed in a randomised controlled trial. Until such a trial is conducted, routine clinical data collected as part of existing TB control programmes could be useful and can be generated relatively easily.

Antitubercular Agents↗

PubMed2005

Anti-CCP antibodies measured at disease onset help identify seronegative rheumatoid arthritis and predict radiological and functional outcome.

OBJECTIVE: Anti-cyclic citrullinated peptide (anti-CCP) antibodies have been identified as highly specific for rheumatoid arthritis (RA). Studies suggest an association with radiographic outcome. The aims of this study were to assess the diagnostic and prognostic utility of the second-generation anti-CCP(2) test in a large cohort of early RA patients compared with connective tissue disease (CTD) controls. METHODS: One hundred and eighty-two patients with RA and 121 patients with CTD were recruited. All RA patients had less than 24 months of symptoms and had CRP, rheumatoid factor (RF), HLA typing (SE) and anti-CCP(2) antibodies measured at baseline. Function was assessed using the Health Assessment Questionnaire (HAQ) and X-rays performed at 0, 12 and 24 months. RESULTS: The anti-CCP(2) antibody test demonstrated a specificity of 91% and sensitivity of 81% for RA when compared with controls. In RF-negative patients, specificity was 92% and sensitivity 60%. Baseline demographics of the RA cohort showed mean age 57 yr, mean symptom duration 7 months, 63% RF-positive patients, 72% SE-positive, 81% CCP-positive and 21% erosive. The only predictor of change in Larsen score from 0 to 24 months in the cohort was the presence of the shared epitope (P<0.05) and in the RF-negative subgroup it was CCP(2) antibody titre >100 (P<0.05). Baseline HAQ was the only significant predictor of HAQ at 24 months, but in the RF-negative subgroup CCP(2) antibody titre >100 predicted a poor functional response at 24 months (P<0.05). CONCLUSIONS: This study confirms the diagnostic utility of anti-CCP(2) antibodies in early RA, particularly in seronegative patients, in whom anti-CCP(2) positivity also conferred prognostic utility for radiographic and functional outcomes.

Arthritis, Rheumatoid↗

PubMed2005

Antibiotic prophylaxis for bacterial infections in afebrile neutropenic patients following chemotherapy.

BACKGROUND: Bacterial infections are a major cause of morbidity and mortality in neutropenic patients following chemotherapy for malignancy. Trials have shown the efficacy of antibiotic prophylaxis in decreasing the incidence of bacterial infections, but not in reducing mortality rates. OBJECTIVES: This review aimed to evaluate whether antibiotic prophylaxis in afebrile neutropenic patients reduced mortality when compared to placebo or no intervention. SEARCH STRATEGY: Electronic searches on The Cochrane Cancer Network Register of Trials (2004), Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 4, 2004), MEDLINE (1966 to 2004) and EMBASE (1980 to 2004) and abstracts of conference proceedings; references of identified studies; the first author of each included trial was contacted. SELECTION CRITERIA: RCTs or quasi-RCTs comparing different types of antibiotic prophylaxis with placebo or no intervention, or another antibiotic to prevent bacterial infections in afebrile neutropenic patients. DATA COLLECTION AND ANALYSIS: Two authors independently appraised the quality of each trial and extracted data from the included trials. Relative risks (RR) or average differences, with their 95% confidence intervals (CI) were estimated. MAIN RESULTS: One hundred trials (10,274 patients) performed between the years 1973 to 2004 met inclusion criteria. Antibiotic prophylaxis significantly decreased the risk for death when compared with placebo or no intervention (RR, 0.66 [95% CI 0.54 to 0.81]). The authors estimated the number needed to treat (NNT) in order to prevent 1 death from all causes as 60 (95% CI 34 to 268). Prophylaxis resulted in a significant decrease in the risk of infection-related death, RR 0.58 (95% CI 0.45 to 0.74) and in the occurrence of fever, RR 0.78 (95% CI 0.75 to 0.82). A reduction in mortality was also evident when the more recently conducted quinolone trials were analysed separately. Quinolone prophylaxis reduced the risk for all-cause mortality, RR 0.52 (95% CI, 0.37 to 0.84). AUTHORS' CONCLUSIONS: Our review demonstrated that prophylaxis significantly reduced all-cause mortality. The most significant reduction in mortality was observed in trials assessing prophylaxis with quinolones. The benefit demonstrated in our review outweighs harm, such as adverse effects, and development of resistance, since all-cause mortality is reduced. Since most trials in our review were of patients with haematologic cancer, prophylaxis, preferably with a quinolone, should be considered for these patients.

Anti-Bacterial Agents↗

PubMed2005

The unmet need for anti-tumour necrosis factor (anti-TNF) therapy in ankylosing spondylitis.

OBJECTIVES: Anti-tumour necrosis factor (anti-TNF) therapy is effective in the treatment of ankylosing spondylitis (AS), but guidelines are needed because of the cost. The primary aim of this study was to evaluate the proportion of patients with AS who meet the criteria for anti-TNF therapy as well as to explore the relationship between disease activity, health status and quality of life in patients with AS who would potentially meet the criteria compared with those who would not. METHODS: All patients with a confirmed diagnosis of AS were identified via a search through the clinic correspondence database and sent postal questionnaires. Data captured included demographics, disease activity, aspects of functional impairment, activity limitation and quality of life using the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), pain scores (using a visual analogue scale), the Bath Ankylosing Spondylitis Functional Index (BASFI), Health Assessment Questionnaire (HAQ), short-form 36 (SF-36) and the Ankylosing Spondylitis Quality of Life (ASQoL) questionnaire. The unpaired Student's t-test, chi(2) test and Mann-Whitney U-test were performed for comparisons of groups where appropriate. RESULTS: Out of 325 mailed questionnaires, 246 (76%) were returned. The mean age of the patients who replied to the questionnaire was 52 yr (+/-12 yr) and 25% (62) were females. Mean BASDAI was 49 (+/-24) and 64% had a BASDAI > or = 40. There were significant differences between the groups with a BASDAI above and below 40 in pain by VAS, functional ability (BASFI, HAQ), health status (SF-36) and quality of life (ASQoL). Almost two-thirds (64%) of patients would meet the criteria for anti-TNF therapy under recommended guidelines. CONCLUSION: Patients with AS demonstrated poor functional status and poor quality of life. There is a large unmet need for effective therapy in AS, with almost two-thirds of patients meeting the proposed criteria for biological therapy. Patients with a BASDAI > or = 40 had a worse functional status and quality of life than those who have a BASDAI of <40. These results indicate that the need for effective intervention for AS is a priority area.

Adult↗

PubMed2005

Additional anti-Gram-positive antibiotic treatment for febrile neutropenic cancer patients.

BACKGROUND: The pattern of infections among neutropenic cancer patients has shifted in the last decades to a predominance of Gram-positive infections. Some of these Gram-positive bacteria are increasingly resistant to beta-lactams and necessitate specific antibiotic treatment. OBJECTIVES: To assess the effectiveness of empirical anti-Gram-positive (antiGP) antibiotic treatment for febrile neutropenic cancer patients in terms of mortality and treatment failure. To assess the rate of resistance development, further infections and adverse events associated with additional antiGP treatment. SEARCH STRATEGY: We searched The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 4, 2004), MEDLINE (1966 to 2004), EMBASE (January 1980 to 2004), LILACS (1982 to 2004), conference proceedings, and all references of included studies. First authors of all included and potentially relevant trials were contacted. SELECTION CRITERIA: Randomised controlled trials comparing one antibiotic regimen to the same regimen with the addition of an antiGP antibiotic for the treatment of febrile neutropenic cancer patients. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial eligibility, methodological quality and extracted all data. Relative risks (RR) with 95% confidence intervals (CI) were calculated. A random effects model was used for all comparisons showing substantial heterogeneity (I(2 )> 50%). Outcomes were extracted by intention-to-treat and the analysis was patient-based whenever possible. MAIN RESULTS: Thirteen trials and 2392 patients or episodes were included. Empirical antiGP antibiotics were tested at the onset of treatment in eleven studies and for persistent fever in two studies. The antiGP treatment was a glycopeptide in nine trials. Seven studies were assessed in the overall mortality comparison and no significant difference between the comparator arms was seen, RR 0.82 (95% CI 0.56 to 1.20, 852 patients). Ten trials assessed failure including modifications as failures, while six assessed overall failure, disregarding treatment modifications. Failure with modifications was significantly reduced, RR 0.76 (95% CI 0.68 to 0.85, 1779 patients) while overall failure was equal, RR 1.00, 95% CI (0.79 to 1.27, 943 patients). Both mortality and failure did not differ significantly among patients with Gram-positive infections, but comparisons were small. Data regarding other patient subgroups likely to benefit from antiGP treatment were not available. Glycopeptides did not increase fungal superinfection rates, and were associated with a reduction in documented Gram-positive superinfections. Resistant colonisation was not documented in the studies. AUTHORS' CONCLUSIONS: Current evidence shows that the addition of antiGP treatment, namely glycopeptides, prior to documentation of a Gram-positive infection does not improve outcomes.

Anti-Bacterial Agents↗

PubMed2005

Close association between valvar heart disease and central nervous system manifestations in the antiphospholipid syndrome.

BACKGROUND: Heart valves lesions and central nervous system involvement are among the most common manifestations of the antiphospholipid syndrome (APS). OBJECTIVE: To evaluate possible interrelations between these manifestations in a large group of APS patients. METHODS: 284 APS patients were evaluated retrospectively, 159 of whom had primary APS. Cardiac-CNS associations were determined for the entire study population, and for subgroups of patients with primary APS or APS associated with systemic lupus erythematosus (SLE). RESULTS: Significant associations where found between cardiac vegetations and epilepsy (p < 0.02), and between cardiac valve thickening or dysfunction and migraine (p = 0.002). Borderline association was found between valvar vegetations and migraine (p = 0.09). A significant association was also found between all valvar lesions and stroke or transient ischaemic attacks. Subanalyses showed that patients with primary APS had significant associations between cardiac valve pathology and all CNS manifestations, while patients with APS associated with SLE had no such associations. CONCLUSIONS: The study suggests potential differences in biological behaviour between primary APS and APS associated with SLE. The presence of cardiac valve pathology may be a risk factor for several types of CNS involvement in PAPS.

Adolescent↗

PubMed2005

Antibiotics for preventing meningococcal infections.

BACKGROUND: Meningococcal disease is a contagious bacterial disease caused by Neisseria meningitidis (N. meningitidis). The highest documented risk of disease is for household contacts during the first seven days of a case being detected. Prophylaxis is considered for those in close contact with people with a meningococcal infection and in populations with known high carriage rates as carriers are at increased risk of disease and may pose a risk of infection to others. OBJECTIVES: To study the effectiveness of different prophylactic treatment regimens in: (1) preventing secondary cases of meningococcal disease after contact with a case; (2) preventing cases of meningococcal disease in populations with a high rate of N. meningitidis carriers; (3) eradicating N. meningitidis from the pharynx in healthy carriers of N. meningitidis;This review also addresses the issues of adverse affects and development of drug resistance. SEARCH STRATEGY: Electronic searches on The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 2, 2004), MEDLINE (January 1966 to July 2004), EMBASE (1980 to September 2004), LILACS (1982 to July 2004), and searches of references of all identified studies. SELECTION CRITERIA: Randomised or quasi-randomised clinical trials addressing the effectiveness of different antibiotic treatments for (a) prophylaxis of/against meningococcal disease; (b) eradication of N. meningitidis. DATA COLLECTION AND ANALYSIS: Two reviewers independently appraised the quality of each trial and extracted data from the included trials. Dichotomous data were analysed by calculating the relative risk (RR) and 95% confidence interval for each trial. MAIN RESULTS: There were no cases of meningococcal disease during follow up in any of the trials, thus effectiveness regarding prevention of future disease cannot be directly assessed. Ciprofloxacin (relative risk (RR) 0.04; 95% CI 0.01 to 0.12), rifampin (RR 0.17; 95% CI 0.12 0.24), minocycline (RR = 0.30; 95% CI 0.19 to 0.45) and ampicillin (RR 0.41; 95% CI 0.25 0.66) proved effective at eradicating N. meningitidis one week after treatment, compared with placebo. However, after one to two weeks only rifampin (RR 0.20; 95% CI 0.14 to 0.29) and ciprofloxacin (RR 0.03; 95% CI 0.00 to 0.42) still proved effective. No trials evaluated ceftriaxone against placebo. Ceftriaxone was more effective than rifampin, after one to two weeks of follow up (RR 5.93; 95% CI 1.22 to 28.68). Rifampin continued to be effective compared to placebo until up to four weeks of post treatment follow up but resistant isolates were seen following prophylactic treatment. AUTHORS' CONCLUSIONS: Given the fact that the use of rifampin in an outbreak setting might lead to the circulation of isolates resistant to rifampin, use of ciprofloxacin or ceftriaxone should be considered.Placebo-controlled trials do not seem ethical as prophylactic treatment has been proven to reduce the risk of disease among household contacts. More trials comparing the effectiveness of ceftriaxone, ciprofloxacin and rifampin for eradicating N. meningitidis could provide important insights.

Ampicillin↗

PubMed2005

Prophylactic use of antibiotics for prevention of meningococcal infections: systematic review and meta-analysis of randomised trials.

A systematic review and meta-analysis of randomised controlled trials was performed in order to study the effectiveness of prophylactic treatment regimens in preventing secondary cases of meningococcal disease (i.e., those contracted after contact with a person with meningococcal disease) and in eradicating Neisseria meningitidis from the pharynx of healthy colonised individuals. The Medline, Embase, and Lilacs databases, the Cochrane Library, and the references of all studies identified were systematically searched for relevant trials. Two reviewers independently applied selection criteria, performed quality assessment, and selected data. Relative risks were pooled using a fixed effects model unless heterogeneity assessed by the I2 statistic and chi-square test was found. In such cases, a random effect model was used. There were no cases of meningococcal disease following treatment with antibiotics or placebo, thus effectiveness regarding prevention of future disease could not be directly assessed. Compared with placebo, ciprofloxacin (RR = 0.04; 95%CI, 0.01-0.12), rifampin (RR = 0.17; 95%CI, 0.12-0.24), minocycline (RR = 0.30; 95%CI, 0.19-0.45), and penicillin (RR = 0.47; 95%CI, 0.24-0.94), proved effective at eradicating Neisseria meningitidis 1 week after treatment. After 1-2 weeks, only ciprofloxacin (RR = 0.03; 95%CI, 0.00-0.42) and rifampin (RR = 0.20; 95%CI, 0.14-0.29) still proved significantly effective when compared with placebo. Rifampin continued to be effective (RR = 0.24; 95%CI, 0.16-0.37) compared with placebo until up to 4 weeks post treatment. Rifampin was the only drug to which resistance developed. Given that the use of rifampin in an outbreak setting might lead to the circulation of isolates resistant to rifampin, the use of ciprofloxacin and ceftriaxone should be considered.

Anti-Bacterial Agents↗

PubMed2005

Impact of mycophenolate mofetil loading on drug exposure in the early posttransplant period.

UNLABELLED: Achieving adequate therapeutic levels of immunosuppressive medications is important in rejection prevention. This study examined exposure to mycophenolic acid (MPA) in kidney transplant patients within the first 5 days posttransplantation. METHODS: This single-center, nonrandomized study of first solitary kidney allograft recipients receiving cyclosporine (n = 116) or tacrolimus (n = 50) included patients who received either 1 g or 1.5 g of mycophenolate mofetil twice daily starting postoperatively. Exposure to MPA was measured at days 3 and 5 posttransplant using published limited sampling time equations. RESULTS: There were no significant differences in exposure in the cyclosporine-treated patients receiving 3-g (n = 22) compared to 2-g (n = 94) daily doses (AUC([0-12]) 33.8 +/- 10.0 mg*h/L versus 30.1 +/- 9.7 mg*h/L, P = .20, respectively). About half the patients in both groups had AUC([0-12]) <30 mg*h/L on days 3 and 5 posttransplant. On the other hand, there was significantly greater exposure on day 3 in the tacrolimus-treated patients receiving 3 g (n = 21) compared to 2 g (n = 29) daily (AUC([0-12]) 43.1 +/- 9.0 mg*h/L versus 36.8 +/- 11.1 mg*h/L, P = .016, respectively). On day 3 one (4.8%) patient receiving 3 g had an AUC([0-12]) of <30 mg*h/L; whereas, eight (27.5%) receiving 2 g were below this level (P = .068). The AUC([0-12]) levels were not different on day 5. CONCLUSIONS: Loading with higher doses of mycophenolate mofetil results in greater exposure and a trend toward more patients in the therapeutic window within the first week for tacrolimus- but not for cyclosporine-treated patients.

Adult↗

PubMed2005

Basiliximab lowers the cyclosporine therapeutic threshold in the early post-kidney transplant period.

Early adequate cyclosporine exposure has been shown to predict low acute rejection rate in kidney transplantation. The aim of this study is to determine the importance of exceeding the early cyclosporine therapeutic exposure threshold with basiliximab induction. A retrospective analysis of 166 first cadaveric and non-identical live donor transplant recipients treated with or without basiliximab induction, Neoral, mycophenolate mofetil and prednisone, was performed. Adequate exposure was defined as a 2-h post-Neoral dose cyclosporine level (C2) >1700 ng/mL at day 3. The primary outcome was acute rejection within the first 6 months. In the no basiliximab (control) group (n = 74), rejection occurred in 23% (17 of 74) of recipients and was strongly associated with low cyclosporine exposure on day 3. Acute rejection occurred in 38% (11 of 29) with C2 <1700 ng/mL compared with 13% (six of 45) with C2 >/=1700 ng/mL (p = 0.014). In the basiliximab group (n = 92), rejection occurred in only 11% (10 of 92) of recipients and did not correlate with cyclosporine exposure. Acute rejection occurred in 10% (four of 40) with C2 <1700 ng/mL compared with 12% (six of 52) with C2 >/=1700 ng/mL (p = 0.81). Therefore achieving cyclosporine therapeutic targets by day 3 may not be required when anti-IL2 receptor antibody induction is used.

Acute Disease↗

PubMed2005

Screening for cervical cancer--an evidence-based approach.

INTRODUCTION: The Papanicolau (Pap) smear is widely accepted by both the public and health authorities as a useful tool for detection of cervical cancer and its precursors. In Israel only opportunistic screening exists and still the incidence of invasive cervical cancer is among the lowest in the world. OBJECTIVES: To examine the existing evidence for the effectiveness of cervical cancer screening by Pap smears; to apply the findings to Israeli data, and to assess the implications for the current cervical cancer screening policy. METHODS: Search of Medline (1966-June 2003) and the Cochrane Library for relevant systematic reviews, controlled trials and cohort studies. RESULTS: There have been no trials of screening for cervical cancer and its precursors and therefore, no direct evidence that screening improves outcomes. A single retrospective cohort study estimated the age-adjusted RR for invasive cervical cancer in women with at least one Pap smear, whether normal or abnormal, compared to women with no smear at 0.4 (95% CI 0.2-0.9). In Israel some 27,800 (range: 20,800-167,000) women need to be screened in order to prevent one case of cervical cancer. The cost of preventing a single case of invasive cervical is approximately 1.288 million NIS (range: 1.643-13.193 million NIS). CONCLUSIONS: An evidence-based approach to the question of the effectiveness of cervical cancer screening using Pap smears has yielded weak evidence. Based on this weak evidence and rough estimations of the effectiveness and cost of mass screening for cervical cancer in Israel, we conclude that the current policy should be maintained.

Adult↗

PubMed2004

Genome sequence of the enterobacterial phytopathogen Erwinia carotovora subsp. atroseptica and characterization of virulence factors.

The bacterial family Enterobacteriaceae is notable for its well studied human pathogens, including Salmonella, Yersinia, Shigella, and Escherichia spp. However, it also contains several plant pathogens. We report the genome sequence of a plant pathogenic enterobacterium, Erwinia carotovora subsp. atroseptica (Eca) strain SCRI1043, the causative agent of soft rot and blackleg potato diseases. Approximately 33% of Eca genes are not shared with sequenced enterobacterial human pathogens, including some predicted to facilitate unexpected metabolic traits, such as nitrogen fixation and opine catabolism. This proportion of genes also contains an overrepresentation of pathogenicity determinants, including possible horizontally acquired gene clusters for putative type IV secretion and polyketide phytotoxin synthesis. To investigate whether these gene clusters play a role in the disease process, an arrayed set of insertional mutants was generated, and mutations were identified. Plant bioassays showed that these mutants were significantly reduced in virulence, demonstrating both the presence of novel pathogenicity determinants in Eca, and the impact of functional genomics in expanding our understanding of phytopathogenicity in the Enterobacteriaceae.

Base Sequence↗