Vitamin D and progression of carotid intima-media thickness in HIV-positive Canadians.

OBJECTIVES: Based on a growing body of evidence implicating low vitamin D status in the development of cardiovascular disease (CVD), we hypothesized that in Canadian HIV-positive adults, low 25-hydroxyvitamin D (25(OH)D) concentration would be associated with increased subclinical vascular disease progression. METHODS: We prospectively studied the relationship between baseline 25(OH)D and subsequent progression of carotid intima-media thickness (CIMT) between 2002 and 2011, in the Canadian HIV Vascular Study using stored blood specimens. RESULTS: Of the 128 participants, 89.1% were men, the mean age (standard deviation [SD]) was 46.5 (8.2) years, 93.8% were white, and 36.7% were current smokers. Mean (SD) annual CIMT follow-up was 5.9 (1.8) years (maximum 8.5 years), providing approximately 750 patient-years of follow-up. Mean (SD) CIMT progression was 0.027 (0.030) mm/year. Mean (SD) 25(OH)D was 95.0 (46.9) nmol/L. Only 13.3% of participants were vitamin D deficient (25(OH)D < 50 nmol/L), whereas 61.7% had a 25(OH)D exceeding the sufficiency threshold (75 nmol/L). Vitamin D quartiles were inversely associated with body mass index (BMI) (P = 0.034), total cholesterol to high-density lipoprotein (HDL) cholesterol ratio (P = 0.001) and parathyroid hormone concentration (P = 0.003), but not efavirenz exposure (P = 0.141). In linear regression analyses, baseline 25(OH)D as a continuous variable was inversely associated with CIMT progression in univariable (P < 0.001) and multivariable (P < 0.001) models. CONCLUSIONS: Baseline 25(OH)D was associated with CIMT progression in this relatively vitamin D replete, predominately white and male, Canadian HIV-positive population. Future research needs to establish causality as this may warrant more targeted screening or supplementation.

Antiviral activity and safety of aplaviroc, a CCR5 antagonist, in combination with lopinavir/ritonavir in HIV-infected, therapy-naïve patients: results of the EPIC study (CCR100136).

BACKGROUND: This phase IIb study explored the antiviral activity and safety of the investigational CC chemokine receptor 5 (CCR5) antagonist aplaviroc (APL) in antiretroviral-naïve patients harbouring R5- or R5X4-tropic virus. METHODS: A total of 191 patients were randomized 2:2:2:1 to one of three APL dosing regimens or to lamivudine (3TC)/zidovudine (ZDV) twice daily (bid), each in combination with lopinavir/ritonavir (LPV/r) 400 mg/100 mg bid. Efficacy, safety and pharmacokinetic parameters were assessed. RESULTS: This study was terminated prematurely because of APL-associated idiosyncratic hepatotoxicity. A total of 141 patients initiated treatment early enough to have been able to complete 12 weeks on treatment [modified intent-to-treat (M-ITT) population]; of these, 133 completed the 12-week treatment phase. The proportion of subjects in the M-ITT population with HIV-1 RNA <400 copies/mL at week 12 was 50, 48, 54 and 75% in the APL 200 mg bid, APL 400 mg bid, APL 800 mg once a day (qd) and 3TC/ZDV arms, respectively. Similar responses were seen in the few subjects harbouring R5X4-tropic virus (n=17). Common clinical adverse events (AEs) were diarrhoea, nausea, fatigue and headache. APL demonstrated nonlinear pharmacokinetics with high interpatient variability. CONCLUSIONS: While target plasma concentrations of APL were achieved, the antiviral activity of APL+LPV/r did not appear to be comparable to that of 3TC/ZDV+LPV/r.

Asymptomatic bacteriuria and symptomatic urinary tract infections in pregnancy.

Symptomatic and asymptomatic bacteriuria is common in pregnant women. A history of previous urinary tract infections and low socioeconomic status are risk factors for bacteriuria in pregnancy. Escherichia coli is the most common aetiologic agent in both symptomatic and asymptomatic infection and quantitative culture is the gold standard for diagnosis. Treatment of asymptomatic bacteriuria has been shown to reduce the rate of pyelonephritis in pregnancy and therefore screening for and treatment of asymptomatic bacteriuria has become a standard of obstetrical care. Antibiotic treatment of asymptomatic bacteriuria is associated with a decrease in the incidence of low birth weight, but the methodological quality of the studies limits the strength of the conclusions that can be drawn. Debate exists in the literature as to whether treated pyelonephritis is associated with adverse fetal outcomes. There is no clear consensus in the literature on antibiotic choice or duration of therapy for infection. With increasing antibiotic resistance, consideration of local resistance rates is necessary when choosing therapy.

A large prospective study assessing injection site reactions, quality of life and preference in patients using the Biojector vs standard needles for enfuvirtide administration.

OBJECTIVES: To determine the severity of injection site reactions (ISRs), patient quality of life (QoL) and preference when enfuvirtide is administered by the Biojector (Bioject, Medical Technologies, Inc., Tualatin, OR, USA) relative to standard needles. METHODS: A total of 201 HIV-positive patients on stable enfuvirtide-based therapy (n=184) or initiating such therapy (n=17) were evaluated prospectively after switching from standard needles to the Biojector system. Patients used needles for a minimum of 2 weeks prior to switching to the Biojector. Questionnaires to assess the incidence and severity of ISRs (31-item score) and QoL [Medical Outcomes Study HIV Health Survey (MOS-HIV)] were administered at baseline and following a minimum of 14 days of Biojector use. RESULTS: The median changes in ISR score and number of ISRs following a median of 1.0 month [interquartile range (IQR) 0.9, 1.3] of Biojector use were -3 (IQR -7, 1) and -1 (IQR -3, 1), respectively. The severity of pain (P<0.0001), induration (P<0.0001), pruritus (P<0.0001), nodules (P<0.0001) and erythema (P<0.0001) all decreased with the Biojector. Administration of enfuvirtide with the Biojector was associated with an improved patient QoL (P<0.0001), and was preferred by 72% of patients. CONCLUSIONS: Compared with needles, the Biojector was associated with a decreased severity of ISRs and improved QoL in patients taking enfuvirtide.

Antibiotics for asymptomatic bacteriuria in pregnancy.

BACKGROUND: Asymptomatic bacteriuria occurs in 2% to 10% of pregnancies and, if not treated, up to 30% of mothers will develop acute pyelonephritis. Asymptomatic bacteriuria has been associated with low birthweight and preterm delivery. OBJECTIVES: To assess the effect of antibiotic treatment for asymptomatic bacteriuria on persistent bacteriuria during pregnancy, the development of pyelonephritis and the risk of low birthweight and preterm delivery. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (January 2007). SELECTION CRITERIA: Randomized trials comparing antibiotic treatment with placebo or no treatment in pregnant women with asymptomatic bacteriuria found on antenatal screening. DATA COLLECTION AND ANALYSIS: We assessed trial quality. MAIN RESULTS: Fourteen studies were included. Overall the study quality was poor. Antibiotic treatment compared to placebo or no treatment was effective in clearing asymptomatic bacteriuria (risk ratio (RR) 0.25, 95% confidence interval (CI) 0.14 to 0.48). The incidence of pyelonephritis was reduced (RR 0.23, 95% CI 0.13 to 0.41). Antibiotic treatment was also associated with a reduction in the incidence of low birthweight babies (RR 0.66, 95% CI 0.49 to 0.89) but a difference in preterm delivery was not seen. AUTHORS' CONCLUSIONS: Antibiotic treatment is effective in reducing the risk of pyelonephritis in pregnancy. A reduction in low birthweight is consistent with current theories about the role of infection in adverse pregnancy outcomes, but this association should be interpreted with caution given the poor quality of the included studies.

Occult hepatitis B virus infection in the setting of hepatitis C virus (HCV) and human immunodeficiency virus (HIV) co-infection: clinically relevant or a diagnostic problem?

The clinical relevance of occult hepatitis B virus (HBV) infection, defined as detectable HBV DNA serum/liver, in the absence of hepatitis B surface antigen (HBsAg), is unclear. We determined the prevalence of serum occult HBV infection in HIV/HCV co-infected patients enrolled in APRICOT, a randomized multinational trial that investigated the efficacy and safety of peginterferon alfa-2a (40 kDa) plus ribavirin for treatment of HCV. We also examined the effect of prior HBV exposure to liver histology at baseline. Only HBsAg-negative patients were eligible. At screening, serum HBV DNA was assessed by commercial assay (detection limit = 200 copies/mL). Patients were divided into four serological groups: anti-HBs+/anti-HBc+; anti-HBs-/anti-HBc+; anti-HBs+/ anti-HBc-; anti-HBs-/anti-HBc-. Baseline liver biopsy grade and stage were compared among groups. Serum HBV DNA was undetectable in all patients, (n = 866). Results of anti-HBs and anti-HBc was available for 176 patients: 60 (34.1%) anti-HBs+/anti-HBc+; 60 (34.1%) anti-HBs-/anti-HBc+; 11 (6.3%) anti-HBs+/anti-HBc-; 45 (25.6%) anti-HBs-/anti-HBc-. There were no differences among the groups in the histological grade or stage at baseline liver biopsies. Occult HBV infection in serum was not detected in this large immunocompetent cohort. Moreover, prior exposure to HBV did not appear to have any affect on baseline liver histology.

Assay of HIV gp41 amino acid sequence to identify baseline variation and mutation development in patients with virologic failure on enfuvirtide.

In this study, we retrospectively assessed a gp41 genotypic assay in 404 enfuvirtide-naïve individuals (340 clade B, 64 non-B clade) to determine the prevalence of baseline polymorphisms and in 41 patients virologically failing enfuvirtide to determine correlates of resistance to this agent. Conserved and polymorphic regions of gp41 were identified in clade B isolates, with 127 of 328 codons (38.7%) being highly conserved (<1.0% variation) and 74 of 328 codons (22.6%) being partially conserved (1.0-5.0% variation). Polymorphisms were observed throughout gp41 in non-B clade virus sequences compared to the clade B reference strain, ranging from 53 natural substitutions in clade D to 76 in clade A. Insertions were common at positions 3, 105, 215 and 276. In the patients failing enfuvirtide, mutations were detected in the 10 amino acid region at positions 36-45 in all plasma virus sequences. Six additional mutations were selected outside of the common region which may be clinically significant at positions 33, 73, 75, 126, and 138. Two or three mutations at positions 36-45 were observed in the majority of plasma virus sequences from patients with virologic failure following the use of enfuvirtide. Further study is required to determine the clinical relevance of the clade related polymorphisms and the new mutations identified in the patients with virologic failure.

A community randomized controlled clinical trial of mixed carotenoids and micronutrient supplementation of patients with acquired immunodeficiency syndrome.

OBJECTIVE: This clinical trial aims to evaluate if natural mixed carotenoids supplementation can improve the health and survival of acquired immunodeficiency syndrome (AIDS) patients. DESIGN: A placebo-controlled, prospective, randomized, double-blind, multicenter clinical trial. SETTING: Community, tertiary care human immunodeficiency virus (HIV) clinics of the Canadian HIV Trials Network (CTN). PARTICIPANTS: Three hundred and thirty-one adults with advanced AIDS on conventional management were recruited during routine clinic visits. INTERVENTIONS: All participants, including 166 controls, received daily oral specially formulated multivitamins including vitamin A and trace elements; 165 treatment group participants received additional daily oral natural mixed carotenoids, equivalent to 120,000 IU (72 mg) of beta-carotene daily. Follow-up was quarterly at routine clinic visits. RESULTS: Mean (s.d.) follow-up was for 13 (6) months. Thirty-six participants died by 18 months. Serum carotene concentration <1.0 micromol/l was present in 16% participants at baseline. Despite variation in carotene content of the treatment medication, serum carotene concentrations increased significantly to twice the baseline levels to 18 months follow-up in participants who received carotenoids treatment compared with controls (P < 0.0001). Although not statistically significant, mortality was increased in participants who did not receive carotenoids treatment compared with those who did (HR time to death 1.76, 95% CI 0.89, 3.47, P = 0.11). In multivariate analysis, survival was significantly and independently improved in those with higher baseline serum carotene concentrations (P = 0.04) or higher baseline CD4 T-lymphocyte counts (P = 0.005). Adjusted mortality was also significantly and independently increased in those who did not receive carotenoids treatment compared with those who did (HR time to death 3.15, 95% CI 1.10, 8.98, P = 0.03). CONCLUSIONS: Low serum carotene concentration is common in AIDS patients and predicts death. Supplementation with micronutrients and natural mixed carotenoids may improve survival by correction of a micronutrient deficiency. Further studies are needed to corroborate findings and elucidate mechanism of action.

Antibiotic regimens for endometritis after delivery.

BACKGROUND: Postpartum endometritis, which is more common after cesarean section, occurs when vaginal organisms invade the endometrial cavity during labor and birth. Antibiotic treatment is warranted. OBJECTIVES: The effect of different antibiotic regimens for the treatment of postpartum endometritis on failure of therapy and complications was systematically reviewed. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group's trials register (30 January 2004). SELECTION CRITERIA: Randomized trials of different antibiotic regimens for postpartum endometritis, after cesarean section or vaginal birth, where outcomes of treatment failure or complications were reported were selected. DATA COLLECTION AND ANALYSIS: We abstracted data independently and made comparisons between different types of antibiotic regimen based on type of antibiotic and duration and route of administration. Summary relative risks were calculated. MAIN RESULTS: Thirty-eight trials with 3983 participants were included. Fifteen studies comparing clindamycin and an aminoglycoside with another regimen showed more treatment failures with the other regimen (relative risk (RR) 1.44; 95% confidence interval (CI) 1.15 to 1.80). Failures of those regimens with poor activity against penicillin resistant anaerobic bacteria were more likely (RR 1.94; 95% CI 1.38 to 2.72). In three studies that compared continued oral antibiotic therapy after intravenous therapy with no oral therapy, no differences were found in recurrent endometritis or other outcomes. In four studies comparing once daily with thrice daily dosing of gentamicin there were fewer failures with once daily dosing. There was no evidence of difference in incidence of allergic reactions. Cephalosporins were associated with less diarrhea. REVIEWERS' CONCLUSIONS: The combination of gentamicin and clindamycin is appropriate for the treatment of endometritis. Regimens with activity against penicillin- resistant anaerobic bacteria are better than those without. There is no evidence that any one regimen is associated with fewer side effects. Once uncomplicated endometritis has clinically improved with intravenous therapy, oral therapy is not needed.

Multilaboratory comparison of proficiencies in susceptibility testing of Helicobacter pylori and correlation between agar dilution and E test methods.

Susceptibility testing was performed at seven Canadian microbiology laboratories and the Helicobacter Reference Laboratory, Halifax, Nova Scotia, Canada, to assess susceptibility testing proficiency and the reproducibility of the results for clarithromycin and metronidazole and to compare the Epsilometer test (E test) method to the agar dilution reference method. Control strain Helicobacter pylori ATCC 43504 (American Type Culture Collection) and 13 clinical isolates (plus duplicates of four of these strains including ATCC 43504) were tested blindly. The National Committee for Clinical Laboratory Standards (NCCLS) guidelines for agar dilution testing were followed, and the same suspension of organisms was used for agar dilution and E test. Antimicrobials and E test strips were provided to the investigators. Methods were provided on a website (www.Helicobactercanada.org). Each center reported MICs within the stated range for strain ATCC 43504. Compared to the average MICs, interlaboratory agreements within 2 log(2) dilutions were 90% (range, 69 to 100%) for clarithromycin by agar dilution, with seven very major errors [VMEs], and 85% (range, 65 to 100%) by E test, with three VMEs. Interlaboratory agreements within 2 log(2) dilutions were 83% (range, 50 to 100%) for metronidazole by agar dilution, with six VMEs and eight major errors (MEs), and 75% (range, 50 to 94%) by E test, with four VMEs and four MEs. At lower and higher concentrations of antibiotic, E test MICs were slightly different from agar dilution MICs, but these differences did not result in errors. When a standardized protocol based on NCCLS guidelines was used, most participants in this study correctly identified clarithromycin- and metronidazole-susceptible and -resistant strains of H. pylori 93% of the time by either the agar dilution or E test method, and the numbers of errors were relatively equivalent by both methods.

Antibiotic prophylaxis for cesarean section.

BACKGROUND: The single most important risk factor for postpartum maternal infection is cesarean delivery. OBJECTIVES: The objective of this review was to assess the effects of prophylactic antibiotic treatment on infectious complications in women undergoing cesarean delivery. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group trials register (January 2002) and the Cochrane Controlled Trials Register (The Cochrane Library, Issue 4, 2001). SELECTION CRITERIA: Randomized trials comparing antibiotic prophylaxis or no treatment for both elective and non-elective cesarean section. DATA COLLECTION AND ANALYSIS: Two reviewers assessed trial quality and extracted data. MAIN RESULTS: Eighty-one trials were included. Use of prophylactic antibiotics in women undergoing cesarean section substantially reduced the incidence of episodes of fever, endometritis, wound infection, urinary tract infection and serious infection after cesarean section. The reduction in the risk of endometritis with antibiotics was similar across different patient groups: the relative risk (RR) for endometritis for elective cesarean section (number of women = 2037) was 0.38 (95% confidence interval (CI) 0.22 to 0.64); the RR for non-elective cesarean section (n = 2132) was 0.39 (95% CI 0.34 to 0.46); and the RR for all patients (n = 11,937) was 0.39 (95% CI 0.31 to 0.43). Wound infections were also reduced: for elective cesarean section (n = 2015) RR 0.73 (95% CI 0.53 to 0.99); for non-elective cesarean section (n = 2780) RR 0.36 95% CI 0.26 to 0.51]; and for all patients (n = 11,142) RR 0.41 (95% CI 0.29 to 0.43). REVIEWER'S CONCLUSIONS: The reduction of endometritis by two thirds to three quarters and a decrease in wound infections justifies a policy of recommending prophylactic antibiotics to women undergoing elective or non-elective cesarean section.

Antibiotic regimens for management of intraamniotic infection.

BACKGROUND: Intraamniotic infection is associated with maternal morbidity and neonatal sepsis, pneumonia and death. Although antibiotic treatment is accepted as the standard of care, few studies have been conducted to examine the effectiveness of different antibiotic regimens for this infection and whether to administer antibiotics intrapartum or postpartum. OBJECTIVES: To study the effects of different maternal antibiotic regimens for intraamniotic infection on maternal and perinatal morbidity and mortality. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group trials register (May 2002) and the Cochrane Controlled Trials Register (The Cochrane Library, Issue 2, 2002). SELECTION CRITERIA: Trials where there was a randomized comparison of different antibiotic regimens to treat women with a diagnosis of intraamniotic infection were included. The primary outcome was perinatal morbidity. DATA COLLECTION AND ANALYSIS: Data were extracted from each publication independently by the authors. MAIN RESULTS: Two eligible trials (181 women) were included in this review. No trials were identified that compared antibiotic treatment with no treatment. Intrapartum treatment with antibiotics for intraamniotic infection was associated with a reduction in neonatal sepsis (relative risk (RR) 0.08; 95% confidence interval (CI) 0.00, 1.44) and pneumonia (RR 0.15; CI 0.01, 2.92) compared with treatment given immediately postpartum, but these results did not reach statistical significance (number of women studied = 45). There was no difference in the incidence of maternal bacteremia (RR 2.19; CI 0.25, 19.48). There was no difference in the outcomes of neonatal sepsis (RR 2.16; CI 0.20, 23.21) or neonatal death (RR 0.72; CI 0.12, 4.16) between a regimen with and without anaerobic activity (number of women studied = 133). There was a trend towards a decrease in the incidence of post-partum endometritis in women who received treatment with ampicillin, gentamicin and clindamycin compared with ampicillin and gentamicin alone, but this did not reach statistical significance (RR 0.54; CI 0.19, 1.49). REVIEWER'S CONCLUSIONS: The conclusions that can be drawn from this meta-analysis are limited due to the small number of studies. For none of the outcomes was a statistically significant difference seen between the different interventions. Current consensus is for the intrapartum administration of antibiotics when the diagnosis of intraamniotic infection is made; however, the results of this review neither support nor refute this although there was a trend towards improved neonatal outcomes when antibiotics were administered intrapartum. No recommendations can be made on the most appropriate antimicrobial regimen to choose to treat intraamniotic infection.

Antibiotic regimens for endometritis after delivery.

BACKGROUND: Post-partum endometritis, which is more common after cesarean section, occurs when vaginal organisms invade the endometrial cavity during labour and birth. Antibiotic treatment is warranted. OBJECTIVES: The effect of different antibiotic regimens for the treatment of postpartum endometritis on failure of therapy and complications was systematically reviewed. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group's trials register and the Cochrane Controlled Trials Register. Date of last search: June 2001. SELECTION CRITERIA: Randomised trials of different antibiotic regimens for postpartum endometritis, after cesarean section or vaginal birth, where outcomes of treatment failure or complications were reported were selected. DATA COLLECTION AND ANALYSIS: Data were abstracted independently by the reviewers. Comparisons were made between different types of antibiotic regimen, based on type of antibiotic and duration and route of administration. Summary relative risks were calculated. MAIN RESULTS: Forty-seven trials were included. Overall the studies were methodologically poor. In the intent-to-treat analysis, fifteen studies comparing clindamycin and an aminoglycoside with another regimen showed more treatment failures with another regimen (relative risk (RR) 1.32; 95% confidence interval (CI) 1.09-1.60). Failures of those regimens with poor activity against penicillin resistant anaerobic bacteria were more likely (RR 1.53; 95% CI 1.10-2.13). In four studies that compared continued oral antibiotic therapy after intravenous therapy, no differences were found in recurrent endometritis or other outcomes. There was no evidence of difference in incidence of allergic reactions. Cephalosporins were associated with less diarrhea. REVIEWER'S CONCLUSIONS: The combination of gentamicin and clindamycin is appropriate for the treatment of endometritis. Regimens with activity against penicillin resistant anaerobic bacteria are better than those without. There is no evidence that any one regimen is associated with fewer side effects. Once uncomplicated endometritis has clinically improved with intravenous therapy, oral therapy is not needed.

Antibiotics for asymptomatic bacteriuria in pregnancy.

BACKGROUND: Up to 30% of mothers develop acute pyelonephritis if asymptomatic bacteriuria is untreated. Asymptomatic bacteriuria may have a role in preterm birth or it may be a marker for low socioeconomic status which is associated with low birth weight. OBJECTIVES: The objective of this review was to assess the effect of antibiotic treatment for asymptomatic bacteriuria on persistent bacteriuria during pregnancy, the risk of preterm delivery, and the development of pyelonephritis. SEARCH STRATEGY: I searched the Cochrane Pregnancy and Childbirth Group trials register. Date of last search: December 2000. SELECTION CRITERIA: Randomised trials comparing antibiotic treatment with placebo or no treatment in pregnant women with asymptomatic bacteriuria found on antenatal screening. DATA COLLECTION AND ANALYSIS: Trial quality was assessed. MAIN RESULTS: Fourteen studies were included. Overall the study quality was not strong. Antibiotic treatment compared to placebo or no treatment was effective in clearing asymptomatic bacteriuria (odds ratio 0.07, 95% confidence interval 0.05 to 0.10). The incidence of pyelonephritis was reduced (odds ratio 0.24, 95% confidence interval 0.19 to 0.32). Antibiotic treatment was also associated with a reduction in the incidence of preterm delivery or low birth weight babies (odds ratio 0.60, 95% confidence interval 0.45 to 0.80). REVIEWER'S CONCLUSIONS: Antibiotic treatment is effective in reducing the risk of pyelonephritis in pregnancy. An apparent reduction in preterm delivery is consistent with current theories about the role of infection in preterm birth, but this association should be interpreted with caution.

Implications of antibiotic resistance in the management of Helicobacter pylori infection: Canadian Helicobacter Study Group.

Eradication of Helicobacter pylori from the gastric and duodenal mucosa is an important clinical goal in the treatment of infected patients with peptic ulcer disease and other H pylori-associated conditions. Although several oral drug combination regimens are associated with eradication rates of approximately 85% in controlled trials, the success rate in patients infected with a resistant strain of H pylori is closer to 75%. Resistance to metronidazole and clarithromycin, which are common components of combination treatment regimens, is of greatest concern. Reported rates of H pylori resistance to various antibiotics vary considerably. In Canada, the data documenting H pylori susceptibility are limited but suggest that resistance to these antibiotics varies geographically and within specific treatment groups. Although susceptibility testing is not a prerequisite for initial treatment of individual patients infected with H pylori, formal efforts to identify and monitor both the causes and prevalence of antibiotic resistance across Canada are a much needed step in the ongoing management of this important infection. Recommended treatment regimens may be useful, even for treating apparently resistant H pylori strains. However, it is important to understand the mechanisms of the development of resistant strains to manage patients with treatment failure better.

Antibiotic susceptibility and resistance testing: an overview.

The results of in vitro antibiotic susceptibility testing can predict the clinical response to treatment and guide the selection of antibiotics. The minimum inhibitory concentration (MIC) of an organism is the lowest concentration of an antibiotic that will inhibit its growth. Bacteria are classified as sensitive, intermediate or resistant based on breakpoint MIC values that are arbitrarily defined and reflect the achievable levels of the antibiotic, the distribution of MICs for the organism and their correlation with clinical outcome. Broth dilution, agar dilution and gradient diffusion (the 'E test'), where twofold serial dilutions of antibiotic are incorporated into tubes of broth, agar plates or on a paper strip, respectively, are different methods to measure the MIC of an organism. The disk diffusion method defines an organism as sensitive or resistant based on the extent of its growth around an antibiotic-containing disk. MIC values are influenced by several laboratory factors. To ensure reproducible results, the laboratory must closely follow methods developed by the National Committee for Clinical Laboratory Standards, which defines standard growth media, incubation temperature and environment, the inoculum and quality control parameters.

An outbreak of influenza A in a neonatal intensive care unit.

OBJECTIVES: Investigation of an outbreak of influenza A in a neonatal intensive care unit (NICU) with examination of risk factors for infection and outcomes. DESIGN: Retrospective cohort study of infants admitted to the unit during the outbreak period. Prospective survey of NICU staff and mothers of infants in the cohort study. SETTING: Level III nursery in a university-affiliated tertiary referral center. RESULTS: Nineteen infants in the NICU were infected with influenza A There were six symptomatic cases and one death who had evidence of virus-associated hemophagocytic syndrome at autopsy. Amantadine prophylaxis was offered to the NICU staff, and amantadine therapy was given to five of the six symptomatic infants. Mechanical ventilation, gestational age, birth weight, Clinical Risk Index for Babies score, and twin pregnancy were associated with acquisition of influenza A on univariate analysis. Mechanical ventilation (odds ratio [OR], 6.2; P=.02) and twin pregnancy (OR, 7.0; P=.04) remained as significant risk factors for infection on multiple logistic regression analysis. Only 15% of respondents to the NICU staff survey were vaccinated against influenza. There was no association between a history of an influenza-like illness during pregnancy and acquisition of influenza A by infants of mothers who responded to the maternal survey (OR, 0.91; P=1.0). CONCLUSIONS: Influenza A is an important pathogen in the neonatal population and is readily transmissible in the NICU setting.

Factors contributing to the lack of human immunodeficiency virus type 1 (HIV-1) transmission in HIV-1-discordant partners.

Correlates of resistance to infection by human immunodeficiency virus type 1 (HIV-1) are important for defining potential therapeutic interventions and for prophylactic vaccination. In this study, 11 couples discordant in their HIV-1 infection status were prospectively evaluated for the presence of protective factors. Behavioral characteristics of all subjects entailed a high risk of transmission. Cytotoxic T lymphocyte (CTL) responses against viruses isolated from the infected partner, and against laboratory virus isolates, were detected in 5 (45%) of 11 HIV-negative partners, including a CCR5Delta32-homozygous and a heterozygous subject. No CTL responses were observed in 6 control unexposed subjects. Marked variation in lymphocyte susceptibility to viral infection was noted. Resistance attributable to major histocompatibility complex discordance or anti-major histocompatibility complex antibodies was not identified. These results suggest that a combination of factors, including cellular immunity, viral characteristics, and coreceptor integrity, may be involved in the persistent nontransmission of HIV.

Intrapartum antibiotics for group B streptococcal colonisation.

BACKGROUND: Group B streptococcal infection is common in pregnant women without causing harm. However it is also a significant cause of neonatal morbidity and mortality. OBJECTIVES: The objective of this review was to assess the effects of intrapartum administration of antibiotics to women on infant colonization with group B streptococcus, early onset neonatal group B streptococcus sepsis and neonatal death from infection. SEARCH STRATEGY: The Cochrane Pregnancy and Childbirth Group trials register was searched. SELECTION CRITERIA: Controlled trials of pregnant women colonized with group B streptococcus comparing intrapartum antibiotic administration with no treatment, and providing data on infant colonization with group B streptococcus and/or neonatal infection. DATA COLLECTION AND ANALYSIS: Eligibility and trial quality assessment were done by one reviewer. MAIN RESULTS: Five trials were included. Overall quality was poor, with potential selection bias in all the identified studies. Intrapartum antibiotic treatment reduced the rate of infant colonization (odds ratio 0.10, 95% confidence interval 0.07 to 0.14) and early onset neonatal infection with group B streptococcus (odds ratio 0.17, 95% confidence interval 0.07 to 0. 39). A difference in neonatal mortality was not seen (odds ratio 0. 12, 95% confidence interval 0.01 to 2.00). REVIEWER'S CONCLUSIONS: Intrapartum antibiotic treatment of women colonized with group B streptococcus appears to reduce neonatal infection. Effective strategies to detect maternal colonization with group B streptococcus and better data on maternal risk factors for neonatal group B streptococcus infection in different populations are required.