Differential impact of lactose/lactase phenotype on colonic microflora

BACKGROUND:

The ability to digest lactose divides the world’s population into two phenotypes that may be risk variability markers for several diseases. Prebiotic effects likely favour lactose maldigesters who experience lactose spilling into their colon.

OBJECTIVE:

To evaluate the effects of fixed-dose lactose solutions on fecal bifidobacteria and lactobacilli in digesters and maldigesters, and to determine whether the concept of a difference in ability to digest lactose is supported.

METHODS:

A four-week study was performed in 23 lactose mal-digesters and 18 digesters. Following two weeks of dairy food withdrawal, subjects ingested 25 g of lactose twice a day for two weeks. Stool bifidobacteria and lactobacilli counts pre- and postintervention were measured as the primary outcome. For secondary outcomes, total anaerobes, Enterobacteriaceae, beta-galactosidase and N-acetyl-beta-D-glucosaminidase activity in stool, as well as breath hydrogen and symptoms following lactose challenge tests, were measured.

RESULTS:

Lactose maldigesters had a mean change difference (0.72 log₁₀ colony forming units/g stool; P=0.04) in bifidobacteria counts compared with lactose digesters. Lactobacilli counts were increased, but not significantly. Nevertheless, reduced breath hydrogen after lactose ingestion correlated with lactobacilli (r=−0.5; P<0.001). Reduced total breath hydrogen and symptom scores together, with a rise in fecal enzymes after intervention, were appropriate, but not significant.

CONCLUSIONS:

Despite failure to achieve full colonic adaptation, the present study provided evidence for a differential impact of lactose on microflora depending on genetic lactase status. A prebiotic effect was evident in lactose maldigesters but not in lactose digesters. This may play a role in modifying the mechanisms of certain disease risks related to dairy food consumption between the two phenotypes.     

Adult lactose digestion status and effects on disease

BACKGROUND:

Adult assimilation of lactose divides humans into dominant lactase-persistent and recessive nonpersistent phenotypes.

OBJECTIVES:

To review three medical parameters of lactose digestion, namely: the changing concept of lactose intolerance; the possible impact on diseases of microbial adaptation in lactase-nonpersistent populations; and the possibility that the evolution of lactase has influenced some disease pattern distributions.

METHODS:

A PubMed, Google Scholar and manual review of articles were used to provide a narrative review of the topic.

RESULTS:

The concept of lactose intolerance is changing and merging with food intolerances. Microbial adaptation to regular lactose consumption in lactase-nonpersistent individuals is supported by limited evidence. There is evidence suggestive of a relationship among geographical distributions of latitude, sunhine exposure and lactase proportional distributions worldwide.

DISCUSSION:

The definition of lactose intolerance has shifted away from association with lactose maldigestion. Lactose sensitivity is described equally in lactose digesters and maldigesters. The important medical consequence of withholding dairy foods could have a detrimental impact on several diseases; in addition, microbial adaptation in lactase-nonpersistent populations may alter risk for some diseases. There is suggestive evidence that the emergence of lactase persistence, together with human migrations before and after the emergence of lactase persistence, have impacted modern-day diseases.

CONCLUSIONS:

Lactose maldigestion and lactose intolerance are not synonymous. Withholding dairy foods is a poor method to treat lactose intolerance. Further epidemiological work could shed light on the possible effects of microbial adaptation in lactose maldigesters. The evolutionary impact of lactase may be still ongoing.     

Prevalence of abnormal lactose breath hydrogen tests in children with functional abdominal pain

Objectives

The study was undertaken to determine the prevalence of abnormal lactose breath hydrogen test in children with non-organic chronic abdominal pain.

Methods

Children with chronic abdominal pain were examined and investigated for organic causes. All children without a known organic cause underwent lactose and glucose breath hydrogen test. After a standard dose of 2 g/kg of lactose to a maximum of 50 g, hydrogen in breath was measured at 15 min intervals for 3 h. A rise of 20 ppm above baseline was considered suggestive of lactose malabsorption.

Results

Of 108 children screened, organic causes were found in 46 children. Sixty-two patients without any organic cause underwent hydrogen breath test. Lactose hydrogen breath test (HBT) was positive in 36 of 62 (58%), while 11 (17%) had positive HBT with glucose suggestive of small intestinal bacterial overgrowth (SIBO). Twenty out of 34 (59%) improved on lactose free diet while 8 out of 11 (72%) children of SIBO improved on antibiotics.

Conclusions

Lactose malabsorption was seen in 58% of children with non-organic chronic abdominal pain.

     

Prevalence of lactose maldigestion

Ninety-eight adults ranging from 20 to 89 years in age (52 blacks, 46 whites; 48 males, 50 females) were tested for lactose maldigestion by breath hydrogen analysis after consuming milk containing 16.5 g lactose (360 ml milk). Older adults (50 years) displayed a significantly higher incidence (46%) of lactose maldigestion than younger adults (<50 years, 26%). In younger adults there were 2.4 times more maldigesters in blacks than in whites, while in older groups this ratio was 3.6. Level of breath hydrogen significantly increased with age up to the age group of 60–69 years. The interaction between age groups and race was highly significant. Of the maldigesters, 63% reported symptoms and 3% of the total sample reported severe symptoms. Results of this study indicate that the prevalance of lactose maldigestion significantly increases with age in blacks compared to whites and that the magnitude of the problem may be greater in black maldigesters than in white maldigesters.     

Inverse Dose Effect of Pretest Dietary Lactose Intake on Breath Hydrogen Results and Symptoms in Lactase Nonpersistent Subjects

The aim of this study was to determine a relationship between pretest intake of lactose and outcome of lactose breath hydrogen test. Patients presented at a testing laboratory participated in the study. A 3-hour breath hydrogen, 50-g lactose challenge was carried out. Results were tabulated and patients completed a 3-day recall diet questionnaire. Daily lactose intake was independently calculated and was associated with breath hydrogen and total symptom score. Statistical analysis used Spearman's correlation, Mann-Whitney U-test and χ² or Fisher exact test. Of 118 patients, 50% were lactose maldigesters. In these patients, measured breath hydrogen and symptom scores were significantly higher in the lowest intake group (< 5 g/d) than in the highest intake group (> 20 g/d) (P < .05). In the presumed lactose digesters, 59% experienced some symptoms during testing for unclear reasons. Pretest dietary intake of lactose inversely affects results of breath hydrogen.     

Persistent sputum cellularity and neutrophils may predict bronchiectasis

BACKGROUND:

Quantitative cell counts in sputum provide an accurate assessment of the type and severity of bronchitis.

OBJECTIVE:

To examine whether sputum cell counts could identify bronchiectasis in patients with recurrent bronchitis.

METHODS:

A retrospective survey of a clinical database (January 2004 to January 2005) of quantitative cell counts from sputum selected from expectorate in patients with obstructive airways diseases was used to identify predictors of bronchiectasis using ROC curves. This was prospectively evaluated (February 2005 to April 2008) using high-resolution computed tomography scans of thorax that were independently scored by a radiologist who was blinded to the clinical details.

RESULTS:

The retrospective survey identified 41 patients with bronchiectasis among 490 patients with airway diseases. Total cell count of 60×10⁶/g or greater of the selected sputum with predominant neutrophils on two occasions had a sensitivity of 86.7%, a specificity of 87.5%, and positive and negative predictive values of 93% and 78%, respectively, to identify bronchiectasis. In the prospective study, 10 of 14 (71%) patients who met these criteria were identified to have bronchiectasis. Both total cell count and the percentage of neutrophils correlated with radiographic bronchiectasis severity.

CONCLUSIONS:

Persistent or recurrent intense sputum cellularity with neutrophilia is suggestive of bronchiectasis.     

Helicobacter pylori infection: Is sequential therapy superior to standard triple therapy? A single-centre Italian study in treatment-naive and non-treatment-naive patients

BACKGROUND:

Clarithromycin resistance has decreased the eradication rates of Helicobacter pylori.

AIMS:

To determine whether a 10-day course of sequential therapy (ST) is more effective at eradicating H pylori infection than triple therapy (TT) in the first or second line, and to assess side effects and compliance with therapy.

METHODS:

One hundred sixty treatment-naive and 40 non-treatment-naive patients who were positive for H pylori infection by ¹³C-urea breath test or endoscopy were enrolled. Eighty of 160 patients underwent TT, while 80 of 160 underwent ST with omeprazole (20 mg) plus amoxicillin (1 g) twice/day for five days, followed by omeprazole (20 mg) with tinidazole (500 mg) twice/day and clarithromycin (500 mg) twice/day for five consecutive days. H pylori eradication was evaluated by ¹³C-urea breath test no sooner than four weeks after the end of treatment.

RESULTS:

Eradication was achieved in 59 of 80 treatment-naive patients treated with TT (74%), in 74 of 80 patients treated with ST (93%), and in 38 of 40 non-treatment-naive patients (95%). Eradication rates in treatment-naive patients with ST were statistically significantly higher than TT (92.5% versus 73.7%; P=0.0015; OR 4.39 [95% CI 1.66 to 11.58]). Mild adverse effects were reported for both regimens.

CONCLUSIONS:

ST appears to be a well-tolerated, promising therapy; however, randomized controlled trials with larger and more diverse sample populations are needed before it can be recommended as a first-line treatment.     

A kit to facilitate and standardize the processing of sputum for measurements of airway inflammation

BACKGROUND:

The use of inflammometry has been shown to be effective for managing asthma. However, sputum processing can be time consuming. Furthermore, methods of sputum processing can vary among facilities. To help with standardization and to simplify the procedure for laboratory staff, a novel, commercially available processing device (Accufilter, Cellometrics Inc, Canada) has been developed.

OBJECTIVE:

To assess the validity of the Accufilter device and kit for recovery of treated specimens, and for quantitative sputum inflammatory cell counts by comparing intrasample measurements with those using the same procedure without the Accufilter device and kit.

METHODS:

The present study was a wet laboratory comparison of induced sputum cell counts obtained from sputum processed with versus without the device and kit. Comparisons of each sputum specimen were performed by the same technologist in random order.

RESULTS:

A total of 39 samples were processed using both the standard method and the Accufilter device. The intraclass correlation coefficients were high for the weight of the filtrate, and for eosinophil and neutrophil differential counts.

CONCLUSION:

A good degree of agreement of results was apparent when the two methods were compared. The differences noted between both methods were minimal and did not modify clinical interpretation. The use of the Accufilter device and kit can be used in place of the standard method for sputum quantitative analysis, especially in centres with large sample loads.     

Heterogeneity of bronchitis in airway diseases in tertiary care clinical practice

BACKGROUND:

Sputum cell counts have identified inflammatory subtypes of bronchitis in relatively small numbers of subjects with asthma, chronic obstructive pulmonary disease (COPD) and chronic cough in research studies. The prevalence of different subtypes of bronchitis in routine clinical practice, however, has not been reported.

OBJECTIVE:

To examine the heterogeneity of bronchitis and its relationship to the severity of airflow obstruction.

METHODS:

A retrospective cross-sectional survey based on a computerized database of spontaneous or induced sputum cell counts examined in a large university tertiary respiratory outpatient clinic.

RESULTS:

The database contained 4232 consecutive sputum records from 2443 patients with chronic cough (39%), asthma (37%), asthma with COPD (9%), COPD (13%) and bronchiectasis (3%). Total and differential cell counts were obtained from 86% of successful sputum samples. Induced sputum provided more viable samples than spontaneous expectorate. Approximately one-third of patients with asthma and one-fifth of patients with COPD experience eosinophilic bronchitis. Asthmatic patients with moderate to severe airflow obstruction had a greater number of sputum eosinophils. There was a significantly higher number of total cell counts and percentage of neutrophils in the sputum of COPD patients with moderate and severe airflow obstruction than in those with mild airflow obstruction.

CONCLUSION:

There is heterogeneity in the cellularity of sputum in various airway diseases. Patients with clinically stable airway diseases may have high sputum cell counts. During exacerbations, more patients may experience neutrophilic bronchitis. Severity of airflow obstruction is associated with eosinophilic bronchitis in patients with asthma, and neutrophilic bronchitis in patients with nonasthmatic COPD.     

Estimating the number of coronary artery bypass graft and percutaneous coronary intervention procedures in Canada: A comparison of cardiac registry and Canadian Institute for Health Information data sources

BACKGROUND:

Provincial cardiac registries and the Canadian Institute for Health Information (CIHI) pan-Canadian administrative databases are invaluable tools for understanding Canadian cardiovascular health and health care. Both sources are used to enumerate cardiovascular procedures performed in Canada.

OBJECTIVE:

To examine the level of agreement between provincial cardiac registry data and CIHI data regarding procedural counts for coronary artery bypass grafts (CABGs) and percutaneous coronary interventions (PCIs).

METHODS:

CIHI staff obtained CABG and PCI counts from seven provinces that, in 2004, performed these procedures and had a cardiac registry (ie, British Columbia, Alberta, Saskatchewan, Manitoba, Ontario, Nova Scotia, and Newfoundland and Labrador). Structured mail questionnaires, and e-mail and telephone follow-ups elicited information from a designated registry respondent. The CIHI derived its counts of CABG and PCI procedures by applying the geographical boundaries, procedural definitions and analytical case criteria used by the cardiac registries to CIHI inpatient and day procedure databases. Steps were taken to reduce double-counting procedures when combining results from the two CIHI databases. Two measures were calculated: the absolute difference between registry and CIHI estimates, and the per cent agreement between estimates from the two sources.

RESULTS:

All seven cardiac registries identified as eligible for the study participated. Agreement was high between the two sources for CABG (98.8%). For PCI, the level of agreement was high (97.9%) when CIHI sources were supplemented with day procedure data from Alberta.

CONCLUSIONS:

The high level of agreement between cardiac registry and CIHI administrative data should increase confidence in estimates of CABG and PCI counts derived from these sources.     

Management of Lactose Maldigestion by Consuming Milk Containing Lactobacilli

The influence of nonfermented milk containing L.acidophilus or L. bulgaricus on lactose utilization bylactose maldigesters was investigated. Nonfermentedmilks containing L. acidophilus or L. bulgaricus at 10⁸ and 10⁹ CFU/mlwere prepared using 2% low-fat milk. Lactosemaldigestion was monitored by measuring breath hydrogenat hourly intervals for 8 hr following consumption of400 ml of each diet. Nonfermented milk containing L. acidophilus B at10⁸ CFU/ml were not effective in reducingbreath hydrogen and symptoms. Nonfermented milkcontaining L. acidophilus B at 10⁹ CFU/mlonly slightly decreased breath hydrogen production; however, the symptoms weresignificantly improved. Nonfermented milks containing L.bulgaricus 449 at 10⁸ and 10⁹CFU/ml were effective in reducing breath hydrogen andsymptoms. The results for bulgaricus milk were all significant. Inthis study, L. acidophilus B and L. bulgaricus 449 werechosen because of their similar -galactosidaseactivity and bile sensitivity. L. acidophilus and L. bulgaricus are both thermophiliclactobacilli and an active transport (permease) systemis found in both species for lactose transport. Themajor factor affecting in vivo lactose digestion in thisstudy appears to be the bacterial cell wall/membranestructures. That the cell wall/membrane structures of L.acidophilus are different from those of L. bulgaricuscan be indirectly proven by the results of sonication time for maximum -galactosidase activitymeasurement. The results of this study indicate that L.bulgaricus is usually a better choice than L.acidophilus for manufacturing nonfermented milks forlactose maldigesters.     

Do we eradicate Helicobacter pylori in hospitalized patients with peptic ulcer disease?

BACKGROUND:

Helicobacter pylori infection is the most common chronic infection in humans. It is a major contributor to the cause of duodenal and gastric ulcers worldwide. Its eradication has been shown to reduce rates of H pylori-related ulcers as well as other complications such as gastric cancer.

OBJECTIVE:

To determine the rate of appropriate treatment in patients following a diagnosis of H pylori infection on biopsy during esophagoduodenoscopy for upper gastrointestinal bleeding over a four-year period at a tertiary centre in Vancouver, British Columbia. Also evaluated was the rate of eradication confirmation using the urea breath test.

METHODS:

A retrospective review of 1501 inpatients who underwent esophagoduodenoscopy for upper gastrointestinal bleeding (January 2006 to December 2010) was undertaken. Patients who were biopsy stain positive for H pylori were selected for drug review either via a provincial database (PharmaNet) or via records from patients’ family practitioners. Data were also obtained via two provincial laboratories that perform the urea breath test to determine the rates of confirmation of eradication.

RESULTS:

Ninety-eight patients had biopsy-proven H pylori. The mean (± SD) age was 56.13±17.9 years and 65 were male. Data were not available for 22 patients; the treatment rate was 52.6% (40 of 76). Of those treated, 12 patients underwent a post-treatment urea breath test for eradication confirmation.

CONCLUSION:

There was substantial discrepancy between the number of diagnosed H pylori infections and the rate of treatment as well as confirmation of eradication. Numerous approaches could be taken to improve treatment and eradication confirmation.     

Bacterial communities in neonatal feces are similar to mothers’ placentae

BACKGROUND:

The gut microbiota plays an important role in human health. It is essential to understand how the composition of the gut microbiota in neonates is established.

OBJECTIVES:

To investigate the nature of the microbial community in the first feces of newborn infants compared with the mothers’ placentae and vaginas.

METHODS:

One infant who was delivered via Cesarean section was compared with an infant who was delivered vaginally. Bar-coded pyro-sequencing of 16S ribosomal RNA genes was used to investigate the bacterial community composition and structure of each site.

RESULTS:

Neonatal feces of both infants had similar bacterial communities, and they were similar to the mother’s placenta regardless of the method of delivery. The vaginal bacterial community differed between the two mothers, but not different sites within the vagina. The bacteria in the neonatal feces and the mothers’ placentae demonstrated considerably higher diversity compared with the vaginas. The family Lactobacillaceae dominated in the vaginal samples, while the most abundant family in the fecal and placental samples was Micrococcineae.

CONCLUSIONS:

These results may provide new directions for the study of infant gut microbial formation.     

Identification and validation of nebulized aerosol devices for sputum induction

Induced sputum cell count measurement has proven reliability for evaluating airway inflammation in patients with asthma and other airway diseases. Although the use of nebulizer devices for sputum induction is commonplace, they are generally labelled as single-patient devices by the manufacturer and, therefore, cannot be used for multiple patients in large clinical sputum induction programs due to infect ion-control requirements. Accordingly, this study investigated the aerosol characteristics of alternative devices that could be used in such programs.

BACKGROUND:

Induced sputum cell counts are a noninvasive and reliable method for evaluating the presence, type and degree of airway inflammation in patients with asthma. Currently, standard nebulizer devices used for sputum induction in multiple patients are labelled as single-patient devices by the manufacturer, which conflicts with infection prevention and control requirements. As such, these devices cannot feasibly be used in a clinical sputum induction program. Therefore, there is a need to identify alternative nebulizer devices that are either disposable or labelled for multi-patient use.

OBJECTIVE:

To apply validated rigorous, scientific testing methods to identify and validate commercially available nebulizer devices appropriate for use in a clinical sputum induction program.

METHODS:

Measurement of nebulized aerosol output and size for the selected nebulizer designs followed robust International Organization for Standardization methods. Sputum induction using two of these nebulizers was successfully performed on 10 healthy adult subjects. The cytotechnologist performing sputum cell counts was blinded to the type of nebulizer used.

RESULTS:

The studied nebulizers had variable aerosol outputs. The AeroNeb Solo (Aerogen, Ireland), Omron NE-U17 (Omron, Japan) and EASYneb II (Flaem Nuova, Italy) systems were found to have similar measurements of aerosol size. There was no significant difference in induced sputum cell results between the AeroNeb Solo and EASYneb II devices.

DISCUSSION:

There is a need for rigorous, scientific evaluation of nebulizer devices for clinical applications, including sputum induction, for measurement of cell counts.

CONCLUSION:

The present study was the most comprehensive analysis of different nebulizer devices for sputum induction to measure cell counts, and provides a framework for appropriate evaluation of nebulizer devices for induced sputum testing.     

Silent ischemia: Silent after all?

OBJECTIVE:

To examine the association of nonpain symptoms in men and women with exercise-related silent ischemia, as well as the independence of these findings from other clinical factors.

METHODS:

A prospective study of 482 women and 425 men (mean age 58 years) undergoing exercise stress testing with myocardial perfusion imaging. Analyses were performed on 60 women and 155 men with no angina but medical perfusion imaging evidence of ischemia during exercise.

MEASURES:

The presence of various non-pain-related symptoms. Ischemia is indicated by myocardial perfusion defects on exercise stress testing with single photon emission computed tomography.

RESULTS:

Women reported more nonangina symptoms than men (P<0.05). They experienced fatigue, hot flushes, tense muscles, shortness of breath and headaches more frequently (P<0.05). Symptoms relating to muscle tension and diaphoresis were associated with ischemia after controlling for pertinent clinical covariates. However, the direction of association differed according to sex and history of coronary artery disease events or procedures. Sensitivity of the detection models showed modest improvements with the addition of these symptoms.

CONCLUSIONS:

While patients who experience silent ischemia experience a number of nonpain symptoms, those symptoms may not be sufficiently specific to ischemia, nor sensitive in detecting ischemia, to be of particular help to physicians in the absence of other clinical information.     

Association of Sweetened Beverage Intake with Incident Hypertension

BACKGROUND

Consumption of sugar-sweetened beverages (SSBs) is associated with an increased risk of hypertension in cross-sectional studies. However, prospective data are limited.

OBJECTIVE

To examine the associations between SSBs and artificially sweetened beverages (ASBs) with incident hypertension.

DESIGN AND SETTING

Prospective analysis using Cox proportional hazards regression to examine the association between SSBs and ASBs with incident hypertension in three large, prospective cohorts, the Nurses'' Health Studies I (n = 88,540 women) and II (n = 97,991 women) and the Health Professionals'' Follow-Up Study (n = 37,360 men).

MEASUREMENTS

Adjusted hazard ratios for incident clinically diagnosed hypertension.

RESULTS

Higher SSB and ASB intake was associated with an increased risk of developing hypertension in all three cohorts. In a pooled analysis, participants who consumed at least one SSB daily had an adjusted HR for incident hypertension of 1.13 (95 % CI, 1.09–1.17) compared with those who did not consume SSBs; for persons who drank at least one ASB daily, the adjusted HR was 1.14 (95 % CI, 1.09–1.18). The association between sweetened beverage intake and hypertension was stronger for carbonated beverages versus non-carbonated beverages, and for cola-containing versus non-cola beverages in the NHS I and NHS II cohorts only. Higher fructose intake from SSBs as a percentage of daily calories was associated with increased hypertension risk in NHS I and NHS II (p-trend = 0.001 in both groups), while higher fructose intake from sources other than SSBs was associated with a decrease in hypertension risk in NHS II participants (p-trend = 0.006).

LIMITATIONS

Residual confounding factors may interfere with the interpretation of results.

CONCLUSIONS

SSBs and ASBs are independently associated with an increased risk of incident hypertension after controlling for multiple potential confounders. These associations may be mediated by factors common to both SSBs and ASBs (e.g., carbonation or cola), but are unlikely to be due to fructose.KEY WORDS: sweetened beverages, fructose, hypertension, artificial sweetener, risk     

The efficiency of sputum cell counts in cystic fibrosis

BACKGROUND:

Technical factors relating to processing viscid sputum in cystic fibrosis (CF) and their influence on the reproducibility and validity of cell counts need to be evaluated. In addition, the methods need to be standardized so that they can be applied clinically and in research.

OBJECTIVE:

To examine the efficiency, reliability and validity of processing small volumes of spontaneously expectorated sputum from subjects with CF.

METHODS:

Sputum was collected from adults with CF (n=35) and compared with sputum from adults with infective bronchitis or bronchiectasis (IB/B) (n=16), or with asthma or chronic obstructive pulmonary disease (AS/COPD) (n=25). Selected sputum (100 mg to 200 mg) was processed with dithiothreitol (0.1%) and filtered. Total cell count (TCC) and viability were obtained in a counting chamber and cytospins were prepared and stained with Wright’s for a differential cell count. Sputum and filter remnant were processed for TCC, viability and differential cell count, and the efficiency was determined by comparing the mean loss in cell yield to the filter. Two different portions from the same sputum sample were processed for cell counts to determine reproducibility. Results were compared with those from IB/B and AS/COPD groups.

RESULTS:

Efficiency of cell dispersal was excellent and similar to that in AS/COPD and IB/B groups. Reproducibility of cell counts from two portions of a sputum sample was high (R≥0.80). CF sputum demonstrated a raised TCC and neutrophilia similar to IB/B but significantly higher than AS/COPD.

CONCLUSION:

The selection method of evaluating cell counts in viscid CF sputum is efficient, reproducible and valid.     

A vignette-based survey to assess clinical decision making regarding antibiotic use and hospitalization of patients with probable aseptic meningitis

BACKGROUND:

The many etiologies of meningitis influence disease severity – most viral causes are self-limiting, while bacterial etiologies require antibiotics and hospitalization. Aided by laboratory findings, the physician judges whether to admit and empirically treat the patient (presuming a bacterial cause), or to treat supportively as if it were viral.

OBJECTIVE:

To determine factors that lead infectious disease specialists to admit and treat in cases of suspected meningitis.

METHODS:

A clinical vignette describing a typical case of viral meningitis in the emergency department was presented to clinicians. They were asked to indicate on a Likert scale the likelihood of administering empirical antibiotics and admitting the patient from the vignette and for eight subsequent scenarios (with varied case features). The process was repeated in the context of an inpatient following initial observation and/or treatment.

RESULTS:

Participants were unlikely to admit or to administer antibiotics in the baseline scenario, but a low Glasgow Coma Score or a high cerebrospinal fluid (CSF) white blood cell count with a high neutrophil percentage led to empirical treatment and admission. These factors were less influential after a negative bacterial CSF culture. These same clinical variables led to maintaining treatment and hospitalization of the inpatient.

CONCLUSIONS:

Most participants chose not to admit or treat the patient in the baseline vignette. Confusion and CSF white blood cell count (and neutrophil predominance) were the main influences in determining treatment and hospitalization. A large range of response scores was likely due to differing regional practices or to different levels of experience.     

Diagnostic algorithm using a sensitive broth culture method for detection of Clostridium difficile toxin from stool samples

BACKGROUND:

The two-step glutamate dehydrogenase antigencytotoxicity neutralization assay algorithm has been found to be reliable for the diagnosis of toxigenic Clostridium difficile. However, the high sensitivity of the screening method is compromised by the relative low sensitivity of the second step, the direct cytotoxin neutralization assay (DCNA) using a fecal filtrate. The objective of the present study was to compare the DCNA with an indirect cytotoxin neutralization assay (ICNA).

METHODS:

For ICNA, the cytotoxin B of C difficile was obtained from a broth culture of the stools and neutralized according to a standard cytotoxin assay using MRC-5 fibroblast cells.

RESULTS:

A total of 923 stool specimens from adults were tested during a three-month period from June to August 2008. The prevalence of toxigenic C difficile was 13.5%. The sensitivity of the two-step algorithm was 88%. With the ICNA, 12% toxigenic C difficile were detected that were missed by DCNA.

CONCLUSIONS:

The use of broth for the ICNA is convenient, and results in increased sensitivity of detection of toxigenic C difficile. It can be implemented in routine diagnosis.