By Carol A. Kemper, MD, FACP, Section Editor: Updates, Clinical Associate Professor of Medicine, Stanford University, Division of Infectious Diseases; Santa Clara Valley Medical Center, is Associate Editor for Infectious Disease Alert.
Half of U.S. TB cases in four States
Centers for Disease Control and Prevention. Trends in Tuberculosis – United States, 2012. MMWR 2012; 61: 181-185.
National data available for 2011 indicate that a total of 10,521 new TB cases were reported last year in the United States (incidence 3.4 cases/100,000 population), representing an overall decline of 3.8% from 2010. TB continues to disproportionately affect foreign born persons, and Asians became the single largest racial/ethnic group affected by TB, with a case rate 25 times higher than non-Hispanic whites. TB cases among Hispanics and non-Hispanic blacks fell slightly, but remained 7 and 8 times higher than non-Hispanic whites, respectively.
Remarkably, half (50.4%) of all TB cases in the United States occurred in 4 States in 2011 (California, Florida, New York, and Texas), although the case rate per population was the highest for Alaska (case rate 9.3 per 100,000 population).
Since 2000, a steady increase in TB has been observed in foreign born persons, with 62.5% of all TB cases in 2011 occurring in those who are foreign born. In contrast, cases in U.S.-born persons declined to a rate of 1.5 cases/100,000 population – an 80% decrease from 2003.
HIV test results were available for 81% of reported cases; among those with an available HIV test result, 7.9% were co-infected with TB and HIV.
Finally, drug resistance data (which was only available for 2010 and not yet available for 2011) indicates that 1.3% of all cases were multi-drug resistant. This figure is relatively stable compared with 2009. A total of 109 cases of MDR-TB and 4 cases of XDR-TB (all in foreign-born individuals) were reported in 2010. The risk for MDR-TB was four times greater in persons previously treated for TB compared with those receiving first time therapy.
Programs targeting high risk ethnic groups have been associated with a lower risk of reactivation TB. For example, one program targeting predominantly black and Hispanic neighborhoods in Texas, emphasizing INH treatment for anyone with latent TB, resulted in a definite decrease in active TB cases. Perhaps larger clinics in certain high risk areas of the United States, like Sutter Health and the Kaiser Permanente systems could consider similar programs.
Probiotics a Plus
Hempel S, et al. Probiotics for the prevention and treatment of antibiotic-associated diarrhea. A systematic review and meta-analysis. JAMA 2012; 307(18), p 1959-1968.
It seems that everyone receiving antibiotics nowadays requests probiotics, although they are not inexpensive and their use in the prevention of Clostridium difficile enterocolitis (CDI) has not been demonstrated. Antibiotic-associated diarrhea (AAD) affects up to 30% of persons receiving antibiotics, and several studies have observed reductions in AAD in persons receiving various probiotic compounds. But how helpful are they, and are they worth the expense?
These investigators performed a meta-analysis of reported clinical trial data on the effectiveness of various probiotics in the prevention and treatment of AAD. An extensive query was conducted, without language restriction, specifically looking for randomized controlled trial data for the use of any of several probiotics (including Lactobacillus, Bifidobacterium, Saccharomyces Streptococcus, Enterococcus, and/or Bacillus), alone or in combination. Participants of any age group, any underlying disease, outpatient/inpatient, and any type of antibiotic use were included. Most trials indicated that probiotics were administered for the prevention and/or treatment of AAD, although most gave the probiotic substance simultaneously with the antibacterial, before the development of symptoms. The investigators noted that most of the studies provided limited follow-up, generally for the period of antibacterial treatment. The authors observed that the quality of the reporting for most of the studies was low, and only two of the studies met their criteria for high quality/low bias. Fifty-nine of the studies lack information by which to even gauge potential bias. Furthermore, most of the studies were not sufficiently powered to detect a statistically significant reduction in benefit.
A total of 82 randomized clinical trials met the study criteria for inclusion in the analysis. Most of the clinical trials were performed in the outpatient setting (24 included hospital patients); most included adults (n = 52). Twenty-four of the studies involved treatment for H. pylori. Sixteen studies evaluated the risk of AAD with the use of a single antibacterial agent (i.e., azithromycin, clarithromycin), although most did not restrict nor specify the type or duration of antibacterial therapy used. The products used were quite variable, and included lactobacillus alone/or in combination with other genera in 57 studies; yeast based products (e.g., S boulardii (cerevisiae)) were exclusively used in 16 studies.
Most of the clinical trials failed to demonstrate a statistically significant benefit for probiotic use. However, when probiotic use was examined across all 62 studies with sufficient participant data available (n = total 11, 811 participants), patients receiving probiotics were at significantly lower risk of developing diarrhea compared with those not receiving probiotics (pooled RR, 0.58, p <.001). To test the robustness of these results, each study was sequentially eliminated from the analyses, and all 63 results were similar. When the analysis was limited to those 44 studies that were specifically double-blinded, a significant reduction in AAD was observed in favor of probiotics (pooled RR, 0.61, p < .001). Further meta-analysis found the results for blinded and non-blinded trials were similar.
Results specific to different age groups were also examined where possible, including children (<18 years of age), adults, and older adults (>65 years of age), although most of the studies included 2 or more of these age groups. Sixteen clinical trials specifically enrolling children found a statistically significant reduction in the risk of AAD with probiotic use compared with controls (RR 0.55, p < .002). Similar results were observed for adults alone. Only 3 of the clinical trials examined the effectiveness of probiotic use specifically in the elderly. The pooled results from these studies failed to demonstrate a statistically significant benefit to probiotic use in the older age group.
In 20 studies enrolling hospitalized patients who received adjuvant probiotics in conjunction with antibacterial therapy, the risk of AAD was significantly lower (RR .55, p < .001) in the active treatment group compared with controls. The authors commented that in hospital patients especially, there was a wide range of antibacterial use and duration, not all of which was clearly specified, and the observed effectiveness of probiotic therapy was generally limited to the period of antibiotic use and not longer.
The effect on the risk of developing CDI in these studies was more difficult to gauge. Thirty-one of the clinical trials specified criteria for more severe diarrheal symptoms leading to a change in treatment or testing for C. difficile. CDI data was apparently available for only 14 of these studies. In pooled analysis of these 14 studies, it appears that the relative risk for developing CDI was statistically significantly lower in patients receiving probiotics compared with those who did not (RR 0.29, 95% CI, 0.17-0.48, p < .001).
Seventeen of the studies used products containing only lactobacillus; pooled data demonstrated a statistically significant reduction in risk for AAD, which was similar to those studies using exclusively yeast-based products. Those few studies that provided a head to head comparison between different products found no clear difference.
Thus, the use of various probiotics, whether lactobacillus-based or yeast-based, in conjunction with differing antibacterial agents, appeared in this meta-analysis to have had a similarly beneficial effect and lowered the risk of AAD. The authors recommend that larger and better quality studies be performed, with clear symptom definition for diarrhea severity, and endpoints for C difficile testing. Complications of probiotic therapy, such as S. cerevisiae fungemia, albeit uncommon, were not reported or addressed by most of the clinical trials evaluated here. A larger trial could help to examine those types of adverse events, in addition to examining cost-benefit.National data available for 2011 indicate that a total of 10,521 new TB cases were reported last year in the United States (incidence 3.4 cases/100,000 population), representing an overall decline of 3.8% from 2010. TB continues to disproportionately affect foreign born persons, and Asians became the single largest racial/ethnic group affected by TB, with a case rate 25 times higher than non-Hispanic whites.
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