Updates by Carol A. Kemper, MD, FACP
Updates
By Carol A. Kemper, MD, FACP, Clinical Associate Professor of Medicine, Stanford University, Division of Infectious Diseases; Santa Clara Valley Medical Center, Section Editor, Updates; Section Editor, HIV, is Associate Editor for Infectious Disease Alert.
Wound VAC for war injuries
BE Leininger, et al. Experience with wound VAC and delayed primary closure of contaminated soft tissue injuries in Iraq. J Trauma. 2006;61:1207-1211.
Trauma in wartime is especially high risk given the nature of the injuries, the high risk of infection, and the limited access to optimal medical care. High-energy injuries, such as those caused by shrapnel, IEDs (improvised explosive devices), and missiles may be complicated by infection in up to 80% of cases because of the presence of foreign bodies, clothing, and dirt. In most of these cases, the military follows general wound care principles, and allows such wounds to close by secondary intent.
Given the complexities of care in Balad, Iraq, and a lack of outpatient resources and wound care, military physicians pursued an alternate approach for injured Iraqi citizens (military personnel were evacuated for care). This entailed initial aggressive debridement and pulse lavage, with application of a negative pressure dressing (wound VAC), followed by repeated intraoperative debridement and lavage, as needed, until the wounds appeared clean, at which time they were closed by delayed primary closure.
A total of 88 high-energy wounds in 77 persons were managed with this approach. The mean size of the wounds was 32 cm2 (range 12-160 cm2). The mean number of days from injury to wound closure was 4.24 (range, 2 to 14 days), and required a mean of 2.16 surgeries (range, 2 to 5). The average length of stay in hospital was a little more than one week, and the infection rate was remarkably zero. No complications were reported in the post-operative period.
Aggressive wound management with the use of a wound VAC, for high energy wounds from war, resulted in a significantly shorter recovery period and number of days of hospitalization, with a remarkable zero infection rate.
The military hospital in Balad maintained 30 VAC units for use at any time, and reportedly never ran short.
Never question Darwin
ProMED-mail post, February 2, 2008, www.promedmail.org
Concerns have been raised about the emergence of resistance to ivermectin in parasitic species, especially given the high frequency of use of this agent in animal and human populations around the world. Since the mid-1990s, the African Programme for Onchocerciasis Control has conducted regular mass treatment campaigns, on a quarterly basis, in at least 19 African countries, in an attempt to control this infection in large numbers of people. Onchocerciasis can cause debilitating skin lesions and ocular involvement, resulting in "river blindness." It is estimated that up to 70 million people may have received treatment through this program, significantly reducing morbidity from onchocerciasis in Africa. However, an increase in the number of infections, despite ongoing treatment campaigns in certain countries, such as Ghana, has prompted further study.
Researchers working in Cameroon have been tracking potential resistance markers to ivermectin in a cohort of patients since 1994. Their work has focused on a P-glycoprotein-like protein called beta-tubulin, which is present in O. volvulus. Evidence suggests that the homozygous presence of the gene encoding for this protein confers greater drug susceptibility than organisms heterozygous for this gene. Although the mechanism of resistance is not thoroughly understood, ivermectin appears to interfere with the release of microfilariae from the adult female uterus. Studies have shown fewer microfilariae in the uteri of adult females heterozygous for the beta-tubulin gene following treatment compared with homozygous worms.
Since 1994, researchers have noted a significant increase in the proportion of worms heterozygous for the betatubulin gene, relative to other stable genetic markers (up from 21% to 69%). In other words, repeated exposure to drugs may select for those worms better able to compete and produce young (eg, microfilariae). For now, experts have elected to continue the current ivermectin campaign, but plan to monitor a new cohort of patients entering treatment for confirmation of these results.
The Yogurt Challenge for VRE
Manley KJ, et al. Probiotic treatment of vancomycin-resistant enterococci: a randomised controlled trial. Med J Aust. 2007;186:454-457.
Probiotics are increasingly a popular subject, especially with the increased frequency of C. difficile infections and increasing colonization with VRE. Even patients are requesting probiotic "treatment", with their routine antibacterial therapy. Probiotics are essentially living microbes present in foods, a common example of which is Lactobacillus rhamnosus, present in yogurt.
The clearance of VRE was examined in 27 patients colonized with VRE in stool, who were randomized to receive a daily dose of 100 grams of either a commercially available unpasteurized "active" yogurt or a pasteurized product for four weeks. Three stool swab specimens were collected weekly for 4 weeks, and then again at 8 weeks. A majority of the patients were receiving concomitant antibacterials.
Fourteen patients received "active" yogurt and 13 control subjects received the pasteurized product. Twenty-three patients completed the study (four patients were lost to follow-up or died). Of those 11 patients who completed four weeks of daily live yogurt, all became VRE-culture negative at four weeks. Three relapsed by week eight. All three had received antibacterials with activity against Lactobacillus spp. In contrast, only one of 12 control subjects became culture negative. Eleven of these were crossed over to the active yogurt treatment for an additional four weeks, eight of whom completed therapy and were also culture-negative.
This study suggests that patients receiving antibacterial therapy who are colonized with VRE, are more likely to clear their colonization with daily doses of lactobacillus-containing yogurt, at least as long as they do not receive agents active against lactobacillus. The study contrasts with reports that spontaneous clearance of VRE from stool generally occurs slowly, over an average of 7 months, as long as the patient does not received additional antibacterial therapy. The risks of active yogurt therapy appear limited; although lactobacillus bacteremia has been reported in ill patients with cancer or immune deficiency. Larger clinical trials would be welcome.
When to start ART?
Braithwaite RS, et al. Influence of alternative thresholds for initiating HIV treatment on quality-adjusted life expectancy: a decision model. Ann Intern Med. 2008;148:178-185.
The optimal time to initiate antiretroviral therapy has see-sawed over the years, from "treat early, hit hard," to later recommendations to intervene when CD4 counts declined to 300-350 and/or with viral loads greater than 50,000 per mL, to more present day recommendations, which advocate starting HAART a little earlier than this. The relative merits of these approaches has been difficult to gauge, especially given concerns about the impact of treatment on quality of life, treatment-related toxicities, and related medical complications (eg, lipdystrophy and cardiac complications).
This computer model attempts to piece out the relative balance of the beneficial effects of HAART therapy and reduction in HIV-related mortality vs the potential harmful effects of treatment and non-HIV-related increases in mortality in a group of newly HIV-diagnosed patients. The negative effect of treatment on both the quantity and quality of life was factored into the analysis. An earlier analysis, based on a sample of HIV-infected patients cared for by the Veterans Administration, found that HIV treatment was associated with a 3.8-fold increase in the long-term hazard of non-HIV-related mortality in adjusted analysis.
Cox proportional hazard model was used to compare the life expectancy for 5742 HIV-infected subjects and 11,484 HIV-negative controls who met criteria for inclusion in the study, matched by age, sec, race, and site of care. The mean age of the patients and controls was 46 years; 98% were male and 69% were non-white. Life expectancy was estimated for individuals first diagnosed at ages 30, 40, and 50, at varying plasma viral loads (10,000 to 300,000 copies/mL), who initiated therapy at alternate thresholds of CD4 count (200, 350, and 500 cells/mm3).
The simulation found that earlier initiation of treatment was associated with an improved quality-adjusted life expectancy for younger people, regardless of viral load. In other words, 30-year-olds who began therapy at a CD4 count of 500 did better than those who started therapy at either of the lower thresholds of 200 or 350 cells/mm3. For 30-year-olds with a viral load of 10,000, the estimated life expectancy ranged from 17.3, 17.6, and 18.2 years for CD4 counts of 200, 350, and 500, compared with those with viral loads of 300,000, where the estimated life expectancy was 14.5, 15.9, and 17.3, respectively. The long-term beneficial effect of treatment at higher starting CD4 counts was largely due to the fact that these patients continued to have higher CD4 counts.
However, as patients aged, the benefit of treatment was limited by increasing non-HIV-related mortality. In patients who were 40 years of age at initiation of therapy, the benefit of therapy was limited to those with higher viral loads of 300,000 copies/mL, resulting in an average quality-adjusted life expectancy of 11.4 years vs 12.5 years for those with CD4 counts of 250 vs 500 cells/mm3. And, in patients who were age 50 at diagnosis, earlier initiation of therapy was, on balance, more harmful, especially at lower viral loads.
Earlier initiation of therapy would be more favorable, especially in older patients, if the harmful effects of treatment, in terms of quality of life, treatment-related toxicities, and non-HIV-related morbidity and mortality were improved.
Trauma in wartime is especially high risk given the nature of the injuries, the high risk of infection, and the limited access to optimal medical care.Subscribe Now for Access
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