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.
Verrucous Skin Disease in Micronesia: A Medical Mystery
Source: Lillis JV, et al. Sequelae of World War II: An outbreak of chronic cutaneous nontuberculous mycobacterial infection among Satowanese islanders. Clin Infect Dis. 2009;48:1541-1546.
This investigation began when a young 29-year-old Taro farmer from one of the Micronesian islands, Satowan (population 650), presented to an indigent care clinic in Portland, OR, with an 18-year history of progressive plaque-like verrucas covering his lower extremities. Mycobacterium marinum grew in culture from a skin biopsy, and he responded to doxycycline. He reported that many people living on Satowan had similar lesions.
Indeed, upon investigation, approximately 6% of residents on Satowan Island were affected by, with what was referred to locally as "spam." The disease generally involved the extremities, and sometimes involved more than 50% of the skin area in some individuals. A total of 39 persons from Satowan with skin lesions were identified and recruited for investigation. The median age was 26 years (range, 8-82 years), with an average duration of disease of 12.5 years. Nineteen biopsies taken for culture were negative for mycobacteria (although the investigators reported there was a five-day lag before the cultures could be processed, and the temperature may not have been controlled). Nine of the specimens submitted for histology demonstrated necrotizing granulomatous inflammation, and GMS and AFB stains were negative.
Because biopsies from the index case grew to M. marinum, the investigators focused on this possibility. Using PCR primers for mycobacteria other than TB or leprosy, a 97-bp band was identified from the index case and seven additional patients, as well as a control positive for M. marinum. Of all the PCR products, only material from the index case, two case patients, and the control could be sequenced. The index case sequence was identical to a GenBank M. marinum hsp65 gene; sequences from the two case patients showed 87% and 95% similarity to the hsp65 gene.
All of the patients evaluated received doxycycline 100 mg twice daily, with plans to continue the drug for at least three months. Rifampin was added as a second agent in six patients with more extensive disease. Follow-up in this remote island population was limited, but local health care personnel reported that many of the patients were re-sponding to treatment.
The epidemiologic investigation focused on water exposures for the out-break. All 39 of the case patients were taro farmers, as were 73% of control subjects (p <.01). Swimming or bathing in water-filled, WWII bomb craters also was more frequent in case patients (87% vs. 36% of controls, OR 12.2, p < .01). Interestingly, local lore has it that this verrucous skin disease only began to occur on the island after WWII, when the island was bombed by Allied forces. Bomb craters fill with rainwater run-off and generally are stagnant. Residents of a neighboring island, only 1.5 miles away, called Ta, apparently have not been affected, although residents of another neighboring island, called Chuuk, are now reporting similar skin lesions.
Ooowww! Poop Transplants?
Source: Louie TJ, et al. Home-based fecal flora infusion to arrest multiply-recurrent Closdtrium difficile infections. 48th Annual Interscience Conference on Antiimicrobial Agents and Chemotherapy/Infectious Disease Society 46th Annual Meeting. Washington DC, October 25-28, 2008. Page 579, Abstract K-4202.
Based on anecdotal information, this Canadian researcher has been using fecal transplants (or fecal transfers) as a last ditch measure in hard-to-beat C. difficile infection (CDI) cases.
Increasingly, my partner and I are seeing patients with chronically recurrent C. difficile, who experience multiple relapses of CDI, most of whom eventually respond to vancomycin therapy but generally relapse within days to weeks of attempted vancomycin taper or discontinuation of drug. Some of these patients are immunosuppressed, such as those with CLL, hypogammaglobulemia, or myelodysplasia, but several have simply been treated with antibacterial therapy. Such "vancomycin dependence" becomes a vicious trap, where the vancomycin is essential to control a regenerated organism from residual spores in the gut, and yet, continues to suppress fecal flora.
Faced with similar patients, this investigator began doing colonic instillations of conditioned feces from family and friends of affected patients. A total of 48 patients received fecal transfers between 1996-2007, 46 of whom had resolution of CDAD. The mean age was 62 years (range, 30-91 years), with a mean duration of CDAD of 10 months.
Stool donors were healthy, with no antibiotic use in the previous six months. They were screened using the same methods employed by blood banks and transplant groups. Stools were collected over three days, and kept chilled at 4-8° C until they could be treated with a buffered saline solution and filtered through a mesh to remove larger particles. Before the procedures, recipients received a two-week course of vancomycin, and then were instructed to stop the drug and do an enema and to clear out any residual vancomycin on the day of the procedure. On the day of the procedure, they rested for four hours, took a valium, and could ingest only clear liquids to slow peristalsis and elimination stool.
Forty-one patients responded to the initial transfer; four patients responded to two attempts, and one patient to three attempts. Of the two who failed fecal transfer therapy, one developed recurrent disease when restarting proton pump inhibitor treatment; the other was anticipated to try again. The transfers were generally well tolerated. Of 10 patients who received donor stool from spouses, four reported abdominal bloating, cramps, and gas for 3-6 months. The investigator theorizes that feces from first-degree relatives may be better tolerated.
The procedures were done at home, in large part because of convenience and comfort, allowing patients to rest at home after the procedure, but also because the local health care facility staff were unwilling to participate.
Are Two Agents Better Than One in CDAD?
Source: Hames A, et al. In vitro effect of metronidazole and vancomycin in combination on Clostridium diarrhea (letter). J Antimicrob Chemother. 2009;1076.
Clinicians are increasingly resorting to combination therapy for CDAD, commonly employing combination oral vancomycin plus parenterally administered metronidazole, especially for those patients with more severe disease, or those unable to tolerate oral therapy or with poor intestinal motility. While this approach has not been rigorously evaluated, it has been advocated by some experts. However, there is little in vitro evidence examining the in vitro interaction of these two agents against C. difficile.
Fifteen differing ribotypes of C. difficile were plated on agar medium, including two NCTC strains and 13 clinical strains. The final inoculum size was 104 cfu/test spot. Both vancomycin and metronidazole were tested at concentrations ranging from 0.125 to 2 mg/dL, separately and in combination. No in vitro antagonism was observed. The MIC90 of metronidazole was 1 mg/L, and 0.5 mg/L for vancomycin. The fractional inhibitory index concentration ranged from 1.5 to 3, which is a fairly narrow range, implying indifference between the two agents.
These data suggest no microbiological basis for the increasingly common practice of double-drug therapy using vancomycin and metronidazole in the treatment of CDAD. Whether patients with more CDAD clinically benefit from the addition of a parenteral agent, either because of ileus, or for other reasons, requires further investigation. Limited data suggest that such patients do not fail treatment because of metronidazole resistance, and use of combination therapy may increase the risk of relapse by further suppressing fecal flora.
Artesunate in P. falciparum Malaria
Source: A promed mail post, May 28, 2009. www.promedmail.org
A recent clinical case of acute P. falciparum malaria, which presented to our local urgent care, and imported that day from Ghana, nearly prompted having to secure a course of artesunate from San Francisco International Airport, but the patient fortunately responded to quinidine and doxycycline. But almost before I ever get a chance to use artesunate, reports suggest that emergence of more artesunate-tolerant strains of P. falciparum may be occurring along the Thai-Cambodian border. Previously, artemisinin compounds reliably and rapidly cleared the bloodstream of parasites within a couple of days. In May 2009, a teacher in the local area who received treatment with an artemisinin compound had persistently positive smears after four days of therapy. Researchers from the U.S. Armed Forces Research Institute, who are conducting an ongoing study of malaria therapy in the Battambang Province in Cambodia (near Thailand), are acknowledging that at least one-third to one-half of the 90 patients enrolled in the study have been slower to respond to artesunate than anticipated, with positive smears after three days of therapy, and some even after 4-5 days of therapy. This is of obvious concern, as these compounds have been well tolerated and reliably effective in the treatment of even mefloquine-resistant P. falciparum malaria, and are the only drugs in the pipeline for malaria for several years.
This investigation began when a young 29-year-old Taro farmer from one of the Micronesian islands, Satowan (population 650), presented to an indigent care clinic in Portland, OR, with an 18-year history of progressive plaque-like verrucas covering his lower extremities.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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