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
Daptomycin Resistance During Treatment for MRSA
Clin Infect Dis. 2005:40:1058-1060.
In vitro resistance to daptomycin associated with clinical failure during treatment for MRSA infection has not been well documented. In vitro resistance to daptomycin is uncommon, de novo-resistant clinical isolates have not yet been reported, and the incidence of resistance, occurring during treatment is believed to be very low. The mechanism of resistance is not even known.
Mangili and colleagues describe a case of a critically ill man who presented in January 2004, with high grade, sustained MRSA bacteremia of unclear source (possibly related to a vertebral osteomyelitis). He received a 10-day course of vancomycin 1 g iv Q12h, but blood cultures remained positive. At that time, the organism remained sensitive to vancomycin, linezolid, and daptomycin. He was switched to daptomycin (4 mg/kg iv), but despite 4 days of therapy, blood cultures continued to be positive, and the dose was increased to 6 mg/kg iv.
Despite a total of 27 days of treatment with daptomycin, his blood cultures remained positive—but now showed resistance to daptomycin with an MIC of 2 mcg/mL(cut-off £ 1 mcg/mL). (The cut-offs for intermediate and high-level daptomycin resistance have not been established because of a lack of clinically-resistant isolates.) Finally, blood cultures became negative after 5 days of linezolid, but progressive cytopenias complicated by gastrointestinal bleeding necessitated further changes in his therapy. Following an additional 15 days of combined vancomycin and gentamicin, blood cultures remained negative, ~2 months after the patient initially presented for care. Unfortunately, other complicating medical problems led to comfort care measures.
Subsequent time killing experiments with multiple MRSA isolates obtained from the patient revealed that linezolid and vancomycin were bacteriostatic at all concentrations tested, and daptomycin was bacteriostatic at concentrations of 1, 2, and 4 mcg/mL.Only at concentrations of 8 mcg/mL was daptomycin bacteriocidal.
Clinicians should be aware that daptomycin resistance may occur during treatment, and patients with persistent bacterima on treatment should have repeated susceptibility testing. Treatment of more severe MRSA infections probably warrants the use of higher-dose daptomycin (6 mg/kg/day).
Bogus Testing for Lyme Disease
MMWR. 2005;54(05):125.
A young woman presented to our office with probable ALS, who in a desperate attempt to identify some other cause for her lower extremity complaints, had tested positive for lyme antibodies at an undisclosed laboratory. Multiple bands were positive for IgM and IgG by their Western Blot. She was convinced she had lyme, and had already started doxycycline with the hope it would cure her symptoms. My experience with this laboratory was poor, and repeat testing on 2 occasions through a more reliable lab yielded negative test results.
This is not the first patient to present to our office with questionable lyme blood test results, as well as more questionable lyme urine antigen tests. More than 70 serologic assays for diagnostic testing of lyme have been approved by the FDA for use in the United States. These include enzyme immunoassays (EIA) and immunofluorescent assays (IFA), both of which are used for initial screening purposes. Positive specimens should be further tested by standard Western immunoblot assay, the interpretation of which should meet specific validated criteria.
Any laboratory test results using urine antigen tests, immunoblot staining for cell wall deficient forms of Borrelia burgdorferi, and lymphocyte transformation studies should be disregarded. PCR testing should be reserved for specific specimens, such as tissue or skin biopsies, not blood or urine.
Splitting Your Pills: Good or Bad Idea?
The Medical Letter. 2004;46:89-91.
Tablet splitting is a common and often cost-saving practice that may or may not be a good idea,depending on several factors. Studies suggest that the accuracy of tablet splitting often misses the mark, with widely varying pill content and weight. However, this may not matter a great deal with certain medications, especially those with a wide margin of effectiveness and safety, and those which are long-acting (eg, levothyroxine). For some tablets, it may be exactly what the manufacturer intended, and the scored tablets, which have been approved by the FDA, have often been tested with this in mind.
The accuracy of tablet splitting was assessed in 3 larger studies which examined 22 US-manufactured scored and unscored drugs. The resulting half-tablets were considered acceptable if they contained 85% to 115% of the expected meanweight. Even when the tablets were split by a pharmacy technician, the results for the 3 trials were acceptable for only 7 of 22 drugs (32%), 3 of 11 drugs (27%), and 8 of 12 drugs (67%). The use of a pill cutter gave half tablets ranging from 69% to130% of their expected weight, whereas the use of a kitchen knife resulted in half tablets weighing 50% to 150% of their expected weight.
Only some tablets that were specifically designed to be split fared better, such as paroxetine and metoprolol—both are well scored and easily split. Other drugs, like sildenafil, split poorly (it was difficult to locate the middle of the diamond shaped tablet).
On the other hand, 2 clinical studies designed to assess difference between patients randomized to receive split or whole pills, the same intended dosage, found no statistically significant difference in the success of treating hypertension or hypercholesterolemia.
Some drugs should not be split, including extended release medications (eg, Cipro XR) or combination medications, where one of the active ingredients is contained in amounts essential to the effectiveness of the drug (eg, amoxicillin-clavulanic acid).Even for those drugs which may not split precisely, most physicians advise that tablets should be split one at time with use, and the 2 halves taken as consecutive doses—ensuring the most accurate dosing profile over a 2-day period.
Foodborne Chagas Disease in Brazil
ProMED-mail post, March 24 and April 1, 2005; www.promedmail.org
In the middle of a hectic day in the office 2 weeks ago, I received one of those funny phone calls, where somebody thinks they’ve been exposed to something bizarre. The story seldom makes sense. A father was calling because his teenage daughter had been travelling in Brazil, visiting friends, and had drunk sugar cane-sweetened juice. His was concerned she had Chagas disease, and could she be tested? He was frantic with worry. Huh?
Sure enough, within 24 hours, an alert crossed my desk about a possible foodborne outbreak of acute trypanosomiasis in Santa Catarina, which is a favorite tourist destination in South of Brazil, where the young woman had been traveling. The exact mode of transmission was not yet known, but the suspected source was contaminated sugar cane juice, which is a widely drunk beverage in that part of the world. Sales and distribution of sugar cane juice had been halted. At least 25 people were ill, 3 had died, and it was feared that up to 50,000 individuals may have been exposed to contaminated sugar cane juice sometime in February or March, including foreign travelers. Initial recommendations off the web suggested that asymptomatic persons with exposure within 30 days should be screened with IgM and IgG serologies for T. cruzi, with repeat serologic testing in 2-4 weeks. Screening was not needed for persons who remained asymptomatic more than 30 days following possible exposure.
As of last week, at least 24 cases of acute Chagas have been confirmed, with 6 deaths; 4 persons with positive test results were found to have chronic infection. The outbreak appears to have been traced to a single kiosk along a highway between Picarras and Italjai, where it is suspected that a triatomid bug somehow got crushed in the juice. Another infected triatomid bug was found at the site, along with several infected animals living in the area. More than 90% of the cases have been traced to this kiosk, although the investigation is ongoing.
Foodborne-related trypanosomiasis has rarely been reported, but this is the first outbreak to occur on such a large scale. As a result of this outbreak, the National Sanitary Surveillance Unit has announced that persons who were traveling in Brazil along this highway, who drank sugar cane juice between February 1 and March 23, are prohibited from donating blood.
In vitro resistance to daptomycin associated with clinical failure during treatment for MRSA infection has not been well documented. In vitro resistance to daptomycin is uncommon, de novo-resistant clinical isolates have not yet been reported, and the incidence of resistance, occurring during treatment is believed to be very low. The mechanism of resistance is not even known.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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