Resistant Salmonella from Pet Rodents

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.

Source: Swanson SJ, et al. Multi-drug resistant Salmonella enterica Serotype Typhimurium associated with Pet Rodents. N Engl J Med. 2007;356:21-28.

An outbreak of highly drug-resistant S. enterica Serotype Typhimurium — which was resistant to all drugs tested — was first identified in 2 young boys in 2004 in Minnesota and North Carolina who had been in contact with pet mice. These events prompted further investigation, and ultimately, a total of 28 cases with matching S. enterica isolates were identified in 10 states. Twenty-two available patients were interviewed, including 13 children and adults with exposure to pet hamsters, mice or rats, 2 (9%) with secondary exposure, and 7 patients without documented rodent exposure. Forty percent required hospitalization, higher than generally expected with Salmonella infection, but common with drug-resistant isolates. Susceptibility studies showed resistance to ampicillin, sulfisoxazole, tetracycline, streptomycin and chloramphenicol.

Shortly after being purchased, many of the pet rodents became ill with diarrhea and lethargy, and, in the Minnesota case, a young 5-year old boy cradled his dying mouse only one week after receiving it as a gift, and shortly before becoming ill himself.

Investigation revealed identical isolates (S. enterica serotype Typhimurium phage type 120) in pet rodents from 13 different pet stores, supplied by 7 different distributors, in 10 different states. The organism was also isolated from pet cages and reusable transport cartons. Salmonella can survive from more than one year in the environment. Even exposure to reusable contaminated transport bins could risk infection of an entire population of rodents being shipped for sale. In addition, the stress associated with transport may lead to reactivation of S. enterica in animals, resulting in increased diarrhea and bacterial shedding.

Four different breeders or distributors were found to routinely administer antimicrobials for non-specific diarrheal symptoms in animals. In addition, investigators found that tetracycline was routinely used in feed, and that rodents received antimicrobials in their drinking water at weaning, and before and after transport. This undoubtedly contributed to the broad resistance of these organisms.

Stricter infection-control practices should be implemented for the sale and distribution of pet rodents. Parents should be appraised of the risks of illness in purchased pets, and instructed as to good cage hygiene and handling of animals with special attention to hand cleansing.

Decolonization of MRSA is Effective

Source: Simor AE, et al. Randomized controlled trial of chlorhexidine gluconate for washing, intranasal mupirocin, and rifampin and doxycycline versus no treatment for the eradication of methicillin-resistant Staphylococcus aureus colonization. CID. 2007;44:178-185.

It is estimated that at least 2,000,000-3,000,000 people in the United States are colonized with MRSA. While aggressive decolonization and work-restriction policies have been utilized in some European countries, attempts at decolonization have not been endorsed by health agencies in the United States. Fears of emerging resistance, toxicity, expense, and a lack of data demonstrating durable effectiveness have diminished interest in routine decolonization of individuals colonized with MRSA. And yet, an increasing amount of data indicates that colonization with MRSA results in an increased risk of bacteremia, surgical wound infection, and other infectious complications in hospitalized patients.

For this reason, Simor and colleagues' data is welcome information. A total of 146 patients were enrolled in a randomized (3:1) controlled trial of systemic and topical antimicrobial treatment (topical chlorhexidine gluconate body scrubs, topical mupirocin, and combination oral rifampin and doxycycline for 7 days) vs no treatment. To enroll, patients had to have positive MRSA cultures from one or more body sites on 2 occasions within a 2-week interval. Prior treatment specific for MRSA was acceptable but previous attempts at decolonization were not. Follow-up cultures of nares, perineum, skin lesions, catheter exit sites, and previous sites of infection were obtained monthly for up to 8 months. The primary study endpoint was clearance of all sites at 3 months post-treatment.

Remarkably, 64 (74%) of patients in the treatment group had negative follow-up cultures at 3 months, compared with only 8 (32%) in the non-treatment group (p = 0.0003). A Kaplan-Meier colonization-free survival curve demonstrated a significant decrease in colonization over time in the treated group (P < 0.0001). In those with positive cultures at 3 months post-treatment, 82% were colonized with the same organism, as identified by PFGE typing, but 18% had differing isolates. Given the high frequency of certain MRSA organisms circulating in long-term care facilities or hospitals, it may not be possible to determine if a patient was successfully decolonized but then re-colonized from an outside source with an identical organism.

Persistence of MRSA occurred in 60% of patients with high-level mupirocin resistance. High-level mupirocin resistance, identified in 19% of isolates, was the major risk factor leading to failure of the regimen but, surprisingly, impaired functional status and the presence of open wounds or medical devices was not. The significance of low- level mupirocin resistance, found in 5%, could not be assessed given its low frequency. However, a worrisome finding of this study was the emergence of high-level resistance to mupirocin in 5% of treated patients during study.

Interestingly, none of the isolates proved to be USA300, the most common community acquired MRSA isolate in our area in Northern California. The most common strains identified were CMRSA-2 in 46% (similar to USA100 ST5), and CMRSA-1 in 24% (USA 600 ST4.5).

Combinations of systemic and topical antimicrobials are safe and effective in eradicating MRSA in a majority of colonized patients. Given the high frequency of failure in those with pre-existing mupirocin resistance, testing for mupirocin resistance before attempting decolonization would seem appropriate. Commercial testing is now available through some laboratories.

Sensitivity of Interferon Assay in Active TB

Source: Dewan PK, et al. Low sensitivity of a whole-blood interferon-gamma release assay for detection of active tuberculosis. CID. 2007; 44:69-73.

New tests based on the gamma interferon immune response to M. tuberculosis have many potential benefits over standard TST skin testing in the detection of latent TB. Such assays have a high degree of specificity in clinical trials (99.8%), which eliminates the need for 2-step skin testing, and decreases health care personnel time and office visits. In addition, previous BCG vaccination does not interfere with these assays. One of these products, the Quantiferon-TB Gold assay (QFT-G, Cellestis), has been approved for use in the United States and is already being broadly utilized for screening of health care workers. A limitation of these assays is the diminished sensitivity in patients with T-cell dysfunction. And, the assay cannot distinguish between latent and active disease.

These authors at the San Francisco public health department evaluated the utility of interferon-gamma assay in the assessment of persons with suspected TB. A total of 442 subjects with suspected or documented TB were identified through a review of clinical records in 2005, 242 (55%) of whom were tested using the QFT-G assay. Of these, 45(19%) were diagnosed with TB, 37(82%) of whom were confirmed by culture. In patients diagnosed with active TB, QFT-G results were positive in 55%, negative in 38%, and indeterminate in 7% (overall sensitivity 60% for this group, with a negative predictive value of 86%). A similar sensitivity (64%) was observed for those with culture-confirmed disease.

Interestingly, patients with extra-pulmonary disease were more likely to have a false-negative result compared with those with pulmonary disease (35% vs 4%, p < 0.05). The timing of the testing or duration of therapy did not appear to affect the results.

Of those 45 patients diagnosed with TB, 24 had paired skin TST test and QFT-G results. Both test were positive in 50%, both tests were negative in 4%, 38% had positive skin testing and a negative QFT-G result, and 8% had negative skin testing and an indeterminate QFT-G results. No patient diagnosed with TB had a negative skin test and a positive interferon assay test result.

Only 3 patients with HIV were diagnosed with TB; QFT-G results were positive, negative and indeterminate in one patient each.

The QFT-G assay, while very helpful in the recognition of patients with latent TB, has a diminished sensitivity (60%) in patients with active TB disease. Clinicians should be mindful that a negative interferon-gamma assay does not rule-out TB, similar to the experience with skin testing.

On a similar note, clinicians are inquiring whether patients with latent disease based on TST findings (some of whom may have had BCG vaccination in the past) can stop their treatment for latent TB based on a negative QFT-G result. Until such time as data exists to define the sensitivity of the assay in a partially treated population, patients should continue their ongoing treatment based on current public health recommendations.