Antibiotic Resistant Salmonella Infections
Antibiotic Resistant Salmonella Infections
Abstract & Commentary
Synopsis: Salmonella infections cause approximately 1.4 million episodes of foodborne illness in the United States each year. Severe infections due to Salmonellae warrant antimicrobial treatment, yet use of agents such as ampicillin, chloramphenicol, and trimethoprim-sulfamethoxazole has been limited due to increasing antimicrobial resistance. Fluoroquinolones such as ciprofloxacin are commonly used to treat adult patients with acute gastroenteritis and are relied upon for treatment of salmonellosis. Until this year, a single case of a fluoroquinolone-resistant Salmonella infection had been reported in the United States, although others were reported worldwide. This report is a description of the first recognized outbreak of fluoroquinolone-resistant Salmonella infection in the United States, and issues regarding policies that may be contributing to the changing epidemiology of Salmonella infections.
Source: Olsen SJ, et al. A nosocomial outbreak of fluoroquinolone-resistant Salmonella infection. N Engl J Med. 2001; 344:1572-1579.
In February of 1997, an epidemiologic investigation was initiated through the Oregon Health Division when 3 culture-confirmed cases of Salmonellae enterica serotype Schwarzengrund infections were reported. The index patient had been hospitalized in the Philippines for 3 months after a severe pontine cerebrovascular accident that occurred during travel. The patient was transferred to a hospital in the United States for long-term care in December 1995. Two months later, culture of a suprapubic urinary catheter with purulent discharge grew S enterica serotype Schwarzengrund. Twelve months later, the patient was still shedding the organism, which was identified in stool. Cultures of the staff and other patients did not yield Salmonellae.
Two months later, a second case was identified in the same nursing home, (Nursing Home A), and 2 cases were also detected county during March and September 1997 in a second nursing home (Nursing Home B) located in an adjacent county. Eighteen months after the last patient with culture-confirmed Salmonella infection was discharged from Nursing home A, another case was detected there. Antimicrobial susceptibility testing showed that the isolates were resistant to fluoroquinolones, and the CDC was invited to join the investigation. A year later, another patient who had occupied the same room as the index patient was shown to have culture-confirmed Salmonella infection. Thirty samples were collected on swabs from various surfaces and materials in the room. Two material samples yielded the same organism: one came from a foam mattress from the index patient’s room, and the other came from the door handle of that room 29 months after the patient had been discharged. Cultures of urine and stool from the asymptomatic roommate of the newly infected patient also yielded this organism. In March and April of 2000, 2 more cases were identified, but no further cases occurred during 11 subsequent months of follow-up.
Further investigation via a case-control study was conducted to determine risk factors for the transmission of fluoroquinolone-resistant Salmonella infections in Nursing home A. Also, a survey of antimicrobial agents used was conducted to estimate the quantities of antimicrobial agents used. Antimicrobial susceptibility testing was done at the CDC. Resistance was defined by the guidelines of the National Committee for Clinical Laboratory Standards. Isolates were also tested for resistance to ciprofloxacin by the E test according to manufacturer’s recommendations. Mechanisms of resistance were explored with PCR amplification of the region of the gyrA gene in the isolates that determine quinolone resistance.
All isolates arose from the same source based upon the finding that all isolates had the same 2 mutations in the gyrA gene. Altogether, 7 women and 4 men with median age of 85 years old were identified between February 1996 and April 2000 to have culture-confirmed, fluoroquinolone-resistant S enterica serotype Schwarzengrund infection. Urinary isolates were obtained in persons who had a positive culture from stool or who had clinical signs of cloudy urine, fever, and abdominal pain. The median length of stay in the nursing home was longer for the patients with Salmonella infection than for the controls.
Interestingly, patients with Salmonella infection were more likely than the controls to have taken fluoroquinolones in the 6 months before a culture was obtained (4 of 5 patients compared with 2 of 13 controls.). These 4 patients took fluoroquinolones for a median of 14 days (range, 7-55 days) before their first positive culture. Use of other antimicrobial agents, including trimethoprim-sulfamethoxazole, during the 6 months before a culture was obtained was not associated with the acquisition of Salmonella infections. Fluoroquinolones were documented to be the most commonly used antimicrobial agents in the nursing home facilities.
Comment by Maria D. Mileno, MD
This case-control study demonstrated that fluoroquinolone use during the 6 months prior to specimen collection for culture of Salmonella was significantly associated with an increased likelihood of fluoroquinolone-resistant Salmonella infection. This is consistent with findings of an earlier study that examined previous use of antimicrobial agents as a risk factor for drug-resistant salmonellosis.1 These findings suggest that the use of fluoroquinolones may select for and contribute to the transmission of the resistant strain identified, perhaps by lowering the inoculum required to cause infection. Given that fluoroquinolones are the drugs of choice for the treatment of severe Salmonella infections in adults, the potential continued emergence and dissemination of fluoroquinolone-resistant Salmonella are of great concern.
In the Philippines, several factors contribute to the increasing fluoroquinolone resistance (4.7% nontyphoidal Salmonellae were resistant to fluoroquinolones in 1998). They include over-the-counter availability of fluoroquinolones, and use of fluoroquinolones in animal feeds. The reservoir for most nontyphoidal Salmonellae in the United States is food-producing animals, and the emerging resistance of Salmonella is largely a consequence of the use of antimicrobial agents in animals. The isolation of antibiotic-resistant Salmonella from retail ground meats was reported recently.2,3 Twenty percent of 200 samples of ground meats purchased in the Washington DC area contained Salmonella, with a total of 13 different serotypes. Eighty-four percent were resistant to at least 1 antibiotic and 53% were resistant to at least 3 antibiotics. Sixteen percent were resistant to ceftriaxone, the drug of choice for treatment of Salmonella infection in children. Although all strains were susceptible to ciprofloxacin and nalidixic acid, resistance to these agents may readily emerge.
Are we selecting for importation of drug-resistant salmonellosis by the empiric use of ciprofloxacin in travelers? Improved detection methods enable us to monitor potential changes in food-associated serotypes of Salmonellae as well as isolates from humans and even reptiles.4,5 Studies in returned travelers may shed light on the epidemiology of salmonellosis in the United States.
References
1. Paiva AT, et al. Epidemiologic evidence that prior antimicrobial exposure decreases resistance to infection by antimicrobial-sensitive Salmonella. J Infect Dis. 1990;161:255-260.
2. White DG, et al. The isolation of antibiotic-resistant salmonella from retail ground meats. N Engl J Med. 2001;345:1147-1154.
3. Gorbach SL. Antimicrobial use in animal feed-time to stop. Editorial. N Engl J Med. 2001;345:1202-1203.
4. Lin JS, Tsen HY. Development and use of polymerase chain reaction for the specific detection of Salmonella typhimurium in stool and food samples. J Food Prot. 1999;62(10):1103-1110.
5. Olsen SJ, et al. The changing epidemiology of salmonella: trends in serotypes isolated from humans in the United States. J Infect Dis. 2001;183(5):753-761.
Dr. Mileno, Director, Travel Medicine, The Miriam Hospital, and Assistant Professor of Medicine, Brown University, Providence, RI, is Associate Editor of Travel Medicine Advisor.
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