Case Studies
The Trials of the Returning Traveler
Ciprofloxacin Failure in Enteric Fever
By Alison M. Bormann, M.D., and David R. Boulware, M.D., M.P.H, DTM&H
A previously healthy 24-year-old male presented with high fevers, vomiting, diarrhea, and headaches 2 weeks after visiting family in India. He was diagnosed with enteric fever, and blood cultures grew Salmonella paratyphi A. He was initially hospitalized, treated with 2 days of intravenous ceftriaxone, and then transitioned to ciprofloxacin as an outpatient. The isolate was reported as sensitive to all the antibiotics tested (cephalosporins, fluoroquinolones, sulfa, and ampicillin), and the patient was prescribed a 2-week course of ciprofloxacin (minimum inhibitory concentration [MIC]=1 mg/L).
At the time of discharge, his fevers had resolved, and he returned to his normal state of health within a few days. However, 2 weeks after completing therapy, he developed similar symptoms including fevers, chills, nausea, and diarrhea. He was seen by his primary care physician who did a blood culture and prescribed azithromycin. Three days later, he presented to the emergency department with worsening fevers and vomiting. He was readmitted to the hospital, and blood cultures again grew S. paratyphi A with the same susceptibility pattern. The infectious disease service was consulted. Because of increasing fluoroquinolone clinical failures reported from the Indian subcontinent, the patient was prescribed ceftriaxone. His fever subsided over the next 72 hours, and he was discharged home on amoxicillin for 2 weeks.
Enteric fever, a clinical diagnosis for either typhoid (S. typhi) or paratyphoid (S. paratyphi) infection, occurs in 2.9% of returning travelers, particularly those who have spent time on the Indian subcontinent (14.1%).1 Individuals who visit friends and relatives are much more likely to acquire enteric fever than tourists and business travelers, accounting for 77% of typhoid cases in the United States.2 With increasing worldwide use of fluoroquinolones, resistance is emerging in Salmonella species. This is because of genetic mutations in gyrase A that lead to detectable naladixic acid resistance, the first of 2 steps necessary for complete fluoroquinolone resistance. When nalidixic acid resistance is present, there is a higher MIC to ciprofloxacin, yet the isolates are still considered susceptible within the official breakpoints published by the National Committee for Clinical Laboratory Specialists. Unfortunately, clinical failure frequently occurs when the ciprofloxacin MIC is >0.25 mg/L.3 Therefore, it is now recommended that Salmonella species be tested for nalidixic acid resistance.
By current criteria, treatment failure can occur when patients receive ciprofloxacin when the organism is characterized as susceptible but has an elevated MIC.4 In this patient, treatment failure occurred with a standard dose of ciprofloxacin (500 mg twice daily with a MIC of 1.0 mg/L, below the cutoff for resistance). Subsequent testing by the Minnesota Department of Health confirmed nalidixic acid resistance. Clinical failure with ciprofloxacin treatment has similarly been reported in enteric fever in the presence of elevated MICs.3 Clinicians treating returning travelers should be aware of increasing fluoroquinolone resistance in India and Southeast Asia and consider using alternative agents. Fortunately, multidrug resistance remains rare, although the incidence is increasing.5 And, at present, the Salmonella species are usually susceptible to alternative treatments such as third-generation cephalosporins, ampicillin, and sulfa derivatives.
Alison Bormann is an infectious disease fellow and David Boulware is an assistant professor of infectious disease at the University of Minnesota.
References
1. Freedman DO, Weld LH, Kozarsky PE, et al. Spectrum of disease and relation to place of exposure among ill returned travelers. N Engl J Med. 2006;354(2):119-30.
2. Bacaner N, Stauffer B, Boulware DR, Walker PF, Keystone JS. Travel medicine considerations for North American immigrants visiting friends and relatives. JAMA. 2004;291(23):2856-64.
3. Slinger R, Desjardins M, McCarthy AE, et al. Suboptimal clinical response to ciprofloxacin in patient with enteric fever due to Salmonella spp. with reduced fluoroquinolone susceptibility: a case series. BMC Infect Dis. 2004;4:36-9.
4. Dimitrov T, Udo EE, Albaksami O, Kilani AA, Shehab el-DM. Ciprofloxacin treatment failure in a case of typhoid fever caused by Salmonella enterica serotype paratyphi A with reduced susceptibility to ciprofloxacin. J Med Microbiol. 2007;56(Pt2):277-9.
5. Manchanda V, Bhalla P, Sethi M, Sharma VK. Treatment of enteric fever in children on the basis of current trends of antimicrobial susceptibility of Salmonella Serovar Typhi and Paratyphi A. Indian J Med Microbiol.
2006;24(2):101-6.