Case of Shigella flexneri infection with treatment failure due to azithromycin resistance in an HIV-positive patient.

Dear Editor,We read the paper by Hoffmann et al. on the high rates ofquinolone-resistant strains of Shigella sonnei in humanimmunodeficiency virus (HIV)-infected men who have sexwith men (MSM) in Germany [1]. The authors report that,due to these high rates of resistant isolates, the empiricaluse of quinolones in HIV-infected patients presenting withS. sonnei infection is no longer recommended. We fullyagree with this statement. Further, traditional antibioticscan no longer be used as the first-line treatment, becausemultidrug resistance is already widespread among Shigellaisolates. As a consequence of the emergence of quinoloneresistance in Campylobacter isolates, azithromycin isalready widely used as the empirical treatment of bacterialgastroenteritis. Patients with a gastroenteritis caused by aShigella infection will, therefore, often be treated withazithromycin as the first-line treatment. Although no clin-ical breakpoints are available, cases of Shigella isolateswith increased minimum inhibitory concentrations (MICs)for azithromycin have already been documented in Asiancountries [2]. Recently, the first observations of increasedMICs for azithromycin in Shigella isolates have beenreported in the United States [3]. Therefore, we would liketo describe the first report of treatment failure in an HIV-positive patient with a Shigella bacteremia which wetreated with azithromycin.A Dutch untreated HIV-positive man with a CD4 countof 650/mL was hospitalized in April 2012 with fever,abdominal pain, and bloody diarrhea. He had a sexualencounter with another man in Berlin, Germany 7 daysearlier. As clusters of sexually transmitted Shigella infec-tions among MSM have been reported previously, wesuspected a Shigella infection. To cover Campylobacterand Salmonella as well, which are the most frequent causesof bacterial gastroenteritis in the Netherlands, we initiatedtherapy with azithromycin 500 mg per day. 48 h later,Shigella flexneri infection was confirmed in the blood andfeces cultures. Because, at that time, the patient continuedto have diarrhea, abdominal pain, and high fevers, weinitiated intravenous therapy with ceftriaxone 2 g QD andazithromycin was discontinued. Antimicrobial susceptibil-ity testing showed susceptibility to ciprofloxacin (MICB0.25), ceftriaxone (MIC B1), and trimethoprim/sulfa-methoxazole (MIC B1 mg/L), but the isolate was resistantto azithromycin (MIC [256 mg/L). To confirm theincreased azithromycin MIC, initially obtained by theEtest, the MIC was determined by the broth microdilutionmethod with Mueller–Hinton II cation-adjusted broth(MIC = 128 mg/L). Repeated blood cultures after treat-ment were negative. The patient became afebrile 48 h afterthe initiation of ceftriaxone and he fully recovered withoutcomplications.