First Report of Salmonella enterica Serotype Paratyphi A Azithromycin Resistance Leading to Treatment Failure

Abstract

The prevalence of Salmonella enterica serotype Paratyphi A infection is increasing, and multidrug resistance is a well-recognized problem. Resistance to fluoroquinolones is common and leads to more frequent use of newer agents like azithromycin. We report the first case of azithromycin resistance and treatment failure in a patient with S. Paratyphi A infection. CASE REPORTA 48-year-old male doctor presented to the accident and emergency department with a 2-week history of rigors, fever, and lethargy following a 10-day vacation in Islamabad, Pakistan. He had not been vaccinated against typhoid or taken antimalarial chemoprophylaxis. He developed diarrhea 2 days prior to the end of his stay in Pakistan and took oral metronidazole at 400 mg three times daily for 5 days. The diarrhea resolved, but his temperature continued to spike to 39°C over the following 2 weeks. He had a prior medical history of hypercholesterolemia and gout and had had an appendectomy as a young student. His regular medications consisted of allopurinol at 200 mg once daily and simvastatin at 20 mg once daily. Clinical examination on presentation was unremarkable other than a temperature of 38.5°C.Initial laboratory investigations revealed a raised alanine transaminase (ALT) level of 93 IU/liter (normal value, 10 to 50 IU/liter), a bilirubin level of 20 mol/liter (normal value, 3 to 17 mol/liter), and a C-reactive protein (CRP) level of 70 mg/liter (normal value, Ͻ5 mg/liter). Full blood count, serum electrolytes, and creatinine were within normal limits. Chest and abdominal radiographs showed no abnormalities. A malaria blood film and antigen test were negative.In view of the possibility of enteric fever, he was started on oral ciprofloxacin at 500 mg twice daily according to the hospital antibiotic policy. He was reluctant to be admitted to the hospital and was discharged with a follow-up appointment in the infectious diseases outpatient clinic. Blood cultures taken on admission yielded Salmonella enterica serotype Paratyphi A, which was reported as sensitive to ciprofloxacin on disc testing.The patient presented again following 7 days of treatment with persistent fever and rigors. He remained reluctant to be admitted, and so antimicrobial therapy was changed to oral azithromycin.His symptoms worsened over the next 3 days, and he was admitted to the hospital. He complained of increasing frequency of rigors and fevers, occurring every 4 h and lasting for 2 h, and a dry cough. He had been fully adherent to the antimicrobial therapy prescribed. On examination he had a temperature of 38°C and the spleen was palpable 1 cm below the costal margin. In view of the poor response to treatment, antimicrobial therapy was changed to intravenous ceftriaxone at 2 g once daily.Laboratory investigations revealed a raised CRP level of 65 mg/liter (normal value, Ͻ5 mg/liter), an ALT level of 358 IU/liter (normal value, 10 to 50 IU/liter), an alkaline phosphatase level of 256 IU/liter (normal value, 30 to 200 IU/liter), and a negative malaria film. A repeat ches...

Antimicrobial Susceptibility of Salmonella Enterica Serovars in a Tertiary Care Hospital in Koshi Region (Northern Bihar), India

“…[36] All isolates in our study were sensitive to ceftriaxone in contrast to some studies that reported resistance to ceftriaxone. [37,38] A limitation of our study was that clinical outcomes were not analysed. Quinolones may remain effective despite in vitro resistance and ceftriaxone may be associated with prolonged time to fever resolution despite in vitro sensitivity.…”

ANTIMICROBIAL RESISTANCE OF Salmonella enterica serovars typhi and paratyphi FROM BLOOD ISOLATES IN CHILDREN FROM A NORTH DELHI TERTIARY CARE HOSPITAL

“…In our study, all the isolates tested were resistant to nalidixic acid (NAR), which is a very serious matter of concern posing challenge in effective treatment and management of these infections. Other treatment options for enteric fever includes azithromycin, a microcline antimicrobial, used widely now a day with good clinical response because of intra cellular accumulation of the drug [ 7,14]. Unfortunately, some authors have reported resistance to azithromycin too from different parts of the world [14][15][16][17].…”

“…Other treatment options for enteric fever includes azithromycin, a microcline antimicrobial, used widely now a day with good clinical response because of intra cellular accumulation of the drug [ 7,14]. Unfortunately, some authors have reported resistance to azithromycin too from different parts of the world [14][15][16][17]. Based on the results of our study, especially low level resistance observed towards first line antimicrobials used in the treatment of enteric fever, it can be suggested that these can be recommended either alone or in combination with cephalosporin or azithromycin as part of empirical treatment regimen.…”

“…Furthermore, various other studies across the globe documented an increase in resistance towards quinolones and third generation cephalosporins, commonly used for empirical treatment of enteric fever [8][9][10][11][12][13]. Azithromycin, a broad-spectrum macrolide antimicrobial, although costly, introduced later for the treatment of enteric fever, as a very good option because of its property of intra cellular concentration and good clinical response [14][15][16][17]. Unfortunately, many researchers have reported emergence of resistance for azithromycin from various parts of the world [14][15][16][17].…”

“…Azithromycin, a broad-spectrum macrolide antimicrobial, although costly, introduced later for the treatment of enteric fever, as a very good option because of its property of intra cellular concentration and good clinical response [14][15][16][17]. Unfortunately, many researchers have reported emergence of resistance for azithromycin from various parts of the world [14][15][16][17]. This variable and changing susceptibility pattern worldwide among the isolates of Salmonella typhi and Salmonella paratyphi emphasizes upon the importance of continuous monitoring and evaluation of locally prevalent antibiogram pattern for making suitable treatment guidelines for enteric fever.…”