Azithromycin for Salmonella infection: don’t presume it works

Salmonella infection manifests as enteritis and enteric fever, predominantly acquired overseas. When required, therapy with azithromycin, ciprofloxacin or ceftriaxone is recommended by the Therapeutic guidelines: antibiotic;1 however, reduced susceptibility to fluoroquinolones in Asia limits the use of ciprofloxacin unless susceptibility is confirmed.2 The Australian Bureau of Statistics recorded a 546% increase in short term departures to Indonesia over 10 years, with 1.2 million nationally in 2016.3

A 31-year-old man was taking long term azithromycin 250 mg daily to prevent bronchiolitis obliterans syndrome after a bilateral lung transplant several years earlier for cystic fibrosis. Three weeks after returning from Bali, he was admitted with fatigue, fever, diarrhoea and abdominal pain. He had acute kidney injury. His C-reactive protein level was 190 mg/L (reference interval [RI], < 5 mg/L) and procalcitonin concentration was 3.5 μg/L (RI, < 0.05 μg/L). A single set of blood cultures was negative. Stool culture isolated Salmonella enterica serovar Paratyphi B var Java, sensitive to ceftriaxone and ciprofloxacin, with a raised azithromycin minimum inhibitory concentration (MIC) of 64 mg/L by ETEST (bioMérieux); an MIC > 16 mg/L indicates non-wild-type4 and is associated with treatment failures. Owing to his immunocompromised state, the patient received a 14-day course of ciprofloxacin (MIC, 0.016 mg/L).

Our review of 2015–2017 data from the Western Australian public pathology provider revealed that two of 31 typhoidal Salmonella isolates (Salmonella Paratyphi A and Salmonella Typhi bacteraemia, each acquired in India) and one of 15 non-typhoidal Salmonella isolates (S. typhimurium, no clinical details provided) had an azithromycin MIC > 16 mg/L. Ceftriaxone resistance was low at 0% (0/117) of typhoidal Salmonella and 0.4% (7/1648) of non-typhoidal Salmonella; ciprofloxacin resistance was higher at 48.0% (47/98) of typhoidal Salmonella and 6.8% (94/1384) of non-typhoidal Salmonella. By comparison, azithromycin MIC > 16 mg/L was found in 16.1% of typhoidal Salmonella from travellers returning to the Netherlands,5 and in 1.3% of non-typhoidal Salmonella in the United States.4

Azithromycin use while travelling probably selected for resistant Salmonella infection in this case. However, our data show that azithromycin susceptibility cannot be assumed in Salmonella infections; testing should therefore occur in serious cases, along with ongoing surveillance for evolving resistance.