Azithromycin and Ciprofloxacin Resistance in Salmonella Bloodstream Infections in Cambodian Adults

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Abstract
Salmonella enterica is a frequent cause of bloodstream infection (BSI) in Asia but few data are available from Cambodia. We describe Salmonella BSI isolates recovered from patients presenting at Sihanouk Hospital Centre of Hope, Phnom Penh, Cambodia (July 2007–December 2010). Blood was cultured as part of a microbiological prospective surveillance study. Identification of Salmonella isolates was performed by conventional methods and serotyping. Antibiotic susceptibilities were assessed using disk diffusion, MicroScan and E-test macromethod. Clonal relationships were assessed by Pulsed Field Gel Electrophoresis; PCR and sequencing for detection of mutations in Gyrase and Topoisomerase IV and presence of qnr genes. Seventy-two Salmonella isolates grew from 58 patients (mean age 34.2 years, range 8–71). Twenty isolates were identified as Salmonella Typhi, 2 as Salmonella Paratyphi A, 37 as Salmonella Choleraesuis and 13 as other non-typhoid Salmonella spp. Infection with human immunodeficiency virus (HIV) was present in 21 of 24 (87.5%) patients with S. Choleraesuis BSI. Five patients (8.7%) had at least one recurrent infection, all with S. Choleraesuis; five patients died. Overall, multi drug resistance (i.e., co-resistance to ampicillin, sulphamethoxazole-trimethoprim and chloramphenicol) was high (42/59 isolates, 71.2%). S. Typhi displayed high rates of decreased ciprofloxacin susceptibility (18/20 isolates, 90.0%), while azithromycin resistance was very common in S. Choleraesuis (17/24 isolates, 70.8%). Two S. Choleraesuis isolates were extended spectrum beta-lactamase producer. Resistance rates in Salmonella spp. in Cambodia are alarming, in particular for azithromycin and ciprofloxacin. This warrants nationwide surveillance and revision of treatment guidelines. Salmonella enterica is a bacterium that causes important morbidity and mortality worldwide, especially in tropical low-resource settings. Over the past two decades, increasing rates of resistance for the commonly available oral antibiotics have been reported in Salmonella spp., especially from South(east) Asia. As microbiology laboratories are extremely scarce in Cambodia, data on the presence and resistance of Salmonella spp. in this country are limited. The authors describe the different types and antibiotic resistance of 72 Salmonella isolates from blood cultures sampled in 58 adult Cambodian patients with fever. The most common serovars were Salmonella Typhi and Salmonella Choleraesuis. The latter serovar causes illness in pigs, and may occasionally infect humans through contact with contaminated animals or environments, especially those with decreased immunity. The authors noted resistance for the first line oral antibiotics in nearly three quarters of all Salmonella isolates. In addition, 90% of all S. Typhi had decreased susceptibility for ciprofloxacin, while around 70% of S. Choleraesuis showed resistance to azithromycin. These results seriously limit the treatment options for typhoid fever and other invasive Salmonella infections and warrant nationwide surveillance of antibiotic resistance. This is the first report to describe such high rates of azithromycin resistance in Salmonella enterica.

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