Suitable disk antimicrobial susceptibility breakpoints defining Salmonella enterica serovar Typhi isolates with
Christopher M Parry1, Chau Tran Thuy, Sabina Dongol
1The Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, 190 Ben Ham Tu, Quan 5, Ho Chi Minh City, Vietnam. cmparry59@gmail.com
Abstract:
Infections with Salmonella enterica serovar Typhi isolates that have reduced susceptibility to ofloxacin (MIC ≥ 0.25 μg/ml) or ciprofloxacin (MIC ≥ 0.125 μg/ml) have been associated with a delayed response or clinical failure following treatment with these antimicrobials. These isolates are not detected as resistant using current disk susceptibility breakpoints. We examined 816 isolates of S. Typhi from seven Asian countries. Screening for nalidixic acid resistance (MIC ≥ 16 μg/ml) identified isolates with an ofloxacin MIC of ≥0.25 μg/ml with a sensitivity of 97.3% (253/260) and specificity of 99.3% (552/556). For isolates with a ciprofloxacin MIC of ≥0.125 μg/ml, the sensitivity was 92.9% (248/267) and specificity was 98.4% (540/549). A zone of inhibition of ≤28 mm around a 5-μg ofloxacin disc detected strains with an ofloxacin MIC of ≥0.25 μg/ml with a sensitivity of 94.6% (246/260) and specificity of 94.2% (524/556). A zone of inhibition of ≤30 mm detected isolates with a ciprofloxacin MIC of ≥0.125 μg/ml with a sensitivity of 94.0% (251/267) and specificity of 94.2% (517/549). An ofloxacin MIC of ≥0.25 μg/ml and a ciprofloxacin MIC of ≥0.125 μg/ml detected 74.5% (341/460) of isolates with an identified quinolone resistance-inducing mutation and 81.5% (331/406) of the most common mutant (carrying a serine-to-phenylalanine mutation at codon 83 in the gyrA gene). Screening for nalidixic acid resistance or ciprofloxacin and ofloxacin disk inhibition zone are suitable for detecting S. Typhi isolates with reduced fluoroquinolone susceptibility.
Insights
Salmonella Typhi isolates with reduced susceptibility to ofloxacin or ciprofloxacin are not detected by current methods. Nalidixic acid resistance screening and disk diffusion tests effectively identify these challenging Salmonella Typhi strains.
Area of Science:
- Microbiology
- Infectious Diseases
- Antimicrobial Resistance
Background:
- Salmonella enterica serovar Typhi (S. Typhi) infections with reduced fluoroquinolone susceptibility are linked to treatment failure.
- Current susceptibility testing methods may not detect isolates with intermediate resistance to ofloxacin and ciprofloxacin.
- This poses a challenge for effective typhoid fever management.
Purpose of the Study:
- To evaluate the efficacy of nalidixic acid resistance screening and disk diffusion tests in identifying S. Typhi isolates with reduced susceptibility to ofloxacin and ciprofloxacin.
- To determine the sensitivity and specificity of these screening methods.
Main Methods:
- Analysis of 816 S. Typhi isolates from seven Asian countries.
- Testing for nalidixic acid resistance (MIC ≥ 16 μg/ml).
- Assessing ofloxacin (MIC ≥ 0.25 μg/ml) and ciprofloxacin (MIC ≥ 0.125 μg/ml) minimum inhibitory concentrations (MICs).
- Evaluating disk diffusion zone sizes for ofloxacin (5-μg disc) and ciprofloxacin.
Main Results:
- Nalidixic acid resistance screening showed high sensitivity (97.3%) and specificity (99.3%) for detecting reduced ofloxacin susceptibility.
- Disk diffusion tests for ofloxacin (≤28 mm) and ciprofloxacin (≤30 mm) also demonstrated good sensitivity and specificity.
- These methods identified isolates with quinolone resistance-inducing mutations, including the common gyrA mutation.
Conclusions:
- Screening for nalidixic acid resistance is a sensitive and specific method for detecting S. Typhi with reduced fluoroquinolone susceptibility.
- Disk diffusion tests provide a practical alternative for identifying these challenging isolates.
- Implementing these screening methods can improve the detection of antimicrobial resistance in S. Typhi, aiding in better treatment strategies.
