90 Chapter 5 Susceptibility and resistance genes All MRSA isolates tested susceptible for the antibiotics used in the eradication treatments, and this was in line with the sequencing data that showed the absence of acquired resistance genes to these drugs (Table S2). Treatment failure was therefore not the result of resistance against the antibiotics used for the treatment. A significant association was found between ciprofloxacin resistance and failure of eradication (OR 4.20, 95%CI 1.11–15.96, P =0.04) (Table 2). None of the patients had been treated with ciprofloxacin. The ciprofloxacin-resistant isolates belonged to ST5 (5), ST8 (2), ST22 (3), ST30 (1), ST97 (2), ST105 (1), ST398 (1), ST5544 (1), ST7119 (1), and ST8018 (1). In the ciprofloxacin-resistant isolates (n =18), we detected one or more of the associated point-mutations S84L (10/18) in the gyrase GyrA, S80F (14/18) or S80Y (3/18) or E84G (2/18) or I45M (1/18) in the DNA topoisomerase IV GrlA, and P585S (1/18) in GrlB (Table S3). In the isolates of all patients with treatment failure, mutations associated with ciprofloxacin resistance were identified in 7/12 (58%) of the isolates, whereas in the isolates of patients with successful decolonization, these mutations were identified in 13/44 (30%) isolates (Figure 3). Two isolates with the unique point mutation I45M in GrlA did not show increased MICs to ciprofloxacin. All seven persons with ciprofloxacin-resistant MRSA with failure to eradication treatment were either healthcare workers, or most likely had acquired the MRSA during hospitalization or after medical interventions. Rifampicin resistance-associated point-mutations were found in four isolates (I527L [3/4] and D471Y [1/4] in rpoB). While all four of these isolates had a rifampicin MIC≤0.03, these isolates belonged to four patients with treatment failure (Table S3). No other associations were found between phenotypic antibiotic resistance or resistance genes and failure of eradication treatment (Table 3). Table 2. Phenotypic resistance to antibiotics used in eradication therapy Antibiotic (R) Treatment failure Successful decolonization P N = 12 (%) N = 44 (%) Doxycycline 4 (33.3) 15 (34.1) 1.00 Ciprofloxacin 7 (58.3) 11 (25.0) 0.04 Trimethoprim 0 (0.0) 10 (25.6) 0.09 Cotrimoxazole 0 (0.0) 9 (20.9) 0.18 Clindamycin 6 (50.0) 15 (35.7) 0.50 Rifampicin 0 0 n.a Mupirocin 0 0 n.a Phenotypic resistance per antibiotic agent, stratified by decolonization outcome
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