During the study period (2005 to 2010), a total of 146 Staphylococcus spp. isolates were recovered from endophthalmitis patients at our institution. The most frequent species was S. epidermidis, which accounted for 63.7% (93) of the isolates. Among the S. epidermidis isolates, 59.1% (55) were methicillin resistant and 40.9% (38) were methicillin susceptible. Methicillin resistance ranged from 33.3% in 2005 to 92.3% in 2010. Consequently, the percentage of MSSE declined from 66.7% in 2005 to 7.7% in 2010. Resistance increased for all fluoroquinolone antibiotics during the period of study. The ciprofloxacin resistance rate was 66.7% and ranged from 58% in 2005 to 77% in 2010. The frequency of isolates resistant to 8-methoxyfluoroquinolones was 58.4% and ranged from 55% in 2005 to 69% in 2010 ().
Frequency of ciprofloxacin and 8-methoxyfluoroquinolone resistance rates for MSSE, MRSE, and all S. epidermidis isolates from 2005 to 2010 at BPEIa
No significant increase in resistance to ciprofloxacin or the 8-methoxyfluoroquinolones was observed for MRSE isolates during the study period. However, ciprofloxacin and 8-methoxyfluoroquinolone resistance rates among MSSE isolates were more than double in 2007 compared to 2005 and 2006 and remained high in the following 2 years, 2008 and 2009. In 2010, only one MSSE isolate was recovered (also fluoroquinolone susceptible). The ciprofloxacin resistance rate among MSSE was 52.6% (20 out of 38) and ranged from 37.5% in 2005 to 80% in 2009. The resistance rate to 8-methoxyfluoroquinolones was 39.5% (15 out of 38) and ranged from 25% in 2005 to 50% in 2009 (). These selected MSSE isolates (n = 15) resistant to 8-methoxyfluoroquinolones were further analyzed.
Clinical features, ocular history, and prophylactic antibiotic usage among the 15 patients diagnosed with endophthalmitis caused by MSSE isolates resistant to 8-methoxyfluoroquinolones are summarized in . The mean age was 73 years (range, 56 to 92 years). Most of the patients were female (53.3%). At the time of clinical diagnosis, 13 patients (86.6%) were using prophylactic topical antibiotics. Information on the prophylaxis regimen for 2 patients was not available. Four patients had received gatifloxacin, 7 received moxifloxacin, 1 received gatifloxacin and ofloxacin, and 1 received moxifloxacin and vancomycin. Most cases were postoperative (6 acute and 1 delayed). Four patients experienced an infection after intravitreal injection of vascular epithelial growth factor (VEGF) antagonists, and 1 patient's infection occurred after severe fungal keratitis. Initial visual acuity at presentation ranged from counting finger to light perception, and final visual acuity ranged from 20/30 to hand motion.
Clinical features, ocular history, prophylactic antibiotic usage, and outcomes for patients with endophthalmitis from whom MSSE isolates resistant to 8-methoxyfluoroquinolones were recovereda
Microbiology and molecular characterizations of the 15 MSSE isolates resistant to 8-methoxyfluoroquinolones are summarized in . The MIC90 for oxacillin among these isolates was 0.25 μg/ml; 6 (40%) of isolates had an oxacillin MIC of 0.19 μg/ml, and for the remaining 9 (60%) it was 0.25 μg/ml. High-level resistance to 8-methoxyfluoroquinolones (MIC, >32 μg/ml) was documented in 46.7% (7 out of 15) of the isolates. Low-level resistance (MIC, 2 to 4 μg/ml) was identified for the remaining 8 (53.3%) isolates. All isolates were also resistant to ciprofloxacin, levofloxacin, and ofloxacin, with MICs of >32 μg/ml. All isolates were susceptible to linezolid (MICs raging from 1 to 4 μg/ml) and vancomycin (MICs ranging from 1.5 to 3 μg/ml).
Mutations in the QRDRs of gyrA and parC and MICs for fluoroquinolones and comparator agents
Mutations in the QRDRs of the gyrA and parC genes were found for the 14 tested isolates (). In the gyrA gene, the substitution of a serine for a phenylalanine at codon 84 (Ser84Phe) was found for all isolates. In addition, a second point mutation at codon 88 (Glu88Lys) was also identified for 7 out of 14 isolates (50%), which was associated with a higher MIC of 8-methoxyfluoroquinoles. All isolates with a double point mutation in the gyrA gene demonstrated high-level resistance to moxifloxacin and gatifloxacin (MICs, >32 μg/ml), regardless of the number and combination of point mutations in the QRDR of parC.
In the parC gene, a single point mutation (Ser80Phe) was found in only one isolate, and all the other (13/14) harbored a double point mutation with four different combinations, including Ser80Tyr and Asp84Tyr in 5 isolates (35.7%), Ser80Phe and Asp84Asn in 4 isolates (28.6%), Ser80Phe and Asp84Gly in 3 isolates (21.4%), and Ser80Phe and Asp84Val in 1 isolate (7.1%).