Abstract
The LEADER surveillance program monitors the in vitro activity of linezolid and comparator agents against Gram-positive bacteria in the United States. In its eighth consecutive year (2011), a total of 60 medical centers from the United States, including seven medical centers specializing in children's health care contributed a total of 7,303 Gram-positive pathogens. The MIC90 value for Staphylococcus aureus was 2 μg/ml, and for coagulase-negative staphylococci, enterococci, Streptococcus pneumoniae, β-hemolytic streptococci, and viridans group streptococci, the MIC90 was 1 μg/ml. The “all organism” linezolid-resistant and nonsusceptible rate was only 0.19%.
TEXT
Linezolid, approved in 2000, is the only oxazolidinone marketed for human use in the United States (1). It has been shown to be clinically effective against a variety of Gram-positive pathogens (2–7). The LEADER surveillance program, which began in 2004, has monitored the activity, spectrum, and resistance rate of this agent in the United States for eight consecutive years (8–14). In this report of the 2011 LEADER Program, 60 medical centers (5 to 8 per U.S. Census Bureau region), including seven medical centers specializing in children's health care, contributed a total of 7,303 Gram-positive pathogens.
Susceptibility tests and confirmation of linezolid-resistant isolates were performed as described previously (14) applying current Clinical Laboratory and Standards Institute (CLSI) methods and criteria (15–17). Staphylococcus aureus strains that were resistant to erythromycin but susceptible to clindamycin were screened by the CLSI D-test (disk approximation) to detect inducible clindamycin resistance (16).
A total of 3,025 S. aureus and 761 coagulase-negative staphylococcus (CoNS) isolates were tested (Tables 1 and 2). U.S. Census Bureau region sample sizes for S. aureus ranged from 200 (Mountain) to 512 (East North Central) isolates (data not shown). The overall methicillin-resistant S. aureus (MRSA) rate was 49.8% (50.8% in 2010; has been declining since 2007, when it was 58.2%) (8, 11, 12, 14). The MRSA rate varied by region from 39.4% (Middle Atlantic) to 59.2% (East South Central). The MIC50 and modal MIC for MRSA and methicillin-susceptible S. aureus (MSSA) were the same at 1 μg/ml (Table 1). All MSSA and 99.8% of MRSA were susceptible to linezolid. The overall linezolid MIC50 and MIC90 for CoNS were 0.5 and 1 μg/ml, respectively (Table 1). The oxacillin-resistant CoNS rate was 63.5%, which had decreased from 70.6% in 2010 (14). The MIC50 and MIC90 values for methicillin-susceptible and methicillin-resistant CoNS were 0.5 and 1 μg/ml, respectively, and the overall linezolid susceptibility rate was 98.8%. Other resistances of note were the high rate of fluoroquinolone resistance (45.9 and 47.2%, respectively, for levofloxacin and ciprofloxacin) and tetracycline resistance (14.6%). Daptomycin and vancomycin were highly active (99.9 and 100.0% susceptible), and teicoplanin susceptibility was at 98.3%.
Table 1.
Isolate inhibition at different linezolid MICs in a study of 7,303 isolates in the 2011 LEADER Programa
| Organism groupb or species (no. of isolates tested) | Cumulative no. of isolates (%) inhibited at linezolid MIC (μg/ml) of: |
|||||||
|---|---|---|---|---|---|---|---|---|
| ≤0.12 | 0.25 | 0.5 | 1 | 2 | 4 | 8 | >8 | |
| β-Hemolytic streptococci (895) | 0 (0) | 4 (4.5) | 235 (26.3) | 892 (99.7) | 895 (100.0) | |||
| S. pneumoniae (943) | 3 (0.3) | 29 (3.1) | 363 (38.5) | 930 (98.6) | 943 (100.0) | |||
| Enterococci (1,160) | 1 (0.1) | 4 (0.3) | 115 (9.9) | 1,048 (90.3) | 1,156 (99.7) | 1,159 (99.9) | 1,160 (100.0) | |
| S. aureus (3,025) | 0 (0) | 2 (0.1) | 197 (6.5) | 2,689 (88.9) | 3,020 (99.8) | 3,022 (99.9) | 3,025 (100.0) | |
| MRSA (1,505) | 0 (0) | 0 (0) | 123 (8.2) | 1,388 (92.2) | 1,500 (99.7) | 1,502 (99.8) | 1,505 (100.0) | |
| MSSA (1,520) | 0 (0) | 2 (0.1) | 74 (4.9) | 1,301 (85.6) | 1,520 (100.0) | |||
| Viridans group streptococci (519) | 1 (0.2) | 21 (4.0) | 210 (40.5) | 506 (97.5) | 518 (99.8) | 518 (99.8) | 518 (99.8) | 519 (100.0) |
| CoNS (761) | 2 (0.3) | 55 (7.2) | 591 (77.7) | 749 (98.4) | 752 (98.8) | 752 (98.8) | 752 (98.8) | 761 (100.0) |
| MRCoNS (483) | 1 (0.2) | 42 (8.7) | 377 (78.1) | 472 (97.7) | 475 (98.3) | 475 (98.3) | 475 (98.3) | 483 (100.0) |
| MSCoNS (278) | 1 (0.4) | 13 (4.7) | 214 (77.0) | 277 (99.6) | 277 (99.6) | 277 (99.6) | 277 (99.6) | 278 (100.0) |
Number of isolates inhibited at each linezolid MIC in a test of six different groups of Gram-positive cocci isolated from all U.S. Census Board regions (LEADER Program, 2011). A total of 7,303 isolates were tested.
MRSA, methicillin-resistant S. aureus; methicillin-susceptible S. aureus (MSSA); CoNS, coagulase-negative staphylococcus (CoNS); MRCoNS, methicillin-resistant CoNS; MSCoNS, methicillin-susceptible CoNS.
Table 2.
Comparative activity of linezolid tested against 7,303 Gram-positive pathogens isolated during the 2011 LEADER Program
| Organism, resistance group (no. of strains tested), and antimicrobial agent | MIC(μg/ml) |
CLSI %S/%Ra | ||
|---|---|---|---|---|
| 50% | 90% | Range | ||
| S. aureus | ||||
| Oxacillin-susceptible (1,520) | ||||
| Linezolid | 1 | 2 | 0.25–2 | 100.0/0.0 |
| Ceftriaxoneb | 4 | 4 | 1–8 | 96.8/0.0 |
| Piperacillin-tazobactam | 1 | 2 | ≤0.5–8 | 100.0/0.0 |
| Vancomycin | 1 | 1 | 0.25–2 | 100.0/0.0 |
| Teicoplanin | ≤2 | ≤2 | ≤2 | 100.0/0.0 |
| Daptomycin | 0.25 | 0.5 | ≤0.06–1 | 100.0/NA |
| Erythromycin | 0.25 | >16 | ≤0.12–>16 | 65.5/30.9 |
| Clindamycinc | ≤0.25 | ≤0.25 | ≤0.25–>2 | 95.4/4.5 |
| Tetracycline | ≤0.25 | 0.5 | ≤0.25–>8 | 96.0/3.5 |
| Tigecyclined | 0.06 | 0.06 | ≤0.03–0.25 | 100.0/NA |
| Gentamicin | ≤1 | ≤1 | ≤1–>8 | 98.9/1.0 |
| Levofloxacin | ≤0.12 | 2 | ≤0.12–>4 | 89.1/9.8 |
| Ciprofloxacin | 0.25 | >4 | ≤0.03–>4 | 87.5/11.3 |
| Trimethoprim-sulfamethoxazole | ≤0.5 | ≤0.5 | ≤0.5–>4 | 99.0/1.0 |
| Oxacillin-resistant (1,505) | ||||
| Linezolid | 1 | 1 | 0.5–8 | 99.8/0.2 |
| Vancomycin | 1 | 1 | ≤0.25–2 | 100.0/0.0 |
| Teicoplanin | ≤2 | ≤2 | ≤2–4 | 100.0/0.0 |
| Daptomycin | 0.25 | 0.5 | 0.12–1 | 100.0/NA |
| Erythromycin | >16 | >16 | ≤0.12–>16 | 10.1/88.5 |
| Clindamycinc | ≤0.25 | >2 | ≤0.25–>2 | 72.3/27.6 |
| Tetracycline | ≤0.25 | 0.5 | ≤0.25–>8 | 95.2/4.5 |
| Tigecyclined | 0.06 | 0.12 | ≤0.03–0.5 | 100.0/NA |
| Gentamicin | ≤1 | ≤1 | ≤1–>8 | 97.3/2.4 |
| Levofloxacin | 4 | >4 | ≤0.12–>4 | 31.4/65.0 |
| Ciprofloxacin | >4 | >4 | ≤0.03–>4 | 29.5/68.8 |
| Trimethoprim-sulfamethoxazole | ≤0.5 | ≤0.5 | ≤0.5–>4 | 97.7/2.3 |
| CoNS | ||||
| Oxacillin-susceptible (278)e | ||||
| Linezolid | 0.5 | 1 | ≤0.12–>8 | 99.6/0.4 |
| Piperacillin-tazobactam | ≤0.5 | ≤0.5 | ≤0.5–2 | 100.0/0.0 |
| Ceftriaxoneb | 2 | 4 | 0.25–>8 | 95.3/1.1 |
| Vancomycin | 1 | 2 | 0.25–4 | 100.0/0.0 |
| Teicoplanin | ≤2 | 4 | ≤2–16 | 97.8/0.0 |
| Daptomycin | 0.25 | 0.5 | ≤0.06–1 | 100.0/NA |
| Erythromycin | 0.25 | >16 | ≤0.12–>16 | 59.4/39.9 |
| Clindamycinc | ≤0.25 | >2 | ≤0.25–>2 | 84.2/13.0 |
| Tetracycline | ≤0.25 | 2 | ≤0.25–>8 | 90.6/7.6 |
| Tigecyclined | 0.06 | 0.12 | ≤0.03–0.25 | NA |
| Gentamicin | ≤1 | ≤1 | ≤1–>8 | 95.0/3.6 |
| Levofloxacin | 0.25 | >4 | ≤0.12–>4 | 77.0/21.9 |
| Ciprofloxacin | 0.25 | >4 | ≤0.03–>4 | 77.0/23.0 |
| Trimethoprim-sulfamethoxazole | ≤0.5 | >4 | ≤0.5–>4 | 79.9/20.1 |
| Oxacillin-resistant (483)f | ||||
| Linezolid | 0.5 | 1 | ≤0.12–>8 | 98.3/1.7 |
| Vancomycin | 2 | 2 | ≤0.12–4 | 100.0/0.0 |
| Teicoplanin | ≤2 | 8 | ≤2–16 | 98.6/0.0 |
| Daptomycin | 0.25 | 0.5 | ≤0.06–2 | 99.8/NA |
| Erythromycin | >16 | >16 | ≤0.12–>16 | 28.0/68.3 |
| Clindamycinc | ≤0.25 | >2 | ≤0.25–>2 | 62.7/34.6 |
| Tetracycline | 1 | >8 | ≤0.25–>8 | 81.0/18.6 |
| Tigecyclined | 0.06 | 0.12 | ≤0.03–0.5 | NA |
| Gentamicin | ≤1 | >8 | ≤1–>8 | 68.5/24.6 |
| Levofloxacin | >4 | >4 | ≤0.12–>4 | 38.7/59.6 |
| Ciprofloxacin | >4 | >4 | ≤0.03–>4 | 38.1/61.1 |
| Trimethoprim-sulfamethoxazole | 2 | >4 | ≤0.5–>4 | 55.3/44.7 |
| Enterococcus spp. (1,160)g | ||||
| Linezolid | 1 | 1 | ≤0.12–8 | 99.7/0.1 |
| Ampicillin | 1 | >8 | ≤0.25–>8 | 71.9/28.1 |
| Piperacillin-tazobactam | 4 | >64 | ≤0.5–>64 | 71.9/NA |
| Vancomycin | 1 | >16 | 0.25–>16 | 72.7/26.6 |
| Teicoplanin | ≤2 | >16 | ≤2–>16 | 74.6/24.5 |
| Daptomycin | 1 | 2 | ≤0.06–8 | 99.9/NA |
| Erythromycin | >16 | >16 | ≤0.12–>16 | 8.0/62.8 |
| Tigecyclined | 0.06 | 0.06 | ≤0.03–2 | 99.7/NA |
| Levofloxacin | 2 | >4 | 0.25–>4 | 50.3/48.4 |
| Ciprofloxacin | 2 | >4 | ≤0.03–>4 | 42.8/49.9 |
| S. pneumoniae (943) | ||||
| Linezolid | 1 | 1 | ≤0.12–2 | 100.0/NA |
| Penicillinh | ≤0.06 | 4 | ≤0.06–8 | 84.4/2.0 |
| Penicillini | ≤0.06 | 4 | ≤0.06–8 | 57.7/22.8 |
| Amoxicillin-clavulanate | ≤1 | 8 | ≤1–>8 | 81.0/14.7 |
| Ceftriaxone | ≤0.06 | 2 | ≤0.06–8 | 87.6/1.2 |
| Vancomycin | 0.25 | 0.5 | ≤0.12–1 | 100.0/NA |
| Erythromycin | ≤0.12 | >16 | ≤0.12–>16 | 55.1/44.5 |
| Clindamycin | ≤0.25 | >2 | ≤0.25–>2 | 77.5/22.0 |
| Levofloxacin | 1 | 1 | ≤0.12–>4 | 98.9/1.1 |
| Tetracycline | 0.5 | >8 | ≤0.25–>8 | 73.0/26.3 |
| Tigecyclined | ≤0.03 | 0.06 | ≤0.03–0.12 | 99.9/NA |
| Trimethoprim-sulfamethoxazole | ≤0.5 | >4 | ≤0.5–>4 | 66.6/24.9 |
| Viridans group and other streptococci (519)j | ||||
| Linezolid | 1 | 1 | ≤0.12–>8 | 99.8/NA |
| Penicillin | ≤0.06 | 1 | ≤0.06–>8 | 74.0/3.3 |
| Ceftriaxone | 0.12 | 1 | ≤0.06–8 | 91.7/3.9 |
| Vancomycin | 0.5 | 1 | ≤0.12–1 | 100.0/NA |
| Daptomycin | 0.25 | 1 | ≤0.06–2 | 99.8/NA |
| Erythromycin | 1 | >16 | ≤0.12–>16 | 46.2/51.6 |
| Clindamycin | ≤0.25 | >2 | ≤0.25–>2 | 84.0/15.0 |
| Levofloxacin | 1 | 2 | ≤0.12–>4 | 91.3/7.7 |
| Tetracycline | 1 | >8 | ≤0.25–>8 | 58.2/35.8 |
| Tigecyclined | ≤0.03 | 0.06 | ≤0.03–0.25 | 100.0/NA |
| Trimethoprim-sulfamethoxazole | ≤0.5 | 4 | ≤0.5–>4 | NA |
| β-Hemolytic streptococci (895)k | ||||
| Linezolid | 1 | 1 | 0.25–2 | 100.0/NA |
| Penicillin | ≤0.06 | ≤0.06 | ≤0.06–0.12 | 100.0/NA |
| Ceftriaxoneb | ≤0.06 | 0.12 | ≤0.06–1 | 99.9/NA |
| Vancomycin | 0.5 | 0.5 | ≤0.12–1 | 100.0/NA |
| Daptomycin | 0.12 | 0.25 | ≤0.06–0.5 | 100.0/NA |
| Erythromycin | ≤0.12 | >16 | ≤0.12–>16 | 65.4/33.4 |
| Clindamycin | ≤0.25 | >2 | ≤0.25–>2 | 82.3/17.4 |
| Levofloxacin | 0.5 | 1 | ≤0.12–>4 | 99.2/0.7 |
| Tetracycline | >8 | >8 | ≤0.25–>8 | 45.9/52.5 |
| Tigecyclined | ≤0.03 | 0.06 | ≤0.03–0.25 | 100.0/NA |
CLSI %S/%R, percent susceptible/percent resistant by criteria as published by the CLSI (16). NA, not available.
U.S. FDA breakpoints were applied when available (Rocephin package insert, 2010; Hoffman-La Roche).
Results based on MIC susceptibility test results and do not include results from testing for inducible clindamycin resistance.
U.S. FDA breakpoints were applied when available (Tygacil product insert, 2010; Pfizer Inc.).
Includes Staphylococcus auricularis (1 strain), S. capitis (15 strains), S. epidermidis (57 strains), S. haemolyticus (5 strains), S. hominis (6 strains), S. lugdunensis (1 strain), S. warneri (5 strains). Not all strains were identified to the species level (188 strains).
Includes Staphylococcus auricularis (1 strain), S. capitis (4 strains), S. carnosus (1 strain), S. cohnii (1 strain), S. epidermidis (102 strains), S. haemolyticus (5 strains), S. hominis (10 strains), S. lugdunensis (18 strains), S. saprophyticus (6 strains), S. sciuri (1 strain), and S. warneri (4 strains). Not all strains were identified to the species level (330 strains).
Includes Enterococcus avium (8 strains), E. casseliflavus (2 strains), E. durans (2 strains), E. faecalis (766 strains), E. faecium (355 strains), E. gallinarum (7 strains), E. hirae (2 strains), E. raffinosus (7 strains). Not all strains were identified to the species level (11 strains).
Criteria as published by the CLSI (16) for “Penicillin parenteral (nonmeningitis).”
Criteria as published by the CLSI (16) for “Penicillin (oral penicillin V).”
Includes Streptococcus acidominimus (1 strain), S. alactolyticus (1 strain), S. anginosus (44 strains), S. bovis (19 strains), S. constellatus (12 strains), S. gallolyticus (5 strains), S. gordonii (5 strains), S. intermedius (8 strains), S. milleri (5 strains), S. mitis (45 strains), S. mutans (1 strain), S. oralis (6 strains), S. parasanguinis (5 strains), S. salivarius (9 strains), and S. sanguinis (11 strains). Not all strains were identified to the species level (20 strains for alpha-hemolytic streptococci and 322 strains for viridans group streptococci).
Includes Streptococcus dysgalactiae (1 strain), S. equisimilis (5 strains), group A Streptococcus (316 strains), group B Streptococcus (409 strains), group C Streptococcus (62 strains), group F Streptococcus (14 strains), group G Streptococcus (86 strains), and beta-hemolytic streptococci. Not all strains were not identified to the species level (2 strains).
Among the 1,160 enterococcal strains (66.0% Enterococcus faecalis, 30.6% Enterococcus faecium), the ampicillin-susceptible rate was 71.9%. Vancomycin-resistant enterococcus (VRE) vancomycin resistance rates (26.6% overall) varied by U.S. Census Bureau region, ranging from 19.4% (West North Central) to 38.5% (Middle Atlantic). The VanA resistance phenotype, defined as resistance to vancomycin and teicoplanin, represented 93.1% (95.8% in 2010) of the VRE identified in 2011. Linezolid, daptomycin, and tigecycline were the most active agents tested against enterococci with susceptibility rates at 99.7, 99.9, and 99.7%, respectively (Table 2).
Penicillin nonsusceptibility for Streptococcus pneumoniae (MIC, ≥0.12 μg/ml [Table 2]) occurred at a rate of 42.3%, higher than the rate in 2010 (38.0%) (14). Erythromycin resistance (MIC, ≥1 μg/ml) at 44.5% was also higher than the 2010 rate of 38.5%. Susceptibility rates to the most active β-lactams ranged from only 81.0% (amoxicillin-clavulanate) to 84.4% (for penicillin at ≤2 μg/ml; high-dose breakpoint) to 87.6% (ceftriaxone). Resistance rates for other agents were 22.0% for clindamycin, 1.1% for levofloxacin, 26.3% for tetracycline, and 24.9% for trimethoprim-sulfamethoxazole (TMP-SMX). Linezolid was very active against pneumococci (MIC50 and MIC90, 1 μg/ml; 100.0% susceptible), and the linezolid MIC for only 1.4% of strains was 2 μg/ml (susceptible breakpoint) (Table 1). Other agents with potent activity against the pneumococci were vancomycin (MIC90, ≤1 μg/ml; 100.0% susceptible) and tigecycline (MIC90, ≤0.06 μg/ml; 99.9% susceptible).
Penicillin nonsusceptibility (MIC, ≥0.25 μg/ml) was noted in 26.0% of the viridans group streptococci (Table 2). Erythromycin was less active (46.2% susceptible), and the clindamycin susceptibility rate was 84.0%. The levofloxacin resistance rate was 7.7%. Linezolid MIC values among the viridans streptococci were dominantly 1 μg/ml (MIC50 and MIC90, 1 μg/ml and 99.8% susceptible [Tables 1 and 2]). Daptomycin (99.8% susceptible), tigecycline (100.0%), and vancomycin (100.0%) were also highly active against all or nearly all viridans group streptococci tested (Table 2).
The most common species of β-hemolytic streptococci were Streptococcus agalactiae (409; 45.7%) and Streptococcus pyogenes (316; 35.3%). High levels of resistance were identified for erythromycin (33.4%), clindamycin (17.4%), and tetracycline (52.5%) (12, 14). All isolates were susceptible to linezolid, tigecycline, daptomycin, penicillin, and vancomycin (Table 2). As for the viridans group streptococci, levofloxacin resistance (0.7%) was observed in these β-hemolytic species. The linezolid MIC range was 0.25 to 2 μg/ml, with a clear modal value and MIC90 at 1 μg/ml (Table 2).
Three MRSA strains and nine CoNS strains were not susceptible to linezolid (Table 3). One MRSA strain had a G2576 point mutation only (Texas), one strain was positive for cfr only (Kentucky), and one strain had both mechanisms (California). In addition, two more MRSA strains had linezolid MIC values at 4 μg/ml (Ohio and Wisconsin). The isolate from Akron, Ohio had a PFGE USA100 pattern that was distinct from cfr-positive strains reported in 2007 and 2009, neither of which exhibited a USA100 profile. These most recent cfr-positive strains of MRSA presented with the usual modest elevation of linezolid resistance (MIC, 4 to 8 μg/ml). The isolate from Milwaukee, Wisconsin had only a L3 alteration. The nine linezolid-resistant CoNS isolates, all of which were Staphylococcus epidermidis (1.18% of all CoNS strains; all S. epidermidis) came from seven hospitals in 6 states (2 isolates from Tennessee, 2 isolates from Texas, 2 isolates from New Jersey, and one isolate each from Ohio, Louisiana, and Pennsylvania). The resistance mechanisms detected in these isolates were G2576T (8 isolates; 88.9% [percentage of all CoNS strains in Table 3]), L3 (7 isolates; 77.8%), and L4 (5 isolates; 55.6%).
Table 3.
Staphylococcus species with elevated or resistant-level linezolid MICs (≥4 μg/ml) in the 2011 LEADER Program
| Isolate ID no.a | Organism | City | State | Patient |
Linezolid MIC (μg/ml)c | Resistance mechanism(s)d | PFGE profilee | |
|---|---|---|---|---|---|---|---|---|
| Age (yr) | Sexb | |||||||
| 004-1889 | S. aureus | Akron | Ohio | 85 | M | 4 | cfr | SA4If |
| 027-4723 | S. aureus | Louisville | Kentucky | 67 | M | 8 | cfr | SA27Eg |
| 146-24935 | S. aureus | Long Beach | California | 20 | M | 8 | cfr, G2576T | |
| 024-29147 | S. aureus | Houston | Texas | 67 | M | 8 | G2576T | |
| 013-38867 | S. aureus | Milwaukee | Wisconsin | 28 | M | 4 | L3 (S145 del) | |
| 458-6281 | S. epidermidis | Cleveland | Ohio | 69 | F | 32 | G2576T, L3 (M156T, H146P, G137S, F147Y), L4 (71G72 ins) | |
| 448-11893 | S. epidermidis | New Orleans | Louisiana | 61 | M | 64 | G2576T | SEPI448Fh |
| 436-16828 | S. epidermidis | Memphis | Tennessee | 55 | F | 128 | G2576T, L3 (V154L, M156T, H146R), L4 (71G72 ins) | SEPI436A |
| 436-16831 | S. epidermidis | Memphis | Tennessee | 82 | M | 128 | G2576T, L3 (V154L, M156T, H146R), L4 (71G72 ins) | SEPI436A |
| 453-31261 | S. epidermidis | Hershey | Pennsylvania | 32 | F | 64 | G2576T, L3 (V154L, M156T, H146R) | SEPI453Ci |
| 442-34539 | S. epidermidis | Hackensack | New Jersey | 84 | F | 64 | G2576T, L3 (V154L, M156T, H146R, G137D), L4 (71G72 ins) | |
| 116-39867 | S. epidermidis | Houston | Texas | 62 | F | 64 | G2576T, L3 (M156T, H146P, G137S) | SEPI116D |
| 116-45408 | S. epidermidis | Houston | Texas | 70 | M | 16 | L3 (V154L. H146Q, A157R), L4 (71G72 ins) | SEPI116E |
| 129-51470 | S. epidermidis | New Brunswick | New Jersey | 37 | M | 64 | G2576T | |
ID, identification.
M, male; F, female.
Frozen form reference MIC panel was used.
del, deletion; ins, insertion.
Tenover et al. (19) criteria used for relatedness (indistinguishable, closely related, possibly related, and different). The pulsed-field gel electrophoresis (PFGE) grouping nomenclature used is based on a letter code for the organism (e.g., SA for S. aureus and SEPI for S. epidermidis), a number for the site (e.g., 436), and then a letter for the related group (e.g., A).
PFGE profile similar to that of a representative of the USA100 clone (NRS382), which was distinct from those observed in cfr-carrying strains isolated in 2007 and 2009, which did not exhibit a USA100 profile.
PFGE profile similar to that of a representative of USA300 clone (NRS384), which is distinct from that observed in cfr-carrying strain isolated in 2009 (i.e., USA100-like profile).
PFGE profile distinct from that observed in strain isolated in 2010.
PFGE profile indistinguishable from that observed among strains isolated in 2010.
Four enterococci (one E. faecalis and three E. faecium) had linezolid MIC values at ≥4 μg/ml, and each contained G2576T mutations. A nonsusceptible viridans group streptococcus, Streptococcus sanguis (MIC > 8 μg/ml), was encountered for the first time in the LEADER Program. The patient had a chronic left ventricular assist device endocarditis, caused by an oxacillin-resistant S. epidermidis and underwent multiple hospitalizations and courses of therapy, including long-term linezolid treatment. Multiple mutations associated with linezolid resistance, including T2211C and T2406C in the 23S rRNA and L22 (I59V) were identified in the isolate (18).
CLSI interpretive criteria indicated that clindamycin resistance in S. aureus was 16.0%, 4.5% for MSSA and 27.6% for MRSA (Table 2). To further characterize these strains, induction testing was performed on strains that tested erythromycin resistant and clindamycin susceptible (ERCS). The CLSI D-test detected an overall resistance induction rate of 29.6% among ERCS S. aureus. These results indicated the true clindamycin resistance rate for all S. aureus strains was 28.9%, and not 16.0%.
In summary, results of the eighth year of the LEADER Program (2011) demonstrated the potent activity of linezolid and its sustained susceptibility rate at 99.8% overall. The rates were 99.7 and 99.6% in 2009 and 2010, respectively (12, 14). Continued surveillance allows researchers to assess current levels of antimicrobial resistance in order to identify potential opportunities for future drug development and regulators to identify risks associated with trends in resistance development. Further, it is a tool to assist the participating sites to address evolving resistance challenges as data from the centralized testing are made available to the individual sites.
ACKNOWLEDGMENTS
We express appreciation to the following persons for significant contributions to the manuscript: M. G. Stilwell, P. R. Rhomberg, and M. Castanheira.
We are employees of JMI Laboratories who were paid consultants to Pfizer Inc. in connection with the development of the manuscript. This study was supported by Pfizer Inc. Specialty Business Unit (Collegeville, PA) via the SENTRY Antimicrobial Surveillance Program platform. JMI Laboratories, Inc. has received research and educational grants in 2009 to 2011 from the following companies: American Proficiency Institute (API), Anacor, Astellas, AstraZeneca, Bayer, Cempra, Cerexa/Forest, Contrafect, Cubist, Daiichi, Dipexium, Enanta, Furiex, GlaxoSmithKline, Johnson & Johnson (Ortho McNeil), LegoChem Biosciences Inc., Meiji Seika Kaisha, Merck, Nabriva, Novartis, Pfizer, Rempex, Rib-X Pharmaceuticals, Seachaid, Shionogi, The Medicines Co., Theravance, ThermoFisher, Kalidex Pharmaceuticals, and Paratek Pharmaceuticals. Some JMI employees are advisors/consultants for Astellas, Cubist, Pfizer, Cempra, Cerexa/Forest, J&J, and Theravance.
Footnotes
Published ahead of print 17 December 2012
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