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Activity of linezolid against a worldwide collection of uncommonly isolated Gram-positive organisms (3,251 strains)
Abstract number: 1732_26
Jones R., Ross J., Stilwell M.
Objectives: To assess the worldwide spectrum of linezolid when tested by CLSI reference methods (M7-A7, 2006) against species of Gram-positive cocci that are rare in occurrence (<1%) and are not within the indicated organisms approved by regulatory agencies (US-FDA or EMEA). Using a large surveillance platform (SENTRY Antimicrobial Surveillance Program, 1997–2006), these organisms were tested to provide knowledge of oxazolidinone potency and emerging resistance (R) rates to ensure potential efficacy when needed for chemotherapy of serious infections. Methods: Linezolid was tested against 3,251 strains distributed among 9 major bacterial groups: Aerococcus spp. (22), Bacillus spp. (202), Corynebacteria (342), various enterococci (6 species; 378), Listeria monocytogenes (137), Micrococcus luteus (29), Rothia mucilaginosus (18), beta-haemolytic (BST; 3 serotypes, 865) and viridans group streptococci (VGS; 12 spp.; 1,258). All strains were tested by CLSI broth microdilution methods with appropriate supplements; all quality control results were within published CLSI limits (M100-S16, 2006). Linezolid-R strains (MIC, ≥8 mg/L) were processed by PCR for target site mutations. Results: Generally, linezolid was very active against all 32 species examined with 4 strains (0.12%) having a MIC at ≥4 mg/L (E. avium [1], E. casseliflavus [2], E. gallinarum [1]) tested and only 1 R (S. oralis; MIC at >8 mg/L) isolate having a proven G2576T mutation. Streptococci (2,123) overall had a MIC90 of 1 mg/L (range, 1–2 mg/L), and the 378 rarely cultured enterococci had a MIC90 of 2 mg/L (range, 2 mg/L). Corynebacterium spp. (342) were most susceptible (S) to linezolid (MIC50, 0.25 mg/L) while enterococci and Listeria were 4- to 8-fold less S (MIC50, 2 mg/L). Evaluations of R trends in those species failed to identify any MIC creep over the seven years monitored (data not shown). Table. Linezolid potency against uncommonly isolated Gram-positive organisms (3,251). | Organism (no. tested) | Cumulative % inhibited at MIC (mg/L) | MlC (mg/L) |
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| 0.25 | 0.5 | 1 | 2 | 4 | 50% | 90% | |
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| Aerococcus spp. (92) | 4.5 | 31.8 | 63.6 | 100.0 | – | 1 | 2 | | Bacillus spp. (142) | 4.9 | 31.7 | 97.2 | 100.0 | - | 1 | 1 | | B. cereus (60) | 3.3 | 30.0 | 98.3 | 100.0 | - | 1 | 1 | | Corynebacterium spp. (238) | 68.2 | 92.4 | 99.6 | 100.0 | 0.25 | 0.5 | | | C. amycolatum (11) | 100.0 | - | - | - | - | 0.25 | 0.25 | | C. jeikium (59) | 67,8 | 98.3 | 100.0 | - | - | 0.25 | 0.5 | | C. pseudodiphtherificum (11) | 36.4 | 90.9 | 100.0 | - | - | 0.5 | 0.5 | | C. striatum (25) | 88.0 | 100.0 | - | - | - | 0.25 | 0.5 | | Enterococcus avium (116) | 0.0 | 4.3 | 52.6 | 99.1 | 100.0 | 1 | 2 | | E. casseliflavus (65) | 0.0 | 0.0 | 23.1 | 96.9 | 100.0 | 2 | 2 | | E. durans (49) | 2.0 | 8.2 | 32.7 | 100.0 | - | 2 | 2 | | E. gallinarum (119) | 0.0 | 1.7 | 30.3 | 99.2 | 100.0 | 2 | 2 | | E. hirae (16) | 0.0 | 0.0 | 37.5 | 100.0 | - | 2 | 2 | | E. raffinosus (13) | 0.0 | 0.0 | 46.2 | 100.0 | - | 2 | 2 | | Listeria monocytogenes (137) | 0.0 | 0.7 | 29.2 | 100.0 | - | 2 | 2 | | Micrococcus luteus (29) | 3.4 | 75.9 | 100.0 | - | - | 0.5 | 1 | | Rothia mucilaginosus (18) | 16.7 | 83.3 | 94.4 | 100.0 | - | 0.5 | 1 | | Streptococci (2,123) | 4.5 | 39.5 | 96.9 | 99.9 | 99.9 | 1 | 1 |
Conclusions: Linezolid, the first oxazolidinone to be used in clinical practice, has maintained excellent activity against these rare Gram-positive species as well as frequently cultured and indicated species S. aureus, coagulase-negative staphylococci and enterococci (E. faecium, E. faecalis). All but 5/1 isolates were inhibited by ≤2/≤4 mg/L (>99.8% S) of linezolid if CLSI breakpoints were applied to the testing of these species. Continued R surveillance should be considered for linezolid especially for these rarely isolated Gram-positive species as this agent is more widely used.
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