Abstract
LTX-109 and eight other antimicrobial agents were evaluated against 155 methicillin-resistant Staphylococcus aureus (MRSA) isolates, including strains resistant to vancomycin and strains with decreased susceptibility to daptomycin and linezolid, by microdilution tests to determine MICs. Time-kill assays were performed against representative MRSA, vancomycin-intermediate S. aureus (VISA), and vancomycin-resistant S. aureus (VRSA) isolates. LTX-109 demonstrated a MIC range of 2 to 4 μg/ml and dose-dependent rapid bactericidal activity against S. aureus. This activity was not influenced by resistance to other antistaphylococcal agents.
TEXT
Staphylococcus aureus demonstrating decreased susceptibility to β-lactams and glycopeptides poses a serious threat to patients. S. aureus isolates with reduced susceptibility, intermediate resistance, and high-level vancomycin resistance have also emerged in parallel with vancomycin's widespread use and now pose a significant therapeutic challenge (4, 12).
New classes of antimicrobial agents that do not demonstrate cross-resistance to available agents are desirable for the treatment of these infections.
Synthetic antimicrobial peptidomimetics (SAMPs) are a new class of drugs with activity against Gram-positive and Gram-negative bacterial species (14). LTX-109 (Lytixar; Lytix Biopharma AS, Oslo, Norway) is one such novel SAMP which rapidly kills bacteria via membrane disruption and has not been associated with cross-resistance to other available drugs. LTX-109 has also been shown to have a low propensity for the development of resistance (5, 6, 8).
In this study, a collection of 155 strains of methicillin-resistant S. aureus (MRSA) were selected for evaluation. Methicillin-resistant S. aureus strains (n = 96) were isolated from patients admitted to St. John Hospital and Medical Center, Detroit, MI, from 2003 to 2008. The samples were collected from blood (n = 30), respiratory (n = 33) wound or tissue (n = 31), catheter tip (n = 1), and a percutaneous endoscopic gastrostomy site (n = 1). Daptomycin-nonsusceptible S. aureus (DNSSA) strains (n = 7) were cultured from blood samples collected from patients at the same hospital. There were no duplicate isolates from patients. Vancomycin-intermediate S. aureus (VISA) isolates (n = 33) were cultured from 33 patients, and the vancomycin-resistant S. aureus (VRSA) isolates (n = 13) were obtained from 11 patients, with two patients having two different isolation sites for their VRSA strains. The linezolid-nonsusceptible S. aureus (LNSSA) isolates (n = 6) were cultured from blood (n = 2), sputum (n = 1), and an unknown source (n = 3). The VISA, VRSA, and 4 of the LNSSA isolates were obtained through the Network on Antimicrobial Resistance in S. aureus (NARSA) program supported under NIAID/NIH contract HHSN272207700055C, which describes the site of isolation and the city of origin (http://www.narsa.net). The remaining two LNSSA stains were collected at Robinson Memorial Hospital in Ohio.
In vitro susceptibility tests were performed with the antimicrobials LTX-109 (Lytix Biopharma), vancomycin-HCl (Sigma), daptomycin (Cubist), clindamycin-HCl (Sigma), linezolid (Pfizer), trimethoprim-sulfamethoxazole (Sigma), quinupristin-dalfopristin (IHMA), minocycline, and mupirocin (U.S. Pharmacopoeia). All of the antimicrobial agents were received as standard powders, which were reconstituted according to Clinical and Laboratory Standards (CLSI) guidelines (3).
Determinations of MICs and minimal bactericidal concentrations (MBCs) were performed in duplicate and according to the CLSI guidelines (2). Microdilution tests with cation-adjusted Mueller-Hinton (M-H) broth were used to identify the MICs of all agents tested. For the testing of daptomycin, calcium was added to the broth for a final concentration of 50 mg/liter. The MICs were the lowest drug concentration with no visible growth. The MBC was defined as the concentration that reduced the number of viable cells by ≥99.9%. This was based on colony counts from the control well and rejection values determined by tables provided by Pearson (13).
Isolates with a mupirocin MIC of 8 to 256 μg/ml were identified as having low-level resistance (LLR), and those with a MIC of ≥512 μg/ml were identified as having high-level resistance (HLR) (16). S. aureus ATCC 29213 and Enterococcus faecalis ATCC 29212 were used as the control strains for the MIC determinations, and S. aureus ATCC 25923 was used as the control strain for the MBC determinations.
Time-kill assays were performed according to procedures described in the American Society for Microbiology Clinical Microbiology Procedures Handbook (7). The assays were performed in triplicate. The lower limit of detection was determined to be 100 CFU/ml, and bactericidal activity was defined as a ≥3-log10 decrease in CFU/ml compared to the time zero count. LTX-109 and vancomycin were tested against five MRSA isolates characterized by SCCmec typing and the presence of Panton-Valentine leukocidin (PVL) genes. In addition, LTX-109 and linezolid were tested against a VRSA isolate. Three to five colonies from an overnight growth were inoculated into M-H broth and incubated until the logarithmic growth phase was achieved. The inoculated broth was then diluted to achieve a starting inoculum with a density of 106 CFU/ml. To perform colony counts, aliquots (100 μl) were removed from the cultures at 0, 0.5, 1, 2, 4, 6, and 24 h and diluted in cold, normal saline before plating for colony counts. To lower the limit of detection, larger aliquots (1 ml) were removed and centrifuged to prevent antibiotic carryover. All of the isolates and antibiotics were tested at 2× MIC, 4× MIC, and 8× MIC.
The results of MIC and MBC determinations are summarized in Tables 1 and 2. LTX-109 provided consistent results irrespective of the decreased susceptibility to β-lactams, vancomycin, daptomycin, linezolid, clindamycin, trimethoprim-sulfamethoxazole, and mupirocin. The highest LTX-109 MIC seen was 4 μg/ml. In addition, susceptibility to LTX-109 was not influenced by the SCCmec type or the presence of Panton-Valentine leukocidin (PVL) genes.
Table 1.
MIC and MBC values for activities of all antimicrobials tested against MRSA, VISA, and VRSA isolatesa
| Isolate and agent | MIC (μg/ml)b |
% susceptible | MBC (μg/ml)c |
||||
|---|---|---|---|---|---|---|---|
| Range | 50% | 90% | Range | 50% | 90% | ||
| MRSA (n = 96) | |||||||
| LTX-109 | 2–4 | 2 | 4 | NAd | 2–8 | 4 | 4 |
| VAN | 0.5–2 | 1 | 1 | 100 | 0.5–2 | 1 | 1 |
| DAP | 0.25–1 | 0.5 | 1 | 100 | 0.25–2 | 0.5 | 1 |
| LZD | 1–4 | 2 | 2 | 100 | 2–>8 | >8 | >8 |
| CLI | 0.06–>64 | 0.12 | >64 | 62 | 1–>64 | 8 | >64 |
| SXT | 1.2/0.06–>76/4 | 2.4/0.12 | 9.5/0.5 | 98 | 1.2/0.06–>76/4 | 2.4/0.12 | 19/1 |
| Q-D | 0.12–0.5 | 0.25 | 0.5 | 100 | 0.25–>8 | 0.5 | >8 |
| MUP | 0.06–>512 | 0.12 | 0.25 | 94 | 4–>512 | 16 | 32 |
| MIN | 0.06–8 | 0.12 | 0.5 | 97 | 0.5–>16 | >16 | >16 |
| VISA (n = 33) | |||||||
| LTX-109 | 2–4 | 4 | 4 | NA | 2–8 | 4 | 4 |
| VAN | 4–8 | 4 | 8 | 0 | 4–16 | 4 | 8 |
| DAP | 1–8 | 2 | 4 | 30 | 1–8 | 2 | 8 |
| LZD | 0.5–4 | 2 | 2 | 100 | 2–>8 | 8 | >8 |
| CLI | 0.06–>64 | >64 | >64 | 30 | 0.12–>64 | >64 | >64 |
| SXT | 0.12/0.06–>76/4 | 9.5/0.5 | >76/4 | 70 | 2.4/0.12–>76/4 | 1/19 | >76/4 |
| Q-D | 0.03–2 | 0.5 | 0.5 | 97 | 0.03–>8 | 1 | >8 |
| MUP | 0.03–>512 | 0.25 | >512 | 82 | 0.5–>512 | 8 | >512 |
| MIN | 0.03–16 | 0.12 | 4 | 97 | 0.06–>16 | 16 | >16 |
| VRSA (n = 13) | |||||||
| LTX-109 | 2–4 | 4 | 4 | NA | 2–4 | 4 | 4 |
| VAN | 32–>64 | >64 | >64 | 0 | 64–>64 | >64 | >64 |
| DAP | 0.12–1 | 0.5 | 1 | 100 | 0.25–1 | 0.5 | 1 |
| LZD | 0.5–4 | 2 | 2 | 100 | 8–>8 | >8 | >8 |
| CLI | >64 | >64 | >64 | 0 | >64 | >64 | >64 |
| SXT | 1.2/0.06–>4/76 | 2.4/0.12 | 38/2 | 92 | 2.4/0.12–>76/4 | >76/4 | >76/4 |
| Q-D | 0.25–0.5 | 0.5 | 0.5 | 100 | 1–>8 | >8 | >8 |
| MUP | 0.06–32 | 0.25 | 16 | 77 | 0.5–>512 | 4 | >512 |
| MIN | 0.03–2 | 0.12 | 2 | 100 | 8–>16 | >16 | >16 |
Abbreviations: VAN, vancomycin; DAP, daptomycin; LZD, linezolid; CLI, clindamycin; SXT, trimethoprim-sulfamethoxazole; Q-D, quinupristin-dalfopristin; MUP, mupirocin; MIN, minocycline.
50% and 90%, MIC50 and MIC90, respectively.
50% and 90%, MBC50 and MBC90, respectively.
NA, not applicable.
Table 2.
MIC50 and MBC50 and geometric mean MICs and MBCs for all antimicrobials tested against DNSSA and LNSSA isolatesa
| Isolate and agent | MIC (μg/ml) |
% susceptible | MBC (μg/ml) |
||||
|---|---|---|---|---|---|---|---|
| Range | 50%b | Geometric mean | Range | 50%c | Geometric mean | ||
| DNSSA (n = 7) | |||||||
| LTX-109 | 2–4 | 4 | 3.28 | NAd | 2–8 | 4 | 4 |
| VAN | 1–2 | 2 | 1.64 | 100 | 2 | 2 | 2 |
| DAP | 4 | 4 | 4 | 0 | 4–8 | 8 | 5.94 |
| LZD | 1–2 | 2 | 1.48 | 100 | 2–>8 | >8 | 10.7 |
| CLI | <0.03–>64 | >64 | 38.76 | 14 | 2–>64 | >64 | 70.66 |
| SXT | 1.2/0.06–>76/4 | 2.4/0.12 | 5.6/0.40 | 71 | 2.4/0.12–>76/4 | 4.8/0.25 | 11.65/0.60 |
| Q-D | 0.12–0.5 | 0.25 | 0.25 | 100 | 0.12–>8 | 1 | 1.8 |
| MUP | 0.06–0.25 | 0.12 | 0.13 | 100 | 8–32 | 16 | 13 |
| MIN | 0.03–4 | 0.06 | 0.12 | 100 | 8–>16 | >16 | 26 |
| LNSSA (n = 6) | |||||||
| LTX-109 | 4 | 4 | 4 | NA | 4 | 4 | 4 |
| VAN | 1–2 | 1 | 1.12 | 100 | 1–2 | 1 | 1.26 |
| DAP | 0.5–1 | 0.5 | 0.63 | 100 | 0.5–1 | 0.5 | 0.7 |
| LZD | 16–64 | 16 | 28.5 | 0 | 32–>64 | >64 | 90.5 |
| CLI | 0.06–>64 | 1 | 2.8 | 33 | 0.12–>64 | 4 | 10 |
| SXT | 1.2/0.06–>76/4 | 1.2/0.06 | 3.8/0.19 | 83 | 1.2/0.06–>76/4 | 2.4/0.12 | 6/0.3 |
| Q-D | 0.25–4 | 0.25 | 0.5 | 83 | 0.5–8 | 0.5 | 1.26 |
| MUP | 0.12–16 | 0.12 | 0.3 | 83 | 4–>512 | 16 | 25 |
| MIN | 0.12–4 | 0.5 | 0.7 | 100 | 1–>16 | >16 | 17.9 |
Abbreviations: VAN, vancomycin; DAP, daptomycin; LZD, linezolid; CLI, clindamycin; SXT, trimethoprim-sulfamethoxazole; Q-D, quinupristin-dalfopristin; MUP, mupirocin; MIN, minocycline.
50%, MIC50.
50%, MBC50.
NA, not applicable.
Table 3 provides results for individual VISA and VRSA isolates for future studies of new antimicrobial agents that might be tested against these standard reference strains from the NARSA repository.
Table 3.
MIC results for antimicrobial agents against strains provided by NARSAa
| Isolate | MIC (μg/ml) |
||||||||
|---|---|---|---|---|---|---|---|---|---|
| LTX-109 | MUP | MIN | Q-D | VAN | DAP | LZD | SXT | CLI | |
| VISA | |||||||||
| NRS-1 | 4 | 0.25 | 16 | 0.25 | 8 | 2 | 2 | 0.12/2.4 | >64 |
| NRS-3 | 2 | 0.5 | 0.5 | 1 | 8 | 4 | 2 | 19/1 | >64 |
| NRS-4 | 2 | 0.12 | 0.12 | 0.5 | 4 | 1 | 2 | 2.4/0.12 | >64 |
| NRS-12 | 4 | 1 | 0.03 | 0.25 | 4 | 4 | 4 | 0.12/2.4 | 0.12 |
| NRS-14 | 4 | 0.5 | 0.03 | 0.5 | 8 | 4 | 4 | 0.12/2.4 | 0.06 |
| NRS-17 | 2 | 0.12 | 0.06 | 0.25 | 8 | 4 | 1 | 2.4/0.12 | 0.06 |
| NRS-18 | 2 | 16 | 0.12 | 0.25 | 4 | 1 | 2 | 2.4/0.12 | >64 |
| NRS-19 | 2 | 0.25 | 0.12 | 0.5 | 4 | 2 | 1 | 9.5/0.5 | >64 |
| NRS-21 | 4 | >512 | 2 | 0.06 | 4 | 1 | 2 | >4/76 | 0.06 |
| NRS-22 | 2 | 0.12 | 0.06 | 0.5 | 4 | 2 | 1 | >76/4 | >64 |
| NRS-23 | 2 | 0.25 | 0.12 | 0.5 | 4 | 2 | 2 | >76/4 | >64 |
| NRS-24 | 2 | 16 | 0.12 | 0.5 | 4 | 2 | 2 | 9.5/0.5 | >64 |
| NRS-26 | 4 | >512 | 0.06 | 1 | 4 | 4 | 1 | >76/4 | >64 |
| NRS-27 | 2 | >512 | 0.12 | 0.5 | 4 | 1 | 1 | >76/4 | >64 |
| NRS-39 | 4 | 0.5 | 2 | 0.5 | 8 | 2 | 1 | 0.5/9.5 | >64 |
| NRS-49 | 4 | 0.12 | 16 | 0.25 | 8 | 2 | 2 | 0.25/4.8 | >64 |
| NRS-51 | 2 | 0.12 | 0.12 | 0.5 | 4 | 1 | 2 | 2.4/0.12 | >64 |
| NRS-52 | 4 | 0.25 | 0.06 | 0.5 | 8 | 2 | 2 | 0.25/4.8 | >64 |
| NRS-54 | 4 | >512 | 4 | 0.5 | 4 | 1 | 2 | >4/76 | >64 |
| NRS-56 | 4 | 0.25 | 4 | 0.5 | 4 | 4 | 2 | >4/76 | >64 |
| NRS-63 | 4 | 0.25 | 4 | 0.25 | 4 | 2 | 2 | >4/76 | 0.12 |
| NRS-65 | 4 | 0.25 | 4 | 0.12 | 4 | 1 | 0.5 | >4/76 | 0.12 |
| NRS-68 | 2 | 0.25 | 0.12 | 0.5 | 4 | 1 | 1 | 4.8/0.25 | >64 |
| NRS-73 | 2 | 0.25 | 2 | 0.25 | 4 | 2 | 1 | >76/4 | 0.06 |
| NRS-74 | 4 | 0.12 | 0.12 | 2 | 4 | 4 | 2 | 2.4/0.12 | >64 |
| NRS-76 | 4 | 0.25 | 0.12 | 0.25 | 4 | 2 | 2 | 2.4/0.12 | 0.06 |
| NRS-118 | 4 | 0.06 | 2 | 0.5 | 8 | 4 | 1 | 19/1 | >64 |
| NRS-126 | 4 | 0.25 | 0.12 | 0.5 | 4 | 2 | 2 | 2.4/0.12 | >64 |
| NRS-272 | 2 | 0.12 | 0.25 | 0.03 | 4 | 1 | 1 | 0.5/9.5 | 0.12 |
| NRS-283 | 4 | 0.25 | 0.12 | 0.5 | 4 | 1 | 2 | 0.12/2.4 | >64 |
| NRS-402 | 2 | 0.03 | 0.03 | 0.25 | 8 | 8 | 0.5 | 1.2/0.06 | >64 |
| NRS-403 | 2 | 0.25 | 0.06 | 0.5 | 4 | 2 | 1 | 2.4/0.12 | >64 |
| NRS-404 | 4 | 0.12 | 0.12 | 0.25 | 8 | 2 | 2 | 9.5/0.5 | 0.06 |
| VRSA | |||||||||
| VRS-1 | 2 | 32 | 0.5 | 0.5 | >64 | 1 | 2 | 38/2 | >64 |
| VRS-2 | 4 | 0.06 | 0.12 | 0.5 | 32 | 0.5 | 2 | 19/1 | >64 |
| VRS-3a | 4 | 0.25 | 2 | 0.5 | 32 | 0.5 | 2 | 1.2/0.06 | >64 |
| VRS-3b | 4 | 0.25 | 2 | 0.5 | >64 | 0.5 | 2 | 2.4/0.12 | >64 |
| VRS-4 | 4 | 0.25 | 0.12 | 0.5 | >64 | 0.5 | 2 | 2.4/0.12 | >64 |
| VRS-5 | 4 | 0.25 | 0.12 | 0.5 | >64 | 1 | 4 | 1.2/0.06 | >64 |
| VRS-6 | 4 | 0.12 | 0.25 | 0.5 | >64 | 1 | 1 | 1.2/0.06 | >64 |
| VRS-7 | 4 | 0.12 | 0.25 | 0.5 | >64 | 0.5 | 1 | 1.2/0.06 | >64 |
| VRS-8 | 4 | 0.12 | 0.06 | 0.5 | >64 | 0.5 | 1 | >76/4 | >64 |
| VRS-9 | 4 | 0.12 | 0.12 | 0.5 | >64 | 0.5 | 2 | 38/2 | >64 |
| VRS-10 | 4 | 0.12 | 0.06 | 0.5 | >64 | 0.25 | 2 | 2.4/0.12 | >64 |
| VRS-11a | 4 | 8 | 0.03 | 0.25 | >64 | 0.12 | 0.5 | 2.4/0.12 | >64 |
| VRS-11b | 4 | 16 | 0.03 | 0.5 | >64 | 0.25 | 2 | 2.4/0.12 | >64 |
Abbreviations: MUP, mupirocin; MIN, minocycline; Q-D, quinupristin-dalfopristin; VAN, vancomycin; DAP, daptomycin, LZD, linezolid; SXT, trimethoprim-sulfamethoxazole; CLI, clindamycin.
The results for time-kill curves are provided in Table 4. MRSA strains for these studies were selected based on the presence or absence of PVL genes, SCCmec type IV or II isolates, and/or reduced susceptibility or resistance to vancomycin. Noteworthy is the fact that a greater than 3-log reduction in CFU was seen with LTX-109 within 4 h for all time-kill studies at a concentration of 4× MIC and within 2 h at concentrations of 8× MIC. LTX-109 demonstrated superior killing in all time-kill studies compared to vancomycin and compared to linezolid for the VRSA isolate studied.
Table 4.
Time-kill results for MRSA, VISA, and VRSA isolates by SCCmec type and presence of PVL genes
| Strain, agent, and MIC | Count reduction (Δlog10 CFU/ml) ata: |
|||||
|---|---|---|---|---|---|---|
| 0.5 h | 1 h | 2 h | 4 h | 6 h | 24 h | |
| MRSA | ||||||
| USA 300 (SCCmec type IVa, PVL+) | ||||||
| LTX-109 | ||||||
| 2× MIC | 0.5 | 1 | 1.5 | 3.3 | 3.7 | 3.7 |
| 4× MIC | 1.9 | 3.3 | 3.6 | 3.6 | 3.6 | 3.6 |
| 8× MIC | 3.5 | 3.5 | 3.5 | 3.5 | 3.5 | 3.5 |
| Vancomycin | ||||||
| 2× MIC | 0 | 0.1 | 0.2 | 0.5 | 0.9 | 2.7 |
| 4× MIC | +0.1 | 0.1 | 0.2 | 0.5 | 1 | 2.6 |
| 8× MIC | 0 | 0.1 | 0.3 | 0.7 | 1.4 | 2.7 |
| USA 100 (SCCmec type II, PVL−) | ||||||
| LTX-109 | ||||||
| 2× MIC | 1 | 1.3 | 1.6 | 3.6 | 3.7 | 3.7 |
| 4× MIC | 3 | 3.7 | 3.7 | 3.7 | 3.7 | 3.7 |
| 8× MIC | 3.7 | 3.7 | 3.7 | 3.7 | 3.7 | 3.7 |
| Vancomycin | ||||||
| 2× MIC | 0.1 | 0.1 | 0.1 | 0.2 | 0.3 | 3 |
| 4× MIC | 0 | 0 | 0 | 0.4 | 0.3 | 3.3 |
| 8× MIC | 0 | 0 | 0.1 | 0.4 | 0.9 | 3.5 |
| VISA (SCCmec type II, PVL−) | ||||||
| LTX-109 | ||||||
| 2× MIC | +0.1 | 0.7 | 1.2 | 2.4 | 3.6 | 3.6 |
| 4× MIC | 1.2 | 1.6 | 2.4 | 3.7 | 3.7 | 3.7 |
| 8× MIC | 2 | 2.6 | 3.6 | 3.6 | 3.6 | 3.6 |
| Vancomycin | ||||||
| 2× MIC | 0 | 0 | 0.1 | 0.4 | 0.5 | 2.1 |
| 4× MIC | +0.1 | 0 | 0 | 0.3 | 0.5 | 2 |
| 8× MIC | 0 | 0.1 | 0.1 | 0.3 | 0.5 | 2.2 |
| VRSA (SCCmec type II, PVL−) | ||||||
| LTX-109 | ||||||
| 2× MIC | 0.7 | 1.1 | 1.7 | 3.2 | 3.5 | 3.5 |
| 4× MIC | 2.3 | 3.3 | 3.5 | 3.5 | 3.5 | 3.5 |
| 8× MIC | 3.4 | 3.4 | 3.4 | 3.4 | 3.4 | 3.4 |
| Linezolid | ||||||
| 2× MIC | 0 | 0 | +0.1 | 0 | 0 | 0.5 |
| 4× MIC | 0 | 0 | +0.1 | 0 | 0.1 | 1 |
| 8× MIC | 0.2 | 0.1 | 0.1 | 0.1 | 0.2 | 1 |
Shown is the Δlog10-CFU/ml count reduction in relation to the total count of CFU/ml in the time zero count. Reductions of ≥3 log CFU are highlighted in boldface.
LTX-109 demonstrated bactericidal activity against all isolates tested, and in vitro activity did not vary based on susceptibility to vancomycin, daptomycin, and linezolid or SCCmec type or the presence of PVL genes. The formulation of LTX-109 has a concentration of 20,000 μg/ml, which is far in excess of the MBCs of 2 to 8 μg/ml seen for the isolates tested in this study (11). When given intranasally, the maximum serum concentration was <12.5 ng/ml and was not associated with any hemolytic reactions.
Compared to vancomycin, LTX-109 demonstrated a rapid bactericidal effect against a representative isolate of community-acquired (CA) USA 300, hospital-acquired USA 100, VISA, and VRSA. This effect was seen within 4 h at concentrations as low as 2× MIC and within 0.5 to 4 h at concentrations of 4× MIC.
It is noteworthy that LTX-109 demonstrated excellent activity against the mupirocin low- and high-level-resistance strains. This is of interest in view of recent reports of cases of daptomycin-nonsusceptible and mupirocin-resistant S. aureus (15, 1).
Animal model work has shown LTX-109 to be effective against CA-MRSA (USA 300) and Streptococcus pyogenes in a mouse skin infection model (10). This model demonstrated LTX-109 given at 0.5 to 2% topically to be effective by showing at least a 3-log reduction in CFU for skin biopsy specimens compared to the level in controls and to be more effective in animals than treatment with mupirocin or topical fusidic acid. Early work has shown LTX-109 to be safe, tolerated, and effective in the eradication of nasal carriage of S. aureus by day 4 for all patients receiving topical instillation of 2 to 5% LTX-109 for 3 days and for the topical treatment of skin infections (9, 11).
LTX-109 demonstrated in vitro bactericidal activity against a number of S. aureus isolates resistant to several classes of antimicrobial agents evaluated in this study.
Footnotes
Published ahead of print 14 May 2012
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