This study is aimed to make a comprehensive introduction to the anti-MRSA drugs, and also to compare the safety and efficacy among a variety of anti-MRSA drugs. Finally, it is pointed that we should select the anti-MRSA drugs precisely according to different situation of disease when treating the infection with MRSA.Then we can make the individualized treatment for patients and provide a basis for the disease when treatment of patients as well.
CAVALCANT AB,GONCALVES AR,ALMEIDA CS,et al. Teicoplanin versus vancomycin for proven ot suspected infection[J].Cochrane Database Syst Rev,2010,16(6): CD007022.
BACKGROUND: Vancomycin and teicoplanin are commonly used to treat gram-positive infections, particularly those caused by methicillin-resistant Staphylococcus aureus (MRSA). There is uncertainty regarding the effects of teicoplanin compared to vancomycin on kidney function with some previous studies suggesting teicoplanin is less nephrotoxic than vancomycin. OBJECTIVES: To investigate the efficacy and safety of vancomycin versus teicoplanin in patients with proven or suspected infection. SEARCH STRATEGY: We searched the Cochrane Renal Group's Specialised Register, CENTRAL, MEDLINE, EMBASE, reference lists of nephrology textbooks, review articles with relevant studies and sent letters seeking information about unpublished or incomplete studies to investigators involved in previous studies. SELECTION CRITERIA: We searched for randomised controlled trials (RCTs) in any language comparing teicoplanin to vancomycin for patients with proven or suspected infection. DATA COLLECTION AND ANALYSIS: Two authors independently evaluated methodological quality and extracted data using standardised data extraction forms. Study investigators were contacted for information not available in the original manuscripts. Random effects model was used to estimate the pooled risk ratio (RR) with 95% confidence interval (CI). MAIN RESULTS: We included 24 studies (2,610 patients) in this review. Teicoplanin reduced the risk of nephrotoxicity compared to vancomycin (RR 0.66, 95% CI 0.48 to 0.90).The effects of teicoplanin or vancomycin were similar for clinical cure (RR 1.03, 95% CI 0.98 to 1.08), microbiological cure (RR 0.98, 95% CI 0.93 to 1.03) and mortality (RR 1.02, 95% CI 0.79 to1.30). Six studies reported no cases of acute kidney injury (AKI) needing dialysis. Adverse events were less frequent with teicoplanin including cutaneous rash (RR 0.57, 95% CI 0.35 to 0.92), red man syndrome (RR 0.21, 95% CI 0.08 to 0.59) and total adverse events (RR 0.73, 95% CI 0.53 to 1.00). A lower risk of nephrotoxicity with teicoplanin was observed in patients either with (RR 0.51, 95% CI 0.30 to 0.88) or without aminoglycosides (RR 0.31, 95% 0.07 to 1.50), and also when vancomycin dosing was guided by serum levels (RR 0.22, 95% CI 0.10 to 0.52). AUTHORS' CONCLUSIONS: Teicoplanin and vancomycin are both effective in treating those with proven or suspected infection; however the incidence of adverse effects including nephrotoxicity was lower with teicoplanin. There were no cases of AKI needing dialysis. It remains unclear whether the differential effect on kidney function should influence which antibiotic be prescribed, although it may be reasonable to consider teicoplanin for patients at higher risk for AKI needing dialysis.
目的 比较替考拉宁与万古霉素对老年患者耐甲氧西林金黄色葡萄球菌（MRSA）、耐甲氧西林表皮葡萄球菌（MRSE）肺部感染的疗效。方法 对38例肺部MRSA／MRSE感染的老年患者，分别给予替考拉宁和万古霉素治疗，观察并比较两种方法的药敏结果、疗程及预后。结果 （1）MRSA／MRSE对替考拉宁及万古霉素均全部敏感；（2）老年患者万古霉素代谢率明显下降，常规剂量易发生药物蓄积，致肾功能损害，有必要进行常规血药浓度监测以调整剂量；（3）替考拉宁不调整剂量，未发现明显肝肾功能损害及其他严重并发症；（4）替考拉宁与万古霉素治疗结果比较，总痰菌清除率相近（89％ vs 85％），痰菌清除时间较短（8．3±2．5d vs 21．1±11．0d）。结论 对于老年患者肺部MRSA／MRSE感染，替考拉宁与万古霉素敏感率均很高，总体疗效相似，前者安全性较好，敏感菌清除时间短。
NORRBYR.Linezolid-a review of the first oxazolidinone[J]. Exp Opin Pharmacother,2001,2(2):293-302.
Linezolid is the first of a truly new class of antibiotics, the oxazolidinones. It acts as an inhibitor of bacterial protein synthesis by blocking the formation of the 70S ribosomal initiation complex. Its activity is bacteriostatic against some species (e.g., enterococci) and bactericidal against others (e.g., pneumococci). The antibacterial spectrum of linezolid includes Gram-positive pathogens and some Gram-negative anaerobic species but not Gram-negative aerobes. Importantly, multi-drug resistant organisms such as methicillin-resistant staphylococci, staphylococci with reduced susceptibility to vancomycin, penicillin- and macrolide-resistant pneumococci and vancomycin-resistant enterococci are fully susceptible to linezolid. Linezolid has almost 100% bioavailability and the area under the plasma concentration curve is identical after oral and iv. administration. This enables initial oral administration of linezolid in those patients who can absorb the drug normally and also an early step-down therapy from iv. to oral. Controlled, randomised clinical studies have documented efficacy and safety of linezolid in hospital- and community-acquired pneumonia, uncomplicated and complicated skin and soft tissue infections and infections caused by vancomycin-resistant enterococci. The safety and tolerability of linezolid are advantageous. Linezolid is a weak and reversible monoamine oxidase (MAO) inhibitor and although no increased frequency of adrenergic or serotonergic adverse events has been reported, it is recommended that linezolid is used with caution in patients treated with other MAO inhibitors.
BOSELLIE.Pharmacokinetics and intrapulmonary concentrations of linezolid administered to critically ill patients with ventilator associated pneumonia[J].Crit Care Med,2005,33(7):1529-1533.
To determine the steady-state plasma pharmacokinetic variables and epithelial lining fluid concentrations of linezolid administered to critically ill patients with ventilator-associated pneumonia.Prospective, open-label study.An intensive care unit and research ward in a university hospital.Sixteen critically ill adult patients with ventilator-associated pneumonia.All subjects received 1-hr intravenous infusions of linezolid 600 mg twice daily. After 2 days of therapy, the steady-state plasma pharmacokinetic variables and epithelial lining fluid concentrations of linezolid were determined by high-performance liquid chromatography.The mean +/- sd linezolid peak and trough concentrations were 17.7 +/- 4.0 mg/L and 2.4 +/- 1.2 mg/L in plasma and 14.4 +/- 5.6 mg/L and 2.6 +/- 1.7 mg/L in epithelial lining fluid, respectively, showing a mean linezolid percentage penetration in epithelial lining fluid of approximately 100%. The mean +/- sd area under concentration-time curve during the observational period (AUC0-12) was 77.3 +/- 23.7 mg x hr/L, corresponding to a mean AUC0-24 of 154.6 mg x hr/L.Our study shows satisfactory results, with linezolid concentrations exceeding the susceptibility breakpoint for Gram-positive bacteria in both plasma and epithelial lining fluid. This suggests that a dosage of 600 mg administered intravenously twice daily to critically ill patients with Gram-positive ventilator-associated pneumonia would achieve success against organisms with minimum inhibitory concentrations as high as 2-4 mg/L in both plasma and epithelial lining fluid.
BREEDTJ,TERASJ,GARDOVSKISJ,et al.Safety and efficacy of tigecycline in treatment of skin and skin structure infections: Results of a double-blind Phase 3 comparison study with vancomycin-aztreonam[J].Antimicrob Agents Chemother, 2005,49(11):4658-4666.
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SACCHIDANANDS,PENN RL,EMBIL JM,et al.Efficacy and safety of tigecycline monotherapy compared with vancomycin plus aztreonam in patients with complicated skin and skin structure infections: Results from a Phase 3 randomised double-blind trial[J]. Int J Infect Dis,2005,9(5):251-261.
To compare the effect of tigecycline monotherapy, a first-in-class, expanded broad spectrum glycylcycline, with the combination of vancomycin and aztreonam (V + A) in the treatment of complicated skin and skin structure infections (cSSSI). A phase 3, double-blind study conducted in 8 countries enrolled adults with cSSSI who required intravenous (IV) antibiotic therapy for 5 days. Patients were randomly assigned (1:1) to receive either tigecycline or V + A for up to 14 days. Primary endpoint was the clinical cure rate at the test-of-cure visit. Secondary endpoints included microbiologic efficacy and in vitro susceptibility to tigecycline of bacteria that cause cSSSI. Safety was assessed by physical examination, laboratory analyses, and adverse event reporting. A total of 596 patients were screened for enrollment, 573 were analyzed for safety, 537 were included in the clinical modified intent-to-treat (c-mITT) population, 397 were clinically evaluable (CE), and 228 were microbiologically evaluable (ME). At test-of-cure, cure rates were similar between tigecycline and V + A groups in the CE population (82.9% versus 82.3%, respectively) and in the c-mITT population (75.5% versus 76.9%, respectively). Microbiologic eradication rates (subject level) at test-of-cure in the ME population were also similar between tigecycline and V + A. Frequency of adverse events was similar between groups, although patients receiving tigecycline had higher incidence of nausea, vomiting, dyspepsia, and anorexia, while increased ALT/SGPT, pruritis, and rash occurred significantly more often in V + A-treated patients. This study demonstrates that the efficacy of tigecycline monotherapy for the treatment of patients with cSSSI is statistically noninferior to the combination of V + A.
MORTIN LI,LIT,VAN PRAAGH A D,et al. Rapid bactericidal activity of daptomycin against methicillin-resistant and methicillin-susceptible Staphylococcus aureus peritonitis in mice as measured with bioluminescent bacteria[J]. Antimicrob Agents Chemother,2007,51(5):1787-1794.
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LAPLANTE KL, RYBAK MJ.Impact of high-inoculum Staphylococcus aureus on the activities of nafcillin, vancomycin, linezolid,and daptomycin, alone and in combination with gentamicin, in an in vitro pharmacodynamic model[J]. Antimicrob Agents Chemother,2004,48(12):4665-4672.
We evaluated the impact of high (9.5 log(10) CFU/g) and moderate (5.5 log(10) CFU/g) inocula of methicillin-susceptible and -resistant Staphylococcus aureus (MSSA and MRSA, respectively) on the activities of nafcillin, linezolid, vancomycin, and daptomycin, alone and in combination with gentamicin in an in vitro pharmacodynamic model with simulated endocardial vegetations over 72 h. Human therapeutic dosing regimens for nafcillin, daptomycin, vancomycin, linezolid, and gentamicin were simulated. At a moderate inoculum, nafcillin (MSSA only), vancomycin, and daptomycin demonstrated equivalent and significant (P < 0.01) bactericidal (99.9% kill) activities (decreases of 3.34 +/- 1.1, 3.28 +/- 0.4, and 3.34 +/- 0.8 log(10) CFU/g, respectively). Bactericidal activity was demonstrated at 4 h for nafcillin and daptomycin and at 32 h for vancomycin. Linezolid demonstrated bacteriostatic activity over the course of the study period. At a high inoculum, daptomycin exhibited bactericidal activity against both MSSA and MRSA by 24 h (decrease of 5.51 to 6.31 +/- 0.10 log(10) CFU/g). Nafcillin (versus MSSA), vancomycin, and linezolid (MSSA and MRSA) did not achieve bactericidal activity throughout the 72-h experiment. The addition of gentamicin increased the rate of 99.9% kill to 8 h for daptomycin (P < 0.01) and 48 h for nafcillin (MSSA only) (P = 0.01). The addition of gentamicin did not improve the activity of vancomycin or linezolid for either isolate for the 72-h period. Overall, high-inoculum Staphylococcus aureus had a significant impact on the activities of nafcillin and vancomycin. In contrast, daptomycin was affected minimally and linezolid was not affected by inoculum.
Daptomycin is approved at a dose of 4-6 mg/kg/day for the treatment of complicated skin and soft-tissue infection and Staphylococcus aureus bloodstream infection. Clinical experience with doses >6 mg/kg/day is limited, but data reported to date suggest that daptomycin can be safe and effective at higher doses. We describe our experience with daptomycin at doses >6 mg/kg/day and 6 mg/kg/day for S. aureus infections. A retrospective chart review of all patients treated with daptomycin from January 2008 to 28 February 2010 was performed. During the study period, 53 patients received daptomycin, including 22 patients receiving daptomycin at a standard dose (SD) (mean 5 mg/kg/day, range 4-6 mg/kg/day) and 31 patients receiving a higher dose (HD) (mean 8 mg/kg/day, range 7-9 mg/kg). The median treatment duration was 13.5 days and 19 days for the SD and HD groups, respectively. Clinical success was observed in 16/22 patients (73%) in the SD group and 29/31 patients (94%) in the HD group (P=0.05). Microbiological success was observed in 13/19 patients (68%) and 27/29 patients (93%) in the SD and HD groups, respectively (P<0.05). Of the 53 patients, 2/22 treated with SD daptomycin and 3/31 treated with HD daptomycin experienced a grade 1 adverse event while receiving therapy (i.e. anaemia, diarrhoea, nausea, hypokalaemia and arthralgia) but did not require discontinuation of daptomycin treatment. These results suggest that daptomycin may be used at doses higher than 6 mg/kg/day without toxicity and possibly with better outcome than conventional doses. We recommend further randomised controlled prospective studies with higher doses of daptomycin.
CHAFTARI AM,HACHEMR,MULANOVICHV,et al.Efficacy and safety of daptomycin in the treatment of Gram-positive catheter-related bloodstream infections in cancer patients[J]. Int J Antimicrob Agents,2010,36(2):182-186.
Excessive vancomycin usage has contributed to the emergence of vancomycin-resistant enterococci, and a high vancomycin minimal inhibitory concentration (MIC) >1.0 渭g/mL has been associated with poor outcome in patients with meticillin-resistant Staphylococcus aureus (MRSA) infection. In view of these limitations, there is a need for an alternative agent. We evaluated the clinical efficacy and safety of daptomycin given as an alternative agent in the treatment of Gram-positive catheter-related bloodstream infections (CRBSIs) in cancer patients. Between June 2006 and March 2008, 40 patients with probable or definite CRBSI caused by Gram-positive organisms were prospectively enrolled to receive daptomycin intravenous 6. mg/kg/day for up to 4 weeks. In addition, 40 historical matched control patients treated with vancomycin were retrospectively identified. The control group was matched based on underlying disease, organism and neutropenic status. The daptomycin group was comparable with the vancomycin group in terms of neutropenia rate, complications, adverse events, length of hospital stay and death. However, more patients in the daptomycin group achieved symptom resolution at 48. h compared with the vancomycin group (76% vs. 53%; P=0.04). Similarly, more patients in the daptomycin group achieved microbiological eradication at 48. h compared with the vancomycin group (78% vs. 34%; P<0.001). Although not significant, nephrotoxicity was almost three-fold lower in the daptomycin group. The overall response was significantly better for daptomycin compared with vancomycin (68% vs. 32%; P=0.003). In conclusion, compared with vancomycin, daptomycin treatment of Gram-positive CRBSI in cancer patients was significantly associated with earlier clinical and microbiological response as well as improved overall response.
DAVIS SL,MCKINNON PS,HALL LM,et al.Daptomycin versus vancomycin for complicated skin and skin structure infections:clinical and economic outcomes[J]. Pharmacotherapy,2007,27(12):1611-1618.
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FOWLER VG JR,BOUCHER HW, COREY GR,et al. Daptomycin versus standard therapy for bacteremia and endocarditis caused by Staphylococcus aureus[J].N Engl J Med,2006,355(7):653-655.
Safety and efficacy of tigecycline in treatment of skin and skin structure infections: Results of a double-blind Phase 3 comparison study with vancomycin-aztreonam
Efficacy and safety of tigecycline monotherapy compared with vancomycin plus aztreonam in patients with complicated skin and skin structure infections: Results from a Phase 3 randomised double-blind trial
Rapid bactericidal activity of daptomycin against methicillin-resistant and methicillin-susceptible Staphylococcus aureus peritonitis in mice as measured with bioluminescent bacteria
Impact of high-inoculum Staphylococcus aureus on the activities of nafcillin, vancomycin, linezolid,and daptomycin, alone and in combination with gentamicin, in an pharmacodynamic model
, 高胜男
