Teicoplanin. A pharmacoeconomic evaluation of its use in the treatment of gram-positive infections

Teicoplanin, a glycopeptide antibiotic, is active against Gram-positive organisms, including methicillin-resistant staphylococci. It has demonstrated similar efficacy to vancomycin in the treatment of Gram-positive infections in febrile patients with neutropenia; fewer comparative data are available in patients with other infection types. Compared with vancomycin, teicoplanin is associated with less nephrotoxicity, appears to cause fewer anaphylactoid reactions, requires less monitoring and is more convenient to administer (once daily by intravenous bolus or intramuscular injection vs 2 to 4 times daily by intravenous infusion). Two European cost-minimisation studies have demonstrated that while the acquisition cost per dose of teicoplanin was approximately twice that of vancomycin, the cost of 2 weeks' therapy with either agent was similar (difference of 1 to 2%). However, in order to fully explore potential differences between these agents, a full economic analysis which considers all treatment-related costs is needed. Home therapy of Gram-positive infections, a setting in which teicoplanin may be preferred over vancomycin because of its tolerability profile and ease of administration, is particularly worthy of future economic study. Thus, there are a number of areas needing further study before the optimum formulary positioning of teicoplanin can be definitely stated. Nevertheless, present evidence suggests that teicoplanin is likely to have pharmacoeconomic advantages over vancomycin in at least some situations.     

Teicoplanin. A review of its antibacterial activity, pharmacokinetic properties and therapeutic potential

Teicoplanin is a glycopeptide antibiotic with a molecular structure which is related to that of vancomycin. Gram-positive bacteria such as staphylococci (including methicillin-resistant strains), streptococci, enterococci and many anaerobic Gram-positive bacteria are susceptible to teicoplanin in vitro. Teicoplanin has an exceptionally long half-life, allowing once-daily intramuscular or intravenous administration. Teicoplanin is clinically and bacteriologically effective against a wide variety of Gram-positive infections such as septicaemia, endocarditis, skin and soft tissue infections and infections associated with venous catheters. The drug is equally efficacious against methicillin-resistant and -susceptible staphylococci. Adverse effects with teicoplanin are generally limited to local effects or hypersensitivity reactions. While teicoplanin has the potential for ototoxicity and nephrotoxicity, the incidence appears to be quite low when recommended serum concentrations are maintained. Teicoplanin is a valuable alternative to vancomycin, and providing controlled comparative studies prove equivalent safety and efficacy between the 2 glycopeptides the more easily administered teicoplanin should become the preferred antibacterial agent.     

Teicoplanin: a new glycopeptide antibiotic complex

The chemistry, microbiology, pharmacokinetics, clinical efficacy, and adverse effect profile of teicoplanin are reviewed and, where appropriate, compared with vancomycin. Teicoplanin is a glycopeptide antibiotic with potent bactericidal activity against a wide variety of aerobic and anaerobic gram-positive bacteria. In contrast to the structurally related vancomycin, teicoplanin has a prolonged elimination half-life of approximately 60 hours and it may be safely administered by the intramuscular route. Adverse effects of teicoplanin include ototoxicity, nephrotoxicity, skin rash, eosinophilia, neutropenia, and transient elevation of serum aminotransferases. Teicoplanin may be beneficial as an alternative to vancomycin for patients with poor vascular access and in those requiring long-term outpatient therapy. The role of teicoplanin in the treatment and prophylaxis of gram-positive infections will ultimately depend on its unfolding safety and efficacy profile.     

Nephrotoxicity of teicoplanin in rats

Teicoplanin, a glycopeptide antibiotic, is marketed in a number of European countries and has recently been put on the market in Japan. The spectrum of antibacterial activity of teicoplanin is equivalent or superior to that of vancomycin. The aim of the present study is to examine the nephrotoxicity of teicoplanin compared with vancomycin in rats. Wistar male rats, housed in a light-controlled room at room temperature for 1 week, were used. They were injected with either 15 or 50 mg/kg/day of teicoplanin or 50 or 200 mg/kg/day of vancomycin at 13:00 daily for 14 days. The rats were randomly assigned to groups of five rats each and were housed individually in metabolic cages to collect urine. Urine samples were collected 24 hours prior to the drug treatment and every 24 hours thereafter for 14 days. N-Acetyl-beta-D-glucosaminidase (NAG) activity was determined in the supernatant and expressed in international units per total urine collected for 24 hours. The group which was given vancomycin 200 mg/kg/day had significantly elevated urinary NAG levels compared with the other groups (p < 0.05). No significant differences were observed in the NAG levels in urine among the remaining three groups. These results suggest that the nephrotoxicity of teicoplanin may be only one-fourth that of vancomycin in rats. It appears that by extrapolating the dose amount required for the treatment in humans to rats, the high dose of teicoplanin was set at 50 mg/kg/day and that of vancomycin, 200 mg/kg/day. The recommended dose for teicoplanin will probably be 200 mg/day compared to 2 g/day of vancomycin. If the teicoplanin dose is only one-tenth that of the vancomycin dose, then teicoplanin should be better tolerated than vancomycin in terms of nephrotoxicity.     

Clinical outcomes of teicoplanin use in the OPAT setting

Teicoplanin possesses several convenient properties for use in the delivery of outpatient parenteral antimicrobial therapy (OPAT) services. However, its use is not widespread and data on its efficacy in the OPAT setting are limited. Here we present a case series of patients undergoing OPAT care being treated by either teicoplanin-based (n = 107) or ceftriaxone-based (n = 191) antibiotic regimens. Clinical failure with teicoplanin occurred in five episodes of care (4.7%) compared with only two episodes of ceftriaxone-based OPAT care (1.0%). Teicoplanin-associated clinical failure was observed in 2 (33.3%) of 6 patients with Enterococcus infections compared with 3 (3.0%) of 101 patients with non-Enterococcus infections. Overall, there were four (2.9%) drug-related adverse events for teicoplanin and four (1.8%) for ceftriaxone, prompting a switch to teicoplanin in three patients. These findings support the continued use of teicoplanin in OPAT as well as its consideration in centres where it is not currently being offered.     

替考拉宁在重症肺炎患者中的血药浓度监测与应用分析

目的：评价分析替考拉宁在重症肺炎患者中的血药浓度范围及临床疗效。方法：前瞻性纳入某院重症医学科重症肺炎且需使用替考拉宁治疗的患者,给予替考拉宁常规负荷剂量（400 mg,q 12 h,3剂）以及维持剂量（400 mg,qd）,给药后第5天收集替考拉宁稳态谷浓度血样,运用高效液相色谱法监测其浓度,统计分析血药浓度与临床疗效、细菌学有效率以及不良反应的相关性。采用SPSS19.0对本研究数据进行处理。结果：替考拉宁在4~100 μg·mL^-1范围内线性关系良好,标准曲线回归方程为：Y=6 471.14X-2 065.43,R²=0.999 6,平均日内精密度和日间精密度RSD为3.35%和4.66%,稳定性试验RSD为5.13%。平均提取回收率和方法回收率为82.71%和98.34%。共62例重症肺炎患者纳入本研究,替考拉宁平均稳态谷浓度为（11.98±4.82）μg·mL^-1,总体临床有效率为64.52%,细菌学有效率为66.13%,7例（11.29%）出现肾功能损伤,4例（6.45%）出现肝功能损伤。质量浓度<10 μg·mL^-122例,占35.48%,浓度<15 μg·mL^-1的45例,占72.58%。Logistic回归分析显示替考拉宁谷浓度与细菌学有效率以及肾毒性分别具有独立相关性,并确定目标谷浓度范围为9~17 μg·mL^-1。结论：对于重症肺炎患者,为保证临床疗效建议适当增加替考拉宁给药剂量,必要时可开展血药浓度监测,使其有效浓度维持在9~17 μg·mL^-1范围。     

Teicoplanin vs vancomycin: cost-effectiveness comparisons

The rising incidence of methicillin-resistant staphylococci and resistant enterococci in recent years has led to increased use of vancomycin as an active combatant in the treatment of gram-positive infections. Teicoplanin is an investigational glycopeptide that shares a similar spectrum of activity with vancomycin and appears to have similar efficacy. Teicoplanin offers several theoretical advantages compared with vancomycin including once-daily dosing, fewer side effects, and the option for intramuscular administration. While these may be perceived as substantial advances in the glycopeptide class of antibiotics, teicoplanin will probably not replace the now generically available vancomycin on hospital formularies. If competitively priced as a once-daily dosing regimen, teicoplanin will likely gain initial acceptance as an alternative in patients with an intolerance to vancomycin infusion-related side effects or in patients placed on combination aminoglycoside therapy for extended periods of treatment, as an intramuscular antibiotic in patients with poor venous access, and for routine antibiotic prophylaxis where protection from resistant gram-positive pathogens is important. The use of teicoplanin in the hospital may become more widespread as its side effect profile and economic advantages of less frequent dosing compared with vancomycin become better understood.     

Teicoplanin for therapy of gram-positive infections in neutropenic patients

Teicoplanin was evaluated in 20 febrile neutropenic patients as additional treatment for suspected Gram-positive infections after inadequate response to initial empiric ceftazidime monotherapy. Five patients with primary septicaemia, four with secondary septicaemia, 12 with localized infections and three with pyrexia of unknown origin were treated with teicoplanin (200 mg bolus intravenously, once daily after a 400 mg loading dose), whilst ceftazidime (2 g, 8-hourly, 30 min infusions) was continued. Four patients were unassessable (tuberculous, viral, protocol violation, and non-infectious pyrexial episode). Clinical cure for the combination was achieved in 11 or the 16 assessable cases (69%). Ten of the eleven (91%) bacteriologically confirmed infections were cured after addition of teicoplanin. Three strains of Staphylococcus aureus, four of Staphylococcus epidermidis (two methicillin resistant), and three strains of Streptococcus faecalis were isolated from successfully treated patients. One patient with Aerococcus and Enterobacter cloacae infection only improved after addition of erythromycin. One superinfection occurred with signs of interstitial pneumonitis in a patient following bone marrow transplantation. Neither ototoxicity nor nephrotoxicity occurred during treatment. A transient rise of liver transaminases was observed in four patients, but was attributable to teicoplanin in only one case. It is concluded that teicoplanin is a potentially effective and well-tolerated antimicrobial agent in neutropenic patients with infections due to Gram-positive organisms.     

Serum and bone concentrations of teicoplanin and vancomycin: study in an animal model

Teicoplanin and vancomycin are antibiotics widely used in the therapy of bone and joint infections. The aim of this study was to compare bone and serum concentrations of each antibiotic in guinea pigs after administration of 50 mg/kg of teicoplanin or vancomycin by the intravenous route. Serum and bone concentrations were determined immediately before and 0.5, 1, 2, 6, 12 and 24 h after drug administration by means of high performance liquid chromatography. Teicoplanin concentrations were always higher than vancomycin levels. Area under the concentration/time curve was significantly greater for teicoplanin than for vancomycin. In bone, teicoplanin concentration increased up to 6 h, while vancomycin reached its peak after 2 h. Moreover, teicoplanin showed markedly higher levels at 6, 12 and 24 h than vancomycin. In conclusion, the ability of teicoplanin to penetrate bone in greater amount than vancomycin confirms the potential use of teicoplanin in the treatment of bone infections and in the prophylaxis of orthopedic surgery.     

替考拉宁治疗G+菌感染的疗效和安全性

目的：评价替考拉宁治疗G^ 菌感染的疗效和安全性。方法：采用随机对照及开放试验，以万古霉素为对照。完成病例60例，其中试验组30例，替考拉宁0．2～0．4g，qd，静脉滴注；对照组30例，万古霉素0．5g，tid，静脉滴注。疗程均为7～14d。结果：试验组痊愈率、有效率、细菌清除率分别为50％，80％和83．3％，对照组分别为46．7％，76．7％和76．7％，2组差异无显著性。不良反应发生率分别为10％和13．3％，2组差异亦无显著性。结论：替考拉宁治疗G^ 菌感染安全有效。     

Therapy of serious gram-positive infections with teicoplanin

Teicoplanin was used as monotherapy in 17 seriously ill patients (mean age 51 years, range 18-71) with infection due to Gram-positive organisms. The dose used was 200 mg teicoplanin intravenously once daily after an initial intravenous dose of 400 mg. Most of the patients (15 out of 17) were septicaemic (confirmed by blood culture), the other two had deep abscesses. The pathogens isolated were Staphylococcus epidermidis [15], Streptococcus faecium [1] and JK Coryneform [1]. The 15 patients with Staph. epidermidis infections had all been treated previously with a beta-lactam (usually flucloxacillin)/aminoglycoside combination to which Staph. epidermidis was resistant. All patients were still pyrexial after 48 h of therapy and were then changed to teicoplanin as monotherapy. Patients were treated with teicoplanin for 5 to 7 days. One was withdrawn because of vomiting associated with the teicoplanin infusion, and another was withdrawn because she was given amikacin for a separate Gram-negative infection, but all the other 15 patients responded well to therapy, usually becoming apyrexial within 48 h. All 15 septicaemic patients had central lines in situ: 10 responded to therapy with the line left in situ but in 5 the lines were removed, either before or during teicoplanin therapy. Teicoplanin levels were determined in all patients, usually on day 2, with no evidence of toxicity from these levels. Teicoplanin was found to be effective as monotherapy for septicaemia mainly due to Staph. epidermidis in patients with severe underlying disease.     

替考拉宁与万古霉素治疗革兰阳性菌感染疗效和安全性评价

目的:系统评价替考拉宁与万古霉素治疗G+感染的疗效及不良反应发生情况。方法:应用国际Cochrane协作网系统方法评价替考拉宁与万古霉素治疗G+感染的临床随机对照试验(RCT)。计算机检索Cochrane临床对照试验资料库、MEDLINE(1994-2010.12)和中文科技期刊数据库(1994-2010.12),纳入考拉宁与万古霉素治疗G+感染的RCT。由两名评价者独立提取资料并进行质量评估。试验数据的统计分析采用Cochrane协作网提供的Rev Man5.1软件。结果:最终纳入了10个RCT并对其疗效进行了Meta分析,共纳入758例患者,其中替考拉宁组358例,万古霉素组400例。Meta分析结果显示,替考拉宁组与万古霉素组治疗G+感染临床痊愈率分别为44.1%和39.8%;有效率分别为80.16%和80.00%;细菌清除率分别为86.12%和85.23%;不良反应发生率分别为18.16%和22.92%;其各自的综合OR值分别为0.98(95%CI为0.68～1.40),P=0.45;0.98(95%CI为0.68～1.40),P=0.90;1.05(95%CI为0.65～1.69),P=0.84;0.79(95%CI为0.54～1.15),P=0.22,差异均无统计学意义。结论:现有临床证据表明,替考拉宁与万古霉素治疗G+感染有效性和安全性相比,两药的疗效与不良反应相似。但万古霉素的"红人综合征"不良反应发生率要大一些。     

Teicoplanin in the therapy of staphylococcal neuroshunt infections

Three patients with staphylococcal infection of neuroshunt, two with ventriculoperitoneal and one with external ventricular derivation, were treated with teicoplanin given intravenously (iv) or intraventricularly (ivt), two patients were adults, while the third was an infant. The causative organisms were methicillin-sensitive Staphylococcus epidermidis (MSSE) in the first two cases and methicillin-sensitive Staphylococcus aureus (MSSA) in the paediatric patient. Patient No. 1 was given teicoplanin iv (400 mg/day) and subsequently ivt (20 mg/day). CSF teicoplanin levels were always below 1 microgram/ml during the first part of the treatment; after the institution of ivt therapy, drug levels ranged from 20 to 35 micrograms/ml (mean 26.4). The patient was cured after 20 days of a combination treatment (ivt teicoplanin plus rifampin, 900 mg/day, iv). Patient No. 2 was given teicoplanin 400 mg/day, iv, for two weeks; its low levels in CSF (always below 0.5 microgram/ml) accounted for the failure to eradicate the MSSE. A new regimen with teicoplanin, 20 mg/day plus netilmycin, 15 mg/day, both ivt, cured the patient in two weeks. Teicoplanin levels in the CSF ranged from 12.5 to 33 micrograms/ml (mean 18.3). Patient No. 3, an 8-month-old infant, was placed on teicoplanin, 5 mg/day ivt plus chloramphenicol, 180 mg/day iv, after several other antibiotic trials had failed to eradicated a MSSA infection of his external ventricular derivation. The therapy cleared the infection in one week (CSF teicoplanin levels: 30 to 38, mean 34 micrograms/ml). Teicoplanin (iv or ivt) was well tolerated without any significant side-effects; its role in the treatment of staphylococcal neuroshunt infections deserves further studies.     

替考拉宁治疗慢性阻塞性肺疾病合并革兰阳性球菌感染患者的临床效果

目的 探讨替考拉宁(Teicoplanin,TCL)治疗慢性阻塞性肺疾病(COPD)合并革兰阳性球菌(GPC)感染患者的临床效果.方法 选择2012年5月至2014年1月于本院诊治的COPD合并GPC感染患者80例,随机将其分为观察组(TCL治疗)和对照组[万古霉素(Vancomycin,VCM)治疗],各40例.记录两组临床疗效、细菌学疗效和不良反应发生情况.结果 观察组有效率85.0％,明显高于对照组65.0％(P＜0.05).TCL治疗后,52株GPC中,40株被清除或部分清除,清除率为76.9％;VCM治疗后,44株GPC中,28株被清除或部分清除,清除率为63.6％;两组差异无统计学意义(P＞0.05).观察组不良反应发生率12.5％,显著低于对照组的32.5％ (P＜0.05).结论 使用TCL治疗COPD合并GPC感染的患者较VCM具有更好的临床效果,GPC清除率更高,且毒副反应小,造成的不良反应更小.     

Current treatment of gram-positive infections: focus on efficacy, safety, and cost minimalization analysis of teicoplanin

The current health care environment has had a significant impact on hospital Pharmacy and Therapeutics Committee formulary decisions. In evaluating a new therapy for formulary inclusion, a cost savings along with equivalent or an improvement in patient care and safety is optimal. Teicoplanin is an investigational glycopeptide antimicrobial agent with a spectrum of activity similar to vancomycin. Unlike vancomycin, however, teicoplanin has a long elimination half-life permitting administration once daily, and is well tolerated when given intramuscularly. In addition, teicoplanin is associated with a favorable safety profile. Red man syndrome does not appear to be a significant clinical problem. Results of our cost minimalization analysis using the average acquisition costs of vancomycin revealed that teicoplanin (400 mg), at an average acquisition cost of less than $28.46 when administered intravenously and $30.93 when administered intramuscularly, offers a clinically efficacious, safe, and less expensive alternative to vancomycin therapy.     

Clinical predictors of nephrotoxicity associated with teicoplanin: Meta-analysis and meta-regression

Teicoplanin is a glycopeptide antibiotic against methicillin-resistant Staphylococcus aureus infections. However, the impact of clinical characteristics on nephrotoxicity associated with teicoplanin has not been determined. This meta-analysis aimed to investigate the relationship between clinical characteristics and nephrotoxicity associated with teicoplanin. We identified clinical research published from January 1975 to June 2021 using PubMed, Cochrane Library, and Scopus, which described the nephrotoxicity associated with teicoplanin. Meta-analysis determined the incidence of nephrotoxicity. Using meta-regression analysis, we evaluated the impact of clinical characteristics on outcomes. Of the 567 articles, eight articles including 634 patients were analysed. The overall incidence of nephrotoxicity associated with teicoplanin was 11.0% (95% confidence interval: 8.0–13.0) for the fixed-effect model. Additionally, patients with >65 years had a high trend for the risk of nephrotoxicity compared to those with ≤65 years (>65 years; 12.0% [95% confidence interval: 9.0–15.0] vs. ≤65 years; 7.0% [95% confidence interval: 3.0–12.0], p = 0.09) for the fixed-effect model. Meta-regression analysis demonstrated that only serum albumin level negatively correlated with the risk of nephrotoxicity (y = ?17.0 x + 56.7, r = 0.74, p = 0.01). This meta-analysis ascertained that hypoalbuminemia leads to nephrotoxicity associated with teicoplanin.     

Teicoplanin: an investigational glycopeptide antibiotic

The chemistry, mechanism of action, antimicrobial spectrum, pharmacokinetics, adverse effects, and clinical uses of teicoplanin are reviewed. Teicoplanin, a novel glycopeptide that is similar to vancomycin, was isolated in the mid-1970s. A fermentation product of Actinoplanes teicomyceticus, teicoplanin is a structurally complex compound made up of six fatty-acid components attached to a common aglycone. Teicoplanin's mechanism of action, like that of vancomycin, is inhibition of cell-wall biosynthesis. In vitro activity is comparable to that of vancomycin and includes staphylococci, streptococci, corynebacterium, listeria, and anaerobic cocci. Resistance to teicoplanin has been reported with coagulase-negative staphylococci. Teicoplanin is 50 to 100 times more lipophilic than vancomycin. Teicoplanin is poorly absorbed after oral administration but is 90% bioavailable when administered intramuscularly. The drug distributes widely into body tissue and is eliminated primarily renally. Optimal dosing regimens and therapeutic serum drug concentrations have not been well established. Reported adverse effects have included irreversible ototoxicity, allergic reactions with maculopapular rash and eosinophilia, pain at intramuscular injection site, and elevation of aminotransferases. Initial clinical trials have yielded conflicting results in gram-positive bacteremia, endocarditis, osteomyelitis, and soft-tissue infections. Teicoplanin has shown promise in surgical and dental prophylaxis. Comparative trials with vancomycin and other antimicrobial agents must be completed before teicoplanin's role as a therapeutic agent in the treatment of systemic gram-positive infections is defined.     

Teicoplanin in perspective A critical comparison with vancomycin

Teicoplanin is a new glycopeptide antibiotic with a chemical structure related to vancomycin. The proposed advantages of teicoplanin over vancomycin are discussed. These include lower incidence of side-effects, lower toxicity (especially in combination with aminoglycosides), lower dosage frequency and the possibility of intramuscular administration. There is only a limited number of studies comparing both agents; more studies are still needed before firm conclusions can be drawn. Therapeutic drug monitoring is not usually necessary for teicoplanin; the situation is not clear for vancomycin. There is some doubt whether the incidence of resistance is as infrequent for teicoplanin as it is for vancomycin. Teicoplanin appears to be a promising alternative to vancomycin, but more data are needed on the relative clinical efficacy and the development of resistance to both drugs.     

高龄下呼吸道感染患者的替考拉宁血药浓度监测及安全性评价

目的探讨替考拉宁在高龄下呼吸道感染患者中的血药浓度与临床疗效、不良反应之间的关系。方法高龄下呼吸道感染病例52例,用替考拉宁治疗5—24d,观察患者疗效、给药前后肝肾功能指标及不良反应情况;监测患者替考拉宁的谷浓度。结果替考拉宁的谷浓度为（17．1±10．1）mg·L^-1,治疗有效组和无效组在血药浓度等方面差异无统计学意义;给药前后肝、肾功能指标差异无统计学意义。结论替考拉宁在治疗下呼吸道感染患者时,血药浓度与疗效之间未见显著相关性,临床应用时应在血药浓度的监测下行个体化治疗。     

Microbiological and clinical study of methicillin-resistant Staphylococcus aureus (MRSA) carrying VraS mutation: changes in susceptibility to glycopeptides and clinical significance

The VraSR two-component regulatory system is involved in glycopeptide resistance in Staphylococcus aureus. We examined the relationship between VraS mutation and susceptibility to various antimicrobial agents in 400 clinical isolates of methicillin-resistant S. aureus (MRSA) from Cancer Institute Hospital between 1998 and 2004. The prevalence of MRSA isolates with teicoplanin minimum inhibitory concentrations (MICs) of 4-8 microg/mL rose between 2000 and 2002 (52% in 2000). Among the isolates displaying reduced susceptibility to teicoplanin (78 isolates), 99% harboured the Ile5Asn (I5N) mutation in VraS. In addition, MICs of oxacillin and imipenem tended to be higher for I5N mutants compared with those for non-I5N isolates. By contrast, no significant change was noted in susceptibility to arbekacin or vancomycin. In this hospital, I5N mutants emerged at an early stage after the introduction of teicoplanin and thereafter declined in number upon increased usage of arbekacin instead of glycopeptides. Outcomes from 18 patients who were infected with MRSA with reduced susceptibility to teicoplanin were analysed microbiologically in a retrospective manner. Teicoplanin was effective in 50% of the patients treated with this drug. On the other hand, arbekacin and vancomycin were effective in all cases. The results indicate the relationship between antimicrobial susceptibility and therapeutic effect.