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.     

Oral ciprofloxacin in refractory gram-negative bacillary infections

The 13 patients included in this series: had chronic Gram-negative bacillary infections that were refractory to prior antibiotic therapy; were unable or unwilling to receive intravenous antibiotics; and had altered host defenses or environmental factors that contributed to persistent infection. Five patients had chronic polymicrobic Gram-negative osteomyelitis, three had urinary tract infections caused by Pseudomonas aeruginosa, two had Pseudomonas skin infections and three had respiratory tract infections with Gram-negative bacilli. The overall bacteriological cure rate for Gram-negative bacilli was four of five osteomyelitis, all three urinary tract infections, both skin infections and one out of three respiratory infections. Secondary infections occurred in two patients with bone infections, one with prostatitis and one with deep seated cellulitis and myonecrosis. Two patients with end-stage lung disease had emergence of resistant strains during therapy. Ciprofloxacin was well tolerated and effective in most of the ambulatory patients with refractory Gram-negative bacillary infection. It appears to be especially promising for Pseudomonas infections of the bone, urinary tract and soft tissue.     

Teicoplanin vs. vancomycin for the treatment of serious infections: a randomised trial

A prospective, randomised study of 56 patients comparing teicoplanin with vancomycin for suspected or proven severe Grampositive infection was conducted. The majority of infections were soft tissue infections (8 teicoplanin; 16 vancomycin) and by chance a significantly higher number of Hickman catheter-related infections occurred in the vancomycin arm (4 vs. 14, P < 0.01). Teicoplanin was administered as a single daily dose of 400 mg iv or im; 5 patients received 200 mg following the initial dose of 400 mg. Vancomycin was given 1 g every 12 h. Fifty-four patients were evaluable for efficacy (26 teicoplanin, 28 vancomycin). Of these, 18 episodes in 17 patients (teicoplanin) and 19 episodes in 18 patients (vancomycin) gave an evaluable clinical response, the success rates being similar (76% teicoplanin; 68% vancomycin). Staphylococcus aureus was the most common pathogen isolated; all pathogens were susceptible to both glycopeptides with MICs < 4 mg/l. Bacteriological elimination rates were similar in both groups (71% teicoplanin; 78% vancomycin). Significantly more patients given vancomycin experienced adverse events (7 teicoplanin; 16 vancomycin; P = 0.03). This caused treatment to be discontinued in 4 cases, compared with only one receiving teicoplanin. The most common vancomycin-related events were histamine-associated reactions (15 patients), including 2 cases of Red Man Syndrome, and nephrotoxicity (5 patients). There were no histamine-mediated events and only one case of nephrotoxicity with teicoplanin. Teicoplanin and vancomycin show similar clinical and bacteriological efficacy and teicoplanin is significantly less toxic and easier to use in patients with severe infection.     

Retrospective study of teicoplanin as home continuation of hospital-initiated therapy

Data were collected retrospectively on 69 cases of infection in 57 patients who had received teicoplanin on a non-inpatient basis for at least part of a course of therapy. A total of 52 records related to patients who were undergoing treatment for a hematological malignancy, most of whom had central venous catheter infection or catheter-related septicemia. Eleven cases were related to the treatment of bone and/or joint infection, two were concerned with the treatment of endocarditis and two were linked to soft tissue infections. In most cases in which bacteriological identification was made, coagulase-negative staphylococci were the causative organisms. Other pathogens included Staphylococcus aureus, streptococci, enterococci and diphtheroids. In most cases, the dose of teicoplanin used corresponded to the recommended dose for serious infections. All patients received teicoplanin intravenously and some patients administered the drug themselves. Clinical success (cure plus improvement) was achieved in 94% of evaluable cases and bacteriological success in 83%. Two adverse events were reported, but neither related to problems of antibiotic administration in a non-inpatient setting.     

Ceftaroline fosamil: a novel broad-spectrum cephalosporin

Ceftaroline fosamil is a new extended-spectrum cephalosporin with activity against drug-resistant Grampositive pathogens such as methicillin-resistant Staphylococcus aureus (MRSA) and penicillin-resistant Streptococcus pneumoniae. At the same time, its Gramnegative spectrum of coverage includes common respiratory pathogens such as Haemophilus influenzae and Moraxella catarrhalis, as well as wild-type Enterobacteriaceae. In vivo efficacy for the treatment of experimental endocarditis, pneumonia, myositis and osteomyelitis has been demonstrated in animal models, while efficacy in the treatment of complicated skin and soft tissue infections and community-acquired pneumonia has been demonstrated in phase II and III clinical trials in humans. The drug is well tolerated and has a low rate of reported adverse events. The dose of ceftaroline fosamil used is 600 mg i.v. every 12 h for patients with normal renal function or mild renal dysfunction. In patients with moderate renal dysfunction, it has been suggested that ceftaroline fosamil be dosed at 400 mg i.v. over 60 min every 12 h. Ceftaroline fosamil is still under review by the U.S. FDA, and when approved, will be one of the first commercially available β-lactams with the ability to treat infections due to MRSA and other drug-resistant Gram-positive pathogens.     

Use of a glycopeptide antibiotic, teicoplanin, in the treatment of septicaemia caused by gram-positive bacteria

Teicoplanin, a recently introduced glycopeptide antibiotic, has been used, in combination with other antibiotics, to treat 31 episodes of septicaemia caused by Gram-positive organisms. Teicoplanin has double the activity of vancomycin against many Gram-positive bacteria, but allergic reactions and toxicity appear to be infrequent. A single daily dose is sufficient to maintain therapeutic levels, which is an advantage in conditions requiring long-term treatment. Of the 31 episodes treated, 16 were associated with infective endocarditis, 11 with Hickman catheter infection, two with bone and joint infection, and two with infection of other indwelling prosthetic devices. Staphylococcus epidermidis was isolated in 18 infections, of which seven treatment courses were unsuccessful. One death occurred from an uncontrolled infection, three deaths from underlying disease (one of which had relapsed twice), and one after withdrawal of treatment following febrile reaction. Eleven episodes were cured. Six episodes of Staphylococcus aureus septicaemia were treated, of which two failed to respond, two relapsed, one improved and one was cured. The remaining seven episodes were caused by streptococci (including Streptococcus faecalis), and in all of them cure was achieved despite the lack of consistent serum bactericidal activity in vitro.     

Clinically significant Streptococcus anginosus (Streptococcus milleri) infections: a review of 186 cases

We describe clinically significant infections due to Streptococcus anginosus in 186 patients; 114 (61.3%) males and 72 (38.7%) females, median age 42 years, range 9 months to 93 years. In 101 (54.3%) cases S anginosus alone caused infection and in 85 (45.7%) cases it was associated with other microorganisms. Abscesses accounted for 110 (59.1%) infections. Sites of infection were: miscellaneous skin and soft tissue, 64 (34.4%), intraabdominal 41 (22%), head and neck 34 (18.3%), pleuropulmonary 22 (11.8%), genitourinary 9 (4.8%), musculoskeletal 6 (3.2%), endocarditis 5 (2.7%) and primary bacteraemia 5 (2.7%). Treatment consisted of antibiotic therapy which was often prolonged, median 30 days, range 2-90 days, and surgery in 159 (85.5%). S anginosus infection was a contributory factor in two of the three deaths which occurred.     

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.     

Linezolid in children: recent patents and advances

Linezolid is the first approved member of a new generation of antibiotics, the synthetic oxazolidinones, to become available, with a broad spectrum of in vitro activity against Gram-positive organisms, including methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus faecalis and vancomycin-resistant Enterococcus faecium. It has an excellent bioavailability both intravenously and orally and a very good safety profile both in adults and in children. With regards to its antimicrobial action, linezolid has a predominantly bacteriostatic action, rather than a bacteriocidal effect and is active against Gram-positive bacteria that are resistant to other antibiotics. Linezolid is currently showing great promise for the treatment of multi-resistant Gram-positive infections, both in the community and in a hospital setting. Clinical indications so far include skin and soft tissue infections, community-acquired or nosocomial pneumonia due to MRSA, VRE bacteremia and community-acquired pneumonia due to penicillin-resistant Streptococcus pneumoniae. We anticipate that this new generation of antimicrobial agents will provide adequate cover in the future for infections that cause significant treatment failures so far, such as VRE- associated endocarditis, bone and joint multi-drug resistant infections and possibly central nervous system infections, both in adult and children populations. Some patents on linezolid are also discussed in this review.     

Community-acquired methicillin-resistant Staphylococcus aureus infections

Methicillin-resistant Staphylococcus aureus (MRSA) should no longer be regarded as a strictly nosocomial pathogen. During the past decade, community-acquired MRSA (CA-MRSA) infections among young persons without healthcare-associated (HCA) risk factors have emerged in several areas worldwide. These infections are caused by strains that almost exclusively carry the staphylococcal cassette chromosome mec type IV element and the Panton-Valentine leukocidin genes and, unlike HCA-MRSA strains, are not multiresistant. Although the majority of CA-MRSA infections are mild skin and soft tissue infections, severe life-threatening cases of necrotizing pneumonia, necrotizing fasciitis, myonecrosis and sepsis have been reported. Clindamycin is an effective agent for skin and soft tissue infections, however attention should be paid to the possibility of the emergence of resistance during treatment in strains with the macrolide, lincosamide and group B streptogramin (MLS(B))-inducible resistance phenotype. For patients with invasive infections that may be caused be CA-MRSA, vancomycin, teicoplanin and linezolid represent appropriate empirical therapeutic options.     

Registered and investigational drugs for the treatment of methicillin-resistant Staphylococcus aureus infection

First isolated in the 1960s methicillin-resistant Staphylococcus aureus (MRSA) has become a leading hospital acquired (HA) pathogen, although community acquired isolates (CA-MRSA) are on the rise, particularly in the USA. Treatment of serious MRSA infections has been based for many years upon the use of glycopeptides, i.e. vancomycin and teicoplanin. Other drugs indicated in particular clinical settings, such as prosthetic valve endocarditis or osteomyelitis, are rifampin, gentamycin, fusidic acid, minocycline, co-trimoxazole, clindamycin. Quinolones and doxycycline may be active on some MRSA isolates, and add some this important clinical setting. In the last few years new anti-MRSA drugs have been registered and patented, expanding therapeutic opportunities, i.e. linezolid, the first oxazolidinone, available both as oral and parenteral formulation in being the most widely used new anti-MRSA agent, quinupristin-dalfopristin, daptomycin, a novel lipopeptide, active on germs both in the replicating and in the resting phase, and tigecycline, the first approved glycylcycline. Other drugs from different classes are in the pipeline and will further enhance in the next few years our therapeutic armamentarium: three glycopeptides, i.e. dalbavancin, telavancin, and oritavancin, two broad spectrum cephalosporins, ceftobiprole and ceftaroline, iclaprim, a diaminopyrimidine, as well as a carbapenem, CS-023/RO-4908463, and adjuvant therapies such as the monoclonal antibody tefibazumab.     

感染性心内膜炎患者的血培养病原菌分布及耐药性分析

目的 分析感染性心内膜炎患者的血培养病原菌构成及药敏结果，为患者的临床用药提供参考依据。方法 选取我科(广东省人民医院二区)2015年1月-2018年12月473例住院治疗的感染性心内膜炎患者作为对象，对其血培养结果进行病原菌分布和耐药性分析。结果 473例感染性心内膜炎患者血培养阳性97例，阳性率20.8%。共分离出病原菌102株，其中革兰阳性菌92株占90.20%，革兰阴性菌4株占3.92%，真菌6株占5.88%。链球菌属对青霉素、头孢曲松敏感率分别81.43%、87.30%，左氧氟沙星敏感率为79.37%，对克林霉素、红霉素、四环素耐药率较高，对氯霉素耐药率低。葡萄球菌对青霉素的耐药率为100%、对苯唑西林耐药率50%，克林霉素、红霉素次之，对左氧氟沙星、庆大霉素和利福平的耐药率较低，均<10.00%。耐甲氧西林葡萄球菌检出率较高，耐甲氧西林金黄色葡萄球菌(MRSA)4株占66.7%，耐甲氧西林凝固酶阴性葡萄球菌(MRCNS)4株占50%，肠球菌属对青霉素、庆大霉素耐药率均为16.67%，对喹诺酮类敏感，对红霉素、四环素耐药率较高。均未见对万古霉素、替考拉宁、利奈唑胺耐药菌株。真菌均对5-氟胞嘧啶、氟康唑、伊曲康唑、伏立康唑、两性霉素B均敏感。结论 链球菌和葡萄球菌是感染性心内膜炎的主要致病菌。结合药敏分析结果，在经验性治疗感染性心内膜炎时，选用青霉素联合氨基糖苷类药物治疗存在较大风险，尤其对于急性重症感染合并耐药菌感染高危因素的患者，万古霉素是理想的选择。     

Dalbavancin in the treatment of different gram-positive infections: a real-life experience

Dalbavancin is a lipoglycopeptide with a very prolonged half-life enabling treatment with a single intravenous administration that has been approved to treat complicated skin and soft-tissue infections. Information on the efficacy and safety of dalbavancin in other situations is very scarce. This retrospective study included adult patients who received at least one dose of dalbavancin between 2016 and 2017 in 29 institutions in Spain. The primary objective was to report the use of dalbavancin in clinical practice, including its efficacy and tolerability. The potential impact of dalbavancin on reducing the length of hospital stay and hospital costs was also evaluated. A total of 69 patients received dalbavancin during the study period (58.0% male; median age 63.5 years). Dalbavancin was used to treat prosthetic joint infection (29.0%), acute bacterial skin and skin-structure infection (21.7%), osteomyelitis (17.4%) and catheter-related bacteraemia (11.6%). These infections were mainly caused by Staphylococcus aureus (27 isolates), coagulase-negative staphylococci (24 isolates) and Enterococcus spp. (11 isolates). All but two patients received previous antibiotics for a median of 18 days. Dalbavancin was administered for a median of 21 days (range 7–168 days), and concomitant antimicrobial therapy was prescribed to 25 patients (36.2%). The overall clinical success rate of dalbavancin was 84.1%. Adverse events, mainly mild in intensity, were reported in nine patients. Overall, dalbavancin was estimated to reduce hospitalisation by 1160 days, with an estimated overall cost reduction of €211 481 (€3064 per patient). Dalbavancin appears to be an effective therapy for many serious Gram-positive infections.     

Neglected Pathogens: Bacterial Infections in Persons With Human Immunodeficiency Virus Infection A Review of the Literature (First of Two Parts)

Bacterial infections, including those that cause infection in the healthy host as well as those that are more opportunistic, occur very commonly among persons infected with the human immunodeficiency virus (HIV). Bacterial infections are a direct result of the severe humoral and cellular immune defects found in these patients. Epidemiologic factors such as intravenous drug use and stage of HIV infection may also play important roles. Pulmonary, bloodstream, gastrointestinal, central nervous system, skin and soft tissue, and catheter-related infections are common, as are endocarditis, prostatitis, and others. Frequently reported pathogens are common organisms such as Staphylococcus aureus, Haemophilus influenzae, Streptococcus pneumoniae, and enteric gram-negative pathogens, as well as less typical ones such as Listeria monocytogenes and Nocardia sp. The frequency of infection is specific to organ system and pathogen, often being many times higher than in immunocompetent hosts. Prompt recognition and aggressive therapy are required to reduce morbidity and mortality due to these infections.     

替考拉宁在耐甲氧西林金黄色葡萄球菌所致感染性心内膜炎的应用评价

目的：评价替考拉宁在耐甲氧西林金黄色葡萄球菌（MRSA）所致感染性心内膜炎的应用。方法：通过比较2014-2015年国内外相关指南、共识及《抗菌药物临床应用指导原则（2015年版）》对MRSA所致感染性心内膜炎的推荐方案,提出有争议的问题：替考拉宁是否适用于治疗MRSA所致感染性心内膜炎？通过查询国内外文献,从循证医学证据、替考拉宁在心脏赘生物的分布、给药方案、治疗药物浓度监测等4个方面进行评价。结果：替考拉宁治疗MRSA所致感染性心内膜炎的循证医学证据还很少,有限的证据表明,替考拉宁常规剂量治疗感染性心内膜炎时,出现更高的失败率。定量放射自显影术显示,替考拉宁只分布在心脏赘生物的外围。替考拉宁用于治疗严重感染时,需要优化给药方案,并进行血药浓度监测。目前替考拉宁的治疗药物浓度监测还未广泛开展,不利于替考拉宁用于严重感染的治疗。结论：不推荐替考拉宁用于治疗MRSA所致的感染性心内膜炎。     

Clinical and economic effect of ciprofloxacin as an alternative to injectable antimicrobial therapy

The effect of the use of oral ciprofloxacin on patient outcome and the cost of antimicrobial therapy was investigated. In 1988 ciprofloxacin was placed on the antimicrobial formulary at a Veterans Affairs medical center. Patients with urinary tract infections, soft tissue infections, osteomyelitis, or pneumonia due to organisms that were documented as being susceptible to ciprofloxacin and either resistant to other oral antimicrobials or susceptible to other oral antimicrobials in patients allergic to such agents were monitored in a prospective open study over 12 months. When a patient was enrolled, the physician was asked to select the i.v. antimicrobial regimen that would have been used if ciprofloxacin were not available. Patient outcome was determined from medical records, and the difference in the costs of the oral and i.v. regimens was calculated. Clinical cure occurred in 96/100 (96%) of patients with urinary tract infection, 19/22 (86%) with soft tissue infection, 14/16 (88%) with osteomyelitis, and 10/12 (83%) with pneumonia. The overall cure rate was 139/150 (93%). The 11 clinical failures occurred in patients infected with methicillin-resistant Staphylococcus aureus (MRSA) alone, group D enterococcus alone, MRSA and Pseudomonas sp., and Pseudomonas sp. alone. The total cost avoidance achieved by using oral ciprofloxacin instead of i.v. antimicrobials was $77,158. Oral ciprofloxacin was an effective and cost-efficient alternative to traditional i.v. antimicrobial therapy in the patients studied.     

Biodegradable implantable teicoplanin beads for the treatment of bone infections

Parenteral antibiotic therapy for acute bone infections, soft tissue infections and osteomyelitis may result in high serum concentrations, associated with nephrotoxic, ototoxic and allergic complications. After taking these above mentioned disadvantages into consideration, recent investigations have explored the use of antibiotic-loaded biodegradable implants, incorporating antibiotics for potential use in the treatment of bone infections. In this study, biodegradable implants containing teicoplanin for the prevention or the treatment of bone infections were designed by using sodium alginate as the polymer material. Therefore, teicoplanin, a glycopeptide antibiotic, active against gram-positive bacteria was incorporated in a natural polymer in order to prepare bead formulation for implantation purpose in bone for the localized treatment of osteomyelitis. In vitro characterization was realized by determining particle size, surface characteristics, loading capacity and in vitro release characteristics of the beads.     

Factors associated with outcome and duration of therapy in outpatient parenteral antibiotic therapy (OPAT) patients with skin and soft-tissue infections

This study was designed to identify factors associated with adverse outcomes and increased duration of parenteral therapy in patients with skin and soft-tissue infections (SSTIs) managed with outpatient parenteral antibiotic therapy (OPAT). A retrospective cohort study interrogating variables recorded prospectively in an electronic OPAT patient database was performed. ‘OPAT failure’ was defined as hospitalisation following initiation of OPAT, or adverse event or progression of infection necessitating a change in antibiotic therapy. Variables associated with failure or increased duration of therapy were identified via univariate and multiple logistic regression analyses. In total, 963 first patient episodes of OPAT-treated SSTIs were observed; 84% were treated with daily ceftriaxone and 15% with teicoplanin (three daily loading doses then three times per week). Progression of infection was observed in 2.8% of cases, inpatient management was required in 6% and significant adverse events occurred in 7.1%. Overall OPAT success was 87.1%. Female sex, diabetes and treatment with teicoplanin were independently associated with OPAT failure. A significant reduction in duration of OPAT therapy was observed over time. A longer duration of intravenous therapy was associated with meticillin-resistant Staphylococcus aureus (MRSA), older age, vascular disease, a diagnosis of bursitis, and treatment with teicoplanin. Non-inpatient referrals, management via a nurse-led patient group direction, and treatment with ceftriaxone were associated with reduced duration of OPAT. For selected patients with SSTIs, OPAT was generally safe and effective, but specific patient groups were identified with more complex management pathways and poorer outcomes.     

Vosaroxin: a novel antineoplastic quinolone

The alarming increase in the incidence of Gram-positive infections, including those caused by resistant bacteria, has sparked renewed interest in novel antibiotics. One such agent is daptomycin, a novel lipopeptide antibiotic with proven bactericidal activity in vitro against all clinically relevant Gram-positive bacteria. These include resistant pathogens, such as vancomycin-resistant enterococci (VRE), methicillin-resistant Staphylococcus aureus (MRSA), glycopeptide intermediately susceptible Staphylococcus aureus (GISA), coagulase-negative staphylococci (CNS) and penicillin-resistant Streptococcus pneumoniae (PRSP), for which there are very few therapeutic alternatives. Daptomycin provides rapid, concentration-dependent killing and a relatively prolonged concentration-dependent post-antibiotic effect in vitro. Spontaneous acquisition of resistance to daptomycin occurs rarely. Daptomycin exhibits linear pharmacokinetics, minimal accumulation with once-daily dosing, and low plasma clearance and volume of distribution. Phase II clinical trials indicate that daptomycin at doses of 2 mg/kg q24 h and 3 mg/kg q12 h is efficacious against skin and soft tissue infections and bacteremia, respectively. In addition, results in endocarditis suggested potential efficacy with higher doses. On the basis of clinical trials to date, it appears that daptomycin has an excellent safety profile, with the incidence and nature of serious adverse events comparable to those observed with conventional therapy. Adverse events associated with other classes of antimicrobials (nephrotoxicity, local irritation, ototoxicity, hypersensitivity, and gastrointestinal effects) were uncommon with daptomycin. Minimal skeletal muscle toxicity was seen at only the highest dose tested (4 mg/kg q12 h), predicted by elevations in serum creatinine phosphokinase, and readily reversible upon discontinuation of treatment. There were no signs of toxicity in cardiac or smooth muscle. Phase II and III clinical trials are underway to evaluate daptomycin for the treatment of Gram-positive bacteremia and complicated skin and soft tissue infections, respectively. Daptomycin holds promise as a rapidly acting and highly effective antibiotic for Gram-positive infections.     

Daptomycin: a novel agent for Gram-positive infections

The alarming increase in the incidence of Gram-positive infections, including those caused by resistant bacteria, has sparked renewed interest in novel antibiotics. One such agent is daptomycin, a novel lipopeptide antibiotic with proven bactericidal activity in vitro against all clinically relevant Gram-positive bacteria. These include resistant pathogens, such as vancomycin-resistant enterococci (VRE), methicillin-resistant Staphylococcus aureus (MRSA), glycopeptide intermediately susceptible Staphylococcus aureus (GISA), coagulase-negative staphylococci (CNS) and penicillin-resistant Streptococcus pneumoniae (PRSP), for which there are very few therapeutic alternatives. Daptomycin provides rapid, concentration-dependent killing and a relatively prolonged concentration-dependent post-antibiotic effect in vitro. Spontaneous acquisition of resistance to daptomycin occurs rarely. Daptomycin exhibits linear pharmacokinetics, minimal accumulation with once-daily dosing, and low plasma clearance and volume of distribution. Phase II clinical trials indicate that daptomycin at doses of 2 mg/kg q24 h and 3 mg/kg q12 h is efficacious against skin and soft tissue infections and bacteremia, respectively. In addition, results in endocarditis suggested potential efficacy with higher doses. On the basis of clinical trials to date, it appears that daptomycin has an excellent safety profile, with the incidence and nature of serious adverse events comparable to those observed with conventional therapy. Adverse events associated with other classes of antimicrobials (nephrotoxicity, local irritation, ototoxicity, hypersensitivity, and gastrointestinal effects) were uncommon with daptomycin. Minimal skeletal muscle toxicity was seen at only the highest dose tested (4 mg/kg q12 h), predicted by elevations in serum creatinine phosphokinase, and readily reversible upon discontinuation of treatment. There were no signs of toxicity in cardiac or smooth muscle. Phase II and III clinical trials are underway to evaluate daptomycin for the treatment of Gram-positive bacteremia and complicated skin and soft tissue infections, respectively. Daptomycin holds promise as a rapidly acting and highly effective antibiotic for Gram-positive infections.