Treatment Of Gram-positive Infections Research Articles

#13 Dalbavancin Activity against Bacterial Isolates from Pediatric Patients: Results from the International Dalbavancin Evaluation of Activity (IDEA) Program for the United States and Europe (2019-2021)

Abstract Background Dalbavancin is a lipoglycopeptide approved in the United States (US; 2014) and Europe (2015) to treat skin and skin structure infections in adults with a convenient parenteral administration of either a single dose of 1500 mg or a dose of 1000 mg followed by 500 mg a week later. We evaluated dalbavancin in vitro spectrum and potency against Gram-positive isolates from pediatric patients. Method 4,487 consecutive, unique pediatric patient isolates of clinical significance were collected from 32 US and 34 European medical centers and tested for susceptibility to dalbavancin and comparators by broth microdilution. The most common organisms were Staphylococcus aureus (n=2,633), Streptococcus pneumoniae (n=689), and beta-hemolytic streptococci (BHS; n=584). Susceptibility results were analyzed by patient age group: ≤1 years old (yo; n=1,459), 2-5 (1,106), 6-12 (1,164), and 13-17 (758). Results Dalbavancin showed complete activity against S. aureus (100% susceptibility), with a highest MIC value of 0.12 mg/L and consistent activity against all age groups (MIC50/90 of 0.03/0.03 mg/L for the US and Europe as well as the MSSA and MRSA subsets). MRSA rates were higher in the US (32.4% overall) than Europe (14.0%). In the US, MRSA rates were 38.7%, 34.2%, 28.4%, and 25.0% in the ≤1, 2-5, 6-12, and 13-17 yo groups, respectively; whereas, in Europe, it was slightly lower in the 2-5 yo group (11.5%) compared to the other age groups (14.1-14.8%). Ceftaroline was consistently active against S. aureus isolates from all age groups, with susceptibility rates ranging from 99.4% (13-17 yo) to 99.8% (2-5 yo) in the US and from 95.3% (≤1 yo) to 100.0% (2-5 yo) in Europe. Dalbavancin showed consistent activity against S. pneumoniae from all age groups (MIC50/90 of 0.008/0.015 mg/L for all age groups in the US and Europe) with a highest MIC value of 0.06 mg/L (1 isolate). All S. pneumoniae isolates were susceptible to ceftaroline, and susceptibility to ceftriaxone (at ≤1 mg/L; non-meningitis breakpoint) ranged from 92.7% (13-17 yo) to 100.0% (≤1 yo), or 97.8% overall. Dalbavancin was also highly active against BHS (n=584; MIC50/90, 0.008/0.015 mg/L; highest MIC, 0.06 mg/L), coagulase-negative staphylococci (n=240; MIC50/90, 0.03/0.06 mg/L; highest MIC, 0.25 mg/L), Enterococcus faecalis (n=200; MIC50/90, 0.03/0.06 mg/L; highest MIC, 0.06 mg/L), viridans group streptococci (n=102; MIC50/90, 0.008/0.03 mg/L; highest MIC, 0.12 mg/L), and vancomycin-susceptible E. faecium (n=26; MIC50/90, 0.03/0.12 mg/L; highest MIC, 0.25 mg/L), but showed limited activity against vancomycin-resistant E. faecium (VREFM; n=13 [0.3% of the organism collection]; MIC50/90, >2/>2 mg/L). Conclusion Dalbavancin showed potent in vitro activity against a large collection of Gram-positive isolates from pediatric patients, independent of patient age and geographic region (US and Europe). Only 13 of 4,487 (0.3%) isolates exhibited a dalbavancin MIC >0.25 mg/L, all of which were VREFM. These in vitro results support further clinical development of dalbavancin for treatment of Gram-positive infections in children.

1056. Safety and Tolerability of Dalbavancin in Vancomycin Allergic Patients – A Case Series

BackgroundVVancomycin and dalbavancin, both in the glycopeptide class of antibiotics, are used in the treatment of Gram-positive infections, including methicillin-resistant Staphylococcus aureus. Antibiotics in this class contain a heptapeptide core that has potential for cross-sensitivity. Due to this risk, dalbavancin carries a warning in the package insert for use in patients with a glycopeptide allergy. Dalbavancin, a semi-synthetic derivative of vancomycin, has lipophilic side chains which reduce the risk of cross-sensitivity to vancomycin. This case series evaluated patients with a listed vancomycin allergy in their electronic health record who received dalbavancin as an outpatient infusion.MethodsThis study was a non-randomized, retrospective chart review of adult patients who had a documented vancomycin allergy and received dalbavancin between February 2016 and February 2021 for any indication in the outpatient setting. The primary objective was to evaluate dalbavancin tolerability in patients allergic to vancomycin. Patient characteristics and the specifics of dalbavancin infusion – dose, volume, infusion rate, intravenous line access, and receipt of premedication before infusion – were collected on each patient.Results559 unique patients received dalbavancin over the time frame. Of these, ten had a documented, subjective vancomycin allergy. Patient-reported allergic reactions were rash (4), hives (3), anaphylaxis (2), red man syndrome (2), renal failure (2), and general malaise (1). Six patients had at least 1 additional subjective drug allergy. The various infections treated included cellulitis/abscess (8), osteomyelitis (1), and bacteremia (2). Most patients received 1500mg (2 received 1125mg) of dalbavancin in 300-500mL of dextrose 5% in water infused at either 600 or 1000mL/hr via a peripheral (6) or central (4) intravenous line. All patients tolerated the infusion with no adverse events reported and no receipt of premedication before administration. ConclusionDalbavancin may be a reasonable treatment option in vancomycin allergic patients, despite possible cross-sensitivity. Further investigation into cross-sensitivity between vancomycin, dalbavancin, and other glycopeptide class agents is warranted.Disclosures Kerry O. Cleveland, M.D., AbbVie (Speaker’s Bureau)Merck (Speaker’s Bureau)Pfizer (Speaker’s Bureau) Bruce M. Jones, PharmD, BCPS, Abbvie (Consultant, Advisor or Review Panel member, Speaker’s Bureau)La Jolla (Speaker’s Bureau)Melinta (Consultant)Merck (Consultant)Paratek (Consultant, Speaker’s Bureau)

1553. Efficacy and Safety of Dalbavancin and Oritavancin in the Treatment of Gram-Positive Infections

BackgroundLipoglycopeptides are approved for acute bacterial skin and skin structure infections (ABSSSI), but are often used in other infections, including osteomyelitis (OM) and bloodstream infections (BSI).MethodsThis retrospective cohort study included VA St. Louis Health Care System patients aged ≥18 through ≤89 years treated for ABSSSI, BSI, or OM with lipoglycopeptides. Patients were excluded if they received ≥72 hours (ABSSSI, BSI) or ≥7 days (OM) of antibiotics prior to lipoglycopeptide administration or other intravenous antibiotics were administered for ≥48 hours after lipoglycopeptide. The primary efficacy outcome was clinical success in the lipoglycopeptide cohort, defined per infection. Secondary outcomes were a comparison of clinical success in the lipoglycopeptide cohort to historical controls of patients treated at the VA St. Louis for ABSSSI, BSI, or OM. A multivariate regression was also conducted to find factors in the lipoglycopeptide group independently associated with clinical success. Safety outcomes compared adverse drug reactions between single- and 2-dose regimens of lipoglycopeptides.ResultsA total of 36 patients were included in the analysis; no patients met inclusion for bloodstream infection. Twenty-nine patients were treated for ABSSSI and 7 patients met inclusion for OM treatment. Dalbavancin was the agent used most often for both OM (4/7) and ABSSSI (22/29). The primary outcome of clinical success occurred in 77.7% (28/36) of the lipoglycopeptide cohort. There was no difference in clinical success between the lipoglycopeptide cohort and historical controls for ABSSSI (86% [5/29] vs 84% [159/189], p >0.05) or OM (43% [3/7] vs 58% [83/143], p >0.05). No difference in adverse outcomes between single- and 2-dose regimens of lipoglycopeptide were observed.ConclusionClinical success for patients treated with lipoglycopeptides for ABSSSI and OM in this small cohort were comparable to historical controls. No difference was identified in the safety between single- and 2-dose regimens of lipoglycopeptides.Disclosures All Authors: No reported disclosures

The comparative risk of acute kidney injury of vancomycin relative to other common antibiotics

The glycopeptide antibiotic vancomycin is a mainstay in the treatment of Gram-positive infection. While its association with acute kidney injury (AKI) has waxed and waned, recent data suggest nephrotoxicity, even as mono-therapy. Our study aimed to evaluate the 2-week risk of AKI after at least 3 days of intravenous vancomycin mono-therapy initiated within 5 days of hospitalization compared to other intravenous antibiotics used for similar indications. We used a new user-active comparator study design and identified patients with a first hospitalization during which they received vancomycin or comparator, from commercial claims based in the United States. We estimated incidence rates, hazard ratios using adjusted cox-regression models, and standardized mortality/morbidity ratio weighted cox-regression models. In the 32,997 patients vancomycin was used in 17% of patients and 129 cases of AKI were observed. Overall incidence of AKI was 9.3 (95% CI 0.78–1.22) per 100 person-years. The adjusted hazard ratio for vancomycin versus all other comparators was 0.74 (95% CI 0.45–1.21). Separate models for respective comparators resulted in hazard ratios below the null, except for vancomycin vs. cefazolin. Intravenous vancomycin mono-therapy does not increase the risk of AKI compared to other intravenous antibiotics used for similar indication in this cohort of hospitalized patients.

Correlation between serum vancomycin trough level and therapeutic response in septic patients during augmented renal clearance phase

Background: Vancomycin is a glycopeptide antibiotic that was extensively used for treatment of gram positive infections. Therapeutic drug monitoring (TDM) is recommended to optimize efficacy and safety of vancomycin. Data regarding TDM of vancomycin are scant in septic patients especially during augmented renal clearance (ARC) phase. Methods: In this observational study, 39 patients with diagnosis of sepsis that were in ARC phase were evaluated. The breakpoint for serum trough level of vancomycin was considered as 15 mg/l. The patients were stratified in two groups based on the measured serum trough levels (< 15 mg/l versus ≥15 mg/l). Results: Clinical response and microbiological clearance were compared between the groups. In terms of clinical response, there was no significant difference between the groups (P = 0.677). Also, the microbiological clearance was not different between the groups (P= 1.00). Conclusion: Septic patients during ARC phase had comparable clinical and microbial responses regardless of serum trough levels of vancomycin.

Current Perspectives on Treatment of Gram-Positive Infections in India: What Is the Way Forward?

The emerging antimicrobial resistance leading to gram-positive infections (GPIs) is one of the major public health threats worldwide. GPIs caused by multidrug resistant bacteria can result in increased morbidity and mortality rates along with escalated treatment cost and hospitalisation stay. In India, GPIs, particularly methicillin-resistant Staphylococcus aureus (MRSA) prevalence among invasive S. aureus isolates, have been reported to increase exponentially from 29% in 2009 to 47% in 2014. Apart from MRSA, rising prevalence of vancomycin-resistant enterococci (VRE), which ranges from 1 to 9% in India, has raised concerns. Moreover, the overall mortality rate among patients with multidrug resistant GPIs in India is reported to be 10.8% and in ICU settings, the mortality rate is as high as 16%. Another challenge is the spectrum of adverse effects related to the safety and tolerability profile of the currently available drugs used against GPIs which further makes the management and treatment of these multidrug resistant organisms a complex task. Judicious prescription of antimicrobial agents, implementation of antibiotic stewardship programmes, and antibiotic policies in hospitals are essential to reduce the problem of drug-resistant infections in India. The most important step is development of newer antimicrobial agents with novel mechanisms of action and favourable pharmacokinetic profile. This review provides a synopsis about the current burden, treatment options, and the challenges faced by the clinicians in the management of GPIs such as MRSA, Quinolone-resistant Staphylococcus, VRE, and drug-resistant pneumococcus in India.

Experience with the use of daptomycin in patients with infective endocarditis oncohematological and cardiosurgical profile

The study of the effectiveness of antibacterial therapy with daptomycin in the treatment of gram-positive infection in 44 patients with infectious endocarditis was conducted. Primary infectious endocarditis developed in 15 patients, including 3 patients who were observed for oncohematological diseases (acute leukemia, myelodysplastic syndrome). In 29 patients secondary endocarditis was diagnosed, among the secondary forms of the disease endocarditis prevailed after cardiac surgery. In 32 patients, the bacteriological study revealed the pathogen. Among the identified pathogens included: 7 patients - methicillin-sensitive S. aureus,5 - methicillin-resistant S. aureus, 3 - methicillin-resistant S. Epidermidis in 9 - Enterococcus faecalis, 8 - Streptococcus bovis. All patients were prescribed antibacterial therapy with daptomycin, in monotherapy and in combination with beta-lactams, and surgical treatment was also performed. The average dose of daptomycin was 6,9±0,8 mg/kg/ day, the average duration of treatment 26,2±9,4 days. In 20 (45,4%) patients, repeated surgical treatment with a positive result were performed, there were no fatal outcomes among the operated patients. Of the 44 patients treated with daptomycin, 5 died (due to the inability to provide surgical treatment), in 1 case an early relapse of infectious endocarditis developed, in other cases there was a positive dynamics on the background of treatment, the resolution of infectious complications. No cases of resistance of the infectious agent to daptomycin have been reported. Thus, the use of daptomycin in the treatment of gram-positive infections in patients with cardiosurgical and oncohematological profile is justified and shows good results in tolerability and effectiveness both in monotherapy and in combination with other antibiotics.

Clinical and pharmacokinetic drug evaluation of delafloxacin for the treatment of acute bacterial skin and skin structure infections

ABSTRACTIntroduction: In the era of multi-drug resistant pathogens, the adequate treatment of skin and skin structure infections remains a challenge for clinicians. Delafloxacin, with its broad spectrum against Gram-positive, Gram-negative and anaerobic organisms, represents a new therapeutic option in this setting, especially when coverage of methicillin-resistant Staphylococcus aureus is required in the empirical or targeted approach.Areas covered: In this drug evaluation, the Authors have reviewed the pharmacokinetic and pharmacodynamic characteristics of delafloxacin. In addition, recent data on clinical efficacy and safety from clinical trials have been included.Expert opinion: Delafloxacin represents an attractive therapeutic option due to a broad antimicrobial and favorable pharmacokinetic and pharmacodynamic profile. Several in vitro studies have demonstrated the low potential for resistance selection if used in empirical regimens. Delafloxacin is a promising candidate for the treatment of Gram-positive infections, especially if co-infection with other pathogens is suspected. This is because of the very low MIC of the agent for Gram-positive (including MRSA) and anaerobic bacteria and because of the wide spectrum of activity against Gram-negative organisms. For these interesting microbiological and PK/PD characteristics we expect future uses of this drug in other indications such as diabetic foot infection, osteomyelitis, prosthetic joint infections, abdominal infections and central nervous system infections.

Daptomycin: an evidence-based review of its role in the treatment of Gram-positive infections.

Infections caused by Gram-positive pathogens remain a major public health burden and are associated with high morbidity and mortality. Increasing rates of infection with Gram-positive bacteria and the emergence of resistance to commonly used antibiotics have led to the need for novel antibiotics. Daptomycin, a cyclic lipopeptide with rapid bactericidal activity against a wide range of Gram-positive bacteria including methicillin-resistant Staphylococcus aureus, has been shown to be effective and has a good safety profile for the approved indications of complicated skin and soft tissue infections (4 mg/kg/day), right-sided infective endocarditis caused by S. aureus, and bacteremia associated with complicated skin and soft tissue infections or right-sided infective endocarditis (6 mg/kg/day). Based on its pharmacokinetic profile and concentration-dependent bactericidal activity, high-dose (>6 mg/kg/day) daptomycin is considered an important treatment option in the management of various difficult-to-treat Gram-positive infections. Although daptomycin resistance has been documented, it remains uncommon despite the increasing use of daptomycin. To enhance activity and to minimize resistance, daptomycin in combination with other antibiotics has also been explored and found to be beneficial in certain severe infections. The availability of daptomycin via a 2-minute intravenous bolus facilitates its outpatient administration, providing an opportunity to reduce risk of health care-associated infections, improve patient satisfaction, and minimize health care costs. Daptomycin, not currently approved for use in the pediatric population, has been shown to be widely used for treating Gram-positive infections in children.

Oritavancin: A New Lipoglycopeptide Antibiotic in the Treatment of Gram-Positive Infections

Resistance among Gram-positive organisms has been steadily increasing over the last several years; however, the development of new antibiotics to treat infections caused from these organisms has fallen short of the emergent need. Specifically, resistance among Staphylococcus aureus and Enterococcus spp. to essential antibiotics is considered a major problem. Oritavancin is a semisynthetic lipoglycopeptide antibiotic that was recently approved for the treatment of acute bacterial skin and skin structure infections (ABSSSI). While structurally related to vancomycin, oritavancin also possesses unique mechanisms of action that greatly enhance its antimicrobial potency against multi-drug resistant pathogens including both VanA- and VanB-mediated vancomycin-resistant enterococci. Owing to the addition of the highly hydrophobic tail group, oritavancin possesses a prolonged half-life ranging from 200–300 h. Although oritavancin is only currently Food and Drug Administration approved for ABSSSI, this agent may eventually play a role in additional indications where new innovative therapy is needed including bacteremia and deep-seeded, Gram-positive infections such as infective endocarditis or osteomyelitis. This review will focus on oritavancin’s spectrum of activity, mechanisms of action and resistance, pharmacokinetic and pharmacodynamic properties, and the completed and ongoing clinical studies evaluating its use.Electronic supplementary materialThe online version of this article (doi:10.1007/s40121-016-0103-4) contains supplementary material, which is available to authorized users.

Speciation of Enterococcal Isolates in a Tertiary Care Hospital and Molecular Characterisation of Vancomycin Resistant Enterococci (VRE)

Background: Enterococci are gram positive cocci which reside as commensal microbial flora in gastrointestinal tract, vagina, biliary tract and male urethra. E.faecalis is the predominant species followed by E.faecium. Resistance against glycopeptides and aminoglycosides are being increasingly demonstrated and that is conferred upon largely by van A gene. Aims: To isolate and speciate Enterococci from various clinical samples, antibiogram pattern determination, followed by genotyping of vancomycin resistant Enterococci. Settings and Design: Prospective study. Materials and Methods: 200 Enterococcal isolates were collected and processed for speciation based on battery of phenotypic characteristics. Antibiotic sensitivity testing was performed as per CLSI guidelines 2014 for glycopeptide and aminoglycoside antibiotics. Enterococci which were resistant to vancomycin were subjected to polymerase chain reaction for van A gene detection. Statistical analysis used: Nil. Results: Of the 200 isolates 5 were resistant to vancomycin and teicoplanin (2.5%), 30 were resistant to high level gentamicin (15%). van A gene was detected in 3 of the 5 vancomycin resistant isolates. E.faecium was observed to be more resistant to the antimicrobials. Conclusions: If the vancomycin resistance in Enterococci gets dispersed throughout the world, it may pose a challenge in the treatment of Gram positive infections and may lead to treatment failure. Further treatment options may not be available. Hence these infections have to be prevented and the sequence of development of resistance to higher drugs has to be controlled by active surveillance and prevention. Key-words: E.faecalis, E.faecium, High-level Gentamicin resistance, Vancomycin-resistance, Van A gene Key Messages: Implementation of vigorous surveillance and provision of timely data

Treatment of Gram-positive infections in critically ill patients.

Gram-positive bacteria to include methicillin-resistant Staphylococcus aureus (MRSA), methicillin-susceptible Staphylococcus aureus (MSSA), and enterococci, to include vancomycin-resistant enterococci (VRE), display a remarkable array of resistance and virulence factors, which have contributed to their prominent role in infections of the critically ill. Over the last three decades infections with these pathogens has increased as has their overall resistance to available antimicrobial agents. This has led to the development of a number of new antibiotics for the treatment of Gram-positive bacteria. At present, it is important that clinicians recognize the changing resistance patterns and epidemiology of Gram-positive bacteria as these factors may impact patient outcomes. The increasing range of these pathogens, such as the emergence of community-associated MRSA clones, emphasizes that all specialties of physicians treating infections should have a good understanding of the infections caused by Gram-positive bacteria in their area of practice. When initiating empiric antibiotics, it is of vital importance that this therapy be timely and appropriate, as delays in treatment are associated with adverse outcomes. Although vancomycin has traditionally been considered a first-line therapy for serious MRSA infections, multiple concerns with this agent have opened the door for alternative agents demonstrating efficacy in this role. Similarly, the expansion of VRE as a pathogen in the ICU setting has required the development of agents targeting this important pathogen.

Brazilian experience in EU-CORE: daptomycin registry and treatment of serious Gram-positive infections

ObjectivesTo collect data about non-controlled prescribing use of daptomycin and its impact among Brazilian patients with serious Gram positive bacterial infection, as well as the efficacy and safety outcomes. Materials and methodsThis is a multi-center, retrospective, non-interventional registry (August 01, 2009 to June 30, 2011) to collect data on 120 patients (44 patients in the first year and 76 patients in the second year) who had received at least one dose of commercial daptomycin in Brazil for the treatment of serious Gram-positive bacterial infection. ResultsRight-sided endocarditis (15.8%), complicated skin and soft tissue infections (cSSTI)-wound (15.0%) and bacteremia-catheter-related (14.2%) were the most frequent primary infections; lung (21.7%) was the most common site for infection. Daptomycin was used empirically in 76 (63.3%) patients, and methicillin-resistant Staphylococcus aureus (MRSA) was the most common suspected pathogen (86.1%). 82.5% of the cultures were obtained prior to or shortly after initiation of daptomycin therapy. Staphylococcus spp. – coagulase negative, MRSA, and methicillin-susceptible S. aureus were the most frequently identified pathogens (23.8%, 23.8% and 12.5%, respectively). The most common daptomycin dose administered for bacteremia and cSSTI was 6mg/kg (30.6%) and 4mg/kg (51.7%), respectively. The median duration of inpatient daptomycin therapy was 14 days. Most patients (57.1%) did not receive daptomycin while in intensive care unit. Carbapenem (22.5%) was the most commonly used antibiotic concomitantly. The patients showed clinical improvement after two days (median) following the start of daptomycin therapy. The clinical success rate was 80.8% and the overall rate of treatment failure was 10.8%. The main reasons for daptomycin discontinuation were successful end of therapy (75.8%), switched therapy (11.7%), and treatment failure (4.2%). Daptomycin demonstrated a favorable safety and tolerability profile regardless of treatment duration. ConclusionsDaptomycin had a relevant role in the treatment of Gram-positive infections in the clinical practice setting in Brazil.

GRP-184 The Impact of Pharmaceutical Interventions on the Treatment of Gram Positive Infections

BackgroundInappropriate use of antibiotics results in increased antibiotic resistance and poor efficiency, which should be avoided through pharmaceutical interventions.PurposeTo evaluate the impact of pharmaceutical interventions (PIs) on the effectiveness, safety...

Unexpected death due to cefuroxime-induced disulfiram-like reaction

Cefuoxime, a second-generation cephalosporin, is used in the treatment of Gram-positive infections. Here, we report a case cefuroxime-induced disulfiram-like reaction which led to sudden death of the patient.

Daptomycin in treatment of Gram-positive infections in children with hematological disorders

The study of efficacy and toxicity of daptoycin in treatment of Gram-positive infectons n children with hematological disorders was performed. Twelve patients (4 girls and 8 boys) with signs of Gram-positive infections were examined. Staphylococcus aureus was found in 66,6% (8 patients), among them in 3 patients strains were methicillin-resistant; Staphylococcus epidermidis — was found in 16,6% (2 patients); Enterococcus faecalis — in 16,6% (2 patients). By the time of development of infectious complications 7 patients (58,3%) have received antibiotic treatment, in 5 other patients daptomycin was the first-line antibacterial drug. The mean dosage of the drug was 5,8 mg/kg/day. In order to reveal the drug toxicity the monitoring of biochemical serum markers (fibrinogen, ALT, AST, LDG, CPK, creatinine) was performed. The complete resolution of infectious complications occurred in 12,1 ± 4,3 days. The mean duration of daptomycin treatment was 14,2 ± 3,2 days. During the treatment reliable lower of fibrinogen (6,4 ± 1,1 g/l and 3,1 ± 0,9 g/l, р = 0,05) and c-reactive protein (CRP) (12,5 ± 7,1 mg/dL and 3,4 ± 1,8 mg/dL, р = 0,04) was observed. No side effects were observed in all the patients. The performed study allowed to make a conclusion, that daptomycin is an effective and safe drug in treatment of Grampositive infections in children with hematological disorders even with concomitant hypogranulocytosis. Key words : daptomycin, Gram-positive infections, onco-hematology.

Clinical experience with daptomycin in Italy: results from a registry study of the treatment of Gram-positive infections between 2006 and 2009

The purpose of this study was to evaluate post-marketing efficacy and safety data for therapy with daptomycin (DAP) in Italy. Data from patients treated with DAP at 30 centres between January 2006 and July 2009 were analysed according to the protocol of the EU-CORESM. In 359 patients, DAP was most commonly prescribed for skin and skin-structure infections (55%), infective endocarditis (13%), and bacteraemia (12·5%). DAP was associated with rapid improvement, and clinical success rates ranging from 77 to 91%, despite almost half of the patient population being ⩾65 years of age, 86% having significant underlying disease, and many being affected by drug-resistant pathogens. Staphylococcus aureus represented 35% of all pathogens isolated. Success rates for all staphylococcal and enterococcal infections were >80%, including methicillin-resistant S. aureus (MRSA) and methicillin-susceptible S. aureus (MSSA). Clinical outcomes were similar for DAP whether used as first- or second-line therapy. DAP was well tolerated even with prolonged treatment.

Tratamiento con daptomicina en pacientes diabéticos

In diabetic patients, there is a high prevalence of skin or nasal carriage of Staphylococcus aureus, which is associated with an increased risk of local or systemic infections and consequently with greater morbidity and mortality. The microorganisms causing most infections in diabetic ulcers and diabetic foot are S. aureus and Streptococcus pyogenes, although chronic diabetic foot infections are generally polymicrobial, including Pseudomonas aeruginosa and enterobacteria. The present article describes experience with daptomycin in the treatment of the most frequent infectious complications in diabetic patients. The Cubicin Outcomes Registry and Experience (CORE) registry contains information on 60 patients with skin and soft tissue infections treated with daptomycin, with a success rate of 83%. Other recent studies comparing daptomycin with vancomycin or semi-synthetic penicillins have also shown the efficacy and safety of daptomycin with cure rates of between 70% and 80%. In the European version of the CORE registry, the EUROCORE, diabetic patients who developed bacteremia or endocarditis due to Gram-positive pathogens and who received daptomycin showed success rates of 76.8% and 72%, respectively. No significant differences were found in a study comparing daptomycin or standard therapy with vancomycin in methicillin-resistant S. aureus (MRSA) or antistaphylococcal penicillin in methicillin-susceptible S. aureus (MSSA) in diabetic patients with bacteremia or endocarditis. Because of its rapid bactericidal action and scarce adverse effects, daptomycin is an attractive antimicrobial agent in the treatment of Gram-positive infections in diabetic patients, whether in monotherapy or in association with other agents.

Daptomicina en el tratamiento de las infecciones por grampositivos en pacientes con insuficiencia renal crónica

Daptomycin is a cyclic lipopeptide that is effective in the treatment of Gram-positive infections, including those caused by multiresistant pathogens. This drug has rapid bactericidal action and low nephrotoxicity. Patients with severe renal failure show a dicrease in its renal clearance and an increase in the elimination half-life. The recommended dose in patients with creatinine clearance (CrCl) < 30ml/min is 4mg/kg/48h in skin and soft tissue infections and is 6mg/kg/48h in bacteremia and right endocarditis. Pharmacokinetic studies and data from the CORE Registry have allowed improved the dosing regimen in patients under hemodialysis, peritoneal dialysis and other extrarenal depuration techniques. Patients with a CrCl < 30ml/ min have rates of efficacy ranging between 69.2% and 96%, these rates being similar to or lower than those observed in patients with a CrCl > 30ml/min. Patients under hemodialysis may have higher rates of clinical failure. This article presents the preliminary results of the EUCORE in Spain. The presence of renal failure at the start of daptomycin therapy is not associated with an increase in the rates of severe adverse effects. Daptomycin has a good safety and efficacy profile for the treatment of infections in patients with chronic renal insufficiency. The consensus documents of distinct societies have incorporated the use of daptomycin in the treatment of bacteremia due to methicillin-resistant Staphylococcus aureus in patients with renal insufficiency.

Linezolid: safety and efficacy in special populations

Linezolid has been in general use in the UK since 2000. Although toxicity, particularly haematological and neurological, has been an issue, linezolid has proved to be an effective alternative to glycopeptides in the treatment of Gram-positive infections. Since its original licence for the treatment of skin and soft tissue infections and pneumonia, there have been reports of its successful use in the treatment of bone and joint infections, endocarditis, and other difficult-to-treat infections.