Metastatic infection during Staphylococcus aureus bacteremia

Staphylococcus aureus causes various infections, including skin and soft tissue infections and pneumonia via both, community-associated and nosocomial infection. These infectious diseases can lead to bacteremia, and may subsequently result in metastatic infections in several cases. Metastatic infections are critical complications in patients with S. aureus bacteremia, since the optimal duration of the antimicrobial treatment differs in patients with and without metastatic infection. Notably, two weeks of antimicrobial treatment is recommended in case of uncomplicated S. aureus bacteremia, whereas in patients with S. aureus bacteremia-associated endocarditis or vertebral osteomyelitis, six weeks of antimicrobial administration is vital. In addition, misdiagnosis or insufficient treatment in metastatic infection is associated with poor prognosis, functional disability, and relapse. Although echocardiography is recommended to examine endocarditis in the patients with S. aureus bacteremia, it remains unclear which patients should undergo additional examinations, such as CT and MRI, to detect the presence of other metastatic infections. Clinical studies have revealed that permanent foreign body and persistent bacteremia are predictive factors for metastatic infections, and experimental studies have demonstrated that the virulence factors of S. aureus, such as fnbA and clfA, are associated with endocarditis; however, these factors are not proven to increase the risk of metastatic infections. In this review, we assessed the incidence, predictive factors, diagnosis, and treatment for metastatic infections during S. aureus bacteremia.     

Progression to bacteremia in critical care patients colonized with methicillin-resistant Staphylococcus aureus expressing Panton–Valentine leukocidin

The role of Panton–Valentine leukocidin (PVL) in methicillin-resistant Staphylococcus aureus (MRSA) infections is unclear. PVL has been long associated with soft tissue infections and necrotizing pneumonia, but inconsistently with other site infections or mortality. The retrospective cohort study explores the association between PVL and bacteremia in colonized medical intensive care unit (ICU) patients with surveillance isolates and blood cultures. A total of 840 patients were screened by nasal swab, with 266 patients found to be colonized and 46 with bacteremia. Colonization by PVL⁺ MRSA increased the odds of bacteremia (odds ratio, 2.40; confidence interval, 1.23–4.57), and invasive infection developed earlier in these patients (relative risk, 0.44; confidence interval 0.25–0.85) compared to those colonized with PVL⁰ MRSA. PVL was not associated with infections at other sites, length of ICU stay, or mortality. PVL decreases the time to bacteremia in colonized patients but does not otherwise contribute to disease course or clinical outcome.     

Efficacy and safety of daptomycin in Japanese pediatric participants with complicated skin and soft tissue infections or bacteremia caused by gram-positive cocci

IntroductionComplicated skin and soft tissue infections (cSSTIs) and bacteremia caused by Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA), are common causes of infection for children worldwide. Here, the safety and efficacy of daptomycin in Japanese pediatric participants are reported.MethodsThis open-label, single-arm phase 2 study (NCT03643952) enrolled Japanese pediatric participants (age 1–17 years) with cSSTI or bacteremia caused by gram-positive cocci. Participants received age-adjusted doses of intravenous daptomycin for 5 to up to 14 days (cSSTI) or 5 to up to 42 days (bacteremia). The primary objective was safety and tolerability; efficacy among participants with infections caused by MRSA was a secondary objective.ResultsA total of 18 participants (cSSTI, n = 14; bacteremia, n = 4) were enrolled across 12 study sites in Japan. The most common pathogen was S. aureus (15/18 [83.3%]), including methicillin-susceptible and -resistant isolates. Adverse events (AE) were reported in 42.9% (6/14) of participants with cSSTI and 100% (4/4) of participants with bacteremia. No deaths, serious AEs, discontinuations of study medication due to an AE, or events of clinical interest occurred in the study. In participants with infections caused by MRSA, 87.5% [7/8] achieved favorable clinical response at test of cure (TOC) visit (cSSTI, 85.7% [6/7]; bacteremia, 100% [1/1]). In this population, favorable microbiological response at TOC was achieved by 71.4% (5/7) of participants with cSSTI and 100% (1/1) of participants with bacteremia.ConclusionsDaptomycin was well tolerated, exhibited a favorable safety profile, and was effective for the treatment of cSSTI or bacteremia in Japanese children.     

The use of ceftaroline fosamil in methicillin-resistant Staphylococcus aureus endocarditis and deep-seated MRSA infections: a retrospective case series of 10 patients

There are many limitations to the current antibiotics used for the treatment of severe methicillin-resistant Staphylococcus aureus (MRSA) infections. Ceftaroline is a new fifth-generation cephalosporin approved for the treatment of skin and soft tissue infections caused by MRSA and community-acquired pneumonia. We propose that ceftaroline can also be used successfully in more severe MRSA infections, including endocarditis. We conducted a retrospective chart review in a university-affiliated Department of Veterans Affairs hospital in San Diego, California (USA) of ten inpatients treated with ceftaroline for severe MRSA infection, including five cases of probable endocarditis (including two endocardial pacemaker infections), one case of pyomyositis with possible endocarditis, two cases of pneumonia (including one case of empyema), two cases of septic arthritis (including one case of prosthetic joint infection), and two cases of osteomyelitis. Seven of the 10 patients achieved microbiological cure. Six of the 10 patients achieved clinical cure. Seven patients were discharged from the hospital. Three patients were placed on comfort care and expired in the hospital; one achieved microbiological cure before death, and two remained bacteremic at time of death. In most patients, ceftaroline was effective for treatment of MRSA bacteremia and other severe MRSA infections. Adverse effects seen included rash, eosinophilia, pruritus, and Clostridium difficile infection. Ceftaroline can be a safe and effective drug for treatment of severe MRSA infections, and further comparative studies are warranted.     

The use of intravenous and aerosolized polymyxins for the treatment of infections in critically ill patients: a review of the recent literature

Intravenous and aerosolized polymyxins are being used increasingly, especially in the critical care setting, for treating patients with infections due to multidrug-resistant Gram-negative bacteria, mainly Acinetobacter baumannii and Pseudomonas aeruginosa. Recent literature suggests that intravenous colistin and polymyxin B have acceptable effectiveness for the treatment of patients with bacteremia, as well as infections of various systems and organs, including pneumonia, bacteremia, skin and soft tissue, and urinary tract infections. Although data from recent studies have suggested that the toxicity of intravenous polymyxins is probably less than reported in the older literature, caution should be taken to monitor the renal function of patients who receive these antibiotics.     

Board-certified emergency physicians' treatment of skin and soft tissue infections in the community-acquired methicillin-resistant Staphylococcus aureus era

Background

Emergency physicians commonly treat skin and soft tissue infections. Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) has become the prominent etiologic agent in these infections. The CA-MRSA is resistant to many antibiotics traditionally used to treat skin and soft tissue infections.

Study objectives

We aim to identify how the increased prevalence of CA-MRSA has changed emergency medicine physician (EMP) prescribing and treatment practices for community-acquired skin and soft tissue infections.

Methods

The EMPs in the United States were surveyed between June and December of 2006. Two cases of skin and soft tissue infection were presented, and questions were asked about management.

Results

Two hundred seventy-five surveys were returned. The EMPs used a variety of approaches in the antibiotic treatment of skin and soft tissue infections. Two hundred seven (75.3%) of 275 were board-certified EMPs and were included in the analysis. Commonly used agents for outpatient treatment include trimethoprim/sulfamethoxazole, clindamycin, cephalexin, rifampin, and tetracyclines. For patients requiring admission, 60% of providers would include vancomycin in their treatment regimen.

Conclusion

Many clinicians have changed their practice patterns to include antibiotics that usually display activity against CA-MRSA. However, cephalexin remains a popular agent used for these infections.     

Can Levofloxacin Be a Useful Alternative to Trimethoprim-Sulfamethoxazole for Treating Stenotrophomonas maltophilia Bacteremia?

A retrospective study was conducted to evaluate the efficacy of levofloxacin in the treatment of Stenotrophomonas maltophilia bacteremia. The 30-day mortality rates were similar between the trimerthoprim-sulfamethoxazole (TMP-SMX) and levofloxacin treatment groups. Adverse events related to antibiotics occurred more frequently in patients receiving TMP-SMX, and recurrent bacteremia due to levofloxacin-resistant S. maltophilia strains developed in patients treated with levofloxacin. Our data suggest that levofloxacin can be a useful alternative option for treating S. maltophilia infections.     

Clinical and Laboratory Investigation of Cefamandole in Infections of Infants and Children

Forty-seven infants and children with a variety of infections including bacteremia, ethmoiditis, and periorbital cellulitis, soft tissue infection, pneumonia, and lymphadenitis were treated with intravenous cefamandole. The infections were due to Staphylococcus aureus, Streptococcus pyogenes, Streptococcus pneumoniae, and Haemophilus influenzae. The clinical response was prompt, and, with the exception of two cases who developed skin rash, significant side effects were not noted. In vitro cefamandole was very effective in inhibiting the growth of H. influenzae, including ampicillin-resistant isolates.     

Soft tissue and cartilage infection by Salmonella oranienburg in a healthy girl

Focal extraintestinal infections from nontyphoid salmonellae have increased in incidence during the past decade. Typically, they are manifested as either osteomyelitis or meningitis as a complication of either bacteremia or enteric fever. Isolated salmonellal soft tissue infections, however, are rare and occur mostly in adults with chronic underlying conditions such as human immunodeficiency virus (HIV) infection, diabetes mellitus, and cell-mediated immunity defects. We report a case of an otherwise healthy adolescent who was exposed to a guinea pig with a skin mass. She subsequently had an isolated soft tissue infection with cartilaginous involvement of the anterior chest wall due to Salmonella enterica serogroup C1 (bioserotype oranienburg).     

Randomized study of vancomycin versus teicoplanin for the treatment of gram-positive bacterial infections in immunocompromised hosts.

Seventy-four immunocompromised patients with severe infection due to gram-positive organisms were randomized to receive either vancomycin or teicoplanin. Extensive cancer was present in 71 patients, of whom 47 died within a month. The types of infections were 46 bacteremias (39 associated with central catheters), 24 skin and soft tissue infections (3 with bacteremia), and 7 others (mainly bronchopneumonia). The most frequent pathogen was Staphylococcus epidermidis, followed by Staphylococcus aureus. Microbiological eradication was obtained in 23 of 35 evaluable patients treated with vancomycin (65.7%) and 28 of 36 patients treated with teicoplanin (77.8%) (P = 0.4). Clinical cure and improvement were obtained in 26 of 35 patients (74.3%) and 27 of 36 patients (75.0%), respectively. No significant side effects were observed with teicoplanin, in contrast to reversible increases in serum creatinine (three patients) and skin rashes (four patients) with vancomycin. Superinfection was observed in five patients treated with vancomycin and two patients treated with teicoplanin. No relation was found between peak concentration in serum (at steady state) or bactericidal titers and outcome.     

Methicillin-resistant Staphylococcus aureus infection epidemiology and clinical response from tigecycline soft tissue infection trials

Given increasing resistance, therapeutic options to treat MRSA soft tissue infections should be evaluated. This pooled analysis evaluated data from subjects enrolled in 6 tigecycline clinical trials with documented MRSA complicated skin and skin structure infections or diabetic foot infections (DFIs). Baseline characteristics were compared between subjects with and without molecularly classified community-acquired (CA) MRSA, specifically staphylococcal cassette chromosome mec (SCCmec) IV. Clinical response was compared by CA-MRSA designation and treatment group. A total of 378 subjects with MRSA soft tissue infections were identified, including 79 with DFI. A total of 249 (65.9%) were molecularly classified as CA-MRSA. Clinical response rates for MRSA soft tissue infection were similar between tigecycline and vancomycin (treatment difference, 1.0%; 95% confidence interval: −9.3, 12.0) as well as by infection type, SCCmec, and Panton-Valentine leukocidin (PVL) status. Tigecycline demonstrated comparable efficacy for treatment of MRSA soft tissue infections regardless of infection type, SCCmec, or PVL status.     

Relationship between Adherence to Oral Antibiotics and Postdischarge Clinical Outcomes among Patients Hospitalized with Staphylococcus aureus Skin Infections

Skin and soft tissue infections are common and frequently recur. Poor adherence to antibiotic therapy may lead to suboptimal clinical outcomes. However, adherence to oral antibiotic therapy for skin and soft tissue infections and its relationship to clinical outcomes have not been examined. We enrolled adult patients hospitalized with uncomplicated skin and soft tissue infections caused by Staphylococcus aureus who were being discharged with oral antibiotics to complete therapy. We fit the participants'' pill bottles with an electronic bottle cap that recorded each pill bottle opening, administered an in-person standardized questionnaire at enrollment, 14 days, and 30 days, and reviewed the participants'' medical records to determine outcomes. Our primary outcome was poor clinical response, defined as a change in antibiotic therapy, new incision-and-drainage procedure, or new skin infection within 30 days of hospital discharge. Of our 188 participants, 87 had complete data available for analysis. Among these participants, 40 (46%) had a poor clinical response at 30 days. The mean electronically measured adherence to antibiotic therapy was significantly different than the self-reported adherence (57% versus 96%; P < 0.0001). In a multivariable model, poor clinical response at 30 days was associated with patients having lower adherence, being nondiabetic, and reporting a lack of illicit drug use within the previous 12 months (P < 0.05). In conclusion, we found that patient adherence to oral antibiotic therapy for a skin and soft tissue infection after hospital discharge was low (57%) and associated with poor clinical outcome. Patients commonly overstate their medication adherence, which may make identification of patients at risk for nonadherence and poor outcomes challenging. Further studies are needed to improve postdischarge antibiotic adherence after skin and soft tissue infections.     

Predicting observation unit treatment failures in patients with skin and soft tissue infections

Background

Skin and soft tissue infections are a common admission diagnosis to emergency department (ED) observation units (OU). Little is known about which patients fail OU treatment.

Aims

This study evaluates clinical factors of skin or soft tissue infections associated with further inpatient treatment after OU treatment failure.

Methods

A structured retrospective cohort study of consecutive adults treated for abscess or cellulitis in our OU from April 2005 to February 2006 was performed. Records were identified using ICD-9 codes and were abstracted by two trained abstractors using a structured data collection form. Significant variables on univariate analysis P?Results A total of 183 patient charts were reviewed. Four patients with a non-infectious diagnosis were excluded, leaving 179 patients. The median age was 41 (interquartile range: 20–74). Following observation treatment, 38% of patients required admission. The following variables were evaluated for association with failure to discharge home: intravenous drug use, gender, a positive community-acquired methicillin-resistant Staphylococcus aureus culture, age, presence of medical insurance, drainage of an abscess in the ED, diabetes and a white blood cell count (WBC) greater than 15,000. Following multivariate analysis only female gender odds ratio (OR) 2.33 [95% confidence interval (CI): 1.06–5.15] and WBC greater than 15,000 OR 4.06 (95% CI: 1.53–10.74) were significantly associated with failure to discharge.

Conclusions

Among OU patients treated for skin and soft tissue infections, women were twice as likely to require hospitalization and patients with a WBC?>?15,000 on presentation to the ED, regardless of gender, were 4 times more likely to require hospitalization.     

Persistent methicillin-resistant Staphylococcus aureus bacteremia in an adult patient with Netherton's syndrome: A case report

Netherton's syndrome, a rare congenital disorder, is clinically characterized by chronic dermatologic disorders such as ichthyosiform erythroderma and ichthyosis linearis circumflexa. Curable treatment is yet to be established, and corticosteroid ointment is required to maintain good dermatological condition. Because of the permanent skin barrier impairment, patients with Netherton's syndrome are considered to be vulnerable to cutaneous infections. However, its clinical characteristics are yet to be elucidated due to the limited number of reported cases. Herein, we describe the clinical course of a patient who developed persistent methicillin-resistant Staphylococcus aureus (MRSA) bacteremia. A 19-year-old Japanese woman who had been diagnosed with Netherton's syndrome in her infancy and had been applying topical corticosteroid agents all over her body since her then, was referred to our hospital because of persistent MRSA bacteremia and secondary adrenal insufficiency. The patient was diagnosed with a central line-associated bloodstream infection and was appropriately treated with antibiotics and corticosteroid therapies. We assume that the damaged skin barrier due to the congenital dermatological disorder causes a disruption in the normal bacterial flora of the skin, leading to the invasion of harmful bacteria, such as S. aureus. In addition, internal (humoral immunodeficiency by decreased antibody against bacterial polysaccharide antigens) and external (prolonged and systemic use of corticosteroid ointment) factors bring about an immunodeficiency state in such patients. We highlight that in the absence of radical treatment, clinicians need to recognize that patients with Netherton's syndrome are vulnerable to bacterial infections owing to the mixture of immunosuppressive factors.     

Impact of Different Antimicrobial Therapies on Clinical and Fiscal Outcomes of Patients with Bacteremia Due to Vancomycin-Resistant Enterococci

Vancomycin-resistant enterococci (VRE) are a growing health problem, and uncertainties exist regarding the optimal therapy for bloodstream infection due to VRE. We conducted systematic comparative evaluations of the impact of different antimicrobial therapies on the outcomes of patients with bloodstream infections due to VRE. A retrospective study from January 2008 to October 2010 was conducted at Detroit Medical Center. Unique patients with blood cultures due to VRE were included and reviewed. Three major therapeutic classes were analyzed: daptomycin, linezolid, and β-lactams. Three multivariate models were conducted for each outcome, matching for a propensity score predicting the likelihood of receipt of one of the therapeutic classes. A total of 225 cases of bacteremia due to VRE were included, including 86 (38.2%) cases of VR Enterococcus faecalis and 139 (61.8%) of VR Enterococcus faecium. Bacteremia due to VR E. faecalis was more frequent among subjects treated with β-lactams than among those treated with daptomycin or linezolid. The median dose of daptomycin was 6 mg/kg of body weight (range, 6 to 12 mg/kg). After controlling for propensity score and bacteremia due to VR E. faecalis, differences in mortality were nonsignificant among the treatment groups. Therapy with daptomycin was associated with higher median variable direct cost per day than that for linezolid. This large study revealed the three therapeutic classes (daptomycin, linezolid, and β-lactams) are similarly efficacious in the treatment of bacteremia due to susceptible strains of VRE.     

Anaerobic bacteremia in a cancer center

Seventy-five episodes of clinically relevant anaerobic bacterial bacteremia observed in cancer patients were reviewed. Gastrointestinal (22.7%), hematological (22.7%) and female genital tract (18.6%) cancers were the most common underlying malignant diseases. Among 84 strains of strict anaerobic bacteria recovered in the 75 patients, gram-negative rods were isolated in 49 patients (58.3%), gram-positive rods in 29 patients (34.5%) and gram-positive cocci in 6 patients (8%). Bacteroides spp. and Clostridium spp. were the most frequent pathogens (85.7%). Twenty-one episodes of bacteremia were polymicrobial, aerobic gram-positive cocci being the most frequently associated pathogens. When identified, the primary sites were the gastrointestinal tract (40%), the female genital tract (17.3%), skin and soft tissue (14.6%), the oropharynx (12%) and the lower respiratory tract (6.7%). The source remained unknown in 7 cases (9.3%). The overall survival (evaluated 10 days after the occurrence of bacteremia) was 82.5%. There was no difference in mortality between patients with monomicrobial and polymicrobial bacteremia. Pulmonary complications were more frequent in patients with fatal outcome in comparison to patients who survived. The mortality rate of the patients adequately treated was 10.3% compared to 41% for the patients not treated or treated inadequately (P=0.016, X₂).     

Clinical Presentation,Management, and Outcomes of Cardiovascular Implantable Electronic Device Infections Due to Gram-Negative Versus Gram-Positive Bacteria

ObjectiveTo describe and compare the clinical presentation, management, and outcomes of cardiovascular implantable electronic device (CIED) infections due to gram-negative bacteria (GNB) and CIED infections due to gram-positive bacteria (GPB).Patients and MethodsWe retrospectively reviewed all CIED infection cases at Mayo Clinic from January 1, 1992, through December 31, 2015. Cases were classified based on positive microbiology data from extracted devices or blood cultures.ResultsOf the 623 CIED infections during the study period, 31 (5.0%) were caused by GNB and 323 (51.8%) by GPB. Patients in the GNB group were more likely to present with local inflammatory findings at the pocket site (90.3% vs 72.4%; P=.03). All patients with bacteremia due to GNB had concomitant pocket infection compared with those with GPB (100% vs 33.9%; P=.002). After extraction, 41.9% of patients in the GNB group were managed with oral antibiotics vs 2.4% in the GPB group (P<.001). There were no statistically significant differences in infection relapse/recurrence or 1-year survival rates between the 2 groups.ConclusionCompared with CIED infections caused by GPB, those due to GNB are more likely to present with pocket infection. Device-related GNB bacteremia almost always originates from the generator pocket. After extraction, oral antibiotic drug therapy may be a reasonable option in select cases of pocket infections due to GNB. No difference in outcomes was observed between the 2 groups.     

皮瓣移植结合封闭式负压引流修复下肢皮肤及软组织缺损

背景：各种创伤引起的下肢皮肤及软组织缺损十分常见,常伴有严重的血运破坏和创面感染,患肢感染率高,不易愈合。目的：系统回顾关于下肢皮肤及软组织感染性缺损治疗的相关文献,结合华中科技大学同济医学院附属普爱医院治疗的下肢皮肤及软组织感染性缺损23例患者治疗效果,探讨皮瓣移植结合封闭式负压引流治疗感染性下肢皮肤及软组织缺损的适应症、方法及临床应用价值。方法：文章选取2004年8月至2011年11月在华中科技大学同济医学院附属普爱医院治疗的下肢皮肤及软组织感染性缺损患者共23例,男15例,女8例;年龄17-56岁,平均31.4岁。对23例下肢皮肤及软组织感染性缺损患者采用皮瓣移植结合负压封闭引流治疗,随访时间为4-15个月,平均7.3个月,观察临床效果。同时检索下肢皮肤及软组织感染性缺损治疗的相关文献,找出治疗对象相似、疗效评价标准相同的病例进行比较。结果与结论：23例下肢皮肤及软组织感染性缺损患者伤口感染菌中革兰阳性菌占52.2%,革兰阴性菌占47.8%,多重耐药菌占43.5%,应用封闭式负压吸引技术处理后,创面感染得到有效的控制,创面肉芽组织生长良好,通过皮瓣移植修复创面均痊愈。结果显示,皮瓣移植结合封闭式负压引流治疗感染性下肢皮肤及软组织缺损,可缩短创面愈合时间。     

Economic outcomes of inappropriate initial antibiotic treatment for complicated skin and soft tissue infections: a multicenter prospective observational study

This study examined economic outcomes associated with inappropriate initial antibiotic treatment (IIAT) in complicated skin and soft tissue infections using data from adults hospitalized and treated with intravenous antibiotic therapy. We specifically analyzed for the subsets of patients infected with methicillin-resistant Staphylococcus aureus (MRSA), with healthcare-associated (HCA) infections, or both. Data from 494 patients (HCA: 360; MRSA:175; MRSA + HCA: 129) showed the overall mean length of stay (LOS) was 7.4 days and 15.0% had the composite economic outcome of any subsequent hospital admissions, emergency department visits, or unscheduled visits related to the study infection. A total of 23.1% of patients had IIAT; after adjustments, these patients had longer LOS than patients without IIAT in the HCA cohort (marginal LOS = 1.39 days, P = 0.03) and the MRSA + HCA cohort (marginal LOS = 2.43 days, P = 0.01) and were significantly more likely to have the composite economic outcome in all study cohorts (odds ratio: overall = 1.79; HCA = 3.09; MRSA = 3.66; MRSA + HCA = 6.92; all P < 0.05).     

Clinical outcomes of patients receiving daptomycin for the treatment of Staphylococcus aureus infections and assessment of clinical factors for daptomycin failure: A retrospective cohort study utilizing the Cubicin® Outcomes Registry and Experience

Background: Daptomycin is most commonly used as a second-line treatment. Previous studies have not differentiated the effect of prior antibiotic therapy on daptomycin clinical outcomes.Objectives: The primary objective of this study was to compare clinical outcomes of patients treated with daptomycin as first-line therapy versus after prior antibiotic therapy (specifically, vancomycin). A secondary objective was to identify other factors associated with the clinical failure of daptomycin therapy.Methods: This was a retrospective cohort study using data from a postlabeling registry database. The effects of relevant patient characteristics on the clinical outcome of individuals treated for Staphylococcus aureus infections with daptomycin were examined in an unblinded approach using univariate and multivariate analyses. Only patients with an evaluable clinical outcome (ie, cure, improvement, failure) and culture-confirmed S aureus infection were included in the analysis cohort.Results: Of 1227 clinically evaluable patients, 250 (20%) received daptomycin as first-line therapy and 977 (80%) received daptomycin after other prior antibiotic therapy. Overall, 53% of patients were male; 64% were aged 31 to 65 years and 26% were aged ≥66 years. Race information was collected beginning in 2007; of the patients studied, 71% were white and 18% were black. The initial daptomycin dose (mean [SD]) overall was 5.1 (1.1) mg/kg and was highest for patients with endocarditis (5.9 [1.2] mg/kg) and lowest for those with uncomplicated skin and skin structure infections (4.4 [0.9] mg/kg). Clinical success, defined as an outcome of cured or improved at the end of daptomycin therapy, was reported for 1140 (93%) of the 1227 evaluable patients. The clinical success rates for first-line therapy with daptomycin and after prior antibiotics were both 93%. Using univariate analysis, 8 variables were associated with clinical failure (receipt of daptomycin in an intensive care unit setting, severe renal dysfunction [creatinine clearance <30 mL/min], dialysis, diabetes mellitus (DM), concomitant antibiotics, bacteremia, endocarditis, and failure of prior vancomycin therapy) and 3 with clinical success (outpatient daptomycin therapy and complicated and uncomplicated skin and skin structure infections). Using the stepwise multivariate regression analysis, only the presence of endocarditis (odds ratio [OR] = 2.56; 95% CI, 1.18–5.54; P = 0.017), bacteremia (OR = 1.77; 95% CI, 1.04–3.02; P = 0.037), severe renal dysfunction (OR = 1.78; 95% CI, 1.05–3.03; P = 0.034), and DM (OR = 1.79; 95% CI, 1.10–2.93; P = 0.02) were identified as factors independently associated with clinical failure of daptomycin therapy. Of the remaining patients, 9% were aged 18 to 30 years and 0.7% were aged 12 to 17 years.Conclusions: In this retrospective study, after controlling for clinical factors that are associated with suboptimal outcomes, clinical outcomes with daptomycin did not differ whether it was used as first-line therapy or after other antibiotics. Endocarditis, bacteremia, severe renal dysfunction, and DM were associated with higher rates of clinical failure of daptomycin treatment.