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Tristan O’Driscoll,1 Christopher W Crank2 1Department of Pharmacy Practice, Chicago College of Pharmacy, Downers Grove, IL, USA; 2Pharmacy Services, Rush-Copley Medical Center, Aurora, IL, USA Abstract: Since its discovery in England and France in 1986, vancomycin-resistant Enterococcus has increasingly become a major nosocomial pathogen worldwide. Enterococci are prolific colonizers, with tremendous genome plasticity and a propensity for persistence in hospital environments, allowing for increased transmission and the dissemination of resistance elements. Infections typically present in immunosuppressed patients who have received multiple courses of antibiotics in the past. Virulence is variable, and typical clinical manifestations include bacteremia, endocarditis, intra-abdominal and pelvic infections, urinary tract infections, skin and skin structure infections, and, rarely, central nervous system infections. As enterococci are common colonizers, careful consideration is needed before initiating targeted therapy, and source control is first priority. Current treatment options including linezolid, daptomycin, quinupristin/dalfopristin, and tigecycline have shown favorable activity against various vancomycin-resistant Enterococcus infections, but there is a lack of randomized controlled trials assessing their efficacy. Clearer distinctions in preferred therapies can be made based on adverse effects, drug interactions, and pharmacokinetic profiles. Although combination therapies and newer agents such as tedizolid, telavancin, dalbavancin, and oritavancin hold promise for the future treatment of vancomycin-resistant Enterococcus infections, further studies are needed to assess their possible clinical impact, especially in the treatment of serious infections. Keywords: Gram-positive, Enterococcus faecalis, Enterococcus faecium, VRE, antibiotic resistance, multidrug resistance

We used the time-kill methods to determine the presence, or lack of antagonism resulting from the combination of voriconazole and amphotericin B against several fluconazole susceptible and resistant Candida isolates. The drug combination was tested both sequentially and concurrently, by the means of a pre-exposure period to voriconazole. No antagonism was found to result from simultaneous exposure to voriconazole and amphotericin B. However, marked antagonism was found in all tested isolates after pre-exposure to voriconazole, followed by concurrent exposure to both agents. Furthermore, isolates susceptible to fluconazole also displayed antagonism of amphotericin B following pre-exposure to voriconazole followed by azole removal and introduction of amphotericin B alone. These data provide further evidence that concurrent use of azole amphotericin B combination therapy against Candida species should be discouraged. Additionally, the persistence of antagonism following the removal of voriconazole, suggests that physiochemical differences among the azoles significantly affects the expression of antagonism. [ABSTRACT FROM AUTHOR]

Clinical preference for a semisynthetic penicillin (oxacillin or nafcillin) over cefazolin for deep-seated methicillin-susceptible Staphylococcus aureus (MSSA) bloodstream infections (BSI) perseveres despite limited data to support this approach. A retrospective cohort study of patients treated for MSSA BSI with either oxacillin or cefazolin was performed across two medical centers in Chicago, IL. The outcome measures included documented in-hospital treatment failure, all-cause in-hospital mortality, duration of MSSA BSI, and incidence of documented adverse events. Of 161 patients with MSSA BSI, 103 (64%) received cefazolin, and 58 (36%) received oxacillin. The identified sources of BSI were central line (37.9%), osteoarticular (18%), and skin and soft tissue (17.4%). Patients with endocarditis (29/52 [44.2%]) and other deep-seated infections (23/52 [55.8%]) were classified under the subset of deep-seated infections (52/161 [32.3%]). Multivariate models found deep-seated infection (adjusted odds ratio [aOR], 4.52; 95% confidence interval [CI], 1.23 to 16.6; P = 0.023), metastatic disease (aOR, 4.21; 95% CI, 1.13 to 15.7; P = 0.033), and intensive care unit (ICU) onset of infection (aOR, 4.80; 95% CI, 1.26 to 18.4; P = 0.022) to be independent risk factors for in-hospital treatment failure. Treatment group was not an independent predictor of failure (aOR, 3.76; 95% CI, 0.98 to 14.4; P = 0.053). The rates of treatment failure were similar among cefazolin-treated (5/32 [15.6%]) and oxacillin-treated (4/20 [20.0%]) patients (P = 0.72) in the subset of deep-seated infections. Mortality was observed in 1 (1%) and 3 (5.2%) cases of cefazolin- and oxacillin-treated patients, respectively (P = 0.13). Cefazolin was not associated with higher rates of treatment failure and appears to be an effective alternative to oxacillin for treatment of deep-seated MSSA BSI., (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)

Since its discovery in England and France in 1986, vancomycin-resistant Enterococcus has increasingly become a major nosocomial pathogen worldwide. Enterococci are prolific colonizers, with tremendous genome plasticity and a propensity for persistence in hospital environments, allowing for increased transmission and the dissemination of resistance elements. Infections typically present in immunosuppressed patients who have received multiple courses of antibiotics in the past. Virulence is variable, and typical clinical manifestations include bacteremia, endocarditis, intra-abdominal and pelvic infections, urinary tract infections, skin and skin structure infections, and, rarely, central nervous system infections. As enterococci are common colonizers, careful consideration is needed before initiating targeted therapy, and source control is first priority. Current treatment options including linezolid, daptomycin, quinupristin/dalfopristin, and tigecycline have shown favorable activity against various vancomycin-resistant Enterococcus infections, but there is a lack of randomized controlled trials assessing their efficacy. Clearer distinctions in preferred therapies can be made based on adverse effects, drug interactions, and pharmacokinetic profiles. Although combination therapies and newer agents such as tedizolid, telavancin, dalbavancin, and oritavancin hold promise for the future treatment of vancomycin-resistant Enterococcus infections, further studies are needed to assess their possible clinical impact, especially in the treatment of serious infections.

Objectives: Despite significant medical advances, infective endocarditis (IE) remains an infection associated with high morbidity and mortality. The objective was to assess the safety and efficacy of high-dose daptomycin, defined as ≥ 8 mg/kg/day, in patients with confirmed or suspected staphylococcal and/or enterococcal IE., Methods: This was a multicentre, retrospective observational study (2005-11). Adult patients, not undergoing haemodialysis, with blood cultures positive for staphylococci or enterococci and a definitive or possible diagnosis of IE, who received daptomycin ≥ 8 mg/kg/day (based on total body weight) for ≥ 72 h were included., Results: Seventy patients met the inclusion criteria and comprised 33 (47.1%) with right-sided IE (RIE), 35 (50%) with left-sided IE (LIE) and 2 with both RIE and LIE. Several patients had concomitant sites of infection, with bone/joint infection being most prevalent (12.9%). Sixty-five patients received daptomycin as salvage therapy. Pathogens were isolated from 64 patients, with methicillin-resistant Staphylococcus aureus as the most common organism (84.4%), followed by vancomycin-resistant Enterococcus faecium (7.8%). The median (IQR) daptomycin dose was 9.8 mg/kg/day (8.2-10.0 mg/kg/day), and was similar in RIE and LIE patients (9.8 and 9.3 mg/kg/day, respectively). A total of 24 (34.3%) received combination therapy. For those patients with pathogens isolated (n = 64), the organism was eradicated in 57 (89.1%) patients. Among 64 clinically evaluable patients, 55 (85.9%) achieved clinical success. No patients required discontinuation of high-dose daptomycin due to creatine phosphokinase elevations., Conclusions: Patients with both RIE and LIE had successful outcomes with high-dose daptomycin therapy. Additional clinical trials evaluating high daptomycin dosages in patients with IE are warranted.

Enterococci are among the leading pathogens isolated in hospital-acquired infections. Current antimicrobial options for vancomycin-resistant enterococci (VRE) are limited. Prior data suggest that daptomycin at >6 mg/kg of body weight/day may be used to treat enterococcal infections. We retrospectively evaluated the effectiveness and safety of high-dose daptomycin (HD-daptomycin) therapy (>6 mg/kg) in a multicenter cohort of adult patients with enterococcal infections to describe the characteristics and outcomes. Two hundred forty-five patients were evaluated. Enterococcus faecium was identified in 175 (71%), followed by Enterococcus faecalis in 49 (20%) and Enterococcus spp. in 21 (9%); overall, 204 (83%) isolates were VRE. Enterococcal infections included bacteremia (173, 71%) and intra-abdominal (35, 14%) and bone and joint (25, 10%) infections. The median dosage and duration of HD-daptomycin were 8.2 mg/kg/day (interquartile range [IQR], 7.7 to 9.7) and 10 days (IQR, 6 to 15), respectively. The overall clinical success rate was 89% (193/218), and microbiological eradication was observed in 93% (177/191) of patients. The median time to clearance of blood cultures on HD-daptomycin was 3 days (IQR, 2 to 5). The 30-day all-cause mortality rate was 27%, and 5 (2%) patients developed daptomycin-nonsusceptible enterococcal strains while on HD-daptomycin. Seven patients (3%) had creatine phosphokinase (CPK) elevation, yet no HD-daptomycin regimen was discontinued due to an elevated CPK and all patients were asymptomatic. Overall, there was a high frequency of clinical success and microbiological eradication in patients treated with HD-daptomycin for enterococcal infections, even in patients with complicated and difficult-to-treat infections. No adverse event-related discontinuation of HD-daptomycin was noted. HD-daptomycin may be an option for the treatment of enterococcal infections.

Purpose: Pharmacists have been shown to improve medication reconciliation at hospital admission. Limited resources may obligate pharmacy departments to target resources for medication reconciliation rather than extend services to the entire hospital. We conducted a prospective, randomized, nonblinded assessment of the effectiveness and feasibility of pharmacist-led admission medication reconciliation for geriatric patients., Methods: Eighty-one geriatric patients were randomized 1:1 to receive medication reconciliation per current hospital practice or to pharmacist-led medication reconciliation at admission. The primary end point was medication profile appropriateness by pharmacist review at 48 hours postadmission. Secondary end points involved in determining the impact and feasibility of this program., Results: Pharmacist-led medication was superior to standard hospital practice, with 48% of controls and 71% of intervention patients having appropriate medication profiles at 48 hours postadmission (P = .033). Pharmacists identified 116 discrepancies among 81 patients including predominantly omissions (41%) and a composite of wrong dose, route, or frequency (35%). Pharmacists spent a median 15 minutes per patient., Conclusion: Pharmacists improved admission medication reconciliation for geriatric patients. Pharmacists identified a significant number of discrepancies, including predominantly omissions and wrong dose, dosage form, or frequency. Pharmacists' contributions to medication reconciliation could yield substantial benefit to patient care.

The group 2 carbapenems (imipenem, meropenem and, more recently, doripenem) have been a mainstay of treatment for patients with serious hospital infections caused by Pseudomonas aeruginosa, Enterobacteriaceae and other difficult-to-treat Gram-negative pathogens as well as mixed aerobic/anaerobic infections. When ertapenem, a group 1 carbapenem, was introduced, questions were raised about the potential for ertapenem to select for imipenem- and meropenem-resistant Pseudomonas. Results from ten clinical studies evaluating the effect of ertapenem use on the susceptibility of Pseudomonas to carbapenems have uniformly shown that ertapenem use does not result in decreased Pseudomonas susceptibility to these antipseudomonal carbapenems. Here we review these studies evaluating the evidence of how ertapenem use affects P. aeruginosa as well as provide considerations for ertapenem use in the context of institutional stewardship initiatives., (Copyright © 2011 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.)

Purpose: Rasburicase is a recombinant urate oxidase enzyme generally reserved for the treatment or prevention of hyperuricemia in patients that are at high risk of developing tumor lysis syndrome (TLS). The primary objective of this study is to evaluate and characterize the outcomes of patients receiving low dose rasburicase for treatment or prophylaxis of hyperuricemia secondary to TLS., Patients/methods: A retrospective chart review between April 1, 2007 and September 31, 2008 was completed. All adult patients who received a dose of 0.05mg/kg with either a leukemia or lymphoma diagnosis in addition to at least two TLS risk factors: WBC ≥ 50 × 109/L, LDH 2 × ULN, uric acid ≥ 8 mg/dl, SCr ≥ 1.5 mg/dl were included. Forty-eight patients received rasburicase for prophylaxis (n = 18) or treatment (n = 30) of TLS., Results: Forty patients achieved and maintained a uric acid less than 8 mg/dL, 24 h after receipt of a single dose of rasburicase without the requirement for renal replacement therapy. A statistically significant decrease in UA was achieved in all patients when compared to baseline (p < 0.001). Cost analysis revealed a $ 1.96 million (96%) direct cost savings for the 48 patients in this study when compared to the cost of manufacturer's dosing recommendation., Conclusions: Low dose rasburicase was efficacious and cost effective for both prophylaxis and treatment of TLS. Administration of a single dose of 0.05mg/kg of rasburicase was sufficient in correcting uric acid levels for most patients.

Study Objective: To evaluate the clinical response and safety of high-dose daptomycin for treatment of complicated gram-positive infections., Design: Multicenter, retrospective, observational, case series analysis., Setting: Five academic medical centers in four major United States cities., Patients: Two hundred fifty adults, not undergoing dialysis, who received high-dose daptomycin (≥ 8 mg/kg/day) for at least 72 hours for complicated gram-positive infections between January 1, 2005, and March 1, 2010., Measurements and Main Results: Clinical and microbiologic outcomes were assessed at the end of high-dose daptomycin therapy. Safety evaluations were recorded for all patients, and when available, baseline, end-of-therapy, and highest observed serum creatine phosphokinase (CPK) levels were recorded. Methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecium (VRE) were the primary organisms isolated. The median dose of daptomycin was 8.9 mg/kg/day (interquartile range [IQR] 8.0-10.0 mg/kg/day). The median duration of daptomycin during hospitalization for MRSA and VRE infection was 10 days (IQR 5-16 days) and 13 days (IQR 6-18 days), respectively. Among the 250 patients, high-dose daptomycin was primarily used as salvage therapy after vancomycin treatment (184 patients [73.6%]). Primary infections included complicated bacteremia (119 patients [47.6%]), endocarditis (59 [23.6%]), skin or wound (70 [28.0%]), and bone or joint (67 [26.8%]). Overall, clinical response and microbiologic success were assessed in 83.6% (209/250 patients) and 80.3% (175/218 patients), respectively. Isolates from 13 patients (5.2%) developed nonsusceptibility to daptomycin, with most of these patients having extended vancomycin exposure. Three patients (1.2%) developed an adverse event attributable to high-dose daptomycin therapy, with the event considered either mild or moderate in severity. The median end-of-therapy CPK level was 39 U/L (IQR 26-67 U/L). No significant correlation was found between daptomycin dose and highest observed CPK level., Conclusion: Daptomycin dosages of 8 mg/kg/day or greater may be safe and effective in patients with complicated gram-positive infections. Further clinical studies are warranted.

Hepatic and renal functions are important considerations when selecting antifungal therapy. This investigation of liposomal amphotericin B (L-AMB) was conducted to determine the incidence and factors associated with the development of hepatotoxicity and nephrotoxicity. A retrospective chart review was conducted of 100 consecutive patients receiving L-AMB at doses of 1, 3, and 5 mg/kg. Hepatotoxicity was defined as an increase of bilirubin greater than 1.5 mg/dl or AST and ALT greater than three times the normal range. Nephrotoxicity was defined as an increase in serum creatinine of 0.5 mg/dl or an increase of 50% from baseline. Patients were included if they were 18 years of age or older. Patients were excluded if they had developed hepatic or renal dysfunction prior to L-AMB administration. Seventy-five patients were included based upon the predefined inclusion/exclusion criteria. Twenty-one percent (16/75) developed hepatotoxicity based upon the predefined criteria. There were no additive correlates for this adverse effect. Overall, 56% (42/75) of patients developed nephrotoxicity. Seventy-four percent (31/42) were exposed to IV contrast, and 90% (38/42) were receiving nephrotoxins concurrently. Age, cumulative dose, concomitant nephrotoxins, and IV contrast exposure were associated with increased nephrotoxicity (p<0.001). The development of hepatotoxicity was observed; however, no correlates (age, dose escalation, or cumulative dose) were significantly associated with its occurrence. Overall nephrotoxicity with L-AMB was common and often multifactorial. Lipid amphotericin B products are associated with lower rates of nephrotoxicity than conventional amphotericin; however, in this analysis, L-AMB was associated with a high incidence of nephrotoxicity., (© American College of Medical Toxicology 2010)

Background: The optimal treatment for bloodstream infections (BSIs) with vancomycin-resistant enterococci (VRE) is unknown., Objective: This study examined outcomes in patients treated with daptomycin or linezolid for VRE BSI., Methods: A retrospective, multicenter, cohort study was performed via chart review. Hospitalized patients treated for VRE BSI with daptomycin or linezolid from September 1, 2003, to June 30, 2007, were identified via pharmacy and microbiology reports at each institution. Patients aged <18 years or with polymicrobial bacteremia were excluded from analysis. Linezolid and daptomycin were included because the participating institutions used either of the 2 agents as first-line treatment for VRE BSI. Univariate and multivariate analyses were performed to determine the effect of drug selection on mortality and duration of BSI. Duration of BSI was defined as the amount of time from the draw date of the first positive blood culture to the draw date of the first finalized negative blood culture. Adverse events were not assessed., Results: One-hundred one patients from 3 participating US hospitals experiencing VRE BSI were identified. Sixty-seven patients were treated with daptomycin and 34 with linezolid. Baseline characteristics appeared comparable between the daptomycin- and linezolidtreated groups, with the exception of shock (P = 0.049), prior vancomycin treatment (P = 0.002), and prior linezolid treatment (P < 0.001), all of which occurred significantly more often in daptomycin-treated patients. Inpatient mortality occurred in 31 daptomycin- and 10 linezolid-treated patients (46.3% vs 29.4%; P = NS). Linear regression found that shock (P = 0.015), infective endocarditis (P = 0.021), and concurrent rifampin or gentamicin treatment (P = 0.01) were associated with prolonged duration of positive cultures. Logistic regression revealed that shock (odds ratio [OR] = 14.24; P = 0.008), infection with Enterococcus faecium (OR = 53.10; P = 0.024), previous linezolid treatment (OR = 6.63; P = 0.031), concurrent rifampin or gentamicin treatment (OR = 6.48; P = 0.046), and a nonline source of infection (OR = 6.67; P = 0.019) were associated with increased mortality., Conclusions: In this retrospective cohort analysis, there were no significant differences in mortality of VRE BSI between patients receiving daptomycin or linezolid. Underlying comorbidities appeared to best predict outcome; however, given the retrospective nature of this study, larger, prospective, randomized, comparative studies are needed to control for potential biases and determine definitive outcome differences between these 2 antimicrobials., (Copyright © 2010 Excerpta Medica Inc. All rights reserved.)

Background: Evidence-based guidelines have been published for the acute management of severe sepsis and septic shock. Key goals of institution-driven protocols include timely fluid resuscitation and antibiotic selection, as well as source control., Objective: This study assessed the impact of a sepsis protocol on the timeliness of antibiotic administration, the adequacy of fluid resuscitation, and 28-day mortality in patients with fluid-refractory septic shock., Methods: This was a single-center, before-and-after study (18 months before July 2007 and 18 months after) with prospective data collection evaluating the outcomes of a sepsis protocol in adult patients with fluid-refractory septic shock. All patients received a fluid challenge and antibiotics; those who did not were excluded from this analysis. Preprotocol findings led to the development of the sepsis protocol, which emphasized fluid resuscitation, timely administration of antibiotic therapy, and collection of specimens for culture at the onset of septic shock. In the pre- and postprotocol phases of the study, data were collected prospectively and analyzed for demographic characteristics; Acute Physiology and Chronic Health Evaluation (APACHE) II score; appropriateness of fluid resuscitation; antibiotic use; number of vasopressor, ventilator, and intensive care unit (ICU) days; and 28-day mortality. Outcomes were measured prospectively at any time during the patient's hospital admission. The primary end points were the time to administration of antimicrobial therapy and the appropriateness of fluid resuscitation before and after implementation of the sepsis protocol., Results: A total of 118 patients were included in the analysis: 64 and 54 in the pre- and postprotocol groups, respectively. Patients in the preprotocol group were primarily women (53% [34/64]) and had a mean (SD) age of 61 (15.5) years and a mean APACHE II score of 28 (6.0). Patients in the postprotocol group were primarily men (54% [29/54]) and had a mean age of 52 (18.0) years and a mean APACHE II score of 27 (6.4). Implementation of the sepsis protocol resulted in a greater percentage of patients receiving timely antibiotic therapy (ie, within 4.5 hours of refractory shock; 85% [46/54] vs 56% [36/64]; P = 0.001) and adequate fluid resuscitation (72% [39/54] vs 31% [20/64]; P < 0.001) compared with the preprotocol group. Post hoc analysis found significant decreases in the number of vasopressor days (mean [SD], 3.8 [2.7] to 1.4 [1.5]; P < 0.001), ventilator days (9.1 [12.2] to 2.7 [4.0]; P < 0.001), and ICU days (12.3 [12.6] to 4.9 [3.9]; P < 0.001) in the postprotocol group. In-hospital mortality was not significantly different between the groups (survival 46% [28/61] before vs 54% [33/61] after the protocol). Multivariate analysis for predictors of in-hospital mortality identified an interval between shock and empiric antibiotic administration of >4.5 hours (odds ratio [OR] = 5.54; 95% CI, 1.91-16.07; P < 0.002), vasopressor duration in days (OR = 1.27; 95% CI, 1.01-1.59; P = 0.037), APACHE II score (OR = 1.14; 95% CI, 1.05-1.24; P = 0.003), and type of infection (community vs nosocomial, OR = 0.18; 95% CI, 0.05-0.61; P = 0.006) as significant predictors. The 28-day mortality decreased from 61% (39/64) to 33% (18/54) after implementation of the protocol (P = 0.004)., Conclusion: Implementation of a sepsis protocol emphasizing early administration of antibiotic therapy and adequate fluid resuscitation was associated with improved clinical outcomes and lower 28-day mortality in patients with fluid-refractory septic shock at this institution., (2010 Excerpta Medica Inc. All rights reserved.)

The treatment of methicillin-resistant Staphylococcus aureus (MRSA) in the critically ill patient is challenging. Data for treatment of critically ill patients are often lacking because many such patients are excluded from industry-sponsored prospective randomized clinical trials. Infections due to MRSA are common in the critical care setting. Up to 24% of patients in intensive care units are colonized with MRSA, and 20% of all nosocomial bloodstream infections are due to MRSA. It is also one of the leading bacterial causes of ventilator- and hospital-acquired pneumonia. Vancomycin has been the drug of choice for treatment of MRSA in the critical care setting. Recent data showing vancomycin resistance, increasing numbers of MRSA isolates with higher vancomycin minumum inhibitory concentrations, and an apparent increase in vancomycin clinical failures have brought vancomycin's utility into question. A variety of treatment options for MRSA are available. Quinupristin-dalfopristin was the first alternative to vancomycin. However, its safety profile and potential for drug interactions limit its use. Linezolid has been shown to be effective in the treatment of pneumonia and skin and skin-structure infections due to MRSA. The drug's potential to cause bone marrow suppression limits its use, especially in treatment durations extending beyond 14 days. Daptomycin has been shown to be effective for the treatment of MRSA bloodstream and of MRSA skin and skin-structure infections. Tigecycline is the newest available drug with MRSA activity. It has demonstrated noninferiority to vancomycin in skin and skin-structure infections. However, its role in the treatment of ventilator- and hospital-acquired pneumonia is still unclear.

Objective: To review the literature concerning the in vitro activity, pharmacokinetic properties, in vivo efficacy, and adverse events associated with a new penem antibiotic, faropenem medoxomil., Data Sources: We conducted a search of MEDLINE/PubMed and International Pharmaceutical Abstracts databases for articles or abstracts using the terms faropenem, faropenem daloxate, faropenem medoxomil, SUN5555, SY5555, WY49605, RU67655, ALP201, BLA 857, and YM 044 and published through July 2007. Information on poster presentations was obtained from the drug's manufacturer. Additional articles were identified from citations in the bibliographies of review articles. Articles written in languages other than English were excluded., Study Selection and Data Extraction: All published reports that evaluated faropenem (or its chemical synonyms) and faropenem medoxomil were used in this review. Abstracts subsequently published as full reports were excluded, and only the resulting reports were included. Abstracts without subsequently published reports were included., Data Synthesis: The in vitro activity of faropenem has been evaluated extensively against respiratory pathogens and less extensively against aerobic gram-positive, gram-negative, and anaerobic organisms. Prospective, randomized, multicenter clinical trials have demonstrated noninferiority of faropenem to comparators for the treatment of acute bacterial sinusitis, community-acquired pneumonia, acute exacerbation of chronic bronchitis, and uncomplicated skin and skin structure infections. Adverse events associated with faropenem appear to be minimal and include nausea, vomiting, and diarrhea., Conclusions: Faropenem has demonstrated excellent in vitro activity against common respiratory pathogens, many aerobic gram-positive organisms, and anaerobes. Activity against gram-negative organisms is more reserved. In vivo data suggest that faropenem is efficacious in treating community-acquired infections including uncomplicated skin and skin structure infections; however, more data may help to characterize faropenem's place in antimicrobial therapy. Replidyne, Inc., the manufacturer of faropenem, is conducting studies to address the Food and Drug Administration's concerns that resulted in a nonapprovable letter in October 2006.

Study Objective: To evaluate the outcomes in patients with bacteremia and/or infective endocarditis who were treated with daptomycin., Design: Retrospective chart review., Setting: A university-affiliated medical center in Chicago, Illinois, and a regional hospital in Fountain Valley, California., Patients: Thirty-one inpatients treated with daptomycin for bacteremia and/or infective endocarditis., Measurements and Main Results: Patients were given daptomycin 4-6 mg/kg intravenously every 24-48 hours based on the practitioner's discretion and depending on the patient's clinical condition and presence of comorbidities. Primary end points were resolution of signs and symptoms of infection and discharge from the hospital. Methicillin-resistant Staphylococcus aureus ([MRSA] 11 patients) and vancomycin-resistant entercocci ([VRE] 11 patients) were the most common pathogens, whereas 7 patients had methicillin-sensitive S. aureus infection and 1 patient had coagulasenegative Staphylococcus infection. One patient with endocarditis had a negative culture result. Overall, 24 (77%) of the 31 patients achieved clinical resolution and were discharged, including all patients infected with MRSA; 7 patients died, 6 of whom had VRE infection. Duration of treatment for infective endocarditis lasted longer (typically 22-43 days) than that for bacteremia only (< or = 14 days), and no patients discontinued daptomycin because of adverse events., Conclusion: In these patients, daptomycin was safe and well tolerated even for extended durations of treatment. Daptomycin may provide an effective option for treating drug-resistant gram-positive bloodstream infections and endocarditis.

Objective: Drug-resistant, Gram-positive bacteria are a growing concern in treating bone and joint infections, including osteomyelitis. This report describes the experience in a series of cases of the use of a novel antibiotic, daptomycin, for the treatment of bone and joint infections., Research Design and Methods: This retrospective analysis included patients from two medical centers diagnosed with Gram-positive bone and joint infections and treated with daptomycin., Results: A total of 10 patients were included in this report, of which nine received previous antibiotic therapy, including vancomycin, linezolid, and quinupristin/dalfopristin. Methicillin-resistant Staphylococcus aureus was isolated from eight patients while the remaining patients were infected with enterococci or streptococci. All patients initially resolved the infection while undergoing daptomycin treatment and were discharged from the hospital. One patient was switched to ampicillin (after receiving daptomycin for 4 days) once the infection was identified due to vancomycin-susceptible enterococcus. However, one patient was readmitted after 18 days due to a clinical relapse, possibly caused by under-dosing of daptomycin., Conclusion: Eight out of nine patients who received daptomycin for at least 8 days were successfully treated with the agent for Gram-positive bone and joint infections. Daptomycin was found to be well tolerated, even up to 44 days of treatment.