Oritavancin vs Standard of Care for Treatment of Nonendovascular Gram-Positive Bloodstream Infections.

Background: Data is limited comparing oritavancin (ORT) to the standard-of-care (SOC) for the treatment gram-positive blood stream infections (BSI). Methods: This was a retrospective study of all patients in the Veteran's Affairs Health Care System treated with at least 1 dose of oritavancin or at least 5 days of vancomycin, daptomycin, ceftaroline, ampicillin, ampicillin-sulbactam, nafcillin, oxacillin, or cefazolin for a documented gram-positive BSI from 1 January 2015 to 30 June 2021. Patients with polymicrobial blood cultures or positive cultures from other sites were included if the organisms were sensitive to the incident antimicrobial; no concomitant antimicrobials could be used once the incident agent was started. Individuals were also excluded if they were diagnosed with endocarditis, had a neutrophil count 96-hours of treatment before the incident antimicrobial was started.The primary composite outcome was clinical failure, defined as all-cause mortality within 30-days from the end of therapy, or blood cultures positive for the incident organisms ≥72 hours after administration of the first dose and ≤30 days after the administration of the final dose of the study antimicrobial, or any drug or line-related readmissions within 30-days of hospital discharge. Results: Two hundred-forty patients were identified for screening with 96 meeting criteria (27 in ORT and 69 in SOC groups). Baseline characteristics were generally balanced between groups except more patients in the ORT group received >96-hours of treatment before the incident antimicrobial was started (70.3% (19/27) vs 13.04% 9/69); P < .001). The pathogen most prevalent was methicillin susceptible Staphylococcus aureus (MSSA) (ORT 33.3% (9/27) vs SOC 46.4% (32/69)). Clinical failure occurred in 7.4% (2/27) in the ORT group and 17.4% (12/69) in SOC (P = .34). No components of the primary outcome were significantly different between groups, but AKI did occur more commonly in the SOC group (27.5% (19/69) vs 3.7% (1/27); P = .01). Conclusions: ORT appears to be a safe and effective option when directly compared to the SOC for non-endocarditis BSIs.

Comparing Safety and Efficacy of Direct Oral Anticoagulants Versus Warfarin in Extreme Obesity.

Background: Limited clinical data exists regarding use of direct oral anticoagulants (DOACs) in extreme obesity, specifically those ≥140 kg or having a body mass index (BMI) ≥ 50 kg/m2. Objective: Evaluate the safety and efficacy of DOACs in extreme obesity. Patients/Methods: A retrospective chart review was performed at a single center of patients aged 18-89 years and weight ≥140 kg or BMI ≥50 kg/m2 receiving warfarin or DOAC therapy. Patients were followed for 1 year from prescribing/study inclusion. The primary outcome was the difference in rates of any bleed (composite of major, nonmajor clinically relevant, or minor bleeding events as defined by International Society of Thrombosis and Haemostasis (ISTH) criteria) between groups. Secondary outcomes included individual components of the composite primary outcome and effectiveness in preventing thrombotic events within 12 months. Post-hoc multivariate analysis evaluated potential predictors of bleeding events within overall patient population. Results: Two-hundred eighty-five patients were included, 80 and 205 in the DOAC and warfarin groups, respectively. Rates of any documented bleeding event were comparable in DOAC and warfarin groups (17.5% vs 17.1%, P > .05). No significant difference in rates of minor (P = .067), nonmajor clinically relevant (P = .825), and major (P = 1) bleeding events were observed. Two thrombotic events occurred in the warfarin group compared to none in the DOAC group. Increasing weight was associated with bleeding events in multivariate analysis. Conclusions: This data did not demonstrate a difference in safety or efficacy outcomes between DOACs and warfarin when utilized in patients with extreme obesity.

Impact of pharmacist contact via telephone vs letter on rate of acquisition of naloxone rescue kits by patients with opioid use disorder.

Background: Limited data describes the effectiveness of strategies to optimize naloxone rescue kit distribution. Mental health clinical pharmacy specialists (CPS) at VA St. Louis HCS aimed to increase distribution of naloxone rescue kits to patients with Opioid Use Disorder (OUD). An informational letter detailing the purpose of rescue kits and how to obtain one were sent to patients with OUD who had no active order for a naloxone rescue kit within the previous year. Roughly half of these patients were targeted for follow-up education via telephone. Methods: A retrospective study was conducted comparing the effectiveness of these contact methods. Study groups included those contacted by letter alone and those contacted by both letter and phone call. The primary outcome was order placement for a rescue kit within 90 days of contact. Post-hoc analysis included a multivariate regression, case-control evaluation of variables potentially associated with kit distribution. Results: In total, 335 patients were included. Of 185 patients targeted for phone follow-up, 81 were reached (43.8%), and 254 received the letter alone. The primary outcome was achieved by 13 (5.1%) and 52 (64.2%) participants in the letter alone and letter plus phone contact groups, respectively (p < 0.001). In multivariate analysis, phone contact (OR 38.6; 95% CI 17.5-85.0), nonwhite race (OR 3.4; 95% CI 1.5-7.6), prior participation in the substance abuse rehabilitation treatment program (OR 3.2; 95% CI 1.3-8.0), and current active opioid prescription (OR 3.7; 95% CI 1.3-10.2) were independently associated with an order for a naloxone rescue kit. Conclusions: In patients with OUD, those contacted by phone in addition to receiving a letter were significantly more likely to receive a naloxone kit than those contacted via letter alone. In addition to contact by phone, nonwhite race, prior participation in rehabilitation and active opioid prescription were associated with a higher rate of kit obtainment.

Comparison of Adverse Drug Reactions Between Patients Treated With Ceftaroline or Ceftriaxone: A Single-Center, Matched Cohort Study.

BACKGROUND: Little information is available on the relative tolerability of ceftaroline versus other cephalosporins in clinical practice. We sought to compare adverse drug reactions (ADRs) associated with ceftaroline with those associated with ceftriaxone in hospitalized patients. MATERIALS AND METHODS: This was a retrospective, single-center matched cohort (according to age, indication, and duration) study of patients treated with ceftaroline or ceftriaxone at the VA St Louis Health Care System between 29 October 2010 and 28 March 2017, to compare rates of ADRs between the agents. Patients included received ≥2 doses of either medication to treat osteomyelitis, acute bacterial skin and skin structure infection, blood stream infection, pneumonia, infective endocarditis, septic arthritis, prosthetic joint infection, or empyema. The primary and secondary outcomes were the composite of any ADR during therapy and any ADR leading to premature discontinuation of therapy. The ADRs evaluated included rash, neutropenia, acute kidney injury, eosinophilia, thrombocytopenia, transaminitis, and hyperbilirubinemia. RESULTS: After matching, 50 patients per group were included and analyzed. An ADR occurred in 20% (10 of 50) of patients treated with ceftriaxone and 16% (8 of 50) of those treated with ceftaroline (P = .60). Two percent (1 of 50) of those treated with ceftriaxone and 16% (8 of 50) treated with ceftaroline had therapy discontinued owing to an ADR (P = .03). The most common ADR was eosinophilia (3 of 50) in the ceftriaxone group and rash (5 of 50) in the ceftaroline group. Ceftaroline therapy was identified as an independent risk factor for an ADR requiring premature discontinuation (odds ratio, 10.2; 95% confidence interval, 1.19-87.8; P = .03). CONCLUSIONS: Although there was no difference in the rates of ADRs between patients in the ceftriaxone and ceftaroline groups, significantly more ceftaroline-treated patients required premature discontinuation.

Association Between Baseline Creatinine Clearance and Treatment Failure in Patients With Hepatitis C Virus Treated With Ledipasvir and Sofosbuvir.

BACKGROUND: Hepatitis C remains a major cause of liver disease globally and is responsible for approximately 500 000 deaths annually. Newer direct-acting antivirals achieve cure rates at or above 90% with excellent tolerability for most patients. The literature focusing on identification of predictors of efficacy and safety with specific hepatitis C therapies has been inconclusive and often conflicting. METHODS: A retrospective, single-center, case-control analysis of all veteran patients aged ≥18 through ≤89 years who completed a treatment course of 8, 12, or 24 weeks with ledipasvir and sofosbuvir (LDV/SOF) combination therapy for hepatitis C infection was conducted. Patients who were identified and met inclusion criteria were assigned to either the case group (SVR12 failure; hepatitis C viral load detectable at least 11 weeks after therapy completion) or the control group (SVR12 success; hepatitis C viral load undetectable at least 11 weeks after therapy completion). RESULTS: Twenty-nine SVR12 failures and 411 SVR12 successes were included in the analysis. The overall failure rate was consistent with the current literature, at 6.6% (29/440). Bivariate analysis identified only baseline creatinine clearance >80 mL min-1 (Cockcroft-Gault) as a possible predictor of SVR12 failure (P = .026). In the multivariate analysis, pretreatment creatinine clearance >80 mL min-1 remained independently associated with SVR12 failure (odds ratio, 2.95; 95% confidence interval, 1.17-7.46; P = .023). CONCLUSIONS: In hepatitis C patients treated with LDV/SOF, a pretreatment creatinine clearance of >80 mL min-1 was associated with SVR12 failure.

Identification of Predictors for Treatment Failure in Hepatitis C Virus Patients Treated With Ledipasvir and Sofosbuvir.

BACKGROUND: New hepatitis C virus (HCV) therapies report cure rates of ~90% but are expensive. Identification of predictors for treatment failure could help decrease health care costs, limit unnecessary drug exposure and adverse events, and prevent drug-drug interactions. Failure to achieve rapid viral response (RVR), defined as detectable viral load at 4 weeks, has previously been identified as a predictor of treatment failure with some previous HCV therapies. OBJECTIVE: To evaluate RVR, and other potential variables, as predictors of treatment failure in patients treated with ledipasvir and sofosbuvir (LDV/SOF). METHODS: A retrospective, case-control analysis of adult veterans treated with LDV/SOF was conducted. Included patients had a viral load obtained between weeks 3 and 6 of therapy (RVR) and between weeks 12 and 16 after the end of therapy for sustained viral response (SVR12) evaluation. Identified SVR12 failures (viral load detectable) constituted the case population. The control population was randomly selected in a 1:4 case: control ratio from all identified SVR12 successes. RESULTS: In all, 12 SVR12 failures were identified; 48 of 144 SVR12 successes were randomly selected for inclusion. Overall failure rate was 7.7% (12/156). Univariate analysis identified histamine-2 receptor antagonist, previous treatment failure, and pretreatment creatinine clearance (CrCl; Cockcroft-Gault) >90 mL/min as potential predictors of SVR12 failure; these variables were included in the regression model with RVR per protocol. In multivariate analysis, pretreatment CrCl >90 mL/min was independently associated with SVR12 failure (odds ratio = 7.27; 95% CI = 1.33 to 39.72; P = 0.022). CONCLUSIONS: Patients with pretreatment CrCl >90 mL/min were more likely to fail SVR12 than patients with CrCl <90 mL/min.

Effect of piperacillin/tazobactam restriction on usage and rates of acute renal failure.

A piperacillin/tazobactam (PT) restriction was initiated at our institution on 15 July 2012 requiring clinical pharmacy or infectious diseases approval for durations exceeding 72 h. A retrospective review was undertaken to determine whether this restriction decreased PT usage and/or rates of acute renal failure (ARF) (defined as a 50% increase or 0.5 mg dl(-1) increase in serum creatinine from baseline). Patients prescribed at least 1 day of PT with a creatinine clearance of ≥ 39 ml min(-1) at the time of initiation in the 3 months prior to the restriction were compared with patients in the 5 months after restriction implementation. Overall, 115 unique patients were included in the pre-implementation group and compared with 117 unique patients in the post-implementation group. The pre-implementation group received a mean of 5.22 days of PT, compared with 4.71 days in the post-implementation group (P = 0.224). Ten per cent (12/115) of patients in the pre-implementation group developed ARF compared with 9.17% (11/120) of patients in the post-implementation group (P = 0.0309). Ninety-five patients in the pre-implementation group and 91 in the post-implementation group received combination therapy with vancomycin. ARF occurred in 11.6% (11/95) of those in the pre-implementation group and 12.1% (11/91) in the post-implementation (P>0.05). Overall, 11.8% (22/186) of patients who received therapy with PT and vancomycin developed ARF, compared with 1.7% (1/56) who received PT monotherapy (P < 0.0001). This restriction resulted in a numeric reduction in the number of PT days in the post-implementation group and a significant reduction in the rate of ARF.

The potential role of newer gram-positive antibiotics in the setting of osteomyelitis of adults.

WHAT IS KNOWN AND OBJECTIVE: To summarize available literature regarding the potential role of linezolid, daptomycin, telavancin, tigecycline and ceftaroline for the treatment of osteomyelitis caused by resistant gram-positive organisms. METHODS: Literature was obtained through PubMed searches from January 1980 to October 2011 using the terms osteomyelitis, bone, linezolid, daptomycin, telavancin, tigecycline and ceftaroline. Results were limited to those published in English. All articles identified from the PubMed searches were evaluated. Any published data related to bone penetration (animal or human) or clinical outcomes in adult osteomyelitis of these agents were included in the review. RESULTS AND DISCUSSION: Animal models report bone concentrations of 2·3 mcg/dL (vertebral) for linezolid, 0·45 mcg/mL (tibiae) for daptomycin, 0·78 mcg/mL (tibiae) for tigecycline and 0·27 mcg/mL (tibiae) for telavancin; no data are available for ceftaroline. Human studies demonstrate bone concentrations of 4·6, 17·0 and 3·9 mcg/mL (sternal, metatarsal and cancellous bone respectively) for linezolid, 4·7 mcg/mL (metatarsal) for daptomycin and 0·078 mcg/mL (unspecified) for tigecycline; no data are available for telavancin and ceftaroline. Retrospective cohort data, and prospective/retrospective case series support the use of linezolid in this setting; however, side-effects may limit use. Retrospective and prospective cohort data support daptomycin use. A retrospective case series is available supporting the use of telavancin. No data are available supporting clinical effectiveness for ceftaroline or tigecycline in the setting of osteomyelitis. WHAT IS NEW AND CONCLUSION: Limited data are available evaluating the safety and efficacy of these agents in osteomyelitis in adults. Daptomycin and telavancin may be potential alternatives or second-line agents to vancomycin in selected patients. Linezolid, because of an increase in clinically important ADRs with prolonged use, should be reserved as a second- or third-line agent. Due to a lack of clinical data and poor bone penetration, along with concerns regarding outcomes in severe infections, tigecycline's potential is limited. Little data exist regarding ceftaroline use in osteomyelitis.

Daptomycin compared to vancomycin for the treatment of osteomyelitis: a single-center, retrospective cohort study.

BACKGROUND: Osteomyelitis (OM) is a serious infection with high rates of recurrence. Vancomycin has been used for decades in the treatment of OM, but, despite adequate dosing, 30% to 50% of patients experience infection recurrence within 12 months. Daptomycin, a novel lipopetide antibiotic, is also active against resistant gram-positive organisms, but there is little published about its efficacy and tolerability in the treatment of OM. OBJECTIVE: Our aim was to compare the recurrence rates of OM in patients treated with daptomycin or vancomycin. METHODS: A retrospective cohort study of all patients at a VA Medical Center between January 1, 2003, and July 31, 2009, who received daptomycin for the treatment of OM was undertaken. Patients with a diagnosis of OM who received at least 2 weeks of daptomycin and had at least 1 follow-up visit within 6 months after completion of therapy were included. Each patient was matched with 2 controls treated with at least 2 weeks of vancomycin for OM. Matching criteria included previous OM, diabetes, peripheral vascular disease, hardware involvement, and surgical therapy. Patients were excluded from the evaluation if they received <14 days of therapy, had no follow-up in the 6 months after therapy was discontinued, had an absolute neutrophil count <500 cells/mm(3), or were receiving vancomycin and daptomycin concurrently. The primary outcome was recurrence of infection within 6 months after the discontinuation of therapy. Secondary outcomes included mean change in creatine phosphokinase (CPK), incident thrombocytopenia, and mean doses of antibiotics. The χ(2) test was used to compare rates of recurrence between groups. RESULTS: Seventeen patients received at least 2 weeks of daptomycin for the treatment of OM and were matched to 34 vancomycin controls. Twenty-nine percent of patients receiving daptomycin had a recurrence of infection compared with 61.7% in the vancomycin group (P = 0.029). The mean change in CPK for the daptomycin group was +28.8 U/L. No thrombocytopenia developed in any patients receiving daptomycin compared with 2 (5.9%) patients in the vancomycin group. CONCLUSIONS: In a limited number of cases, significantly fewer patients treated with daptomycin for OM had a recurrence of their infection. Daptomycin may be a tolerable and effective alternative to vancomycin for the treatment of OM.