Pharmacokinetics of Cefazolin in Patients With Obesity Undergoing Surgery Requiring Cardiopulmonary Bypass.

OBJECTIVE: The authors' objective was to determine the adequacy of an institutional standard dosing practice for infection prophylaxis in open cardiac surgery in patients heavier than 120 kg undergoing cardiopulmonary bypass. DESIGN: A prospective, single-center, open-label study was used to determine if cefazolin serum concentrations were maintained above the minimum inhibitory concentration (MIC) throughout surgery. A pharmacokinetic model describing cefazolin disposition was developed for perioperative patients with morbid obesity, based on these values. Probability of target attainment was evaluated across the clinically relevant MIC spectrum. SETTING: Maine Medical Center is an academic hospital in Portland, Maine, affiliated with Tufts University School of Medicine. PARTICIPANTS: Twenty patients scheduled for cardiac surgery requiring cardiopulmonary bypass who weighed at least 120 kg. INTERVENTIONS: All patients received 2 g of cefazolin intravenously (IV) within 1 hour before incision, an additional 1 g injected into the cardiopulmonary bypass circuit at the initiation of bypass, and 2 g administered IV every 3 hours after the initial IV dose. MEASUREMENTS AND MAIN RESULTS: Cefazolin serum concentrations were collected after incision, after initiation of bypass, each hour of bypass, at the end of bypass, and at sternal closure. For patients weighing >120 kg undergoing cardiac surgery, the studied dosing regimen met or exceeded targeted cefazolin concentrations for all study patients. The authors conducted probability of target attainment analyses using both 65% and 100% of time with unbound drug concentrations across clinically relevant MICs. CONCLUSION: The authors found that their current dosing strategy achieved a probability of target attainment >90% throughout surgery for both total and unbound cefazolin concentrations, independent of cardiopulmonary bypass times.

Fluoroquinolone Prescribing for Diabetic Foot Infections following an FDA Drug Safety Communication for Aortic Aneurysm Risk.

In 2018, the U.S. Food and Drug Administration (FDA) issued a Drug Safety Communication regarding fluoroquinolone-associated aortic aneurysm. This quasi-experimental study assessed antibiotic prescribing for 198 patients hospitalized with diabetic foot infection. Following the warning, median inpatient fluoroquinolone days of therapy (DOT) decreased from 3 to 0 days (P < 0.001), corresponding to increased beta-lactam DOT and outpatient parenteral antimicrobial therapy enrollment. FDA communications may influence antibiotic selection and transitions of care, representing opportunities for antimicrobial stewardship.

Treatment and outcomes of Enterococcus faecium bloodstream infections in solid organ transplant recipients.

Optimal antimicrobial therapy for Enterococcus faecium bloodstream infection (EFBSI) in the solid organ transplant (SOT) population is not well defined. The purpose of this study was to describe the pharmacotherapy and outcomes of EFBSI in SOT patients. This was a single-center retrospective cohort of SOT patients with EFBSI from 2013 to 2019. Susceptibility testing was performed with Vitek® 2 or Etest. Estimates of optimal DAP pharmacokinetic/pharmacodynamic exposures (dose <10 mg/kg, fAUC/MIC >27.4) were made from previously established literature and equations. Fifty-one unique cases were included in the analysis. The median age was 61 years and liver (64%), intestinal (19%), and kidney (12%) were the most common organs transplanted. Most patients had indwelling central lines (75%) at the time of bacteremia; intra-abdominal abscesses/fluid collections were present in 44% of patients and 8% had endocarditis. Nineteen (37%) patients had polymicrobial infections. The most common definitive antimicrobial regimens were as follows: DAP plus beta-lactam (46%), DAP monotherapy (18%), and LZD (25%). Of the 33 patients that received DAP, 21% of E faecium isolates developed DAP resistance. 30-day mortality was 25% overall but higher in patients who received an initial DAP dose <10 mg/kg (43% vs 13%). Vancomycin-resistance, severity of illness, neutropenia, and source control were also associated with mortality. Inadequate DAP dosing for EFBSI may be associated with mortality in the SOT population. Larger, controlled analyses are necessary to determine the impact of optimized pharmacodynamics in this population.

Stewardship opportunities in viral pneumonia: Why not the immunocompromised?

Antimicrobial management of viral pneumonia has proven to be a challenge in hospitalized immunocompromised patients. A host of factors contribute to the dilemma, such as diagnostic uncertainty, lack of organism identification, and clinical status of the patient. Respiratory virus panel (RVP) use was compared between 131 immunocompromised patients who received send-out (n = 56) vs in-house (n = 75) testing. Antimicrobial optimization interventions consisted of antiviral addition/discontinuation, antibiotic discontinuation/de-escalation, or modification of immunosuppressive regimen. After implementation of an in-house test with audit and feedback, turnaround time of the RVP was reduced from 46.7 to 5.5 hours (P < .001) and time to intervention was reduced from 52.1 to 13.9 hours (P < .001), yet the frequency of antimicrobial optimization interventions was unchanged (30.7% vs 35.7%). Differences were not observed in duration of empiric antibiotic therapy or length of stay. The overall discontinuation rate for patients tested with a RVP was low (4.6%), and those with positive RVP (n = 43) had antibiotics stopped in 14% of cases. Bacterial pneumonia coinfection was confirmed in 2 patients. Further systematic efforts should be taken to reduce antibiotic use in viral pneumonia and identify the major barriers in the immunocompromised population.

Case report: Successful treatment of OXA-23 Acinetobacter baumannii neurosurgical infection and meningitis with sulbactam-durlobactam combination therapy.

Meningitis caused by Acinetobacter species is a rare complication of neurosurgical procedures, although it is associated with high morbidity and mortality. Carbapenem-resistant Acinetobacter is particularly difficult to treat, considering the limited selection and tolerability of effective antimicrobials. Sulbactam-durlobactam was approved by the FDA in 2023 for treatment of hospital-acquired and ventilator-associated pneumonia due to susceptible strains of Acinetobacter, including carbapenem-resistant Acinetobacter baumannii. Here, we present a case of carbapenem-resistant Acinetobacter baumannii neurosurgical infection and meningitis successfully treated with sulbactam-durlobactam combination therapy.

Outcomes associated with empiric cefepime for bloodstream infections caused by ceftriaxone-resistant, cefepime-susceptible Escherichia coli and Klebsiella pneumoniae.

BACKGROUND: Cefepime is a first-line agent for empiric sepsis therapy; however, cefepime use may be associated with increased mortality for extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-E) in an MIC-dependent manner. This study aimed to compare the efficacy of empiric cefepime versus meropenem for bloodstream infections (BSI) caused by ceftriaxone-resistant Escherichia coli and Klebsiella pneumoniae with cefepime MICs ≤ 2 mg/L. METHODS: This single-center retrospective cohort study included patients admitted from October 2010 to August 2020 who received cefepime or meropenem empirically for sepsis with a blood culture growing ceftriaxone-resistant Escherichia coli or Klebsiella pneumoniae. The primary outcome was 30-day mortality; secondary endpoints included 14-day mortality, recurrent BSI, readmission and recurrent infection within 90 days, time to clinical resolution of infection, time to clinical stability, and clinical stability at 48 hours. RESULTS: Fifty-four patients met inclusion criteria: 36 received meropenem and 18 received cefepime. The median (IQR) treatment durations of cefepime and meropenem were 3 (2-6) days and 7 (5-10) days, respectively. Thirty-day and 14-day mortality were similar between cefepime and meropenem (11.1% vs. 2.8%; P = 0.255 and 5.6% vs. 2.8%; P = 1.00, respectively). Cefepime was associated with longer time to clinical stability compared with meropenem (median 38.48 hours vs. 21.26; P = 0.016). CONCLUSION: Mortality was similar between groups, although most patients who received cefepime empirically were ultimately transitioned to a carbapenem to complete the full treatment course. Empiric cefepime was associated with a delay in achieving clinical stability when compared with meropenem to treat BSI caused by ceftriaxone-resistant Enterobacterales, even when cefepime-susceptible.

Uncomplicated Streptococcal Bacteremia: The Era of Oral Antibiotic Step-down Therapy?

BACKGROUND: The purpose of this study was to compare the clinical outcomes of adults with uncomplicated streptococcal bacteremia who received either oral (PO) step-down or continued intravenous (IV) therapy. METHODS: This was a retrospective, single-center, cohort study, including adults admitted with Streptococcal bloodstream infection between January 1, 2013, and December 31, 2020. Only patients with uncomplicated Streptococcal bloodstream infections were included. Patients who transitioned to PO therapy within 5 days from bacteremia onset were compared to patients receiving continued IV therapy. The primary outcome was clinical failure, defined by either 90-day hospital readmission or mortality. Secondary outcomes included hospital length of stay (LOS) and antibiotic-related adverse events (AAEs). RESULTS: Of the 264 patients included, 42% were transitioned to PO therapy. Group B Streptococcus (22.7%) was the most common isolate. The most common sources of infection were skin and soft tissue (35%) and pulmonary (25%). Intensive care unit (ICU) stay was more common in the continued IV therapy group (22.2%) than in the PO step-down group (5.4%). The frequency of clinical failure was similar in the IV and PO groups (24.2% vs. 18.0%, P=0.23). The IV group had longer hospital LOS (median, [interquartile range (IQR)]) compared with the PO group (7 [5-13.5] vs. 4 [3-5] days, P<0.001). The incidence of AAEs was similar in the IV and PO groups (1.3% vs. 1.8%, P=0.74). CONCLUSION: Oral antibiotic step-down therapy may be appropriate for the treatment of uncomplicated Streptococcal bacteremia, with consideration of factors such as patient comorbidities, type of infection, source control and clinical progress.

Prevalence and Predictors of Pseudomonas aeruginosa Among Hospitalized Patients With Diabetic Foot Infections.

Background: Diabetic foot infections (DFIs) are commonly associated with antibiotic overuse. Empiric DFI treatment often includes coverage for Pseudomonas aeruginosa (PsA), but the frequency of PsA DFIs is poorly understood. The study objectives were to quantify the prevalence of and determine predictors for PsA DFIs. Methods: This multicenter, retrospective cohort included hospitalized patients with DFI from 2013 through 2020 who were age ≥18 years; diabetes mellitus diagnosis; and DFI based on International Classification of Diseases, Tenth Revision coding, antibiotic treatment, and DFI culture with organism growth. Osteomyelitis was excluded. Patient characteristics were described and compared; the primary outcome was presence of PsA on DFI culture. Predictors of PsA DFI were identified using multivariable logistic regression. Results: Two hundred ninety-two patients were included. The median age was 61 (interquartile range [IQR], 53-69) years; the majority were men (201 [69%]) and White (163 [56%]). The most commonly isolated organisms were methicillin-susceptible Staphylococcus aureus (35%) and streptococci (32%); 147 (54%) cultures were polymicrobial. Two hundred fifty-seven (88%) patients received empiric antibiotics active against PsA, but only 27 (9%) patients had PsA DFI. Immunocompromised status (adjusted odds ratio [aOR], 4.6 [95% confidence interval {CI}, 1.3-16.7]) and previous outpatient DFI antibiotic treatment failure (aOR, 4.8 [95% CI, 1.9-11.9]) were associated with PsA DFI. Conclusions: PsA DFI is uncommon, but most patients receive empiric antipseudomonal antibiotics. Empiric broad-spectrum antibiotics are warranted given the frequency of mixed infections, but patient-specific risk factors should be considered before adding antipseudomonal coverage.

Pharmacist-Driven Transitions of Care Practice Model for Prescribing Oral Antimicrobials at Hospital Discharge.

Importance: Although prescribers face numerous patient-centered challenges during transitions of care (TOC) at hospital discharge, prolonged duration of antimicrobial therapy for common infections remains problematic, and resources are needed for antimicrobial stewardship throughout this period. Objective: To evaluate a pharmacist-driven intervention designed to improve selection and duration of oral antimicrobial therapy prescribed at hospital discharge for common infections. Design, Setting, and Participants: This quality improvement study used a nonrandomized stepped-wedge design with 3 study phases from September 1, 2018, to August 31, 2019. Seventeen distinct medicine, surgery, and specialty units from a health system in Southeast Michigan participated, including 1 academic tertiary hospital and 4 community hospitals. Hospitalized adults who had urinary, respiratory, skin and/or soft tissue, and intra-abdominal infections and were prescribed antimicrobials at discharge were included in the analysis. Data were analyzed from February 18, 2020, to February 28, 2022. Interventions: Clinical pharmacists engaged in a new standard of care for antimicrobial stewardship practices during TOC by identifying patients to be discharged with a prescription for oral antimicrobials and collaborating with primary teams to prescribe optimal therapy. Academic and community hospitals used both antimicrobial stewardship and clinical pharmacists in a multidisciplinary rounding model to discuss, document, and facilitate order entry of the antimicrobial prescription at discharge. Main Outcomes and Measures: The primary end point was frequency of optimized antimicrobial prescription at discharge. Health system guidelines developed from national guidelines and best practices for short-course therapies were used to evaluate optimal therapy. Results: A total of 800 patients prescribed oral antimicrobials at hospital discharge were included in the analysis (441 women [55.1%]; mean [SD] age, 66.8 [17.3] years): 400 in the preintervention period and 400 in the postintervention period. The most common diagnoses were pneumonia (264 [33.0%]), upper respiratory tract infection and/or acute exacerbation of chronic obstructive pulmonary disease (214 [26.8%]), and urinary tract infection (203 [25.4%]). Patients in the postintervention group were more likely to have an optimal antimicrobial prescription (time-adjusted generalized estimating equation odds ratio, 5.63 [95% CI, 3.69-8.60]). The absolute increase in optimal prescribing in the postintervention group was consistent in both academic (37.4% [95% CI, 27.5%-46.7%]) and community (43.2% [95% CI, 32.4%-52.8%]) TOC models. There were no differences in clinical resolution or mortality. Fewer severe antimicrobial-related adverse effects (time-adjusted generalized estimating equation odds ratio, 0.40 [95% CI, 0.18-0.88]) were identified in the postintervention (13 [3.2%]) compared with the preintervention (36 [9.0%]) groups. Conclusions and Relevance: The findings of this quality improvement study suggest that targeted antimicrobial stewardship interventions during TOC were associated with increased optimal, guideline-concordant antimicrobial prescriptions at discharge.

Diminishing returns, increasing risks: Impact of antibiotic duration of therapy on respiratory bacterial isolates in hospitalized patients during the coronavirus disease 2019 (COVID-19) pandemic.

In 829 hospital encounters for patients with COVID-19, 73.2% included orders for antibiotics; however, only 1.8% had respiratory cultures during the first 3 hospital days isolating bacteria. Case-control analysis of 30 patients and 96 controls found that each antibiotic day increased the risk of isolating multidrug-resistant gram-negative bacteria (MDR-GNB) in respiratory cultures by 6.5%.

Antimicrobial never events: Objective application of a framework to assess vancomycin appropriateness.

To address appropriateness of antibiotic use, we implemented an electronic framework to evaluate antibiotic "never events" (NEs) at 2 medical centers. Patient-level vancomycin administration records were classified as NEs or non-NEs. The objective framework allowed capture of true-positive vancomycin NEs in one-third of patients identified by the electronic strategy.

Clinical Utility of Lefamulin: If Not Now, When?

PURPOSE OF REVIEW: The looming threat of antimicrobial resistance requires robust stewardship and new developments in infectious diseases pharmacotherapy. This review discusses the pertinent spectrum and clinical data of lefamulin (Xenleta®), with a focus on potential real-world use. RECENT FINDINGS: Lefamulin is a novel pleuromutilin antibiotic that obtained Food and Drug Administration labeling for community-acquired bacterial pneumonia (CABP) in 2019. Lefamulin is available in both intravenous and oral formulations, and it inhibits bacterial protein synthesis inhibition through interactive binding to unique sites of the peptidyl transferase center of the 50s bacterial ribosome subunit. Resistance, including cross-resistance with other antibiotics, is infrequent. Lefamulin demonstrates activity against most Gram-positive pathogens and other organisms commonly associated with CABP, i.e., Streptococcus pneumoniae, Haemophilus influenzae, Mycoplasma pneumoniae, Legionella pneumophila, and Chlamydophila pneumoniae. Lefamulin may also be an option for serious public health threats like methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus faecium, and multi-drug-resistant organisms associated with sexually transmitted infections, e.g., Neisseria gonorrhoeae, Mycoplasma genitalium. Lefamulin lacks activity against Pseudomonas aeruginosa, Acinetobacter baumannii, Enterobacterales, most anaerobes, and E. faecalis. In Phase III trials, lefamulin monotherapy was non-inferior to moxifloxacin with or without linezolid for CABP. SUMMARY: Lefamulin is a well-tolerated agent with a unique mechanism, availability in both IV and PO formulations, and it has been rigorously studied for safety and efficacy for CABP.

Risk of QT Interval Prolongation Associated With Use of Hydroxychloroquine With or Without Concomitant Azithromycin Among Hospitalized Patients Testing Positive for Coronavirus Disease 2019 (COVID-19).

IMPORTANCE: Administration of hydroxychloroquine with or without azithromycin for the treatment of coronavirus disease 2019 (COVID-19)-associated pneumonia carries increased risk of corrected QT (QTc) prolongation and cardiac arrhythmias. OBJECTIVE: To characterize the risk and degree of QT prolongation in patients with COVID-19 in association with their use of hydroxychloroquine with or without concomitant azithromycin. DESIGN, SETTING, AND PARTICIPANTS: This was a cohort study performed at an academic tertiary care center in Boston, Massachusetts, of patients hospitalized with at least 1 positive COVID-19 nasopharyngeal polymerase chain reaction test result and clinical findings consistent with pneumonia who received at least 1 day of hydroxychloroquine from March 1, 2020, through April 7, 2020. MAIN OUTCOMES AND MEASURES: Change in QT interval after receiving hydroxychloroquine with or without azithromycin; occurrence of other potential adverse drug events. RESULTS: Among 90 patients given hydroxychloroquine, 53 received concomitant azithromycin; 44 (48.9%) were female, and the mean (SD) body mass index was 31.5 (6.6). Hypertension (in 48 patients [53.3%]) and diabetes mellitus (in 26 patients [28.9%]) were the most common comorbid conditions. The overall median (interquartile range) baseline QTc was 455 (430-474) milliseconds (hydroxychloroquine, 473 [454-487] milliseconds vs hydroxychloroquine and azithromycin, 442 [427-461] milliseconds; P < .001). Those receiving concomitant azithromycin had a greater median (interquartile range) change in QT interval (23 [10-40] milliseconds) compared with those receiving hydroxychloroquine alone (5.5 [-15.5 to 34.25] milliseconds; P = .03). Seven patients (19%) who received hydroxychloroquine monotherapy developed prolonged QTc of 500 milliseconds or more, and 3 patients (8%) had a change in QTc of 60 milliseconds or more. Of those who received concomitant azithromycin, 11 of 53 (21%) had prolonged QTc of 500 milliseconds or more and 7 of 53 (13 %) had a change in QTc of 60 milliseconds or more. The likelihood of prolonged QTc was greater in those who received concomitant loop diuretics (adjusted odds ratio, 3.38 [95% CI, 1.03-11.08]) or had a baseline QTc of 450 milliseconds or more (adjusted odds ratio, 7.11 [95% CI, 1.75-28.87]). Ten patients had hydroxychloroquine discontinued early because of potential adverse drug events, including intractable nausea, hypoglycemia, and 1 case of torsades de pointes. CONCLUSIONS AND RELEVANCE: In this cohort study, patients who received hydroxychloroquine for the treatment of pneumonia associated with COVID-19 were at high risk of QTc prolongation, and concurrent treatment with azithromycin was associated with greater changes in QTc. Clinicians should carefully weigh risks and benefits if considering hydroxychloroquine and azithromycin, with close monitoring of QTc and concomitant medication usage.

Impact of unit-specific metrics and prescribing tools on a family medicine ward.

OBJECTIVE: Prescribing metrics, cost, and surrogate markers are often used to describe the value of antimicrobial stewardship (AMS) programs. However, process measures are only indirectly related to clinical outcomes and may not represent the total effect of an intervention. We determined the global impact of a multifaceted AMS initiative for hospitalized adults with common infections. DESIGN: Single center, quasi-experimental study. METHODS: Hospitalized adults with urinary, skin, and respiratory tract infections discharged from family medicine and internal medicine wards before (January 2017-June 2017) and after (January 2018-June 2018) an AMS initiative on a family medicine ward were included. A series of AMS-focused initiatives comprised the development and dissemination of: handheld prescribing tools, AMS positive feedback cases, and academic modules. We compared the effect on an ordinal end point consisting of clinical resolution, adverse drug events, and antimicrobial optimization between the preintervention and postintervention periods. RESULTS: In total, 256 subjects were included before and after an AMS intervention. Excessive durations of therapy were reduced from 40.3% to 22% (P < .001). Patients without an optimized antimicrobial course were more likely to experience clinical failure (OR, 2.35; 95% CI, 1.17-4.72). The likelihood of a better global outcome was greater in the family medicine intervention arm (62.0%, 95% CI, 59.6-67.1) than in the preintervention family medicine arm. CONCLUSION: Collaborative, targeted feedback with prescribing metrics, AMS cases, and education improved global outcomes for hospitalized adults on a family medicine ward.

Improving care for critically ill patients with community-acquired pneumonia.

PURPOSE: The purpose of this study was to improve antimicrobial management and outcomes of critically ill patients with community-acquired pneumonia (CAP) through implementation of a pharmacist-driven bundle for ordering evidence-based diagnostic tests in a medical intensive care unit (MICU). METHODS: An inpatient collaborative practice agreement (CPA) was established for MICU pharmacists to order criteria-driven diagnostic testing for CAP from November 2017-March 2018. Adults admitted to the MICU and started on empiric antibiotics for CAP were included. The intervention arm was compared with a standard of care (SOC) group from November 2016-March 2017. RESULTS: Ninety-one patients were included in each group. There was no difference in the median antibiotic duration between SOC and CPA, at 7 days (interquartile range [IQR], 6-10) versus 7 days (IQR, 6-8), respectively. The overall use of evidence-based diagnostic tests increased in the CPA group. Patients in the CPA group had more frequent pathogen identification (SOC and CPA, respectively: 31 [34%] versus 46 [51%], p = 0.035) and antimicrobial deescalation (24 [26%] versus 53 [58%], p < 0.001). There was no significant difference in length of intensive care unit stay, at 4 days for SOC (IQR, 2-10) versus 6 days for CPA (IQR, 3-10), and no significant difference in inpatient all-cause mortality (13 [14%] versus 7 [8%]), retreatment 14 [15%] versus 11 [12%]), or 30-day readmission 16 ([18%] versus 13 [14%]) for SOC and CPA, respectively. The CPA was the only variable that was independently associated with antimicrobial deescalation (odds ratio, 4.030; 95% confidence interval, 2.101-7.731) in a multiple logistic regression. CONCLUSION: Implementation of a pharmacy-driven pneumonia diagnostic stewardship bundle improved the use of evidence-based diagnostics and increased the frequency of pathogen identification. This intervention was associated with increased antimicrobial deescalation without a negative impact on patient safety outcomes.

It is time to define antimicrobial never events.

Inappropriate antibiotic use is associated with increased antimicrobial resistance and adverse events that can lead to further downstream patient harm. Preventative strategies must be employed to improve antibiotic use while reducing avoidable harm. We use the term "antibiotic never events" to globally recognize and define the most inappropriate antibiotic use.

Retrospective analysis comparing oral stepdown therapy for enterobacteriaceae bloodstream infections: fluoroquinolones versus ß-lactams.

Enterobacteriaceae bloodstream infections (EB-BSIs) are a common manifestation of Gram-negative sepsis and are initially managed with empirical intravenous antibiotics. Upon stabilisation and source control, patients are often transitioned to an oral agent. Fluoroquinolones (FQs) plays a prominent role in stepdown therapy for severe infections owing to favourable pharmacokinetic parameters; however, serious adverse events (AEs) have been documented with their use. A total of 224 adults with EB-BSI initiated on empirical intravenous antibiotics with stepdown to oral ß-lactam (BLM) (n = 84) or FQ (n = 140) were studied to compare clinical success and identify risk factors for treatment failure. Subgroups of early versus late oral stepdown and short versus extended duration of therapy (DOT) were assessed. Stepdown therapy with oral BLM was non-inferior to oral FQ (86.9% vs. 87.1%; mean difference 0.2%, 97.5% CI -10.3 to 10.7). Microbiological success (94.0% vs. 97.9%; P > 0.05) and 30-day re-admission (14.3% vs. 14.3%; P > 0.05) were similar. Patients were more likely to complete their BLM course without an AE compared with FQs (91.7% vs. 82.1%; P = 0.049). Clinical success was comparable between early and late stepdown (86.7% vs. 87.5%; P > 0.05) and short versus extended DOT (88.2% vs. 86.7%; P > 0.05). Negative predictors of clinical success identified by logistic regression were complicated diabetes (OR = 0.35, 95% CI 0.15-0.83) and urinary abnormality (OR = 0.39, 95% CI 0.16-0.94). These findings suggest that oral BLMs were non-inferior to FQs as stepdown therapy for EB-BSI, with less AEs.

Combatting resistant enterococcal infections: a pharmacotherapy review.

INTRODUCTION: The role of enterococci in infectious diseases has evolved from a gut and urinary commensal to a major pathogen of concern. Few options exist for resistant enterococci, and appropriate use of the available agents is crucial. AREAS COVERED: Herein, the authors discuss antibiotics with clinically useful activity against Enterococcus faecalis and E. faecium. The article specifically discusses: antibiotics active against enterococci and their mechanism of resistance, pharmacokinetic and pharmacodynamic principles, in vitro combinations, and clinical studies which focus on urinary tract, intra-abdominal, central nervous system, and bloodstream infections due to enterococci. EXPERT OPINION: Aminopenicillins are preferred over all other agents when enterococci are susceptible and patients can tolerate them. Daptomycin and linezolid have demonstrated clinical efficacy against vancomycin-resistant enterococci (VRE). Synergistic combinations are often warranted in complex infections of high inoculum and biofilms while monotherapies are generally appropriate for uncomplicated infections. Although active against resistant enterococci, the pharmacokinetics, efficacy and safety of tigecycline and quinupristin/dalfopristin can problematical for severe infections. For cystitis, amoxicillin, nitrofurantoin, or fosfomycin are ideal. Recently, approved agents such as tedizolid and oritavancin have good in vitro activity against VRE but clinical studies against other resistant enterococci are lacking.

Delafloxacin: Place in Therapy and Review of Microbiologic, Clinical and Pharmacologic Properties.

Delafloxacin (formerly WQ-3034, ABT492, RX-3341) is a novel fluoroquinolone chemically distinct from currently marketed fluoroquinolones with the absence of a protonatable substituent conferring a weakly acidic character to the molecule. This property results in increased intracellular penetration and enhanced bactericidal activity under acidic conditions that characterize the infectious milieu at a number of sites. The enhanced potency and penetration in low pH environments contrast what has been observed for other zwitterionic fluoroquinolones, which tend to lose antibacterial potency under acidic conditions, and may be particularly advantageous against methicillin-resistant Staphylococcus aureus, for which the significance of the intracellular mode of survival is increasingly being recognized. Delafloxacin is also unique in its balanced target enzyme inhibition, a property that likely explains the very low frequencies of spontaneous mutations in vitro. Delafloxacin recently received US Food and Drug Administration approval for the treatment of acute bacterial skin and skin structure infections and is currently being evaluated in a phase 3 trial among patients with community-acquired pneumonia. In the current era of a heightened awareness pertaining to collateral ecologic damage, safety issues and antimicrobial stewardship principles, it is critical to describe the unique properties of delafloxacin and define its potential role in therapy. The purpose of this article is to review available data pertaining to delafloxacin's biochemistry, pharmacokinetic/pharmacodynamics characteristics, in vitro activity and potential for resistance selection as well as current progress in clinical trials to ultimately assist clinicians in selecting patients who will benefit most from the distinctive properties of this agent.