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  • 1
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    A Multicenter Evaluation of Vancomycin-Associated Acute Kidney Injury in Hospitalized Patients with Acute Bacterial Skin and Skin Structure Infections
    Springer Science and Business Media LLC ; 2020
    In:  Infectious Diseases and Therapy Vol. 9, No. 1 ( 2020-03), p. 89-106
    Details
    In: Infectious Diseases and Therapy, Springer Science and Business Media LLC, Vol. 9, No. 1 ( 2020-03), p. 89-106
    Abstract: We sought to determine the real-world incidence of and risk factors for vancomycin-associated acute kidney injury (V-AKI) in hospitalized adults with acute bacterial skin and skin structure infections (ABSSSI). Methods Retrospective, observational, cohort study at ten U.S. medical centers between 2015 and 2019. Hospitalized patients treated with vancomycin (≥ 72 h) for ABSSSI and ≥ one baseline AKI risk factor were eligible. Patients with end-stage kidney disease, on renal replacement therapy or AKI at baseline, were excluded. The primary outcome was V-AKI by the vancomycin guidelines criteria. Results In total, 415 patients were included. V-AKI occurred in 39 (9.4%) patients. Independent risk factors for V-AKI were: chronic alcohol abuse (aOR 4.710, 95% CI 1.929–11.499), no medical insurance (aOR 3.451, 95% CI 1.310–9.090), ICU residence (aOR 4.398, 95% CI 1.676–11.541), Gram-negative coverage (aOR 2.926, 95% CI 1.158–7.392) and vancomycin duration (aOR 1.143, 95% CI 1.037–1.260). Based on infection severity and comorbidities, 34.7% of patients were candidates for oral antibiotics at baseline and 39.3% had non-purulent cellulitis which could have been more appropriately treated with a beta-lactam. Patients with V-AKI had significantly longer hospital lengths of stay (9 vs. 6 days, p  = 0.001), higher 30-day readmission rates (30.8 vs. 9.0%, p   〈  0.001) and increased all-cause 30-day mortality (5.1 vs. 0.3%, p  = 0.024) Conclusions V-AKI occurred in approximately one in ten ABSSSI patients and may be largely prevented by preferential use of oral antibiotics whenever possible, using beta-lactams for non-purulent cellulitis and limiting durations of vancomycin therapy.
    Type of Medium: Online Resource
    ISSN: 2193-8229 , 2193-6382
    URL: Article
    DOI: 10.1007/s40121-019-00278-1
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2020
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  • 2
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    Multicenter Cohort Study of Ceftaroline Versus Daptomycin for Treatment of Methicillin-Resistant Staphylococcus aureus Bloodstream Infection
    Oxford University Press (OUP) ; 2022
    In:  Open Forum Infectious Diseases Vol. 9, No. 3 ( 2022-03-01)
    Details
    In: Open Forum Infectious Diseases, Oxford University Press (OUP), Vol. 9, No. 3 ( 2022-03-01)
    Abstract: Observational data suggest ceftaroline may be effective for methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infection (BSI), but comparative data with standard of care are limited. This analysis compares the outcomes of MRSA BSI treated with ceftaroline or daptomycin. Methods Multicenter, retrospective, observational cohort study of adult patients with MRSA BSI from 2010 to 2017. Patients treated with ≥72 hours of ceftaroline or daptomycin were included. Those clearing BSI before study drug and those with a pneumonia source were excluded. The primary outcome was composite treatment failure, defined as 30-day mortality, BSI duration ≥7 days on study drug, and 60-day MRSA BSI recurrence. Inverse probability of treatment weighted risk difference in composite failure between daptomycin and ceftaroline groups was computed and 15% noninferiority margin applied. Results Two hundred seventy patients were included; 83 ceftaroline and 187 daptomycin. Ceftaroline was noninferior to daptomycin with respect to composite failure (39% daptomycin, 32.5% ceftaroline; weighted risk difference, 7.0% [95% confidence interval, –5.0% to 19.0%]). No differences between treatment groups was observed for 30-day mortality or other secondary efficacy outcomes. Creatine phosphokinase elevation was significantly more common among daptomycin patients (5.3% vs 0%, P = .034). Rash was significantly more common among ceftaroline patients (10.8 vs 1.1%, P = .001). Conclusions No difference in treatment failure or mortality was observed between MRSA BSI treated with ceftaroline or daptomycin. These data support future study of ceftaroline as a primary MRSA BSI treatment and current use of ceftaroline when an alternative to vancomycin and daptomycin is required.
    Type of Medium: Online Resource
    ISSN: 2328-8957
    URL: Article
    DOI: 10.1093/ofid/ofab606
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
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  • 3
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    Nephrotoxicity of Vancomycin in Combination With Beta-Lactam Agents: Ceftolozane-Tazobactam vs Piperacillin-Tazobactam
    Oxford University Press (OUP) ; 2023
    In:  Clinical Infectious Diseases Vol. 76, No. 3 ( 2023-02-08), p. e1444-e1455
    Details
    In: Clinical Infectious Diseases, Oxford University Press (OUP), Vol. 76, No. 3 ( 2023-02-08), p. e1444-e1455
    Abstract: Vancomycin (VAN)-associated acute kidney injury (AKI) is increased when VAN is combined with certain beta-lactams (BLs) such as piperacillin-tazobactam (TZP) but has not been evaluated with ceftolozane-tazobactam (C/T). Our aim was to investigate the AKI incidence of VAN in combination with C/T (VAN/C/T) compared with VAN in combination to TZP (VAN-TZP). Methods We conducted a multicenter, observational, comparative study across the United States. The primary analysis was a composite outcome of AKI and risk, injury, failure, loss, end stage renal disease; Acute Kidney Injury Network; or VAN-induced nephrotoxicity according to the consensus guidelines. Multivariable logistic regression analysis was conducted to adjust for confounding variables and stratified Kaplan–Meir analysis to assess the time to nephrotoxicity between the 2 groups. Results We included VAN/C/T (n = 90) and VAN-TZP (n = 284) at an enrollment ratio of 3:1. The primary outcome occurred in 12.2% vs 25.0% in the VAN-C/T and VAN-TZP groups, respectively (P = .011). After adjusting for confounding variables, VAN-TZP was associated with increased odds of AKI compared with VAN-C/T; with an adjusted odds ratio of 3.308 (95% confidence interval, 1.560–6.993). Results of the stratified Kaplan–Meir analysis with log-rank time-to-nephrotoxicity analysis indicate that time to AKI was significantly shorter among patients who received VAN-TZP (P = .004). Cox proportional hazards analysis demonstrated that TZP was consistent with the primary analysis (P = .001). Conclusions Collectively, our results suggest that the AKI is not likely to be related to tazobactam but rather to piperacillin, which is a component in VAN-TZP but not in VAN-C/T.
    Type of Medium: Online Resource
    ISSN: 1058-4838 , 1537-6591
    URL: Article
    DOI: 10.1093/cid/ciac670
    RVK:
    XA 10000
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
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  • 4
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    1422. A Multi-Center Evaluation of Omadacycline for Multi-Drug Resistant Infections
    Oxford University Press (OUP) ; 2022
    In:  Open Forum Infectious Diseases Vol. 9, No. Supplement_2 ( 2022-12-15)
    Details
    In: Open Forum Infectious Diseases, Oxford University Press (OUP), Vol. 9, No. Supplement_2 ( 2022-12-15)
    Abstract: Multi-drug resistant (MDR) pathogens are a continuously evolving threat for which there are limited effective treatment modalities. Omadacycline (OMC) is a novel oral and intravenously administered aminomethylcycline with potent in-vitro activity against MDR gram-negative and gram-positive pathogens. Post-marketing data investigating its potential place in the antibiotic armamentarium is limited. This study aimed at describing the clinical success and tolerability of patients receiving OMC for various infections. Methods This was a multicenter, retrospective, observational study conducted from January 2020 to March 30, 2022. We included all patients ≥ 18 years of age that received OMC for any infection not related to Mycobacterium spp. for ≥72 hours. The primary outcome was clinical success at 30 days, defined as survival, the absence of persistence or re-emergence of infection during or after therapy, and the absence of escalation or alteration of OMC. Incidence of adverse effects while on OMC and reasons for OMC utilization were also analyzed. Results This analysis included 19 patients from 10 distinct academic centers. The median age was 50 years (IQR, 37-63), 58% were male, 63% were Caucasian, and the median APACHE II, Charlson and SOFA scores were 10 (IQR 5-12.5), 4 (IQR 2-6.3), and 1 (IQR 0 – 2.25), respectively. Most patients had a bone and joint (8/19, 42.1%) or intra-abdominal infections (4/19, 21.1%), all with positive cultures. Eight patients (44.1%) had a polymicrobial infection and 4 (22.2%) had bacteremia. The most common pathogens encountered were Carbapenem-resistant A. baumannii (5/19, 27.8%), E. coli (5/19, 27.8%), Vancomycin-resistant Enterococcus spp. (4/19, 22.2%), and K. pneumoniae (3/19, 16.7%). Clinical success was observed in 14 patients (74%) and 7 (36.8%) received combination therapy. Adverse drug reactions were reported in 3 patients (15.8%) and of those patients, none discontinued therapy. Reasons for prescribing OMC were mostly attributed to oral availability (12/14, 85.7%) and resistance to other agents (7/14, 50%). Conclusion OMC demonstrated clinical effectiveness and safety against a large number of MDR pathogens. More robust, prospective, comparative studies are needed to confirm our preliminary findings. Disclosures P. Brandon Bookstaver, PharmD, Spero Therapeutics: Advisor/Consultant.
    Type of Medium: Online Resource
    ISSN: 2328-8957
    URL: Article
    DOI: 10.1093/ofid/ofac492.1251
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
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  • 5
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    Clinical Outcomes of Eravacycline in Patients Treated Predominately for Carbapenem-Resistant Acinetobacter baumannii
    American Society for Microbiology ; 2022
    In:  Microbiology Spectrum Vol. 10, No. 5 ( 2022-10-26)
    Details
    In: Microbiology Spectrum, American Society for Microbiology, Vol. 10, No. 5 ( 2022-10-26)
    Abstract: Forty-six patients were treated with eravacycline (ERV) for Acinetobacter baumannii infections, where 69.5% of isolates were carbapenem resistant (CRAB). Infections were primarily pulmonary (58.3%), and most patients received combination therapy (84.4%). The median (IQR) ERV duration was 6.9 days (5.1 to 11.1). Thirty-day mortality was 23.9% in the cohort and 21.9% in CRAB patients. One patient experienced an ERV-possible adverse event. IMPORTANCE Acinetobacter baumannii , particularly when carbapenem resistant (CRAB), is one of the most challenging pathogens in the health care setting. This is complicated by the fact that there is no consensus guideline regarding management of A. baumannii infections. However, the recent Infectious Diseases Society of America guidelines for treatment of resistant Gram-negative infections provided expert recommendations for CRAB management. The panel suggest using minocycline among tetracycline derivatives rather than eravacycline (ERV) until sufficient clinical data are available. Therefore, we present the largest multicenter real-world cohort in patients treated with ERV for A. baumannii , where the majority of isolates were CRAB (69.5%). Our analysis demonstrate that patients treated with ERV-based regimens achieved a 30-day mortality of 23.9% and had a low incidence of ERV-possible adverse events (2.1%). This study is important as it fills the gap in the literature regarding the use of a novel tetracycline (i.e., ERV) in the treatment of this challenging health care infection.
    Type of Medium: Online Resource
    ISSN: 2165-0497
    URL: Article
    DOI: 10.1128/spectrum.00479-22
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2022
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  • 6
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    1288. Evaluation of Predictors for Clinical Success in Patients Treated with Eravacycline for Various Infections
    Oxford University Press (OUP) ; 2021
    In:  Open Forum Infectious Diseases Vol. 8, No. Supplement_1 ( 2021-12-04), p. S733-S733
    Details
    In: Open Forum Infectious Diseases, Oxford University Press (OUP), Vol. 8, No. Supplement_1 ( 2021-12-04), p. S733-S733
    Abstract: Eravacycline (ERV) is approved in the United States (US) for the treatment of complicated intra-abdominal infections in adults. We aimed to evaluate the independent predictors of clinical success in patients treated with ERV for various infections. Methods Multicenter, retrospective, observational study conducted from September, 2018 to April, 2021. We included adults treated with ERV for ≥ 72hours. Clinical success was defined as 30-day survival, lack of 30-day infection-recurrence, and resolution of infection signs/symptoms. All outcomes were measured from ERV initiation. Multivariable logistic regression (MLR) was performed to identify independent predictors of clinical success. Clinically relevant variables were selected for model entry based on bivariate comparisons (P & lt; 0.2) in a backward fashion. Results We included 223 patients from 16 medical centers in 13 geographically unique states. The median (IQR) age was 61 (50-69) years, 57% were male and 62% were Caucasian. Median (IQR) APACHE II, and Charlson Comorbidity scores were 15 (10-21), and 3 (1-5), respectively. Sources of infection were primarily intra-abdominal (27%) and respiratory (27%). Common pathogens included Acinetobacter baumannii (21%) and those of the Enterobacterales order (36%). Infectious diseases consultation and surgical interventions were obtained in 93.7% and 52% respectively. Clinical success occurred in 64%, specifically 30-day survival in 78%, absence of 30-day infection-recurrence in 93%, and 74% experienced resolution of infection signs/symptoms. Since characteristics and outcomes were similar among various pathogens, MLR was conducted using the overall cohort. Skin as a source and combination therapy with ERV were independently associated with higher clinical success: odds ratio 3.3 [CI 1.1-10.2] and 2.9 [1.4-5.9] , respectively. Whereas, ICU admission at culture time and undergoing surgery within 30 days of culture were independently associated with reduced odds of clinical success: 0.4 [0.17-0.80] and 0.3 [0.11-0.63] respectively. Conclusion Although most ERV treated patients experienced clinical success, factors independently associated with higher clinical success are crucial to consider for optimum antibiotic selection. Disclosures Kimberly C. Claeys, PharmD, GenMark (Speaker’s Bureau) Madeline King, PharmD, tetraphase (Speaker’s Bureau) Michael P. Veve, Pharm.D., Cumberland (Grant/Research Support)Paratek Pharmaceuticals (Research Grant or Support) Bruce M. Jones, PharmD, BCPS, Abbvie (Consultant, Advisor or Review Panel member, Speaker’s Bureau)La Jolla (Speaker’s Bureau)Melinta (Consultant)Merck (Consultant)Paratek (Consultant, Speaker’s Bureau) Susan L. Davis, PharmD, Nothing to disclose Michael J. Rybak, PharmD, MPH, PhD, Paratek Pharmaceuticals (Research Grant or Support)
    Type of Medium: Online Resource
    ISSN: 2328-8957
    URL: Article
    DOI: 10.1093/ofid/ofab466.1480
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
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  • 7
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    Weighing the Odds: Novel β-Lactam/β-Lactamase Inhibitor Use in Hospital-Acquired and Ventilator-Associated Pseudomonas aeruginosa Pneumonia for Patients Who Are Morbidly Obese
    Oxford University Press (OUP) ; 2023
    In:  Open Forum Infectious Diseases Vol. 10, No. 9 ( 2023-09-01)
    Details
    In: Open Forum Infectious Diseases, Oxford University Press (OUP), Vol. 10, No. 9 ( 2023-09-01)
    Abstract: Pseudomonas aeruginosa is a leading cause of hospital-acquired and ventilator-associated bacterial pneumonia (HABP/VABP). Novel β-lactam/β-lactamase inhibitor (BL/BLI) combinations are often used for these infections; however, limited data exist to guide the dosing of BL/BLI in patients who are morbidly obese. Thus, we sought to evaluate the clinical and safety endpoints of patients who are morbidly obese (body mass index ≥35 kg/m2) and non–morbidly obese ( & lt;35 kg/m2) and receiving BL/BLI for P aeruginosa HABP/VABP. Methods This retrospective study was based on a cohort of patients hospitalized at 2 urban academic medical centers in Detroit, Michigan, from August 2014 through February 2021 with P aeruginosa HABP/VABP who were receiving BL/BLI (ceftazidime/avibactam, ceftolozane/tazobactam, or meropenem/vaborbactam) for ≥72 continuous hours. The primary endpoint was presumed treatment failure, defined as the presence of all-cause in-hospital mortality or the continuation of infectious symptoms. Analyses were adjusted for possible confounding with inverse probability of treatment weighting. Multivariable regression was used to identify predictors of treatment failure. Results In total, 285 patients with HABP (61.4%) and/or VABP (56.1%) were enrolled (morbidly obese, n = 95; non–morbidly obese, n = 190). The median Acute Physiology and Chronic Health Evaluation II score was 23 (IQR, 13–26), and 60% of patients were admitted to the intensive care unit at index culture collection. Patients who were morbidly obese demonstrated significantly greater odds of presumed treatment failure vs those who were non–morbidly obese (58.9% vs 37.9%, respectively; adjusted odds ratio, 1.675 [95% CI, 1.465–1.979]). In multivariable analysis, morbid obesity (1.06; 95% CI, 1.02–1.79), prolonged time to BL/BLI initiation (1.47; 95% CI, 1.28–2.66), renal dose–adjusted BL/BLI in the first 48 hours of therapy (1.12; 95% CI, 1.09–1.75), and continuous renal replacement therapy during BL/BLI therapy (1.35; 95% CI, 1.06–1.68) were independently associated with increased odds of presumed treatment failure. Conclusions Among hospitalized patients receiving BL/BLI for P aeruginosa HABP/VABP, those who were morbidly obese had significantly greater odds of presumed treatment failure when compared with those who were non–morbidly obese.
    Type of Medium: Online Resource
    ISSN: 2328-8957
    URL: Article
    DOI: 10.1093/ofid/ofad454
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
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  • 8
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    High-dose Cefepime vs Carbapenems for Bacteremia Caused by Enterobacterales With Moderate to High Risk of Clinically Significant AmpC β-lactamase Production
    Oxford University Press (OUP) ; 2023
    In:  Open Forum Infectious Diseases Vol. 10, No. 3 ( 2023-03-03)
    Details
    In: Open Forum Infectious Diseases, Oxford University Press (OUP), Vol. 10, No. 3 ( 2023-03-03)
    Abstract: Limited data suggest that serious infections caused by Enterobacterales with a moderate to high risk of clinically significant AmpC production can be successfully treated with cefepime if the cefepime minimum inhibitory concentration (MIC) is ≤2 µg/mL. However, isolates with a cefepime-susceptible dose-dependent (SDD) MIC of 4–8 µg/mL should receive a carbapenem due to target attainment and extended-spectrum β-lactamase (ESBL) concerns. Methods This was a retrospective cohort study of hospitalized patients with E. cloacae, K. aerogenes, or C. freundii bacteremia from January 2015 to March 2022 receiving high-dose cefepime or a carbapenem. Cox regression models were used with incorporation of inverse probability of treatment weighting and time-varying covariates. Results Of the 315 patients included, 169 received cefepime and 146 received a carbapenem (ertapenem n = 90, meropenem n = 56). Cefepime was not associated with an increased risk of 30-day mortality compared with carbapenem therapy (adjusted hazard ratio [aHR], 1.45; 95% CI, 0.79–2.14), which was consistent for patients with cefepime SDD isolates (aHR, 1.19; 95% CI, 0.52–1.77). Multivariable weighted Cox models identified Pitt bacteremia score & gt;4 (aHR, 1.41; 95% CI, 1.04–1.92), deep infection (aHR, 2.27; 95% CI, 1.21–4.32), and ceftriaxone-resistant AmpC-E (aHR, 1.32; 95% CI, 1.03–1.59) to be independent predictors associated with increased mortality risk, while receipt of prolonged-infusion β-lactam was protective (aHR, 0.67; 95% CI, 0.40–0.89). Conclusions Among patients with bacteremia caused by Enterobacterales with moderate to high risk of clinically significant AmpC production, these data demonstrate similar risk of 30-day mortality for high-dose cefepime or a carbapenem as definitive β-lactam therapy.
    Type of Medium: Online Resource
    ISSN: 2328-8957
    URL: Article
    DOI: 10.1093/ofid/ofad034
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
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  • 9
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    1082. Real-World Experience with Omadacycline for Nontuberculous Mycobacterial Infections: A Multicenter Evaluation
    Oxford University Press (OUP) ; 2021
    In:  Open Forum Infectious Diseases Vol. 8, No. Supplement_1 ( 2021-12-04), p. S632-S633
    Details
    In: Open Forum Infectious Diseases, Oxford University Press (OUP), Vol. 8, No. Supplement_1 ( 2021-12-04), p. S632-S633
    Abstract: Nontuberculous mycobacteria (NTM) are resistant to numerous antibiotics and lead to significant morbidity and mortality. Omadacycline (OMC) is an aminomethylcycline antibiotic that is Food and Drug Administration-approved for acute bacterial skin and skin structure infections and community-acquired bacterial pneumonia. Furthermore, OMC has shown in vitro activity against NTM. Given that real-world evidence is lacking, our primary objective was to evaluate the clinical success and tolerability of OMC when used for a variety of NTM infections. Methods This was a multicenter, retrospective, observational study conducted from January 2020 to June 2021. We included all patients ≥ 18 years of age that received OMC of any indication for Mycobacterium spp. The primary outcome was clinical success, defined as a lack of all-cause mortality, lack of persistence or re-emergence of infection during or after therapy, and lack of alteration of OMC. Incidence of adverse effects potentially attributable to OMC and reasons for OMC utilization were also analyzed. Results A total of 31 patients were included from 12 geographically distinct academic health systems (median age: 57 (IQR, 45-63) years; 45% male; 81% Caucasian). The majority of isolated pathogens were Mycobacterium abscessus complex (84%) and of those with subspeciation performed (54%), the majority (86%) were subsp. abscessus. The primary infections were of pulmonary origin (67%) and the median (IQR) duration of OMC therapy was 5.3 (3.2-9.4) months. Most isolates did not have OMC susceptibility conducted (87%), while the majority did for tigecycline (90%). Clinical success was reported in 81% of the population. Most patients were on combination antimicrobial therapy, and 39% of patients reported an adverse effect while on OMC (58% gastrointestinal distress). The majority of patients were prescribed OMC due to ease of administration (61%) and antimicrobial resistance to previous antibiotics (42%). Conclusion OMC may be a potential option for the therapy of NTM infections. Prospective, randomized clinical trials are needed to confirm our preliminary findings. Disclosures Julie V. Philley, MD, Paratek Pharmaceuticals (Advisor or Review Panel member)Paratek Pharmaceuticals, Inc. (Consultant) Michael P. Veve, Pharm.D., Cumberland (Grant/Research Support)Paratek Pharmaceuticals (Research Grant or Support) Michael J. Rybak, PharmD, MPH, PhD, Paratek Pharmaceuticals (Research Grant or Support)
    Type of Medium: Online Resource
    ISSN: 2328-8957
    URL: Article
    DOI: 10.1093/ofid/ofab466.1276
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
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  • 10
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    Real-World, Multicenter Case Series of Patients Treated with Oral Omadacycline for Resistant Gram-Negative Pathogens
    Springer Science and Business Media LLC ; 2022
    In:  Infectious Diseases and Therapy
    Details
    In: Infectious Diseases and Therapy, Springer Science and Business Media LLC
    Type of Medium: Online Resource
    ISSN: 2193-8229 , 2193-6382
    URL: Article
    DOI: 10.1007/s40121-022-00645-5
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
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