1625. Real-World Outpatient Utilization of Ceftolozane/Tazobactam in Physician Office Infusion Centers (OICs)

Abstract Background Ceftolozane/tazobactam (C/T) is indicated for the treatment (tx) of complicated Gram-negative infections including urinary tract infection (cUTI), intra-abdominal infection (cIAI), and hospital-acquired/ventilator-associated bacterial pneumonias caused by susceptible bacteria. Real-world data on the use of C/T are limited. We present a multicenter observational review of C/T outpatient utilization in Infectious Disease OICs. Methods Medical records of patients (pts) who received C/T for ≥3 doses from May 2015 to Sept 2019 were reviewed. Data included demographics, diagnosis, disease history, pathogens, C/T tx hospitalizations, emergency department (ED) visits and clinical outcomes. Clinical success was defined as complete or partial symptom resolution at completion of C/T with oral antibiotics as needed. Persistent infection and early discontinuation (D/C) of C/T were deemed non-successful. Indeterminant outcomes were deemed non-evaluable. Chi Square, Fisher’s exact, and t-tests were used to identify characteristics associated with clinical outcome. Results 120 pts (mean age: 59±15 years, 60% male) from 33 OICs were identified. Median Charlson score was 5 (IQR, 3-7), with 43% immunocompromised, and 77% refractory/recurrent disease. Primary infections were bone and joint (25%), cUTI, (24%), respiratory tract (18%), cIAI (18%), complicated skin and skin-structure (12%), and bacteremia/endocarditis (3%). Most pts had multi-drug resistant Gram-negative pathogens (80/108; 74%), predominantly Pseudomonas aeruginosa. Polymicrobial infections were reported in 44%. Median duration of C/T therapy was 21 days (IQR, 14-34). C/T was initiated in the OIC in 59% of pts. Overall clinical success was 86% (100/117), with rates by infection type in Fig 1. Non-success was reported in 17, 10 due to persistent infection and 7 due to adverse events. The adverse events led to early D/C of C/T, all with resolution. Statistically, infection type did not impact success rate. Hospitalizations and ED visits during tx occurred in 5% of pts with successful outcomes and 35% of pts with non-successful outcomes (p < 0.001). Fig 1. Clinical success rates of C/T by infection type Conclusion These real-world results support the effectiveness of C/T in a wide variety of complicated Gram-negative infections treated in the outpatient setting. Disclosures Lucinda J. Van Anglen, PharmD, Merck & Co. (Grant/Research Support) Ramesh V. Nathan, MD, FIDSA, Merck & Co. (Other Financial or Material Support, Grant Steering Committee Member) Brian S. Metzger, MD, MPH, Allergan (Speaker’s Bureau)Cumberland (Speaker’s Bureau)Melinta (Speaker’s Bureau)

Download Full-text

Systematic Literature Review of Real-World Evidence of C Eftolozane/Tazobactam for the Treatment of Respiratory Infections

10.21203/rs.3.rs-415191/v1 ◽

2021 ◽

Author(s):

Laura Puzniak ◽

Ryan Dillon ◽

Thomas Palmer ◽

Hannah Collings ◽

Ashley Enstone

Keyword(s):

Clinical Trials ◽

Literature Review ◽

Systematic Literature Review ◽

Real World ◽

Bacterial Pneumonia ◽

Respiratory Infections ◽

Clinical Success ◽

Multidrug Resistant ◽

Success Rates ◽

Gram Negative

Abstract Background: Gram-negative nosocomial pneumonia (NP), including hospital-acquired bacterial pneumonia (HABP), ventilated HABP (vHABP), and ventilator-associated bacterial pneumonia (VABP), is a significant cause of morbidity and mortality. Common pathogens, including Enterobacterales and Pseudomonas aeruginosa are highly prevalent in healthcare settings and have few effective treatment options due to high rates of antibacterial resistance. Resistant pathogens are associated with significantly worse outcomes and higher costs, relative to patients with susceptible infections. Ceftolozane/tazobactam (C/T) has established efficacy in clinical trials of patients with NP. This review aimed to collate data on C/T use for HABP/vHABP/VABP infections in real-world clinical practice. Methods: This systematic literature review searched online biomedical databases for real-world studies of C/T for gram-negative respiratory tract infections (RTIs) up to June 2020. Relevant study, patient, and treatment characteristics, microbiology, and efficacy outcomes were captured.Results: Thirty-three studies comprising 658 patients were identified. Pneumonia was the most common infection C/T was used to treat (85%), with a smaller number of unspecified RTIs (9%) and tracheobronchitis (5%) reported. Data on severity of illness and comorbidity were inconsistently reported. The majority of patients had respiratory infections caused by P. aeruginosa (92.8%), of which 88.1% were multidrug-resistant (including extensively drug-resistant or pandrug-resistant). Examination of these studies demonstrated an increase in the percentage of patients receiving the recommended dose of C/T for respiratory infections (3 g q8h or renal impairment-adjusted) over time (36.8% of patients in 2017 to 71.5% in 2020). Clinical success rates ranged from 51.4–100%, with 10 studies (55.6% of studies reporting clinical success) reporting clinical success rates of >70%; microbiological success rates ranged from 57.0–100.0%, with three studies (60.0% of studies reporting microbiological success) reporting microbiological success rates of >70%. Thirty-day mortality ranged from 0.0–33.0%, with nine studies (90% of studies reporting mortality) reporting 30-day mortality of <30%. Conclusions: The studies identified in this review demonstrate that C/T shows similar outcomes as those seen in clinical trials, despite the higher frequency of multidrug-resistant pathogens, and comorbidities/conditions that may have been excluded from the trials.

Download Full-text

2248. Clinical and Microbiological Outcomes Associated with Real-World Use of Ceftolozane/Tazobactam

Open Forum Infectious Diseases ◽

10.1093/ofid/ofz360.1926 ◽

2019 ◽

Vol 6 (Supplement_2) ◽

pp. S768-S769 ◽

Cited By ~ 1

Author(s):

Nicolo Cabrera ◽

Truc T Tran ◽

William R Miller ◽

An Q Dinh ◽

Blake Hanson ◽

...

Keyword(s):

Urinary Tract ◽

Real World ◽

Clinical Success ◽

Therapeutic Option ◽

Signs And Symptoms ◽

Outcome Data ◽

Advisory Board ◽

Hospital System ◽

Gram Negative ◽

Tract Infections

Abstract Background Ceftolozane/tazobactam (C/T) is a novel cephalosporin/β-lactamase inhibitor combination for treating Gram-negative infections, particularly Pseudomonas aeruginosa (PA). C/T has been FDA-approved for complicated intra-abdominal and urinary tract infections and has just completed a trial in ventilator nosocomial pneumonia, but real-world outcome data are still emerging. Methods Demographic, microbiologic, treatment and outcome data of patients who received C/T for ≥48 hours from January 2016 to August 2018 at multiple centers within a single hospital system were retrospectively collected. Available isolates were analyzed for C/T susceptibility (by Etest) and whole-genome sequencing (WGS). Spades v.3.11.1 was used for assembly, multi-locus sequence typing v2.10 performed for in silico MLST with the PubMLST database and Abricate v0.7 was used for resistance gene screening with the CARD database. Results Among 45 patients, 58% were non-white, 53% were female and 13% were immunocompromised. The median age was 64 years (IQR, 50 to 69). At the time of the index event, a high proportion of patients required ICU care (42%) and pressor support (13%) as well as had invasive devices in place (64%). A minority (2.4%) had prior exposure to C/T. Respiratory infections were most common (38%) followed by urinary tract (20%). Concomitant Gram-negative agents were used in 18%. 69% achieved clinical success (i.e., recovery from infection-related signs and symptoms). The in-hospital mortality rate was 16% of which 5 out of 7 were attributed to infection. Microbiology was available for 91% of patients; 84% had PA isolates resistant to at least 3 antipseudomonal classes (Figures 1 and 2). Ten PA isolates were analyzed with WGS (Table 1). C/T resistance arose during therapy in one patient (MIC increase from 1 to 128 µg/mL). WGS showed a substitution in AmpC β-lactamase (A46D) and presence of blaCARB-2. Conclusion Although C/T was used in a critically ill population with highly resistant organisms, cure rates were high and mortality was low. Acquired β-lactamases were not frequently seen among the PA isolates. C/T is a vital therapeutic option, particularly on MDR isolates for which options are limited. Disclosures Samuel L. Aitken, PharmD, Melinta Therapeutoics: Grant/Research Support, Research Grant; Merck, Sharpe, and Dohme: Advisory Board; Shionogi: Advisory Board.

Download Full-text

1290. Real-World Experience with Omadacycline for Nontuberculous Mycobacterial and Gram-Negative Infections: A Multicenter Evaluation

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.1473 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S660-S660

Author(s):

Taylor Morrisette ◽

Julie V Philley ◽

Carly Sigler ◽

Jeremy J Frens ◽

Andrew J Webb ◽

...

Keyword(s):

Real World ◽

Primary Outcome ◽

Clinical Success ◽

Outpatient Setting ◽

Mycobacterium Abscessus ◽

Oral Agent ◽

Gram Negative ◽

Gastrointestinal Distress ◽

Gram Negative Organisms

Abstract Background Omadacycline (OMC) is an aminomethylcycline antibiotic in the tetracycline class that has been Food and Drug Administration-approved for acute bacterial skin and skin structure infections and community-acquired bacterial pneumonia. OMC has been shown to have potent in vitro activity against a broad-spectrum of Gram-positive and Gram-negative organisms, as well as Nontuberculous Mycobacteria (NTM). Due to it’s unique activity and availability as an oral agent, off-label use of OMC has been increasing. We evaluated the real-world effectiveness and safety of OMC for a variety of infections. Methods This was a multicenter, retrospective, observational study that was conducted from January 2020 to June 2020. We included all patients ≥ 18 years of age that received OMC for ≥ 72 hours for any indication and/or pathogen. The primary outcome was clinical success, defined as a lack of 30-day (non-NTM) or 90-day (NTM) mortality or microbiologic recurrence and absence of therapy escalation or alteration. Reasons for OMC utilization and incidence of potential adverse effects attributable to OMC were also analyzed. Results A total of 18 patients were included from six geographically distinct academic health systems (median age: 56 (IQR, 49-60.5) years; 61% male; 72% Caucasian). The majority of OMC use was in NTM (61%; 100% Mycobacterium abscessus) and in Acinetobacter baumannii (22%) for bone/joint (39%) and respiratory tract (33%) infections. OMC was used primarily in the outpatient setting alone (83%) and most isolates did not have OMC susceptibility conducted (89%). Clinical success was reported in 83% of the total population (71% non-NTM and 91% NTM). The majority of patients were prescribed OMC due to antimicrobial resistance to previous antibiotic(s) (61%) and/or due to OMC’s availability as an oral agent (44%). Three patients experienced side effects while on therapy (serum creatinine elevation, AST/ALT increase, and gastrointestinal distress). Conclusion OMC appears to be effective and well-tolerated for a variety of infections caused by various pathogens, including M. abscessus and A. baumannii. Disclosures Michael J. Rybak, PharmD, MPH, PhD, Paratek (Grant/Research Support)

Download Full-text

Real-world use of ceftolozane/tazobactam: a systematic literature review

Antimicrobial Resistance and Infection Control ◽

10.1186/s13756-021-00933-8 ◽

2021 ◽

Vol 10 (1) ◽

Author(s):

Laura Puzniak ◽

Ryan Dillon ◽

Thomas Palmer ◽

Hannah Collings ◽

Ashley Enstone

Keyword(s):

Clinical Practice ◽

Literature Review ◽

Systematic Literature Review ◽

Real World ◽

Comparative Studies ◽

Clinical Success ◽

Mortality Rates ◽

Success Rates ◽

Gram Negative ◽

Seriously Ill

Abstract Background Antibacterial-resistant gram-negative infections are a serious risk to global public health. Resistant Enterobacterales and Pseudomonas aeruginosa are highly prevalent, particularly in healthcare settings, and there are limited effective treatment options. Patients with infections caused by resistant pathogens have considerably worse outcomes, and incur significantly higher costs, relative to patients with susceptible infections. Ceftolozane/tazobactam (C/T) has established efficacy in clinical trials. This review aimed to collate data on C/T use in clinical practice. Methods This systematic literature review searched online biomedical databases for real-world studies of C/T for gram-negative infections up to June 2020. Relevant study, patient, and treatment characteristics, microbiology, and efficacy outcomes were captured. Results There were 83 studies comprising 3,701 patients were identified. The most common infections were respiratory infections (52.9% of reported infections), urinary tract infections (UTIs; 14.9%), and intra-abdominal infections (IAIs; 10.1%). Most patients included were seriously ill and had multiple comorbidities. The majority of patients had infections caused by P.aeruginosa (90.7%), of which 86.0% were antimicrobial-resistant. C/T was used as both a 1.5 g q8h and 3 g q8h dose, for a median duration of 7–56 days (varying between studies). Outcome rates were comparable between studies: clinical success rates ranged from 45.7 to 100.0%, with 27 studies (69%) reporting clinical success rates of > 70%; microbiological success rates ranged from 31 to 100%, with 14 studies (74%) reporting microbiological success rates of > 70%. Mortality rates ranged from 0 to 50%, with 31 studies (69%) reporting mortality rates of ≤ 20%. In comparative studies, C/T was as effective as aminoglycoside- or polymyxin-based regimens, and in some instances, significantly more effective. Conclusions The studies identified in this review demonstrate that C/T is effective in clinical practice, despite the diverse group of seriously ill patients, different levels of resistance of the pathogens treated, and varying dosing regimens used. Furthermore, comparative studies suggest that C/T offers a successful alternative to standard of care (SoC).

Download Full-text

1270. Early Real-world Evidence in the Use of Eravacycline for the Management of Draconian Infections

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.1454 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S651-S652

Author(s):

Amy Carr ◽

Amer El Ghali ◽

Parminder Kaur ◽

Sarah B Minor ◽

Anthony M Casapao

Keyword(s):

Clinical Outcome ◽

Median Duration ◽

Real World ◽

Clinical Success ◽

Infection Type ◽

Case Series ◽

Retrospective Case ◽

Off Label ◽

Carbapenem Resistant

Abstract Background Eravacycline (ERV) is a next-generation tetracycline approved for complicated intra-abdominal infections (cIAI) with in-vitro activity to multidrug-resistant organisms such as carbapenem resistant Enterobacteriaceae, extended spectrum beta-lactamase, and carbapenem-resistant Acinetobacter baumannii (CRAB). The purpose of this study was to identify the utility of ERV in clinical practice. Methods Retrospective case series was conducted on patients at AdventHealth that received at least two doses of ERV. Primary endpoint for the study was clinical success while on ERV, meeting none of the following criteria: changing therapy, mortality, or lack of improvement from sign/symptoms. Results Of 23 patients, 74% were males with a mean age of 55 ±18 years and mean body weight of 79 ±27 kg. Mean APACHE II and Charleson scores were 20 (±11) and 6 (±4), respectively. 91% received ERV for an off-label indication or organism. Infection types were respiratory (44%), cIAI (35%), skin (9%), and other (13%). All patients had positive cultures, while 61% were treated as a polymicrobial infection and 17% had bacteremia. Microorganisms included A. xylosoxidans, S. maltophilia, CRAB, and K pneumoniae. 48% had ERV susceptibilities from .06-4 mcg/mL, including two MIC ≥32mcg/mL for S. maltophilia. 70% were given another antibiotic prior to ERV with a median duration of 5 (1-35) days. Median duration of ERV was 8 (3-30) days. 83% percent received ERV in combination with another antibiotic. During treatment, 26% had a Child-Pugh Class C at baseline and 30% had elevated liver function tests. No adverse drug reactions were reported. Upon discharge, 35% continued ERV. Clinical success was observed in 57% (12/21) of patients. Clinical outcome by infection type is summarized in Figure 1. Of 9 cases of clinical failure, 14% were changed to alternative, 19% died while on ERV, and 10% failed to resolve signs/symptoms. Two cases of M. abscessus infections had insufficient follow-up to assess clinical outcome. Figure 1. Eravacycline Clinical Outcome by Infection Type Conclusion Initial real-world experience with ERV differs significantly from the trials regarding severity of illness, types of infection, and clinical outcomes. Further evaluation is necessary for using ERV as combination therapy and in off-label indications. Disclosures All Authors: No reported disclosures

Download Full-text

Real-world Use of Ceftolozane/tazobactam: a Systematic Literature Review

10.21203/rs.3.rs-136462/v1 ◽

2020 ◽

Author(s):

Laura Puzniak ◽

Ryan Dillon ◽

Thomas Palmer ◽

Hannah Collings ◽

Ashley Enstone

Keyword(s):

Clinical Practice ◽

Literature Review ◽

Systematic Literature Review ◽

Real World ◽

Comparative Studies ◽

Clinical Success ◽

Mortality Rates ◽

Success Rates ◽

Gram Negative ◽

Seriously Ill

Abstract Background: Antibacterial-resistant gram-negative infections are a serious risk to global public health. Resistant Enterobacterales and Pseudomonas aeruginosa are highly prevalent, particularly in healthcare settings, and there are limited effective treatment options. Patients with infections caused by resistant pathogens have considerably worse outcomes, and significantly higher costs, relative to patients with susceptible infections. Ceftolozane/tazobactam (C/T) has established efficacy in clinical trials. This review aimed to collate data on C/T use in clinical practice.Methods: This systematic literature review searched online biomedical databases for real-world studies of C/T for gram-negative infections. Relevant study, patient, and treatment characteristics, microbiology, and efficacy outcomes were captured.Results: There were 83 studies comprising 3,701 patients were identified. The most common infections were respiratory infections (52.9% of reported infections), urinary tract infections (UTIs; 14.9%), and intra-abdominal infections (IAIs; 10.1%). Most patients included were seriously ill and had multiple comorbidities. The majority of patients had infections caused by P. aeruginosa (90.7%), of which 86.0% were antimicrobial-resistant. C/T was used as both a 1.5 g q8h and 3 g q8h dose, for a median duration of 7–56 days (varying between studies). Outcome rates were comparable between studies: clinical success rates ranged from 45.7–100.0%, with 27 studies (69%) reporting clinical success rates of >70%; microbiological success rates ranged from 31–100%, with 14 studies (74%) reporting microbiological success rates of >70%. Mortality rates ranged from 0–50%, with 31 studies (69%) reporting mortality rates of ≤20%. In comparative studies, C/T was as effective as aminoglycoside- or polymyxin-based regimens, and in some instances, significantly more effective.Conclusions: The studies identified in this review demonstrate that C/T is effective in clinical practice, despite the diverse group of seriously ill patients, different levels of resistance of the pathogens treated, and varying dosing regimens used. Furthermore, comparative studies suggest that C/T offers a successful alternative to standard of care (SoC).

Download Full-text

1242. Efficacy and Safety of Intravenous Fosfomycin for the Treatment of Multi-resistant Gram Negative Infections

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab466.1434 ◽

2021 ◽

Vol 8 (Supplement_1) ◽

pp. S710-S710

Author(s):

Tasneem Abdallah ◽

Reem Elajez ◽

Tawheeda Ibrahim ◽

Abeir Alimam ◽

Ali S Omrani

Keyword(s):

Adverse Events ◽

Safety Profile ◽

Primary Outcome ◽

Clinical Success ◽

Signs And Symptoms ◽

Resistance Pattern ◽

Efficacy And Safety ◽

Gram Negative ◽

Microbiological Characteristics

Abstract Background To describe the clinical use, efficacy and safety of intravenous (IV) fosfomycin in the treatment of infections caused by Gram-negative bacteria (GNB). Methods Hospitalized patients who received ≥48 hours of IV fosfomycin therapy during September 27, 2017 thru January 31, 2020 were included. The primary outcome was the proportion of subjects with clinical improvement at the end of IV fosfomycin therapy; defined as resolution of baseline signs and symptoms of infection. Results Thirty patients were included, of which 19 (63.3%) were males, and the median age was 63.5 years (interquartile range 46─73). Frequent risk factors for GNB infection included hospitalization (23, 76%), receipt of broad-spectrum antibiotics (15, 50%), and surgery (10, 33.3%), all within the preceding 90 days. Urinary tract infection (17, 56.7%) was the most common indication for use of IV fosfomycin, followed by bacteremia (4, 13.3), and skin and soft tissue infections (4, 13.3%). Kelbsiella pneumoniae (17, 56.7%), Escherichia coli (7, 23.3%) and Pseudomonas species (4, 13.3%) were the most common target pathogens. Almost all target pathogens (29, 96.7%) were resistant in vitro to ≥1 agent from ≥3 different antimicrobial classes. The primary outcome was achieved in 22 (73.3%) patients. The most frequently observed adverse events were hypokalemia (13, 43.3%) and hypernatremia (7, 23.3%). However, the majority of adverse events were classified as Grade 1 or Grade 2 severity. Microbiological characteristics The table describes microbiological characteristics of the isolated organism species, resistance pattern, development of fosfomycin resistance Management outcomes and safety profile The table describes percentage of primary outcome (clinical success ) along with safety profile and mortality rate Conclusion IV fosfomycin is a potentially effective and safe option for the treatment of patient with GNB infections. Disclosures All Authors: No reported disclosures

Download Full-text

Real-world Multicenter Analysis of Clinical Outcomes and Safety of Meropenem-Vaborbactam in Patients Treated for Serious Gram-Negative Bacterial Infections

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa051 ◽

2020 ◽

Vol 7 (3) ◽

Cited By ~ 5

Author(s):

Sara Alosaimy ◽

Sarah C J Jorgensen ◽

Abdalhamid M Lagnf ◽

Sarah Melvin ◽

Ryan P Mynatt ◽

...

Keyword(s):

Clinical Outcomes ◽

Real World ◽

Bacterial Infections ◽

Clinical Success ◽

Gram Negative ◽

Carbapenem Resistant ◽

Multicenter Analysis ◽

Carbapenem Resistant Enterobacteriaceae

Abstract Fourty patients were treated with meropenem-vaborbactam (MEV) for serious Gram-negative bacterial (GNB) infections. Carbapenem-resistant Enterobacteriaceae (CRE) comprised 80.0% of all GNB infections. Clinical success occurred in 70.0% of patients. Mortality and recurrence at 30 days were 7.5% and 12.5%, respectively. One patient experienced a probable rash due to MEV.

Download Full-text

Clinical Experience with Ceftazidime-Avibactam for the Treatment of Infections due to Multidrug-Resistant Gram-Negative Bacteria Other than Carbapenem-Resistant Enterobacterales

Antibiotics ◽

10.3390/antibiotics9020071 ◽

2020 ◽

Vol 9 (2) ◽

pp. 71 ◽

Cited By ~ 9

Author(s):

Antonio Vena ◽

Daniele Giacobbe ◽

Nadia Castaldo ◽

Annamaria Cattelan ◽

Cristina Mussini ◽

...

Keyword(s):

Adverse Events ◽

Primary Infection ◽

Clinical Success ◽

Therapeutic Option ◽

Gram Negative Bacteria ◽

Gram Negative ◽

Extended Spectrum Beta Lactamase ◽

Carbapenem Resistant ◽

Serious Infections

Background: Experience in real clinical practice with ceftazidime-avibactam for the treatment of serious infections due to gram−negative bacteria (GNB) other than carbapenem-resistant Enterobacterales (CRE) is very limited. Methods: We carried out a retrospective multicenter study of patients hospitalized in 13 Italian hospitals who received ≥72 h of ceftazidime-avibactam for GNB other than CRE to assess the rates of clinical success, resistance development, and occurrence of adverse events. Results: Ceftazidime-avibactam was used to treat 41 patients with GNB infections other than CRE. Median age was 62 years and 68% of them were male. The main causative agents were P. aeruginosa (33/41; 80.5%) and extended spectrum beta lactamase (ESBL)-producing Enterobacterales (4/41, 9.8%). Four patients had polymicrobial infections. All strains were susceptible to ceftazidime-avibactam. The most common primary infection was nosocomial pneumonia (n = 20; 48.8%), primary bacteremia (n = 7; 17.1%), intra-abdominal infection (n = 4; 9.8%), and bone infection (n = 4; 9.8%). Ceftazidime-avibactam was mainly administered as a combination treatment (n = 33; 80.5%) and the median length of therapy was 13 days. Clinical success at the end of the follow-up period was 90.5%, and the only risk factor for treatment failure at multivariate analysis was receiving continuous renal replacement therapy during ceftazidime-avibactam. There was no association between clinical failures and type of primary infection, microbiological isolates, and monotherapy with ceftazidime-avibactam. Only one patient experienced recurrent infection 5 days after the end of treatment. Development of resistance to ceftazidime-avibactam was not detected in any case during the whole follow-up period. No adverse events related to ceftazidime-avibactam were observed in the study population. Conclusions: Ceftazidime-avibactam may be a valuable therapeutic option for serious infections due to GNB other than CRE.

Download Full-text

A Randomized, Evaluator-Blind, Phase 2 Study Comparing the Safety and Efficacy of Omadacycline to Those of Linezolid for Treatment of Complicated Skin and Skin Structure Infections

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00948-12 ◽

2012 ◽

Vol 56 (11) ◽

pp. 5650-5654 ◽

Cited By ~ 58

Author(s):

Gary J. Noel ◽

Michael P. Draper ◽

Howard Hait ◽

S. Ken Tanaka ◽

Robert D. Arbeit

Keyword(s):

Adverse Events ◽

Clinical Success ◽

Phase 2 ◽

Success Rates ◽

Safety And Efficacy ◽

Content Type ◽

Skin Structure ◽

Phase 2 Trial ◽

Complicated Skin ◽

Intent To Treat

ABSTRACTA randomized, investigator-blind, multicenter phase 2 trial involving patients with complicated skin and skin structure infections (cSSSI) compared the safety and efficacy of omadacycline, a broad-spectrum agent with activity against methicillin-resistantStaphylococcus aureus(MRSA), to those of linezolid (with or without aztreonam). Patients were randomized 1:1 to omadacycline (100 mg intravenously [i.v.] once a day [QD] with an option to transition to 200 mg orally QD) or linezolid (600 mg i.v. twice daily [BID] with an option to transition to 600 mg orally BID) at 11 U.S. sites. Patients suspected or documented to have infections caused by Gram-negative bacteria were given aztreonam (2 g i.v. every 12 h [q12h]) if randomized to linezolid or matching placebo infusions if randomized to omadacycline. Adverse events were reported in 46 (41.4%) omadacycline-treated and 55 (50.9%) linezolid-treated patients. Adverse events related to treatment were assessed by investigators in 24 (21.6%) omadacycline-treated and 33 (30.6%) linezolid-treated patients. The gastrointestinal tract was most commonly involved, with adverse events reported in 21 (18.9%) patients exposed to omadacycline and 20 (18.5%) exposed to linezolid. Rates of successful clinical response in the intent-to-treat (ITT) and clinical evaluable (CE) populations favored omadacycline (ITT, 88.3% versus 75.9%; 95% confidence interval [CI], 1.9 to 22.9; CE, 98.0% versus 93.2%; 95% CI, −1.7 to 11.3). For microbiologically evaluable (ME) patients withS. aureusinfections, the clinical success rates were 97.2% (70/72) in omadacycline-treated and 92.7% (51/55) in linezolid-treated patients. This phase 2 experience supports conclusions that omadacycline is well tolerated in cSSSI patients and that this aminomethylcycline has potential to be an effective treatment for serious skin infections.

Download Full-text