Baxdela Drug Information
Generic name: DELAFLOXACIN MEGLUMINE
Uses of Baxdela
Acute Bacterial Skin and Skin Structure Infections
BAXDELA is indicated in adults for the treatment of acute bacterial skin and skin structure infections (ABSSSI) caused by the following susceptible microorganisms: Staphylococcus aureus (including methicillin-resistant and methicillin-susceptible isolates), Staphylococcus haemolyticus, Staphylococcus lugdunensis, Streptococcus agalactiae, Streptococcus anginosus Group (including Streptococcus anginosus, Streptococcus intermedius, and Streptococcus constellatus ), Streptococcus pyogenes, Enterococcus faecalis, Escherichia coli, Enterobacter cloacae, Klebsiella pneumoniae, and Pseudomonas aeruginosa.
Community-Acquired Bacterial Pneumonia
BAXDELA is indicated in adults for the treatment of community-acquired bacterial pneumonia (CABP) caused by the following susceptible microorganisms: Streptococcus pneumoniae, Staphylococcus aureus (methicillin-susceptible isolates only), Klebsiella pneumoniae, Escherichia coli, Pseudomonas aeruginosa, Haemophilus influenzae, Haemophilus parainfluenzae, Chlamydia pneumoniae, Legionella pneumophila, and Mycoplasma pneumoniae.
Usage To reduce the development of drug-resistant bacteria and maintain the effectiveness
of BAXDELA and other antibacterial drugs, BAXDELA should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.
Dosage & Administration of Baxdela
| Oral | Intravenous | |
| 30-89 | No dosage adjustment | |
| 15-29 | No dosage adjustment | |
| End Stage Renal Disease (ESRD) (< 15 including hemodialysis) | Not Recommended |
Side Effects of Baxdela
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in clinical trials of BAXDELA cannot be directly compared to rates in the clinical trials of another drug and may not reflect rates observed in practice. Overview of the Safety Evaluation of BAXDELA BAXDELA was evaluated in three Phase 3 multicenter, multinational, randomized, double-blind clinical trials. These trials included two trials in ABSSSI patients (Trial 1 and Trial 2) and one trial in CABP (Trial 3). A total of 1170 patients were treated with BAXDELA across all Phase 3 trials (741 patients in the two ABSSSI trials and 429 patients in the CABP trial). Acute Bacterial Skin and Skin Structure Infections (ABSSSI) BAXDELA was evaluated in two multicenter, multinational, randomized, double-blind, double-dummy, non-inferiority trials (Trial 1 and Trial 2) in adults with ABSSSI. In Trial 1 patients received BAXDELA 300 mg by intravenous infusion every 12 hours and in Trial 2 the patients received BAXDELA 300 mg by intravenous infusion every 12 hours for 6 doses then were switched to BAXDELA 450 mg tablets every 12 hours.
The total treatment duration was 5 to 14 days. Adverse reactions were evaluated for 741 patients treated with BAXDELA and 751 patients treated with comparator antibacterial drugs. The median age of patients treated with BAXDELA was 49 years, ranging between 18 and 94 years old; 15% were age 65 years and older.
Patients treated with BAXDELA were predominantly male (62%) and Caucasian (86%). The BAXDELA treated population included 44% obese patients (BMI ≥ 30 kg/m 2 ), 11% with diabetes, and 16% with baseline renal impairment (calculated creatinine clearance less than 90 mL/min). Serious Adverse Reactions and Adverse Reactions Leading to Discontinuation Serious adverse reactions occurred in 3/741 (0.4%) of patients treated with BAXDELA and in 6/751 (0.8%) of patients treated with the comparator. BAXDELA was discontinued due to an adverse reaction in 7/741 (0.9%) patients and the comparator was discontinued due to an adverse reaction in 21/751 (2.8%) patients. The most commonly reported adverse reactions leading to study discontinuation in the BAXDELA arm included urticaria (2/741; 0.3%) and hypersensitivity (2/741; 0.3%); whereas, the most commonly reported adverse reactions leading to study discontinuation in the comparator arm included urticaria (5/751; 0.7%), rash (4/751; 0.5%), hypersensitivity and infusion site extravasation (2/751; 0.3%). Most Common Adverse Reactions The most common adverse reactions in patients treated with BAXDELA were nausea (8%), diarrhea (8%), headache (3%), transaminase elevations (3%), and vomiting (2%). Table 4 lists selected adverse reactions occurring in ≥ 2% of patients receiving BAXDELA in the pooled adult Phase 3 clinical trials.
Table 4 Selected Adverse Reactions Occurring in ≥ 2% of Patients Receiving BAXDELA in the Pooled Adult Phase 3 ABSSSI Clinical Trials Adverse Reactions BAXDELA N = 741 (%) Vancomycin/aztreonam N = 751 (%) Nausea 8% 6% Diarrhea 8% 3% Headache The data are not an adequate basis for comparison of rates between the study drug and the active control. 3% 6% Transaminase Elevations Pooled reports include hypertransaminasaemia, increased transaminases, and increased ALT and AST. 3% 4% Vomiting 2% 2% Community-Acquired Bacterial Pneumonia BAXDELA was evaluated in one multicenter, multinational, randomized, double-blind trial in adults with CABP (Trial 3). Patients received BAXDELA 300 mg over 60 minutes every 12 hours for a minimum of 6 doses with an option to switch to oral BAXDELA tablet 450 mg every 12 hours for the remaining doses (total of 10 to 20 doses of intravenous infusion and oral combined). Adverse reactions were evaluated for 429 patients treated with BAXDELA and 427 patients treated with moxifloxacin. The median age of patients treated with BAXDELA was 63 years, ranging between 18 and 89 years; 47.1% were 65 years of age and older and 19.6% were 75 years of age and older. Patients treated with BAXDELA were predominantly male (58.3%) and white (92.3%). The BAXDELA-treated population included patients with obesity (BMI greater than or equal to 30) (24.0%), COPD/asthma (14.2%), cardiac disease (24.2%), diabetes (16.3%), and baseline renal impairment including 36.4% with moderate renal impairment (CrCl less than 30-59 mL/min), and 4.0% with severe renal impairment (CrCl less than 29 mL/min). Overall, approximately 12.4% of patients were in PORT Risk Class II, 60.1% were in PORT Risk Class III, 26.6% were in PORT Risk Class IV, and 0.9% were in PORT Risk Class V. Serious Adverse Reactions and Adverse Reactions Leading to Discontinuation Serious adverse reactions occurred in 2/429 (0.5%) of patients treated with BAXDELA and in 1/427 (0.2%) of patients treated with moxifloxacin.
Discontinuation due to an adverse reaction occurred in 9/429 (2.1%) patients treated with BAXDELA and in 4/427 (0.9%) treated with moxifloxacin. The most commonly reported adverse reactions leading to study drug discontinuation in the BAXDELA arm were transaminase elevations (2/429; 0.5%). The most commonly reported adverse reactions leading to study drug discontinuation in the comparator arm were infusion site reactions (1/427; 0.2%). Most Common Adverse Reactions The most common adverse reactions in patients treated with BAXDELA were diarrhea (5%) and transaminase elevations (5%). Table 5 lists selected adverse reactions occurring in ≥ 2% of patients receiving BAXDELA in the adult Phase 3 CABP clinical trial. Table 5 Selected Adverse Reactions Occurring in ≥ 2% of Patients Receiving BAXDELA in the Adult Phase 3 CABP Clinical Trial Adverse Reactions BAXDELA N = 429 Moxifloxacin N = 427 Diarrhea 5% 3% Transaminase elevations Includes hepatic enzyme increased, transaminases increased and alanine aminotransferase (ALT) increased. 5% 3% Adverse Reactions Occurring in Less Than 2% of Patients Receiving BAXDELA in the ABSSSI (Trials 1 and 2) and CABP (Trial 3) Clinical Trials The following selected adverse reactions were reported in BAXDELA-treated patients at a rate of less than 2% in the ABSSSI (Trials 1 and 2) and CABP (Trial 3) clinical trials: Blood and Lymphatic System Disorders: agranulocytosis, anemia, leukopenia, neutropenia, pancytopenia Cardiac Disorders : sinus tachycardia, palpitations, bradycardia, ventricular extrasystoles Ear and Labyrinth Disorders: tinnitus, vertigo, vestibular disorder Eye Disorders : vision blurred General disorders and administration site conditions: infusion related reactions Gastrointestinal Disorders : abdominal pain, dyspepsia Immune System Disorders : hypersensitivity Infections and Infestations : Clostridium difficile infection, fungal infection, oral candidiasis, vulvovaginal candidiasis Laboratory Investigations : blood alkaline phosphatase increased, blood creatinine increased, blood creatine phosphokinase increased Metabolism and Nutrition Disorders: hyperglycemia, hypoglycemia Musculoskeletal and Connective Tissue Disorders: myalgia Nervous System Disorders : dizziness, hypoesthesia, paraesthesia, dysgeusia, presyncope, syncope Psychiatric Disorders : agitation, anxiety, confusional state, insomnia, abnormal dreams Renal and Urinary: renal impairment, renal failure Skin and Subcutaneous Tissue Disorders : pruritus, urticaria, dermatitis, rash Vascular Disorders: flushing, hypotension, hypertension
Warnings & Cautions for Baxdela
Disabling and Potentially Irreversible Serious Adverse Reactions Including Tendinitis and Tendon Rupture
Peripheral Neuropathy and Central Nervous System Effects Fluoroquinolones have been associated with disabling and potentially irreversible serious adverse reactions from different body systems that can occur together in the same patient. Commonly seen adverse reactions include tendinitis, tendon rupture, arthralgia, myalgia, peripheral neuropathy, and central nervous system effects (hallucinations, anxiety, depression, insomnia, severe headaches, and confusion). These reactions could occur within hours to weeks after starting a fluoroquinolone. Patients of any age or without pre-existing risk factors have experienced these adverse reactions . Discontinue BAXDELA immediately at the first signs or symptoms of any serious adverse reaction.
In addition, avoid the use of fluoroquinolones, including BAXDELA, in patients who have experienced any of these serious adverse reactions associated with fluoroquinolones.
Tendinitis and Tendon Rupture Fluoroquinolones have been associated with an increased risk
of tendinitis and tendon rupture in all ages. This adverse reaction most frequently involves the Achilles tendon, and has also been reported with the rotator cuff (the shoulder), the hand, the biceps, the thumb, and other tendons. Tendinitis or tendon rupture can occur, within hours or days of starting a fluoroquinolone, or as long as several months after completion of fluoroquinolone therapy.
Tendinitis and tendon rupture can occur bilaterally. This risk of developing fluoroquinolone-associated tendinitis and tendon rupture is increased in patients over age 60 years of age, in patients taking corticosteroid drugs, and, in patients with kidney, heart, and lung transplant. Other factors that may independently increase the risk of tendon rupture include strenuous physical activity, renal failure, and previous tendon disorders such as rheumatoid arthritis.
Tendinitis and tendon rupture have also occurred in patients taking fluoroquinolones who do not have the above risk factors. Discontinue BAXDELA immediately if the patient experiences pain, swelling, inflammation or rupture of a tendon. Advise patients, at the first sign of tendon pain, swelling, or inflammation, to stop taking BAXDELA, to avoid exercise and use of the affected area, and to promptly contact their healthcare provider about changing to a non-quinolone antimicrobial drug.
Avoid BAXDELA in patients who have a history of tendon disorders or have experienced tendinitis or tendon rupture.
Peripheral Neuropathy Fluoroquinolones have been associated with an increased risk of peripheral
neuropathy. Cases of sensory or sensorimotor axonal polyneuropathy affecting small and/or large axons resulting in paresthesias, hypoesthesias, dysesthesias, and weakness have been reported in patients receiving fluoroquinolones, including BAXDELA. Symptoms may occur soon after initiation of fluoroquinolones and may be irreversible in some patients. Discontinue BAXDELA immediately if the patient experiences symptoms of peripheral neuropathy including pain, burning, tingling, numbness, and/or weakness or other alterations of sensation including light touch, pain, temperature, position sense, and vibratory sensation and/or motor strength in order to minimize the development of an irreversible condition.
Avoid fluoroquinolones, including BAXDELA in patients who have previously experienced peripheral neuropathy .
Central Nervous System Effects Psychiatric Adverse Reactions Fluoroquinolones, including
BAXDELA, have been associated with an increased risk of psychiatric adverse reactions, including: toxic psychosis; hallucinations, or paranoia; depression, or suicidal thoughts or acts; delirium, disorientation, confusion, or disturbances in attention; anxiety, agitation, or nervousness; insomnia or nightmares; memory impairment. These adverse reactions may occur following the first dose. If these reactions occur in patients receiving BAXDELA, discontinue BAXDELA immediately and institute appropriate measures.
Central Nervous System Adverse Reactions Fluoroquinolones have been associated with an increased risk of seizures (convulsions), increased intracranial pressure (including pseudotumor cerebri), dizziness, and tremors. As with all fluoroquinolones, use BAXDELA when the benefits of treatment exceed the risks in patients with known or suspected CNS disorders (e.g., severe cerebral arteriosclerosis, epilepsy) or in the presence of other risk factors that may predispose to seizures or lower the seizure threshold. If these reactions occur in patients receiving BAXDELA, discontinue BAXDELA immediately and institute appropriate measures.
Exacerbation of Myasthenia Gravis Fluoroquinolones have neuromuscular blocking activity and may exacerbate
muscle weakness in persons with myasthenia gravis. Post-marketing serious adverse reactions, including death and requirement for ventilator support, have been associated with fluoroquinolone use in persons with myasthenia gravis. Avoid BAXDELA in patients with known history of myasthenia gravis .
Hypersensitivity Reactions Serious and occasionally fatal hypersensitivity (anaphylactic) reactions, some following the
first dose, have been reported in patients receiving fluoroquinolone therapy. Some reactions were accompanied by cardiovascular collapse, loss of consciousness, tingling, pharyngeal or facial edema, dyspnea, urticaria, and itching. Hypersensitivity reactions have been reported in patients receiving BAXDELA. These reactions may occur after first or subsequent doses of BAXDELA. Discontinue BAXDELA at the first appearance of a skin rash or any other sign of hypersensitivity.
Clostridium difficile -Associated Diarrhea Clostridium difficile -associated diarrhea (CDAD) has been reported
in users of nearly all systemic antibacterial drugs, including BAXDELA, with severity ranging from mild diarrhea to fatal colitis. Treatment with antibacterial agents can alter the normal flora of the colon and may permit overgrowth of C. difficile. C. difficile produces toxins A and B, which contribute to the development of CDAD. Hypertoxin-producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antibacterial therapy and may require colectomy.
CDAD must be considered in all patients who present with diarrhea following antibacterial use. Careful medical history is necessary because CDAD has been reported to occur more than 2 months after the administration of antibacterial agents. If CDAD is suspected or confirmed, ongoing antibacterial use not directed against C. difficile should be discontinued, if possible.
Appropriate measures such as fluid and electrolyte management, protein supplementation, antibacterial treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated.
Risk of Aortic Aneurysm and Dissection Epidemiologic studies report an increased risk
of aortic aneurysm and dissection within two months following use of fluoroquinolones, particularly in elderly patients. The cause for the increased risk has not been identified. In patients with a known aortic aneurysm or patients who are at greater risk for aortic aneurysms, reserve BAXDELA for use only when there are no alternative antibacterial treatments available.
Development of Drug-Resistant Bacteria Prescribing
BAXDELA in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria. 5.10 Blood Glucose Disturbances Fluoroquinolones have been associated with disturbances of blood glucose, including symptomatic hyperglycemia and hypoglycemia, usually in diabetic patients receiving concomitant treatment with an oral hypoglycemic agent (e.g., glyburide) or with insulin. In these patients, careful monitoring of blood glucose is recommended. Severe cases of hypoglycemia resulting in coma or death have been reported with other fluoroquinolones.
If a hypoglycemic reaction occurs in a patient being treated with BAXDELA, discontinue BAXDELA and initiate appropriate therapy immediately .
Drug Interactions with Baxdela
Chelation Agents: Antacids, Sucralfate, Metal Cations, Multivitamins Fluoroquinolones form chelates with alkaline
earth and transition metal cations. Oral administration of BAXDELA with antacids containing aluminum or magnesium, with sucralfate, with metal cations such as iron, or with multivitamins containing iron or zinc, or with formulations containing divalent and trivalent cations such as didanosine buffered tablets for oral suspension or the pediatric powder for oral solution, may substantially interfere with the absorption of BAXDELA, resulting in systemic concentrations considerably lower than desired. Therefore, BAXDELA should be taken at least 2 hours before or 6 hours after these agents . There are no data concerning an interaction of intravenous BAXDELA with oral antacids, sucralfate, multivitamins, didanosine, or metal cations.
However, BAXDELA should not be co-administered with any solution containing multivalent cations, e.g., magnesium, through the same intravenous line .
Pregnancy Safety for Baxdela
Pregnancy Risk Summary The limited available data with BAXDELA use in pregnant women are insufficient to inform a drug-associated risk of major birth defects and miscarriages. When delafloxacin (as the N-methyl glucamine salt) was administered orally to rats during the period of organogenesis, no malformations or fetal death were observed at up to 7 times the estimated clinical exposure based on AUC. When rats were dosed intravenously in late pregnancy and through lactation, there were no adverse effects on offspring at exposures approximating the clinical intravenous (IV) exposure based on AUC. The background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2–4% and 15–20%, respectively.
Data Animal Data In embryo-fetal studies, oral administration of delafloxacin to pregnant rats during the period of major organogenesis resulted in maternal toxicity and reduced fetal body weights at the highest dose (1600 mg/kg/day) and fetal ossification delays at all doses. No malformations were reported up to the highest dose tested (approximately 7 times the estimated human plasma exposure based on AUC). The lowest dose, 200 mg/kg/day (approximately 2.5 times the estimated human plasma exposure based on AUC), was still toxic to the fetus, based on ossification delays. In rabbits, a species known to be extremely sensitive to maternal toxicity of antibacterial drugs, no embryo-fetal developmental toxicity was observed up to the highest dose which induced maternal toxicity (1.6 mg/kg/day, or approximately 0.01 times the estimated human plasma exposure based on AUC). In a pre-postnatal study in rats of IV administered delafloxacin, dams at the highest dose tested (120 mg/kg/day) exhibited slightly lower body weights and slightly longer gestation length than control animals.
Exposure at that dose was estimated to be approximately 5 times human plasma exposure based on AUC, as determined in a separate shorter term study at an earlier stage of pregnancy. Effects on pups at that dose included increased mortality during lactation, small stature, and lower body weights, but no changes in learning and memory, sensory function, locomotor activity, developmental landmarks, or reproductive performance were reported. The No Adverse Effect Level (NOAEL) for maternal toxicity pup development in that study was 60 mg/kg/day (approximately 580 mg/day IV for a 60 kg patient, or just below the clinical IV dose).
Pediatric Use of Baxdela
Pediatric Use Use in patients under 18 years of age is not recommended. Safety and effectiveness in pediatric patients below the age of 18 years have not been established. Pediatric studies were not conducted because risk-benefit considerations do not support the use of BAXDELA for ABSSSI in this population.
Fluoroquinolones cause arthropathy in juvenile animals.
Contraindications for Baxdela
is contraindicated in patients with known hypersensitivity to delafloxacin or any of the fluoroquinolone class of antibacterial drugs, or any of the components of BAXDELA . Known hypersensitivity to BAXDELA or other fluoroquinolones.
Overdosage Information for Baxdela
Treatment of overdose with BAXDELA should consist of observation and general supportive measures. Hemodialysis removed about 19% of delafloxacin and 56% of SBECD (Sulfobutylether β cyclodextrin) after intravenous administration of BAXDELA.
Clinical Studies of Baxdela
Acute Bacterial Skin and Skin Structure Infections
A total of 1510 adults with acute bacterial skin and skin structure infections (ABSSSI) were randomized in 2 multicenter, multinational, double-blind, double-dummy, non-inferiority trials. Trial 1 compared BAXDELA 300 mg via intravenous infusion every 12 hours to comparator. In Trial 2, patients received BAXDELA 300 mg via intravenous infusion every 12 hours for 6 doses then made a mandatory switch to oral BAXDELA 450 mg every 12 hours.
In both studies, the comparator was the intravenous combination of vancomycin 15 mg/kg actual body weight and aztreonam. Aztreonam therapy was discontinued if no gram-negative pathogens were identified in the baseline cultures. In Trial 1, 331 patients with ABSSSI were randomized to BAXDELA and 329 patients were randomized to vancomycin plus aztreonam.
Patients in this trial had the following infections: cellulitis (39%), wound infection (35%), major cutaneous abscess (25%), and burn infection (1%). The overall mean surface area of the infected lesion as measured by digital planimetry was 307 cm 2. The average age of patients was 46 years (range 18 to 94 years). Patients were predominately male (63%) and white (91%); 32% had BMI ≥ 30 kg/m 2. The population studied in Trial 1 included a distribution of patients with associated comorbidities such as hypertension (21%), diabetes (9%), and renal impairment (16%; 0.2% with severe renal impairment or ESRD). Current or recent history of drug abuse, including IV drug abuse, was reported by 55% of patients. Bacteremia was documented at baseline in 2% of patients. In Trial 2, 423 patients were randomized to BAXDELA and 427 patients were randomized to vancomycin plus aztreonam.
Patients in this trial had the following infections: cellulitis (48%), wound infection (26%), major cutaneous abscess (25%), and burn infection (1%). The overall mean surface area of the infected lesion, as measured by digital planimetry, was 353 cm 2. The average age of patients was 51 years (range 18 to 93 years). Patients were predominately male (63%) and white (83%); 50 % had a BMI ≥ 30 kg/m 2. The population studied in Trial 2 included a distribution of patients with associated comorbidities such as hypertension (31%), diabetes (13%) and renal impairment (16%; 0.2% with severe renal impairment or ESRD). Current or recent history of drug abuse, including IV drug abuse, was reported by 30% of patients. Bacteremia was documented at baseline in 2% of patients. In both trials, objective clinical response at 48 to 72 hours post initiation of treatment was defined as a 20% or greater decrease in lesion size as determined by digital planimetry of the leading edge of erythema.
Table 7 summarizes the objective clinical response rates in both of these trials. Table 7 Clinical Response at 48–72 hours Objective clinical response was defined as a 20% or greater decrease in lesion size as determined by digital planimetry of the leading edge of erythema at 48 to 72 hours after initiation of treatment without any reasons for failure (less than 20% reduction in lesion size, administration of rescue antibacterial therapy, use of another antibacterial or surgical procedure to treat for lack of efficacy, or death). Missing patients were treated as failures. in the ITT Population with ABSSSI in Trial 1 and Trial 2 CI = Confidence Interval; ITT = Intent To Treat and includes all randomized patients Trial BAXDELA (300 mg IV) Vancomycin 15 mg/kg + Aztreonam Treatment Difference Treatment difference, expressed as percentage, and CI based on Miettinen and Nurminen method without stratification. (2-sided 95% CI) Trial 1 Total N 331 329 Responder, n (%) 259 (78.2%) 266 (80.9%) -2.6 (-8.8, 3.6) BAXDELA (300 mg IV and 450 mg oral) Vancomycin 15 mg/kg + Aztreonam Trial 2 Total N 423 427 Responder, n (%) 354 (83.7%) 344 (80.6%) 3.1 (-2.0, 8.3) In both trials, an investigator assessment of response was made at Follow-up (Day 14 ± 1) in the ITT and CE populations. Success was defined as "cure + improved," where patients had complete or near resolution of signs and symptoms, with no further antibacterial needed.
The success rates in the ITT and CE populations are shown in Table 8. Table 8 Investigator-Assessed Success at the Follow-up Visit in ABSSSI —ITT Population and CE Population in Trial 1 and 2 CI = Confidence Interval; ITT = Intent To Treat and includes all randomized patients; CE = Clinically Evaluable consisted of all ITT patients who had a diagnosis of ABSSSI, received at least 80% of expected doses of study drug, did not have any protocol deviations that would affect the assessment of efficacy and had investigator assessment at the Follow-Up Visit. Trial BAXDELA (300 mg IV) Vancomycin 15 mg/kg + Aztreonam Treatment Difference Treatment difference, expressed as percentage, and CI based on Miettinen and Nurminen method without stratification. (2-sided 95% CI) Trial 1 Success Success was cure + improved where patients had complete or near resolution of signs and symptoms with no further antibacterial needed., n/N (%) ITT 270/331 (81.6%) 274/329 (83.3%) -1.7 (-7.6, 4.1) Success, n/N (%) CE 232/240 (96.7%) 238/244 (97.5%) -0.9 (-4.3, 2.4) BAXDELA (300 mg IV and 450 mg Oral) Vancomycin 15 mg/kg + Aztreonam Trial 2 Success, n/N (%) ITT 369/423 (87.2%) 362/427 (84.8%) 2.5 (-2.2, 7.2) Success, n/N (%) CE 339/353 (96.0%) 319/329 (97.0%) -0.9 (-3.9, 2.0) Six delafloxacin patients had baseline S. aureus bacteremia with ABSSSI. Five of these 6 patients (83.3%) were clinical responders at 48 to 72 hours and 5/6 (83.3%) were considered clinical success for ABSSSI at Day 14 ± 1. Two delafloxacin patients had baseline Gram-negative bacteremia ( K. pneumoniae and P. aeruginosa ), and both were clinical responders and successes. The investigator assessments of clinical success rates were also similar between treatment groups at Late Follow-up (LFU, day 21-28). Objective clinical response and investigator-assessed success by baseline pathogens from the primary infection site or blood cultures for the microbiological ITT (MITT) patient population pooled across Trial 1 and Trial 2 are presented in Table 9. Table 9 Outcomes by Baseline Pathogen (Pooled across Trial 1 and Trial 2; MITT Microbiological ITT (MITT) consists of all randomized patients who had a baseline pathogen identified that is known to cause ABSSSI. Population) Clinical Response Objective clinical response was defined as a 20% or greater decrease in lesion size as determined by digital planimetry of the leading edge of erythema at 48 to 72 hours after initiation of treatment. at 48–72 hours Investigator-Assessed Success Investigator-assessed success was defined as complete or near resolution of signs and symptoms, with no further antibacterial needed at Follow-up Visit (Day14 ± 1). at Follow-up BAXDELA Comparator BAXDELA Comparator Pathogen n/N (%) n/N (%) n/N (%) n/N (%) Staphylococcus aureus 271/319 269/324 275/319 269/324 Methicillin-susceptible Discrepancy in the total numbers is due to the multiple subjects having both MRSA and MSSA isolates. 149/177 148/183 154/177 153/183 Methicillin-resistant 125/144 121/141 122/144 116/141 Streptococcus pyogenes 17/23 9/18 21/23 16/18 Staphylococcus haemolyticus 11/15 7/8 13/15 7/8 Streptococcus agalactiae 10/14 9/12 12/14 11/12 Streptococcus anginosus Group 59/64 55/61 54/64 47/61 Staphylococcus lugdunensis 8/11 6/9 10/11 8/9 Enterococcus faecalis 11/11 12/16 9/11 14/16 Escherichia coli 12/14 16/20 12/14 18/20 Enterobacter cloacae 10/14 8/11 12/14 10/11 Klebsiella pneumoniae 19/22 22/23 20/22 21/23 Pseudomonas aeruginosa 9/11 11/12 11/11 12/12
Community-Acquired Bacterial Pneumonia
A total of 859 adults with CABP were randomized in a multicenter, multinational, double-blind, double-dummy, noninferiority trial comparing BAXDELA to moxifloxacin (Trial 3, NCT 02679573). In this trial, BAXDELA for injection 300 mg was administered intravenously (IV) every 12 hours with an option to switch to BAXDELA tablet 450 mg orally every 12 hours. Moxifloxacin 400 mg was administered IV every 24 hours with an option to switch to moxifloxacin tablet 400 mg orally every 24 hours. Switch to oral treatment was allowed after a minimum of 3 days of IV dosing.
Total treatment duration was 5 to 10 days. In the moxifloxacin arm, the investigator could switch patients to linezolid 600 mg every 12 hours if methicillin-resistant Staphylococcus aureus (MRSA) was confirmed. A total of 431 patients were randomized to BAXDELA and 428 to moxifloxacin.
Patient demographic and baseline characteristics were balanced between the treatment arms. In this trial, 12.9% of patients were in PORT Risk Class II, 60.3% were in PORT Risk Class III, 25.4% were in PORT Risk Class IV, and 1.4% were in PORT Risk Class V. The average age of patients was 60 years (range 18 to 93 years). Patients were predominantly male (58.7%) and white (91.5%); average BMI was 26.9 kg/m 2. Associated comorbidities included pre-existing pulmonary disease (13.6%), cardiac disease (23.9%), diabetes (15.3%), and mild to severe renal impairment (76.9%). Bacteremia was documented at baseline in 1.5% of patients. The majority of sites were in Eastern Europe, which accounted for 82.8% of enrollment.
One subject (0.2%) was enrolled in the BAXDELA arm and 5 (1.2%) in the moxifloxacin arm from the United States. Early clinical response (ECR) at 72-120 hours after the first dose was defined as survival with improvement in at least two of four symptoms (cough, sputum production, chest pain, dyspnea) from baseline without deterioration in any of these symptoms, and without use of additional antimicrobial therapy for treatment of the current CABP infection due to lack of efficacy. Table 10 Early Clinical Response Early Clinical Response (ECR) at 72-120 hours after the first dose, was defined as survival with improvement in at least two of four symptoms (cough, sputum production, chest pain, dyspnea) from baseline without deterioration in any of these symptoms, and without use of additional antimicrobial therapy for treatment of the current CABP infection due to lack of efficacy. at 72 to 120 hours in the ITT Population with CABP (Trial 3) Trial 3 BAXDELA (300 mg IV and 450 mg oral) Moxifloxacin (400 mg IV and 400 mg oral) Treatment Difference Treatment difference, expressed as percentage, and CI based on Miettinen and Nurminen method without stratification. (2-sided 95% CI) CI = Confidence Interval; ITT = Intent To Treat includes all randomized patients Total N 431 428 Responder n (%) 383 381 -0.2 (-4.4, 4.1) Clinical response was also assessed by the investigator at the test of cure (TOC) visit and defined as survival with resolution or near resolution of the symptoms of CABP present at study entry, and no use of additional antimicrobial therapy for the current CABP infection, and no new symptoms associated with the current CABP infection.
Clinical response rates at the TOC visit for the ITT and Clinically Evaluable (CE) populations are presented in Table 11. Table 11 Investigator-Assessed Success at the TOC Visit in CABP —ITT Population and CE Population in Trial 3 Trial 3 BAXDELA (300 mg IV and 450 mg oral) Moxifloxacin (400 mg IV and 400 mg oral) Treatment Difference Treatment difference, expressed as percentage, and CI based on Miettinen and Nurminen method without stratification. (2-sided 95% CI) CI = Confidence Interval; ITT = Intent To Treat and includes all randomized patients; CE = Clinically Evaluable Clinically Evaluable consisted of all ITT patients who had evidence of acute CABP, received at least 80% of expected doses of the correct study drug, did not receive any concomitant, systemic antibacterial therapy except for lack of efficacy, and did not have any protocol deviations that would affect the assessment of efficacy. Success Success was survival with resolution or near resolution of the symptoms of CABP present at study entry, and no use of additional antimicrobial therapy for the current infection, and no new symptoms associated with the current CABP infection., n/N (%) ITT 390/431 384/428 0.8 (-3.3, 4.8) Success, n/N (%) CE 376/397 373/394 0.0 (-3.2, 3.3) Early clinical response and investigator-assessed clinical response at the TOC visit is presented in Table 12 by baseline pathogen for the Microbiological ITT (MITT) population which comprised all randomized patients who had a baseline pathogen identified that is known to cause CABP. Table 12 Outcome by Baseline Pathogen (CABP, Trial 3, MITT Population) Excludes patients with baseline pathogens resistant or non-susceptible to moxifloxacin. Early Clinical Response Early Clinical Response (ECR) at 72-120 hours after the first dose, was defined as survival with improvement in at least two of four symptoms (cough, sputum production, chest pain, dyspnea) from baseline without deterioration in any of these symptoms, and without use of additional antimicrobial therapy for treatment of the current CABP infection due to lack of efficacy. at 96 hours ± 24 hours Investigator-Assessed Success Investigator-assessed success was defined as survival with resolution or near resolution of the symptoms of CABP present at study entry, and no use of additional antimicrobial therapy for the current infection, and no new symptoms associated with the current CABP infection at Test of Cure (TOC) visit at (5 to 10 days after last dose of study drug). at Test-of Cure (TOC) BAXDELA Moxifloxacin BAXDELA Moxifloxacin Pathogen n/N (%) n/N (%) n/N (%) n/N (%) Staphylococcus aureus 24/26 25/28 24/26 26/28 Methicillin-susceptible 22/24 25/28 22/24 26/28 Streptococcus pneumoniae 66/71 51/62 64/71 54/62 Haemophilus influenzae 25/26 31/35 24/26 31/35 Haemophilus parainfluenzae 30/32 27/33 30/32 26/33 Escherichia coli 15/16 8/11 15/16 10/11 Klebsiella pneumoniae 13/17 15/16 14/17 16/16 Pseudomonas aeruginosa 12/13 10/11 11/13 11/11 Chlamydia pneumoniae 24/25 14/16 25/25 16/16 Legionella pneumophilia 27/29 28/33 27/29 32/33 Mycoplasma pneumoniae 30/35 29/30 34/35 30/30
Drug information sourced from the FDA. This content is for informational purposes only and does not constitute medical advice. Consult a healthcare professional before making any medication decisions.
Ready to save on Baxdela?
Compare prescription prices at over 70,000 pharmacies and start saving today—no enrollment required.
Compare Baxdela Prices