Comparative study of polymyxin B and colistin sulfate in the treatment of severe comorbid patients infected with CR-GNB.

BACKGROUND: With the difficulties in choosing colistin sulfate and polymyxin B sulfate (PBS) for carbapenem-resistant gram-negative bacteria (CR-GNB), we compared the efficacy and safety of these two old polymyxins in treatment of critically ill patients infected with CR-GNB infection. METHODS: One hundred four patients infected with CR-GNB in ICU were retrospectively grouped by PBS (68 patients) or colistin sulfate (36 patients). Clinical efficacy including symptoms, inflammatory parameters, defervescence, prognosis and microbial efficacy were analyzed. Hepatotoxicity, nephrotoxicity, and hematotoxicity were evaluated by TBiL, ALT, AST, creatinine, and thrombocytes. RESULTS: Demographic characteristics between colistin sulfate and PBS were not significantly different. Most of the CR-GNB were cultured in respiratory tract (91.7% vs 86.8%), and almost all were polymyxin-sensitive (98.2% vs 100%, MIC ≤ 2 µg/ml). The microbial efficacy in colistin sulfate (57.1%) was significantly higher than PBS (30.8%) (p = 0.022), however, no significant difference in clinical success was seen in both groups (33.8% vs 41.7%), as well as mortality, defervescence, imaging remission, days in the hospital, microbial reinfections, and prognosis, and almost all patients defervesce within 7 days (95.6% vs 89.5%). CONCLUSIONS: Both polymyxins can be administrated in critically ill patients infected with CR-GNB and colistin sulfate is superior to PBS in microbial clearance. These results highlight the necessity of identifying CR-GNB patients who may benefit from polymyxin and who are at higher risk of mortality.

Efficacy and Safety of Oral and IV Levonadifloxacin Therapy in Management of Bacterial Infections: Findings of a Prospective, Observational, Multi-center, Post-marketing Surveillance Study.

Background Antimicrobial resistance by bacteria poses a substantial threat to morbidity and mortality worldwide, and treatment of resistant infections is a challenge for the treating clinician. Levonadifloxacin is a novel broad-spectrum agent belonging to the benzoquinolizine subclass of quinolone, which can be used by both oral and intravenous administration for the treatment of infections caused by gram-positive organisms, including methicillin-resistant Staphylococcus aureus (MRSA). Patients and methods This prescription event monitoring study captured data from 1266 patients receiving levonadifloxacin (oral and/or IV) in a real-world setting to assess the safety and efficacy in the treatment of various bacterial infections. The duration of the study was 18 months. Study outcomes were clinical success and microbial success at the end of therapy. Global assessments were done for safety and efficacy at the end of therapy using a 5-point Likert scale (excellent, very good, good, satisfactory, and poor). Results The mean (median) duration of therapy was 7.2 (7.0) days, with a median time to clinical improvement of four days. Oral therapy was administered to 224 patients; 940 received IV, and 102 received IV followed by oral therapy. Patients were prescribed levonadifloxacin for gram-positive infections, skin and soft tissue infections, diabetic foot infections, septicemia, catheter-related blood-stream infections, bone and joint infections, febrile neutropenia, and respiratory infections, including COVID-19 pneumonia. The clinical cure on the eighth day was 95.7%, whereas the microbial success on the eighth day was 93.3% (n=60). For different types of infections, the clinical success rates ranged from 85.2% to 100%. There were only 30 treatment-emergent adverse events reported in 29 patients. Overall, about 95.6% of patients rated the efficacy as good to excellent, whereas only 3.8% of patients rated it satisfactory; for safety, 95.7% of patients rated it as good to excellent, with only 3.9% of patients rated it as satisfactory. Conclusions The excellent safety and efficacy profile of levonadifloxacin, when administered as an oral or intravenous therapy, makes it a desirable treatment modality for the management of various bacterial infections, including those caused by resistant pathogens such as MRSA and quinolone-resistant Staphylococcus aureus (QRSA). Features of levonadifloxacin, such as availability in both IV and oral form, minimal drug-drug interactions, lack of the need to adjust dosages in renal and hepatically impaired patients along with a broad spectrum of coverage, make it a suitable agent that meets several unmet clinical needs of physicians.

Real-World Evidence of Efficacy and Safety of Levonadifloxacin (Oral and IV) in the Management of Acute Bacterial Skin and Skin Structure Infections (ABSSSI): Findings of a Retrospective, Multi-Center Study.

Background Antimicrobial resistance by bacteria poses a substantial threat to the success in the treatment of acute bacterial skin and skin structure infections (ABSSSI). Levonadifloxacin is a novel benzoquinolizine subclass of quinolone which has a broad spectrum of activity, available in both oral and intravenous formulations for the treatment of skin structure infections caused by Gram-positive pathogens including methicillin-resistant Staphylococcus aureus (MRSA). Patients and methods This prescription event monitoring study captured data of 227 patients receiving levonadifloxacin (oral and/or IV) in a real-world setting to assess the safety and efficacy in the treatment of ABSSSI. Study outcomes were a clinical and microbial success at the end of therapy and safety was assessed based on adverse events reported. Results One hundred and forty patients received IV levonadifloxacin therapy, 76 patients received oral alalevonadifloxacin, and 11 received IV followed by oral therapy. The mean duration of therapy was 7.3 days. Out of 227 patients, MRSA isolates were identified in 79 patients. Clinical success rates with oral, IV, and IV followed by oral levonadifloxacin therapy were 97.3%, 97.8%, and 100% respectively. The overall microbial success rate was 99.2% and only two patients reported two adverse events. Conclusions The excellent safety and efficacy profile of levonadifloxacin on oral and/or intravenous therapy, makes it a desirable treatment modality for management of ABSSSI. Unique features of levonadifloxacin such as availability of both IV and oral form, minimal drug-drug interactions, exemption from dosage adjustment in renal and hepatic impaired patients and a broad spectrum of coverage, makes it a suitable agent meeting several unmet clinical needs in contemporary patients.