Effectiveness of Ceftazidime-Avibactam in Gram-Negative Nosocomial Pneumonia: A Real-World Study in India.

BACKGROUND AND OBJECTIVE: The incidences of nosocomial pneumonia in intensive care units (ICUs) in India have been reported to range from 9% to 58% and are associated with a mortality rate of 30-70%. Ceftazidime-avibactam has activity against OXA-48-like carbapenem-resistant Enterobacterales (CRE) and has a safer adverse effect profile as compared to the nephrotoxic colistin. The current study aimed to assess the effectiveness and usage pattern of ceftazidime-avibactam in gram-negative hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) in real-world settings in India. METHODS: Electronic medical records of hospitalized patients in three prominent medical centers in India (Fortis Memorial Research Centre, Gurugram, S L Raheja Hospital, Mumbai, and Fortis Hospital, Anandapur, Kolkata) with nosocomial pneumonia and documented gram-negative Klebsiella pneumoniae (KP)-confirmed infection were collected. This study assessed the effectiveness, usage pattern of ceftazidime-avibactam, and clinical and microbiological cure rates. RESULTS: Among the 116 patients included, 78.45% (91/116) showed clinical cure. Microbiological cure was observed in nine out of 13 (69.23%) patients. In the subset analysis, a clinical cure rate of 84.85% (28/33) and microbiological recovery rate of 62.50% (5/8) were observed when ceftazidime-avibactam was initiated within 72 hours of diagnosis. Ceftazidime-avibactam was administered for a mean (±SD) duration of 7.79 ± 4.43 days, with improvement in signs and symptoms reported among 91.38% (106/116). Ceftazidime-avibactam showed a susceptibility of 56% (28/56) in the study. CONCLUSION: The current study showed a better clinical and microbiological cure rate with a safer tolerability profile of ceftazidime-avibactam in carbapenem-resistant KP nosocomial pneumonia and VAP. This study has further demonstrated that ceftazidime-avibactam may be used as one of the viable treatment choices in carbapenem-resistant KP with favorable clinical outcomes.

Treatment challenges in the management of difficult-to-treat gram-positive infections: A consensus view apropos therapeutic role of novel anti-MRSA antibiotics, levonadifloxacin (IV) and alalevonadifloxacin (oral).

PURPOSE: Treatment of antibiotic-resistant Gram-positive infections (GPIs), including methicillin-resistant Staphylococcus aureus (MRSA) is becoming increasingly difficult, particularly in patients with multiple co-morbidities who require antibiotics with greater safety and a consistent pharmacokinetic/pharmacodynamic (PK/PD) profile. Such difficult-to-treat GPIs are often associated with poor outcomes, extended hospital stay and increased expenditure. This can be partly attributed to the limited safety and aberrant PK/PD profile of existing anti-MRSA antibiotics. In this context, intravenous levonadifloxacin and its oral prodrug alalevonadifloxacin are novel anti-MRSA antibiotics that have significant advantages over conventional anti-Gram-positive antibiotics. The purpose of this paper was to generate a consensus on the optimal use of levonadifloxacin and alalevonadifloxacin for tackling resistant Gram-positive infections in patients with multiple co-morbidities. METHOD: Using a modified Delphi approach that combines critical appraisal of evidence and expert opinion, therapeutic use of levonadifloxacin and alalevonadifloxacin in various clinical scenarios and specific unmet conditions was deliberated. Fifteen expert members from medicine, critical-care, emergency, microbiology, and intensive-care disciplines participated and voted on 11 pre-conceived statements. When there was at least 70 % agreement, a consensus was reached. RESULTS: Following the voting, agreements were reached on 10 out of the 11 statements. Broadly, a consensus was reached in defining the therapeutic role of levonadifloxacin and alalevonadifloxacin in the treatment of various clinical indications involving resistant Gram-positive pathogens, including MRSA, in patients with co-morbidities, such as co-existing or increased risk for kidney dysfunction or hepatic disease and/or immunosuppression; also, in therapeutically challenging conditions caused by Gram-positive bacteria such as bacteraemia, bone and joint infection, diabetic foot infection, febrile neutropenia, and hospital-acquired pneumonia. CONCLUSIONS: This consensus supports the therapeutic use of levonadifloxacin and alalevonadifloxacin in the treatment of antibiotic-resistant GPIs, including those caused by MRSA and certain polymicrobial infections, in patients with multiple co-morbidities requiring drug with adequate safety and consistent efficacy.

Meeting the Unmet Need in the Management of MDR Gram-Positive Infections with Oral Bactericidal Agent Levonadifloxacin.

Levonadifloxacin (intravenous) and its oral prodrug alalevonadifloxacin are broad-spectrum antibacterial agents developed for the treatment of difficult-to-treat infections caused by multidrug-resistant Gram-positive bacteria, especially methicillin-resistant Staphylococcus aureus, atypical bacteria, anaerobic bacteria, and biodefence pathogens as well as Gram-negative bacteria. Levonadifloxacin has a well-defined mechanism of action involving a strong affinity for DNA gyrase as well as topoisomerase IV. Alalevonadifloxacin with widely differing solubility and oral bioavailability has pharmacokinetic profile identical to levonadifloxacin. Unlike existing MRSA drugs such as vancomycin and linezolid, which cause unfavorable side effects like nephrotoxicity, bone-marrow toxicity, and muscle toxicity, levonadifloxacin/alalevonadifloxacin has demonstrated superior safety and tolerability features with no serious adverse events. Levonadifloxacin/alalevonadifloxacin could be a useful weapon in the battle against infections caused by resistant microorganisms and could be a preferred antibiotic of choice for empirical therapy in the future.