Tigecycline: Role in the Management of cIAI and cSSTI in the Indian Context

The current millennium has witnessed an increased antimicrobial resistance which poses a mammoth challenge for public health management. This has resulted in an increase in morbidity and mortality, resulting in an increase in financial burden to the patients. A recent analysis from 10 hospitals in India reported that mortality rate increases by 1.57 times in patients suffering from multidrug resistance (MDR) bacterial infections as compared to patients infected with similar but susceptible infections. Due to the emergence of MDR and extensively drug-resistant (XDR) bacteria, most of the broad-spectrum antibiotics have been rendered ineffective. The mortality rate with Gram-negative strains is higher than with Gram-positive strains. Tigecycline is the first in class glycylcycline antibiotic with an expanded broad-spectrum activity. Tigecycline enters bacterial cells through energy-dependent pathways or via passive diffusion, to reversibly bind to the 30S ribosomal subunit. It has potent in vitro activity against Gram-negative carbapenemase producers, except Pseudomonas aeruginosa and Proteus spp. It also has good in vitro activity against Carbapenem-resistant Klebsiella pneumoniae strains. Hence, it is considered as a therapeutic option in XDR isolates. Recent meta-analyses have shown tigecycline to be as effective as its comparators with reducing mortality rates. Due to increased resistance reported in carbapenem-resistant isolates in Indian health-care settings, a colistin/polymyxin B-based combination therapy as a treatment option is being sought. A lower mortality rate has been reported with colistin-based combination therapy in Carbapenem-resistant Enterobacteriaceae-associated infections. Combinations with tigecycline, Fosfomycin, and chloramphenicol have shown to improve treatment outcomes. Tigecycline can be a good alternative in MDR and XDR complicated intra-abdominal and complicated skin and soft tissue infections. Appropriately designed clinical trials in Indian health-care setups will reinforce clinician’s confidence in using tigecycline in complex clinical situations.

Anti-SARS-CoV-2 human antibodies retaining neutralizing activity against SARS-CoV-2 B.1.1.529 (omicron)

SARS-CoV-2 B.1.1.529, designated omicron, was recently identified as a new variant of concern by WHO and is rapidly replacing SARS-CoV-2 delta as the most dominant variant in many countries. Unfortunately, because of the high number of mutations present in the spike of SARS-CoV-2 omicron, most monoclonal antibodies (mAbs) currently approved for treatment of COVID-19 lose their in vitro neutralizing activity against this variant. We recently described a panel of human anti-SARS-CoV-2 mAbs that potently neutralize SARS-CoV-2 Wuhan, D614G and variants alpha, beta, gamma and delta. In this work, we evaluated our mAb panel for potential in vitro activity against SARS-CoV-2 delta and omicron. Three mAbs from our panel retain neutralizing activity against both delta and omicron, with mAb 3B8 still resulting in complete neutralization at a concentration as low as 0.02 ug/ml for both variants. Overall, our data indicate that mAb 3B8 may have the potential to become a game-changer in the fight against the continuously evolving SARS-CoV-2.

In Vitro Activity of Gepotidacin Against Gram-negative and Gram-positive Anaerobes

Gepotidacin (formerly GSK2140944) is a first in class triazaacenaphthylene antibacterial currently in Phase III clinical trials. When tested against Gram-negative ( n =333) and Gram-positive ( n =225) anaerobes by agar dilution, gepotidacin inhibited 90% of isolates (MIC 90 ) at concentrations of 4 and 2 μg/ml, respectively. Given gepotidacin’s in vitro activity against the anaerobic isolates tested, further study is warranted to better understand gepotidacin’s utility in the treatment of infections caused by clinically relevant anaerobic organisms.