by Burden of Acinetobacter Pneumonia Therapeutics Industry
Acinetobacter baumannii is a gram-negative bacterium that is an emerging cause of hospital-acquired and ventilator-associated pneumonia worldwide. It has the ability to survive for prolonged periods in the hospital environment and is increasingly resistant to many commonly used antibiotics. According to the World Health Organization (WHO), Acinetobacter infections are associated with significant patient morbidity and mortality. The bacterium is labeled as a critical priority pathogen by the WHO due to the rising threat of multidrug-resistance. Data from the United States, Europe, and Asia indicate that Acinetobacter infections including pneumonia continue to rise in incidence. The increasing antimicrobial resistance exhibited by Acinetobacter makes treatment challenging. New therapeutic approaches are urgently needed.
Challenges in Treating Drug-Resistant Infections
The ability of Global Acinetobacter Pneumonia Therapeutics to spread and develop resistance to multiple classes of antimicrobials poses major challenges to clinicians. Most isolates of Acinetobacter baumannii are now resistant to all β-lactam antibiotics like penicillins and cephalosporins. Resistance to fluoroquinolones, carbapenems (considered drugs of last resort), and aminoglycosides is also widespread. Treatment options are limited to last line agents like colistin and tigecycline. However, resistance to even these drugs is being reported from different parts of the world. Treatment failure and infections relapses are common with available therapies. The pipeline of new antibacterial drugs remains sparse despite the need being classified as critical by the WHO. New agents with novel mechanisms of action are required to tackle this threat.
Novel Antibacterial Candidates in Clinical Trials
Several biotech and pharmaceutical companies are working to develop new agents active against multidrug-resistant gram-negatives like Acinetobacter. Plazomicin, a next-generation aminoglycoside, demonstrated activity against carbapenem-resistant strains in two phase 3 trials for complicated urinary tract infections and bloodstream infections. It received FDA approval in 2018. Lefamulin, the first pleuromutilin antibiotic approved, showed efficacy in two phase 3 clinical trials for community-acquired bacterial pneumonia. Other agents in late-stage clinical testing against Acinetobacter include cefiderocol, a novel siderophore cephalosporin with activity against carbapenem-resistant strains; eravacycline, a fluorocycline with a broad spectrum of activity; and zoliflodacin, an oritavancin-like agent with activity against drug-resistant gram-positives and gram-negatives. Though promising, these agents will need to demonstrate clinical benefit in treating Acinetobacter pneumonia to address the most serious infections caused by the pathogen. Larger clinical efficacy and safety studies are ongoing.
Passive Immunotherapies Gaining Interest
Considering the slow pace of new antibacterial discovery, researchers are evaluating alternative therapeutic approaches against multi-drug resistant infections. One strategy gaining interest is the use of antibodies or monoclonal antibody therapies. As the human immune system has co-evolved with infectious agents for millennia, antibodies represent naturally optimized biologics against pathogens. Several pharmaceutical companies are conducting clinical trials evaluating immunoglobulin therapies for treating pneumonia and bloodstream infections caused by drug-resistant gram-negatives such as Acinetobacter, Pseudomonas, and Klebsiella. The proposed mechanisms are neutralization of bacterial toxins and opsonization leading to enhanced phagocytosis and clearance. Some of these therapies include polyclonal immunoglobulin products from donor blood plasma as well as human or humanized monoclonal antibodies against virulence factors. Preliminary clinical data indicate these intravenous immunotherapies may represent an adjunct approach for managing infections when antibacterial options are lacking. Larger studies are underway to better define the role compared to antibiotics alone.
Re-purposing Acinetobacter Pneumonia Therapeutics Industry
While novel agents are urgently needed, researchers are also exploring ways to re-purpose older antibiotics and re-sensitize bacteria. Synergistic antibiotic combinations against resistant pathogens are being studied extensively. Combinations aim to prevent or delay resistance development by targeting different cellular processes simultaneously. Studies show certain antibiotic pairs have synergistic activity against Acinetobacter strains in vitro and in animal models. The potential for combinatorial therapies to reduce resistance and allow use of clinically important but compromised agents like carbapenems and aminoglycosides is being evaluated. Attempts are also being made to restore the activity of polymyxins like colistin that are facing increasing resistance. Inhibitors of resistance mechanisms such as enzyme inactivators are being combined with polymyxins and tested against resistant isolates. Elucidating the molecular mechanisms of how bacteria develop resistance can suggest ways to circumvent it and re-purpose existing therapeutics. More research is warranted on optimizing combination therapies against this challenging pathogen.
Infection Prevention Remains Critical
Even with the promise of novel agents in the pipeline, prudent use of antibiotics and strict infection control practices will remain cornerstones of tackling the rise of drug-resistant Acinetobacter infections globally. Efforts must continue towards improving hospital hygiene, disinfection, and enforcing antimicrobial stewardship protocols. Adopting universal contact precautions in healthcare settings is key for limiting the spread of epidemic multi-drug resistant strains. Preventing ventilator-associated and catheter-related infections through optimizing care practices can help curb pneumonia and bloodstream infections due to Acinetobacter and other multidrug-resistant gram-negatives. It will take coordinated efforts between pharmaceutical innovation, judicious clinical use of available therapies, and diligent infection prevention practices to address the emergence of untreatable bacterial pathogens worldwide. The high unmet medical need warrants urgent evaluation of alternative treatment strategies alongside traditional approaches.
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1. Source: Coherent Market Insights, Public sources, Desk research
2. We have leveraged AI tools to mine information and compile it
