Hospital-acquired pneumonia (non COVID-19) - Emerging treatments

Aerosolised antibiotic therapy

New data are available regarding the use of inhaled antibiotics. One prospective, randomised, double-blind, placebo-controlled trial found reduced signs of respiratory infection with the use of aerosolised antibiotics.[79] A meta-analysis of 7 small studies found that monotherapy with aerosolised antibiotics was non-inferior to conventional therapy.[80] It recommended such therapy only if intravenous therapy is not available. A review published by the Society of Infectious Diseases Pharmacists (SIDP) provides evidence-based recommendations, including dosing, for several antibiotics for HAP.[81] It states that the best candidates are those who are not responding to intravenous antibiotics, have recurrent HAP, or have HAP due to an MDR organism. The 2016 guidelines for HAP/VAP recommend inhaled antimicrobials for patients infected with a pathogen only susceptible to aminoglycosides or polymyxins.[1] Negative studies in this population exist.[82]

New antibiotic therapy

Ceftobiprole, a fifth-generation cephalosporin, is approved in Europe for the treatment of HAP and community-acquired pneumonia (CAP). It covers MRSA and gram-negative bacteria, including Pseudomonas aeruginosa. Another fifth-generation cephalosporin, ceftaroline (which includes coverage against MRSA), is approved for CAP, but not HAP. The cephalosporin/beta-lactamase inhibitor combination ceftolozane/tazobactam, and the arbapenem/renal dehydropeptidase inhibitor/beta-lactamase inhibitor combination, imipenem/cilastatin/relebactam, have been approved in Europe and the US for the treatment of HAP. Cefiderocol, a novel siderophore cephalosporin, has been approved in Europe and the US for the treatment of HAP. Meropenem/vaborbactam, a carbapenem/beta-lactamase inhibitor combination, has been approved in Europe for the treatment of HAP. Plazomicin is a new generation of aminoglycoside in phase 3 studies for HAP. It covers Gram-negative organisms, such as Escherichia coli, Klebsiella pneumoniae, Enterobacter spp and Acinetobacter baumannii, without the ototoxicity or nephrotoxicity of older aminoglycosides.[83] Iclaprim, related to trimethoprim, was granted orphan drug designation in the US for the treatment of Staphylococcus aureus lung infections in patients with cystic fibrosis, but phase 2 studies were terminated due to financial resource limitations. Use of prophylactic antibiotics is controversial. One study has shown that patients who received intravenous prophylactic antibiotics had a lower rate of HAP;[84] other studies showed that patients became colonised with MDR pathogens that subsequently led to infections.[85][86]

Monoclonal antibodies

There are two monoclonal antibodies to treat pneumonia that have been granted fast-track status by the US FDA for development. The first is a broadly reactive monoclonal antibody (immunoglobulin G) against P aeruginosa. A phase 1 study evaluated three different doses of the drug for 84 days.[87] It found no serious adverse events, and low-grade adverse events that were not drug-related. The second monoclonal antibody is AR-301, an immunoglobulin G1 against the toxin of Staphylococcus aureus, including MRSA. AR-301 is in phase 3 clinical development. The European Union has granted orphan drug designation to AR-301. Other monoclonal antibodies under investigation include a lipopolysaccharide against P aeruginosa, another against Acinetobacter species, and yet another against respiratory syncytial virus.

Osteopathic manipulation

In a randomised, double-blind, controlled trial from the US, patients admitted to hospital who received 2 daily 15-minute osteopathic manipulative treatments (e.g., thoracic inlet myofascial release) had statistically significant reductions in length of stay, intravenous antibiotic duration, and respiratory failure or death among the per-protocol populations, but not among the intention-to-treat populations.[88]

Continuous lateral rotational therapy

Continuous lateral rotational therapy is occasionally used in ICU patients. A meta-analysis in trauma patients showed that it reduced the level of nosocomial pneumonia, but had no effect on mortality.[89]