Secondary bacterial infections manifest during or after a viral infection(s) and can lead to negative outcomes and sometimes fatal clinical complications. Research and development of clinical interventions is largely focused on the primary pathogen, with research on any secondary infection(s) being neglected. Here we highlight the impact of secondary bacterial infections and in particular those caused by antibiotic-resistant strains, on disease outcomes. We describe possible non-antibiotic treatment options, when small molecule drugs have no effect on the bacterial pathogen and explore the potential of phage therapy and phage-derived therapeutic proteins and strategies in treating secondary bacterial infections, including their application in combination with chemical antibiotics.
Introduction
The past two decades have seen the emergence of four severe viral outbreaks including the 2002 Severe Acute Respiratory Syndrome (SARS) Coronavirus (CoV) epidemic, the 2009 influenza A H1N1 pandemic, 2012 Middle East Respiratory Syndrome (MERS) outbreak, and most recently the COVID-19 pandemic. Emergence of novel lethal CoV strains in human populations are becoming more frequent and are of increasing global concern; SARS-CoV-2, a novel CoV that caused a first major outbreak in China in 2019 has now infected almost 8 million people globally and resulted in 434,000 deaths (as of June 15, 2020), a far greater disease burden than SARS and MERS (Guarner, 2020;Â Kannan et al., 2020). The spectrum of clinical presentations of COVID-19 is highly variable; infections range from being asymptomatic to severe viral pneumonia with respiratory failure, often leading to death (Li et al., 2020). During an epidemic, or pandemic, early development and roll-out of antiviral treatments that can reduce morbidity and mortality is critical. However, even with many potential repurposed and new anti-viral drug candidates able to inhibit replication or attachment of the virus, a major consequence of disease progression in patients at later stages of infection, are secondary bacterial infections. At least one in seven COVID-19 patients was found to be additionally infected with a secondary bacterial infection with 50% of the fatalities during the SARS-CoV-2 epidemic caused by untreated or untreatable secondary bacterial infections, in most cases in the lung (Zhou et al., 2020). While antibiotics do not have impact on the virus itself, almost all seriously ill patients are treated with antibiotics to attempt to prevent the occurrence of secondary bacterial infections. Any surge in antibiotic use during the COVID-19 pandemic will have a detrimental effect on antibiotic resistance rates for nosocomial bacterial pathogens, fueling global growth of antibiotic resistant bacterial pathogens (Reardon, 2020).
https://doi.org/10.3389/fmicb.2020.01434
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