A landmark US study challenges the notion that infection risk is lower for hospital outpatients compared with inpatients.
Outpatients with cancer face significantly higher rates of antimicrobial-resistant infections compared to patients without cancer – posing serious challenges to treatment and public health, a large US study has found.
The research challenges what the authors said was a “general understanding that the risk of infection in outpatient settings is lower than in the hospital setting”.
The researchers, who have published their findings in The Lancet Oncology, said this was to their knowledge, the first large multicentre study to quantify antimicrobial resistant infections (AMR) in outpatients with cancer in the US.
“We found a significantly higher prevalence of non-susceptible bacterial pathogens and higher incidence rate ratios of AMR in patients with cancer compared with those without cancer in most evaluated pathogens, regardless of the culture site,” they said.
“The combined findings from this study and our previous analysis of inpatients with cancer might help to inform clinicians about the risk of AMR in patients with cancer.
“Our data show a need for enhanced infection prevention programs and timely diagnostic stewardship efforts to improve antibiotic prescribing and stewardship efforts in patients with cancer in the outpatient setting.”
The researchers analysed bacterial cultures from nearly 200 US health facilities and discovered that cancer patients had up to three times the rate of resistance for certain dangerous pathogens, including vancomycin-resistant Enterococci and multidrug-resistant Pseudomonas aeruginosa.
They found that AMR incidence for all key pathogens studied was higher in blood cultures from patients with cancer than in those without cancer.
“Bloodstream infections have been reported to be responsible for 92 (32.8%) of 280 total infections in patients with cancer,” the authors wrote.
“Bloodstream infections and sepsis clearly adversely affect the outcomes of patients with cancer and a greater incidence of AMR in this population makes the treatment of such infections even more challenging.”
They said one contributing factor may be the common use of antibiotic prophylaxis, particularly fluoroquinolones, in cancer patients undergoing chemotherapy. This practice, while intended to prevent infection during periods of immunosuppression, may inadvertently be fostering resistance.
Overall AMR rates were also high in isolates obtained from skin and wound sites. This finding has important implications for the care of patients with cancer given their need for intravascular access for therapy, debulking surgeries in solid tumours and other procedures that require devices that traverse the skin barrier.
Skin and soft tissue infections are common in individuals receiving systemic cancer therapy.
“Although the epidemiology of skin infections has been well studied in inpatients with cancer, data in the ambulatory setting are scarce,” the authors wrote.
“To the best of our knowledge, our study is the first multicentre study that provides an analysis of isolates obtained from skin and wounds in outpatients with cancer.
“Our data showed that patients with cancer had a higher percentage of non-susceptible isolates obtained from skin and wound sources for all pathogens, except for MRSA.”
Though the study had limitations, including the absence of patient-level clinical data and the potential for more frequent testing in cancer patients, the authors said the implications were clear.
“Infections are the second leading cause of death in patients with cancer. AMR infections can be difficult to treat and are associated with increased morbidity and mortality,” they concluded.
“Our study found that the proportion of AMR, the percentage of non-susceptible isolates, and the rates for key pathogens were up to three-times higher in patients with cancer than patients without cancer in the outpatient setting.
“The increased rates of AMR in patients with cancer in the outpatient setting highlight the need for enhanced infection prevention programmes and focused antibiotic and diagnostic stewardship efforts to improve timely AMR identification and antibiotic prescribing in patients with cancer.”
In an associated comment piece in The Lancet Oncology, Professor Samuel Shelburne and researcher William Shropshire, of the University of Texas MD Anderson Cancer Center, wrote that the findings had “substantial effects across multiple levels”.
“First, from the perspective of practitioners working with patients with cancer, this is the most comprehensive dataset providing estimates of AMR rates in the outpatient setting for specific infection sites,” they wrote.
“Second, these data serve as a warning to facilities caring for patients with cancer from an infection control perspective. Much emphasis is placed on keeping patients with cancer in hospital settings where they are safe from acquisition of AMR pathogens, such as by isolating patients with active methicillin-resistant Staphylococcus aureus or multidrug resistant Pseudomonas aeruginosa infections.
“However, infection control in the outpatient cancer setting is much less systematically implemented.”
Addressing the challenge of AMR in patients with cancer required both immediate and long-term strategies, they wrote.
“Historically, the use of novel antimicrobials, such as carbenicillin for P aeruginosa bacteraemia in patients with haematological malignancies in the late 1960s, dramatically improved bacterial infection outcomes.
“Similarly, the use of newer generation antibiotics approved since 2015, such as cefiderocol, can help patients with cancer currently infected with AMR pathogens. However, resistance has inevitably followed the introduction of novel agents.
“With few new antimicrobials in the pipeline, a potentially more sustainable, complementary approach is to avert AMR infections by understanding where and how patients with cancer acquire resistant pathogens.”
They said the gastrointestinal tract, as the probable primary site of initial colonisation by AMR bacteria, had a central role in the process, with the microbiome acting as a key defence.
“The growing interest in harnessing the microbiome to optimise cancer therapy presents an opportunity to simultaneously improve our understanding of AMR colonisation and infection risk,” they wrote.
“Advances in metagenomics and large-scale sequencing, including environmental surveillance of AMR reservoirs, such as wastewater, offer new tools to trace and interrupt AMR transmission within both healthcare and community settings.
“Future strategies could involve microbiome-based interventions to either prevent colonisation or to perform targeted decolonisation.”
