Carbapenemase‑producing organisms (CPOs) are Gram‑negative bacteria that are usually resistant to carbapenem antibiotics, the 'drug of last resort' for many bacterial infections (Papp‑Wallace et al. 2011) because they are often used when other courses of antibiotic treatment have failed.
Normal gut bacteria can acquire the characteristics of CPOs (Walsh 2007). People who are identified as carriers of CPOs are said to be 'colonised', but do not need to be treated. However, if these CPOs spread outside of the gut causing infection, treatment is necessary but difficult because they have high levels of antibiotic resistance.
CPOs include enterobacteriaceae and non‑fermenting bacteria that have become resistant to carbapenems by acquiring genes that make carbapenemases, which are powerful types of beta‑lactamases. These are enzymes that break down the beta‑lactam antibiotics, meaning they are no longer effective (Queenan and Bush 2007). Carbapenemases include the following gene families:
K. pneumoniae carbapenemase (KPC)
New Delhi metallo‑beta‑lactamase (NDM)
Verona integron‑encoded metallo‑beta‑lactamase (VIM)
imipenemase metallo‑beta‑lactamase (IMP)
These bacteria usually also possess genes encoding for resistance to other classes of antibiotics, including the aminoglycosides and fluoroquinolones (Ageevets et al. 2013).
People who are particularly at risk of CPO colonisation are typically tested when admitted to hospital. These include people who in the last 12 months have been:
an inpatient in a hospital abroad
an inpatient in a UK hospital which has problems with the spread of CPOs
previously colonised with CPOs.
The NICE accredited joint working party guidance on multidrug‑resistant Gram‑negative bacteria describes the following risk factors for CPO: prior antimicrobial use, length of stay, severity of illness, mechanical ventilation, admission to ICU, high procedure score, presence of wounds, positive culture from a blood isolate, transfer between hospital units within the same hospital, prior surgery, prior hospital stay, proximity to other colonised/infected patients, presence of a biliary catheter and recent transplantation. For NDM, prior hospitalisation on the Indian subcontinent and, for OXA‑48, prior hospitalisation in the Middle East, are additional risk factors (Wilson et al. 2016).
People who carry these bacteria harmlessly in their gut can transmit them to other people in hospitals through faecal contamination of hands, shared equipment and the hospital environment. These people may then become infected with the bacteria, or become colonised without symptoms, contributing to further transmission. Without being able to identify people who are colonised, and implementing appropriate infection prevention and control measures, these bacteria can quickly become established in a hospital.
Few treatment options are currently available for infections caused by CPOs. Polymyxins, some aminoglycosides and tigecycline generally retain activity against CPOs, and are the most commonly used treatments (van Duin et al. 2013). However, infections with CPOs are associated with increased hospital length of stay, mortality and healthcare costs. Specifically, patients colonised with these bacteria have on average a 1.79‑times greater risk of dying in intensive care than non‑colonised patients, primarily linked to an increased length of hospital stay (Dautzenburg et al. 2015).