Characterization of Antibiotic Use, Documented Infection and Prevalence of Multidrug-Resistant Organisms in Palliative Care Patients Admitted to a Private Hospital in Brazil: A Retrospective, Cohort Study

INTRODUCTION

Antibiotic use in palliative care patients is controversial and constitutes a frequent ethical dilemma.^[1,2] Rosenberg et al.^[3]argued that infections are very frequent in these patients and antibiotics administration could improve symptoms and prolong life. Givens et al.,^[4] however, suggested that antibiotics should not be part of the medications used to improve end-of-life care because the increased survival is not associated with improved comfort or symptoms relief.

There is also an emerging fear of an increased prevalence of multidrug-resistant organisms (MDROs) mainly as a result of frequent exposure to health-care facilities, recurrent hospital admissions and use of broad-spectrum antibiotics.^[5]

The previous studies^[6,7] reported that approximately 90% of advanced cancer hospitalised patients and 25% of hospice patients receive antibiotics in their final week of life. Antibiotics are prescribed for terminal patients even without evidence of bacterial infection.^[6]

Although antibiotics administration is less aggressive than invasive procedures, their use is not innocuous, being associated with pharmacodermy, drug interaction, Clostridioides difficile infection and MDRO colonisation and/ or infection.^[8]

Therefore, the primary objective of the present study was to retrospectively characterise the palliative care population admitted to a private hospital in Brazil according to an infectious or non-infectious diagnosis at hospital admission. The secondary objectives were to characterise their antibiotic use (number and type), possible source of infection (at admission or later during hospital stay) and the main causative organisms, presence of MDRO colonisation and their impact on mortality.

MATERIALS AND METHODS

This study was approved by the Local Ethics Committee of São Camilo Ipiranga Hospital (approval number 1.880.538). Because of the retrospective nature of data collection with minimal risk of harm to individual patients except a possible breach of confidentiality, informed verbal or written consent from the patients or their relatives was waived by the local ethics committee. All patients admitted during the year of 2016 who were selected for palliative care in the current or in a previous hospital stay were included. Data from subsequent admission of the same patients at the hospital were not included in the analysis. General characteristics were retrospectively retrieved from electronic medical records with no missing data and patients were divided according to a diagnosis at hospital admission of infection or not. The diagnosis that motivated current hospital internment appearing in the medical record was used for dividing patients. Information regarding culture results, infection sites and antibiotics administered were retrieved from the Infection Control Department of the hospital. The International Classification of Diseases, Tenth Revision (ICD-10) classification system was used for both infectious and non-infectious diagnosis. The following data were obtained: Age, gender, comorbidities, main reason for current hospital admission, main reason for palliation, palliative care institution before or at the current hospital admission, type of palliative care (therapeutic proportionality or exclusive comfort care), intensive care unit (ICU) admission at the current hospital stay (related to palliation or not), use of antibiotics (all types of antibiotics available at our hospital), infection source, organisms isolated in cultures, presence of MDRO colonisation, (which means the presence of vancomycin-resistant enterococci, methicillin-resistant Staphylococcus aureus or multidrug-resistant Gram-negative bacilli in some part of the human body but not causing harm or symptoms, as stated by the National Healthcare Safety Network of the Centre for Disease Control USA: NHSNCDC) and hospital mortality. We have considered a suspected infectious diagnosis a condition in which infection was not microbiologically documented but physical examination or laboratory examinations suggested its presence. A confirmed infectious diagnosis was made when there was a strong clinical and laboratory suspicion and an infectious agent isolated in culture. Large spectrum antibiotics were defined as antibiotics with action against a broad range of bacteria, frequently both Gram-positive and Gram-negative organisms and healthcare-associated infection as infections affecting patients in a hospital or health-care facility not present or incubating at the time of admission as stated by the World Health Organisation. Community-acquired infections were those that were contracted outside of a hospital or health-care facility or diagnosed in 48 h of hospital admission without any previous health care encounter. The Clinical and Laboratory Standard Institute methodology was used for testing antimicrobial susceptibility of clinical isolates. The choice of initial antibiotic was made by the assistant physician as well as subsequent changes during hospital stay. The institution of palliative care occurred after referral from the responsible medical team, assessment of the palliative care group and family agreement.

RESULTS

A total of 114 patients admitted to the hospital in 2016 were included in the analysis. General characteristics of these patients are shown in [Table 1]. Of these, 89 patients (78%) started palliative care follow-up in the current hospital stay and 25 patients (22%) were under palliative care since a previous hospital admission. One-hundred and two patients (89.5%) had some limitations of invasive procedures (mostly due to a ‘do-not-intubate’ order) and 12 patients (10.5%) were not candidates to any invasive life-sustaining method.

One-hundred and nine patients (95.6%) used antibiotics during the current hospital stay. Of these, 19 patients (17.4%) used only a single antibiotic, 39 patients (35.8%) used two antibiotics, 16 patients (14.7%) used three antibiotics and 35 patients (32.1%) used four or more antibiotics. Thirteen patients who used antibiotics also used antifungal agents and five patients who used antibiotics also used antiviral medications.

Eighty-nine patients (78.1%) had at least one suspected or confirmed infectious diagnosis at hospital admission [Table 1]. They were significantly older than the patients admitted due to a non-infectious diagnosis. Of the 25 patients without a suspected or confirmed infectious diagnosis at hospital admission, 20 patients (80%) have used at least one antibiotic during hospital stay. Only 5 of these 20 patients (25%) had a subsequent confirmed infectious diagnosis.

One-hundred and two patients (89.5%) were admitted to the ICU during hospital stay: 74 patients once, 21 patients twice and 7 patients were admitted 3 times to the ICU [Table 1].

DISCUSSION

In the present single centre, retrospective study, we were able to characterise the population of palliative care patients admitted to a private hospital in Brazil including main diagnosis (infectious vs. non-infectious), main reason for palliation and, most importantly, MDRO colonisation prevalence, antibiotic use and their impact on mortality.

In addition to the expected findings that palliative care patients are usually old (even older if infection was the reason for admission) and have serious terminal illnesses, this study highlights the high prevalence of patients with suspected or confirmed infectious diagnosis at hospital admission. Furthermore, our study is in line with the findings of a previous investigation,^[1] indicating that infection is the main reason for hospital admission in this population. Most of our patients were admitted to the ICU at least once during hospital stay, and this suggests a severe stage of their acute illnesses, frequently infectious in origin, which then demands a large amount of resources for the appropriate care. However, we observed that antibiotic use in this population is widespread and not restricted to patients with a well-documented infection. Most patients, even those with no clear evidence of infection, received two or more large spectrum antibiotics during their hospitalisation. Unfortunately, our study was not powered to evaluate a causal relationship between this practice and the emergence of MDRO colonisation or infection. Interestingly, mortality was similar between patients admitted with an infectious or a non-infectious diagnosis and the presence of previous MDRO colonisation was also similar between these two groups and did not have an impact on mortality. A previous study^[9] has also found a MDRO prevalence at hospital admission of around 20% and no difference in overall mortality during follow-up comparing carriers and non-carriers.

Most of the antibiotic use during hospital stay was empirical and not culture guided. Even in patients admitted with an infectious diagnosis, most of them were empirically treated for respiratory tract infection [Table 2] for which no cultures are routinely obtained, except in tracheostomised patients.

In addition, these patients usually live in hospice care or other health-care facilities and are repeatedly admitted to the hospital over a short period of time. This may be the cause of the recurring use of large spectrum antibiotics as those infections are considered healthcare-associated infections from the outset. The considerable number of patients admitted with a non-infectious diagnosis who used first- and second-generation cephalosporins was explained by their use as surgical prophylaxis. Macrolides and clindamycin were not used in the group of patients with a non-infectious diagnosis at admission because these antibiotics are commonly used for community-acquired infections in our service. In this group of patients, the majority of antibiotics was prescribed for lately, hospital-acquired infections.

Our study has some limitations. First, the retrospective nature could lead to potential bias regarding the availability of relevant data or misinformation in the electronic medical records. Fortunately, at least the presence of significant missing data did not seem to be the case in the present analysis. Second, the fact that it was a single-centre study precludes an extrapolation of our results to other hospitals with distinct characteristics which include different palliative care management as well as different microbiological profile and antibiotic therapy choices. We cannot affirm that all antibiotics were correctly prescribed or indicated and if adequate preventive measures were followed which certainly could be of help in reduce hospital-acquired infections. Finally, the limited sample might be a cause of type II error, which means unrevealed statistical differences when they actually exist.

CONCLUSION

Our data confirm the previous finding that infectious complications are very common in palliative care patients leading to disseminated use of antibiotics as well as other expensive medical care resources for their treatment. However, the lack of well-documented presence of infection or isolated agent in most cases has possibly led to an excessive use of antibiotics and also an overestimation of infection occurrence in our population. Although the presence of previous MDRO colonisation did not seem to have an impact in terms of increased mortality in our study, it emphasises the harm of widespread empirical large spectrum antibiotic use. Since mortality was similar in patients admitted with an infectious diagnosis or not, it is hard to define the real impact of antibiotic treatment in improving survival. Therefore, the fact that mortality was significantly high regardless of the presence of infection or large spectrum antibiotic use confirms that further studies are needed to determine in which cases antibiotics and ICU admission are meaningful rather than expensive, stressful and futile interventions for end-of-life patients.