Supportive Care in Cancer (2018) 26:1361–1367

https://doi.org/10.1007/s00520-018-4090-8

REVIEW ARTICLE

Antimicrobial therapy in palliative care: an overview

Filipa Macedo 1 & Catarina Nunes 2 & Katia Ladeira 2 & Filipa Pinho 2 & Nadine Saraiva 1 & Nuno Bonito 1 & Luísa Pinto 2 &
Francisco Gonçalves 2

Received: 23 September 2017 / Accepted: 30 January 2018 / Published online: 12 February 2018
# Springer-Verlag GmbH Germany, part of Springer Nature 2018

Abstract
In the advanced stages of illness, patients often face challenging decisions regarding their treatment and overall medical care.
Terminal ill patients are commonly affected by infections. However, in palliative care, the use of antimicrobials can be an ethical
dilemma. Deciding whether to treat, withhold, or withdraw the antimicrobial treatment for an infection can be difficult.
Antimicrobial administration can lead to adverse outcomes but the two main benefits, longer survival and symptom relief, are
the main reasons why physicians prescribe antimicrobial when treating terminally ill patients. For the patient who has an
irreversible advanced heart or lung disease, or an advanced dementia, or a metastatic cancer, it is easier the decision of with-
holding mechanical ventilation, tube feeding, and dialysis than antibiotherapy. To characterize infections, agents, and their
treatments in palliative care, we conducted a review of the literature. We also included some tips to help health professionals
to guide their clinical approach.

Keywords Palliative care . End of life . Antimicrobians . Antibiotics . Infections . Survival

Introduction
Palliative care has been defined by the World Health
Organization (WHO) as Ban approach that improves the quality
of life of patients and their families facing the problems associ-
ated with life-threatening illness, through the prevention and
relief of suffering by means of early identification and impecca-
ble assessment and treatment of pain and other problems, phys-
ical, psychosocial and spiritual^ [1]. Many cancer patients can
now expect to recover from cancer, due to new advances in
treatment. For some people, however, cancer either recurs or it
is diagnosed as advanced or it does not respond to treatment [2].
In these cases, palliative care is offered. Palliative care utilization
is expected to increase with the aging and increases in the prev-
alence of chronic and terminal diseases.
The majority of the patients with cancer will need palliative
care in some point of their lives. In developing countries, the
proportion of patients requiring palliative care is no less than
* Filipa Macedo
Filipa.c.macedo@gmail.com
1
Portuguese Oncology Institute of Coimbra, Coimbra, Portugal
2
Braga Hospital, Braga, Portugal
80%. In the world, most cancers are diagnosed when already
advanced or incurable [1]. Nowadays, there is the intention of
admitting patients in palliative care earlier, while still under
treatment [3, 4].
The goal of palliative care is helping people die with dig-
nity [5], but there comes a time when treatment may do more
harm than good [6]. The most common complications experi-
enced by terminal patients are infections and fever [7]. Almost
90% of patients hospitalized with advanced cancer are treated
with antimicrobials during the week before their death [7].
Two retrospective reviews reported that it is common that
incurably dying patients receive empirically systemic antibi-
otics in their last days or weeks of life, even in patients with
Bdo not resuscitate^ or Bcomfort measures only^ orders [8, 9].
The frequency of infections among palliative cancer pa-
tients (non-neutropenic) being cared for in a palliative care
unit is around 50–55% [10, 11]. Nagy-Agren reviewed eight
reports with an overall rate of 41.6% [12]. Patients with ad-
vanced cancer have more susceptibility to infection caused by
factors like asthenia, failure of host barriers, malnutrition, im-
munosuppression, immobility, lethargy, and the use of foreign
bodies in the care of these patients (such as urinary catheters)
[10, 13, 14].
Currently, there is no consensus among physicians regard-
ing the use of antibiotics for patients in palliative care.
1362
Uncertainty remains regarding the ethical and legal issues
such as withdrawal and withholding of antibiotic therapy.
Adverse outcomes can arise from antimicrobial administration
such as the following: use of invasive devices such as intra-
venous lines, acquisition of multidrug-resistant organisms,
drug interactions, drugs reactions, additional suffering from
side effects, clostridium difficile infection, and increased
health care costs. The potential benefits of antimicrobials are
the following: symptom relief and prolonged survival.
Several studies evaluated the patients, families, and health
care professionals’ attitudes about antibiotic therapy.
For families and patients, antibiotics were a therapeutic
option accepted and were more accepted than cardiopulmo-
nary resuscitation or mechanical ventilation. On the other
hand, physicians preferred to withdrawal of blood products
than antibiotics, but they were more disposed to retire antibi-
otics than intravenous fluids or mechanical ventilation [15].
Useful vs non-useful
Thompson A performed a retrospective study with 145 pa-
tients experiencing cancer-related death. From 145 patients,
86.9% received antimicrobials, from which only 69.8% had
clinical findings suggestive of infection, and 51.6% were
treated empirically [16].
Pereira J showed that 71.6% of diagnosed infections were
treated with antibiotics. The remaining 28.4% were not treated
due to either poor general condition or the patients’/families’
option [10].
Albrecht J, from 3884 patients who died in palliative care,
concluded that 27% of the patients received at least one anti-
biotic during the final 7 days of life, and 1.3% received three
or more antibiotics. It was also observed that from patients
who received antibiotics, only 15% had an infectious disease
diagnosed [17]. This practice has great impact in costs and in
microbial resistance.
Everes M, in a study performed with 303 patients from a
chronic care facility, found that narcotic pain medications
were prescribed only in 14% of the patients and systemic
antibiotic use were 53%. During 15 years, we watched an
increasing tendency to prescribe nonnarcotic and narcotic pain
medications, but the antibiotic prescription did not modify
significantly over the time. Therefore, although pain manage-
ment information may have affected clinical practice during
that time period, it would seem that the data on the use of
antibiotics did not have a similar impact. [18]
Yao C showed that from 201 patients with terminal cancer,
45.8% manifested the wish of use antibiotics even in the final
stage of the disease, 27.8% were uncertain, and 26.4%
whished not to have antimicrobials. Medical professionals
were considered the most important advisors, which indicate
Support Care Cancer (2018) 26:1361–1367
the responsibility of medical professionals in educating pa-
tients and families [19].
White P concluded that 79.2% of 255 terminal patients
choose to get antimicrobial administration only for symptom-
atic use or no administration at all. However, the actual usage
was significantly higher. This restricted choice for the use of
antimicrobials was more common among older patients who
had lower performance status [20].
Stiel S concluded that from 448 patients, 63.8% received
antimicrobial treatment and physicians alone often decided
the initiation of therapy, whereas pulling out treatment re-
quired more often the participation of other team members
in the decision process. The most frequent reasons for with-
drawal were the following: the wish of patient or family, ther-
apy failure, worsening of the performance status, and adverse
effects [21].
Clayton J monitored 41 patients that had received 43
courses of parental antibiotics. This use was considered help-
ful in 62% and unhelpful in 19% of cases [22].
Vitetta L, from 102 terminally patients, one-third devel-
oped infections during the last stage of care, and in 40%, the
infection was not the direct cause of death. The patients with
documented infection had longer median survival, possibly
because the longer the survival, the greater the chance of in-
fection [14].
On the other hand, in the study performed by White P, the
survival rate was not significantly different between the group
of infected patients and the uninfected ones. The use of anti-
biotics or the choice of the patient did not significantly affect
the infection-related deaths and the patients’ overall survival
[20] (Table 1).
Albrecht J concluded that patients with longer stays in a
hospice care institution had greater probability to receive an-
tibiotics. Patients who reside in hospice care institutions may
have developed infections as a result of a longer stay or be-
cause receiving antimicrobials may have prolonged their lives
[17].
Brown N demonstrated that, during febrile episodes, the
patients who received antibiotics had a significantly lower
mortality rate when compared with expectant attitude (9 vs.
59%) [24].
Fabiszewski K studied a total of 104 institutionalized pa-
tients with Alzheimer’s disease and concluded that persons
with severe dementia do not have a survival improvement
when infections are aggressively treated, and it has been as-
sociated with a faster progression of the severity of dementia
[25]. On the other hand, Chen L showed that patients without
antimicrobial therapy had a smaller mean survival and a
higher mortality rate than the patients with antimicrobial ther-
apy [26]. Reinbolt R showed that the use of antibiotics or the
existence of infection did not affect the survival, but the ad-
ministration of antibiotics caused symptomatic relief in pa-
tients with urinary tract infections. The symptomatic control
Support Care Cancer (2018) 26:1361–1367 1363

Table 1 Distribution of studies’ conclusions about antimicrobial therapy in survival of patients

Vitetta Albrecht White P. Reinbolt Brown N. Fabiszewski Chen

L. [14] J. [17] [20] R. [23] [24] K. [25] L. [26]

Longer survival with antibiotic therapy ✓ ✓ ✓ ✓

No difference between treated and not treated ✓ ✓ ✓

was more difficult in blood, skin, and respiratory tract infec-
tions. This lack of symptom response was interpreted as due to
co-morbid conditions or the existence of a cancer in the symp-
tomatic organ [23]. In fact, there are other studies that con-
clude the same [14, 20, 22].
Patterns of antibiotics and infections
In many studies, the urinary tract and lower respiratory tract
were the most usual sites of infection (Table 2). The catheter-
related infections were less common with totally implanted
ones [30], and the catheter removal rate varies between 3
and 28% [31–34]. The totally implanted access ports were
associated with lower incidence of catheter-related infections
than central venous catheters [30].
The causative agents of infections could be bacterial path-
ogens, viruses, and fungi. The bacteria account for more than
75% of nosocomial infections and fungus were isolated in
nearly 3–10% of the infections. Viral microorganisms were
responsible in only 2% of the cases and rare agents such
Pneumocystis carinii accounted for the rest [27, 35].
The most frequent bacterial agents identified were
Staphylococcus aureus (S. aureus) and Escherichia coli
(E.coli) (Table 3).
The most frequently antibiotic therapy prescribed was
trimethoprim-sulfamethoxazole and fluoroquinolones
(Table 4).
Vitetta L concluded that antibiotic therapy had an overall
success rate for symptom relief of 40%, and these 40% pa-
tients recovered from their diagnosed infections [14].
The study of White P included the anti-fungal therapy and
fluconazole accounts for 7.8% of the prescriptions [20].
The diagnosis
The diagnosis of infections may be delayed due to the inability
to express their complaints. The presence of multiple comor-
bidities becomes the findings on physical examination diffi-
cult to valorize, and the infection in elderly patients presents
differently from younger adults.
The clinical signs that an older person could be infected
include fever, cough, yellow sputum, and purulence or skin
injury; however, clinical manifestations could not be present
or be too subtle to be recognized. Infection could more fre-
quently be noticed as a change in mental or cognitive function
or deterioration in functional status [36]. The Infectious
Diseases Society established that infection should be
suspected in patients with any of the following characteristics:
decline in functional status, define as deteriorating mobility,
failure to cooperate with staff, new or increasing confusion,
reduced food intake, falling or incontinence; fever define as
the following: (1) an increase in temperature of > 1.1 °C over
the baseline temperature; (2) a single oral temperature >
37.8 °C; or (3) rectal temperatures > 37.5 °C or repeated oral
temperatures > 37.2 °C [37].
As of yet, it has not been established the specific diagnostic
tests to assess fever and infection in palliative patients and,
when recommended, they have not been studied [38].
Diagnostic tests should only be made if they enhance the
probability of diagnosis, if they improve patient management,
have low risk, and are reasonable in cost. A test should not be
ordered if its result would not produce an alteration in clinical
conduct or treatment strategy [39].
The most used diagnosis tests are the following:
– Complete blood cell count with differential. The elevation
of the total white blood cell count (with leukocytosis

Table 2 Distribution of infection sites

Pereira Lagman Vitetta Albrecht Evers M. White Clayton Reinbolt Robinson Kuehn Homsi
J. [10] R. [11] L. [14] J. [17] [18] P. [20] J. [22] R. [23] G. [27] N. [28] J. [29]

Urinary tract infection 39.2% – 42.5% 4% 30% 41.9% 37% 41.9% 2.6% – 66%
Respiratory Infection 36.5% 22% 22.5% 7% 42% 34.9% 26% 34.9% 1.9% 16% 21%
Skin/subcutaneous 12.2% – 12.5% 3% – 9.3% 16% 9.3% 1.9% 22% –
infection
Blood/bacteremia 5.4% 31% 12.5% – – 3.9% – 3.9% 2.2% 2% 31%
1364 Support Care Cancer (2018) 26:1361–1367

Table 3 Distribution by main

agents of infections Pereira J. [10] Vitetta L. [14] White P. [20] Reinbolt R. [23]

Staphilococcus aureus 20.0% 10.5% 14.9% 14.9%

Escherichia coli 22.9% 36.8% 22.9% 27%
Enterococcus 11.4% – 11% 14.7%
Enterobacter Faecalis – 15.8% – –

defined as ≥ 14000 cells/mm3) and a left shift (percent
band neutrophils > 6% or total band count ≥ 1500/mm3)
had the highest likelihood ratio for the detection of a
bacterial infection [40].
– Urinalysis and urine culture, however, the majority of
elderly persons with bacteriuria are asymptomatic [41].
– Blood cultures. The mortality rates correlated with
bacteriemia range from 20 to 35%. In the first 24 h from
the diagnosis of bacteriemia occur 50% of deaths, despite
appropriate therapy [42].
– Chest scans. Despite the more precise and accurate imag-
ing methods that available nowadays, chest radiography
continues to be the most reliable method of diagnosing a
suspected pneumonia [43, 44].
– Sputum examination, which is performed in only 5–10%
of the patients with pneumonia [44].
– Skin and soft tissue culture obtained from cellulitis and
infected pressure ulcer.
Discussion
Good practice guidelines in antimicrobial use in palliative care
patients have not been established. Their frequency and deter-
minants have not been well described. The prescription pat-
terns need a better understanding to achieve a consensus for
structured guidelines about antimicromial use in this popula-
tion [17].
Some physicians are anxious about suspension of antibiotic
treatment since it may risk shortening the patient’s life. On the
other hand, others are concerned that this therapy could pro-
long the dying process. It is not possible to calculate if antibi-
otics will increase the chance of a cure or whether withholding
them will lead to death. Consequently, antibiotics do not fall
into the category of life-sustaining treatments, as do mechan-
ical ventilator support or tube feeding [12].
The diagnosis of infection in a palliative cancer patient is
not always easy. Indicators that make physicians think about a
possible infection such as fever or elevation of white blood
cells are not always present. Palliative patients use frequently
drugs such as acetaminophen, nonsteroidal anti-inflammatory
drugs, and corticosteroids, which could potentially blur the
febrile response. Corticosteroids can increase the peripheral
white blood cells count, confusing the laboratory diagnosis
of an infection. Patients having cognitive impairment may
have difficulty in exposing their symptoms. A fever may not
necessarily represent an infection; it could be neoplasm-in-
duced. Moreover, acute phase proteins like reactive C protein
and erythrocyte sedimentation rate are not good tools in dif-
ferentiating between cancer and infection because cancer pa-
tients tend to have higher acute phase protein levels than in-
dividuals who do not have cancer [43]. However, there is a
potential role for procalcitonin in the diagnosis of infection in
cancer patients [44, 45].

Table 4 Distribution by
antimicrobial therapy Pereira Vitteta Albrecht White Homsi J.
J. [10] L. [14] J. [17] P. [20] [29]

Levofloxacin – 26%* 18.2% 34.4%

Ciprofloxacin 23.6% 11.9%
TMP/SMX 44.4% 28.6% 19.1%
Trimethoprim – 20%
Cephalexin – 8.9% 7.8%
Macrolides –
Amoxicillin/clavulanate – 49% 9%
Fluconazole – 7.8%

TMP/SMX trimethoprim-sulfamethoxazole
*Fluoroquinolones
Support Care Cancer (2018) 26:1361–1367
In many cases, the existence of fever by itself led to a
medical diagnosis of infection, thus the true rate of infection
remains uncertain. In these cases, fever could have a potential
non-infectious origin, like drug-induced fever and fever sec-
ondary to underlying malignancy, particularly in the setting of
lymphoma, accelerated tumor growth or necrosis, or central
nervous system or hepatic spread [12]. Another potential
cause of fever is pulmonary embolism/deep venous thrombo-
sis [46], for which cancer is one of the most relevant risk factor
[47]. In the Urokinase Pulmonary Embolism Trial, 50% of the
patients with pulmonary embolism presented temperature >
37.5 °C [48]. In the Prospective Investigation of Pulmonary
Embolism Diagnosis Study, low-grade fever was presented in
14% of the patients with pulmonary embolism and no other
source of fever [49]. For the diagnostic process, there are
important components like history, physical examination,
and clinical features (pain, tenderness, or swelling of the leg;
shortness of breath, dyspnea, chest pain aggravated by inspi-
ration (pleuritic-type pain), or hemoptysis.
Antibiotic therapy may be beneficial in palliative symptom
control [14]. Antimicrobial therapy produces a substantial and
quick improvement in pain management. Green et al. reported
two cases of cancer patients treated with antimicrobials with
successful symptomatic control. One patient with the diagno-
sis of pneumonia had severe respiratory symptoms, and the
second patients had a delirium due to sepsis [50].
MacKey et al. reported a patient with a large abscess in
psoas muscle complaining of severe abdominal pain. A good
symptomatic control was achieved with surgical drainage and
antimicrobial treatment [51]. In other studies evoked in this
review were reported an antibiotic-induced symptom control
[14, 20, 22].
The decision-making process about the initiation of antibi-
otic therapy must have consideration in some aspects like the
patient’s and family’s desires, the uncontrolled pain, the main
diagnosis and its stage, and the level of multisystemic deteri-
oration. Since it is not possible to say if an antimicrobial treat-
ment will have a positive effect on symptomatic control, it
seems wise to initiate a therapeutic trial. If the clinical status
of the patient declines despite antimicrobial treatment, the
physician may decide to stop the administration. The
American Society of Clinical Oncology is against the use of
palliative chemotherapy in patients who have an Eastern
Cooperative Oncology Group (ECOG) performance status
score of ≥ 3 since it was not associated with quality of life
improvement and it was even associated with worse quality
of life in patients with good performance status [52]. The
authors think the same conclusion could be taken in concern
to antimicrobial therapy; a patient with a lower ECOG perfor-
mance status does not benefit from antimicrobial therapy.
Antibiotic therapy is often prescribed, possibly since there
are no guidelines about such a problem. Physicians have no
formal training in conversations about end-of-life decisions
1365
and are not sure about the clinical course of certain diseases
[18].
Healthcare providers must be stimulated to actively discuss
with patients and their families all the way through the course
of illness [18]. The increasing trend of hospice care and the
lack of clear guidelines regarding antibiotic use may lead to a
growing number of patients receiving potentially unnecessary
treatment for infections or not receiving the necessary pallia-
tive treatments. Consequently, further research is required to
guide antibiotic use in hospice care [17].
Miller D presents two cases for which the suspension of
antimicrobial therapy may be ethically accepted. The first sit-
uation is when antibiotics do not offer comfort or prolongation
of life. The second situation is when the quality of life of the
patient is getting worse, thus the patients himself do not con-
sider prolongation to be valuable [53]. Some authors recom-
mended an antimicrobial trial when in doubt about the treat-
ment; an approach that comforts both the medical staff and
family [54].
Another important concept is the palliative surgery, whose
primary intention is to improve the patient’s quality of life and
symptom relief, in particularly advanced diseases which can-
not be treated in another way. The effectiveness of a palliative
surgery is measured by the control and the durability of symp-
tom control. To perform this kind of procedure, the symptom,
the objectives of the patient, the impact of the procedure in the
quality of life and in the function of the patient, the prognostic
of the disease, the expected time of survival of the patient, the
existence of non-surgical options, and experience of the sur-
geon and technical considerations like adherences, must all be
considered. Some examples of procedures are the following:
paracentesis, toracocentesis, pericardiocentesis, derivation of
bile duct or choledochus, citorreduction, implantation of
endoprosthesis to overcome an obstruction, pleurodesis, cra-
niotomy, pathologic fracture fixation, amputation, tumor em-
bolization, tracheostomy, and many others. The derivative
procedures of the digestive tube have some contraindications,
like ascites, peritoneal carcinomatosis, multiple sites of ob-
struction, very advanced disease, and low-performance status.
No two patients are equal; therefore, the decision to perform a
procedure or not must be made on a case-by-case basis and
always taking into consideration the opinion of the patients,
family, and physician.
Suggestions for antibiotic use in palliative care
& Patients and family should be heard and involved in the
discussion regarding how to best treat their infections.
& Consider the symptomatic control as the main indication
for the use of antimicrobials (antimicrobial treatment of
urinary tract infections improves symptoms in a large ma-
jority of patients but is much less successful in respiratory
and skin infections, and bacteremia is very poorly con-
trolled) [14, 20, 22, 23].
1366
& When the risk of danger and rare complications is irrele-
vant, consider the use of old-fashioned antibiotics, like
chloramphenicol (it has good bioavailability, good cover
range, and is inexpensive) [15].
& When an infection do not contribute to debilitating symp-
toms, when multisystem affection is present or the patients
can no longer swallow, antimicrobial therapy should not
be considered palliative [12].
& Discontinuing a medical therapy may be more difficult than
initiating one. If a treatment is initiated and considered no
longer helpful for the patient, it can be stopped. Although
informed consent is not habitually required, the decision
should be deliberated with the patient and family [55].
& In all situations, the decision on starting an anitimicrobial
therapy depends on the predictable prognosis of survival
and the course of the illness, as the expected survival time
of the patient should be long enough to finish and profit
from the antibiotics [21].
Compliance with ethical standards
Conflict of interest The authors declare that they have no conflicts of
interest.
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