Principles of initiating antimicrobial therapy and empiric

prescribing
pharmaceutical-journal.com/cpd-and-learning/cpd-article/principles-of-initiating-antimicrobial-therapy-
and-empiric-prescribing/20201507.cpdarticle
Clinical Pharmacist 11 AUG 2016 By Shilpa
Jethwa

Healthcare professionals should be aware of the principles of antimicrobial treatment

and the need to reduce inappropriate prescribing to retain the effectiveness of drugs
currently available.

Source: Nicolle R Fuller / Science Photo Library

Computer illustration showing antimicrobial peptides penetrating a bacterium’s membrane (lower centre). A
micelle (spherical formation, upper centre) forms from the microbial lipid bilayer (the fatty molecules), and the
cell is punctured

An antimicrobial agent is defined as a substance that inhibits the growth of

microorganisms[1] . Antimicrobial agents act by targeting specific sites in a wide range of
organisms, including bacteria, viruses, fungal, protozoa and helminths; antibiotics are a
subcategory of this large group and have the ability to kill or inhibit the growth of
bacteria [1] . Originally, antibiotics were substances produced by microorganisms that
selectively inhibit the growth of another[1] ; however, many of these drugs are
manufactured synthetically and achieve comparable outcomes.

Antimicrobial therapy was integrated into medicine in the 1930s, and these agents have 1/20
Antimicrobial therapy was integrated into medicine in the 1930s, and these agents have
made procedures such as arthroplasties and transplants possible[1],[2] . With few new
antibiotic agents currently in trials or development, the increase of antimicrobial
resistance represents a major global health problem[3],[4],[5] . Inappropriate use of
antimicrobials and broad-spectrum antibiotics contributes to the selection pressure for
the emergence of resistant pathogens[3],[6],[7] .
The UK government has recognised that antimicrobial resistance is a significant health
issue and in 2013 produced a five-year strategy to slow its development and spread[8] .
Healthcare professionals should be aware of the basic principles of antimicrobial
treatment[1] and the need to reduce inappropriate prescribing of antibiotics in order to
retain effectiveness of the drugs currently available[3],[4],[5],[6],[7],[8] . This article mainly
focuses on antibiotics, however, the principles relevant to this class of antimicrobial
agent can be applied to others. The mode of action of antibiotics and resistance
mechanisms, whether intrinsic or acquired, is outside the scope of this article and is
covered elsewhere[9] .

Misuse and overuse of antibiotics

Published studies from the UK and the United States estimate that around 30% of
patients receive antibiotics while in hospital[10],[11],[12].
Since their introduction, antimicrobials have been misused and inappropriately
prescribed, resulting in the selection of resistant organisms. Examples include[13]:
Prescribing antibiotics without clear evidence of bacterial infection;
Prolonged empiric antimicrobial treatment without clear evidence of infection;
Treatment of a positive culture in the absence of disease – patients can be
colonised with an organism without having clinical symptoms of an infection (e.g.
asymptomatic bacteriuria or identification of coagulase negative Staphylococci in
blood cultures[14],[15]);
Failure to de-escalate patients to a narrow spectrum agent once the causative
organism has been identified. Often this does not occur as prescribers are
resistant to change because the patient has improved on the current antibiotics;
Prolonged prophylactic therapy, which is unnecessary and promotes the evolution
of resistant organisms. However, prophylactic antibiotics are useful and
recommended for certain procedures to prevent post-operative infections[16].

Judicious prescribing will reduce the selective pressure on bacteria and slow the
emergence of resistance. Several national initiatives have been proposed to combat
antimicrobial resistance and promote appropriate prescribing, which include:
For further information on national and international initiatives, please see ‘Box 1:
National and international initiatives’.

Box 1: National and international initiatives

Antimicrobial resistance is a healthcare priority, which is being addressed both
nationally and internationally through various routes. These include:

TARGET

Treat Antibiotics Responsibly, Guidance, Education, Tools (TARGET) is designed to be 2/20

Treat Antibiotics Responsibly, Guidance, Education, Tools (TARGET) is designed to be
used by the whole primary care team within the GP practice or out-of-hours setting,
but it is also relevant to mental healthcare settings. The toolkit aims to help influence
prescribers’ and patients’ attitudes, beliefs and perceived barriers to optimal
antibiotic prescribing[19].

‘Start smart – then focus’

An outline of evidence-based antimicrobial stewardship practice for use in secondary
care settings, this guidance from Public Health England provides information on
strategies to improve antibiotic use within secondary care, as well as suggested audits
to improve practice[20].

English surveillance programme for antimicrobial utilisation and

resistance
The 2015 English surveillance programme for antimicrobial utilisation and resistance
(ESPAUR) report[21] highlighted that the majority of antibiotics in England (74%) are
prescribed in general practice. Overall, the total consumption of antibiotics in England
(measured as defined daily doses per 1,000 inhabitants per day) increased by 6.5%
between 2011 and 2014. Prescribing by dentists decreased by 2.8% but general
practice consumption increased by 6.2% and secondary care prescribing for
inpatients increased by 11.7%. Essentially, antimicrobial use is rising, which leads to
increased resistance, increased frequency of treatment failure, decreased treatment
options available and increased costs. It is imperative that the guidance provided is
used and antimicrobial stewardship activities are incorporated within healthcare
sectors[22].

Antimicrobial stewardship
Stewardship is defined as the right antibiotic for the right patient, administered at the
right time, at the right dose and via the right route, causing the least harm to the
patient and future patients[23]. The three major goals for antimicrobial stewardship
are to optimise therapy for individual patients, prevent overuse, misuse and abuse of
antimicrobials, and minimise the development of resistance at patient and
community levels[24].

National Institute for Health and Care Excellence guidance

The aim of the National Institute for Health and Care Excellence guidance is to
“change prescribing practice to help slow the emergence of antimicrobial resistance
and ensure that antimicrobials remain an effective treatment for infection” by
providing advice on the effective use of antimicrobials in children, young people and
adults, not only for healthcare professionals but for commissioners, the social sector
and the public. It is divided into four parts, covering: stewardship programmes,
prescribing, the introduction of new antibiotics and suggestions on how to change
prescribing practice [18].

World Health Organization resolution

In May 2014, the World Health Organization (WHO) passed a resolution that reflects 3/20
 In May 2014, the World Health Organization (WHO) passed a resolution that reflects
global agreement on the huge threat that antimicrobial resistance poses to human
health. Many countries have national action plans in place that follow the WHO
strategy[25]. The global action plan seeks to preserve and maintain responsible and
accessible use of antimicrobials for all. The main strategic objectives focus on
improving the understanding and awareness of antimicrobial resistance,
strengthening knowledge via research and surveillance, reducing infection incidence,
optimising the use of antimicrobial treatments and countering antimicrobial
resistance through sustainable investment[25]. The UK has a plan in place to slow the
development and spread of antimicrobial resistance, which is supported by the
ESPAUR[21],[25].

Empiric versus definitive therapy

Antimicrobial therapy should only be initiated when there is a strong suspicion of an
infection[1] . The patient’s presenting symptoms, as well as imaging and biochemical
parameters, should be used to aid diagnosis[1],[26]. Symptoms of infection often include
fever, changes in respiratory rate and blood pressure, confusion and tachycardia.
Laboratory and radiological tests are important considerations for the assessment of the
patient in conjunction with clinical findings[1] . It should be noted that radiological
improvement frequently lags behind clinical improvement and a repeat chest X-ray is not
always indicated[2] . Biochemistry tests include measurement of C-reactive protein (CRP)
to determine if inflammation is resolving, and monitoring of the patient’s temperature,
white cell and neutrophil count to determine the response to treatment. These should be
considered together with clinical symptoms[1],[2],[26].
Empiric therapy for infections can be described as ‘best guess’ therapy because no
information is available regarding the causative organism and the likely antimicrobial
susceptibility. It is not an exact science and can be better described in mathematical
terms as the treatment of an infection with an agent, where there is a high probability
that the causative organism is sensitive to that agent[1],[13],[26],[27] and will depend on
national as well as local resistance patterns. For most cases, treatment of an infection is
empiric and the most likely microbiological etiology can be inferred from the clinical
presentation[13]. For example, the common causative organisms in cellulitis are
Streptococci and Staphylococci, and therefore appropriate antibiotics can be administered
in the absence of a positive culture[28].
Clinical presentation acts a guide for most empiric treatment because microbiology test
results are not usually available for 48–72 hours after initial therapy. Patients presenting
with acute and increasingly severe infections require prompt treatment to decrease
morbidity and mortality[27]. Therapeutic treatment usually involves a broad-spectrum
antibiotic (either as a single agent or combination of agents) against the most common
likely causative bacteria; therapeutic inadequacies are associated with poor outcomes,
including increased morbidity, mortality and increased length of inpatient hospital
stay[13],[29].
Diagnosis should be supported by laboratory investigations, if possible, to establish the
causative organism and its susceptibility to antimicrobial agents[27]. When the organism
responsible for the infection is known, targeted treatment with an agent the organism is
susceptible to in vitro can commence (known as definitive therapy)[13]. Focused therapy
(i.e. de-escalating or escalating treatment)[13], can help reduce adverse drug reactions,
optimise treatment, prevent the emergence of resistance and reduce costs[13].

The aim of treatment is to eradicate the infection efficiently and achieve good clinical 4/20
The aim of treatment is to eradicate the infection efficiently and achieve good clinical
outcomes (a clinical or bacteriologic cure and no relapse) with the least toxicity[27],[30].

Bactericidal versus bacteriostatic agents

Antimicrobial agents are often described as bactericidal or bacteriostatic [27],[30].
Bacteriostatic agents prevent the growth of bacteria — that is, they are maintained in the
stationary phase of growth (e.g. clindamycin, linezolid and tetracyclines), whereas
bactericidal agents kill bacteria (e.g. beta-lactam agents, aminoglycosides and
fluoroquinolones[30]). However, this is overly simplistic; in reality, there are not two pure
categories. The in vitro microbiological determination of whether an antibacterial agent is
bactericidal or bacteriostatic may be influenced by growth conditions, bacterial density,
test duration and the extent of reduction in bacterial numbers[30]. Therefore, most
antibacterials can be better described as being potentially both bactericidal and
bacteriostatic. At high concentrations, bacteriostatic agents are often bactericidal against
some susceptible organisms[30],[31]. Macrolides are considered to be one of the classic
bacteriostatic drug classes, but erythromycin, azithromycin and clarithromycin have
shown bactericidal activity in vitro against Streptococcuspyogenes and
Streptococcuspneumoniae[32],[33],[34],[35]. Similarly, chloramphenicol is bactericidal against
S. pneumoniae but bacteriostatic against Staphylococcus aureus and group B
Streptococcus[36],[37],[38],[39]. Clindamycin may be bactericidal in vitro, depending on the
organism and growth conditions[40],[41]. In vitro, linezolid has bacteriostatic activity
against Staphylococci and Enterococci but bactericidal activity against Streptococci,
including S. pneumoniae[42],[43].
There are clinical conditions where a bactericidal agent is necessary. In endocarditis, for
example, bacteria within cardiac vegetations can reach very high concentrations, and the
rates of metabolism and cell division appear to be reduced, resulting in reduced
susceptibility to bactericidal agents[30]. Clinical cure is often achieved but this usually
requires prolonged administration of relatively high doses of bactericidal agents. By
contrast, studies have described the successful use of bacteriostatic agents for the
treatment of infective endocarditis[30].
For the treatment of meningitis, it is important to choose a bactericidal agent that
penetrates the cerebrospinal fluid to eradicate the infection as rapidly as possible (e.g.
ceftriaxone)[44]. Certain bacteriostatic agents have been used successfully to treat Gram-
positive bacterial meningitis[30].
Osteomyelitis can be difficult to treat on account of decreased vascular supply and
penetration of adequate concentrations of the drug in bone. For this reason, a
bactericidal agent may seem a logical choice, however, clindamycin, a bacteriostatic
agent, achieves high concentrations in bone and is considered an appropriate agent for
the treatment of Gram-positive bacterial osteomyelitis[45],[46] in combination with
appropriate adjuvant therapy.

Pharmacokinetics and pharmacodynamics

The current definition of pharmacokinetics is the study of the time course of drug
absorption, distribution, metabolism and excretion. Pharmacodynamics refers to the
relationship between drug concentration at the site of action and the resulting effect,
including the time course, and intensity of therapeutic and adverse effects [1],[13],[26],[27].

Certain antibiotics (e.g. beta-lactams and glycopeptides) can be described as time- 5/20
Certain antibiotics (e.g. beta-lactams and glycopeptides) can be described as time-
dependent — the duration of time the drug concentration remains above the minimum
inhibitory concentration (MIC) — while others (e.g. aminoglycosides amikacin and
gentamicin) can be described as concentration-dependent — the ratio of the maximal
drug concentration to the MIC and the ratio of the area under the concentration time
curve at 24 hours to the MIC [26],[27],[30].
For antibiotics to be effective, there must be sufficient concentrations of the agent(s) at
the site of the infection. This differs according to the type of infection and antibiotic
administered. Concentrations of antibiotics rise and fall after administration, and
frequency of administration of antibiotic is dependent on several drug and host factors.
Post-antibiotic effect can be defined as the continued inhibition of bacterial growth,
beginning when the organisms are exposed to an antibiotic until the bacterial survivors
begin to replicate again to a significant degree. Significant post-antibiotic effects are
observed with aminoglycosides, macrolides and quinolones against Gram-negative
bacteria [26],[27].

Selecting which antimicrobial agent to prescribe

The choice of agent, or agents, is dependent on many drug and host factors. Patient
factors that need to be considered when selecting the most suitable treatment for an
infection include [1],[13],[26],[27]:
Differential diagnosis/indication;
The most likely organism(s) causing the infections;
The patient’s allergy status;
The severity and duration of the infection;
Whether the patient is immunocompromised;
The patient’s renal and hepatic function;
Whether the patient has had previous antibiotic exposure;
Genetic factors;
Local epidemiology;
Colonisation with resistant organisms;
The patient’s age and gender;
If the patient on any other concomitant medication;
Whether the patient is pregnant or breastfeeding;
The patient’s vaccination history;
Whether the patient has been travelling;
If the patient has any history of drug abuse;
The presence of any risk factors.

Gathering information, including taking a detailed patient history[47], is necessary to

ensure that the most suitable agent is prescribed[26],[27]. Any previous microbiology
results may inform the healthcare professional of whether the patient is infected with
resistant organisms (e.g. methicillin- resistantS. aureus [MRSA], vancomycin-resistant
Enterococci [VRE], an extended spectrum beta-lactamase [ESBL]-producing organism or a
carbapenemase-producing Enterobacteriaceae [CPE]). Together with the type of infection
and working (until proven) diagnosis, this information should guide the healthcare
professional as to which agent(s) to prescribe empirically.

Certain drugs should always be prescribed in combination (e.g. rifampicin and fusidic 6/20
Certain drugs should always be prescribed in combination (e.g. rifampicin and fusidic
acid) because the use of these drugs individually can result in the emergence of resistant
bacteria [1],[26]. When agents exhibit synergistic activity against a microorganism,
combination therapy is recommended to extend the antimicrobial spectrum beyond that
achieved by the use of a single agent, especially in polymicrobial infections and to
prevent the emergence of resistance[13]. In patients without a penicillin allergy,
combination therapy with a beta-lactam agent and an aminoglycoside is common as
first-line treatment for certain infections (e.g. sepsis[48]). For the management of
community-acquired pneumonia, the severity of infection and, consequently, choice of
agent is dictated by the CURB score in hospitals and CRB score in primary care[49]. By
contrast, the treatment of infective endocarditis requires treatment with high doses of a
parenteral antibiotic for a longer duration than normal[50]. It has also been demonstrated
that for infective endocarditis, an aminoglycoside plus benzylpenicillin provides a
synergistic response that is favourable, compared with when each drug is prescribed
alone[50].
However, combination therapy of antimicrobials is not always beneficial and can be
antagonistic in vitro. For example, a study by Lepper et al. showed worse clinical
outcomes when a penicillin and tetracycline were prescribed in combination compared
with either drug being prescribed alone[26],[51].

Prescribing in special groups

The pharmacokinetics of antimicrobial agents are different in the following groups and,
therefore, pose an increased risk of drug toxicity[8] :
Paediatric patients;
Older patients;
Patients with low/increased body weight;
Patients with renal/hepatic insufficiency;
Patients with allergy.

These factors contribute to the decision-making process when determining choice, dose,
route, formulation and frequency of drug.
The pharmacokinetics and pharmacodynamics in premature infants, neonates and
paediatrics differ to adults because of their relatively immature systems. This again
differs in older patients because of multiple comorbidities and age-related renal
insufficiency[26],[27]. The use of antibiotics in pregnancy is warranted when the benefits
outweigh the risks. Since some antibiotics have a greater potential to pass through the
placenta to foetal tissues, antibiotic prescribing in pregnancy should be restricted unless
necessary, especially during the first trimester when organogenesis is maximal[27].
Antibiotics also have the potential to be excreted into breast milk. For most, the
concentrations are too small to have an adverse effect on the baby; however, certain
drugs (e.g. metronidazole, tetracyclines and erythromycin) are readily excreted into
breast milk and are contraindicated[52].

Obesity plays a major factor in the dosing of antibiotic agents, affecting both the 7/20
Obesity plays a major factor in the dosing of antibiotic agents, affecting both the
clearance and volume of distribution of the agent[53]. Antibiotics can also be described as
being hydrophilic (e.g. beta-lactams, glycopeptides and aminoglycosides) or lipophilic
(e.g. fluoroquinolones, quinolones and clindamycin). Hydrophilic drugs mainly distribute
in the extracellular fluid (not fat), whereas lipophilic drugs distribute into fat[27]. It can be
complicated to calcuate the correct dose for obese patients[27] because around 30% of
adipose tissue is water; therefore, total body weight overestimates renal function in
these patients, while the use of ideal body weight underestimates renal function[53].
Furthermore, obese patients are generally underrepresented in clinical trials and,
therefore, data on appropriate dosing and effectiveness are limited in this patient
group[54],[55]. Specific advice should be sought from an antimicrobial pharmacist,
consultant microbiologist, infectious diseases physician or medicines information
department before commencing treatment in obese patients.
Many antibiotics are either renally or hepatically cleared, which poses a problem in
patients with renal or hepatic impairments. Dose reduction should be exercised in
patients with renal insufficiency [13],[27]. However, for drugs that have a narrow
therapeutic index, treatment should be adjusted according to clinical response and
serum drug concentrations. For patients with liver disease, hepatically metabolised
antibiotics should be used with caution and the dose adjusted if necessary according to
the patient’s liver function tests (LFTs). LFTs should be monitored throughout the
duration of treatment to ensure the antibiotics are not damaging the patient’s liver.

Route of administration
Antibiotics are administered via a number of routes (e.g. topically, orally, intravenously,
intramuscularly, intraperitoneally or nebulised). The bioavailability (the amount of active
drug that reaches systemic circulation) of oral formulations varies: some have excellent
bioavailability (e.g. the fluoroquinolones[56],[57],[58]), while others have little-to-no
absorption (e.g. the glycopeptides[59]). Other antibiotics lie somewhere in between and
for some agents their bioavailability is affected by the presence of food, iron or calcium
products[60]. In increasingly severe infections, intravenous preparations are the
preferred choice to achieve optimal drug concentrations.

Intravenous to oral switch

Not all patients who are admitted to secondary care because of the severity of their
illness are initiated on parenteral antibiotics. Some patients admitted for other reasons
(e.g. dehydration, pain control or with no gastro-intestinal dysfunction) are prescribed
and administered antibiotics with good oral bioavailability, such as fluoroquinolones[1] .
Patients prescribed intravenous antibiotics should be reviewed after 48 hours and
switched to an oral equivalent if they are clinically improving (i.e. they are
haemodynamically stable, apyrexial and CRP, white cell and neutrophil count trending
towards normal[58]). Patients should be able to swallow, tolerate oral fluids and a suitable
oral agent or equivalent should be available. Prescribing or switching to oral agents has a
number of advantages: it facilitates the removal of any in-dwelling catheters/venflons,
treatment costs are decreased, there are fewer adverse drug reactions, the patient may
be discharged earlier from hospital and they are consequently less likely to develop
hospital-acquired infections[58],[61],[62]. For some infections (e.g. osteomyelitis, infective
endocarditis, line infections and deep seated infections), an oral switch is not
recommended[50],[63].

Duration of therapy
8/20
The duration of treatment is controversial because there are few published studies
regarding this and many of the recommendations are based on expert
opinion[13],[44],[45],[46],[50]. The optimal duration of therapy is one that is short enough to
treat the infection without the peripheral effects (e.g. adverse drug reactions and
resistance[1] ). Treatment should continue for as long as necessary until all
microorganisms are eliminated, or the infection has been sufficiently controlled for the
host defenses to eradicate it. Cessation of antibiotics should be supported by clinical,
microbiological and biochemistry parameters[1],[13],[26],[27],[64]. Most infections require
treatment of between five and seven days and, depending on the patient’s response and
difficult-to-treat infections, an extended course may be required to achieve
microbiological eradication [65]. There are exemptions that warrant long-term treatment
(e.g. endocarditis, osteomyelitis and Mycobacterium tuberculosis) to prevent recurrence or
worsening of the infection[27],[50],[66], or short-term treatment (e.g. uncomplicated urinary
tract infection in females) when a three-day course of antibiotics is sufficient [67].

Therapeutic drug monitoring

Serum concentration should be monitored for drugs with a narrow therapeutic index to
ensure treatment failure does not occur because of low levels, or toxicity does not occur
because of high levels[1],[13],[26],[27]. Most antimicrobial agents have a wide therapeutic
index and, therefore, in most scenarios, standard doses can be used[1] . Vancomycin and
aminoglycosides are common antibiotics that have a narrow therapeutic window and,
therefore, therapeutic drug monitoring is indicated[68],[69],[70].

Adverse drug reactions

Obtaining a history and assessing the patient may prevent inadvertent administration of
an agent that the patient may react to[1],[71]. All drugs have the potential to cause an
adverse drug reaction[72] but not all patients experience them. Around one in five
patients experience very minor intolerant reactions (e.g. gastrointestinal disturbances),
while others may develop a rash, urticaria, laryngeal oedema, bronchospasm or
hypotension[71]. The beta-lactams are recognised as one of the most frequent causes of
adverse drug reactions[71]. The symptoms that a patient experiences should be managed
according to the nature and severity of the reaction. Healthcare professionals involved in
prescribing, screening and administering an antibiotic should be aware that the risk of a
patient experiencing an adverse drug reaction increases with the number of antibiotic
prescriptions [73],[74].

Failure to respond
Patients do not always respond to antibiotic therapy; there are a number of reasons why
this may occur[1],[13],[26],[27],[75],[76],[77]:

Source control/adjuvant therapy is required, persistent bacteraemia is often an 9/20

 Source control/adjuvant therapy is required, persistent bacteraemia is often an
indication that source control is required before the infection can be completely
resolved.
Source control encompasses a spectrum of interventions with the objective
of the physical control of the foci of infection and the restoration of optimal
function and quality of life. Source-control measures can be categorised as
surgical drainage, debridement (i.e. the physical removal of solid necrotic
tissue), device removal or more definitive measures to restore optimal
function to the involved area[78],[79];
Incorrect choice of antibiotic(s);
Wrong dose or poor penetration – pharmacokinetic and pharmacodynamic
properties.
A report that a pathogen is susceptible to an antibiotic in the laboratory does
not assure treatment success. Inadequate penetration of the infection site is
one of the principal factors related to failure of antibacterial therapy[30]. The
active drug needs to reach the bacteria in appropriate body fluids and tissues
at concentrations necessary to kill or suppress the pathogen’s growth. The
ability of antibacterial agents to cross the blood–brain barrier is an important
consideration for the treatment of meningitis;
Causative bacteria becoming resistant to the current agents prescribed;
Etiology may not be infective;
Poor compliance (oral prescription);
Impaired host defense mechanisms;
Site of infection;
Underlying disease.

Antimicrobial prophylaxis
The prophylactic use of antibiotics is necessary in some scenarios to prevent or reduce
the risk of an infection post-operatively. Some procedures are associated with a high
infection rate, for example surgical interventions involving the implantation of a
prosthetic material[16]. The antibiotic(s) prescribed should be effective against the
bacteria most likely to cause infection, the antibiotics should be present in the tissues
when the initial incision is made and adequate serum concentrations should be
maintained during the procedure. Duration of prophylaxis for surgical site infection
should not exceed 24 hours in most cases[16],[80].

Cost of treatment
Selection of the most suitable antimicrobial agent and cost are important considerations
when developing empiric guidelines. Acquisition costs for parenteral antibiotics are
generally greater than oral formulations[1] . However, the biggest economic burden is
attributed to inpatient hospital stay[1] . Administration of parenteral antibiotics includes
additional costs (e.g. fluids for reconstitution and administration, as well as nursing and
administration time). There is also an ecologic impact of the use of these agents on
resistant pathogens and several antibiotic stewardship activities are underway to
minimise the inappropriate use of these agents, as well as to slow down the rate of
resistance[1] .

Guideline development

In addition to costs, empiric guidelines consider the most likely organism(s) causing the 10/20
In addition to costs, empiric guidelines consider the most likely organism(s) causing the
infection, national and local resistant patterns, and patient factors when contemplating
choice of drugs. Guidelines should have first-line, second-line and third-line
recommendations for empiric treatment of common infections. First-line agents are
recommendations for patients with no known allergies. Second-line agents are
recommendations for patients who do not have an anaphylactic reaction to penicillin or
related agents, and third-line agents are recommendations for patients who have a type
1 reaction to penicillin or related agents[81].

Financial and conflicts of interest disclosure:

The author has received fees for an advisory board meeting from MSD. The author
has no other relevant affiliations or financial involvement with any organisation or
entity with a financial interest in or financial conflict with the subject matter or
materials discussed in the manuscript apart from those disclosed. No writing
assistance was utilised in the production of this manuscript.

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CPD Questions:
1. For women who are breast feeding, the prescription of metronidazole is not
recommended because it can be excreted into the mother’s breast milk. True or false?
2. A patient who has been prescribed intravenous antibiotics, who is clinically improving,
can be switched to an oral equivalent after 24 hours. True or false?

3. To help slow the emergence of resistance to antimicrobials, patients with bacterial 16/20
3. To help slow the emergence of resistance to antimicrobials, patients with bacterial
infection should be de-escalated to a narrow spectrum agent once the causative
organism has been identified. True or false?
4. Owing to its narrow therapeutic window, therapeutic drug monitoring is
recommended for vancomycin. True or false?
5. A patient may not respond to an antibiotic due to a variety of reasons, including that
the incorrect dose has been prescribed, the bacteria has become resistant to the
antibiotic or the patient has poor compliance to their oral prescription. True or false?
6. Prescribing benzylpenicillin alone is favourable for patients with infective endocarditis.
True or false?
7. When treating Gram-positive bacterial osteomyelitis, clindamycin, in combination with
appropriate adjuvant therapy, is not recommended. True or false?
8. Antibiotics should never be prescribed during pregnancy. True or false?
9. All oral and intravenous preparations have equal bioavailability, therefore, in very
severe infections, both formulations are equally effective. True or false?
10. A patient who is prescribed multiple antibiotics is not at an increased risk of adverse
drug reactions. True or false?
11. To reduce the risk of an infection post-operatively, prophylactic use of antibiotics
must always exceed one day. True or false?
12. The delayed regrowth of bacteria following exposure to an antibiotic is known as the
post-antibiotic effect. True or false?
13. When determining choice, dose, route, formulation and frequency of an antibiotic,
the patient’s age and body weight should be taken into consideration. True or false?
14. Tetracyclines are considered as potentially bacteriostatic agents and their action
prevents the growth of bacteria, maintaining them in the stationary phase of growth.
True or false?
15. To prevent bacterial resistance, rifampicin should not be prescribed in combination
with fusidic acid. True or false?
Citation: Clinical Pharmacist, August 2016, Vol 8, No 8, online | DOI:
10.1211/CP.2016.20201507

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