The Value of C-reactive Proteinin Primary Health Care PO

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The Value of C-reactive Proteinin Primary Health Care PO

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Disclaimer This booklet is intended to provide health care practitioners with an overview of QuikRead CRP, a rapid C-reactive

protein assay, its diagnostic potential and value in routine primary care practice.

Although every effort has been made to provide accurate information, Orion Diagnostica accepts no respon-

sibility whatsoever for the accuracy, correctness or completeness of the information contained in this booklet. It is

the responsibility of the health care practitioner to evaluate the contents of this booklet and to verify the informa-

tion presented. The ultimate judgement regarding the care and appropriate treatment of a particular individual

must always be made by the health care practitioner in the light of all the clinical information available about the

individual.

Orion Diagnostica therefore accepts no liability for any injury or damage to person or property resulting from

acceptance of the information in this booklet. Hence, liability claims regarding possible injury or damage will be

rejected.

The information in this booklet may contain references to products that are not available or approved by the

regulatory authorities in your country. Orion Diagnostica assumes no responsibility for you accessing information

that may not comply with legislation, regulations or usage applicable in your country. You are advised to consult

Orion Diagnostica’s local business contact or marketing partner for information about the availability of Orion

Diagnostica products in your country.

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Contents

Introduction .................................................................................. 7

Antibiotic use and resistance ......................................................... 8 Antibiotic resistance on the rise ........................................................................ 8

Development of new antibiotics on the decline ................................................. 9

Variation in antibiotic use and antibiotic resistance among countries ............... 10

C-reactive protein (CRP) .............................................................. 11 CRP in distinguishing between bacterial and viral infections ............................ 11

CRP in monitoring the efficacy of antibiotic therapy ........................................ 12

CRP versus erythrocyte sedimentation rate (ESR) ............................................. 13

CRP versus white blood cell count (WBC) ........................................................ 13

CRP versus procalcitonin (PCT) ........................................................................ 13

CRP is a good servant ..................................................................................... 13

QuikRead CRP guides the use of antibiotics ................................. 14 Diagnostic dilemma ........................................................................................ 14

QuikRead CRP ................................................................................................ 14

Interpreting the QuikRead CRP test result .................................... 16QuikRead CRP in various clinical situations .................................. 17 Serious bacterial infections ............................................................................. 18

Acute respiratory tract infections .................................................................... 18

Upper respiratory tract infections.............................................................. 19

Common cold .................................................................................... 19

Acute sinusitis .................................................................................... 19

Acute pharyngitis ............................................................................... 19

Acute otitis media .............................................................................. 20

Lower respiratory tract infections.............................................................. 20

Acute bronchitis................................................................................. 20

Community-acquired pneumonia ....................................................... 21

Urinary tract infections ................................................................................... 22

QuikRead CRP in the routine diagnosis of acute respiratory tract infection ................................................... 23

References .................................................................................. 26

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Introduction

This booklet is intended to give primary care practitioners an overview of

QuikRead® CRP, a rapid C-reactive protein (CRP) assay, its diagnostic po-

tential and value in routine practice. The emphasis is on situations in which

an immediately available, quantitative CRP result can help to make adequate

and timely diagnostic and treatment decisions.

CRP is a protein normally present in very low concentrations in the

blood of healthy people. In bacterial infections, CRP concentrations mark-

edly increase, whereas viral infections usually only induce very modest CRP

elevation or none at all.

In primary care, a large proportion of antibiotics is prescribed to treat

conditions in which antibiotics are of little or no benefit. Excessive and

inappropriate use of antibiotics, leading to the emergence of increasingly

resistant bacteria, has become a severe problem worldwide. Against this

background, the individual health care practitioner often faces the dilemma

of how to identify patients who need – and particularly those who do not

need – antibiotic therapy.

QuikRead CRP is an easy-to-use test for quantitative measurement of

CRP. The test is designed to be performed on a finger-prick blood sample and

the test result is available in a couple of minutes during the patient consulta-

tion. QuikRead CRP is a valuable tool helping the primary care practitioner

to distinguish between bacterial and viral infections and to target antibiotic

treatment to patients most likely to benefit from it.

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Antibiotic use and resistance

Antibiotics are a cornerstone for the management of bacterial infections.

Therefore, antibiotics should be used with caution and only when absolutely

necessary.

Like all medicines, antibiotics can cause side effects. The most common

side effects are generally considered to be mild, and include conditions such

as headache, dizziness, gastrointestinal upset, nausea and vomiting.1,2,3

However, antibiotics may alter the normal microbial flora of the patient

and lead to acute or even chronic disease in some individuals.4,5,6,7,8,9,10 The

effects of antibiotic treatment on the native gut microbial flora are well

established and range from self-limiting mild diarrhea to life-threatening

pseudomembranous colitis.11,12,13,14 Vaginal yeast infections are also common

after taking antibiotics.15,16,17,18 Being a cause for concern and discomfort for

many women, they may even be a reason for not wanting to take prescribed

antibiotics.15 Even a short-term antibiotic course can cause long-term altera-

tions in the commensal microbial flora of the individual patient4,5,6,19, and

therefore unnecessary antibiotic courses should be avoided.

Antibiotics can also cause allergic reactions ranging from skin rash to

severe life-threatening attacks that require immediate medical attention.20

Other serious adverse reactions that warrant for the judicious and cautious

use of antibiotics include alterations in blood glucose levels, QTc interval

prolongation, seizures, phototoxity and tendinopathy.3,21

Recently, antibiotic use in early life has also been linked to childhood

asthma.22,23,24

Antibiotic resistance on the rise

Frequent use of antibiotics results in antibiotic resistance which is one of the

most serious public health concerns today.25–28 A strong correlation between

frequent use of antibiotics and a rising rate of antibiotic resistance has been

established in many studies (Fig. 1).27, 29–31

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Antibiotic-resistant bacteria have steadily increased and present a threat to

disease management32 not only in hospitals but also in primary care.33 Many

previously effective antibiotics are now ineffective, and the appearance of

multidrug-resistant bacteria is contributing substantially to the problem.26,32–34

About 80–90% of antibiotics are prescribed within primary care27,35–37,

and as many as 50% of these prescriptions are likely to be unnecessary.33,36

Moreover, broad-spectrum antibiotics are substantially overused, even for

conditions where antibiotic therapy is not indicated at all, a practice addi-

tionally driving up resistance problems.38,39

Development of new antibiotics on the decline

Development of new antibiotics is not keeping pace with the increase of anti-

biotic resistance. Despite the critical need for new antibiotics, the development

of these drugs is declining.25,31,32,40 It is estimated that the development of a

new antibiotic takes 10–15 years from discovery to approval.31,41

Total antibiotic use (DDD/1,000 pop/day)

Pen

icill

i-n

on

susc

epti

ble

S. p

neu

mo

nia

e (%

)

Fig. 1. Total antibiotic use in the out patient

setting versus prevalence of penicillin-

nonsusceptible Streptococcus pneumoniae in

20 industrial countries. DDD = defined daily

doses.30

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Variation in antibiotic use and antibiotic resistance among countries

The use of antibiotics in primary care differs among countries (Fig. 2), which

is unlikely to be caused by differences in frequencies of bacterial infections.42

Antibiotic-prescribing practices, attitudes towards antibiotic use and regula-

tory control of prescribing have been found to have an impact on the preva-

lence of antibiotic-resistant bacteria.28,42–45

Most antibiotic prescriptions in primary health care are for acute respi-

ratory tract infections. Antibiotic treatment of these conditions is, however,

often inappropriate, since the vast majority have a viral cause (see Acute

respiratory tract infection, page 15). A diagnostic test providing an objective

and immediate result that confirms or rules out a viral infection could have

an important role in ensuring more precise diagnoses and reducing inap-

propriate use of antibiotics.

Fig. 2. Outpatient antibiotic use in 21 European countries in 2006. DDD = defined daily doses.46

0

5

10

15

20

25

30

35

Gre

ece

† ‡

Cyp

rus

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Fran

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Ital

y

Bel

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Port

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Cro

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Icel

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Spai

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Hu

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ia

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DD

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100

0 in

abit

ants

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ay

Other antibacterials (J01X)

Aminoglycosides (J01G)

Amphenicols (J01B)

TMP and sulphamides (J01E)

Quinolones (J01M)

MLS (J01F)

Tetracyclines (J01A)

Cephalosporins (J01D)

Penicillins (J01C)

† = Total use; ‡ = 2005 use; TMP = Trimethoprim; MLS = Macrolides, Lincosamides and Streptogramins

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C-reactive protein (CRP)

CRP is an acute-phase protein synthesised in the liver. CRP concentrations are

normally low in the blood of healthy people; 99% have levels under 10 mg/ll47

which is generally considered as the cut-off for inflammatory disease48-51 (see

also QuikRead CRP in various clinical situations, page 14).

Production of CRP is rapidly induced by cytokines in response to infec-

tion, inflammation and tissue injury.47,52,53 Elevated CRP concentrations can

be detected within 6–12 hours of the onset of an inflammatory stimulus54,55,

and the concentrations peak within 24–48 hours.47,51,56 The elevation can even

be more than 1000-fold.47,57, 58

CRP has been found to reflect closely the extent, activity and severity

of disease.47 With resolution of an infection or inflammatory process, CRP

levels decline rapidly owing to the short half-life (19 hours) of CRP in the

bloodstream.47,51

Although elevated CRP concentration is not specific to any particular

disease, quantitative measurement of CRP adds valuable information to the

diagnosis, treatment and monitoring of an inflammatory process and the

associated disease.

In a primary care setting, CRP can assist doctors in

• distinguishing between bacterial and viral infections

• monitoring the efficacy of antibiotic therapy.

CRP in distinguishing between bacterial and viral infections

Combined with careful clinical assessment, CRP can help

to differentiate bacterial infection from viral infection.

CRP levels are increased markedly by invasive

bacterial infection. 50–85% of patients with a CRP

concentration exceeding 100 mg/l will have a bacterial

infection.58–60 Acute Gram-positive and Gram-negative

CRP levels are increased markedly by

invasive bacterial infection.

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bacterial infections are among the most potent stimuli for CRP production.47

Bacterial infection without a clearly elevated CRP concentration is un-

likely but may occasionally be encountered. Patients may have low or only

moderately elevated CRP concentrations if the sample is taken during the

first 6–12 hours after onset of the infection. Therefore, a normal CRP value

on the first day of illness should be interpreted with caution.55 CRP results

should also be interpreted with great care in the early neonatal period. The

amount of CRP produced depends on the invasiveness and location of the

infection in the body. Superficial or localised, minor bacterial infection may

not stimulate CRP production significantly.47

Uncomplicated viral infection usually has little effect on CRP concentra-

tion.47 A moderately elevated CRP concentration (10–60 mg/l) may, neverthe-

less, be found in some upper respiratory tract infections with a peak

during days 2–4 of illness.55,61 The elevation may, however, in

some cases reflect secondary bacterial infection.47 Higher

CRP values can be found in infections caused by adenovi-

ruses.62 In patients with signs and symptoms of common

cold, a minor part of cases are, however, associated with

adenoviruses.63-65

CRP in monitoring the efficacy of antibiotic therapy

CRP concentrations drop rapidly, at roughly 50% a day51, in response to

effective treatment. Serial measurement of CRP is therefore of great value in

monitoring the effect of antibiotic therapy, and antibiotics can usu-

ally be stopped upon normalisation of the CRP value.47,51,66,67

In contrast, inadequate treatment is reflected in persistently

high CRP levels which may even rise further if the infec-

tion takes a turn for the worse.47,59 Monitoring of CRP

concentration can alert to complications and predict the

outcome earlier than clinical signs.68

Serial measurement of CRP is of great

value in monitoring the effect of

antibiotic therapy.

Uncomplicated viral infection

usually has little effect on CRP concentration.

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CRP versus erythrocyte sedimentation rate ESR

ESR is a nonspecific inflammation marker and a commonly performed

laboratory analysis.47,69 CRP has many advantages over ESR. ESR is greatly

influenced by the size, shape and number of erythrocytes, gender and age of

the patient, as well as serum proteins such as fibrinogen and immunoglobulins.

Therefore, ESR results can vary and sometimes mislead.58 As a patient’s condi-

tion worsens or improves, ESR changes rather slowly, whereas plasma CRP

concentration reacts rapidly.58,70 ESR is also greatly affected by technical fac-

tors, such as assay temperature, sample dilution and tilting of the ESR tube.69

CRP versus white blood cell count WBC

CRP has been found to be more sensitive and specific than WBC for differ-

entiation between bacterial and viral infection.71-73 In young febrile children,

CRP is superior to WBC in predicting which febrile children have occult

severe bacterial infection74-77 requiring antibiotic therapy. WBC values are

also not consistent enough to be used in monitoring the effect of antibiotic

treatment in bacterial infections.68

CRP versus procalcitonin PCT

Similarly to CRP, PCT is a general marker of bacterial infection.73,75,76,78-83

However, PCT measured at central laboratory is not ideal for routine primary

care84-86 where timely results often are needed to support therapy decisions.

CRP is a good servant

CRP must not be used as the only measure of a patient’s condition. Yet, in-

terpreted in the context of the patient’s symptoms and history, a timely CRP

result is a substantial aid helping the health care practitioner reach the right

diagnosis and correct treatment decision.

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QuikRead® CRP guides the use of antibiotics

Diagnostic dilemma

The primary care practitioner has to make

judgement on the cause of patients’ infec-

tions more or less every day. A key ques-

tion is whether the presenting symptoms

are related to a serious bacterial infection

requiring antibiotic treatment or a benign,

self-limiting viral illness.87,88

The clinical signs and symptoms of

patients with bacterial and viral infections frequently overlap and may not

clearly differentiate between these groups of patients.54,87-93 This, together with

pressure from patients, time constraints and the lack of diagnostic tools, may

lead to prescription of unnecessary antibiotics.44,94-96

Although a sample or the patient may be sent to a laboratory for testing,

a test result that is received hours or days later seldom has any effect on the

treatment decision or the course of treatment. Today’s technology allows the

health care practitioner to rapidly perform a diagnostic test and obtain the

result during patient consultation without unnecessary delay.97

QuikRead CRP

QuikRead CRP is an easy-to-use test for quantitative measurement of CRP

on a finger-prick blood sample. The system – consisting of a small portable

instrument and a ready-to-use kit – is especially designed for use in the primary

care setting. When the test is performed near the patient, the result will be

available in a couple of minutes during the patient consultation to support

diagnosis and therapeutic decision-making.

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In combination with patient history, physical examination and careful

clinical judgement, QuikRead CRP is a valuable tool assisting the health care

practitioner in differentiating between viral and bacterial infections.

A clearly elevated QuikRead CRP result indicates bacterial infection

warranting antibiotic treatment. Conversely, QuikRead CRP can also pro-

vide reassurance to both the health care practitioner and the patient in cases

where prescription of antibiotics does not appear justified. By confirming a

likely viral infection, QuikRead CRP can help to reduce unjustified use of

antibiotics98 particularly in connection with respiratory tract infections.99-101

Avoidance of unnecessary antibiotic use will substantially reduce the number

of patients who experience antibiotic-associated adverse events.20 Appropriate

use of antibiotics may also contribute to slowing down or even reversing the

development of antibiotic resistance.102,103

QuikRead CRP provides a reproducible and quantitative result that is as

accurate as that obtained using clinical chemistry analyzers.98,104-107

QuikRead CRP features

• assists in differentiating between viral and bacterial infections

• immediate test result allows the treatment decision to be made during

patient consultation

• small finger-prick blood sample convenient for the patient

• aids in targeting antibiotic therapy to patients most likely to benefit from it

• contributes to reducing unjustified antibiotic prescribing in respiratory tract

infections

• allows monitoring of the efficacy of antibiotic therapy

• simple to operate, easy to read, no special laboratory skills required

• consistent day-to-day results

• quantitative CRP result within the range 5–200 mg/l for QuikRead go and

within the range 8–160 mg/l for QuikRead 101

• comparable to clinical chemistry analysers in accuracy

• in-built calibration

• instrument requires minimum servicing

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Interpreting the QuikRead® CRP test resultOptimally, a diagnostic test should have high sensitivity (= the ability of the

test to correctly identify diseased individuals) and high specificity (= the ability

of the test to correctly identify non-diseased individuals).

A cut-off point – a clinical decision threshold – is usually set to discriminate

between diseased and non-diseased individuals. As diagnostic tests, however,

rarely demonstrate 100% sensitivity and specificity, using any single value

as a cut-off will usually cause some overlap, yielding following categories

of test results:

• True positive (TP) = a positive/abnormal test result on a diseased individual

• True negative (TN) = a negative/normal test result on a non-diseased

individual

• False negative (FN) = a negative/normal test result on a diseased individual

• False positive (FP) = a positive/abnormal test result on a non-diseased

individual

The positioning of the cut-off affects both the sensitivity and specificity

of the test (Fig. 3). When the result of a quantitative test such as QuikRead

CRP is interpreted, various cut-off levels may be set depending on what is

considered optimal for each condition – as evidenced by the clinical examples

cited in the following chapter.

Test with low cut-off Test with high cut-off

• high sensitivity, low specificity

• likely to identify all diseased

individuals

• negative/normal result indicates

non-diseased individual: the

disease can be excluded

• will give some false positive results

• high specificity, low sensitivity

• likely to identify all non-diseased

individuals

• positive/abnormal result indicates

a diseased individual: the disease is

confirmed

• will give some false negative results

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A low CRP cut-off is generally used to exclude infections of bacte-

rial aetiology. On the other hand, a high CRP cut-off is needed to confirm

bacterial aetiology of an infection. Low and high cut-offs also can be used

simultaneously. Results falling between the cut-offs (“grey area”) require

special consideration.

Fig. 3. Effects of changing the cut-off point of a diagnostic test.108 By permission of Cambridge University Press.

As with any diagnostic test, the QuikRead CRP test result should always

be evaluated in the light of all clinical findings before making the final diag-

nosis and therapeutic decision.

QuikRead® CRP in various clinical situations

The following sections discuss the value of QuikRead CRP in various clinical

situations with emphasis on infections commonly encountered in primary care.

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Serious bacterial infections

Septicaemia, endocarditis, osteomyelitis, septic arthritis, bacterial pneumonia

and meningitis as well as pyelonephritis are usually associated with markedly

elevated CRP concentrations.70,71,73,92,109-119

Measurement of CRP is also useful in the management of feverish condi-

tions without localising signs. Fever is a common symptom in self-limiting,

benign viral illness. However, some febrile patients without apparent source

of infection may have an occult severe bacterial infection that a CRP test

can help confirm.74-76,115

Acute respiratory tract infections

Acute respiratory tract infection (ARTI) is the most frequent reason for

seeking medical attention in primary care121, 122, also accounting for most

antibiotic prescriptions.27,36,37,100,121-126 ARTIs are caused by viruses, bacteria

or a combination of both, and cases of different aetiology often present with

similar symptoms. Identifying patients with a viral infection and patients

suffering from a bacterial infection requiring antibiotics is therefore a daily

challenge in primary health care.

CRP > 10–20 mg/l has been regarded as elevated. 66,67,70-

77,109,114,117,119

CRP < 50 mg/l may rule out serious

bacterial infection.73,74

CRP > 100 mg/l sug-gests severe bacterial

infection.55,60,73,120

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Upper respiratory tract infections

Common cold. The common cold is a viral illness in which symptoms like run-

ny nose, sneezing, sore throat and cough are present but not prominent. The

common cold usually resolves spontaneously, although a small

proportion may be complicated by bacterial co-infection.127,128

Despite the viral origin, antibiotics are widely prescribed for

patients with the common cold.100,127-129

A normal CRP concentration can help to identify

patients with the common cold for which antibiotics are

not indicated.

Acute sinusitis. Most cases of sinusitis are viral and

uncomplicated but patients are frequently prescribed antibiotics.90,130-132

Up to 90% of patients with a cold exhibit symptoms of sinusitis in the early

stages of their illness but only a minor part develop bacterial sinusitis.130,133

Bacterial and viral sinusitises are difficult to differentiate based

on clinical symptoms and signs only.54,80,91 Measurement of

CRP assists in diagnosing bacterial sinusitis and in deciding

whether to prescribe antibiotics to a patient with symptoms

of sinusitis.54,100,134

Implementing the CRP test in primary care may lead

to reduction in antibiotic prescribing to patients with

sinusitis.54

Acute pharyngitis. Most cases of acute pharyngitis are caused by viruses. The

most common bacterial cause of acute pharyngitis is Streptococcus pyogenes,

also known as group A ß-haemolytic streptococcus (Strep A). Strep A infec-

tion is the only commonly occuring form of sore throat warranting antibiotic

treatment.136-139

Only a minority of sore throats in adults are caused by Strep A, while

children have a higher incidence.136–141 Antibiotics are nonetheless prescribed

to most patients140-142, often to avoid such potentially severe, but nowadays

rare, complications as rheumatic fever and acute glomerulonephritis.139,143

CRP > 10-50 mg/l may suggest

bacterial sinusitis.55,130,135

Uncomplicated viral infections

mostly induce very modest elevation

of CRP concentration or none at all.47

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As the signs and symptoms of Strep A infection and

those of pharyngitis caused by other micro-organisms

(most commonly viral) often overlap137,138, it is difficult to

make an accurate diagnosis on clinical grounds only.89 To

avoid inappropriate antibiotic treatment of large numbers

of patients with pharyngitis, it is important to verify or

exclude Strep A infection using a diagnostic test136,137,

such as the QuikRead Strep A test.

An immediately available CRP result may also increase the proportion of

sore-throat patients diagnosed correctly and treated adequately.89 Elevated

CRP concentrations have been found in patients with Strep A pharyngi-

tis.89,144-146

Acute otitis media. The incidence of acute otitis media (AOM) is highest

between the ages of 6–12 months147,148, and more than 70% of

children have AOM before their second birthday147.

AOM is generally considered to be a bacterial infec-

tion149,150, although also viruses seem to have a role in the

development of AOM.149 Bacterial and viral AOM cannot

be differentiated on clinical signs and symptoms alone.151

An elevated CRP concentration has been found to

suggest bacterial AOM.151

Lower respiratory tract infections

Acute bronchitis. In acute bronchitis cough is the most frequently observed

symptom, and the illness usually lasts one to three weeks.152–154 About

70–95% of cases of acute bronchitis are caused by viruses.152,155,156 Bacterial

aetiology has been established in only about 5–10% of patients with acute

bronchitis.152,155

Despite its overwhelmingly viral nature, an estimated 50–90% of doctor’s

office visits for acute bronchitis result in an antibiotic prescription.152,153,157,158

There is little evidence to support the effectiveness of such an approach in

CRP > 20 mg/l may suggest bacterial

otitis media.151

A CRP concen-tration of 35 mg/l

is a useful cut-off point for differentiating

bacterial and nonbacterial pharyngitis.89

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acute bronchitis88,152,156,159, and routine antibiotic treatment

of this illness is therefore not recommended.152,155,159

The evaluation of patients should focus on ruling

out community-acquired pneumonia (CAP) caused by

bacteria.92,152,155,160 Quantitative measurement of CRP

can help to distinguish acute bronchitis from bacterial

CAP.92,154,161 Low CRP concentration along with a history

and clinical findings suggesting a viral infection indicates

that antibiotics are not needed.

Community-acquired pneumonia. A wide variety of viruses, bacteria and

atypical agents can cause community-acquired pneumonia (CAP).165,166

While antibiotics are seldom required for acute lower respiratory tract

infections, which are to a great extent of viral origin, antibiotics are nearly

always indicated for bacterial CAP. A delay in treatment of bacterial CAP

increases the risk of a fatal outcome.167

The prevalence of bacterial CAP is about 5% among patients suspected

of having the infection.160,167

In primary care, CAP is often diagnosed on the basis of symptoms and

physical examination alone, which may be insufficient to identify patients

with bacterial CAP requiring antibiotic treatment.73,92,93,125,160,161 This is

particularly true in primary care because of the lower incidence and lower

severity of CAP found there.92

Quantitative measurement of CRP in combination with patient history

and clinical findings can contribute to the diagnosis of CAP.55,73,92,125,161,163,167-171

Patients with confirmed bacterial CAP have considerably higher CRP

levels than patients with other acute lower respiratory tract infection.161,163,171

High CRP values may also correlate with disease severity, which may be of

value in deciding about the necessity of inpatient care.163 CRP is also useful

in monitoring the response to antibiotic therapy.161,170

CRP < 10-11

mg/l is usually found in patients with bronchitis of viral ori-

gin61,162,163 and excludes bacterial CAP.161,163,164

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Urinary tract infections

Acute uncomplicated cystitis (lower urinary tract infection) is one of the

most common bacterial infections.172-174 As almost 80–90% of uncomplicated

urinary tract infections in primary care are caused by Escherichia coli172,175,

typical clinical cases are usually managed with minimal evaluation and routine

prescription of an antibiotic.176,177

The most severe form of urinary tract infection is acute pyelonephritis

(upper urinary tract infection), which is associated with significant short-

term morbidity and can cause permanent renal damage.174 If pyelonephritis

is suspected, further investigation is required.

While increased CRP concentration is seldom encountered

in patients with acute uncomplicated cystitis, it is com-

monly found in patients with acute pyelonephritis.119,178

Quantitative measurement of CRP therefore provides

diagnostic support for differentiating between cystitis

and pyelonephritis. A high CRP concentration in a patient

with urinary tract infection indicates the possibility of

pyelonephritis.119,178-180

CRP > 20–40 mg/l suggests

pyelonephritis.176,178,181,182

CRP < 10–11 mg/l: bacterial CAP can usually be ruled

out.55,161,163,164

CRP < 20 mg/l: antibiotics are not

indicated in low-risk patients.92

CRP < 50 mg/l:

antibiotics can often be withheld.73,125,167

CRP 50–100 mg/l: chest X-ray, new consultation within 1-2 days or

prescription of antibiotics, depending

on the clinical situation.125

CRP > 100 mg/l: strong indication

of bacterial CAP.56,73,161,164,170,171

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QuikRead® CRP in the routine diagnosis of acute respiratory tract infectionThe decision tree on the following page illustrates potential courses of action

when QuikRead CRP is used to support clinical decision-making in acute

respiratory tract infection.

In this scheme, a CRP concentration of 10 mg/l is used as the clinical cut-

off for excluding bacterial infection, although it may lead to overdiagnosis

and unnecessary treatment in some patients without bacterial infection. The

health care practitioner is therefore advised to set an optimal cut-off value

for each condition to achieve the best possible treatment outcome.

An increase in CRP concentration between successive measurements is

usually a sign of the patient’s infection having taken a turn for the worse. A re-

duction in CRP concentration, on the other hand, is a sign of patient recovery.

This decision tree should be considered only a guide for clinical decision-

making and should never be relied upon as a substitute for professional

medical judgement.

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The decision tree

Asthma, allergy, COPD etcruled out

Clinical signs, duration of symptoms

ACUTE RESPIRATORY TRACT INFECTION

Measure CRPCRP <10 mg/l

Probable viralcause

CRP >10 mg/l

CRP >50 mg/l

Most likely bacterial cause

Antibiotic prescription (if clinical picture requires)

Measure CRP

*)

Additionalinvestigations / possible change of antibiotics

Symptomatictreatment

Patient returns: symptoms persist / turn to worse

Measure CRP

CRP >10 mg/l

Probable bacterialcause

Additionalinvestigations / treatment based on clinical picture

CRP <10 mg/l

CRP <10 mg/l

Patient recovers

Patient recovers

Patient returns: symptoms persist / turn to worse

Patient recovers

*) CRP increased compared to previous measurement / not considerably decreased

25

The QuikRead® CRP System

QuikRead 101 Instrument

and QuikRead CRP kit with buffer bottle

QuikRead 101 Instrument

and QuikRead CRP kit with prefilled cuvettes

Please also visit

www.quikread.com

QuikRead go Instrument and QuikRead go CRP kit

26

1. Dancer SJ. How antibiotics can make us sick: the less obvious adverse effects of antimicrobial chem-otherapy. Lancet Infect Dis 2004;4(10):611-9.

2. Scott LJ et al. Cefuroxime axetil: an updated re-view of its use in the management of bacterial infections. Drugs 2001;61(10):1455-500.

3. Oliphant CM and Green GM. Quinolones: a comprehensive review. Am Fam Physician 2002;65:455-64.

4. Löfmark S et al. Clindamycin-induced enrichment and long-term persistence of resistant Bacteroides spp. and resistance genes. J Antimicrob Chemother 2006;58:1160-7.

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