CAP-Do We Know What, When and For How Long to …...Community-acquired pneumonia refers to pneumonia acquired outside of hospitals or extended-care facilities (e.g. Nursing homes)

CAP-Do We Know What, When and

For How Long to Treat?

Wahu. g.r

KPA conference Kisumu 2017

ROADMAP

• Definition

• Aim

• Introduction

• Case presentation

• Value of clinical signs

• Imaging

• Microbiological aetiology

• Antibiotics in childhood pneumonia

AIM

Try to identify the various reasons that make it difficult to establish a rational approach to the treatment of pediatric CAP, including the definition of CAP, the absence of specific radiological signs and the difficulty of identifying the etiology

Consider critically the available data concerning the diagnosis and treatment of uncomplicated pediatric CAP

Consider when, how and for how long it should be treated

Definition

• Pneumonia is an infection of the lung parenchyma

• Definition of pneumonia is complex and varies widely in different guidelines: some guidelines are based on clinical judgment only, whereas others also take radiographic findings or laboratory data into account

• Hard to decide whether to include other lung infections- aspiration pneumonia, TB

Definition • Community-acquired pneumonia refers to pneumonia acquired outside of

hospitals or extended-care facilities (e.g. Nursing homes)

• CAP occurs within 48 hours of hospital admission or in a patient presenting with pneumonia who does not have any of the characteristics of healthcare-associated pneumonia (i.e, hospitalized in an acute care hospital for 2 or more days within 90 days of infection; resided in a nursing home or long-term care facility; received recent intravenous antibiotic therapy, chemotherapy, or wound care within the past 30 days of the current infection; or attend a hospital or hemodialysis clinic

• Signs and symptoms of acute pneumonia develop over hours to days, whereas the clinical presentation of chronic pneumonia often evolves over weeks to months

Perspectives

• Community-acquired pneumonia (CAP) is a common cause of morbidity among children in developed countries and accounts for an incidence of 10–40 cases per 1000 children in the first 5 years of life

• It has been estimated that there are about 151 million new episodes a year among Third World children aged <5 years, leading to an incidence of 0.29 episodes per child-year and a mortality rate of 1.3-2.6%, or >2 million per year

• In industrialized countries: an incidence of 0.05 episodes per child year risk of mortality is extremely low in otherwise healthy children and relatively important only in subjects with severe chronic underlying disease

Perspectives

• Incidence and mortality rate are significantly higher in developing countries than in the industrialized world:

• These differences are due to a number of factors:

i. Incidence of risk factors such as malnutrition, crowding, low birth weight, HIV and the lack of measles and pneumococcal immunization is much higher among children in developing countries

ii. They are more likely to be affected by other likely or possible risk factors such as zinc and vitamin A deficiency, poor maternal education and living in polluted areas

iii. Profound differences between developing and developed countries in the organization and efficiency of their health systems exist

Case • S.B is a twelve year old girl who presented at AgaKhan University Hospital,

Nairobi (AKUHN), with a two weeks history of cough and fever for which she had previously received antibiotics on two occasions as an outpatient

• Two days prior to this third presentation, she developed difficulty in breathing associated with worsening of the cough

• Clinically, she had signs of pneumonia evidenced by respiratory distress with right-sided crackles and reduced breath sounds

• We embarked on a search for the causative pathogen with a high index of suspicion of tuberculosis (TB) given the high prevalence of TB in the region

• The initial Chest radiograph (CXR) showed a near complete opacification of the right hemithorax with only minimal aeration in the right apices associated with tracheal deviation to the right

Case

• Other investigations were as follows: iron deficiency anaemia [haemoglobin of 8.9 g/dl; MCV 60.1, MCH 19.2]; leukocytosis [white blood cell count 21.1×109/l, neutrophils 80% (absolute 16.8 ×109/l), lymphocytes 17% (absolute 3.57×109/l)], thrombocytosis [701×109/l], and elevated serum procalcitonin [10.7ng/ml]

• Biochemistry including liver function tests were normal

• Blood cultures (two samples) were negative and Elisa for HIV was negative

• A pleural tap was performed and pus was obtained; Test for Acid Fast bacilli (AAFB) was negative, microscopically showed numerous pus cells but no growth on culture.

Case

• A chest CT-scan showed septated empyema with fluid and calcified components arising from the mediastinum and occupying almost the entire right hemi-thorax

• There was resultant atelectasis of almost the entire right lung and mediastinal shift to the left (FIG III and IV)

• Open thoracotomy to drain the pus was done and she was successfully treated empirically for staphylococcal pneumonia with intravenous ceftriaxone and vancomycin

• The pus o tai ed at thora oto y as sterile pro a ly as a result of prior antibiotic use.

Consideration

• A-OPD

Does this child with respiratory symptoms need antibiotics?-Of all infants, 30% will attend a doctor with a respiratory symptom thought to be suggestive of infection and 2% will be hospitalized

Tachypnea is the most sensitive sign of pneumonia

The majority of doctors consider antibiotics or asthma treatment for isolated and persistent cough but very few children with cough have bacterial infection

Consideration

• B- History and examination needs to answer these questions:

Which, if any, investigations are helpful?

Is these pneumonia or do I need to consider other diagnosis- acute abdomen, diabetic ketoacidosis, malaria?

Does the child need to stay in hospital and at what level of care?

Are oxygen, intravenous antibiotics and intravenous fluids needed?

Are there underlying problems or complications?

Consideration

• CAP is not simple to manage; To establish an etiological diagnosis and initiate appropriate antibiotic treatment is frequently a complex task

• Testing complicated due to the low yield of blood cultures; difficulty in obtaining adequate sputum specimens and the reluctance to perform pulmonary aspirates

• Samples from a sterile site are the gold sta dard i the diagnosis-invasive

VALUE OF CLINICAL SIGNS

IN DIAGNOSING

PNEUMONIA

Clinical features and severity

WHO features of pneumonia Fever > 38.5

Cough

Tachypnoea (Fast breathing)

Chest recession, use of accessory muscles, head nodding

Paradoxical movement of chest and abdomen

No wheeze

Severe • Poor feedi g a d lethargy

• Ta hyp oea followed y pausi g

• Diffi ulty i sustai i g or al SaO2

Clinical features

• The common presentation of children under five with pneumonia is fever, cough, fast and/ or difficult breathing

• Fever is not an efficient criterion as it is present in other common diseases like malaria, upper respiratory infection and diarrhoea

• Fast breathing (FB) is also seen with bronchiolitis, asthma, wheezing associated with acute lower respiratory infection (WALRI) and croup syndromes

• Congestive heart failure, metabolic acidosis and raised intracranial pressure can also cause FB in the absence of any chest infection

• Clinical features remain a ery i porta t e try riteria -tachypnea very useful sign-more specific and more reproducible than auscultatory signs.

Clinical features

• There is no evidence so far to indicate that some clinical signs may be associated with certain aetiological pathogens in CAP

• Korppi et al. evaluated the value of clinical signs/symptoms in differentiating between viral, pneumococcal and atypical bacterial pneumonia

• They evaluated 101 previously healthy children with radiologically confirmed pneumonia and found no significant association between any of the clinical signs or symptoms and the aetiology of pneumonia

AUSCULTATION

• Interobserver agreement about abnormal auscultatory sounds is poor

• Symptoms and signs which can be observed are more reliable

• At the start of a bacterial pneumonia abnormal auscultatory signs may not be present

• No auscultatory sounds associated with any Aetiological pathogen

• Plays little part in the diagnosis of pneumonia in primary care settings

IMAGING

ROLE OF CXR

• Chest Radiology is often used to diagnose pneumonia but its

interpretation is fraught with risks of over as well as under

diagnosis and wide observer variability common

• A severely ill child could have minimal radiological findings and

one with significant radiologic findings may have a relatively

mild illness

ROLE OF CXR

• The alveolar opacities on the chest radiograph are often

considered as pathognomic of bacterial pneumonia; however,

bacterial origin for these alveolar opacities was established in

only 2/3 cases in a study

• Equally importantly they also found that nearly a half of the

children with interstitial infiltrates as the sole radiographic

finding (usually considered to represent pneumonia of viral

origin) had bacterial infection

ROLE OF CXR

• Much disagreement over what specific radiological changes constitute pneumonia and whether any changes are more likely to represent a bacterial, viral or atypical etiology

• Alveolar (or lo ar ) i filtrates ith air spa e opacification, with or without air bronchograms, are an insensitive but reasonably specific indication of bacterial infection

• Pleural effusions may be associated with bacterial infections (particularly Streptococcus pneumoniae and Staphylococcus aureus); rarely with mycoplasmal or viral infections

• Viral disease manifests with a typically bilateral, symmetrical process of increased peri-bronchial opacities, hyperinflation from diffuse small-airway narrowing and subsegmental atelectasis

ROLE OF CXR

• In most resource limited settings, CXR is not easily available; Chest

radiography is associated with considerable practical delays related to

processing

• When available, there may be discrepancies in interpretation among

radiologists.

• Neumann assessed the reliability of CXR interpretations by radiologists

when diagnosing pneumonia in a study performed using 110 chest

radiographs of children presenting to the emergency department with

suspected pneumonia

• They found that the radiographic finding of an alveolar infiltrate is very

reliable among pediatric radiologists but the finding of an interstitial

infiltrate is less reliable

ROLE OF CXR

• Boersma Wim G and others assessed inter-observer reliability (IR) of

radiographic findings and the relationship to different causative pathogens

in CAP.

• They reviewed chest radiographs of 192 patients with pneumonia, reviewed

by 2 radiologists and a respiratory physician without specific clinical

information

• They concluded that only simple features such as presence of pleural fluid,

the extent of pneumonia and identifying the involved lobes show fair to

excellent IR.

ROLE OF CXR-TAKE HOME

• A chest X-ray should be obtained in infants under 3 months

when signs of respiratory distress are present

• If all the physical signs of pneumonia are not present, chest

radiograph findings are unlikely to be helpful

• CXR is useful in cases of complicated pneumonia and in

distinguishing respiratory illness from non-respiratory causes

of breathing difficulty.

Other radiology • CT imaging is regarded as the gold standard allowing for the

diagnosis of pneumonia earlier; has a higher sensitivity and

specificity

• May not always be available; charged with a high radiation dose;

high cost that- precludes its use in the routine diagnostic process

of patients with suspected pneumonia

• Reserved for preoperative planning or for complex pulmonary

conditions, such as a suspected lung abscess not accessible by

US, a broncho-pleural fistula, or an underlying pulmonary

structural abnormality and interstitial lung disease

Other radiology • Ultrasound has been shown to be highly effective in evaluating a

range of pathologic pulmonary conditions

• Most widely practiced applications is the evaluation of pneumonia with ultrasound

• Point-of-care ultrasou d i agi g, perfor ed at the patie t s bedside, decreases the delays of chest radiography in the diagnosis of pneumonia-

• If a pleural effusion or empyema is detected, ultrasound can be helpful in planning treatment

• Complicated empyema which is slow to resolve will be better described by CT scan

Role of chest ultrasound

• Indications of chest US widely vary depending on the patient's disease and

condition as well as regional imaging concepts and needs

• Common reasons to consider a chest US – besides echocardiographic queries –

are:

to evaluate a chest wall lesion

to confirm and characterize pleural effusions

to detect pleural thickening and/or a pleural tumor

to assess an abnormal high or lobulated diaphragm as well as diaphragmatic motion

to assess an radiologically opaque lung

to confirm pulmonary consolidations and to detect complications

to evaluate a widened mediastinum

and to assess patency of systemic veins at thoracic inlet

microbiological

aetiology In the majority, a definitive microbiological diagnosis is not made despite the presence of signs and symptoms suggestive of pneumonia

ROLE OF MICROBIOLOGICAL INVESTIGATIONS

• The advantage of pursuing a microbiological diagnosis of the causative organism(s) is three-fold.

I. While many common pathogens can be predicted by the experienced clinician surprises will always occur

II. Identification of pathogens allows targeted antibiotic therapy, improving bacterial eradication and clinical response, reducing the development of resistance.

III. Identification of some organisms carries significant prognostic implication for the patient, e.g. isolation of Burkholderia cepacia complex from a child with cystic fibrosis;

Some organisms can help elucidate a clinical problem,

e.g. isolation of Fusobacterium necrophorum in

u suspe ted Le ierre s sy dro e

Sputum

• The sensitivity of the Gram stain of good quality sputum cultures in adults has been estimated to be around 50–80% in community-acquired pneumonia

• Successful expectoration of sputum can only really be achieved by children aged approximately 8 years or older and the usefulness of sputum culture results depends greatly on the quality of the specimen

• Many laboratories will not process sputum samples showing a high count of epithelial cells (>20/lpf) for this reason

• Involvement of experienced physiotherapy or nursing staff in the production of a sputum sample can assist in decreasing the number of poor quality

• Although the mechanism is not fully understood, the inhalation of nebulized hypertonic or isotonic saline solution enables the production and subsequent expectoration of sputum where this was otherwise not possible, and has been used effectively in children as young as 2 years of age

BLOOD CULTURES

• Blood cultures: not useful in exacerbations of chronic suppurative lung disease and have a limited role in most acute respiratory suppuration

• They are positive only in around 20% of parapneumonic empyemas,and are rarely positive in lung abscesses, particularly primary abscesses

• In a few notable conditions involving suppurative foci in the lung, they can be diagnostic

• Usually positive in 5-10% of patients; description of resistance patterns of isolates is the only reason for culturing blood

• Encouraged in all admitted children with severe pneumonia

Value of other laboratory parameters-

Nasopharyngeal cultures

• Nasopharyngeal aspirates are often helpful in promptly identifying respiratory viruses by immunofluorescence;

• Positive culture, may not reflect the organisms in the lower respiratory tract

• The same is true for throat swabs, but a properly performed cough swab may be more useful in young children unable to expectorate sputum-Evidence for this has yet to be provided

Value of other laboratory parameters- Pleural

fluid

• Significant pleural fluid on clinical or radiological examination should be aspirated for diagnosis by microscopy, culture and antigen detection

• Any fluid which can be seen on an antero-posterior chest radiograph reflects at least 50 mls in the chest, i.e., a rim of fluid on the film indicates a large amount of fluid in the chest


Urea and electrolytes

• Severe pneumonia may cause inappropriate secretion of antidiuretic

hormone and therefore urea and electrolytes and osmolality should be measured in an ill child

• Should be considered in a child who is vomiting, poor feeding with dehydration


Haemogram

• Full blood count (FBC), Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP); None helps in diagnosis as abnormal values neither confirm nor disprove bacterial pneumonia

• White cell count, neutrophil count and CRP are of such poor sensitivity and specificity that they are not investigations which will add to the diagnosis or management of bacterial pneumonia

• Additional blood work that may provide information when diagnosing pneumonia include the evaluation of risk factors (malaria, hemoglobinopathies, HIV infection)

OTHERS

• Urine samples: Several infectious causes of pneumonia can be detected with urinary antigen tests

• Although they can be used to diagnose pneumococcal pneumonia in adults, they lack specificity in children due to the high prevalence of pneumococcal colonization in childhood

• Testing for antigenuria in pneumococcal disease is not specific as pneumococcal otitis media can also produce antigenuria

• Post-mortem lung tissue samples: Identifying the cause of deadly pneumonia is critical to the understanding and prevention of pneumonia-related deaths; however, there are many cultural and social limitations to post-mortem examinations in many countries

• Immediate post-mortem percutaneous lung biopsy provides a simpler and less invasive method to obtain pulmonary tissue

Practice Points

• Little progress in the last 30 years in the value of diagnostic tools.

• Clinical features most important; tachypnea, fever, Recession, Wheeze unilaterally

• Cough may not be present at the outset

• Radiology neither sensitive nor specific

• Identification of pathogens unrewarding

• Inflammatory biomarkers neither specific or sensitive

CHECK POINT- ARE YOU STILL AWAKE??????

Antibiotics in childhood

pneumonia

TREATMENT

• Once all clinical and laboratory parameters have been considered, a decision has to be made on whether empirical antibiotics are indicated, and if so which ones

• Antibiotics may be withheld in the non-toxic child in whom signs and symptoms suggest a viral aetiology and a CXR is not usually necessary

• In childhood CAP, an agent effective against pneumococcus is required in the first instance; Amoxicillin is a reasonable first choice for the empirical oral therapy of bacterial childhood CAP in industrialized countries

Choice of antibiotic

• Penicillin is the first choice of antibiotic especially in children 2 months to 48 months with no underlying condition

• Effective against S. pneumoniae, (commonest), Haemophilus influenzae and S. pyogenes

• The knowledge of local resistance pattern is crucial in guiding selection of appropriate and optimal antimicrobial agent

• Penicillin resistance among pneumococci is increasing and a double dosage of amoxicillin (90 mg/kg/day) should be used if there is a high risk of pneumococcal penicillin resistance


• In resource limited settings, there is paucity of data as to the commonest aetiological cause of CAP due to limited number of studies

• However, a large worldwide study of penicillin resistance amongst S. pneumoniae isolates from children reported that in 1999 – 2000, 25% of respiratory cultures were resistant to penicillin

• Due to indiscriminate use of antibiotics, there is much more resistance to first line antibiotics in the developing countries

• Studies from developed countries have quoted levels of resistance of 9% for S. pneumonia


• Though all parts of the world are not uniformly affected, the emergence of antimicrobial resistance has been documented in virtually any part of the globe

• Atypical organisms such as Mycoplasma pneumonia, Chlamydia pneumonia and Legionella pneumophila are also increasingly being thought to be an important cause of CAP

• They pose a challenge both in diagnosis and in their non-response to penicillin


• Some studies have shown high rates of atypical organisms in some areas; Most clinicians diagnose atypical pneumonia using certain criteria such as the age of the patient (usually children older than five), the clinical presentation (child is not very ill), and radiological findings

• The chest X-ray shows hyperinflated lungs with diffuse bilateral interstitial infiltrates and atelectasis

• These criteria albeit useful, have not been standardized and it may not be unusual to miss out atypical organisms or include viral pneumonia

• Mixed infections may also occur and treatment with monotherapy may result in worsening of the pneumonia and or even lead to death. Atypical organisms have been shown to respond to macrolide antibiotics


• There are some studies that have shown that addition of an extended-spectrum macrolide such as azithromycin to an extended-spe tru β-lactam such as ceftriaxone in the treatment of patients hospitalized with non-severe CAP appears to be associated with improved outcomes

• Adding a macrolide to the treatment regimen has resulted in shorter lengths of stay (LOS), less treatment failure, and lower mortality

• The a rolide effe t is thought to o ur either due to a effe t o o-existing atypical organisms or through the inherent anti-inflammatory properties of macrolides

Optimal route of antibiotic therapy

• There is no consensus on the optimal route of antibiotic therapy in CAP.

• In Gambia, representing low resource settings, Campel and others compared the use of a single dose of procaine penicillin followed by a five days of oral ampicillin to oral co-trimoxazole for 5 days

• They found no difference in both arms after two weeks

• Different guidelines have different recommendations for antibiotic treatment of bacterial pneumonia but a review Ruuskanen and Mertsolaby noted that most guideline recommend amoxicillin/penicillin as cefuroxime as first line options

• These drugs can be given orally or intravenously.

Optimal route of antibiotic therapy

• In the developed world, Atkinson and others in a study comparing oral and intravenous antibiotic found that oral therapy may be adequate even in severe pneumonia (except very severe pneumonia)

• Oral therapy has the advantage of being painless compared to parenteral injections and also low in both direct and indirect costs

• It would therefore be prudent to conclude that oral antibiotics preferable to parenteral given their comparable efficacy and other added advantages

Optimal Duration of Antibiotic Therapy

• The optimal duration of duration of antibiotic therapy remains uncertain;

• Seven days is proposed for mild-to-moderate CAP in most developed countries

• There is paucity of well- designed clinical studies that investigate the duration of therapy and most guidelines are based mainly on observational studies, expert opinions, clinical experience and consensus

• A Cochrane review by Haider and others found no difference in outcome between short (3 day) and longer courses of oral antibiotics

• A short duration of therapy thus, seems to be adequate especially in uncomplicated cases of CAP- this is preferred since it increases compliance, reduces cost and has potential of reducing antimicrobial resistance.

HOW LONG TO TREAT

• Although the duration of antimicrobial therapy has not been defined on the basis of the findings of randomized controlled studies, around 7 days is proposed for mild-to-moderate CAP in most developed countries

• However, a shorter duration of treatment for uncomplicated CAP appeared effective in some studies, although further researches are needed to confirm its efficacy

• A longer treatment (i.e, ≥14 days) should e used i ases of severe and/or complicated CAP

Practice Points • Community-acquired pneumonia (CAP) remains a is a leading cause of

• morbidity and mortality, especially in children under 5 years of age

• Clinical features most important; tachypnea, fever, Recession, Wheeze unilaterally

• Cough may not be present at the outset

• Little progress in the last 30 years in the value of diagnostic tools

• Radiology neither sensitive nor specific

• Identification of pathogens unrewarding

• Pneumococcal pneumonia commonest of bacterial infections; Mycoplasma pneumonia — schoolchildren; Staphylococcal pneumonia rare in developed countries

END-Thanks for your Attention

References

1. Peterson LR. Penicillins for treatment of pneumococcal pneumonia: Does in vitro resistance really matter? Clin Infect Dis 2006; 42:224–33

2. Stralin K. Usefulness of aetiological tests for guiding antibiotic therapy in community-acquired pneumonia. Intel J of Antimicrobial Agents 31 (2008) 3–11

3. Varinder Singh.Pneumonia – Management in the Developing World: Paediatric Respiratory Reviews 12 (2011), 52-59

4. Marilia Rita Pinzone. Duration of Antimicrobial Therapy in Community Acquired Pneumonia: Less Is More; The scientific world journal: 2014: Jan 21

5. Donowitz GR. Mandell, Douglas, and Bennett's, Principles and Practice of Infectious Diseases. Philadelphia, Pa, USA: Churchill Livingstone, Elsevier; 2010. Acute pneumonia; pp. 891–916

Documents

CAP-Do We Know What, When and For How Long to …...Community-acquired pneumonia refers to pneumonia acquired outside of hospitals or extended-care facilities (e.g. Nursing homes)