Acute Community-Acquired Pneumonia (CAP and VAP/HAP)

Community-acquired pneumonia	Antibiotic	Dose	Alternative
Mild – outpatient treatment	Amoxycillin or Doxycycline or Clarithromycin	1 gram orally, 8-hourly for 5 to 7 days 200mg orally for the first dose then 100mg daily for a further 5 days 250mg orally, 12-hourly for 5 to 7 days	Penicillin allergy – use doxycycline or macrolide (clarithromycin or azithromycin)
Moderate to severe	Benzyl penicillin plus either doxycycline or clarithromycin	1.2g IV 6-hourly until significant improvement then amoxycillin 1 g orally 8-hourly 100mg orally, 12-hourly for 7 days 500mg orally, 12-hourly for 7 days	Penicillin allergy – uss a respiratory fluoroquinolone (moxifloxacin or levofloxacin)
If Gram negative bacilli identified in sputum or blood	see for severe CAP
Severe	Ceftriaxone or benzyl penicillin plus gentamicin or Cefotaxime plus macrolide/azithromycin	1 g IV daily 1.2g IV, 4-hourly 4 to 6 mg/kg for 1 dose, then determine dosing interval for a maximum of either 1 or 2 further doses based on renal function 1 g IV, 8-hourly 500mg IV, daily	For patients with immediate penicillin hypersensitivity use a respiratory fluoroquinolone plus azithromycin
If Pseudomonas is a consideration	Ceftazidime or piperacillin/tazobactam or Cefipime or Carbapenem and gentamicin and a macrolide
If community-acquired methicillin-resistant S. aureus is a consideration	Add vancomycin or linezoid to severe CAP regimen

When to switch to oral antibiotics and length of treatment.

For patients with low to moderate severity CAP, there is no contraindication to oral therapy. For patients initially treated with parenteral antibiotics, the switch to an oral regimen should occur as soon as clinical improvement occurs and temperature has been normal for 24 hours.

The length of treatment is determined by the severity of disease. Patients managed in the community and for most patients admitted with low or moderate severity, 5-7 days of appropriate antibiotics are recommended. For those with high severity, 7-10 days of treatment should be given. For more uncommon causes of CAP, such as CAP due to S. aureus or Gram-negative bacilli, longer courses may be required.

2. Next list other key therapeutic modalities.

• Consider the requirement for supplemental oxygen

• Intravenous hydration if the patient is dehydrated or unable to maintain an oral intake

• Analgesia for pleuritic chest pain

• Control of underlying comorbidities, such as heart failure

• Bronchodilators to treat airflow limitations or improve mucociliary clearance

• Respiratory physiotherapy to improve clearance of secretions

• Steroids are not recommended for severe CAP.

What complications could arise as a consequence of Acute Community-Acquired Pneumonia?

Potential complications of acute community-acquired pneumonia include empyema and lung abscess, as well as sterile parapneumonic effusions

What should you tell the family about the patient's prognosis?

• There are a number of factors that impact on a given patients prognosis. Although the severity scoring systems can be used to predict 30 day mortality or need for ICU admission, the performance of the scoring system differs between different patient populations and different healthcare settings. To be useful, they should be validated in each locale.

• Poorer prognosis is seen in the elderly patient with multiple comorbidities and extensive disease at presentation.

How do you contract Acute Community-Acquired Pneumonia and how frequent is this disease?

Acute pneumonia is among the top ten most common causes of death in those 65 years of age or older and the single most common cause of infection-related mortality. About 156 million new episodes of pneumonia occurred in children worldwide in 2000. The vast majority occurred in children in developing countries, and childhood pneumonia is the leading single cause of mortality in children 5 years of age or younger.

The incidence in children younger than 5 years of age is estimated to be 0.29 episodes per child-year in developing countries and 0.05 episodes per child-year in developed countries. The annual incidence in adults is more difficult to determine because of different approaches used to determine the incidence. The overall annual rate of pneumonia in the United States is 12/1000 persons, and the incidence of CAP requiring hospitalization in adults is 2.6/1000.1 Recent studies report an incidence of CAP in the range of 3.7-10.1/1000 inhabitants in a community in Germany, an annual incidence of 1.62/1000 inhabitants in Barcelona, Spain, and an overall incidence of 233/100,000 person-years in the United Kingdom. In North America, pneumonia and influenza continue to be common causes of death, ranked eighth in the United States and seventh in Canada,^{and there were more than 60,000 deaths due to pneumonia in persons 15 years of age or older in the United States alone. The incidence is higher in children younger than 5 years of age, adults older than 65 years of age, males, and those living in socially deprived areas.}

The pathogens that cause acute pneumonia are commonly transmitted by the respiratory route.

Zoonotic transmission of respiratory pathogens is uncommon. Several pathogens that can cause acute pulmonary infections are associated with animal hosts; these include Bacillus anthracis, Coxiella burnetti, Francisella tularensis, Yersinia pestis,Hantavirus,dimorphic molds, C. psittaci,and Brucellaspp. A thorough history of occupation, exposure to animals, and travel should alert the clinician to consider these organisms.

What pathogens are responsible for this disease?

The most common organisms causing acute community-acquired pneumonia are:

Streptococcus pneumoniae

Haemophilus influenzae

Mycoplasma pneumoniae

Chlamydophila pneumoniae

Chlamydia psittaci

Legionellaspp.

Staphylococcus aureus

Respiratory viruses, such as influenza, rhinovirus, respiratory syncytial virus, human metapneumovirus, coronavirus, parainfluenza virus, adenovirus, and bocavirus

Streptococcus pneumoniae– the most common cause of acute community-acquired pneumonia; affects all age groups; typically causes lobar pneumonia

Haemophilus influenzae – more common in patients with underlying lung disease

Mycoplasma pneumoniae -commonly affects older children and young adults, particularly during autumn; cough may be prominent; extra-pulmonary manifestations may be seen, such as rash; and rarely neurological symptoms, including ataxia, aseptic meningitis, cranial nerve palsies, and encephalitis

Chlamydophila pneumoniae- an uncommon cause of pneumonia; affects all age groups

Chlamydia psittaci – occurs mainly in persons with contact with pet birds and in those employed in the poultry industry

Legionellaspp. – L. pneumophila (serogroup 1-14), L. longbeachae, L. micdadei, and L. bozemanii cause more than 85% of cases of Legionellosis; occurs following exposure to water and soil harboring these organisms; occurs sporadically, in clusters, or in large outbreaks; Legionellosis occurs mainly in the elderly, smokers, immunocompromised, and those with underlying cardiac, respiratory, and renal disease

Staphylococcus aureus – may follow an episode of influenza; may also occur in otherwise healthy young people in association with community-acquired methicillin-resistant strains of S. aureus; strains of S. aureusproducing the Panton Valentine leukocidin virulence factor can cause severe necrotizing pneumonia

Mycobacterium tuberculosisis a very uncommon cause of acute pneumonia. It is usually seen in patients with a chronic cough longer than 2 weeks duration.

Dimorphic molds, such as Histoplasma capsulatum, Blastomyces dermatitidis,and Coccidioides immitis, can cause pulmonary infections but are rare outside of specific geographical regions.

Viral pneumonitis can be caused by a number of viruses, including influenza A and B, adenovirus, human metapneumovirus, respiratory syncytial virus (especially the older adult and immunosuppresses patient), and parainfluenza virus, which are the most common. Infections can be mixed, either with bacteria, predominantly S. pneumoniae, or dual viral pathogens.

How do these pathogens cause Acute Community-Acquired Pneumonia?

Particulate material and microbes are inhaled with inspired air. These tiny particles can evade the upper airways defense mechanisms and are deposited in the lower airways. Microaspiration of oral secretions can also occur. Once in the normally sterile lower airways, the alveolar lining fluid can bind a variety of organisms, including viruses, bacteria, and fungi, and decrease their virulence or enhance phagocytosis by neutrophils and alveolar macrophages. The phagocytic cells have a role in eliminating the pathogen and initiating the inflammatory response leading to neutrophil recruitment and dendritic cell activation with production of cytokines and chemokines. Other lung parenchymal cells also help to regulate the immune response. Cell mediated immunity is central to adaptive immune responses, and it is especially important against viruses and intracellular organisms.

What other clinical manifestations may help me to diagnose and manage Acute Community-Acquired Pneumonia?

The history should elicit symptoms consistent with pneumonia, the clinical setting in which the pneumonia has arisen, risk factors in the patient that may have led to the development of pneumonia, and possible exposures to specific pathogens.

Legionellosis may be associated with gastrointestinal symptoms. Ear pain can be seen with M. pneumoniaeinfection.

The patient with pneumonia will typically be febrile, have an elevated respiratory rate, and may have an elevated heart rate. There may be dullness on percussion with bronchial breath sounds or rales heard on auscultation. A relative bradycardia may be seen in patients with legionellosis, psittacosis, or Q fever.

Additional features seen on examination that may point to a specific pathogen include: herpes labialis is seen in up to 40% of patients with pneumococcal pneumonia; bullous myringitis is an infrequent but significant finding in mycoplasma pneumonia; the presence of poor dentition may suggest aspiration pneumonia; and rash may be seen with mycoplasma pneumonia.

What other additional laboratory findings may be ordered?

Other laboratory investigations that may provide an etiology include:

1. Blood cultures – the yield is low but when positive it is highly likely that this is the pathogen causing the pneumonia

2. Sputum – Gram stain and culture of expectorated sputum can be performed only if a good quality sputum can be obtained prior to starting antimicrobials. , The laboratory should apply specific criteria to assess the quality of the sputum and not culture if these are not achieved

3. Urinary antigens –available for L. pneumophila serogroup 1, S. pneumoniae and Histoplasma capsulatum. The sensitivity and specificity for detection of L. pneumophila serogroup 1 using a lateral flow assay is 97% and 98%, respectively and for S. pneumonia the sensitivity is 66-87% when blood or pleural fluid culture is the comparator and the specificity is 80-100%. The sensitivity is much lower in colonised children. Testing for H. capsulatum urinary antigen should only be performed if there is a strong history of exposure.

4. Molecular testing for respiratory pathogens.

• Nasopharyngeal swab/aspirate –detection of viral and bacterial DNA/RNA using single and multiplexed PCR or nested PCR with filmarray assays.

• Lower respiratory tract – detection of viral and bacterial DNA/RNA using single or multiplexed PCR assays

A good understanding of the limitations of the PCR method used by the local microbiology laboratory is necessary when interpreting the results of these tests

5. Serum transaminases may be elevated in patients with psittacosis, Q fever, or legionellosis.

6. Cold-agglutinins are elevated in about 75% of patients with M. pneumoniae.

7. Serological testing – acute and convalescent sera should be collected for diagnosing M. pneumoniae, C. pneumoniae, C. psiitaci,and Legionellaspp. infections. A single acute sample is of limited value. A convalescent sample taken greater than 2 weeks after onset of the illness is required. Seroconversion may take up to 6 weeks especially if antimicrobial therapy is started promptly.

Serum procalcitonin (PCT) levels rapidly increase in patients with invasive bacterial disease. How PCT fits in the innate immune response is poorly understood. Which respiratory pathogens stimulate the synthesis of PCT and is there a difference in the response between different bacterial and viral pathogens is also poorly understood. Some studies have shown rates increased in patients with bacterial infections compared those of viral origin, but there has been no attempt to correlate PCT levels with the microbial etiology of the patient’s respiratory tract infection. The PCT showed good sensitivity and negative predictive value for bacterial pneumonia in critically ill patients during the 2009 influenza pandemic but it has low sensitivity in diagnosing bacterial pneumonia. Studies have shown that the PCT result may be normal in patients with bacterial pneumonia or mixed viral and bacterial pneumonia.

What newer technologies are available for the detection of respiratory pathogens?

The 2009 H1N1 influenza A pandemic and the outbreaks associated with the newly recognized coronaviruses, SARS and MERS, has resulted in improved diagnostic tests for respiratory pathogens. Molecular tests have an increased yield over routine culture. Molecular tests enable the screening of upper and lower respiratory tract specimens for a wide variety of viral and atypical bacterial pathogens and increase the microorganism detection rate to about 80% at best. It is more difficult to interpret PCR results for more typical bacterial pathogens such as S. pneumoniae, because the same microorganisms exist in oropharyngeal flora. Quantification of the bacterial load may assist with differentiating infection from oropharyngeal contamination in sputum. Currently there are few studies reporting on this approach.

How can Acute Community-Acquired Pneumonia be prevented?

Vaccination against influenza and, in some high risk groups, against S. pneumoniae,are important for preventing pneumonia

How do you define hospital-acquired pneumonia (HAP), ventilator –associated pneumonia (VAP), and healthcare-associated pneumonia (HCAP)?

HAP is defined as pneumonia that occurs more than 48 hours after admission to hospital and was not incubating at the time of admission.

VAP is defined as a type of HAP that develops 48 hours after endotracheal incubation.

HCAP requires healthcare contact, as defined by 1 or more of the following modes: intravenous therapy, wound care, intravenous chemotherapy during the prior 30 days, residence in a nursing home or other long-term care facility, hospitalization in an acute care hospital for 2 days or more during the prior 90 days, or attendance at a hospital or hemodialysis outpatient service during the prior 30 days.

How are hospital-acquired pneumonia (HAP), ventilator –associated pneumonia (VAP), and healthcare-associated pneumonia (HCAP) diagnosed?

The diagnosis of HAP/VAP/HCAP is suspected in a patient with new or progressive radiologic infiltrate in the context of clinical features suggesting infection. The clinical features include new onset of fever, leukocytosis, purulent sputum, and increasing oxygenation requirements.

The diagnosis of HAP/VAP/HCAP is difficult with most diagnoses made on clinical grounds alone; the patient has fever and a productive cough. The diagnostic criteria of a radiologic infiltrate and at least one clinical feature (i.e., fever, leukocytosis, or purulent tracheal secretions) has a high sensitivity but low specificity for HAP and VAP. Combinations of signs and symptoms increase the specificity.

Hospitalized patients, including those who are ventilated are highly likely to have colonized upper airways. Colonization precedes infection, but the routine monitoring of tracheal aspirate cultures as a means of predicting the likely pathogen is not warranted as it has been found to be misleading in a significant proportion of cases. Antibiotic treatment of simple colonization is not recommended.

The absence of a “gold standard” diagnostic test has made interpreting studies looking at diagnostic tests for HAP/VAP/HCAP difficult. Prior antibiotic use and recent changes in antibiotic treatment make interpreting cultures difficult.

The etiologic diagnosis requires lower respiratory tract culture, endotracheal aspirates, bronchoalveolar lavages, or protected specimen brush. Blood cultures may be positive in up to 25% of cases of HAP and may not necessarily be directly attributable to HAP. Pleural fluid may occasionally be cultured but is seldom useful for determining the etiology.

A sterile culture from lower respiratory tract symptoms has a high negative predictive value and can be used to exclude HAP/VAP/HCAP as a cause of fever. Also, the absence of multiple-antibiotic resistant organisms from these cultures is strong evidence that they are not causing infection and narrowing of the antibiotic spectrum can occur.

Quantitative cultures of lower respiratory tract secretions may be useful in sorting out colonization from true infection. Quantitative cultures are not routinely performed by most diagnostic laboratories.

Culture of lower respiratory tract specimens for viruses has a low yield. PCR assays for respiratory viruses can be performed on upper and lower respiratory tract specimens. Hospital transmission of respiratory viruses is well described, particularly in immunocompromised patient groups.

Legionellosis is an under-recognised cause of both HAP and HCAP. The diagnosis should be considered in patients with exposure to potable water and with risk factors for micro-aspiration.

Should all patients with healthcare-associated pneumonia receive empiric treatment with broad spectrum antimicrobials?

The 2005 American Thoracic Society guideline for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia recommends early, appropriate, broad spectrum antimicrobial therapy prescribed at an appropriate dose. Combination therapy should be used judiciously, and a short-course of beta-lactam and aminoglycoside therapy may be used to treat Pseudomonas aeruginosa infections. De-escalation should occur in response to microbiology culture results.

Patients with HCAP are a heterogeneous population, and not all patients share the same risks for severe pneumonia. The main driver for the use of empiric broad spectrum antibiotics in this group is to provide adequate cover for multiple antibiotic resistant organisms. Local epidemiological data should be used to determine if this approach is warranted in ambulatory patients, those from residential care facilities, and those using outpatient hemodialysis services. Monotherapy can be used in this group of patients who present with mild to moderate pneumonia.

Should combination therapy be routinely used for confirmed or suspected Gram-negative HAP/VAP/HCAP?

Combination therapy in this situation, usually with a beta-lactam and aminoglycoside, is recommended in some guidelines. The justification for this approach is to achieve synergy against Pseudomonas aeruginosa. However, synergy has only been demonstrated in vitro and in patients with neutropenia or concurrent bacteremia.

Combination therapy is also proposed as a means to avoid the development of resistance of treatment. This is a common phenomenon when P. aeruginosais treated with monotherapy and when Enterobacterare treated with third generation cephalosporins. Prevention of the development of resistance by combination therapy has been poorly documented.

Another justification is to provide a broad spectrum empiric treatment likely to include at least one drug active against multiple antibiotic resistant organisms. This is only a concern if resistance is a major issue.

If combination therapy is used, its ongoing use should be reviewed early in the course of treatment and de-escalation to monotherapy should occur if the patient is clinically improving.

What is the duration of antibiotics for HAP/VAP/HCAP?

Significant clinical improvement should be observed over the first 3-5 days of therapy. The standard duration of treatment is 7-8 days for most pathogens and longer (usually 14 days) for non-fermenting Gram-negative bacteria, such as P. aeruginosa, Acinetobacter,and Stenotrophomonas maltophilia.

Longer courses of treatment are associated with the emergence of dug resistance.

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