Empiric therapy of Pneumonia
Pneumonia is an infection that affects one or both lungs. It causes the air sacs, or alveoli, of the lungs to fill up with fluid or pus. Bacteria, viruses, or fungi may cause pneumonia. Symptoms can range from mild to serious and may include a cough with or without mucus (a slimy substance), fever, chills, and trouble breathing. How serious your pneumonia is depends on your age, your overall health, and what caused your infection.
To diagnose pneumonia, your healthcare provider will review your medical history, perform a physical exam, and order diagnostic tests such as a chest X-ray. This information can help determine what type of pneumonia you have.
Treatment for pneumonia may include antibiotic, viral, or fungal medicines. It may take several weeks to recover from pneumonia. If your symptoms get worse, you should see a healthcare provider right away. If you have severe pneumonia, you may need to go to the hospital for antibiotics given through an intravenous (IV) line and oxygen therapy.
Pneumonia occurs in two major forms: community-acquired pneumonia (CAP) and hospital-acquired pneumonia (HAP). As suggested by their names, these entities are defined by where the infectious agent is acquired. Whereas CAP typically occurs in individuals residing in their homes, HAP afflicts those who are in a hospital.
The importance of this distinction is that the circumstances under which the pneumonia was acquired dictate to a large extent the type of pathogens that may cause it and, therefore, the most appropriate empiric therapy. Note that an increasingly large number of individuals fall between these two extremes; they reside in nursing homes or long-term care facilities, or they are frequently exposed to medical personnel or medical settings such as dialysis centers. When these individuals develop pneumonia, they are said to have health care–associated pneumonia (HCAP) and should be treated similarly to those with HAP.
Acute CAP has been divided into two categories: typical and atypical. Although these classifications are useful in understanding the etiology of pneumonia, significant overlap occurs between them, and the clinical presentations of typical and atypical pneumonia are not distinct enough to be useful in decisions about therapy.
Typical CAP usually presents with the sudden onset of fever, chills, pleuritic chest pain, and a productive cough. Afflicted individuals are usually older than 50 years of age. Radiographic examination shows a lobar or subsegmental infiltrate. The usual suspects in cases of typical CAP are Streptococcus pneumoniae and Haemophilus influenza. Other aerobic gram-negative bacteria and Staphylococcus aureus are less common.
In contrast, atypical CAP is often preceded by a mild respiratory illness manifested by pharyngitis and rhinorrhea. The pneumonia is often, but not always, mild and is accompanied by a nonproductive cough. Patients are frequently younger than those with typical CAP, and chest radiographs may show interstitial infi ltrates instead of lobar or subsegmental infi ltrates. Legionella
Optimal empiric therapy for CAP is controversial but in all cases is based on the most common etiologic bacteria, host predisposing factors, and the severity of illness.
The symptoms of pneumonia can be mild or serious. Young children, older adults, and people who have serious health conditions are at risk for developing more serious pneumonia or life-threatening complications.
The symptoms of pneumonia may include:
- Chest pain when you breathe or cough
- Cough with or without mucus
- Low oxygen levels in your blood, measured with a pulse oximeter
- Shortness of breath
You may also have other symptoms, including a headache, muscle pain, extreme tiredness, nausea (feeling sick to your stomach), vomiting, and diarrhea.
Older adults and people who have serious illnesses or weakened immune systems may not have the typical symptoms. They may have a lower-than-normal temperature instead of a fever. Older adults who have pneumonia may feel weak or suddenly confused.
Sometimes babies don’t have typical symptoms either. They may vomit, have a fever, cough, or appear restless or tired and without energy. Babies may also show the following signs of breathing problems:
- Bluish tone to the skin and lips
- Pulling inward of the muscles between the ribs when breathing
- Rapid breathing
- Widening of the nostrils with each breath
Diagnostic tests and procedures
If your provider thinks you have pneumonia, he or she may do one or more of the following tests.
- A chest X-ray looks for inflammation in your lungs. A chest X-ray is often used to diagnose pneumonia.
- Blood tests, such as a complete blood count (CBC) see whether your immune system is fighting an infection.
- Pulse oximetry measures how much oxygen is in your blood. Pneumonia can keep your lungs from getting enough oxygen into your blood. To measure the levels, a small sensor called a pulse oximeter is attached to your finger or ear.
If you are in the hospital, have serious symptoms, are older, or have other health problems, your provider may do other tests to diagnose pneumonia.
- A blood gas test may be done if you are very sick. For this test, your provider measures your blood oxygen levels using a blood sample from an artery, usually in your wrist. This is called an arterial blood gas test.
- A sputum test, using a sample of sputum (spit) or mucus from your cough, may be used to find out what germ is causing your pneumonia.
- A blood culture test can identify the germ causing your pneumonia and also show whether a bacterial infection has spread to your blood.
- A polymerase chain reaction (PCR) test quickly checks your blood or sputum sample to find the DNA of germs that cause pneumonia.
- A bronchoscopy looks inside your airways. If your treatment is not working well, this procedure may be needed. At the same time, your doctor may also collect samples of your lung tissue and fluid from your lungs to help find the cause of your pneumonia.
- A chest computed tomography (CT) scan can show how much of your lungs are affected by pneumonia. It can also show whether you have complications such as lung abscesses or pleural disorders. A CT scan shows more detail than a chest X-ray.
- A pleural fluid culture can be taken using a procedure called thoracentesis, which is when a doctor uses a needle to take a sample of fluid from the pleural space between your lungs and chest wall. The fluid is then tested for bacteria.
Drugs of choice
For individuals with mild disease that can be treated in the outpatient setting, experts recommend an oral macrolide (azithromycin, clarithromycin, erythromycin) or doxycycline unless the patient has comorbidities or is otherwise at risk for infection with penicillin-resistant S. pneumoniae.
In this case, treatment should be with (1) an oral antistreptococcal quinolones (moxifl oxacin, levofl oxacin, gemifl oxacin) or (2) an oral β-lactam agent (amoxicillin, amoxicillin/clavulanate, cefuroxime) given in high doses plus a macrolide (azithromycin, clarithromycin, erythromycin). Macrolides and doxycycline are effective against atypical pathogens, H. infl uenzae, and some strains of S. pneumoniae. In contrast, the strength of the β-lactams is their activity against S. pneumoniae.
When given in high doses, β-lactam antibiotics achieve levels within the lung that are suffi cient to kill all strains of S. pneumoniae except those that are highly resistant to these agents. The β-lactams amoxicillin/clavulanate and cefuroxime also have excellent activity against H. infl uenzae. Given the complementary strengths of these agents, experts feel that they should be used together to treat CAP in patients at risk for penicillin-resistant S. pneumoniae.
Oral antistreptococcal quinolones are highly effective against penicillin-resistant S. pneumoniae, H. influenzae, and atypical pathogens and are also efficacious for the treatment of CAP in the outpatient setting if there is concern for penicillin-resistant S. pneumoniae. Obviously, quinolones and doxycycline should be avoided in small children.
For patients with moderately severe CAP requiring admission to the hospital, intravenous therapy is usually given. It is recommended that these patients receive either (1) a combination of a macrolide (azithromycin, clarithromycin, erythromycin) and β-lactam (cefotaxime, ceftriaxone, high-dose ampicillin) or (2) monotherapy with an antistreptococcal quinolone (moxifl oxacin, levofl oxacin). Either of these regimens is effective against S. pneumoniae (including most penicillin-resistant strains), H. infl uenzae, Legionella spp., and atypical pathogens.
Patients with severe CAP requiring admission to an intensive care unit should receive a combination of a β-lactam (cefotaxime, ceftriaxone, ampicillin/ sulbactam) plus either azithromycin or an antistreptococcal quinolone (moxifloxacin, levofl oxacin). If risk factors for Pseudomonas aeruginosa infection are present (e.g., a history of bronchiectasis, steroid use, or broad-spectrum antibiotic therapy), regimens should include two antipseudomonal agents.
Likewise, if risk factors for community-acquired methicillin-resistant Staphylococcus aureus (MRSA) are present, an appropriate antistaphylococcal agent (vancomycin, linezolid) should be added.
HAP is divided into early-onset (occurring within the fi rst 5 days following admission) and late-onset (occurring after 5 days of hospitalization) disease.
Early-onset HAP often resembles CAP in that the etiologic pathogens are acquired in the community. These pathogens are Streptococcus pneumoniae, H. infl uenzae, methicillin-sensitive Staphylococcus aureus, and antibiotic-sensitive enteric gramnegative bacilli (Table 16-3). In contrast, late-onset HAP is caused by bacteria acquired in the hospital, such as P. aeruginosa, Acinetobacter spp., antibiotic-resistant enteric gram-negative bacilli, and MRSA. In some hospitals, Legionella pneumophila also causes a signifi cant proportion of these pneumonias. Bacteria acquired in the hospital are often resistant to multiple antibiotics and are associated with poorer clinical outcomes in patients with HAP. For these reasons, the treatments of early and late-onset HAP differ.
Exceptions to the distinction between early- and late-onset HAP are those patients who have early-onset HAP (or CAP) but who have been recently (within the preceding 3 months) hospitalized, who reside in a nursing home or an extended care facility, or who have otherwise been exposed to the health care environment, or those who have received prolonged antimicrobial therapy. Such individuals are said to have HCAP and may have acquired antibiotic-resistant bacteria normally associated with the hospital setting and thus should be treated as if they have late-onset HAP.
The choice of initial empiric therapy for HAP is particularly important because inappropriate treatment regimens (e.g., antibiotics that are not effective against the causative bacteria) are associated with increased mortality, even when subsequently adjusted after culture data become available. Obviously, a risk factor for inappropriate antimicrobial therapy is infection by a multidrug-resistant organism because these organisms are more likely to be resistant to empirically prescribed treatment regimens.
Because the bacteria that cause early-onset HAP are similar to those that cause CAP, the antimicrobial therapies for these two syndromes are similar.
Empiric antibiotic therapy for early-onset HAP (without risk factors for multidrugresistant organisms) consists of ceftriaxone, quinolone (levofl oxacin, moxifl oxacin, ciprofl oxacin), ampicillin/sulbactam, or ertapenem.
Treatment of late-onset HAP or pneumonia in patients with other risk factors for multidrug-resistant organisms is more complex. To maximize the likelihood of giving at least one agent that is effective against the highly resistant bacteria that cause this type of pneumonia, combination therapy using antibiotics from at least two different classes is recommended. In addition, these agents should have activity against P. aeruginosa, one of the most common causes of late-onset HAP. Useful regimens include an antipseudomonal cephalosporin (ceftazidime, cefepime), carbapenem (imipenem, meropenem) or piperacillin/tazobactam in combination with a quinolone (ciprofl oxacin, levofl oxacin), or aminoglycoside (gentamicin, tobramycin, amikacin). In patients suspected of being infected with MRSA, linezolid or vancomycin should be added. Such patients would be those with gram positive cocci in a tracheal aspirate sample or those in an intensive care unit with a high incidence of MRSA.
Several issues should be kept in mind when choosing antibiotics from this list for individual patients. First, it is best to use agents that the patient has not recently received because prior exposure to an antibiotic increases the risk of resistance. Second, local resistance patterns should be used to guide the choice of an agent. Finally, antibiotics should be chosen to minimize the chance of an allergic or adverse drug reaction. For example, if possible, the prolonged use of aminoglycosides should be avoided in elderly patients and those with chronic renal insuffi ciency because of the risk of nephrotoxicity.