Medication Summary
Drug therapy for pneumonia is tailored to the situation. Because the etiologic agents vary, drug choice is affected by the patient's age, exposure history, likelihood of drug resistance (eg, pneumococcus), and clinical presentation.
Beta-lactam antibiotics (eg, amoxicillin, cefuroxime, cefdinir) are preferred for outpatient management. Macrolide antibiotics (eg, azithromycin, clarithromycin) are useful in most school-aged children to cover the atypical organisms and pneumococcus. Local variations in microbial drug resistance require different approaches to therapy, including cases caused by pneumococcus. Any child with a positive purified protein derivative (PPD) test result and infiltrate on chest radiographs requires additional testing for tuberculosis and polymicrobial treatment.
Agents typically used initially in the treatment of newborns and young infants with pneumonia include a combination of ampicillin and either gentamicin or cefotaxime. The selection of cefotaxime or gentamicin must be based on experience and considerations at each specific medical center and in each patient. Combination therapy provides reasonable antimicrobial efficacy against the pathogens that typically cause serious infection in the first days of life. Other agents or combinations may be appropriate for initial empiric therapy if justified by the range of pathogens and susceptibilities encountered in a particular clinical setting.
Isolation of a specific pathogen from a normally sterile site in the infant allows revision of therapy to the drug that is least toxic, has the narrowest antimicrobial spectrum, and is most effective. Dosing intervals for ampicillin, cefotaxime, gentamicin, and other antimicrobial agents typically require readjustment in the presence of renal dysfunction.
In a randomized, placebo-controlled study of 820 pediatric patients with mild pneumonia, researchers found that treatment with oral amoxicillin (50 mg/kg/day) twice daily was as effective as amoxicillin given 3 times a day. Treatment failure occurred in 23% of the twice-daily group and 22.8% of the thrice-daily group in the intention-to-treat analysis, and in 21.3% and 20.1% of these groups, respectively, in the per-protocol analysis. Among the 277 patients with radiologically confirmed pneumonia, treatment failure occurred in 18.8% of patients in both groups. [70]
Penicillins
Class Summary
The penicillins are bactericidal antibiotics that work against sensitive organisms at adequate concentrations and inhibit the biosynthesis of cell wall mucopeptide. Examples of penicillins include amoxicillin (Amoxil, Trimox), penicillin VK, and ampicillin.
Amoxicillin (Amoxil, Trimox)
Amoxicillin interferes with synthesis of cell wall mucopeptides during active multiplication, resulting in bactericidal activity against susceptible bacteria. This drug is an appropriate first-line agent in children in whom pneumococcal disease is strongly suspected. Amoxicillin offers the advantages of being relatively palatable and having a tid-dosing schedule, but it has limited activity against gram-negative bacteria due to resistance.
Ampicillin (Marcillin, Omnipen, Polycillin)
Ampicillin has bactericidal activity against susceptible organisms and is used as an alternative to amoxicillin when patients are unable to take medication orally.
Penicillin VK (Beepen-VK, Pen Vee K)
Penicillin VK inhibits the biosynthesis of cell wall mucopeptide and is bactericidal against sensitive organisms when adequate concentrations are reached. This drug is most effective during the stage of active multiplication, but inadequate concentrations may produce only bacteriostatic effects. Penicillin VK may be used as an alternative to amoxicillin in the treatment of outpatients with pneumonia in whom pneumococcal disease is strongly suspected, but it has limited activity against gram-negative bacteria.
Cephalosporins
Class Summary
Cephalosporins are structurally and pharmacologically related to penicillins. They inhibit bacterial cell wall synthesis, resulting in bactericidal activity. Cephalosporins are divided into first, second, and third generation. First-generation cephalosporins have greater activity against gram-positive bacteria, and succeeding generations have increased activity against gram-negative bacteria and decreased activity against gram-positive bacteria.
Cefpodoxime (Vantin)
Cefpodoxime inhibits bacterial cell wall synthesis by binding to one or more of the penicillin-binding proteins. The tablet should be administered with food.
Cefprozil (Cefzil)
Cefprozil binds to one or more of the penicillin-binding proteins, which, in turn, inhibits cell wall synthesis and results in bactericidal activity.
Cefdinir (Omnicef)
Cefdinir binds to one or more of the penicillin-binding proteins, which, in turn, inhibits cell wall synthesis and results in bactericidal activity.
Ceftriaxone (Rocephin)
Ceftriaxone is a third-generation cephalosporin with broad-spectrum gram-negative activity that arrests bacterial growth by binding to one or more penicillin-binding proteins. Ceftriaxone has lower efficacy against gram-positive organisms but higher efficacy against resistant organisms.
Cefotaxime (Claforan)
Cefotaxime is a third-generation cephalosporin with gram-negative spectrum that arrests bacterial cell wall synthesis, which, in turn, inhibits bacterial growth. This drug has a lower efficacy against gram-positive organisms.
Cefuroxime (Zinacef, Ceftin, Kefurox)
Cefuroxime is a second-generation cephalosporin that maintains the gram-positive activity first-generation cephalosporins have. This drug adds activity against P mirabilis, H influenzae, E coli, K pneumoniae, and M catarrhalis. The condition of the patient, severity of infection, and susceptibility of the causative microorganism determines the proper dose and route of administration.
Ceftaroline (Teflaro)
Beta-lactam cephalosporin with activity against aerobic and anaerobic gram-positive and aerobic gram-negative bacteria. It is indicated in children aged ≥2 months for treatment of community-acquired bacterial pneumonia (CABP) caused by susceptible isolates of Streptococcus pneumoniae (including cases with concurrent bacteremia), Staphylococcus aureus (methicillin-susceptible isolates only), Haemophilus influenzae, Klebsiella pneumoniae, Klebsiella oxytoca, and Escherichia coli.
Ceftazidime/avibactam (Avycaz)
Indicated for treatment of hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia (HABP/VABP) now includes pediatric patients aged 3 months and older caused by the following susceptible Gram-negative microorganisms: Klebsiella pneumoniae, Enterobacter cloacae, Escherichia coli, Serratia marcescens, Proteus mirabilis, Pseudomonas aeruginosa, and Haemophilus influenzae.
Avibactam is a diazabicyclooctanone, non-β-lactam, β-lactamase inhibitor. Alone has no antibacterial activity at clinically relevant doses. When combined with ceftazidime, avibactam protects ceftazidime from degradation by β-lactamase enzymes and effectively extends the antibiotic spectrum of ceftazidime to include many gram-negative bacteria normally not susceptible to ceftazidime.
Glycopeptides
Class Summary
Anti-infectives such as vancomycin are effective against some types of bacteria that have become resistant to other antibiotics.
Vancomycin (Vancocin)
Vancomycin is a tricyclic glycopeptide antibiotic with bactericidal action that primarily results from the inhibition of cell-wall biosynthesis. In addition, vancomycin alters bacterial cell membrane permeability and RNA synthesis. Antibiotic therapy should include vancomycin (particularly in areas where penicillin-resistant streptococci have been identified) and a second- or third-generation cephalosporin.
Macrolide Antibiotics
Class Summary
Macrolide antibiotics have bacteriostatic activity and exert their antibacterial action by binding to the 50S ribosomal subunit of susceptible organisms, resulting in inhibition of protein synthesis.
Erythromycin-sulfisoxazole (Pediazole)
Erythromycin is a macrolide antibiotic with a large spectrum of activity that binds to the 50S ribosomal subunit of the bacteria, which inhibits protein synthesis. Sulfisoxazole expands erythromycin's coverage to include gram-negative bacteria and inhibits bacterial synthesis of dihydrofolic acid by competing with para-aminobenzoic acid (PABA). The dose for the combination of the 2 drugs is based on the erythromycin component.
Azithromycin (Zithromax)
Azithromycin is used to treat mild to moderate microbial infections. Bacterial or fungal overgrowth may result with prolonged antibiotic use.
Clarithromycin (Biaxin)
Clarithromycin inhibits bacterial growth, possibly by blocking dissociation of peptidyl t-RNA from ribosomes, causing RNA-dependent protein synthesis to arrest.
Erythromycin (E.E.S., E-Mycin, Ery-Tab)
Erythromycin inhibits bacterial growth, possibly by blocking dissociation of peptidyl t-RNA from ribosomes, causing RNA-dependent protein synthesis to arrest. This drug is used for the treatment of staphylococcal and streptococcal infections. In children, age, weight, and severity of infection determine the proper dosage. When bid dosing is desired, half-total daily dose may be taken q12h. For more severe infections, double the dose.
Aminoglycosides
Class Summary
Aminoglycosides are bactericidal antibiotics used to primarily treat gram-negative infections. They interfere with bacterial protein synthesis by binding to 30S and 50S ribosomal subunits.
Gentamicin
Gentamicin is an aminoglycoside antibiotic for gram-negative coverage that is typically used in combination with agents against gram-positive organisms. When administered parenterally, this agent offers antimicrobial efficacy against many gram-negative pathogens commonly encountered in the first few days of life, including E coli, Klebsiella species, and other enteric organisms, as well as many strains of nontypeable H influenzae.
Gentamicin is also variably effective against some strains of certain gram-positive organisms, including S aureus, enterococci, and L monocytogenes. Gentamicin crosses the blood-brain barrier into the CNS less well and theoretically poses a greater risk of renal toxicity or ototoxicity than cefotaxime and other third-generation cephalosporins, which are the common alternatives.
Gentamicin is associated with much less rapid emergence of resistant organisms in a closed environment (eg, neonatal ICU), and has a broader range of susceptible gram-negative organisms. Gentamicin has been reported to offer additive or synergistic activity against enterococci when used with ampicillin.
Antituberculosis Agents
Class Summary
These agents are used in the treatment of patients with TB. Antimycobacterial agents are a miscellaneous group of antibiotics whose spectrum of activity includes Mycobacterium species. They are used to treat TB, leprosy, and other mycobacterial infections.
Isoniazid (Laniazid, Nydrazid)
Isoniazid has the best combination of effectiveness, low cost, and minor side effects of this class of drugs. Isoniazid should be the first-line agent unless the patient has known resistance or another contraindication. Therapeutic regimens for less than 6 months demonstrate unacceptably high relapse rate.
Coadministration of pyridoxine is recommended if peripheral neuropathies secondary to isoniazid therapy develop. Prophylactic doses of 6-50 mg of pyridoxine daily are recommended.
Ethambutol (Myambutol)
Ethambutol diffuses into actively growing mycobacterial cells, such as tubercle bacilli and impairs cell metabolism by inhibiting synthesis of one or more metabolites, which, in turn, causes cell death.
No cross-resistance has been demonstrated; however, mycobacterial resistance is common with previous therapy. Use ethambutol in these patients in combination with second-line drugs that have not been previously administered. Administer q24h until permanent bacteriologic conversion and maximal clinical improvement is observed. Absorption of this drug is not significantly altered by food.
Rifampin (Rifadin, Rimactane)
Rifampin is used in combination with at least one other antituberculous drug and inhibits RNA synthesis in bacteria by binding to the beta subunit of DNA-dependent RNA polymerase, which in turn blocks RNA transcription. Rifampin treatment duration is for 6-9 months or until 6 months have elapsed from conversion to sputum culture negativity.
Streptomycin
Streptomycin sulfate is used in combination with other antituberculous drugs (eg, isoniazid, ethambutol, rifampin). The total period of treatment for TB is a minimum of 1 year; however, indications for terminating streptomycin therapy may occur at any time. Streptomycin is recommended when less potentially hazardous therapeutic agents are ineffective or contraindicated.
Pyrazinamide
Pyrazinamide is a pyrazine analog of nicotinamide that may be bacteriostatic or bactericidal against Mycobacterium tuberculosis, depending on the concentration of the drug attained at the site of infection. Its mechanism of action is unknown.
For patients who are drug susceptible, administer for the initial 2 months of a 6-month or longer treatment regimen. Treat patients who are drug resistant with individualized regimens.
Antiviral Agents
Class Summary
These agents must be initiated early to adequately inhibit the replicating virus. This is difficult because the clinical situation usually deteriorates over several days, such that by the time the child's condition is poor enough to require medical attention, the window of opportunity has passed.
Unfortunately, oseltamivir resistance emerged in the United States during the 2008-2009 influenza season; the CDC issued revised interim recommendations for antiviral treatment and prophylaxis of influenza. Thus, zanamivir (Relenza) is recommended as the initial choice for antiviral prophylaxis or treatment when influenza A infection or exposure is suspected. Complete recommendations are available from the CDC.
Ribavirin (Virazole)
Ribavirin inhibits viral replication by inhibiting DNA and RNA synthesis and is effective against RSV, influenza virus, and herpes simplex virus. However, there has been little evidence to demonstrate that ribavirin has much clinical benefit in a hospital setting.
Oseltamivir (Tamiflu)
Oseltamivir inhibits neuraminidase, which is a glycoprotein on the surface of influenza virus that destroys an infected cell's receptor for viral hemagglutinin. By inhibiting viral neuraminidase, oseltamivir decreases the release of viruses from infected cells and, thus, viral spread. This drug has been effective for treatment of influenza A or B infection and is administered within 40 h of symptom onset.
Unfortunately, oseltamivir resistance emerged in the United States during the 2008-2009 influenza season; the CDC issued revised interim recommendations for antiviral treatment and prophylaxis of influenza. Thus, zanamivir (Relenza) is recommended as the initial choice for antiviral prophylaxis or treatment when influenza A infection or exposure is suspected. Complete recommendations are available from the CDC.
A second-line alternative is a combination of oseltamivir plus rimantadine, rather than oseltamivir alone. Local influenza surveillance data and laboratory testing can assist the physician regarding antiviral agent choice.
Zanamivir (Relenza)
Zanamivir is an inhibitor of neuraminidase, which is a glycoprotein on the surface of the influenza virus that destroys the infected cell's receptor for viral hemagglutinin. By inhibiting viral neuraminidase, release of viruses from infected cells and viral spread are decreased. Zanamivir is effective against both influenza A and B and is administered by inhalation through a Diskhaler oral inhalation device. Circular foil discs that contain 5-mg blisters of drug are inserted into supplied inhalation device.
Acyclovir (Zovirax)
Acyclovir inhibits activity of both HSV-1 and HSV-2 and is the drug of choice for the treatment of pneumonia in children with herpes viruses (eg, herpes simplex, varicella). Patients experience less pain and faster resolution of cutaneous lesions when used within 48 hours from rash onset.
Vaccines
Class Summary
Aside from avoiding infectious contacts, vaccination is the primary mode of prevention. Vaccines provide immunity to a disease by stimulating antibody formation and can be either killed or attenuated live.
Influenza virus vaccine quadrivalent (Afluria Quadrivalent, Fluarix Quadrivalent, FluLaval Quadrivalent)
Quadrivalent vaccines contain two strains of influenza A and two of influenza B. The vaccine induces antibodies specific to virus strains contained in vaccine. Each year, the US Public Health Service determines which viral strains will be included in the seasonal influenza vaccine that will antigenically represent the viral strains most likely to circulate in the next flu season. It is administered as an IM injection. Afluria, Fluzone, FluLaval, and Fluarix Quadrivalent vaccines are approved for children aged 6 months or older.
Influenza virus vaccine quadrivalent, cell-cultured (Flucelvax Quadrivalent)
Cell-derived (ie, egg-free) vaccine indicated for adults and pediatric patients aged 2 years or older.
Influenza virus vaccine quadrivalent, intranasal (FluMist Quadrivalent)
Indicated for immunization in patients aged 2-49 years.The Advisory Committee on Immunization Practices (ACIP) recommended return of intranasal flu vaccine in the U.S. for 2018-2019 season. The recommendation was based on positive results from a U.S. study in children between the ages of 2 to <4 years evaluating the shedding and antibody responses of the H1N1 strain in the live attenuated influenza vaccine (LAIV).
Pneumococcal vaccine 13-valent (Prevnar 13)
Indicated for routine vaccination in infants. Also for high-risk who are immunocompromised (eg, HIV, cancer, renal disease) or have functional or anatomic asplenia, cerebrospinal fluid leaks, or cochlear implants.
Capsular polysaccharide vaccine against 13 strains of S pneumoniae, conjugated to nontoxic diphtheria protein, including serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F.
Pneumococcal vaccine 15-valent (Vaxneuvance)
Indicated for active immunization for prevention of invasive disease caused by Streptococcus pneumoniae in individuals aged 6 weeks and older.
Use for primary vaccination and catch-up immunization in children aged 6 weeks and older is interchangeable with PCV13.
Recommended for routine vaccination in adults aged 65 years and older who have not previously received a pneumococcal conjugate vaccine or whose previous vaccination history is unknown. If PCV15 is used, this should be followed 1 year later by a dose of PPSV23.
Also indicated for adults aged 19-64 years with certain underlying medical conditions or other risk factors who have not previously received a pneumococcal conjugate vaccine or whose previous vaccination history is unknown (followed by a dose of PPSV23).
Contains all serotypes in the PVC13 vaccine plus 22F and 33F.
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(Left) Gram stain demonstrating gram-positive cocci in pairs and chains and (right) culture positive for Streptococcus pneumoniae.
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A breakdown of test results and recommended treatment for pneumonia with effusion. Gm = Gram; neg = negative; pos = positive; VATS = video-assisted thoracic surgery
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(A) Anteroposterior radiograph from a child with presumptive viral pneumonia. (B) Lateral radiograph of the same child with presumptive viral pneumonia.
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Radiograph from a patient with bacterial pneumonia (same patient as in the preceding image) a few days later. This radiograph reveals progression of pneumonia into the right middle lobe and the development of a large parapneumonic pleural effusion.
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Right lower lobe consolidation in a patient with bacterial pneumonia.
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(A) Anteroposterior radiograph from a child with a left lower lobe infiltrate. (B) Lateral radiograph of the same child with a left lower lobe infiltrate.
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Anteroposterior radiograph from a child with a round pneumonia.
Tables
Category |
Laboratory and Imaging Findings |
Clinical Findings |
Differential Diagnosis |
1 |
Persistent or recurrent radiologic findings |
Persistent or recurrent fever and symptoms |
Cystic fibrosis, immunodeficiencies, obstruction (intrinsic [eg, foreign body] or extrinsic [eg, compressing nodes or tumor]), pulmonary sequestration, bronchial stenosis, or bronchiectasis |
2 |
Persistent radiologic findings |
No clinical findings |
Anatomic abnormality (eg, sequestration, fibrosis, pleural lesion) |
3 |
Recurrent pulmonary infiltrates with interval radiologic clearing |
No clinical findings |
Asthma and atelectasis that has been misdiagnosed (for example, as a bacterial pneumonia); aspiration syndrome, hypersensitivity pneumonitis, idiopathic pulmonary hemosiderosis, or a mild immunodeficiency disorder |
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