Medication Summary
The goals of pharmacotherapy are to reduce morbidity and prevent complications.
Antibiotics
Class Summary
Therapy must be comprehensive and cover all likely pathogens in the context of this clinical setting. Initiate therapy with intravenous antibiotics and transition to oral agents or equivalent agents based on clinical response. Oral antibiotics can be used to transition from intravenous therapy; they allow completion of a full course of therapy without the need for intravascular access or inpatient hospitalization. The antibiotic choice should focus on the most likely pathogens, ranging from anaerobic infections to community-acquired pathogens, to nosocomial or healthcare–associated pathogens, to resistant gram-positive pneumonias.
Penicillin G (Pfizerpen)
Penicillin G interferes with the synthesis of cell wall mucopeptide during active multiplication, resulting in bactericidal activity against susceptible microorganisms.
Penicillin VK (Beepen-VK, Betapen-VK, Pen.Vee K, Robicillin VK, V-Cillin K, Veetids)
Penicillin VK is preferred to penicillin G because of increased resistance to gastric acid. Treatment must continue for 10 full days. The probability of relapse of a GAS infection after therapy is 50% if penicillin is discontinued after 3 days of therapy.
Amoxicillin (Amoxil, Biomox, Trimox)
Amoxicillin has better absorption than penicillin VK and administration is every 8 hours instead of every 6 hours. For minor infections, some authorities advocate administration every 12 hours. This is probably the most active of penicillins for non–penicillin-susceptible S pneumoniae.
Ampicillin and sulbactam (Unasyn)
This is a drug combination of a beta-lactamase inhibitor with ampicillin. It interferes with bacterial cell wall synthesis during active replication, causing bactericidal activity against susceptible organisms. It is an alternative to amoxicillin when the patient is unable to take medication orally. It covers skin, enteric flora, and anaerobes, but is not ideal for nosocomial pathogens.
Clindamycin (Cleocin, Cleocin Pediatric, ClindaMax Vaginal)
Clindamycin is a semisynthetic antibiotic produced by 7(S)-chloro-substitution of 7(R)-hydroxyl group of the parent compound lincomycin. It inhibits bacterial growth, possibly by blocking dissociation of peptidyl tRNA from ribosomes, causing RNA-dependent protein synthesis to arrest. Clindamycin widely distributes in the body without penetration of the CNS. It is protein bound and excreted by the liver and kidneys.
Clindamycin is available in parenteral form (ie, clindamycin phosphate) and oral form (ie, clindamycin hydrochloride). Oral clindamycin is absorbed rapidly and almost completely and is not appreciably altered by the presence of food in the stomach. Appropriate serum levels are reached and sustained for at least 6 hour following an oral dose. No significant levels are attained in cerebrospinal fluid. It is also effective against aerobic and anaerobic streptococci (except enterococci).
Moxifloxacin (Avelox)
Moxifloxacin inhibits the A subunits of DNA gyrase, resulting in the inhibition of bacterial DNA replication and transcription. It is indicated for community-acquired pneumonia, including multidrug-resistant S pneumoniae.
Amoxicillin and clavulanate (Augmentin, Augmentin XR)
This combination inhibits bacterial cell wall synthesis by binding to penicillin-binding proteins. The addition of clavulanate inhibits beta-lactamase producing bacteria. It is a good alternative antibiotic for patients allergic to or intolerant of the macrolide class. It is usually well tolerated and provides good coverage of most infectious agents. It is not effective against Mycoplasma and Legionella species. The half-life of an oral dosage form is 1-1.3 hours. It has good tissue penetration but does not enter cerebrospinal fluid.
For children older than 3 months, base dosing on the amoxicillin content. Because of the different amoxicillin/clavulanic acid ratios in the 250-mg tablet (250/125) versus the 250-mg chewable tablet (250/62.5), do not use the 250-mg tablet until child weighs more than 40 kg.
Cefoxitin (Mefoxin)
Cefoxitin is a second-generation cephalosporin with activity against some gram-positive cocci, gram-negative rod infections, and anaerobic bacteria. It inhibits bacterial cell wall synthesis by binding to one or more of the penicillin-binding proteins; it inhibits the final transpeptidation step of peptidoglycan synthesis, resulting in cell wall death. Infections caused by cephalosporin- or penicillin-resistant gram-negative bacteria may respond to cefoxitin.
Ceftriaxone (Rocephin)
Ceftriaxone is a third-generation cephalosporin with broad-spectrum, gram-negative activity; it has lower efficacy against gram-positive organisms and higher efficacy against resistant organisms. The bactericidal activity results from inhibiting cell wall synthesis by binding to one or more penicillin-binding proteins. It exerts its antimicrobial effect by interfering with the synthesis of peptidoglycan, a major structural component of the bacterial cell wall. Bacteria eventually lyse because of the ongoing activity of cell wall autolytic enzymes while cell wall assembly is arrested.
Ceftriaxone is highly stable in the presence of beta-lactamases, both penicillinase and cephalosporinase, of gram-negative and gram-positive bacteria. Approximately 33-67% of the dose is excreted unchanged in urine, and the remainder is secreted in bile and ultimately in feces as microbiologically inactive compounds. It reversibly binds to human plasma proteins, and binding has been reported to decrease from 95% bound at plasma concentrations less than 25 mcg/mL to 85% bound at 300 mcg/mL.
Cefepime (Maxipime)
Cefepime is a fourth-generation cephalosporin. Its gram-negative coverage is comparable to ceftazidime but it has better gram-positive coverage (comparable to ceftriaxone). Cefepime is a zwitter ion; it rapidly penetrates gram-negative cells. It is the best beta-lactam for intramuscular administration. Its poor capacity to cross the blood-brain barrier precludes its use for the treatment of meningitis. It may be more active than ceftazidime against Enterobacter species because of enhanced stability against beta-lactamases.
Cefuroxime (Ceftin, Kefurox, Zinacef)
Cefuroxime is a second-generation cephalosporin that maintains gram-positive activity of the first-generation cephalosporins; adds activity against Proteus mirabilis, Haemophilus influenzae, Escherichia coli, Klebsiella pneumoniae, and Moraxella catarrhalis. Cefuroxime binds to penicillin-binding proteins and inhibits the final transpeptidation step of peptidoglycan synthesis, resulting in cell wall death. The condition of the patient, the severity of the infection, and the susceptibility of the microorganism determine the proper dose and route of administration. It resists degradation by beta-lactamase.
Cefaclor (Ceclor)
Cefaclor is a second-generation cephalosporin that binds to one or more of the penicillin-binding proteins, which, in turn, inhibits cell wall synthesis and results in bactericidal activity. It has gram-positive activity that first-generation cephalosporins have and adds activity against P mirabilis, H influenzae, E coli, K pneumoniae, and M catarrhalis. It is indicated for infections caused by susceptible mixed aerobic-anaerobic microorganisms. Determine the proper dosage and route based on the condition of the patient, the severity of the infection, and the susceptibility of the causative organism.
Piperacillin and tazobactam sodium (Zosyn)
Nosocomial pneumonia caused by P aeruginosa should be treated in combination with an aminoglycoside. This is an antipseudomonal penicillin plus beta-lactamase inhibitor. It inhibits the biosynthesis of the cell wall mucopeptide and is effective during the stage of active multiplication.
Cefprozil (Cefzil)
Cefprozil is a second-generation cephalosporin that binds to one or more of the penicillin-binding proteins, which, in turn, inhibits cell wall synthesis and results in bactericidal activity. It has gram-positive activity that first-generation cephalosporins have and adds activity against P mirabilis, H influenzae, E coli, K pneumoniae, and M catarrhalis. Determine the proper dosage and route based on the condition of the patient, the severity of the infection, and the susceptibility of the causative organism.
Levofloxacin (Levaquin)
Levofloxacin is rapidly becoming a popular choice in pneumonia. It is good monotherapy for pseudomonal infections and infections due to multidrug-resistant gram-negative organisms.
Ertapenem (Invanz)
The bactericidal activity results from the inhibition of cell wall synthesis and is mediated through ertapenem binding to penicillin-binding proteins. It is stable against hydrolysis by a variety of beta-lactamases, including penicillinases, cephalosporinases, and extended-spectrum beta-lactamases. It is hydrolyzed by metallo-beta-lactamases. Ertapenem is indicated for community-acquired pneumonia due to S pneumoniae (penicillin-susceptible isolates only), including cases with concurrent bacteremia, H influenzae (beta-lactamase–negative isolates only, or M catarrhalis).
Clarithromycin (Biaxin)
Clarithromycin is a semisynthetic macrolide antibiotic that reversibly binds to the P site of 50S ribosomal subunit of susceptible organisms and may inhibit RNA-dependent protein synthesis by stimulating dissociation of peptidyl t-RNA from ribosomes, causing bacterial growth inhibition.
Imipenem and cilastatin (Primaxin)
This combination is an extremely potent broad-spectrum beta-lactam antibiotic. It is rapidly hydrolyzed by the enzyme dehydropeptidase I located on the brush border of renal tubular cells, hence its combination with cilastatin (a reversible inhibitor of dehydropeptidase I). It is used for the treatment of multiple-organism infections in which other agents do not have wide-spectrum coverage or are contraindicated because of a potential for toxicity.
Meropenem (Merrem IV)
Meropenem is a carbapenem, not a beta-lactam antibiotic. It is a bactericidal broad-spectrum carbapenem antibiotic that inhibits cell wall synthesis. It is effective against most gram-positive and gram-negative bacteria. It has slightly increased activity against gram-negative bacteria and slightly decreased activity against staphylococci and streptococci compared with imipenem.
Azithromycin (Zithromax)
Meropenem acts by binding to the 50S ribosomal subunit of susceptible microorganisms and blocks dissociation of peptidyl tRNA from ribosomes, causing RNA-dependent protein synthesis to arrest. Nucleic acid synthesis not affected. It concentrates in phagocytes and fibroblasts as demonstrated by in vitro incubation techniques. In vivo studies suggest concentration in phagocytes may contribute to drug distribution to inflamed tissues. It treats mild-to-moderate microbial infections. Plasma concentrations are very low, but tissue concentrations are much higher, giving it value in treating intracellular organisms. Meropenem has a long tissue half-life. Newer macrolides offer decreased GI upset and the potential for improved compliance through reduced dosing frequency. They also afford more improved action against H influenzae compared with erythromycin.
Vancomycin (Lyphocin, Vancocin, Vancoled)
Vancomycin is classified as a glycopeptide agent that has excellent gram-positive coverage, including methicillin-resistant S aureus. To avoid toxicity, the current recommendation is to assay vancomycin trough levels after a third dose drawn 0.5 hours prior to the next dosing. Use creatinine clearance to adjust the dose in patients diagnosed with renal impairment.
Linezolid (Zyvox)
Linezolid prevents the formation of functional 70S initiation complex, which is essential for the bacterial translation process. It is bacteriostatic against enterococci and staphylococci and bactericidal against most strains of streptococci. It is used as an alternative in patients allergic to vancomycin and for the treatment of vancomycin-resistant enterococci.
Metronidazole (Flagyl, Protostat)
Metronidazole is an imidazole ring-based antibiotic active against various anaerobic bacteria and protozoa. It is used in combination with other antimicrobial agents (except for C difficile enterocolitis). It is not standard practice to use metronidazole alone because some anaerobic cocci and most microaerophilic streptococci are resistant. Use it in combination with a beta-lactam in the treatment of anaerobic pneumonia and complicated pleuropulmonary infections.
Fibrinolytic agents
Class Summary
Fibrinolytic agents are indicated for the restoration of circulation through previously occluded vessels by dissolution of intraluminal thrombus or embolus not dissolved by the endogenous fibrinolytic system. In pleuropulmonary infections, fibrinolytic activity and dissolution of fibrin strands increases drainage of pleural fluid, which, in turn, may facilitate resolution of the infection. Important to note is that streptokinase and urokinase are no longer available in the United States.
Alteplase (Activase)
Alteplase is a tissue plasminogen activator that exerts effect on the fibrinolytic system to convert plasminogen to plasmin. Plasmin degrades fibrin, fibrinogen, and procoagulant factors V and VIII. Its serum half-life is 4-6 minutes but its half-life is lengthened when bound to fibrin in a clot. It is used in the management of acute myocardial infarction, acute ischemic stroke, and pulmonary embolism. Heparin and aspirin are not given for 24 hours after a tissue plasminogen activator. It must be given within 3 hours of stroke onset. Exclude hemorrhage by CT scan. If hypertensive, lower blood pressure with labetalol, 10 mg intravenously. The safety and efficacy of concomitant administration with aspirin and heparin during the first 24 hours after the onset of symptoms have not been investigated.
Mucolytic Agents
Class Summary
Large amounts of neutrophil-derived DNA released from dead neutrophils increase sputum viscosity. Mucolytics, such as dornase alfa, an enzyme that hydrolyses the DNA, are used to improve airway clearance.
Dornase alfa (Pulmozyme)
Dornase alfa is a recombinant human DNase (rhDNase) that cleaves and depolymerizes extracellular DNA and separates DNA from proteins. This allows endogenous proteolytic enzymes to break down the proteins, thus decreasing viscoelasticity and surface tension of purulent sputum.
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Left pleural effusion developed 4 days after antibiotic treatment for pneumococcal pneumonia. Patient developed fever, left-sided chest pain, and increasing dyspnea. During thoracentesis, purulent pleural fluid was removed, and the Gram stain showed gram-positive diplococci. The culture confirmed this to be Streptococcus pneumoniae.
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Left lateral chest radiograph shows a large, left pleural effusion.
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A right lateral decubitus chest radiograph shows a free-flowing pleural effusion, which should be sampled with thoracentesis for pH determination, Gram stain, and culture.
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CT scan of thorax shows loculated pleural effusion on left and contrast enhancement of visceral pleura, indicating the etiology is likely an empyema.
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Chest CT scan with intravenous contrast in a patient with mixed Streptococcus milleri and anaerobic empyema following aspiration pneumonia, showing a thickened contrast-enhanced pleural rind, high-density pleural effusion, loculation, and septation. Thoracentesis yielded foul-smelling pus.
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Chest CT scan with intravenous contrast in a patient with mixed Streptococcus milleri and anaerobic empyema following aspiration pneumonia, 3 days following thoracostomy and intrapleural fibrinolysis (Reteplase).
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Chest CT scan with intravenous contrast (axial, coronal, and sagittal views) of an alcoholic male patient with an anaerobic empyema demonstrating the split pleura sign.
