Parapneumonic Pleural Effusions and Empyema Thoracis Medication
- Author: Atikun Limsukon, MD; Chief Editor: Ryland P Byrd, Jr, MD more...
The goals of pharmacotherapy are to reduce morbidity and prevent complications.
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.
Interferes with synthesis of cell wall mucopeptide during active multiplication, resulting in bactericidal activity against susceptible microorganisms.
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 d of therapy.
Has better absorption than penicillin VK and administration is q8h instead of q6h. For minor infections, some authorities advocate administration q12h. Probably most active of penicillins for non–penicillin-susceptible S pneumoniae.
Drug combination of beta-lactamase inhibitor with ampicillin. Interferes with bacterial cell wall synthesis during active replication, causing bactericidal activity against susceptible organisms. Alternative to amoxicillin when unable to take medication orally.
Covers skin, enteric flora, and anaerobes. Not ideal for nosocomial pathogens.
Semisynthetic antibiotic produced by 7(S)-chloro-substitution of 7(R)-hydroxyl group of parent compound lincomycin. Inhibits bacterial growth, possibly by blocking dissociation of peptidyl tRNA from ribosomes, causing RNA-dependent protein synthesis to arrest. Widely distributes in the body without penetration of CNS. Protein bound and excreted by the liver and kidneys.
Available in parenteral form (ie, clindamycin phosphate) and oral form (ie, clindamycin hydrochloride). Oral clindamycin absorbed rapidly and almost completely and is not appreciably altered by presence of food in stomach. Appropriate serum levels reached and sustained for at least 6 h following oral dose. No significant levels are attained in cerebrospinal fluid. Also effective against aerobic and anaerobic streptococci (except enterococci).
Inhibits the A subunits of DNA gyrase, resulting in inhibition of bacterial DNA replication and transcription. Indicated for community-acquired pneumonia, including multidrug-resistant S pneumoniae.
Inhibits bacterial cell wall synthesis by binding to penicillin-binding proteins. Addition of clavulanate inhibits beta-lactamase producing bacteria.
Good alternative antibiotic for patients allergic to or intolerant of macrolide class. Usually well tolerated and provides good coverage of most infectious agents. Not effective against Mycoplasma and Legionella species. Half-life of oral dosage form is 1-1.3 h. Has good tissue penetration but does not enter cerebrospinal fluid.
For children >3 mo, base dosing on amoxicillin content. Due to different amoxicillin/clavulanic acid ratios in 250-mg tab (250/125) vs 250-mg chewable tab (250/62.5), do not use 250-mg tab until child weighs >40 kg.
Second-generation cephalosporin with activity against some gram-positive cocci, gram-negative rod infections, and anaerobic bacteria. Inhibits bacterial cell wall synthesis by binding to one or more of the penicillin-binding proteins; inhibits 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.
Third-generation cephalosporin with broad-spectrum, gram-negative activity; lower efficacy against gram-positive organisms; higher efficacy against resistant organisms. Bactericidal activity results from inhibiting cell wall synthesis by binding to one or more penicillin-binding proteins. Exerts antimicrobial effect by interfering with synthesis of peptidoglycan, a major structural component of bacterial cell wall. Bacteria eventually lyse because of the ongoing activity of cell wall autolytic enzymes while cell wall assembly is arrested.
Highly stable in presence of beta-lactamases, both penicillinase and cephalosporinase, of gram-negative and gram-positive bacteria. Approximately 33-67% of dose excreted unchanged in urine, and remainder secreted in bile and ultimately in feces as microbiologically inactive compounds. Reversibly binds to human plasma proteins, and binding has been reported to decrease from 95% bound at plasma concentrations < 25 mcg/mL to 85% bound at 300 mcg/mL.
Fourth-generation cephalosporin. Gram-negative coverage comparable to ceftazidime but has better gram-positive coverage (comparable to ceftriaxone). Cefepime is a zwitter ion; rapidly penetrates gram-negative cells. Best beta-lactam for IM administration. Poor capacity to cross blood-brain barrier precludes use for treatment of meningitis.
May be more active than ceftazidime against Enterobacter species because of enhanced stability against beta-lactamases.
May be more active than ceftazidime against Enterobacter species because of its enhanced stability against beta lactamases.
Second-generation cephalosporin maintains gram-positive activity of first-generation cephalosporins; adds activity against Proteus mirabilis, Haemophilus influenzae, Escherichia coli, Klebsiella pneumoniae, and Moraxella catarrhalis.
Binds to penicillin-binding proteins and inhibits final transpeptidation step of peptidoglycan synthesis, resulting in cell wall death. Condition of patient, severity of infection, and susceptibility of microorganism determine proper dose and route of administration. Resists degradation by beta-lactamase.
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. Has gram-positive activity that first-generation cephalosporins have and adds activity against P mirabilis, H influenzae, E coli, K pneumoniae, and M catarrhalis. Indicated for infections caused by susceptible mixed aerobic-anaerobic microorganisms. Determine proper dosage and route based on condition of patient, severity of infection, and susceptibility of causative organism.
Nosocomial pneumonia caused by P aeruginosa should be treated in combination with an aminoglycoside. Antipseudomonal penicillin plus beta-lactamase inhibitor. Inhibits biosynthesis of cell wall mucopeptide and is effective during stage of active multiplication.
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. Has gram-positive activity that first-generation cephalosporins have and adds activity against P mirabilis, H influenzae, E coli, K pneumoniae, and M catarrhalis. Condition of patient, severity of infection, and susceptibility of microorganism determine proper dose and route of administration.
Rapidly becoming a popular choice in pneumonia. Good monotherapy for pseudomonal infections and infections due to multidrug-resistant gram-negative organisms.
Bactericidal activity results from inhibition of cell wall synthesis and is mediated through ertapenem binding to penicillin-binding proteins. Stable against hydrolysis by a variety of beta-lactamases including penicillinases, cephalosporinases, and extended-spectrum beta-lactamases. Hydrolyzed by metallo-beta-lactamases.
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).
Semisynthetic macrolide antibiotic that reversibly binds to 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.
Extremely potent broad-spectrum beta-lactam antibiotic. Rapidly hydrolyzed by enzyme dehydropeptidase I located on brush border of renal tubular cells, hence its combination with cilastatin (a reversible inhibitor of dehydropeptidase I). For treatment of multiple-organism infections in which other agents do not have wide-spectrum coverage or are contraindicated because of potential for toxicity.
A carbapenem, not a beta-lactam antibiotic. Bactericidal broad-spectrum carbapenem antibiotic that inhibits cell wall synthesis. Effective against most gram-positive and gram-negative bacteria. Has slightly increased activity against gram-negative bacteria and a slightly decreased activity against staphylococci and streptococci compared with imipenem.
Acts by binding to 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.
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.
Treats mild-to-moderate microbial infections.
Plasma concentrations are very low, but tissue concentrations are much higher, giving it value in treating intracellular organisms. Has a long tissue half-life.
Newer macrolides offer decreased GI upset and potential for improved compliance through reduced dosing frequency. Also afford more improved action against H influenzae compared with erythromycin.
Classified as glycopeptide agent that has excellent gram-positive coverage, including methicillin-resistant S aureus. To avoid toxicity, current recommendation is to assay vancomycin trough levels after third dose drawn 0.5 h prior to next dosing. Use CrCl to adjust dose in patients diagnosed with renal impairment.
Prevents formation of functional 70S initiation complex, which is essential for bacterial translation process. Bacteriostatic against enterococci and staphylococci and bactericidal against most strains of streptococci. Used as alternative in patients allergic to vancomycin and for treatment of vancomycin-resistant enterococci.
Imidazole ring-based antibiotic active against various anaerobic bacteria and protozoa. Used in combination with other antimicrobial agents (except for C difficile enterocolitis).
Not standard practice to use metronidazole alone because some anaerobic cocci and most microaerophilic streptococci are resistant. Use in combination with beta-lactam in treatment of anaerobic pneumonia and complicated pleuropulmonary infections.
Indicated for 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.
Tissue plasminogen activator exerts effect on fibrinolytic system to convert plasminogen to plasmin. Plasmin degrades fibrin, fibrinogen, and procoagulant factors V and VIII. Serum half-life is 4-6 min but half-life lengthened when bound to fibrin in clot. Used in management of acute MI, acute ischemic stroke, and PE. Heparin and aspirin are not given for 24 h after tPA. Must be given within 3 h of stroke onset. Exclude hemorrhage by CT scan. If hypertensive, lower BP with labetalol, 10 mg IV. Safety and efficacy of concomitant administration with aspirin and heparin during first 24 h after onset of symptoms have not been investigated.
Streptokinase (Kabikinase, Streptase)
Acts with plasminogen to convert plasminogen to plasmin. Plasmin degrades fibrin clots as well as fibrinogen and other plasma proteins. Increase in fibrinolytic activity that degrades fibrinogen levels for 24-36 h takes place with IV infusion of streptokinase. Absorbed from the pleural space.
Direct plasminogen activator that acts on endogenous fibrinolytic system and converts plasminogen to enzyme plasmin, which, in turn, degrades fibrin clots, fibrinogen, and other plasma proteins. Most often used for local fibrinolysis of thrombosed catheters and superficial vessels. Advantage is that agent is nonantigenic; however, more expensive than streptokinase, limiting use. When used for local fibrinolysis, urokinase is administered as local infusion directly into area of thrombus and with no bolus administered. Dose of medication should be adjusted to achieve clot lysis or patency of affected vessel.
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 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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