eMedicine Specialties > Pulmonology > Pleural Disorders

Parapneumonic Pleural Effusions and Empyema Thoracis: Treatment & Medication

Author: Atikun Limsukon, MD, Instructor, Department of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, Thailand
Coauthor(s): Guy W Soo Hoo, MD, MPH, Clinical Professor of Medicine, Geffen School of Medicine at the University of California at Los Angeles; Director, Medical Intensive Care Unit, Pulmonary and Critical Care Section, West Los Angeles Healthcare Center, Veteran Affairs Greater Los Angeles Healthcare System
Contributor Information and Disclosures

Updated: Sep 17, 2009

Treatment

Medical Care

The initial treatment of a patient with pneumonia and pleural effusion involves 2 major decisions. The first decision involves selection of an appropriate antibiotic that will cover likely pathogens. The second decision involves the need for drainage of pleural fluid and is be guided by the American College of Chest Physicians (ACCP) guideline recommendations for the medical and surgical treatment of parapneumonic effusions.⁷

The initial antibiotic selection is usually based on whether the pneumonia is community or hospital acquired and on the severity of the patient's illness. For a patient with community-acquired pneumonia, the recommended agents are second- or third-generation cephalosporins in addition to a macrolide. For patients hospitalized with severe community-acquired pneumonia, initiate treatment with a macrolide plus a third-generation cephalosporin with antipseudomonal activity. Enteric gram-negative bacilli frequently cause pneumonia acquired in institutions (eg, hospitals, nursing homes). Therefore, initial antibiotic coverage should include an antibiotic effective against pseudomonads. If aspiration is evident or suspected, oral anaerobes should also be covered.

Infectious Diseases Society of America (IDSA)/American Thoracic Society (ATS) consensus guidelines on the management of community-acquired pneumonia, hospital-acquired pneumonia, ventilator-associated pneumonia, and healthcare-associated pneumonia in adults are published elsewhere.^8,9 Also see Pneumonia, Bacterial.

Effusions with pleural fluid layering less than 10 mm on decubitus chest radiographs almost always resolve with appropriate systemic antibiotics. Patients with pleural effusions that have a pleural fluid layering greater than 10 mm on lateral decubitus radiographs must have a diagnostic thoracentesis. If the diagnostic thoracentesis yields thick pus, the patient has an empyema thoracis and definitive pleural drainage is absolutely required. If the pleural fluid is not thick pus, then results of pleural fluid Gram stain or culture, pleural fluid pH and glucose levels, and the presence or absence of pleural fluid loculations should guide the course of action as recommended in the guidelines.⁷

Of note, the strength of recommendations by the expert panel in this guideline is somewhat limited because of the small number of randomized, controlled trials, and methodological weakness resulted in heterogeneous data. The panel urged review of these recommendations cautiously; they purposefully avoided specific recommendations or preferences on primary management approaches (ie, no drainage, therapeutic thoracentesis, tube thoracostomy, fibrinolytics, video-assisted thoracoscopic surgery [VATS], thoracotomy). Despite these limitations, consistent and possibly clinically meaningful trends formed for the pooled data and the results of the randomized, controlled trials and the historically controlled series on the primary management approach to parapneumonic pleural effusions.

In summary, the recommendations are as follows:

• In all patients with acute bacterial pneumonia, the presence of a parapneumonic pleural effusion should be considered (level C evidence).
• In patients with parapneumonic pleural effusions, the estimated risk for poor outcome, using the panel-recommended approach based on pleural space anatomy, pleural fluid bacteriology, and pleural fluid chemistry, should be the basis for determining whether the parapneumonic pleural effusions should be drained (level D evidence). Poor outcomes could result from any or all of the following: prolonged hospitalization, prolonged evidence of systemic toxicity, increased morbidity from any drainage procedure, increased risk for residual ventilatory impairment, increased risk for local spread of the inflammatory reaction, and increased mortality. The 4 risk categories are as follows:
  • Category 1 (very low risk): The effusion is small (<10-mm thickness on decubitus) and free flowing (A₀). Because the effusion is small, no thoracentesis is performed and the bacteriology (B_x) and chemistry (C_x) of the fluid are unknown.
  • Category 2 (low risk): The effusion is small to moderate (≥10 mm and less than half the hemithorax) and free flowing (A₁) with negative culture and Gram stain regardless of prior use of antibiotics (B₀); pH is higher than or equal to 7.20 (C₀).
  • Category 3 (moderate risk): The effusion meets one of the following criteria: large (greater than or equal to half the hemithorax), loculated effusion, thicken pleura on contrast-enhanced CT scan (A₂), positive Gram stain or culture (B₁), or pH less than 7.20 (C₁).
  • Category 4 (high risk): This is when pleural fluid consists of pus.
• Patients with category 1 or category 2 risk for poor outcome with parapneumonic pleural effusions may not require drainage (level D evidence).
• Drainage is recommended for management of category 3 or 4 parapneumonic pleural effusions based on pooled data for mortality and the need for second interventions with the no-drainage approach (level C evidence).
• Based on the pooled data for mortality and the need for second interventions, therapeutic thoracentesis or tube thoracostomy alone appears to be insufficient treatment for treating most patients with category 3 or 4 parapneumonic pleural effusions (level C evidence). However, the panel recognizes that in the individual patient, therapeutic thoracentesis or tube thoracostomy, as planned interim steps before a subsequent drainage procedure, may result in complete resolution of the parapneumonic pleural effusions. Careful evaluation of the patient for several hours is essential in these cases. If resolution occurs, no further intervention is necessary (level D evidence).
• Fibrinolytics, VATS, and surgery are acceptable approaches for managing patients with category 3 and category 4 parapneumonic pleural effusions based on cumulative data across all studies that indicate that these interventions are associated with the lowest mortality and need for second interventions (level C evidence).

Chest tubes (tube thoracostomy)

Insert chest tubes immediately after a complicated parapneumonic pleural effusion or empyema thoracis is diagnosed (see Media File 6). The key to resolution involves prompt drainage of pleural fluid because delay leads to the formation of loculated pleural fluid.

Position the chest tube in a dependent part of the pleural effusion. Previously, large-bore (38-32F) tubes were recommended, but smaller tubes are similarly effective, and at least a 28F tube should be placed. These can be placed either using a guidewire-assisted serial dilatation technique or the more traditional cut-down approach.

Smaller pigtail catheters (8-14F) can also be placed under ultrasound or CT guidance. Consider these in smaller, difficult-to-access, multiple-loculated effusions and nonloculated, nonpurulent effusions. These catheters have also been successful in draining empyemas. The variation in success rates for these catheters (72–82%) is associated with patient selection, operator expertise, and the stage of the parapneumonic pleural effusions. The major advantage of small-bore catheters is better patient tolerance and avoidance of major complications.¹

Continue closed-tube drainage as long as clinical and radiologic improvement are observed. The chest tube can be removed once the volume of the pleural drainage is less than 100 mL/24 h, with clearance of the pleural fluid turbidity seen in complicated pleural effusions.

If the patient does not demonstrate clinical or radiologic improvement with declining pleural fluid drainage, perform a pleural space ultrasound examination or chest CT scanning to look for pleural fluid loculations and ensure proper tube placement.

Undrained pleural fluid may respond to intrapleural thrombolytic therapy or may require placement of another tube. Closed chest tube drainage yields satisfactory results in approximately 60% of patients with aerobic infections and 25% of patients with anaerobic infections.

Since the 1970s, several studies have reported success of thrombolytic therapy for loculated complicated parapneumonic pleural effusions.^{10,11,12,13,14,15,16,17,18} The thrombolytic agents used in parapneumonic pleural effusions are more effective if administered in the early fibrinopurulent stage of parapneumonic pleural effusions.

With thrombolytic therapy, success rates of 70-90% have been reported. Streptokinase has been used in a dose of 250,000 IU in 100 mL of normal saline once or twice a day. Urokinase was also effective and in a randomized trial of patients with multiloculated pleural effusions. Subjects in the urokinase group drained significantly more pleural fluid, required less surgical intervention, and required fewer days in the hospital.

Following instillation, the chest tube is clamped for 2-4 hours. These agents may be administered daily for as many as 14 days. Streptokinase may lead to sensitization with production of an antibody response and subsequent allergic reaction if used for systemic thrombolysis.

Streptokinase and urokinase are probably equally effective, although neither has been compared to each other in a research trial. The potential for developing antibodies to streptokinase has generally favored urokinase as a pleural thrombolytic. However, urokinase is not currently commercially available.

While thrombolytic agents may facilitate and increase pleural fluid drainage, their effect on improving patient outcomes and avoiding surgical intervention has not been established.

A prospective randomized trial of intrapleural thrombolytic agent streptokinase (MIST1 group) was conducted on the drainage of infected pleural fluid collections. In this double-blind trial, 454 patients with pleural infection (either purulent pleural fluid or pleural fluid with a pH <7.20 with signs of infection) received either intrapleural streptokinase (250,000 IU bid for 3 d) or placebo. Among the 427 patients who received streptokinase or placebo, no benefit was reported for streptokinase in terms of mortality, rate of surgery, radiographic outcomes, or length of hospital stay; serious adverse events (chest pain, fever, or allergy) were more common with streptokinase.¹⁴

Tokuda et al performed a meta-analysis of all properly randomized trials, comparing intrapleural thrombolytic agents with placebo in adult patients with empyema thoracis and complicated parapneumonic pleural effusions. The outcome of primary interest was the reduction of death and surgical intervention. Five trials totaling 575 patients were included.¹⁵

The MIST1 trial constituted the bulk of patients in the meta-analysis, and its nonbeneficial findings contributed significantly to the final conclusion. The meta-analysis did not support the routine use of thrombolytic therapy for all patients who required chest tube drainage for empyema thoracis or complicated parapneumonic pleural effusions.

Note that the meta-analysis described a nonsignificant reduction in death and surgery even despite including the MIST1 trial. Because of significant heterogeneity of the treatment effects, selected patients might benefit from thrombolytic treatment.¹⁵

Intrapleural recombinant tissue plasminogen activator (r-TPA) or alteplase has been successfully evaluated in pediatric patients with complicated parapneumonic pleural effusion and pleural empyema. Some authors have suggested that r-TPA might be a more effective therapeutic agent than streptokinase.

A small, noncomparative study of consecutive adult patients using r-TPA or alteplase administered intrapleurally in a single daily dose of 25 mg reported the treatment was well tolerated and effective.¹⁶ Another retrospective review of 22 consecutive patients also demonstrated improved drainage of pleural fluid with alteplase, with 2 mg administered into the pleural space 3 times a day for 3 days.

This has led to a prospective, randomized comparison of alteplase with placebo in the management of complicated pleural effusions and empyema. The study has been completed, and the final report of this experience is pending.

The latest Cochrane Database systematic review on this topic published in 2008 had identified 7 studies and 761 patients.¹⁸ A significant reduction in the need for surgical intervention was identified, but the authors also noted the discrepancy between this conclusion and results of the MIST1 trial. The authors note subgroup analysis that suggests the greatest benefit is in patients with loculated effusions, but the data are very limited and due caution is advised. No increase in adverse events was noted with thrombolytic therapy.

Surgical Care

Thoracoscopy

Thoracoscopy is an alternate therapy for multiloculated empyema thoracis. In patients with multiloculated parapneumonic pleural effusions, the loculations in the pleural space can be disrupted with a thoracoscope, and the pleural space can be drained completely. If extensive adhesions are present or thick pleural peel entraps the lung, the procedure may be converted to open thoracostomy and decortication.

Luh et al published their experience in the treatment of complicated parapneumonic pleural effusions and empyema thoracis by VATS in 234 patients (108 women, 126 men). More than 85% (200 patients) received preoperative diagnostic or therapeutic thoracentesis, tube thoracostomy, or fibrinolytics. Of 234 patients, 202 patients (86.3%) achieved satisfactory results with VATS. Only 40 patients required open decortication or repeat procedures. VATS is safe and effective for treatment; earlier intervention with VATS can produce better clinical results.¹⁹

Hope et al reviewed outcomes of surgical treatment for parapneumonic empyema thoracis. The use of VATS was compared with thoracotomy. Morbidity and mortality rates were similar among all groups. The conversion rate to open thoracotomy was 21%. Based on a shorter postoperative length of stay with similar morbidity and mortality in patients operated on within 11 days of admission, early aggressive surgery treatment for complicated parapneumonic effusions or empyema thoracis is recommended.²⁰

Retrospective evaluation of 2 different surgical procedures (decortication vs debridement) and approaches (VATS vs thoracotomy) were analyzed by Casali and colleagues. The study included 119 patients; 51 patients had debridement (52% through VATS, 48% through thoracotomy) and 68 patients had decortications through thoracotomy. VATS debridement had a lower postoperative hospital stay and shorter duration of chest drainage and greater improvement in a subjective dyspnea score. The long-term spirometric evaluation was normal in 58 patients (56%). Age older than 70 years old was the only variable associated with poor long-term results (forced expiratory volume in 1 second [FEV₁] <60% and/or dyspnea Medical Research Council grade ≥2) at multivariate analysis. VATS is associated with less postoperative mortality and shorter postoperative hospital stay.²¹

Two other studies that support the use of VATS as a primary drainage procedure are those by Potaris et al²² and Chan et al.²³

Wang and colleagues proposed a new technique using an electronic endoscope (bronchoscope or gastroscope) inserted through the chest tube to directly visualize, irrigate, and break down the loculation effectively in various pleural diseases, including 13 cases of empyema thoracis.²⁴

In a prospective, randomized study comparing VATS and thrombolytic therapy in children with empyema, no differences in outcomes were noted between the 2 methods in a small study involving 36 patients.²⁵ Thrombolytic therapy consisted of 4-mg doses administered 3 times over a 48-hour period. Three (16.7%) of the patients treated with thrombolytic therapy eventually required VATS for management.

Open drainage of the pleural space may be used when closed-tube drainage of the pleural infection is inadequate and the patient does not respond to intrapleural thrombolytic agents. This procedure is recommended only when the patient is too ill to tolerate decortication. The resection of 1-3 ribs overlying the lower part of the empyema thoracis cavity is performed, a large-bore chest tube is inserted into the empyema thoracis cavity, and the tube is drained into a colostomy bag.

Patients treated by open drainage have an open chest wound for a prolonged period. In one series, the median time for healing the drainage site was 142 days. With decortication, the period of convalescence is much shorter, although patients who are markedly debilitated do not tolerate decortication.

Postpneumonectomy empyema thoracis, an uncommon but life-threatening complication, is often associated with a bronchopleural fistula. Treatment of bronchopleural fistula depends on several factors, including the extent of dehiscence, degree of pleural contamination, and general condition of the patient. Early diagnosis and aggressive therapeutic strategies for controlling infection, closing the fistula, and sterilizing the closed pleural space are mandatory. Repeated debridement, VATS, endoscopic application of tissue glue, and stenting may be additional management strategies.²⁶

Consultations

• Most patients can be treated by pulmonary and/or infectious diseases specialists.
• An interventional radiologist may be needed to place small-bore drainage catheters for difficult-to-access loculated effusions.
• Patients with persistently loculated effusions or unresolving empyema thoracis may require surgery and should be seen by a thoracic surgeon.

Diet

No dietary restrictions are recommended for patients with parapneumonia effusions and empyema, other than what is dictated by comorbidities.

Activity

No specific activity restrictions are recommended for patients with parapneumonic effusions and empyema. Their activity level may be limited by comorbidities and any interventions required to treat their infection.

Medication

The goals of pharmacotherapy are to reduce morbidity and prevent complications.

Antibiotics

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)

Interferes with 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)

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.

Amoxicillin (Amoxil, Biomox, Trimox)

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.

Ampicillin and sulbactam (Unasyn)

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.

Clindamycin (Cleocin)

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).

Moxifloxacin (Avelox)

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.

Amoxicillin and clavulanate (Augmentin, Augmentin XR)

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.

Cefoxitin (Mefoxin)

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.

Ceftriaxone (Rocephin)

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.

Cefepime (Maxipime)

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.

Cefuroxime (Ceftin, Kefurox, Zinacef)

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.

Cefaclor (Ceclor)

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.

Piperacillin and tazobactam sodium (Zosyn)

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.

Cefprozil (Cefzil)

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.

Levofloxacin (Levaquin)

Rapidly becoming a popular choice in pneumonia. Good monotherapy for pseudomonal infections and infections due to multidrug-resistant gram-negative organisms.

Ertapenem (Invanz)

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).

Clarithromycin (Biaxin)

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.

Imipenem and cilastatin (Primaxin)

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.

Meropenem (Merrem IV)

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.

Azithromycin (Zithromax)

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.

Vancomycin (Lyphocin, Vancocin, Vancoled)

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.

Linezolid (Zyvox)

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.

Metronidazole (Flagyl, Protostat)

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.

Fibrinolytic agents

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.

Alteplase (Activase)

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.

Urokinase (Abbokinase)

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.

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