eMedicine Specialties > Pulmonology > Infectious Lung Diseases

Pneumonia, Bacterial: Treatment & Medication

Author: Nader Kamangar, MD, FACP, FCCP, FAASM, Associate Professor of Clinical Medicine, Division of Pulmonary, Critical Care and Sleep Medicine, Multi-campus Pulmonary and Critical Care Fellowship Program, University of California, Los Angeles, David Geffen School of Medicine; Medical Director, Hospitalist/Intensivist Program, Olive View-UCLA Medical Center; Associate Program Director, Combined Pulmonary and Critical Care Fellowship Program, Cedars-Sinai/Olive View-UCLA Medical Center/West Los Angeles Veterans Affairs Medical Center
Coauthor(s): Christina Rager, MD, Resident Physician, Internal and Emergency Medicine, Olive View-University of California at Los Angeles Medical Center; Sat Sharma, MD, FRCPC, Professor and Head, Division of Pulmonary Medicine, Department of Internal Medicine, University of Manitoba; Site Director, Respiratory Medicine, St Boniface General Hospital
Contributor Information and Disclosures

Updated: Aug 21, 2009

Treatment

Medical Care

The information in this section is derived mainly from the current Infectious Diseases Society of America/American Thoracic Society (IDSA/ATS) guidelines for the management of community-acquired pneumonia (CAP).¹⁰
 
Almost all major decisions regarding management of pneumonia address the initial assessment of severity. Perhaps the most important initial determination is that of the need for hospitalization.

In determining site or level of care, options include outpatient, medical ward care, or medical ICU care.

Risk stratification

Severity-of-illness scores or prognostic models, such as the CURB-65 criteria or the Pneumonia Severity Index (PSI) can be used to help identify patients that may be candidates for outpatient treatment and those that may require admission.

CURB-65

CURB-65 is a scoring system developed from a multivariate analysis of 1068 patients that identified various factors that appeared to play a role in patient mortality.²⁵ One point is given for the presence of each of the following:

• Confusion
• Uremia - BUN greater than 20 mg/dL
• Respiratory rate of greater than or equal to 30 breaths per minute
• Blood pressure - Systolic less than 90 mm Hg or diastolic less than 60 mm Hg
• Age older than 65 years

Current guidelines suggest that patients may be treated in an outpatient setting or may require hospitalization according to their CURB-65 score, as follows:

• Score of 0-1 - Outpatient treatment
• Score of 2 - Admission to medical ward
• Score of 3 or higher - Admission to ICU

The percent mortality at 30 days associated with the various CURB-65 scores is below; the drastic increase in mortality between scores of 2 and 3 highlights the likely requirement for ICU admission in patients with a score of 3 or higher.

• Score of 0 - 0.7%
• Score of 1 - 2.1%
• Score of 2 - 9.2%
• Score of 3 - 14.5%
• Score of 4 - 40%
• Score of 5 - 57%

Pneumonia Severity Index

The PSI is based on the derivation of a prediction rule for mortality and its validation based on characteristics of cohorts of hospitalized patients.³¹ For each of the various characteristics, a predetermined value of points assigned, as follows:

• Demographic factors
  • Age, men - Age in years
  • Age, women - Age in years minus 10 points
  • Nursing home resident - Add 10 points
• Coexisting illnesses
  • Neoplasia - Add 30 points
  • Liver disease - Add 20 points
  • Congestive heart failure - Add 10 points
  • Cerebrovascular disease - Add 10 points
  • Renal disease - Add 10 points
• Physical examination findings
  • Altered mental status - Add 20 points
  • Respiratory rate greater than or equal to 30 breaths per minute - Add 20 points
  • Systolic blood pressure lower than 90 mm Hg - Add 20 points
  • Temperature lower than 35°C or greater than or equal to 40°C - Add 15 points
  • Pulse greater than or equal to 125 bpm - Add 10 points
• Laboratory and radiographic findings
  • Arterial pH less than 7.35 - Add 30 points
  • BUN greater than or equal to 30 mg/dL - Add 20 points
  • Sodium level less than 130 mmol/L - Add 20 points
  • Glucose level greater than or equal to 250 mg/dL - Add 10 points
  • Hematocrit value less than 30% - Add 10 points
  • PaO₂ less than 60 mm Hg or oxygen saturation (SpO₂) less than 90% - Add 10 points
  • Pleural effusion - Add 10 points

The total points added together make up the risk score, which stratifies patients into 5 mortality risk classes:

• Class I is 0-50 points - 0.1% mortality
• Class II is 51-70 points - 0.6% mortality
• Class III is 71-90 points - 0.9% mortality
• Class IV is 91-130 points - 9.3% mortality
• Class V is greater than 130 points - 27% mortality

Current guidelines suggest that patients may be treated in an outpatient setting or may require hospitalization depending on their risk class, as follows:

• Classes I and II - Outpatient management
• Class III - Admission to an observation unit or for short hospital stay
• Classes IV and V - Treatment in inpatient setting

Importantly, remember that objective criteria and scores should be used as guides only and should always be supplemented with physician determination of the patient's therapeutic needs. The risks and benefits of hospitalization should be weighed carefully because hospitalization can put patients at additional risk (eg, thromboembolic events, nosocomial superinfection).

Severe CAP

Additional criteria that can help determine the need for ICU admission are the presence of 3 minor criteria that compose the definition of severe CAP.

Minor criteria are as follows:

• Respiratory rate greater than or equal to 30 breaths per minute
• Ratio of PaO₂ to fraction of inspired oxygen (ie, PaO₂/FiO ₂ ) of less than or equal to 250
• Need for noninvasive ventilation (bilevel positive airway pressure [BiPAP] or continuous positive airway pressure [CPAP])
• Multilobar infiltrates
• Confusion/disorientation
• Uremia (BUN greater than or equal to 20 mg/dL)
• Leukopenia (WBC count <4000 cells/µL)
• Thrombocytopenia (platelet count <100,000/µL)
• Hypothermia (core temperature <36°C)
• Hypotension requiring aggressive fluid resuscitation

• Invasive mechanical ventilation
• Septic shock requiring vasopressor support

Consultations

Consultation with infectious disease and/or pulmonary specialists is suggested in difficult cases.

• Patients requiring noninvasive mechanical ventilation or intubation may need consultation with a critical care medicine specialist to aid in management after admission to the ICU.
• A pharmacist and/or infection control specialist may be of assistance in providing information on hospital or regional bacterial resistance and sensitivity patterns.

Medication

The goals of pharmacotherapy for bacteria pneumonia are to eradicate the infection, reduce morbidity, and prevent complications.

Treatment of pneumonia depends largely on the empiric use of antibiotic regimens directed against potential pathogens as determined by the setting in which the infection took place (ie, community-acquired pneumonia [CAP], health care–associated pneumonia [HCAP], hospital-acquired pneumonia [HAP], ventilator-associated pneumonia [VAP]). Discussion of empiric antibiotic therapy can be based on hospitalization status.

Outpatient empiric antibiotic therapy
 
Antibiotic choices in the outpatient setting should be driven by the presence of patient risk factors, including recent exposure to antibiotics, comorbidities, and local trends in antibiotic resistance¹⁰ :

In previously healthy patients with no exposure to antibiotics within the previous 90 days, use the following: 

• Macrolide or doxycycline (weak recommendation)

In patients with comorbidities such as chronic disease of the heart, lung, liver, or kidneys; diabetes mellitus; alcoholism; malignancy; immunosuppression (drug- or disease-induced); or use of antimicrobials within the last 90 days, use the following:

• Respiratory fluoroquinolone or beta-lactam plus macrolide

If the patient was exposed to antibiotics within the previous 90 days for systemic treatment of any type of bacterial infection, an alternative from a different class should be selected for treatment of the current illness.

Inpatient empiric antibiotic therapy
 
Inpatient treatment of pneumonia, according to 2009 Joint Commission and the Centers for Medicare and Medicaid Services consensus guidelines, should be given within 6 hours of hospital admission (or in the emergency department if this is where the patient initially presented) and should consist of the following antibiotic regimens³² :

• Non-ICU patients (choice of one option)
  • Beta-lactam (IV or IM) plus macrolide (IV or PO)
  • Antipneumococcal quinolone monotherapy (IV or IM) 
  • Beta-lactam (IV or IM) plus doxycycline (IV or oral)
  • If patient younger than 65 years with no risk factors for drug-resistant pneumococcus - Macrolide monotherapy (IV or oral)
• ICU Patients (choice of one option)
  • Beta-lactam (IV) plus macrolide (IV)
  • Beta-lactam (IV) plus antipneumococcal quinolone (IV)
  • If patient has documented beta-lactam allergy - Antipneumococcal quinolone (IV) plus aztreonam (IV)
• Patients at increased risk of infection with Pseudomonas (acceptable for both ICU and non-ICU patients) (choice of one option)
  • Antipseudomonal beta-lactam (IV) plus antipseudomonal quinolone (IV; PO in non-ICU only)
  • Antipseudomonal beta-lactam (IV) plus aminoglycoside (IV) plus one of the following:
    • Macrolide (IV)
    • Antipneumococcal quinolone (IV; PO in non-ICU only)
    • If patient has documented beta-lactam allergy - Aztreonam (IV) plus aminoglycoside (IV) plus antipneumococcal quinolone (IV; PO in non-ICU only)

A note on antibiotics in HAP and VAP
 
The prevalence and resistance patterns of multidrug-resistant (MDR) pathogens vary between institutions and even between ICUs within the same institution; therefore, appropriate initial antibiotic therapy for HAP and VAP may vary markedly according to hospital site. Antimicrobial prescribing practices should not necessarily be based on national guidelines, but rather on patterns of MDR organisms at individual institutions.⁶

A note on MRSA
 
For suspected infection with methicillin-resistant S aureus (MRSA), vancomycin or linezolid may be added to the antibiotic regimen until the organism's identity and antibiotic sensitivities are known, at which point the medications can be adjusted accordingly. Neither vancomycin nor linezolid is an optimal agent for treatment of methicillin-sensitive S aureus (MSSA).¹⁰ Other agents that may be considered for use against MRSA include clindamycin, trimethoprim- sulfamethoxazole (TMP-SMZ), gentamicin, ciprofloxacin, and rifampin; still other antibiotics are being evaluated for activity against MRSA.³³

Aspiration pneumonia empiric therapy
 
Although the causative organisms in aspiration pneumonia have been noted to be similar to those of CAP or HCAP, patients with severe periodontal disease, putrid sputum, or a history of alcoholism with suspected aspiration pneumonia may be at greater risk of anaerobic infection. One of the following antibiotic regimens is suggested for such patients^8,10 :

• Piperacillin-tazobactam
• Imipenem
• Clindamycin or metronidazole plus a respiratory fluoroquinolone plus ceftriaxone

Pathogen-driven antibiotic choices¹⁰

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Other medications

Corticosteroids

The role of supplementing corticosteroids in patients with hypotension from septic shock remains controversial; however, screening for occult adrenal insufficiency is recommended in hypotensive, fluid-resuscitated patients with severe CAP.

Drotrecogin alfa 

A recombinant version of human activated protein C, drotrecogin alfa is the first immunomodulatory drug approved for the treatment of severe sepsis. It is recommended in patients with CAP who have persistent septic shock despite adequate fluid resuscitation. Its use is recommended in patients at high risk of death.

Antibiotic, Penicillin

Amoxicillin (Amoxil, Biomox, Trimox)

Derivative of ampicillin and has similar antibacterial spectrum, namely certain gram-positive and gram-negative organisms. Superior bioavailability and stability to gastric acid and has broader spectrum of activity than penicillin. Somewhat less active than that of penicillin against S pneumococcus. Penicillin-resistant strains also resistant to amoxicillin, but higher doses may be effective. More effective against gram-negative organisms (eg, N meningitidis, H influenzae) than penicillin. Interferes with synthesis of cell wall mucopeptides during active multiplication, resulting in bactericidal activity against susceptible bacteria.

Ampicillin (Principen)

Broad-spectrum penicillin. Interferes with bacterial cell wall synthesis during active replication, causing bactericidal activity against susceptible organisms. Alternative to amoxicillin when unable to take medication orally.
HACEK bacteria previously were uniformly susceptible to ampicillin; however, beta-lactamase–producing strains of HACEK have been identified.

Penicillin G (Pfizerpen)

Interferes with synthesis of cell wall mucopeptide during active multiplication, resulting in bactericidal activity against susceptible microorganisms.

Piperacillin and tazobactam sodium (Zosyn)

Antipseudomonal penicillin plus beta-lactamase inhibitor. Inhibits biosynthesis of cell wall mucopeptide and is effective during stage of active multiplication.

Antibiotic, Penicillin & Beta-Lactamase Inhibitor

Amoxicillin and clavulanate (Augmentin, Augmentin XR)

Amoxicillin 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 or intolerant to the macrolide class. Usually is well tolerated and provides good coverage to 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 protocol 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.

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.

Antibiotic, Macrolide

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 is not affected.
Concentrates in phagocytes and fibroblasts as demonstrated by in vitro incubation techniques. In vivo studies suggest that concentration in phagocytes may contribute to drug distribution to inflamed tissues.
Treats mild-to-moderate microbial infections.

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.
Used to treat CAP caused by H influenzae, M pneumoniae, S pneumoniae, M catarrhalis, H parainfluenzae, or C pneumoniae (TWAR strain).

Erythromycin (E.E.S., E-Mycin, Eryc, Ery-Tab, Erythrocin)

Inhibits bacterial growth, possibly by blocking dissociation of peptidyl t-RNA from ribosomes, causing RNA-dependent protein synthesis to arrest. May result in GI upset, causing some to prescribe an alternative macrolide or change to tid dosing. Covers most potential etiologic agents, including Mycoplasma species. PO regimen may be insufficient to adequately treat Legionella species. Erythromycin is less active against H influenzae. Although standard course of treatment seems to be 10 d, treating until patient has been afebrile for 3-5 d seems to be a more rational approach.

Antibiotic, Miscellaneous

Aztreonam (Azactam)

A monobactam, not a beta-lactam, antibiotic that inhibits cell wall synthesis during bacterial growth. Active against gram-negative bacilli but very limited gram-positive activity and not useful for anaerobes. Lacks cross-sensitivity with beta-lactam antibiotics. May be used in patients allergic to penicillins or cephalosporins.
Duration of therapy depends on severity of infection and continued for at least 48 h after patient asymptomatic or evidence of bacterial eradication obtained. Doses smaller than indicated should not be used.
Transient or persistent renal insufficiency may prolong serum levels. After initial loading dose of 1 or 2 g, reduce dose by half for estimated CrCl of 10-30 mL/min/1.73 m². When only serum creatinine concentration available, the following formula (based on sex, weight, and age) can approximate CrCl. Serum creatinine should represent a steady state of renal function.
Males: CrCl = [(weight in kg)(140 - age)] divided by (72 X serum creatinine in mg/dL)
Females: 0.85 X above value
In patients with severe renal failure (CrCl <10 mL/min/1.73 m2), those supported by hemodialysis (HD), usual dose of 500 mg, 1 g, or 2 g, is given initially.
Maintenance dose is one fourth of usual initial dose given at usual fixed interval of 6, 8, or 12 h.
For serious or life-threatening infections, supplement maintenance doses with one eighth of initial dose after each HD session.
Elderly persons may have diminished renal function. Renal status is a major determinant of dosage in these patients. Serum creatinine may not be an accurate determinant of renal status. Therefore, as with all antibiotics eliminated by kidneys, obtain estimates of CrCl and make appropriate dosage modifications. Data insufficient regarding IM administration to pediatric patients or dosing in pediatric patients with renal impairment. Administered IV only to pediatric patients with normal renal function.

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 liver and kidneys.
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 presence of food in stomach. Appropriate serum levels reached and sustained for at least 6 h following oral dose. No significant levels attained in cerebrospinal fluid. Also effective against aerobic and anaerobic streptococci (except enterococci).

Vancomycin (Vancocin)

Classified as glycopeptide agent that has excellent gram-positive coverage, including MRSA. To avoid toxicity, current recommendation is to assay trough levels after third dose drawn 0.5 h prior to next dosing. Use CrCl to adjust dose in patients diagnosed with renal impairment.

Antibiotic, Cephalosporin (Fourth Generation)

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.

Antibiotic, Cephalosporin (Third Generation)

Cefotaxime (Claforan)

Third-generation cephalosporin with broad gram-negative spectrum, lower efficacy against gram-positive organisms, and higher efficacy against resistant organisms. Arrests bacterial cell wall synthesis by binding to one or more penicillin-binding proteins, which, in turn, inhibits bacterial growth. Used for septicemia and treatment of gynecologic infections caused by susceptible organisms.
Lower efficacy against gram-positive organisms.
Lower efficacy against gram-positive organisms.
Third-generation cephalosporin with gram-negative spectrum. Lower efficacy against gram-positive organisms.

Ceftazidime (Ceptaz, Fortaz, Tazicef, Tazidime)

Third-generation cephalosporin with broad-spectrum, gram-negative activity, including Pseudomonas; lower efficacy against gram-positive organisms; higher efficacy against resistant organisms. Arrests bacterial growth by binding to one or more penicillin-binding proteins, which, in turn, inhibits final transpeptidation step of peptidoglycan synthesis in bacterial cell wall synthesis, thus inhibiting cell wall biosynthesis. Condition of the patient, severity of the infection, and susceptibility of the microorganism should determine proper dose and route of administration.

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 due to 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 have been reported to decrease from 95% bound at plasma concentrations <25 mcg/mL to 85% bound at 300 mcg/mL.

Antibiotic, Cephalosporin (Second Generation)

Cefuroxime (Ceftin, Kefurox, Zinacef)

Second-generation cephalosporin maintains gram-positive activity of first-generation cephalosporins; adds activity against P mirabilis, H influenzae, E coli, K pneumoniae, and M 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.

Antibiotic, Quinolone

Ciprofloxacin (Cipro)

Fluoroquinolone that inhibits bacterial DNA synthesis and, consequently, growth, by inhibiting DNA gyrase and topoisomerases, which are required for replication, transcription, and translation of genetic material. Quinolones have broad activity against gram-positive and gram-negative aerobic organisms. Has no activity against anaerobes. Continue treatment for at least 2 d (7-14 d typical) after signs and symptoms have disappeared.

Levofloxacin (Levaquin)

Used to treat community-acquired pneumonia caused by S aureus, S pneumoniae (including penicillin-resistant strains), H influenzae, H parainfluenzae, Klebsiella pneumoniae, M catarrhalis, C pneumoniae, Legionella pneumophila, or Mycoplasma pneumoniae. Fluoroquinolones should be used empirically in patients likely to develop exacerbation due to resistant organisms to other antibiotics. Rapidly becoming a popular choice in pneumonia. This is the L stereoisomer of the D/L parent compound ofloxacin, the D form being inactive. Good monotherapy with extended coverage against Pseudomonas species and excellent activity against pneumococcus. Agent acts by inhibition of DNA gyrase activity. PO form has bioavailability that reportedly is 99%.

Moxifloxacin (Avelox)

Inhibits the A subunits of DNA gyrase, resulting in inhibition of bacterial DNA replication and transcription.

Antibiotic, Tetracycline Derivative

Doxycycline (Bio-Tab, Doryx, Doxy, Periostat, Vibramycin, Vibra-Tabs)

Broad-spectrum, synthetically derived bacteriostatic antibiotic in the tetracycline class. Almost completely absorbed, concentrates in bile, and is excreted in urine and feces as a biologically active metabolite in high concentrations.
Inhibits protein synthesis and, thus, bacterial growth by binding to 30S and possibly 50S ribosomal subunits of susceptible bacteria. May block dissociation of peptidyl t-RNA from ribosomes, causing RNA-dependent protein synthesis to arrest.
Alternative agent for patients who cannot be given macrolides or penicillins.

Antibiotic, Carbapenem

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.

Imipenem and cilastatin (Primaxin)

For treatment of multiple organism infections in which other agents do not have wide spectrum coverage or are contraindicated due to potential for toxicity.

Meropenem (Merrem IV)

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-negatives and slightly decreased activity against staphylococci and streptococci compared with imipenem.

Antibiotic, Aminoglycoside

Gentamicin (Gentacidin)

Aminoglycoside antibiotic for gram-negative coverage. Used in combination with both an agent against gram-positive organisms and one that covers anaerobes.
Not the DOC. Consider if penicillins or other less toxic drugs are contraindicated, when clinically indicated, and in mixed infections caused by susceptible staphylococci and gram-negative organisms.
Dosing regimens are numerous. Adjust dose based on CrCl and changes in volume of distribution. May be administered IV/IM.

Antibiotic, Oxazolidinone

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.

Antibiotic, Sulfonamide Derivative

Sulfamethoxazole and trimethoprim (Bactrim, Bactrim DS, Cotrim, Cotrim DS, Septra, Septra DS)

Inhibits bacterial synthesis of dihydrofolic acid by competing with paraaminobenzoic acid, inhibiting folic acid synthesis. Results in inhibition of bacterial growth. Antibacterial activity of TMP-SMZ includes common urinary tract pathogens, except P aeruginosa.

Human Activated Protein C, Recombinant

Drotrecogin alfa (Xigris)

Indicated for reduction of mortality in patients with severe sepsis associated with acute organ dysfunction and at high risk of death. Recombinant form of human Activated Protein C that exerts antithrombotic effect by inhibiting Factors Va and VIIIa. Has indirect profibrinolytic activity by inhibiting plasminogen activator inhibitor-1 (PAI-1) and limiting formation of activated thrombin-activatable-fibrinolysis-inhibitor. May exert anti-inflammatory effect by inhibiting human TNF production by monocytes, blocking leukocyte adhesion to selectins, and limiting thrombin-induced inflammatory responses within microvascular endothelium.

Glucocorticoid

Hydrocortisone (Cortef, Hydrocort, Hydrocortone)

DOC because of mineralocorticoid activity and glucocorticoid effects.

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