Medication Summary
The goals of pharmacotherapy are to eradicate the infection, reduce morbidity, and prevent complications.
Antibiotics, Other
Class Summary
Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting.
Ampicillin and sulbactam (Unasyn)
Ampicillin and sulbactam 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 and is not ideal for nosocomial pathogens.
Vancomycin
Vancomycin provides gram-positive coverage and good hospital-acquired MRSA coverage. It is now used more frequently because of the high incidence of MRSA. Vancomycin should be given to all septic patients with indwelling catheters or devices. It is advisable for skin and soft-tissue infections.
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. Ceftriaxone is used for increasing prevalence of penicillinase-producing microorganisms. It inhibits bacterial cell wall synthesis by binding to 1 or more penicillin-binding proteins. Cell wall autolytic enzymes lyse bacteria, while cell wall assembly is arrested.
Gentamicin
Gentamicin is an aminoglycoside that is bactericidal for susceptible gram-negative organisms, such as Escherichia coli and Pseudomonas, Proteus, and Serratia species. It is effective in combination with ampicillin for Group B Streptococcus and Enterococcus. Recent publications recommend gentamicin (in combination with ampicillin) as first-line therapy for suspected sepsis in the newborn.
Cefotaxime (Claforan)
Cefotaxime is a third-generation cephalosporin with excellent in vitro activity against Group B Streptococcus and E coli and other gram-negative enteric bacilli. It attains good concentrations in serum and cerebrospinal fluid (CSF). Concern exists that emergence of drug-resistant gram-negative bacteria may occur at a more rapid rate with cefotaxime than with traditional penicillin and aminoglycoside coverage.
Cefotaxime is ineffective against Listeria and enterococci; use it in combination with ampicillin. Cefotaxime is not considered a first-line agent for neonatal sepsis because of its association with increased mortality.
Antifungals, Systemic
Class Summary
Antifungal agents preferentially bind to the primary fungal cell membrane sterol (ergosterol). Amphotericin B increases the permeability of the cell membrane, which, in turn, causes intracellular components to leak. Azoles interfere with an enzyme in the sterol biosynthesis pathway production of cell membrane ergosterol. Echinocandins block fungal cell wall synthesis by inhibiting 1,3-beta glucan synthase.
Caspofungin (Cancidas)
Caspofungin is the first of a new class of antifungal drugs (glucan synthesis inhibitors). It inhibits the synthesis of beta-(1,3)-D-glucan, an essential component of the fungal cell wall. It is used to treat refractory invasive aspergillosis.
Posaconazole (Noxafil)
Posaconazole is a triazole antifungal agent that possesses structural similarities to itraconazole. It blocks ergosterol synthesis by inhibiting the enzyme lanosterol 14-alpha-demethylase and sterol precursor accumulation. This action results in cell membrane disruption.
Posaconazole is available as an oral suspension (200 mg/5 mL). It is indicated for prophylaxis of invasive Aspergillus and Candida infections in patients at high risk because of severe immunosuppression.
Voriconazole (Vfend)
Voriconazole is a triazole antifungal agent that inhibits fungal CYP450-mediated 14 alpha-lanosterol demethylation, which is essential in fungal ergosterol biosynthesis. Case reports describe efficacy in disseminated disease or meningitis refractory to first-line agents.
Itraconazole (Sporanox)
A triazole analogue of ketoconazole, itraconazole is preferred to its parent compound because of enhanced safety and efficacy. It is a synthetic triazole antifungal agent that slows fungal cell growth by inhibiting CYP450-dependent synthesis of ergosterol, a vital component of fungal cell membranes. It is used for mild-to-moderate infections that warrant treatment. Despite poor CSF penetration, it is successfully used to treat coccidioidal meningitis.
An intravenous form is available, but long-term usage is not established. Ketoconazole is also available in an oral solution, which provides better, more consistent absorption than the capsule. Take capsules with full meal to improve absorption, but take oral solution on empty stomach, if possible.
Fluconazole (Diflucan)
Fluconazole is a synthetic triazole antifungal (broad-spectrum bistriazole) that selectively inhibits fungal CYP450 and sterol C-14 alpha-demethylation, which prevents conversion of lanosterol to ergosterol. It is used to treat mild-to-moderate infections or severe or life-threatening infections in patients intolerant of amphotericin B. Metabolic clearance is prolonged in patients with renal dysfunction.
Amphotericin B lipid complex (ABLC, Abelcet)
This agent is amphotericin B in phospholipid complexed form; it is a polyene antifungal with poor oral availability. Amphotericin B is produced by a strain of Streptomyces nodosus; it can be fungistatic or fungicidal. The drug binds to sterols (eg, ergosterol) in the fungal cell membrane, causing leakage of intracellular components and fungal cell death. Toxicity to human cells may occur via this same mechanism.
Amphotericin B, liposomal (AmBisome)
This is a lipid preparation consisting of amphotericin B within unilamellar liposomes. It delivers higher concentrations of the drug, with a theoretical increase in therapeutic potential and decreased nephrotoxicity.
Amphotericin B is a polyene antifungal with poor oral availability. It is produced by a strain of Streptomyces nodosus, and it can be fungistatic or fungicidal. The drug binds to sterols (eg, ergosterol) in the fungal cell membrane, causing leakage of intracellular components and fungal cell death. Toxicity to human cells may occur via this same mechanism.
Amphotericin B colloidal dispersion (Amphotec)
Amphotericin B colloidal dispersion is a lipid preparation consisting of amphotericin B attached to lipid discoid structures. Amphotericin B is a polyene antibiotic with poor oral availability. It is produced by a strain of Streptomyces nodosus, and it can be fungistatic or fungicidal. The drug binds to sterols (eg, ergosterol) in the fungal cell membrane, causing leakage of intracellular components and fungal cell death. Toxicity to human cells may occur via this same mechanism.
Antivirals, Other
Class Summary
These agents inhibit viral replication.
Ganciclovir (Cytovene)
Ganciclovir is a synthetic guanine derivative that is active against cytomegalovirus (CMV). It is an acyclic nucleoside analog of 2'-deoxyguanosine that inhibits replication of herpesviruses in vitro and in vivo. Levels of ganciclovir triphosphate are as much as 100-fold greater in CMV-infected cells than in uninfected cells, possibly because of preferential phosphorylation of ganciclovir in virus-infected cells. In patients with progression of CMV retinitis while receiving maintenance treatment with either form, the induction regimen should be re-administered.
Foscarnet
Foscarnet is an organic analog of inorganic pyrophosphate that inhibits replication of known herpesviruses, including CMV, HSV-1, and HSV-2. It inhibits viral replication at pyrophosphate-binding sites on virus-specific DNA polymerases. Poor clinical response or persistent viral excretion during therapy may be due to viral resistance. Patients who can tolerate foscarnet well may benefit from early maintenance treatment at 120 mg/kg/d. Individualize dosing to renal function.
Corticosteroids
Class Summary
Corticosteroids have anti-inflammatory properties and cause profound and varied metabolic effects. These drugs modify the body's immune response to diverse stimuli.
Methylprednisolone (A-Methapred, Solu-Medrol, Depo-Medrol)
Methylprednisolone is available in intravenous/intramuscular and oral forms. Methylprednisolone may decrease inflammation by reversing increased capillary permeability and suppressing polymorphonuclear leukocyte activity.
Dexamethasone (Baycadron)
This agent is used in various inflammatory diseases. Dexamethasone may decrease inflammation by suppressing the migration of polymorphonuclear leukocytes and reversing increased capillary permeability.
Hemorheologic Agents
Class Summary
Corticosteroids have anti-inflammatory properties and cause profound and varied metabolic effects. These drugs modify the body's immune response to diverse stimuli.
Pentoxifylline (Trental)
Pentoxifylline may alter the rheology of red blood cells, consequently reducing blood viscosity. It increases fibrinolysis and red blood cell deformity and inhibits platelet aggregation.
Immune Globulins
Class Summary
Intravenous immunoglobulin is the usual choice. It is derived from human plasma and is composed of all 4 immunoglobulin G (IgG) subclasses.
Intravenous immunoglobulin (IVIG; Carimune Gammagard S/D, Gamunex-C, Octagam)
Intravenous immunoglobulin (IVIG) uses anti-idiotypic antibodies to neutralize circulating myelin antibodies. IVIG down-regulates proinflammatory cytokines, including interferon-gamma. It blocks Fc receptors on macrophages, suppresses inducer T cells and B cells, and augments suppressor T cells. In addition, IVIG blocks the complement cascade, promotes remyelination, and may increase cerebrospinal fluid (CSF) immunoglobulin G (10%).
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Pathogenesis of sepsis and multiple organ dysfunction syndrome (MODS).
