Medication Summary
The goals of antimicrobial therapy are to eradicate the infection, reduce morbidity, and prevent complications. Knowledge of local organisms and resistance patterns plays an integral role in appropriate antimicrobial selection.
Beta-lactam agents have long been the mainstay of therapy for cellulitis. However, the recent increase in the prevalence of community-acquired MRSA (CA-MRSA) in the general population, [84] especially in cases of cellulitis associated with abscess or purulent drainage, has changed this treatment paradigm to some degree. Common beta-lactam agents that are traditionally used to treat cellulitis do not cover CA-MRSA, so alternative agents or combination therapies are increasingly being used.
In general, the clinician should choose empiric antimicrobial coverage for common pathogens in each given clinical scenario and narrow coverage if culture data become available. Inappropriate antimicrobial selection and dosing have been found to be independent risk factors for clinical failure in patients admitted to the hospital for cellulitis with or without abscess. [85] In patients whose condition is not responding to therapy, consultation with an infectious disease specialist may be helpful. [86]
Treatment of cellulitis caused by uncommon organisms, such as Vibrio species or gram-negative bacteria, should be individualized (eg, tetracyclines, fluoroquinolones or aminoglycosides for Vibrio infection). [87, 88]
Penicillins, Natural
Class Summary
The penicillins are bactericidal antibiotics that work against sensitive organisms at adequate concentrations and inhibit the biosynthesis of cell wall mucopeptide.
Penicillin G aqueous (Pfizerpen)
Penicillin G interferes with the synthesis of cell wall mucopeptide during active multiplication, resulting in bactericidal activity against susceptible microorganisms.
Penicillins, Amino
Class Summary
The aminopenicillins, or third-generation penicillins, are semisynthetic modifications of natural penicillin that have a broader spectrum of activity.
Amoxicillin (Moxatag)
Amoxicillin is a derivative of ampicillin and has a similar antibacterial spectrum—namely, certain gram-positive and gram-negative organisms. It has superior bioavailability and stability to gastric acid and has a broader spectrum of activity than penicillin. Amoxicillin is somewhat less active than penicillin against Streptococcus pneumococcus. Penicillin-resistant strains also are resistant to amoxicillin, but higher doses may be effective. It interferes with the synthesis of cell wall mucopeptides during active multiplication, resulting in bactericidal activity against susceptible bacteria.
Amoxicillin and clavulanate (Augmentin)
Amoxicillin inhibits bacterial cell wall synthesis by binding to penicillin-binding proteins. The addition of clavulanate inhibits beta-lactamase–producing bacteria. Resistance is caused by a change in penicillin-binding proteins. It is recommended for bites from cats, dogs, and humans.
Ampicillin and sulbactam (Unasyn)
This is a drug combination of a beta-lactamase inhibitor and ampicillin. It interferes with bacterial cell wall synthesis during active replication, causing bactericidal activity against susceptible organisms. It is an alternative to amoxicillin-clavulanate if the patient is unable to take medication orally. It covers skin, enteric flora, and anaerobes. It is ideal for mammalian bite wounds, but it is not ideal for nosocomial pathogens because of increasing rates of resistance of gram-negative organisms.
Penicillins, Penicillinase Resistant
Class Summary
The penicillinase-resistant, or second-generation, penicillins are semisynthetic modifications of natural penicillins that are resistant to bacterial enzyme beta-lactamase, which accounts for typical penicillin resistance.
Oxacillin
Oxacillin is a bactericidal antibiotic that inhibits cell wall synthesis. It is used in the treatment of infections caused by penicillinase-producing staphylococci. It may be used to initiate therapy when a methicillin-sensitive staphylococcal infection (MSSA) is suspected.
Dicloxacillin
Dicloxacillin binds to one or more penicillin-binding proteins, which, in turn, inhibits synthesis of bacterial cell walls. It is used for the treatment of infections caused by streptococci and penicillinase-producing staphylococci. It may be used to initiate therapy when staphylococcal or streptococcal infection is suspected. Resistance to this drug results from alterations in penicillin-binding proteins. This drug does not cover MRSA.
Nafcillin
Nafcillin binds to penicillin-binding proteins, which, in turn, inhibits synthesis of bacterial cell walls. Resistance occurs by alterations in penicillin-binding proteins. It is used as initial therapy for suspected streptococcal and penicillin-resistant staphylococcal infections (not MRSA).
Penicillins, Extended-Spectrum
Class Summary
Extended-spectrum, or fourth-generation, penicillins are semisynthetic modifications of natural penicillin that have an extended spectrum of activity, particularly against gram-negative bacteria such as Pseudomonas, Enterobacter, Proteus, and Klebsiella species.
Piperacillin and tazobactam (Zosyn)
Piperacillin-tazobactam is a semisynthetic penicillin with an increased spectrum against gram-negative bacilli. The addition of tazobactam inhibits beta-lactamases produced by bacteria. It is a broad-spectrum drug for gram-positive, gram-negative, and anaerobic bacteria; it covers most gram-positive organisms except MRSA.
Cephalosporins, Other
Class Summary
Cephalosporins are structurally and pharmacologically related to penicillins. They inhibit bacterial cell wall synthesis, resulting in bactericidal activity. Cephalosporins are divided into first, second, third, and fourth generation. First-generation cephalosporins have greater activity against gram-positive bacteria, and succeeding generations have increased activity against gram-negative bacteria and decreased activity against gram-positive bacteria.
Cephalexin (Keflex)
Cephalexin binds to penicillin-binding proteins, which, in turn, inhibits synthesis of bacterial cell walls. Resistance occurs by alteration of penicillin-binding proteins. It is used for the treatment of infections caused by streptococci or penicillinase-producing staphylococci. It may be used to initiate therapy when streptococcal or staphylococcal (non-MRSA) infection is suspected. Because of the drug's short half-life, q8h or q12h dosing is not optimal.
Cefazolin
Cefazolin is a first-generation semisynthetic cephalosporin that arrests bacterial cell wall synthesis, inhibiting bacterial growth. Resistance occurs by alterations in penicillin-binding proteins. It is primarily active against skin flora, including Staphylococcus aureus. Cefazolin is typically used alone for skin and skin-structure coverage but does not cover MRSA.
Ceftriaxone (Rocephin)
Ceftriaxone is a third-generation cephalosporin with broad-spectrum, gram-negative activity; it has lower efficacy against gram-positive organisms. 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 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. It is highly stable in the presence of beta-lactamases, both penicillinase and cephalosporinase, of gram-negative and gram-positive bacteria. Ceftriaxone does not cover MRSA.
Cefuroxime (Ceftin, Zinacef)
Cefuroxime is a second-generation oral cephalosporin antibiotic that inhibits cell wall synthesis and is bactericidal.
Cefadroxil
Cefadroxil is a first-generation semisynthetic cephalosporin that arrests bacterial growth by inhibiting bacterial cell wall synthesis. It has bactericidal activity against rapidly growing organisms, including S aureus (not MRSA), S pneumoniae, S pyogenes, Moraxella catarrhalis, E coli, Klebsiella species, and Proteus mirabilis.
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 zwitterion; it rapidly penetrates gram-negative cells. Cefepime is the best beta-lactam for intramuscular administration. Its poor capacity to cross the blood-brain barrier precludes its use for meningitis.
Ceftazidime (Fortaz, Tazicef)
Ceftazidime is a third-generation cephalosporin with broad-spectrum, gram-negative activity, including pseudomonal activity; it has lower efficacy against gram-positive organisms and higher efficacy against resistant organisms. It arrests bacterial growth by binding to one or more penicillin-binding proteins, which, in turn, inhibits the final transpeptidation step of peptidoglycan synthesis in bacterial cell wall synthesis, thus inhibiting cell wall biosynthesis.
Ceftaroline (Teflaro)
Beta-lactam cephalosporin with activity against aerobic and anaerobic gram-positive and aerobic gram-negative bacteria. Demonstrates activity in vivo against methicillin-resistant Staphylococcus aureus (MRSA) strains and in vitro against vancomycin-resistant and linezolid-resistant S aureus. It is indicated for community-acquired bacterial pneumonia and for acute bacterial skin and skin structure infections, including MRSA.
Macrolides
Class Summary
Macrolides are agents that bind to the 50S ribosomal subunit of susceptible organisms, resulting in inhibition of protein synthesis. Examples such as azithromycin, erythromycin, and clarithromycin are all reasonable alternatives in patients who are allergic to penicillins.
Azithromycin (Zithromax, Zmax)
Azithromycin acts by binding to the 50S ribosomal subunit of susceptible microorganisms and blocking dissociation of peptidyl tRNA from ribosomes, causing RNA-dependent protein synthesis to arrest. Nucleic acid synthesis is not affected. It is used to treat mild to moderate microbial infections.
Erythromycin (Erythrocin, E.E.S., Ery-Tab, EryPed)
Erythromycin inhibits bacterial growth, possibly by blocking dissociation of peptidyl tRNA from ribosomes, causing RNA-dependent protein synthesis to arrest. It is used for the treatment of staphylococcal (not MRSA) and streptococcal infections.
Clarithromycin (Biaxin, Biaxin XL)
Clarithromycin is a semisynthetic macrolide antibiotic that reversibly binds to the P site of the 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. It has a similar susceptibility profile to erythromycin but has fewer adverse effects.
Carbapenems
Class Summary
Carbapenems are structurally related to penicillins and have broad-spectrum bactericidal activity. The carbapenems exert their effect by inhibiting cell wall synthesis, which leads to cell death. They are active against gram-negative, gram-positive, and anaerobic organisms.
Imipenem and cilastatin (Primaxin)
Imipenem-cilastatin is used for severe disease and to treat multiple-organism infections for which other agents do not have broad-spectrum coverage or are contraindicated because of their potential for toxicity.
Ertapenem (Invanz)
Ertapenem has bactericidal activity resulting 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.
Fluoroquinolones
Class Summary
Fluoroquinolones have broad-spectrum activity against gram-positive and gram-negative aerobic organisms. They inhibit DNA synthesis and growth by inhibiting DNA gyrase and topoisomerase, which is required for replication, transcription, and translation of genetic material.
Levofloxacin (Levaquin)
Levofloxacin is used to treat pseudomonal infections and infections due to multidrug-resistant gram-negative organisms.
Ciprofloxacin (Cipro)
Ciprofloxacin inhibits bacterial DNA synthesis and, consequently, growth by inhibiting DNA gyrase and topoisomerases, which are required for replication, transcription, and translation of genetic material.
Delafloxacin (Baxdela)
Delafloxacin inhibits bacterial DNA synthesis and growth by inhibiting bacterial topoisomerase IV and DNA gyrase. Delafloxacin exhibits concentration-dependent bactericidal activity against gram-positive and gram-negative bacteria in vitro.
Antibiotics, Other
Class Summary
Anti-infectives such as metronidazole, clindamycin, aztreonam, and trimethoprim- sulfamethoxazole are effective against some types of bacteria that have become resistant to other antibiotics. Vancomycin, daptomycin, tigecycline, and linezolid are appropriate choices In more severe cases that require parenteral antibiotics in areas where MRSA is thought to be a possible pathogen.
Clindamycin (Cleocin)
Clindamycin is a lincosamide used for the treatment of serious skin and soft-tissue staphylococcal infections, including some community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) infections. It is also effective against aerobic and anaerobic streptococci (except enterococci). It inhibits bacterial growth, possibly by blocking dissociation of peptidyl t-RNA from ribosomes, causing RNA-dependent protein synthesis to arrest.
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, including MRSA and CA-MRSA. Linezolid is bactericidal against most strains of streptococci.
The FDA warns against the concurrent use of linezolid with serotonergic psychiatric drugs, unless indicated for life-threatening or urgent conditions. Linezolid may increase serotonin CNS levels as a result of MAO-A inhibition, increasing the risk of serotonin syndrome. [84]
Tigecycline (Tygacil)
Tigecycline is a glycylcycline antibiotic that is structurally similar to tetracycline antibiotics. It inhibits bacterial protein translation by binding to the 30S ribosomal subunit and blocks entry of amino-acyl tRNA molecules in the ribosome A site. It is indicated for complicated skin and skin-structure infections caused by E coli, E faecalis (vancomycin-susceptible isolates only), S aureus (methicillin-susceptible and methicillin-resistant isolates), S agalactiae, S anginosus group (includes S anginosus, S intermedius, and S constellatus), S pyogenes, and B fragilis.
Vancomycin
Vancomycin is indicated for patients who cannot receive or who have not responded to penicillins and cephalosporins or have infections with resistant staphylococci, including CA-MRSA and MRSA. To avoid toxicity, the current recommendation is to assay vancomycin trough levels after the fourth dose, drawn a half hour before the next dosing. Use creatinine clearance to adjust the dose in patients with renal impairment.
Daptomycin (Cubicin)
Daptomycin binds to bacterial membranes and causes rapid membrane potential depolarization, thereby inhibiting protein, DNA, and RNA synthesis and ultimately causing cell death. It is indicated to treat complicated skin and skin-structure infections caused by Staphylococcus aureus (including methicillin-resistant strains), S pyogenes, S agalactiae, S dysgalactiae, and E faecalis (vancomycin-susceptible strains only). Monitoring for muscle inflammation by monitoring creatinine phosphokinase levels is recommended.
Trimethoprim and sulfamethoxazole (Bactrim, Bactrim DS, Septra DS)
Trimethoprim-sulfamethoxazole inhibits bacterial growth by inhibiting the synthesis of dihydrofolic acid. It may be considered an alternative to vancomycin in some cases of MRSA infection, especially CA-MRSA.
Metronidazole (Flagyl)
Metronidazole is an imidazole ring-based antibiotic that is active against various anaerobic bacteria and protozoa. It is used in combination with other antimicrobial agents.
Tetracyclines
Class Summary
The tetracyclines reversibly bind to the 30S subunit of the bacterial ribosome. They prevent the binding of aminoacyl transfer RNA and inhibit protein synthesis and cell growth. Tetracyclines are effective against both gram-positive and gram-negative organisms.
Doxycycline (Doryx, Adoxa)
Doxycycline inhibits protein synthesis and thus bacterial growth by binding to 30S and possibly 50S ribosomal subunits of susceptible bacteria. It provides good coverage against spirochetes, many gram-negative organisms, anaerobic organisms, atypical bacteria, and many gram-positive organisms, including most CA-MRSA.
Minocycline (Dynacin, Minocin Kit, Minocin, Myrac, Solodyn, Vectrin)
Minocycline inhibits protein synthesis and thus bacterial growth by binding to 30S and possibly 50S ribosomal subunits of susceptible bacteria. This drug covers gram-positive and gram-negative organisms, as well as CA-MRSA. Minocycline is a first-line agent against organisms such as Afipia felis, Borrelia recurrentis, Chlamydia species, Coxiella burnetii, Mycoplasma hominis, Mycobacterium marinum, Mycobacterium smegmatis, and V cholerae.
Omadacycline (Nuzyra)
Aminomethylcycline antibacterial within the tetracycline drug class that binds to the 30S ribosomal subunit and blocks protein synthesis. It is active in vitro against gram-positive bacteria expressing tetracycline resistance active efflux pumps (tetK and tet L) and ribosomal protection proteins (tet M). It is indicated for treatment of acute bacterial skin and skin structure infections (ABSSSIs) caused by susceptible microorganisms including Staphylococcus aureus (methicillin-susceptible and methicillin-resistant isolates), Staphylococcus lugdunensis, Streptococcus pyogenes, Streptococcus anginosus group (includes Streptococcus anginosus, Streptococcus intermedius, and Streptococcus constellatus), Enterococcus faecalis, Enterobacter cloacae, and Klebsiella pneumoniae. Available for IV or PO administration.
Antifungal Agents
Class Summary
Antifungal agents such as itraconazole and terbinafine work by inhibiting the biosynthesis of ergosterol, which is an essential component of the fungal cell membrane.
Itraconazole (Sporanox)
Itraconazole is a synthetic triazole that has fungistatic activity. It slows fungal cell growth by inhibiting cytochrome P-450–dependent synthesis of ergosterol, a vital component of fungal cell membranes.
Terbinafine (Lamisil, Terbinex)
Terbinafine inhibits squalene epoxidase, which decreases ergosterol synthesis, causing fungal cell death. Use medication until symptoms significantly improve.
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Mild cellulitis with a fine lacelike pattern of erythema. This lesion was only slightly warm and caused minimal pain, which is typical for the initial presentation of mild cellulitis.
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Swelling seen in cellulitis involving the hand. In a situation with hand cellulitis, always rule out deep infection by imaging studies or by obtaining surgical consultation.
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Severe cellulitis of the leg in a woman aged 80 years. The cellulitis developed beneath a cast and was painful and warm to the touch. Significant erythema is evident. The margins are irregular but not raised. An ulcerated area is visible in the center of the photograph.
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Burns complicated by cellulitis. The larger lesion is a second-degree burn (left), and the smaller lesion is a first-degree burn (right), each with an expanding zone of erythema consistent with cellulitis.
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Cellulitis due to documented Vibrio vulnificus infection. (Image courtesy of Kepler Davis.)
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A case of cellulitis without associated purulence in an infant. Note the presence of lymphedema, a risk factor for cellulitis.(Photo courtesy of Amy Williams.)
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Patient with cellulitis of the left ankle. This cellulitis was caused by community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA). (Photo courtesy of Texas Dept. of Public Health.)
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Abscess and associated cellulitis caused by community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA). (Photo courtesy of Texas Dept. of Public Health.)
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Guidelines for the management of patients who require hospitalization for cellulitis or cutaneous abscess. AFB = acid-fast bacilli; BID = twice daily; CRP = C reactive protein; CT = computed tomography scanning; DS = double strength; DM = diabetes mellitus; ESR = erythrocyte sedimentation rate; ESRD = end-stage renal disease; HIV = human immunodeficiency virus; ICU = intensive care unit; I&D = incision and drainage; ID = infectious disease; IDU = injection drug user; IV = intravenous; LRINEC = Laboratory Risk Indicator for Necrotizing Fasciitis; MRI = magnetic resonance imaging; MSRA = methicillin-resistant Staphylococcus aureus; NSAIDS = nonsteroidal anti-inflammatory drugs; PO = by mouth; SSTI = skin and soft-tissue infections; TID = 3 times daily. Adapted from Jenkins TC, Knepper BC, Sabel AL, et al. Decreased antibiotic utilization after implementation of a guideline for inpatient cellulitis and cutaneous abscess. Arch Intern Med. 2011;171(12):1072-9.
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A male patient with orbital cellulitis with proptosis, ophthalmoplegia, and edema and erythema of the eyelids. The patient also exhibited pain on eye movement, fever, headache, and malaise.
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A male patient with orbital cellulitis with proptosis, ophthalmoplegia, and edema and erythema of the eyelids. The patient also exhibited chemosis and resistance to retropulsion of the globe.
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Gross photograph of complicated cellulitis. Instead of the presence of yellow fat, the tissue is hemorrhagic and necrotic.
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Hematoxylin and eosin (H&E) stain, high power. This image shows deeper subcutaneous tissue involved in a case of cellulitis, with acute inflammatory cells and fat necrosis.
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Hematoxylin and eosin (H&E) stain, high power. This image shows cellulitis caused by herpes simplex virus, with the multinucleated organism in the center of the picture.