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,[79especially 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. [80]In
patients whose condition is not responding to therapy, consultation with an infectious disease
specialist may be helpful.[81]
Treatment of cellulitis caused by uncommon organisms, such asVibriospecies or gram-
negative bacteria, should be individualized (eg, tetracyclines, fluoroquinolones or
aminoglycosides forVibrioinfection).[82,83]

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 Klebsiellaspecies.
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, EES, 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 includingStaphylococcus aureus(methicillin-
susceptible and methicillin-resistant isolates),Staphylococcus lugdunensis, Streptococcus
pyogenes, Streptococcus anginosusgroup (includesStreptococcus anginosus, Streptococcus
intermedius, andStreptococcus constellatus),Enterococcus faecalis, Enterobacter
cloacae,andKlebsiella 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.