Medication Summary
For specific information concerning the evaluation and management of diabetic foot infections, including choices of antimicrobial agents, the reader is referred to authoritative guidelines published by the Infectious Diseases Society of America. [21]
Patients with mild infections can be treated in outpatient settings with oral antibiotics that cover skin flora including streptococci and Staphylococcus aureus. Agents such as cephalexin, dicloxacillin, amoxicillin-clavulanate, or clindamycin are effective choices. If methicillin-resistant S aureus (MRSA) infection is suspected, then clindamycin, trimethoprim-sulfamethoxazole, minocycline, or linezolid may be used. If gram-negative aerobes and/or anaerobes are suspected, dual drug treatment with trimethoprim-sulfamethoxazole plus amoxicillin-clavulanate or clindamycin plus a fluoroquinolone such as levofloxacin or moxifloxacin may be used.
For moderate-to-severe infections, patients should be hospitalized for parenteral antibiotic therapy. Empiric choices should cover streptococci, MRSA, aerobic gram-negative bacilli, and anaerobes. MRSA is covered by vancomycin, linezolid, or daptomycin. Acceptable choices for gram-negative aerobic organisms and anaerobes include ampicillin-sulbactam, piperacillin-tazobactam, meropenem, or ertapenem. Alternatively, ceftriaxone, cefepime, levofloxacin, moxifloxacin, or aztreonam plus metronidazole would be sufficient to cover aerobic gram-negative and anaerobic organisms. Tigecycline has been studied, but published experience is limited.
Duration of therapy should be individualized. For those treated in outpatient settings with oral antibiotics, duration of treatment is usually 7-14 days. In those treated parenterally but without osteomyelitis, 2-4 weeks is sufficient. Longer duration of therapy is required for those with osteomyelitis—4-6 weeks at a minimum is suggested. Duration of treatment may be shortened in those patients who undergo amputation as part of the treatment regimen.
Consultation with an infectious diseases expert is recommended.
Penicillins
Class Summary
The penicillins are bactericidal antibiotics that work against sensitive organisms at adequate concentrations and inhibit the biosynthesis of cell wall mucopeptide.
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 penicillinase-producing staphylococci. It may be used as initial therapy when staphylococcal infections are suspected.
Ampicillin/sulbactam (Unasyn)
Ampicillin/sulbactam is a drug combination of 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 patients are unable to take medication orally. It covers skin, enteric flora, and anaerobes but is not ideal for nosocomial pathogens.
Amoxicillin/clavulanate (Augmentin, Augmentin XR)
Amoxicillin inhibits bacterial cell wall synthesis by binding to penicillin-binding proteins. The addition of clavulanate inhibits beta-lactamase–producing bacteria. It is a good alternative antibiotic for patients allergic to or intolerant of the macrolide class. Usually, it is well tolerated and provides good coverage of most infectious agents. It is not effective against Mycoplasma and Legionella species.
Piperacillin/tazobactam (Zosyn)
The piperacillin/tazobactam drug combination is composed of an antipseudomonal penicillin plus a beta-lactamase inhibitor. It inhibits biosynthesis of cell wall mucopeptide and is effective during the active multiplication stage.
Ticarcillin/clavulanate (Timentin)
Ticarcillin/clavulanate inhibits the biosynthesis of cell wall mucopeptide and is effective during the stage of active growth. It is an antipseudomonal penicillin plus beta-lactamase inhibitor that provides coverage against most gram-positives, most gram negatives, and most anaerobes.
Cephalosporins
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 is a first-generation cephalosporin that inhibits bacterial replication by inhibiting bacterial cell wall synthesis. It is bactericidal and effective against rapidly growing organisms forming cell walls. Resistance occurs by alteration of penicillin-binding proteins. It is effective for the treatment of infections caused by streptococcal or staphylococcal organisms, including penicillinase-producing staphylococci. It may be used as initial therapy when streptococcal or staphylococcal infection is suspected.
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. 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 the synthesis of peptidoglycan, a major structural component of the bacterial cell wall. Bacteria eventually lyse from the ongoing activity of cell wall autolytic enzymes while cell wall assembly is arrested.
Cefoxitin
Cefoxitin is a second-generation cephalosporin with activity against some gram-positive cocci, gram-negative rod infections, and anaerobic bacteria. It inhibits bacterial cell wall synthesis by binding to one or more of the penicillin-binding proteins. It inhibits the 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.
Cefuroxime (Ceftin)
Cefuroxime is a second-generation cephalosporin that maintains the gram-positive activity of first-generation cephalosporins. It adds activity against P mirabilis, H influenzae, E coli, K pneumoniae, and Moraxella catarrhalis. It binds to penicillin-binding proteins and inhibits the final transpeptidation step of peptidoglycan synthesis, resulting in cell wall death. The condition of the patient, the severity of the infection, and the susceptibility of the microorganism determine the proper dose and route of administration.
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.
Meropenem (Merrem)
Meropenem is a bactericidal broad-spectrum carbapenem antibiotic that inhibits cell-wall synthesis. It is effective against most gram-positive and gram-negative bacteria. It has slightly increased activity against gram-negatives and slightly decreased activity against staphylococci and streptococci compared with imipenem.
Ertapenem (Invanz)
The bactericidal activity of ertapenem results 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 for infections caused by various gram-negative organisms and antipseudomonal infections due to multidrug resistant gram-negative organisms.
Moxifloxacin (Avelox)
Moxifloxacin is a fluoroquinolone that inhibits A subunits of DNA gyrase, inhibiting bacterial DNA replication and transcription.
Anti-Infective Agents
Class Summary
Anti-infectives such as metronidazole, clindamycin, tigecycline, linezolid, and vancomycin are effective against many types of bacteria that have become resistant to other antibiotics.
Clindamycin (Cleocin)
Clindamycin is a semisynthetic antibiotic produced by 7(S)-chloro-substitution of 7(R)-hydroxyl group of the parent compound lincomycin. It 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 serious skin and soft-tissue staphylococcal infections. It is also effective against aerobic and anaerobic streptococci, except enterococci.
Metronidazole (Flagyl, Flagyl ER)
Metronidazole is an imidazole ring-based antibiotic active against various anaerobic bacteria and protozoa. It is used in combination with other antimicrobial agents.
Vancomycin (Vancocin)
Vancomycin is used in prophylaxis. It is a potent antibiotic directed against gram-positive organisms and is active against Enterococcus species. It is useful in the treatment of septicemia and skin structure infections. It is indicated for patients who cannot receive or have not responded to penicillins and cephalosporins or have infections with resistant staphylococci.
Linezolid (Zyvox)
Linezolid is indicated to treat diabetic foot infections without osteomyelitis that are caused by gram-positive bacteria, including resistant strains (eg, methicillin-resistant S aureus [MRSA]). It prevents the formation of functional 70S initiation complex, which is essential for the bacterial translation process. It is bacteriostatic against enterococci and staphylococci and is bactericidal against most streptococci strains.
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. [15]
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 it blocks the 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, Enterococcus faecalis (vancomycin-susceptible isolates only), S aureus (methicillin-susceptible and methicillin-resistant isolates), Streptococcus agalactiae, Streptococcus anginosus group (includes S anginosus, Streptococcus intermedius, and Streptococcus constellatus), S pyogenes, and B fragilis.
Cyclic Lipopeptides
Class Summary
Daptomycin is the first in the new antibiotic class called cyclic lipopeptides.
Daptomycin
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 for complicated skin and skin structure infections caused by S aureus (including methicillin-resistant strains), S pyogenes, S agalactiae, S dysgalactiae, and E faecalis (vancomycin-susceptible strains only).
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Chronic diabetic ulceration with underlying osteomyelitis. Plain film radiograph exhibiting cortical disruption at the medial aspect of the first MTP joint.
