Soft Tissue and Bone Infections

Has UTI in here

What are the two most common causative organisms in acute bacterial skin and soft structure infections (ABSSSI)?

• Staphylococcus aureus

• Streptococcus species (Gram positives)

What are the most commonly implicated organisms in impetigo?

• B-Hemolytic streptococci (Streptococcus pyogenes or Group A Streptococcus [GAS])

• S. aureus

What populations are most commonly affected by impetigo?

Most frequently in children 2-5 years old (but can occur at any age)

• Spreads easily especially in settings of poor hygiene and crowding, particularly during the summer months

How does impetigo present?

• Lesions most common on face and extremities (but can occur anywhere)

• Lesions are numerous, well-localized, and and erythematous

• Small thin-walled blisters --> rupture --> discharge forms honey colored crust

• Lesions are pruritic, but rarely painful

What non-pharmacologic measures should be used for patients with impetigo?

• Time and hygiene measures, soaking and cleansing lesions in mild soap and water

• Use of skin emollients to areas of dry skin may reduce spread and urge to scratch itchy lesions

• Natural remedies are controversial, but tea tree oil and Manuka honey may provide some benefit

What are the preferred antibiotics for impetigo?

• Oral penicillinase-stable penicillin’s - Dicloxacillin

• 1st generation cephalosporins - Cephalexin

What are some possible alternative antibiotics for impetigo in patients with allergy/intolerances?

• Clindamycin

• Sulfamethoxazole-Trimethoprim

• Doxycycline

What drug(s) can be used for mild impetigo few lesions?

Topical Mupirocin or Retapamulin BID for 5 days

What duration of oral antibiotics should be used for impetigo?

5-7 days (7 days for MRSA)

• per Sanford guide

What is the clinical manifestation of non-purulent cellulitis?

• Cellulitis

  • a common, potentially serious bacterial skin infection (usually Streptococcus or Staphylococcus) affecting deep dermis layers, causing red, hot, swollen, and painful skin

• Erysipelas

  • bacterial skin infection of the upper dermis, often caused by Group A Streptococcus, characterized by a fiery red, shiny, tender rash with well-defined borders, usually appearing on the legs or face

What is the initial presentation of non-purulent cellulitis?

• Diffuse redness

• edema

• warm

• tenderness

Should incision and drainage be used for non-purulent cellulitis?

NOT recommended

What are common causative pathogens of non-purulent cellulitis?

Streptococcus pyogenes

What is the clinical manifestation of purulent cellulitis?

• Abscess

• Carbuncle

• Furuncle

What is the initial presentation of purulent cellulitis?

Painful and tender localized lesion

Should incision and drainage be used for purulent cellulitis?

IS recommended

What are common causative pathogens of purulent cellulitis?

Staphylococcus aureus, including MRSA

When should incision and drainage be used?

Needed for abscesses

• May be the only treatment needed if abscesses are small

What are the preferred oral antibiotics for non-purulent cellulitis?

• Penicillin

• Amoxicillin

• Amoxicillin-Clavulanate

• Dicloxacillin

• Cephalexin

• Clindamycin

What are the preferred IV antibiotics for non-purulent cellulitis?

• Cefazolin

• Ceftriaxone

• Penicillin

• Clindamycin

What is the drug of choice for severe cellulitis caused by MRSA (i.e. purulent infection)?

Vancomycin

What is a D-test?

• Detects inducible clindamycin resistance

• For erythromycin-resistant but clindamycin-susceptible strains of S. aureus (especially MRSA)

When should empiric coverage for resistant organisms (MRSA, P. Aeruginosa) be utilized?

• Severe ABSSSI

  • Acute Bacterial Skin and Skin Structure Infection

• Severe systemic illness

How is "severe" for ABSSSI defined by IDSA guidelines?

• Have failed incision and drainage PLUS oral antibiotics

• Signs of sepsis (i.e SIRS criteria)

• Immunocompromised patients

When empiric coverage for resistant organisms (MRSA, P. Aeruginosa) is indicated what is used?

• Vancomycin or Linezolid

  • PLUS

• Antipseudomonal B-lactam (Pip-Tazo, Cefepime, Meropenem)

When are oral antibiotics used for cellulitis?

• Mild cellulitis

• Outpatient treatment

• "Step down" from parenteral inpatient therapies

What are oral antibiotics for non-purulent cellulitis?

• Cephalexin

• Dicloxacillin

• Penicillin VK

• Clindamycin

What are oral antibiotics for purulent cellulitis?

• Trimethoprim-Sulfamethoxazole

• Doxycycline

• Linezolid

• Clindamycin

When are IV antibiotics used for cellulitis?

• Moderate/severe cellulitis

• Hospitalized pt.'s

What are IV antibiotics for non-purulent cellulitis?

• Cefazolin

• Nafcillin

• Penicillin

• Clindamycin

What are IV antibiotics for purulent cellulitis?

• Vancomycin

• Linezolid

• Daptomycin

• Ceftaroline

How long should cellulitis be treated in a typical, uncomplicated course?

5-10 days (normally 5-7 days is enough)

How long should cellulitis be treated if the patient is slow to respond?

May extend beyond 10 days

When can you step down from IV to oral antibiotics in patients with cellulitis?

Once patient is afebrile and skin findings begin to resolve

• Usually after 3-5 days

What are the most commonly implicated organisms in acute (early/mild) diabetic foot infections?

• Staphylococcus aureus

• streptococcal species

What are the most commonly implicated organisms in chronic (late/severe diabetic foot infections?

• Gram-positive - Enterococci, MRSA

• Gram-negative - Enterobacterales, P. aeruginosa

• Anaerobic bacteria (especially if wound is malodorous)

What are non-pharmacologic treatment options for diabetic foot ulcers?

• Debridement of necrotic or nonviable tissue

• Wound care

• Vascular or orthopedic surgery

• Pressure offloading from the wound

Do all diabetic foot ulcers require antibiotic treatment?

NO

• Only treat if infected

Which organisms should you target in mild diabetic foot infections?

Staphylococcus aureus and streptococcal species

• Can include MRSA coverage based on pt. history and local resistance

What antibiotics are used for mild diabetic foot infections, when MRSA is not suspected?

• Cephalexin

• Dicloxacillin

• Clindamycin

• Amoxicillin-Clavulanate

• Levofloxacin

What antibiotics are used for mild diabetic foot infections, when MRSA is suspected?

• Trimethoprim-Sulfamethoxazole

• Doxycycline

• Clindamycin (do D-test)

• Linezolid

What is the duration of antibiotic therapy for mild diabetic foot infections?

10-21 days

What antibiotics are used for moderate diabetic foot infections, when MRSA is not suspected?

• Amoxicillin-Clavulanate or Ampicillin-Sulbactam

• Cefoxitin

• Ceftriaxone

• Ertapenem

• Levofloxacin + Clindamycin

• Moxifloxacin

• Oral therapy, or IV in more severe infections

What antibiotics are used for moderate diabetic foot infections, when MRSA is suspected?

• Doxycycline

• Trimethoprim-Sulfamethoxazole

• Clindamycin (do D-test)

• Linezolid

• Daptomycin

• Vancomycin

  • Oral therapy, or IV in more severe infections

What antibiotics are used for severe diabetic foot infections, with gram negative/anaerobic activity?

• Ampicillin-Sulbactam

• Aztreonam

• Cefepime

• Ceftazidime

• Ceftriaxone

• Ertapenem

• Imipenem-Cilastatin

• Piperacillin-Tazobactam

• Meropenem

• Moxifloxacin

• Levofloxacin + Clindamycin

  • IV therapy

What antibiotics are used for severe diabetic foot infections, with MRSA activity?

• Vancomycin

• Daptomycin

• Linezolid

  • IV therapy

What is the duration of antibiotic therapy for late stage (moderate/severe) diabetic foot infections?

3-6 weeks

How does duration of therapy for soft tissue infections differ if there is no osteomyelitis versus when osteomyelitis is present?

• Soft tissue infections w/o osteomyelitis: usually 10-21 days

• Bone involvement w/ debridement: 3-6 weeks

• Bone involvement w/o surgery: ≥ 6 weeks

What are the 3 most common "biters"

Dogs > Cats > Humans

Do bite wounds usually involve one pathogen or multiple?

Generally polymicrobial

What are common organisms seen in cat and dog bite wounds?

• Staphylococcus

• Streptococcus

• Pasteurella multocida (gram-negative aerobe)

• Others: Moraxella spp., Eikenella corrodens, Capnocytophaga canimorsus, Actinomyces,Fusobacterium, Prevotella, and Porphyromonas spp.

What non-pharmacologic measure should be applied first in any bite wound?

Irrigation with normal saline

• Wound should also be elevated and immobilized

Which patients are at high risk of bite infection are more likely to benefit from antibiotic prophylaxis?

• Immunocompromised, asplenic patients, or advanced liver disease

• Preexisting/resultant edema of the affected area

• Severe injuries to the hand, face, or penetrated the periosteum or joint capsule

What is the preferred antibiotic for bite wounds?

Amoxicillin-Clavulanate

• Most effective agent for treatment (and prophylaxis) of human and animal bite-wound infections

What are alternative antibiotics for bite wounds?

• Cefuroxime PLUS Clindamycin or Metronidazole

• Moxifloxacin

• Doxycycline

• Carbapenem

What is the duration of therapy for treatment of infected bite wounds?

5-10 days (but usually 5-7 is enough)

• Extend beyond 10 days if slow clinical response

• (same as cellulitis)

What is the duration of therapy for bite wound prophylaxis?

3-5 days

How do you objectively determine if your antibiotic is working in a skin and soft tissue infection?

Reduction in temperature, WBC count, erythema, edema and pain

• S/S should begin to resolve within 48-72 hours of treatment

What is the predominant pathogen in all types of osteomyelitis?

Staphylococcus aureus (increasing MRSA)

What pathogens are common in acute contiguous osteomyelitis in patients with uncontrolled diabetes and/or peripheral vascular disease?

• Usually polymicrobial

• MRSA

• Enterobacterales

• Pseudomonas aeruginosa

What empiric antimicrobial coverage should be considered for all cases of osteomyelitis?

S. aureus, including MRSA

What empiric antimicrobial coverage should be added for contagious osteomyelitis with vascular insufficiency (diabetic)?

• Enterobacterales

• P. aeruginosa

• Anaerobes

• (on top of S. aureus/MRSA coverage)

What is the therapeutic drug monitoring goal recommended for vancomycin in osteomyelitis?

AUC/MIC target: 400-600 mg*h/L

What are recommended agents for targeted MSSA osteomyelitis therapy?

• Nafcillin/Oxacillin

• Cefazolin

What are recommended agents for targeted MRSA osteomyelitis therapy?

• Vancomycin

• Daptomycin

• Linezolid

• Clindamycin

• Trimethoprim-Sulfamethoxazole PLUS Rifampin

What are recommended agents for targeted Enterococcus osteomyelitis therapy?

• If Ampicillin-sensitive: Ampicillin

• If Ampicillin-resistant: Vancomycin

• If Vancomycin-resistant: Daptomycin, Linezolid

What are recommended agents for targeted Streptococcus osteomyelitis therapy?

• Penicillin G

• Ceftriaxone

What are recommended agents for targeted Pseudomonas osteomyelitis therapy?

• Imipenem/Cilastatin

• Meropenem

• Ceftazidime

• Cefepime

• Piperacillin/Tazobactam

• Ciprofloxacin

• Levofloxacin

What are recommended agents for targeted Enterobacerales osteomyelitis therapy?

• Ceftriaxone

• Cefotaxime

• Ertapenem

• Moxifloxacin

What are recommended agents for targeted Anaerobe osteomyelitis therapy?

• Clindamycin

• Metronidazole

What route of therapy is used initially in osteomyelitis?

IV - often use IV for the entire course

• Patient may also be managed with oral therapy upfront after surgical intervention

When can switch to oral antibiotics be considered in osteomyelitis?

• Good clinical response

• Strict adherence

• Reliable outpatient follow-up

What are commonly used oral antimicrobials (with high bioavailability) for osteomyelitis?

• Fluoroquinolones

• Doxycycline

• Clindamycin

• Linezolid

• Trimethoprim-Sulfamethoxazole

Rifampin may be used adjunctively in staphylococcal osteomyelitis associated with what type of infection?

Osteomyelitis associated with prosthetic material

• OR part of step-down therapy for MRSA osteomyelitis in combo with Trimethoprim-Sulfamethoxazole

What is the typical duration of therapy for osteomyelitis?

4 to 8 weeks

What is the duration of therapy for osteomyelitis with MRSA involvement?

6 to 8 weeks

What is the duration of therapy for osteomyelitis chronic or recalcitrant infection?

Suppressive therapy (>3 months)

What labs should be monitored for efficacy when treating osteomyelitis?

• WBC

• CRP

• ESR

• Procalcitonin

What are some unique risks of using Daptomycin (anti-MRSA drug) in osteomyelitis?

• Muscle pain or weakness, especially in distal extremities

• Temporarily stop HMG-CoA reductase inhibitors

• Peripheral neuropathy

• Decreased efficacy in patients with moderate baseline renal impairment

What are some unique risks of using Vancomycin (anti-MRSA drug) in osteomyelitis?

• AUC/MIC target of 400-600 mg*/L is recommended for serious infections such as osteomyelitis

• Renal dysfunction

• Potential for additive renal toxicity if being co-administered with a nephrotoxic agent (e.g. aminoglycoside)

What are some unique risks of using Linezolid (anti-MRSA drug) in osteomyelitis?

• Myelosuppression

• Interaction w/ MAO inhibitors

• Serotonin syndrome

• Peripheral and/or optic neuropathy w/ long-term therapy

• Elevation of BP in certain patients (e.g. uncontrolled HTN)

• Hypoglycemia in patients with DM receiving insulin or oral hypoglycemic agents

What is the maximum duration listed in the linezolid package insert?

28 days

Which of the following is consistent with the mechanism of ciprofloxacin?

A) inhibition of topoisomerase II and topoisomerase IV which prevents bacterial DNA replication

B) increase in the permeability of the cell membrane to chloride ions and results in hyperpolarization of the cell

C) forms free radicals which interact directly with intracellular DNA resulting in the inhibition of DNA synthesis

D) Inhibition of the bacterial cell wall through configuration of peptidoglycan

A) inhibition of topoisomerase II and topoisomerase IV which prevents bacterial DNA replication

• The quinolones inhibit of topoisomerase II (DNA gyrase) and topoisomerase IV which prevents bacterial DNA replication, replication, transcription, repair, and recombination.

• This results in a bactericidal effect. 

A pregnant woman in her 1st trimester experiences cellulitis of her right leg. Which of the following should NOT be offered as treatment due to fetal risks?

A) Amoxicillin/clavulanate

B) clindamycin

C) cephalexin

D) Trimethoprim-sulfamethoxazole 

D) Trimethoprim-sulfamethoxazole

• Because trimethoprim and sulfamethoxazole are folate antagonists, this will disrupt neural tube development.

• Beta lactams and clindamycin are generally considered safe in pregnancy.

A patient is prescribed Augmentin XR. Which would represent a contraindication to using this product?

A) End stage renal disease with CrCL of 12mL/min

B) Cirrhosis, Child-Pugh Class A

C) Breastfeeding mother with an infant that is 16 weeks

D) Pregnancy, 30 weeks gestation

A) End stage renal disease with CrCL of 12mL/min

• While some other amoxicillin-clavulanate products can be used in patients with renal dysfunction with dose adjustments, Augmentin XR is contraindicated in patients with a CrCL <30ml/min.

• It is safe to use in pregnant and breastfeeding mothers.

• It may be used with caution for patients with liver disease assuming the liver dysfunction has not been caused by amoxicillin-clavulanate.

A parent is picking up a prescription at your pharmacy for amoxicillin-clavulanate chewable tablets for their 7-year-old child who has an ear infection. Which of the following are appropriate counseling points?

A) May cause diarrhea

B) Must be administered with a meal for absorption

C) Will likely require renal and liver function labs in 1 week

D) Causes many drug interactions through the CYP450 system

A) May cause diarrhea

• As much as 1/3rd of patients receiving amoxicillin-clavulanate experience diarrhea due to the clavulanic acid component.

• It can be administered without regard to meals, although administration with meals may help with GI discomfort.

• It does not require routine labs for short courses and does not impact the CYP450 system.

A patient previously reported anaphylaxis when receiving ampicillin. Which of the following agents should be precautioned for possible cross-reactive allergic reactions due to similar side chains?

A) Cefepime

B) Cefdinir

C) Ceftriaxone

D) Cephalexin

D) Cephalexin

• Cephalexin and cefadroxil are 1st generation cephalosporins which have the same R1/R2 side chains as the aminopenicillins (ampicillin, amoxicillin).

• Cefdinir and ceftriaxone are 3rd generation cephalosporins and cefepime is a 4th generation cephalosporin.

• While package inserts of all cephalosporins carry this warning of cross reactions, the 3rd and 4th generation cephalosporins do not have side chains similar to any penicillin.

Which of these muscle relaxants is contraindicated for use with ciprofloxacin?

A) Metaxalone

B) Baclofen

C) Tizanidine

D) Carisoprodol

C) Tizanidine

• Ciprofloxacin is an inhibitor of CYP1A2 resulting in several major drug interactions.

• Tizanidine is listed as a contraindication with ciprofloxacin as it can result in high concentrations of tizanidine and significant decreases in blood pressure.

A 67-year-old female with diabetes, overactive bladder, and myasthenia gravis is started on Cipro for a pseudomonas urinary tract infection. Which of the following is NOT an appropriate counseling point?

A) Monitor your blood glucose carefully while taking this medication

B) Separate this medication from antacids, such as Maalox

C) Cipro is associated with worsening of myasthenia gravis; your muscles may become very weak

D) Cipro is associated with myelosuppression; have your blood cell counts checked soon

D) Cipro is associated with myelosuppression; have your blood cell counts checked soon

• Ciprofloxacin (and all fluoroquinolones) can cause both hyper and hypoglecemia.

• The BlackBox warning on adverse effects of the fluoroquinolones includes myasthenia gravis exacerbations.

• Cation containing antacids will cause a chelation reaction with ciprofloxacin resulting in decreased concentrations.

• Ciprofloxacin is not associated with myelosuppression.

Which of the following is consistent with the mechanism of amoxicillin?

A) Inhibits DNA gyrase (topoisomerase II)

B) Inhibits peptidoglycan synthesis

C) Causes DNA to lose its helical structure

D) Binds to 30s ribosomal subunit

B) Inhibits peptidoglycan synthesis

• Betalactams bind to penicillin binding protein (PBP) which inhibits peptidoglycan synthesis which results in lysis of the cell wall.

Trimethoprim-sulfamethoxazole may interact with ACE inhibitors resulting in:

A) increased risk of hyperkalemia

B) decreased trimethoprim-sulfamethoxazole concentrations

C) increased risk of rash

D) decreased antihypertensive effects of ACE inhibitors

A) increased risk of hyperkalemia

• TMP-SMX may rarely cause hyperkalemia on its own, although this exacerbated in the presence of ACE inhibitors or ARBs. In fact, one study demonstrated increased risks of CV death with the combination.

Which of the following is NOT an FDA approved indication for cephalexin?

A) Intraabdominal infections caused by Enterococcus faecalis

B) Genitourinary infections caused by Escherichia coli

C) Otitis media caused by Streptococcus pneumoniae

D) Skin and Skin Structure Infections caused by Staphylococcus aureus

A) Intraabdominal infections caused by Enterococcus faecalis

• Cephalexin is approved for treatment of respiratory tract infections, otitis media, skin and skin structure infections, bone infections, and urinary tract infections for susceptible microbes.

• While it provides coverage of MSSA, E. coli, and S. pneumoniae, it (like all cephalosporins) does not cover enterococcus.

• While it may be used in treatment of an intraabdominal infection, it has not been approved for this purpose.

Which of these is consistent with the FDA’s Black Box warning for clindamycin?

A) Life-threatening hepatotoxicity

B) C. difficile associated diarrhea and colitis

C) Myasthenia gravis

D) QTc prolongation

B) C. difficile associated diarrhea and colitis

• While all antibiotics have been associated with c. difficile infection, clindamycin is the only agent with a Black Box warning.

Which of the following is a major drug interaction with metronidazole?

A) Increased warfarin levels due to CYP2C9 inhibition

B) Decreased metronidazole levels when used with ciprofloxacin

C) Risk of acute kidney injury when used with ibuprofen

D) Decreased theophylline levels due to CYP1A2 induction

A) Increased warfarin levels due to CYP2C9 inhibition'

• Metronidazole is a CYP2C9 inhibitor. This can result in a severe interaction with warfarin.

Which of the following is considered a contraindication for use according to the Flagyl package insert?

A) Pregnancy

B) Alcohol consumption within 3 days of use

C) Concomitant hemodialysis in patients with chronic kidney disease

D) Child-Pugh Class B Cirrhosis

B) Alcohol consumption within 3 days of use

• Due to a potential disulfram-like reaction, the manufacturer suggests that alcohol should not be consumed within 3 days of use (before or after) of metronidazole. Recent studies have questioned the frequency of this reaction and the CDC now suggests that refraining from alcohol may not be necessary.

• Metronidazole may be used in pregnancy when necessary.

• Patients with cirrhosis have increased exposure to the drug, but it is not a contraindication for use.

• Hemodialysis requires dose adjustment, but not avoidance.

Metronidazole is available in many formulations, including several topical products. Which of the following is NOT an FDA approved topical product?

A) 0.75% lotion for rosacea

B) 1% cream used for rosacea

C) 2% topical solution used for seborrheic dermatitis

D) 0.75% intravaginal gel used for bacterial vaginosis

C) 2% topical solution used for seborrheic dermatitis

• Due to its antiinflammatory effects, metronidazole is used topically for a number of conditions. Creams, gels, and lotions are all available, but there is no FDA approved topical solution.

Which antibiotic is available as a chewable tablet?

A) Azithromycin

B) Ampicillin-sulbactam

C) Clindamycin

D) Amoxicillin

D) Amoxicillin

• Amoxicillin is available as capsules, suspensions, and chewable tablets. Some chewable tablets and liquids contain phenylalanine which cannot be used in patients with phenylketonuria (PKU).

• Azithromycin and clindamycin come in both IV and PO formulations, but not chewable tablets.

• Ampicillin-sulbactam is only IV.

A patient receives a prescription for Bactrim single strength tablets. What are the generic ingredients and strengths of each ingredient?

A) 400mg sulfamethoxazole and 80mg trimethoprim

B)  80mg sulfamethoxazole and 16mg trimethoprim

C) 160mg sulfamethoxazole and 800mg trimethoprim

D) 800mg sulfamethoxazole and 160mg trimethoprim

A) 400mg sulfamethoxazole and 80mg trimethoprim

• All sulfamethoxazole/trimethoprim products have 5:1 ratio.

• A single strength tablet is 400mg sulfamethoxazole and 80mg trimethoprim.

Which of these is consistent with the mechanism of action of metronidazole when used as an antibacterial?

A) Binds to the 50s ribosomal subunit

B) inhibits the demethylation of ergosterol, which is important for cell wall integrity

C) Binds irreversibly to the 30S ribosomal subunit

D) Serves as a free radical intracellularly, disrupting DNA synthesis

D) Serves as a free radical intracellularly, disrupting DNA synthesis

• Metronidazole passively defuses into anaerobic bacteria and forms a nitroso free radical which interacts with intracellular DNA, inhibiting DNA synthesis, and ultimately bacterial death.

• Demethylation of ergosterol is important fungi; this answer is consistent with triazole antifungals

• Macrolides bind to the 50s subunit

• Aminoglycosides bind to the 30s subunit

Which of the following are true regarding Amoxicillin-clavulanate products?

A) Two 250mg tablets cannot be used in place of one 500mg tablet

B) Therapeutic doses are typically calculated based on a clavulanaic acid dose per kilogram

C) Augmentin XR is the only once-daily product available

D) All products contain the same amoxicillin to clavulanate ratio

A) Two 250mg tablets cannot be used in place of one 500mg tablet

• Amoxicillin-clavulanate products are typically expressed in mg of amoxicillin.

• Amoxicillin-clavulanate comes in 2:1, 4:1, 7:1, 14:1, and 16:1 formulations.

• The 500mg and 250mg tablets each contain 125mg of clavulanic acid, therefore two 250mg tablets cannot be used instead of one 500mg.

• Higher weight-based doses of amoxicillin may result in overexposure to clavulanate (>125mg dose or >10mg/kg/day in children) resulting in diarrhea.

• All dosing is either three or two times per day, including Augmentin XR.