Management of complicated skin and soft tissue infections with a special focus on the role of newer antibiotics

Figures & data

Table 1 Skin and soft tissue infections: risk factors and common causative pathogens

Risk factors
Local	Systemic
· Soft tissue trauma	· Poorly controlled diabetes mellitus
· Animal or human bites	· Immunocompromised comorbidities (eg, HIv infection, cellular or humoral
· Burns	immune deficiencies)
· Operative or highly contaminated wounds	· Concomitant drugs (ie, corticosteroids, cyclosporine)
· Diminished perfusion due to peripheral vascular disease, obesity	· Sensory neuropathies
Poor hygiene Exposure to contaminated water Presence of foreign body (eg, piercing, tattoos) Venous insufficiency and stasis	· Chronic systemic illness (eg, cirrhosis)
Infection or risk factor	Causative pathogen
Abscess	Staphylococcus aureus Polymicrobial
Cellulitis	S. aureus GABHS
Associated with injection use	S. aureus
Associated with water exposure	Aeromonas hydrophila, Vibrio vulnificus, Mycobacterium marinum
Associated with animal bite	Pasteurella multocida, Capnocytophaga canimorsus
Associated with human bite	Human oral flora
Surgical site infections	Anaerobes Enterococcus spp. Enterobacter spp. Gram-negative bacilli Staphylococcus spp. Streptococcus spp. Escherichia coli
Necrotizing fasciitis	Monomicrobial:S. pyogenes, S. aureus, Enterobacteriaceae, Bacteroides, and Peptostreptococcus speciesPolymicrobial:Clostridium perfringens, S. aureus, Pseudomonas aeruginosa
Myonecrosis	C. perfringens
Recurrent hospital admissions	MRSA
Diabetes	S. aureus (MRSA and MSSA), GABHS, anaerobes, Gram-negative bacilli
Diabetic foot ulcers	S. aureus, Enterococcus spp., Streptococcus spp.P. aeruginosa, Enterobacter spp., Acinetobacter spp. Bacteroides spp
Cirrhosis	Campylobacter fetus, Klebsiella pneumoniae, E. coli, Capnocytophaga canimorsus, other Gram-negative bacilli, Vibrio vulnificus
Neutropenia	Gram-negative bacilli, P. aeruginosa

Abbreviations: GABHS, group A β-hemolytic streptococci; MRSA, methicillin-resistant Staphylococcus aureus; MSSA, methicillin-sensitive S. aureus.

Figure 1 Diagnosis of complicated skin and soft tissue infections.

Table 2 Recommendations for antibiotic treatment of methicillin-resistant Staphylococcus aureus complicated skin and soft tissue infections

Guidelines	Infection	Recommended therapy
Infectious Diseases Society of America^31	cSSTI (deeper soft-tissue infections, surgical/traumatic wound infection, major abscesses, cellulitis, and infected ulcers and burns)Non-purulent cellulitis	Surgical debridement vancomycin, linezolid, daptomycin, telavancin, clindamycin β-lactam antibiotic active against MRSA
Surgical Infection Society^118	Complex abscesses with cellulitis and polymicrobial cSSTIs	Incision and drainage (in case of abscess) vancomycin, clindamycin, linezolid, or erythromycin
Gruppo Italiano di Studio sulle Infezioni Gravi^41	MRSA-related cSSTIs and severe surgical infections	Use of TNP/VAC (for deep surgical infections) vancomycin, teicoplanin, linezolid, tigecycline, daptomycin
Italian Society of Infectious Diseases and international Society of Chemotherapy^119	MRSA-related cSSTIs	Early surgical treatment wherever feasible vancomycin, teicoplanin, linezolid, tigecycline, daptomycin
Spanish Society of Chemotherapy^35,120	MRSA-related cSSTIs	Linezolid, daptomycin, vancomycin, teicoplanin
British Society of Antimicrobial Chemotherapy^121	Severe cSSTI with MRSA	Linezolid, daptomycin, vancomycin, teicoplanin

Abbreviations: cSSTIs, complicated skin and soft tissue infections; MRSA, methicillin-resistant Staphylococcus aureus; TNP/VAC, topical negative pressure/vacuum-assisted closure.

Table 3 Minimum inhibitory concentration of antibiotics used for cSSTIs (European Committee on Antimicrobial Susceptibility Testing)

Drug	Pathogens	Minimum inhibitory concentrations (μg/mL)
		Susceptible ≤	Resistant >
Older Antibiotics
vancomycin	Staphylococcus aureus	2	2
	Coagulase-negative staphylococci	4	4
	Enterococcus spp.	4	4
	Streptococcus groups A, B, C, and G	2	2
	Streptococcus pneumoniae	2	2
	viridans group streptococci	2	2
	Gram-positive anaerobes except Clostridium difficile	2	2
	C. difficile	2	2
	Corynebacterium spp.	2	2
	Aerococcus sanguinicola and urinae	1	1
Amoxicillin/ clavulanic acid	Enterococcus spp.	4	8
	viridans group streptococci	0.5	2
	Haemophilus influenzae	2	2
	Neisseria meningitidis	0.125	1
	Gram-positive anaerobes except C. difficile	4	8
	Gram-negative anaerobes	0.5	2
	Helicobacter pylori	0.125	0.125
	Pasteurella multocida	1	1
	Kingella kingae	0.125	0.125
	Enterobacteriaceae	8	8
	Enterococcus spp.	4	8
Clindamycin	Staphylococcus spp.	0.25	0.5
	Streptococcus groups A, B, C, and G	0.5	0.5
	S. pneumoniae	0.5	0.5
	viridans group streptococci	0.5	0.5
	Gram-positive anaerobes except C. difficile	4	4
	Gram-negative anaerobes	4	4
	Corynebacterium spp.	0.5	0.5
Teicoplanin	Enterococcus spp.	2	2
	Streptococcus groups A, B, C, and G	2	2
	S. pneumoniae	2	2
	viridans group streptococci	2	2
	Staphylococcus spp.	2	2
	Coagulase-negative staphylococci	4	4
Newer antibiotics**
Linezolid	Staphylococcus spp.	4	4
	Enterococcus spp.	4	4
	Streptococcus groups A, B, C, and G	2	4
	S. pneumoniae	2	4
	Corynebacterium spp.	2	2
Daptomycin	Streptococcus groups A, B, C, and G	1	1
	Staphylococcus spp.	1	1
Tigecycline	Enterobacteriaceae	1	2
	Staphylococcus spp.	0.5	0.5
	Enterococcus spp.	0.25	0.5
	Streptococcus groups A, B, C, and G	0.25	0.5
Ceftaroline	S. pneumoniae	0.25	0.25
	Haemophilus influenzae	0.03	0.03
	Enterobacteriaceae	0.5	0.5
	Staphylococcus spp., S. aureus	1	1
Tedizolid	Staphylococcus spp.	0.5	0.5
	Streptococcus groups A, B, C, and G viridans group streptococci (S. anginosus group)	0.25	0.25
Dalbavancin*	viridans group streptococci (S. anginosus group)	0.125	0.125
	Staphylococcus spp.	0.125	0.125
	Streptococcus groups A, B, C, and G	0.125	0.125
Oritavancin*	viridans group streptococci (S. anginosus group)	0.25	0.25
	Staphylococcus spp. (S. aureus)	0.125	0.125
	Streptococcus groups A, B, C, and G	0.25	0.25

Notes: *Dalbavancin and oritavancin are not approved in Singapore. **“Newer antibiotics” refers to antibiotics which are approved by US FDA from 2000 onward. These data have been produced in part under ECDC service contracts and made available by EUCAST at no cost to the user and can be accessed on the EUCAST website www.eucast.org. EUCAST recommendations are frequently updated and the latest versions are available at www.eucast.org.

Table 4 General features of older and newer antibiotics with activity against MRSA

Antibiotic	Dosage	Route of administration	Mode of action	Tissue penetration	Use in special population	Strengths	Limitations
Older antibiotics
Vancomycin^Citation53	500 mg iv infusion for 60 minutes	Intravenous	Bactericidal	8%— 10%	Dose titration in patients	Gold standard for MRSA	Emerging resistance.
	every 6 hours or 1 g iv infusion		glycopeptide		with renal impairment	infections.	Increasing MIC
	for 100 minutes every 12 hours					Established efficacy and tolerability	Poor tissue penetration
Clindamycin^Citation53	IV: 0.6-2.7 g infusion for 10-60 minute daily in 2-4 divided doses Oral: 150-300 mg every 6 hours, up to 450 mg in severe infections	Intravenous/oral	Bacteriostatic	95%	No dose adjustment in patients with renal impairment	Preferred agent for necrotizing fasciitis as it blocks bacterial toxin production	Emerging resistance Clostridium difficile-associated colitis
Cloxacillin^Citation122	Oral: 0.5 g every 6 hours IV: 1-2 g every 6 hours 2 g every 4 hours in case of severe infections	Oral/intravenous	Bactericidal	NA	No dose adjustment in patients with renal impairment	Main stream agent of treating methicillin-susceptible Staphylococcus aureus (MSSA)	Lack of efficacy against MRSA infections
Newer antibiotics
Linezolid^Citation123	600 mg IV or orally every 12 hours	Intravenous/oral	Bacteriostatic	105%	No dose adjustment in patients with renal impairment	Bioavailable as oral formulation Preferred agent for necrotizing fasciitis as it inhibits bacterial toxin production	Risk of toxicity with prolonged use Oral switch
Daptomycin^Citation124	4-6 mg/kg every 24 or 48 hours	Intravenous	Bactericidal	68%	No dose adjustment in patients with renal impairment	Once-daily iv regimen suitable for outpatient use	Emerging resistance
Tigecycline^Citation125	50 or 100 mg every 12 hours	Intravenous	Bacteriostatic	91%	No dose adjustment in patients with renal impairment	Broad spectrum activity against multidrug resistant Gram- positive and G ram-negative pathogens	Low serum levels
Ceftaro line^Citation126	600 mg iv infusion for 60 minutes every 12 hours	Intravenous	Bactericidal	NA	Dose titration in patients with renal impairment. No dose adjustments in obese patients	Good clinical efficacy and tolerability. Low propensity for C. difficile- related diarrhea	Low activity against Gram- negative pathogens. Bid or tid dosing
Tedizolid^Citation127	200 mg iv infusion for 60 minutes, once daily Oral: 200 mg once daily	Intravenous/ oral	Bacteriostatic	NA	No dose adjustment in patients with renal impairment	Bioavailable as oral formulation Preferred agents for necrotizing fasciitis as it inhibits bacterial toxin production	Lower risk of myelotoxicity and drug-drug interactions. Oral switch
Dalbavancin^68*	1,000 mg iv infusion for 30 minutes	Intravenous	Bactericidal	NA	Dose titration in patients with renal impairment	Long half-life allowing once-daily iv administration suitable for outpatient use	Low activity against Gram- negative pathogens. Cannot be cleared by hemodialysis in case of toxicity Early discharge
Oritavancin^68*	1,200 mg single dose iv infusion for over 3 hours	Intravenous	Bactericidal	NA	Dose titration in patients with renal impairment	Long half-life allowing once-daily iv administration	Low activity against Gram- negative pathogens

Notes: Dosage approved in Singapore mentioned in the table, except for dalbavancin and oritavancin. *Dalbavancin and oritavancin are not approved in Singapore.

Abbreviations: MIC, minimum inhibitory concentration; MRSA, methicillin-resistant Staphylococcus aureus; NA, not available.

Figure 2 Nursing and postoperative care in complicated skin and soft tissue infections.

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