l’antibioticoterapia nei protocolli di trattamento delle

LL’’antibioticoterapia nei protocolli antibioticoterapia nei protocolli

di trattamento delle ulcere cutaneedi trattamento delle ulcere cutanee

L. BerrinoL. Berrino

The reasons for using topical rather than oral therapy include the

reduced risk of systemic side effects, the avoidance of resistance

selection in the gut microflora, the higher achievable concentration of

antibiotic at the site of action and the overall usage of less drug.

Opinions regarding the clinical efficacy of topical antibiotics are

conflicting, and for most indications alternative oral therapies are

available.

It is well known that many antibiotics, when used topically, especially

for prolonged periods, select for antibiotic-resistant staphylococci at the

skin surface.

Drugs Exp Clin Res. 1990;16(8):423-33

Topical antibiotic therapy: current status and future prosp ects .Eady EA , Cove JH .Department of Microbiology, University of Leeds, UK.

J Antimicrob Chemother. 1986 Feb;17(2):135-7.

The effect of antiseptics and topical antimicrobial s on wound healing.Leaper DJ , Simpson RA .

From the Family Physicians Inquiries Network

Do topical antibiotics improve wound healing?Sabina Diehr, MDAndrew HampBarbara Jamieson, MLS Medical College of Wisconsin, MilwaukeeDal Sito www.jfponline.com pubblicato nel Febbraio 2007

The use of topical triple-antibiotic ointments significantly

decreases infection rates in minor contaminated wounds

compared with a petrolatum control. Plain petrolatum

ointment is equivalent to triple-antibiotic ointments for sterile

wounds as a post-procedure wound dressing (strength of

recommendation [SOR]: A, based on randomized controlled

trials [RCTs]).



Mupirocin cream is as effective as oral cephalexin in the treatment

of secondarily infected minor wounds and, because of better

tolerability, is the treatment of choice for the prevention and

treatment of Staphylococcus aureus and Staphylococcus pyogenes

infections. Emerging resistance, including methicillin-resistant S

aureus (MRSA), makes it prudent to check for clinical response in

24 to 48 hours.



Major contaminated wounds requiring parenteral

antibiotics do not appear to additionally benefit from

topical antibiotics (SOR: A, based on RCTs). Topical

antibiotics may also aid in the healing of chronic wounds

(SOR: B, based on a systematic review of low-quality

RCTs).

ClinClin InfectInfect DisDis. 2008 . 2008 DecDec 15;47(12):153715;47(12):1537--4545

Topical versus Systemic Antimicrobial Therapy for Treating MildlTopical versus Systemic Antimicrobial Therapy for Treating Mildly y

Infected Diabetic Foot Ulcers:Infected Diabetic Foot Ulcers: RandomizedRandomized, , ControlledControlled, , DoubleDouble--

BlindedBlinded,,Multicenter Trial of Multicenter Trial of PexigananPexiganan CreamCreamBenjamin A. Lipsky,1,2 Kenneth J. Holroyd,3 and Michael Zasloff4

1Veterans Affairs Puget Sound Health Care System and 2University of Washington School of Medicine, Seattle; 3Vanderbilt University School of

Medicine, Nashville, Tennessee; and 4Georgetown University School of Medicine, Washington, DC

Topical antimicrobial therapy of infected diabetic foot ulcers can focus

on the wound and avoid the adverse effects of systemic anti-infective

agents. We compared the efficacy of outpatient treatment using an

investigational topical antimicrobial peptide( 22- amino acid synthetic

analogue of the peptide magainin II), pexiganan acetate cream, with the

efficacy of systemic therapy using an oral fluoroquinolone antibiotic,

ofloxacin, for mildly infected diabetic foot ulcers.

TopicalTopical pexigananpexiganan mightmight bebe anan effectiveeffective alternative alternative toto oraloral antibioticantibiotic

therapytherapy in in treatingtreating diabeticdiabetic patientspatients withwith a a mildlymildly infectedinfected footfoot ulcerulcer, ,

and and mightmight reduce the reduce the riskrisk ofof selectingselecting antimicrobialantimicrobial--resistantresistant bacteriabacteria..

Canadian Family Physician • Le Médecin de famille cana dien d VOL 5 ��: OCTOBER • OCTOBRE 2005

Approach to infected skin ulcersChristopher Frank, MD, CCFP Imaan Bayoumi, MD, CCFP Claire Westendorp, BNSC, RN

Bacteria in skin ulcers act along a continuum from

contamination through colonization and critical colonization to

infection. Critical colonization is not always associated with

overt signs of infection but can result in failure to heal, poor-

quality granulation tissue, increased wound friability, and

increased drainage. Iodine and silver-based dressings,

topical antibiotics, and systemic antibiotics can be

helpful.

AGENT MICROBIAL COVERAGE COMMENTS

Mupirocin (Bactroban) ‏‏ ‏‏ Gram-positive organisms • 2% cream or ointment

• Good against methicillin resistant

Staphylococcus aureus when clinically

indicated

Fusidic acid (eg, Fucidin) ‏‏ ‏‏ Staphyloccocus, Streptococcus • Comes as 2% gel, ointment, cream, or

impregnated dressing

• Contains lanolin that can cause

sensitization

Neomycin sulfate Gram-negative organisms and

Pseudomonas

• Usually comes with bacitracin and

polymyxin B sulfate (eg, Neosporin

ointment)

• Can cause sensitization

• Can be ototoxic if large areas of skin are

involved

Gentamicin (eg, Garamycin) ‏‏ ‏‏ Gram-negative organisms and

Pseudomonas

• Cream or gel

• Can be ototoxic if large areas of skin

are involved

Bacitracin (eg, Baciguent) ‏‏ ‏‏ Gram-positive organisms • Comes as ointment

• Can cause sensitization

Bacitracin, polymyxin B, and

gramicidin (Polysporin Triple

Antibiotic)

Gram-positive organisms, Gram

negative organisms, and

Pseudomonas

• Cream or ointment

Metronidazole Anaerobes • Gel is most commonly used but also is

available as cream • Useful for odour

Topical antibiotics for infected skin ulcers (Table 2)

Formula chemioterapicaFormula chemioterapica

( continued…)‏

Clin Infect Dis. 2005; 41(10):1373-406.

Activity of antibiotics

TIME -DEPENDENT

CONCENTRATION -DEPENDENT

BetalactamsGlycopeptidesLincosamidesNatural macrolides

Oxazolidinones

AminoglycosidesFluoroquinolonesMetronidazole

Quinopristin/dalfopristinClarithromycinAzithromycin

Ketolides

0

40

30

10

20

Cmax/MIC

PK-PD correlationsC

once

ntra

tion

(mg/

L)‏‏ ‏‏

0 248 16

MIC

JM Hyatt et al., 1995

T > MIC

AUC/MIC

0,5 10

Hours

PAEBetalactams

OxazolidinonesErythromycin

AminoglycosidesFluoroquinolones

VancomycinAzithromycin

ClarithromycinKetolides

Mutant prevention concentration and mutant selection window

MIC MPCC-8-methoxy

Mutantselectionwindow

C-8-hydrogen

MIC MPC

Drug concentration (log 10) ‏‏ ‏‏

Fra

ctio

nof

colo

nies

reco

vere

d(lo

g10

) ‏‏ ‏‏

Cmax

MPC

MIC

Mutantselectionwindow

Time post-administration

Ser

umor

tiss

uedr

ugco

ncen

trat

ion

Drlica K and Schmitz FJ, J Chemother, 2002

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