Topical antibiotic treatment for uncomplicated skin and skin structure infections: review of the literature

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Literature Review

10.1586/ERI.09.74

Ronald Pangilinan, Alan Tice† and Glenn Tillotson†Author for correspondenceInfections Limited Hawaii, 550 South Beretania Street, Suite 400, Honolulu, HI 96822, USA Tel.: +1 808 373 3488Fax: +1 808 585 [email protected]

Uncomplicated skin infections account for almost 200 million physician-office visits in the USA annually. Treating these infections is estimated to cost in excess of US$350 million each year. The primary etiology of these infections is Staphylococcus aureus, over 60% of which is estimated to be methicillin resistant across the USA. Therapeutic options include incision and drainage in combination with antimicrobial therapy, which may be oral, topical or occasionally parenteral. Because the effectiveness of the current oral options, such as b-lactams and other classes, is being eroded due to acquired resistance, older, untested agents such as trimethoprim–sulfamethoxazole or clindamycin are often being used. Thus, topical approaches may offer effective, localized, well-tolerated alternatives to the systemic regimen. However, their value in the management of uncomplicated skin infections is not yet clearly defined. This literature review discusses various topical antibiotic treatment options for uncomplicated skin infections, including over-the-counter and prescribed regimens.

Keywords: antimicrobial resistance • Staphylococcus aureus • topical antibiotics • uncomplicated skin infection

Topical antibiotic treatment for uncomplicated skin and skin structure infections: review of the literatureExpert Rev. Anti Infect. Ther. 7(8), 957–965 (2009)

Uncomplicated skin infections account for almost 200 million physician visits in the USA annually, with treatment costs estimated to be in excess of US$350 million each year. The man-agement of these infections lends itself to more direct or topical therapy for a number of reasons, including the ability to achieve high local drug concentrations at the site of the infection, the low incidence of systemic side effects due to low or no absorption, the ability to combine several agents to empirically treat a range of potential cutaneous pathogens, cost–effectiveness, patient compliance, and the potential to limit anti-microbial resistance selection among other bac-teria in the body compared with oral or parenteral antimicrobials [1].

In the USA, a variety of topical agents are available over the counter (OTC). Antimicrobial ointments containing neomycin, polymyxin B and bacitracin have been used since the 1950s as a prescription product to prevent superficial wound infections and have been made available OTC since the 1970s. The US FDA has pub-lished rules (1977, revised in 1987) that establish

appropriate labeling of OTC topical antibiotics and the conditions under which products are generally recognized as safe and effective for use without medical supervision, stating that OTC topicals are to be used as ‘first aid’ in the preven-tion of infection while noting a lack of evidence for treatment of established infections [101].

From a therapeutic perspective, it is important to appreciate the significant and growing use of topical antibiotics to manage uncomplicated and superficial skin infections. At present, the range of diagnoses representing uncomplicated skin infections in the USA covers five accepted groups, named in descending order of frequency: secondarily infected traumatic lesions (SITLs); cellulitis or abscesses, secondarily infected dermatoses (SIDs), impetigo, and carbuncles or furunculosis. These infections account for over 150 million physician-office visits annu-ally during which over 50 million prescriptions are written. The breadth of agents prescribed is remarkable given the etiology of these infec-tions. The distribution and formulation of anti-microbials written for these five indications is

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Literature Review Pangilinan, Tice & Tillotson

shown in Table 1. Mupirocin (Bactroban®) is the most frequently prescribed topical agent with 5.6 million prescriptions accounting for US$177 million in 2006 [2]; however, the use of OTC topical agents is more difficult to track and measure.

Although there may be fewer systemic adverse effects with topi-cal therapy, there remains the possibility of local allergic reac-tions to topically applied antimicrobials or their vehicles. Resistant organisms may also emerge with prolonged exposure. Despite their potential advantages, topical antimicrobials may be of lim-ited value in established infections because they penetrate poorly into the skin. They have, however, been evaluated for efficacy in mild uncomplicated skin and skin structure infection (uSSSI), including impetigo, SIDs and secondarily infected wounds. Topical antibiotics are not presently indicated for deeper infections such as cellulitis and abscesses, or accompanied systemic disease.

The emergence of methicillin-resistant Staphylococcus aureus (MRSA) and multidrug resistance among both patients and out-patients continues to increase [3]. This has important implications for treatment guidelines to deal with the problem of increasing resistance [4]. Tillotson et al. recently evaluated the incidence of MRSA from community-acquired skin and wound infections cultured in the USA in 2007 [5], and found that the rate of MRSA

did not vary markedly between intensive care, in patient-acquired or community-acquired S. aureus, with almost 60% of isolates being methicillin resistant.

The incidence of problematic resistant pathogens has increased and poses significant empiric prescribing challenges for the pri-mary healthcare provider. Thus, antimicrobials with new mecha-nisms of therapy need to be developed to combat the ever-increas-ing challenge we face from the microbial world. This presentation reviews the literature and FDA criteria to determine the effective-ness of topical antibiotics in the prevention and treatment of uSSSI, including impetigo, SIDs and secondary infected wounds.

MethodsA search was conducted to find clinical trials of topical antimicro-bials for uSSSI. The MEDLINE database was searched for articles from 1966 through to August 2007 using the subject terms ‘topical antibiotic’, ‘mupirocin’, ‘retapamulin’, ‘fusidic acid’, ‘triple anti-biotic ointment’, ‘neosporin’, ‘neomycin’, ‘bacitracin’ and ‘poly-myxin B’. The Cochrane Library was also searched using these same terms. References from these papers were reviewed in an attempt to identify additional articles. Pharmaceutical companies and the FDA were also contacted to obtain unpublished data and/

or additional information regarding studies done with OTC topical agents.

The studies included in this review were limited to randomized clinical trials of topical antibiotics and treatment of uncom-plicated skin infections including impetigo, infected wounds and infected dermatitis. Only clinical trials using human subjects that were published in English were used, and studies were reviewed with regard to outcome criteria. Owing to the hetero-geneity among study populations and vary-ing outcomes, a quantitative summary was not performed.

ResultsThe search strategy identified a total of 230 titles, of which 29 studies met the inclusion criteria described in the Methods section. While major limitations were noted with regard to numbers of patients, con-trols, use of placebo, choice of comparator and outcome criteria, the qualifying studies were grouped and analyzed for data relating to impetigo, secondary infected wounds and prevention of infection (Tables 2–5).

ImpetigoThree trials compared topical treatment with a placebo for impetigo. Superior effi-cacy of antibiotics retapamulin (Altabax®,

GlaxoSmithKline, UK) and fusidic acid over placebo for impetigo was observed in

Table 1. Formulation and distribution of antibiotics prescribed for the five most common uncomplicated skin infections in the USA in 2006.

Antibiotic (%)

SITL SID Cellulitis/abscess

Impetigo Carbuncle/furunculosis

Oral 57 19 80 49 77

Topical 19 77 6 49 20

Intravenous 23 1 13 1 2

Other 1 3 1 1 1

Antibiotic (% prescribed)

Cephalexin 25 12 33 20 19

Mupirocin 0 7 4 41 15

Augmentin 6 0 9 22 7

Doxycycline 0 6 0 0 6

Tetra/minocycline

0 6 5 0 0

Amoxicillin 2 0 0 2 5

TMP-SMX 3 2 7 0 20

Metronidazole 0 28 0 0 0

Fluoroquinolone 8 0 9 0 0

Other* 53 36 31 12 25

OTC 13 3 2 2 2

Total prescription (millions/year)

25 8 11 8 1.4

*Includes dicloxacillin, vancomycin, piperacillin–tazobactam, ceftriaxone, cefazolin, ceftibuten, cefdinir and silver-containing agents.OTC: Over the counter; SID: Secondarily infected dermatoses; SITL: Secondarily infected traumatic lesion; TMP-SMX: Trimethoprim–sulfamethoxazole.

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Literature ReviewTopical antibiotic treatment for uncomplicated skin & skin structure infections

two out of three studies [6,7]. One study using mupirocin, although limited by the low number of patients evaluated, did show a trend towards benefit, but was not significant [8]. Use of mupirocin with impetigo was demonstrated to be comparable with oral therapy (erythromycin) in seven out of seven studies [1,9–13], and one of the studies showed clinical failure due to microbiological resistance to the studied oral antimicrobial [13].

Topical agents, specifically mupirocin and retapamulin, were significantly better than placebo at producing a cure or improve-ment at 7–14 days in patients with impetigo, and were probably

at least as effective as the oral antimicrobials erythromycin and/or flucloxacillin. Owing to better tolerability compared with oral anti-biotics, topical antibiotics should be used initially in treating impe-tigo. Depending on the conditions (e.g., number and location of lesions), these conclusions are consistent with previously published guidelines by the Infectious Disease Society of America and meta-ana lysis by the Cochrane Library, although it is unclear how the rise of community-acquired methicillin-resistant S. aureus (CA-MRSA) should affect treatment choices for impetigo [6,14]. Table 2 summarizes the studies on topical antimicrobials for impetigo.

Table 2. Studies on topical antimicrobials for impetigo.

Antibiotics vs comparator (cases)

Clinical failure (%)

Micro-biologicfailure (%)

Outcome measures Notes Ref.

Mupirocin (18)Placebo (20)

015

1062

Subjective resolution of lesions within 12 days

Follow-up time to 14 daysSmall numbers of patients

[42]

Mupirocin (101)Erythromycin or flucloxacillin (99)

1

6

NR Clinical improvement within 10 days

Susceptibility testing not performed [10]

Mupirocin (30)Erythromycin (32)

07

NR Improvement in number of lesions within 7 days

Clinical cure despite resistance to mupirocinFollow-up 7 days after completion

[11]


410

2935

Improvement within 7 days

One month follow-up demonstrated significant recurrence in erythromycin-treated group (19 vs 6%)

[12]


00

1263‡

Clinical improvement within 21 days

Good clinical cure with erythromycin despite high number of microbiological failuresClinical efficacy determined by scoring for the following features: exudates, crusting, erythema and itching/pain

[13]


98

NR Clinical improvement in 14 days

Susceptibility testing not performed [1]


00

00


Signs of more side effects with erythromycinClinical effectiveness determined by SIRS‡

[12]


224‡


Clinic generally serves a population with crowded households that belong to the lower and middle socioeconomic classes in IsraelFailure was associated with erythromycin resistanceFollow-up continued until 1 week after completion of treatment (relapse of 14%, no side effect sign difference between groups)

[6]

Fusidic acid (78)Placebo (82)

1341*

068*


Significant improvement only seen at week 1, by week 4 similar clinical and microbiological successImprovement defined as a decline in affected area, number of lesions, or both

[7]

Retapamulin (345)Fusidic acid (172)

0.96

1.76.1

Clinical improvement at EOT (5–7 days)

MRSA was isolated in 2.9%; fusidic acid resistance was detected from 5.6%; mupirocin resistance in 3.8%

[43]

Retapamulin (139)Placebo (71)

1548*


No MRSA strains were isolated [8]

*p < 0.05.‡SIRS determined by presence of exudates/pus, crusting, erythema/inflammation, itching and pain.EOT: End of treatment; MRSA: Methicillin-resistant Staphyloccocus aureus; NR: Not reported; SIRS: Skin infection rating scale.



Infected wounds or SITLsIn one study using mupirocin and another using retapamulin, treatment efficacy of topical agents in infected wounds was com-parable with orally administered cephalexin [15,16]. However, one reviewed study representing data from 42 patients did not show clinical advantage of the topical agent mupirocin when compared with vehicle control for SITLs [17].

Mupirocin and retapamulin appeared to be at least equivalent to oral antimicrobial in terms of clinical and bacterial cure rates, but because these studies lacked a control group of vehicle alone, the results are difficult to interpret, since previous studies demon-strated equivalent clinical improvement between topical antibiotic and protectant. In addition, several studies reviewed for the treat-ment of secondary infections combined a significant portion of primary infected individuals in the data sets, further complicating sufficient ana lysis [17–23]. Table 3 summarizes the studies for topical antimicrobials in infected wounds.

Infected dermatitis or SIDsIn one study using mupirocin and one study using retapamulin, efficacy of topical antimicrobials with SIDs was demonstrated as comparable with cephalexin [24,25]. One placebo controlled study failed to find that mupirocin was statistically better in terms of clinical improvement, but it did show significant microbiologi-cal success [26]. A weakness of the studies reviewed was that the authors did not describe how they determined that an existing dermatitis was secondarily infected.

Although mupirocin did show antimicrobial cure in SIDs, it did not show a significantly improved clinical cure rate com-pared with vehicle placebo. Both mupirocin and retapamulin demonstrated high clinical success rate in SIDs, but did not show significant superiority to oral antimicrobials, which decreases the value of these studies as they were not placebo controlled. In addition, the relatively short follow-up makes it impossible to determine if treatment had an impact on recurrence, treatment

Table 3. Topical antimicrobials for infected wounds.

Antibiotics vs comparator (cases)

Clinicalfailure (%)

Micro-biologicfailure (%)

Outcome measures

Notes Ref.

Mupirocin (30) Erythromycin (30)

3 18

019


Wide variation in skin infections included in studyNo statistical ana lysis performed

[20]

Mupirocin (163)Fusidic acid (191)

1414

NR Clinical improvement at 6–8 days

Swabs not taken after treatment to determine bacterial curesMix of primary and secondary infections

[21]

Mupirocin (22)Placebo base (20)

2545

4451

Clinical improvement at 5 weeks

Infected skin leg ulcersTreatment duration: 4 weeksIsolates included Gram-negative and -positive bacteria

[22]

Mupirocin (24) Neosporin (26)

422

013

Clinical improvement at 7 days

Secondary infections were mostly infected ulcersNo statistical ana lysis performed

[23]

Mupirocin (35) Fusidic acid (35)

44

313


Included primary and secondary infections [24]

Mupirocin (53) Tetracycline (58)

1511

220


Included primary and secondary infections [25]

Mupirocin (237)Fusidic acid (138)

37

711


Clinical cure seen despite microbiological failure [26]

Mupirocin (357)Cephalexin (349)

55

31

Clinical improvement within 3 weeks

Secondary infected wounds included small laceration, abrasion or sutured woundAttempted to use objective data to determine if wound was infected along with subjective assessment of investigator

[18]

Retapamulin (1268)Cephalexin (636)

10.58.1

10.89.8

Clinical improvement within 17–19 days

Study design was developed in accordance with the draft guidance issued by the US FDA on antimicrobial drugs for the treatment of uncomplicated and complicated skin and skin structure infectionsPhysician assessment done with SIRS*

[19]

*SIRS determined by presence of exudates/pus, crusting, erythema/inflammation, itching and pain.NR: Not reported; SIRS: Skin infection rating scale.



failure or re-infection, especially in chronic skin conditions. Table 4 summarizes the studies for topical antimicrobials for infected dermatitis.

Prevention of infectionThe studies reviewed varied considerably in etiology, host factors and outcome measures. One large study involving contaminated wounds of varying severity found statistically significant benefit to bacitracin and neomycin compared with placebo [27]. Another study involving excision of neoplasm showed a benefit of pretreat-ment with mupirocin compared with chlorhexidine [28]. By con-trast, a large study done on clean surgical wounds demonstrated no difference using bacitracin when compared with white petro-latum ointment [29], and concluded that the petrolatum ointment is a safe effective ambulatory treatment that possessed an equally low infection rate and minimal risk for induction of allergy. A comparative study of mupirocin with triple-antibiotic ointment (TAO) demonstrated no significant differences between these two agents [30], although a clinical trial showed that a novel TAO con-taining cetrimide, bacitracin and polymyxin B sulfate reduced the incidence of clinical infection from 12.5 to 1.6% when compared with a placebo (p < 0.05) [31].

Overall, when baseline infection rates were low, it was hard to determine a statistical advantage of the topical antimicrobial, although benefits were apparent when using both OTC and pre-scription medications. Disadvantages to using topical antibiotics include the increased costs and potential for local irritation, contact dermatitis and anaphylaxis. Topical agents including the OTC antimicrobials or combinations have been shown to be effective in prevention of infection in minor wounds, and with increasing MRSA infections it is a concern as to how effective these agents will remain. Table 5 summarizes the studies for topical antimicrobials for prevention of infection of wounds.

DiscussionCurrently, there are promising new topical antibiotics, including mupirocin and retapamulin, seeking indication for bacterial skin infections. These topical antibiotics may have a role in the treat-ment of infections as they often have fewer systemic side effects and a lesser impact on the normal flora of the body. Because these theoretical advantages may lead to new opportunities for drug development, it is important to determine their efficacy in the treatment of skin infections. This systematic review of prior data describing outcomes of trials using topical antimicrobials on uncomplicated skin infections was instructive, despite being lim-ited by the lack of well-designed trials. Problems encountered in the literature reviewed included low number of cases, lack of placebo controls, unclear criteria of classifying infections, varying outcome separators, and lack of adequate follow-up. Because of the clinical heterogeneity between studies, conflicting results could not be resolved with meta-ana lysis.

Mupirocin, the most frequently prescribed topical agent, has developed resistance in certain populations, such as nursing-home residents [32–34], Veterans Affairs patients [35] and commu-nity healthcare settings [36], with some populations showing 50% high-level resistance [37]. Simor et al. identified 7% of MRSA strains from across Canada that were high-level mupirocin resist-ant, a significant increase over the previous 5 years (p < 0.001) and that these strains were more likely to be resistant to fusidic acid (21 vs 4%, p < 0.001), a topical agent used outside of the USA [38]. While retapamulin, a new pleuomutilin (Altabax), has been shown to be active in vitro against many high-level mupirocin-resistant strains, the clinical data supporting this are lacking.

Regarding TAO, a recent review concluded that it remains effective for prevention and treatment of infections in minor skin trauma and that its use should be further investigated [39].

Table 4. Studies of topical antimicrobials for infected dermatitis.

Antibiotics vs comparator

Clinical failure (%)

Micro-biologic failure (%)

Outcome measures

Notes Ref.

Mupirocin (49) Placebo (49)

2052‡

11100*

Clinical improvement at 2 weeks

Recolonization to pretreatment levels occurring in 2–4 weeksClinical severity decreased for 4 weeks after transplantationClinical and patient rating scale used to determine improvementCross-over study

[44]

Mupirocin (48)Placebo (44)

2135

3186*

Clinical improvement within 2 weeks

Subset of patients infected with Staphylococcus aureus or Streptococcus pyogenes had signs of better clinical improvement in both infection and dermatitis

[29]

Mupirocin (82) Cephalexin (77)

11 18

5072*


High drop-out rateFollow-up 7–9 days after treatment completion

[27]

Retapamulin (363) Cephalexin (156)

14.110.3

13.3 7.5


Used SIRS‡

Final follow-up at 17–19 days from start of transplantation

[28]

*p < 0.05.‡SIRS determined by presence of exudates/pus, crusting, erythema/inflammation, itching and pain.NR: Not reported; SIRS: Skin infection rating scale.



Studies comparing topical antimicrobials with oral cephalexin or erythromycin, while important in establishing the efficacy of either method, are limited by the increasing rate of infections caused by CA-MRSA. Current practice is to treat mild uncom-plicated infection of the skin that may be due to MRSA with trimethoprim/sulfamethoxazole, clindamycin, doxycycline and minocycline. As CA-MRSA continues to evolve, it is impor-tant to update susceptibility testing, although there are limita-tions of the current testing methods for topical antimicrobials. For example, serum breakpoints are not appropriate for topi-cal agents which, when applied, are several magnitudes higher (5000–20,000 mg/ml) than serum concentrations. A confound-ing factor is that some studies have shown no difference in clini-cal outcomes whether or not organisms were ‘susceptible’ to the compounds applied. Differential penetration of topical antibiotics may also lead to contradictory results.

Well-designed trials of these topical antibiotics are urgently needed to include coverage of CA-MRSA in mild uSSSI. The role of topical antimicrobials remains incompletely defined. Ellis [40] in his review of Rajendran et al. [41] highlighted several issues in the management of uncomplicated skin and soft-tissue infections including the role of adjunctive antibiotics and other approaches. He also confirms that future trials will need to be large, random-ized studies with appropriate controls and appropriate end points

including an adequate follow-up period to determine impacts on prevention of recurrence. Validation of current breakpoints for topical antimicrobials needs to be determined by correlation with clinical outcomes, and trials need to include oral antimicro-bials active in infections due to MRSA. Future studies should also utilize more objective diagnostic criteria to properly classify skin infections, as determining the severity of skin infections is inherently subjective, making treatment decisions difficult. Proper classification of infections may elucidate which infections would benefit the most from this form of treatment. Patient comorbidi-ties should be taken into account to determine population tar-geted treatment and studies need to determine tissue penetration of different topical agents to better predict possible effectiveness in deeper skin infections.

Summary & conclusionThe emergence of MRSA in the community has clearly had an impact on the management of skin infections. The CA-MRSA variants often possess virulence factors which predispose patients to more serious outcomes unless therapy is appropriate and early. Topical agents, although shown to be better than placebo in impe-tigo and less serious conditions, may not be ideal when trying to provide empiric cover for highly virulent strains of MRSA. Use of mupirocin and possibly other topicals to help reduce nasal

Table 5. Studies of topical antimicrobials for prevention of infection of wounds.

Antibiotics (cases) Infection rate (%)

Outcome measures

Notes Ref.

TAON (10)

Placebo (10)0100

Purulence or lack of re-epithelialization at 3–5 days

Minor skin trauma was artificially produced by superficial scarification with a needle or exposure to ammonium hydroxideWounds were inoculated with either Staphylococcus aureus or Streptococcus pyogenesData ana lysis not presented in paper

[45]

Mupirocin (74) Cephalexin (33) Chlorhexidine (23)

0322*

Purulence or dehiscence at 2 days

Wounds from excision and suture of skin neoplasmTreatment was started 2 days prior to excisionWounds were swabbed for bacterial culture if the wound was purulent

[32]

Bacitracin (109)TAO

N (110)

SIL (99)Placebo (108)

5.54.512.117.6*

Clinical infection at 1 week

Traumatic soft tissue wounds (<12 h old) needing suturingMilitary hospitalInfection was determined by the presence of fever, erythema, edema, induration, tenderness, warmth, exudates, adenopathy and lymphangitis

[31]

Bacitracin (444)Placebo (440)

0.92.0

Purulence, erythema or tenderness plus positive culture within 28 days

Patients who underwent a surgical procedure in the dermatology clinicSurgical procedures included shave biopsy, punch biopsy, ED & C, excision, Mohs micrographic surgery and dermabrasionCultures obtained if pus, erythema or tenderness was presentLow total infection rate

[34]

TAOC (62)

Povidone iodine (67)Placebo (48)

1.63.012.5*

Clinical infection in 3 days plus positive cultures

School children presenting to school nurse with scratches, cuts and abrasionsCetrimide not available in the USA

[35]

Mupirocin (50)TAO

N (49)

12 6.1

Clinical infection within 7 days

Patients had uncomplicated soft tissue wound within the last 24 h presenting to EDAll wounds underwent standard wound care and repair procedures.Infection determined by evaluating for fever, erythema, edema, induration, swelling, warmth, exudates, adenopathy and lymphangitis

[36]

*p < 0.05.ED: Excision and drainage; ED & C: Electrodesiccation and curettage; SIL: Secondarily infected lesion; TAO: Triple antibiotic ointment; TAO

C: Cetrimide, bacitracin and

polymyxin B; TAON: Neomycin, bacitracin and polymyxin.



colonization has been shown to be effective in the short term but resistance has developed in some communities, notably in Canada, which negates the effectiveness of this agent. New and alternative topical approaches, perhaps in combination with sys-temic regimen may provide new empiric approaches to managing these increasingly complex infections.

Expert commentary & five-year viewOwing to the lack of routine culture and susceptibility testing over the past 20 years, marked changes in both the causative pathogens in skin and soft tissue infections have gone unnoticed, especially at the primary care level. Lack of funding and access to laboratory facilities may have played a role in this decrease in appropriate testing; however, the inability to recognize new pathogens or dramatic increases in resistance will lead to greater cost increases as patients fail inappropriate therapy.

The recognition of CA-MRSA in the past 5 years has stimu-lated expanded susceptibility testing but often only in failed cases. Awareness of resistance to agents other than b-lactams is essential. The unpredictable susceptibility of the macrolides, fluoroquino-lones and other classes should prevent them from being prescribed empirically in patients at risk of CA-MRSA.

The true pathogenicity mechanism in CA-MRSA is still being debated; however, a major concern as the community-acquired clones ‘merge’ with hospital-acquired strains is the possible acquisition by

the latter of more resistant strains of the Panton–Valentine leuko-cidin (PVL) gene. Potentially, this is a very dangerous ‘superbug’ with a diminishing number of therapy options.

Recognition of PVL-positive MRSA is important in terms of ini-tiation of aggressive and appropriate therapy. Point of care testing must be available at the primary care level.

As MRSA continues to increase in the community, the likeli-hood of these clones becoming more resistant while retaining their virulence mechanisms is a major concern. Whether or not new topical agents are likely to be developed, combinations may be a viable future option for effective treatment, although regu-latory hurdles make this option very difficult both technically and financially. Revisiting TAO may also be an option, until the bacteria figure that out too.

Financial & competing interests disclosureGlenn Tillotson is a full-time employee of ViroPharma Incorporated, PA, USA. Alan Tice has received income for research and consulting from Replidyne, Pfizer and Astellas. This work has been supported by the Staphylococcus Institiute, a component of the OPAT Outcomes Registry (a nonprofit organization). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• The literature and internet information sources as well as recent abstracts were searched for studies relating to topical antimicrobial treatment of uncomplicated skin infections including impetigo, secondary infected wounds and secondary infected dermatitis. Despite major limitations in the studies owing to number of patients, adequate controls, use of placebo and outcome criteria, 29 studies were identified that met the inclusion criteria. A review of these studies noted the following: – Efficacy of antibiotics over placebo for impetigo was demonstrated in two of three studies (using retapamulin [Altabax®] and fusidic acid) – Efficacy with impetigo was demonstrated to be comparable with oral therapy (erythromycin) in seven of seven studies (using mupirocin [Bactroban®])– Prevention of infection in clean or early wounds (vs placebo) was demonstrated in two studies with ‘triple antibiotic ointment’ (e.g., Neosporin®)– Efficacy with infected dermatitis was demonstrated as comparable with cephalexin with one study each of mupirocin and retapamulin, but one study failed to find that mupirocin was statistically better than placebo – Efficacy in wounds already infected was demonstrated comparable with cephalexin with one study each of mupirocin and retapamulin

• In conclusion, this review found evidence for the use of topical antibiotics for impetigo and prevention of skin infections, althougdata are limited. Further research is needed to establish the value of topical antibiotics and indications for their use with infected dermatitis and established wounds.

ReferencesPapers of special note have been highlighted as:• of interest•• of considerable interest

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•• Providesrecentguidelinesandrecommendationsonthemanagementofcommonskininfectionsandisavaluablereferenceforclinicians.

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29 Smack DP, Harrington AC, Dunn C et al. Infection and allergy incidence in ambulatory surgery patients using white petrolatum vs bacitracin ointment. A randomized controlled trial. JAMA 276(12), 972–977 (1996).

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•• Providesevidencefortheuseofanoveltopicalantimicrobialgelcontainingcetrimide,bacitracinandpolymyxinBsulfateforfirst-aidprophylaxisforminorwounds.

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•• Documentsmupirocinresistanceinmethicillin-resistantStaphylococcus aureus isolatesfromsurgicalintensivecareunitpatients,despitelowlevelsofin-hospitalmupirocinuse.

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•• Describestheepidemiologyandlaboratorycharacterizationofmupirocin-resistant MRSAstrainsinCanadianhospitalsandestablishesthatdifferentstrainsofMRSAarerecoveredfrompatientswithdistinctclinicalandepidemiologiccharacteristics.

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