The European Evidence-Based Guidelines for the Treatment of Acne use the relatively straightforward classification

system of comedonal acne; mild to moderate papulopustular acne; severe papulopustular acne and moderate
nodular acne; and severe nodular acne and conglobate acne.
[!

A simple classification system based on predominate lesion morphology was also adopted by the authors of the
Evidence-Based "ecommendations for the #iagnosis and Treatment of $ediatric Acne% comedonal acne with closed
and open comedones; inflammatory acne& characteri'ed by erythematous pustules& papules& nodules& or cystli(e
nodular lesions; or mi)ed& in which both types of lesions are present.
[*!
Acne severity is then designated as mild&
moderate& or severe according to the number and type of lesions and the amount of s(in involved.
Antibiotics wor( for + reasons% ,irst& because antibiotics decrease P acnes levels& and second& because some
antibiotics& namely the tetracycline family& are anti-inflammatory in and of themselves. The tetracycline family
includes tetracycline& minocycline& and do)ycycline& although the newer-generation tetracycline derivatives
-minocycline& do)ycycline. are now the most commonly used antibiotics for the treatment of acne in the /nited
0tates. The tetracycline family has antigranuloma-forming activity through the inhibition of protein (inase 1. The
tetracyclines are antichemotactic for white blood cells and probably have other actions we have not yet discovered;
the tetracyclines are a remar(able group of drugs. 0o there are + mechanisms for tetracyclines and 2 mechanism
for the rest of the antibiotics; namely& (illing P acnes.
There are + issues. 3ne is antibiotic resistance in P acnes, ma(ing P acnes less susceptible to antibiotics& both oral
and topical& that used to wor(. The other issue can be posed in the form of a 4uestion% #oes acne therapy with
antibiotics raise up resistant populations of pathogens on the bodies of people being treated for acne5 6et7s tal(
about the first issue first.
8t is clear that P acnes that is resistant to erythromycin and clindamycin is much less responsive to treatment in
acne& and patients with these resistant organisms do not do as well as patients who have sensitive organisms. The
incidence of resistance to erythromycin and clindamycin has risen steadily since these drugs were introduced about
9: years ago. 8t is now at the point that oral and topical erythromycin and clindamycin are useless as monotherapy
in acne and contribute very little to any acne therapy& even when used in combination therapy. There are patients
who seem to have acne that is resistant because their bugs are resistant to those + drugs. ;ith do)ycycline and
minocycline& you can show that the minimal inhibitory concentration in P acnes has crept upward over the years but
does not reach the level of true resistance.
The bigger issue of whether long-term acne therapy is raising up resistant populations on patients is tougher to
answer. ;e (now that 9: or : years of using oral tetracyclines has not resulted in an increase in 0taphylococcus or
0treptococcus infections in those patients. <owever& at the same time& we note that these patients carry bugs that
could learn to be resistant to do)ycycline with enough e)posure. Staphylococcus aureus would be a particular
tragedy because even the resistant 0taphylococcus infections& such as methicillin-resistant S aureus-="0A.& at
least in most geographic areas& tend to be susceptible to do)ycycline. 8f we overuse do)ycycline and educate the
="0A to resist do)ycycline& we will have lost a very safe and effective drug to treat ="0A infections.
;henever you treat a human with an antibiotic& the presumption is that there is a good reason for it. ,or e)ample&
ta(e a teenager with scarring acne& which is a guaranteed ris( vs a theoretical ris( of generating resistance
somewhere on the patient7s body. 8 will choose to treat the patient7s acne first and worry second about resistance.
This is not being cavalier about the issue of resistance& it is being more concerned about the patient who is in front
of me.
3ral antibiotic use should be minimi'ed to reduce the possibility of resistant strains of P acnes. 8f you can get a
patient better without antibiotics& great. 8f you have to use antibiotics& do it boldly and get it over with as 4uic(ly as
you can.3ral antibiotics are generally used in patients with moderate to severe inflammatory acne. 3ne consensus
panel has recommended limiting the duration of oral antibiotic therapy to 2+ to 2> wee(s.
[?!

There are several ways to limit the duration of oral antibiotic treatment. 3ne would be to not fiddle around with a low
dose but to give a higher dose in combination with a second drug that will wor( to ma(e the acne more treatable in
time. That second drug would be a topical retinoid% ta'arotene& tretinoin& or adapalene. Topical retinoids have a
direct effect on the formation of comedones and also have anti-inflammatory effects. These drugs are used in the
treatment of both comedonal and inflammatory acne and are generally recommended in the initial management of
most patients with acne. All these retinoid drugs will help get patients off oral antibiotics more 4uic(ly if you use one
of them from day 2. $atients who have done well after + or 9 months of oral antibiotic therapy& which will be the
ma@ority of patients& can be ta(en off the antibiotic and maintained @ust on the topical regimen. That is a great way to
get people off oral antibiotics relatively 4uic(ly.
8ncluding ben'oyl pero)ide in acne regimens is another tactic to avoid bacterial resistance. Ben'oyl pero)ide is a
bactericidal agent that is directly to)ic to microorganisms. =a(ing sure that ben'oyl pero)ide is part of any topical
antibiotic regimen will discourage the development of resistance in P acnes and& presumably& any bacteria it comes
in contact with. 8f you are going to use topical clindamycin& ma(e sure ben'oyl pero)ide is on board too& whether it is
in a combination ben'oyl pero)ide-clindamycin product or a ben'oyl pero)ide wash. Erythromycin-ben'oyl pero)ide
combination products are also available.
A fi)ed combination of adapalene and ben'oyl pero)ide is available in a gel formulation. 8n a -wee(& open-label
study& this fi)ed-combination product inhibited both antibiotic-resistant and antibiotic-susceptible P acnes.
[A!

Another way to avoid bacterial resistance is to prescribe isotretinoin for severe& resistant acne. 8n the /nited
Bingdom& for e)ample& the standard of care is 9 months of therapy with an oral antibiotic and a topical retinoid. 8f the
patient is not clear after 9 months& you go right to isotretinoin. 8n the /nited Bingdom& they worry more about
bacterial resistance than they do about birth defects. 8n the /nited 0tates& we ta(e a different approach and worry
more about the teratogenicity of isotretinoin than we worry about antibiotic resistance. 8t is something to ponder
when ma(ing treatment decisions.C
Another option is hormonal treatment. 8t only wor(s in women because men get femini'ed when you inhibit their
androgens& but in women& there are great approaches. 0pironolactone entered the world *: years ago as a diuretic&
but it is also an oral antiandrogen that has been used off-label in the /nited 0tates for the treatment of acne in
women for appro)imately 9: years. 3ral spironolactone is an efficacious way to treat fairly severe acne without
going anywhere near an antibiotic. **
8n the European /nion& cyproterone acetateDethinylestradiol is approved for the treatment of moderate to severe
acne related to androgen sensitivity -with or without seborrhea. in women of reproductive age for whom topical or
systemic antibiotic acne treatment has failed. This drug is not available in the /nited 0tates& and recent concerns
about the ris(s for venous thromboembolism have spurred labeling changes in the European /nion.
[2:!

The problem of antibiotic resistance has informed current guidelines for the treatment of acne vulgaris -Tables 2 to
..
Table 1. Pediatric Treatment Recommendations for Mild Acne
Initial Treatment B$
OR
Topical retinoid
OR Topical 1ombination TherapyC
B$ E Antibiotic
OR
"etinoid E B$
OR
"etinoid E Antibiotic E B$
If Inadequate Response*

Add B$ or retinoid& if not already prescribed

OR
1hange topical retinoid concentration& type& andDor formulation
OR
1hange topical combination therapy
B$ F ben'oyl pero)ide.
CTopical fi)ed-combination prescriptions are available.
GAssess adherence.
,rom Eichenfield 6,& et al.
[*!

Table 2. Pediatric Treatment Recommendations for Moderate Acne
Initial Treatment Topical 1ombination TherapyC
"etinoid E B$
OR
"etinoid E -B$ E Antibiotic.
OR
-"etinoid E Antibiotic. E B$
OR 3ral antibiotic
E
Topical retinoid E B$
OR
Topical retinoid E Antibiotic E B$
If Inadequate
Response*

1hange topical retinoid concentration& type&
andDor formulation
AND/OR
1hange topical combination therapy
AND/
OR
Add or change oral antibiotic
1onsider hormonal therapy for
female patients
H

OR 1onsider oral
isotretinoin
H

B$ F ben'oyl pero)ide.
CTopical fi)ed-combination prescriptions are available.
GAssess adherence.
H1onsider dermatology referral.
,rom Eichenfield 6,& et al.
[*!

Table 3. Pediatric Treatment Recommendations for Seere Acne
Initial Treatment
!
1ombination TherapyC
3ral antibiotic
E
Topical retinoid
E
B$
ED-
Topical antibiotic
If Inadequate Response
!
1onsider changing oral antibiotic
AND
1onsider oral isotretinoin
1onsider hormonal therapy for female patients
H

B$ F ben'oyl pero)ide.
CTopical fi)ed-combination prescriptions are available.
GAssess adherence; consider change of topical retinoid.
H1onsider dermatology referral.
,rom Eichenfield 6,& et al.
[*!

Table ". #uropean Acne Treatment $uidelines
%i&'(stren&t' Recommendations Medium(stren&t' Recommendations Alternaties for )emale Patients
*omedonal acne+ Io high-strength
recommendation
Mild(to(moderate papulopustular
acne+ Adapalene E B$ -fc. OR B$ E
clindamycin -fc.
Seere papulopustular,moderate
nodular acne+ 8sotretinoin
Seere nodular,con&lobate acne+
8sotretinoin
*omedonal acne+ Topical retinoid
Mild(to(moderate papulopustular acne+ A'elaic
acid OR B$ OR topical retinoid OR systemic
antibiotic E adapalene
Seere papulopustular,moderate nodular acne+
0ystemic antibiotics E adapalene OR systemic
antibiotics E a'elaic acid OR systemic antibiotics E
adapalene E B$ -fc.
Seere nodular,con&lobate acne+ 0ystemic
antibiotics E a'elaic acid
Seere papulopustular,moderate nodular
acne+ <ormonal antiandrogens E topical
treatment 3" hormonal antiandrogens E
systemic antibiotics
Seere nodular,con&lobate acne+ <ormonal
antiandrogens E systemic antibiotics
B$ F ben'oyl pero)ide.
,rom Iast A& et al.
[!

Medscape+ -'at is t'e current role of topical antibiotics in t'e treatment of acne. &ien t'e problem of
antibiotic resistance and t'e efficac/ of ot'er topicals suc' as ben0o/l pero1ide and topical retinoids2
3r -ebster+ Topical erythromycin and clindamycin as monotherapy have little role in treating acne because of the
predominance of resistant strains of P acnes. $roducts that pair erythromycin or clindamycin with ben'oyl pero)ide
remain effective.
Medscape+ 4ou 5ere part of t'e &roup t'at deeloped t'e #idence(6ased Recommendations for t'e
3ia&nosis and Treatment of Pediatric Acne. 5'ic' 5ere publis'ed in 2713.
89:
T'ese recommendations 5ere
deeloped t'rou&' t'e American Acne and Rosacea Societ/ and endorsed b/ t'e American Academ/ of
Pediatrics. -'/ are t'ese &uidelines important2
3r -ebster+ Acne is one of the most common s(in conditions in children and adolescents& but until now there have
not been standard guidelines for the management of pediatric acne. 3ne of the messages of the guidelines is that
treatment should be appropriately aggressive. ;hen a (id has acne& even at an age when you do not e)pect acne&
the child7s age is not a reason to not treat or to undertreat. Jounger (ids deserve sufficiently vigorous treatment to
get them better& @ust li(e older (ids. That message needs to be emphasi'ed& especially to pediatricians. Acne is not
nothing& and it is reasonable to treat it properly even in a younger child.
* 8n the /nited Bingdom& isotretinoin must be prescribed under the supervision of a dermatologist with an
understanding of the ris(s of retinoid treatment and the monitoring re4uirements for the use of isotretinoin. A
$regnancy $revention $rogramme is also in place.
[>!

CC/0 ,ood and #rug Administration labeling for spironolactone carries the following bo)ed warning% K0pironolactone
has been shown to be a tumorigen in chronic to)icity studies in rats. 0pironolactone should be used only in those
conditions described under 8ndications and /sage. /nnecessary use of this drug should be avoided.K