Staphylococcus aureus Infections in Children: The Implications of Changing TrendsSheldon L. Kaplan, MD

In this issue of Pediatrics, Sutter et

al1 report the antibiotic susceptibility

trends of Staphylococcus aureus

isolates recovered from >39 000

children who received care at sites

within the US military health system

from 2005 through 2014. S aureus is

the most common pathogen causing

skin and soft tissue infections (SSTIs)

as well as some invasive infections

such as osteomyelitis and septic

arthritis in children.2 S aureus is also

1 of the most common organisms

isolated from children with health

care–associated infections, regardless

of whether these infections had

their onset in the community or

were acquired in the hospital. Thus,

the initial empiric treatment of an

SSTI or invasive infection in a child

almost always includes an antibiotic

effective against S aureus. Before

the 1990s, penicillinase-resistant

β-lactam antibiotics with activity

against methicillin-susceptible S aureus

isolates (methicillin, nafcillin, oxacillin,

or cefazolin for invasive infections

or oral agents such as dicloxacillin or

cephalexin for outpatient SSTIs) were

typically administered for suspected

staphylococcal infections with onset

in the community. Up until that time,

methicillin-resistant S aureus (MRSA)

isolates were almost always associated

with hospital-acquired infections.

In the late 1990s and early 2000s,

investigators around the United States

and subsequently worldwide described

the emergence of different clones of S aureus that were methicillin resistant

but causing infections that were

community-acquired (ie, CA-MRSA).3–6

One clone (USA300) quickly dominated

in the United States, causing SSTIs,

severe invasive infections, and, notably,

recurrent infections. Furthermore, the

USA300 CA-MRSA clone also became

a common nosocomial pathogen.7

Why different clones emerged

simultaneously around the world

remains somewhat of a mystery.

Initially, there was uncertainty

regarding what percentage of

community S aureus isolates labeled

CA-MRSA (10%, 25%, or 50%) would

justify a change in empiric therapy,

especially for invasive infections. Of

course, this situation also meant that

physicians caring for children needed

to know what proportion of S aureus

isolates recovered from children in their

community were indeed methicillin-

resistant, which is not a readily

available piece of information. However,

in a short period of time, the majority

of CA S aureus isolates from children in

many areas of the United States were

the USA300 clone of CA-MRSA, which

appears to have a unique virulence

factor or factors, resulting in a highly

successful pathogen. This information

lead to changes in the recommendations

for empiric treatment of suspected

S aureus infections to include an

antibiotic effective against these

USA300 CA-MRSA isolates, which were

typically susceptible to clindamycin

and trimethoprim/sulfamethoxazole.8

However, over the years, clindamycin

susceptibility among S aureus isolates

has declined, likely related to the

increased use of this agent for empiric

as well as definitive treatment of

Section of Infectious Diseases, Department of Pediatrics,

Baylor College of Medicine, Infectious Disease Service,

Texas Children's Hospital, Houston, Texas

Opinions expressed in these commentaries are

those of the author and not necessarily those of the

American Academy of Pediatrics or its Committees.

DOI: 10.1542/peds.2016-0101

Accepted for publication Jan 12, 2016

Address correspondence to Sheldon L. Kaplan, MD,

Texas Children's Hospital, Feigin Center, Suite 1150,

1102 Bates, Houston, TX 77030. E-mail: skaplan@

bcm.edu

PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online,

1098-4275).

Copyright © 2016 by the American Academy of

Pediatrics

FINANCIAL DISCLOSURE: Dr Kaplan reports

receiving funding for investigator-initiated studies

from Pfi zer and Forest Laboratories, and he was

the principal site investigator for a study supported

by Cubist.

FUNDING: No external funding.

POTENTIAL CONFLICT OF INTEREST: Dr Kaplan has

indicated he has no potential confl icts of interest

to disclose.

COMPANION PAPER: A companion to this article

can be found online at www. pediatrics. org/ cgi/ doi/

10. 1542/ peds. 2015- 3099.

PEDIATRICS Volume 137 , number 4 , April 2016 :e 20160101 COMMENTARY

To cite: Kaplan SL. Infections in Children: The

Implications of Changing Trends. Pediatrics.

2016;137(4):e20160101

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KAPLAN

CA-MRSA infections, encouraging the

transmission of the genes associated

with clindamycin resistance.9

Recent surveillance reports of S aureus infections in children in

the United States have indicated

that the percentage of CA-MRSA

isolates among S aureus–causing

community infections has plateaued

and that the incidence of health

care–associated invasive MRSA

infections has declined.10, 11 In

the study by Sutter et al, 1 isolates

recovered from outpatients and

inpatients were grouped together,

and thus no distinctions were made

for infections that were CA, health

care associated but with community

onset, or hospital acquired. The

most common site of infection was

skin and soft tissue, but the second

most common site was “other”

infections, which were not further

identified. Respiratory infections

were the third most common site,

and it was again unclear what type of

infections these represent (eg, sinus,

eye, pneumonia). When all isolates

were considered, the proportion

of isolates labeled MRSA each year

reached a peak in 2007 (46.4%)

and then declined steadily to 31.6%

in 2014. Similar proportions were

reported just for isolates associated

with SSTIs, although no significant

changes were noted for isolates from

sterile site infections. The authors do

not speculate about the reason(s) for

these findings. In contrast, resistance

to clindamycin slowly increased

over these same years from 9.3% in

2005 to 14% in 2014, and this rise

was primarily related to increases

among methicillin-susceptible S aureus isolates. Trimethoprim/

sulfamethoxazole remained highly

active throughout the years (>98% of

isolates were susceptible).

What are the implications of the

findings from the report by Sutter

et al1 with respect to the selection

of empiric antibiotics for children

with suspected S aureus infections?

Currently, considering the still

substantial MRSA resistance rates

that exceed the 10% to 15% level

suggested by many experts as the

threshold above which agents

effective against CA-MRSA isolates

should be administered for empiric

treatment (http:// www. cdc.

gov/ mrsa/ pdf/ MRSA- Strategies-

ExpMtgSummary2006 . pdf),

changes in the selection of empiric

antibiotics are not warranted. If rates

of MRSA among S aureus isolates

from otherwise normal children

are documented to drop below the

10% to 15% threshold in different

communities, a modification of

current recommendations should

be considered. It would also be

important to understand why

methicillin resistance is declining

among S aureus isolates from

CA infections; this information

may provide clues for preventing

CA-MRSA infections with the use

of vaccines or other means. The

epidemiology of S aureus infections

in children has been changing over

the past 2 decades, which is why it

is critical to keep a very close eye on

this common pathogen.

ABBREVIATIONS

CA:  community-acquired

MRSA:  methicillin-resistant

Staphylococcus aureusSSTI:  skin and soft tissue

infections

REFERENCES

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Pediatrics. 2016;137(4):e20153099

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