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Pediatric MRSA faces antibiotic resistance
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MRSA, an infection that was once typically observed in health care settings, has spread into the community over the past 2 decades, with increased but sporadic rates of colonization with the bacterium observed within the pediatric population since 2001.
Source: Rush University Medical Center
Study results published in The Pediatric Infectious Disease Journal found 0.8% of healthy children colonized in 2001 and 9.2% harboring the infection in their nostrils between 2001 and 2004.
Since then, the prevalence of community-acquired MRSA has varied nationwide. A study conducted by Sheldon L. Kaplan, MD, and colleagues found that the number of CA-MRSA infections decreased 60.4% between 2007 and 2014 within their large children’s hospital; however, the institution still experiences about 600 cases of CA-MRSA annually and CA-MRSA continues to cause the majority of skin and soft tissue infections due to Staphylococcus aureus in otherwise normal children (56% in 2014).
“When we began to observe infections in the late 1990s and early 2000s, we started noticing that a large number of these isolates were methicillin resistant and were coming from children with skin and soft tissue infections — or SSTIs,” said Kaplan, professor, executive vice chair and head of the section of pediatric infectious diseases in the department of pediatrics at Baylor College of Medicine and chief of the Infectious Diseases Service at Texas Children’s Hospital, in an interview with Infectious Diseases in Children.
“Around 2001, 30% isolates were found to be methicillin-resistant. The number of patients that were being seen for community-acquired SSTIs due to staph in otherwise normal, healthy children increased in number and peaked somewhere between 2,200 and 2,500 in 2007,” Kaplan continued. “We were seeing five to six children a day or more.”
Although the rate of CA-MRSA infections in children may have slowed in some areas of the country, the number of antibiotics available to treat infections caused by the bacteria are dwindling. In 2017, WHO labeled MRSA a priority pathogen, meaning there was a high potential of being a threat to human health and a need for new antibiotics for treatment.
To better understand the current epidemiology of MRSA, changing treatment strategies and prevention strategies, Infectious Diseases in Children spoke with researchers and physicians at the forefront of pediatric MRSA research and treatment.
Current epidemiology
The spread of MRSA within the United States is predominately attributed to two strains of S. aureus: USA100 and USA300. According to a review published in Current Pediatric Reports, the strain responsible for most pediatric cases of CA-MRSA is USA300, which was observed to have greater virulence and is able to be transmitted easier than other health care-associated MRSA strains.
CA-MRSA was more commonly developed by pediatric patients than in adults between 2008 and 2009. This trend began in the 1990s, according to the review written by Michael Z. David, MD, PhD, and Robert S. Daum, MD, CM, from the departments of pediatrics and medicine at University of Chicago Medicine, well before increasing rates in adults were observed, with 70% of all pediatric MRSA infections caused by CA-MRSA in 1995.
“The epidemiology of Staphylocci and of MRSA is continually evolving,” Kyle Popovich, MD, MS, FIDSA, associate professor in the section of infectious diseases at Rush University Medical Center, told Infectious Diseases in Children. “USA300 emerged in community settings among people without traditional health care exposures. While typically causing minor skin infections, more serious infections due to this strain have been reported.”
“Since this time, USA300 has spread into health care settings and now is a cause of hospital-onset infections. Infection control and prevention strategies have led to reductions in nosocomial MRSA infections,” she continued. “It is less clear how best to reduce colonization and/or infection among individuals in the community and how best to target prevention strategies.”
The epidemic levels of MRSA resulted in increased rates of skin and SSTIs in children, with 616,375 pediatric hospitalizations occurring between 1996 and 2010. The largest increase, according to the review by David and Daum, was observed between 1996 and 2006, when the incidence increased from less than 1 per 100,000 to 25.5 per 100,000. Difficulties were found when attempting to treat this because methicillin was no longer effective, and other antibiotics had varying efficacy.
“Like any good clinician, I think that when you start to see either more cases of something that you are used to seeing all the time or unusual presentations — either more severe or it is spreading in a way that you were not expecting — it should raise concern,” H. Dele Davies, MD, MS, MHCM, senior vice chancellor at the University of Nebraska Medical Center, told Infectious Diseases in Children. “If you look at USA300 as an example, part of what got the attention was that it was not responding to antibiotics as we had anticipated it would.”
According to Kaplan, most of the children with CA-MRSA SSTIs presenting to his institution have an abscess. The most common areas in which he observes these infections are the lower legs, the buttocks, the arms and the trunk. Transmission of the bacteria can come from many sources, but risk factors include obesity, chronic skin diseases such as eczema, prior SSTIs and the recent use of antibiotics.
“The SSTIs are going to be pretty similar in presentation in both children and adults,” he said. “In adults, you will see more cellulitis without an abscess. We do not see some of the conditions in pediatrics that we see in adults, such as diabetic-related complications. Diabetic foot infections are much more of a problem in adults.”
Additionally, David and Daum note that Native Hawaiians and Pacific Islanders are at increased risk of developing CA-MRSA. Bacteria may transmit through damage to the body, either through a weakened immune system or physical damage in the form of a cut, scrape or insect bite.
“MRSA gets transmitted from one person to another via contact — either direct contact by touching someone who has the infection or something that has been touched by that person,” Bruce Y. Lee, MD, MBA, associate professor of international health at Johns Hopkins Bloomberg School of Public Health and associate professor at Johns Hopkins Carey Business School, told Infectious Diseases in Children. “This could include sharing a blanket, medical instruments and furniture, among other things. If you go through the home of someone who has MRSA, you might be able to find some items with MRSA on them.”
Current treatment includes the use of clindamycin or Bactrim (sulfamethoxazole/trimethoprim, Sun Pharm Industries); however, susceptibility to clindamycin is variable in different parts of the country, and results with sulfamethoxazole/trimethoprim are not as consistent as they are with clindamycin. This makes treatment of MRSA in children exceedingly difficult in certain areas of the country.
Treatment in the face of resistance
When a patient presents to a primary care office with an abscess, standard procedure as defined by the 2014 guidelines established by the Infectious Diseases Society of America call for knowledgeable use of antibiotics and, in some cases, incision and drainage of an abscess. However, a study published in BMC Pediatrics found that few performed incision and drainage, and most clinicians aware of current guidelines.
Although incision and drainage may be an important part of treatment for more severe abscesses, Davies notes that this process may play an even more important role in the prescribing of appropriate antibiotics. These samples should be sent to a lab to better understand both the patient’s and the community’s exposure to MRSA, he said.“I think when we have children who have any type of skin infection, including a boil or any kind of cellulitis, we need to consider MRSA,” Davies said. “Physicians need to know what the predominant strain is within their community. They can do this by asking the lab if strains they are frequently seeing in the community are susceptible to different kinds of antibiotics.”
This information is now of vital importance. Findings published in Pediatrics demonstrate that clindamycin use has wide-ranging results throughout the U.S., with susceptibility dropping from 90% to 83% between 2005 and 2014. Furthermore, researchers from The Hospital for Sick Children, Toronto, Ontario, observed “concerning” levels of clindamycin resistance when used for the treatment of head and neck abscesses caused by MRSA.
According to their findings published in the Canadian Journal of Infectious Diseases and Medical Microbiology, approximately 27% of children treated had an infection that was resistant to the antibiotic. They also observed an increase from four new cases in 2000 to 44 new cases in 2007.
“About 30% to 50% of healthy children and adults are already colonized with S. aureus [and are asymptomatic],” Davies said. “[By giving unnecessary antibiotics], physicians are telling these bugs to learn how to become resistant to them. Judicious use of antibiotics is so important.”
Kaplan noted that his patient population observed an increase in clindamycin resistance since the rise in pediatric MRSA cases. When he first started treating these cases, approximately 2% were resistant to the antibiotic. He said that this rate is now closer to 15%. Resistance creates a dilemma for pediatricians. A study by Derek J. Williams, MD, MPH, from the department of pediatrics at Vanderbilt University, and colleagues found that clindamycin was less likely to fail at treating MRSA infection when compared with sulfamethoxazole-trimethoprim and beta-lactams. Children who received clindamycin were less likely to have recurrent infection, and if incision and drainage was needed, these links became stronger.
“There are several oral and intravenous options for the treatment of MRSA and recently, longer half-life agents have been developed,” Popovich said. “While drug development continues, antibiotic stewardship remains critical to minimize excess antibiotic use and help reduce the development of resistance.”
Sensible use of antibiotics expands far outside of health care settings and can easily affect the communities in which they serve. According to the CDC, prevention of antimicrobial resistance requires an understanding of current drug-resistant infections patients may have and asking for timely alerts when a lab observes these infections in specimens from patients.
“The health care setting and the community are intimately interconnected. In the past, this has not always been realized or considered,” Lee said. “What you do in the health care setting can affect the community. We have seen with CA-MRSA that this has become a community problem, not just a health care problem.”
“One way to ensure sensible use of antibiotics is to screen for MRSA,” Lee continued. “If there is a suspicion or if someone is at higher risk of infection, test them so that you know they are colonized in the first place. You can then tailor your approaches and treatments accordingly. If we have a better idea of how MRSA is being transmitted in the community, we can better understand and identify those who are carrying MRSA. Then, that might help to better target it, prevent it and treat it.”
Prevention strategies
To prevent the spread of MRSA within the community, several steps are required, including proper cleaning of communal areas and personal hygiene practices.
The AAP’s policy statement regarding sports-related pediatric infections stresses measures that could prevent MRSA, such as not sharing equipment and water bottles, reducing contact with surfaces and people who are infected with the bacteria, decontaminating the environment and immediate identification, adequate treatment and close follow-up with those who have been infected.
“Pediatricians can talk to families about good hygienic measures like keeping fingernails cut short and clean because kids may be scratching or injuring the skin, which makes it easier for infection to occur,” Kaplan said. “Changing underwear daily and not sharing towels and washcloths are also important hygienic measures.”
Although hygienic concerns are prevalent in the prevention of infectious disease, decolonization is difficult with MRSA. Current decolonization practices may include the use of nasal mupirocin or chlorhexidine body washes. Additionally, bleach baths may be recommended once daily for 5 to 7 days for those who have been colonized with MRSA.
Decolonization can be an important step to prevent additional spread of the infection; however, the CDC has noted that data do not endorse the use of these products for the elimination of S. aureus. The use of these products may be warranted in situations where multiple recurrent infections have been observed. Additionally, the measures may be recommended if transmission is continuing in a population that is well-defined and closely connected, including the household.
The CDC also notes that these steps toward decolonization should be considered only when traditional prevention measures have not been sufficient to stop transmission of the infection within this area.
In the health care setting, various steps have already been taken to ensure that the spread of MRSA is limited. These measures include proper hand hygiene by using soap and water or alcohol-based sanitizer before and after seeing every patient, according to the CDC. Clean hospital rooms and equipment, separating those with MRSA from the patient population, wearing gloves and proper screening have also limited the spread of MRSA within the health care setting, the agency noted.Although these practices have been embraced within the health care setting, it is important to note that communal areas in the home need to be regularly cleaned, especially high-contact areas like kitchen counters, computer keyboards and bathrooms. The CDC recommends using 1 tablespoon of bleach in 1 quart of water for proper disinfection.
“Prevention and control methods that have been successful in the health care setting need to be brought into the community,” Lee said. “We see many places that are not using these infection control methods, even places that on the surface look fine. When you walk in, the lobby looks clean, but when you look more carefully, the institution is not properly cleaned, and proper hygiene is not being used. This applies to many areas where children can assemble.”
With the changing epidemiology of MRSA, it may be more difficult to predict how these infections will affect the pediatric population within the community.
Future development of MRSA
Popovich noted that although there is a current understanding of USA300 and other CA-MRSA infections within the health care setting, research continues to be conducted regarding the best strategies for management in outpatient settings.
“We need to continue to understand the changing epidemiology of MRSA, particularly in community settings and among specific patient populations,” she said. “Advanced molecular epidemiologic methods, such as whole genome sequencing, are now being used to improve our understanding of the epidemiology of the spread of multidrug-resistant organisms such as MRSA.”
“Using this methodology may help in the targeting of prevention strategies within the community setting, among patient-sharing networks in health care centers and in the hospital,” Popovich continued. “Most importantly, continued emphasis on antibiotic stewardship and infection control strategies known to be effective, such as hand hygiene, are critical.”
In a release issued by WHO in late 2017, the organization stressed that the global availability of effective antibiotics is limited; however, 51 new antibiotics and biological agents are currently in clinical development. Davies notes that stronger pipelines of antibiotics are needed to ensure adequate care of patients with drug-resistant infections.
“I think that we need more pipelines of antibiotics in general, not just for S. aureus, that can be given orally or intravenously,” Davies said. “Ideally, we want one that can be given orally and used in an outpatient setting so that these infections can be managed appropriately. I think that while there has been some development of new antibiotics, the pipeline development is not as good as it used to be.”
Because of the current threat of antimicrobial resistance, future treatment of MRSA will require more judicious use of available antibiotics. This includes not using broad-spectrum antibiotics, such as amoxicillin, for viruses and other conditions that do not require treatment with such medications.
“If a patient does need antibiotics, we as physicians need to prescribe the correct types. We really need to better identify the people who might have MRSA and treat them, but do not use big-gun, broad-spectrum antibiotics for everyone,” Lee said. “Using these broad-spectrum antibiotics [when they are not needed] is like using a missile to blow up an anthill. By using too much, you drive selection pressure for antibiotic-resistant bacteria like MRSA.” – by Katherine Bortz
- References:
- Alexander AJ, et al. Can J Infect Dis Med Microbiol. 2011. doi: 10.1155/2011/261519.
- CDC: Protecting Patients and Stopping Outbreaks. Acccessed Feb. 17, 2018.
- CDC: Strategies for Clinical Management of MRSA in the Community.. Accessed Feb. 17, 2018.
- Creech CB, et al. Pediatr Infect Dis J. 2005. doi: 10.1097/01.inf.0000168746.62226.a4.
- David MZ, Daum RS. Curr Pediatr Rep. 2013. doi: 10.1007/s40124-013-0023-7.
- Davies HD, et al. Pediatrics. 2017. doi: 10.1542/peds.2017.2477.
- Hersh AL, et al. BMC Pediatrics. 2009. doi: 10.1186/1471-2431-9-27.
- Hulten KG, et al. Pediatr Infect Dis J. 2017. doi: 10.1097/INF.0000000000001753.
- Lee BY, et al. Health Aff (Milwood). 2012. doi: 10.1377/hlthaff.2011.0992.
- Lee BY, et al. Med Care. 2013. doi: 10.1097/MLR.0b013e3182836dc2.
- Stevens DL, et al. Clin Infect Dis. 2014. doi: 10.1093/cid/ciu444.
- Sutter DE, et al. Pediatrics. 2016. doi: 10.1542/peds.2015-3099.
- WHO: WHO publishes list of bacteria for which new antibiotics are urgently needed . Accessed Feb. 17, 2018.
- WHO: The world is running out of antibiotics, WHO report confirms. Accessed Feb. 17, 2018.
- Williams DJ, et al. Pediatrics. 2011. doi: 10.1542/peds.2010-3681.
- For more information:
- Sheldon L. Kaplan, MD, can be reached Texas Children’s Hospital, 6621 Fannin St., Houston, TX 77030; email: Jenn Blackmer Jacome, jmjacome@texaschildrens.org.
- Kyle Popovich, MD, MS, FIDSA, can be reached at the Rush University Medical Center, 1653 W. Congress Parkway, Chicago, IL 60612; email: John M. Pontarelli, john_m_pontarelli@rush.edu.
- H. Dele Davies, MD, MS, MHCM, can be reached at the University of Nebraska Medical Center, 42nd and Emile, Omaha, NE 68198; email: Robin J. Jaeckel, rjaeckel@unmc.edu
- Bruce Y. Lee, MD, MBA, can be reached at the Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe St., Baltimore, MD 21205; email: Bruce Y. Lee, brucelee@jhuedu and Maggie Chesson, mchesso2@jhu.edu.
Disclosures: Kaplan reports conducting an investigator-initiated study of pneumococcal surveillance funded by Pfizer, being part of a nationwide pediatric study of Tedizolid use for MRSA infection sponsored by Merck and an investigator-initiated study of ceftaroline use for bone infections in children funded by Allergan. Davies, Lee and Popovich report no relevant financial disclosures.