Antibiotics, prevention strategies needed to control spread of resistant organisms

BOSTON — Rising rates of infections caused by extended-spectrum beta-lactamase-producing pathogens in children require special attention as resistance presents a unique challenge, according to a speaker here at the 50th Interscience Conference on Antimicrobial Agents and Chemotherapy.

“Gram-negative infection is a serious problem for children and increasing resistance is a looming threat,” said Anne J. Blaschke, MD, PhD, assistant professor in the department of pediatrics at the University of Utah School of Medicine.

In an observational study conducted by Blaschke and colleagues at their children’s hospital, 26 extended-spectrum beta-lactamase (ESBL)-producing organisms were isolated from 2,600 Escherichia coli and Klebsiella species cultured between 2003 and 2007. The isolates came from 16 patients. Seventy-five percent of the patients had chronic illness, prolonged or recurrent hospitalization and anatomic abnormalities.

The overall ESBL rate was about 1%. When divided into two, 2.5-year periods, the researchers found a noticeable increase in overall resistance from 0.5% to 1.4%. The overall resistance rates were on par with those reported by SENTRY for 2004 in U.S. pediatric institutions, according to Blaschke.

The researchers noted that although their study cohort included children ranging in ages from 1 month to 17 years, 50% of affected children were aged younger than 2 years and 31% were aged younger than 6 months, said Blaschke. She noted that international SENTRY data stratified by age indicated that ESBL resistance rates for bloodstream infections were higher in children aged younger than 1 year than in all other age groups.

Prior hospitalization and prolonged or recurrent hospitalization are also considered risk factors for infection, according to Blaschke. She noted that the researchers’ data suggested that several of the very young infants with infection might have acquired colonization, although not infection, during their stay in the neonatal ICU. Other studies also indicate that colonization can occur within as little as 9 days in the neonatal ICU, she said.

“As pediatricians, it is important that we note the ESBL rates in the institutions where our patients are born, and we need to support infection control efforts in adult institutions to protect the newborns that we’re going to see as pediatricians,” Blaschke said.

Antibiotic resistance is a major hurdle, Blaschke said. Carbapenems are the mainstay of treatment for infections caused by ESBL-producing bacteria, but resistance to these is also emerging. Furthermore, antibacterials designed to treat gram-negative infections are not widely in development.

“This, of course, is a problem for adults as well, but from the standpoint of pediatrics, we all have to remember that for any antibiotic that’s developed, pediatric safety data, pediatric dosing guidelines and FDA-approval are going to come years later than in adults,” said Blaschke.

Blaschke called for better surveillance systems that involve tracking antibiotic-resistant organisms in children to generate more data for future studies. — by Melissa Foster

For more information:

Blaschke AJ. Extended-spectrum beta lactamase-producing bacteria infections in children. #460. Presented at: 50th Interscience Conference on Antimicrobial Agents and Chemotherapy; Sept. 12-15, 2010; Boston.

PERSPECTIVE

What does this mean? For a child in the outpatient clinic with a serious, suspect urinary tract infection (UTI) where the practitioner did not want to risk failure by using amoxicillin or trimethoprim-sulfamethoxazole (Septra, Bactrim), cefixime or similar oral agent, or even IM ceftriaxone could be used to potentially avoid hospitalization. For those hospitalized, ceftriaxone or cefotaxime have been standard therapy. HOWEVER, the clinician can no longer feel virtually 100% confident that these drugs will be effective to treat UTIs due to the emergence of ESBLs in E. coli and Klebsiella. Nosocomial infections caused by E. coli and Klebsiella, all previously susceptible to these cephalosporins, are now increasingly being caused by ESBL-containing, antibiotic-resistant strains.

Of note, most of Blaschke's resistant isolates came from younger infants and children; 75% came from those with significant medical problems. Although the ESBL-containing strains are more likely to be picked up in the hospitals where broad-spectrum antibiotics are used widely, they have already moved from the hospital into communities in many areas of the world; it's just a matter of time before they become more frequent causes of community-acquired UTI in the U.S. Each hospital is required to keep track of ESBL resistance, so practitioners can contact their community or regional medical centers to see just how bad things are locally.

We have only a few alternative therapies available for these resistant bacteria. Carbapenem-class IV/IM agents, and fluoroquinolone-class IV/oral agents. Appropriate use of antibiotics and appropriate infection control practices are critical to slow the spread of these organisms within hospitals and communities. We are grateful to Blaschke and colleagues for sounding the alarm!

– John Bradley, MD

Rady Children's Hospital, San Diego, CA

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