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Increases in serious invasive CA-MRSA infections a growing concern
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Several trends in cases of invasive community-associated methicillin-resistant Staphylococcus aureus infections and the relatively little existing data on effective therapy in children with these infections have created a growing concern among pediatricians, according to a speaker at the 2008 Pediatric Academic Societies and Asian Society for Pediatric Research joint meeting, held in Honolulu.
“CA-MRSA infections have been associated with some clinical manifestations of S. aureus infections, such as venous thromboses, pyomyositis and meningococcal disease, that have not been seen commonly in serious staphylococcal infections in children previously,” Sheldon L. Kaplan, MD, chief of the infectious disease service at Texas Children’s Hospital and professor of pediatrics and Head of the Section of Pediatric Infectious Diseases at Baylor College of Medicine in Houston, told Infectious Diseases in Children.
“If we focus on the proportion of isolates that are associated with invasive infections in various age groups for children aged younger than 1 year to children aged 6 years, this comprises 2% to 6% of all isolates associated with community-associated S. aureus infections,” Kaplan said during his presentation. “In older kids, it’s slightly more, because I think fewer of the older children are coming to the emergency center with skin and soft tissue infections, and more are coming in with invasive infections.”
The number of cases of MRSA osteomyelitis is increasing.
Complications
Patients with CA-MRSA experience longer duration of fever, prolonged hospital stays and more complicated clinical courses compared with patients who have methicillin-susceptible S. aureus, according to Kaplan, who cited data from a study by Arnold et al in his presentation. These patients are more likely to have subperiosteal abscesses that require surgical procedure, and some experience prolonged bacteremia.
Increases in the number of patients with CA-MRSA from an isolate containing genes encoded with Panton-Valentine leukocidin are another growing concern. “If the genes are present, in isolates from children with osteomyelitis, venous thrombosis and prolonged fever are more common than if the isolates do not contain those genes,” Kaplan said. These patients have greater admission to intensive care units, are more likely to have positive blood cultures and increased frequency of surrounding myositis. “They also had a tendency to have multiple sites of infection more often — 15% of the time compared with 5%,” Kaplan said, citing data from a study by Bocchini et al.
Between 1971 and 2005, only 13 cases of S. aureus osteomyelitis complicated with venous thrombosis were reported. “We saw nine such patients from 1999 to 2004, most due to MRSA, with seven or eight of these cases resulting from the USA300 clone,” Kaplan said. “Now we have well over 20 such cases.”
Diagnosis, treatment issues
The efficacy of imaging practices such as magnetic resonance imaging and bone scintigraphy in patients with community-associated S. aureus and musculoskeletal infection is an area of interest, as these technologies are increasingly important in diagnosis and determining therapeutic interventions. “In evaluation of suspected acute hematogenous osteomyelitis, MRI appears to be the imaging modality of choice, in part, because it may detect thromboses or pyomyositis that will generally not be detected by other imaging studies,” Kaplan said in an interview.
Kaplan and colleagues observed 199 children at the Texas Children’s Hospital diagnosed with community-associated S. aureus who underwent either MRI or bone scintigraphy. Data from this study indicated a 98% efficacy rate in the 160 patients who received MRI compared with a 53% efficacy rate in the 35 patients who received bone scintigraphy.
Additionally, decreases in clindamycin susceptibility have also been reported at varying rates across U.S. cities, so it is important for physicians to take this into consideration during treatment. “Depending on local antibiotic susceptibility patterns for S. aureus, it is prudent to include an antibiotic active against CA-MRSA isolates in the initial empiric regimen for serious infections for which S. aureus is a possible pathogen,” Kaplan said.
Clindamycin resistance was as low as 3% in Baltimore from 2003 to 2005 and as high as 22% in Chicago from 2003 to 2004, according to data from the presentation. From 2001 to 2007, Kaplan and colleagues observed an increase in clindamycin resistance among all S. aureus isolates from 2% to 9% at the Texas Children’s Hospital. Clindamycin remains an important option for treating serious non-endovascular infections in children due to susceptible isolates.
Adult data
AAP guidelines recommend vancomycin for initial management of severe and critically ill patients with S. aureus infections; however, no large studies exist involving children regarding serious CA-MRSA infection treatments.
Data from adult studies involving mostly nosocomial infections are the most prevalent and in these studies vancomycin remains the most commonly used antimicrobials currently available for MRSA treatment.
However, vancomycin resistance is a growing concern as data from several reports suggested a correlation between increases in minimum inhibitory concentrations and treatment failure, according to Kaplan. Increasing the target trough level for adult patients to 15 mcg/mL produced a more favorable outcome compared with patients who did not reach target levels, according to Kaplan. “Pediatric data are really not available to help determine the need to increase the trough levels of vancomycin to between 15 mcg/mL and 20 mcg/mL for serious infections in children,” Kaplan said at the meeting.
The American Thoracic Society currently recommends linezolid as an alternative to vancomycin for treating MRSA ventilator associated pneumonia based on a retrospective analysis of two adult trials involving hospital-associated pneumonia. Data indicated that linezolid was superior to vancomycin in patients with renal toxicity; however, the researchers indicated that optimal dosing with vancomycin was not reached, and a prospective study is needed to confirm these results, according to Kaplan. Although data indicated that linezolid is comparable with vancomycin for the treatment of gram-positive infections in children, no data exist on the efficacy of the drug in treating pediatric patients with pneumonia or osteomyelitis.
Based on these data, Kaplan suggested that researchers conduct pediatric trials to determine the value of the following possible treatment options:
- Establishing vancomycin MICs and E-tests for all S. aureus isolates.
- Establishing higher vancomycin troughs for children.
- Facilitating routine echocardiograms for patients with prolonged bacteremia.
- Combination therapy with vancomycin or daptomycin with clindamycin or linezolid to inhibit protein synthesis.
- Addition of rifampin or gentamicin to routine antibiotics for serious infections.
The IDSA is currently drafting MRSA treatment guidelines that should be available in about 12 months, according to Kaplan. – by Nicole Blazek
For more information:
- Arnold SR, Elias D, Buckingham SC, et al. Changing patterns of acute hematogenous osteomyelitis and septic arthritis: emergence of community-associated methicillin-resistant Staphylococcus aureus. J Pediatr Orthop. 2006;26:703-708.
- Bocchini C, Huten KG, Mason EO, et al. Panton-Valentine leukocidin genes are associated with enhanced inflammatory response and local disease in acute hematogenous Staphylococcus aureus osteomyelitis in children. Pediatrics. 2006;doi:10.1542/peds.2005-0566.
- Browne LP, Mason EO, Kaplan SL. Optimal imaging strategy for community-acquired Staphylococcus aureus musculoskeletal infections in children. Pediatr Radiol. 2008;doi:10.1007/s00247-008-0888-8.
- Kaplan SL. Serious invasive infections caused by community-acquired methicillin-resistant Staphylococcus aureus. Presented at: the 2008 Pediatric Academic Societies and Asian Society for Pediatric Research Joint Meeting; May 3-6, 2008; Honolulu.