Panton-Valentine Leukocidin Positive Methicillin Resistant S. Aureus Infections in Children with Cancer

Background: Staphylococcus aureus is one of the most prevalent organisms isolated from children and adults with cancer. Strains of methicillin resistant S. aureus (MRSA) have emerged in the past decade, that often cause serious infections, in young, otherwise healthy people. Suppurative skin infections and necrotizing pneumonias are some of the diseases most characteristically associated with these new strains. Such MRSA isolates often harbor the Panton-Valentine Leukocidin (PVL) gene, belong to pulsed-field type USA 300, carry the staphylococcal cassette chromosome (SCC) mec IV, and are susceptible to clindamycin. The presence of the PVL gene has been associated with increased virulence and morbidity in these patients. However, the role of these new MRSA strains in causing infections in children and adults with cancer is presently unknown. Studies are needed to determine if the increase in incidence of MRSA infections in the community is paralleled by an increase in MRSA infections in pediatric cancer patients and if infections with these new strains are more virulent in this population.

Methods: The present work represents a retrospective study of all children with cancer diagnosed with MRSA infection over an eight year period from January 2000 to December 2007. Medical record review included patient demographics, underlying disease, and antimicrobial susceptibility patterns of MRSA isolates. Genotyping of isolates was performed using PCR for detection of the PVL gene. SCC mec and spa typing was performed on all PVL positive isolates. Logistic regression models were used to study the trend in the increase of MRSA infection over time. Statistical analysis was performed on frequency data between the different categorical variables among the PVL positive and PVL negative MRSA isolates by the Exact Pearson Chi-square test.

Results: A total of 98 clinical MRSA isolates were collected from 88 children with cancer from Jan 2000 to Dec 2007. The number of MRSA isolates increased sevenfold from 3 in 2000 to 21 in 2006 (p<0.0001). During the same period there was a significant decrease in the incidence of methicillin-sensitive S. aureus (MSSA) isolates (p<0.0001). Ten of the children had recurrent infection. The increase in MRSA infections was predominantly due to an increase in skin and soft tissue infections (p=0.0004). Children with African American ancestry and inpatients were significantly overrepresented in having MRSA infection as compared to other children with cancer (p<0.0001). Outcome was generally favorable; 33% had fever and only 10 patients (10%) had complications. Resistance to ciprofloxacin, clindamycin, erythromycin, gentamicin and mupirocin was 23%, 20%, 80%, 5%, and 2% respectively. All the isolates were sensitive to trimethoprim-sulfamethoxazole and vancomycin. PVL positive isolates bearing the SCC mec IV element comprised 35 of 98 (36%) of MRSA isolates. 32 of the 35 isolates belonged to the USA 300 type. No child had a recurrent infection with a PVL positive strain. Children infected with PVL positive strains had a significantly higher incidence of skin and soft tissue infections (SSTI, p=0.045), and bacteremia (p=0.045), as compared to children with PVL negative strains. A significantly higher number of the PVL positive isolates were susceptible to clindamycin (p=0.0158) and ciprofloxacin (p=0.0045).

Conclusion: This report represents the first description of the changing epidemiology of MRSA infections in children with cancer. The association between PVL positive MRSA infections and bacteremia is a novel finding in this population. PVL positive MRSA infections caused low morbidity and mortality in these immune-suppressed patients. Future studies may determine if patients with colonization from these virulent strains may benefit from preemptive therapy with mupirocin, to eradicate colonization. This approach may reduce the risk of bacteremia in high risk groups such as patients undergoing hematopoietic stem cell transplantation prior to engraftment.