J. Chase McNeil

Staphylococcus aureus infections in pediatric oncology patients: high rates of antimicrobial resistance, antiseptic tolerance and complications.

Background: Patients with malignancies represent a population at high risk for drug-resistant infections. We sought to determine the clinical spectrum and molecular epidemiology of Staphylococcus aureus infections in pediatric oncology patients followed at Texas Children’s Hospital (Houston, TX). Furthermore, we determined the prevalence of the chlorhexidine resistance gene qacA/B from isolates in this unique population. Methods: Patients with a history of malignancy and a culture-proven S. aureus infection were identified from 2001 to 2011. Antibiotic susceptibility, pulsed-field gel electrophoresis and detection of qacA/B by polymerase chain reaction were performed on all isolates. Medical records for all patients were reviewed. Results: During the study period, 213 isolates were identified from 179 patients with malignancies. Thirty-one percent of the isolates were methicillin-resistant S. aureus. The most common infectious diagnosis was bacteremia (85/213 [39.9%], with 72/85 [84.7%] being catheter-associated). Thirteen patients with bacteremia were found to have pulmonary nodules at the time of presentation; only S. aureus was found in tissue in 5 of the 6 patients who underwent lung biopsy. After 2007, 18.2% of isolates were qacA/B positive with a steady increase in prevalence every year (&khgr;2 for trend P = 0.04). Conclusions: S. aureus is a significant cause of morbidity and mortality in pediatric oncology patients at Texas Children’s Hospital. In addition to the more well-known clinical manifestations, this pathogen can also be associated with pulmonary nodules. Furthermore, the prevalence of S. aureus isolates carrying antiseptic resistance genes increased in this population. Additional clinical and molecular studies and surveillance among pediatric oncology patients are warranted to further explore these findings.

Mupirocin Resistance in Staphylococcus aureus Causing Recurrent Skin and Soft Tissue Infections in Children

ABSTRACT Staphylococcus aureus resistance to mupirocin is often caused by acquisition of a novel isoleucyl-tRNA synthetase encoded on the plasmid gene mupA. We tested S. aureus isolates from children at Texas Childrens Hospital with recurrent skin and soft tissue infections for mupirocin resistance and mupA. Of 136 isolates, 20 were resistant to mupirocin (14.7%). Fifteen isolates (11%) carried mupA, and the gene was more common in methicillin-susceptible S. aureus (21.4%) than methicillin-resistant S. aureus (8.3%; P = 0.03). Seven of 20 mupirocin-resistant isolates displayed clindamycin resistance.

Serotype 19A is the most common Streptococcus pneumoniae isolate in children with chronic sinusitis.

Background: The introduction of the heptavalent pneumococcal conjugate vaccine has altered the epidemiology of acute otitis media and invasive pneumococcal disease in children. However, sparse data regarding pediatric sinusitis are available since the licensure of pneumococcal conjugate vaccine. In this study, sinus cultures which grew Streptococcus pneumoniae at Texas Childrens Hospital were evaluated with regard to pneumococcal serotype, antimicrobial susceptibility, and frequency of coinfecting organisms. Methods: S. pneumoniae isolates from sinus cultures were identified from January 1, 2007 to July 31, 2008. A retrospective chart review was performed and information including age, ethnicity, gender, and comorbidities was collected. Isolates were serotyped and their susceptibility to oral penicillin, cefotaxime, erythromycin, clindamycin, and trimethoprim-sulfamethoxazole was determined. Results: During the study period, 24 pneumococcal isolates were recovered from endoscopic sinus surgery cultures; 23 isolates were nonvaccine serotypes. Serotype 19A accounted for 50% of isolates. Eleven of the 12 serotype 19A isolates were nonsusceptible to oral penicillin as compared with 6 isolates of the other serotypes. Five of 12 serotype 19A isolates were nonsusceptible to cefotaxime; in comparison, all of the other serotypes were susceptible to cefotaxime. One third of the 19A isolates were nonsusceptible to all 5 antimicrobials tested. Other organisms were coisolated in 87% of cases. Conclusions: Serotype 19A has become the most common pneumococcal serotype isolated from chronic or recurrent pneumococcal sinusitis in children at Texas Childrens Hospital. Serotype 19A isolates have high rates of antimicrobial resistance and are frequently isolated along with multiple other organisms.

Decreased Susceptibilities to Retapamulin, Mupirocin, and Chlorhexidine among Staphylococcus aureus Isolates Causing Skin and Soft Tissue Infections in Otherwise Healthy Children

ABSTRACT Topical antimicrobial and antiseptic agents are commonly used in the management of minor skin and soft tissue infections (SSTIs). Resistance to mupirocin has been documented in Staphylococcus aureus isolates causing SSTIs. Data are limited, however, on the prevalence of retapamulin resistance or tolerance to antiseptics. We sought to determine the prevalence of decreased susceptibility to retapamulin and mupirocin as well as the potential for decreased chlorhexidine susceptibility of S. aureus isolates from SSTIs in children. Two hundred isolates from patients with a single SSTI and 200 isolates from patients with ≥3 previous episodes from the years 2010 to 2012 were selected from an S. aureus surveillance study. Screening for retapamulin resistance was performed by the broth macrodilution method; mupirocin MICs were determined by Etest. PCR was performed for the presence of the smr gene associated with elevated MICs/minimum bactericidal concentrations (MBCs) to chlorhexidine. Among the isolates screened, 38 isolates (9.5%) exhibited retapamulin resistance, of which 22 (57.9%) were methicillin-resistant S. aureus (MRSA). Two isolates (0.5%) displayed cross-resistance to retapamulin and linezolid. Thirty-nine isolates (9.8%) were found to have mupirocin resistance. smr-positive S. aureus accounted for 14% of isolates. The proportion of smr-positive organisms increased during the study (P = 0.005). The prevalence of in vitro resistance to topical antimicrobials among S. aureus isolates causing SSTI in healthy children in our community is almost 10%. Retapamulin resistance was associated with cross-resistance to linezolid in 0.5% of isolates. In addition, there was an increase in the proportion of smr-positive isolates. Further research including clinical correlations with these findings is warranted.

Metanephric Adenoma in a Five-Year-Old Boy Presenting with Chyluria: Case Report and Review of Literature

Metanephric adenoma and chyluria are rare entities, especially in the pediatric population of North America. To date, no report of chyluria associated with metanephric adenoma has been published. The incidental presentation is most common in the fifth decade of age with this tumor; however, when signs and symptoms are present they include hematuria, palpable mass, flank pain, polycythemia, and hypercalcemia. We present the case of a 5-year-old boy who did not demonstrate the common findings listed, but rather he presented with chyluria.

Clinical and Molecular Features of Decreased Chlorhexidine Susceptibility among Nosocomial Staphylococcus aureus Isolates at Texas Children's Hospital

ABSTRACT One of the strategies utilized to decrease infections in the hospital setting relies on topical antimicrobials and antiseptics. While their use is beneficial, concerns arise over the potential to develop resistance or tolerance to these agents. We examined nosocomial Staphylococcus aureus isolates from 2007 to 2013 for the presence of genes associated with tolerance to chlorhexidine. Isolates and patients were identified from an S. aureus surveillance study at Texas Childrens Hospital. Nosocomial S. aureus isolates (those causing infection at ≥72 h of hospitalization) were identified and underwent PCR for the qacA or qacB (qacA/B) and smr genes associated with elevated minimum bactericidal concentrations of chlorhexidine. Molecular typing with pulsed-field gel electrophoresis (PFGE), multilocus sequence typing (MLST), and agr typing and a review of the medical record were performed. Two hundred forty-seven nosocomial S. aureus infections were identified. Overall, 111 isolates carried one or both genes (44.9%); 33.1% were positive for smr, 22.7% were positive for qacA/B, and 10.9% of the isolates possessed both genes. The smr-positive isolates were more often resistant to methicillin, ciprofloxacin, and/or clindamycin. The isolates positive for qacA/B were more often associated with indwelling central venous catheters and a vancomycin MIC of ≥2 μg/ml. Isolates carrying either smr or qacA/B were associated with a diagnosis of bacteremia. The smr-positive isolates more often belonged to sequence type 8 (ST8) than the isolates that were positive for qacA/B. Mupirocin resistance was detected in 2.8% of the isolates. Antiseptic-tolerant S. aureus strains are common in our childrens hospital and are associated with decreased susceptibility to other systemic antimicrobials and with bloodstream infections. Further work is needed to understand the implications that these organisms have on the hospital environment and antiseptic use in the future.

Staphylococcus aureus Infections in Children With Congenital Heart Disease

BACKGROUND Congenital heart disease (CHD) is the most common risk factor for infective endocarditis (IE) in children. Staphylococcus aureus is among the most common organisms to cause IE, yet there are little data describing the risk factors for invasive S aureus disease in children with CHD. We examined the epidemiology of S aureus infections in children with CHD. METHODS Patients with a history of CHD and S aureus infection were identified from a surveillance study of S aureus infections at Texas Childrens Hospital. Clinical and laboratory data from medical records were reviewed. All isolates were screened for the presence of the antiseptic tolerance gene qacA/B. Dichotomous variables were compared with Fishers exact test and continuous variables with Mann-Whitney U tests, and two-tailed P values of <.05 were considered significant. RESULTS Two hundred forty-eight S aureus infections developed in 216 patients with CHD. Methicillin resistance was seen in 53.6% of isolates. Surgical site infections accounted for 28.2% of cases and bacteremia accounted for 20.4% of cases. Bacteremia was associated with IE in 29.5% of the episodes. Infective endocarditis was more often associated with prolonged bacteremia, thrombocytopenia, and a higher C-reactive protein (CRP) compared with uncomplicated bacteremia. The qacA/B gene was found in 16.9% of isolates and was associated with bacteremia and prolonged hospitalization. CONCLUSIONS Staphylococcus aureus is an important cause of morbidity among children with CHD. Infective endocarditis was common with S aureus bacteremia in this population; in addition, prolonged bacteremia, thrombocytopenia, and CRP >10 mg/dL may serve as diagnostic adjuncts for IE. qacA/B-positive isolates are associated with adverse clinical outcomes.

Staphylococcus aureus - antimicrobial resistance and the immunocompromised child.

Children with immunocompromising conditions represent a unique group for the acquisition of antimicrobial resistant infections due to their frequent encounters with the health care system, need for empiric antimicrobials, and immune dysfunction. These infections are further complicated in that there is a relative paucity of literature on the clinical features and management of Staphylococcus aureus infections in immunocompromised children. The available literature on the clinical features, antimicrobial susceptibility, and management of S. aureus infections in immunocompromised children is reviewed. S. aureus infections in children with human immunodeficiency virus (HIV) are associated with higher HIV viral loads and a greater degree of CD4 T-cell suppression. In addition, staphylococcal infections in children with HIV often exhibit a multidrug resistant phenotype. Children with cancer have a high rate of S. aureus bacteremia and associated complications. Increased tolerance to antiseptics among staphylococcal isolates from pediatric oncology patients is an emerging area of research. The incidence of S. aureus infections among pediatric solid organ transplant recipients varies considerably by the organ transplanted; in general however, staphylococci figure prominently among infections in the early posttransplant period. Staphylococcal infections are also prominent pathogens among children with a number of immunodeficiencies, notably chronic granulomatous disease. Significant gaps in knowledge exist regarding the epidemiology and management of S. aureus infection in these vulnerable children.

Healthcare-associated Staphylococcus aureus bacteremia in children: Evidence for reverse vancomycin creep and impact of vancomycin trough values on outcome

Introduction: Elevated vancomycin minimum inhibitory concentrations (MICs) in Staphylococcus aureus have been associated with worse clinical outcomes in adults. For invasive meticillin-resistant S. aureus (MRSA) infections in adults, the Infectious Diseases Society of America recommends targeting vancomycin serum trough concentrations between 15 and 20 &mgr;g/mL. We evaluated trends in vancomycin MICs from healthcare-associated (HCA) S. aureus bacteremia isolates in children in addition to correlating vancomycin serum trough levels with clinical outcomes. Methods: Patients and isolates were identified from a prospective S. aureus surveillance study at Texas Childrens Hospital (TCH). HCA S. aureus bacteremia isolates from 2003 to 2013 were selected. Vancomycin MICs by E-test were determined and medical records were reviewed. Acute kidney injury (AKI) was defined as doubling of the baseline serum creatinine. Results: Three hundred forty-one isolates met inclusion criteria. We observed a reverse vancomycin creep among MRSA isolates in the study period with a decline in the proportion of isolates with vancomycin MIC ≥ 2 &mgr;g/mL (from 32.7% to 5.6%; P < 0.001). However, the proportion of MSSA isolates with MIC ≥ 2 &mgr;g/mL increased (from 2.9% to 9%; P = 0.04). Among patients who had vancomycin troughs performed, there was no difference in duration of bacteremia or fever with vancomycin trough >15 versus <15 &mgr;g/mL. A vancomycin trough >15 &mgr;g/mL was, however, an independent risk factor for AKI. Conclusions: Vancomycin MICs are shifting among HCA S. aureus bacteremia isolates with significant differences between MRSA and MSSA at TCH. Higher vancomycin troughs did not improve outcomes in pediatric HCA S. aureus bacteremia but were associated with increased nephrotoxicity. Further studies are needed to better understand optimal management of children with S. aureus bacteremia.

The Influence of the Route of Antibiotic Administration, Methicillin-susceptibility, Vancomycin Duration and Serum Trough Concentration on Outcomes of Pediatric Staphylococcus aureus Bacteremic Osteoarticular Infection.

Background: Bacteremia is often one factor used in deciding the need for prolonged intravenous antimicrobial therapy in osteoarticular infections (OAIs). We examined treatment practices and outcomes of Staphylococcus aureus bacteremic osteoarticular infections (BOAIs) evaluated at Texas Children’s Hospital. Methods: Cases of acute hematogenous OAI in children with positive blood cultures for S. aureus at Texas Children’s Hospital between 2011 and 2014 were reviewed. Orthopedic complications included chronic osteomyelitis, growth arrest, pathologic fracture, avascular necrosis and chronic dislocation. Acute kidney injury was defined as a doubling of the baseline creatinine. Results: One hundred and ninety-two cases of S. aureus OAI were identified with 102 cases of BOAI included [35 methicillin-resistant S. aureus (MRSA)]. Twenty-five patients were discharged home on oral antibiotics. Patients discharged on oral antibiotics had a shorter duration of fever, had a more rapid decline in C-reactive protein and were less likely to have MRSA. The frequency of orthopedic complications did not increase in patients who received early transition to oral antibiotics. For patients with MRSA bacteremia, the rates of complications between those who received ≥7 days versus <7 days of vancomycin did not differ. Vancomycin serum troughs >15 µg/mL were not associated with a decreased duration of fever, bacteremia or hospitalization, need for repeat operation or orthopedic complications but were associated with acute kidney injury. Conclusions: S. aureus BOAIs are associated with substantial morbidity. Early transition to oral therapy may be a safe option for select patients with S. aureus BOAI, including those due to MRSA. Prolonged courses of vancomycin and vancomycin troughs >15 &mgr;g/mL were not associated with improved outcomes for MRSA OAI.