Wendy A. Hammerman

Three-Year Surveillance of Community-AcquiredStaphylococcus aureus Infections in Children

BACKGROUND Methicillin-resistant Staphylococcus aureus (MRSA) isolates are increasingly frequent causes of skin and soft-tissue infections or invasive infections in many communities. METHODS Prospective surveillance for community-acquired S. aureus infections at Texas Childrens Hospital was initiated on 1 August 2001. Infections meeting the definition of community-acquired were identified. Demographic and clinical data were collected. Antibiotic susceptibilities, including inducible resistance to macrolide, lincosamide, and streptogramin B (MLSB), were determined in the clinical microbiology laboratory with the methodology of the NCCLS. All data were entered into a computer database. Data were analyzed by chi2 tests. RESULTS From 1 August 2001 to 31 July 2004, the percentage of community-acquired S. aureus isolates that were methicillin resistant increased from 71.5% (551 of 771 isolates) in year 1 to 76.4% (1193 of 1562 isolates) in year 3 (P = .008). The number of both community-acquired MRSA (CA-MSRA) isolates and community-acquired methicillin-susceptible S. aureus (CA-MSSA) isolates increased yearly, but the rate of increase was greater for the CA-MRSA isolates. Among the CA-MRSA isolates, 2542 (95.6%) were obtained from children with skin and soft-tissue infections, and 117 (4.4%) were obtained from children with invasive infections. Overall, 62% of children with CA-MRSA isolates and 53% of children with CA-MSSA isolates were admitted to the hospital (P = .0001). The rate of clindamycin resistance increased significantly for both CA-MRSA isolates (P = .003) and CA-MSSA isolates (P = .00003) over the 3 years. MLSB inducible resistance was found in 27 (44%) of 62 clindamycin-resistant CA-MSSA isolates, compared with 6 (4.5%) of 132 clindamycin-resistant CA-MRSA isolates (P < .000001). CONCLUSIONS CA-MRSA isolates account for an increasing percentage and number of infections at Texas Childrens Hospital. Clindamycin resistance increased among community-acquired S. aureus isolates. Community surveillance of community-acquired S. aureus infections is critical to determine the appropriate empiric antibiotic treatment for either local or invasive infections.

Severe Staphylococcal Sepsis in Adolescents in the Era of Community-Acquired Methicillin-Resistant Staphylococcus aureus

Objective. More than 70% of the community-acquired (CA) staphylococcal infections treated at Texas Childrens Hospital are caused by methicillin-resistant Staphylococcus aureus (MRSA). Since September 2002, an increase in the number of severely ill patients with S aureus infections has occurred. This study provides a clinical description of severely ill adolescent patients and an analysis of their isolates using molecular methods. Methods. We identified adolescent patients meeting criteria for severe sepsis requiring admission to the PICU. Patient records were reviewed, and isolates were obtained for susceptibility testing and DNA extraction. Isolates were tested for the presence of virulence genes (cna, tst, lukS-PV, and lukF-PV) and enterotoxin genes (sea, seb, sec, sed, seh, and sej) by polymerase chain reaction. Genomic fingerprints were determined by repetitive-element polymorphism polymerase chain reaction and pulse-field gel electrophoresis. SCCmec cassette type was determined. Results. Fourteen adolescents with severe CA S aureus infections were identified between August 2002 and January 2004. All were admitted to the PICU with sepsis and coagulopathy. Twelve patients had CA-MRSA infections; 2 had CA methicillin-susceptible Staphylococcus aureus (MSSA) infections. The mean age was 12.9 years (range: 10-15 years). Thirteen patients had pulmonary involvement and/or bone and joint infection; 10 patients had ≥2 bones or joints infected (range: 2-10); 4 patients developed vascular complications (deep venous thrombosis); and 3 patients died. All isolates were identical or closely related to the previously reported predominant clone in Houston, Texas (multilocus sequence type 8, USA300), and carried lukS-PV and lukF-PV genes as well as the SCCmec type IVa cassette (12 MRSA isolates) but did not contain cna or tst. Only 1 strain carried enterotoxin genes (sed and sej). Conclusions. Severe staphylococcal infections in previously healthy adolescents without predisposing risk factors have presented more frequently at Texas Childrens Hospital since September 2002. CA MRSA and clonally related CA MSSA characterized as USA300 and sequence type 8 have been isolated from these patients.

Community-acquired, methicillin-resistant and methicillin-susceptible Staphylococcus aureus musculoskeletal infections in children

Background: The clinical characteristics and virulence factors related to musculoskeletal infections caused by community-acquired, methicillin-resistant Staphylococcus aureus (MRSA) in children are not well-defined. Methods: In this retrospective study, the demographics, hospital course and outcome of children with musculoskeletal infections were reviewed from medical records and by contacting patients or their physicians. Antimicrobial susceptibilities were determined by disk diffusion. Polymerase chain reaction was performed to detect genes encoding for virulence factors. Mann-Whitney, χ2 and Kaplan-Meier tests were used for statistical analysis. Results: Community-acquired MRSA and community-acquired methicillin-susceptible S. aureus (MSSA) caused musculoskeletal infections in 31 and 28 children, respectively. The median numbers of febrile days after start of therapy were 4 and 1 for MRSA and MSSA patients, respectively (P = 0.001). The median numbers of hospital days were 13 and 8 for the MRSA and MSSA groups, respectively (P = 0.014). At follow-up, 2 patients in the MRSA and 1 in the MSSA group had developed chronic osteomyelitis. pvl and fnbB genes were found in 87 and 90% versus 24 and 64% in the MRSA versus MSSA groups, respectively. (P = 0.00001 and 0.017). Ten patients with pvl-positive strains had complications versus no patients with pvl-negative isolates (P = 0.002). Conclusions: Febrile days and hospital days were greater in children with musculoskeletal infection caused by MRSA than in those affected by MSSA, but no significant differences were found in the final outcome. pvl and fnbB genes were more frequent in the MRSA than in the MSSA strains. The presence of the pvl gene may be related to an increased likelihood of complications in children with S. aureus musculoskeletal infections.

Panton-valentine leukocidin genes are associated with enhanced inflammatory response and local disease in acute hematogenous Staphylococcus aureus osteomyelitis in children

BACKGROUND. Staphylococcus aureus strains carrying the genes encoding Panton-Valentine leukocidin (pvl-positive [pvl+]) are associated with more febrile days and higher complication rates of osteomyelitis in children than are pvl-negative (pvl−) strains. OBJECTIVES. Selected clinical, laboratory, and radiographic findings in children with osteomyelitis caused by pvl+ and pvl− S aureus strains were compared. METHODS. The demographics, selected clinical features, laboratory values, and radiographic findings of children with community-acquired S aureus osteomyelitis prospectively identified at Texas Childrens Hospital between August 2001 and July 2004 were reviewed. Polymerase chain reaction was performed to detect the genes for pvl (luk-S-PV and luk-F-PV) and fibronectin-binding protein (fnbB) in S aureus isolates. χ2, 2-sample t test, and multiple logistic regression were used for statistical analysis. RESULTS. Methicillin-susceptible and methicillin-resistant S aureus (MSSA and MRSA, respectively) caused osteomyelitis in 33 and 56 children, respectively. Twenty-six isolates were pvl− (26 MSSA), 59 were pvl+ (3 MSSA, 56 MRSA), and 4 were not available for analysis (4 MSSA). On univariate analysis, patients with pvl+ S aureus isolates had significantly higher erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) level both at presentation and as a maximum value during hospitalization and were more likely to have a blood culture positive for S aureus during their admission. Patients with pvl+ S aureus isolates were significantly more likely to have concomitant myositis or pyomyositis compared with patients with pvl− S aureus isolates on MRI. In a multivariate analysis pvl remained significantly associated with ESR and CRP levels at presentation and blood culture positive for S aureus. pvl+ status and younger age were associated with myositis on MRI. CONCLUSIONS. Osteomyelitis caused by pvl+ S aureus strains were associated with more severe local disease and a greater systemic inflammatory response compared with osteomyelitis caused by pvl− S aureus.

Clindamycin treatment of invasive infections caused by community-acquired, methicillin-resistant and methicillin-susceptible Staphylococcus aureus in children.

Background. Community-acquired, methicillin-resistant Staphylococcus aureus (CA-MRSA) is an established pathogen in several areas of the United States, but experience with clindamycin for the treatment of invasive MRSA infections is limited. We compared the outcome of therapy for MRSA with that of methicillin-susceptible (MSSA) invasive infections in children treated with clindamycin, vancomycin or beta-lactam antibiotics. Methods. The demographics, hospital course and outcome of children at Texas Children’s Hospital between February and November 2000 and between August 2001 and August 2002 with invasive S. aureus infections were reviewed from medical records in this retrospective study. Results. CA-MRSA and community-acquired methicillin-susceptible S. aureus (MSSA) caused invasive infections in 46 and 53 children, respectively. The median ages (range) of the children were: MRSA, 3.5 years (2 months to 18.6 years); MSSA, 4.8 years (3 months to 19.8 years). The sites of infection for MRSA vs. MSSA isolates, respectively, were: bacteremia, 3 vs. 6; osteomyelitis, 14 vs. 14; septic arthritis, 5 vs. 7; pneumonia, 11 vs. 3; lymphadenitis, 7 vs. 14; other, 5 vs. 8. Among MRSA patients 39 (20 received clindamycin only, 18 had vancomycin initially and 8 were treated with a beta-lactam initially) received clindamycin and 6 received vancomycin as primary therapy. Among MSSA patients, clindamycin, nafcillin or other beta-lactam antibiotics were used in 24, 18 and 9, respectively. The median number of febrile days was 3 (0 to 14) and 2 (0 to 6) for MRSA and MSSA patients, respectively (P = 0.07). The median number of days with positive blood cultures was 2 for the MRSA (n = 16) and 1 for the MSSA (n = 18) patients (P = 0.04). Conclusion. Clindamycin was effective in treating children with invasive infections caused by susceptible CA-MRSA isolates.

Pulmonary Manifestations in Children with Invasive Community-Acquired Staphylococcus aureus Infection

BACKGROUND Primary pneumonia and metastatic pulmonary infection have become more common in patients with invasive community-acquired Staphylococcus aureus disease at Texas Childrens Hospital (TCH; Houston). METHODS In this study, we sought to describe pulmonary involvement in children with community-acquired S. aureus invasive infection and to determine whether the presence of genes encoding Panton-Valentine leukocidin (PVL) (luk-S-PV and luk-F-PV) and collagen adhesin (cna) is correlated with pulmonary manifestations. Patients with invasive staphylococcal infections admitted to TCH between 1 August 2001 and 30 June 2004 were studied. Chest imaging and postmortem examination reports were reviewed. Isolates were tested for the presence of genes encoding PVL and collagen adhesin by PCR. RESULTS A total of 47 of 70 patients with community-acquired methicillin-resistant S. aureus (MRSA) infection had abnormal pulmonary imaging findings, compared with 12 of 43 patients with community-acquired methicillin-susceptible S. aureus (MSSA) infection (P < .001). Pneumonia and/or empyema, in addition to septic emboli, were the most common findings. Metastatic pulmonary disease occurred more frequently among patients with osteomyelitis. Severe necrotizing pneumonia was present in 3 children coinfected with influenza and parainfluenza virus. The presence of genes encoding PVL was investigated in 67 MRSA and 36 MSSA isolates. Abnormal chest imaging findings were observed for 51 of 80 patients with PVL-positive isolates, compared with 2 of 23 patients with PVL-negative isolates (P < .001). Only 2 isolates (both of which were MSSA) from patients with abnormal chest radiograph findings carried cna. PVL remained independently associated with abnormal chest imaging findings in patients with secondary pneumonia in a multivariate analysis (P = .03). CONCLUSIONS Pulmonary involvement is commonly observed in patients with invasive community-acquired S. aureus infections. Community-acquired MRSA may cause primary community-acquired pneumonia, as well as metastatic pulmonary disease. The presence of genes encoding PVL is highly associated with pulmonary involvement by S. aureus.

Venous thrombosis associated with staphylococcal osteomyelitis in children

BACKGROUND. Venous thrombosis (VT) in children with Staphylococcus aureus osteomyelitis occurs rarely. We describe clinical features of infections and molecular characterization of isolates of children at Texas Childrens Hospital with S aureus osteomyelitis and VT. METHODS. We reviewed records and imaging studies (chest radiographs, ultrasound, computed tomography, and MRI) of 9 patients at Texas Childrens Hospital with acute S aureus osteomyelitis and new onset VT between August 1999 and December 2004. Isolates were fingerprinted by pulsed-field gel electrophoresis and tested for the presence of genes encoding selective virulence factors. RESULTS. The mean age of the patients was 10.6 years. All 9 of the patients had osteomyelitis with sites of infection adjacent to the VT. The femoral and popliteal veins were most commonly affected. Two patients had VTs develop on the same side in which a central line had been in place. Four patients had chest radiographs consistent with septic emboli; inferior vena cava filters were placed in 3. Evaluation for hypercoagulable state revealed 3 patients with lupus anticoagulant, 1 with anticardiolipin IgG antibody, and 5 with no defect. Most laboratory abnormalities had resolved at follow-up. Seven patients had infections caused by methicillin-resistant S aureus belonging to the same clonal group (USA300); all were community acquired. Seven isolates carried the Panton-Valentine leukocidin (luk-S-PV and luk-F-PV) genes. CONCLUSIONS. The predominant community-acquired, methicillin-resistant S aureus clone in Houston, Texas, (USA300) may have a unique propensity to cause VT in association with osteomyelitis. Management of the venous thrombosis in this setting may be complicated by the rapid evolution of septic emboli.

Emergence of a predominant clone of community-acquired Staphylococcus aureus among children in Houston, Texas

Background: Community-acquired (CA), methicillin-resistant Staphylococcus aureus (MRSA) infections among children are increasing in the United States. At Texas Childrens Hospital (TCH), surveillance has been in place since August 2001. The objectives of this study were to describe the distribution of CA S. aureus among patients at TCH and to study genomic relationships of isolates collected between August 2001 and July 2003. Methods: Genomic relationships were determined with repetitive element-polymerase chain reaction (PCR). Multilocus sequence typing was performed for selected strains representing major clones. Molecular characterization of CA-MRSA was performed with PCR, including staphylococcal cassette chromosome (SCCmec), pvl (lukS-PV plus lukF-PV), hla, hlb and selected microbial surface components recognizing adhesive matrix molecule genes, ie, cna, clfA, fnbA and fnbB. Results: A 62% increase was observed in CA S. aureus infections from year 1 (2001–2002) to year 2 (2002–2003), whereas the annual number of hospital admissions was unchanged. CA methicillin-sensitive S. aureus isolates were more likely to be associated with invasive infections than were CA-MRSA isolates (P < 0.01). TCH clone A, sequence type (ST) 8, was responsible for approximately 94% of all CA-MRSA isolated from children in the greater Houston area. Clone A differed from clones B (ST30) and C (ST1) by lacking the cna gene while carrying the fnbB gene. Conclusions: One CA-MRSA clone, TCH clone A, has become the predominant cause of CA S. aureus infections among children in the Houston area. It causes a wide spectrum of diseases, including complicated pneumonia.

Three-year surveillance of community onset health care-associated Staphylococcus aureus infections in children

Background: Staphylococcus aureus causes skin and soft tissue or invasive infections in children in the community, in the hospital or in other ways associated with the health care system (HCA). Methods: Prospective community-acquired S. aureus infection surveillance at Texas Children’s Hospital was initiated on August 1, 2001. Community onset HCA (CO HCA) infections were identified. Demographic and clinical data were collected. Antibiotic susceptibilities were determined. Data were analyzed by &khgr;2 or Student’s t test. CO HCO-isolates were characterized by pulsed field gel electrophoresis and staphylococcal chromosomal cassette carrying the mecA methicillin-resistant gene (SCCmec) typing. Results: From August 1, 2001 to July 31, 2004, 61.5% of 322 in year 1, 62.9% of 259 in year 2 and 56.9% of 318 in year 3 of CO HCA isolates were methicillin-resistant S. aureus (MRSA). Among the CO HCA-MRSA isolates, 8.9% of 542 were from children with invasive infections compared with 24.1% of 357 CO HCA-methicillin-susceptible S. aureus (MSSA; P < 0.001). Sixty-six percent of children with CO HCA-S. aureus isolates were admitted to the hospital. Clindamycin resistance increased over the 3 years (CO HCA-MRSA, from 3.5% to 18.8%, P < 0.001; CO HCA-MSSA, from 3.2% to 10.2%, P = 0.053). Thirty-three of 35 (94.3%) CO HCA-MRSA carried SCCmecIV; 30 were USA300. Only 3 of 35 MSSA were related to USA300 by pulsed field gel electrophoresis. Conclusions: CO HCA-S. aureus infections remained steady over the 3-year study at Texas Children’s Hospital. Clindamycin resistance increased >4-fold for CO HCA-S. aureus isolates over the 3 years and is no longer appropriate for empiric treatment of invasive infections suspected to be caused by CO HCA-MRSA at our hospital. In our setting, CO HCA-MRSA infections are steady in number despite substantial increases in community-acquired MRSA infections and both being related to the same clone.

Community-acquired Staphylococcus aureus infections in term and near-term previously healthy neonates

BACKGROUND. Community-acquired, methicillin-resistant Staphylococcus aureus infections are increasing among children. OBJECTIVE. Our goal is to describe the clinical presentation of neonatal community-acquired S aureus disease and provide molecular analyses of the infecting isolates. PATIENTS AND METHODS. We retrospectively reviewed the demographics and hospital course of term and near-term previously healthy neonates, ≤30 days of age, with community-acquired S aureus infections presenting after nursery discharge between August 2001 and March 2005 at Texas Childrens Hospital. Prospectively collected isolates were characterized by pulsed-field gel electrophoresis, staphylococcal cassette chromosome mec type, and the presence of PVL genes. RESULTS. Of 89 S aureus infections, 61 were methicillin-resistant S aureus; S aureus infections increased each year. Methicillin-resistant S aureus infections increased from 10 of 20 to 30 of 36 infections from 2002 to 2004. Most subjects, 65 of 89, were male. Symptoms began at 7 to 12 days of age for 26 of 45 male infants with methicillin-resistant S aureus. Most infections, 77 of 89, involved skin and soft tissue; 28 of 61 methicillin-resistant S aureus versus 7 of 28 methicillin-susceptible S aureus infections required drainage. Invasive manifestations included shock, musculoskeletal and urinary tract infection, perinephric abscess, bacteremia, empyema/lung abscess, and a death. Maternal S aureus or skin-infection history occurred with 13 of 61 methicillin-resistant S aureus versus 1 of 28 methicillin-susceptible S aureus infections. The predominant community clone, USA300 (PVL genes +), accounted for 55 of 57 methicillin-resistant S aureus and 3 of 25 methicillin-susceptible S aureus isolates. CONCLUSIONS. Community-acquired methicillin-resistant S aureus is a substantial and increasing proportion of S aureus infections in previously healthy neonates. Male infants 7 to 12 days of age are affected most often. Neonatal community-acquired S aureus infection may be associated with concurrent maternal infection. USA300 is the predominant clone among these neonatal isolates in our region.