Linda B. Lamberth

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.

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.

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.

Streptococcus pneumoniae serogroups 15 and 33: an increasing cause of pneumococcal infections in children in the United States after the introduction of the pneumococcal 7-valent conjugate vaccine.

Background: After the widespread use of the 7-valent pneumococcal conjugate vaccine, replacement serotypes have emerged. Serogroups 15 and 33 have emerged as nonvaccine serotypes causing invasive disease. We describe the clinical characteristics of children with infections caused by these serogroups and determined the genetic relationship of the strains. Materials and Methods: The United States Pediatric Multicenter Pneumococcal Surveillance Group has prospectively identified children with pneumococcal infections since 1993. Charts were reviewed retrospectively, isolates were serogrouped and serotyped and randomly selected strains were fingerprinted with the use of pulsed field gel electrophoresis. Selected strains were further characterized by multilocus sequence typing. Results: Between January 1994 and December 2004, 103 children had pneumococcal disease caused by serogroup 15, and 40 children had infections caused by serogroup 33. There was an increase from a mean of 7 cases per year for serogroup 15 in the prevaccine period to 14 cases per year in the postvaccine period and from 2 cases per year for serogroup 33 to 7 cases per year in the same periods. Isolates were susceptible to penicillin and ceftriaxone in both periods. A predominant clone was found in each serogroup representing 60% (30 of 50) of serogroup 15 strains and 83% (24 of 29) of the serotype 33F strains. The serogroup 15 clone comprised strains of serotypes 15B and 15C, whereas the 33 clone contained only serotype 33F strains. One isolate from each of the 15 and 33 clones was characterized by multilocus sequence typing and were found to be ST199 and 100, respectively. Conclusions: Pneumococcal disease in children caused by penicillin-susceptible clones of serogroups 15 and 33 is increasing in the United States. Clinicians should consider replacement serotypes when encountered with invasive pneumococcal disease in vaccinated children.

Increased rate of isolation of penicillin-resistant Streptococcus pneumoniae in a children's hospital and in vitro susceptibilities to antibiotics of potential therapeutic use.

The isolation of Streptococcus pneumoniae with both high and intermediate resistance to penicillin has increased in our institution since 1989 to an average of 12.1% of all isolates. We determined the susceptibilities of 95 isolates (34 susceptible to penicillin, 42 intermediate in resistance to penicillin, and 19 resistant to penicillin) to 16 antimicrobial agents of potential use in the treatment of disease caused by S. pneumoniae. Susceptibility to penicillin was determined by broth macrodilution with Mueller-Hinton broth supplemented with 5% lysed horse blood. Isolates were classified as highly resistant when the MIC was greater than or equal to 2.0 micrograms/ml, intermediate in resistance when the MIC was between 0.1 and 1.0 microgram/ml, and susceptible when the MIC was less than 0.1 microgram/ml. Fifteen of 19 isolates found to be highly resistant to penicillin were recovered from the middle ear of children. None of the isolates recovered from cerebrospinal fluid was highly resistant to penicillin. Fifteen of these isolates highly resistant to penicillin were found to be serogroup 6. Susceptibilities to other antibiotics were determined by the agar dilution method with Mueller-Hinton agar containing 5% lysed horse blood and an inoculum of 10(4) CFU per spot delivered by a replicator device. The MIC for 90% of isolates increased with increasing penicillin resistance for all antibiotics tested, except chloramphenicol, ciprofloxacin, rifampin, and vancomycin. Regardless of the classification of penicillin resistance, all isolates were classified as susceptible to cefotaxime, cefpirome, cefpodoxime, clarithromycin, imipenem, rifampin, and vancomycin on the basis of National Committee for Clinical Laboratory Standards interpretive guidelines. Interpretation of susceptibilities on the basis of currently available guidelines is difficult in that susceptibility guidelines applicable specifically to S. pneumoniae are not available. Images

Increase of the USA300 Clone Among Community-Acquired Methicillin -Susceptible Staphylococcus aureus Causing Invasive Infections

Background: Methicillin-resistant Staphylococcus aureus (MRSA) USA300 is a predominant cause of community-acquired (CA) infection in the United States. We compared clinical characteristics of children with USA300 versus non-USA300 CA-methicillin-susceptible S. aureus (CA-MSSA) invasive infections at Texas Childrens Hospital (TCH). Methods: Medical records were reviewed from children with invasive CA-MSSA infections at TCH between August 1, 2001 and September 30, 2006. Isolates were characterized by pulsed-field gel electrophoresis and polymerase chain reaction for Panton-Valentine leukocidin genes (pvl). Results: Invasive CA-MSSA infections increased from 14 in year 1 to 36 in year 5 (5-year total = 122 patients). Among the CA-MSSA isolates available for typing in the 5-year period, USA300 MSSA strains increased from 14% (2 of 14) to 35% (11 of 31) (P = 0.03). USA300 MSSA strains were more likely than non-USA300 MSSA strains to be nonsusceptible to erythromycin [66% (19 of 29) versus 28% (25 of 88); P < 0.01]. Osteomyelitis cases increased from 43% (6 of 14) in year 1 to 67% (24 of 36) in year 5. The majority of pvl+ MSSA isolates were USA300 (71% (25 of 35); only 5% (4 of 82) of pvl− MSSA isolates were USA300. Patients with osteomyelitis caused by pvl+ isolates had significantly higher mean values for erythrocyte sedimentation rate at admission (P = 0.005) and erythrocyte sedimentation rate maximum value (P = 0.002), maximum C-reactive protein (P = 0.04), and absolute neutrophil count at presentation (P = 0.04) compared with patients whose isolates were pvl−. Conclusions: USA300 accounted for a growing proportion of CA-MSSA isolates among children and was associated with increased numbers of invasive CA-MSSA infections at TCH, especially osteomyelitis. Associations were found in CA-MSSA osteomyelitis between pvl and increased concentrations of systemic inflammatory markers in patients.

Staphylococcus aureus pneumonia in children in the era of community-acquired methicillin-resistance at Texas Children's Hospital.

Background: Community-acquired Staphylococcus aureus (SA) pneumonia has increased in children, yet few studies have focused on this infection. Methods: Patients with SA pneumonia (not ventilator-associated) were identified from our surveillance database. Medical records were reviewed; isolates were genotyped by PFGE and Panton-Valentine leukocidin genes detected by polymerase chain reaction. Results: From August 2001 to April 2009, 117 patients had SA pneumonia. The rate of SA pneumonia per 10,000 admissions increased from 4.81 hospitalizations in year 1 to 9.75 in year 7 (P = 0.04). Methicillin-resistant SA (MRSA) caused 74% and methicillin-susceptible SA (MSSA) caused 26% of the infections. USA300 represented 75/82 (92%) of the MRSA and 14/28 (50%) of the MSSA isolates (P < 0.01). Patients with MRSA were younger (median [range], 0.8 years [0.1–16.9 years]) than patients with MSSA infections (2.5 years [0.2–20.9 years]) (P = 0.008). Clinical presentation was pneumonia with or without effusion in 30, empyema in 72, or lung abscess in 15 cases. Viral coinfections in 18/68 patients tested were associated with respiratory failure (72% vs. 24% [P < 0.001]). Thirty-five children were intubated and 68 had intensive care unit care; 89, 25, and 3 had video-assisted thoracoscopy (VATS), thoracentesis, and lobectomy, respectively. VATS was used more for USA300 than non-USA300 infections (80% vs. 57% [P = 0.03]). In all, 88 children received clindamycin. Improvement or cure occurred in 103 patients (88%), unscheduled visit or readmission related to the same problem in 6, respiratory sequelae in 7, and death in 1 patient. Conclusions: SA pneumonia increased in frequency over the study years and most were caused by community-acquired MRSA and USA300 isolates. Viral coinfection in 15% of the cases was associated with respiratory failure. Clindamycin is an effective treatment for susceptible-SA pneumonia; VATS was more common in patients with USA300 infections.

Vancomycin MICs for Staphylococcus aureus Vary by Detection Method and Have Subtly Increased in a Pediatric Population Since 2005

ABSTRACT Vancomycin MICs for Staphylococcus aureus isolates in a pediatric hospital with a high rate of staphylococcal infections were examined for any increase over a 7-year period. A broth microdilution scheme allowed direct comparison of the MICs generated by this method to MICs generated by Etest. MICs generated by both methods were determined with the same inoculum suspension. One hundred sixty-five S. aureus isolates were selected on the basis of the patients having been bacteremic or having received vancomycin as the definitive therapy for their infections. Of the 165 isolates, 117 were methicillin-resistant S. aureus and 48 were methicillin-susceptible S. aureus. Forty-seven were acquired in the hospital (nosocomial), 56 were community acquired, and 62 were community onset-health care associated. All but one isolate tested by broth microdilution had MICs of <1.0 μg/ml, while 96% of these same isolates tested by Etest had MICs of ≥1 μg/ml. A significant increase in MICs that occurred after study year 4 (2004 to 2005) was demonstrated by the Etest (P < 0.00007) but not by broth microdilution. MICs were not different for isolates of community or health care origin, regardless of methodology. The proportion of isolates with Etest MICs of <1 and ≥1 μg/ml between children with bacteremia for ≤5 days and >5 days (P = 0.3) was not different. We conclude that MICs for pediatric isolates have increased slightly since 2005 and therapeutic decisions based on vancomycin MICs need to be made by considering the methodology used.

Hospital-acquired staphylococcus aureus infections at Texas children's hospital, 2001-2007

OBJECTIVE To document the introduction of the methicillin-resistant Staphylococcus aureus (MRSA) USA300 clone into a childrens hospital. Current molecular epidemiology of infections due to the USA300 strain of MRSA in the pediatric healthcare setting remains obscure. DESIGN Retrospective study of patients with hospital-acquired S. aureus infection during the period from August 1, 2001, through July 31, 2007, at Texas Childrens Hospital in Houston. METHODS Patients with hospital-acquired S. aureus infection from whom an isolate was available for molecular analysis were included. Clinical information was obtained from patient medical records and the electronic hospital information system. S. aureus isolates underwent antimicrobial susceptibility testing, pulsed-field gel electrophoresis, and polymerase chain reaction testing for staphylococcal cassette chromosome (SCC) mec, agr, the diamine N-acetyltransferase gene, and the Panton-Valentine leukocidin genes (pvl). RESULTS Of 242 patients with hospital-acquired S. aureus infection, 147 (61%) had methicillin-susceptible S. aureus infection. Of the 95 MRSA isolates causing hospital-acquired infection, 69 (73%) were USA300 isolates, and that rate did not increase over time. Skin and soft tissue infection (P < .001), onset of infection less than 10 days after admission (P = .007), and lack of comorbidities (P < .001) were associated with hospital-acquired MRSA infection caused by the USA300 strain, compared with other isolates (hereafter referred to as non-USA300 isolates). Nine of 10 patients with a S. aureus infection at the time of death were infected with a non-USA300 strain. USA300 carried SCCmec IV, agr I, the diamine N-acetyl transferase gene, and pvl. USA300 isolates were more susceptible to clindamycin, gentamicin, and trimethoprim-sulfamethoxazole than were other non-USA300 isolates (P < .01). CONCLUSIONS In our patient population, the annual numbers of observed cases of hospital-acquired S. aureus infection have remained constant. USA300 was the most common clone and, compared with other non-USA300 MRSA isolates, was associated with skin and soft tissue infection, early onset of infection after admission, and greater susceptibility to antimicrobial agents.