Characteristics of Staphylococcus aureus infections, Chicago Pediatric Hospital.Invasive and skin community-associated (CA)--methicillin-resistant Staphylococcus aureus isolates from children were matched with invasive CA-methicillin-sensitive S. aureus strains during 2000-2004, Isolates were analyzed for presence of Panton-Valentine leukocidin. A USA400 lineage clone (n = 6) and the predominant USA300 lineage clone emerged. ********** Community-associated methicillin-resistant Staphylococcus aureus methicillin-resistant Staphylococcus aureus Methicillin-aminoglycoside resistant Staphylococcus aureus, MRSA An organism with multiple antibiotic resistances–eg, aminoglycosides, chloramphenicol, clindamycin, erythromycin, rifampin, tetracycline, (CA-MRSA CA-MRSA Community Acquired Methicillin-Resistant Staphylococcus Aureus ) infections have been increasing in children since the 1990s. Panton-Valentine leukocidin (PVL PVL Periventricular Leukomalacia PVL Prevail PVL Parameter Value Language PVL Pade Via Lanczos (circuit modeling) PVL Physical Volume Library PVL Pascack Valley Line (New Jersey Transit commuter rail line) ) has been associated with CA-MRSA strains (1-4). As CA-MRSA infections have been increasing in previously healthy pediatric patients, we sought to do the following: 1) describe the clonal relatedness of these CA-MRSA isolates by using pulsed-field gel electrophoresis (PFGE PFGE Pulsed-Field Gel Electrophoresis ), 2) detect the presence of PVL genes among CA-MRSA pediatric pediatric /pe·di·at·ric/ (pe?de-at´rik) pertaining to the health of children. pe·di·at·ric adj. Of or relating to pediatrics. isolates causing invasive disease and among isolates causing skin and soft tissue infections (SSTI SSTI State Science & Technology Institute (Westerville, OH) SSTI Skin and Soft Tissue Infection SSTI Small Spacecraft Technology Initiative SSTI Skin and Skin Structure Infection SSTI Six Sigma Technical Institute ), 3) determine clinical and epidemiologic differences among patients with invasive disease caused by community-associated methicillin-sensitive S. aureus (CA-MSSA) versus those with disease caused by CA-MRSA strains, 4) assess the geographic pattern of infection, and 5) measure the antimicrobial agent susceptibility for CA-MRSA strains. The institutional review board at Children's Memorial Hospital With almost 1,100 pediatric specialists focusing on 70 specialties in multiple locations, Children's Memorial Hospital routinely provides more care to more young people than any other Chicago-area hospital or medical center. , a 253-bed, freestanding children's hospital in Chicago, Illinois, approved this study. A CA-MRSA strain was defined as a clinical MRSA MRSA Methicillin-resistant Staphylococcus aureus. See MARSA. isolate recovered from a pediatric patient (<1-18 years of age) who had no established risk factors for MRSA infection (no residence in long-term care facility long-term care facility n. See skilled nursing facility. , no hospitalization except for routine birth, and no permanent indwelling indwelling /in·dwell·ing/ (in´dwel-ing) pertaining to a catheter or other tube left within an organ or body passage for drainage, to maintain patency, or for the administration of drugs or nutrients. medical devices). For most patients, strains were recovered within 72 hours of admission. Exceptions included patients who had clinical evidence of community-associated disease and whose isolates were obtained after 72 hours of hospitalization. Isolates recovered from normally sterile sites were defined as invasive. We identified patients with S. aureus infections retrospectively by reviewing microbiology log books from March 1, 2000, through November 30, 2004. Demographic and clinical data retrieved included age, sex, race, ZIP code of residence, length of hospitalization, and clinical outcomes. When possible, patients with invasive cases were matched to patients with CA-MRSA SSTI and to those with invasive CA-MSSA infections by age (within 12 months for those <18 months or within 3 years for those >18 months), geographic location of patient residence, or year of infection. S. aureus isolates were identified by standard microbiologic methods. For all S. aureus isolates that appeared erythromycin erythromycin (ĭrĭth'rōmī`sĭn), any of several related antibiotic drugs produced by bacteria of the genus Streptomyces (see antibiotic). resistant and clindamycin susceptible, antibiotic double disk diffusion assay was performed (5). Isolates of S. aureus, including control strain NCTC NCTC National Conservation Training Center NCTC National Counterterrorism Center (9/11 Commission Report) NCTC National Cable Television Cooperative NCTC National Collection of Type Cultures (UK laboratory) 8325 (Bio-Rad, Hercules, CA, USA), were analyzed by PFGE after DNA DNA: see nucleic acid. DNA or deoxyribonucleic acid One of two types of nucleic acid (the other is RNA); a complex organic compound found in all living cells and many viruses. It is the chemical substance of genes. digestion with SmaI. Resulting fragments were separated by using the Staphylococcus staphylococcus (stăf'ələkŏk`əs), any of the pathogenic bacteria, parasitic to humans, that belong to the genus Staphylococcus. The spherical bacterial cells (cocci) typically occur in irregular clusters [Gr. program 5 (GenePath System, Bio-Rad), and DNA banding patterns were compared (6, 7). PCR PCR polymerase chain reaction. PCR abbr. polymerase chain reaction Polymerase chain reaction (PCR) was used to detect the PVL genes (8). Categorical variables were analyzed by [chi square] analysis. Variables with non-normal distribution were analyzed by Mann-Whitney U test Mann-Whitney U test, n.pr See test, Mann-Whitney U. ; 2-tailed p value [less than or equal to] 0.05 was statistically significant (SPSS A statistical package from SPSS, Inc., Chicago (www.spss.com) that runs on PCs, most mainframes and minis and is used extensively in marketing research. It provides over 50 statistical processes, including regression analysis, correlation and analysis of variance. Inc., version 11.0, Chicago, IL, USA). From 166 MRSA patient strains noted in the microbiology records, 21 patients with invasive CA-MRSA infection were identified. Three patient isolates were unavailable and were excluded from analysis. Patients with invasive CA-MRSA strains were case-matched with patients with CA-MRSA SSTI (16/18 were matched by age). During the study period, [approximately equal to] 31 cases of invasive CA-MSSA disease were identified and 10 cases were able to be retrieved and matched with cases of invasive CA-MRSA (9/10 case-patients were matched by age). Groups with invasive CA-MRSA and groups with invasive CA-MSSA did not differ significantly regarding sex, initial leukocyte count, duration of fever, or length of hospital stay. Pediatric patients with invasive CA-MRSA infection were more likely to be African American (p = 0.01) and were febrile febrile /feb·rile/ (feb´ril) pertaining to or characterized by fever. feb·rile adj. Of, relating to, or characterized by fever; feverish. significantly longer than patients with invasive CA-MSSA (p = 0.03). One of the patients with invasive CA-MRSA died (Table 1). Among the 18 patients with invasive CA-MRSA, 17 patients required surgical drainage, and 1 patient was given extracorporeal extracorporeal /ex·tra·cor·po·re·al/ (-kor-por´e-al) situated or occurring outside the body. ex·tra·cor·po·re·al adj. Situated or occurring outside the body. membranous membranous /mem·bra·nous/ (mem´brah-nus) pertaining to or of the nature of a membrane. mem·bra·nous adj. 1. Relating to, made of, or similar to a membrane. 2. oxygenation oxygenation /ox·y·gen·a·tion/ (ok?si-je-na´shun) 1. the act or process of adding oxygen. 2. the result of having oxygen added. . Among the 10 patients with invasive CA-MSSA disease, all required surgical intervention, but none died. Of 18 patients with SSTI CA-MRSA disease, 12 were African American, and 2 were Hispanic. The average hospital stay for this group was 2.3 days. Seven children required no hospitalization or hospitalization <24 hours. A representative PFGE result is depicted in the Figure. Two predominant clones emerged among the local and invasive CA-MRSA isolates. The clone A (n = 6) was identified to be of the USA400 lineage, and the B clone (n = 30) was identified to be of the USA300 lineage. No predominant clones emerged from the invasive MSSA MSSA Methicillin-Sensitive Staphylococcus Aureus MSSA Microscopy Society of Southern Africa MSSA Maryland Saltwater Sportfishermen's Association MSSA Military Selective Service Act MSSA Mid-South Sociological Association MSSA Minnesota Social Service Association isolates; 6 unique clones were identified from 10 isolates (data not shown). No isolates were of the USA300 or 400 lineage. The clinical manifestations of invasive disease in patients with CA-MRSA disease from clone A were pneumonia with empyema empyema (ĕmpē-ē`mə), persistent purulent discharge into a cavity such as the pleural space or the gallbladder. Empyema results as a complication of bacterial infections such as pneumonia and lung abscess. , osteomyelitis osteomyelitis (ŏs'tēōmī'əlī`tĭs), infection of the bone and bone marrow. Direct infection of bone usually occurs through open fractures, penetrating wounds, or surgical operations. , bacteremia bacteremia: see septicemia. bacteremia Presence of bacteria in the blood. Short-term bacteremia follows dental or surgical procedures, especially if local infection or very high-risk surgery releases bacteria from isolated sites. , and septic arthritis. The clinical manifestations of invasive disease in patients with clone B infection included sepsis, toxic-shock syndrome, osteomyelitis, fasciitis fasciitis /fas·ci·itis/ (fas-e-i´tis) inflammation of a fascia. eosinophilic fasciitis , bacteremia, pyomyositis, pneumonia with empyema, deep visceral abscesses, and perirectal abscess abscess, localized inflamation associated with tissue necrosis. Abscesses are characterized by inflamation, which is due to the accumulation of pus in the local tissues, and often painful swelling. with prostatitis prostatitis (prŏs'tətī`tĭs), inflammation of the prostate gland. Acute prostatitis is usually a result of infection in the urinary tract or infection carried by the blood; in many cases the infection spreads from the urethra and is ; 1 patient in this group died. Clone A was found in a wide geographic distribution around metropolitan Chicago. In contrast, clone B was located with more frequency within the city limits of Chicago. [FIGURE OMITTED] Antimicrobial susceptibility patterns among CA-MRSA strains are detailed in Table 2. Two CA-MRSA isolates that were positive by 3-D test belonged to the A0 clone. None of the MRSA isolates that caused SSTI was D-test positive. The PVL gene was found in all of the CA-MRSA isolates that caused invasive and SSTI disease but in only 1 of 10 of the invasive CA-MSSA isolates (p<0.001). Conclusions PVL genes can be transmitted by means of bacteriophages, which allows them to be transmitted from 1 organism to another (9). When injected intradermally in·tra·der·mal adj. Within or between the layers of the skin: an intradermal injection. in in rabbits, PVL induces necrotic skin lesions (10), and PVL has been described in S. aureus isolates from patients with necrotizing pneumonia, skin infections, and musculoskeletal musculoskeletal /mus·cu·lo·skel·e·tal/ (-skel´e-t'l) pertaining to or comprising the skeleton and muscles. mus·cu·lo·skel·e·tal adj. Relating to or involving the muscles and the skeleton. infections. These outbreaks have been widespread (1,2,8,11-13). We found a wide range of severity of infection caused by clonally related CA-MRSA, PVL-positive isolates within our community, from superficial skin abscesses to fatal disease. Results of PFGE correlate well with results of other molecular typing methods, such as multilocus sequence typing Multilocus sequence typing (MLST) is a technique in molecular biology for the typing of multiple loci. The procedure characterizes isolates of bacterial species using the DNA sequences of internal fragments of multiple (usually seven) housekeeping genes. (MLST MLST Multi Locus Sequence Typing MLST Medical Logistics Support Team MLST Mini Losi Super Truck (1/18th scale radio control vehicle) ), which characterizes S. aureus species by using sequences of 7 conserved housekeeping genes (7). In accordance with other published studies in the United States, the USA300 strain was the most frequently isolated among CA-MRSA disease (12) in contrast to the invasive CA-MSSA disease, which had no predominant clonality. We also detected isolates of the USA400 lineage that harbored PVL genes. This lineage was previously described as a cause of severe and fatal CA-MRSA disease in children in the Midwest (14). Previous reports from University of Chicago have described a cluster of 4 cases in which USA400 isolates caused empyema and sepsis syndrome with some features of toxic-shock syndrome (4); 3 children died with necrotizing pneumonia and Waterhouse-Friderichsen syndrome due to a PVL-positive, MLST-identified type 1 strain (15). In contrast, our patient with fatal toxic-shock syndrome did not have any primary pulmonary pathology and had disease caused by a USA300 lineage strain. Limitations to our study include its retrospective nature and the limited numbers of patients. The geographic distribution of CA-MRSA isolates within the city likely reflects the geographic distribution of our patient population. Future prospective studies may further elucidate possible epidemiologic risk factors associated with acquiring CA-MRSA invasive infection. References (1.) Baggett HC, Hennessy TW, Rudolph K, Bruden D, Reasonover A, Parkinson A, et al. Community-onset methicillin-resistant Staphylococcus aureus associated with antibiotic use and the cytotoxin cytotoxin /cy·to·tox·in/ (si´to-tok?sin) a toxin or antibody having a specific toxic action upon cells of special organs. cy·to·tox·in n. Panton-Valentine leukocidin during a furunculosis furunculosis /fu·run·cu·lo·sis/ (fu-rung?ku-lo´sis) 1. the persistent sequential occurrence of furuncles over a period of weeks or months. 2. the simultaneous occurrence of a number of furuncles. outbreak in rural Alaska. J Infect Dis. 2004; 189:1565-73. (2.) Martinez-Aguilar G, Avalos-Mishaan A, Hulten K, Hammerman W, Mason EO Jr, Kaplan SL, et al. Community-acquired, methicillin-resistant and methicillin-susceptible Staphylococcus aureus musculoskeletal infections in children. Pediatr Infect Dis J. 2004;23:701-6. (3.) Mishaan AM, Mason EO Jr, Martinez-Aguilar G, Hammerman W, Propst JJ, Lupski JR, Stankiewicz P, et al. Emergence of a predominant clone of community-acquired Staphylococcus aureus among children in Houston, Texas. Pediatr Infect Dis J. 2005;24:201-6. (4.) Mongkolrattanothai K, Mason EO Jr, Martinez-Aguilar G, Hammerman W, Propst JJ, Lupski JR, et al. Severe Staphylococcus aureus infections caused by clonally related community-acquired methicillin-susceptible and methicillin-resistant isolates. Clin Infect Dis. 2003;37:1050-8. (5.) Fiebelkorn KR, Crawford SA, McElmeel ML, Jorgensen JH. Practical disk diffusion method for detection of inducible clindamycin resistance in Staphylococcus aureus and coagulase-negative staphylococci. J Clin Microbiol. 2003;41:4740-4. (6.) Tenover FC, Arbeit RD, Goering RV, Mickelsen PA, Murray BE, Persing DH, et al. Interpreting chromosomal DNA restriction patterns produced by pulsed-field gel electrophoresis: criteria for bacterial strain typing. J Clin Microbiol. 1995;33:2233-9. (7.) McDougal LK, Steward CD, Killgore GE, Chaitram JM, McAllister SK, Tenover FC. Pulsed-field gel electrophoresis typing of oxacillin-resistant Staphylococcus attreus isolates from the United States: establishing a national database. J Clin Microbiol. 2003;41:5113-20. (8.) Lina G, Piemont Y, Godail-Gamot F, Bes M, Peter MO, Gauduchon V, et al. Involvement of Panton-Valentine leukocidin-producing Staphylococcus aureus in primary skin infections and pneumonia. Clin Infect Dis. 1999;29:1128-32. (9.) Narita S, Kaneko J, Chiba J, Piemont Y, Jarraud S, Etienne J, et al. Phage phage: see bacteriophage. phage - A program that modifies other programs or databases in unauthorised ways; especially one that propagates a virus or Trojan horse. See also worm, mockingbird. The analogy, of course, is with phage viruses in biology. conversion of Panton-Valentine leukocidin in Staphylococcus aureus: molecular analysis of a PVL-converting phage, phiSLT. Gene. 2001;268:195-206. (10.) Ward PD, Turner WH. Identification of staphylococcal staphylococcal pertaining to Staphylococcus spp. staphylococcal clumping test used as a means of measuring the quantity of fibrinogen-split products in a sample of blood. Panton-Valentine leukocidin as a potent dermaonecrotic toxin. Infect Immun. 1980;28:393-7. (11.) Prevost G, Couppie P, Prevost P, Gayet S, Petiau P, Cribier B, et al. Epidemiological data on Staphylococcus aureus strains producing synergohymenotropic toxins. J Med Microbiol. 1995;42:237-45. (12.) Francis JS, Doherty MC, Lopatin U, Johnston CP, Sinha G, Ross T, et al. Severe community-onset pneumonia in healthy adults caused by methicillin-resistant Staphylococcus aureus carrying the Panton-Valentine leukocidin genes. Clin Infect Dis. 2005;40:100-7. (13.) Kazakova SV, Hageman JC, Matava M, Srinivasan A, Phelan L, Garfinkel B, et al. A clone of methicillin-resistant Staphylococcus aureus among professional football players. N Engl J Med. 2005;352:468-75. (14.) Centers for Disease Control and Prevention Centers for Disease Control and Prevention (CDC), agency of the U.S. Public Health Service since 1973, with headquarters in Atlanta; it was established in 1946 as the Communicable Disease Center. . Four pediatric deaths from community-acquired methicillin-resistant Staphylococcus aureus--Minnesota and North Dakota, 1997-1999. MMWR MMWR Morbidity & Mortality Weekly Report Epidemiology A news bulletin published by the CDC, which provides epidemiologic data–eg, statistics on the incidence of AIDS, rabies, rubella, STDs and other communicable diseases, causes of mortality–eg, Morb Mortal Wkly Rep. 1999;48:707-10. (15.) Adem PV, Montgomery CP, Husain AN, Koogler TK, Arangelovich V, Humilier M, et al. Staphylococcus attreus sepsis and the Waterhouse-Friderichsen syndrome in children. N Engl J Med. 2005;353:1245-51. Address for correspondence: Tina Q. Tan, Children's Memorial Hospital, 2300 Children's Plaza, Box 20, Chicago, IL, USA 60614; email: titan@childrensmemorial.org Preeti Jaggi, * Suzanne M. Paule, ([dagger]) Lance R. Peterson, ([dagger]) and Tina Q. Tan * * Northwestern University, Chicago, Illinois, USA; and ([dagger]) Evanston Northwestern Healthcare Evanston Northwestern Healthcare, located in Chicago's northern suburbs, is an academic health system affiliated with the McGaw Medical Center of Northwestern University and all attending physicians are on faculty at the Feinberg School of Medicine. , Evanston, Illinois, USA Dr Jaggi is a pediatric infectious disease fellow at Children's Memorial Hospital (Northwestern). Her major research interests have included group A streptococcal infections and pediatric community-associated MRSA infections.
Table 1. Comparison of clinical characteristics between pediatric
patients with invasive CA-MRSA and CA-MSSA *
Characteristic Invasive CA-MRSA, n (%)
Race
Black 16/18 (88)
Caucasian 0
Hispanic 1/18 (6)
Other 0
Unknown 1/18 (6)
Days of discordant therapy
(CA-MRSA)
Mean [+ or -] SD (range) 2.22 [+ or -] 1.76 (0-6)
Days febrile, mean [+ or -] 7.0 [+ or -] 4 (0-17)
SD (range)
Days in hospital, mean 14.2 [+ or -] 7.6 (4-28)
[+ or -] SD (range)
Diagnosis ([dagger])
Osteomyelitis, acute 3/18 (38)
Ostyeomyelitis, chronic 2/18 (11)
Bacteremia 5/18 (28)
Endocarditis 0/18 (0)
Pyomyositis 2/18 (11)
Liver abscess 1/18 (6)
Pneumonia + empyema 6/18 (33)
Septic joint 1/18 (6)
Fasciitis 1/18 (6)
Toxic-shock syndrome 1/18 (6)
Other ([dagger]) 3/18 (38)
Patients with >1 disease 7/18 (39)
manifestation (%)
Days of illness before 6.9 [+ or -] 11.8 (1-45)
hospitalization, mean
[+ or -] SD (range)
Days of positive cultures, 6.94 [+ or -] 9.9 (1-45)
mean [+ or -] SD (range)
Initial leukocyte count 14.8 [+ or -] 13.07 (2.4-57.0)
([section]) (thousand/
[micro]L), mean
[+ or -] SD (range)
Characteristic Invasive CA-MSSA, n (%) p value
Race
Black 3/10 (30) 0.01
Caucasian 2/10 (20) 0.01
Hispanic 5/10 (50) 0.01
Other 0 0.01
Unknown 1/10 (10) 0.01
Days of discordant therapy
(CA-MRSA)
Mean [+ or -] SD (range) N/A
Days febrile, mean [+ or -] 5.20 [+ or -] 10.0 (0-32) 0.03
SD (range)
Days in hospital, mean 13.8 [+ or -] 16.8 (4-60) NS
[+ or -] SD (range)
Diagnosis ([dagger])
Osteomyelitis, acute 1/10 (10) NS
Ostyeomyelitis, chronic 4/10 (40) NS
Bacteremia 2/10 (20) NS
Endocarditis 2/10 (20) NS
Pyomyositis 0/10 (0) NS
Liver abscess 0/10 (0) NS
Pneumonia + empyema 1/10 (10) NS
Septic joint 2/10 (20) NS
Fasciitis 0/10 (0) NS
Toxic-shock syndrome 0/10 (0) NS
Other ([dagger]) 0/10 (0) NS
Patients with >1 disease 1/10 (10) NS
manifestation (%)
Days of illness before 10.9 [+ or -] 15 (2-45) NS
hospitalization, mean
[+ or -] SD (range)
Days of positive cultures, 4.4 [+ or -] 2.98 (1-11) NS
mean [+ or -] SD (range)
Initial leukocyte count 9.95 [+ or -] 4.45 NS
([section]) (thousand/ (3.3-17.0)
[micro]L), mean
[+ or -] SD (range)
* CA-MRSA, community-associated methicillin-resistant Staphylococcus
aureus; MSSA, methicillin-sensitive S. aureus; NS, not significant, SD,
standard deviation. Among patients with invasive CA-MRSA infection,
1 died.
([dagger]) Bonferroni correction for multiple comparisons was applied
for comparisons of diagnosis.
([double dagger]) Other diseases included extensive perineal abscess
with fistula, subgaleal hematoma, and a subscapular abscess and
prostatitis in the same patient.
([section]) One initial leukocyte count was unavailable in each patient
group.
Table 2. Susceptibility data for CA-MRSA isolates from children *
CA-MRSA CA-MRSA
isolates isolates
causing causing local
invasive skin/soft
Susceptibility to disease, tissue
antimicrobial n (%) infections,
agent ([dagger]) n (%) p value
Resistant to erythromycin 16/18 (88.9) 11/18 (61) NS
Apparently susceptible to 18/18 (100) 18/18 (100) NS
clindamycin
Inducible clindamycin 3/16 (19) 0/10 (0) NS
resistance
Resistant to ciprofloxacin 2/18 (11) 1/18 (6) NS
Resistant to levofloxacin 1/18 (6) 1/18 (6) NS
Resistant to tetracycline 1/18 (5) 2/18 (11) NS
* CA-MRSA, community-associated methicillin-resistant Staphylococcus
aureus; NS, not significant.
([dagger]) In addition to the antimicrobial agents listed, all
isolates were susceptible to vancomycin, linezolid, and rifampin.
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