Biomedical subjects

Françoise Perdreau-Remington

Publications and source records attributed to Françoise Perdreau-Remington.

13 recordsLinked to original sources

PubMed2006

Complete genome sequence of USA300, an epidemic clone of community-acquired meticillin-resistant Staphylococcus aureus.

BACKGROUND: USA300, a clone of meticillin-resistant Staphylococcus aureus, is a major source of community-acquired infections in the USA, Canada, and Europe. Our aim was to sequence its genome and compare it with those of other strains of S aureus to try to identify genes responsible for its distinctive epidemiological and virulence properties. METHODS: We ascertained the genome sequence of FPR3757, a multidrug resistant USA300 strain, by random shotgun sequencing, then compared it with the sequences of ten other staphylococcal strains. FINDINGS: Compared with closely related S aureus, we noted that almost all of the unique genes in USA300 clustered in novel allotypes of mobile genetic elements. Some of the unique genes are involved in pathogenesis, including Panton-Valentine leucocidin and molecular variants of enterotoxin Q and K. The most striking feature of the USA300 genome is the horizontal acquisition of a novel mobile genetic element that encodes an arginine deiminase pathway and an oligopeptide permease system that could contribute to growth and survival of USA300. We did not detect this element, termed arginine catabolic mobile element (ACME), in other S aureus strains. We noted a high prevalence of ACME in S epidermidis, suggesting not only that ACME transfers into USA300 from S epidermidis, but also that this element confers a selective advantage to this ubiquitous commensal of the human skin. INTERPRETATION: USA300 has acquired mobile genetic elements that encode resistance and virulence determinants that could enhance fitness and pathogenicity.

Community-Acquired Infections↗

PubMed2006

New Staphylococcus aureus genotyping method based on exotoxin (set) genes.

A variety of methods for genotyping Staphylococcus aureus isolates exists: the two most widely used methods are pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). Here, we describe a sequence-based genotyping method based on genes encoding S. aureus superantigen-like proteins, which belong to a family of exotoxins called staphylococcal exotoxins. The sequences of PCR-amplified internal fragments of three different set genes (set2, set5, and set7) of 61 well-characterized clinical methicillin-resistant S. aureus (MRSA) and methicillin-susceptible S. aureus (MSSA) isolates and reference strains were compared. Phylogenetic analysis was performed based on single-nucleotide polymorphisms (SNP). The SNP dendrograms of the set gene sequences differentiated the 61 isolates into 22 distinct subgroups, designated exotoxin sequence types (ETST), while the standard seven-gene MLST profiles differentiated the same 61 isolates into 19 subgroups. Of the 19 different MLST subgroups, 16 corresponded to 16 distinct ETST groups. However, three MLST subgroups, ST1, ST30, and ST36, were each further separated into more than one ETST subgroup. The exotoxin-based genotyping method was able to discriminate MRSA and MSSA isolates according to their specific epidemiological characteristics. This SNP analysis of the three set genes is thus equally or more discriminatory than the seven-gene MLST method, providing a good alternative typing tool for a laboratory that has sequencing capability.

Bacterial Proteins↗

PubMed2005

Multidrug-resistant Escherichia coli clonal groups causing community-acquired bloodstream infections.

OBJECTIVES: A multidrug-resistant Escherichia coli clonal group (designated CgA) has been isolated from women with cystitis and pyelonephritis in several communities. This study was designed to determine if CgA can cause community-acquired bloodstream infections. METHODS: All community-acquired bloodstream infections caused by E. coli identified at the San Francisco General Hospital between May 2001 and May 2003 were included. The diagnosis of septicemia was based on admission diagnosis. E. coli isolates were characterized by antibiotic susceptibility profile, enterobacterial repetitive intergenic consensus (ERIC2) PCR, serogrouping, and pulsed field gel electrophoresis (PFGE). RESULTS: A total of 127 individuals with a community-acquired bloodstream infection were identified; 48 (39%) were trimethoprim-sulfamethoxazole (SXT)-resistant. CgA, as defined by ERIC2 PCR, was responsible for 19 (15%) of these infections. Infection with a CgA isolate was associated with an admission diagnosis of cystitis or pyelonephritis (p=0.01). By PFGE, none of the CgA isolates were indistinguishable to the prototype cystitis strain; however, nine bloodstream isolates differed by fewer than six bands. CONCLUSIONS: CgA can cause community-acquired bloodstream infections, but does not appear to cause a disproportionate number of severe extraintestinal infections. This study provides evidence that UTI-causing clonal groups can cause a wide spectrum of disease and are an important clinical and public health concern.

Adolescent↗

PubMed2005

Population dynamics of nasal strains of methicillin-resistant Staphylococcus aureus--and their relation to community-associated disease activity.

BACKGROUND: Nasal carriage of methicillin-resistant Staphylococcus aureus (MRSA) plays a key role in the epidemiology and pathogenesis of disease. The purpose of this study was to determine the characteristics and dynamics of nasal strains of MRSA, as well as their relation to community-associated disease activity. METHODS: This study is a cross-sectional survey and molecular epidemiologic analysis of nasal colonization by S. aureus in homeless and runaway youths, an underserved population at high risk for staphylococcal disease. RESULTS: Of the 308 study participants, 27.6% carried S. aureus, and 6.2% carried MRSA. Subgroups of individuals with increased MRSA carriage rates were also at highest risk for community-associated MRSA infection; these subgroups included individuals with either HIV infection or AIDS, injection drug users, patients with abscesses, and those recently hospitalized. Multilocus sequence typing and pulsed-field gel electrophoresis identified 2 genotypes--ST59:P (USA1000) and ST8:S (USA300)--that accounted for 84.2% (16/19) of the MRSA isolates carried. The genotypes were distinct from nosocomial genotypes endemic in the hospital, although they originated from individuals with prior exposure to health care. CONCLUSIONS: Comparison of MRSA strains from asymptomatic carriers versus concurrently collected community-associated clinical strains from patients treated at local health-care facilities allowed for the identification of 3 population dynamics of nasal strains of MRSA: (1) endemic clones--for example, ST8:C and ST59:P--sustained asymptomatic carriage and infection over prolonged periods; (2) an epidemic clone, ST8:S, demonstrated enhanced capacity for rapid transmission and widespread infections; and (3) an outbreak clone, ST30:Z (USA1100), was highly infectious but exhibited poor asymptomatic transmission.

Adolescent↗

PubMed2004

Community-adapted methicillin-resistant Staphylococcus aureus (MRSA): population dynamics of an expanding community reservoir of MRSA.

To define methicillin-resistant Staphylococcus aureus (MRSA) reservoirs in the community and their population dynamics, we studied the molecular epidemiology of a random sample (n=490) from a collection of 2154 inpatient and outpatient MRSA isolates during a 7-year period in San Francisco. We noted a progressive replacement of type II staphylococcal chromosomal cassette (SCC)mec-bearing isolates with type IV SCCmec-bearing isolates, which coincided with >4-fold increase in methicillin resistance between 1998 and 2002. Type IV SCCmec-bearing isolates involved in the increase in methicillin resistance belonged to 4 molecular genotypes. These 4 genotypes were associated predominantly with community-onset disease, rather than hospital- or long-term-care facility-onset disease (76.9% vs. 19.4% vs. 3.7%; P=.0005), suggesting that they are not feral descendants of hospital isolates. The longitudinal results linked the dramatic increase in MRSA infections to an expanding community reservoir of MRSA genotypes with intrinsic community survival advantage.

Anti-Bacterial Agents↗

PubMed2004

Origins of community strains of methicillin-resistant Staphylococcus aureus.

To characterize methicillin-resistant Staphylococcus aureus (MRSA) strains circulating in the community, we identified predictors of isolating community MRSA and genotyped a sample of MRSA collected from a community-based, high-risk population. Computerized databases of the Community Health Network of San Francisco and the Clinical Microbiology Laboratory were searched electronically for the years 1992-1999 to identify community-onset infections caused by MRSA. Sequential analyses were performed to identify predictors of MRSA strains. The majority (58%) of infections were caused by strains traceable to the hospital or to long-term care facilities. Injection drug use was associated with infections that were not associated with health care settings. Genotypes for 20 of 35 MRSA isolates recovered from injection drug users did not match any of >600 genotypes of clinical isolates. In a nonoutbreak setting, the hospital was the main source of community MRSA; however, the presence of genetically distinct and diverse MRSA strains indicates MRSA strains now also originate from the community.

Anti-Bacterial Agents↗

PubMed2004

Clinical, epidemiologic, and molecular evaluation of a clonal outbreak of methicillin-resistant Staphylococcus aureus infection.

San Francisco General Hospital (San Francisco, CA) experienced an overall increase in the recovery of methicillin-resistant Staphylococcus aureus (MRSA) isolates that were shown by pulsed-field gel electrophoresis to have a genotype (genotype A1) that was new to this institution. We performed a case-control study to identify risk factors for acquiring genotype A1 MRSA infection from 1 October 2001 to 19 July 2002. Patients with genotype A1 MRSA infection were compared with 2 control groups: MRSA-infected control patients (i.e., patients with infection due to non-genotype A1 MRSA) and non-MRSA infected control patients (i.e., hospitalized patients without MRSA infection). There were 41 case patients infected with genotype A1 MRSA, 99 control patients infected with MRSA, and 41 control patients without MRSA infection. Pneumonia, surgical wound infections, and line infections occurred more frequently among case patients. Intensive care unit exposure and invasive procedures conferred the greatest risk for genotype A1 MRSA infection in multivariate models. Case patients were not associated with increased mortality, after adjusting for age, comorbidities, and intensive care unit exposure. Genotype A1 MRSA caused a large nosocomial outbreak of infection that was associated with distinct risk factors and clinical manifestations.

Bacterial Typing Techniques↗

PubMed2004

An epidemic of methicillin-resistant Staphylococcus aureus soft tissue infections among medically underserved patients.

HYPOTHESIS: A high prevalence of methicillin-resistant Staphylococcus aureus (MRSA) in soft tissue infections presents a treatment challenge. DESIGN: Retrospective analysis. SETTING: The San Francisco General Hospital Integrated Soft Tissue Infection (ISIS) Clinic. PATIENTS: Patients treated at the ISIS Clinic from July 1, 2000, to June 30, 2003. MAIN OUTCOME MEASURES: Information on patient demographics, surgical procedures, microbiologic studies, and antibiotic treatments was obtained for all patients treated in the ISIS Clinic. Microbial data and antibiotic susceptibility pattern of S aureus, treatment outcome, and antibiotic prescribed were analyzed for all evaluable patients. RESULTS: The ISIS Clinic treated 6156 unique patients for 12,012 episodes of infection. In this cohort, 5164 (84%) were either homeless or had no health insurance. More than half of the patients (58%) were injection drug users, but most had only 1 prior visit to the clinic (62%). Patients underwent a surgical procedure 7707 times (64%). Of the 837 positive cultures obtained, S aureus was recovered 695 times (83%), and 525 (63%) of the cultures contained MRSA. Therefore, a full 76% of all S aureus isolated was MRSA. In a subset analysis of 622 cultures collected prospectively from consecutive patients, 282 (45%) grew organisms, of which 256 (91%) were S aureus. MRSA represented 59% of all S aureus isolated. Homelessness and injection drug use were risk factors for infection by S aureus and MRSA. In another subgroup of patients with soft tissue infections that required admission to the hospital, MRSA was recovered from the cultures in 149 patients. In these patients with MRSA, 44 (30%) only received a beta-lactam antibiotic, inactive against MRSA, and had full resolution of their infection. CONCLUSIONS: The prevalence of MRSA soft tissue infections in the medically underserved ISIS Clinic cohort is extremely high. The transmission of the MRSA seems to be in the community. Antibiotic therapy directed at MRSA may not be needed in a large number of patients with these soft tissue infections. Studies to identify the source and cause of this MRSA outbreak are urgently needed. Clinical trials to examine the need for antibiotic therapy in soft tissue infections should be conducted.

Community-Acquired Infections↗

PubMed2004

Widespread skin and soft-tissue infections due to two methicillin-resistant Staphylococcus aureus strains harboring the genes for Panton-Valentine leucocidin.

Infections caused by community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) are emerging as a major public health problem. CA-MRSA has been associated previously with skin and soft-tissue infection (SSTI) and with carriage of staphylococcal cassette chromosome mec (SCCmec) type IV and the Panton-Valentine leucocidin (PVL) virulence factor. To assess the clonal distribution of PVL-carrying strains and the association with SSTI in the San Francisco Bay area, we surveyed six collections of S. aureus isolates-671 isolates in all-collected between 1997 and 2002 originating from inpatient and outpatient clinical specimens and from a community-based sampling. Isolates were genotyped by pulsed-field gel electrophoresis, multilocus restriction fragment typing, and multilocus sequence typing and assayed for the PVL virulence factor. The S. aureus populations showed a high proportion of PVL-carrying strains, with frequencies ranging up to 70% in MRSA isolated from jail inmate patients and 69% in MRSA from patients receiving surgical treatment at an outpatient clinic specializing in treating SSTIs. PVL-carrying isolates were identified in nine clonal groups, but 88.5% of the PVL-carrying MRSA isolates belonged to only two clonal groups. These two clonal groups carried the SCCmec type IV resistance determinant and were more likely than other clonal groups to be recovered from SSTI sites than from other sites (P < 0.0001). There is evidence of clonal replacement over the period from 1999 to 2002, with one of these two clonal groups being supplanted by the other.

Bacterial Toxins↗

PubMed2003

Increasing prevalence of methicillin-resistant Staphylococcus aureus infection in California jails.

Staphylococcus aureus clinical isolates obtained from patients who were inmates of the San Francisco County jail system showed an increase in the prevalence of methicillin-resistant Staphylococcus aureus (MRSA) from 29%, in 1997, to 74%, in 2002; 91% of the MRSA isolates carried staphylococcal chromosomal cassette mec (SCCmec) type IV. Pulsed field gel electrophoresis and multilocus sequence typing demonstrated 2 major clonal groups. One of these clonal groups is genetically indistinguishable from the strain responsible for an outbreak of MRSA in the Los Angeles County jail system in 2002.

Anti-Bacterial Agents↗

PubMed2003

Vancomycin treatment failure associated with heterogeneous vancomycin-intermediate Staphylococcus aureus in a patient with endocarditis and in the rabbit model of endocarditis.

Heterogeneous resistance to vancomycin is thought to precede emergence of intermediate susceptibility to vancomycin in Staphylococcus aureus, but the clinical significance of heterogeneous resistance is unknown. Paired S. aureus isolates from a patient with endocarditis who relapsed after vancomycin treatment were tested for heterogeneous resistance to vancomycin. The pretreatment and the relapse clinical isolates (strains SF1 and SF2, respectively) were genotyped by pulsed-field gel electrophoresis. Susceptibility to vancomycin was assessed by the broth dilution method, population analysis, and time-kill studies and in the rabbit model of endocarditis. Strains SF1 and SF2 had similar genotypes, and the vancomycin MICs for the strains were </=2 micro g/ml. SF2 exhibited heterogeneous resistance to vancomycin. Vancomycin eradicated SF1 in the rabbit model of endocarditis, while SF2 persisted at pretreatment levels. Vancomycin treatment failure in this patient with endocarditis was attributable to heterogeneous resistance to vancomycin.

Animals↗

PubMed2003

Clonal characterization of Staphylococcus aureus by multilocus restriction fragment typing, a rapid screening approach for molecular epidemiology.

We have developed a rapid and simplified approach for the strain characterization of Staphylococcus aureus on the basis of multilocus sequence typing (MLST) in which sequence variations in the MLST housekeeping gene loci are detected by restriction fragment pattern analysis rather than sequencing; we refer to this approach as multilocus restriction fragment typing (MLRFT). Briefly, MLRFT for S. aureus involves the PCR amplification of each of the seven MLST housekeeping gene loci by using the same primer pairs used in MLST. The amplicons are then digested directly with one or two restriction enzymes and the restriction fragments are resolved by agarose gel electrophoresis. Projection from published MLST data shows that MLRFT captures about 95% of the genetic diversity detected by MLST. The MLRFT approach was validated with a set of 59 methicillin-susceptible and 44 methicillin-resistant S. aureus isolates from community-acquired and nosocomial sources which had previously been characterized by pulsed-field gel electrophoresis (PFGE). MLRFT resolved the 103 isolates into 15 restriction fragment types, giving a discrimination index of 89.0%. Clonal groupings established by MLRFT correlated well with those established by PFGE. In short, MLRFT provides a convenient alternative to MLST and PFGE because it requires minimal laboratory facilities and is relatively simple and inexpensive to perform.

Alleles↗

PubMed2002

Population-based community prevalence of methicillin-resistant Staphylococcus aureus in the urban poor of San Francisco.

The study objective was to determine the prevalence and risk factors for nasal colonization with Staphylococcus aureus and methicillin resistance among the urban poor and to compare antibiotic resistance and genetic similarity to concurrently collected clinical isolates of methicillin-resistant S. aureus (MRSA). A population-based community sample of 833 homeless and marginally housed adults were cultured and compared with 363 clinical isolates of MRSA; 22.8% of the urban poor were colonized with S. aureus. Of S. aureus isolates, 12.0% were methicillin resistant. Overall prevalence of MRSA was 2.8%. Significant multivariate risk factors for MRSA were injection drug use (odds ratio [OR], 9.7), prior endocarditis (OR, 4.1), and prior hospitalization within 1 year (OR, 2.4). Resistance to antimicrobials other than beta-lactams was uncommon. Only 2 individuals (0.24%) with MRSA had no known risk factors. A total of 22 of 23 community MRSA genotypically matched clinical MRSA isolates, with 15 of 23 isolates identical to MRSA clones endemic among hospitalized patients.

Adolescent↗