Robert S. Daum

Staphylococcus aureus is the leading cause of nosocomial and community-acquired infections, including soft tissue and skin infections and bacteremia. However, efforts to develop an effective vaccine against S. aureus infections have not been successful. We evaluated serotypes 5 and 8 capsule polysaccharides (CP) CRM197 conjugates as vaccine candidates in murine models of bacteremia, lethal sepsis, and skin infection. The conjugate vaccines elicited a good antibody response, and active immunization of CP5-CRM or CP8-CRM conjugates protected against staphylococcal bacteremia. In the skin infection model, CP8-CRM but not CP5-CRM protected against dermonecrosis, and CP8-CRM immunization significantly decreased the bacterial burden in the lesion. However, neither CP5-CRM nor CP8-CRM protected against mortality in the lethal sepsis model. The results indicate the capsular vaccines elicit protection against some, but not all, aspects of staphylococcal infection.

Staphylococcus aureus is a commensal species that can also be a formidable pathogen. In the United States, an epidemic of community-acquired methicillin-resistant Staphylococcus aureus (MRSA) infections has been occurring for the last 15 years. In the context of a study in which we identified patients with skin and soft tissue infections (SSTIs) and randomized them to receive one of two antimicrobial treatment regimens, we assessed S. aureus colonization in the nares, throat, and perianal skin on the day of enrollment and 40 days after therapy. We compared the prevalence of colonization between the SSTI patients and an uninfected control population. A total of 144 subjects and 130 controls, predominantly African American, participated in this study, and 116 returned for a 40-day follow-up visit. Of the SSTI patients, 76% were colonized with S. aureus at enrollment, as were 65% of the controls. Patients were more likely than the controls to be colonized with USA300 MRSA (62/144 [43.1%] versus 11/130 [8.5%], respectively; P < 0.001). The nares were not the most common site of colonization. The colonization prevalence diminished somewhat after antibiotic treatment but remained high. The isolates that colonized the controls were more likely than those in the patients to be methicillin-susceptible S. aureus (MSSA) (74/84 [88.1%] versus 56/106 [52.8%], respectively; P < 0.001). In conclusion, the prevalence of S. aureus colonization among SSTI patients was high and often involved USA300 MRSA. The prevalence diminished somewhat with antimicrobial therapy but remained high at the 40-day follow-up visit. Control subjects were also colonized at a high prevalence but most often with a genetic background not associated with a clinical infection in this study. S. aureus is a commensal species and a pathogen. Plans for decolonization or eradication should take this distinction into account.

Staphylococcus aureus is a human pathogen responsible for substantial morbidity and mortality through its ability to cause a number of human infections including bacteremia, pneumonia and soft tissue infections. Of great concern is the emergence and dissemination of methicillin–resistant Staphylococcus aureus strains (MRSA) that are resistant to nearly all β-lactams. The emergence of the USA300 MRSA genetic background among community associated S. aureus infections (CA-MRSA) in the USA was followed by the disappearance of USA400 CA-MRSA isolates. To gain a greater understanding of the potential fitness advantages and virulence capacity of S. aureus USA300 clones, we performed whole genome sequencing of 15 USA300 and 4 USA400 clinical isolates. A comparison of representative genomes of the USA300 and USA400 pulsotypes indicates a number of differences in mobile genome elements. We examined the in vitro gene expression profiles by microarray hybridization and the in vivo transcriptomes during lung infection in mice of a USA300 and a USA400 MRSA strain by performing complete genome qRT-PCR analysis. The unique presence and increased expression of 6 exotoxins in USA300 (12- to 600-fold) compared to USA400 may contribute to the increased virulence of USA300 clones. Importantly, we also observed the up-regulation of prophage genes in USA300 (compared with USA400) during mouse lung infection (including genes encoded by both prophages ΦSa2usa and ΦSa3usa), suggesting that these prophages may play an important role in vivo by contributing to the elevated virulence characteristic of the USA300 clone. We observed differences in the genetic content of USA300 and USA400 strains, as well as significant differences of in vitro and in vivo gene expression of mobile elements in a lung pneumonia model. This is the first study to document the global transcription differences between USA300 and USA400 strains during both in vitro and in vivo growth.

Objective.: To understand the genotypic spectrum of environmental contamination ofStaphylococcus aureusin households and its persistenceDesign.: Prospective longitudinal cohort investigation.Setting.: Index participants identified at 2 academic medical centers.Participants.: Adults and children withS. aureusskin infections and their household contacts in Los Angeles and Chicago.Methods.: Household fomites were surveyed for contamination at baseline and 3 months. All isolates underwent genetic typing.Results.: We enrolled 346 households, 88% of which completed the 3-month follow-up visit.S. aureusenvironmental contamination was 49% at baseline and 51% at 3 months. Among households with a USA300 methicillin-resistantS. aureus(MRSA) body infection isolate, environmental contamination with an indistinguishable MRSA strain was 58% at baseline and 63% at 3 months. Baseline factors associated with environmental contamination by the index subject’s infection isolate were body colonization by any household member with the index subject’s infection isolate at baseline (odds ratio [OR], 10.93 [95% confidence interval (CI), 5.75–20.79]), higher housing density (OR, 1.47 [95% CI, 1.10–1.96]), and more frequent household fomite cleaning (OR, 1.62 [95% CI, 1.16–2.27]). Household environmental contamination with the index subject’s infection strain at 3 months was associated with USA300 MRSA and a synergistic interaction between baseline environmental contamination and body colonization by any household member with the index subject’s infection strain.Conclusions.: We found that infectingS. aureusisolates frequently persisted environmentally in households 3 months after skin infection. Presence of pathogenicS. aureusstrain type in the environment in a household may represent a persistent reservoir that places household members at risk of future infection.Infect Control Hosp Epidemiol2014;35(11):1373–1382

Methicillin-resistant Staphylococcus aureus (MRSA) has been a deadly pathogen in healthcare settings since the 1960s, but MRSA epidemiology changed since 1990 with new genetically distinct strain types circulating among previously healthy people outside healthcare settings. Community-associated (CA) MRSA strains primarily cause skin and soft tissue infections, but may also cause life-threatening invasive infections. First seen in Australia and the U.S., it is a growing problem around the world. The U.S. has had the most widespread CA-MRSA epidemic, with strain type USA300 causing the great majority of infections. Individuals with either asymptomatic colonization or infection may transmit CA-MRSA to others, largely by skin-to-skin contact. Control measures have focused on hospital transmission. Limited public health education has focused on care for skin infections.

(See the Major Article by Price et al on pages 609–18.)

High attack rates and the ability of Staphylococcus aureus to develop resistance to all antibiotics in medical practice heightens the urgency for vaccine development. S. aureus causes many disease syndromes, including invasive disease, pneumonia, and skin and soft tissue infections. It remains unclear whether a single vaccine could protect against all of these. Vaccine composition is also challenging. Active immunization with conjugated types 5 and 8 capsular polysaccharides, an iron scavenging protein, isdB, and passive immunization against clumping factor A and lipoteichoic acid have all proven unsuccessful in clinical trials. Many experts advocate an approach using multiple antigens and have suggested that the right combination of antigens has not yet been identified. Others advocate that a successful vaccine will require antigens that work by multiple immunologic mechanisms. Targeting staphylococcal protein A and stimulating the T-helper 17 lymphocyte pathway have each received recent attention as alternative approaches to vaccination in addition to the more traditional identification of opsonophagocytic antibodies. Many questions remain as to how to successfully formulate a successful vaccine and to whom it should be deployed.

In response to epidemic methicillin-resistant Staphylococcus aureus (MRSA) in the community, the Illinois General Assembly mandated that all patients admitted to intensive care units statewide be screened for MRSA. Screening was instituted at our neonatal intensive care unit (NICU) in September 2007 by a polymerase chain reaction (PCR)-based strategy. The law created an opportunity to determine the rate of MRSA colonization among neonates, to gather information about subsequent MRSA infections, and to evaluate risk factors for MRSA colonization on admission to the NICU.