Epidemic spread of ST1-MRSA-IVa in a neonatal intensive care unit, Italy

Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) has recently emerged as an important pathogen. CA-MRSA was first identified in infection cases with no previous contact with the healthcare system or other well-recognized risk factors, such as recent antimicrobial drug use [1]. However, it has recently become increasingly identified as a healthcare-associated (HA) pathogen [2]. Neonatal intensive care units (NICUs), nurseries and maternity settings are involved in these CA-MRSA events with alarming frequencies, and as many as 12 out of 18 recent outbreaks in healthcare facilities have occurred in these settings, with seven outbreaks affecting NICUs [3].

CA-MRSA outbreaks have usually been traced to the infiltration of a single strain in a healthcare setting [4]. However, their epidemiological patterns are increasingly difficult to understand, as their occurrence and dissemination routes in the community are largely unknown. The boundaries between CA and HA infections have become blurred, casting doubt on some previously defined criteria for distinguishing between CA- and HA-MRSA [5].

CA-MRSA has generally been considered to be susceptible to most non-β-lactam antibiotics, to carry small staphylococcal chromosomal cassette (SCC)mec cassettes (types IV or V), and to frequently produce the Panton-Valentine leucocidin (PVL). These attributes are detected in most strains of USA300, the most successful CA-MRSA strain, which is now endemic in the US, but occur infrequently in other geographical areas, such as Europe [4, 6]. Nonetheless, some increasingly resistant CA-MRSA strains have been described [4]. Moreover, the light IV and V SCCmec types have proven to be peculiar to some epidemic HA-MRSA clones, 4 such as ST22-MRSA-IV (EMRSA-15) [3, 5]. Additionally, PVL-negative CA-MRSA strains have been shown to cause not only community infections, but also healthcare outbreaks [3, 5]. Consequently, highly discriminative molecular typing systems are needed to understand the epidemiology of MRSA.

In this study, we report an outbreak of infection/colonization by an ST1-MRSA-IVa strain in a NICU in Palermo, Italy. The aim of the study was to characterize the bacterial isolates, determine the genetic traits and clonality of CA-MRSA, and to review the characteristics and outcomes of the neonatal cases and investigate the routes of entry and transmission of the MRSA strain in the NICU under study.

MRSA colonization and infection in infants are associated with significant morbidity and economic impact [13]. ELBW infants are particularly fragile individuals who may develop severe diseases. Several possible reservoirs and multiple sources of exposure to MRSA have been reported for infants hospitalized in nurseries and NICUs [14], and transmission of the USA300 strain among postpartum women affected by skin and soft tissue infections has been described [15]. Cases of CA-MRSA transmission associated with breast milk or carriage by a family member have also been reported [16, 17]. MRSA skin and soft tissue infections among full-term newborns were detected in the first 30 days since their delivery in US hospitals, as well as in neonates discharged from a nursery [18]. Moreover, previous studies have identified HCWs as reservoirs [19‐21].

In the current study, the index case was an infected infant born elsewhere. A second, long-stay, cross-colonized patient likely became the main reservoir of MRSA, while subsequent cross-transmission probably occurred via the hands of staff. MRSA screening at admission and HCW screening were not in place when the index case was admitted, but the weekly surveillance nasal swabs were obtained within 24 h of this patient’s admission, suggesting that ST1-MRSA-IV was imported from another healthcare facility on this occasion. However, alternative or concurrent exposure sources, such as previously colonized infants or HCWs, cannot be entirely ruled out. Indeed, early acquisition of MRSA soon after hospitalization has been described previously [21]. Moreover, because the nares were the only surveillance sampling sites, it is possible that infants colonized at other sites could have escaped detection. In this regard, it has been suggested that sampling sites traditionally associated with HA-MRSA, such as the nose, could lack sensitivity when screening for CA-MRSA colonization [22].

The issue of HCWs as a possible exposure source of MRSA, and especially of CA-MRSA, is widely debated [23]. Although HCWs have been implicated as the source of MRSA in many NICU outbreaks, there are conflicting reports regarding the cost-effectiveness of HCW screening and decolonization [18, 19, 24]. Evidence of transmission of MRSA from HCWs to patients in an outbreak setting ranges from 5.8–25.5% of cases, with an even lower proportion caused by asymptomatic carriers [25, 26]. Moreover, data about the positive impact of HCW screening and decolonization are difficult to assess, because both interventions are usually implemented as a part of a composite pattern of infection control procedures [20, 23, 27]. Decolonization of staff and patients by mupirocin proved unable to control a NICU outbreak, according to Lepelletier et al.[28]. In addition, a decline in the incidence of MRSA infections in hospital over a 7-year surveillance period was shown to persist, despite an interruption to routine HCW screening after the first 4 years [29]. However, the involvement of the HCWs was not assessed in the current study, which represents a substantial limitation. ST1-MRSA carriage by the staff of the NICU was, however, thought to be unlikely the because transmission chain was ultimately interrupted without the adoption of screening and decolonization procedures for HCWs. Nonetheless, emergence of CA-MRSA strains as HA pathogens presents a challenge for MRSA control strategies through the increasingly probable reintroduction of CA-MRSA from the community reservoir [29, 30]. Within such an epidemiological framework, HCWs as well as patient’s visitors could play critical roles as potential CA-MRSA traders in NICU outbreaks [3]. Consequently, screening and decolonization of HCWs could be more effective, and should be recommended when dealing with CA-MRSA.

This study had some limitations. As mentioned above, HCWs were not screened either as part of the routine surveillance program or during the outbreak phase. Moreover, infants were not routinely screened at admission, which could have biased the source attribution of the ST1-MRSA-IV strain. Finally, the specific NICU setting and local epidemiology of CA-MRSA make it difficult to generalize from the findings.

The present investigation showed that traditional approaches for the control of HA-MRSA were also effective in terminating CA-MRSA transmission in the NICU setting. Molecular typing by MLVA helped to clarify the epidemiological features of this CA-MRSA outbreak quickly, by identifying the outbreak ST1-MRSA-IVa strains from the background of the endemic EMRSA-15 colonization cases.

HA transmission of CA-MRSA strains, as well as increasing non-β-lactam resistance in CA-MRSA clones, present increasingly serious challenges to infection control and the clinical management of infections caused by these strains. Monitoring of global and local epidemiologies is critical to assess epidemiological trends and to guide empiric antibiotic options.