Transmission of ST8-USA300 Latin American Variant Methicillin-Resistant Staphylococcus aureus on a Neonatal Intensive Care Unit: Recurrent Skin and Soft- Tissue Infections as a Marker for Epidemic Community-Associated-MRSA Colonization

To the Editor—We report a mother-to-newborn transmission of ST8-USA300 Latin American Variant methicillin-resistant Staphylococcus aureus (MRSA) on a neonatal intensive care unit during kangaroo mother care in a German University Hospital, which raises the question of whether recurrent skin and soft-tissue infection (SSTI) is an important marker for colonization with epidemic MRSA clones. The clonal expansion of the particularly virulent MRSA strain pulsotype USA300 is much dreaded. USA300 is the predominant MRSA clone circulating in the community in the United States, and it is recognized as a common cause of nosocomial S. aureus bloodstream infections, increasingly blurring the classic distinction between community- and hospital-associated MRSA. ¹ A variant of this virulent strain, designated as the Latin American Variant of USA300 MRSA (USA300-LV), was able to infiltrate, disseminate, and become the predominant MRSA in the community as well as in healthcare settings across most of Latin America. ²

Although international travel and migration fosters the global spread of S. aureus, ^{3 , 4} detection of USA300-LV in Europe is rare ^{1 , 3} and generally occurs in subjects with close family or travel links to Latin America. ³ Nevertheless, the first observations of its autochthonous spread in the community have been reported in Spain and Italy. ¹ To date, in-hospital transmission of USA300-LV is an entirely unknown phenomenon in Europe, in contrast to Latin America, where it accounts for a substantial proportion of the nosocomial MRSA infections in Columbia and Uruguay. ^{1 , 2}

In October 2016, preoperative screening revealed Panton-Valentine leucocidin–positive (PVL+) MRSA isolated from a nasal swab of a 16-day-old, premature newborn (gestational age 33 weeks 2 days; 1,360 g) that had been hospitalized since birth due to a congenital heart anomaly (index case) (Table 1). Two days later, MRSA was also detected in the nose and breast milk of the mother, who at that time provided kangaroo mother care (ie, skin-to-skin care) to her child on a daily basis. ⁵ Because a postpartum screening of the child had been negative for multidrug-resistant organisms and because no other patients with MRSA colonization or infection had been treated on the same unit at that time, transmission from the mother is the most likely source of USA300-LV in the newborn. This finding is in line with research from Japan that found kangaroo mother care on the neonatal intensive care unit (NICU), although perceived to protect against infectious disease outcomes by increasing the diversity of the baby’s microbiome, ⁵ to be associated with 3.82-fold increased odds of MRSA infection (95% confidence interval, 1.11–13.13). ⁶

TABLE 1 Characteristics of the Index Case, Contact Persons, and Staphylococcus aureus Isolates of a USA300 Latin American Variant Outbreak ^a

NOTE. MRSA, methicillin-resistant S. aureus; PVL, Panton-Valentine leukocidin; MLST, multilocus sequence type; SCCmec, staphylococcal cassette chromosome mec; ACME, arginine catabolic mobile element; NICU, neonatal intensive care unit; pp, post partum; DORV, double outlet right ventricle; neg, negative.

^a No coresistance to quinolones, aminoglycosides, tetracyclines, trimethoprim-sulfamethoxazole, clindamycin, erythromycin, rifampicin, vancomycin, teicoplanin, linezolid, daptomycin, fosfomycin, tigecyclin, fusidic acid and mupirocin in any of the MRSA isolates. All strains bear the copper- and mercury-resistant characteristics (COMER).

^b Molecular characterization revealed SCCmec type IVc, ACME negative MRSA, consistent with the USA300-Latin American Variant, and not SCCmec IVa and ACME-positive MRSA, characteristic for USA300, which is highly prevalent in the United States.

Searching for the source of MRSA, a medical history among family members revealed recurrent SSTIs in the father and the 4-year-old sister of the index case patient. Swabs of the father’s nose and from a resolving purulent SSTI on the sister’s leg screened positive for PVL+MRSA. Although decolonization measures were immediately initiated, the mother’s cesarean section wound became infected and PVL+MRSA USA300-LV could be cultured from the wound and stitch on day 24 after birth.

All family members received immediate MRSA eradication treatment according to the institutional protocol. The child was isolated for the rest of the hospital stay. Active screening did not detect transmissions to other patients on the same ward. No further cases of MRSA infection have occurred on the NICU unit since October 2016.

All strains isolated were of the spa type t008 (ST8), PVL positive, arginine catabolic mobile element (ACME) negative and bear the SCCmec type IVc, which is consistent with the ST8-USA300-LV MRSA clone. None of the family members reported significant travel outside Europe in the last 24 months, in particular, not to the United States or Latin America. However, the father of the index case had returned from a trip to Spain more than 12 months previously and prior to suffering from recurrent SSTI.

Among other risk factors, current guidelines recommend screening of intercontinental travelers and patients with active skin infections, prior hospitalization, or contact to patients carrying multidrug-resistant organisms (MDRO) for carriage of MDRO upon admission. ^{7 , 8} In the presented case, the mother of the index patient did not fulfill any of the locally implemented criteria and was thus not screened on admission for C-section. Hence, to increase the sensitivity of CA-MRSA detection in the future, we propose targeted screening of all patients reporting recurrent SSTI defined as 2 or more episodes within the last 12 months in either (1) themselves or (2) members of the same household. This rationale is supported by reports on (1) recurrent skin infection being linked to PVL-positive S. aureus nasal colonization ^{3 , 4} and (2) nosocomial outbreaks of epidemic PVL+ CA-MRSA other than USA300 being fueled by colonized individuals that suffer from recurrent SSTI. ⁹ Although the impact of the proposed approach has not been systematically evaluated, these observations in conjunction with our report suggests that a history of recurrent SSTI is a potent marker for colonization with epidemic CA-MRSA and could thus prove useful for its early detection and timely eradication in newly admitted patients before invasion of epidemic CA-MRSA into European hospitals becomes an unchangeable fact. A recent report of a USA300 outbreak in a Belgium hospital demonstrates the urgency of this issue ¹⁰ and justifies taking measures before direct evidence is available. Finally, European surveillance activities must address the silent invasion by USA300-LV and must monitor the import and spread of ACME-neg, MLST 8, SCCmec IVc MRSA.