INTRODUCTION

Methicillin-resistant Staphylococcus aureus (MRSA) was initially described as a bacterium associated with nosocomial infections in patients with prolonged hospital stay, recent surgery, dialysis requirement or presence of invasive medical devices ^{1 - 3}. Hospital-acquired MRSA (HA-MRSA) is characterized by being resistant to several families of antimicrobials and carrying the mecA gene, contained in the staphylococcal chromosomal cassette mec (SCCmec) type I, II and III ^{3 - 5}. However, in the 1990s, the first cases of community-acquired MRSA infections (CA-MRSA) began to be described in the USA in people without nosocomial risk factors; subsequently infections spread to all continents ⁴. The most prevalent CA-MRSA clone is USA300, which characteristically carries SCCmec type IV and is usually resistant only to β-lactams ^{5 - 6}.

In Peru, some imported cases of CA-MRSA were described between 2010-2011 ⁷. A study conducted during 2011-2014, using blood cultures, showed that the most prevalent clone in northern South America was the Latin American variant of USA300 (USA300-LV), described in 79%, 72% and 50% of MRSA infections in Colombia, Ecuador and Venezuela, respectively; although no cases were found in Peru ⁸.

The aim of the study was to determine the frequency of CA-MRSA in S. aureus isolates from patients in a hospital in Lima, Peru, and to describe their molecular and antimicrobial resistance characteristics.

THE STUDY

FINDINGS

During 2017, 152 S. aureus isolates were reported (only one per patient), of which 120 were analyzed in this study. Of these, five isolates were excluded: four had discordant findings between cefoxitin susceptibility and the presence of the mecA gene, and one was S. haemolyticus.

Of the 115 isolates positive for S. aureus, most were obtained from unspecified secretions (21.7%), followed by blood (20.0%), tracheobronchial secretions (14.8%) and skin (14.8%) (Table 1). Of the isolates, 46.1% were identified as MRSA. Among the MRSA isolates (n = 53), the distribution of SCCmec types was as follows: I (79.2%), III (1.9%), and IV (7.5%); no isolates with SCCmec type II and V were found. In addition, in six isolates (11.3%) the SCCmec type could not be determined (Table 2).

Regarding the antibiotic susceptibility profile, among methicillin-sensitive S. aureus isolates (MSSA, n = 62), the highest frequency of resistance was found for erythromycin (22.2%), gentamicin (17.2%) and clindamycin (11.1%). On the other hand, the majority of isolates (>75%) of MRSA showed resistance to clindamycin, erythromycin, gentamicin and, in addition, ciprofloxacin; this co-resistance was more common in isolates carrying SCCmec type I and III (n = 43) (Table 2).

Genes encoding PVL were identified in ten isolates (8.7%): six MSSA isolates (9.7%) and four MRSA isolates (7.5%). Of the latter, three isolates were categorized as CA-MRSA, because they carried SCCmec type IV; while only 1 corresponded to HA-MRSA, because it carried SCCmec type I (Table 3).

DISCUSSION

We analyzed 115 strains (75.7%) of the 152 isolates reported during 2017. Within these, a high frequency of MRSA isolates was found (46.1%) and the frequency of CA-MRSA was 2.6%.

Previous multicenter studies that have evaluated S. aureus strains according to their antimicrobial susceptibility and genotype have shown a high prevalence (>40%) of MRSA in Latin America, with a heterogeneous distribution among countries ^{( 14 , 15}. Brazil and Venezuela report the highest frequencies in the region, with 62% and 57%, respectively ¹⁵. In the case of Peru, a frequency of 50%-54% has been reported ^{14 , 15}. The frequencies described are similar to those found in our study; however, the comparison with these studies ^{(14, 15)} is limited, since only cases of bacteremia were considered. To date, no studies have been conducted in the region that consider all types of isolates.

There are few local studies that evaluate the distribution of MRSA strains and their molecular typification. One research conducted at the same hospital as our study, that considered all S. aureus isolates, described a 68% frequency of MRSA in 2002 ¹⁶. Subsequently, a study that included S. aureus isolates from all sources in three referral hospitals in Lima ¹⁷ showed an overall frequency of 58%, obtaining the molecular characteristics of HA-MRSA in almost all isolates. This shows that the presence of MRSA continues to be prevalent in Peruvian hospitals, and measures should be implemented to contain its dissemination ¹⁵.

From the molecular point of view, the SCCmec type of MRSA has a varied distribution in Latin America ^{18 , 20}. In the northern countries of South America, such as Colombia and Ecuador, the USA300 clone carrying SCCmec type IV is the most frequent, followed by the Chilean-Cordovan clone, carrying SCCmec type I; while in countries such as Peru and Chile it has been reported that the majority (>90%) of S. aureus isolates correspond to the Chilean-Cordovan clone ^{( 15}.

In Peru, a multicenter study conducted in Lima ¹⁷ revealed that MRSA carrying SCCmec type I were found with a frequency of 75.2%; furthermore, these isolates showed resistance to ciprofloxacin, clindamycin, erythromycin and gentamicin, similar to what was found in our study. Our findings are similar to previous studies in hospitals in Lima, which confirms that MRSA carrying SCCmec type I non-PVL-producing is the most common nosocomial clone in our setting ^{17 , 18}. Regarding the emergence of CA-MRSA in the last decade in Peru, several multicenter studies have shown that this is a very infrequent event in Peruvian hospitals ^{8 , 14}. In this study, 2.6% of the isolates were found to have molecular characteristics of CA-MRSA, in contrast to neighboring countries such as Brazil, Ecuador, Venezuela and Colombia, where a prevalence of around 27% has been reported ^{15 , 20}. This situation requires continuous surveillance because if this proportion increases significantly, there would be an impact on the empirical antibiotic treatment for skin and soft tissue infections, its most frequent presentation.

Likewise, this study found a frequency of genes encoding PVL of 8.7%, with greater distribution in the MSSA group. This exotoxin was first described in 1932 in sensitive strains, as a factor associated with severe skin infections and necrotizing pneumonia ¹⁹. Subsequently, it was described that its production could be considered a marker for identification of resistant strains, especially CA-MRSA ¹⁹. However, this theory is currently controversial, since the genes encoding PVL are reported in HA-MRSA and MSSA strains. A study conducted in three hospitals in Lima ¹⁷ described a low production of PVL (9.1% of the isolates analyzed), with a higher distribution in the MSSA group than in the MRSA group, which is similar to what was found in our study. These findings favor the current theory that the presence of PVL is not a reliable marker for the identification of CA-MRSA strains.

The first limitation of this study was that the number of isolates analyzed was small, which could have altered the true prevalence of CA-MRSA isolates. This was due to the limited availability of reported S. aureus isolates during the study period and, probably, to the fact that this institution does not perform systematic culture sampling in cases with suspected skin and soft tissue infection, the most frequent presentation of this infection, or that it is performed after the initiation of antibiotics. The second limitation of the study was that the complete review of medical records was not included, which prevented us from completing the clinical definition of HA-MRSA and CA-MRSA. In addition, this study did not allow us to evaluate whether the samples obtained corresponded to cases of infection or colonization, which would provide more information on the impact of the presence of this bacterium in our setting. In addition, there were 11.3% of MRSA isolates in which the SSCmec type could not be identified. The third limitation is related to the external validity of the study. The study was conducted in a public referral hospital located in the northern area of the city of Lima, so the information described only corresponds to that population. This, together with the small number of samples analyzed, limits the extrapolation of the results. However, the intention of our study is to draw attention to the importance of epidemiological surveillance of multidrug-resistant bacteria.

Our study shows a low frequency of CA-MRSA in Lima. However, we consider that close epidemiological surveillance should be continued and studies should be expanded, even more so in the context of increasing migration from countries with higher prevalence.