Article

Staphylococcus aureus nasal carriage as a marker for subsequent staphylococcal infections in intensive care unit patients.

Infectious Disease Service, Hospital de Bellvitge, University of Barcelona, Spain.
European Journal of Clinical Microbiology (Impact Factor: 2.54). 05/1997; 16(5):351-7. DOI: 10.1007/BF01726362
Source: PubMed

ABSTRACT From January to December 1994, 752 consecutive patients admitted to intensive care units (ICU) for more than two days were studied prospectively for Staphylococcus aureus colonization and infection. Nasal swabs were obtained at admission and weekly during the ICU stay. At ICU admission 166 patients (22.1%) were Staphylococcus aureus nasal carriers, while 586 were free of nasal colonization. Of the 166 nasal carriers, 163 harbored methicillin-sensitive Staphylococcus aureus (MSSA) and three methicillin-resistant Staphylococcus aureus (MRSA). During the ICU stay 24 of the 586 noncolonized patients became nasal carriers (11 MSSA and 13 MRSA), and one nasal carrier initially colonized by MSSA was reconlonized by MRSA. Staphylococcal infections were documented in 51 (6.8%) of the total 752 patients. After 14 days of ICU stay, the probability of developing staphylococcal infections was significantly higher for those patients who were nasal carriers at ICU admission than for those found to be initially negative (relative risk 59.6, 95% CI 20.37-184.32; p < 0.0001). In patients with ICU-acquired nasal colonization, most infections were documented prior to or at the time of the detection of the nasal colonization; thus, in this group of patients nasal carriage showed a lower predictive value for subsequent Staphylococcus aureus infections that that described classically. Paired isolates of nasal colonizing and clinical strains were studied by pulsed-field gel electrophoresis (PFGE) and mecA polymorphism analysis in 30 patients; identity was demonstrated in all but two patients. The results suggest that, outside the setting of an outbreak of MRSA, the detection of Staphylococcus aureus nasal carriers on admission may be particularly useful in identifying those patients who are at high risk for developing staphylococcal infections during their ICU stay.

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    ABSTRACT: Staphylococcus aureus is one of the most important bacteria that cause disease in humans, and methicillin-resistant S. aureus (MRSA) has become the most commonly identified antibiotic-resistant pathogen in many parts of the world. MRSA rates have been stable for many years in the Nordic countries and the Netherlands with a low MRSA prevalence in Europe, but in the recent decades, MRSA rates have increased in those low-prevalence countries as well. MRSA has been established as a major hospital pathogen, but has also been found increasingly in long-term facilities (LTF) and in communities of persons with no connections to the health-care setting. In Finland, the annual number of MRSA isolates reported to the National Infectious Disease Register (NIDR) has constantly increased, especially outside the Helsinki metropolitan area. Molecular typing has revealed numerous outbreak strains of MRSA, some of which have previously been associated with community acquisition. In this work, data on MRSA cases notified to the NIDR and on MRSA strain types identified with pulsed-field gel electrophoresis (PFGE), multilocus sequence typing (MLST), and staphylococcal cassette chromosome mec (SCCmec) typing at the National Reference Laboratory (NRL) in Finland from 1997 to 2004 were analyzed. An increasing trend in MRSA incidence in Finland from 1997 to 2004 was shown. In addition, non-multi-drug resistant (NMDR) MRSA isolates, especially those resistant only to methicillin/oxacillin, showed an emerging trend. The predominant MRSA strains changed over time and place, but two internationally spread epidemic strains of MRSA, FIN-16 and FIN-21, were related to the increase detected most recently. Those strains were also one cause of the strikingly increasing invasive MRSA findings. The rise of MRSA strains with SCCmec types IV or V, possible community-acquired MRSA was also detected. With questionnaires, the diagnostic methods used for MRSA identification in Finnish microbiology laboratories and the number of MRSA screening specimens studied were reviewed. Surveys, which focused on the MRSA situation in long-term facilities in 2001 and on the background information of MRSA-positive persons in 2001-2003, were also carried out. The rates of MRSA and screening practices varied widely across geographic regions. Part of the NMDR MRSA strains could remain undetected in some laboratories because of insufficient diagnostic techniques used. The increasing proportion of elderly population carrying MRSA suggests that MRSA is an emerging problem in Finnish long-term facilities. Among the patients, 50% of the specimens were taken on a clinical basis, 43% on a screening basis after exposure to MRSA, 3% on a screening basis because of hospital contact abroad, and 4% for other reasons. In response to an outbreak of MRSA possessing a new genotype that occurred in a health care ward and in an associated nursing home of a small municipality in Northern Finland in autumn 2003, a point-prevalence survey was performed six months later. In the same study, the molecular epidemiology of MRSA and methicillin-sensitive S. aureus (MSSA) strains were also assessed, the results to the national strain collection compared, and the difficulties of MRSA screening with low-level oxacillin-resistant isolates encountered. The original MRSA outbreak in LTF, which consisted of isolates possessing a nationally new PFGE profile (FIN-22) and internationally rare MLST type (ST-27), was confined. Another previously unrecognized MRSA strain was found with additional screening, possibly indicating that current routine MRSA screening methods may be insufficiently sensitive for strains possessing low-level oxacillin resistance. Most of the MSSA strains found were genotypically related to the epidemic MRSA strains, but only a few of them had received the SCCmec element, and all those strains possessed the new SCCmec type V. In the second largest nursing home in Finland, the colonization of S. aureus and MRSA, and the role of screening sites along with broth enrichment culture on the sensitivity to detect S. aureus were studied. Combining the use of enrichment broth and perineal swabbing, in addition to nostrils and skin lesions swabbing, may be an alternative for throat swabs in the nursing home setting, especially when residents are uncooperative. Finally, in order to evaluate adequate phenotypic and genotypic methods needed for reliable laboratory diagnostics of MRSA, oxacillin disk diffusion and MIC tests to the cefoxitin disk diffusion method at both +35°C and +30°C, both with or without an addition of sodium chloride (NaCl) to the Müller Hinton test medium, and in-house PCR to two commercial molecular methods (the GenoType® MRSA test and the EVIGENETM MRSA Detection test) with different bacterial species in addition to S. aureus were compared. The cefoxitin disk diffusion method was superior to that of oxacillin disk diffusion and to the MIC tests in predicting mecA-mediated resistance in S. aureus when incubating at +35°C with or without the addition of NaCl to the test medium. Both the Geno Type® MRSA and EVIGENETM MRSA Detection tests are usable, accurate, cost-effective, and sufficiently fast methods for rapid MRSA confirmation from a pure culture. Metisilliini-resistentistä Staphylococcus aureuksesta (MRSA) näyttää tulleen pysyvä ja lisääntyvä maailmanlaajuinen ongelma. MRSA on ollut jo kauan sairaaloiden vaivana, mutta nykyään sitä löydetään yhä useammin myös pitkäaikaislaitospotilailta sekä henkilöiltä, joilla ei tiedetä olleen yhteyttä terveydenhuollon laitoksiin. Molekyylibiologisten menetelmien avulla on tunnistettu useita MRSA-epidemioita, joista jotkut viittaavat mahdollisiin avohoitoperäisiin tartuntoihin. Suomessa Kansanterveyslaitoksen (KTL) tartuntatautirekisteriin (ttr) ilmoitettujen MRSA-tapausten lukumäärä on lisääntynyt selkeästi viime vuosina. Samaan aikaan myös kliinisen mikrobiologian laboratorioiden KTL:n asiantuntijalaboratorioon lähettämien MRSA-kantojen määrä on noussut. Tässä väitöskirjassa tutkittiin MRSA:n muuttunutta epidemiologiaa analysoimalla ttr:n ilmoituksia sekä asiantuntijalaboratorioon lähetettyjen kantojen ominaisuuksia Suomessa vuosina 1997-2004. Lisäksi arvioitiin MRSA-diagnostisia menetelmiä kliinisen mikrobiologian laboratorioissa, sairaanhoitopiirien MRSA-seulonta-aktiviteettia, ja pitkäaikaishoitolaitosten MRSA-tilannetta vuonna 2001, sekä MRSA-positiivisten henkilöiden näytteenottoperustetta vuosina 2001-2003 kyselytutkimusten avulla. Eri molekyylibiologisten menetelmien avulla KTL:n asiantuntijalaboratoriossa todettiin, että vallitsevat MRSA-kannat ovat vaihdelleet vuosittain eri puolilla Suomea, mutta viimeaikaisen nousun takana oli kaksi kansainvälisesti levinnyttä MRSA-epidemiakantaa. Nämä kaksi kantaa vallitsivat myös jyrkästi lisääntyneissä verilöydöksissä. Myös mahdollisten avohoidon MRSA-kantojen sekä vain ns. beetalaktaameille vastustuskykyisten kantojen osuudet lisääntyivät. Kyselytutkimuksen perusteella voitaneen todeta, että osa näistä vain beetalaktaameille vastustuskykyisistä kannoista on saattanut jäädä havaitsematta kliinisen mikrobiologian laboratorioiden vaihtelevan MRSA-diagnostiikan tason vuoksi. Saman selvityksen perusteella voidaan todeta, että MRSA-löydösten määrä on vaihdellut sairaanhoitopiireittäin, mutta se ei ole korreloinut seulonta-aktiviteetin kanssa. Toisen kyselytutkimuksen perusteella voitiin todeta, että MRSA:n lisääntyminen vanhusväestössä viittaa sen aiheuttamaan lisääntyvään ongelmaan vanhainkodeissa. Kolmannesta kyselytutkimuksesta selvisi, että puolet MRSA-positiivisten potilaiden seulontanäytteistä oli otettu kliinisillä perusteilla, 43 % MRSA-altistumiseen liittyvillä seulontaperusteilla, 3 % ulkomaan sairaalakontakteihin liittyvillä seulontaperusteilla, ja 4 % jonkin muun syyn takia. Koska MRSA on aiheuttanut useita epidemioita pitkäaikaishoitolaitoksissa, väitöskirjassa tutkittiin kahden pitkäaikaishoitolaitoksen potilaiden/asukkaiden MRSA- sekä metisilliinille herkkien S. aureusten (MSSA) -kantajuutta. Ensimmäinen tutkimus keskittyi MRSA:n ja MSSA:n molekyyliepidemiologiseen vertailuun ja toinen siihen, miten eri näytteenottopaikkojen lukumäärä ja rikastusviljelyn käyttö vaikuttavat S. aureuksen (MRSA ja MSSA) löytymiseen. Perimäanalyysin perusteella todettiin, että MRSA ja MSSA-kantojen perimä voi olla samanlainen, mutta vain osa MSSA-kannoista on saanut metisilliinille vastustuskykyä aiheuttavan geenin osan. Tässä tapauksessa kaikilla laitoksesta löytyneillä MRSA-kannoilla oli sama geeniosa kantojen muusta perimästä riippumatta. Toisessa tutkimuksessa todettiin, että perineum-näytteiden otto sekä rikasteviljelyn käyttö yhdistettynä nenä- ja haavanäytteiden ottoon voisi olla vaihtoehto nielunäytteiden otolle. Tämä toimisi etenkin asukkailla, joilta nielunäytteenotto on hankalaa. Väitöskirjassa arvioitiin lisäksi laboratoriodiagnostisia menetelmiä, jotka olisivat tarkoituksenmukaisia MRSA:n tunnistamisessa sekä sen ulkoasun että perimän perusteella kliinisen mikrobiologian laboratorioissa. Todettiin, että kefoksitiini-antibioottikiekkotesti oli ylivertainen ennustamaan S. aureuksen vastustuskykyä metisilliinille verrattuna perinteisiin, oksasilliini-antibiootilla tehtäviin herkkyystesteihin. Lisäksi todettiin, että kaksi yleisesti käytettyä kaupallista molekyylibiologista sovellusta olivat yhtä herkkiä ja tarkkoja kuin kotitekoinen menetelmä, mutta lisäksi nopeampia ja yksinkertaisempia toteuttaa MRSA:n tunnistamisessa bakteeripuhdasviljelystä kuin kotitekoinen menetelmä.