2380 LETTERS TO THE EDITOR
hominis (5), contrary to Dr. Rosenblatt's allegation, the authors appear to have performed normal laboratory tests, including routine aerobic and anaerobic cultures ofblood, synovial fluid, urine, stool, and endocervix (all negative). Had the authors includedaphotomicrographof theorganism as "scientific documentation" or "illustration," most refer-ees probably would have suggested deletion because the parasite is so well described and easy to identify. Dr. Rosenblattappears toquestiontheintegrityandcompetence of theinvestigators. Is it because of their affiliationwith an institutioninJamaica? Probablythey seemore parasites in a monththan acomparablysized hospital in the United States in1 year.
NeitherInorsome 20 other investigators, reportingover 500 cases of B. hominis-associated gastroenteritis, and 2 withopposing views (16 cases) have any vested interest in the organism or its pathogenicity. All have reported their observations and experiences in peer-reviewed journals. Editors and referees of scientific and medical periodicals judge manuscripts ontheirmerit, scientific documentation, and proper interpretation. Expecting them to be narrow-minded is defeating their purpose.
I concur with Dr. Rosenblatt and several previous in-vestigators that more information is needed regarding the epidemiology, mechanism of pathogenicity, immunologic response, radiologicand endoscopic findings, and manage-mentofB. hominisinfections andhopethatthecontroversy surrounding this parasite's role in disease will stimulate researchtoelucidate theseparameters.
LITERATURECITED
1. Babcock, D., R. Houston, D. Kumaki, and D. Shlim. 1986. Blastocystishominis in Kathmandu, Nepal. N. Engl. J. Med. 313:1419.
2. Cohen, A. N. 1985. Ketoconazole and resistant Blastocystis hominisinfection. Ann. Intern. Med. 103:480481.
3. Guirges,S.Y., andN.S.AI-Waili. 1987.Blastocystis hominis: evidence for human pathogenicity and effectiveness of metro-nidazole therapy. Clin. Exp. Pharmacol. Physiol. 14:333-335. 4. Kain, K. C., M. A. Noble, H. J. Freeman, and R. L. Barteluk.
1987.Epidemiology and clinicalfeaturesassociated with Blas-tocystishominisinfection. Diagn. Microbiol. Infect. Dis. 8:235-244.
5. Lee, M. G., S. C.Rawlins, M.Didier, and K. DeCeulaer. 1990. Infective arthritis due to Blastocystis hominis. Ann. Rheum. Dis. 48:192-193.
6. Phillipps, B. P., and C. H. Zierdt. 1976.Blastocystis hominis: pathogenicpotentialin humanpatients and in gnotobiotes. Exp. Parasitol. 39:358-364.
7. Qadri, S.M.H., G.A.Al-Okaili,andF.Al-Dayel.1989. Clinical significance of Blastocystis hominis. J. Clin. Microbiol. 27: 2407-2409.
8. Russo,A.R.,L.Stone,M.E.Taplin,H.J.Snapper,andG.V. Doern.1988. Presumptive evidence for Blastocystis hominis as acauseofcolitis. Arch. Intern. Med. 148:1064.
9. Sangiorgi, G. 1930. Pathogenicity of Blastocystis hominis. Pathologica 22:173-176.
10. Sheehan, D. J., B. G. Raucher, and J. C. McKitrick. 1986. Association of Blastocystis hominis with signs and symptomsof humandisease. J. Clin. Microbiol. 24:548-550.
11. Taylor,D.N.,R.Houston, D. R.Shlim, M.Bhaibulaya, U.L. Ungar, and P. Echeverria. 1988. Etiology of diarrhea among travellersandresidentsinNepal. J. Am. Med. Assoc. 260:1245-1248.
12. Yakimoff, W.L. 1923. Sur laquestion desBlastocystis. Bull. Soc. Pathol. Exot. Fil. 161:326.
13. Zierdt, C.H., C.T.Donnolley, J. Muller,andG. Constantopou-los.1988. Biochemical and ultrastructural study of Blastocystis hominis. J. Clin. Microbiol. 26:965-970.
S.M. HussainQadri
DepartmentofPathology and Laboratory Medicine KingFaisal Specialist Hospital and Research Centre P.O.Box3354
Riyadh 11211, SaudiArabia
Selective
Staphylococcal
Broth
We compliment Dr. Cookson et al. on their extremely
informative articleonstaffcarriage ofepidemic
methicillin-resistant Staphylococcus aureus (MRSA) (3). The authors
make an extremely pertinent statement: "we used broth enrichmentculturingtoincreasethesensitivity of detection of EMRSA [epidemic MRSA] carriage; in fact, without it carriage would have been entirely missed in eight of our
nurses." Theuseof this most sensitive culturemethod for thedetectionof MRSA inepidemiologicalsurveillance can-not be overemphasized. In a recent review of MRSA (1), eachof the epidemiological investigations cited used direct plating methods and showed that the carriageratefor MRSA
was low. It is our contention that the use of insensitive
culturemethods for MRSAinepidemiologicalsurveillance is
one possible reason for the low carriage rates for MRSA reported in the literature.
Inacomparison of plated media, includingBaird-Parker,
Trypticase soy with5% sheep blood (BAP), andchocolate
agarwith staphylococcalbroth, wehave been ableto dem-onstratetheisolationof almost three timesasmanypositive
S. aureus cultures as by any plated agar method (unpub-lished data). Recently, one ofus reported that a selective
staphylococcal broth (Difco Laboratories, Detroit, Mich.)
proved superior to direct plating for the recovery of S. aureus, resulting in
improved
recovery ratesof20%
(nares)
and
66%
(vaginal vestibule) (4). Referring
to thesedata,
Campos
(2)suggested
the use of a broth enrichment fordetecting MRSA in surveillance cultures. We have also
compared
staphylococcal
broth with directplating
for therecovery of MRSA on BAP. In an attempt to
identify
carriers ofepidemic MRSA,
124intensive-care-unit
and 14operating-room
employees
had cultures of the nares. Fouremployees
(2.9%)
carried MRSA.Ail
four MRSA isolateswere
found
in theselective
brothcultures,whileonlytwoofthe four
(50%)
were detected by directplating.
MRSA could be detected only on repeat cultures ofspecimens
from these fouremployees
by theselective
culture tech-nique.Althoughthe useofanenrichment broth for culturesin the laboratory is routine, in
practice
most laboratories do not usebrothenrichment forepidemiological
surveillance.Thefactthat62%of
positive
individuals in theCooksonevalua-tionand50%in ourevaluation wouldnothavebeen
detected
without the use ofan enrichment broth culture
technique
strongly suggests the need to use this culture method forepidemiological
surveillance.J. CLIN.MICROBIOL.
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LETTERS TO THE EDITOR 2381
LITERATURE CITED
1. Brumfitt, W., and J.Hamilton-Miller. 1989.Methicillin resistant Staphylococcus aureus.N.Engl. J. Med.320:1188-1196. 2. Campos, J. M. 1988. Detection ofS. aureus colonization using a
selective medium. Diagn. Test. Alert 4:23.
3. Cookson, B., B. Peters, M. Webster, I. Phillips, M. Rahman, and W. Noble. 1989. Staff carriage of epidemic methicillin-resistant Staphylococcus aureus. J. Clin. Microbiol. 27:1471-1476.
4. Sautter,R.L., W. J. Brown, and L. H. Mattman. 1988. The use ofa selective staphylococcal broth vs. direct plating for the recovery of Staphylococcus aureus. Infect. Control Hosp. Epi-demiol. 9:204-205.
Robert L. Sautter Lester W.Wells
Departmentof Pathology Harrisburg Hospital
Harrisburg,Pennsylvania 17101 Author's Reply
I am glad that Sautter and Wells approve of the use of broth enrichment andagreethat the method hasoften been ignored in studies of methicillin-resistant Staphylococcus aureus (MRSA), although the increased sensitivity ofthe method in thedetection ofS. aureus was noted many years ago. Polakoffet al. (5)detected additional sites ofS. aureus carriage in 361 patients screened with abroth enrichment method: 18(22%)nasal, 22(92%) axillar,74(92%)hand, and 9 (56%) perineal carriers. The method can be made ex-tremelycost-effective ifmultiple swabs areimmersed inthe samebroth,asoneoften needstoknow whether, rather than where, a subjectcarries MRSA(3).
However, there are other issues thatmustbe discussed. Lidwell (4) has suggestedthatthe carriage detectedby broth alone might be light and perhaps temporary, but such detectionmayrevealreservoirsormodes oftransmission of MRSA(2) andpatients otherwise thoughttobe clearduring or following decontamination (3). Moreover, the potential forpatientstobecome infected isnotnecessarily relatedto the amount of S. aureus carriage (8) or whether it is intermittent orpersistent (7).
Brothculture also reducestheincidence of false-negative cultures duetopoorly takenswabs, delayed swabtransport tothelaboratory,unevendistribution of S.aureusorganisms at a site (6), and contamination from an unscreened site. Many of these possibilities were thought tobe relevant to our own
findings
(B. Cookson and I. Phillips, J. Appl. Bacteriol. Symp. Supply, in press), in which broth enrich-mentalone detected MRSA carriage in subjects infected (9 of 26), colonized (17 of 40),oronly transiently carrying(44of 51) MRSA.Anothercriticism of broth enrichment is thedelay in the issue of the final report vis-à-vis the time required for reporting direct swab culture. However, MRSA detection usually requiresaselective medium, e.g., added methicillin
at5
mg/liter,
anddirect cultureonsuchmedia often requires48 hofincubation (inup to40%of cases in myexperience). Incubation in abroth increases the inoculum sizesothat a result willusuallybe seen after 24 h of incubation on such a
medium. Thus, there is often no difference between the two methods in the time taken toobtain aresult.
Unfortunately,broth enrichment detects large numbers of staff transiently carrying MRSA (Cookson and Phillips, in press), usually because screening isdoneafteraduty period (2). Time is better spent inspecting staff for lesions (often minor ones can be heavily colonized). Transient MRSA staff carriage is a fact of life often missed in previous studies becauseof thefailuretousebroth enrichmentorthetiming of screening(2). Certainmeasures should be considered to control continuedspread via this route. These might include the wearing of masks for dressing procedures and the cohortingof staff to MRSA patients,dependingon resources and the sort of patients on the involved wards. A more recentapproach, whichIhaveusedsuccessfullyin a number of surgical wards,isselectivecohortingortargettednursing, in which certain high-risk procedures (e.g., wound dress-ings)are performed on MRSApatients only by designated staff, who must not
perform
such procedures onpatients
clearof MRSA. Decontamination of staff after aperiod of nursing MRSA patients also hastobeconsideredif thestaff are toperform close contactproceduresonpatientsclear of MRSA in another wardorhospital during
thenext24 h. This isofparticularrelevance to agency staff(1).LITERATURE CITED
1. Cookson, B.D. 1988. Problems of agencystaff incurrent prob-lems withmethicillin-resistantStaphylococcus aureus.J. Hosp. Infect. 4:381-392.
2. Cookson, B.,B.Peters, M. Webster,I. Phillips,M.Rahman,and W.Noble. 1989. Staff carriage of epidemic methicillin-resistant Staphylococcusaureus.J.Clin. Microbiol. 27:1471-1476. 3. Cookson, B. D., M. Webster, and I. Phillips. 1987. Control of
epidemic methicillin-resistant Staphylococcus aureus. Lancet i:696.
4. Lidwell,O.M.1982.Some aspects of the transfer andacquisition ofStaphylococcusaureusin hospitals, p. 175-202. In A. Mac-donald and G.Smith(ed.), Thestaphylococci: proceedingsof the AlexanderOgston CentennialConference. AberdeenUniversity PressLtd., Aberdeen, Scotland.
5. Polakoff, S.,I. D. G.Richards, M. T.Parker, andO. M. Lid-well. 1967. Nasal and skin carriage ofStaphylococcus aureus by patients undergoing surgical operation. J. Hyg. 65:559-566.
6. RidleyM. 1959. Perinealcarriage ofStaph. aureus. Br.Med. J. 1:270-274.
7. Sewell, C. M., J. Clarridge, C. Lackn,E.J. Weinmann,andE.J. Young. 1982. Staphylococcalnasal carriage and subsequent in-fection in peritoneal dialysis patients. J. Am. Med. Assoc. 248:1493-1495.
8. Yu, V. L., A. Goetz, M. Wagener, P. B. Smith, J. D. Rihs, J. Hanchett,andJ. J.Zuravleff. 1986.Staphylococcusaureusnasal carriage and infection in haemodialysis: efficacy of antibiotic prophylaxis. N.Engl. J. Med. 315:91-95.
B. D. Cookson
Divisionof Hospital Infection Central Public HealthLaboratory Public HealthLaboratory Service 60ColindaleAvenue
LondonNW9 5HT England
VOL. 28,1990
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JOURNAL OFCLINICAL MICROBIOLOGY'.July 1989. p. 1471-1476 0095-1137/89/071471-06$02 .00/0
Copyright © 1989. American SocietyforMicrobiology
Staff
Carriage
of
Epidemic Methicillin-Resistant
Staphylococcus
aureus
BARRY COOKSON,1: BARRY PETERS,'- MARGARETWEBSTER,' IAN PHILLIPS,1 MARY RAHMAN.- ANDWILLIAM
NOBLE-Diviision
ofMicrohiologyl
aliidllnstitlte oj Derfil(ZtologV . UMDS,St.
Thoinas'
Hospitall
LondIon
SEl
7EH,England
Received2') December1988/Accepted 10March 1989
Twenty-six nurses were repeatedly screened for carriage of epidemic methicillin-resistant Staphylococcus aureus(EMRSA) immediately before and after duty periodsinwhich they solely attended sixpatients widely
colonized withtwo EMRSA strainsdistinguishable by plasmid analysis. EMRSAcarriage wasdetected in 13
nurses. Three EMRSA carriage patterns emerged: transient carriage in 12 nurses, when the EMRSA was
isolated fromnoses orfingers ofnursesafterduty butwasgonebefore theirnextday's duty; short-term nasal carriage, seen on occasion in 4 of these 12 nurses, when EMRSA carriage wasdetected on twoconsecutive
screens; and persistent nasal carriage, seen in 1 nurse only, when the EMRSA was seen on more thantwo
consecutive occasions.Ailbutoneof these incidents ofcarriage couldbeexplained by close patient, ratherthan environmental, exposure and occurred despite an intensive control programme. Transient or short-term
carriage innursesprobably resulted in transfer of the EMRSA between patients. Staff decontamination should
be consideredfollowingaperiod of cohort nursing of EMRSA patients, especially ifstaff membersareshortly
tonurse unaffected patients. Our findings may explainsomeof the difficultiesincontrolling EMRSA.
In recent years nosocomial outbreaks of methicillin- and
multiple-antibiotic-resistant Staphvlococciisaureus (MRSA)
have become a major infection control problem. Although
MRSA strains have notbeen showntobemorevirulent than
otherstrains of S. auraes,(12, 18), very highmortality rates
forpatientswith MRSA infectionshave been reported from severalcenters (2, 16).Our inability to treatthese infections
atanearly stagewithfirst-choice antibiotics and the limited choice anddelayinappropriate systemic chemotherapypose
serious therapeutic problems. Many hospitals in the United Kingdom, includingtwo inour own HealthAuthority, have
experienced a number of outbreaks ofpatient colonization
and infection withepidemic MRSA (EMRSA) which
resem-ble Australian strains (6, 22). EMRSA strains may spread
readily, and some hospitals have found them particularly
difficult to contain (3). Others have commented on the
paucityof information onMRSAcarriageor on the relative
importance of the environment and staff in MRSA spread (4). We reported the phenomenon oftransient MRSA
car-riage (5) during our first EMRSA outbreak. The establish-ment ofan isolation ward forEMRSA patients with cohort nursing provided an opportunity to study the dynamics of the first stages in the spread of EMRSA.
(Part of this work was presented in a poster at the Proceedings of the Third European Congress of Clinical Microbiology, TheHague, TheNetherlands, 1987,abstr.no.
63, p. 34.)
MATERIALS AND METHODS
Study population. Six patients (see Table 1) carrying the
EMRSA were transferred to a ward designated for them at
the South Western Hospital, a hospital with predominately
elderly-care patients situated about 3 mi (ca. 4.8 km) from St. Thomas' Hospital. The ward had acentral corridor with
* Correspondingauthor.
Present address: Department of Immunology. St. Mary's
Hos-pital MedicalSchool. London W2 1PG. England.
eight single-bed rooms, a nurses' office, clean and dirty
utility rooms, and a patients' day room. There was no
controlled ventilation.Althougheachroomhad itsownwash basin, communaltoiletand bathroom facilitieswereused for
ambulant patients and individual commodes were used for those confined totheir rooms (patients D andV).
Twenty-six nurses and two domestic staff members worked solelyon this ward during the 7-week study period.
There werealso twophysiotherapists, who had administra-tive duties butnopatientcontactelsewhere,andtwodoctors allocated, although not solely designated, topatients in the isolation ward.
Three of the patients(D, R, and V)were involved inone
outbreak with a chloramphenicol-susceptible EMRSA, and
three (C, H, and M) were involved in an outbreak with a
chloramphenicol-resistant EMRSA (see Table 1). All were
elderly-care patients, except for patient C. who was
trans-ferred froman acute-care ward.
Decontamination regimen. All patients were
decontami-nated each day with a total-body wash with triclosan
(Aquasept; Hough Hoseason)andtwotriclosanapplications
to the face, nose, axilla, and groin, and chlorhexidine dressings(Bactigras;Smith andNephew)wereappliedtoall infected lesions. Staff members were decontaminated with
four nasal applications of neomycin and chlorhexidine (Naseptin; ICI) and a total-body wash with chlorhexidine
gluconate (Hibiscrub; ICI) only when they left thewardfor the final time.
Screening. Patients were screened for MRSA at least weekly with peptone water-moistened swabs from nose,
throat, perineum, catheter sites, and any abnormal skin or
wounds. Nurses took their own peptone water-moistened nasalswabs before andaftereach8-to 10-hduty period for the 7 weeks, and 240 finger swabs were taken in the last 3
weeks of the study. The physiotherapists were screened
immediately before and after each of 12 physiotherapy sessions involving all patients. The domestic and medical staff memberswerescreenedatthebeginningand endofthe
1471
1472 COOKSON ET AL.
study, and the latter were also screened after examining patients on two occasions. At least once weekly, nose, throat, and perineal swabs were taken from each nurse and examined for methicillin-susceptible S. auireus (MSSA).
Swabs were usually transported and processed on the same day. All media were made with Columbia agar base (CM331;OxoidLtd.). Swabs for MRSAscreeningwerefirst inoculated directly on mannitol salt agar (CM85; Oxoid) containing 5 mg of methicillin per liter (MSM) and then placed in salt broth (no. 2 CM67, with 7.5% added sodium chloride;Oxoid), which was subculturedon MSM after24h. These subcultures were incubated at 37°C, the plates were examined after 24 and 48 h, and mannitol-fermenting colo-nies were tested for coagulase. Swabs for the screening of MSSA were inoculated directly on blood agar with a 10-pg methicillin disk (BAM) and then placed in salt broth, which was subcultured after 24 h on BAM; all BAM plates were incubated for 48 h at 30°C, and any staphylococcal colonies were tested for coagulase.
Antibiotic susceptibilities of all S. aureus isolates were determined on lysed blood agar by the
comparative
disk diffusion method.Each nurse recorded the procedures she
performed
each dayonpredesigned forms,sothat acquisitionof the EMRSA could be correlated with activity. The degree of staff EMRSA exposure was divided into three grades, and the overallgrade for each day was defined by thehighest
grade ofprocedure performed on thatday.(i) Grade 1 was superficial contact-brief exposure to a contaminated environment but no direct contact with a
colonized or infected patient, e.g.,
delivering
meals orspeakingto a patient.
(ii) Grade 2 was casual contact-patient contact but no manipulation of colonized or infected sites, e.g., helping patients to wash and dress themselves.
(iii) Grade 3 was close contact--physical contact with infected orcolonized sites, e.g., changing wound
dressings,
bathing widely colonized patients, or urethral catheteriza-tion. Our infection control policy included theuse of aprons and gloves for all contactprocedures,
but apart from chest physiotherapy, masks were not used by stafffor any close-contactprocedureswith thesepatients.
Theinfection control team repeatedly emphasized theimportance
ofappropriate
hand decontamination with chlorhexidine
preparations
(Hi-biscrub and Hibisol; ICI) afterpatient
contact but did notinform staff members of their carriage unless it was
persis-tent (see Results).Environmental screening. The environment was screened onceeach weekbefore ward
cleaning,
whichwasperformed
oncedaily duringthe first 2weeks and twicedaily
thereafter. Airfrom eachpatient's room, the nurses'station,
corridors. and the day room was sampled with aportable
airsampler
(Surface Air System; Cherwell
Laboratories);
180 liters of air was sampled in 1 min on MSM and BAMplates.
In the last 3 weeks of the study 900 liters of air wassampled
in 5 min; phenolphthalein phosphate (SR31;Oxoid)
agarplates
were substituted for BAM plates. Peptone water-moistened swabs were used to sample floor dust,windowsills,
bed-steads, andpointsoffrequenthandcontact,suchasthedrug
trolley, nurses' patient card index system,telephone,
taps, doorhandles andlightswitches.These swabswereplated
on MSM and then placed in salt broth. BA and MSM settle plates(4.5-in. [ca. 11.4-cm]diameter) wereleftatfloor levelfor2h, 2and8ft(ca.61and244cm,
respectively)
from eachpatient's bed, and others were left in the
corridor,
nurses' office, utilityrooms, andday room.Weekly
MSMsweeporimpression plates
weretakenatpatients'
bedclothes and on30 occasions in the last 3 weeks from nurses'
disposable
aprons andclothes.
Strain identification. The
identity
ofEMRSA isolates wasconfirmed
by
a characteristic antibioticsusceptibility
andphage
typing
pattern(6).
Plasmidanalysis
wasperformed
aspreviously
described(7)
on all EMRSA isolates from staffmembersonEMRSAisolatesfrom
patients
atthestartofthestudy
and whenever thechloramphenicol
susceptibility
pat-tern
changed. Phage
typing
was alsoperformed
on MSSAisolates
by
theStaphylococcus
ReferenceLaboratory
of the Central Public HealthLaboratory,
Colindale,London,
En-gland.
Statistical
analysis.
Anunpaired
t testwasusedtocompare the mean of the number ofdays
of eachactivity grade
and the mean of the number of eachgrade
ofprocedure
per-formedoneachday
fornurseswhocarriedtheEMRSA with thecorresponding
means for nurses who never carried it.Days
ofcarriage wereassumedtofollowaPoissondistribu-tion,
with the meanbeing dependent
on the numberofeachgrade
ofprocedure
performed.
The interaction ofthenum-berof
procedures
(grade
2or3)
performed by
each nurse oneach
patient
was theninvestigated
with the computer pro-gram GLIM3.77(GLIM
system release3.77, 1985,
C. D.Payne, ed.,
NumericalAlgorithms Group,
Oxford).
RESULTS
Strain identification.
All
MRSAphage typed
weakly
withphage
85atRTD100(routine
testdilution x100)
and with theexperimental phages
88A and 932.Plasmid
analysis,
unlikechloramphenicol
susceptibility testing, reliably
distinguished
between thetwooutbreak strains
(Fig.
1).
Chloramphenicol-susceptible
isolates frompatients
D,V,
and Ralways
contained a ca.1-megadalton
(MDa)
cryptic
plasmid
andwere
designated
CY. Plasmidanalysis
of isolates frompatients
C,
M, and H, with thechloramphenicol-resistant
EMRSA,
always
revealed a ca. 3-MDaplasmid,
and theseisolates were
designated
CR.However,
aminority
popula-tion of
chloramphenicol-susceptible
isolates wasoccasion-ally
detected fromsomesitesonpatients
C andM,
and thesehad
merely
lost the 3-MDachloramphenicol
resistance
plas-mid
(designated
CR-).
Patient EMRSA carriage. Table 1
gives
details ofpatient
colonizationand infectionwith the EMRSA and the approx-imate time taken toperform
wounddressings.
The mostheavily
colonizedpatient,
D, died onday
23 of thestudy.
Table 1 alsolists the residual sites colonized after the first2 weeks of decontamination. The decontamination
regimen
produced
adiminution in theextentof EMRSAcolonizationby
week 3 in allpatients
except V, in whom thetriclosan
caused folliculitis and had to bediscontinued.
Environmental
screening.
Environmental EMRSA isolates were obtainedonly
in thefirst fourweekly
screensandwereneverisolatedfrom theroomof
patient
Morinanyof the slitsamples
of ward air.Settle
plates
in the first 3 weeks indicated alow contamination rate of between1and 2 CFU of EMRSA per h in the roomsofpatients
D and R, inoneinstance
immediately
afterachange
ofpatient
D'sdressings.
Only
onesurface swab waspositive
on adirectculture;
twocolonies of EMRSA were isolated from the taps and door
handle ofthe room of
patient
C, the most mobile ofall
thepatients.
All otherpositive
results were from broth enrich-ment cultures of swabs. These indicatedwidespread
but low-level EMRSAcontamination inthedust in the roomsofSTAFF CARRIAGE OF EMRSA 1473
FIG. 1. Ethidium bromide-stained plasmid agarose gel. Lane 1
contains themolecular size standards;al plasmidswereof thesizes
previously reported (7). Theca. 20-MDa plasmid carriesgenes for
resistance to ethidium bromide. propamidine isethionate. several aminoglycoside antibiotics, and often trimethoprim and penicillin (6). CY isolates have ca. 20- and 1-MDa cryptic plasmids. CR isolates have ca. 20- and 3-MDa chloramphenicol resistance plas-mids;anopencircularform of suchaplasmid isalsopresent. CR-isolateshave only theca.20-MDaplasmid. CRCY isolates have the ca. 20-, 3-, and 1-MDaplasmids.
cm) from the bed of patient D. Less contamination was
found in the rooms of patients V and H. where only horizontal surfaces less than 2 ft (ca. 61 cm) from the bed
were positive, and that of patient C where, in addition, a
windowsill 8 ftaway waspositive. EMRSAwasnotdetected
on the nurses' clothes or aprons. The environmental EMRSAisolateswereofaplasmidtypeconsistent withthat found forthe patientin that room.
Staff carnage. Neither physiotherapist acquired the
EMRSAdespite close patientcontact. However, the
proce-duresthey performed, suchasmobilizationorchest
physio-therapy,wererarely classifiableasgrade 3.Themedicalstaff
memberswerealsoclear of carriage,buttheirenvironmental
and patient contact was minimal. The domestic staff
mem-TABLE 2. EMRSAcarrigeand dutydaysof nurses 1 to 13 No.ofacquired No.of dutv No.of clear screens: EMRSA of activitydayswith
of
plasmid
type: grade:Nursegre
Before After the
carriage lastcarnage CR CY CR CY 1 2 3
episode` episode
1" 17. 33NF 8 1 2 O 6 12 10
2'> 10 34 1 0 0 1 8 il
3 39,.1.33, 8 2 4 0 0 7 14
il
41" 1.27 5 1 1 0 0 8 9
5'" 2+.6. 3. 6 0 8 O O 8 10
11F, 3F. 1F.IF
6 1+.42 4 1 2 0 0 10 12
7 4+.5, 5.31 4 3 2 O O 12 9
8h 0+, 1,3.1. 4 1 4 1 0 2 7
9 11.7 36 0 2 0 7 15 6
10"' 19 S 1 0 0 0 6 5
il 1.13 26 1 1 0 0 10 12
12 13 8 1 0 0 0 6 6
13' ' 0 0 8
`All nasal and transient carrigeexceptas follows:NF. nasal andfinger
carriage; F.fingercarriage alone: +. short-termEMRSA carriage. ' Also carriedanS. aureusisolate resistantonlytopenicillin.
Persistentcarrier.
bers werealso clear of carriage despitetheirenvironmental contact.
A total of 870 screens were performed on the 26 nurses, and EMRSA carriagewas detected on 50occasions in 13of them. Threecarriage patternswereobserved in the 13nurses (Table 2).
(i) Transient carnage. Nasal or finger EMRSA carriage wasdetectedimmediately after a duty period butwaslostby thenextday. Thistypeofcarriagewas seenon32occasions innurses1 to 12andwasmostlynasal;EMRSAwascultured ononly 5 occasions from two nurses' fingers.
(ài) Short-term nasal carnage. EMRSA was detected on two consecutive occasions. In three of the four nurses in whom this type of carriage was observed, the EMRSA was detected before and after the same duty period.
Only 4 of the 40 instances of transient or short-term carriage were detected by direct culturing, andin each less than 17 colonies of EMRSA were grown. Table 2 includes details of the number of clear screens before each culture and after the last culture of EMRSA.
TABLE 1. Patient sitescolonized or infected with the EMRSA and EMRSA transmission to staff performing grade 3 procedures
No.ofgrade3 7c ofgrade3
Site(s) colonizedorinfected by EMRSA" procedures performed proceduresperformed Approxtime (h)
Patient (no. of dressingschanged) %(- of dressings taken to change
bynurses: changed)bynurses1 dressings to12 resulting in
Initially After wk 2 14to26 1to12 EMRSAacquisition
V N,ThP.U,R,H+.S+ Ail 17(4) 71(48) 6(4) 1
D N,Th, P.S+, H+, H+ 37 (12) 103(72) 13 (13) 3.5
R N.Th, P, U, R,S+.H+, H+ H+, H+ 28 (10) 73 (41) 7 (12) 1.5
C N. Th, PU.S. A+ A+ 13 (8) 47 (26) 11(12) 1
H N. S, U+ T+ 24 (7) 59 (14) 10 (29) 0.5
M N,P,Th,R. U+ P.R. U+ 31 (5) 33 (7) 0 (0) 0.5
'A,Abdominal wound; H. heel sore;N.nose;P.perineum;R.rectum;S. sacrailsore:T.toesores; Th. throat; U.urethra. +.Infected site.-. The patient died.
1474 COOKSON ET AL.
(iii) Persistent nasal carriage. EMRSA was isolated on three or more consecutive occasions. This typeofcarriage was seen in only one nurse (nurse 13);EMRSA wasisolated onfour and then sixconsecutiveoccasions, although in only two of these occasions was EMRSA detected by direct culturing. This nurse wassubsequently foundtobecarrying the chloramphenicol-resistant EMRSA in her throat and perineum and to be taking a course of trimethoprim and sulfamethoxazole for a urinary tract infection. Hercarriage was subsequently cleared with mupirocin (Bactroban; Beecham Pharmaceuticals). One chloramphenciol-suscep-tiblestrain was isolated from thisnurse(Fig. 1,CR-)but,as with the isolates from patients C and M, this was a CR isolate which had lost the chloramphenicol resistance plas-mid. No other nurses carried the EMRSA at other sites in their weekly screens. We were unable to determine when nurse 13 became a persistent carrier, so she was excluded from the data on EMRSA acquisition. EMRSA carriagewas detected in6% of the screens of the 25 nursesthusanalyzed and 11% of the screens ofnurses 1 to 12.
NoEMRSAacquisition was detectedafter any of14grade 1activity days and after only 1 of 196 grade2 activity days. In marked contrast, grade 3 activity days were associated with all other incidents of transient or short-term EMRSA carriage. There was no significantdifference in the number ofgrade2 (P = >0.2) or three (P = >0.2) activity days for nurses 1 to12, whocarried the EMRSA, and nurses14to26, who did not. However, nurses1 to 12did perform far more wounddressings (P<0.02)andgrade 3activities (P<0.001) on grade 3 days than did nurses 14 to 26 (Table 1). The number of grade 3 procedures performed significantly (P <0.001) increased the mean number of days of EMRSA carriage by nurses, but the differences between patients were notsignificant (P > 0.05).
Table 2 shows the plasmid patterns of the EMRSA ac-quired by nurses 1to 12. Plasmidanalysis confirmed that all thechloramphenicol-susceptible strains had the CY pattern. Thus, we wereable to show that thetwo EMRSA outbreak strains had been acquired at different times in seven of the nurses rather than that there was continued carriage of the CR strain with plasmid loss. Nurse 5 is
particularly
worthy ofcommentin thatsix of hereightCY strainsweredetected solely at the end of duty periods in which she treated only patientswith the CY EMRSA plasmid profile. It was impos-sible to ascertain in two of the four incidents of short-term carriage whether the EMRSA strains had beenreacquired
orpersisted during the duty period, as they had the same plasmid pattern (CR).In athird incident (nurse8)the strains differed in plasmid patternin thatone wasCR and theother was CRCY (containing both cryptic and chloramphenicol resistanceplasmidsandacquiredfrompatient V;seebelow). It appearsthatthis patternwasderivedfrom in vivo
plasmid
transfer between the strains with patterns CR and CY rather than that the two strains were detected at the same site, althoughthesestrains havenotappearedtobe very stableon serial subcultures, even on media containing 50 mg of chloramphenicol per liter.
In 33of the instancesof staff EMRSAacquisition,plasmid analysis enabled us to implicate procedures on
specific
patients. EverypatientexceptMwasinvolved(Table
1).
and patientD was responsibleformost ofthetransmission(Fig.
2), but moregrade3 procedureswere
performed
onher. No obvious relationship could be observed between EMRSA transmission to staff and the length ofthe wounddressing
procedureortheextent of EMRSAcolonization ofpatients. Forinstance,thegreatest percentageofdressingproceduresNo. of EMRSA transmissions
12
-10
-
8-6
-PattentDdled
1 2 3 4 5 6 7
Week of Study
Key _D
eylC MR MV EMH Total
Patient codes
FIG. 2. Patients implicatedeach week in EMRSA transmission
tonursingstaff. The histogramcodes represent eachpatient (Table 1) that could be implicated in that study week for an EMRSA transmissionto a nurse.The dotted line represents the totalofsuch
transmissions.
followed
by
EMRSA transmission to staff occurred withpatient
H, aminimally
colonizedpatient,
whorequired only
brief wound
dressing
of infected toe sores. MSSA wasdetected in nurse 13 and six other nurses in whom the EMRSA was also detected
(Table 2).
Phage
typing
distin-guished
amongalltheisolates,
except thoseofnurses 5and8.
EMRSA transmission betweenpatients.
Acquisition
of the CR EMRSA inpatient
R's sacral sore andperineum
andpatient
V'ssacralsore(both
patients
werecarriersoftheCYstrain)
occurred in week 1of thestudy.
Achloramphenciol-resistant strain with the CRCY pattern wasalso isolated at this time from
patient
V'sperineum.
Theacquired
strains did notestablish themselveson thesepatients
in thatthey
werenot isolated from screens
repeated
48 h later or fromsubsequent
screensin thenext6weeks. Nurse13,
colonizedwith the EMRSA with the CR
plasmid profile,
did notperform
anyprocedures
on either of thesepatients,
and theEMRSA was
thought
to have been transmitted to thesepatients by
nurses with transientor short-termcarriage.
DISCUSSION
Ithasoften been
suggested
thatcertainepidemic
strains of S.aiireushaveaspecial
ability
tocolonizepatients
and staff(20)
and that certain MRSA strains(EMRSA)
are among these(6).
There is little information on thecarriage
and transmissionofMRSA,and inarecentreviewofthesubject
CasewellandHill
(4)
hadtoextrapolate
from theconclusions of studies ofthe carriage ofMSSA,
but even in these therehas been no
comparable
attempt to correlate staffcarriagewithduties
performed.
Inthisstudy
we werepresented
withan
opportunity
to examinestaff EMRSAacquisition
andthusthe
early
stages of itsspread.
A number of factors contributed towards the success of
this
study.
Firstly,
nursecooperation
was achievedby
intensive education and the useof
personal
activity
sheets.Secondly,
many wounddressing procedures
were of such along
duration that thenurses involved would oftenperform
grade
3procedures
ononly
onepatient
on anygiven day.
Thirdly,
thetwice-daily
screening of each nurseyielded
STAFF CARRIAGE OF EMRSA 1475
much more detailed information than that obtained in most
other studies, in which intermittent
screening
has been thenorm.
Fourthly,
we used broth enrichmentculturing
toincreasethe
sensitivity
ofdetection of EMRSA carriage; infact,
without it carriagewould have beenentirely
missed ineight
ofour nurses.Finally, plasmid
analysis
enabled us todistinguish
amongtheoutbreak strains andclarify
thesourceof
carriage.
We were fortunate that the strains did notextensively
cross-colonize thepatients
and that the crypticplasmid
wassuch astable marker. Theemergenceofathird EMRSAplasmid
type(CRCY)
during
thestudy
isinterest-ing, especially
as it is very rare in the UnitedKingdom
(J.Naidoo,
personal
communication).
However, this patternpredominated
in MRSAfromoneof the Australianhospitals.
where similar ifnotidentical strains have been described(6,
23).
Our
study, although
detailed, was notdesigned
to avoid thepossibility
of itcausing
an alteration in the nurses' behavior(the
Hawthorneeffect)
in that weeducatedhighly
motivated nurses in theimportance
ofcorrectprocedures
and hand
hygiene
andthey
screened themselves.Despite
this,
the incidence of transient and short-term carriage wasunexpectedly high.
EMRSAacquisition
was almosttotally
related to close
patient
contact,especially
wounddressing.
rather than
walking
into a contaminated environment orhaving
minorcontactwithapatient
(grade
1or2activities).
Seven of twelve nurses carried each
epidemic
strain atdifferent
times,
supporting thehypothesis
of continuedac-quisition
rather than intermittent detection of EMRSAcar-riage.
Thishypothesis
was alsosupported by
thelarge
number of clear screens between each EMRSA carriage
episode
in many of our nurses andby
the fact that the EMRSA waspredominantly
detectedafter,
rather thanbefore,
aduty period.
We did not
perform
regular
finger
sampling
or screeningimmediately
beforeandafterprocedures
in thisstudy
andsocannot comment on the exact method of EMRSA
acquisi-tion. The observation that EMRSA transmission was not
simply
relatedtotheextentofpatient
colonization butcould followsimple dressing
procedures
onminimally
colonizedpatients
made itdifficult topredict
whichpatient
waslikely
to transmit theorganism.
S. aureus carriage onfingers
has been correlated withperineal
carriage(11),
which was not evident in either ofourtwo nurseswithfinger
carriage,and with nasal carriage(17),
as was observed in one nurse. Nor didthey
have any colonization of minor lesions or overtinfectionwith the EMRSA. The
persistence
of MRSAonthe hands ofnursing
staff and itssubsequent
clearanceby
simplehandwashing
ordisinfection have been demonstratedprevi-ously
(21).
The EMRSA mayhave beenacquired
fromdirect contact with contaminated wounds ordressings
andbed-clothes,
as Hare(10)
hypothesized.
We feel that this isunlikely
in thatgloves
wereusually
worn for contact withpatients, judging by
thelarge
numbers thatwereusedduring thestudy.
We could not demonstrate contamination of nurses' clothes. It is morelikely
that the EMRSA wasacquired
frominhaledairborne EMRSAparticles
suchaswe have observedduring physiotherapy
on apatient with exfo-liative dermatosis(5)
and after wounddressing
and bedmak-ing(B.
D. Cookson,unpublished
observations). EMRSA transmission would thenpresumably
follow transfer from the nose tothe hands.The definitions used in other studies have differed from
ours because of the lower
frequency
ofsubject
sampling used. The first allusion that we found to brief S. (lure(scarriage
was in aweekly
study
of nasal carriage in 500medical studentsover a3-to12-monthperiod(9); 42%c of the students were 'occasional' carriers in that the organism wasdetectedinless than 10% of theirscreens.Theseisolates were ofa phage type different from that previously found, and these workers postulated that these students' noses
were not trueS. auraeshosts but acted rather like filters of the inspired air.
The further elucidation by this study of the phenomenon oftransientorshort-term EMRSAcarriage hasanumber of implications. These forms of carriage probably caused the two instances of EMRSA transfer from one patient to anotherinthat the patients had no contact with each other, the persistent carrier (nurse 13) had no contact with these patients. the environmental contamination did not extend outsidetheroomsof thesepatients, and nofomites could be implicated. We are also convinced that they have contrib-uted tothe failureof standard isolationtechniquestocontrol EMRSA spread. These observationsjustify the use of des-ignated staffwhen the consequences of EMRSA transmis-sion may be especially serious, such as in an intensive-therapy unit(5) or aburn unit (16).
Transient MRSAcarriage in agency staff members might also result in interhospital spread, as these staff members often work in more than one hospital in a 24-h period. A central agency coordinatesthe employment ofallouragency nurses and ensures that we do not employ staff members who haveworked on EMRSA patients elsewhere unlessthey havebeen screenedand decontaminated. A similarapproach is adopted with our own staff nurses who have had close contactwith EMRSA patients.
AIl threetypes ofcarriage shouldbe consideredin MRSA clearance studies with antibiotics or disinfectants. Such studiesrarelystate whether screens were performedonstaff members immediately afterthey had performed procedures on patients. Thus. transient carriers may have been misla-beled aspersistent carriers, leadingto erroneousconclusions as tothe efficacy ofspecific decontamination regimens. We have not previously found chlorhexidine, povidone iodine, orhexachloropheneused alone to be effective ineradicating the EMRSA from wounds. The relationship between staff EMRSA acquisition and wound dressings emphasizes the importance of rapid elimination from wounds. We agree with others (24) that thrice-daily triclosan total-body washes or baths are poorly accepted by patients. Furthermore, tri-closan did not eradicate the EMRSA from our patients' wounds,although only minimal wound exposure would have occurred duringa bath, since dressings were not removed.
Although it was clear that the performance of close-contact (grade 3) procedureswas the mostimportant differ-ence betweennurses1 to 12andthose who did not carry the EMRSA, we could not be certain that other additional factors did not exist. Others have pointed out the possible roles of human leukocyte antigen type (13) and bacterial interference (19) in the carriage ofS. aureus. Only weekly screenswereperformedforcarriage ofMSSA, sowecannot be certain of the dynamics ofbacterial interaction, but it is interestingthat ailthecarriersof MSSA were also carriers of the EMRSA. Bacterial interference might have discouraged the establishment ofprolonged EMRSA colonization, but is unlikely tobe the soleexplanation in that half of nurses 1 to 12 did not carry such S. aureus strains. The association between antibiotic administrationand MRSA acquisition in patientshas beenalludedtopreviously (8); it might alsohave been a factor in staffacquisition, as in nurse 13.
1476 COOKSON ET AL.
azjreus (1, 14, 15). Areas immediately around the beds of our EMRSA patients usuallyharbored the organism. In contrast, the more outlying areas were clear, despite the use of these areas formobilization and rehabilitation. People commonly blame the environment as the source of EMRSA spread, but we demonstrated that walking into a contaminated environ-ment alone didnot lead to EMRSA acquisition. In situations similarto ours, we are confidently able to predict that staff members are unlikely to acquire EMRSA unless a close-contact (grade 3)procedure is performed. We have therefore concentrated our efforts on those procedures most likely to cause EMRSA transmission by the designation of nursing staffand have minimized the control measures imposed on the other staff.
It seems probable that many of our observations are common toall outbreaks of staphylococcal infection. How-ever, one must take care when extrapolating the results of this study to different circumstances. Other hospitals may have a more heavily contaminated environment. Con-versely, in an open ward, even with minimal environmental contamination, staff members may be at risk via the airborne route when passing close to an area where a close-contact (grade 3) procedure is being performed. Further studies of similar detail and intensity of screening, but with different environmental and staffing conditions, are required. Un-doubtedly, the use of plasmid analysis and an activity grading system wouldfacilitate such studies.
ACKNOWLEDGMENTS
Wethank theStaphylococcus Reference Laboratoryforthe phage typing, S. Chinn for the statistical analysis, and al the staffwho participated in this study.
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