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International Journal of Antimicrobial Agents 30 (2007) 210–212

Review

Community-acquired methicillin-resistant Staphylococcus aureus(MRSA): new issues for infection control

Richard P. Wenzel a,∗, Gonzalo Bearman a,b, Michael B. Edmond a,b

a Department of Internal Medicine, Medical College of Virginia Campus, Virginia Commonwealth University, 1101 East Broad Street,P.O. Box 980663, Richmond, VA 23298, USA

b Medical College of Virginia Hospitals, Virginia Commonwealth University, Richmond, VA, USA

bstract

The emergence and clonal expansion of strains of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) have

reated new challenges with their entrance to hospitals. The increased virulence of CA-MRSA in concert with the depressed immunity ofnpatients may cause added morbidity and mortality expected from healthcare-associated infections. Questions about changing prophylacticnd empirical therapy as well as the use of intravenous immunoglobulin for life-threatening infections are addressed.

2007 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

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eywords: Community-acquired Staphylococcus aureus; Sepsis; IVIg; PVL

The emergence of community-acquired methicillin-esistant Staphylococcus aureus (CA-MRSA) has substan-ially altered the treatment of skin and soft-tissue infectionsSSTIs) in clinics and emergency rooms. Unlike traditionalosocomial isolates of MRSA, the community strains aresually susceptible to non-�-lactam antibiotics such as doxy-ycline, clindamycin and trimethoprim/sulfamethoxazole. Aecent study of 422 patients presenting to 11 university-ffiliated emergency rooms in the USA with staphylococcalSTIs showed that ca. 75% of strains were CA-MRSA [1]. Byefinition, all strains are non-susceptible to �-lactam antibi-tics and, not surprisingly, there was a mismatch of therapynd resistance patterns of isolates in 57% of patients. Fortu-ately, with SSTIs patients generally do well, as long as anyeeded incision and drainage procedures are carried out.

Less frequently, clinicians are managing patientsith severe CA-MRSA-associated lung and bloodstream

nfections [2,3]. The clinical presentation with CA-MRSA-ssociated pneumonia is often haemoptysis and hypotension

n a young adult with necrotic lung disease identified on ahest radiograph or chest computed tomography scan. Sincehe progression to shock is frequent and mortality is sub-

∗ Corresponding author. Tel.: +1 804 828 3389; fax: +1 804 828 5566.E-mail address: rwenzel@mcvh-vcu.edu (R.P. Wenzel).

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924-8579/$ – see front matter © 2007 Elsevier B.V. and the International Societyoi:10.1016/j.ijantimicag.2007.04.003

tantial, there is great concern because optimal therapy isnclear. There are no clinical trials data to guide therapy;pecifically, no studies of alternative antibiotics have beenarried out. Similar to the rapidly declining clinical pictureith CA-MRSA pneumonia, bloodstream infections with thisrganism can progress extremely quickly and can be devas-ating.

Almost all strains of CA-MRSA possess genes coding forleukocidin, a white blood cell toxin characterised 70 years

go by Panton and Valentine [4]. Although controversy per-ists, recent data from a murine model strongly suggest thathe Panton–Valentine leukocidin (PVL) directly causes lungecrosis and is not merely a marker for virulence [5]. How-ver, confirmatory studies will be helpful. Importantly, basedn small series or case reports, some authors have postulatedhat antibiotic drug therapy which interferes with PVL toxinroduction is needed to improve outcomes [2].

Epidemiological reports of infection with CA-MRSAave shown its quick dissemination globally. In recent years,ome laboratories have begun to type CA-MRSA isolatessing molecular techniques. Using pulsed-field gel elec-

rophoresis following SmaI digestion of DNA, most strainsre USA300 or USA400 [6]. The electrophoretic patternsf CA-MRSA are easily distinguished from those foundn the typical nosocomial MRSA isolates, which are often

of Chemotherapy. All rights reserved.

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VL-negative and designated as USA100 or USA200. Thus,nalogous to the transmission of virulent strains of penicillin-esistant S. aureus phage type 80/81 decades earlier [7,8], theransmission of CA-MRSA has been clonal and rapid.

Since 2003, a few clusters of healthcare-associated infec-ion due to CA-MRSA have been reported in hospitals9–11]—on obstetric–gynaecology wards, in orthopaedicatients and in critical care units. More recently, transmissionas been reported in neonatal Intensive Care Units (ICUs)12,13]. There is obvious concern because the organisms areore virulent than the usual nosocomial strains of MRSA.urthermore, because inpatients are considerably more com-romised than those in the community, the interaction of anntibiotic-resistant organism with increased virulence in aulnerable population would be expected to increase patientorbidity and mortality.New questions arise for clinicians managing inpatients.

or example, what would be the outcome of criticalare patients suffering from ventilator-associated pneumo-ia (VAP) or bloodstream infections due to CA-MRSA? Thestimated crude mortality of nosocomial bloodstream infec-ions or pneumonia is ca. 25% and 30%, respectively [14,15].

ill it now be exceeded? Furthermore, some patients withurgical-site infections in the hospital may not fare so well ashose in the community with SSTIs. What will be the added

orbidity and costs?Given its clonal expansion, we anticipate further intrusion

f CA-MRSA strains into hospitals and clinics, accountingor an increasing rate of healthcare-associated infections. As aesult, several policy-related questions arise both for hospitalpidemiologists and clinicians.

At what level of CA-MRSA causing surgical-site infec-tions should peri-operative prophylactic antibiotic therapychange from �-lactam antibiotics to alternative drugs?Should the decision be based on a cost–benefit analysisor instead made as an effort to prevent the vast majority ofinfections even if the costs are higher than existing ones?At what proportion of nosocomial bloodstream infectionsor VAP due to CA-MRSA should empirical treatment withantibiotics include therapy for this pathogen? How willclinicians know whether they have made good decisions?In the absence of clinical trials data, what drug or drugcombinations should be employed for empirical or directedtherapy? What data should be collected to evaluate the out-comes of our decision? Are there data to support adjunctivetherapy?

We arbitrarily suggest that if ≥5% of unique hospital-cquired S. aureus strains are CA-MRSA, empiricalntibiotics should change to include a drug with in vitroctivity. Specifically, we would use the 5% threshold for alter-

ng empirical therapy for VAP or nosocomial bloodstreamnfections. Our choice is not based on any cost–benefit anal-sis, instead only a desire to respond quickly to an emergingathogen.

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timicrobial Agents 30 (2007) 210–212 211

In the absence of data other than case series, we recom-end that at least one antibiotic drug that interferes with toxin

PVL) production should be initiated for either empirical orirected therapy of serious pneumonia or bloodstream infec-ions. This suggestion is based on in vitro data showing thatuch antibiotics inhibit the production of PVL [16]. Currently,t is unclear whether combined vancomycin plus a drug inter-ering with protein synthesis would be better than the lattertself without vancomycin. Of interest, recently reported initro studies show that the use of �-lactam antibiotics upregu-ate PVL messenger RNA [17]. The concern is that �-lactamntibiotics may actually worsen the clinical picture. With lim-ted data available, we suggest that therapy of suspected ornown CA-MRSA infections includes the discontinuation ofny �-lactam antibiotics.

Curiously, in the classic article describing PVL, Pantonnd Valentine note clinical success for their severe ‘pyemicases’ when they treated patients with sera containing anti-odies to the leukocidin [4]. More recently, it has been shownhat intravenous immunoglobulin (IVIg) contains biologi-ally active antibodies to PVL [18]. Furthermore, a reportf a child with septicaemia, necrotising pneumonia and sep-ic arthritis due to CA-MRSA suggests a clinical responsenly after instituting IVIg [19]. Although the data are incom-lete, and the existing reports without control groups mayverestimate the effectiveness of IVIg, we conclude that these of IVIg in the therapy of life-threatening CA-MRSAneumonias and bloodstream infections may prove useful.

For the control of antibiotic resistance, we highlight threetrategies:

limit the introduction of the organism to communities andinstitutions;create optimal antibiotic stewardship; andpromote optimal infection control policies and proceduresto prevent transmission.

We underscore the critical component of infection controlf CA-MRSA. Whereas some hospitals have begun screeningll patients being admitted for MRSA and placing colonisedatients in contact precautions, we conclude that the datao support such programmes are currently inconclusive andhat unintended consequences may outweigh any benefits.ompliance with hand hygiene remains the cornerstone forontrol of MRSA as well as many other pathogens in theealthcare setting.

Recently, data from the Michigan ICU study showed theenefits of team-based prevention of central catheter-relatedloodstream infections [20]. One hundred and three ICUs in7 hospitals were studied in the state (375 000 catheter-daysf observations). What was new was the use of ‘team-based’ather than individual healthcare-worker-based approacheso employing evidence-based infection control interventions

21]. Specifically, five interventions known to prevent infec-ions were employed and each team member was empoweredo intervene if compliance was not 100%. This was notew science but instead a new infection control management

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trategy. Specifically, the five interventions included properandwashing compliance, the choice of subclavian vein forhe site of the catheter, removal of the catheter as soon as pos-ible and use of barrier precautions when instituting insertionnd removal of all femoral lines. Over an 18-month period,he mean and median bloodstream infection rates fell from.7 and 2.7, respectively, to 1.4 and 0 per 1000 catheter-days16].

In summary, in the new era of CA-MRSA it is time toeinvigorate infection control programmes, empowering allealthcare workers to insist on 100% compliance in a patient-entred management style. This is essential in the face ofncertainty and limited data with which to make decisions.evertheless, new prophylactic, empirical and directed ther-

pies are needed for CA-MRSA, and the use of IVIg forife-threatening infections may be shown clinically to reduce

orbidity and mortality.Funding: None.Competing interests: None declared.Ethical approval: Not required.

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