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Modeling the Invasion of Community-AcquiredMethicillin-Resistant Staphylococcus aureus intoHospitals Erica M. C. D'Agata,1 Glenn F. Webb,2 Mary Ann Horn,2,3 Robert C. Moellering, Jr.,1 and Shigui Ruan4
1Division of Infectious Diseases, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts; 2Department ofMathematics, Vanderbilt University, Nashville, Tennessee; 3Division of Mathematical Sciences, National Science Foundation, Arlington, Virginia;and 4Department of Mathematics, University of Miami, Coral Gables, Florida Methicillin-resistant Staphylococcus aureus (MRSA) has traditionally been associated with infec- tions in hospitals. Recently, a new strain of MRSA has emerged and rapidly spread in the community, causingserious infections among young, healthy individuals. Preliminary reports imply that a particular clone (USA300)of a community-acquired MRSA (CA-MRSA) strain is infiltrating hospitals and replacing the traditional hospital-acquired MRSA strains. If true, this event would have serious consequences, because CA-MRSA infections inhospitals would occur among a more debilitated, older patient population.
A deterministic mathematical model was developed to characterize the factors contributing to the replacement of hospital-acquired MRSA with CA-MRSA and to quantify the effectiveness of interventions aimedat limiting the spread of CA-MRSA in health care settings.
The model strongly suggests that CA-MRSA will become the dominant MRSA strain in hospitals and health care facilities. This reversal of dominant strain will occur as a result of the documented expanding communityreservoir and increasing influx into the hospital of individuals who harbor CA-MRSA. Competitive exclusion ofhospital-acquired MRSA by CA-MRSA will occur, with increased severity of CA-MRSA infections resulting inlonger hospitalizations and a larger in-hospital reservoir of CA-MRSA.
Improving compliance with hand hygiene and screening for and decolonization of CA-MRSA carriers are effective strategies. However, hand hygiene has the greatest return of benefits and, if compliance isoptimized, other strategies may have minimal added benefit.
Infections caused by methicillin-resistant Staphylococ- tions among young, healthy individuals with no ex- cus aureus (MRSA) cause considerable morbidity and posure to the health care setting [4]. Since then, com- mortality, with estimated mortality rates surpassing munity-acquired MRSA (CA-MRSA) strains have those caused by HIV infection [1, 2]. Until recently, rapidly spread throughout the world [5]. Outbreaks of MRSA has been a health care–associated pathogen that CA-MRSA have been reported among children, ath- affects predominantly the elderly population and de- letes, nurseries, obstetrical wards, and in many other bilitated individuals [3]. In 1998, a new strain of MRSA populations [4, 6–8]. Some strains of CA-MRSA have emerged in the community setting that caused infec- been implicated in severe infections, including necro-tizing skin infections, septic thrombophelbitis, bacter-emia, and infective endocarditis [9–12].
The expanding community reservoir of CA-MRSA Received 18 July 2008; accepted 14 October 2008; electronically published 5 January 2009.
has led to the inevitable infiltration of CA-MRSA into Any opinion, findings, conclusions or recommendations expressed are those of hospitals [11, 13–15). Several reports further suggest the authors and do not necessarily reflect the views of the National ScienceFoundation.
that CA-MRSA may be replacing the traditional hos- Reprints or correspondence: Dr. Erika D'Agata, Beth Israel Deaconess Medical pital-acquired MRSA (HA-MRSA) [11, 13–15]. This Center, Div. of Infectious Diseases, 330 Brookline Ave, East Campus Mailstop SL-435G, Boston, MA 02215 ([email protected]).
event has the potential for catastrophic consequences, Clinical Infectious Diseases
because CA-MRSA can cause severe infections, which  2009 by the Infectious Diseases Society of America. All rights reserved.
will now occur among debilitated, immunocompro- mised hospitalized patients.
274 • CID 2009:48 (1 February) • D'Agata et al.

Figure 1.
A compartment model of the transmission dynamics of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) and hospital-acquired MRSA (HA-MRSA) in a 400-bed hospital. The arrows and parameter values correspond to entry and exit from the 5 compartments.
The number of hospital admissions per day is L, with the fractions of patients admitted with CA-MRSA colonization, CA-MRSA infection, HA-MRSAcolonization, and HA-MRSA infection expressed as l , l , l , and l , respectively. The transition rates between compartments or exit rates from compartments are expressed as follows: g , g , and g are exit rates of susceptible patients, patients colonized with CA-MRSA, and patients colonized with HA-MRSA, respectively (with the mean length of stay defined as 1/g , 1/g , and 1/g H , respectively); the colonization rates of susceptible patients to the CA-MRSA colonization compartment are (1-h)bCC/N and (1-h)bIC/N and to the HA-MRSA colonization compartment are (1-h)bCH/N and(1-h)b / N where h is the compliance with hand washing hygiene (with h p 0 corresponding to 0% compliance and h p 1 corresponding to 100% compliance), b , b , b , and b are the rates of colonization transmission to patients from health care workers contaminated by patients with CA- MRSA colonization, CA-MRSA infection, HA-MRSA colonization, and HA-MRSA infection, respectively, and N is the total number of patients in thehospital. The rates of infection of patients with CA-MRSA colonization and patients with HA-MRSA colonization are f and f , respectively. The cure rates of patients with CA-MRSA infection and HA-MRSA infection are t and t , respectively, and the death rates of these patients are d and dH, respectively. The rates of decolonization of patients with CA-MRSA colonization and HA-MRSA colonization are a and a , respectively.
We hypothesized that CA-MRSA will replace the traditional HA-MRSA strain in the health care setting over time, and we The deterministic differential equa- sought to identify the epidemiological factors that would result tions model describes the transmission dynamics of CA-MRSA in the dominance of CA-MRSA strains and the competitive within a 400-bed tertiary care hospital with ∼25,000 admissions exclusion of HA-MRSA strains. A deterministic mathematical per year. Individuals within the hospital are in 5 mutually ex- model was developed to quantify the temporal patterns of CA- clusive states: susceptible (S), colonized with either CA-MRSA MRSA spread into the hospital setting. Using this model, we (CC) or HA-MRSA (CH), or infected with either CA-MRSA quantified the consequences of the expanding community res- (IC) or HA-MRSA (IH). Individuals enter the hospital in one ervoir and the increased documentation of more-severe infec- of these states and exit via death or hospital discharge. Steady tions caused by CA-MRSA in the dissemination of this new states of MRSA colonization or infection are achieved over time.
strain into the hospital. The model was also extended to de- Within the hospital, susceptible individuals can become colo- termine the optimal strategy or combination of strategies that nized with either CA-MRSA or HA-MRSA and can subse- would prevent the in-hospital cross-transmission of CA-MRSA.
quently become infected with the respective MRSA strain.
CA-MRSA in Hospitals • CID 2009:48 (1 February) • 275
Table. 1.
Estimates and values for the transmission dynamics of community-acquired
methicillin-resistant Staphylococcus aureus (CA-MRSA) and hospital-acquired MRSA

Total no. of patients No. of admissions per day Patients colonized with CA-MRSA Patients colonized with HA-MRSA Patients infected with CA-MRSA Patients infected with HA-MRSA Length of stay, by patient group Susceptible patients Patients colonized with CA-MRSA Patients colonized with HA-MRSA Patients infected with CA-MRSA Patients infected with HA-MRSA Hand hygiene compliance efficacy, % Transmission rate per susceptible patienta Patients colonized with CA-MRSA per patient colonized with CA-MRSA/N Patients colonized with HA-MRSA per patient colonized with HA-MRSA/N Patients colonized with CA-MRSA per patient infected with CA-MRSA/N Patients colonized with HA-MRSA per patient infected with HA-MRSA/N Rate of infection per colonized patient per day of length of stay, % Death rate per infected patient per day of length of stay, % Infection cure rate per infected patient per day of length of stay, % Decolonization rate per colonized patient per day of length of stay, % BI, data obtained from the Beth Israel Deaconess Medical Center.
a Transmission of MRSA from a colonized or infected patient to a susceptible patient with an as- sumption that hand hygiene compliance is 0%.
Transmission of MRSA between individuals occurs through placed on contact precautions, thereby reducing their trans- contact with health care workers. To simplify the model, co- mission risk, compared with that for the unidentified reservoir colonization with CA-MRSA and HA-MRSA and environmen- of asymptomatically colonized patients. The model compart- tal contamination were not included. Control strategies for ments are illustrated schematically in figure 1. Steady states of preventing the spread of MRSA include improving compliance MRSA colonization or infection are achieved over time. Math- with hand hygiene and placing individuals who are infected ematical equations are provided in a separate publication [17].
with MRSA on contact precautions [16]. Patients who are in- A deterministic model was used to better present the basic fected with either HA-MRSA or CA-MRSA are assumed to be reproduction number and to consider the long-term behavior 276 • CID 2009:48 (1 February) • D'Agata et al.

Figure 2.
Numerical simulation using baseline parameter values and showing the proportion of hospitalized patients colonized or infected with community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) and hospital-acquired MRSA (HA-MRSA) over time. The patient subpop-ulations converge to endemic steady states. CC, patients colonized with CA-MRSA; CH, patients colonized with HA-MRSA; IC, patients infected withCA-MRSA; IH, patients infected with HA-MRSA; t, time.
of the models in these large patient populations. Patients were nization and subsequent transmission [22, 23]. The ratios of therefore aggregated into compartments and were considered the transmission parameters for patients colonized or infected to be homogenous. Using stochastic, individual-based models with CA-MRSA and HA-MRSA (bCC/b would allow for patient heterogeneity; however, the increase in therefore set at ∼4:3. A simulation was also performed to de- behavioral detail provides data that are more difficult to in- termine the transmission dynamics of CA-MRSA if there were terpret and apply, compared with data provided by determin- no differences in growth rate between CA-MRSA and HA- istic models [18].
MRSA and, therefore, an equal risk of transmission.
Parameter estimates are obtained from the Beth Israel Deaconess Medical Center's computerized database system, which provides patient and infection-controldata. Values were also extrapolated from population-based sur- Transmission dynamics of CA-MRSA in the hospital.
veillance or multicenter studies of the USA300 and other strains Simulations of the baseline model demonstrate that CA-MRSA (table 1). The length of stay (LOS) of patients colonized with becomes endemic in the hospital over time. At baseline, the CA-MRSA was assumed to equal the LOS of susceptible pa- endemic prevalence of HA-MRSA is higher that the prevalence tients, because patients colonized with CA-MRSA are predom- of CA-MRSA, reflecting a greater admission rate and longer inantly healthy individuals whose colonization status would not LOS among patients who harbor HA-MRSA, compared with affect their LOS. Patients who are colonized with HA-MRSA, patients who harbor CA-MRSA (figure 2). Increasing the influx however, are a group of patients with multiple comorbidities into the hospital of patients who are colonized or infected with and with longer LOS.
CA-MRSA, however, leads to a rapid reversal of dominance, Unique differences in the biology of CA-MRSA, compared with CA-MRSA strains surpassing the endemic prevalence of with HA-MRSA, are incorporated into the transmission pa- HA-MRSA (figure 3). The prevalence of CA-MRSA will further rameter (b). In vitro studies have demonstrated that the growth increase, given the feedback loop dynamics between the com- rate of CA-MRSA is ∼1.33 times faster than the growth rate munity and the hospital, whereby an increase in the influx of of HA-MRSA [22]. The decreased doubling time can provide patients harboring CA-MRSA and a subsequent decrease in the CA-MRSA strains an advantage toward more-successful colo- prevalence of HA-MRSA in the hospital will lead to an overall CA-MRSA in Hospitals • CID 2009:48 (1 February) • 277

Figure 3.
Effect of an increased influx of patients colonized with community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) and the feedback loop that creates a decrease in the influx of patients colonized with hospital-acquired MRSA (HA-MRSA). The percentage of admissionsthat are of patients colonized with HA-MRSA are held constant at 3%, 5%, and a baseline value of 7% as the percentage of admissions that areof patients colonized with CA-MRSA increases from 0% to 15%.
decrease in the number of patients with HA-MRSA exiting and patients infected with CA-MRSA increases the prevalence of subsequently reentering the hospital. Figure 3 illustrates this CA-MRSA (figure 5). This increase is more marked if the LOS among colonized individuals increases, and it reflects the larger To determine whether the increase in the prevalence of CA- reservoir of colonized individuals, compared with infected in- MRSA was attributable only to the greater value for the trans- dividuals. Increasing the influx of patients who are colonized mission parameter of CA-MRSA, based on the decreased dou- with CA-MRSA into the hospital, combined with an increased bling time, a simulation was performed with the transmission LOS of patients who are either colonized or infected with CA- parameter of CA-MRSA equal to the transmission parameter MRSA, leads to even greater numbers of patients colonized of HA-MRSA. This simulation shows findings similar to those with CA-MRSA over time (figure 5).
of the baseline model (figure 3); the prevalence of CA-MRSA The competitive exclu- continues to increase over time and surpasses the prevalence sion of HA-MRSA by CA-MRSA is demonstrated using the of HA-MRSA, but this requires that a greater number of pa- basic reproductive number (R ). R quantifies the mean number tients who harbor CA-MRSA enter the hospital (figure 4).
of secondary cases of MRSA colonization generated by 1 col- Patients who harbor MRSA act as reservoirs for these path- onized individual. If R ! 1, the strain becomes extinct. Baseline ogens and provide a constant source of transmission. Increasing R values for colonized CA-MRSA and HA-MRSA are the LOS of these individuals will, therefore, increase exposure 0.692 respectively. In this case, with no influx to CA-MRSA among susceptible individuals. The baseline of colonized or infected patients, both strains are eliminated.
model assumed that the mean LOS among patients infected In general, the strain with the higher R value becomes endemic with CA-MRSA was 10 days. This value reflects the predom- and drives the other strain to extinction, provided that its R0 inance of skin and soft-tissue infections caused by the com- value is 11. Numerical simulations demonstrate that compet- munity strain. CA-MRSA is also implicated in more-severe in- itive exclusion of HA-MRSA occurs when the LOS of patients fections, which are reported with increasing frequency. These who are either colonized or infected with CA-MRSA increases, infections are associated with longer LOS and, therefore, result R 0 exceeding the critical value of 1. The interpre- in greater exposure to the reservoirs of CA-MRSA [9–11]. The tation of the epidemic reproductive rates for HA-MRSA and numerical simulations demonstrate that prolonging the LOS of CA-MRSA assumes that there are no admissions of colonized 278 • CID 2009:48 (1 February) • D'Agata et al.

Figure 4.
Effect of an increased influx of patients colonized with community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) and the feedback loop that creates a decrease in the influx of patients colonized with hospital-acquired MRSA (HA-MRSA) when the transmission risk ofCA-MRSA is equal to that of HA-MRSA (b p b p or infected individuals with either strain. Ongoing admission bials, or combinations of such strategies) to 0% (to reflect the of either colonized or infected individuals guarantees that the inevitable emergence of resistance to the antimicrobial agents) epidemic is never eliminated. The level of endemicity is com- [28]. We also simulated the effect of these interventions and mensurate with admission rates and parameters in the model, of combinations of these interventions as the rate of entry of as described by the formulas for the steady states.
patients with CA-MRSA increased.
The effects of 3 standard control strategies Simulations demonstrate that all 3 interventions are effective were evaluated: (1) compliance with hand hygiene, (2) screen- in decreasing the spread of CA-MRSA. The magnitude of their ing for MRSA colonization, and (3) decolonization of colonized effect, however, differs substantially, depending on the level of individuals (figure 6). Screening results in the identification of compliance or efficacy of each strategy. Decolonization of pa- previously unrecognized, asymptomatically colonized individ- tients known to be colonized with CA-MRSA is the most ef- uals, who are subsequently placed on contact precautions.
fective strategy and would result in the lowest percentage of Screening is therefore assumed to reduce the transmission risk total patients colonized with CA-MRSA. The greater efficacy of colonized individuals to the transmission risk of infected of decolonization, compared with that of hand hygiene or individuals, who are already on contact precautions (b screening, reflects the first-order effect of decolonization, which would directly eliminate the reservoir of MRSA. The other 2 The identification of the unrecognized reservoirs with screening requires action, including not only strategies, hand hygiene and screening, have a second-order the timely placement of newly identified colonized individuals effect, because they decrease MRSA transmission but do not on contact precautions, but also compliance with these pre- eliminate the source. The impact of reduced efficacy of decol- cautions. Sensitivity analyses were performed to evaluate the onization with the emergence of resistance to the decolonizing "finding is not enough" concept of screening [26]. Decoloni- antimicrobial was also simulated [28].
zation of colonized individuals was simulated by adding the Compliance with hand hygiene had the greatest return of movement of colonized individuals into the susceptible com- benefits, with a decrease in compliance resulting in marked partment. The efficacy of decolonization with topical agents increases in the percentage of patients who were colonized with was set at 66% [27]. The parameter varied from 100% (to reflect CA-MRSA; conversely, improved compliance dramatically de- potentially more-efficient decolonization strategies, such as creased the percentage of colonized patients. In contrast with whole-body antimicrobial washes, use of systemic antimicro- the other 2 interventions, there was no diminishing return as CA-MRSA in Hospitals • CID 2009:48 (1 February) • 279

Figure 5.
The effect of increased admissions of patients colonized with community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) and the effect of an increased length of stay (LOS) among patients colonized with CA-MRSA (A) and patients infected with CA-MRSA (B) on thepercentage of patients colonized with CA-MRSA.
hand hygiene approached 100%, compared with improving the efit if hand hygiene compliance was 190%. Conversely, if there effectiveness of screening and decolonization toward 100%. The was poor compliance with hand hygiene, effective screening simulations also showed that, once compliance with hand hy- strategies reduced the overall spread of CA-MRSA substantially giene surpassed 80%, it became a more effective strategy than (figure 7). Combining screening and decolonization strategies while maintaining a baseline hand hygiene compliance of 60% The efficacy of these interventions as the influx of CA-MRSA had a small additional benefit, even when the efficacy of these into the hospital increased was also evaluated. The simulations interventions was maximized (figure 7).
showed that the relationship between the efficacies of the 3interventions remained comparable, regardless of the rate of entry of patients colonized with CA-MRSA. The magnitude ofeffect however, increased with all 3 interventions as more in- The rapid emergence and spread of CA-MRSA in the com- dividuals with CA-MRSA entered the hospital.
munity has become a major public health threat. Our model Combination of interventions.
Combinations of 2 inter- strongly suggests that CA-MRSA will become the dominant ventions and their impact on the spread of CA-MRSA were MRSA strain in hospitals, with competitive exclusion or near evaluated. These simulations further verified the importance of exclusion of the traditional HA-MRSA strain. Several hospitals including improved hand hygiene compliance with other in- have already documented the predominance of CA-MRSA over terventions and showed that, when compliance with hand hy- HA-MRSA strains as a cause of hospital-acquired infections, giene was maximized, the additional benefit of effective screen- which provides preliminary validation of our model [11, 13, ing or decolonization interventions was small. Screening interventions, for example, had minimal or no additional ben- Our model focused predominantly on the epidemiological 280 • CID 2009:48 (1 February) • D'Agata et al.

Figure 6.
Comparison of the percentage of patients colonized with community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) at steady state for 3 interventions (hand hygiene, screening, and decolonization). In the models shown, patients colonized with CA-MRSA account for3% of admissions per day (baseline; A), 6% per day (B), 10% per day (C), and 20% per day (D).
factors contributing to the reversal of dominance between HA- catastrophic outbreak [31]. Another mathematical model that MRSA and CA-MRSA strains in hospitals. Simulations dem- described the population dynamics of antimicrobial-resistant onstrate that the expanding community reservoir of CA-MRSA bacteria among the community, hospitals, and long-term care will lead to a greater influx of CA-MRSA strains in hospitals, facilities also demonstrated the important role of both the com- with a rapid increase in the endemic hospital prevalence of CA- munity reservoir and the LOS in the spread of antimicrobial- MRSA. The model strongly suggests that even small increases resistant organisms [32].
in the number of patients entering the hospital with CA-MRSA The replacement of the traditional HA-MRSA strain with will contribute substantially to the in-hospital dissemination of CA-MRSA strains, as shown in our model, is further supported CA-MRSA. The second factor that strongly contributes to the by unique bacterial characteristics of CA-MRSA that may pro- replacement of HA-MRSA by CA-MRSA is the expanding in- vide these strains with a competitive advantage over HA-MRSA.
hospital reservoir of CA-MRSA. Recent surveillance studies CA-MRSA carries a smaller version of the staphylococcal cas- have documented that CA-MRSA strains are increasingly im- sette chromosomes mec (type IV SCCmec), which confers meth- plicated in severe hospital-acquired infections, including blood icillin resistance, compared with larger cassettes carried by HA- stream and surgical site infections [11, 13, 15]. The morbidity MRSA (type 1-III SCCmec) [23]. CA-MRSA also tend to carry and mortality associated with these nosocomial infections imply fewer antimicrobial resistance genes, compared with HA-MRSA that the reservoir of patients who harbor CA-MRSA in the [23]. The fitness cost of antibiotic resistance may, therefore, be hospital will expand, because both the number of CA-MRSA– minimized by the carriage of smaller or fewer genes, thereby infected patients and their LOS will increase. A recent model providing CA-MRSA with a competitive advantage over HA- of CA-MRSA transmission in a correctional facility also dem- MRSA strains. The more rapid growth rate among CA-MRSA onstrated that prolonged incarceration time would lead to a strains, compared with that among HA-MRSA strains, would CA-MRSA in Hospitals • CID 2009:48 (1 February) • 281

Figure 7.
Comparison of the percentage of patients colonized with community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) at steady state for hand hygiene compliance, screening, and decolonization interventions. A, Hand hygiene compliance increases from 0% to 100% andthe efficacy of decolonization increases from 0% to 25%, 50%, 75% and 100%. B, Hand hygiene compliance increases from 0% to 100% and theefficacy of the screening intervention increases from 0% to 25%, 50%, 75%, and 100%. C, The efficacy of the decolonization strategy increases from0% to 100% and the efficacy of the screening strategy increases from 0% to 25%, 50%, 75%, and 100%.
further increase this advantage by potentially out-competing have also incorporated the transmission dynamics between HA-MRSA strains and increasing the likelihood of colonization health care workers and patients, and the models have included [22, 23]. Our model included the decreased doubling time of parameters that reflect the staffing ratio, the probability of CA-MRSA in the transmission parameter but avoided the in- health care worker contamination, and the rate of contact be- clusion of greater biological fitness, because studies that directly tween health care workers and patients [35–37]. In this model, compare the fitness between these 2 strains have not been per- it was assumed that health care workers would contribute to formed to date. Our model simulations also showed that, even the spread of HA-MRSA and CA-MRSA equally; therefore, sep- if an assumption is made that there is no difference in growth arate compartments for health care workers were not included.
rate between CA-MRSA and HA-MRSA and, therefore, that The baseline parameters for our model were obtained from the transmission risks are equal, the prevalence of CA-MRSA population-based surveillance and multicenter studies that de- will still increase and surpass that of HA-MRSA over time.
fined CA-MRSA predominantly on the basis of the absence of Our model was extended to evaluate the efficacy of 3 control risk factors for health care exposure. Recent data suggest that strategies aimed at limiting the spread of CA-MRSA strains.
a substantial proportion of patients with health care exposure Decolonization was the most effective strategy. This interven- harbor CA-MRSA at admission to the hospital [38]. Thus, our tion eliminated the reservoir of CA-MRSA, whereas the other baseline values may underestimate the extent of CA-MRSA 2 interventions only decreased the cross-transmission of CA- burden in the hospital. Last, to simplify our model, cocolon- MRSA between patients. Although the decolonization strategy ization with CA-MRSA, HA-MRSA, or methicillin-susceptible was the most effective, clarifications to this conclusion are war- S. aureus and colonization with multiple MRSA strains were ranted. First, CA-MRSA may preferentially colonize sites other not addressed and may lead to different results.
than the nares, and therefore skin-to-skin or skin-to-fomite Our model strongly suggests that CA-MRSA will quickly transmission may play a greater role in the spread of CA-MRSA replace the traditional HA-MRSA strain in hospitals. The ex- than in the spread of HA-MRSA [29]. More-aggressive and panding community reservoir of CA-MRSA, coupled with the costlier decolonization strategies, in addition to nasal decolo- greater growth rate and potentially greater biological fitness of nization (which is used predominantly for HA-MRSA), may this strain, support the conclusions of our model. The con- therefore be indicated. Second, the emergence of resistance to sequences of this reversal in dominance raise great concern, the decolonizing agent, in addition to the high recolonization because the reported serious infections caused by CA-MRSA rates, need to be considered, because this strategy may provide strains will now occur among hospitalized patients, who are a only temporary benefit [28]. Improving compliance with hand more debilitated and older patient population. Effective controlis possible, but it necessitates compliance, especially with hand hygiene was a very effective strategy and had the greatest return of benefits, with rapid decreases in the endemic prevalence ascompliance increased and, conversely, rapid increases as com- pliance decreased. Improving compliance with this simple, in-expensive, and effective practice continues to be at the forefront The joint Division of Mathematical Sciences/Na- tional Institute of General Medicine Sciences Initiative through the National of infection-control strategies. Interestingly, simulations that Institutes of Health (R01GM083607 to E.M.C.D., G.F.W., and S.R.) and combined hand hygiene compliance and screening showed that the National Science Foundation (to M.A.H. and S.R.).
the efficacy of a screening strategy is dependent on the level of Potential conflicts of interest.
R.C.M. has been a consultant for Pfizer, Cubist, and Targanta. All other authors: no conflicts.
hand hygiene compliance. In fact, when compliance with handhygiene was maximized, screening had no additional benefit in decreasing the endemic prevalence of CA-MRSA. When com-pliance was poor, however, screening was effective. These data 1. Klevens RM, Morrison MA, Nadle J, et al. Invasive methicillin-resistant Staphylococcus aureus infections in the United States. JAMA 2007; 298:
may provide some explanation of the contradictory conclusions of 2 recent studies that addressed the efficacy of MRSA screen- 2. Bancroft EA. Antimicrobial resistance, it's not just for hospitals. JAMA ing [33, 34].
3. Kuehnert MJ, Hill HA, Kupronis BA, Tokars JI, Solomon SL, Jernigan The transmission dynamics of CA-MRSA are complex. For DB. Methicillin-resistant Staphylococcus aureus hospitalizations, United CA-MRSA strains, outbreak investigations suggest that skin- States. Emerg Infect Dis 2005; 11:868–72.
to-skin and skin-to-fomite transmission may play a greater role 4. Herold BC, Immergluck LC, Maranan LC, et al. Community-acquired methicillin-resistant Staphylococcus aureus in children with no iden- in the spread of CA-MRSA than in the spread of HA-MRSA tified predisposing risk. JAMA 1998; 279:593–8.
[29]. To simplify our model, environmental contamination and 5. Tristan A, Bes M, Meugnier H, et al. Global distribution of panton- the potential for greater skin-to-skin transmission of CA-MRSA valentine leukocidin–positive methicillin-resistant Staphylococcus au-
2006. Emerg Infect Dis 2007; 13:594–600.
were not assessed. Inclusion of these routes would likely further 6. Methicillin-resistant Staphylococcus aureus infections among compet- increase the spread of CA-MRSA in hospitals. Previous models itive sports participants-Colorado, Indiana, Pennsylvania, and Los An- CA-MRSA in Hospitals • CID 2009:48 (1 February) • 283
geles county, 2000–2003. MMWR Morb Mortal Wkly Rep 2003; 52:
and glove use and to reduce the incidence of antimicrobial resistance.
Infect Control Hosp Epidemiol 2007; 28:42–9.
7. Otter JA, French GL. Nosocomial transmission of community-asso- 22. Okuma K, Iwakawa K, Turnidge JD, et al. Dissemination of new meth- ciated methicillin-resistant Staphylococcus aureus: an emerging threat.
icillin-resistant Staphylococcus aureus clones in the community. J Clin Lancet Infect Dis 2006; 6:753–5.
Microbiol 2002; 40:4289–94.
8. Saiman L, O'keefe M, Graham PL, et al. Hospital transmission of 23. Baba T, Takeuchi F, Kuroda M, et al. Genome and virulence deter- community-acquired methicillin-resistant Staphylococcus aureus among minants of high virulence community-acquired MRSA. Lancet 2002;
postpartum women. Clin Infect Dis 2003; 37:1313–9.
9. Millar BC, Prendergast BD, Moore JE. Community-associated MRSA 24. Burke JP. Infection control: a problem for patient safety. N Engl J Med (CA-MRSA): an emerging pathogen in infective endocarditis. J Anti- microb Chemother 2008; 61:1–7.
25. Selvey LA, Whitby M, Johnson B. Nosocomial methicillin-resistant 10. Miller LG, Perdreau-Remington F, Rieg G, et al. Necrotizing fasciitis Staphylococcus aureus bacteremia: is it any worse than nosocomial caused by community-associated methicillin-resistant Staphylococcus methicillin-sensitive Staphylococcus aureus bacteremia? Infect Control aureus in Los Angeles. New Engl J Med 2005; 352:1445–53.
Hosp Epidemiol 2000; 21:645–8.
11. Seybold U, Kourbatova EV, Johnson JG et al. Emergence of commu- 26. Diekema DJ, Climo M. Preventing MRSA infections: finding it is not nity-associated methicillin-resistant Staphylococcus aureus USA 300 ge- enough. JAMA 2008; 299:1190–2.
notype as a major cause of health care–associated blood stream infec- 27. Wertheim HF, Melles DC, Vos MC, et al. Effect of mupirocin treatment tions. Clin Infect Dis 2006; 42:647–66.
on nasal, pharyngeal, and perineal carriage of Staphylococcus aureus in 12. Severe methicillin-resistant Staphylococcus aureus community-acquired healthy adults. Antimicrob Agents Chemother 2005; 49:1465–7.
pneumonia associated with influenza—Louisiana and Georgia, Decem- 28. Conly JM, Johnston BL. Mupirocin: are we in danger of losing it? Can ber 2006–January 2007. MMWR Morb Mortal Wkly Rep 2007; 56:
J Infect Dis 2002; 13:157–9.
29. Miller LG, Diep BA. Clinical practice: colonization, fomites, and vir- 13. Patel M, Waites KB, Hoesley CJ, Stamm AM, Canupp KC, Moser SA.
ulence: rethinking the pathogenesis of community-associated methi- Emergence of USA-300 MRSA in a tertiary medical centre: implications cillin-resistant Staphylococcus aureus infection. Clin Infect Dis 2008;
for epidemiological studies. J Hosp Infect 2008; 68:208–13.
14. Davis SL, Rybak MJ, Amjad M, Kaatz GW, McKinnon PS. Character- 30. Carleton HA, Diep BA, Charlebois ED, Sensabaugh GF, Pedrau-Rem- istics of patients with healthcare-associated infection due of SCCmec ington F. Community-adapted methicillin-resistant Staphylococcus au- type IV methcillin-resistant Staphylococcus aureus. Infect Control Hosp reus (MRSA): population dynamics of an expanding community res- Epidemiol 2006; 27:1025–31.
ervoir of MRSA. J Infect Dis 2004; 190:1730–8.
31. Kajita E, Okano JT, Bodine EN, Layne SP, Blower S. Modelling an 15. Popovich KJ, Weinstein RA, Hota B. Are community-associated meth- outbreak of an emerging pathogen. Nat Rev Microbiol 2007; 5:700–9.
icillin-resistant Staphylococcus aureus (MRSA) strains replacing tradi- 32. Smith DL, Dushoff J, Perencevich EN, Harris AD, Levin SA. Persistent tional nosocomial MRSA strains? Clin Infect Dis 2008; 46:795–8.
colonization and the spread of antibiotic resistance in nosocomial path- 16. Siegel JD, Rinehart E, Jackson M, Chiarello L; the Healthcare Infection ogens: resistance is a regional problem. Proc Natl Acad Sci U S A Control Practices Advisory Committee. Management of multidrug- resistant organisms in healthcare settings, 2006. Available at: http:// 33. Harbath S, Fankhauser C, Schrenzel J, et al. Universal screening for methicillin-resistant Staphylococcus aureus at hospital admission and 18 December 2008.
nosocomial infection in surgical patients. JAMA 2008; 299:1149–57.
17. Webb GF, Horn M, D'Agata EMC, Moellering RC Jr, Ruan S. Com- 34. Robicsek A, Beaumont JL, Paule SM, et al. Universal surveillance for petition of hospital-acquired and community-acquired methicillin-re- methicillin-resistant Staphylococcus aureus in 3 affiliated hospitals. Ann sistant Staphylococcus aureus strain in hospitals. Available at: http:// Int Med 2008; 148:409–18.
35. Bootsma MCJ, Diekmann O, Bonten MJM. Controlling methicillin- Competition.pdf. Accessed 15 October 2008.
resistant Staphylococcus aureus: quantifying the effects of iterventions 18. D'Agata EMC, Magal P, Olivier D, Ruan S, Webb G. Modeling anti- and rapid diagnostic testing. Proc Natl Acad Sci U S A 2006; 103:
biotic resistance in hospitals: the impact of minimizing duration of treatment. J Theor Biol 2007; 249:487–99.
36. D'Agata EMC, Webb G, Horn M. A mathematical model quantifying 19. Hidron AI, Kourbatova EV, Halvosa JS, et al. Risk factors for colo- the impact of antibiotic exposure and other interventions on the en- nization with methicillin-resistant Staphylococcus aureus (MRSA) in demic prevalence of vancomycin-resistant enterococci. J Infect Dis patients admitted to an urban hospital: emergence of community- associated MRSA nasal carriage. Clin Infect Dis 2005; 15:159–66.
37. Austin DJ, Bonten MJM, Weinstein RA, Slaughter S, Anderson R.
20. Jarvis WR, Schlosser J, Chinn RY, Tweeten S, Jackson M. National Vancomycin-resistant enterococci in intensive-care hospital settings: prevalence of methicillin-resistant Staphylococcus aureus in inpatients transmission dynamics, persistence, and the impact of infection control at US health care facilities, 2006. Am J Infect Control 2007; 35:631–7.
programs. Proc Natl Acad Sci U S A 1999; 96:6908–13.
21. Trick WE, Vernon MO, Welbel SF, Demarais P, Hayden MK, Weinstein 38. David MZ, Glikman D, Crawford SE, et al. What is community-as- RA; Chicago Antimicrobial Resistance Project. Multicenter interven- sociated methicillin-resistant Staphylococcus aureus? J Infect Dis tion program to increase adherence to hand hygiene recommendations 284 • CID 2009:48 (1 February) • D'Agata et al.


C: users elindsley desktop draft fee petition_settlement.wpd

Case: 1:14-cv-06913 Document #: 48 Filed: 04/15/16 Page 1 of 6 PageID #:237 IN THE UNITED STATES DISTRICT COURT FOR THE NORTHERN DISTRICT OF ILLINOIS HEIDBREDER BUILDING GROUP, LLC, on behalf of plaintiff and the class members defined herein, Magistrate Judge Cole ASSOCIATION OF THE WALL AND and JOHN DOES 1-10, PETITION FOR ATTORNEY'S FEES

Dieses Merkblatt wurde erstellt von der orthopädisch-rheumatologischen und chirurgisch-unfallchirurgischen Gemeinschaftspraxis Elmshorn, Dres. Hansens, Herzog, Schwarke, Wolf, Grobe und Hilgert. Vom Tennisarm (lateinisch: "Epicondylitis") spricht man, wenn an der Außenseite des Ellenbogens, genau auf oder um den Knochen herum, Schmerzen in den Sehnenansätzen bestehen. Diese Stellen schmerzen dann auf Druck und insbesondere auch in der Funktion. Das Anheben von Gegenständen bereitet Schmerzen vor allem, wenn dabei der Handrücken nach oben zeigt, auch Drehbewegungen des Unterarmes gehen oft wegen der Schmerzen nicht mehr. Was kann man akut tun? Vor allem schonen und kühlen! Die berühmten "KühlGels" aus der Apotheke helfen vor allem dem Apotheker, seltener dem Ellenbogen. Sie verdunsten auf der Haut, und das fühlt sich kühl an. Halten Sie danach mal ein Thermometer auf die Haut! Es wird die gleiche Temperatur anzeigen wie vorher. Besorgen Sie sich ein "Cool Pack" aus dem Kühlschrank, das kühlt! Alles, was man sonst so tun kann, finden Sie in der Tabelle kurz zusammengefaßt am Ende dieses Merkblattes. Absolute Spitze in der Abwägung von Aufwand, Nutzen und Nebenwirkungen sind eigenständig durchgeführte Dehnungsübungen. Sie kosten nichts,