We simulated a year of pregnancies and live births. Using the number of live births in the United States and the seasonal distribution, simulated pregnant women (average age of 27.4 years) were sent one-by-one through the model, starting from January 1, 2007, and concluding December 31, 2007. During each simulation run, the model drew parameter values from each input’s distribution. The probability distributions were independent of each other (eg, the probability of mastitis is not dependent on whether the patient previously developed a wound infection). Where possible, we used triangular distributions. The base value of life expectancy of each pregnant woman in the model was calculated as 46.72 quality-adjusted life years based on age-related mortality data and conversion of years into quality-adjusted life years.42,43 The effect of a MRSA infection in the puerperal period was designated as a decrement in quality of life for that specific year of the infection of 0.35 quality-adjusted life years. The value for incremental cost-effectiveness ratio used in this analysis that denotes a cost-effective strategy is $50,000.00 per quality-adjusted life year based on usual convention and published literature.44
Performing probabilistic (Monte Carlo) sensitivity analyses involved simultaneously drawing all parameters from probability distributions to account for the natural stochasticity of the subsequent outcomes. We also examined the effects of varying different parameter values individually throughout the ranges listed in Table 1 for each variable.
The model produced the following estimations of national burden of MRSA-associated obstetric infectious morbidity: 8,880±184 cases of mastitis and 5,414±144 cases of wound infection without any surveillance measures (total cases14,294). This total number of MRSA-associated infectious cases (N=14,294) translates into approximately 357.4±5 per 100,000 pregnancies that result in a live birth. Additional attributable morbidity from the mastitis-associated cases are that approximately 157±25 women would require hospitalization and 29±11 of these women would develop a breast abscesses caused by MRSA. The number of national hospitalizations from wound infection was 105±20. Overall, 477±43 women will require home care services related to MRSA-attributable wound infections.
From a societal perspective, economic modeling estimates that on a national scale MRSA-associated infectious morbidity currently generates $8,747,009± 267,867 of costs, including all outcomes considered in the model but not including any costs related to surveillance practices. From a payer perspective, the total economic burden of MRSA is $8,037,789±237,346. The average additional cost per case of MRSA infection is $611.68. Although patient hospitalization that subsequently requires operative room drainage procedures is an overall rare occurrence, these cases engender the highest cost per case.
The results of the multidimensional sensitivity analysis demonstrate that the estimates produced in this model are most sensitive to rates of cesarean delivery (which varied costs from a societal perspective by ±$278, 614), rates of mastitis (which varied costs from a societal perspective by ±$271, 879), and the prevalence of MRSA in the obstetric population (which varied costs from a societal perspective by ±$259, 068). Results from a payer perspective were comparable, with smaller effects on costs (±$216,632 for rates of cesarean delivery, ±$244,695 for rates of mastitis, and ±$219,975 for MRSA colonization rates). Variables that had minimal overall effect in the model on the estimates of rates of disease or costs in this population include rates of hospitalization for wound infection or mastitis-related conditions, costs of antibiotics, costs of home care, and need for operating room drainage procedures.
The results for the analysis, including universal surveillance for MRSA among the entire pregnant population with subsequent attempts to decolonize women with MRSA, are demonstrated in Table 3. None of the incremental cost-effectiveness ratios approximate the benchmark of $50,000.00 per quality-adjusted life year gained, regardless of the assumed success of surveillance and decolonization.
This model suggests that currently, MRSA accounts for a modest burden of infectious morbidity and costs among the obstetric population in addition to those caused by methicillin-susceptible S aureus and other perinatal pathogens. Despite this calculated burden, it does not seem from this investigation that universal screening of the entire pregnant population for MRSA colonization with subsequent attempts to decolonize women is a cost-effective strategy. The estimates of burden of disease in this model are most sensitive to rates of cesarean delivery, mastitis, and MRSA colonization. It is therefore likely that the projected attributable morbidity and costs are likely to increase in the future, given the increasing rate of cesarean delivery, increasing rates of adoption of lactation, and the increasing rates of MRSA-associated infections being reported in the literature.10,17,21,24,29,33
The standardized rate of 357.4 invasive MRSA obstetric infections per 100,000 live births is significantly higher than the rate estimated by Klevens et al of 31.8 per 100,000 persons in the general population.21 Some comparisons from the vaccine preventable disease surveillance estimates provide perspective. These include annual rates of meningococcal disease among children aged 2–19 years (0.68–3.9 per 100,000), annual hepatitis B rates in both the postvaccine and prevaccine era, respectively (2.5 and 11.6 per 100,000 persons), and annual influenza-related hospitalizations in adults (190–560 per 100,000).45
A key component of the model is the estimation of MRSA colonization in the obstetric population that comes from two sources. Available literature suggested a rate of 0.5–2.0%, and local hospital quality control surveillance estimations among admissions to the high-risk obstetric service produced a range of 1–7%.19,20 An important contribution made by predictive modeling is that key areas for further research are identified. From this model, it is apparent that robust longitudinal data on the prevalence of MRSA colonization and any associated subsequent infectious morbidity among pregnant women is needed to appreciate the full scope of the problem.
The costs attributable to MRSA infections in this model are sizable (in excess of 8 million dollars) and are likely to increase over time. Others have demonstrated that infections associated with antibiotic-resistant bacteria, including MRSA, lead to increases in costs of care.46,47 An approach that has been demonstrated to be cost-effective in hospitals to decrease infections from drug-resistant pathogens is active surveillance followed by contact isolation of those colonized and/or infected.48,49 The current investigation did evaluate the cost-effectiveness of universal screening for MRSA colonization among all U.S. pregnant women plus the costs of attempting decolonization of those found to be colonized. Our findings of a lack of cost-effectiveness are not surprising given the high costs of universal surveillance with decolonization and moderate rates of disease noted herein (with no attributable mortality). Future investigations of targeted surveillance in specific pregnant populations at higher risk for MRSA colonization or among those at higher risk for surgical site infectious morbidity (planned cesarean delivery) may prove cost-effective. This investigation does not address the cost-effectiveness of surveillance plus contact isolation, and thus, no conclusions about that practice can be made.
It is important to note that the projections generated by this model are likely underestimates of the overall burden of MRSA in obstetrics. This is primarily due to the fact that only two specific infectious outcomes were included: cesarean wound infections and lactation-associated breast infections. These two clinical entities were chosen because published reports demonstrate that S aureus is a major pathogen in these two outcomes.11,29,50 Other potential burdensome infections of perinatal importance such as chorioamnionitis and/or postpartum endometritis were not included due to the lack of formal reports documenting MRSA as a direct cause of these intrauterine infections. In addition, a recent investigation by Thurman et al51 (including pregnant women) documents a high rate of vulvar abscesses attributable to MRSA, thus highlighting the overall increasing burden.
A few limitations to this investigation based on some of the model assumptions warrant consideration. First and foremost, in lieu of clear data in the obstetric literature regarding actual case rates of MRSA infections, the model assumed that MRSA colonization was an accurate surrogate for infectious cases. This is a reasonable assumption, given that nasal colonization with methicillin-susceptible S aureus has been demonstrated to be a predisposing factor for increased risk from infectious morbidity in other patient populations, including surgical patients.52,53
This assumption, however, does not allow for de novo infections to occur in noncolonized or newly colonized patients, potentially underestimating the full burden of disease. It was assumed that, when patients were managed with antibiotics, the agents were chosen empirically for 48 hours and then were changed to antibiotics that have activity against MRSA. In addition, our treatment courses of 7 days of antibiotics for wound infections and 10 days for breast infections may also not be completely standardized at all institutions. Although this may not accurately depict the exact sequence or length of therapy for all cases, neither of these variables were identified in the sensitivity analysis as key factors and are thus of little consequence for the overall economic estimates. A further recognized limitation is that the model assumed that every patient diagnosed with a breast abscess was hospitalized, which may not completely represent standard practice for all providers. Last, due to the lack of national data on various outcomes and costs, local estimates from Magee-Womens Hospital were used and may not perfectly reflect national estimates. More robust data available in the literature would have improved the precision of our estimates.
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