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Prevalence of and risk factors for methicillin-resistant Staphylococcus aureus colonization and infection among infants at a level III neonatal intensive care unit
Prevalence of and risk factors for methicillin-resistant Staphylococcus aureus colonization and infection among infants at a level III neonatal intensive care unit Nizar F. Maraqa, MD,a Lemuel Aigbivbalu, MD,a Carmen Masnita-Iusan, MS,b Peter Wludyka, PhD,b Zan Shareef,a Christine Bailey, RN, CIC,c and Mobeen H. Rathore, MDa,c Jacksonville, Florida
Background: Methicillin-resistant Staphylococcus aureus (MRSA) is a well-known nosocomial pathogen of neonatal intensive care unit (NICU) patients and can cause both serious infections in preterm neonates and prolonged MRSA outbreaks in NICUs. Objectives: Our objectives were to determine the prevalence of and identify risk factors for MRSA colonization and infection in the NICU and the impact of an active surveillance program on MRSA in the NICU. Methods: We collected weekly nasal MRSA surveillance cultures on 2,048 infants admitted to NICU over 3 years. Data on these infants were collected retrospectively. Characteristics of MRSA colonized and infected infants were analyzed and compared. Results: MRSA colonization was detected in 6.74% of infants, and MRSA infection occurred in 22% of those colonized. Using clinical cultures alone, only 41 (27.5%) of 149 MRSA affected infants were identified. The majority (75%) developed MRSA infection within 17 days of colonization. For every 10-day increment in NICU stay, the odds ratio of being infected and colonized with MRSA increased by 1.32 and 1.29, respectively. Colonization was significantly associated with longer NICU stay, low birth weight, low gestational age, and multiple gestation status. Conclusion: Colonization is a risk factor for infection with MRSA in NICUs. Clinical cultures underestimate MRSA affected infants in NICUs, whereas active surveillance cultures could detect MRSA affected infants earlier and limit nosocomial spread. Key Words: Methicillin-resistant Staphylococcus aureus colonization; MRSA colonization; methicillin-resistant Staphylococcus aureus infection; MRSA infection; surveillance cultures. Copyright ª 2011 by the Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved. (Am J Infect Control 2011;39:35-41.)
Methicillin-resistant Staphylococcus aureus (MRSA) is a well-known nosocomial pathogen of neonatal intensive care unit (NICU) patients.1,2 MRSA can cause both serious infections in preterm neonates and prolonged MRSA outbreaks in NICUs. Aggressive, multifaceted,
From the Division of Pediatric Infectious Diseases and Immunology, Department of Pediatrics, University of Florida College of MedicineJacksonville, Jacksonville, FLa; Department of Mathematics and Statistics, University of North Florida, Jacksonville, FLb; and Wolfson Children’s Hospital, Jacksonville, FL.c Address correspondence to Mobeen H. Rathore, MD, Professor and Chief, Division of Pediatric Infectious Diseases and Immunology, Department of Pediatrics, University of Florida College of MedicineJacksonville, 653-1 W 8th St, LRC-3rd floor, L-13, Jacksonville, FL 32209. E-mail: [email protected]. Conflicts of interest: None to report. 0196-6553/$36.00 Copyright ª 2011 by the Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved. doi:10.1016/j.ajic.2010.07.013
infection control measures are often necessary to terminate these outbreaks.1-6 In recent years, there is an increasing prevalence of community-associated MRSA (CA-MRSA) strains, which creates reservoirs of this pathogen among the family members of NICU patients and among the health workers caring for these patients. Previous studies have shown the penetration of CA-MRSA into the NICUs causing nosocomial infections and outbreaks.7 In addition to cost of containing an outbreak, the cost of managing hospitalized patients with MRSA infection is much higher than patients without such infections.1,8 In 2000, over half of S aureus isolates causing nosocomial infection among patients in ICUs from hospitals participating in the National Nosocomial Infections Surveillance (NNIS) system were found to be MRSA.9 Identified risk factors for developing a nosocomial MRSA infection in older children and adults included prolonged hospitalization, previous antibiotic use, admission to an ICU or burn unit, and exposure to colonized or infected patients.1,10,11 Similar data regarding the prevalence of MRSA colonization in NICUs and 35
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studies delineating the risk factors for becoming colonized or infected with MRSA in the NICU setting are few. The purpose of this study was to determine the prevalence of MRSA colonization and infection in the NICU and identify risk factors for colonization and infection in the NICU patients.
METHODS Between January 2004 and through December 2006, all neonates admitted to the NICU at Wolfson Children’s Hospital (WCH) in Jacksonville, Florida, had nasal MRSA surveillance cultures performed on admission and were kept in contact isolation until culture results were available. If MRSA colonized, infants were cohorted and kept in isolation until their discharge from the unit. In addition, weekly surveillance cultures were performed in those patients who were not MRSA colonized or infected during their stay in the NICU. Initially, all infants born at WCH (inborn) and those referred from an outside hospital (outborn) had MRSA surveillance cultures performed on admission to the NICU. No MRSA colonized inborn infant was identified after 18 weeks of culturing. As a result, surveillance protocol was amended, and inborn neonates were cultured with the first weekly surveillance cultures after their birth. We performed genetic fingerprinting on the initial 36 MRSA isolates recovered from surveillance cultures and found 7 different genetic clones. We did not conduct any further genetic fingerprinting because the infants’ colonization appeared to originate from multiple sources and not from a single point source. Anterior nares were cultured with swabs premoistened with nonbacteriostatic saline solution. Swabs were streaked onto a differential media, BBL CHROMagar MRSA plates (Becton Dickinson and Co, Franklin Lakes, NJ), and incubated aerobically at 358C to 378C for 24 6 4 hours. All plates were then examined for mauve colored colonies consistent with MRSA. If negative, the plates were reincubated for another 24 hours, and, if mauve colonies were detected (at 48 hours), then the specimen was reported as positive for MRSA, as recommended by the manufacturer.12 No further susceptibility testing was performed. All other specimens from sterile (eg, blood, urine [acquired via catheter or suprapubic aspiration], cerebrospinal fluid, peritoneal fluid, soft tissue) and nonsterile sites (eg, skin, stool, umbilicus) for routine clinical care were collected by the NICU staff as necessary and processed by the microbiology laboratory according to the accepted standards of clinical laboratory practice. Susceptibility of all clinical isolates to methicillin and other antimicrobial agents was performed and reported according to interpretive criteria of the Clinical and Laboratory Standards Institute (CLSI). Results of the weekly active surveillance MRSA cultures of anterior nares were made available to the
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NICU team. However, the day-to-day management of all infants in the NICU including the investigation of sepsis and acquisition of specimen for culture as well as the use of antimicrobials and duration of therapy were left to the discretion of the attending neonatologist caring for the infant at the time. All infants with MRSA colonization or infection were placed in contact isolation and cohorted. Nasal mupirocin ointment was applied for 5 days; however, its impact on colonization status was not studied. Enhanced infection control activities, including staff in-services, were ongoing providing education on hand hygiene and information on control of MRSA spread as well as limiting visits to parents and grandparents only. Other measures described to terminate outbreaks in NICUs, such as discharge baths or unit closures, were not carried out during our study. Demographic data were collected retrospectively on all infants admitted to the NICU. Perinatal information as well as NICU hospital course and outcome were extracted from the electronic database used in the unit (NeoData; Isoprime Corporation, Lisle, IL). Colonization was defined as isolation of MRSA from anterior nares without evidence of infection, whereas infection was defined as isolation of MRSA from normally sterile sites (including, but not limited to, blood, urine, or cerebrospinal fluid) or from nonsterile sites (eg, skin, eye, or umbilical stump) in the presence of clinical signs of infection using the National Healthcare Safety Network (NHSN) criteria for nosocomial infection as a guide.13 We defined low birth weight (BW) infants as those whose birth weight was # 2,500 g, whereas low gestational age (GA) infants were those born at 32 weeks of gestation or earlier. The study was approved by the institutional review boards of the University of Florida-Jacksonville and Baptist Medical Center/WCH in Jacksonville, Florida. Statistical analyses and modeling were done using SAS 9.1 software (Cary, NC). Categorical comparisons, such as comparing race, delivery type, or gender between noncolonized and colonized infants or noninfected and infected infants, were done using x2 tests, which was also used to compare the rate of infection among colonized infants by year. The 2-sample t test was performed to show whether there was a significant difference in birth weight, multiple gestation status, and gestational age between noncolonized and colonized infants and noninfected and infected infants. Additionally, the nonparametric Wilcoxon test was used to compare medians on interval variables that had a wide range. Multiple logistic regression analysis was used to predict the probability of MRSA infection by colonization status and length of stay (LOS) for 3 different gestational ages. The McNemar test was used to compare colonization to infection rates.
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RESULTS The total numbers of annual NICU admissions for 2004, 2005, and 2006 were 602, 706, and 740, respectively, and the average daily census was 40. There were no significant differences in the number of admissions among the 3 years of the study. There were 1,616 (79%) inborn infants compared with 432 (21%) outborn infants admitted to the unit. A total of 4,759 specimens from 2,048 infants was cultured for MRSA: 1,154 (56%) were male; 1,433 (70%) were white, 471 (23%) were black, and 144 (7%) were from other races. Delivery was by cesarean section (C/S) in 1,221 (60%) and vaginal in 827 (40%) infants. Vaginal delivery was assisted (ie, by vacuum or forceps extraction) in 62 (3%) cases. The average GA was 34.62 weeks (range, 22-42 weeks; median, 35 weeks). The average BW was 2,466 g (range, 431-5,920 g; median, 2,476 g), with 1040 (51%) infants being low BW, and 417 (20%) infants were low GA. The average LOS was 21 days (range, 0-236 days; median, 11 days). MRSA colonization was detected in 138 (6.74%) infants of whom 30 were infected: 9 of 44 in 2004, 14 of 56 in 2005, and 7 of 38 in 2006. Overall, 41 (2%) infants developed MRSA infections: 30 (21.74%) of 138 colonized infants compared with 11 (0.58%) of 1910 noncolonized infants (P , .001, x2). The relative risk (RR) of MRSA infection for colonized infants is 37.75 (95% confidence interval [CI] for RR: 19.35-73.69) as compared with the noncolonized. The annual incidence of MRSA infection per 1,000 patient-days was 0.915 for 2004, 1.169 for 2005, and 0.893 for 2006. One hundred nineteen (7.36%) of 1,616 inborn infants developed MRSA colonization (RR, 1.67; 95% CI: 1.042.69) compared with 19 (4.4%) of 432 outborn infants (P 5 .03; Fisher exact test). The prevalence rate (per 1,000 patient-days) for MRSA (colonization or infection [ie, MRSA affected]) in our NICU was 3.624 (95% CI: 3.043-4.205). MRSA infection prevalence was 0.997 (95% CI: 0.692-1.302), and colonization prevalence was 3.356 (95% CI: 3.0434.205) (P , .0001, Fisher exact test). There was no significant difference between the individual years of study (Table 1). The mean duration to MRSA colonization was 20 days (range, 1-164 days; median, 14 days). Interquartile analysis revealed that 25% became colonized in # 9 days after admission and 75% in # 22 days. The mean duration to MRSA infection after colonization was 16 days (range, 0-95 days; median, 6.5 days) with 25% developing MRSA infection in # 3 days after colonization and 75% in # 17 days after colonization. T test analysis (of the means) and Wilcoxon test analysis (of the medians) on interval variables (GA, BW, and LOS) produced similar results. The mean LOS was 31.69 days longer in colonized than noncolonized infants
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(95% CI: 24.11-39.07). The difference in proportion of multiple gestation between colonized and noncolonized infants was 9% (95% CI: 1.4-16.62). Conversely, the colonized infants’ mean BW was 0.81 kg (95% CI: 0.660.95) lower than for noncolonized, and the mean GA for the colonized infants was 3.58 weeks (95% CI: 2.854.31) less than for noncolonized infants (Table 2). Testing by x2 revealed that colonization rate was not significantly different between males and females (6.15 vs 7.49, respectively, P 5 .2296). However, the rate of colonization was significantly higher for black race vs non-blacks (8.92 vs 6.09, respectively, P 5 .0316), for C/S vs vaginal delivery (8.11 vs 4.72, respectively, P 5 .0026) and for inborn vs outborn infants (7.36 vs 4.4, respectively, P 5 .0289). When comparing MRSA infected infants (n 5 41) with noninfected infants (n 5 2007) regardless of colonization status, the LOS was significantly longer in infected than in noninfected (69 vs 20 days, respectively, 95% CI: 30.6-67.2, P , .0001). BW (1.72 vs 2.48 kg, respectively, 95% CI: 0.46-1.06, P , .0001) and GA (31.59 vs 34.68 weeks, respectively, 95% CI: 34.51-34.87, P , .0001) were significantly lower in MRSA infected than noninfected infants. The only independent variable significantly different between infected and noninfected infants was race (3.18 for black vs 1.65 for non-black, P 5 .036). The relative risk of MRSA infection for black infants was 1.96 (95% CI: 1.03-3.61) relative to non-blacks. Among the colonized infants (n 5 138), the MRSA infected (n 5 30) and noninfected (n 5 108) were compared. For the colonized infants, only the LOS was significantly higher for infected vs noninfected (78 vs 43 days, respectively, P , .0055). The difference between these 2 groups was not significant for BW, GA, race, mode of delivery, or multiple gestation status. Controlling for the year of study, the probability of infection among colonized infants did not differ significantly (2004 5 20.45% vs 2005 5 25% vs 2006 5 18.42%, P 5 .7267; x2). Using multiple logistic regression analysis, MRSA infection was significantly associated with colonization (P 5 .0249) and LOS (P 5 .0279). GA was significantly associated with MRSA infection when combined with colonization (P 5 .031) and LOS (P 5 .0064). For every 10-day increment in the LOS, the odds ratio of being infected and colonized with MRSA increased by 1.32 and 1.29, respectively. There were 1170 (57%) infants with GA $ 35 weeks whose mean LOS was 69 days (range, 0-113 days), 652 (32%) infants with GA between 28 and 35 weeks whose mean LOS was 25 days (range, 0-197 days), and 226 (11%) infants with GA # 28 weeks whose mean LOS was 69 days (range, 0-236 days). We determined the predicted probability of infection and colonization for 3 different gestational ages (25, 33, and 39 weeks)
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Table 1. Annual prevalence of MRSA in infants MRSA affected*
MRSA Infected
Year
No.
Patient-days
n
Cases per 1,000 pd (95% CI)
n
Cases per 1,000 pd (95% CI)
Colonization probability % (95% CI)
2004 2005 2006 Total
602 706 740 2048
12,023 14,536 14,556 41,115
46 60 43 149
3.826 4.217 2.954 3.624 (3.043-4.205)
11 17 13 41
0.915 1.169 0.893 0.997 (0.692-1.302)
7.31 (5.23-9.39) 7.93 (5.94-9.93) 5.14 (3.54-6.73) 6.74 (5.65-7.82)
CI, confidence interval; pd, patient-days. *MRSA affected: colonized or infected.
Table 2. Comparison of MRSA colonized and noncolonized infants
Mean (median) length of stay (days) Mean (median) birth weight (kg) Rate of multiple gestation (per 100 births) Mean (median) gestational age (wks) Black race (per 100 births) C/S delivery rate (per 100 births) Inborn birth rate (per 100 births)
Colonized infants (n 5 138)
Noncolonized infants (n 5 1910)
P value
50.65 (38.5) 1.71 (1.73) 26.08 31.29 (31) 8.92 8.11 7.36
18.96 (10) 2.52 (2.53) 17.07 34.87 (36) 6.09 4.72 4.4
,.0001* ,.0001* .0204y ,.0001* .0316y .0026y .0289y
C/S, cesarean section. *T test to compare means and Wilcoxon test to compare medians produced identical results. y 2 x Test.
(Fig 1) using logistic regression analysis model that incorporated LOS, GA, and colonization status. At a LOS of 100 days, the predicted probability of infection was 0.2 for a 25-week GA infant (Fig 1A), 0.5 for a 33week GA infant (Fig 1B), and 0.7 for a 39-week GA infant (Fig 1C). Clinical cultures identified 41 cases of MRSA infection, and active surveillance cultures identified 108 infants colonized but never infected with MRSA: this difference was significant (6.74% vs 2%, respectively; McNemar test, 79.06; P , .0001). Using clinical cultures alone would have identified only 41 (27.5%) of the 149 MRSA affected infants. Sixteen (39%) of the 41 infants with MRSA infection had bacteremia, 11 (26.8%) pneumonia, 3 (7.3%) wound infection, 8 (19.5%) conjunctivitis, and 3 (7.3%) other infections. Nine (56.3%) of 16 bacteremic patients were known to be previously colonized with MRSA. Of the 89 (4.35%) infants who died during the study period, 10 (11%) were MRSA colonized. Three of 6 with bacteremia and 3 of 11 with pneumonia who died were previously colonized.
DISCUSSION The NICU at WCH is a 48-bed level III NICU that is located in the only children’s hospital in northeast Florida. Patient care in the NICU is delivered by a team of attending neonatologists, neonatal nurse practitioners, and neonatal nurses. Consultant physicians, respiratory
therapists, physical therapists, occupational therapists, radiology technicians, and other ancillary staff are common to the entire Children’s hospital. Over the past few years, there has been an increase in MRSA infections among children who are admitted to children’s hospitals.14 MRSA causes a significant proportion of S aureus infection in NICU resulting in substantial morbidity and mortality whether the infecting strain is health care associated or CA-MRSA.1,2,15-17 The ratios of infection-tocolonization reported with NICU MRSA outbreaks have ranged from 1.4:1 to 1:2.1 The infection-to-colonization rate in our study was 1:3.37, much lower than what was seen in outbreaks that were reported previously. We believe that this difference was attributable to our surveillance program and isolation and cohorting of our patients, which may have averted an outbreak. It is believed that the major mode of transmission of MRSA in the hospital is patient to patient or from hospital personnel.1,2,18 Published studies noted that overcrowding, understaffing, and use of antibiotics and of long-term indwelling intravascular catheters can contribute to MRSA outbreaks in the NICU setting.2,19,20 Although mother-to-infant transmission of MRSA is considered rare, perinatal studies have reported contradictory results regarding maternal colonization as a risk factor for transmission of MRSA during the birth process.21-26 The anterior nares are regarded as the main site of MRSA carriage in NICU patients; however, other
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Fig 1. The predicted probability of MRSA infection by colonization status and length of stay (LOS) for gestational ages (GA) 25 weeks (A), 33 weeks (B), and 39 weeks (C). anatomical sites such as the umbilicus, groin, axillae, hands, ears, and sinuses have been reported as reservoirs.27 Culture of nasal or nasopharyngeal specimens alone is sufficiently sensitive to detect MRSA colonization in neonates.28 However, it is possible that some colonized patients were not identified. Contact isolation is the cornerstone of infection control efforts to prevent the spread of MRSA among hospitalized patients.
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Cohorting, of infants and of health care workers, has also been shown to be an effective intervention to control MRSA outbreaks in NICUs.5,18,28 Studies have supported the use of active surveillance for MRSA to allow earlier recognition and prevent outbreaks in NICU.27 No standard guidelines are currently available for the prevention and control of MRSA outbreaks in this high-risk and highly vulnerable population of patients, such as those in the NICU. In 2006, a working group recommended periodic screening for MRSA colonization and use of isolation and nursing cohorts as measures to prevent and control MRSA colonization and infection in NICUs.28 More recently, Gregory et al described their experience with active MRSA surveillance and isolation program in the NICU setting and found that it attenuated but did not eliminate MRSA. They proposed that an MRSA surveillance and isolation program will be more effective in reducing nosocomial spread of MRSA when coupled with rigorous attention to environmental decontamination and hand hygiene.29 Our results reveal that implementing active surveillance cultures for MRSA identifies MRSA affected infants significantly more than depending on clinical cultures alone. Surveillance cultures allow earlier isolation and cohorting of affected infants and further reduce the potential spread of MRSA in the NICU. MRSA colonized infants who became infected would have remained out of isolation and posed a risk of transmission for an average of more than 15 days (range, 0-95 days; median, 12 days) before their clinical cultures would have identified them as MRSA infected. The design of the NICU to allow for cohorting and isolation of these infants is critical for the successful implementation of such a program. Risk factors for colonization with MRSA in our NICU population included longer LOS, multiple gestation, low birth weight, and delivery by C/S. Seybold et al found that vaginal delivery along with maternal smoking during pregnancy, both in infants of mothers receiving systemic antibacterial therapy immediately before delivery, were risk factors for colonization with CA-MRSA as opposed to health care-associated MRSA clones.30 Further study of the impact of mode of delivery on the type of MRSA colonization in the NICU is required. Additionally, black infants had a higher risk than others of being colonized with MRSA. This may be related to family, social, or environmental factors that require further study. We found that inborn infants were more likely to develop MRSA colonization in our population. This is likely due to the significantly longer LOS, lower birth weight, and higher rate of multiple gestation (since the highest risk pregnancies are usually delivered at WCH) when compared with outborn infants, all of which were risk factors for MRSA colonization in our study.
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We demonstrated that the probability of infection with MRSA in our NICU is higher with colonization than noncolonization, and it increases with increasing LOS, although less than what has previously been reported in MRSA outbreaks in the NICU.5,18,28 We also found that, at the same LOS, MRSA colonized infants with higher gestational age have a higher probability of developing infection. This finding was reproducible at all gestational ages. We demonstrated that by selecting ages (25 weeks, 33 weeks, and 39 weeks) that correspond well to the types of infants seen most commonly in an NICU: extremely/very low birth weight infants, low birth weight infants, and near-term/full-term infants, respectively. This is likely explained by the higher complexity of problems that require the infants with higher gestational age to stay that long in the NICU and to be discharged later than healthier infants with the same gestational age. Our retrospective collection of data and lack of genotyping of MRSA isolates are some of the limitations of our study. The genotyping conducted on the initial 36 MRSA isolates from the surveillance cultures identified 7 different clones, and we believe that these multiple clones indicated colonization from several different sources rather than a single point source. Similar results were recently reported by Gregory et al29; nevertheless, further research in this area may prove valuable in characterizing the epidemiology of MRSA in the NICU. We believe that, during the study period, the prevalence of colonization and infection with CAMRSA in our NICU was increasing, as is the case in NICUs around the United States and the world. Healy et al reported that bacteremia because of MRSA among infants treated in their NICU was predominantly caused by isolates genetically identical to CA-MRSA strains rather than health care-associated MRSA.15 However, most clinical laboratories lack the means and capabilities to do genetic fingerprinting of all MRSA isolates, and infection control professionals apply their intervention without the availability of genetic information about the MRSA isolates. Identifying the prevalence of MRSA in an NICU is critical to develop the necessary intervention to prevent outbreaks. Utilizing active surveillance to detect colonized infants earlier, rather than relying on clinical cultures once they develop infection, could limit the spread of MRSA among infants in the NICU. The risk factors for colonization and subsequent infection with MRSA in the NICU setting need to be studied further to help decrease the burden of MRSA in this highly vulnerable population. Realizing early on that we will not be able to eliminate MRSA from our NICU, we decided that continuous surveillance would be the best policy to prevent transmission of MRSA. We believe we may have successfully averted outbreaks of MRSA
or increased infections with MRSA in the NICU because of our surveillance program. The authors thank the staffs of the NICU, the microbiology laboratory, and the infection control/epidemiology team at Wolfson Children’s Hospital for their help with specimen collection and reporting of data; the State of Florida Laboratory in Jacksonville, Florida, for performing genetic finger printing; and Diane Halstead, PhD, for providing valuable assistance.
References 1. Song X, Perencevich E, Campos J, Short B, Singh N. Clinical and economic impact of methicillin-resistant Staphylococcus aureus colonization or infection on neonates in intensive care units. Infect Control Hosp Epidemiol 2010;31:177-82. 2. Lessa FC, Edwards JR, Fridkin SK, Tenover FC, Horan TC, Gorwitz RJ. Trends in incidence of late-onset methicillin-resistant Staphylococcus aureus infection in neonatal intensive care units: data from the National Nosocomial Infections Surveillance System, 1995-2004. Pediatr Infect Dis J 2009;28:577-81. 3. Noel GJ, Kreiswirth BN, Edelson PJ, Nesin M, Projan S, Eisner W, et al. Multiple methicillin-resistant Staphylococcus aureus strains as a cause for a single outbreak of severe disease in hospitalized neonates. Pediatr Infect Dis J 1992;11:184-8. 4. Reboli AC, John JF Jr, Levkoff AH. Epidemic methicillin-gentamicinresistant Staphylococcus aureus in a neonatal intensive care unit. Am J Dis Child 1989;143:34-9. 5. Haddad Q, Sobayo EI, Basit OB, Rotimi VO. Outbreak of methicillinresistant Staphylococcus aureus in a neonatal intensive care unit. J Hosp Infect 1993;23:211-22. 6. Fujimura S, Kato S, Hashimoto M, Takeda H, Maki F, Watanabe A. Survey of methicillin-resistant Staphylococcus aureus from neonates and the environment in the NICU. J Infect Chemother 2004;10: 131-2. 7. Regev-Yochay G, Rubinstein E, Barzilai A, Carmeli Y, Kuint J, Etienne J, et al. Methicillin-resistant Staphylococcus aureus in neonatal intensive care unit. Emerg Infect Dis 2005;11:453-6. 8. Rubin RJ, Harrington CA, Poon A, Dietrich K, Greene JA, Moiduddin A. The economic impact of Staphylococcus aureus infection in New York City hospitals. Emerg Infect Dis 1999;5:9-17. 9. National Nosocomial Infections Surveillance (NNIS) System report, data summary from January 1992 to June 2001, issued August 2001. Am J Infect Control 2001;29:404-21. 10. McHugh CG, Riley LW. Risk factors and costs associated with methicillin-resistant Staphylococcus aureus bloodstream infections. Infect Control Hosp Epidemiol 2004;25:425-30. 11. von Baum H, Schmidt C, Svoboda D, Bock-Hensley O, Wendt C. Risk factors for methicillin-resistant Staphylococcus aureus carriage in residents of German nursing homes. Infect Control Hosp Epidemiol 2002;23:511-5. 12. Becton Dickinson and Co. Product Center, BBL CHROMagar MRSA Product Information. 2008; 2010 (01/12). 13. Edwards JR, Peterson KD, Mu Y, Banerjee S, Allen-Bridson K, Morrell G, et al. National Healthcare Safety Network (NHSN) Report, data summary for 2006 through 2008, issued December 2009. Am J Infect Control 2009;37:783-805. 14. Gerber JS, Coffin SE, Smathers SA, Zaoutis TE. Trends in the incidence of methicillin-resistant Staphylococcus aureus infection in children’s hospitals in the United States. Clin Infect Dis 2009;49:65-71. 15. Healy CM, Hulten KG, Palazzi DL, Campbell JR, Baker CJ. Emergence of new strains of methicillin-resistant Staphylococcus aureus in a neonatal intensive care unit. Clin Infect Dis 2004;39:1460-6. 16. Carey AJ, Duchon J, Della-Latta P, Saiman L. The epidemiology of methicillin-susceptible and methicillin-resistant Staphylococcus aureus in a neonatal intensive care unit, 2000-2007. J Perinatol 2010;30: 135-9.
www.ajicjournal.org Vol. 39 No. 1 17. Hitomi S, Kubota M, Mori N, Baba S, Yano H, Okuzumi K, et al. Control of a methicillin-resistant Staphylococcus aureus outbreak in a neonatal intensive care unit by unselective use of nasal mupirocin ointment. J Hosp Infect 2000;46:123-9. 18. McDonald JR, Carriker CM, Pien BC, Trinh JV, Engemann JJ, Harrell LJ, et al. Methicillin-resistant Staphylococcus aureus outbreak in an intensive care nursery: potential for interinstitutional spread. Pediatr Infect Dis J 2007;26:678-83. 19. Andersen BM, Lindemann R, Bergh K, Nesheim BI, Syversen G, Solheim N, et al. Spread of methicillin-resistant Staphylococcus aureus in a neonatal intensive unit associated with understaffing, overcrowding and mixing of patients. J Hosp Infect 2002;50:18-24. 20. Haley RW, Cushion NB, Tenover FC, Bannerman TL, Dryer D, Ross J, et al. Eradication of endemic methicillin-resistant Staphylococcus aureus infections from a neonatal intensive care unit. J Infect Dis 1995;171: 614-24. 21. Nguyen DM, Bancroft E, Mascola L, Guevara R, Yasuda L. Risk factors for neonatal methicillin-resistant Staphylococcus aureus infection in a well-infant nursery. Infect Control Hosp Epidemiol 2007;28:406-11. 22. Mitsuda T, Arai K, Fujita S, Yokota S. Demonstration of mother-toinfant transmission of Staphylococcus aureus by pulsed-field gel electrophoresis. Eur J Pediatr 1996;155:194-9. 23. Pinter DM, Mandel J, Hulten KG, Minkoff H, Tosi MF. Maternal-infant perinatal transmission of methicillin-resistant and methicillin-sensitive Staphylococcus aureus. Am J Perinatol 2009;26:145-51.
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24. Andre P, Thebaud B, Guibert M, Audibert F, Lacaze-Masmonteil T, Dehan M. Maternal-fetal Staphylococcal infections: a series report. Am J Perinatol 2000;17:423-7. 25. Andrews WW, Schelonka R, Waites K, Stamm A, Cliver SP, Moser S. Genital tract methicillin-resistant Staphylococcus aureus: risk of vertical transmission in pregnant women. Obstet Gynecol 2008;111:113-8. 26. Kitajima H. Prevention of methicillin-resistant Staphylococcus aureus infections in neonates. Pediatr Int 2003;45:238-45. 27. Bertin ML, Vinski J, Schmitt S, Sabella C, Danziger-Isakov L, McHugh M, et al. Outbreak of methicillin-resistant Staphylococcus aureus colonization and infection in a neonatal intensive care unit epidemiologically linked to a healthcare worker with chronic otitis. Infect Control Hosp Epidemiol 2006;27:581-5. 28. Gerber SI, Jones RC, Scott MV, Price JS, Dworkin MS, Filippell MB, et al. Management of outbreaks of methicillin-resistant Staphylococcus aureus infection in the neonatal intensive care unit: a consensus statement. Infect Control Hosp Epidemiol 2006;27:139-45. 29. Gregory ML, Eichenwald EC, Puopolo KM. Seven-year experience with a surveillance program to reduce methicillin-resistant Staphylococcus aureus colonization in a neonatal intensive care unit. Pediatrics 2009;123:e790-6. 30. Seybold U, Halvosa JS, White N, Voris V, Ray SM, Blumberg HM. Emergence of and risk factors for methicillin-resistant Staphylococcus aureus of community origin in intensive care nurseries. Pediatrics 2008;122: 1039-46.
Background: Methicillin-resistant Staphylococcus aureus (MRSA) is a well-known nosocomial pathogen of neonatal intensive care unit (NICU) patients and can cause both serious infections in preterm neonates and prolonged MRSA outbreaks in NICUs. Objectives: Our objectives were to determine the prevalence of and identify risk factors for MRSA colonization and infection in the NICU and the impact of an active surveillance program on MRSA in the NICU. Methods: We collected weekly nasal MRSA surveillance cultures on 2,048 infants admitted to NICU over 3 years. Data on these infants were collected retrospectively. Characteristics of MRSA colonized and infected infants were analyzed and compared. Results: MRSA colonization was detected in 6.74% of infants, and MRSA infection occurred in 22% of those colonized. Using clinical cultures alone, only 41 (27.5%) of 149 MRSA affected infants were identified. The majority (75%) developed MRSA infection within 17 days of colonization. For every 10-day increment in NICU stay, the odds ratio of being infected and colonized with MRSA increased by 1.32 and 1.29, respectively. Colonization was significantly associated with longer NICU stay, low birth weight, low gestational age, and multiple gestation status. Conclusion: Colonization is a risk factor for infection with MRSA in NICUs. Clinical cultures underestimate MRSA affected infants in NICUs, whereas active surveillance cultures could detect MRSA affected infants earlier and limit nosocomial spread. Key Words: Methicillin-resistant Staphylococcus aureus colonization; MRSA colonization; methicillin-resistant Staphylococcus aureus infection; MRSA infection; surveillance cultures. Copyright ª 2011 by the Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved. (Am J Infect Control 2011;39:35-41.)
Methicillin-resistant Staphylococcus aureus (MRSA) is a well-known nosocomial pathogen of neonatal intensive care unit (NICU) patients.1,2 MRSA can cause both serious infections in preterm neonates and prolonged MRSA outbreaks in NICUs. Aggressive, multifaceted,
From the Division of Pediatric Infectious Diseases and Immunology, Department of Pediatrics, University of Florida College of MedicineJacksonville, Jacksonville, FLa; Department of Mathematics and Statistics, University of North Florida, Jacksonville, FLb; and Wolfson Children’s Hospital, Jacksonville, FL.c Address correspondence to Mobeen H. Rathore, MD, Professor and Chief, Division of Pediatric Infectious Diseases and Immunology, Department of Pediatrics, University of Florida College of MedicineJacksonville, 653-1 W 8th St, LRC-3rd floor, L-13, Jacksonville, FL 32209. E-mail: [email protected]. Conflicts of interest: None to report. 0196-6553/$36.00 Copyright ª 2011 by the Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved. doi:10.1016/j.ajic.2010.07.013
infection control measures are often necessary to terminate these outbreaks.1-6 In recent years, there is an increasing prevalence of community-associated MRSA (CA-MRSA) strains, which creates reservoirs of this pathogen among the family members of NICU patients and among the health workers caring for these patients. Previous studies have shown the penetration of CA-MRSA into the NICUs causing nosocomial infections and outbreaks.7 In addition to cost of containing an outbreak, the cost of managing hospitalized patients with MRSA infection is much higher than patients without such infections.1,8 In 2000, over half of S aureus isolates causing nosocomial infection among patients in ICUs from hospitals participating in the National Nosocomial Infections Surveillance (NNIS) system were found to be MRSA.9 Identified risk factors for developing a nosocomial MRSA infection in older children and adults included prolonged hospitalization, previous antibiotic use, admission to an ICU or burn unit, and exposure to colonized or infected patients.1,10,11 Similar data regarding the prevalence of MRSA colonization in NICUs and 35
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studies delineating the risk factors for becoming colonized or infected with MRSA in the NICU setting are few. The purpose of this study was to determine the prevalence of MRSA colonization and infection in the NICU and identify risk factors for colonization and infection in the NICU patients.
METHODS Between January 2004 and through December 2006, all neonates admitted to the NICU at Wolfson Children’s Hospital (WCH) in Jacksonville, Florida, had nasal MRSA surveillance cultures performed on admission and were kept in contact isolation until culture results were available. If MRSA colonized, infants were cohorted and kept in isolation until their discharge from the unit. In addition, weekly surveillance cultures were performed in those patients who were not MRSA colonized or infected during their stay in the NICU. Initially, all infants born at WCH (inborn) and those referred from an outside hospital (outborn) had MRSA surveillance cultures performed on admission to the NICU. No MRSA colonized inborn infant was identified after 18 weeks of culturing. As a result, surveillance protocol was amended, and inborn neonates were cultured with the first weekly surveillance cultures after their birth. We performed genetic fingerprinting on the initial 36 MRSA isolates recovered from surveillance cultures and found 7 different genetic clones. We did not conduct any further genetic fingerprinting because the infants’ colonization appeared to originate from multiple sources and not from a single point source. Anterior nares were cultured with swabs premoistened with nonbacteriostatic saline solution. Swabs were streaked onto a differential media, BBL CHROMagar MRSA plates (Becton Dickinson and Co, Franklin Lakes, NJ), and incubated aerobically at 358C to 378C for 24 6 4 hours. All plates were then examined for mauve colored colonies consistent with MRSA. If negative, the plates were reincubated for another 24 hours, and, if mauve colonies were detected (at 48 hours), then the specimen was reported as positive for MRSA, as recommended by the manufacturer.12 No further susceptibility testing was performed. All other specimens from sterile (eg, blood, urine [acquired via catheter or suprapubic aspiration], cerebrospinal fluid, peritoneal fluid, soft tissue) and nonsterile sites (eg, skin, stool, umbilicus) for routine clinical care were collected by the NICU staff as necessary and processed by the microbiology laboratory according to the accepted standards of clinical laboratory practice. Susceptibility of all clinical isolates to methicillin and other antimicrobial agents was performed and reported according to interpretive criteria of the Clinical and Laboratory Standards Institute (CLSI). Results of the weekly active surveillance MRSA cultures of anterior nares were made available to the
American Journal of Infection Control February 2011
NICU team. However, the day-to-day management of all infants in the NICU including the investigation of sepsis and acquisition of specimen for culture as well as the use of antimicrobials and duration of therapy were left to the discretion of the attending neonatologist caring for the infant at the time. All infants with MRSA colonization or infection were placed in contact isolation and cohorted. Nasal mupirocin ointment was applied for 5 days; however, its impact on colonization status was not studied. Enhanced infection control activities, including staff in-services, were ongoing providing education on hand hygiene and information on control of MRSA spread as well as limiting visits to parents and grandparents only. Other measures described to terminate outbreaks in NICUs, such as discharge baths or unit closures, were not carried out during our study. Demographic data were collected retrospectively on all infants admitted to the NICU. Perinatal information as well as NICU hospital course and outcome were extracted from the electronic database used in the unit (NeoData; Isoprime Corporation, Lisle, IL). Colonization was defined as isolation of MRSA from anterior nares without evidence of infection, whereas infection was defined as isolation of MRSA from normally sterile sites (including, but not limited to, blood, urine, or cerebrospinal fluid) or from nonsterile sites (eg, skin, eye, or umbilical stump) in the presence of clinical signs of infection using the National Healthcare Safety Network (NHSN) criteria for nosocomial infection as a guide.13 We defined low birth weight (BW) infants as those whose birth weight was # 2,500 g, whereas low gestational age (GA) infants were those born at 32 weeks of gestation or earlier. The study was approved by the institutional review boards of the University of Florida-Jacksonville and Baptist Medical Center/WCH in Jacksonville, Florida. Statistical analyses and modeling were done using SAS 9.1 software (Cary, NC). Categorical comparisons, such as comparing race, delivery type, or gender between noncolonized and colonized infants or noninfected and infected infants, were done using x2 tests, which was also used to compare the rate of infection among colonized infants by year. The 2-sample t test was performed to show whether there was a significant difference in birth weight, multiple gestation status, and gestational age between noncolonized and colonized infants and noninfected and infected infants. Additionally, the nonparametric Wilcoxon test was used to compare medians on interval variables that had a wide range. Multiple logistic regression analysis was used to predict the probability of MRSA infection by colonization status and length of stay (LOS) for 3 different gestational ages. The McNemar test was used to compare colonization to infection rates.
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RESULTS The total numbers of annual NICU admissions for 2004, 2005, and 2006 were 602, 706, and 740, respectively, and the average daily census was 40. There were no significant differences in the number of admissions among the 3 years of the study. There were 1,616 (79%) inborn infants compared with 432 (21%) outborn infants admitted to the unit. A total of 4,759 specimens from 2,048 infants was cultured for MRSA: 1,154 (56%) were male; 1,433 (70%) were white, 471 (23%) were black, and 144 (7%) were from other races. Delivery was by cesarean section (C/S) in 1,221 (60%) and vaginal in 827 (40%) infants. Vaginal delivery was assisted (ie, by vacuum or forceps extraction) in 62 (3%) cases. The average GA was 34.62 weeks (range, 22-42 weeks; median, 35 weeks). The average BW was 2,466 g (range, 431-5,920 g; median, 2,476 g), with 1040 (51%) infants being low BW, and 417 (20%) infants were low GA. The average LOS was 21 days (range, 0-236 days; median, 11 days). MRSA colonization was detected in 138 (6.74%) infants of whom 30 were infected: 9 of 44 in 2004, 14 of 56 in 2005, and 7 of 38 in 2006. Overall, 41 (2%) infants developed MRSA infections: 30 (21.74%) of 138 colonized infants compared with 11 (0.58%) of 1910 noncolonized infants (P , .001, x2). The relative risk (RR) of MRSA infection for colonized infants is 37.75 (95% confidence interval [CI] for RR: 19.35-73.69) as compared with the noncolonized. The annual incidence of MRSA infection per 1,000 patient-days was 0.915 for 2004, 1.169 for 2005, and 0.893 for 2006. One hundred nineteen (7.36%) of 1,616 inborn infants developed MRSA colonization (RR, 1.67; 95% CI: 1.042.69) compared with 19 (4.4%) of 432 outborn infants (P 5 .03; Fisher exact test). The prevalence rate (per 1,000 patient-days) for MRSA (colonization or infection [ie, MRSA affected]) in our NICU was 3.624 (95% CI: 3.043-4.205). MRSA infection prevalence was 0.997 (95% CI: 0.692-1.302), and colonization prevalence was 3.356 (95% CI: 3.0434.205) (P , .0001, Fisher exact test). There was no significant difference between the individual years of study (Table 1). The mean duration to MRSA colonization was 20 days (range, 1-164 days; median, 14 days). Interquartile analysis revealed that 25% became colonized in # 9 days after admission and 75% in # 22 days. The mean duration to MRSA infection after colonization was 16 days (range, 0-95 days; median, 6.5 days) with 25% developing MRSA infection in # 3 days after colonization and 75% in # 17 days after colonization. T test analysis (of the means) and Wilcoxon test analysis (of the medians) on interval variables (GA, BW, and LOS) produced similar results. The mean LOS was 31.69 days longer in colonized than noncolonized infants
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(95% CI: 24.11-39.07). The difference in proportion of multiple gestation between colonized and noncolonized infants was 9% (95% CI: 1.4-16.62). Conversely, the colonized infants’ mean BW was 0.81 kg (95% CI: 0.660.95) lower than for noncolonized, and the mean GA for the colonized infants was 3.58 weeks (95% CI: 2.854.31) less than for noncolonized infants (Table 2). Testing by x2 revealed that colonization rate was not significantly different between males and females (6.15 vs 7.49, respectively, P 5 .2296). However, the rate of colonization was significantly higher for black race vs non-blacks (8.92 vs 6.09, respectively, P 5 .0316), for C/S vs vaginal delivery (8.11 vs 4.72, respectively, P 5 .0026) and for inborn vs outborn infants (7.36 vs 4.4, respectively, P 5 .0289). When comparing MRSA infected infants (n 5 41) with noninfected infants (n 5 2007) regardless of colonization status, the LOS was significantly longer in infected than in noninfected (69 vs 20 days, respectively, 95% CI: 30.6-67.2, P , .0001). BW (1.72 vs 2.48 kg, respectively, 95% CI: 0.46-1.06, P , .0001) and GA (31.59 vs 34.68 weeks, respectively, 95% CI: 34.51-34.87, P , .0001) were significantly lower in MRSA infected than noninfected infants. The only independent variable significantly different between infected and noninfected infants was race (3.18 for black vs 1.65 for non-black, P 5 .036). The relative risk of MRSA infection for black infants was 1.96 (95% CI: 1.03-3.61) relative to non-blacks. Among the colonized infants (n 5 138), the MRSA infected (n 5 30) and noninfected (n 5 108) were compared. For the colonized infants, only the LOS was significantly higher for infected vs noninfected (78 vs 43 days, respectively, P , .0055). The difference between these 2 groups was not significant for BW, GA, race, mode of delivery, or multiple gestation status. Controlling for the year of study, the probability of infection among colonized infants did not differ significantly (2004 5 20.45% vs 2005 5 25% vs 2006 5 18.42%, P 5 .7267; x2). Using multiple logistic regression analysis, MRSA infection was significantly associated with colonization (P 5 .0249) and LOS (P 5 .0279). GA was significantly associated with MRSA infection when combined with colonization (P 5 .031) and LOS (P 5 .0064). For every 10-day increment in the LOS, the odds ratio of being infected and colonized with MRSA increased by 1.32 and 1.29, respectively. There were 1170 (57%) infants with GA $ 35 weeks whose mean LOS was 69 days (range, 0-113 days), 652 (32%) infants with GA between 28 and 35 weeks whose mean LOS was 25 days (range, 0-197 days), and 226 (11%) infants with GA # 28 weeks whose mean LOS was 69 days (range, 0-236 days). We determined the predicted probability of infection and colonization for 3 different gestational ages (25, 33, and 39 weeks)
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Table 1. Annual prevalence of MRSA in infants MRSA affected*
MRSA Infected
Year
No.
Patient-days
n
Cases per 1,000 pd (95% CI)
n
Cases per 1,000 pd (95% CI)
Colonization probability % (95% CI)
2004 2005 2006 Total
602 706 740 2048
12,023 14,536 14,556 41,115
46 60 43 149
3.826 4.217 2.954 3.624 (3.043-4.205)
11 17 13 41
0.915 1.169 0.893 0.997 (0.692-1.302)
7.31 (5.23-9.39) 7.93 (5.94-9.93) 5.14 (3.54-6.73) 6.74 (5.65-7.82)
CI, confidence interval; pd, patient-days. *MRSA affected: colonized or infected.
Table 2. Comparison of MRSA colonized and noncolonized infants
Mean (median) length of stay (days) Mean (median) birth weight (kg) Rate of multiple gestation (per 100 births) Mean (median) gestational age (wks) Black race (per 100 births) C/S delivery rate (per 100 births) Inborn birth rate (per 100 births)
Colonized infants (n 5 138)
Noncolonized infants (n 5 1910)
P value
50.65 (38.5) 1.71 (1.73) 26.08 31.29 (31) 8.92 8.11 7.36
18.96 (10) 2.52 (2.53) 17.07 34.87 (36) 6.09 4.72 4.4
,.0001* ,.0001* .0204y ,.0001* .0316y .0026y .0289y
C/S, cesarean section. *T test to compare means and Wilcoxon test to compare medians produced identical results. y 2 x Test.
(Fig 1) using logistic regression analysis model that incorporated LOS, GA, and colonization status. At a LOS of 100 days, the predicted probability of infection was 0.2 for a 25-week GA infant (Fig 1A), 0.5 for a 33week GA infant (Fig 1B), and 0.7 for a 39-week GA infant (Fig 1C). Clinical cultures identified 41 cases of MRSA infection, and active surveillance cultures identified 108 infants colonized but never infected with MRSA: this difference was significant (6.74% vs 2%, respectively; McNemar test, 79.06; P , .0001). Using clinical cultures alone would have identified only 41 (27.5%) of the 149 MRSA affected infants. Sixteen (39%) of the 41 infants with MRSA infection had bacteremia, 11 (26.8%) pneumonia, 3 (7.3%) wound infection, 8 (19.5%) conjunctivitis, and 3 (7.3%) other infections. Nine (56.3%) of 16 bacteremic patients were known to be previously colonized with MRSA. Of the 89 (4.35%) infants who died during the study period, 10 (11%) were MRSA colonized. Three of 6 with bacteremia and 3 of 11 with pneumonia who died were previously colonized.
DISCUSSION The NICU at WCH is a 48-bed level III NICU that is located in the only children’s hospital in northeast Florida. Patient care in the NICU is delivered by a team of attending neonatologists, neonatal nurse practitioners, and neonatal nurses. Consultant physicians, respiratory
therapists, physical therapists, occupational therapists, radiology technicians, and other ancillary staff are common to the entire Children’s hospital. Over the past few years, there has been an increase in MRSA infections among children who are admitted to children’s hospitals.14 MRSA causes a significant proportion of S aureus infection in NICU resulting in substantial morbidity and mortality whether the infecting strain is health care associated or CA-MRSA.1,2,15-17 The ratios of infection-tocolonization reported with NICU MRSA outbreaks have ranged from 1.4:1 to 1:2.1 The infection-to-colonization rate in our study was 1:3.37, much lower than what was seen in outbreaks that were reported previously. We believe that this difference was attributable to our surveillance program and isolation and cohorting of our patients, which may have averted an outbreak. It is believed that the major mode of transmission of MRSA in the hospital is patient to patient or from hospital personnel.1,2,18 Published studies noted that overcrowding, understaffing, and use of antibiotics and of long-term indwelling intravascular catheters can contribute to MRSA outbreaks in the NICU setting.2,19,20 Although mother-to-infant transmission of MRSA is considered rare, perinatal studies have reported contradictory results regarding maternal colonization as a risk factor for transmission of MRSA during the birth process.21-26 The anterior nares are regarded as the main site of MRSA carriage in NICU patients; however, other
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Fig 1. The predicted probability of MRSA infection by colonization status and length of stay (LOS) for gestational ages (GA) 25 weeks (A), 33 weeks (B), and 39 weeks (C). anatomical sites such as the umbilicus, groin, axillae, hands, ears, and sinuses have been reported as reservoirs.27 Culture of nasal or nasopharyngeal specimens alone is sufficiently sensitive to detect MRSA colonization in neonates.28 However, it is possible that some colonized patients were not identified. Contact isolation is the cornerstone of infection control efforts to prevent the spread of MRSA among hospitalized patients.
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Cohorting, of infants and of health care workers, has also been shown to be an effective intervention to control MRSA outbreaks in NICUs.5,18,28 Studies have supported the use of active surveillance for MRSA to allow earlier recognition and prevent outbreaks in NICU.27 No standard guidelines are currently available for the prevention and control of MRSA outbreaks in this high-risk and highly vulnerable population of patients, such as those in the NICU. In 2006, a working group recommended periodic screening for MRSA colonization and use of isolation and nursing cohorts as measures to prevent and control MRSA colonization and infection in NICUs.28 More recently, Gregory et al described their experience with active MRSA surveillance and isolation program in the NICU setting and found that it attenuated but did not eliminate MRSA. They proposed that an MRSA surveillance and isolation program will be more effective in reducing nosocomial spread of MRSA when coupled with rigorous attention to environmental decontamination and hand hygiene.29 Our results reveal that implementing active surveillance cultures for MRSA identifies MRSA affected infants significantly more than depending on clinical cultures alone. Surveillance cultures allow earlier isolation and cohorting of affected infants and further reduce the potential spread of MRSA in the NICU. MRSA colonized infants who became infected would have remained out of isolation and posed a risk of transmission for an average of more than 15 days (range, 0-95 days; median, 12 days) before their clinical cultures would have identified them as MRSA infected. The design of the NICU to allow for cohorting and isolation of these infants is critical for the successful implementation of such a program. Risk factors for colonization with MRSA in our NICU population included longer LOS, multiple gestation, low birth weight, and delivery by C/S. Seybold et al found that vaginal delivery along with maternal smoking during pregnancy, both in infants of mothers receiving systemic antibacterial therapy immediately before delivery, were risk factors for colonization with CA-MRSA as opposed to health care-associated MRSA clones.30 Further study of the impact of mode of delivery on the type of MRSA colonization in the NICU is required. Additionally, black infants had a higher risk than others of being colonized with MRSA. This may be related to family, social, or environmental factors that require further study. We found that inborn infants were more likely to develop MRSA colonization in our population. This is likely due to the significantly longer LOS, lower birth weight, and higher rate of multiple gestation (since the highest risk pregnancies are usually delivered at WCH) when compared with outborn infants, all of which were risk factors for MRSA colonization in our study.
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We demonstrated that the probability of infection with MRSA in our NICU is higher with colonization than noncolonization, and it increases with increasing LOS, although less than what has previously been reported in MRSA outbreaks in the NICU.5,18,28 We also found that, at the same LOS, MRSA colonized infants with higher gestational age have a higher probability of developing infection. This finding was reproducible at all gestational ages. We demonstrated that by selecting ages (25 weeks, 33 weeks, and 39 weeks) that correspond well to the types of infants seen most commonly in an NICU: extremely/very low birth weight infants, low birth weight infants, and near-term/full-term infants, respectively. This is likely explained by the higher complexity of problems that require the infants with higher gestational age to stay that long in the NICU and to be discharged later than healthier infants with the same gestational age. Our retrospective collection of data and lack of genotyping of MRSA isolates are some of the limitations of our study. The genotyping conducted on the initial 36 MRSA isolates from the surveillance cultures identified 7 different clones, and we believe that these multiple clones indicated colonization from several different sources rather than a single point source. Similar results were recently reported by Gregory et al29; nevertheless, further research in this area may prove valuable in characterizing the epidemiology of MRSA in the NICU. We believe that, during the study period, the prevalence of colonization and infection with CAMRSA in our NICU was increasing, as is the case in NICUs around the United States and the world. Healy et al reported that bacteremia because of MRSA among infants treated in their NICU was predominantly caused by isolates genetically identical to CA-MRSA strains rather than health care-associated MRSA.15 However, most clinical laboratories lack the means and capabilities to do genetic fingerprinting of all MRSA isolates, and infection control professionals apply their intervention without the availability of genetic information about the MRSA isolates. Identifying the prevalence of MRSA in an NICU is critical to develop the necessary intervention to prevent outbreaks. Utilizing active surveillance to detect colonized infants earlier, rather than relying on clinical cultures once they develop infection, could limit the spread of MRSA among infants in the NICU. The risk factors for colonization and subsequent infection with MRSA in the NICU setting need to be studied further to help decrease the burden of MRSA in this highly vulnerable population. Realizing early on that we will not be able to eliminate MRSA from our NICU, we decided that continuous surveillance would be the best policy to prevent transmission of MRSA. We believe we may have successfully averted outbreaks of MRSA
or increased infections with MRSA in the NICU because of our surveillance program. The authors thank the staffs of the NICU, the microbiology laboratory, and the infection control/epidemiology team at Wolfson Children’s Hospital for their help with specimen collection and reporting of data; the State of Florida Laboratory in Jacksonville, Florida, for performing genetic finger printing; and Diane Halstead, PhD, for providing valuable assistance.
References 1. Song X, Perencevich E, Campos J, Short B, Singh N. Clinical and economic impact of methicillin-resistant Staphylococcus aureus colonization or infection on neonates in intensive care units. Infect Control Hosp Epidemiol 2010;31:177-82. 2. Lessa FC, Edwards JR, Fridkin SK, Tenover FC, Horan TC, Gorwitz RJ. Trends in incidence of late-onset methicillin-resistant Staphylococcus aureus infection in neonatal intensive care units: data from the National Nosocomial Infections Surveillance System, 1995-2004. Pediatr Infect Dis J 2009;28:577-81. 3. Noel GJ, Kreiswirth BN, Edelson PJ, Nesin M, Projan S, Eisner W, et al. Multiple methicillin-resistant Staphylococcus aureus strains as a cause for a single outbreak of severe disease in hospitalized neonates. Pediatr Infect Dis J 1992;11:184-8. 4. Reboli AC, John JF Jr, Levkoff AH. Epidemic methicillin-gentamicinresistant Staphylococcus aureus in a neonatal intensive care unit. Am J Dis Child 1989;143:34-9. 5. Haddad Q, Sobayo EI, Basit OB, Rotimi VO. Outbreak of methicillinresistant Staphylococcus aureus in a neonatal intensive care unit. J Hosp Infect 1993;23:211-22. 6. Fujimura S, Kato S, Hashimoto M, Takeda H, Maki F, Watanabe A. Survey of methicillin-resistant Staphylococcus aureus from neonates and the environment in the NICU. J Infect Chemother 2004;10: 131-2. 7. Regev-Yochay G, Rubinstein E, Barzilai A, Carmeli Y, Kuint J, Etienne J, et al. Methicillin-resistant Staphylococcus aureus in neonatal intensive care unit. Emerg Infect Dis 2005;11:453-6. 8. Rubin RJ, Harrington CA, Poon A, Dietrich K, Greene JA, Moiduddin A. The economic impact of Staphylococcus aureus infection in New York City hospitals. Emerg Infect Dis 1999;5:9-17. 9. National Nosocomial Infections Surveillance (NNIS) System report, data summary from January 1992 to June 2001, issued August 2001. Am J Infect Control 2001;29:404-21. 10. McHugh CG, Riley LW. Risk factors and costs associated with methicillin-resistant Staphylococcus aureus bloodstream infections. Infect Control Hosp Epidemiol 2004;25:425-30. 11. von Baum H, Schmidt C, Svoboda D, Bock-Hensley O, Wendt C. Risk factors for methicillin-resistant Staphylococcus aureus carriage in residents of German nursing homes. Infect Control Hosp Epidemiol 2002;23:511-5. 12. Becton Dickinson and Co. Product Center, BBL CHROMagar MRSA Product Information. 2008; 2010 (01/12). 13. Edwards JR, Peterson KD, Mu Y, Banerjee S, Allen-Bridson K, Morrell G, et al. National Healthcare Safety Network (NHSN) Report, data summary for 2006 through 2008, issued December 2009. Am J Infect Control 2009;37:783-805. 14. Gerber JS, Coffin SE, Smathers SA, Zaoutis TE. Trends in the incidence of methicillin-resistant Staphylococcus aureus infection in children’s hospitals in the United States. Clin Infect Dis 2009;49:65-71. 15. Healy CM, Hulten KG, Palazzi DL, Campbell JR, Baker CJ. Emergence of new strains of methicillin-resistant Staphylococcus aureus in a neonatal intensive care unit. Clin Infect Dis 2004;39:1460-6. 16. Carey AJ, Duchon J, Della-Latta P, Saiman L. The epidemiology of methicillin-susceptible and methicillin-resistant Staphylococcus aureus in a neonatal intensive care unit, 2000-2007. J Perinatol 2010;30: 135-9.
www.ajicjournal.org Vol. 39 No. 1 17. Hitomi S, Kubota M, Mori N, Baba S, Yano H, Okuzumi K, et al. Control of a methicillin-resistant Staphylococcus aureus outbreak in a neonatal intensive care unit by unselective use of nasal mupirocin ointment. J Hosp Infect 2000;46:123-9. 18. McDonald JR, Carriker CM, Pien BC, Trinh JV, Engemann JJ, Harrell LJ, et al. Methicillin-resistant Staphylococcus aureus outbreak in an intensive care nursery: potential for interinstitutional spread. Pediatr Infect Dis J 2007;26:678-83. 19. Andersen BM, Lindemann R, Bergh K, Nesheim BI, Syversen G, Solheim N, et al. Spread of methicillin-resistant Staphylococcus aureus in a neonatal intensive unit associated with understaffing, overcrowding and mixing of patients. J Hosp Infect 2002;50:18-24. 20. Haley RW, Cushion NB, Tenover FC, Bannerman TL, Dryer D, Ross J, et al. Eradication of endemic methicillin-resistant Staphylococcus aureus infections from a neonatal intensive care unit. J Infect Dis 1995;171: 614-24. 21. Nguyen DM, Bancroft E, Mascola L, Guevara R, Yasuda L. Risk factors for neonatal methicillin-resistant Staphylococcus aureus infection in a well-infant nursery. Infect Control Hosp Epidemiol 2007;28:406-11. 22. Mitsuda T, Arai K, Fujita S, Yokota S. Demonstration of mother-toinfant transmission of Staphylococcus aureus by pulsed-field gel electrophoresis. Eur J Pediatr 1996;155:194-9. 23. Pinter DM, Mandel J, Hulten KG, Minkoff H, Tosi MF. Maternal-infant perinatal transmission of methicillin-resistant and methicillin-sensitive Staphylococcus aureus. Am J Perinatol 2009;26:145-51.
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24. Andre P, Thebaud B, Guibert M, Audibert F, Lacaze-Masmonteil T, Dehan M. Maternal-fetal Staphylococcal infections: a series report. Am J Perinatol 2000;17:423-7. 25. Andrews WW, Schelonka R, Waites K, Stamm A, Cliver SP, Moser S. Genital tract methicillin-resistant Staphylococcus aureus: risk of vertical transmission in pregnant women. Obstet Gynecol 2008;111:113-8. 26. Kitajima H. Prevention of methicillin-resistant Staphylococcus aureus infections in neonates. Pediatr Int 2003;45:238-45. 27. Bertin ML, Vinski J, Schmitt S, Sabella C, Danziger-Isakov L, McHugh M, et al. Outbreak of methicillin-resistant Staphylococcus aureus colonization and infection in a neonatal intensive care unit epidemiologically linked to a healthcare worker with chronic otitis. Infect Control Hosp Epidemiol 2006;27:581-5. 28. Gerber SI, Jones RC, Scott MV, Price JS, Dworkin MS, Filippell MB, et al. Management of outbreaks of methicillin-resistant Staphylococcus aureus infection in the neonatal intensive care unit: a consensus statement. Infect Control Hosp Epidemiol 2006;27:139-45. 29. Gregory ML, Eichenwald EC, Puopolo KM. Seven-year experience with a surveillance program to reduce methicillin-resistant Staphylococcus aureus colonization in a neonatal intensive care unit. Pediatrics 2009;123:e790-6. 30. Seybold U, Halvosa JS, White N, Voris V, Ray SM, Blumberg HM. Emergence of and risk factors for methicillin-resistant Staphylococcus aureus of community origin in intensive care nurseries. Pediatrics 2008;122: 1039-46.