There are limited long-term data on the trends in incidence and characteristics of methicillin-resistant Staphylococcus aureus (MRSA) bacteremia (MRSAB) in intensive care units (ICUs) in which infection control measures have been adopted. We evaluated the trend of incidence and changes in characteristics of MRSA bacteremia in ICUs at a tertiary-care hospital over 10 years using prospective cohort data. ICU-acquired bacteremia was defined as S. aureus bacteremia (SAB) that occurred 48 h or more after ICU admission.
KEYWORDS: bacteremia, genotype, incidence, intensive care unit, methicillin-resistant Staphylococcus aureus, vancomycin MIC
ABSTRACT
There are limited long-term data on the trends in incidence and characteristics of methicillin-resistant Staphylococcus aureus (MRSA) bacteremia (MRSAB) in intensive care units (ICUs) in which infection control measures have been adopted. We evaluated the trend of incidence and changes in characteristics of MRSA bacteremia in ICUs at a tertiary-care hospital over 10 years using prospective cohort data. ICU-acquired bacteremia was defined as S. aureus bacteremia (SAB) that occurred 48 h or more after ICU admission. MRSA isolates were collected and subjected to microbiological and genotypic analyses. A total of 529 SAB episodes were identified among 367,175 ICU patients. Of these episodes, 288 (54.4%) were ICU acquired, 238 (82.6%) of which were MRSAB. The incidence density of ICU-acquired MRSAB decreased from 1.32 per 1,000 patient-days to 0.19 per 1,000 patient-days (a decrease of 20% annually; P < 0.001 for trend), whereas that of non-ICU-acquired MRSAB fluctuated and did not decrease significantly. The decline in ICU-acquired MRSAB was due to lower catheter-related infection and less pneumonia. Rates of persistent bacteremia and 12-week mortality also fell significantly. A total of 183 isolates were collected from 238 ICU-acquired MRSAB cases. There were no significant changes in the geometric means of vancomycin MICs, vancomycin heteroresistance, or the sequence types of MRSA isolates over time. Chlorhexidine MICs decreased (P < 0.001 for trend) in association with a decline in frequency of the qacA or qacB gene that was related to reductions in specific spa types. The incidence of MRSAB in ICUs has decreased dramatically over time, but most of the microbiological and genotypic characteristics of MRSA isolates have not changed.
INTRODUCTION
Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most common causes of serious infections in intensive care units (ICUs), including bloodstream infections, ventilator-associated pneumonia, and surgical site infections, and MRSA infection is associated with high mortality and morbidity in critically ill patients. MRSA colonization leads to subsequent MRSA infection and plays important roles in the transmission of MRSA in ICUs (1, 2). In the mid-2000s in the United States and Europe, in response to increased rates of nosocomial MRSA infections, many hospitals initiated infection control measures that included various MRSA bundles and chlorhexidine gluconate bathing with or without topical nasal mupirocin application (3). MRSA bundles usually consist of universal nasal surveillance of MRSA colonization, contact precautions for MRSA patients, hand hygiene, and a change in institutional culture (3–6).
Several studies showed that multiple infection control measures, including targeted decolonization, universal decolonization, and chlorhexidine gluconate bathing with or without nasal mupirocin application, could reduce rates of MRSA infection (7–10). As a result, in a study conducted in the United States between 2002 and 2006, nosocomial MRSA infections were reduced by 75% in a surgical ICU (11). In addition, MRSA genotypes such as multilocus sequence type (MLST) and vancomycin susceptibility have changed in both hospital-onset and community-onset MRSA infections (12–14). Chlorhexidine and mupirocin resistance increased in MRSA blood isolates due to exposure to chlorhexidine gluconate bathing and nasal mupirocin application (15, 16). We have evaluated trends in the incidence and clinical characteristics of MRSA bacteremia and investigated long-term changes in the microbiological and genotypic characteristics and antiseptic susceptibilities of MRSA blood isolates in ICUs over 10 years.
RESULTS
Incidence density of ICU-acquired S. aureus bacteremia.
During the study period, 529 S. aureus bacteremia episodes were identified in 524 of 367,175 ICU patients. Of these 529 episodes, 288 (54.4%) were ICU-acquired bacteremia and 241 (45.6%) were non-ICU-acquired bacteremia. Of the 288 ICU-acquired bacteremia episodes, 238 (82.6%) were MRSA bacteremia and 50 (17.4%) were methicillin-susceptible S. aureus (MSSA) bacteremia (see Fig. S1 in the supplemental material).
The incidence density of ICU-acquired S. aureus bacteremia decreased significantly over time, mainly due to a reduction of MRSA bacteremia (Fig. 1). The incidence density of ICU-acquired MRSA bacteremia decreased from 1.32 per 1,000 patient-days in 2009 to 0.19 per 1,000 patient-days in 2018, a decrease of 20% annually (P < 0.001 for trend), whereas the incidence density of non-ICU-acquired MRSA bacteremia did not change (P = 0.15 for trend). The decline in ICU-acquired MRSA bacteremia was due to a decrease of catheter-related bloodstream infections and MRSA pneumonia (Fig. 2). The incidence density of ICU-acquired MRSA bacteremia due to catheter-related infections decreased from 0.83 to 0.08 per 1,000 patient-days, a fall of 24% annually (P < 0.001 for trend). The incidence density of MRSA bacteremia due to pneumonia also fell, from 0.30 to 0.03 per 1,000 patient-days, a decline of 20% annually (P < 0.001 for trend). However, there was no statistically significant change in the incidence density of primary MRSA bacteremia (P = 0.98 for trend). The temporal relationship between the timing of major infection control measures and the incidence density of MRSA bacteremia is shown in Fig. S2 in the supplemental material.
FIG 1.
Incidence density of S. aureus bacteremia. (A) ICU-acquired S. aureus bacteremia (bacteremia >48 h after ICU admission) and (B) non-ICU-acquired S. aureus bacteremia (bacteremia within 48 h of ICU admission).
FIG 2.
Incidence density of ICU-acquired MRSA bacteremia according to site of infection.
Clinical characteristics of patients with ICU-acquired MRSA bacteremia.
The clinical characteristics of the 238 patients with ICU-acquired MRSA bacteremia are presented in Table 1. The median age was 64 years (interquartile range [IQR], 53 to 72 years), and 172 (72.3%) were male. The most common comorbidities were solid tumor (34%), diabetes mellitus (22.7%), and liver cirrhosis (21.8%). The most common form of infection was catheter-related infection (60.1%), followed by pneumonia (18.9%) and primary bacteremia (8.8%). When the study period was divided into three periods, this cohort showed significant increases in the proportion of liver cirrhosis, solid organ transplantation, and immunosuppressive treatment (P < 0.02, P = 0.001, and P = 0.02, respectively).
TABLE 1.
Clinical characteristics of patients with ICU-acquired methicillin-resistant S. aureus bacteremia
| Characteristice | Period 1a (n = 129) | Period 2b (n = 68) | Period 3c (n = 41) | All patients (n = 238) | Pf |
|---|---|---|---|---|---|
| Median age (no. of yrs [IQR]) | 65 (55–73) | 64.5 (51–73) | 62 (55–68) | 64 (53–72) | 0.47 |
| Male gender | 95 (73.6) | 44 (64.7) | 33 (80.5) | 172 (72.3) | 0.76 |
| Site of infection | |||||
| Catheter-related bacteremia | 85 (65.9) | 40 (58.8) | 18 (43.9) | 143 (60.1) | 0.01 |
| Pneumonia | 23 (17.8) | 14 (20.6) | 8 (19.5) | 45 (18.9) | 0.72 |
| Skin and soft tissue infection | 0 | 0 | 0 | 0 | NA |
| Bone and joint infection | 0 | 0 | 0 | 0 | NA |
| Infective endocarditis | 0 | 0 | 1 (2.4) | 1 (0.4) | 0.07 |
| Postoperative wound infection | 11 (8.5) | 6 (8.8) | 3 (7.3) | 20 (8.4) | 0.85 |
| Primary bacteremia | 7 (5.4) | 5 (7.4) | 9 (22.0) | 21 (8.8) | 0.003 |
| Underlying disease/condition | |||||
| Solid tumor | 43 (33.3) | 18 (26.5) | 20 (48.8) | 81 (34.0) | 0.21 |
| Hematologic malignancy | 1 (0.8) | 1 (1.5) | 0 (0) | 2 (0.8) | 0.81 |
| Diabetes mellitus | 31 (24.0) | 14 (20.6) | 9 (22.0) | 54 (22.7) | 0.68 |
| Hemodialysis dependence | 8 (6.2) | 12 (17.6) | 3 (7.3) | 23 (9.7) | 0.33 |
| Liver cirrhosis | 21 (16.3) | 18 (26.5) | 13 (31.7) | 52 (21.8) | 0.02 |
| Solid organ transplantation | 15 (11.6) | 14 (20.6) | 14 (34.1) | 43 (18.1) | 0.001 |
| Neutropenia | 5 (3.9) | 1 (1.5) | 0 (0) | 6 (2.5) | 0.13 |
| Immunosuppressive treatmentd | 53 (41.1) | 31 (45.6) | 26 (63.4) | 110 (46.2) | 0.02 |
| Recent chemotherapy | 6 (4.7) | 1 (1.5) | 1 (2.4) | 8 (3.4) | 0.44 |
| Persistent bacteremia (≥7 days) | 24 (18.6) | 1 (1.5) | 5 (12.2) | 30 (12.6) | 0.04 |
| Mortality | |||||
| 14 days | 34 (26.4) | 16 (23.5) | 6 (14.6) | 56 (23.5) | 0.14 |
| 30 days | 57 (44.2) | 28 (41.2) | 11 (26.8) | 106 (44.5) | 0.07 |
| 12 wks | 73 (56.6) | 33 (48.5) | 15 (36.6) | 131 (55.0) | 0.02 |
From 2009 to 2011.
From 2012 to 2014.
From 2015 to 2018.
Immunosuppressive treatment includes immunosuppressant use (≥7 days), steroid use (≥14 days), or radiation therapy (within 1 month).
Data are given as no. (%) of patients unless otherwise indicated. IQR, interquartile range.
NA, not applicable.
Of the 238 patients with ICU-acquired MRSA bacteremia, 30 (12.6%) had persistent bacteremia (≥7 days). The rate of persistent bacteremia decreased from 18.6% in period 1 to 12.2% in period 3 (P = 0.04). A total of 121 (50.8%) patients with ICU-acquired MRSA bacteremia died in hospital. The 12-week mortality rate decreased from 56.6% in period 1 to 36.6% in period 3 (P = 0.02), and 30-day mortality rate showed a tendency to decrease (P = 0.07).
Microbiological and genotypic characteristics of the MRSA isolates.
Table 2 summarizes the microbiological and genotypic characteristics of the MRSA isolates from the ICU-acquired MRSA bacteremias. A total of 183 MRSA blood isolates were collected from the 238 cases of ICU-acquired MRSA bacteremia. Of these isolates, 65 (35.5%) had the heterogeneous vancomycin-intermediate S. aureus (hVISA) phenotype, 160 (87.4%) were sequence type 5 (ST5), 95 (51.9%) were spa type t2460, and the geometric mean of vancomycin MIC for all isolates was 1.53 mg/liter (standard deviation [SD], 0.50). There were no significant changes in the geometric means of vancomycin MICs (P = 0.62 for trend) or in the proportions of hVISA phenotypes (P = 0.21 for trend) (Fig. 3A) or MLST genotypes over time (P = 0.07 for trend; Fig. 3B). However, there was a significant decrease in the combined proportion of t2460 and t9353 (P = 0.02 for trend; see Fig. S3 in the supplemental material).
TABLE 2.
Microbiological and genotypic characteristics of MRSA isolates from ICU-acquired bacteremia
| Characteristicd | Period 1a (n = 85) | Period 2b (n = 58) | Period 3c (n = 40) | All isolates (n = 183) |
|---|---|---|---|---|
| Vancomycin MIC (Etest) | ||||
| MIC (mean ± SD) | 1.47 ± 0.5 | 1.69 ± 0.6 | 1.43 ± 0.5 | 1.53 ± 0.5 |
| ≤1.0 mg/liter | 27 (31.8) | 11 (19.0) | 14 (35.0) | 52 (28.4) |
| 1.5 mg/liter | 38 (44.7) | 23 (39.7) | 16 (40.0) | 77 (42.1) |
| ≥2.0 mg/liter | 20 (23.5) | 24 (41.3) | 10 (25.0) | 54 (29.5) |
| hVISA phenotype | 33 (38.8) | 19 (32.8) | 13 (32.5) | 65 (35.5) |
| Genotype | ||||
| Multilocus sequence type | ||||
| ST5 | 76 (89.4) | 53 (91.4) | 31 (77.5) | 160 (87.4) |
| ST72 | 4 (4.7) | 3 (5.2) | 6 (15.0) | 13 (7.1) |
| ST239 | 3 (3.5) | 1 (1.7) | 0 | 4 (2.2) |
| Others | 2 (2.4) | 1 (1.7) | 3 (7.5) | 6 (3.3) |
| spa type | ||||
| t2460 | 44 (51.8) | 38 (65.5) | 13 (32.5) | 95 (51.9) |
| t9353 | 14 (16.5) | 5 (8.6) | 4 (10.0) | 23 (12.6) |
| t002 | 5 (5.9) | 4 (6.9) | 5 (12.5) | 14 (7.7) |
| t148 | 3 (3.5) | 0 | 2 (5.0) | 5 (2.7) |
| t264 | 3 (3.5) | 0 | 1 (2.5) | 4 (2.2) |
| t9363 | 2 (2.4) | 2 (3.4) | 0 | 4 (2.2) |
| Others | 14 (16.5) | 9 (15.5) | 15 (37.5) | 38 (20.8) |
| Chlorohexidine MIC | ||||
| MIC, mean ± SD | 3.02 ± 1.2 | 2.66 ± 1.2 | 1.95 ± 1.1 | 2.67 ± 1.3 |
| 1.0 mg/liter | 13 (15.3) | 12 (20.7) | 16 (40.0) | 41 (22.4) |
| 2.0 mg/liter | 22 (25.9) | 21 (36.2) | 17 (42.5) | 60 (32.8) |
| 4.0 mg/liter | 50 (58.8) | 25 (43.1) | 7 (17.5) | 82 (44.8) |
| Mupirocin resistance | ||||
| Low-level resistance | 17 (20.0) | 21 (36.2) | 20 (50.0) | 58 (31.7) |
| High-level resistance | 2 (2.4) | 3 (5.2) | 4 (10.0) | 9 (4.9) |
| Presence of resistance gene | ||||
| qacA or qacB | 69 (81.2) | 38 (65.5) | 16 (40.0) | 123 (67.2) |
| smr | 0 | 2 (3.4) | 5 (12.5) | 7 (3.8) |
| mupA | 2 (2.4) | 3 (5.2) | 5 (12.5) | 10 (5.5) |
From 2009 to 2011.
From 2012 to 2014.
From 2015 to 2018.
Data are given as no. (%) of patients unless otherwise indicated. hVISA, heterogenous vancomycin-intermediate Staphylococcus aureus.
FIG 3.
Changes in microbiological and genotypic characteristics of MRSA blood isolates in ICUs. (A) Geometric means of vancomycin MICs (P = 0.62 for trend) and frequencies of hVISA phenotype (P = 0.21 for trend), (B) MLST (P = 0.07 for trend), and (C) geometric means of chlorhexidine MICs (P < 0.001 for trend) and frequencies of qacA or qacB (P < 0.001 for trend) and smr (P = 0.01 for trend).
Of the 183 MRSA isolates, 123 (67.2%) had qacA or qacB and 7 (3.8%) had smr genes, and the geometric mean of chlorhexidine MICs for all isolates was 2.7 mg/liter (SD, 1.3). The qacA and qacB genes were significantly associated with ST5 MRSA (P < 0.001), especially with two spa types (t2460 and t9353, P = 0.001 and P = 0.002, respectively) (see Table S1 in the supplemental material). The proportion of qacA or qacB-positive isolates decreased from 84.8% to 33.3% (P < 0.001 for trend), and the geometric means of chlorhexidine MICs decreased from 3.2 mg/liter to 1.7 mg/liter (P < 0.001 for trend) (Fig. 3C). In addition, 58 (31.7%) the MRSA isolates had low-level mupirocin resistance, 9 (4.9%) had high-level mupirocin resistance, and 10 (5.5%) had mupA genes. There was a significant increase in the proportion of low-level mupirocin resistance (P < 0.001 for trend) (see Fig. S4 in the supplemental material).
DISCUSSION
In this study, we found that the incidence density of ICU-acquired MRSA bacteremia decreased by 20% annually (from 1.32 per 1,000 patient-days to 0.19 per 1,000 patient-days; P < 0.001 for trend), whereas the incidence density of non-ICU-acquired MRSA bacteremia fluctuated and followed a decreasing trend from 2014 (P = 0.15 for trend). However, there were no significant changes in vancomycin MICs, vancomycin heteroresistance, MLST genotypes, or high-level mupirocin resistance over time. In terms of antiseptic susceptibility, chlorhexidine MICs, frequency of qacA or qacB, and low-level mupirocin resistance all changed during the study period. As a result of specific measures such as the central line care bundle in our ICUs, MRSA bacteremia due to catheter-related infections and pneumonia was reduced, and this contributed to the decreased incidence density of ICU-acquired MRSA bacteremia.
In South Korea, vancomycin has been the standard treatment for MRSA infection, and daptomycin has not been available. Therefore, vancomycin MICs could have increased in a setting with high vancomycin usage. Several studies have shown that vancomycin MIC creep appears to be associated with increased vancomycin usage (17, 18). However, we found that vancomycin MICs did not change (P = 0.62 for trend), consistent with previous studies that examined MRSA isolates from all hospital patients (19–21). In addition, the proportion of vancomycin heteroresistance did not change in the present study (P = 0.21 for trend), which is consistent with the finding that the frequency of vancomycin heteroresistance is vancomycin MIC dependent (19).
Due to the influence of multiple infection control measures, there may be an increase in the proportion of genotypes that could adapt to the new environment. Our study did not reveal any changes in MLST genotypes during the study period. This finding was similar to those of previous studies (12). Interestingly, the present study revealed that qacA or qacB positivity and chlorhexidine MIC decreased over time. There are several possible explanations for these changes. The first is that our hospital only started routine chlorhexidine bathing for all ICU patients at the end of the study period. Second, the proportion of major spa types in ST5 MRSA (t2460 and t9353) that were closely associated with qacA or qacB genes declined during the study period (P = 0.02 for trend). This may have influenced the decreases in qacA or qacB positivity and chlorhexidine MIC. The clonal association of these chlorhexidine resistance genes has been documented in other countries (22, 23). Interestingly, the t2460 spa type has been identified mostly in Asia (24–26), and t2460 isolates reported from China carried qacA or qacB genes (22, 27). In South Korea, both t2460 and t9353 are the major spa types of MRSA (28–30), and t2460 was reported to be associated with qacA or qacB genes (29).
In addition, there was an increase in the proportion of low-level mupirocin resistance. However, there were no significant changes in the proportion of high-level mupirocin resistance and mupA positivity that were related to decolonization failure (31, 32). This finding is probably explained by the fact that our hospital does not perform routine intranasal MRSA decolonization with mupirocin.
This prospective study had several limitations. First, it was conducted in a single tertiary-care hospital, and relatively few ICU-acquired MRSA bacteremia cases occurred toward the end of the study period. To increase study power, a large longitudinal multicenter study is needed. Second, the rate of collection of MRSA blood isolates was somewhat low (76.9%), although the isolates were randomly distributed. Therefore, caution is needed in generalizing the results to other situations. Third, qacA and qacB were not distinguished in our qacA or qacB-positive MRSA isolates. QacA confers more resistance to divalent cationic agents than QacB (33). Therefore, the proportions of qacA and qacB might have changed during the study period. Fourth, we could not demonstrate how each individual infection control measure affected the changes in the incidence density of MRSA bacteremia and the characteristics of the MRSA isolates. However, a hand hygiene campaign, a central venous catheter bundle, MRSA active surveillance, and contact precautions for MRSA patients could have mainly contributed to the reduction of ICU-acquired MRSA bacteremia (Fig. S2). Several studies have shown that the antimicrobial susceptibilities of MRSA, including that to vancomycin, have changed over time (13, 34). However, to the best of our knowledge, there are limited long-term data on the changes of other microbiological and genotypic characteristics of MRSA isolates. Therefore, our data provide important information on how the microbiological and genotypic characteristics and antiseptic susceptibilities of MRSA isolates were changed by infection control measures over a long period. It is worth noting that we collected only MRSA blood isolates to evaluate trends, in contrast to other studies that included nasal swab or sputum cultures (13, 35). Therefore, our findings could provide valuable information about the changes in microbiological and genotypic characteristics of MRSA isolates that cause invasive infections.
In conclusion, the incidence density of MRSA bacteremia in ICUs has decreased dramatically over 10 years due to the implementation of infection control measures, including improved hand washing, central venous catheter bundles, and chlorhexidine bathing. However, most of the microbiological and genotype characteristics of MRSA isolates have not changed.
MATERIALS AND METHODS
Study population and design.
We evaluated the trend of incidence and changes in the characteristics of MRSA bacteremia in ICUs using prospective cohort data. A prospective observational cohort study was conducted in adult patients (≥16 years old) with S. aureus bacteremia at the Asan Medical Center, a 2,700-bed tertiary referral center with 118 beds in adult ICUs, between January 2009 and December 2018. All adult patients with SAB were prospectively identified and enrolled according to the inclusion criteria of the cohort study and observed over a 12-week period (36). To correctly evaluate the incidence of bacteremia, patients who had been excluded because of polymicrobial bacteremia or early death (within 48 h of blood culture collection) in the prospective cohort study were retrospectively evaluated and included in the analysis. S. aureus blood isolates obtained on the first day of bacteremia were collected and stored for further testing.
The first episode of S. aureus bacteremia in each ICU patient was included in the analysis. Recurrent S. aureus bacteremia after 3 months from the first bacteremia episode was regarded as a new episode and was also included in the analysis. Adult ICUs in our hospital are medical ICU, surgical ICU, neurology ICU, neurosurgery ICU, cardiac surgery ICU, and cardiology ICU. ICU-acquired bacteremia was defined by a positive blood culture obtained from patients who had been hospitalized in ICU for ≥48 h or who were transferred out of the ICU to the ward within 48 h. Non-ICU-acquired bacteremia was defined by a positive blood culture obtained from patients who had been hospitalization in the ICU for less than 48 h, that is, bacteremia related to an infection acquired outside the ICU (37, 38). The incidence density of S. aureus bacteremia in the ICUs was evaluated, and then clinical characteristics of ICU-acquired MRSA bacteremia, microbiological, and genotypic characteristics of their isolates were analyzed.
Data collection and study definitions.
In patients with ICU-acquired MRSA bacteremia, demographic characteristics, underlying diseases or conditions, site of infection, antibiogram results, patient management, and clinical outcomes were reviewed. Site of infection causing ICU-acquired MRSA bacteremia was defined according to the Centers for Disease Control and Prevention criteria (39). Primary bacteremia was defined as MRSAB occurring in the absence of an apparent portal of entry. Infective endocarditis was defined according to the modified Duke criteria (40). Catheter-related infection was the source of bacteremia in patients with an intravascular device according to the Infectious Diseases Society of America guidelines (41). Treatment outcome of bacteremia was evaluated based on 14-day, 30-day, and 12-week all-cause mortality.
Microbiological data and genotypic assays.
All S. aureus isolates were identified using standard methods. Antimicrobial susceptibilities were determined using a MicroScan system (Dade Behring, West Sacramento, CA) and the standard criteria of the Clinical and Laboratory Standards Institute. Methicillin resistance was confirmed by PCR detection of the mecA gene. Heterogeneous vancomycin-intermediate S. aureus (hVISA) was detected by population analysis profiling of all MRSA isolates as previously described (42, 43). Vancomycin MICs of MRSA isolates were determined by the vancomycin Etest (AB Biodisk, Piscataway, NJ) on Mueller-Hinton agar according to the manufacturer’s instructions.
Multilocus sequence typing (MLST) and Staphylococcus protein A gene (spa) polymorphism typing were performed for all MRSA strains as described elsewhere (44, 45). MLST allele numbers and sequence types (STs) are available at the MLST database (http://www.mlst.net). Chlorhexidine MICs of MRSA isolates were determined by the broth microdilution test. Mupirocin resistance (low and high level) was detected using the disk diffusion method. Low-level and high-level mupirocin resistance were determined with 5-μg and 200-μg mupirocin disks (Oxoid, Hampshire, UK), respectively (46). In addition, high-level mupirocin resistance was confirmed by PCR detection of the mupA gene (47, 48). The presence of qacA or qacB, smr, and mupA was detected by PCR using primers described elsewhere (48, 49).
Infection control measures.
During the study period, our hospital implemented multiple infection control measures in ICUs. A hand hygiene campaign started in August 2008. All patients who were admitted to ICUs from January 2010 underwent active surveillance testing for MRSA by nasal swab within 24 h of admission. Contact precautions involving the use of vinyl gowns, gloves, and strict hand hygiene were applied to all patients with MRSA infection or colonization, and they underwent follow-up active surveillance testing weekly until three consecutive cultures were negative. In addition, the central venous catheter bundle was implemented in ICUs from January 2010. This included hand hygiene, maximum barrier precautions during the insertion of a central venous catheter, aseptic skin cleaning with 2% chlorhexidine gluconate in 70% alcohol, avoiding the femoral site, and removing unnecessary catheters (6). Chlorhexidine bathing once daily was applied to patients with MRSA infection or colonization for a short period, during which time the incidence of MRSA infection increased, in surgical ICU from August 2011 and in medical ICU from April 2013. Chlorhexidine gluconate-impregnated film dressing was used from 2016. All patients in ICUs have undergone chlorhexidine bathing since August 2018. Monitoring and feedback on adherence to infection control measures have been continuously performed. Hand hygiene compliance rate was maintained at about 90%, and for the central venous catheter bundle, the compliance rate with all bundle elements was 80 to 85%. Mupirocin nasal decolonization has not been routinely used in ICU patients.
Statistical analysis.
We analyzed categorical variables using the chi-square or Fisher’s exact tests, and continuous variables using Student’s t test or the Mann-Whitney U test. The incidence density of S. aureus bacteremia was evaluated using the patient-day method, and an exact confidence interval (CI) was estimated based on the Poisson distribution. The study period was divided into three periods. Period 1 was from 2009 to 2011, period 2 was from 2012 to 2014, and period 3 was from 2015 to 2018. The changes in the proportions of categorical variables were analyzed by chi-square test, and continuous variables over time were analyzed by linear regression for trend. All tests of significance were two-tailed, and P < 0.05 was considered statistically significant. All statistical analyses were performed with the SPSS version 24.0 K for Windows software package (SPSS, Inc., Chicago, IL) and MedCalc software (Mariakerke, Belgium).
Supplementary Material
ACKNOWLEDGMENTS
We sincerely thank Su-Jin Park and Mi Young Kim for supporting the data collection.
This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (grant NRF 2017R1D1A1A09000920).
We have no potential conflicts of interest.
Footnotes
Supplemental material is available online only.
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