Incidence and Outcomes Associated With Clostridium difficile Infections: A Systematic Review and Meta-analysis.

Importance: An understanding of the incidence and outcomes of Clostridium difficile infection (CDI) in the United States can inform investments in prevention and treatment interventions. Objective: To quantify the incidence of CDI and its associated hospital length of stay (LOS) in the United States using a systematic literature review and meta-analysis. Data Sources: MEDLINE via Ovid, Cochrane Library Databases via Wiley, Cumulative Index of Nursing and Allied Health Complete via EBSCO Information Services, Scopus, and Web of Science were searched for studies published in the United States between 2000 and 2019 that evaluated CDI and its associated LOS. Study Selection: Incidence data were collected only from multicenter studies that had at least 5 sites. The LOS studies were included only if they assessed postinfection LOS or used methods accounting for time to infection using a multistate model or compared propensity score-matched patients with CDI with control patients without CDI. Long-term-care facility studies were excluded. Of the 119 full-text articles, 86 studies (72.3%) met the selection criteria. Data Extraction and Synthesis: Two independent reviewers performed the data abstraction and quality assessment. Incidence data were pooled only when the denominators used the same units (eg, patient-days). These data were pooled by summing the number of hospital-onset CDI incident cases and the denominators across studies. Random-effects models were used to obtain pooled mean differences. Heterogeneity was assessed using the I2 value. Data analysis was performed in February 2019. Main Outcomes and Measures: Incidence of CDI and CDI-associated hospital LOS in the United States. Results: When the 13 studies that evaluated incidence data in patient-days due to hospital-onset CDI were pooled, the CDI incidence rate was 8.3 cases per 10 000 patient-days. Among propensity score-matched studies (16 of 20 studies), the CDI-associated mean difference in LOS (in days) between patients with and without CDI varied from 3.0 days (95% CI, 1.44-4.63 days) to 21.6 days (95% CI, 19.29-23.90 days). Conclusions and Relevance: Pooled estimates from currently available literature suggest that CDI is associated with a large burden on the health care system. However, these estimates should be interpreted with caution because higher-quality studies should be completed to guide future evaluations of CDI prevention and treatment interventions.

Effect of travel distance and rurality of residence on initial surveillance for hepatocellular carcinoma in VA primary care patient with cirrhosis.

OBJECTIVE: To determine the relationship between travel distance and surveillance for hepatocellular carcinoma among veterans with cirrhosis. DATA SOURCES: Veterans Health Administration (VHA) inpatient and outpatient administrative data were linked to geocoded enrollee files. CMS-VHA merged data were used to assess receipt of Medicare-financed non-VA imaging. STUDY DESIGN: A retrospective cohort of US veterans diagnosed with cirrhosis between 2009 and 2015 was examined. First available abdominal imaging following the diagnosis of cirrhosis was analyzed separately as a function of travel distance to the nearest VA medical center (VAMC) and to the patient's assigned VA primary care provider. Veterans with dual use of Medicare and VA services were also examined for receipt of imaging outside of the VA. PRINCIPAL FINDINGS: Veterans who resided more than 30 miles from the nearest VAMC were less likely to receive any imaging for HCC surveillance. Among dual users, increased travel distance between the patient's residence and nearest VAMC was associated with an increased likelihood of receiving any abdominal imaging at non-VA facilities. CONCLUSION: Increased travel distance to the nearest VA medical center reduces the likelihood of receiving imaging for HCC surveillance in cirrhotic veterans. Future efforts should focus on reducing geographic barriers to HCC surveillance.

Cefazolin vs. anti-staphylococcal penicillins for treatment of methicillin-susceptible Staphylococcus aureus bloodstream infections in acutely ill adult patients: Results of a systematic review and meta-analysis.

A systematic literature review and meta-analysis was conducted to evaluate the comparative efficacy and tolerability of cefazolin vs. anti-staphylococcal penicillins (ASPs) for methicillin-susceptible Staphylococcus aureus (MSSA) bloodstream infections (BSI). Utilizing published regression models, included studies were stratified into subgroups of high and low pre-probability of mortality. Cefazolin was associated with significantly lower rates of treatment failure (odds ratio [OR]: 0.70; 95% confidence interval [CI]: 0.61-0.82; P<0.001; I2 = 14%) and crude, all-cause mortality (OR: 0.69; 95% CI: 0.59-0.81; P<0.001; I2 = 18%) compared with ASP therapy. Overall risk of treatment-related adverse drug reactions was numerically lower with cefazolin (OR: 0.39; 95% CI: 0.15-1.00; P = 0.05). Subgroup sensitivity analyses of studies conducted in less severely ill patients were similar to the combined analysis. The role of cefazolin in the most severely ill patients with MSSA BSI should be prospectively evaluated.

Antimicrobial Nonsusceptibility of Gram-Negative Bloodstream Isolates, Veterans Health Administration System, United States, 2003-20131.

Bacteremia caused by gram-negative bacteria is associated with serious illness and death, and emergence of antimicrobial drug resistance in these bacteria is a major concern. Using national microbiology and patient data for 2003-2013 from the US Veterans Health Administration, we characterized nonsusceptibility trends of community-acquired, community-onset; healthcare-associated, community-onset; and hospital-onset bacteremia for selected gram-negative bacteria (Escherichia coli, Klebsiella spp., Pseudomonas aeruginosa, and Acinetobacter spp.). For 47,746 episodes of bacteremia, the incidence rate was 6.37 episodes/10,000 person-years for community-onset bacteremia and 4.53 episodes/10,000 patient-days for hospital-onset bacteremia. For Klebsiella spp., P. aeruginosa, and Acinetobacter spp., we observed a decreasing proportion of nonsusceptibility across nearly all antimicrobial drug classes for patients with healthcare exposure; trends for community-acquired, community-onset isolates were stable or increasing. The role of infection control and antimicrobial stewardship efforts in inpatient settings in the decrease in drug resistance rates for hospital-onset isolates needs to be determined.

Comparative Effectiveness of Cefazolin Versus Nafcillin or Oxacillin for Treatment of Methicillin-Susceptible Staphylococcus aureus Infections Complicated by Bacteremia: A Nationwide Cohort Study.

Background: To treat patients with methicillin-susceptible Staphylococcus aureus (MSSA) infections, ß-lactams are recommended for definitive therapy; however, the comparative effectiveness of individual ß-lactams is unknown. This study compared definitive therapy with cefazolin vs nafcillin or oxacillin among patients with MSSA infections complicated by bacteremia. Methods: This retrospective study included patients admitted to 119 Veterans Affairs hospitals from 2003 to 2010. Patients were included if they had a blood culture positive for MSSA and received definitive therapy with cefazolin, nafcillin, or oxacillin. Cox proportional hazards regression and ordinal logistic regression were used to identify associations between antibiotic therapy and mortality or recurrence. A recurrent infection was defined as a MSSA blood culture between 45 and 365 days after the first MSSA blood culture. Results: Of 3167 patients, 1163 (37%) patients received definitive therapy with cefazolin. Patients who received cefazolin had a 37% reduction in 30-day mortality (hazard ratio [HR], 0.63; 95% confidence interval [CI], .51-.78) and a 23% reduction in 90-day mortality (HR, 0.77; 95% CI, .66-.90) compared with patients receiving nafcillin or oxacillin, after controlling for other factors. The odds of recurrence (odds ratio, 1.13; 95% CI, .94-1.36) were similar among patients who received cefazolin compared with patients who received nafcillin or oxacillin, after controlling for other factors. Conclusions: In this large, multicenter study, patients who received cefazolin had a lower risk of mortality and similar odds of recurrent infections compared with nafcillin or oxacillin for MSSA infections complicated by bacteremia. Physicians might consider definitive therapy with cefazolin for these infections.

The Effect of a Nationwide Infection Control Program Expansion on Hospital-Onset Gram-Negative Rod Bacteremia in 130 Veterans Health Administration Medical Centers: An Interrupted Time-Series Analysis.

BACKGROUND: The Veterans Health Administration (VHA) introduced the Methicillin-Resistant Staphylococcus aureus (MRSA) Prevention Initiative in March 2007. Although the initiative has been perceived as a vertical intervention focusing on MRSA, it also expanded infection prevention and control programs and resources. We aimed to assess the horizontal effect of the initiative on hospital-onset (HO) gram-negative rod (GNR) bacteremia. METHODS: This retrospective cohort included all patients who had HO bacteremia due to Escherichia coli, Klebsiella species, or Pseudomonas aeruginosa at 130 VHA facilities from January 2003 to December 2013. The effects were assessed using segmented linear regression with autoregressive error models, incorporating autocorrelation, immediate effect, and time before and after the initiative. Community-acquired (CA) bacteremia with same species was also analyzed as nonequivalent dependent controls. RESULTS: A total of 11 196 patients experienced HO-GNR bacteremia during the study period. There was a significant change of slope in HO-GNR bacteremia incidence rates from before the initiative (+0.3%/month) to after (-0.4%/month) (P < .01), while CA GNR incidence rates did not significantly change (P = .08). Cumulative effect of the intervention on HO-GNR bacteremia incidence rates at the end of the study period was estimated to be -43.2% (95% confidence interval, -51.6% to -32.4%). Similar effects were observed in subgroup analyses of each species and antimicrobial susceptibility profile. CONCLUSIONS: Within 130 VHA facilities, there was a sustained decline in HO-GNR bacteremia incidence rates after the implementation of the MRSA Prevention Initiative. As these organisms were not specifically targeted, it is likely that horizontal components of the initiative contributed to this decline.

Increased Mortality Rates Associated with Staphylococcus aureus and Influenza Co-infection, Maryland and Iowa, USA(1).

We retrospectively analyzed data for 195 respiratory infection patients who had positive Staphyloccocus aureus cultures and who were hospitalized in 2 hospitals in Iowa and Maryland, USA, during 2003-2009. Odds for death for patients who also had influenza-positive test results were >4 times higher than for those who had negative influenza test results.

Association between microbial characteristics and poor outcomes among patients with methicillin-resistant Staphylococcus aureus pneumonia: a retrospective cohort study.

BACKGROUND: Methicillin-resistant S. aureus (MRSA) pneumonia is associated with poor clinical outcomes. This study examined the association between microbial characteristics and poor outcomes among patients with methicillin-resistant Staphylococcus aureus pneumonia. FINDINGS: This retrospective cohort study included 75 patients with MRSA pneumonia who were admitted to two large tertiary care medical centers during 2003-2010. Multivariable models were created using Cox proportional hazards regression and ordinal logistic regression to identify predictors of mortality or increased length of stay (LOS). None of the microbial characteristics (PFGE type, agr dysfunction, SCCmec type, and detection of PVL, ACME, and TSST-1) were significantly associated with 30-day mortality or post-infection hospital length of stay, after adjusting for gender, age, previous hospital admission within 12 months, previous MRSA infection or colonization, positive influenza test, Charlson Comorbidity Index score, and treatment (linezolid or vancomycin). CONCLUSION: Large prospective studies are needed to examine the impact of microbial characteristics on the risk of death and other adverse outcomes among patients with MRSA pneumonia.

Comparative effectiveness of beta-lactams versus vancomycin for treatment of methicillin-susceptible Staphylococcus aureus bloodstream infections among 122 hospitals.

BACKGROUND: Previous studies indicate that vancomycin is inferior to beta-lactams for treatment of methicillin-susceptible Staphylococcus aureus (MSSA) bloodstream infections. However, it is unclear if this association is true for empiric and definitive therapy. Here, we compared beta-lactams with vancomycin for empiric and definitive therapy of MSSA bloodstream infections among patients admitted to 122 hospitals. METHODS: This retrospective cohort study included all patients admitted to Veterans Affairs hospitals from 2003 to 2010 who had positive blood cultures for MSSA. Hazard ratios (HR) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards regression. Empiric therapy was defined as starting treatment 2 days before and up to 4 days after the first MSSA blood culture was collected. Definitive therapy was defined as starting treatment between 4 and 14 days after the first positive blood culture was collected. RESULTS: Patients who received empiric therapy with a beta-lactam had similar mortality compared with those who received vancomycin (HR, 1.03; 95% CI, .89-1.20) after adjusting for other factors. However, patients who received definitive therapy with a beta-lactam had 35% lower mortality compared with patients who received vancomycin (HR, 0.65; 95% CI, .52-.80) after controlling for other factors. The hazard of mortality decreased further for patients who received cefazolin or antistaphylococcal penicillins compared with vancomycin (HR, 0.57; 95% CI, .46-.71). CONCLUSIONS: For patients with MSSA bloodstream infections, beta-lactams are superior to vancomycin for definitive therapy but not for empiric treatment. Patients should receive beta-lactams for definitive therapy, specifically antistaphylococcal penicillins or cefazolin.

Determination of risk factors for recurrent methicillin-resistant Staphylococcus aureus bacteremia in a Veterans Affairs healthcare system population.

OBJECTIVE: To identify important risk factors for recurrent methicillin-resistant Staphylococcus aureus (MRSA) to assist clinicians in identifying high-risk patients for continued surveillance and follow-up. METHODS: In this retrospective cohort study, we examined patients with MRSA bacteremia at 122 Veterans Affairs medical facilities from January 1, 2003, through December 31, 2010. Recurrent MRSA bacteremia was identified by a positive blood culture result from 2 to 180 days after index hospitalization discharge. Subset analyses were performed to evaluate risk factors for early-onset (2-60 days after discharge) and late-onset (61-180 days after discharge) recurrence. Risk factors were evaluated using Cox proportional hazards regression. RESULTS: Of 18,425 patients, 1,159 (6.3%) had recurrent MRSA bacteremia. The median time to recurrence was 63 days. Longer duration of index bacteremia, increased severity of illness, receipt of only vancomycin, community-acquired infection, and several comorbidities were risk factors for recurrence. Congestive heart failure, hypertension, and rheumatoid arthritis/collagen disease were risk factors for early-onset but not late-onset recurrence. Geographic region and cardiac arrhythmias were risk factors for late-onset but not early-onset recurrence. CONCLUSIONS: Risk factors for recurrent MRSA bacteremia included comorbidities, severity of illness, duration of bacteremia, and receipt of only vancomycin. Awareness of risk factors may be important at patient discharge for implementation of quality improvement initiatives including surveillance, follow-up, and education for high-risk patients.

Methicillin-resistant Staphylococcus aureus prevention practices in hospitals throughout a rural state.

BACKGROUND: The Institute for Healthcare Improvement (IHI) created an evidence-based bundle to help reduce methicillin-resistant Staphylococcus aureus (MRSA) health care-associated infections. The study aim was to identify which components of the IHI's MRSA bundle that rural hospitals have implemented and to identify barriers that hindered implementation of bundle components. METHODS: Four surveys about the IHI's MRSA bundle were administered at the Iowa Statewide Infection Prevention Seminar between 2007 and 2011. Surveys were mailed to infection preventionists (IPs) who did not attend the meetings. RESULTS: The percentage of IPs reporting that their hospital implemented a hand hygiene program (range by year, 87%-94%) and used contact precautions for patients infected (range by year, 97%-100%) or colonized (range by year, 77%-92%) with MRSA did not change significantly. The number of hospitals that monitored the effectiveness of environmental cleaning significantly increased from 23%-71% (P < .01). Few hospitals assessed daily if central lines were necessary (range by year, 22%-26%). IPs perceived lack of support to be a major barrier to implementing bundle components. CONCLUSION: Most IPs reported that their hospitals had implemented most components of the MRSA bundle. Support within the health care system is essential for implementing each component of an evidence-based bundle.

Continued emergence of USA300 methicillin-resistant Staphylococcus aureus in the United States: results from a nationwide surveillance study.

BACKGROUND: The epidemiology of methicillin-resistant Staphylococcus aureus (MRSA) is changing, with USA300 emerging first in community and then in healthcare settings. We performed nationwide surveillance to assess recent trends in the molecular epidemiology of MRSA. METHODS: One hundred consecutive unique clinically significant S. aureus isolates were recovered from patients at each of 43 US centers between July 1, 2011, and December 31, 2011. Susceptibility testing, pulsed-field gel electrophoresis (PFGE), staphylococcal protein A gene (spa) and staphylococcal cassette chromosome mec typing, and Panton-Valentine leukocidin detection were performed on all MRSA isolates. RESULTS: Of 4,131 isolates collected, 2,093 (51%) were MRSA. Specimen sources of MRSA isolates included wound or abscess (54%), blood (24%), lower respiratory tract (11%), and other sterile site (10%). Thirty percent were isolated more than 48 hours after hospital admission (ie, were associated with nosocomial acquisition of infection). USA300 was the most common PFGE type (1,269 isolates; 61%), overall and in all regions, followed by USA100 (368 isolates; 18%). Among 173 spa types found, the most common were t008 (51%) and t002 (18%); no other spa type accounted for more than 2% of isolates. One strain type (USA300/t008/IV) constituted almost half of all MRSA isolates (1,005 isolates; 48%) and was the most common at all body sites, causing 37% of MRSA bloodstream infections (BSIs) and 38% of nosocomial MRSA infections. Multidrug-resistant phenotypes were found among 34 USA300 isolates (3%) from 18 states. CONCLUSIONS: The USA300 PFGE type continues to advance nationwide. A single strain type (USA300/t008/IV) predominates in all regions and infection sites and is now more common than USA100 as a cause of MRSA BSI and nosocomial infections. Although most USA300 retain typical susceptibility profiles, multidrug-resistant phenotypes are emerging.

Activities of vancomycin, ceftaroline, and mupirocin against Staphylococcus aureus isolates collected in a 2011 national surveillance study in the United States.

Forty-two medical centers from throughout the United States participating in a longitudinal surveillance program were asked to submit 100 consecutive Staphylococcus aureus isolates during July to December 2011. Susceptibility testing using CLSI broth microdilution and mecA detection by PCR analysis was performed on the 4,131 isolates collected. Methods employing Etest glycopeptide resistance detection (GRD; bioMérieux) and brain heart infusion agar containing 4 µg/ml vancomycin (BHIV) were used to screen methicillin-resistant S. aureus (MRSA) isolates for heterogeneous intermediate-level resistance to vancomycin (hVISA). Isolates with positive hVISA screen results were confirmed by population analysis profiling-area under the curve (PAP-AUC) determinations. The genetic relatedness of hVISA, ceftaroline-nonsusceptible, or high-level (HL) mupirocin resistance MRSA isolates was assessed by pulsed-field gel electrophoresis (PFGE). Among 2,093 MRSA isolates, the hVISA screen results were positive with 47 isolates by Etest GRD and 30 isolates by BHIV agar screen. Twenty-five of the GRD- or BHIV screen-positive isolates were confirmed as hVISA by PAP-AUC testing. Results of the current study were compared to results obtained from prior surveillance performed in 2009. The prevalence of hVISA among MRSA isolates was higher in 2011 than in 2009 (1.2% versus 0.4%, P = 0.003), especially for isolates with a vancomycin MIC of 2 (45.4% versus 14.3%, P = 0.01). The overall rate of ceftaroline susceptibility in the current study was 99.4% (one hVISA isolate had an intermediate ceftaroline MIC). HL mupirocin resistance increased from 2.2% in 2009 to 3.2% in 2011 (P = 0.006). Although overall rates of hVISA and HL mupirocin resistance are low, they have increased since 2009.

Chlorhexidine and mupirocin susceptibilities of methicillin-resistant staphylococcus aureus from colonized nursing home residents.

Chlorhexidine and mupirocin are used in health care facilities to eradicate methicillin-resistant Staphylococcus aureus (MRSA) carriage. The objective of this study was to assess the frequency of chlorhexidine and mupirocin resistance in isolates from nares carriers in multiple nursing homes and to examine characteristics associated with resistance. Nasal swab samples were collected from approximately 100 new admissions and 100 current residents in 26 nursing homes in Orange County, CA, from October 2008 to May 2011. MRSA isolates were tested for susceptibility by using broth microdilution, disk diffusion, and Etest; for genetic relatedness using pulsed-field gel electrophoresis; and for qac gene carriage by PCR. Characteristics of the nursing homes and their residents were collected from the Medicare Minimum Data Set and Long-Term Care Focus. A total of 829 MRSA isolates were obtained from swabbing 3,806 residents in 26 nursing homes. All isolates had a chlorhexidine MIC of ≤4 µg/ml. Five (0.6%) isolates harbored the qacA and/or qacB gene loci. Mupirocin resistance was identified in 101 (12%) isolates, with 78 (9%) isolates exhibiting high-level mupirocin resistance (HLMR). HLMR rates per facility ranged from 0 to 31%. None of the isolates with HLMR displayed qacA or qacB, while two isolates carried qacA and exhibited low-level mupirocin resistance. Detection of HLMR was associated with having a multidrug-resistant MRSA isolate (odds ratio [OR], 2.69; P = 0.004), a history of MRSA (OR, 2.34; P < 0.001), and dependency in activities of daily living (OR, 1.25; P = 0.004). In some facilities, HLMR was found in nearly one-third of MRSA isolates. These findings may have implications for the increasingly widespread practice of MRSA decolonization using intranasal mupirocin.

Staphylococcus aureus colonization before infection is not associated with mortality among S. aureus-infected patients: a meta-analysis.

BACKGROUND AND OBJECTIVE: The literature is conflicted as to whether people colonized with Staphylococcus aureus are at an increased risk of mortality. The aim of this meta-analysis was to review and analyze the current literature to determine whether prior history of S. aureus colonization is associated with mortality among S. aureus-infected patients. METHODS: The PUBMED databases were searched with keywords related to S. aureus colonization and mortality. After reviewing 380 article abstracts and 59 articles in detail, only 7 studies had data on the association between S. aureus colonization and mortality among S. aureus-infected patients. Crude estimates of study odds ratios (ORs) were calculated on the basis of data from subset analyses. We pooled crude ORs from the 7 studies using a random-effects model. Woolf's test for heterogeneity was assessed. RESULTS: When all studies were pooled in a random-effects model, no association between S. aureus colonization and mortality among S. aureus-infected patients was seen (pooled OR, 1.08 [95% confidence interval (CI), 0.32-3.66]; [Formula: see text]; heterogeneity [Formula: see text]). When the analyses were restricted to infection-attributable mortality, the association between colonization and mortality among S. aureus-infected patients was not statistically significant (pooled OR, 0.42 [95% CI, 0.15-1.21]; [Formula: see text]; heterogeneity [Formula: see text]). CONCLUSIONS: S. aureus colonization was not associated with mortality among patients who developed an S. aureus infection. Interventions to decolonize S. aureus carriers may prevent S. aureus infections but may not be sufficient to prevent mortality.