Treatment, clinical outcomes, and predictors of mortality among a national cohort of hospitalized patients with Stenotrophomonas maltophilia infection.

OBJECTIVES: To analyze treatment, clinical outcomes, and predictors of inpatient mortality in hospitalized patients with Stenotrophomonas maltophilia infection. STUDY DESIGN: Retrospective cohort study. METHODS: We included patients admitted to Veterans Affairs hospitals nationally with S. maltophilia cultures and treatment from 2010 to 2019. We described patient and clinical characteristics, antibiotic treatment, and clinical outcomes. Univariate and multivariable logistic regression were used to evaluate predictors of inpatient mortality. RESULTS: We identified 3891 hospitalized patients treated for an S. maltophilia infection, of which 13.7% died during admission. The most common antibiotic agents were piperacillin/tazobactam (39.7%), sulfamethoxazole/trimethoprim (23.3%), and levofloxacin (23.2%). Combination therapy was used in 16.6% of patients. Independent predictors of inpatient mortality identified in multivariable analysis included the following: presence of current acute respiratory failure (adjusted odds ratio [aOR] 4.74, 95% confidence interval [CI] 3.63-6.19), shock (aOR 3.00, 95% CI 2.31-3.90), acute renal failure (aOR 2.06, 95% CI 1.64-2.60), and septicemia (aOR 1.90, 95% CI 1.49-2.42), age 65 years and older (aOR 2.05, 95% CI 1.07-3.94, reference age 18-49 years), hospital-acquired infection (aOR 1.87, 95% CI 1.48-2.37), Black (aOR 1.58, 95% CI 1.21-2.06) and other races (aOR 1.65, 95% CI 1.41-2.41, reference White), liver disease (aOR 1.51, 95% CI 1.02-2.22), and median Charlson comorbidity score or higher (aOR 1.36, 95% CI 1.08-1.71, reference less than median). Clinical outcomes were similar between patients infected with sulfamethoxazole/trimethoprim-resistant, levofloxacin-resistant, and multidrug-resistant S. maltophilia strains compared to non-resistant strains. CONCLUSIONS: In our national cohort of hospitalized patients with S. maltophilia infection, 13.7% of patients died during admission and several predictors of inpatient mortality were identified. Predictors related to the severity of infection were among the strongest identified. It is important that in severely ill patients presenting to the hospital, S. maltophilia be considered as a cause.

Predictors of potentially suboptimal treatment of urinary tract infections in long-term care facilities.

BACKGROUND: Suboptimal antibiotic treatment of urinary tract infection (UTI) is high in long-term care facilities (LTCFs) and likely varies between facilities. Large-scale evaluations have not been conducted. AIM: To identify facility-level predictors of potentially suboptimal treatment of UTI in Veterans Affairs (VA) LTCFs and to quantify variation across facilities. METHODS: This was a retrospective cohort study of 21,938 residents in 120 VA LTCFs (2013-2018) known as Community Living Centers (CLCs). Potentially suboptimal treatment was assessed from drug choice, dose frequency, and/or treatment duration. To identify facility characteristics predictive of suboptimal UTI treatment, LTCFs with higher and lower rates of suboptimal treatment (≥median, < median) were compared using unconditional logistic regression models. Joinpoint regression models were used to quantify average percentage difference across facilities. Multilevel logistic regression models were used to quantify variation across facilities. FINDINGS: The rate of potentially suboptimal antibiotic treatment varied from 1.7 to 34.2 per 10,000 bed-days across LTCFs. The average percentage difference in rates across facilities was 2.5% (95% confidence interval (CI): 2.4-2.7). The only facility characteristic predictive of suboptimal treatment was the incident rate of UTI per 10,000 bed-days (odds ratio: 4.9; 95% CI: 2.3-10.3). Multilevel models demonstrated that 94% of the variation between facilities was unexplained after controlling for resident and CLC characteristics. The median odds ratio for the full multilevel model was 1.37. CONCLUSION: Potentially suboptimal UTI treatment was variable across VA LTCFs. However, most of the variation across LTCFs was unexplained. Future research should continue to investigate factors that are driving suboptimal antibiotic treatment in LTCFs.

Genotype and phenotype in 12 additional individuals with SATB2-associated syndrome.

SATB2-associated syndrome (SAS) is a multisystemic disorder caused by alterations of the SATB2 gene. We describe the phenotype and genotype of 12 individuals with 10 unique (de novo in 11 of 11 tested) pathogenic variants (1 splice site, 5 frameshift, 3 nonsense, and 2 missense) in SATB2 and review all cases reported in the published literature caused by point alterations thus far. In the cohort here described, developmental delay (DD) with severe speech compromise, facial dysmorphism, and dental anomalies were present in all cases. We also present the third case of tibial bowing in an individual who, just as in the previous 2 individuals in the literature, also had a truncating pathogenic variant of SATB2. We explore early genotype-phenotype correlations and reaffirm the main clinical features of this recognizable syndrome: universal DD with severe speech impediment, mild facial dysmorphism, and high frequency of craniofacial anomalies, behavioral issues, and brain neuroradiographic changes. As the recently proposed surveillance guidelines for individuals with SAS are adopted by providers, further delineation of the frequency and impact of other phenotypic traits will become available. Similarly, as new cases of SAS are identified, further exploration of genotype-phenotype correlations will be possible.

Changing epidemiology of methicillin-resistant Staphylococcus aureus in the Veterans Affairs Healthcare System, 2002-2009.

PURPOSE: The epidemiology of infections caused by methicillin-resistant Staphylococcus aureus (MRSA) is changing. Temporal trends and differences between healthcare settings must be described in order to better predict future risk factors associated with this dangerous bacterial infection. METHODS: A national MRSA-infected cohort was identified from 2002 to 2009 in the Veterans Affairs Healthcare System of the United States: hospital (HOS), long-term care (LTC), and outpatient (OPT). We analyzed within-setting time trends using generalized linear mixed models and between-setting differences with χ(2) and Wilcoxon rank-sum tests. RESULTS: The incidence of S. aureus, methicillin-susceptible S. aureus (MSSA), and MRSA infections increased significantly over time in all three settings based on modeled annual percentage changes (P < 0.001). MRSA incidence rates rose by 14, 10, and 37% per year in the HOS, LTC, and OPT settings, respectively. Among 56,345 MRSA-infected patients, the comorbidity burden was highest among LTC inpatients (n = 4,427) and lowest among outpatients (n = 7,250), with an average absolute difference in specific comorbidities of +2 and -7%, respectively, compared to HOS inpatients (n = 44,668). Over time, there was a significant (P ≤ 0.02) decrease in previous inpatient admissions and surgeries (all settings); diabetes with complications and surgical site infections (HOS, OPT); and median length of stay and inpatient mortality (HOS, LTC). Alternatively, obesity, chronic renal disease, and depression were more common between 2002 and 2009 (P ≤ 0.02). CONCLUSIONS: Over the past 8 years, we observed significant changes in the epidemiology of MRSA infections, including decreases in traditional MRSA risk factors, improvements in clinical outcomes, and increases in other patient characteristics that may affect risk.

Risk factors associated with mupirocin resistance in meticillin-resistant Staphylococcus aureus.

Implementation of meticillin-resistant Staphylococcus aureus (MRSA) decolonisation programmes has been increasing and the emergence of mupirocin resistance has been reported. However, the patient-level risk factors associated with mupirocin resistance are not clear. In this study, independent predictors of mupirocin resistance in MRSA among Providence Veterans Affairs Medical Center patients with MRSA-positive culture dates between 1 July 2004 and 30 June 2008 were identified using a frequency-matched case-control study. Forty cases (mupirocin-resistant) were matched on culture date quarter and year to 270 controls (mupirocin-susceptible). The adjusted conditional logistic regression model identified three significant independent predictors associated with mupirocin resistance in MRSA: (1) exposure to mupirocin in the year prior to the culture date [odds ratio (OR): 9.84; 95% confidence interval (CI): 2.93-33.09]; (2) Pseudomonas aeruginosa infection in the year before the culture-related admission (4.85; 1.20-19.61); and (3) cefepime use in the year prior to culture (2.80; 1.03-7.58). In sensitivity analyses, previous mupirocin exposure was associated with low-level [minimum inhibitory concentration (MIC) 8-128mg/L; 23 cases, 202 controls; OR: 6.32; 95% CI: 1.58-25.33] and high-level (MIC ≥256mg/L; 17 cases, 151 controls; OR: 11.18; 95% CI: 1.89-66.30) mupirocin resistance. To our knowledge, this is the first case-control study to reveal a strong association between previous mupirocin exposure and subsequent mupirocin resistance in MRSA, with demonstrated robustness in low- and high-level mupirocin resistance. Mupirocin susceptibility monitoring is critical for facilities instituting decolonisation with mupirocin as increased use may reduce effectiveness through resistance.